Abstract: This randomized multicenter trial evaluated individualization of treatment duration with peginterferon alfa-2a 180 microg/wk plus ribavirin 1000/1200 mg/day in patients with chronic hepatitis C genotype 1/4 based on the rapidity of virologic response (VR).
Abstract: To determine European intensive care unit (ICU) nurses' knowledge of guidelines for preventing central venous catheter-related infection from the Centers for Disease Control and Prevention.
Abstract: The 2-5-year results for the treatment of deep infection of total knee arthroplasty (TKA) after two-stage reimplantation are presented. An articulating temporary antibiotic spacer prosthesis (TASP) and a standardized antibiotic regimen were used.
Abstract: Infections in orthopedics and traumatology are particularly challenging for the treating physician due to changing epidemiology and bacteriology, in particular immunosenescent patients and antimicrobial resistance. Numerous exogenous and endogenous factors contribute to the onset of bone/joint infection. Known clinical entities include osteitis/osteomyelitis, arthritis, prosthesis-associated infection and spondylitis/spondylodiscitis. Knowledge of epidemiology, bacteriology, and clinic and healing processes in infections leads to a better understanding of the various treatment strategies. Cephalosporin, fosfomycin, glycopeptide, lincosamide, oxazolidinones, ansamycins und fusidic acids represent the standard therapeutic agents in orthopedics and traumatology. Fluoroquinolones, glycylcyclines and lipopeptides are new and possibly promising alternatives. The most important indices of antibiotic agents used in everyday practice are discussed. In complicated cases, collaboration with a specialist for infectious diseases results in improved therapeutic results.
Abstract: As part of a needs analysis preceding the development of an e-learning platform on infection prevention, European intensive care unit (ICU) nurses were subjected to a knowledge test on evidence-based guidelines for preventing ventilator-associated pneumonia (VAP). A validated multiple-choice questionnaire was distributed to 22 European countries between October 2006 and March 2007. Demographics included nationality, gender, ICU experience, number of ICU beds and acquisition of a specialised degree in intensive care. We collected 3329 questionnaires (response rate 69.1%). The average score was 45.1%. Fifty-five percent of respondents knew that the oral route is recommended for intubation; 35% knew that ventilator circuits should be changed for each new patient; 38% knew that heat and moisture exchangers were the recommended humidifier type, but only 21% knew that these should be changed once weekly; closed suctioning systems were recommended by 46%, and 18% knew that these must be changed for each new patient only; 51% and 57%, respectively, recognised that subglottic drainage and kinetic beds reduce VAP incidence. Most (85%) knew that semi-recumbent positioning prevents VAP. Professional seniority and number of ICU beds were shown to be independently associated with better test scores. Further research may determine whether low scores are related to a lack of knowledge, deficiencies in training, differences in what is regarded as good practice, and/or a lack of consistent policy.
Abstract: diagnostic dilemma in toxic shock syndrome (TSS) is that the results of microbiologic investigations are often not available immediately because of the need for incubation, or no obvious entry point can be found.
Abstract: Standards for medical clearance for private or business missions abroad are--at least in the German speaking countries--not clearly defined and mostly derived from the old terminus "Tropentauglichkeit" which means fit for mission in the tropics. The authors now define a new standard, called "Entsendungstauglichkeitsuntersuchung" which means clearance of fitness for all types of missions abroad, independent of distinct climatic zones. To meet the inhomogenous requirements of different institutions and different types of missions the medical examination proposed follows a modular structure to optimize economic and medical use of resources. Moreover, as Austria, Germany and Switzerland have different legal and economic postulates, the medical examination has to be adapted to the different premises. The definition and description of this special type of "medical clearance for missions abroad" is supplemented by recommendations for definitions of clients who should undergo such an investigation and the professionals who should perform this type of investigation. Additionally, results of this type of medical clearance are defined and prophylactic aspects in terms of pre-travel advice are mentioned.
Abstract: The number of Methicillin-resistant Staphylococcus aureus (MRSA) pneumonia cases is increasing in many European countries. In this observational study in one medical and three surgical ICUs multiple interventions for the treatment and eradication of nosocomial MRSA-pneumonia were used.
Abstract: Perioperative antibiotic prophylaxis in orthopaedics is only indicated if a foreign body such as a prosthetic joint remains in the operation site. For this indication first or second generation cephalosporins should be preferred. It is essential to administer the antibiotic within 30 min before incision. In the case of an extended intervention (more than 3 h) a repeated dose should be considered. It is evidence-based that prolonged perioperative antibiotic prophylaxis (more then 24 h) is not beneficial. To avoid the emergence of resistances or hygienic insufficiencies surveillance of surgical site infections should be enforced. Optimal conditions are necessary to achieve a rate of surgical site infection in orthopaedics below 1% in patients with normal infection risk profile.
Abstract: Treatment of deep infection of total knee arthroplasty by two-stage reimplantation. Using an articulating spacer may reduce the disadvantages of a static spacer (ligament contracture, muscle atrophy, muscle contraction, arthrofibrosis, and bone loss). Restoration of pain-free loading and ability to walk.
Abstract: Dengue is the most important human viral disease transmitted by an arthropod vector. The steadily increasing numbers of tourists visiting endemic areas coupled with the present resurgence of dengue, raises the risk of exposure for large numbers of travelers and imported dengue cases are increasingly observed in non-endemic countries. We aimed to study the epidemiology, clinical manifestations and laboratory findings in imported dengue at a City of Vienna hospital. Medical records of 93 patients (age: 17-68 years, 43f, 50m) with imported dengue in Vienna between 1990 and April 2005 were analyzed retrospectively. Forty-eight (52%) were classified as confirmed and 45 (48%) as probable dengue, according to the CDC criteria. The patients acquired the infection in South East Asia (56%), the Indian subcontinent (18%), Africa (10%) and Oceania (3%). The most important symptoms were fever, headache, arthralgia and myalgia, nausea and vomiting, diarrhea, chills, extreme fatigue and dizziness. A rash was observed in 43%, and lymphadenopathy in 22%. Laboratory findings were thrombocytopenia, leukopenia and elevated hepatic enzymes. Eighteen patients showed hemorrhagic manifestations, and 7 fulfilled the criteria of dengue hemorrhagic fever; 1 of them had dengue shock syndrome. Case fatality rate was nil. Dengue has to be considered in all febrile travelers returning from endemic areas. Prompt diagnosis and symptomatic treatment is warranted and should prevent patients from unnecessary and potentially harmful diagnostic and therapeutic procedures.
Abstract: The failure rate of primary empirical anti-infective treatment of community-acquired pneumonia is reported to range between 2 and 7%. These patients are subject to a greater risk of intensive medical treatment and a higher mortality rate than patients who respond to primary treatment. We investigated 63 patients in a "real life scenario" who were admitted to the hospital after failure of primary outpatient therapy for community-acquired pneumonia. Thirty-three patients received intravenous standard therapy (betalactam 14, macrolide 3, levofloxacin 6, doxycycline 1, combinations 9 patients) while 30 patients were treated with intravenous moxifloxacin. The oral antibiotic pretreatment that failed most frequently was clarithromycin (n = 25), followed by amoxicillin/clavulanic acid (n = 16), cefixime (n = 10), cefuroxime/axetil (n = 5), doxycycline (3), cefpodoxime, and ciprofloxacin (2 each). There were no differences between the two groups in respect of age, gender, numbers of patients in nursing homes, numbers of patients with different underlying diseases (chronic bronchitis, coronary heart disease, diabetes mellitus, smoking, etc.), severity of pneumonia at the time of admission, numbers of patients requiring intensive care, and lethality. The group that underwent standard therapy experienced failure of the empirical intra-hospital antibiotic therapy more often during therapy [10 (30%) patients vs 2 (6%) in the moxifloxacin group, p = 0.009] and clinical failure of treatment on day 28 after initiation of therapy [7 (21%) patients vs 2 (6%) in the moxifloxacin group, p = 0.003]. In cases of failure of empirical preclinical antibiotic treatment for community-acquired pneumonia, subsequent intrahospital treatment with moxifloxacin is more successful than standard therapy in our study reflecting a "real life scenario".
Abstract: We analyzed retrospectively 21 immune-competent travelers with chronic traveler's diarrhea (3-6 weeks) after returning from recreational travel to the tropics with stool samples positive for microsporidia. Nine patients had been treated with albendazole and 12 patients had been treated symptomatically. Diarrhea resolved in 8 of 9 and 12 of 12 patients, respectively. In the albendazole group, Encephalitozoon intestinalis was cleared in 4 of 4 patients and Enterocytozoon bieneusi persisted in 7 of 7 patients (2 patients were lost to follow-up). In the symptomatic treated group microsporidia persisted in stool samples of all patients. We conclude that there is only a transient correlation between detection of microsporidia in stool and gastrointestinal symptoms, and suggest that microsporidia infection may cause clinical symptoms during the early stages of infection that resolve even though the microsporidia may persist.
Abstract: The clinical management of late stage Borreliosis can be difficult due to various associated symptoms and signs and cumbersome microbiological tests. We report a case of successful antibiotic treatment of Borreliosis-associated pseudolymphomatous infiltrates in bone marrow and lymph nodes, which were diagnosed by bone marrow trephine biopsy and positron emission tomography.
