Abstract: Mycoplasma pneumoniae infection occurs worldwide and is the most common cause of community-acquired pneumonia (CAP) in 5- to 20-year-olds. The most reliable diagnostic test is the enzyme immunoassay, which allows immunoglobulin (Ig)G and IgM titration and presents 92% sensitivity and 95% specificity on paired samples. Potentially active drugs are tetracyclines, macrolides, ketolides, lincosamides, streptogamines, chloramphenicol, and fluoroquinolones. Chlamydia pneumoniae accounts for 6 to 20% of CAP cases, depending on several factors such as setting of the studied population, age group examined, and diagnostic methods used. The current gold standard for serological diagnosis of acute infection is microimmunofluorescence testing. Tetracyclines and erythromycin show good in vitro activity and so far have been the most commonly employed drugs in the treatment of C. pneumoniae infection. New macrolides, ketolides, and new fluoroquinolones are other potentially effective drugs.
Abstract: We analyzed 795 sputa from 315 patients (233 males, mean age 69.3+/-8.8 years, mean number of exacerbations 2.52/patient) with acute exacerbations of moderate-to-severe chronic obstructive pulmonary disease (COPD) (mean steady-state FEV1 42.5+/-7.8% of predicted). 581/795 sputa were considered adequate. Sputum was analyzed by a quali-quantitative colorimetric scale allowing both color distinction and color degree of intensity. Quantitative culture was then performed (threshold: >10(6)CFU/mL). Samples were distinguished in mucoid (145) and purulent (436) sputa. Absence of bacterial growth was observed in 22% and 5% of mucoid and purulent sputa, respectively. Among mucoid sputa, Gram positive bacterial growth occurred more commonly compared to Gram negative and Pseudomonas aeruginosa/Enterobacteriaceae (56%, 24%, 20%, respectively). In purulent sputa, Gram positives were found in 38% of cases, Gram negatives in 38%, and P. aeruginosa/Enterobacteriaceae in 24%. We evaluated whether functional impairment (FEV1) orientates as to the infectious etiology of exacerbations. Significant differences were observed in the distribution of pathogens. Gram negative and P. aeruginosa/Enterobacteriaceae were isolated more frequently in the sputum when FEV1 was <35%. Our study indicates that purulent sputum is strongly associated with bacterial growth in COPD exacerbations. Deepening sputum color (from yellowish to brownish) was associated with increased yield of Gram negative and P. aeruginosa/Enterobacteriaceae.
Abstract: Azithromycin is a macrolide antibiotic that has been structurally modified from erythromycin with an expanded spectrum of activity and improved tissue pharmacokinetic characteristics relative to erythromycin. This allows once-daily administration for 3-5 days of treatment compared with traditional multi dosing 7-10-day treatment regimens. It has been successfully employed in lower respiratory tract infections. Recent data indicate that azithromycin may exert anti-inflammatory/immunomodulatory effects that may be of use in the treatment of both acute and chronic airway diseases. This review examines the role of azithromycin in lower respiratory tract infections analysing published data on exacerbations of chronic bronchitis, community-acquired pneumonia and cystic fibrosis both in adults and children. In addition, pharmacokinetic and pharmacodynamic properties of the drug are also considered.
Abstract: PURPOSE OF REVIEW: In this review, we highlight some of the developments achieved over the past 2 years in the field of novel antimicrobial compounds. RECENT FINDINGS: Modification of existing compound classes to create more powerful compounds capable of overcoming pathogen resistance and the introduction of completely new classes of antibiotics and inhibitors of new bacterial targets or inhibitors of genes relating to virulence or pathogenesis are the strategies more commonly employed in pharmacologic research. Ketolides, oxazolidinones, streptogramins, glycylcyclines, and peptide deformylase inhibitors are among the most promising classes of antibiotics. Recently, several lines of research have documented that it is effective to target the infection process rather than killing bacteria. This is important because it is likely that such a therapeutic strategy could ablate infection without inducing resistance. SUMMARY: Emergence of resistance to the antibiotics currently employed in clinical practice is a continual stimulus for further research aimed at identifying novel antimicrobial compounds. These drugs will perhaps effectively fight against bacteria that now are scarcely controlled by the traditional antimicrobial agents. Health care personnel must appreciate that only judicious use of antimicrobial drugs will prevent the further uncontrolled spread of bacterial resistance. Implementation of reference guidelines would probably be an effective way to limit antibiotic misuse.
