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Argyris Michalopoulos
Director of ICU, Henry Dunant Hospital, 107 Mesogeion Ave, 11526 Athens, Greece
amichalopoulos@hol.gr
Dr Argyris Michalopoulos, MD, FCCP, FCCM. Director of a general ICU (24 beds). Special interest on ICU-acquired infections. > 150 per-reviewed publications. > 1000 citations. H-index=18. Reviewer in > 15 journals.

Journal articles

2009
 
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Vardakas, Michalopoulos, Kiriakidou, Siampli, Samonis, Falagas (2009)  Candidaemia: incidence, risk factors, characteristics and outcomes in immunocompetent critically ill patients.   Clin Microbiol Infect Jan  
Abstract: Abstract A matched case-control study was conducted to determine the risk factors for development of candidaemia in patients requiring intensive-care unit (ICU) treatment for more than 48 h. Patients were matched according to length of ICU stay, age, department of admission, year of admission and sex. Forty-five patients with candidaemia were identified (0.6 cases/1000 patient-days). Candidaemia developed mainly in critically ill patients with multiple organ failure and end-stage disease. Candida colonization and gastrointestinal surgery were independently associated with candidaemia. ICU and total in-hospital mortality were 40% and 66.7%, respectively. Candidaemia-related mortality was 20%. Candidaemia treatment failure was the only variable associated with in-hospital mortality (p 0.008).
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2008
 
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Argyris Michalopoulos, Matthew E Falagas (2008)  Colistin and polymyxin B in critical care.   Crit Care Clin 24: 2. 377-91, x Apr  
Abstract: The emergence of gram-negative bacteria resistant to most available antibiotics has led to the readministration of polymyxins B and E (colistin) as "salvage" therapy in critically ill patients. Recent studies demonstrated acceptable effectiveness and considerably less toxicity than reported in older studies of polymyxins. These old antibiotics may be administered for the treatment of intensive care unit-acquired infections of various types, including ventilator-associated pneumonia, urinary tract infections, bacteremia, and meningitis caused by multidrug resistant gram-negative pathogens, such as Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, and Enterobacter species. Randomized controlled trials are urgently needed to further clarify various issues regarding the effectiveness and safety of polymyxins, however.
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Argyris Michalopoulos, Dimitrios Fotakis, Simona Virtzili, Christodoulos Vletsas, Sylvia Raftopoulou, Zefi Mastora, Matthew E Falagas (2008)  Aerosolized colistin as adjunctive treatment of ventilator-associated pneumonia due to multidrug-resistant Gram-negative bacteria: a prospective study.   Respir Med 102: 3. 407-412 Mar  
Abstract: BACKGROUND: Ventilator-associated pneumonia (VAP) remains the leading cause of death in patients with intensive care unit (ICU) acquired infections associated with an attributable mortality around 30%. Increasing antimicrobial resistance in patients with VAP challenges intensivists to search for alternative therapeutic options. There is scarcity of data in the literature concerning the administration of aerosolized colistin in critically ill patients with VAP due to multidrug-resistant (MDR) Gram-negative pathogens. METHODS: To assess the safety and effectiveness of aerosolized colistin as an adjunctive to the intravenous antimicrobial therapy for the treatment of VAP due to MDR Gram-negative pathogens, we prospectively examined all patients, who received inhaled colistin. RESULTS: Sixty critically ill patients with a mean APACHE II score 16.7, received aerosolized colistin for the treatment of VAP due to MDR pathogens [Acinetobacter baumannii (37/60 cases), Pseudomonas aeruginosa (12/60 cases) and Klebsiella pneumoniae strains (11/60 cases)]. Half of the isolated pathogens were susceptible only to colistin. Mean (+/-SD) daily dosage of aerosolized colistin was 2.2 (+/-0.7) million international units (IU). All patients received 2946 inhalations of colistin and the mean duration of administration was 16.4 days. Fifty-seven patients received concomitant intravenous treatment with colistin or other antimicrobial agents. Bacteriological and clinical response of VAP was observed in 50/60 (83.3%) patients. No adverse effects related to inhaled colistin were recorded. All cause hospital mortality was 25% while mortality attributable to VAP was 16.7%. CONCLUSIONS: Aerosolized colistin may be considered as adjunctive to intravenous treatment in patients with VAP due to MDR Gram-negative bacteria susceptible to colistin in critically ill patients. Although colistin is safe and effective, the best route of administration remains unclear. In addition, controlled comparative studies are needed to establish its effectiveness and safety.
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Ekaterini Mastoraki, Argyris Michalopoulos, Ioannis Kriaras, Ero Mouchtouri, Matthew Falagas, Dimitra Karatza, Stefanos Geroulanos (2008)  Incidence of postoperative infections in patients undergoing coronary artery bypass grafting surgery receiving antimicrobial prophylaxis with original and generic cefuroxime.   J Infect 56: 1. 35-39 Jan  
Abstract: OBJECTIVE: The aim of this study was to compare the incidence of post-operative infections in patients undergoing coronary artery bypass grafting (CABG) surgery who received generic cefuroxime (gCFX) instead of original cefuroxime (oCFX) as antimicrobial prophylaxis. METHODS: The study had two parts, a prospective and a retrospective one (4 weeks with oCFX followed by 4 weeks with gCFX in each part; total study duration of 16 weeks). The studied patient population was 618 consecutive adult patients who underwent on pump CABG surgery. Patients were divided into two groups according to type of formulation they received: 313 patients received oCFX and 305 gCFX. RESULTS: Eight (2.5%) and 39 (12.8%) patients in the oCFX and gCFX group, respectively, developed postoperative infections (p<0.001). There were 6 (1.9%) surgical site infections in the oCFX group and 31 (10.1%) in the gCFX group (p<0.001). Bacteremia occurred in 2 (0.6%) patients in the oCFX group and in 8 (2.6%) patients in the gCFX group (p=0.1). In addition, septic shock occurred in 6 cases (2.0%, p=0.04) and multiple organ failure in another 4 patients (1.3%, p=0.1) in the gCFX group. The most common pathogens isolated were Gram-positive cocci in both groups. CONCLUSIONS: This study revealed a higher incidence of postoperative infections in adult patients undergoing CABG surgery receiving gCFX compared to oCFX as antimicrobial prophylaxis. The findings of our study provide additional evidence regarding the problem of substandard drugs, in our case a formulation of a generic antibiotic, even in developed countries. ULTRAMINI-SUMMARY: The incidence of post-operative infections following CABG surgery was higher in adult patients receiving generic instead of original cefuroxime as antimicrobial prophylaxis. The findings of our study provide additional evidence regarding the problem of substandard drugs, in our case a formulation of a generic antibiotic, even in developed countries.
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Dimitrios K Matthaiou, Argyris Michalopoulos, Petros I Rafailidis, Drosos E Karageorgopoulos, Vassiliki Papaioannou, Georgia Ntani, George Samonis, Matthew E Falagas (2008)  Risk factors associated with the isolation of colistin-resistant gram-negative bacteria: a matched case-control study.   Crit Care Med 36: 3. 807-811 Mar  
Abstract: OBJECTIVE: The emergence of multidrug-resistant gram-negative bacteria has led to the re-use of colistin, but resistance to this agent has already been reported. We aimed to investigate the potential risk factors for the isolation of colistin-resistant Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa from hospitalized patients. DESIGN: Matched case-control study. SETTING: Tertiary care hospital in Athens, Greece. PATIENTS: Case patients were those who had provided a clinical specimen from which a colistin-resistant K. pneumoniae, A. baumannii, or P. aeruginosa was isolated. Controls were selected from a pool of patients who had susceptible to colistin isolates and were matched (1:1) to cases for species of microorganism and site of isolation. Susceptibility to colistin was determined with the Etest. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data regarding patient demographics, comorbidities, admission to the intensive care unit, prior antibiotic use, and invasive procedures performed were analyzed as risk factors in a matched bivariable model. Variables significantly associated with colistin-resistant isolates (p < .05) were entered in a backward multivariable logistic regression model. Forty-one colistin-resistant unique patient isolates were identified from January 1, 2006, until March 31, 2007. These isolates represented infection in 35 of 41 patients. Risk factors significantly associated with the isolation of colistin-resistant isolates were age, duration of intensive care unit stay, [corrected] surgical procedures, use of colistin, use of monobactams, duration of use of colistin and duration of use of antifungal agents [corrected] In the multivariable model, use of colistin was identified as the only independent risk factor (adjusted odds ratio = 7.78, p = .002). CONCLUSIONS: Colistin-resistant K. pneumoniae, A. baumannii, and P. aeruginosa pathogens may be encountered in clinical practice, in association with inappropriate colistin use. To prevent this phenomenon, colistin should be used judiciously, given that treatment options for colistin-resistant gram-negative bacteria are limited.
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Falagas, Siempos, Rafailidis, Korbila, Ioannidou, Michalopoulos (2008)  Inhaled colistin as monotherapy for multidrug-resistant gram (-) nosocomial pneumonia: A case series.   Respir Med Dec  
Abstract: BACKGROUND: Reports of patients with polymyxin-only susceptible gram-negative nosocomial pneumonia treated with inhaled, but without concurrent intravenous, colistin are rare. METHODS: Patients admitted in a tertiary 450-bed tertiary care centre during the period 05/01/2005-05/31/2007 and receiving colistin through nebulization, but not systemically, were included in this retrospective case series. RESULTS: Five patients (three with ventilator-associated pneumonia and two with nosocomial pneumonia) received colistin through nebulization without concomitant intravenous colistin. The isolated pathogens were Acinetobacter baumannii (three cases), Pseudomonas aeruginosa (one case) and the combination of Klebsiella pneumoniae, A. baumannii and P. aeruginosa (one case). They were susceptible only to colistin (three cases) or to colistin and gentamicin (two cases). Intravenous antimicrobial agents given concurrently were piperacillin/tazobactam, meropenem, ceftriaxone and ciprofloxacin; isolated pathogens were resistant to these agents. Four (80%) out of the five patients were cured, survived and were discharged. One patient died. No colistin-related adverse event was observed. CONCLUSIONS: The experience from this case series and other relevant recent reports suggest that treatment of pneumonia due to polymyxin-only susceptible gram-negative bacilli with inhaled colistin (without concurrent systemic administration) deserves further careful investigation.
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Matthew E Falagas, Alexandros P Grammatikos, Argyris Michalopoulos (2008)  Potential of old-generation antibiotics to address current need for new antibiotics.   Expert Rev Anti Infect Ther 6: 5. 593-600 Oct  
Abstract: Despite the constantly increasing need for new antimicrobial agents, antibiotic drug discovery and development seem to have greatly decelerated in recent years. Presented with the significant problem of advancing antimicrobial resistance, the global scientific community has attempted to find alternative solutions; one of the most promising ones is the evaluation and use of old antibiotic compounds. Due to the low-level use of many of the old antibiotic compounds, these have remained active against a large number of currently prevalent bacterial isolates. Thus, clinicians are beginning to re-evaluate their use in various patient populations and infections, despite the fact that they were previously thought to be less effective and/or more toxic than newer agents. A number of old antibiotic compounds, such as polymyxins, fosfomycin, fusidic acid, cotrimoxazole, aminoglycosides and chloramphenicol, are re-emerging as valuable alternatives for the treatment of difficult-to-treat infections. The availability of novel genetic and molecular modification methods provides hope that the toxicity and efficacy drawbacks presented by some of these agents can be surpassed in the future.
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Alexandros P Grammatikos, Ilias I Siempos, Argyris Michalopoulos, Matthew E Falagas (2008)  Optimal duration of the antimicrobial treatment of ventilator-acquired pneumonia.   Expert Rev Anti Infect Ther 6: 6. 861-866 Dec  
Abstract: The optimal duration of antimicrobial treatment of patients with ventilator-associated pneumonia is a major concern for clinicians. We looked for the evidence that a short course of therapy (< or =10 days) is as effective as a traditional long-course therapy (14-21 days). Unfortunately, only one trial (PneumA trial) has focused directly on this question. To further evaluate this issue, we identified trials in which the duration of anti-infective treatment was used as the outcome. Such trials, by providing data on mortality, length of intensive care unit stay and recurrence, may allow for estimating the association between duration of therapy and the aforementioned outcomes. Nine such trials were identified; all reported a decrease in the total length of antibiotic administration (statistically significant in seven) with the application of the intervention studied. Short, as opposed to long, courses of antibiotics did not adversely affect mortality, length of intensive care unit stay or recurrence rates. In conclusion, the available evidence seems to support the use of short-course antimicrobial treatments (< or =10 days) for patients with ventilator-acquired pneumonia not caused by nonfermenting Gram-negative bacilli.
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Matthew E Falagas, Petros I Rafailidis, Dimitrios K Matthaiou, Simona Virtzili, Dimitra Nikita, Argyris Michalopoulos (2008)  Pandrug-resistant Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii infections: characteristics and outcome in a series of 28 patients.   Int J Antimicrob Agents 32: 5. 450-454 Nov  
Abstract: We describe the characteristics and outcome of pandrug-resistant (PDR) Gram-negative bacterial infections (23 Klebsiella pneumoniae isolates, 3 Pseudomonas aeruginosa and 3 Acinetobacter baumannii) of hospitalised patients at a tertiary-care centre (1 January 2006-31 May 2007). The site of infection was central venous catheter-related in 5 of 24 patients with clinical infection, bacteraemia in 5, the respiratory system in 5, surgical site in 5, the urinary system in 2, the ascitic fluid in 1 and the central nervous system in one. Twenty of 24 patients with infection received an antibiotic regimen containing colistin (in combination with meropenem in 8 patients). The overall in-hospital mortality was 41.7% (10/24); 8 patients died because of the PDR infection (infection-related mortality 33.3%). Significant co-morbidity was present not only in the patients who died but also in survivors. PDR Gram-negative bacterial infections are associated with considerable mortality, although not as high as expected given the fact that the isolates were resistant to all tested antibiotics, including polymyxins. Antibiotics that are ineffective in vitro may prove life-saving for some of these patients, especially combination regimens containing colistin.
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2007
 