Abstract: Endogenous infections with multi-resistant S. epidermidis are among the leading causes of nosocomial infections. The effect of hospitalization and antimicrobial therapy on antimicrobial resistance of colonizing staphylococci was determined from swabs of the nose, hand, axilla and groin from 157 patients on one day. Hospitalization for >72 hours, compared with <72 hours, was associated with a higher percentage of isolates resistant to oxacillin (56% versus 19%), gentamicin (40% versus 15%), trimethoprim (36% versus 17%), clindamycin (56% versus 17%), and fusidic acid (20% versus 4%; p < 0.01 for all), but not to rifampicin (6% versus 1%) or fosfomycin (43% versus 34%, p > 0.05 for both). Concurrent antimicrobial therapy resulted in increased resistance to oxacillin (61% versus 28%), gentamicin (43% versus 20%), and clindamycin (60% versus 26%; p < 0.01 for all), but not to trimethoprim (39% versus 23%), fusidic acid (19% versus 9%), rifampicin (6% versus 3%), or fosfomycin (46% versus 38%, p > 0.05 for all). The increase in resistant isolates was not independent, since hospitalization and antimicrobial therapy were correlated (p < 0.001). After adjustment for potential risk factors such as diabetes mellitus, central venous catheters, and hemodialysis, the odds ratio for oxacillin resistance was 2.8-3.6. None of the risk factors showed statistically significant results, except for the presence of neoplastic disease, which had a significant interaction (P=0.035). The within-subgroup odds ratios for patients with and without neoplasm were 4.2 (95% CI, 2.3-5.7) and 2.1 (95% CI, 0.78-3.12), respectively. These results show that hospitalization for more than three days, with or without antimicrobial therapy, and the presence of neoplastic disease are associated with increased antimicrobial resistance in colonizing S. epidermidis.
Abstract: A small but significant proportion of blood cultures processed by the BACTEC 9000 series systems is signaled positive, while subsequent Gram's stain and culture on solid media yield no pathogens. In this study, 15 "false-positive" vials (7 aerobes, 8 anaerobes) from 15 patients were investigated for the presence of bacteria and fungi by eubacterial 16S rDNA and panfungal 18S rDNA amplification, respectively. All samples turned out negative by both methods. Most patients (7) had neutropenia, which does not support the theory that high leukocyte counts enhance the generation of false-positive results. In conclusion, the results of this study indicate that false-negative results generated by the BACTEC 9000 series are inherent to the automated detection and not due to the growth of fastidious organisms.
Abstract: For febrile neutropenic patients who received hematopoietic stem cell transplantation, the Gram stain-acridine orange leukocyte cytospin (AOLC) test and the differential-time-to-positivity method (DTP) were performed. As a diagnostic tool for catheter-related bloodstream infections in these patients, the Gram stain-AOLC test has a lower sensitivity than does the DTP method but acceptable positive and negative predictive values.
Abstract: Presented here are three cases of severe leptospirosis, one icteric and two pulmonary hemorrhagic, that occurred in patients in Styria, Austria. Leptospirosis presents with protean and nonspecific manifestations. Thus, as these three cases emphasize, the key to diagnosis may be maintaining a high index of suspicion for the disease in previously healthy febrile patients with septic shock, acute renal and hepatic dysfunction and respiratory failure requiring intensive care.
Abstract: Diagnosis of Mycoplasma pneumoniae infection is challenging due to the fastidious nature of the pathogen, the considerable seroprevalence, and the possibility of transient asymptomatic carriage. During recent years, various new techniques have been adapted for the diagnosis of M. pneumoniae infection, notably in the field of molecular biology. Standard polymerase chain reaction (PCR) is currently the method of choice for direct pathogen detection, but several PCR-related methods provide enhanced sensitivity or more convenient handling procedures, and have been successfully applied for research purposes. Among these techniques are real-time PCR, nested PCR, reverse transcriptase PCR (RT-PCR) and multiplex PCR. Generally, amplification-based methods have replaced hybridization assays and direct antigen detection. Serology, which is the basic strategy for mycoplasma diagnosis in routine clinical practice, has been improved by the widespread availability of sensitive assays for separate detection of different antibody classes. For the diagnosis of mycoplasma pneumonia, serology and direct pathogen detection should be combined. Extrapulmonary diseases may be diagnosed by direct pathogen detection alone, but the value of this diagnostic approach is limited by the probably immunologically mediated pathogenesis of some manifestations. This review summarizes the current state of Mycoplasma pneumoniae diagnosis, with special reference to molecular techniques. The value of different methods for routine diagnosis and research purposes is discussed.
Abstract: To assess the role of soluble fecal substances in the elevation of fecal Candida counts in patients with antibiotic-associated diarrhea (AAD), we investigated the growth of Candida albicans in vitro in serially diluted stool fluids from patients with AAD and healthy subjects. There were significantly higher Candida albicans counts in stool fluids diluted 1:10 from AAD patients than in healthy subjects and the phosphate-buffered saline growth control, which may be due to reduced soluble Candida inhibitors and increased availability of growth factors and nutrients.
Abstract: Two immunocompetent patients with cat-scratch disease due to infection with Bartonella henselae developed monoclonal and biclonal gammopathy. Neither patient had evidence of any other known cause of plasma cell dyscrasia, and antibiotic eradication of Bartonella henselae infection resulted in the prompt disappearance of the gammopathy. Hence, cat-scratch disease should be added to the list of possible underlying disorders in individuals presenting with monoclonal and biclonal gammopathy.
Abstract: In order to determine whether a blood culture positive for coagulase-negative staphylococci (CNS) represents bacteremia or contamination, a prospective study was conducted using molecular typing to analyze CNS blood culture isolates and corresponding CNS skin isolates collected after skin disinfection from 431 subjects. CNS bacteremia was not found in any of the 301 subjects not suspected of having bacteremia. In 130 patients suspected of having bacteremia, the rate of actual CNS bacteremia was 6%. The overall rate of CNS blood culture contamination was 1%. Chart analysis showed good agreement between our microbiological definitions of bacteremia and the clinical definitions previously published. Bacteremia and contamination can be differentiated using pulsed-field gel electrophoresis and molecular typing of CNS isolates obtained from cultures of blood and corresponding skin samples.
Abstract: Two-stage reimplantation remains the gold standard in the treatment of late infected total knee arthroplasties. The reported disadvantages include difficult exposure at the time of reimplantation and less functional outcome by using static spacers. Patients who receive an articulating spacer retain a functional joint before second-stage reimplantation. This may reduce the disadvantages of static spacers (ligament contracture, extensor lag, arthrofibrosis). There is no difference in the success rates of eradicating infection (range: 90-96%). In a prospective study 24 consecutive patients were treated with an articulating spacer. The articulating spacer is made by cleaning and autoclaving the removed femoral component and the tibial polyethylene insert. These are reinserted during the same operation with antibiotic-loaded cement. The average time during which the spacer was in place was 16 weeks (range: 7-28 weeks). During an average follow-up period of 14.8 months (range: 5-33 months) one patient had a secondary reinfection. Use of an articulating spacer is economical and decreases the risk of complications in reimplantation with good functional outcome.
Abstract: In the study presented here, the aim was to investigate the frequency and clinical significance of bacteremia with urogenital mycoplasmas in immunocompetent patients following gynecological surgery. Among 56 patients undergoing elective hysterectomy (mean age, 55 years; range, 32-82 years), Mycoplasma hominis and Ureaplasma urealyticum were detected in urine by PCR in 2 and 11 patients, respectively. Pre- and postoperative blood samples of the colonized patients were investigated for the colonizing species by PCR. In 4 of the 11 patients colonized by Ureaplasma urealyticum the pathogen was also detected from one of the postoperative blood samples, while no case of bacteremia with Mycoplasma hominis was detected. The postoperative course was uncomplicated in all patients.
Abstract: Infectious processes cause the majority part of all clinically relevant pleural effusions which frequently complicate the course of pneumonia. The assessment of an inflammatory effusion requires a careful history, physical examination, imaging techniques and clinical workup. The presence of polymorphonuclear leukocytes, high LDH-activity (> 200 U/L) and protein level (> 3 g/dL) in a pleural effusion indicates acute inflammation. An effusion is usually called empyema, when large numbers of neutrophils form thick, turbid exudates within preexisting body cavities. A thoracic empyema may occur as a result of primary or secondary pleural pathologies and in most cases involves infection with bacteria, frequently provided by progressing pneumonia. There are several therapeutic options for treatment of parapneumonic effusions and of thoracic empyemata, respectively. Optimal therapeutic management and antimicrobial medication to the infected pleural space depend in part on the stage of the empyema at presentation. Treatment can vary from a conservative medical approach in uncomplicated or small parapneumonic effusions to invasive surgical interventions in fibroprulent or organizational stages of empyema. Empyemata usually progress from a parapneumonic exudative stage (stage I), when the fluid is still sterile, with low leukocyte counts, low LDH, physiological pH, and normal glucose, to the fibropurulent [figures: see text] stage (stage II) with high leukocyte counts, high LDH activity, low pH, and low glucose, and finally to the organizational stage (stage III), in which fibroblasts convert fibrin strands into inelastic membranes. Pleural peels and pockets may compartmentalize the viscous empyematous fluid and can cause serious restrictive ventilatory impairment. Each patient must be individually evaluated to determine the nature of the exudate and the stage of the pleural space infection. Due to its high mortality rate (5%) a thoracic empyema requires prompt treatment. Diagnostic thoracentesis and withdrawal of liquid for the microbiological, cytological and biochemical analysis is urgently recommended in all cases to assess severity of the disease and the likelihood of a complicated or uncomplicated course, and to select the most appropriate treatment option.
Abstract: Increasing worldwide antibacterial resistance among respiratory pathogens, especially S. pneumoniae, are an emerging problem in the treatment of respiratory tract infections. In some areas penicillin-resistant S. pneumoniae increased to 80% and macrolide-resistance and MLSb-resistance are an evolving problem. In addition, increasing resistance to quinolones has been documented in Hong Kong and in Spain. One way to combat increasing resistance is the development of new antimicrobial drugs. However, the practice of just changing one drug for another without also altering poor prescribing habits merely results in different resistance issues. In the long-term, to prevent increasing resistance, clinicians must be aware of restrictive antibiotic prescription and adequate dosages.