Abstract: Although the role of antibiotic treatment in asthma is still disputed, clinical use of antimicrobials in this setting is more widespread than warranted on the basis of indications in the literature. Viral upper respiratory tract infections are known to be involved in asthma exacerbations. More recently, evidence of Mycoplasma pneumoniae and Chlamydia pneumoniae involvement in asthma attacks has been reported both in adult and paediatric populations. These pathogens are also involved in chronic asthma, and both in vitro and animal model studies indicate that atypical agents may play a role in the pathogenesis of the disease. Recent studies on asthma patients with evidence of atypical infection suggest that specific antimicrobial treatment (basically macrolides or fluoroquinolones) may confer additional advantages compared to standard therapy alone. Furthermore, a considerable amount of data has been gathered describing additional effects associated with macrolide treatment (reduced bronchial hyper-responsiveness, altered cytokine production, etc.). These non-antimicrobial effects have been defined as "anti-inflammatory activity". Should this information be confirmed, the use of macrolides in patients with asthma may be twofold: eradication of occult atypical infection; and reduction in the airway inflammation burden. Future lines of research in this field should attempt to determine whether specific antibiotic treatment may alter the natural history of asthma.
Abstract: Studies employing noninvasive pressure support ventilation in cardiogenic pulmonary edema have been performed in the intensive care unit when overt respiratory failure is already present and in small groups of patients. In this multicenter study, performed in emergency departments, 130 patients with acute respiratory failure were randomized to receive medical therapy plus O2 (65 patients) or noninvasive pressure support ventilation (65 patients). The primary end point was the need for intubation; secondary end points were in-hospital mortality and changes in some physiological variables. Noninvasive pressure support ventilation improved PaO2/FIO2, respiratory rate, and dyspnea significantly faster. Intubation rate, hospital mortality, and duration of hospital stay were similar in the two groups. In the subgroup of hypercapnic patients noninvasive pressure support ventilation improved PaCO2 significantly faster and reduced the intubation rate compared with medical therapy (2 of 33 versus 9 of 31; p=0.015). Adverse events, including myocardial infarction, were evenly distributed in the two groups. We conclude that during acute respiratory failure due to cardiogenic pulmonary edema the early use of noninvasive pressure support ventilation accelerates the improvement in PaO2/FIO2, PaCO2, dyspnea, and respiratory rate, but does not affect the overall clinical outcome. Noninvasive pressure support ventilation does, however, reduce the intubation rate in the subgroup of hypercapnic patients.
Abstract: The impact of respiratory infections on public health is increasing and lower respiratory tract infections are a major cause of morbidity and mortality. We are also facing a worldwide burst of antibiotic bacterial resistance. The new fluoroquinolones have an excellent spectrum covering the most important respiratory pathogens, including atypical and 'typical' pathogens. Pharmacokinetic and dynamic properties of the new fluoroquinolones have a significant impact on their clinical and bacteriological efficacy. They cause a concentration-dependent killing with a sustained postantibiotic effect. Fluoroquinolones combine exceptional efficacy with cost-effectiveness. Not surprisingly, different guidelines have inserted these agents among the drugs of choice in the empirical therapy of community-acquired pneumonia. This review discusses the more recent data on bacteriological and clinical activity and critically analyses the risks of a potential overuse of this valuable new class of drugs.
Abstract: BACKGROUND: A study was undertaken to evaluate Chlamydia pneumoniae chronic infection, other respiratory infections, and functional impairment in patients with chronic bronchitis (stage 1) and to examine chronic C pneumoniae infection, rate of acute exacerbations of chronic bronchitis, and rate of C pneumoniae eradication following antibiotic treatment (stage 2). METHODS: In the stage 1 study respiratory specimens from 42 patients with steady state chronic bronchitis were analysed for Gram staining, sputum culture, and C pneumoniae DNA detection by nested touchdown polymerase chain reaction (PCR). On the basis of the results of stage 1, a second population of 141 consecutive patients with steady state mild to moderate chronic bronchitis (FEV(1) >or=50% predicted) was studied. On admission, at regular intervals, and at exacerbation all patients underwent serological testing for C pneumoniae (microimmunofluorescence) and a nested touchdown PCR to detect C pneumoniae DNA was performed on peripheral blood mononuclear cells (PBMCs). Patients were assessed over a 12 month period. Information regarding the previous 12 months was taken from medical records. RESULTS: Chronic colonisation of the sputum with C pneumoniae was significantly associated with lower FEV(1) and greater airway bacterial colonisation. On admission to the stage 2 study, 80 patients were PCR negative and 61 were PCR positive. Over the 2 years a mean (SD) of 1.43 (1.32) acute exacerbations occurred in PCR negative patients and 2.03 (1.21) in PCR positive patients (p<0.01). During the 12 month follow up period 34 PCR positive patients had acute exacerbations and were treated with azithromycin for 6 weeks. Serological evidence of acute C pneumoniae reinfection/reactivation was found in two of the 34 patients. The rate of C pneumoniae DNA clearance from blood following treatment was 29% at follow up. CONCLUSION: Chronic colonisation with C pneumoniae is associated with a higher rate of exacerbations of chronic bronchitis. Long term treatment is required to obtain clearance of the organism from the blood.