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Sotiria Mastoraki, Argyris Michalopoulos, Ioannis Kriaras, Stefanos Geroulanos (2007)  Cefuroxime as antibiotic prophylaxis in coronary artery bypass grafting surgery.   Interact Cardiovasc Thorac Surg 6: 4. 442-446 Aug  
Abstract: Nosocomial-acquired infections remain a serious problem in patients undergoing coronary artery bypass grafting (CABG) surgery. The objective of this retrospective study was to compare the incidence of nosocomial infections in patients undergoing CABG surgery within two periods (1994 and 2003). A single dose of a second generation cephalosporin (cefuroxime) was administered as antibiotic prophylaxis in all patients. There was no statistical significant difference regards to the incidence of hospital-acquired infections between these two periods (4.9% in 1994 and 5.6% in 2003, P=0.62). The most frequent types of postoperative infections were the respiratory tract infection (2.3%) in the first period and the superficial surgical site infection (3.1%) in the second period. The majority of isolated pathogens were Gram-positive cocci (68%) in both periods. The majority of incisional surgical site infections and of central venous catheter-related infections were attributed to Staphylococcus coagulase negative strains. Only one episode of hospital-acquired infection due to a resistant Gram-negative bacterium was recorded during the second period. A single-dose of cefuroxime remains the antibiotic prophylaxis of choice in adult patients submitted to CABG surgery. It is still associated with a low incidence of postoperative infections mainly due to sensitive pathogens.
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M E Falagas, I A Bliziotis, A Michalopoulos, G Sermaides, V E Papaioannou, D Nikita, N Choulis (2007)  Effect of a policy for restriction of selected classes of antibiotics on antimicrobial drug cost and resistance.   J Chemother 19: 2. 178-184 Apr  
Abstract: Based on the instructions of the National Organization of Pharmaceutical Agents (Greece) from July 1, 2003, quinolones, 3( rd )and 4(th )generation cephalosporins, carbapenems, monobactams, glycopeptides, oxazolidinones, and streptogramins were considered as "restricted" antibiotics that could be used only with the approval of an Infectious Disease specialist. We analyzed the effect of the policy on the consumption and cost of antibiotics as a group and of specific classes, adjusted for the patient load, as well as on the antimicrobial resistance of isolated bacteria. We analyzed 5 trimesters (2 prior and 3 after the implementation of the new policy). A 20% and 16% reduction in adjusted consumption [in daily defined doses (DDDs)] and cost, respectively, of the restricted antibiotics was accomplished during the first trimester after implementation of the new policy. However, this was accompanied by a 36% and 56% increase in adjusted consumption and cost, respectively, of unrestricted antibiotics. A logistic regression model that we performed showed that the new policy had an independent positive effect on the in vitro antimicrobial susceptibility of Pseudomonas aeruginosa (p=0.051) but not of Acinetobacter baumannii and Escherichia coli isolates. Our data suggest that there are considerable limitations to the programs aiming to reduce the consumption of restricted antibiotics through the approval of their use by specialists, at least in some settings.
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C Christodoulou, M Rizos, E Galani, K Rellos, D V Skarlos, A Michalopoulos (2007)  Performance status (PS): a simple predictor of short-term outcome of cancer patients with solid tumors admitted to the intensive care unit (ICU).   Anticancer Res 27: 4C. 2945-2948 Jul/Aug  
Abstract: BACKGROUND: Admission of cancer patients with serious medical complications to the Intensive Care Unit (ICU) remains controversial. The aim of this study was to examine the 30-day all-cause mortality in cancer patients with solid tumors admitted to the ICU and to identify factors predicting 30-day mortality. PATIENTS AND METHODS: A retrospective study was conducted in 69 consecutive cancer patients with solid tumors admitted to the ICU of a 400-bed general hospital in Greece, between October 2001 and October 2005. Demographics, ECOG performance status (PS) prior to hospitalization, stage of cancer, metastases, number of metastatic sites, prior chemotherapy, primary site of tumor, APACHE II score on ICU admission, development of ICU acquired infection, sepsis, multiple organ failure (MOF), need for mechanical ventilation (MV), length of ICU stay, hospital stay and 30-day mortality were examined. RESULTS: The observed 30-day hospital mortality rate was 66.6% (n=46) with most deaths (n=32) occurring in the ICU. Univariate negative predictors of 30-day mortality were PS 3-4 (p=0.03), APACHE II score (p=0.001), MOF (p=0.001) and need for MV (p=0.001). Only PS 3-4 was an independent predictor in multivariate analysis (p=0.02). CONCLUSION: ECOG PS 3-4 prior to hospitalization was found to be a simple negative predictor of short-term outcome of cancer patients with solid tumors admitted to the ICU.
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Petros Kopterides, Patra K Koletsi, Argyris Michalopoulos, Matthew E Falagas (2007)  Exposure to quinolones is associated with carbapenem resistance among colistin-susceptible Acinetobacter baumannii blood isolates.   Int J Antimicrob Agents 30: 5. 409-414 Nov  
Abstract: In this study, we explored risk factors associated with bacteraemia caused by colistin-susceptible/carbapenem-resistant (Co(S)/Ca(R)) Acinetobacter baumannii. A retrospective cohort study of hospitalised patients with A. baumannii bacteraemia was performed at a tertiary care hospital over a 44-month period. Thirty-nine patients with bacteraemia due to A. baumannii (35 Intensive Care Unit and 4 ward patients) were included in the analysis. Twenty-five patients (64%) had bacteraemia due to Co(S)/Ca(R)A. baumannii and 14 patients (36%) had bacteraemia due to colistin-susceptible/carbapenem-susceptible A. baumannii. Mortality was 56% (14/25) and 35.7% (5/14) for patients in the two groups, respectively (P=0.22). Bivariate analysis showed that prior exposure to fluoroquinolones (P=0.01) and antipseudomonal penicillins (P=0.004) as well as a higher number of antibiotics in use on the day of bacteraemia (P=0.02) were associated with isolation of a Co(S)/Ca(R) strain among patients with A. baumannii bacteraemia. Multivariate analysis using a backward logistic regression model showed that only exposure to fluoroquinolones was associated with development of Co(S)/Ca(R)A. baumannii bacteraemia (odds ratio=11.6; 95% confidence interval 2.4-55.9; P=0.02). The appearance of Co(S)/Ca(R)A. baumannii infections represents a major threat to critically ill hospitalised patients. Exposure to fluoroquinolones is an independent risk factor for development of Co(S)/Ca(R)A. baumannii bacteraemia.
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M E Falagas, V D Pappas, A Michalopoulos (2007)  Gangrenous, hemorrhagic, bullous cellulitis associated with pseudomonas aeruginosa in a patient with Waldenström's macroglobulinemia.   Infection 35: 5. 370-373 Oct  
Abstract: BACKGROUND: Patients with Waldenström's macroglobulinemia may manifest several types of skin lesions. We present our experience with a patient with the disease that adds to the literature on the topic. CASE DESCRIPTION: A 57-year-old man with history of multiple sclerosis and Waldenström's macroglobulinemia was admitted to the intensive care unit in shock. His family members reported that the patient had complained of fever and the gradual development of gangrenous, hemorrhagic, bullous cellulitis lesions on the abdomen and lower extremities for 7 days prior to his admission to the hospital. Pseudomonas aeruginosa was isolated from fluid specimens collected from the cutaneous lesions. Appropriate antimicrobial treatment including continuous intravenous administration of meropenem (6 g every 24 h) led to the cure of the infection. CONCLUSIONS: We postulate that the underlying Waldenström's macroglobulinemia contributed to the pathophysiology of the development of the rare skin manifestations of the infection observed in our patient.
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Matthew E Falagas, Petros I Rafailidis, Diamantis Kofteridis, Simona Virtzili, Fotini C Chelvatzoglou, Vassiliki Papaioannou, Sofia Maraki, George Samonis, Argyris Michalopoulos (2007)  Risk factors of carbapenem-resistant Klebsiella pneumoniae infections: a matched case control study.   J Antimicrob Chemother 60: 5. 1124-1130 Nov  
Abstract: BACKGROUND: Carbapenems are frequently used to treat infections due to extended-spectrum beta-lactamase-producing Klebsiella pneumoniae. Thus, the emergence of infections due to carbapenem-resistant K. pneumoniae (CRKp) is a major public health concern. OBJECTIVES: To identify risk factors associated with the development of CRKp infections. METHODS: We conducted a matched case-control study in two hospitals (Henry Dunant Hospital, Athens, Greece and University Hospital of Heraklion, Crete, Greece). The controls were selected among patients with carbapenem-susceptible K. pneumoniae (CSKp) and were matched with CRKp cases for site of infection. RESULTS: One hundred and six patients were included in our study (53 cases and 53 controls). Mortality was 30.1% and 33.9% for patients with CRKp and CSKp infections, respectively (P = 0.83). Bivariable analysis showed that exposure to anti-pseudomonas penicillins (P = 0.004), carbapenems (P = 0.01), quinolones (P < 0.001) and glycopeptides (P < 0.001), as well as admission to the intensive care unit (P = 0.002), tracheostomy (P = 0.02), chronic obstructive pulmonary disease (P = 0.04), surgery with use of foreign body (P = 0.04) and mechanical ventilation (P = 0.02) were associated with CRKp infection. The multivariable analysis showed that exposure to fluoroquinolones [odds ratio (OR) 4.54, 95% confidence intervals (CIs) 1.78-11.54, P = 0.001] and exposure to antipseudomonal penicillins (OR 2.57, 95% CI 1.00-6.71, P = 0.04) were independent risk factors for CRKp infections. CONCLUSIONS: Our data suggest that prior exposure to fluoroquinolones and antipseudomonal penicillins are independent risk factors for the development of CRKp infections.
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Evangelos S Rosmarakis, Sotirios N Prapas, Konstantinos Rellos, Argyris Michalopoulos, George Samonis, Matthew E Falagas (2007)  Nosocomial infections after off-pump coronary artery bypass surgery: frequency, characteristics, and risk factors.   Interact Cardiovasc Thorac Surg 6: 6. 759-767 Dec  
Abstract: We evaluated the frequency, risk factors, and characteristics of infections in 360 patients after off-pump coronary artery bypass grafting (OPCABG). A prospective study was performed during the period June 2004-October 2005 at Henry Dunant Hospital, Athens, Greece. C-reactive protein (CRP) and procalcitonin were assayed from 222 patients preoperatively, and 1-3 days following OPCABG. Variables independently associated with infection were identified by a multivariable logistic regression model. Eighteen of 360 (5%) patients developed postoperative infections; 1.7% developed superficial wound infection, 1.4% pneumonia, 1.1% bacteremia, 0.3% mediastinitis, and 0.3% intra-aortic balloon pump related infection. The mean increase of CRP and procalcitonin levels in the first two or three days, respectively, after surgery was significantly higher (P<0.05) in patients with infection. Independent risk factors of infection (P<0.05) were history of major nervous system disorder, left ventricular heart failure preoperatively, emergent operation, transfusions of red blood cells during ICU stay, and duration of central venous catheter placement. The identification of risk factors for infection in combination with the appropriate evaluation of the increased CRP and procalcitonin values may help clinicians for the early diagnosis of infection after OPCABG.
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2006
 