Abstract: We describe a severe and recurrent septicemia due to Campylobacter in a 75-year-old immunocompetent patient. Two Campylobacter strains were detected in several blood cultures. Campylobacter fetus and Campylobacter lari were identified with PCR tests based on species-specific nucleotide sequences for the 16S rRNA gene.
Abstract: Neutrophils play a crucial role in host defense against infectious disease. The objective was to analyze the effect of omeprazole treatment on indexes of neutrophil function in healthy subjects.
Abstract: Reported here is a case of severe necrotizing pneumonia following Mycoplasma pneumoniae infection that occurred in a 55-year-old man. The histological changes of lung parenchyma included granulomas and bronchiolitis obliterans. Mycoplasma infection was diagnosed by repeated antibody determination (complement fixation test) and confirmed using the polymerase chain reaction to detect the pathogen from a tracheal aspirate. Prior to this episode of pneumonia, the patient had been healthy, except for Reiter's disease that had been diagnosed 18 years previously. In addition to severe pulmonary involvement, the patient developed rhabdomyolysis with subsequent acute renal failure, Stevens-Johnson syndrome, biochemical pancreatitis, severe anemia, and an effusion of the right knee. Contrary to the symptoms of pulmonary disease, all of the extrapulmonary manifestations except anemia were transient. Due to persistent respiratory insufficiency and long-term failure to wean the patient from a respirator, a lung transplantation was performed. Five weeks after transplantation the patient died as a result of intrapulmonary hemorrhage. To the best of our knowledge, this is the first report of pneumonia due to Mycoplasma pneumoniae leading to lung transplantation. Furthermore, the multiple extrapulmonary manifestations in this case make it exceptional.
Abstract: Between January 1996 and September 1999, 13,650 serum samples from 12,337 patients were examined for antibodies to Mycoplasma pneumoniae at the Institute of Hygiene, University Hospital Vienna in the course of routine diagnosis. Antibody determination was performed by means of the microparticle agglutination assay Serodia Myco II. Overall, positive results (antibody titer > or = 1:40) were obtained in 2028 patients (16.4%). Age details were available for analysis in 2016 positive patients. Young children (< or = 9 y) who tested positive showed a geometric mean titer of 1:137.9 (95% confidence interval: 117.7-161.4). The geometric mean titers of positive patients decreased significantly with age (Spearman's correlation coefficient -0.20; p < 0.0001). Only 1/87 patients with serological evidence of M. pneumoniae infection aged > or = 70 y showed a titer of > or = 1:320. These data highlight the fact that, in the elderly, acute M. pneumoniae infection has to be considered in cases with slightly elevated antibody titers, which are usually referred to as borderline in children and young adults.
Abstract: In order to assess the role of Candida-secreted phospholipase in antibiotic-associated diarrhea (AAD), 43 fecal Candida isolates from patients with AAD and from controls were tested on egg yolk agar for production of phospholipase. Phospholipase zones did not differ between the isolates from patients with AAD and from controls. The data indicate that the fungal virulence factor phospholipase may not be responsible for AAD in adults.
Abstract: We report two cases of bacteremia with Ochrobactrum anthropi in patients on hemodialysis. Bacteremia became clinically manifest by recurrent febrile episodes during and after dialysis. In one patient, bacteremia persisted after ciprofloxacin therapy and was cleared only by removal of the dialysis catheter and a 3-week course of gentamicin. The second patient remained intermittently bacteremic for more than 3 months, although the dialysis catheter had been replaced. A MEDLINE search revealed only one previous report of O anthropi bloodstream infection in a patient on hemodialysis, but the pathogen is recognized increasingly as a causative agent of human disease, most importantly in debilitated patients. In contrast to most previously described cases, the two patients reported here had no malignancies and were not on immunosuppressive therapy. Treatment of O anthropi infection is challenging because of widespread and unpredictable resistance to antimicrobial agents and discrepancies between in vitro susceptibility and in vivo efficacy.
Abstract: Fosfomycin (cis-1,2-epoxypropyl phosphonic acid) is a cell wall synthesis-inhibiting antibiotic. We investigated the effect of fosfomycin on several indices of neutrophil function. Neutrophil phagocytosis was analysed by flow cytometry. Cytosolic calcium kinetics were assessed fluorometrically and neutrophil bactericidal ability was assessed by fluorescence microscopy. Intracellular reactive oxygen intermediate (ROI) production was analysed by flow cytometry and extracellular ROI by cytochrome c reductase assay. After fosfomycin incubation, phagocytosis was unaffected as assessed by the FACS assay. Fosfomycin incubation resulted in enhanced bactericidal ability, in increased intracellular calcium concentrations, elevated extracellular ROI production and decreased chemotaxis but it did not affect intracellular ROI production and chemokinesis.
Abstract: Patients with septic shock are shown to have decreased neutrophil phagocytic function by multiple assays, and their assessment by whole-blood assays (fluorescence-activated cell sorter analysis) correlates with assays requiring isolated neutrophils (microscopic and spectrophotometric assays). For patients with similar underlying conditions but without septic shock, this correlation does not occur.
Abstract: High-intensity exercise leads to an increased risk of upper respiratory tract infections in athletes, which had been related to an exercise-induced impairment of neutrophil function. In this study, several indices of neutrophil function were analysed before and after a biathlon and the effect of oral vitamin C on neutrophil function was determined. Six athletes took 2 g vitamin C daily for 1 week prior to a biathlon and four athletes did not take any supplementation. Neutrophil phagocytosis was analysed by fluorescence microscopy and flow cytometry. Cytosolic calcium kinetics were assessed fluorometrically and neutrophil bactericidal ability was assessed by fluorescence microscopy. Reactive oxygen production was analysed by flow cytometry. Catecholamines were analysed by high-performance liquid chromatography. After high-intensity exercise there were significant reductions in the number of phagocytosed Escherichia coli per neutrophil and in neutrophil bactericidal ability. There was a significant exercise-dependent increase of catecholamines. There was no difference between the two groups of athletes. These results do not support the concept that vitamin C supplementation corrects neutrophil dysfunction after strenuous exercise.
Abstract: Susceptibility testing of fungi by flow cytometry (also called fluorescence-activated cell sorting [FACS]) using vital staining with FUN-1 showed a good correlation with the standard M27-A procedure for assessing MICs. In this study we determined MICs for blood culture isolates from patients with candidemia by NCCLS M27-A and FACS methods and correlated the clinical outcome of these patients with in vitro antifungal resistance test results. A total of 24 patients with candidemia for whom one or more blood cultures were positive for a Candida sp. were included. Susceptibility testing was performed by NCCLS M27-A and FACS methods. The correlation of MICs (NCCLS M27-A and FACS) and clinical outcome was calculated. In 83% of the cases, the MICs of fluconazole determined by FACS were within 1 dilution of the MICs determined by the NCCLS M27-A method. For proposed susceptibility breakpoints, there was 100% agreement between the M27-A and FACS methods. In the FACS assay, a fluconazole MIC of <1 microg/ml was associated with cure (P < 0.001) whereas an MIC of > or =1 microg/ml was associated with death (P < 0.001). The M27-A-derived fluconazole MICs did not correlate with outcome (P = 1 and P = 0.133).
Abstract: To quantitatively assess the role of Candida species in antibiotic-associated diarrhea (AAD), stool samples from a total of 395 patients and control subjects were cultured in differential isolation medium: 98 patients had AAD, 93 patients were taking antibiotics but did not have diarrhea (A(+)D(-)), 97 patients were not taking antibiotics but had diarrhea (A(-)D(+)), and 107 patients were control subjects (A(-)D(-)). In addition, secreted aspartyl proteinase (Sap) production was tested. In AAD patients, Candida positivity (77/98) and Candida overgrowth (62/98) were not different from that among A(+)D(-) patients (75/93 [P= .860] and 52/93 [P= .375], respectively). Candida overgrowth among A(-)D(+) patients (40/97, P= .003) was less frequent than among AAD patients, but Candida positivity was not different (80/97, P= .612). In control subjects, Candida positivity and overgrowth were less common than in all other groups. Production of Sap did not differ between patients with AAD and control subjects (P= .568 and P= .590, respectively). Data indicate that elevated Candida counts are a result of antibiotic treatment or diarrhea rather than a cause of AAD.
Abstract: Neutrophil granulocytes have been described as agents of defence and destruction. The effect of two flavonoid compounds (trihydroxyethylrutin and disodium flavodate) on the phagocytic ability and generation of reactive oxygen radicals of neutrophils was studied at concentrations of 5 mg/l, 50 mg/l and 100 mg/l. Flow cytometry was used to study phagocytic ability by measuring uptake of fluorescein-labelled bacteria. The generation of reactive oxygen intermediates was estimated by means of a CD16 phycoerythrin-conjugated mouse anti-human monoclonal antibody. In vitro trihydroxyethylrutin (THET) and disodium flavodate (DF) treatment reduced reactive oxygen production (DF at 5 mg/l--40%, at 50 mg/l--71% and at 100 mg/l--82%; THET at 5 mg/l--53%, at 50 mg/l--88%, at 100 mg/l--93%; all p < 0.001). This was rapidly reversible after plasma exchange. Both flavonolds did not affect neutrophil phagocytic ability. We conclude that THET and DF could decrease oxidative tissue damage by neutrophils. A beneficial effect in peripheral vein disease could be anticipated from these results.
Abstract: Cancer surgery is known to lead to a deterioration in host defence mechanisms and an increase in susceptibility to infection after operation. Filgrastim enhances important antimicrobial functions of neutrophils including chemotaxis, phagocytosis and oxidative killing mechanisms.
