Spotlight on inhaled ciprofloxacin and its potential in the treatment of non-cystic fibrosis bronchiectasis.

Non-cystic fibrosis bronchiectasis (NCFB) is a severe chronic illness characterized by irreversible dilation of airways and thickening of bronchial walls, chronic inflammation, repeated infections, and progressive obstruction of the airways. In contrast to cystic fibrosis bronchiectasis (CFB), which is a well-defined genetic disorder, NCFB is a heterogeneous disease caused by many different medical entities. Inhaled antibiotics are effective for patients with CFB, but their efficacy in NCFB has not been proven. The main pathogens involved in the colonization of patients with bronchiectasis are Haemophilus influenza, Moraxella catarrhalis, Staphylococcus aureus, and Pseudomonas aeruginosa. The latter is associated with increased morbidity and mortality. In addition, in NCFB, P. aeruginosa strains are frequently more resistant than those in CFB. At present, there are no approved inhaled antibiotic therapies for NCFB patients. Inhaled ciprofloxacin has been under investigation in the last few years. In two phase II randomized, double-blind, placebo-controlled trials, the use of inhaled ciprofloxacin was significantly associated with reduction in sputum bacterial density and greater eradication rates. In four phase III randomized, double-blind, placebo-controlled trials, the results regarding the time of the first exacerbation and the rate of exacerbations were inconsistent. Specifically, ORBIT-4 and RESPIRE-1 trials showed clinical benefit (prolongation of the time of the first exacerbation and reduced rate of exacerbations in the treatment group compared to the placebo group), whereas the ORBIT-3 and RESPIRE-2 failed to achieve their primary endpoints. The RESPIRE-1 was the first trial that examined the 14-days on/off course separate from the standard 28-days on/off regimen, which is based on CFB protocol treatments. The current data on the efficacy of inhaled ciprofloxacin are encouraging, but further evaluation is needed to determine the appropriate target group and the ideal duration of treatment.

Women Physicians in Byzantium.

Women were allowed to practice the medical profession during the Byzantine Empire. The presence of female physicians was not an innovation of the Byzantine era but actually originated from ancient Greece and Rome. The studies and the training of women doctors were apparently equivalent to those of their male colleagues. The principal medical specialties of the female doctors were gynecology and midwifery. Byzantine legislation treated relatively equally both female and male doctors. For this reason, it can be assumed that the presence of female doctors was correlated with the position of women in Byzantine society. However, there is not sufficient information in the literature to clarify whether female and male doctors used to earn equal payment for the same service.

The antibiotic pipeline for multi-drug resistant gram negative bacteria: what can we expect?

INTRODUCTION: A real concern in the medical community is the increasing resistance of bacteria, especially that of Gram-negative types. New antibiotics are currently under clinical development, promising to tackle severe infections caused, especially, by multi-drug resistant (MDR) bacteria and broaden the armamentarium of clinicians. AREAS COVERED: We searched PUBMED and GOOGLE databases. Combinations of already approved ß-lactams or monobactams with new ß-lactamase inhibitors [imipenem-cilastatin/MK-7655 (relebactam), meropenem/RPX7009 (vaborbactam), ceftaroline/avibactam, aztreonam/avibactam], new ß-lactams (S-649266, BAL30072), aminoglycosides (plazomicin), quinolones (finafloxacin) and tetracyclines (eravacycline) were included in the review. Expert commentary: For the majority of the upcoming antibiotics the currently available data is limited to their microbiology and pharmacokinetics. Their effectiveness and safety against infections due to MDR bacteria remain to be proved. Significant issues are also the impact of these antibiotics on the human intestinal microbiota and their possible co-administration with already-known antimicrobial agents in difficult-to-treat-infections; further studies should be conducted for these objectives.

Options for treating carbapenem-resistant Enterobacteriaceae.

