Early treatment of COVID-19 with anakinra guided by soluble urokinase plasminogen receptor plasma levels: a double-blind, randomized controlled phase 3 trial.

Early increase of soluble urokinase plasminogen activator receptor (suPAR) serum levels is indicative of increased risk of progression of coronavirus disease 2019 (COVID-19) to respiratory failure. The SAVE-MORE double-blind, randomized controlled trial evaluated the efficacy and safety of anakinra, an IL-1α/ß inhibitor, in 594 patients with COVID-19 at risk of progressing to respiratory failure as identified by plasma suPAR ≥6 ng ml-1, 85.9% (n = 510) of whom were receiving dexamethasone. At day 28, the adjusted proportional odds of having a worse clinical status (assessed by the 11-point World Health Organization Clinical Progression Scale (WHO-CPS)) with anakinra, as compared to placebo, was 0.36 (95% confidence interval 0.26-0.50). The median WHO-CPS decrease on day 28 from baseline in the placebo and anakinra groups was 3 and 4 points, respectively (odds ratio (OR) = 0.40, P < 0.0001); the respective median decrease of Sequential Organ Failure Assessment (SOFA) score on day 7 from baseline was 0 and 1 points (OR = 0.63, P = 0.004). Twenty-eight-day mortality decreased (hazard ratio = 0.45, P = 0.045), and hospital stay was shorter.

Daptomycin versus other antimicrobial agents for the treatment of skin and soft tissue infections: a meta-analysis.

BACKGROUND: Skin and soft tissue infections (SSTIs) are common in everyday clinical practice. Daptomycin has been shown to achieve very good concentrations in skin and soft tissues. OBJECTIVE: To compare the effectiveness and toxicity of daptomycin with that of other antimicrobials for the treatment of SSTIs. METHODS: PubMed, Scopus, and the Cochrane Central Register of Controlled Trials were searched for articles published up to March 2009. Comparative studies in which daptomycin was used in the intervention group were included in this meta-analysis. The primary outcome of interest was clinical success; secondary outcomes were microbiologic success, clinical success in subsets with complicated SSTIs (cSSTIs) or infections due to methicillin-resistant Staphylococcus aureus (MRSA), clinical success of daptomycin-versus vancomycin-treated patients, time to clinical cure, treatment-related adverse events, withdrawal from treatment due to toxicity, all-cause mortality, and development of resistance. RESULTS: Four studies were included in the analysis (3 were randomized controlled trials [RCTs]). Vancomycin and semisynthetic penicillins were used in the comparator arm. Three studies reported on patients with cSSTIs. The intention-to-treat (ITT) population was 1557 patients. No statistically significant difference between daptomycin and comparators was found regarding clinical success in clinically evaluable (OR 0.89; 95% CI 0.63 to 1.25 in the 3 RCTs and OR 1.34; 95% CI 0.38 to 4.66 with all 4 studies included), ITT, MRSA-infected patients, and those with cSSTIs. Two studies reported that significantly fewer patients with cSSTIs required prolonged treatment in the daptomycin arm and that clinical cure was faster than with comparators. No difference between the compared regimens was found in other outcomes. CONCLUSIONS: Daptomycin is effective and safe for the treatment of SSTIs. Studies evaluating the optimal duration of daptomycin therapy for cSSTIs, comparing daptomycin with new agents, and focusing on proven MRSA SSTIs will be helpful for the further evaluation of the drug.

Unusual climatic conditions and infectious diseases: observations made by Hippocrates.

About 2500 years ago, Hippocrates made noteworthy observations about the influence of climate on public health. He believed that people living in cities with different climate may suffer from different diseases. Hippocrates also observed that abrupt climatic changes or unusual weather conditions affect public health, especially the incidence and severity of various infectious diseases, including gastrointestinal infections, tuberculosis, and central nervous system infections. We believe that Hippocrates' scientific observations are great early historic examples that stress to modern infectious diseases researchers and clinicians the need to study intensively the effect of the occurring global climate changes to infectious diseases in order to help in the prevention of possible epidemics of infections.

Comparison of utility of blood cultures from intravascular catheters and peripheral veins: a systematic review and decision analysis.