Abstract: The current use of antimicrobials has become more complex due to the extensive emergence of antibiotic resistance. The single most important approach in resistance control is probably the judicious use of chemotherapeutic agents. New agents that may be of use in the treatment of community-acquired pneumonia are currently in development. Antimicrobials can be grouped according to their mechanism of action. These include protein synthesis inhibitors (ketolides, oxazolidinones, streptogramins and glycylcyclines), nucleic acid synthesis inhibitors (fluoroquinolones), peptidoglycan synthesis inhibitors (beta-lactams and glycopeptides) and agents interfering with membrane function (cationic peptides and lipopeptides). Among those agents under development, only the oxazolidinones, the cationic peptides and the lipopeptide antibiotics can be truly regarded as structurally novel inhibitors as the other agents are analogues of existing compounds which have been in clinical use for many years.
Abstract: The association between respiratory infections and asthma exacerbations was first observed in the early '70s. In particular, the role of viral upper respiratory tract infections has been evaluated both in pediatric and adult populations. More recently, evidence of Mycoplasma and Chlamydia pneumoniae involvement in asthma attacks has been reported. These pathogens are also involved in chronic asthma, and both in vitro and animal model studies indicate that atypical agents may play a role in the pathogenesis of the disease. Further research is required to determine whether specific antibiotic treatment may alter the natural history of asthma.
Abstract: The study was designed to extend retrospectively the analysis of a previously reported study on chronic bronchitis patients with acute exacerbations treated with amoxicillin-clavulanic acid or matched placebo. We retrospectively re-clustered patients on the basis of severity of baseline lung function: Cluster 1 (104 patients) mean screening FEV(1)32.67+/-6.83 (SD); Cluster 2 (109 patients) mean screening FEV(1)54.12+/-5.56; Cluster 3 (122 patients) mean screening FEV(1)71.54+/-5.51. The success rate in the antibiotic group was significantly greater compared to the placebo group (P<0.001). When clinical improvement was analysed on the basis of patient re-clustering, 31.4% of Cluster 1 (severe COPD) patients treated with amoxicillin/clavulanate showed clinical improvement, whereas success was recorded in 58.8%. Conversely, 13.2% of Cluster 1 patients receiving placebo improved and 17% successfully recovered (P<0.001). Mild and moderate COPD patients (Clusters 2 and 3) were grouped together. In these two groups, 31.2% and 53.6% of patients receiving antibiotic treatment showed improvement or recovery, respectively, compared to 29.2% improvements and 30.2% successful recoveries among placebo-treated patients (P<0.001). In placebo-treated patients the improvement/success vs. failure rate was significantly different in Cluster 1 patients compared to Cluster 2+3 subjects (P<0.01, (2)test). The differences in final FEV(1)values in the treatment group and placebo group were significantly different (P<0.01) in favour of the active treatment group. Among more severe patients (Cluster 1), the comparison between screening and follow up FEV(1)values showed an improvement following antibiotic treatment and worsening after placebo (P<0.01). In Clusters 2 and 3 the difference between screening and follow up FEV(1)values was not significant for both treatment groups. Our patients with severe functional impairment and higher number of exacerbations per year are those who derive the greatest benefit from antibiotic treatment. Copyright Academic Press.
Abstract: M. pneumoniae infection occurs world-wide and is the most common cause of community-acquired pneumonia (CAP) in the 5 to 20 year-old age group. The most reliable diagnostic test is enzyme immunoassay that allows immunoglobulin (Ig)G and IgM titration and presents 92% sensitivity and 95% specificity on paired samples. Potentially active drugs are tetracyclines, macrolides, ketolides, lincosamides, streptogamines, chloramphenicol, and fluoroquinolones. The incidence of Legionella infection, in spite of its world-wide diffusion, is highly variable in different studies, ranging from 1% to 27% of CAP. The most likely mode of transmission is direct inhalation from Legionella-contaminated water-supply systems. Extrapulmonary manifestations are relatively common but nonspecific. However, some signs and symptoms may raise the suspicion of Legionella infection: a sputum Gram stain with a high number of neutrophils without any organism, hyponatremia, and diarrhea in a critically ill patient. Urinary radioimmunoassay (RIA) antigen detection is the method of choice for L. pneumophila serogroup 1. The best treatment regimen is a full three-week treatment with a macrolide (erythromycin, clarithromycin, azithromycin). An alternative treatment regimen may be the association of second generation fluoroquinolones with tetracyclines. A notable improvement in most of the new fluoroquinolones is their activity against Legionella, so that their use as single agent may be hypothesised even if clinical data are still insufficient for a definitive indication. Chlamydia pneumoniae account for 6-20% of CAP depending on several factors such as setting of the studied population, age group examined, and diagnostic methods used. The current gold standard for serological diagnosis of acute infection is microimmunofluorescence testing. Tetracyclines and erythromycin show good in vitro activity and so far have been the most commonly employed drugs in the treatment of C. pneumoniae infection. New macrolides, ketolides, and new fluoroquinolones are other potentially effective drugs.