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Argyris Michalopoulos, Matthew E Falagas (2006)  Multi-systemic methicillin resistant Staphylococcus aureus (MRSA) community-acquired infection.   Med Sci Monit 12: 5. CS39-CS43 May  
Abstract: BACKGROUND: An alarming increase of the incidence of community-acquired infections due to methicillin resistant Staphylococcus aureus (MRSA) has been noted in several countries during the recent years. CASE REPORT: We present the case of a 64-year-old male who complained of fever, shortness of breath, productive cough, and mild low back pain. The patient was diagnosed to have severe community-acquired pneumonia caused by methicillin resistant Staphylococcus aureus. Due to the severity of his respiratory symptoms and the history of back injury, the mild low back pain did not receive the appropriate attention. It became clear later that the back pain was caused by an extra-pulmonary focus of the MRSA infection. CONCLUSIONS: Staphylococcus aureus has been reported to be the cause of considerably different proportions of patients with community-acquired pneumonia in studies from various parts of the world. Our case emphasizes the occasionally multi-systemic manifestations of community-acquired MRSA infections and the difficulties in their control.
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Antonios Vassiloyanakopoulos, Matthew E Falagas, Maria Allamani, Argyris Michalopoulos (2006)  Aspergillus fumigatus tricuspid native valve endocarditis in a non-intravenous drug user.   J Med Microbiol 55: Pt 5. 635-638 May  
Abstract: Invasive aspergillosis is an emerging infection mainly affecting immunocompromised patients. This report details a case of Aspergillus fumigatus tricuspid native valve endocarditis complicated by recurrent septic pulmonary emboli in a young, non-intravenous drug user. He was treated by surgical resection of the posterior leaflet of the tricuspid valve and the vegetations, as well as by valvuloplasty, which was followed by a combination of liposomal amphotericin B and voriconazole as acute-phase therapy and voriconazole alone as suppression therapy.
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Konstantinos Z Vardakas, George Samonis, Argyris Michalopoulos, Elpidoforos S Soteriades, Matthew E Falagas (2006)  Antifungal prophylaxis with azoles in high-risk, surgical intensive care unit patients: a meta-analysis of randomized, placebo-controlled trials.   Crit Care Med 34: 4. 1216-1224 Apr  
Abstract: OBJECTIVE: The use of antifungal prophylaxis remains controversial in most populations including surgical intensive care unit patients. A meta-analysis of randomized controlled trials was performed to evaluate the safety and effectiveness of azoles as antifungal prophylaxis in high-risk patients receiving treatment in the surgical intensive care unit. DATA SOURCE: Data were obtained from PubMed, Current Contents, Cochrane central register of controlled trials, and references from relevant articles. STUDY SELECTION: Randomized controlled trials using azoles as antifungal prophylaxis vs. placebo were included in the study. DATA EXTRACTION: Two independent reviewers extracted data concerning the development of fungal infections (superficial or invasive), adverse effects, and mortality. SYNTHESIS: Six randomized controlled trials were included in the main analysis. Publication bias and statistically significant heterogeneity were not observed among the analyzed studies. Patients receiving antifungal prophylaxis developed fewer episodes of candidemia (odds ratio [OR] = 0.28, 95% confidence interval [CI] 0.09-0.86), nonbloodstream invasive fungal infections (OR = 0.26, 95% CI 0.12-0.53), and noninvasive (superficial) fungal infections (OR = 0.22, 95% CI 0.11-0.43), respectively. No reduction in mortality was observed among patients who received azole prophylaxis (OR = 0.74, 95% CI 0.52-1.05). There was no significant difference in reported adverse effects (OR = 1.28, 95% CI 0.82-1.98). CONCLUSIONS: Despite its limitations, our meta-analysis suggests that the prophylactic use of azoles in high-risk surgical intensive care unit patients is associated with a reduction of fungal infections but not in all-cause mortality. However, although not noted in the analyzed randomized controlled trials, there is concern about the use of azoles due to possible shift toward non-albicans species and development of resistance to azoles.
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Konstantinos Rellos, Matthew E Falagas, Konstantinos Z Vardakas, George Sermaides, Argyris Michalopoulos (2006)  Outcome of critically ill oldest-old patients (aged 90 and older) admitted to the intensive care unit.   J Am Geriatr Soc 54: 1. 110-114 Jan  
Abstract: OBJECTIVES: To compare the outcomes of critically ill oldest-old patients (> or = 90) with those of younger patients. DESIGN: Prospective cohort study. SETTING: General intensive care unit (ICU) of a tertiary care hospital in Athens, Greece. PARTICIPANTS: The oldest-old and younger patients. MEASUREMENTS: In-hospital and ICU mortality and stay, demographics, comorbidity, and complications. RESULTS: Of 5,505 consecutive patients admitted to the ICU, 60 (1.1%) were in the oldest-old group (aged 90-98). Their mean length of ICU and hospital stay+/-standard deviation was 5.3+/-6.8 and 23.3+/-35.7 days, respectively. ICU mortality was 20%. Total in-hospital mortality was 40%, compared with 8.9% (P=.001) in younger patients. Acute Physiology and Chronic Health Evaluation II score was independently associated with in-hospital mortality (odds ratio=1.18, 95% confidence interval=1.05-1.33). Of 24 oldest-old patients who died, 22 (91.7%) died in the ICU or in the ward within 30 days after ICU discharge. CONCLUSION: All-cause in-hospital mortality was higher in the oldest-old group than in younger patients, but the mortality of this cohort of patients did not seem to reach a figure that would make physicians, relatives, and healthcare administrators decide against ICU care in this population.
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Matthew E Falagas, Patra K Koletsi, Petros Kopterides, Argyris Michalopoulos (2006)  Risk factors for isolation of strains susceptible only to polymyxin among patients with Pseudomonas aeruginosa bacteremia.   Antimicrob Agents Chemother 50: 7. 2541-2543 Jul  
Abstract: We conducted a case-control study to identify risk factors associated with the isolation of Pseudomonas aeruginosa strains susceptible only to polymyxin from blood by comparing data between 16 patients with blood isolates that were susceptible only to polymyxins and 40 patients with blood isolates that were susceptible to carbapenems. The multivariable analysis showed that exposure to carbapenems was associated with the development of P. aeruginosa bacteremia susceptible only to polymyxin (odds ratio, 9.0; 95% confidence interval, 2.4 to 34.3; P = 0.001).
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Argyris Michalopoulos, Stefanos Geroulanos, Evangelos S Rosmarakis, Matthew E Falagas (2006)  Frequency, characteristics, and predictors of microbiologically documented nosocomial infections after cardiac surgery.   Eur J Cardiothorac Surg 29: 4. 456-460 Apr  
Abstract: OBJECTIVE: Nosocomial infections still remain a serious problem in patients undergoing open heart surgery. The objective of this study was to evaluate frequency, characteristics, and predictors of nosocomial infections after cardiac surgery. METHODS: This prospective case-control study was conducted in adult patients who underwent open heart surgery with use of extracorporeal circulation over a period of 16 months. Cases were patients who developed microbiologically documented nosocomial infection. Controls were patients who had open heart surgery within a randomly selected two-month period of the study (defined before the start of the study) and did not develop nosocomial infection. Various variables, available before, during or within the first two days after operation, were examined as possible risk factors of nosocomial infections in bi-variable analysis. Then, variables that were found to be statistically associated with nosocomial infections in the bi-variable analysis were included in a multivariable logistic regression model to identify independent risk factors associated with nosocomial infections after open heart surgery. RESULTS: One hundred and seven of 2122 (5.0%) patients developed microbiologically documented nosocomial infection after open cardiac surgery. The majority of nosocomial infections were respiratory tract infections (45.7%) and central venous catheter-related infections (25.2%). All cause hospital mortality was 16.8% in patients with nosocomial infection and 3.5% in the control group (p=0.005). Out of 20 variables studied as possible risk factors, 12 had a statistically significant association with postoperative infection. History of immunosuppression (OR=3.6, 95% CI 1.2-11.0%), transfusion of more than five red blood cell units in both the operating room and during the first ICU postoperative day (OR=21.2, 95% CI 11.9-37.8%), and development of acute renal failure within the first two days after operation (OR=49.9, 95% CI 22.4-111.0%), were found to be independent predictors of nosocomial infections after cardiac surgery in a multivariable logistic regression model. CONCLUSIONS: Postoperative nosocomial infections are a considerable problem in cardiac surgery patients. The identified independent predictors of nosocomial infection may be useful in identifying those at high risk for development of such infection in cardiac surgery patients.
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M E Falagas, P I Rafailidis, S K Kasiakou, P Hatzopoulou, A Michalopoulos (2006)  Effectiveness and nephrotoxicity of colistin monotherapy vs. colistin-meropenem combination therapy for multidrug-resistant Gram-negative bacterial infections.   Clin Microbiol Infect 12: 12. 1227-1230 Dec  
Abstract: A retrospective cohort study evaluated the effectiveness and nephrotoxicity of intravenous colistin monotherapy vs. colistin-meropenem combination therapy for patients with multidrug-resistant Gram-negative bacterial infections. Fourteen patients received intravenous colistin monotherapy and 57 received colistin-meropenem. No significant differences were found concerning clinical response of the infection (12/14 (85.7%) vs. 39/57 (68.4%), p 0.32) and development of nephrotoxicity (0/14 (0%) vs. 4/57 (7%), p 0.58). A favourable association was revealed between survival and treatment with colistin monotherapy compared to colistin-meropenem (0/14 (0%) vs. 21/57 (36.8%) deaths, p 0.007), even after adjusting for the variables for which significant differences were found.
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Matthew E Falagas, Sofia K Kasiakou, Sotirios Tsiodras, Argyris Michalopoulos (2006)  The use of intravenous and aerosolized polymyxins for the treatment of infections in critically ill patients: a review of the recent literature.   Clin Med Res 4: 2. 138-146 Jun  
Abstract: Intravenous and aerosolized polymyxins are being used increasingly, especially in the critical care setting, for treating patients with infections due to multidrug-resistant Gram-negative bacteria, mainly Acinetobacter baumannii and Pseudomonas aeruginosa. Recent literature suggests that intravenous colistin and polymyxin B have acceptable effectiveness for the treatment of patients with bacteremia, as well as infections of various systems and organs, including pneumonia, bacteremia, skin and soft tissue, and urinary tract infections. Although data from recent studies have suggested that the toxicity of intravenous polymyxins is probably less than reported in the older literature, caution should be taken to monitor the renal function of patients who receive these antibiotics.
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Matthew E Falagas, Argyris S Michalopoulos, Ioannis A Bliziotis, Elpidoforos S Soteriades (2006)  A bibliometric analysis by geographic area of published research in several biomedical fields, 1995-2003.   CMAJ 175: 11. 1389-1390 Nov  
Abstract: We summarized the findings of several studies of ours to compare the quantity and quality of published research from around the world for the years 1995 to 2003. We evaluated the number of articles published and their mean journal impact factor. We also studied the research productivity of various areas adjusted for gross domestic product (GDP) and population. We found that Western Europe leads the world in published research on infectious diseases-microbiology (82,342 articles [38.8%]) and in cardiopulmonary medicine (67,783 articles [39.5%]), whereas the United States ranks first in the fields of preventive medicine, public health and epidemiology both in quantity (23,918 articles [49.1%]) and quality of published papers. However, after adjustments for GDP, Canada ranked first, with the United States and Oceania following closely behind. All of the developing regions had only small research contributions in all of the biomedical fields examined.
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S Batzios, A Michalopoulos, L Kaklamanis, J Stathopoulos, M Christopoulou, J Koutantos, G P Stathopoulos (2006)  Angiosarcoma of the heart: case report and review of the literature.   Anticancer Res 26: 6C. 4837-4842 Nov/Dec  
Abstract: BACKGROUND: Primary angiosarcoma of the heart is an extremely rare malignant disease. PATIENTS AND METHODS: A 32-year-old female with primary angiosarcoma of the heart at an advanced stage with lung and bone metastases is presented. The tumor showed extensive expression of c-erb-B2 and a moderate expression of c-kit. Chemotherapy (cisplatin, epirubicin and ifosfamide) was administered. Herceptin as well as glivec were added to the above combination. RESULTS: There was a good partial response and the lung deposits almost disappeared. The duration of response was 6 months. CONCLUSION: This case of angiosarcoma of the heart is presented because of the extreme rarity of this disease, and its responsiveness to chemotherapy in combination with imatinib and herceptin.
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Matthew E Falagas, Ilias I Siempos, Ioannis A Bliziotis, Argyris Michalopoulos (2006)  Administration of antibiotics via the respiratory tract for the prevention of ICU-acquired pneumonia: a meta-analysis of comparative trials.   Crit Care 10: 4.  
Abstract: INTRODUCTION: The administration of prophylactic antibiotics via the respiratory tract is one of several strategies for the prevention of ICU-acquired pneumonia. We systematically examined the available evidence regarding the effect of prophylactic antibiotics administered via the respiratory tract on the development of ICU-acquired pneumonia, mortality, colonization of the respiratory tract, emergence of antimicrobial resistance, and toxicity. METHODS: We searched the PubMed database (1/1950 to 9/2005) and references from relevant articles to identify trials that provided comparative data regarding the above-mentioned outcomes. Two investigators independently performed the data extraction to calculate the effect of the studied intervention on clinically relevant outcomes. RESULTS: 8 comparative trials (5 randomized controlled trials (RCTs) and 3 non-randomized trials) studying gentamicin (3 trials) polymyxins (3 trials), tobramycin (1 trial), and ceftazidime (1 trial) that studied 1,877 patients were included in our meta-analysis. Our primary analysis that included the 5 RCTs, revealed that ICU-acquired pneumonia was less common in the group of patients that received the antibiotic prophylaxis (OR = 0.49, 95% CI 0.32-0.76). No difference in mortality was found between the compared groups (OR = 0.86, 95% CI 0.55-1.32). There were limited data to permit an analysis of colonization with Pseudomonas aeruginosa. A secondary analysis by adding the 3 non-randomized comparative trials did not reveal substantially different results regarding ICU-acquired pneumonia and mortality, while fewer patients were colonized with Pseudomonas aeruginosa in the group that received prophylaxis, compared to the group of patients that received no prophylaxis (OR = 0.51, 95% CI 0.30-0.86). No serious drug-related toxicity was noted. No meaningful systematic analysis of the evidence regarding the emergence of resistance could be performed in the studies included in our meta-analysis. CONCLUSIONS: The limited available evidence supports that prophylactic administration of antibiotics via the respiratory tract is associated with reduction of occurrence of ICU-acquired pneumonia. However, there is evidence from non-comparative studies that this preventive strategy may lead to an increase in the emergence of resistant bacteria. Thus, further investigation, at least in ICU patients at high risk for development of ICU-acquired pneumonia is warranted, including a more systematic evaluation of issues related to the emergence of resistance.
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Matthew E Falagas, Evangelos S Rosmarakis, Konstantinos Rellos, Argyris Michalopoulos, George Samonis, Sotirios N Prapas (2006)  Microbiologically documented nosocomial infections after coronary artery bypass surgery without cardiopulmonary bypass.   J Thorac Cardiovasc Surg 132: 3. 481-490 Sep  
Abstract: OBJECTIVE: This study was undertaken to evaluate the frequency, characteristics, and risk factors of microbiologically documented nosocomial infections after off-pump coronary artery bypass grafting. METHODS: A prospective cohort study was performed at Henry Dunant Hospital, Athens, Greece. It included all adult patients who underwent coronary artery bypass grafting with no valve surgery and without the use of cardiopulmonary bypass during a period of 3 years. Case patients were those with development of microbiologically documented nosocomial infections. Various variables were examined as possible risk factors for nosocomial infections. RESULTS: Twenty-one of 782 studied patients (2.7%) acquired 26 microbiologically documented nosocomial infections after off-pump coronary artery bypass grafting. Eight of 782 studied patients had pneumonia (1.02%), 7 of 782 (0.90%) had bacteremia, 4 of 782 (0.51%) had superficial wound infection at the sternotomy site, 4 of 782 (0.51%) had urinary tract infection, 2 of 782 (0.26%) had mediastinitis, and 1 of 782 (0.13%) had pressure sore infection. Twenty-one infections were monomicrobial, whereas 5 were polymicrobial. All polymicrobial infections were wound infections. There was a statistically significant difference in mortality between patients with and without nosocomial infection (23.8% vs 1.2%, P < .001). Clinical response of the infection to the treatment administered was observed in 21 of 26 episodes (80.8%) in 21 patients. A backward stepwise multivariable logistic regression model showed that independent risk factors (P < .05) associated with development of microbiologically documented nosocomial infection were arterial hypertension, previous vascular surgery, urgent operation, postoperative atrial fibrillation, number of inotropes used during and after operation, transfusion of fresh-frozen plasma during the intensive care unit stay, and intensive care unit stay until development of infection. CONCLUSION: Nosocomial infection after off-pump coronary artery bypass grafting is an uncommon but potentially life-threatening complication. The identification of independent risk factors, including arterial hypertension, associated with development of postoperative infection may help in the development of clinical strategies for the prevention, early diagnosis, and treatment of these infections.
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Matthew E Falagas, Ioannis A Bliziotis, Sofia K Kasiakou, George Samonis, Panayiota Athanassopoulou, Argyris Michalopoulos (2005)  Outcome of infections due to pandrug-resistant (PDR) Gram-negative bacteria.   BMC Infect Dis 5: 1. 04  
Abstract: BACKGROUND: The increasing problem of infections due to multidrug-resistant Gram-negative bacteria has led to re-use of polymyxins in several countries. However, there are already clinical isolates of Gram-negative bacteria that are resistant to all available antibiotics, including polymyxins. METHODS: We present a case series of patients with infections due to pathogens resistant to all antimicrobial agents tested, including polymyxins. An isolate was defined as pandrug-resistant (PDR) if it exhibited resistance to all 7 anti-pseudomonal antimicrobial agents, i.e. antipseudomonal penicillins, cephalosporins, carbapenems, monobactams, quinolones, aminoglycosides, and polymyxins. RESULTS: Clinical cure of the infection due to pandrug-resistant (PDR) Gram-negative bacteria, namely Pseudomonas aeruginosa or Klebsiella pneumoniae was observed in 4 out of 6 patients with combination of colistin and beta lactam antibiotics. CONCLUSION: Colistin, in combination with beta lactam antibiotics, may be a useful agent for the management of pandrug-resistant Gram-negative bacterial infections. The re-use of polymyxins, an old class of antibiotics, should be done with caution in an attempt to delay the rate of development of pandrug-resistant Gram-negative bacterial infections.
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Argyris Michalopoulos, Ioannis A Bliziotis, Michael Rizos, Matthew E Falagas (2005)  Worldwide research productivity in critical care medicine.   Crit Care 9: 3. R258-R265 Jun  
Abstract: INTRODUCTION: The number of publications and the impact factor of journals are accepted estimates of the quantity and quality of research productivity. The objective of the present study was to assess the worldwide scientific contribution in the field of critical care medicine. METHOD: All research studies published between 1995 and 2003 in medical journals that were listed in the 2003 Science Citation Index (SCI) of Journal Citation Reports under the subheading 'critical care' and also indexed in the PubMed database were reviewed in order to identify their geographical origin. RESULTS: Of 22,976 critical care publications in 14 medical journals, 17,630 originated from Western Europe and the USA (76.7%). A significant increase in the number of publications originated from Western European countries during the last 5 years of the study period was noticed. Scientific publications in critical care medicine increased significantly (25%) from 1995 to 2003, which was accompanied by an increase in the impact factor of the corresponding journals (47.4%). Canada and Japan had the better performance, based on the impact factor of journals. CONCLUSION: Significant scientific progress in critical care research took place during the period of study (1995-2003). Leaders of research productivity (in terms of absolute numbers) were Western Europe and the USA. Publications originating from Western European countries increased significantly in quantity and quality over the study period. Articles originating from Canada, Japan, and the USA had the highest mean impact factor. Canada was the leader in productivity when adjustments for gross domestic product and population were made.
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Argyris Michalopoulos, Sofia K Kasiakou, Zefi Mastora, Kostas Rellos, Anastasios M Kapaskelis, Matthew E Falagas (2005)  Aerosolized colistin for the treatment of nosocomial pneumonia due to multidrug-resistant Gram-negative bacteria in patients without cystic fibrosis.   Crit Care 9: 1. R53-R59 Feb  