Blood cultures are sometimes obtained from intravascular catheters for convenience. However, there is controversy regarding this practice. The authors compared the diagnostic test characteristics of blood cultures obtained from intravascular catheters and peripheral veins. Relevant studies for inclusion in this review were identified through PubMed (January 1970-October 2005) and the Cochrane Central Register of Controlled Trials. Studies that reported clear definitions of true bacteraemia were included in the analysis. Two reviewers independently extracted the data. Six studies were included in the analysis, providing data for 2677 pairs of blood cultures obtained from an intravascular catheter and a peripheral venipuncture. A culture obtained from an intravascular catheter was found to be a diagnostic test for bacteraemia with better sensitivity (OR 1.85, 95 % CI 1.14-2.99, fixed effects model) and better negative predictive value (almost with statistical significance) (OR 1.55, 95 % CI 0.999-2.39, fixed effects model) but with less specificity (OR 0.33, 95 % CI 0.18-0.59, random effects model) and lower positive predictive value (OR 0.41, 95 % CI 0.23-0.76, random effects model) compared to a culture taken by peripheral venipuncture. In a group of 1000 patients, eight additional patients with true bacteraemia would be identified and 59 falsely diagnosed as having bacteraemia by a blood culture obtained from an intravascular catheter compared to results of the peripheral blood culture. Given the consequences of undertreating patients with bacteraemia, the authors believe that, based on the available evidence, at least one blood culture should be obtained from the intravascular catheter.

Trends in the methodological quality of published randomized controlled trials on antibacterial agents.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Randomized controlled trials (RCTs) are believed to be one of the best methods of clinical research because they can minimize systematic errors of various types. Temporal trends in the various aspects of RCTs have been studied in several medical fields (e.g. nephrology, hepatology, oncology). However, there is lack of data regarding the trends in the methodological quality of RCTs focusing on antimicrobial agents. WHAT THIS STUDY ADDS: Several important methodological aspects of RCTs on antibacterial agents, such as description of randomization, double blinding, description of the blinding and allocation concealment, have not improved during the last 30 years. AIM To investigate the trends of the methodological quality of randomized controlled trials (RCTs) of antimicrobial agents published during the last 30 years. METHODS: We randomly selected from the Cochrane Central Register of Controlled Trials database 70 RCTs of antibacterial agents that were published during a 30-year study period (1975-2005); specifically, we randomly selected 10 RCTs published during each of the following years: 1975, 1980, 1985, 1990, 1995, 2000 and 2005. In each of the selected RCTs, we searched for information on various methodological aspects and graded the methodological quality of the RCTs to evaluate trends for possible improvement. RESULTS: No improvement was noted in most of the analysed methodological aspects of the RCTs during the 30-year study period. Description of randomization, double blinding, description of the blinding, and allocation concealment were rather scarce among the evaluated RCTs, without observing a trend for improvement during the study period. We noted improvement in reporting power of the study calculations, baseline data as well as in reporting the presence or not of statistical significance and the statistical cut-off of significance. In only 1/70 RCTs were all 13 of the examined methodological quality aspects met and in one more RCT 12 of them were met. CONCLUSIONS: We did not observe considerable improvement in the quality of the reporting and methodology of RCTs on antibacterial agents during the last 30 years. The methodological quality aspects that need most improvement are those that help safeguard against various types of biases.

Helicobacter pylori infection in symptomatic HIV-seropositive and -seronegative patients: a case-control study.

We conducted a case-control study in a Greek hospital to evaluate the prevalence and morbidity of Helicobacter pylori in HIV-infected patients. HIV-seropositive patients were infected by H. pylori less often than HIV-seronegative controls [12/58 (20.7%) versus 38/58 (65.5%),p < 0.001]. The mean CD4 count was lower for H. pylori-negative than H. pylori-positive HIV-infected patients (p < 0.007). Also, among HIV patients, prior use of antibiotics or proton pump inhibitors was more common in those without H. pylori infection, however, this difference was not statistically significant (p = 0.06). The grading of the density of H. pylori infection and the grading of the histomorphological findings according to the Sydney classification were similar between HIV-seropositive and -seronegative patients with H. pylori infection.

Oral rifampin for eradication of Staphylococcus aureus carriage from healthy and sick populations: a systematic review of the evidence from comparative trials.