PURPOSE OF REVIEW: To address the therapeutic management of carbapenem-resistant Enterobacteriaceae on the basis of literature of the last 12 months. RECENT FINDINGS: Retrospective and prospective (nonrandomized noncontrolled) studies provide data regarding the management of infections due to carbapenem-resistant Enterobacteriaceae. The combination of a carbapenem with colistin or high-dose tigecycline or aminoglycoside or even triple carbapenem-containing combinations if the minimum inhibitory concentration (MIC) range of carbapenem (meropenem and imipenem) resistance is 8 mg/l or less seems to have an advantage over monotherapy with either colistin or tigecycline or fosfomycin. For Enterobacteriaceae with MIC for carbapenems over 8 mg/l, combination regimens involve colistin, tigecycline usually administered in a double dose than that suggested by its manufacturer, fosfomycin and aminoglycosides in various combinations. SUMMARY: Suggestions based on the limited literature cannot be made safely. Combination regimens involving carbapenems for Enterobacteriaceae with MICs 8 mg/l or less for carbapenems (in dual combination with colistin or high-dose tigecycline or aminoglycoside or even triple combinations) seem to confer some therapeutic advantage over monotherapy. For Enterobacteriaceae with higher than the above-mentioned MICs, a combination of two or even three antibiotics among colistin, high-dose tigecycline, aminoglycoside and fosfomycin seems to confer decreased mortality.

Effectiveness and safety of high-dose tigecycline-containing regimens for the treatment of severe bacterial infections.

Here we review the effectiveness and safety of high-dose tigecycline (200mg daily). A systematic search was performed in PubMed and Scopus databases as well as of abstracts presented at scientific conferences. Eight studies (263 patients; 58% critically ill) were included, comprising one randomised controlled trial (RCT), four non-randomised cohorts and three case reports. Klebsiella pneumoniae was the most commonly isolated pathogen (reported in seven studies). In the RCT, response in the clinically evaluable patients was 85.0% (17/20) in the 100mg every 12h (q12h) group and 69.6% (16/23) in the 75mg q12h group (P=0.4). More episodes of diarrhoea, treatment-related nausea and vomiting developed in the high-dose group (14.3% vs. 2.8%, 8.6% vs. 2.8% and 5.7% vs. 2.8%, respectively; P>0.05 for all comparisons). Three (8.6%) and 7 (19.6%) patients died in the 200mg and 150mg daily dose groups, respectively. The cohort studies enrolled patients with severe infections, including ventilator-associated pneumonia and complicated intra-abdominal infections. Mortality with high-dose tigecycline (100mg q12h) in the cohort studies ranged from 8.3% to 26%; mortality in the low-dose groups (50mg q12h) ranged from 8% to 61% and depended on the severity of the underlying infection. There are limited available data regarding the effectiveness and safety of high-dose tigecycline. Most of the data come from critically ill patients with difficult-to-treat infections. Pharmacokinetic/pharmacodynamic properties of tigecycline suggest that high-dose regimens may be more effective than low-dose regimens. Candidates for administration of high-dose tigecycline should be also defined.

Antimicrobial activity and clinical effectiveness of sisomicin: an evaluation of the literature (1995-2011).

The authors sought to evaluate whether sisomicin has a place in the current therapeutic armamentarium. PubMed and Scopus databases were systematically searched. Ten cohort studies and 11 case reports and case series were included evaluating, in total, 383 Gram-positive and 83 Gram-negative isolates. Sisomicin was active in vitro against 41% of Enterococcus spp., 97% of Staphylococcus spp. and was the most active in vitro (74%) aminoglycoside against Stenotrophomonas maltophilia isolates in one study. Regarding clinical effectiveness, sisomicin topical cream was effective in all 290 patients with pyoderma in one study, while the intravenous formulation of sisomicin was effective as prophylaxis for the development of postoperative pneumonia in 91% of lung surgery patients in another. In conclusion, sisomicin may be useful against certain pathogens; however, clinical data are scarce. Further studies are needed and may shed additional light in this area.

Impact of vancomycin minimum inhibitory concentration on clinical outcomes of patients with vancomycin-susceptible Staphylococcus aureus infections: a meta-analysis and meta-regression.