Abstract: Chlamydia pneumoniae is a significant cause of both upper and lower respiratory tract infections. The spectrum of diseases ranges from asymptomatic infection to serious disease, including severe pneumonia and exacerbations of chronic bronchitis requiring mechanical ventilation. There is increasing evidence of involvement of C. pneumoniae infection in bronchial asthma, and the role of this agent in immunocompromised patients has also begun to be appreciated.
Abstract: Temporal arteritis is a clinical manifestation of giant cell arteritis. The etiology of this disease is still unknown. Sudden onset and wide variations of incidence are reported in different parts of the world. Acute onset is often associated with flu-like symptoms, indicating that infectious factors probably act as precipitating agents. We describe a 72-year-old man referred to our department in January 1999 for unremitting fever and temporal arteritis associated with Chlamydia pneumoniae infection.
Abstract: BACKGROUND: Chronic Chlamydia pneumoniae and Helicobacter pylori infections could be a risk factor for ischemic heart disease (IHD), possibly by increasing fibrinogen levels. The aim of our study was to evaluate changes in fibrinogen level in patients with IHD and H pylori and/or C pneumoniae positivity randomly assigned to antibiotic treatment. METHODS AND RESULTS: Eighty-four patients with chronic IHD, H pylori and/or C pneumoniae antibodies, and normal acute-phase reactants were randomly assigned to treatment or no treatment. Treatment consisted of omeprazole, clarithromycin, and tinidazole in H pylori-positive patients and clarithromycin alone in C pneumoniae-positive patients. The effect of treatment and other baseline variables on fibrinogen levels, determined at 6 months, was evaluated by multivariate analysis. Treatment significantly reduced fibrinogen level at 6 months in the overall study population and in the groups of patients divided according to H pylori or C pneumoniae positivity. In the 43 treated patients, mean (+/-SD) basal fibrinogen was 3.65+/-0.58 g/L, and mean final fibrinogen was 3. 09+/-0.52 g/dL (P<0.001), whereas in the 41 untreated patients, mean basal and final fibrinogen levels were 3.45+/-0.70 and 3.61+/-0.71 g/L, respectively. The largest decrease was observed in patients with both infections. Fibrinogen changes were also significantly and negatively correlated with age. CONCLUSIONS: Our data suggest that a short, safe, and effective course of antibiotic therapy might be suggested as a means of interacting with an "emerging" risk factor.
Abstract: Abdominal aortic aneurysm tissue and peripheral blood mononuclear cells (PBMC) of 41 consecutive subjects undergoing abdominal aortic aneurysm surgery were analyzed by polymerase chain reaction (PCR) for the presence of Chlamydia pneumoniae, Mycoplasma pneumoniae, and Helicobacter pylori DNA. Twenty patients (49%) were positive for C. pneumoniae DNA-16 (39%) in both PBMC and aneurysm tissue, 3 (7.3%) in PBMC only, and 1 (2.4%) in the artery specimen only. Previous exposure to C. pneumoniae was confirmed in 19 (95%) of the 20 PCR positive subjects by C. pneumoniae-specific serology, using the microimmunofluorescence test. None was positive for H. pylori or M. pneumoniae DNA, either in the PBMC or in the artery specimens. In conclusion, carriage of C. pneumoniae DNA is common both in PBMC and in abdominal aortic tissue from patients undergoing abdominal aneurysm surgery. Blood PCR may be a useful tool for identifying subjects carrying C. pneumoniae in the vascular wall.
Abstract: The presence of Chlamydia pneumoniae in atheromas has been demonstrated in several studies. Culture of the organism from arterial tissue has been difficult. We report the use of a reverse transcriptase polymerase chain reaction to detect viable Chlamydia pneumoniae in carotid atheromas. We analyzed 30 patients (14 females, mean age 69.6 +/- 8.8 years) who underwent surgery for the removal of atherosclerotic plaques from carotid arteries. During surgery, samples of lingual vein and superior thyroideal artery were also taken. We applied two molecular biology techniques to the carotid plaques on lingual vein or thyroideal artery samples: 1) polymerase chain reaction (PCR) and 2) reverse transcriptase-PCR (RT-PCR) for the detection of bacterial mRNA, employing PCR primers designed to detect a fragment of the 16S rRNA gene. Blood samples were obtained from the patients for determination of Chlamydia pneumoniae IgG, IgA, and IgM antibody titers by a microimmunofluorescence technique. The results of the present study confirmed the presence of viable Chlamydia pneumoniae in atheromas and support the hypothesis that the organism may be an active factor in the pathogenesis of atherosclerosis.
