Penicillins vs trimethoprim-based regimens for acute bacterial exacerbations of chronic bronchitis: meta-analysis of randomized controlled trials.

OBJECTIVE: To compare the effectiveness and toxicity of semisynthetic penicillins (SSPs) (amoxicillin, ampicillin, pivampicillin) and trimethoprim-based regimens (trimethoprim, trimethoprim-sulfamethoxazole, trimethoprim-sulfadiazine) in treating acute bacterial exacerbations of chronic bronchitis (ABECB). DATA SOURCES: We searched MEDLINE, EMBASE, Current Contents, and the Cochrane Central Register of Controlled Trials to identify and extract data from relevant randomized controlled trials (RCTs). STUDY SELECTION: Only RCTs comparing penicillins with trimethoprim-based regimens for the treatment of patients with ABECB that reported data on effectiveness, toxicity, or mortality were considered eligible for this meta-analysis. SYNTHESIS: Out of 134 RCTs identified in the search, 5 RCTs involving 287 patients were included in the analysis. There were no differences between patients with ABECB treated with SSPs and those treated with trimethoprim, alone or in combination with a sulfonamide, in treatment success (intention-to-treat patients: n = 262, odds ratio [OR] 1.68, 95% confidence interval [CI] 0.91-3.09; clinically evaluable patients: n = 246, OR 1.59, 95% CI 0.79-3.20) or number of drug-related adverse events in general (n = 186 patients, OR 0.37, 95% CI 0.11-1.24), frequency of diarrhea or skin rashes, or number of withdrawals due to adverse events (n = 179 patients, OR 0.27, 95% CI 0.07-1.03). CONCLUSION: Based on limited evidence leading to wide CIs of the estimated treatment effects, SSPs and trimethoprim-based regimens seem to be equivalent in terms of effectiveness and toxicity for ABECB.

Investigational antimicrobial drugs for bloodstream infections.

Bloodstream infections, especially those arising from multidrug-resistant strains, are an alarming public health threat requiring continuous efforts for new drug development. In this review, antibiotics at an advanced development stage for the treatment of patients with bloodstream infections are identified through a search of the available literature sources. Eight compounds currently undergoing phase II and/or phase III trials were identified. Isavuconazole, a triazole, is undergoing a phase III trial for the potential treatment of candidemia. Ceftobiprol medocaril, which belongs to the cephalosporin class, is undergoing regulatory review for the treatment of skin infections. Three lipoglycopeptides, oritavancin, dalbavancin and telavancin, are being tested against Gram-positive cocci in clinical trials. Also, human lactoferrin peptide 1-11, which appears to be a promising agent, is being tested in patients with Staphylococcus epidermidis bacteremia and in patients with candidemia. Iclaprim, a novel dihydrofolate reductase inhibitor, has completed two phase III trials for complicated skin and skin structure infections. The revival of an old class of antibiotics, polymyxins, in an effort to combat resistance, has also necessitated further investigation of these agents; colistin (polymyxin E) is at the forefront of this class of compounds, and is being assessed in a phase III efficacy trial. This overview of investigational antibiotics for bloodstream infections highlights that the pace of antimicrobial drug research and development is slower than the evolution of resistance. Only eight relevant compounds were identified in the pipeline of antibiotic research, none of which demonstrate a novel mechanism of action.

Respiratory fluoroquinolones for the treatment of community-acquired pneumonia: a meta-analysis of randomized controlled trials.

BACKGROUND: We investigated whether the use of respiratory fluoroquinolones was associated with better clinical outcomes compared with the use of macrolides and beta- lactams among adults with pneumonia. METHODS: We searched PubMed, Current Contents, Scopus, EMBASE, ClinicalTrials.gov and Cochrane with no language restrictions. Two reviewers independently extracted data from published trials that compared fluoroquinolones (levofloxacin, moxifloxacin, gemifloxacin) with macrolides or beta-lactams or both. A meta-analysis was performed with the clinical outcomes of mortality, treatment success and adverse outcomes. RESULTS: We included 23 trials in our meta-analysis. There was no difference in mortality among patients who received fluoroquinolones or the comparator antibiotics (OR 0.85, 95% CI 0.65-1.12). Pneumonia resolved in more patients who received fluoroquinolones compared with the comparator antibiotics for the included outcomes in the intention-to-treat population (OR 1.17, 95% CI 1.00-1.36), clinically evaluable population (OR 1.26, 95% CI 1.06-1.50) and the microbiologically assessed population (OR 1.67, 95% CI 1.28-2.20). Fluoroquinolones were more effective than a combination of beta-lactam and macrolide (OR 1.39, 95% CI 1.02-1.90). They were also more effective for patients with severe pneumonia (OR 1.84, 95% CI 1.02-3.29), those who required admission to hospital (OR = 1.30, 95% CI 1.04-1.61) and those who required intravenous therapy (OR = 1.44, 15% CI 1.13-1.85). Fluoroquinolones were more effective than beta-lactam and macrolide in open-label trials (OR = 1.35, 95% CI 1.08-1.69) but not in blinded randomized controlled trials (OR = 1.13, 95% CI 0.85-1.50). INTERPRETATION: Fluoroquinolones were associated with higher success of treatment for severe forms of pneumonia; however, a benefit in mortality was not evident. A randomized controlled trial that includes patients with severe pneumonia with or without bacteremia is needed.