Although the vancomycin minimum inhibitory concentration (VMIC) susceptibility breakpoint for Staphylococcus aureus was recently lowered to ≤2 mg/L, it is argued that isolates in the higher levels of the susceptible range may bear adverse clinical outcomes. Clinical outcomes (all-cause mortality and treatment failure) of patients with S. aureus infections by 'high-VMIC' (conventionally defined as VMIC >1 mg/L but ≤2 mg/L) and 'low-VMIC' (VMIC≤1 mg/L) isolates were compared by performing a systematic review and meta-analysis. The effect of potential confounders was assessed by univariate meta-regression analyses. In total, 33 studies (6210 patients) were included. Most studies were retrospective (28/33), used the Etest (22/33) and referred to meticillin-resistant S. aureus (MRSA) infections (26/33) and bacteraemia (23/33). Irrespective of VMIC testing method, meticillin resistance and site of infection, the high-VMIC group had higher mortality [relative risk (RR)=1.21 (95% confidence interval 1.03-1.43); 4612 patients] and more treatment failures [RR=1.67 (1.26-2.21); 2049 patients] than the low-VMIC group. The results were not affected by the potential confounders and were reproduced in the subset of patients with MRSA infections [mortality, RR=1.19 (1.02-1.40), 2956 patients; treatment failure, RR=1.69 (1.26-2.25), 1793 patients]. In conclusion, infection by vancomycin-susceptible S. aureus with VMIC>1mg/L appears to be associated with higher mortality than VMIC≤1mg/L. Further research is warranted to verify these results and to assess the impact of VMIC on meticillin-susceptible S. aureus infections. Evaluation of alternative antimicrobial agents also appears justified.

Stenotrophomonas maltophilia infections in a general hospital: patient characteristics, antimicrobial susceptibility, and treatment outcome.

INTRODUCTION: Stenotrophomonas maltophilia is acquiring increasing importance as a nosocomial pathogen. METHODS: We retrospectively studied the characteristics and outcome of patients with any type of S. maltophilia infection at the University Hospital of Heraklion, Crete, Greece, between 1/2005-12/2010. S. maltophilia antimicrobial susceptibility was tested with the agar dilution method. Prognostic factors for all-cause in-hospital mortality were assessed with multivariate logistic regression. RESULTS: Sixty-eight patients (median age: 70.5 years; 64.7% males) with S. maltophilia infection, not related to cystic fibrosis, were included. The 68 patients were hospitalized in medical (29.4%), surgical (26.5%), hematology/oncology departments (23.5%), or the intensive care units (ICU; 20.6%). The most frequent infection types were respiratory tract (54.4%), bloodstream (16.2%), skin/soft tissue (10.3%), and intra-abdominal (8.8%) infection. The S. maltophilia-associated infection was polymicrobial in 33.8% of the cases. In vitro susceptibility was higher to colistin (91.2%), trimethoprim/sulfamethoxazole and netilmicin (85.3% each), and ciprofloxacin (82.4%). The empirical and the targeted treatment regimens were microbiologically appropriate for 47.3% and 63.6% of the 55 patients with data available, respectively. Most patients received targeted therapy with a combination of agents other than trimethoprim/sulfamethoxazole. The crude mortality and the mortality and the S. maltophilia infection-related mortality were 14.7% and 4.4%, respectively. ICU hospitalization was the only independent prognostic factor for mortality. CONCLUSION: S. maltophilia infection in a general hospital can be associated with a good prognosis, except for the patients hospitalized in the ICU. Combination reigmens with fluoroquinolones, colistin, or tigecycline could be alternative treatment options to trimethoprim/sulfamethoxazole.

Impact of antibiotic MIC on infection outcome in patients with susceptible Gram-negative bacteria: a systematic review and meta-analysis.