BACKGROUND: Rifampin has been used for the eradication of Staphylococcus aureus (S. aureus) colonization in various populations of healthy and sick people. METHODS: We performed a systematic review of the evidence from randomized and nonrandomized controlled trials that compared the effectiveness and safety of a rifampin-based regimen with another regimen in eradicating S. aureus colonization from healthy and sick people. RESULTS: Nine comparative trials (6 of which were randomized controlled trials) were included in our analysis. S. aureus was eradicated more commonly in patients receiving rifampin-containing regimens compared to monotherapy with other systemic agents (ciprofloxacin, cloxacillin, minocycline, or vancomycin), both during early and late (>1 month after therapy) post treatment evaluations (odds ratio [OR] 46.2, 95% confidence interval [CI] 14.4-148, and OR 8.8, 95% CI 3.4-22.5 respectively, 4 studies included). There was no statistically significant difference between rifampin monotherapy and combinations of rifampin with other topical (bacitracin) or systemic (cloxacillin and minocycline) antibiotics in eradicating S. aureus both in early and late evaluations (OR 1.5, 95% CI 0.5-4.4, and OR 1.6, 95% CI 0.7-3.7, respectively, 3 studies included). Eradication of methicillin-resistant S. aureus (MRSA) varied according to the type and duration of the rifampin-containing regimen. It ranged from 25% for the combination of rifampin with trimethoprim/sulfamethoxazole for 5 days to 100% for the combination of oral rifampin and minocycline for 14 days. Discontinuation of rifampin due to drug-related toxicity was necessary in 2% of 282 studied patients. Development of resistance of S. aureus to rifampin during and after treatment with a regimen containing rifampin ranged from 0% to 40% (7 studies) and overall 17% of the 236 patients for whom relevant data was reported. CONCLUSION: The available evidence suggests that oral rifampin is an effective agent for the eradication of S. aureus carriage. However, development of antimicrobial resistance during and after treatment with rifampin occurs in a considerable proportion of patients; using rifampin in combination with another antimicrobial agent may decrease this resistance.

Pandrug-resistant Gram-negative bacteria: the dawn of the post-antibiotic era?

The evolving problem of antimicrobial resistance in Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella pneumoniae has led to the emergence of clinical isolates susceptible to only one class of antimicrobial agents and eventually to pandrug-resistant (PDR) isolates, i.e. resistant to all available antibiotics. We reviewed the available evidence from laboratory and clinical studies that reported on polymyxin-resistant and/or PDR P. aeruginosa, A. baumannii or K. pneumoniae clinical isolates. Eleven laboratory studies reported on isolates with resistance to polymyxins, three of which (including two surveillance studies) also included data regarding PDR isolates. In addition, two clinical studies (from Central and Southern Europe) reported on the clinical characteristics and outcomes of patients infected with PDR isolates. These data suggest that polymyxin-resistant or PDR P. aeruginosa, A. baumannii and K. pneumoniae clinical isolates are currently relatively rare. However, they have important global public health implications because of the therapeutic problems they pose. The fears for the dawn of a post-antibiotic era appear to be justified, at least for these three Gram-negative bacteria. We must increase our efforts to preserve the activity of available antibiotics, or at least expand as much as possible the period of their use, whilst intense research efforts should be focused on the development and introduction into clinical practice of new antimicrobial agents.

Intraventricular or intrathecal use of polymyxins in patients with Gram-negative meningitis: a systematic review of the available evidence.

Several reports have described the use of polymyxins by the intraventricular or intrathecal route for multidrug-resistant Gram-negative meningitis. We reviewed the available clinical evidence regarding intraventricular/intrathecal administration of polymyxins in patients with meningitis, focusing on effectiveness and safety. Relevant studies were identified from PubMed (January 1950 to April 2006) as well as from the references of relevant articles. We identified 31 case reports/series that matched our inclusion criteria. Sixty-four episodes of Gram-negative meningitis (34 in adults) were reviewed. Monotherapy with polymyxins via the intraventricular or intrathecal route was used in 11 episodes and combination of systemic and local polymyxins was used in 25 episodes. In the remaining episodes, various combinations of local polymyxins with systemic and/or local antibiotics were administered. Cure was achieved in 51/64 episodes (80%); in 26/30 episodes (87%) due to Pseudomonas aeruginosa and in 10/11 episodes (91%) due to Acinetobacter spp. Toxicity related to local administration of polymyxins was noted in 17/60 (28%) patients. The most common toxicity was meningeal irritation (12 cases). Discontinuation of treatment was necessary in four episodes and dose reduction in four episodes; irreversible toxicity was not reported. The limited available evidence suggests that therapy with intraventricular/intrathecal polymyxins alone or in combination with systemic antimicrobial agents is effective against Gram-negative meningitis. Toxicity is not uncommon but it is dose-dependent and reversible. Further studies are needed to evaluate the criteria for initiation of local central nervous system treatment with polymyxins, the optimal dosages and the role of adjuvant systemic or local therapy.