Abstract: Limited information is available for humans on whether blood viscosity affects total peripheral resistance and, hence, blood pressure. Our study was aimed at assessing the effects of acute changes in blood viscosity on both clinic and 24-hour ambulatory blood pressure (BP) values. In 22 normotensive and hypertensive patients with polycythemia, clinic and 24-hour ambulatory BPs were measured before and 7 to 10 days after isovolumic hemodilution; this was performed through the withdrawal of 400 to 700 mL of blood, with concomitant infusion of an equivalent volume of saline-albumin solution. Hematocrit, plasma renin activity, plasma endothelin-1, right atrial diameter (echocardiography), and blood viscosity were measured under both conditions. Plasma renin activity and right atrial diameter were used as indirect markers of blood volume changes. Plasma endothelin-1 was used to obtain information on a vasomotor substance possibly stimulated by our intervention, which could counteract vasomotor effects. Isovolumic hemodilution reduced hematocrit from 0.53+/-0.05 to 0.49+/-0.05 (P<.01). Plasma renin activity, plasma endothelin-1 and right atrial diameter were unchanged. Clinic blood pressure was reduced by hemodilution (systolic, 144.3+/-5.4 to 136.0+/-3.9 mm Hg[mean+/-SEM]; diastolic, 87.0+/-2.8 to 82.1+/-2.6 mm Hg, P<.05 for both) and a reduction was observed also for 24-hour average ABP (systolic, 133.6+/-2.9 to 129.5+/-2.7 mm Hg; diastolic, 80.0+/-2.0 to 77.3+/-1.7 mm Hg, P<.05 for both). The reduction was consistent in hypertensive patients (n = 12), whereas in normotensive patients (n = 10) it was small and not significant. Both clinic and 24-hour average heart rates were unaffected by the hemodilution. Thus, in polycythemia, reduction in blood viscosity without changing blood volume causes a significant fall in both clinic and 24-hour ambulatory BPs; this is particularly true when, as can often happen, blood pressure is elevated. This emphasizes the importance this variable may have in the determination of blood pressure and the potential therapeutic value of its correction when altered.
Abstract: The rate of seroconversion for antibody to Chlamydia pneumoniae was analysed in blood samples of 26 vertically HIV-1 infected children and 14 seroreverter children (HIV-negative children born to HIV-positive mothers) during a 3-year study period. Seroconversion for Chlamydia pneumoniae was found in 13 of 26 HIV-1 infected children and in 1 of 14 in the seroreverter group (P=0.013). A lower mean CD4+ cell count and p24 antigen positivity at enrolment were significantly associated with seroconversion for Chlamydia pneumoniae. Signs and symptoms of acute respiratory infection were recorded in the 30 to 40 days preceding collection of the blood samples showing seroconversion for Chlamydia pneumoniae in 8 of 13 HIV-1 infected children and in the single seroreverter. This study confirms the potential role of Chlamydia pneumoniae in the pathogenesis of respiratory tract infections in HIV-1 infected subjects.
Abstract: The pathogenesis of sarcoidosis is not yet known. On the basis of seroepidemiological data, an association between Chlamydia pneumoniae infection and sarcoidosis has been suggested, but so far no study has addressed the direct detection of this agent in the affected tissues. The aim of the present study was to detect C. pneumoniae deoxyribonucleic acid (DNA) within sarcoid tissue specimens by means of a two-step polymerase chain reaction. Lung biopsy specimens of 33 patients with histologically confirmed pulmonary sarcoidosis and 21 control lung biopsies or pathology specimens of patients with pulmonary carcinoma or emphysema were retrospectively analysed. A nested polymerase chain reaction was applied using two sets of primers designed to detect a fragment of the 16 strand ribosomal ribonucleic acid (rRNA) gene of C. pneumoniae. The results of the study failed to demonstrate the presence of C. pneumoniae in biopsy specimens of sarcoid tissue and in the control lung biopsies or pathology specimens. Our results, therefore, tend to rule out the possibility of a direct involvement of Chlamydia pneumoniae in the pathogenesis of sarcoidosis.
Abstract: STUDY OBJECTIVES: We conducted a retrospective study on patients with acute myocardial infarction (AMI) and evaluated the incidence and prevalence of Chlamydia pneumoniae infection. METHODS: Sixty-one consecutive patients with AMI aged younger than 65 years were enrolled. Within 24 h of hospital admission, serum samples and pharyngeal swab specimens were obtained from all patients. In 49 of 61 patients, after a mean of 28 days from hospital admission, a second serum sample was drawn. A third serum sample was obtained in 23 of 61 patients. Serologic testing for Chlamydia pneumoniae was performed by a microimmunofluorescence test. We applied a nested-polymerase chain reaction for C pneumoniae DNA detection to pharyngeal swab specimens. Simultaneously, we performed a serologic study for C pneumoniae infection on 61 serum samples obtained from blood donors, matched for age, sex, and smoking habits. RESULTS: Serologic test results for C pneumoniae were consistent with acute reinfection in 12 patients, with chronic infection in 23 patients, and results were negative in 26 patients with AMI. In 3 of 12 patients with acute reinfection pattern and in 3 of 23 patients with chronic infection pattern, C pneumoniae DNA was detected on pharyngeal swab specimens. A significantly higher prevalence of IgG titers was observed in patients with AMI (35/61) compared to blood donors (18/61) (p=0.003). CONCLUSION: Our data confirm the possible role of C pneumoniae infection in coronary heart disease and suggest that reinfection may trigger the onset of AMI.