The objective of this study was to analyze the impact of MIC values within the susceptible range of antibiotics on the outcomes of patients with Gram-negative infections. The PubMed and Scopus electronic databases were searched. We identified 13 articles (1,469 patients) that studied the impact of antibiotic MICs on the outcomes of infections; ß-lactams were studied in 10 of them. Infections due to Salmonella enterica strains with high fluoroquinolone MICs were associated with more treatment failures than those due to strains with low MICs (relative risk [RR], 5.75; 95% confidence interval [CI], 1.77 to 18.71). Among non-Salmonella enterobacteriaceae, there was no difference in treatment failures depending on the MIC value (RR, 1.18; 95% CI, 0.71 to 1.97); however, a higher all-cause mortality was observed for patients infected with strains with high MICs (RR, 2.03; 95% CI, 1.05 to 3.92). More treatment failures were observed for patients infected with nonfermentative Gram-negative bacilli when strains had high MICs (RR, 5.54; 95% CI, 2.72 to 11.27). The mortality rate for patients with infections with Gram-negative nonfermentative bacilli with high MICs was also higher than for those with low MICs (RR, 2.39; 95% CI, 1.19 to 4.81). The limited available data suggest that there is an association between high MICs, within the susceptible range, and adverse outcomes for patients with Gram-negative infections.

Therapeutic options for infections with Enterobacteriaceae producing carbapenem-hydrolyzing enzymes.

Enterobacteriaceae that produce serine carbapenemases or metallo-ß-lactamases, such as KPC, OXA-48, VIM or NDM, respectively, are spreading mostly as nosocomial pathogens worldwide. Such strains are typically resistant to most if not all available antimicrobials. Specific relevant clinical data are scarce to guide the determination of the most appropriate treatment options. Data on antimicrobial susceptibility, resistance development, synergy, pharmacokinetic and pharmacodynamic parameters of the candidate regimens, as well as the experience from the treatment of infections with nonfermenting Gram-negative pathogens, can aid in this regard. Colistin and tigecycline are most likely to be active in vitro against Enterobacteriaceae producing carbapenem-hydrolyzing ß-lactamases, but resistance development is of concern. Individual members of the aminoglycoside class can also be active in vitro, while carbapenems or aztreonam (specifically for metallo-ß-lactamase producers) can have low minimum inhibitory concentrations. Current data do not reliably support the use of these agents as monotherapy for systemic infections. Several expanded-spectrum cephalosporins, such as ceftazidime, may be active against OXA-48 type producers. Fosfomycin might be useful as a last-resort option as part of combination regimens. Combination antimicrobial therapy with agents exhibiting synergy might also be of benefit, until novel effective agents could become clinically available.

Resistance to polymyxins: Mechanisms, frequency and treatment options.

Polymyxins act by binding to lipid A moiety of the bacterial lipopolysaccharide and subsequently disintegrating the bacterial membranes. The most important mechanism of resistance includes modifications of the bacterial outer membrane structure, including lipopolysaccharide. Lipopolysaccharide modification is mostly mediated by PmrA/PmrB and PhoP/PhoQ two-component regulatory systems. These mechanisms exist with some differences in many gram-negative bacterial species. Resistance to polymyxins is generally less than 10%. In specific regions, such as the Mediterranean basin, Korea and Singapore, they tend to be higher. Heteroresistance to polymyxins is associated with exposure to polymyxins and especially suboptimal therapeutic dosage. Polymyxin combination regimens, tigecycline and fosfomycin may be useful options for the treatment of polymyxin-resistant gram-negative infections.

The pleiotropic effects of statins and omega-3 fatty acids against sepsis: a new perspective.

The available therapeutic options for sepsis are restricted by their effectiveness and high cost. Emerging preliminary data suggest that statins and omega-3 fatty acids (OM3FA) may be associated with improved outcomes in terms of prevention and treatment of sepsis. We sought to review the current evidence on the effectiveness of their combined administration against sepsis, by carrying out a review of PubMed and Scopus databases for relevant studies, without imposing language or time restrictions. No clinical studies were identified regarding the effect of the combination treatment with statins and OM3FA on sepsis in terms of prevention or treatment. However, there is experimental evidence that both statins and OM3FA inhibit the inflammatory process at different levels, but also enhance inhibition at those levels that are common. There are also preliminary data supporting the beneficial effect of this combination on platelet function and other haemostatic mechanisms. Appropriately designed and powered clinical trials are warranted to investigate the effectiveness and safety of the combined administration of statins and OM3FA for the prevention and treatment of sepsis.

Increasing contribution of China in modern biomedical research. Statistical data from ISI Web of Knowledge.