Albendazole for the treatment of human echinococcosis: a review of comparative clinical trials.

BACKGROUND: Albendazole has been used in various ways in the treatment of cystic echinococcosis (CE). METHODS: We reviewed the available evidence regarding the role of albendazole for the treatment of patients with CE. The available comparative clinical trials (randomized or not) that examined the use of albendazole in CE were identified from the PubMed and the ISI Web of Science databases. Relevant data from the trials were extracted and evaluated. RESULTS: Thirteen studies were included in the review. Albendazole is superior to placebo for inoperable, symptomatic patients (1 study). In addition, in 4 trials that tested albendazole as a preoperative adjuvant therapy, the drug resulted in degeneration of hydatid cysts at the time of surgery in a considerable proportion of patients. Furthermore, combined therapy with albendazole and PAIR (Puncture, Aspiration, Injection of scolicidal agent, and Re-aspiration) technique was found more effective than albendazole or PAIR treatment alone, in a randomized controlled trial examining this issue. Finally, although existing evidence shows some superiority for albendazole compared to mebendazole, there is no definite proof about this. CONCLUSIONS: Although the available comparative trials provide considerable evidence for the role of albendazole in patients with CE, there are some important clinical questions that remained unanswered by the studies. One of them is whether the combination of albendazole with praziquantel is superior to albendazole alone when both effectiveness and drug toxicity are taken into account. Also, further studies should also compare the combination of albendazole/PAIR with albendazole/surgery focusing on both short and long term outcomes.

Eighteen years of research on AIDS: contribution of and collaborations between different world regions.

The scientific community invests significant resources on HIV/AIDS research to confront the current epidemic. We reviewed the medical literature in order to evaluate the contribution of different world regions on HIV/AIDS research during the past 18 years. We retrieved articles, using an elaborate methodology, from three journals focusing on HIV/AIDS between 1986 and 2003, indexed in the Journal Citation Reports (JCR) and the Web of Science databases of the Institute for Scientific Information (ISI). Comparisons were made by dividing the world into nine geographic regions, and by using the human development index (HDI) categorization. A total of 9502 articles on HIV/AIDS were retrieved from three AIDS journals over an 18-year study period. The United States and Western Europe together and five developed out of nine world regions made up a striking 83% and 92% of the world's research production on HIV/AIDS, respectively. Scientists from the developing world participated in 10.4% of the articles published during 1986-1991, 14.7% during 1992-1997, and 21.3% during 1998-2003. Researchers from countries included in the high, medium, and low HDI category produced 2240, 9, and 15 articles per billion population, respectively. About half of articles originating in Latin America and the Caribbean and half in Asia were produced in collaboration with the United States. However, 40% of articles from Africa and 58% from Eastern Europe were produced in cooperation with Western Europe. Collaboration between researchers within developing regions was negligible. The vast majority of the world's research on AIDS is produced in the developed world. Although research production was minimal in the developing world, we found that regions included in the low and medium HDI categories showed a higher proportion of increase in research productivity than the developed countries. International collaborations should significantly increase and expand beyond the traditional cultural and political lines of international relationships.

Impact of initial discordant treatment with beta-lactam antibiotics on clinical outcomes in adults with pneumococcal pneumonia: a systematic review.