Abstract: Antibiotics reduce the mortality from infectious diseases but not the prevalence of these diseases. Use, and often abuse, of antimicrobial agents encourages the evolution of bacteria toward resistance, often resulting in therapeutic failure. There are two factors which influence potential utility of a drug in a specific clinical situation. The first is the measure of potency of the antibiotic for the pathogen in question (minimal inhibitory concentration [MIC], minimal bactericidal concentration [MBC]). The second is whichever relationship between the concentration-time profile and potency of the antibiotic linked most robustly to clinical outcome (time above MIC or MBC [T > MIC or T > MBC]; Peak/MIC or MBC; area under the curve [AUC]/MIC or AUC/MBC). Herein the effects of pharmacokinetics of antimicrobials on the evolution of antimicrobial resistance with particular reference to azithromycin are considered.
Abstract: Neutrophil phagocytosis, reactive oxygen intermediate production (intra- and extracellular), neutrophil bactericidal activity, and chemotaxis/chemokinesis were assessed in three age groups: 21-36, 38-56, and 62-83 years. A significant age-dependent reduction in the number of phagocytized Escherichia coli per neutrophil (measured by acridine orange staining) and Staphylococcus aureus phagocytosis (measured by flow cytometry) was seen (r = 0.669 and r = 0.684, P<0.001 for both). These findings correlated with an age-dependent increase in intracellular calcium concentrations in resting neutrophils (r = 0.698, P<0.001) and a reduced hexose uptake (r = 0.591, P<0.01). In addition, a significant reduction in the intracellular reactive oxygen production was seen after stimulation with S. aureus (P<0.001) with increasing age. In contrast, no differences between the groups in reactive oxygen production was seen after stimulation with E. coli. The neutrophil bactericidal activity was impaired with increasing age (64+/-4% of the phagocytized bacteria were killed in group 1; 66+/-2 in group 2, and 59+/-6 in group 3; P<0.01). In addition, a trend toward a reduced neutrophil chemotaxis was seen with increasing age (P = 0.022). The findings suggest that increased intracellular calcium concentrations in resting neutrophils and/or a reduced hexose uptake result in reduced phagocytic ability and decreased bactericidal activity of neutrophils in the elderly.
Abstract: Thrombopoietin (TPO) is the key growth factor for platelet production and is elevated in states of platelet depletion. As thrombocytopenia is a common finding in malaria, we analysed TPO regulation before, during and after antimalarial treatment. Before treatment, TPO serum levels were significantly higher in patients with severe malaria (n = 35) than in patients with uncomplicated malaria (n = 44; P = 0.024), normalizing within 14-21 d of therapy. The rapid normalization of TPO levels and increase in low peripheral platelet counts after treatment indicate that the biosynthesis of TPO and its regulation in malaria patients are normal.
Abstract: Neuraminidase promotes influenza virus release from infected cells and facilitates virus spread within the respiratory tract. Several specific inhibitors of these enzyme have been developed. Zanamivir and oseltamivir are the nowadays available neuraminidase inhibitors. In contrast to amantadine and rimantadine, which target the M2 protein of influenza A, they inhibit the replication of both influenza A and B. Zanamivir is delivered by inhalation because of its low oral bioavailability. Oseltamivir can be administered orally. Early treatment reduces the severity and duration of illness and associated complications. These drugs are not effective at afebrile, mild courses, or if the influenza symptoms have existed already for more than 2 days. They are not effective against other respiratory viruses. For an optimal usage of the neuraminidase inhibitors a rapid and reliable diagnosis is necessary. The clinical diagnosis is sufficient only in proven epidemics. An increased availability of sensitive and specifically diagnostical tests is necessary for individual therapy decisions. The influenza vaccination is the most effective measure against influenza.
Abstract: Reported here is the case of a 29-year-old male with cervical lymphadenopathy, fever and weight loss, followed by acute painful osteomyelitis of the left hip joint due to cat-scratch disease. The diagnosis was established by detection of IgG antibodies to Bartonella henselae in serum and histologic examination of a lymph node including a positive polymerase chain reaction test. Treatment consisted of clarithromycin and cefotiam for 2 weeks. Four weeks after discharge, all of the patient's symptoms had completely resolved. Magnetic resonance imaging of the left hip joint showed marked regression of bone inflammation 4 months later and normalization after 8 months. Cat-scratch disease should be considered in the differential diagnosis of osteomyelitis in an adult, especially when lymphadenitis is present.
Abstract: The effect of immunoglobulin (Ig) preparations on neutrophil phagocytic ability and oxidative burst in response to Escherichia coli stimulation was analyzed in 14 patients with gram-negative septicemia by an ex vivo whole blood assay using flow cytometry. In patients, neutrophils exhibited a decreased capacity to phagocytize E. coli and generate reactive oxygen products compared to healthy controls (median -68%, P < 0.01). The addition of both 7S-Ig and 19S-Ig enriched preparations in vitro resulted in a dose-dependent increase in neutrophil reactive oxygen production at concentrations of 10 g/l (median +153% and +211%, P < 0.01, respectively) and 20 g/l (median +205% and +282%, P < 0.01, respectively). A decreased neutrophil phagocytic ability was seen in patients with septicemia (median -58%) compared to healthy controls (P < 0.01). Again, the addition of 7S and 19S-Igs enhanced the phagocytic ability in a dose-dependent manner (10 g/l: median +56 and +126%; 20 g/l: median +126% and +165%, P < 0.01 for all). It can be concluded that both polyclonal Igs can increase depressed neutrophil reactive oxygen production and neutrophil phagocytosis in patients with gram-negative septicemia.
Abstract: Plasma levels of interleukin (IL)-6, soluble IL-6 receptor, soluble gp130, leukemia inhibitory factor (LIF), and ciliary neutrophic factor (CNTF) were analyzed in 32 patients with severe malaria. Ten had renal failure, 8 had cerebral malaria, and 14 had other causes of severity. Before treatment, the IL-6 and soluble IL-6 receptor plasma levels were significantly higher in persons with cerebral malaria or renal failure than in other groups (P<.01 for both). After initiation of therapy, IL-6 levels dropped within 24 h, but soluble IL-6 receptor levels increased. CNTF levels were significantly reduced in persons with cerebral malaria or renal failure but normalized within 24 h. Plasma concentrations of gp130 and LIF did not differ between the malaria groups or normal controls. Excessive levels of IL-6 could be controlled by a subsequent shedding of the soluble IL-6 receptor, and low-level CNTF expression could contribute to or even result from cerebral malaria or renal failure.
Abstract: Laminin, a major component of the basement membrane, plays a critical role in normal cell adhesion and also during tissue invasion of pathogenic microorganisms.
Abstract: Pentoxifylline, an inhibitor of tumor necrosis factor, has been evaluated as an antimalarial agent in combination with artesunate in 45 patients with severe falciparum malaria. Patients were admitted to the intensive care unit at the Hospital for Tropical Diseases in Bangkok, Thailand, and randomly assigned to treatment for 72 hr with a combination of intravenously administered artesunate and 1) placebo, 2) low-dose pentoxifylline (0.83 mg/kg/hr), or 3) high-dose pentoxifylline (1.67 mg/kg/hr). All 45 patients had one or more manifestations of severe malaria such as cerebral malaria (n = 18), renal failure requiring hemodialysis (n = 9), azotemia (n = 8), jaundice (n = 25), or hyperparasitemia (n = 30). The overall severity was comparable in the three groups. Clinical outcome was assessed with respect to the parasite clearance time and the fever clearance time in all patients. In addition, a number of subsidiary outcome variables were examined in specific subgroups, including the recovery time from coma for patients with cerebral malaria, the duration of intubation in patients with respiratory distress, the number of hemodialysis treatments needed for patients with acute renal failure, and the number of units of blood administered to patients requiring transfusion. Concentrations of tumor necrosis factor were reduced in all three groups at 48 hr after treatment. No significant differences among the three treatment groups were found for any of the outcome variables examined. We conclude that the addition of pentoxifylline to artesunate therapy for severe malaria produced no evident clinical benefit.
Abstract: The effect of pentoxifylline (PTX) was tested for its capacity to modulate cytokine responses during therapy of severe Plasmodium falciparum malaria in a placebo-controlled, randomized study in 45 adult patients in Bangkok, Thailand. The patients received standard antimalarial treatment with artesunate (120 mg intravenously given immediately, then 60 mg every 12 hr for a total dose of 600 mg). The patients received either low-dose PTX (20 mg/kg/day, n = 15), high-dose PTX (40 mg/kg/day, n = 15), or placebo (n = 15) as continuous infusion for the first three days of antimalarial treatment. Tumor necrosis factor (TNF) and interleukin-6 (IL-6) plasma levels were markedly elevated in all patients prior to treatment. After 6 hr of high-dose PTX treatment, TNF and IL-6 levels significantly decreased while an increase in TNF and IL-6 levels was seen after 6 hr of low-dose PTX or placebo treatment (P < 0.01). After 12 and 24 hr of high-dose PTX infusion, TNF-receptor plasma concentrations were lower than in low-dose PTX- or placebo-treated patients (P < 0.01), whereas no differences between the groups with regard to IL-6 receptor levels were observed. We conclude that 40 mg/kg/day of PTX reduces plasma levels of TNF, IL-6, and TNF-receptor in patients with severe malaria. Whether this reduction improves clinical outcome remains to be determined.