Abstract: INTRODUCTION: The clinical and economic consequences of the emergence of multidrug-resistant Gram-negative bacteria in the intensive care unit (ICU) setting, combined with the high mortality rate among patients with nosocomial pneumonia, have stimulated a search for alternative therapeutic options to treat such infections. The use of adjunctive therapy with aerosolized colistin represents one of these. There is extensive experience with use of aerosolized colistin by patients with cystic fibrosis, but there is a lack of data regarding the use of aerosolized colistin in patients without cystic fibrosis. METHODS: We conducted the present study to assess the safety and effectiveness of aerosolized colistin as an adjunct to intravenous antimicrobial therapy for treatment of Gram-negative nosocomial pneumonia. We retrospectively reviewed the medical records of patients hospitalized in a 450-bed tertiary care hospital during the period from October 2000 to January 2004, and who received aerosolized colistin as adjunctive therapy for multidrug-resistant pneumonia. RESULTS: Eight patients received aerosolized colistin. All patients had been admitted to the ICU, with mean Acute Physiological and Chronic Health Evaluation II scores on the day of ICU admission and on day 1 of aerosolized colistin administration of 14.6 and 17.1, respectively. Six of the eight patients had ventilator-associated pneumonia. The responsible pathogens were Acinetobacter baumannii (in seven out of eight cases) and Pseudomonas aeruginosa (in one out of eight cases) strains. Half of the isolated pathogens were sensitive only to colistin. The daily dose of aerosolized colistin ranged from 1.5 to 6 million IU (divided into three or four doses), and the mean duration of administration was 10.5 days. Seven out of eight patients received concomitant intravenous treatment with colistin or other antimicrobial agents. The pneumonia was observed to respond to treatment in seven out of eight patients (four were cured and three improved [they were transferred to another facility]). One patient deteriorated and died from septic shock and multiple organ failure. Aerosolized colistin was well tolerated by all patients; no bronchoconstriction or chest tightness was reported. CONCLUSION: Aerosolized colistin may be a beneficial adjunctive treatment in the management of nosocomial pneumonia (ventilator associated or not) due to multidrug-resistant Gram-negative bacteria.
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Matthew E Falagas, Michael Rizos, Ioannis A Bliziotis, Kostas Rellos, Sofia K Kasiakou, Argyris Michalopoulos (2005)  Toxicity after prolonged (more than four weeks) administration of intravenous colistin.   BMC Infect Dis 5: 1. Jan  
Abstract: BACKGROUND: The intravenous use of polymyxins has been considered to be associated with considerable nephrotoxicity and neurotoxicity. For this reason, the systemic administration of polymyxins had been abandoned for about 20 years in most areas of the world. However, the problem of infections due to multidrug-resistant (MDR) Gram-negative bacteria such us Pseudomonas aeruginosa and Acinetobacter baumanniii has led to the re-use of polymyxins. Our objective was to study the toxicity of prolonged intravenous administration of colistin (polymyxin E). METHODS: An observational study of a retrospective cohort at "Henry Dunant" Hospital, a 450-bed tertiary care center in Athens, Greece, was undertaken.Patients who received intravenous colistin for more than 4 weeks for the treatment of multidrug resistant Gram-negative infections were included in the study. Serum creatinine, blood urea, liver function tests, symptoms and signs of neurotoxicity were the main outcomes studied. RESULTS: We analyzed data for 19 courses of prolonged intravenous colistin [mean duration of administration (+/- SD) 43.4 (+/- 14.6) days, mean daily dosage (+/- SD) 4.4 (+/- 2.1) million IU, mean cumulative dosage (+/- SD) 190.4 (+/- 91.0) million IU] in 17 patients. The median creatinine value increased by 0.25 mg/dl during the treatment compared to the baseline (p < 0.001) but returned close to the baseline at the end of treatment (higher by 0.1 mg/dl, p = 0.67). No apnea or other evidence of neuromuscular blockade was noted in any of these patients who received prolonged treatment with colistin. CONCLUSIONS: No serious toxicity was observed in this group of patients who received prolonged intravenous colistin. Colistin should be considered as a therapeutic option in patients with infections due to multidrug resistant Gram-negative bacteria.
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A S Michalopoulos, S Tsiodras, K Rellos, S Mentzelopoulos, M E Falagas (2005)  Colistin treatment in patients with ICU-acquired infections caused by multiresistant Gram-negative bacteria: the renaissance of an old antibiotic.   Clin Microbiol Infect 11: 2. 115-121 Feb  
Abstract: A retrospective case series study was performed in a 30-bed general intensive care unit (ICU) of a tertiary care hospital to assess the effectiveness and safety of colistin in 43 critically ill patients with ICU-acquired infections caused by multiresistant Gram-negative bacteria. Various ICU-acquired infections, mainly pneumonia and bacteraemia caused by multiresistant strains of Pseudomonas aeruginosa and/or Acinetobacter baumannii, were treated with colistin. Good clinical response (cure or improvement) was noted in 74.4% of patients. Deterioration of renal function occurred in 18.6% of patients during colistin therapy. Nephrotoxicity was elevated significantly in those patients with a history of renal failure (62.5%). All-cause mortality amounted to 27.9%. In this group of critically ill patients, an age of >50 years (OR, 5.4; 95% CI 1.3-24.9) and acute renal failure (OR, 8.2; 95% CI 2.9-23.8) were independent predictors of mortality. Colistin should be considered as a treatment option in critically ill patients with infection caused by multiresistant Gram-negative bacilli.
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Sofia K Kasiakou, Argyris Michalopoulos, Elpidoforos S Soteriades, George Samonis, George J Sermaides, Matthew E Falagas (2005)  Combination therapy with intravenous colistin for management of infections due to multidrug-resistant Gram-negative bacteria in patients without cystic fibrosis.   Antimicrob Agents Chemother 49: 8. 3136-3146 Aug  
Abstract: Colistin, an antibiotic almost abandoned for intravenous administration for many years due to its reported toxicity, has been recently reintroduced in clinical practice due to the emergence of multidrug-resistant gram-negative bacteria and the lack of development of new antibiotics to combat them. To assess the safety and effectiveness of intravenous colistin, in combination with other antimicrobial agents, in the treatment of serious infections in patients without cystic fibrosis, a retrospective cohort study in a 450-bed tertiary-care hospital in Athens, Greece, was performed. Patients who were hospitalized from 1 October 2000 to 31 January 2004 and received intravenous colistin for more than 72 h were further analyzed. The primary outcome measure was the in-hospital mortality; secondary end points were the clinical outcome of the infections and the occurrence of colistin toxicity. Fifty patients received intravenous colistin with a median (mean) daily dose of 3 (4.5) million IU for 16.5 (21.3) days for the management of 54 episodes of infections due to multidrug-resistant gram-negative bacteria. The predominant infections were pneumonia (33.3%), bacteremia (27.8%), urinary tract infection (11.1%), and intra-abdominal infection (11.1%). The responsible pathogens were Acinetobacter baumannii (51.9%), Pseudomonas aeruginosa (42.6%), and Klebsiella pneumoniae (3.7%) strains (no pathogen was isolated from one case). In-hospital mortality was 24% (12/50 patients). Clinical response (cure or improvement) of the infection was observed in 66.7% of episodes (36/54). In the studied group, serum creatinine levels were decreased, at the end of colistin treatment, by an average of 0.2 +/- 1.3 mg/dl compared to baseline levels. Deterioration of renal function during colistin therapy was observed in 4/50 patients (8%). Coadministration of other antimicrobial agents with spectrum against gram-negative microorganisms and the absence of a control group constitute the major limitations of this study. The use of intravenous colistin for the treatment of infections due to multidrug-resistant gram-negative bacteria appears to be safe and effective.
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Argyris Michalopoulos, Sofia K Kasiakou, Evangelos S Rosmarakis, Matthew E Falagas (2005)  Cure of multidrug-resistant Acinetobacter baumannii bacteraemia with continuous intravenous infusion of colistin.   Scand J Infect Dis 37: 2. 142-145  
Abstract: Continuous intravenous colistin (2,000,000 units per 24 h) was administered in a 41-y-old patient with Acinetobacter baumannii bacteraemia, which led to the cure of the infection. The isolated microorganism was a multi-resistant strain (it was sensitive only to colistin). In addition, the patient had developed allergic reactions to previously administered antimicrobial agents of several classes during his hospitalization. Continuous intravenous infusion of colistin proved to be a salvage regimen, which led to cure of a bacteraemia due to a multi-resistant isolate, without showing any allergic cross-reactivity with other antibiotics.
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Spyros D Mentzelopoulos, Maria Tzoufi, Kostas Rellos, Argyris S Michalopoulos, Elissavet Stamataki, Charris Roussos, Spyros G Zakynthinos (2005)  An evaluation of McCoy balloon laryngoscopy in patients with moderate-to-major endotracheal intubation difficulty.   Anesth Analg 101: 4. 1233-7, table of contents Oct  
Abstract: We hypothesized that combined McCoy-balloon laryngoscopy may facilitate airway management relative to McCoy or balloon laryngoscopy. In 10 anesthetized/paralyzed patients with prior intubation difficulty scale scores of >5, McCoy-balloon laryngoscopy versus conventional/balloon/McCoy laryngoscopies resulted in greater laryngeal aperture exposure (2.3 +/- 0.6 versus 0.6 +/- 0.2/1.4 +/- 0.4/1.5 +/- 0.6 cm2, respectively), lower intubation difficulty scale score (0.00 (0.00-0.00) versus 6.00 (6.00-8.25)/1.50(0.00-4.00)/2.00(0.75-5.00), respectively, median [interquartile range]), and 9%-74% shorter time to intubation confirmation (P < 0.05-0.001 for all). Balloon and McCoy laryngoscopies improved laryngoscopic/intubating conditions relative to conventional laryngoscopy. In patients with moderate-to-major conventional airway management difficulty, McCoy-balloon laryngoscopy further improves laryngoscopic/intubating conditions. IMPLICATIONS: This study shows that, in patients with moderate-to-major conventional airway management difficulty, combined McCoy-balloon laryngoscopy results in improved laryngoscopic/intubating conditions when compared with the conventional, McCoy, and balloon laryngoscopic techniques. McCoy-balloon laryngoscopy combines the merits of McCoy and balloon laryngoscopy and can be recommended for patients with moderate-to-major intubation difficulty.
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Yasser Sakr, Jean-Louis Vincent, Konrad Reinhart, Johan Groeneveld, Argyris Michalopoulos, Charles L Sprung, Antonio Artigas, V Marco Ranieri (2005)  High tidal volume and positive fluid balance are associated with worse outcome in acute lung injury.   Chest 128: 5. 3098-3108 Nov  
Abstract: STUDY OBJECTIVES: Recent data have suggested that ventilatory strategy could influence outcomes from acute lung injury (ALI) and ARDS. We tested the hypothesis that infection/sepsis and use of higher tidal volumes than those applied in the ARDS Network (ARDSnet) study (> 7.4 mL/kg of predicted body weight) would worsen outcome in patients with ALI/ARDS. DESIGN: International cohort, observational study. SETTING: One hundred ninety-eight European ICUs participating in the Sepsis Occurrence in Acutely Ill Patients study. PATIENTS OR PARTICIPANTS: All 3,147 adult patients admitted to one of the participating ICUs between May 1, 2002, and May 15, 2002. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Patients were followed up until death, hospital discharge, or for 60 days. Of the 3,147 patients, 393 patients (12.5%) had ALI/ARDS. ICU and hospital mortality was higher in patients with ALI/ARDS than those without ALI/ARDS (38.9% vs 15.6% and 45.5% vs 21.0%, respectively; p < 0.001). A multivariable logistic regression analysis with ICU outcome as the dependent factor showed that the independent risks for mortality were as follows: presence of cancer, use of tidal volumes higher than those used by the ARDSnet study, degree of multiorgan dysfunction, and higher mean fluid balance. Sepsis, septic shock, and oxygenation at the onset of ALI/ARDS were not independently associated with higher mortality rates. CONCLUSIONS: In addition to comorbidities and organ dysfunction, high tidal volumes and positive fluid balance are associated with a worse outcome from ALI/ARDS.
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Argyris Michalopoulos, Matthew E Falagas (2005)  A bibliometric analysis of global research production in respiratory medicine.   Chest 128: 6. 3993-3998 Dec  
Abstract: STUDY OBJECTIVES: To evaluate the contribution of different world regions in respiratory research productivity. METHODS: The world was divided into nine regions based on a combination of geographic, economic, and scientific criteria. Using the PubMed database, we retrieved information about the origin of articles from 30 journals included in the Respiratory System category of the Journal Citation Reports database for a 9-year period (1995 to 2003). We estimated the total number of publications, their mean impact factor, the product of these two parameters, and the research productivity per million of population of the world area divided by the gross national income per capita (GNIPC), for every year and the whole period of the study, for all defined world regions. MEASUREMENTS AND RESULTS: Data on the country of origin of the publications was available for 48,614 of 49,382 retrieved articles (98.5%). The majority of articles published between 1995 and 2003 originated from Western Europe (40.4%) and the United States (35.4%). The research productivity compared to population and the GNIPC was found to be higher for Canada and Oceania compared to the United States and Western Europe. The rate of increase of the total published research product (number of published articles multiplied by the impact factor) was higher in the United States and Europe. The total research contribution of Asia, Eastern Europe, Central and Latin America, and Africa regarding the number of published articles was notably very low (approximately 8%). CONCLUSIONS: The data suggest that there was a significant research activity in the field of respiratory medicine during the studied period. Although leaders of production of respiratory medicine research were from Western Europe and the United States, Canada, and Oceania had the best performance after adjustment for population and GNIPC.
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Sofia K Kasiakou, George J Sermaides, Argyris Michalopoulos, Elpidoforos S Soteriades, Matthew E Falagas (2005)  Continuous versus intermittent intravenous administration of antibiotics: a meta-analysis of randomised controlled trials.   Lancet Infect Dis 5: 9. 581-589 Sep  
Abstract: Intermittent intravenous administration of antibiotics is the first-line approach in the management of severe infections worldwide. However, the potential benefits of alternate modes of administration of antibiotics, including continuous intravenous infusion, deserve further evaluation. We did a meta-analysis of randomised controlled trials comparing continuous intravenous infusion with intermittent intravenous administration of the same antibiotic regimen. Nine randomised controlled trials studying beta-lactams, aminoglycosides, and vancomycin were included. Clinical failure was lower, although without statistical significance, in patients receiving continuous infusion of antibiotics (pooled OR 0.73, 95% CI 0.53-1.01); the difference was statistically significant in a subset of randomised controlled trials that used the same total daily antibiotic dose for both intervention arms (0.70, 0.50-0.98, fixed and random effects models). Regarding mortality and nephrotoxicity, no differences were found (mortality 0.89, 0.48-1.64; nephrotoxicity 0.91, 0.56-1.47). In conclusion, the data suggest that the administration of the same total antibiotic dose by continuous intravenous infusion may be more efficient, with regard to clinical effectiveness, compared with the intermittent mode. In an era of gradually increasing resistance among most pathogens, the potential advantages of continuous intravenous administration of antibiotics on several clinical outcomes should be further investigated.
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Matthew E Falagas, Konstantinos N Fragoulis, Sofia K Kasiakou, George J Sermaidis, Argyris Michalopoulos (2005)  Nephrotoxicity of intravenous colistin: a prospective evaluation.   Int J Antimicrob Agents 26: 6. 504-507 Dec  
Abstract: Twenty-one patients who received intravenous colistimethate sodium (CMS) for at least 7 days for the treatment of multidrug-resistant Gram-negative bacterial infections were included in a prospective cohort study at 'Henry Dunant' Hospital in Athens, Greece. The mean (+/- standard deviation) and median daily doses, cumulative doses and duration of treatment of intravenous CMS were, respectively, 5.5 (+/- 1.9) and 6 million IU, 90.2 (+/- 52.0) and 72 million IU, and 17.7 (+/- 11.7) and 15 days (range 7-54 days). Three patients (14.3%) developed nephrotoxicity during treatment with CMS. The cumulative dose of administered CMS was statistically correlated with the difference in values of serum creatinine between the end and start of CMS treatment (r = 0.6, P = 0.004 by Spearman's test).
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Dimitris Georgopoulos, Dimitris Matamis, Christina Routsi, Argiris Michalopoulos, Nina Maggina, George Dimopoulos, Epaminondas Zakynthinos, George Nakos, George Thomopoulos, Kostas Mandragos, Alice Maniatis (2005)  Recombinant human erythropoietin therapy in critically ill patients: a dose-response study [ISRCTN48523317].   Crit Care 9: 5. R508-R515 Oct  
Abstract: INTRODUCTION: The aim of this study was to assess the efficacy of two dosing schedules of recombinant human erythropoietin (rHuEPO) in increasing haematocrit (Hct) and haemoglobin (Hb) and reducing exposure to allogeneic red blood cell (RBC) transfusion in critically ill patients. METHOD: This was a prospective, randomized, multicentre trial. A total of 13 intensive care units participated, and a total of 148 patients who met eligibility criteria were enrolled. Patients were randomly assigned to receive intravenous iron saccharate alone (control group), intravenous iron saccharate and subcutaneous rHuEPO 40,000 units once per week (group A), or intravenous iron saccharate and subcutaneous rHuEPO 40,000 units three times per week (group B). rHuEPO was given for a minimum of 2 weeks or until discharge from the intensive care unit or death. The maximum duration of therapy was 3 weeks. RESULTS: The cumulative number of RBC units transfused, the average numbers of RBC units transfused per patient and per transfused patient, the average volume of RBCs transfused per day, and the percentage of transfused patients were significantly higher in the control group than in groups A and B. No significant difference was observed between group A and B. The mean increases in Hct and Hb from baseline to final measurement were significantly greater in group B than in the control group. The mean increase in Hct was significantly greater in group B than in group A. The mean increase in Hct in group A was significantly greater than that in control individuals, whereas the mean increase in Hb did not differ significantly between the control group and group A. CONCLUSION: Administration of rHuEPO to critically ill patients significantly reduced the need for RBC transfusion. The magnitude of the reduction did not differ between the two dosing schedules, although there was a dose response for Hct and Hb to rHuEPO in these patients.
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DOI   
PMID 
Konstantinos Z Vardakas, Argyris Michalopoulos, Matthew E Falagas (2005)  Fluconazole versus itraconazole for antifungal prophylaxis in neutropenic patients with haematological malignancies: a meta-analysis of randomised-controlled trials.   Br J Haematol 131: 1. 22-28 Oct  
Abstract: Fluconazole and itraconazole are used as antifungal prophylaxis in neutropenic patients with haematological malignancies. A meta-analysis of randomised-controlled trials (RCTs) was performed in order to compare their safety and effectiveness in this population. Data were obtained from PubMed, Current Contents, Cochrane Central Register for Controlled Trials and references from relevant articles. Five RCTs were included in the analysis. Publication bias and statistically significant heterogeneity was not observed among the analysed studies. Fewer patients were withdrawn due to the development of adverse effects associated with fluconazole when compared with itraconazole [odds ratio (OR) = 0.27, 95% confidence interval (CI): 0.18-0.41]. On the contrary, prophylactic use of fluconazole resulted in significantly more fungal infections (documented and suspected infections combined, OR = 1.62, 95% CI: 1.06-2.48). There were no statistically significant differences regarding documented fungal infections (OR = 1.51, 95% CI: 0.97-2.35), invasive fungal infections (OR = 1.44, 95% CI: 0.96-2.17), overall mortality (OR = 0.89, 95% CI: 0.63-1.24) and mortality attributed by the authors to fungal infections (OR = 1.30, 95% CI: 0.75-2.25) between the two medications. These data suggest that, even though itraconazole is more effective than fluconazole in the prevention of fungal infections in neutropenic patients with haematological malignancies, the development of more adverse effects may limit its use.
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PMID 
Ioannis A Bliziotis, Argyris Michalopoulos, Sofia K Kasiakou, George Samonis, Christos Christodoulou, Stavroula Chrysanthopoulou, Matthew E Falagas (2005)  Ciprofloxacin vs an aminoglycoside in combination with a beta-lactam for the treatment of febrile neutropenia: a meta-analysis of randomized controlled trials.   Mayo Clin Proc 80: 9. 1146-1156 Sep  
Abstract: OBJECTIVE: To compare the effectiveness and toxicity of ciprofloxacin vs an aminoglycoside, both in combination with a beta-lactam, for the treatment of febrile neutropenia in the inpatient setting. METHODS: For this meta-analysis of randomized controlled trials (RCTs) that compared the ciprofloxacin/beta-lactam combination vs an aminoglycoside/beta-lactam combination for the treatment of febrile neutropenia and reported data on effectiveness, mortality, and/or toxicity, we searched PubMed (1950-2004), Current Contents, Cochrane Central Register of Controlled Trials, and reference lists of retrieved articles, including review articles, as well as abstracts presented at international conferences. Data for 3 primary and 2 secondary outcomes were extracted by 2 investigators. RESULTS: Eight RCTs were included in the analysis. Comparable or better outcomes were observed with the ciprofloxacin/beta-lactam combination vs an aminoglycoside/beta-lactam combination: clinical cure without modification of the initial regimen (odds ratio [OR], 1.32; 95% confidence interval [CI], 1.00-1.74; P=.05), clinical cure in the subset of patients with documented Infections (OR, 1.56; 95% CI, 1.05-2.31; P=.03), all-cause mortality (OR, 0.85; 95% CI, 0.54-1.35; P=.49), withdrawal of the study drugs due to toxicity (OR, 0.87; 95% CI, 0.57-1.32; P-.51), and nephrotoxicity (OR, 0.30; 95% CI, 0.16-0.59; P<.001). The ciprofloxacin/beta-lactam combination was also associated with better clinical cure compared to the aminoglycoside/beta-actam combination in the subset of RCTs with non-low-risk patients (OR, 1.38; 95% CI, 1.01-1.88; P=-.04), as well as in the subset of studies that included the same beta-lactam in both treatment arms (OR, 1.47; 95% CI, 1.06-2.05; P=.02). CONCLUSION: The combination of ciprofloxacin with a beta-actam antibiotic should be considered an important therapeutic option in hospitalized febrile neutropenic patients who have not received a quinolone for prevention of infections and in settings in which quinolone resistance is not common.
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2004
 