Comparison of first-line with second-line antibiotics for acute exacerbations of chronic bronchitis: a metaanalysis of randomized controlled trials.

BACKGROUND: Although acute exacerbations of chronic bronchitis (AECBs) are common, there has been no metaanalysis that focused on the optimum regimen. METHODS: To evaluate the comparative effectiveness and safety of first-line antimicrobial agents (ie, amoxicillin, ampicillin, pivampicillin, trimethoprim/sulfamethoxazole, and doxycycline) and second-line antimicrobial agents (ie, amoxicillin/clavulanic acid, macrolides, second-generation or third-generation cephalosporins, and quinolones) for the treatment of patients with AECB, in an era of increasing antimicrobial resistance among the microbes responsible for AECB, we performed a metaanalysis of randomized controlled trials (RCTs) retrieved through searches of the PubMed and the Cochrane databases. RESULTS: Twelve RCTs were included in the metaanalysis. First-line antibiotics were associated with lower treatment success compared to second-line antibiotics in the clinically evaluable patients (odds ratio [OR], 0.51; 95% confidence interval [CI], 0.34 to 0.75). There were no differences among the compared regimens regarding mortality (OR, 0.64; 95% CI, 0.25 to 1.66) or treatment success (OR, 0.56; 95% CI, 0.22 to 1.43) in microbiologically evaluable patients, or adverse effects in general (OR, 0.75; 95% CI, 0.39 to 1.45) or diarrhea in particular (OR, 1.58; 95% CI, 0.74 to 3.35). CONCLUSIONS: Compared to first-line antibiotics, second-line antibiotics are more effective, but not less safe, when administered to patients with AECB. The available data did not allow for stratified analyses according to the presence of risk factors for poor outcome, such as increased age, impaired lung function, airway obstruction, and frequency of exacerbations; this fact should be taken into consideration when interpreting the findings of this metaanalysis.

Trends of mortality due to septicemia in Greece: an 8-year analysis.

BACKGROUND: Infectious diseases are among the major causes of death worldwide. We evaluated the trends of mortality due to septicemia in Greece and compared it with mortality due to other infections. METHODS: Data on mortality stratified by cause of death during 2003-2010 was obtained from the Hellenic Statistical Authority. Deaths caused by infectious diseases were grouped by site of infection and analyzed using SPSS 17.0 software. RESULTS: 45,451 deaths due to infections were recorded in Greece during the 8-year period of time, among which 12.2% were due to septicemia, 69.7% pneumonia, 1.5% pulmonary tuberculosis, 0.2% influenza, 0.5% other infections of the respiratory tract, 7.9% intra-abdominal infections (IAIs), 2.5% urinary tract infections (UTIs), 2.2% endocarditis or pericarditis or myocarditis, 1.6% hepatitis, 1% infections of the central nervous system, and 0.7% other infections. A percentage of 99.4% of deaths due to septicemia were caused by bacteria that were not reported on the death certificate (noted as indeterminate septicemia). More deaths due to indeterminate septicemia were observed during 2007-2010 compared to 2003-2006 (3,558 versus 1,966; p<0.05). CONCLUSION: Despite the limitations related to the quality of death certificates, this study shows that the mortality rate due to septicemia has almost doubled after 2007 in Greece. Proportionally, septicemia accounted for a greater increase in the mortality rate within the infectious causes of death for the same period of time. The emergence of resistance could partially explain this alarming phenomenon. Therefore, stricter infection control measures should be urgently applied in all Greek healthcare facilities.

MRSA in Africa: filling the global map of antimicrobial resistance.