Abstract: The effect of dihydroartemisinin, artemisinin and artesunate (0.1, 0.5, 5 and 50 mg/L) on phagocytic function and release of reactive oxygen products by neutrophils was studied by flow cytometry. Incubation with dihydroartemisinin, artemisinin and artemether resulted in a decreased capacity to phagocytose Escherichia coli (0.1-50 mg/L: 62-40%, 66-32% and 59-47% of the control values, respectively; P < 0.001 for all). Conversely, the derivatives enhanced the intracellular generation of reactive oxygen intermediates (0.1-50 mg/L: 146-140%, 174-197% and 188-136% of the control values, respectively; P < 0.001 for all). Artemisia derivatives enhance the reactive oxygen response of neutrophils but depress their phagocytic ability at therapeutic blood levels.
Abstract: A 1-h assay for antifungal susceptibility testing measuring the impairment of fungal metabolic activity was developed. Yeast viability was analyzed by flow cytometry with a novel fluorescent probe, FUN-1, which emits a red fluorescence when the yeast is metabolically active. For nine Candida albicans strains tested, this method yielded results comparable to those obtained by the standard M27 procedure for amphotericin B, flucytosine, fluconazole, and ketoconazole. Whether the flow cytometry antifungal susceptibility test results correlate with the in vivo activities of the drugs remains to determined.
Abstract: Patients with serious staphylococcal infections, e.g. endocarditis and osteomyelitis, need prompt and prolonged parenteral antibiotic treatment to ensure eradication of the causative pathogen. The major cost in the treatment of these infections is the long period of hospitalisation required for the administration of intravenous antibiotics. To shorten the hospitalisation period, outpatient treatment can be given to some patients. In this study, patients with acute exacerbations of chronic osteomyelitis (n = 44) or endocarditis (n = 10) were treated with intravenous teicoplanin. The pathogens were Staphylococcus aureus (n = 41, 13 of which were methicillin resistant) and coagulase-negative staphylococci (n = 13, one of which was methicillin resistant). After a mean loading dose of 15 mg/kg for 3 to 10 days, patients received teicoplanin 3 times a week at a dose (mean 15 mg/kg) individualised to achieve serum trough concentrations of approximately 10 mg/L for osteomyelitis and 20 mg/L for endocarditis. Treatment duration ranged from 28 to 150 (mean 62) days for patients with osteomyelitis and from 28 to 88 (mean 49) days for patients with endocarditis. 37 (84%) patients with osteomyelitis and 8 (80%) patients with endocarditis were treated successfully. Adverse events were observed in 9 patients and included rash (n = 3), thrombocytopenia (n = 3), and drug fever, pseudomembranous colitis, nausea, leucopenia and transient hearing impairment (one patient each). In conclusion, this study demonstrates that teicoplanin can be administered successfully in an outpatient setting according to a 3-times weekly schedule for the treatment of patients with staphylococcal osteomyelitis and endocarditis.
Abstract: One day after drinking what she thought to be a tea made from borage leaves a 72-year-old woman developed nausea, vomiting and diarrhoea, later also flickering in her eyes and palpitations. She was in a good general state with a blood pressure of 120/75 mm Hg and an irregular heart rate of 52/min. Physical examination was otherwise unremarkable. She had not been on any medication.
Abstract: We determined indices of plasma complement activation (C3, C4, Bb, C4d, iC3b, and SC5b-9), levels of tumor necrosis factor (TNF) and interleukin-6, and the APACHE II score in 23 patients with complicated Plasmodium falciparum malaria. On admission, plasma concentrations of Bb, SC5b-9, and C4d were markedly increased compared to healthy control subjects (n = 24) (4.5 +/- 1.9 vs 1.5 +/- 0.6 mg/L; 1125.7 +/- 496.9 vs 183.2 +/- 76.5 microg/L; and 15.7 +/- 5.7 vs 7.2 +/- 1.4 mg/L, P < 0.01 for all). In contrast C3 and iC3b concentrations were decreased (631.4 +/- 247 vs 947.3 +/- 243.2 and 105 +/- 17.9 vs 151.3 +/- 14.5 mg/L; P < 0.01 for both). Plasma C4 concentrations in malaria were not different from normal controls. Plasma Bb, C3, and iC3b levels normalized on day 7 of treatment, whereas SC5b-9 and C4d levels remained elevated. A significant correlation between elevated TNF levels and Bb (r = 0.507) and SC5b-9 (r = 0.448, P < 0.01 for both) and a negative correlation between iC3b and SC5b-9 and TNF levels existed (r = -0.537 and r = -0.466, P < 0.01 for both). In addition, a significant correlation between C3 and iC3b (r = 0.689) and C4 and C4d (r = 0.737) existed. However, no relation between clinical disease severity and complement fragments existed. The results demonstrate that both the classical and the alternative pathways of the complement system are profoundly activated in complicated malaria.
Abstract: The effects of cefodizime and cefuroxime on neutrophil phagocytosis and reactive oxygen production in 54 patients undergoing elective coronary artery bypass grafting were studied. Both drugs were administered twice at a dosage of 40 mg/kg of body weight (pre- and intraoperative). Phagocytic capacity was assessed by measuring the uptake of fluorescein isothiocyanate-labeled Escherichia coli and Staphylococcus aureus by flow cytometry. Reactive oxygen generation after phagocytosis was estimated by determining the amount of dihydrorhodamine 123 converted to rhodamine 123 intracellularly. In both groups the mean phagocytic ability for E. coli and S. aureus decreased during surgery (-21 and -8%, respectively, for the cefodizime group and -39 and -38%, respectively, for the cefuroxime group; P < 0.05 for all). In the cefodizime group a normalization of mean E. coli and S. aureus neutrophil phagocytosis was seen on day 5 (+9 and -4% compared to preoperative values; P > 0.35 for both), whereas in cefuroxime-treated patients phagocytic ability remained depressed (-37 and -31%; P < 0.04 for both). In both groups mean neutrophil reactive oxygen intermediate (ROI) production after E. coli and S. aureus phagocytosis increased during cardiopulmonary bypass (+44 and +83%, respectively, in the cefodizime group and +58 and +73%, respectively, in the cefuroxime group; P < 0.05 for all). One day after surgery E. coli- and S. aureus-driven neutrophil ROI production was not different from the preoperative values (-2 and +12%, respectively, for the cefodizime group and +7 and +15%, respectively, for the cefuroxime group; P > 0.15 for all). Postoperative serum levels of the C-reactive protein on days 2 and 7 were lower in cefodizime-treated patients (19 +/- 6 and 4 +/- 2 mg/liter versus 23 +/- 6 and 11 +/- 5 mg/liter; P < 0.05 for both). In addition to cefodizime's antimicrobial activity during perioperative prophylaxis, its use in coronary artery bypass grafting can prevent procedure-related prolonged postoperative neutrophil phagocytosis impairment.
Abstract: Neutrophil granulocytes have been described as agents of defence and destruction. The effect of pentoxifylline on the phagocytic ability and generation of reactive oxygen radicals of neutrophils was studied at concentrations of 1, 10 and 100 mg/L. Flow cytometry was used to study phagocytic ability by measuring uptake of fluorescein-labelled bacteria. The generation of reactive oxygen intermediates was estimated by the quantification of the intracellular conversion of dihydrorhodamine 123 to rhodamine 123. In vitro pentoxifylline treatment diminished neutrophil reactive oxygen production (at 10 mg/L -45% and at 100 mg/L -63%; p < 0.001 for both) and reduced neutrophil phagocytic ability (at 100 mg/L -23%; p < 0.05). Both effects were rapidly reversible after plasma exchange. We conclude that pentoxifylline could decrease oxidative tissue damage by neutrophils in septicaemia or after IV granulocyte transfusion.
Abstract: Plasma concentrations of big endothelin-1 were determined by ELISA in 18 patients with complicated Plasmodium falciparum malaria in Bangkok. Before therapy, elevated levels were recorded (21 +/- 12 vs. 2.9 +/- 1.1 pmol/L in age- and sex-matched healthy subjects; P < .001). Even 7 days after therapy, elevated concentrations were seen (25 +/- 14 pmol/L). Plasma endothelin levels were correlated with levels of tumor necrosis factor-alpha (r = .632, P < .01), and a negative correlation with platelet counts was seen (r = .783, P < .005). No relation between plasma endothelin concentrations and parasitemia, fever, or other indices of severe infection (hypotension, renal, hepatic or pulmonary impairment, cerebral malaria) existed. During and after complicated malaria, increased levels of plasma endothelin could contribute to malarial pathology or reflect endothelial damage or both.
Abstract: Mild hypothermia directly impairs numerous immune functions in vitro. However, the in vivo effects of mild hypothermia on neutrophil phagocytosis and oxidative killing remain unknown. We tested the hypothesis that mild intraoperative hypothermia decreases neutrophil phagocytic capacity and generation of reactive oxygen intermediates (a measure of oxidative killing). Additionally, we evaluated the effects of in vitro temperature manipulations on each function. Thermal management was randomly assigned in 10 surgical patients, causing intraoperative core temperatures to range from 33 to 37 degrees C. Production of reactive oxygen intermediates and neutrophil phagocytosis were evaluated using flow cytometry at ambient temperature. Phagocytic capacity was assessed by uptake of fluorescein isothiocyanate-labeled Escherichia coli. Reactive oxygen production was estimated by the intracellular conversion of dihydrorhodamine 123 to rhodamine 123. Blood samples were obtained preoperatively, 1 h after surgery started, and 2 h postoperatively. Blood was also obtained from 10 matched control subjects and tested at 32, 37, and 40 degrees C. Neutrophil oxidative and phagocytic capacities were significantly reduced intraoperatively, compared with preoperative and postoperative values. Intraoperative production of reactive oxygen species was linearly related to core temperature. In contrast, there was no correlation between core temperature and phagocytic activity. In vitro production of reactive oxygen intermediates increased sixfold from 32 to 40 degrees C. In vitro phagocytic capacity increased fourfold in this temperature range. Production of oxidative intermediates was most closely related to intraoperative core temperature, decreasing nearly fourfold over a 4 degree C range. This in vitro temperature dependence was matched in vitro. Impaired neutrophil oxidative killing may contribute to the observed hypothermia-induced reduction in resistance to infection.