DOI   
PMID 
M Rizos, M E Falagas, S Tsiodras, A Betsou, P Foukas, A Michalopoulos (2004)  Usual interstitial pneumonia associated with cytomegalovirus infection after percutaneous transluminal coronary angioplasty.   Eur J Clin Microbiol Infect Dis 23: 11. 848-850 Nov  
Abstract: An unusual case of cytomegalovirus (CMV) pneumonia in a diabetic patient is presented. The diagnosis was based on typical histopathological findings including intranuclear inclusion bodies combined with molecular identification of CMV in tissue specimens. The possibility of CMV reactivation associated with a previous cardiac procedure, which led to the development of usual interstitial pneumonia, is discussed. Clinicians should be aware of CMV-associated severe bilateral pneumonia developing after cardiac procedures even in non-transplant patients. The correct diagnosis depends on clinical awareness in the appropriate setting along with proof of viral infection.
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2003
 
PMID 
Spyros D Mentzelopoulos, Spyros G Zakynthinos, Charris Roussos, Maria J Tzoufi, Argyris S Michalopoulos (2003)  Prone position improves lung mechanical behavior and enhances gas exchange efficiency in mechanically ventilated chronic obstructive pulmonary disease patients.   Anesth Analg 96: 6. 1756-67, table of contents Jun  
Abstract: Pronation might favorably affect respiratory system (rs) mechanics and function in volume-controlled, mode-ventilated chronic obstructive pulmonary disease (COPD) patients. We studied 10 COPD patients, initially positioned supine (baseline supine [supine(BAS)]) and then randomly and consecutively changed to protocol supine (supine(PROT)), semirecumbent, and prone positions. Rs mechanics and inspiratory work (W(I)) were assessed at baseline (0.6 L) (all postures) and sigh (1.2 L) (supine(BAS) excluded) tidal volume (V(T)) with rapid airway occlusion during constant-flow inflation. Hemodynamics and gas exchange were assessed in all postures. There were no complications. Prone positioning resulted in (a) increased dynamic-static chest wall (cw) elastance (at both V(Ts)) and improved oxygenation versus supine(BAS), supine(PROT), and semirecumbent, (b) decreased additional lung (L) resistance-elastance versus supine(PROT) and semirecumbent at sigh V(T), (c) decreased L-static elastance (at both V(Ts)) and improved CO(2) elimination versus supine(BAS) and supine(PROT), and (d) improved oxygenation versus all other postures. Semirecumbent positioning increased mainly additional cw-resistance versus supine(BAS) and supine(PROT) at baseline. V(T) W(I)-sub-component changes were consistent with changes in rs, cw, and L mechanical properties. Total rs-W(I) and hemodynamics were unaffected by posture change. After pronation, five patients were repositioned supine (supine(POSTPRO)). In supine(POSTPRO), static rs-L elastance were lower, and oxygenation was still improved versus supine(BAS). Pronation of mechanically ventilated COPD patients exhibits applicability and effectiveness and improves oxygenation and sigh-L mechanics versus semirecumbent ("gold standard") positioning. IMPLICATIONS: By assessing respiratory mechanics, inspiratory work, hemodynamics, and gas exchange, we showed that prone positioning of mechanically ventilated chronic obstructed pulmonary disease patients improves oxygenation and lung mechanics during sigh versus semirecumbent positioning. Furthermore, certain pronation-related benefits versus preprone-supine positioning (reduced lung elastance and improved oxygenation) are maintained in the postprone supine position.
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PMID 
Argyris S Michalopoulos, Stefanos Geroulanos, Spyros D Mentzelopoulos (2003)  Determinants of candidemia and candidemia-related death in cardiothoracic ICU patients.   Chest 124: 6. 2244-2255 Dec  
Abstract: STUDY OBJECTIVES: To develop and prospectively validate models of independent predictors of candidemia and candidemia-related death in cardiothoracic ICU (CICU) patients. DESIGN: (1) An initial, prospective, one-center, case-control, independent predictor-model determining study; and (2) a prospective, two-center, model-validation study. SETTING: The initial study was performed at the 14-bed CICU of the Onassis Cardiac Surgery Center, Athens, Greece; the model-validation study was performed at the Onassis Cardiac Surgery Center CICU and the 12-bed CICU of Henry Dunant General Hospital, Athens, Greece. PATIENTS: In the initial study, 4,312 patients admitted to the Onassis Center CICU between March 1997 and October 1999 were considered for enrollment; 30 candidemic and 120 control patients (case/control ratio, 1/4) matched according to potential confounders were ultimately enrolled. In the model-validation study, 2,087 patients admitted to the Onassis and Henry Dunant CICUs between November 1999 and May 2002 were prospectively enrolled. MEASUREMENTS AND RESULTS: Models of predictors of candidemia and associated death were constructed with stepwise logistic regression and subsequently validated. Independent candidemia predictors were ongoing invasive mechanical ventilation (IMV) > OR =10 days, hospital-acquired bacterial infection and/or bacteremia, cardiopulmonary bypass duration > 120 min, and diabetes mellitus. Model performance was as follows: sensitivity, 53.3%/57.9%; specificity, 100%/100%; positive predictive value (PPV), 100%/100%; negative predictive value (NPV), 88.9%/99.6%; and accuracy, 90.1%/99.6% (initial/model-validation study values, respectively). IMV > or =10 days and hospital-acquired bacterial infection/bacteremia were the two strongest candidemia predictors. APACHE (acute physiology and chronic health evaluation) II score > or =30 at candidemia onset independently predicted candidemia-related death with 80.0%/85.7% sensitivity, 80%/75% specificity, 66.7%/66.7% PPV, 88.9%/88.9% NPV, and 80.0%/78.9% accuracy (initial/model-validation study values, respectively). CONCLUSIONS: We provided a set of easily determinable independent predictors of the occurrence of candidemia in CICU patients. Our results provide a rationale for implementing preventive measures in the form of independent predictor control, and initiating antifungal prophylaxis in high-risk CICU patients.
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PMID 
Stavroula Georgopoulou, Ekaterini Kounougeri, Chrisostomos Katsenos, Michael Rizos, Argyris Michalopoulos (2003)  Rhinocerebral mucormycosis in a patient with cirrhosis and chronic renal failure.   Hepatogastroenterology 50: 51. 843-845 May/Jun  
Abstract: Mucormycosis is an opportunistic fungal infection caused by Mucorales. The disease is uncommon and produces serious and rapidly fatal infection in diabetic or immunocompromised patients. The classical presentation of rhinocerebral mucormycosis is involvement of nasal mucosa with invasion of paranasal sinuses and orbit. Early diagnosis is based on (direct) histological examination and computed tomography scan. Unfortunately the clinical signs and symptoms do not occur in all cases. A high index of suspicion is needed not only in typical groups of immunocompromised patients or diabetics, but also in patients with serious chronic diseases. We report a patient who was not diabetic, but she had a history of cirrhosis and well compensated renal failure.
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2002
 