OBJECTIVE: To systematically examine the available evidence regarding the effect of initial discordant therapy with beta-lactam antibiotics on mortality, clinical success, and bacteriological eradication in patients with pneumococcal pneumonia. METHODS: We analyzed prospective studies that compared the clinical effectiveness of concordant (active in vitro) beta-lactam monotherapy with discordant (inactive in vitro) monotherapy with the same beta-lactam in patients with pneumococcal pneumonia. Relevant studies were identified from searches of the PubMed database (1950 to November 2005) and references from articles. Outcomes between groups of patients who received concordant and discordant treatment were compared by simple pooling of data and by estimation of pooled odds ratios or risk difference (RD), when applicable. RESULTS: Six prospective studies were included in our analysis. No statistically significant difference was found in mortality of patients treated with beta-Iactam concordant and discordant therapy (51/275 [19%] vs 9/42 [21%]; P = .66; data from 6 studies; RD, -0.05; 95% confidence interval [CI], -0.23 to 0.12; data from 5 studies). In addition, no statistically significant difference was found regarding clinical success (37/42 [88%] vs 5/6 [83%]; P = .57; odds ratio, 2.57; 95% CI, 0.46 to 14.34; RD, 0.07; 95% CI, -0.36 to 0.50; data from 3 studies) or bacteriological success (24/30 [80%] vs 3/3 [100%]; P = .99; and RD, -0.18; 95% CI, -0.79 to 0.42; data from 2 studies) between concordant and discordant therapy. CONCLUSION: The initial discordant treatment with beta-lactam antibiotics was not associated with a statistically significant Increase in mortality or clinical or bacteriological failure of therapy for pneumococcal pneumonia.

The diversity of definitions of multidrug-resistant (MDR) and pandrug-resistant (PDR) Acinetobacter baumannii and Pseudomonas aeruginosa.

Different definitions of the terms multidrug-resistant (MDR) and pandrug-resistant (PDR) Acinetobacter baumannii and Pseudomonas aeruginosa have been used in the biomedical literature. The authors searched for relevant studies indexed in the PubMed database (01/2000-09/2005) to systematically examine the various definitions of MDR and PDR for these bacteria. Initially 107 retrieved relevant studies were reviewed. Ninety-two studies were further analysed, 50 of which focused on A. baumannii and 42 on P. aeruginosa. A considerable diversity of definitions of the terms MDR and PDR A. baumannii and P. aeruginosa was found. Of note, the term PDR was inappropriately used in all five studies that used it. The review reveals that various definitions have been used for the terms MDR and PDR A. baumannii and P. aeruginosa, a fact that causes confusion to researchers and clinicians. The authors believe that at least a widely accepted definition for PDR A. baumannii and P. aeruginosa should be uniformly used worldwide.

Ciprofloxacin/metronidazole versus beta-lactam-based treatment of intra-abdominal infections: a meta-analysis of comparative trials.

Intra-abdominal infections are polymicrobial and result in substantial morbidity and mortality. The combination of ciprofloxacin/metronidazole as well as several beta-lactam-based regimens are among the commonly used regimens for the treatment of patients with such infections. Thus, we sought to review the evidence from available comparative clinical trials studying ciprofloxacin/metronidazole versus broad-spectrum beta-lactam-based regimens in the treatment of intra-abdominal infections. Studies for the meta-analysis were retrieved from searches of the PubMed database. Five available comparative trials (four randomised controlled trials and one non-randomised comparative trial) including 1431 patients with intra-abdominal infections were included in the meta-analysis. There was a statistically significant difference between the compared arms with regard to cure in favour of the ciprofloxacin/metronidazole combination (odds ratio (OR)=1.69, 95% confidence interval (CI) 1.20-2.39). There was no statistically significant difference between the compared arms with regard to total mortality (OR=1.10, 95% CI 0.71-1.69), mortality attributable to infection (OR=1.42, 95% CI 0.66-3.06) and toxicity (OR=1.25, 95% CI 0.66-2.35). In conclusion, pooled data from the available comparative trials suggest that the ciprofloxacin/metronidazole combination may be superior to beta-lactam-based therapeutic regimens in the treatment of intra-abdominal infections with regard to cure of infections, although no difference in mortality was found.

A bibliometric analysis of global trends of research productivity in tropical medicine.