Abstract: Four of 30 patients with Plasmodium falciparum infection in Bangkok, Thailand, were positive for anti-neutrophil cytoplasmic antibodies by indirect immunofluorescence 1 month after antimalarial therapy. No myeloperoxidase, proteinase 3, lactoferrin, or elastase reactivity was found. Since no evidence of vasculitis was seen in these patients, anti-neutrophil cytoplasmic antibody production in malaria-infected susceptible patients probably represents a secondary response, indicating neutrophil activation.
Abstract: We conducted a prospective, randomized study to compare the efficacy of oral fusidic acid, oral metronidazole, oral vancomycin, and oral teicoplanin for the treatment of Clostridium difficile-associated diarrhea. Treatment resulted in clinical cure for 94% of the patients who were treated with vancomycin, 96% of those treated with teicoplanin, 93% of those treated with fusidic acid, and 94% of those treated with metronidazole. Clinical symptoms recurred in 16% of patients treated with vancomycin, 7% of those treated with teicoplanin, 28% of those treated with fusidic acid, and 16% of those treated with metronidazole. There was asymptomatic carriage of C. difficile toxin in 13% of patients treated with vancomycin, 4% of those treated with teicoplanin, 24% of those treated with fusidic acid, and 16% of those treated with metronidazole. No adverse effects related to therapy with vancomycin or teicoplanin were observed. Considering the costs of treatment, our findings suggest that metronidazole is the drug of choice for C. difficile-associated diarrhea and that glycopeptides should be reserved for patients who cannot tolerate metronidazole or who do not respond to treatment with this drug.
Abstract: We determined serum levels of the carboxy-terminal-cross-linked telopeptide and carboxy-terminal propeptide of type I collagen (ICTP and PICP) in 24 patients with acute complicated Plasmodium falciparum malaria prior to and 7, 14, 21, and 28 days after therapy by radioimmunoassay in Bangkok, Thailand. Elevated levels of ICTP were observed in patients (mean +/- SD concentration 16.7 +/- 5.8 ng/ml), compared with normal controls (3.1 +/- 1.3 ng/ml), during the acute phase of the disease. In contrast, serum concentrations PICP were not different between patients and controls (168 +/- 63 and 144 +/- 57 ng/ml, respectively). After therapy serum ICTP concentrations decreased but remained elevated even 28 days after the malaria attack (10.3 +/- 2.9 ng/ml). These findings suggest an increased production or release of ICTP in P. falciparum malaria, which could implicate an alteration of extracellular matrix during P. falciparum malaria.
Abstract: The authors determined serum levels of the carboxy-terminal cross-linked telopeptide and the carboxy-terminal propeptide of type I collagen (ICTP and PICP) in 18 patients with Gramnegative septicaemia before (day 0) and 28 days after therapy and in 18 age- and sex-matched controls by radioimmunoassay. Elevated levels of ICTP were observed in septicaemic patients [median (range): 15 (7-49) mu g L-1 before therapy and 14 (6-45) mu g L-1 28 days after therapy vs. 2 center dot 1 (1 center dot 4-4 center dot 3) mu g L-1 in normal subjects; P < 0 center dot 01 for both], whereas PICP levels were not different between patients and controls [median (range): 119 (52-275) mu g L-1 (day 0) and 133 (79-288) mu g L-1 (day 28) vs. 91 (54-213) mu g L-1 in normal subjects, P > 0 center dot 05 for all]. The findings suggest an increased production or release of ICTP in Gram-negative septicaemia, presumably owing to an alteration of extracellular matrix during septicaemia-related vascular inflammation.
Abstract: Azithromycin was given as a single oral dose (20 mg/kg of body weight) to 12 volunteers in a crossover study with roxithromycin (8 to 12 mg/kg) and clarithromycin (8 to 12 mg/kg). Flow cytometry was used to study the phagocytic functions and the release of reactive oxygen products following phagocytosis by neutrophil granulocytes prior to administration of the three drugs, 16 h after azithromycin administration, and 3 h after clarithromycin and roxithromycin administration. Phagocytic capacity was assessed by measuring the uptake of fluorescein isothiocyanate-labeled bacteria. Reactive oxygen generation after phagocytosis of unlabeled bacteria was estimated by the amount of dihydrorhodamine 123 converted to rhodamine 123 intracellularly. Azithromycin resulted in decreased capacities of the cells to phagocytize Escherichia coli (median [range], 62% [27 to 91%] of the control values; P < 0.01) and generate reactive oxygen products (75% [34 to 26%] of the control values; P < 0.01). Clarithromycin resulted in reduced phagocytosis (82% [75 to 98%] of control values; P < 0.01) but did not alter reactive oxygen production (84% [63 to 113%] of the control values; P > 0.05). Roxithromycin treatment did not affect granulocyte phagocytosis (92% [62 to 118%] of the control values; P > 0.05) or reactive oxygen production (94% [66 to 128%] of the control value; P > 0.05). No relation between intra- and/or extracellular concentrations of azithromycin and/or roxithromycin and the polymorphonuclear phagocyte function and/or reactive oxygen production existed (P > 0.05 for all comparisons). These results demonstrate that the accumulation of macrolides in neutrophils can suppress the response of phagocytic cells to bacterial pathogens after a therapeutic dose.
Abstract: Candida sepsis during pregnancy is a rare but life-threatening complication of infection with Candida albicans. In contrast to the situation with other antimicrobial agents, there exists only limited experience with systemic antifungal therapy during pregnancy. A recent report focuses on amphotericin B treatment in systemic fungal infection during pregnancy. The present report discusses a pregnant patient with Candida albicans sepsis and endophthalmitis as well as candida infection of the oral and genital mucous membranes, after hyperalimentation and broad spectrum antibiotic therapy via a central venous catheter. The patient was treated with 10 mg/kg fluconazole from week 16 of gestation for a total duration of 50 days. Adverse effects did not occur and the rest of the pregnancy proceeded favourably for both the mother and the baby.
Abstract: In HIV-infected patients there is an increased frequency of fungal infections. Dysregulation of the response of phagocytic cells to fungal pathogens may be involved.
Abstract: Increased serum sCD14 concentrations are associated with poor outcome in Gram-negative sepsis and trauma patients. In the present study serum sCD14 concentrations were measured in patients with Gram-positive sepsis and compared with Gram-negative septic and nonseptic intensive care unit patients. Furthermore, serum sCD14 concentration was correlated with patient's outcome. Serum samples of 28 Gram-positive (8 nonsurvivors/20 survivors) and 10 Gram-negative bacteriemic patients (3 nonsurvivors/7 survivors) were obtained at the day they met the sepsis criteria defined by Bone et al. (Day 0) and at Days 4 and 7 and compared with 10 nonseptic ICU patients and 10 healthy volunteers. Serum concentrations of sCD14 were measured by ELISA. Significantly higher sCD14 serum concentrations were found on Days 4 and 7 in Gram-positive nonsurvivors than in Gram-positive survivors (Day 4: 5.85 +/- 0.48 vs 4.07 +/- 0.43 microgram/ml, P < 0.05; Day 7: 6.12 +/- 0.46 vs 3.53 +/- 0.33 microgram/ml, P < 0.01). In addition, sCD14 concentrations of Gram-positive nonsurvivors were significantly higher than those of nonseptic ICU patients and healthy volunteers at any time of observation. However, no significant difference was calculated between Gram-positive and Gram-negative patients. Summarizing our results, the serum level of sCD14 could be proven to be a good prognostic marker in the course of Gram-positive sepsis. Increased levels are associated with a high mortality.
Abstract: Serum sCD14, tumour necrosis factor-alpha (TNF-alpha), IL-6, and endotoxin were analysed in 45 patients with complicated malaria, in 14 patients with Gram-negative septicaemia and in 24 healthy subjects by ELISA. Malaria patients with renal failure (n = 16) had higher levels than patients without renal failure (n = 29) (8116 + 1440 micrograms/l versus 9453 + 1017 micrograms/l; P < 0.05) and both had higher levels than patients with septicaemia (6155 + 1635 micrograms/l) and normal subjects (2776 + 747 micrograms/l). A significant correlation between sCD14 and IL-6 (r = 0.756) and TNF (r = 0.822) existed. However, no relation between sCD14 and serum endotoxin or indices of clinical disease severity (parasitaemia, fever, parasite or fever clearance time) was seen. Although the role of sCD14 in malaria remains to be determined, elevated levels may participate in the inflammatory response in complicated malaria.
Abstract: Flow cytometry was used to study phagocytic function (uptake of fluorescein isothiocyanate-labeled bacteria) and release of reactive oxygen products (dihydrorhodamine 123 converted to rhodamine 123) following phagocytosis by neutrophil granulocytes of heparinized whole blood treated with adrenaline, noradrenaline, dopamine, dobutamine, or orciprenaline. Reduced neutrophil phagocytosis and reactive oxygen production were seen at 12 micrograms of adrenaline per liter (72% each compared with control values); at 120 micrograms of noradrenaline (72% each), dobutamine (83 and 80%, respectively), and orciprenaline (81 and 80%, respectively) per liter; and at 100 micrograms of dopamine per liter (66 and 70%) (P < 0.05 for all). At these dosages, neutrophil chemotaxis was reduced to < 50% of control values for all catecholamines. Treatment with catecholamines at lower dosages had no significant effect on phagocytosis or generation of reactive oxygen products or chemotaxis. The phagocytic capacity of granulocytes was related to the generation of reactive oxygen products (r = 0.789; P < 0.05). The results demonstrate that catecholamines have a suppressive effect on the response of phagocytic cells to bacterial pathogens at high therapeutic levels in blood.