BACKGROUND: China is one of the most rapidly developing countries with a huge population spreading on a chaotic area. For centuries Chinese medicine was based on tradition, religion and experience. However, the last two decades under the pressure of globalization Chinese medicine is turning gradually to evidence-based medicine, contributing in international biomedical research. MATERIAL/METHODS: A bibliometric analysis through the ISI Web of Knowledge was performed. We collected data regarding the amount of Chinese publications in different biomedical fields, the presence of Chinese authors in high impact international journals, the contribution of China's universities in research and finally the number and the quality of local Chinese journals, which have entered the ISI database. RESULTS: According to ISI database a significant increase occurred in both the quantity and quality of the Chinese biomedical publishing activity. This was indicated by the major rise in the amount of published papers, the average augmentation of citations per paper and the constantly increasing presence of Chinese researchers in top medical journals. Chinese institutions appeared also more productive and local journals gained more representation in the ISI database. CONCLUSIONS: China's contribution in biomedical research really blossomed after 1990 and especially after 2000. The extent of this contribution may not be proportional to the total research activity performed in China, but it is this part of knowledge that becomes exported and interacts with the rest of the international research activity, promoting research potential in biomedicine.

New antibiotics: optimal use in current clinical practice.

The optimal choice of antibacterial therapy among the few available options for infections caused by pathogens with advanced antimicrobial drug resistance is fundamental to maximize clinical effectiveness and minimize the likelihood for further resistance development. We herein review the available data on the effectiveness of antibiotics introduced in clinical practice during the past 10 years for specific clinical indications. Quinupristin-dalfopristin, linezolid, daptomycin and tigecycline have increased the available therapeutic options against specific types of meticillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium infections. The newer fluoroquinolones, moxifloxacin and gemifloxacin, along with the ketolide telithromycin and the oral third-generation cephalosporin cefditoren are particularly valuable for the treatment of specific types of multidrug-resistant Streptococcus pneumoniae infections. Tigecycline appears as a promising therapeutic option for infections caused by Enterobacteriaceae producing extended spectrum beta-lactamases (ESBLs), or multidrug-resistant Acinetobacter baumannii. Ertapenem and doripenem may be particularly useful against infections caused by ESBL-producing Enterobacteriaceae and multidrug-resistant Pseudomonas aeruginosa, respectively.

Fosfomycin for the treatment of infections caused by Gram-positive cocci with advanced antimicrobial drug resistance: a review of microbiological, animal and clinical studies.

BACKGROUND: The advancing antimicrobial drug resistance in Gram-positive cocci complicates the selection of appropriate therapy. The re-evaluation of older antibiotics may prove useful in expanding relevant therapeutic options. OBJECTIVE: We sought to evaluate fosfomycin for the treatment of infections caused by methicillin-resistant staphylococci, vancomycin-resistant enterococci, and penicillin-non-susceptible pneumococci. METHODS: We searched in PubMed, Scopus, and the Cochrane Library for studies evaluating the antimicrobial activity of fosfomycin against the above-mentioned pathogens, or the in vivo or clinical effectiveness of fosfomycin for the treatment of infections caused by these pathogens. RESULTS/CONCLUSIONS: As reported in the identified studies, the susceptibility rate of methicillin-resistant Staphylococcus aureus to fosfomycin was > or = 90% in 12/22, and 50-90% in 7/22 studies; the cumulative susceptibility rate was 87.9% (4240/4892 isolates). The cumulative susceptibility rate of vancomycin-resistant enterococci to fosfomycin was 30.3% (183/604 isolates), and that of penicillin-non-susceptible pneumococci was 87.2% (191/219 isolates). Clinical data show that fosfomycin, primarily in combination regimens, has been associated with clinical success in 28/29 (96.6%) cases of infection (mainly pneumonia, bacteremia, and meningitis) by fosfomycin-susceptible isolates of methicillin-resistant S. aureus. The above data support further research on the role of fosfomycin against infections caused by Gram-positive cocci with advanced antimicrobial drug resistance.