Abstract: Between July 1992 and June 1993, 61 patients with severe community-acquired pneumonia were admitted to our semi-intensive care unit. For all patients chest X-ray, blood gas analysis while breathing room air, Gram stain and culture of bronchoaspirate, determination of acute and convalescent anti-body titers for Legionella pneumophila, Mycoplasma pneumoniae and Chlamydia pneumoniae, blood culture when body temperature was greater than 38 degrees C, and pharyngeal swab for C. pneumoniae detection by means of an indirect immunofluorescence test were obtained. Among the patients enrolled, 15 suffered from chronic obstructive pulmonary disease, 18 had serious chronic diseases, 9 were immunodeficient and 15 had cardiovascular diseases, and only 4 had no underlying disease. Etiologic diagnosis was reached in 30 cases (49%). As expected, due to the high rate of seriously ill patients, gram-negative pathogens were identified most commonly (15%), followed by Streptococcus pneumoniae (10%) and, surprisingly, by C. pneumoniae (10%). These data, showing the possible emergence of Pseudomonas aeruginosa and C. pneumoniae, warrant further studies in order to verify whether the epidemiological pattern of severe community-acquired pneumonia is actually changing.
Abstract: The emergence of new pathogens and the increasing antimicrobial resistance patterns of old pathogens are contributing factors to the high epidemiologic impact of lower respiratory tract infections. Hantaviruses, Chlamydia pneumoniae, and penicillin-resistant Streptococcus pneumoniae have recently gained most of the attention of international researchers. Hantavirus pulmonary syndrome has been confirmed in 100 cases with a very high mortality (52%). Risk factors for infection are peridomestic cleaning, agricultural activities, and an increased number of small rodents like deer mouse, mainly Peromyscus maniculatus. Pulmonary capillary leak and multiorgan involvement characterise Hantavirus pulmonary syndrome. Most recent reports rank C. pneumoniae among the three most common etiologic agents in community-acquired pneumonia, but it is also involved in chronic diseases such as chronic obstructive pulmonary disease and asthma. Several recent reports indicate the striking increase of penicillin-resistant S. pneumoniae strains. These data emphasize the crucial need for new therapeutic agents and more effective prevention programs.
Abstract: Recent reports suggest an association between Chlamydia pneumoniae and Helicobacter pylori bacteria and atherosclerosis. We studied 51 patients (mean age, 68.3 years) who underwent abdominal aortic aneurysm surgery. For each patient we performed a microimmunofluorescence test for immunoglobulin G (IgG), IgA, and IgM antibodies to C. pneumoniae specific antigen (TW-183). Anti-H. pylori antibodies were determined by means of an EIA-G test. Each aortic aneurysm surgical specimen was sampled into multiple sections of 0.3 cm2 each and frozen at -20 degrees C. Two samples of each aneurysm were used for a nested PCR with two sets of C. pneumoniae and two sets of H. pylori specific primers. Specimens were treated with a solution containing 20 mM Tris-HCl, Tween 20-Nonidet P-40 (0.5% [vol/vol] each), and 100 micrograms of proteinase K per ml and incubated at 60 degrees C for 1 h and at 98 degrees C for 10 min. DNA was extracted twice with phenol-chloroform-isoamylic alcohol and precipitated with sodium acetate-ethanol by standard methods. Forty-one patients were seropositive for C. pneumoniae with past-infection patterns in 32 patients (16 < or = IgG < 512; 32 < or = IgA < 256) and high antibody titers in 9 patients (IgG > or = 512). In 26 of 51 patients, C. pneumoniae DNA was detected in aortic aneurysm plaque specimens. Of these patients, 23 had a serologic past-infection pattern, 2 had an acute reinfection pattern, and 1 was seronegative. Forty-seven of 51 patients were seropositive for H. pylori. In all cases PCR showed no evidence of H. pylori presence in plaque specimens. This study provides data on a possible C. pneumoniae involvement in the pathogenesis of aortic aneurysm and additional evidence for an association between this agent and atherosclerosis. Conversely, notwithstanding a high H. pylori seroprevalence observed, our results tend to rule out the possibility of a direct involvement of H. pylori in atherosclerosis.