Abstract: Polymorphonuclear leukocytes (PMNs) of twelve patients with gram-negative septicemia exhibited a decreased capacity to phagocytize Escherichia coli and generate reactive oxygen products which normalized within 7 days of treatment. Ex vivo exchange of plasma from age-, sex-, and blood-group-identical normal controls resulted in an increase of both phagocytic capacity and reactive oxygen intermediate generation in PMNs of septicemic patients and transiently reduced phagocytosis and reactive oxygen intermediate production in PMNs of normal controls. These results suggest that extrinsic factors are crucial for PMN function.
Abstract: Apart from cellular immunity and immunopathology, various cytokines have been implicated in malaria-associated immunosuppression. In this study, serum levels of transforming growth factor-beta (TGF-beta) were determined with an enzyme-linked immunosorbent assay in 37 patients with acute Plasmodium falciparum malaria prior to, during, and after therapy and in 17 healthy controls in Bangkok, Thailand. Patients were treated with artesunate and mefloquine. TGF-beta serum levels were found decreased prior to treatment (14 +/- 11 pg/ml versus 63 +/- 15 pg/ml in healthy controls; P < 0.05). The serum concentrations of TGF-beta increased after initiation of treatment and were within normal range on day 21. Serum levels of both tumor necrosis factor-alpha (TNF-alpha) and soluble TNF-receptor 55 kDa were inversely correlated to serum levels of TGF-beta (r = -0.667 and r = -0.592, n = 37; respectively, P < 0.05 for both). No correlation between parasitemia and serum levels of TGF-beta could be found. The results are compatible with a decreased production and release, an enhanced clearance or utilization, or tissue accumulation of TGF-beta in acute P. falciparum malaria.
Abstract: Serum levels of interleukin-10 (IL-10) and interferon-gamma (IFN-gamma) were determined in 37 patients with acute Plasmodium falciparum malaria in Bangkok, Thailand. Serum levels of IL-10 and IFN-gamma were markedly elevated in patients with malaria prior to treatment (717 +/- 260 pg/ml versus 2.2 +/- 1.3 pg/ml in healthy controls; 123 +/- 71 pg/ml versus 29 +/- 9 pg/ml, respectively; mean +/- SD). Serum levels of IFN-gamma and IL-10 dropped significantly during treatment and were normal 14 and 21 days, respectively, after treatment was started. Prior to therapy a correlation between serum levels of IFN-gamma and IL-10 existed (r = 0.563). These results suggest that stimulatory and inhibitory cytokines for macrophage activation and/or antibody production (i.e., TH1- and TH2-type immunoreaction, respectively) are coexpressed during acute P. falciparum infection and stress the multifactorial network between host and parasite in malaria immunology.
Abstract: Flow cytometry was used to study phagocytic function and release of reactive oxygen intermediates (ROI) following phagocytosis by granulocytes in 14 patients (six female, eight male) with gram-negative septicaemia prior to, during, and after therapy compared with a group of healthy controls. Phagocytic capacity was assessed by measuring uptake of fluorescein isothiocyanate (FITC)-labelled bacteria. Reactive oxygen generation after phagocytosis was measured by the quantification of dihydrorhodamine 123 converted to rhodamine 123 intracellulary. Compared with results in healthy controls granulocytes of septicaemic patients exhibited a decreased capacity to phagocytize Escherichia coli and to generate reactive oxygen products. Both phagocytosis and ROI production increased after initiation of therapy and normalized within 7 days of treatment. The results suggest that granulocytes do not only participate in, but are also a target of, the septic host inflammatory response.
Abstract: It is increasingly evident that sepsis triggers a complex host reaction that is responsible for a variety of pathophysiologic changes during the inflammatory process. Pentoxifylline (PTX) is a methylxanthine with selective anti-inflammatory activity. Because of the current concept of an exaggerated immune response during severe inflammatory response syndrome (SIRS), this drug has received interest as a potential beneficial modulator of SIRS. Animal studies suggest that randomized clinical trials should be carefully planned with regard to dose-response relationship, disease severity, etiologic pathogens, and mechanisms that result in SIRS. The efficacy of PTX has been promising in human malaria. It is probably also effective in other hyper-tumor necrosis factor (TNF) states. The effective dosage is unclear to date, and its use is restricted by intolerance. Potential adverse effects may be related to the selective depression of TNF expression and to the depression of granulocyte phagocytic activity and the neutrophil/endothelium interaction. However, it is unlikely that any single agent will prove to be the magic bullet in the therapy of sepsis and SIRS. Multiple agents, perhaps tailored to individual circumstances, will most probably be needed, raising dramatic economic and ethical challenges.
Abstract: Thirty patients with severe bacterial infections were treated with 50 mg of cefodizime per kg of body weight once daily or 50 mg of ceftriaxone per kg once daily for 10 +/- 3 days. The effect of cefodizime and ceftriaxone on the phagocytic capacity and generation of reactive oxygen intermediates after phagocytosis by granulocytes was assessed prior to, during, and after therapy. Flow cytometry was used to study phagocytic capacity by measuring the uptake of fluorescein-labeled bacteria. The generation of reactive oxygen intermediates after phagocytosis was estimated by the quantification of the intracellular conversion of dihydrorhodamine 123 to rhodamine 123. Prior to therapy, patients in both groups exhibited a decreased capacity to phagocytize Escherichia coli and subsequently to generate reactive oxygen intermediates. Granulocyte function increased after the initiation of therapy and normalized within 7 days for the ceftriaxone-treated patients and within 3 days for the cefodizime group (P < 0.05). In the cefodizime group, an enhancement of phagocytic capacity was observed 14 days after the initiation of therapy (P < 0.05). Prior to therapy, phagocytic capacity was significantly correlated with the generation of reactive oxygen products (r = 0.674 and P < 0.005).
Abstract: We determined serum levels of laminin in 23 patients with Graves' disease (GD) and in 24 patients with toxic nodular goiter (TNG). Elevated levels of soluble laminin were observed in patients with GD prior to treatment (median concentration 1376 ng mL-1 [range 712-2402]), compared to patients with TNG (median 442 ng mL-1 [284-891]), and normal controls (median 492 ng mL-1 [range 235-675], n = 26), respectively. In GD patients serum laminin levels decreased during thiamazole treatment and normalized within 8 weeks of therapy. There was no correlation between serum laminin levels and serum levels of thyroid hormones and/or auto-antibodies, respectively. Whether serum laminin is a marker for alterations of extracellular matrix during GD and release of basement membrane components in the circulation and/or reflects an impaired clearance remains to be elucidated.
Abstract: The chemokines are a superfamily of small proteins secreted primarily by leukocytes and related by a conserved four-cystein motif. In the present study we investigated the serum levels of macrophage inflammatory protein 1 alpha (MIP-1 alpha) and interleukin-8 (IL-8). MIP-1 alpha is a neutrophil chemotactic protein important in acute and chronic inflammation. Recent studies demonstrated that MIP-1 alpha may also act as potent inhibitor of hemopoetic stem cell proliferation, which may be important in the development of prolonged anemia in patients suffering from Plasmodium falciparum malaria. IL-8 serum concentrations correlate with severity and outcome of infectious diseases. Moreover, recent reports indicate that IL-8 plays a major role in fatal gram-negative sepsis. It was the aim of this study to investigate the time course of MIP-1 alpha and IL-8 concentrations in patients suffering from acute P. falciparum infection. Blood samples of 20 patients suffering from severe P. falciparum malaria were investigated. MIP-1 alpha and IL-8 concentrations were determined using ELISA technique at admission, on Days 7, 14, 21, and 28. Maximal concentrations of MIP-1 alpha and IL-8 were found on Day 14, at a time when parasites were not detected in the smears. The serum levels of IL-8 on the day of admission were correlated to the parasite count. No correlation was seen between the hematokrit values and the MIP-1 alpha concentrations at any time.
Abstract: We determined serum levels of laminin, carboxy-terminal cross-linked telopeptide, and carboxy-terminal propeptide of type I collagen (ICTP and PICP) in 27 patients with Graves' disease (GD) and in 31 patients with toxic nodular goiter (TNG). Elevated levels of soluble laminin and ICTP were observed in patients with GD prior to treatment (mean +/- SD concentration 1444 +/- 404 and 8.6 +/- 3.5 ng/ml, respectively), compared to patients with TNG (476 +/- 103 and 4.2 +/- 1.5 ng/ml) and normal controls (492 +/- 112 and 3.1 +/- 1.3 ng/ml, n = 34). In contrast, serum PICP concentrations were not different between patients with GD or TNG and normal controls. In GD patients serum ICTP and laminin levels decreased during thiamazole treatment and normalized within 4 and 8 weeks of therapy. There was no correlation between serum ICTP and laminin levels and serum levels of thyroid hormones and/or autoantibodies, respectively. Serum ICTP and laminin could be markers for alterations of extracellular matrix during GD and release of matrix components in the circulation and/or reflect an impaired clearance.