Fosfomycin for the treatment of infections caused by multidrug-resistant non-fermenting Gram-negative bacilli: a systematic review of microbiological, animal and clinical studies.

The treatment of multidrug-resistant (MDR), extensively drug-resistant or pandrug-resistant non-fermenting Gram-negative bacterial infections constitutes a challenge in an era of few new antibiotic choices. This mandates the re-evaluation of already existing antibiotics such as fosfomycin. We systematically reviewed the literature to assess the clinical and microbiological effectiveness of fosfomycin in the treatment of these infections by searching PubMed, Scopus and the Cochrane Library databases. In 23 microbiological studies identified, 1859 MDR non-fermenting Gram-negative bacterial isolates were examined. The susceptibility rate to fosfomycin of MDR Pseudomonas aeruginosa isolates was >or=90% and 50-90% in 7/19 and 4/19 relevant studies, respectively. Cumulatively, 511/1693 (30.2%) MDR P. aeruginosa isolates were susceptible to fosfomycin. Serotype O12 isolates exhibited greater susceptibility. Only 3/85 (3.5%) MDR Acinetobacter baumannii and 0/31 MDR Burkholderia spp. isolates were susceptible to fosfomycin. Variable criteria of susceptibility were used in the included studies. Fosfomycin was synergistic in combination with a beta-lactam, aminoglycoside or ciprofloxacin in 46/86 (53.5%) MDR P. aeruginosa isolates. One animal study found a good therapeutic effect of the combination fosfomycin/gentamicin against MDR P. aeruginosa endocarditis. In six clinical studies, 33 patients with MDR P. aeruginosa infections (mainly pulmonary exacerbations of cystic fibrosis) received fosfomycin (25/33 in combination with other antibiotics); 91% of the patients clinically improved. In conclusion, fosfomycin could have a role as a therapeutic option against MDR P. aeruginosa infections. Further research is needed to clarify the potential utility of this agent.

Tigecycline for the treatment of multidrug-resistant (including carbapenem-resistant) Acinetobacter infections: a review of the scientific evidence.

OBJECTIVES: New antibacterial agents are required for the treatment of infections caused by multidrug-resistant (MDR) Acinetobacter spp. Whether tigecycline constitutes an effective treatment option or not, is not well established. We sought to evaluate the available evidence regarding the microbiological activity and clinical effectiveness of tigecycline for MDR (including the subset of carbapenem-resistant) Acinetobacter spp. METHODS: We searched PubMed for relevant articles and extracted/evaluated the available evidence. RESULTS: We identified 22 microbiological studies reporting data for 2384 Acinetobacter spp. (1906 Acinetobacter baumannii). Susceptibility of at least 90% of the Acinetobacter isolates to tigecycline (with an MIC breakpoint of susceptibility < or =2 mg/L) was noted in 9/18 studies reporting data on MDR Acinetobacter and in 7/15 studies reporting specific data on carbapenem-resistant Acinetobacter. In an additional study reporting data for both resistance categories, adequate susceptibility of Acinetobacter spp. was observed by one (broth microdilution) of the methods employed. The effectiveness of tigecycline for MDR Acinetobacter infections was evaluated in eight identified clinical studies, reporting retrospective data regarding 42 severely ill patients, among whom 31 had respiratory tract infection (in 4 cases with secondary bacteraemia) and 4 had bacteraemia. Tigecycline therapy (in combination with other antibiotics in 28 patients) was effective in 32/42 cases. In three cases, resistance to tigecycline developed during treatment. CONCLUSIONS: Tigecycline showed considerable, though not consistent, antimicrobial activity against MDR (including carbapenem-resistant) Acinetobacter spp. However, data to support its clinical use, particularly for ventilator-associated pneumonia or bacteraemia, caused by these pathogens, are still limited.

Fluoroquinolones compared with beta-lactam antibiotics for the treatment of acute bacterial sinusitis: a meta-analysis of randomized controlled trials.