We sought to assess the prevalence of methicillin-resistance among Staphylococcus aureus isolates in Africa. We included articles published in 2005 or later reporting for the prevalence of MRSA among S. aureus clinical isolates. Thirty-two studies were included. In Tunisia, the prevalence of MRSA increased from 16% to 41% between 2002-2007, while in Libya it was 31% in 2007. In South Africa, the prevalence decreased from 36% in 2006 to 24% during 2007-2011. In Botswana, the prevalence varied from 23-44% between 2000-2007. In Algeria and Egypt, the prevalence was 45% and 52% between 2003-2005, respectively. In Nigeria, the prevalence was greater in the northern than the southern part. In Ethiopia and the Ivory Coast, the prevalence was 55% and 39%, respectively. The prevalence of MRSA was lower than 50% in most of the African countries, although it appears to have risen since 2000 in many African countries, except for South Africa.

Extended or continuous versus short-term intravenous infusion of cephalosporins: a meta-analysis.

The authors sought to study whether extended or continuous infusion of cephalosporins is associated with better clinical outcomes than short-term infusion. PubMed and Scopus databases were systematically searched. Studies reporting the clinical outcomes of patients receiving extended or continuous infusion (≥3 or 24 h, respectively) versus short-term infusion (≤1 h) of cephalosporins were considered eligible. Eleven studies (1250 clinically evaluable patients) were included. Clinical cure and mortality were not statistically different between the compared groups (risk ratio: 1.14; 95% CI: 0.94-1.37 and risk ratio: 0.96; 95% CI: 0.80-1.15, respectively). This meta-analysis did not show a difference in clinical cure or mortality regarding extended or continuous versus short-term intravenous infusion of cephalosporins. However, in most of the included studies, patients in the extended/continuous infusion group received a substantially lower total dosage of antibiotic than those in the short-term group for the total duration of treatment.

Age distribution of cases of 2009 (H1N1) pandemic influenza in comparison with seasonal influenza.

INTRODUCTION: Several aspects of the epidemiology of 2009 (H1N1) pandemic influenza have not been accurately determined. We sought to study whether the age distribution of cases differs in comparison with seasonal influenza. METHODS: We searched for official, publicly available data through the internet from different countries worldwide on the age distribution of cases of influenza during the 2009 (H1N1) pandemic influenza period and most recent seasonal influenza periods. Data had to be recorded through the same surveillance system for both compared periods. RESULTS: For 2009 pandemic influenza versus recent influenza seasons, in USA, visits for influenza-like illness to sentinel providers were more likely to involve the age groups of 5-24, 25-64 and 0-4 years compared with the reference group of >64 years [odds ratio (OR) (95% confidence interval (CI)): 2.43 (2.39-2.47), 1.66 (1.64-1.69), and 1.51 (1.48-1.54), respectively]. Pediatric deaths were less likely in the age groups of 2-4 and <2 years than the reference group of 5-17 years [OR (95% CI): 0.46 (0.25-0.85) and 0.49 (0.30-0.81), respectively]. In Australia, notifications for laboratory-confirmed influenza were more likely in the age groups of 10-19, 5-9, 20-44, 45-64 and 0-4 years than the reference group of >65 years [OR (95% CI): 7.19 (6.67-7.75), 5.33 (4.90-5.79), 5.04 (4.70-5.41), 3.12 (2.89-3.36) and 1.89 (1.75-2.05), respectively]. In New Zealand, consultations for influenza-like illness by sentinel providers were more likely in the age groups of <1, 1-4, 35-49, 5-19, 20-34 and 50-64 years than the reference group of >65 years [OR (95% CI): 2.38 (1.74-3.26), 1.99 (1.62-2.45), 1.57 (1.30-1.89), 1.57 (1.30-1.88), 1.40 (1.17-1.69) and 1.39 (1.14-1.70), respectively]. CONCLUSIONS: The greatest increase in influenza cases during 2009 (H1N1) pandemic influenza period, in comparison with most recent seasonal influenza periods, was seen for school-aged children, adolescents, and younger adults.

Inhaled colistin for the treatment of tracheobronchitis and pneumonia in critically ill children without cystic fibrosis.