Abstract: Thirty-seven patients with acute exacerbations of chronic osteomyelitis caused by methicillin-susceptible Staphylococcus aureus (n = 13), methicillin-resistant Staphylococcus aureus (n = 12), methicillin-susceptible coagulase-negative staphylococci (n = 9), methicillin-resistant coagulase-negative staphylococci (n = 1) and enterococci (n = 2) were treated intravenously with teicoplanin. After a loading dose of 7 to 16 mg/kg (median 11 mg/kg) for 4 to 7 days, patients received 9 to 25 mg/kg (median 14 mg/kg) on Mondays, Wednesdays and Fridays in an outpatient setting to reach trough serum levels between 5 mg/l and 15 mg/l. The duration of treatment ranged from 28 to 150 days (median 60 days). Cure was obtained in 14 (38%) and improvement in 17 (46%) cases, and failure was observed in 6 (16%) patients. Adverse effects occurred in 6 patients, and caused discontinuation of treatment in 3 patients. The financial savings exceeded US$60,000 per patient compared with the high hospitalization costs of inpatient treatment.
Abstract: Serum concentrations of soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble E-selectin (sE-selectin), soluble P-selectin, and soluble L-selectin (sL-selectin), tumor necrosis factor-alpha, and interleukin-6 were measured in patients with Graves' disease (GD) (n = 33), in patients with toxic nodular goiter (n = 34), and in a group of healthy controls (n = 36). The serum levels of sICAM-1, sVCAM-1, sE-selectin, and sL-selectin were markedly elevated in patients with GD and in patients with toxic nodular goiter before treatment with methimazole (P < 0.05 for all). After 8 weeks of therapy, serum concentrations of sVCAM-1 and sE-selectin normalized, whereas serum levels of sL-selectin and sICAM-1 remained elevated. Hormone concentrations normalized after 2 weeks, clearly preceding falling levels of circulating adhesion molecules. Serum concentrations of soluble P-selectin, TNF-alpha, and interleukin-6 did not differ among patients with GD and toxic nodular goiter and healthy subjects. Serum levels of sVCAM-1 and sICAM-1 correlated with the serum concentrations of TSH receptor antibodies (n = 33; r = 0.921 and r = 0.792, respectively) and thyroid peroxidase antibodies (n = 33; r = 0.682 and r = 0.761, respectively) but not thyroglobulin antibodies. However, no correlation between serum levels of sE-selectin, sL-selectin, and soluble P-selectin or cytokines and serum levels of thyroid peroxidase antibodies, TSH receptor antibodies, or thyroglobulin antibodies, respectively, was found. In addition, no correlation between serum levels of adhesion molecules or cytokines and thyroid hormones was seen. We conclude that both the action of thyroid hormones and the autoimmune process in GD may contribute to elevated levels of soluble adhesion molecules.
Abstract: Adhesion of Plasmodium falciparum-infected erythrocytes to vascular endothelium is in part mediated by ICAM-1 and ELAM-1 (E-selectin), which can be induced via the 55-kDa TNF-receptor (TNF-R55kDa). We have studied serum levels of soluble ICAM-1 (sICAM-1), ELAM-1 (sELAM-1), and soluble TNF-R55kDa (sTNF-R55kDa) in 37 patients with uncomplicated P. falciparum infection and in 17 control subjects in Bangkok, Thailand. The serum levels of sICAM-1 were markedly elevated in patients prior to treatment (601 +/- 239 ng/ml versus 160 +/- 47 ng/ml in healthy controls). In addition, elevated levels of sELAM-1 (53.6 +/- 23.1 ng/ml versus 21.5 +/- 10.1 ng/ml) and sTNF-R55kDa (4.7 +/- 3.2 ng/ml versus 1.0 +/- 0.4 ng/ml) were observed (P < 0.05 for all). Soluble ELAM-1 reached normal levels on Day 3, and sTNF-R55kDa on Day 14, while sICAM-1 was still significantly elevated 28 days after treatment was started (P < 0.05 for all). A correlation between sTNF-R55kDa (P < 0.05) and sELAM-1 (P < 0.05), respectively, with parasitemia prior to antimalarial treatment was found. These results suggest that a TNF-mediated expression of adhesion molecules induced by the asexual stage of malaria parasites serves as an immune-evasion mechanism.
Abstract: We report the first case of onchocerciasis in Austria in a African patient who was admitted to hospital for psychiatric reasons initially. The clinical diagnosis was confirmed by skin-snip examination and staining of the microfilariae. Pathophysiology and therapeutic possibilities are discussed.
Abstract: Complicated and recurrent urinary tract infections present intriguing clinical management problems. The underlying conditions in patients with complicated urinary tract infections are anatomical abnormalities of the genitourinary tract, neurologic disorders resulting in urinary stasis, obstruction, instrumentation, surgery, diabeters mellitus, renal transplantation, and renal calculi. In comparative studies the quinolones have been shown to be effective in 7-14-day treatment courses in complicated urinary tract infection. Several comparative trials which compare the fluoroquinolones with beta-lactam antibiotics or cotrimoxazole yielded equal or better results for the quinolones. A cost-saving option is given with some of the fluoroquinolones that can be administered parenterally and orally which enables the patient to be discharged from the hospital earlier. There are few differences in antimicrobial activity between the newer quinolones, but differences in the pharmacokinetic properties are evident. The fluoroquinolones are suitable therapeutics for complicated urinary tract infection, because they offer rapid oral absorption, high tissue concentration, broad activity against most Gram-negative and Gram-positive organisms, the possibility of a once-a-day administration, and relatively few side effects.
Abstract: The targeting and recruitment of inflammatory cells to vascular endothelium in Graves' disease (GD) is mediated by intercellular adhesion molecule-1 (ICAM-1), endothelial leucocyte adhesion molecule-1 (ELAM-1), and vascular cell adhesion molecule-1 (VCAM-1). We have studied serum levels of soluble ICAM-1 (sICAM-1), soluble ELAM-1 (sELAM-1), and soluble VCAM-1 (sVCAM-1) in patients with GD (n = 21) and in patients with iodine-deficient goitre (IDG) (n = 23). The serum levels of sICAM-1 were markedly elevated in patients with GD before treatment with thiamazole (median 560 ng/ml versus 185 ng/ml in patients with IDG). In addition, elevated serum concentrations of sELAM-1 (median 85 ng/ml versus 33 ng/ml, respectively) and sVCAM-1 (median 42 ng/ml versus 15 ng/ml, respectively) were observed in patients with GD (P < 0.01 for all). The serum levels of sELAM-1 and sVCAM-1 dropped significantly after initiation of therapy and were within the normal range after 4, and 8 weeks of therapy, respectively. Serum levels of sICAM-1 were elevated even after 8 weeks of therapy. Serum levels of sVACM-1 and sICAM-1 correlated with the serum concentrations of anti-thyroid-stimulating hormone (TSH)-receptor antibodies (TSHR-R) (n = 21; r = 0.929 and r = 0.810, respectively) and anti-thyroid peroxidase antibodies (TPO-Ab) (n = 21; r = 0.673 and r = 0.750, respectively). However, no correlation between sELAM-1 and TPO-Ab, TSHR-R, and anti-thyroglobulin antibodies (Tg-Ab), respectively, could be found. In addition to thyroid hormones and autoantibodies, serum concentrations of sELAM-1 and sVCAM-1, but not sICAM-1, could be useful as clinical markers for disease activity.
Abstract: There has been renewed interest in drug-host defence interaction because of increasing numbers of immunocompromised individuals in whom even a marginal influence on host response may have a beneficial effect on clinical outcome. The immunomodulating activity of several antibiotics has been investigated in the past. Unfortunately most of these studies have focussed on in vitro effects. Many controversies arise from the use of non-standardized techniques. In vivo experiments performed in animals might be far from the clinical situation. The effect of antibiotics on pagocyte function has been studied most intensively. Immunostimulating and depressing activities of antibiotics have been described. The clinical relevance is still controversial, e.g., the intracellular uptake of an antibiotic does not necessarily mean better microbial killing. Synergistic activities have been found with some macrolides and newer cephalosporins, but until now clinical studies in humans are still missing. Not only patients with abnormal host defence mechanisms, but also patients with transient immunosuppression during operations or after burns, could benefit from antibiotics with additional immunomodulating activities. More studies in humans are required before optimal clinical applications can be recommended.
Abstract: A 59-year-old man with the diagnosis of endocarditis of the mitral valve due to Streptococcus mitis was treated with penicillin G, gentamicin, and later with clindamycin as inpatient for 3 weeks. Thereafter outpatient therapy with parenteral teicoplanin 3 x per week was initiated. After 17 days of teicoplanin treatment he developed severe diarrhea, and stool samples were positive for Clostridium difficile toxin. In addition to the ongoing parenteral therapy with teicoplanin, oral teicoplanin was administered. On the third day of this regimen the diarrhea and other disabling symptoms subsided, and test results for C. difficile toxin became negative. Oral teicoplanin was continued for 10 days and cleared C. difficile effectively after treatment as assessed by consecutive stool cultures (until 60 days thereafter). The parenteral administration of teicoplanin could not prevent the onset of C. difficile associated diarrhea in this patient, who previously had been treated with clindamycin. Thus, the administration of parenteral teicoplanin does not seem to be a treatment option for C. difficile associated diarrhea in patients in which oral therapy is not possible.
Abstract: Infections of the female genitals are among the most common conditions seen by primary care physicians. Approximately 75% of all women experience at least one episode of vaginitis during their reproductive life. Bacterial flora of the female genital tract is complex and dynamic. Those organisms which may cause gynecological infections in the appropriate setting are often present at a different stage in the woman's life as normal flora. The treatment of gynecological infections is dependent on the symptoms of the patient, the pathogen, and the medical history with regard to recurrences of the same disease. Since identification of the pathogen is often difficult, empirical therapy is administered frequently, which requires detailed knowledge of the most common bacterial pathogens and the resistance pattern of these organisms. An accurate initial diagnosis is the best basis for appropriate therapy, especially in view of the fact that once empirical antibiotic therapy has been administered, signs and symptoms are modified and the site of infection is rendered much more obscure.