PMID 
S D Gatzonis, Ch Zournas, A Michalopoulos, S Prapas, S Argentos, S Geroulanos (2002)  Area-selective stimulus-provoked seizures in post-anoxic coma.   Seizure 11 Suppl A: 294-297 Apr  
Abstract: We describe the case of a 70-year-old patient in whom hemiconvulsive seizures occurred during metabolic derangement, multiple stroke and post-anoxic coma following cardiac arrest. We employed the methods of clinical and EEG evaluation and CT brain scan. We found that hemiconvulsive seizures were provoked following a light tactile stimulus in the left-trigeminal area and occasionally a strong tapping in the right-trigeminal area. We conclude that this type of stimulus-provoked seizure is extremely rare and could be explained by diffuse and severe brain damage.
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PMID 
Argyris S Michalopoulos, Maria J Tzoufi, George Theodorakis, Spyros D Mentzelopoulos (2002)  Acute postoperative pulmonary thromboembolism as a result of intravascular migration of a pigtail ureteral stent.   Anesth Analg 95: 5. 1185-8, table of contents Nov  
Abstract: IMPLICATIONS: The symptomatic obstruction of a pulmonary arterial branch secondary to the intravascular migration of a pigtail ureteral stent is reported. This iatrogenic complication may cause dyspnea, chest pain, or both after uneventful urologic procedures involving ureteral stents.
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PMID 
Revekka Tzanetea, Kostas Konstantopoulos, Anna Xanthaki, Vassiliki Kalotychou, Chara Spiliopoulou, Argyris Michalopoulos, Yannis Rombos (2002)  Plesiomonas shigelloides sepsis in a thalassemia intermedia patient.   Scand J Infect Dis 34: 9. 687-689  
Abstract: Bacteremia due to Plesiomonas shigelloides was associated with rapidly fulminant septicemia, disseminated intravascular coagulation and massive adrenal hemorrhage in a splenectomized patient suffering from thalassemia intermedia who was treated with hydroxyurea. P. shigelloides was isolated in blood cultures; despite a vigorous combination of antibiotics the patient died after 24 h in the ICU. Lethal sepsis due to P. shigelloides has not previously been reported in Greece.
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2001
 