Abstract: During autumn 1992, we observed two unrelated family outbreaks of Chlamydia pneumoniae infection. Family A consisted of grandmother (aged 77 yrs), father (aged 41 yrs), mother (aged 38 yrs), daughter (aged 10 yrs), and two sons (aged 6 yrs and 3 months, respectively). The grandmother and daughter suffered from pneumonia, father from pharyngitis and bronchitis and the older son from mild bronchitis. No symptoms were recorded in the mother and younger son. Symptomatic subjects showed a fourfold increase in immunoglobulin G (IgG) titre for Chlamydia pneumoniae, determined by a microimmunofluorescence test with specific antigen (TW-183). Other serological studies against Mycoplasma pneumonia, Legionella pneumophila, influenza virus type A and B, adenovirus and respiratory syncytial virus (RSV) were negative. Sputum culture gave a positive result for Haemophilus influenzae, colony forming units (cfu) = 10(4).ml-1 in the grandmother. No serum positivity was recorded in the mother and younger son, who remained asymptomatic. All symptomatic patients were successfully treated with macrolides. Family B consisted of mother (aged 63 yrs) and daughter (aged 36 yrs). Both suffered from Chlamydia pneumoniae pneumonia. Diagnosis was made by means of serological microimmunofluorescence test, and direct identification using an indirect immunofluorescence test on pharyngeal swab. Sputum culture and other serological tests remained negative. Both patients were successfully treated with macrolides. These observations emphasize the relevance of Chlamydia pneumoniae in family cluster respiratory infections.
Abstract: In a retrospective analysis of lower respiratory tract infections in an ex-injection-drug users community, we found an outbreak (April to July 1991) of Chlamydia pneumoniae infection. The epidemic occurred in a group of 26 community members (23 men and 3 women, mean age, 28.9--3 years) living and working together, who underwent acute and convalescent serologic tests for Mycoplasma pneumoniae, Legionella pneumophila, cytomegalovirus, adenovirus, Coxiella burnetii, and Chlamydia pneumoniae. All subjects were submitted to chest radiograph, while sputum and blood cultures were performed in symptomatic patients. Antibodies to C pneumoniae were determined by a microimmunofluorescence test. Among all subjects studied (13 HIV-1 positive and 13 HIV-1 negative), 11 (8 HIV-positive and 3 HIV-negative) developed pneumonia, 2 (1 HIV-positive and 1 HIV-negative) developed pharyngitis, and 2 (1 HIV- positive and 1 HIV-negative) developed flu-like syndromes sustained by C pneumoniae; in 4 subjects (2 HIV-positive and 2 HIV-negative) suffering from flu-like syndrome, no causal agents were found. Seven subjects (one HIV-positive and six HIV- negative) remained asymptomatic without any evidence of infection. The prevalence of antibodies to C pneumoniae in HIV-1-positive subjects observed in a sample of community members was significantly higher than in HIV-1-negative subjects. C pneumoniae seems to be involved in respiratory tract infections in HIV-1-infected subjects. Our data suggest that C pneumoniae should be included in the diagnostic approach of respiratory infections in HIV-infected subjects.
Abstract: Respiratory infections precipitate wheezing in many asthmatic patients and may be involved in the aetiopathogenesis of asthma. Several studies have demonstrated that viral infections may provoke asthma. Bacterial infections seem to play a minor role. However, Chlamydia pneumoniae has been recently reported as a possible cause of asthma. The aim of the present study was to evaluate the role of C. pneumoniae infection in acute exacerbations of asthma in adults. Seventy four adult out-patients with a diagnosis of acute exacerbation of asthma were studied. Acute and convalescent (> or = 3 weeks) serological determination of antibodies to cytomegalovirus, respiratory syncytial virus, adenovirus, influenza A and B, parainfluenza 1 and 3, Mycoplasma pneumoniae and Legionella pneumophila were performed by means of immunofluorescence tests. C. pneumoniae specific antibodies were detected by two microimmunofluorescence tests using a specific antigen (TW-183) and a kit with three chlamydial antigens. Pharyngeal swab specimens were also obtained for C. pneumoniae identification. Samples for bacterial culture were obtained in patients with productive cough (15 out of 74 patients). Fifteen patients (20%) presented seroconversion to at least one of the studied pathogens. Seven were found to be infected by virus, six by C. pneumoniae alone, and one by M. pneumoniae. One more patient showed seroconversion to C. pneumoniae and cytomegalovirus.(ABSTRACT TRUNCATED AT 250 WORDS)
Abstract: The incidence of Chlamydia pneumoniae as a cause of community-acquired pneumonia was evaluated in a one-year prospective study in 108 patients with community-acquired pneumonia. The bacteriological diagnosis was based on culture of sputum or bronchial aspirate and examination of acute and convalescent phase sera for Mycoplasma pneumoniae, Legionella pneumophila and Chlamydia pneumoniae. A definitive microbiological diagnosis was obtained in 58 (54%) patients. Chlamydia pneumoniae was the causative agent in 14 patients (13%) on the basis of positive serological tests; in 10 of the 14 patients Chlamydia pneumoniae was also detected by means of an indirect immunofluorescence test using pharyngeal swab specimens. In conclusion, Chlamydia pneumoniae seems to be a common etiological agent of community-acquired pneumonia, as increasingly reported in the last six to seven years.