BACKGROUND: The presumed superiority of newer fluoroquinolones for the treatment of acute bacterial sinusitis is based on laboratory data but has not yet been established on clinical grounds. METHODS: We performed a meta-analysis of randomized controlled trials comparing the effectiveness and safety of fluoroquinolones and beta-lactams in acute bacterial sinusitis. RESULTS: We identified 8 randomized controlled trials investigating the newer "respiratory" fluoroquinolones moxifloxacin, levofloxacin and gatifloxacin. In the primary effectiveness analysis involving 2133 intention-to-treat patients from 5 randomized controlled trials, the extent of clinical cure and improvement did not differ between fluoroquinolones and beta-lactams (odds ratio [OR] 1.09, 95% confidence interval [CI] 0.85-1.39) at the test-of-cure assessment, which varied from 10 to 31 days after the start of treatment. Fluoroquinolones were associated with an increased chance of clinical success among the clinically evaluable patients in all of the randomized controlled trials (OR 1.29, 95% CI 1.03-1.63) and in 4 blinded randomized controlled trials (OR 1.45, 95% CI 1.05-2.00). There was no statistically significant difference between fluoroquinolones and amoxicillin-clavulanate (OR 1.24, 95% CI 0.93-1.65). Eradication or presumed eradication of the pathogens isolated before treatment was more likely with fluoroquinolone treatment than with beta-lactam treatment (OR 2.11, 95% CI 1.09-4.08). In the primary safety analysis, adverse events did not differ between treatments (OR 1.17, 95% CI 0.86-1.59). However, more adverse events occurred with fluoroquinolone use than with beta-lactam use in 2 blinded randomized controlled trials. The associations described here were generally consistent when we included 3 additional studies involving other fluoroquinolones (ciprofloxacin and sparfloxacin) in the analysis. INTERPRETATION: In the treatment of acute bacterial sinusitis, newer fluoroquinolones conferred no benefit over beta-lactam antibiotics. The use of fluoroquinolones as first-line therapy cannot be endorsed.

Arrhythmias associated with fluoroquinolone therapy.

Fluoroquinolones are widely used and well tolerated antibacterial agents. However, prolongation of the QT interval is an adverse effect associated with the use of fluoroquinolones. According to the available case reports and clinical studies, moxifloxacin carries the greatest risk of QT prolongation from all available quinolones in clinical practice and it should be used with caution in patients with predisposing factors for Torsades de pointes (Tdp). Although gemifloxacin, levofloxacin and ofloxacin are associated with a lower risk of QT prolongation compared with moxifloxacin, they should also be used with caution in patients with risk factors for QT prolongation. Ciprofloxacin appears to be associated with the lowest risk for QT prolongation and the lowest rate of Tdp. The overall risk of Tdp is small with the use of fluoroquinolones. Clinicians can minimise that risk by avoiding prescriptions of multiple medications associated with QT interval prolongation, especially in high-risk patients.

A bibliometric analysis in the fields of preventive medicine, occupational and environmental medicine, epidemiology, and public health.

BACKGROUND: Research in the fields of Preventive Medicine, Occupational/Environmental Medicine, Epidemiology and Public Health play an important role in the advancement of knowledge. In order to map the research production around the world we performed a bibliometric analysis in the above fields. METHODS: All articles published by different world regions in the above mentioned scientific fields and cited in the Journal Citation Reports (JCR) database of the Institute for Scientific Information (ISI) during the period 1995 and 2003, were evaluated. The research production of different world regions was adjusted for: a) the gross domestic product in 1995 US dollars, and b) the population size of each region. RESULTS: A total of 48,861 articles were retrieved and categorized. The USA led the research production in all three subcategories. The percentage of articles published by USA researchers was 43%, 44% and 61% in the Preventive Medicine, Epidemiology, and Public Health subcategories, respectively. Canada and Western Europe shared the second position in the first two subcategories, while Oceania researchers ranked second in the field of Public Health. CONCLUSION: USA researchers maintain a leadership position in the production of scientific articles in the fields of Preventive Medicine, Occupational/Environmental Medicine and Epidemiology, at a level similar to other scientific disciplines, while USA contribution to science in the field of Public Health is by all means outstanding. Less developed regions would need to support their researchers in the above fields in order to improve scientific production and advancement of knowledge in their countries.