Data regarding the role of inhaled colistin in critically ill pediatric patients without cystic fibrosis are scarce. Three children (one female), admitted to the intensive care unit (ICU) of a tertiary-care pediatric hospital in Athens, Greece, during 2004-2009 received inhaled colistin as monotherapy for tracheobronchitis (two children), and as adjunctive therapy for necrotizing pneumonia (one child). Colistin susceptible Acinetobacter baumannii and Pseudomonas aeruginosa were isolated from the cases' bronchial secretions specimens. All three children received inhaled colistin at a dosage of 75 mg diluted in 3 ml of normal saline twice daily (1,875,000 IU of colistin daily), for a duration of 25, 32, and 15 days, respectively. All three children recovered from the infections. Also, a gradual reduction, and finally total elimination of the microbial load in bronchial secretions was observed during inhaled colistin treatment in the reported cases. All three cases were discharged from the ICU. No bronchoconstriction or any other type of toxicity of colistin was observed. In conclusion, inhaled colistin was effective and safe for the treatment of two children with tracheobronchitis, and one child with necrotizing pneumonia. Further studies are needed to clarify further the role of inhaled colistin in pediatric critically ill patients without cystic fibrosis.

Inhaled colistin as monotherapy for multidrug-resistant gram (-) nosocomial pneumonia: a case series.

BACKGROUND: Reports of patients with polymyxin-only susceptible gram-negative nosocomial pneumonia treated with inhaled, but without concurrent intravenous, colistin are rare. METHODS: Patients admitted in a tertiary 450-bed tertiary care centre during the period 05/01/2005-05/31/2007 and receiving colistin through nebulization, but not systemically, were included in this retrospective case series. RESULTS: Five patients (three with ventilator-associated pneumonia and two with nosocomial pneumonia) received colistin through nebulization without concomitant intravenous colistin. The isolated pathogens were Acinetobacter baumannii (three cases), Pseudomonas aeruginosa (one case) and the combination of Klebsiella pneumoniae, A. baumannii and P. aeruginosa (one case). They were susceptible only to colistin (three cases) or to colistin and gentamicin (two cases). Intravenous antimicrobial agents given concurrently were piperacillin/tazobactam, meropenem, ceftriaxone and ciprofloxacin; isolated pathogens were resistant to these agents. Four (80%) out of the five patients were cured, survived and were discharged. One patient died. No colistin-related adverse event was observed. CONCLUSIONS: The experience from this case series and other relevant recent reports suggest that treatment of pneumonia due to polymyxin-only susceptible gram-negative bacilli with inhaled colistin (without concurrent systemic administration) deserves further careful investigation.

Informed consent: how much and what do patients understand?

OBJECTIVE: We sought to evaluate the degree of patients' understanding of several aspects of the informed consent process for surgery and clinical research. METHODS: We conducted a systematic search of PubMed (1961-2006) to identify relevant articles. RESULTS: We retrieved 23 and 30 eligible for inclusion articles regarding informed consent for surgery and clinical research, respectively. Regarding surgery, adequate overall understanding of the information provided and of the risks associated with surgery was shown in 6 of 21 (29%) and 5 of 14 (36%) studies providing relevant data, respectively. Regarding clinical research, adequate understanding of the aim of the study, the process of randomization, voluntarism, withdrawal, and the risks and the benefits of treatment was shown in 14 of 26 (54%), 4 of 8 (50%), 7 of 15 (47%), 7 of 16 (44%), 8 of 16 (50%), and 4 of 7 (57%) of studies providing relevant data, respectively. Satisfaction by the amount of the given information was shown in 7 of 12 (58%) studies involving surgery and 12 of 15 (80%) studies involving clinical research. CONCLUSIONS: Further attention should be drawn on enhancing patients' understanding regarding several components of the informed consent process for surgery and clinical research.

Antibiotic-lock therapy for long-term catheter-related bacteremia: a review of the current evidence.

Catheter-related bloodstream infections (CRBSIs) are a major cause of morbidity and mortality, especially among patients receiving hemodialysis, parenteral nutrition and chemotherapy. Antibiotic-lock therapy (ALT) represents a promising technique in the modern treatment of CRBSIs. In this review, we attempt to clarify the potential role of ALT in the treatment of long-term catheter-related bacteremia, based on the available evidence from published studies reporting on this issue. We identified 28 articles that were considered appropriate to be included in our review, only three of which were comparative studies. There is some evidence that ALT administered concurrently with systemic therapy may represent a significant therapeutic approach for CRBSIs involving long-term catheters. Prolonged infection-free catheter survival in the reported series is suggestive of sterilization of the catheters by ALT. The only reported comparison shows better outcome with ALT than with catheter exchange. Immunodeficient states, such as HIV, and the use of totally implanted devices instead of tunneled catheters may predispose to CRBSI treatment failure. No serious adverse effects, such as emergence of resistance or increased infectious complications, were found to be associated with the use of ALT in the reviewed studies. However, more comparative studies should be performed to examine this important therapeutic issue further.