Abstract: BACKGROUND--Chlamydia pneumoniae is drawing increasing attention as an agent of respiratory tract infection. Specific antibody prevalence in western countries is low in preschool children and reaches more than 50% in adults. However, little is known about the prevalence of this infection in immunocompromised subjects such as HIV-I infected patients. The aim of this study was to evaluate the seroprevalence of Chl pneumoniae in immunocompetent and immunocompromised (HIV-1 infected) paediatric and adult populations. METHODS--Between March 1991 and September 1992 764 healthy subjects (421 men and 343 women, age range six months-81 years), 96 HIV-I infected (73 men and 23 women, age range 18-35 years) and 126 HIV-I negative intravenous drug users (92 men and 34 women, age range 18-37 years), and 50 children (23 boys and 27 girls, age range 8-123 months) with vertically transmitted HIV-I infection were studied. For each subject an HIV-I test (ELISA and Western blot) was performed, together with a microimmunofluorescence test for IgG and IgM antibodies to Chl pneumoniae specific antigen (TW-183). RESULTS--In the healthy population a low prevalence (11%) was observed in children under 10 years of age, which increased progressively to 58% in adults over 70 years. In the HIV-I infected population Chl pneumoniae seroprevalence was higher than in immunocompetent controls (children, 26% v 11%; drug users, 60% v 40%). Moreover, in drug users this difference was also observed in comparison with HIV-1 negative intravenous drug users (60% v 33%). CONCLUSIONS--Our data on Chl pneumoniae seroprevalence in a healthy population are consistent with those reported by others in western countries. Moreover, HIV-I infected subjects seem to be at higher risk of developing Chl pneumoniae infections.
Abstract: The effects of bezafibrate on 14C-acetate incorporation into non-saponifiable lipids and on degradation of native and acetylated [125I] low-density lipoproteins (LDL) in cultured human monocytes has been evaluated. The presence of bezafibrate in the incubation medium resulted in a decrease of labelled acetate incorporation into non-saponifiable lipids. In parallel with the decrease in sterol synthesis, bezafibrate produced an increase in total and specific degradation of native low-density lipoproteins, whereas the degradation of acetylated low-density lipoproteins was not affected by the drug. These data, though obtained with concentrations of bezafibrate in the incubation medium greater than those encountered in ordinary therapeutic conditions, support the hypothesis that bezafibrate inhibits cholesterol biosynthesis and increases removal of low-density lipoproteins by activating the specific receptor pathway.
Abstract: In incubated blood mononuclear cells from normal subjects bezafibrate inhibited the incorporation of 14C-acetate into squalene, methylsterols and cholesterol. Similarly, the drug produced a sharp decrease of the incorporation of labelled 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) into non-saponifiable lipids, while the incorporation of 14C-mevalonate was unaffected by the presence of bezafibrate in the incubation mixture. This strongly suggests that bezafibrate inhibits HMG-CoA reductase activity. In cultured cells from patients with heterozygous familial hypercholesterolaemia the presence of bezafibrate in the incubation medium resulted in an inhibition of the incorporation of labelled acetate into non-saponifiable lipids. Bezafibrate then inhibits cholesterol biosynthesis in cells from normal and hypercholesterolaemic patients and this effect is likely, to contribute to the hypocholesterolaemic activity of the drug.
Abstract: Bezafibrate was given for 15 days at a dose of 200 mg t.i.d. to 4 normolipidemic subjects, to 5 patients with putative heterozygous familial hypercholesterolemia, and to 6 patients with primary hypercholesterolemia of the non-familial type. At the end of the treatment, the rate of incorporation of labelled acetate into non-saponifiable lipids in freshly isolated blood mononuclear cells decreased in all subjects. On the average, acetate incorporation decreased by 31% in cells from normolipidemic subjects, 41% in cells from familial, and 45% in cells from non-familial hypercholesterolemia patients. Results of the present study suggest that the lowering effect of bezafibrate on serum cholesterol is mainly due to the inhibition of cholesterol synthesis through the suppression of HMG-CoA reductase as was demonstrated in rat hepatocytes and in cultured human blood mononuclear cells.
Abstract: The hypocholesterolaemic drug Benfluorex has been shown to inhibit the rate of sterol synthesis in rat hepatocytes. At present no data on a similar effect in human cells are available. The results of the present study demonstrate that Benfluorex has an inhibitory activity on the incorporation of 14C-acetate and of 14C-HMG-CoA into non-saponifiable lipids in human blood mononuclear cells incubated in lipid-deficient medium. The lack of effect on the incorporation of 14C-mevalonate into non-saponifiable lipids strongly suggests that the reduction of sterol biosynthesis is mainly due to the inhibition of HMG-CoA reductase activity.