DOI   
PMID 
S D Gatzonis, C Zournas, A Michalopoulos, S Prapas, S Argentos, S Geroulanos (2001)  Area-selective stimulus-provoked seizures in post-anoxic coma.   Seizure 10: 4. 294-297 Jun  
Abstract: We describe the case of a 70-year-old patient in whom hemiconvulsive seizures occurred during metabolic derangement, multiple stroke and post-anoxic coma following cardiac arrest. We employed the methods of clinical and EEG evaluation and CT brain scan. We found that hemiconvulsive seizures were provoked following a light tactile stimulus in the left-trigeminal area and occasionally a strong tapping in the right-trigeminal area. We conclude that this type of stimulus-provoked seizure is extremely rare and could be explained by diffuse and severe brain damage.
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PMID 
A Michalopoulos, S Geroulanos, L Papadimitriou, E Papadakis, K Triantafillou, K Papadopoulos, G Palatianos (2001)  Mild or moderate chronic obstructive pulmonary disease risk in elective coronary artery bypass grafting surgery.   World J Surg 25: 12. 1507-1511 Dec  
Abstract: A history of chronic obstructive pulmonary disease (COPD) is considered a risk factor in patients undergoing coronary artery bypass grafting (CABG) surgery. The objective of this study was to examine the impact of history of mild or moderate COPD on outcome in patients undergoing elective CABG surgery. In this prospective, case-controlled study, we compared two groups of adult patients undergoing elective CABG surgery. In this prospective, case-controlled study, we compared two groups of adult patients undergoing elective CABG surgery. There were no statistically significant differences regarding early postoperative complications between the groups (p > 0.05). The median duration of mechanical ventilation and ICU length of stay were 0.4 and 1 days, respectively, in the two groups. The mean (+/- SD) hospital stay was 7.8 +/- 1.6 days in the COPD group and 7.5 +/- 1.3 days in the control group (p = 0.1). The mortality rate was found 1.4% in COPD patients and 0.7% in the control group (p = 0.5). We concluded that patients with a history of mild or moderate COPD undergoing elective CABG had morbidity and mortality rates comparable with those of controls (p > 0.05).
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2000
 
PMID 
I Kriaras, A Michalopoulos, M Turina, S Geroulanos (2000)  Evolution of antimicrobial prophylaxis in cardiovascular surgery.   Eur J Cardiothorac Surg 18: 4. 440-446 Oct  
Abstract: OBJECTIVE: To examine the optimal duration of antibiotic prophylaxis in major cardiovascular surgery. MTHODSs: In the past 15 years, four prospective randomized, controlled studies, conducted by the same group of authors, compared seven prophylactic antimicrobial regimens in 2970 patients undergoing major cardiovascular surgery. In 1980/81, a 4-day cefazolin (CFZ) prophylaxis was compared with a 2-day cefuroxime (CFX) administration (n=566). In 1982/83, a 2-day CFX prophylaxis was compared with a two shot ceftriaxone (CRO) prophylaxis (n=512). In 1984/87, a 1-day CFZ prophylaxis was compared with a single shot prophylaxis of CRO (n=883). In 1994/1995, a 4 day combination of amoxicillin (AM) and netilmicin (NET) prophylaxis was compared with a single shot prophylaxis of CFX (n=1009). RESULTS: Total infection rate varied between 4.5 and 5.7%, despite different antimicrobial regimen used and their varying duration. Wound infection rate was 1.1% (range 0.4-2.5%), sepsis rate was 0.8% (range 0.4-1.6%), pneumonia rate 2% (0.7-2.9%), urinary tract infection rate 0.4% (range 0-1.4%), and central venous catheter-related infection rate was 0.4% (0-1%). The 30-day mortality rate was 1.3% (range 0.4-2%). All these differences were not statistically significant. CONCLUSIONS: A low infection rate (range 4.5-5.7%) occurred despite changes in duration of various prophylactic antibiotic regimen with cephalosporins of first, second or third generation. As a single shot prophylaxis could nowadays successfully be used in cardiovascular surgery, no postoperative antibiotics should be used, unless an intraoperative or a postoperative infection is documented or in presence of major perioperative complications.
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1999
 
PMID 
A Michalopoulos, G Tzelepis, U Dafni, S Geroulanos (1999)  Determinants of hospital mortality after coronary artery bypass grafting.   Chest 115: 6. 1598-1603 Jun  
Abstract: OBJECTIVES: To examine causes of death and to find predictors of hospital mortality after elective coronary artery bypass graft (CABG) surgery. DESIGN: Case-control study. SETTING: Tertiary teaching hospital. METHODS: We prospectively collected various preoperative, operative, and immediate postoperative variables in a cohort of patients undergoing elective CABG surgery. RESULTS: Of the 2,014 consecutive patients (mean [+/- SD] age of 61.3+/-6.7 years old) undergoing elective CABG over a 2-year period, 27 patients (1.3%) died during their hospitalization. The main causes of death (either isolated or in combination) were cardiogenic shock (n = 13), brain death or stroke (n = 7), septic shock (n = 4), ARDS (n = 2), and pulmonary embolism (n = 1). A univariate statistical analysis revealed factors that significantly correlate with outcome: patient age, preoperative left ventricular ejection fraction, bypass time, aortic cross-clamp time, number of blood units transfused, number of inotropic agents administered in the operating room during the first postoperative day (POD), history of arterial hypertension, intra-aortic balloon pump usage, and perioperative development of shock. A logistic regression analysis showed that the combination of the number of inotropes and the number of blood units administered in the operating room during POD 1 was the most important determinant of outcome, with an overall positive predictive value of 91.7%. CONCLUSIONS: We conclude that the analysis of simple variables enhances our ability to accurately predict hospital mortality in patients undergoing elective CABG surgery. The number of inotropic agents and blood transfusions administered during the immediate postoperative period is the most important independent predictor of hospital mortality.
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1998
 
PMID 
A Michalopoulos, A Anthi, K Rellos, S Geroulanos (1998)  Effects of positive end-expiratory pressure (PEEP) in cardiac surgery patients.   Respir Med 92: 6. 858-862 Jun  
Abstract: The role of positive end-expiratory pressure (PEEP) in the postoperative course of cardiac surgery patients remains questionable. In this prospective study, we examined the effect of different levels of PEEP on arterial oxygenation, SvO2 and PvO2 values, and on haemodynamic indices, during the early postoperative period in cardiac surgery patients. Upon transfer to the ICU, 67 adult patients with normal preoperative respiratory status were randomly assigned to receive zero PEEP (Group A), 5 cmH2O (Group B), or 10 cmH2O PEEP (Group C) during mechanical ventilatory support. PaO2/FIO2 ratio, mixed venous PvO2 and SvO2, and cardiac index, were measured 30 min, 4 h and 8 h after application of mechanical ventilation in the ICU, just prior to extubation, half an hour after extubation, and 4 h post-extubation. We found no statistically significant differences (P = n.s.) in arterial oxygenation expressed by PaO2/FIO2 ratio, SvO2 and PvO2 values, and in cardiac index among the three groups at any study interval. We conclude that low levels of PEEP have no advantage over zero PEEP in improving gas exchange in the early postoperative course of patients following open heart surgery.
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PMID 
A Michalopoulos, G Stavridis, S Geroulanos (1998)  Severe sepsis in cardiac surgical patients.   Eur J Surg 164: 3. 217-222 Mar  
Abstract: OBJECTIVE: To elucidate the incidence, determinants, and consequences of severe sepsis after cardiac surgery. DESIGN: Prospective study. SETTING: Cardiac surgical unit, Greece. SUBJECTS: 2615 adult patients having cardiac operations. MAIN OUTCOME MEASURES: Microbiological evidence of sepsis, mortality, and duration of stay in the intensive care unit (ICU) and hospital. RESULTS: Severe sepsis developed in 41/2615 patients (2%), all during their stay in the ICU: there were 30 men and 11 women, mean (SD) age 65 (10) years. It was most common after combined coronary artery bypass grafting and valve-related operations (7/95, 7%), followed by miscellaneous cardiac operations (7/147, 5%), valve replacement (8/359, 2%), and coronary artery bypass grafting (19/2014, 1%). When the 41 patients who developed severe sepsis were compared with those who did not (n = 2574) by univariate analysis, there were significant differences in age (p = 0.004); type of operation (p < 0.0001); duration of operation (p < 0.001); bleeding that necessitating either reoperation or significantly more blood transfused (p < 0.0001); and the incidence of low cardiac output syndrome (p = 0.0001). Of the 41 patients with severe sepsis, 19 (46%) had serious operative complications, 40 (98%) had severe complications in the ICU, and 16 (39%) required reintubation for hypoxaemia. Among the 41 there were 54 bacteraemic episodes of which 37 (69%) were caused by gram positive cocci, 6 (11%) by gram negative bacteria, and 11 (20%) by Candida albicans. Staphylococcus epidermidis was the most common pathogen isolated (n = 26, 48%). Sepsis associated with bacterial infection usually developed during the first two weeks, and that caused by fungal infection was most common after the twentieth postoperative day. Patients with severe sepsis required longer mechanical ventilation (31 (21) days compared with 0.9 (0.1) days); longer stay in the ICU (40 (25) days) compared with 2 (1) days); longer stay in hospital (48 (27) days compared with 10 (2) days); and significantly more of them died (13 (32%) compared with 41 (2%), p < 0.0001 in each case). CONCLUSIONS: We concluded that severe sepsis mainly developed in cardiac surgery patients with serious operative and postoperative complications and was associated with a longer stay in both ICU and hospital, and a higher mortality.
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PMID 
A Michalopoulos, A Nikolaides, C Antzaka, M Deliyanni, A Smirli, S Geroulanos, L Papadimitriou (1998)  Change in anaesthesia practice and postoperative sedation shortens ICU and hospital length of stay following coronary artery bypass surgery.   Respir Med 92: 8. 1066-1070 Aug  
Abstract: We randomized prospectively 144 patients, undergoing elective coronary artery bypass surgery, to either early or to routine extubation [mechanical ventilatory support for 4-7 h (Group A), or 8-14 h (Group B)]. Anaesthesia was modified for both groups. The groups were well matched in terms of sex, age, NYHA class, preoperative left ventricular ejection fraction, bypass time and aortic cross-clamp time, number of grafts used, and blood units transfused. All patients had normal preoperative respiratory, renal, hepatic and cerebral functions. Mechanical ventilatory support (mean +/- SD) was 6.3 +/- 0.7 h for Group A and 11.6 +/- 1.3 h for Group B. Mean ICU stay was 17 +/- 1.3 h for Group A and 22 +/- 1.2 h for Group B, while the mean hospital stay was 7.3 +/- 0.8 days and 8.4 +/- 0.9, respectively. There were no statistically significant differences in the frequency of all postoperative complications among the two groups. There were no reintubation, readmission to the ICU or death in either group. We concluded that change in anaesthesia practice and early postoperative sedation in patients undergoing elective coronary artery bypass graft (CABG) surgery resulted in earlier tracheal extubation, shorter ICU and hospital length of stay without organ dysfunction or postoperative complications. Early extubation was only possible due to the modification of anaesthesia and ICU sedation regime.
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1997
 
PMID 
J Schilling, A Michalopoulos, S Geroulanos (1997)  Antibiotic prophylaxis in gastroduodenal surgery.   Hepatogastroenterology 44: 13. 116-120 Jan/Feb  
Abstract: BACKGROUND/AIMS: In a retrospective process quality control trial, proper use of antimicrobial prophylaxis in gastroduodenal operations according to the standard guidelines was studied. PATIENTS AND METHODS: A total of 132 consecutive adult patients (pts), who underwent gastroduodenal surgery in a University Hospital, were enrolled to this study protocol. There were 88 males and 44 females of with mean (+/-SD) age of 58.7 (+/-9.1) years old. The patients were divided into 4 groups based on surgical antibiotic prophylaxis policy. Group A consisted of surgical pts receiving appropriate antibiotic prophylaxis (a 2nd generation cephalosporin) when there was indication. Group B consisted of pts without indication who did not receive prophylaxis, Group C pts who, although antibiotic prophylaxis was indicated, were not given prophylaxis, and Group D pts without indication who received prophylaxis. RESULTS: Of 132 pts examined, appropriate antibiotic prophylaxis was received by 28 pts (21%) (Group A). In 62 pts (47%), antibiotic prophylaxis was not indicated and not administered (Group B). On the contrary, in 42 pts (32%), although antibiotic prophylaxis was indicated, it was not given (Group C). No patient received prophylaxis without indication. The following infections were found: wound infection (n = 10), pneumonia (n = 6), severe sepsis (n = 2), urinary tract infection (n = 2), and fever of unknown origin (n = 2). Where correct antibiotic prophylaxis policy was followed (Groups A and B), 6 post-operative infections occurred (6.7%), with a mean (+/-SD) hospital length of stay 14.4 (+/-3.2) days. In contrast, in the group with incorrect antibiotic prophylaxis policy (group D), 16 infectious complications occurred (38%) (p = 0.001), with a mean (+/-SD) hospital length of stay 22.5 (+/-4.4) days (p = 0.001). Total hospitalization costs were much higher in this group compared with Groups A and B (p = 0.01). Mortality rate was 9.5% in Group D, while no deaths occurred in the other groups (p = 0.01). CONCLUSION: Antimicrobial prophylaxis policy is an important issue, targeting lower morbidity or avoidable costs.
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PMID 
A Michalopoulos, P Alivizatos, S Geroulanos (1997)  Hepatic dysfunction following cardiac surgery: determinants and consequences.   Hepatogastroenterology 44: 15. 779-783 May/Jun  
Abstract: BACKGROUND/AIMS: We prospectively studied the determinants, characteristics, and consequences of hepatic dysfunction in the early postoperative period following cardiac surgery. METHODOLOGY: We examined 3041 adult patients, mean age 60.6 (+/- 8.9), with normal pre-operative liver function who consecutively underwent open heart surgery in a newly established Cardiac Surgery Center. Patients were divided into two groups; Group A included all patients who developed hepatic dysfunction, defined as the presence of jaundice associated with an elevated serum bilirubin above 3 mg/dl, in the early postoperative period. The control group included cardiac surgical patients who did not develop such dysfunction. RESULTS: Hepatic dysfunction developed in 96 patients (3.2%). The affected patients consisted of 63 males and 33 females, mean age 60.8 (+/- 9.4). Determinants of hepatic dysfunction based on univariate analysis were sex, NYHA class, type of surgery, operative times, low cardiac output syndrome necessitating administration of inotropic agents and/or IABP usage, cardiac arrest, presence of hematomas, and number of blood transfusions. Patients with hepatic dysfunction required prolonged mechanical ventilation, stayed longer in the ICU (and in the hospital) and experienced a much higher mortality rate (11.4%) compared to the control group (p = 0.001). CONCLUSION: Although the pathogenesis of hepatic dysfunction seems to be multifactorial, liver cell damage due to decreased perioperative hepatic flow and increased bilirubin load seem to be of critical importance. Early postoperative hepatic dysfunction resulted in increased morbidity and mortality.
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PMID 
A Michalopoulos, J Kriaras, S Geroulanos (1997)  Systemic candidiasis in cardiac surgery patients.   Eur J Cardiothorac Surg 11: 4. 728-731 Apr  
Abstract: OBJECTIVE: To examine the frequency, predisposing factors and consequences of systemic candidiasis in cardiac surgery patients. We also examined fluconazole efficacy in the treatment of disseminated fungal disease. METHODS: A total of 2615 adult patients of mean +/- S.D. age 60.8 +/- 8.7 years who underwent open heart surgery between July 1993 and April 1995, were enrolled in the initial protocol. Patients were divided in two groups according to length of stay in the intensive care unit (ICU). The cut-off was a length of stay of 9 days. RESULTS: In the group of patients with prolonged stay (n = 54), 11 patients (20.3%) developed systemic candidiasis, usually after the twentieth postoperative day. Predisposing factors were patient age, history of diabetes mellitus, presence of central venous catheters, prolonged mechanical ventilatory support, prolonged ICU stay, and administration of antibiotics and of total parenteral nutrition for a prolonged period. The patients who developed systemic candidiasis had a median ICU and hospital stay of 58 and 60 days respectively. The mortality rate was 27.2%. Patients receiving fluconazole, improved and eventually negative cultures were obtained. CONCLUSIONS: We concluded that a significant percentage of patients who remained in the cardiothoracic ICU for more than 9 days developed systemic candidiasis. Systemic candidiasis resulted in a significant prolongation of ICU and hospital length of stay, thus increasing extensively total hospitalization costs. Fluconazole seems to be an effective and well-tolerated agent in the treatment of severe life-threatening systemic candidiasis, and a very good alternative to amphotericin B, in cardiac surgery patients.
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PMID 
I Kriaras, A Michalopoulos, A Michalis, G Palatianos, G Economopoulos, C Anagnostopoulos, S Geroulanos (1997)  Antibiotic prophylaxis in cardiac surgery.   J Cardiovasc Surg (Torino) 38: 6. 605-610 Dec  
Abstract: BACKGROUND: A prospective, randomised study was conducted among 1009 cardiac surgery patients in order to compare the prophylactic efficacy of a second generation cephalosporin (cefuroxime) given as single shot, versus a broad spectrum double regimen (amoxycillin-netilmicin). METHODS: Cefuroxime received 501 patients (Group A), while a 4-day combination of amoxycillin-netilimicin 508 patients (Group B). RESULTS: There were found no statistically significant differences either in infection rate or the kind of infection between the two groups. Single shot cefuroxime prophylaxis was just as effective, as a 4-day combination of amoxycillin and netilmicin. Total infection rate was 5.6% (n=28) in Group A and 5.7% (n=29) in Group B. Respiratory tract infection was the most frequently registered in both groups; 2.6% in Group A and 2.9% in Group B. Sternal wound and catheter-related infection rates were 0.6% and 1% in both groups, respectively. There were no side effects due to the given antibiotics. CONCLUSIONS: A single shot of cefuroxime prophylaxis is equally effective and safe as a 4-day regimen with amoxycillin and netilmicin.
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1996
 
PMID 
A Michalopoulos, G Tzelepis, G Pavlides, J Kriaras, U Dafni, S Geroulanos (1996)  Determinants of duration of ICU stay after coronary artery bypass graft surgery.   Br J Anaesth 77: 2. 208-212 Aug  
Abstract: Prediction of duration of a patient's stay in the ICU after cardiac surgery is difficult. In 652 consecutive adult patients undergoing elective coronary artery bypass graft (CABG) surgery, we analysed prospectively preoperative and immediate postoperative variables thought to influence duration of stay in the ICU. With univariate analysis, we found that age, preoperative left ventricular ejection fraction, bypass time, aortic cross-clamp time, blood transfusions and the number of inotropic agents administered in the immediate postoperative period (for at least 6 h) were significant correlates of duration of stay in the ICU. However, logistic regression analysis showed that the number of inotropes was the most important determinant of stay in the ICU, with an overall prediction accuracy of 94.8%. The main cause of prolonged stay in the ICU (more than 2 days) was low cardiac output syndrome. We conclude that analysis of perioperative variables enhanced our ability to accurately predict duration of stay in the ICU in cardiac surgery patients. The number of inotropic agents administered during the first 6 h after operation was the most important determinant of duration of stay in the ICU.
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PMID 
G Tzelepis, V Kadas, A Michalopoulos, S Geroulanos (1996)  Comparison of gastric air tonometry with standard saline tonometry.   Intensive Care Med 22: 11. 1239-1243 Nov  
Abstract: OBJECTIVE: To compare partial pressure of carbon dioxide (PCO2) measurements obtained by sampling gastric intraluminal air with those obtained by standard saline tonometry. DESIGN: Prospective, unblinded study. SETTING: Intensive care unit in a tertiary cardiac surgical center. PATIENTS: 20 patients undergoing cardiac surgery. INTERVENTIONS: Gastric tonometric catheters were inserted, gastric fluid was aspirated, and 100 cc of air was injected into the stomach. MEASUREMENTS: After an equilibration period of 30 min, samples of gastric air and saline were anaerobically aspirated and analyzed on a standard blood gas machine. The reproducibility of PCO2 measurements in a given patient was assessed by analyzing consecutive samples of gastric air and calculating the coefficient of variation (CV). RESULTS: PCO2 values measured in samples of gastric air (PCO2 air) were highly correlated with those derived by saline tonometry (PCO2ss)(r2 = 0.95, p = 0.0001); PCO2 air was significantly greater than PCO2ss (50 +/- 17 vs 48 +/- 17 mmHg, p = 0.0001). Intramucosal pH (pHi) calculated from PCO2 air was significantly lower than that calculated from PCO2ss (7.26 +/- 0.23 vs 7.28 +/- 0.24, p = 0.0001). Analysis of intermethod differences showed significant bias for both PCO2 (2.4 +/- 7.6 mmHg, mean +/- 2SD, bias +/- precision) and pHi ( -0.023 +/- 0.074, mean +/- 2SD, bias +/- precision). The within-subject variability of replicate PCO2 measurements in gastric air was low (CV = 2.6 +/- 0.8). CONCLUSION: We conclude that intraluminal PCO2 can be accurately determined in postoperative cardiac surgery patients by instilling air into the stomach and analyzing samples of gastric air on a standard blood gas machine, In comparison with saline tonometry, air tonometry consistently yields lower pHi values.
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