The field of tropical medicine has a long history due to the significance of the relevant diseases for the humanity. We estimated the contribution of different world regions to research published in the main journals of tropical medicine. Using the PubMed and the Institute for Scientific Information (ISI) "Web of Science" databases, we retrieved articles from 12 journals included in the "Tropical Medicine" category of the "Journal Citation Reports" database of ISI for the period 1995-2003. Data on the country of origin of the research were available for 11,860 articles in PubMed (98.1% of all articles from the tropical medicine category). The contribution of different world regions during the studied period, as estimated by the location of the affiliation of the first author, was: Western Europe 22.7%, Africa 20.9%, Latin America and the Caribbean 20.7%, Asia (excluding Japan) 19.8%, USA 10.6%, Oceania 2.1%, Japan 1.5%, Eastern Europe 1.3%, and Canada 0.6%. The contribution of regions, estimated by the location of the affiliation of at least one author of the published papers (retrieved from the ISI database), was similar: Western Europe 36.6%, Africa 27.7%, Latin America and the Caribbean 24.4%, and Asia 23.3%. The mean impact factor of articles published in tropical medicine journals was highest for the USA (1.65). Our analysis suggests that the developing areas of the world produce a considerable amount of research in tropical medicine; however, given the specific geographic distribution of tropical diseases they probably still need help by the developed nations to produce more research in this field.

A bibliometric analysis by geographic area of published research in several biomedical fields, 1995-2003.

We summarized the findings of several studies of ours to compare the quantity and quality of published research from around the world for the years 1995 to 2003. We evaluated the number of articles published and their mean journal impact factor. We also studied the research productivity of various areas adjusted for gross domestic product (GDP) and population. We found that Western Europe leads the world in published research on infectious diseases-microbiology (82,342 articles [38.8%]) and in cardiopulmonary medicine (67,783 articles [39.5%]), whereas the United States ranks first in the fields of preventive medicine, public health and epidemiology both in quantity (23,918 articles [49.1%]) and quality of published papers. However, after adjustments for GDP, Canada ranked first, with the United States and Oceania following closely behind. All of the developing regions had only small research contributions in all of the biomedical fields examined.

A bibliometric analysis of research productivity in Parasitology by different world regions during a 9-year period (1995-2003).

BACKGROUND: The objective of this study was to estimate the research productivity of different world regions in the field of Parasitology. METHODS: Using the PubMed database we retrieved articles from journals included in the "Parasitology" category of the "Journal Citation Reports" database of the Institute for Scientific Information for the period 1995-2003. Research productivity was evaluated based on a methodology we developed and used in other bibliometric studies by analysing: (1) the total number of publications, (2) the mean impact factor of all papers, and (3) the product of the above two parameters, (4) the research productivity in relation to gross domestic product of each region, and (5) the research productivity in relation to gross national income per capita and population of each region. RESULTS: Data on the country of origin of the research was available for 18,110 out of 18,377 articles (98.6% of all articles from the included journals). Western Europe exceeds all world regions in research production for the period studied (34.8% of total articles), with USA ranking second (19.9%), and Latin America & the Caribbean ranking third (17.2%). The mean impact factor in articles published in Parasitology journals was highest for the USA (1.88). Oceania ranked first in research productivity when adjustments for both the gross national income per capita (GNIPC) and population were made. Eastern Europe almost tripled the production of articles from only 1.9% of total production in 1995 to 4.3% in 2003. Similarly, Latin America and the Caribbean and Asia doubled their production. However, the absolute and relative production by some developing areas, including Africa, is still very low, despite the fact that parasitic diseases are major public health problems in these areas. CONCLUSION: Our data suggest that more help should be provided by the developed nations to developing areas for improvement of the infrastructure of research.

Attributable mortality of Acinetobacter baumannii infections in critically ill patients: a systematic review of matched cohort and case-control studies.

INTRODUCTION: There has been a continuing controversy about whether infection with Acinetobacter baumannii increases morbidity and mortality independently of the effect of other confounding factors. METHODS: We performed a systematic review of matched case-control and cohort studies examining the mortality attributable to infection with or acquisition of A. baumannii (infection or colonization). We included in our review studies that compared mortality and/or morbidity of patients with acquisition of or infection with A. baumannii (cases) with the outcomes of matched patients without A. baumannii isolation from clinical specimens (controls). The relevant studies were identified from searches of the PubMed and the Cochrane Library databases. Two independent reviewers performed the literature search, study selection, and data extraction from nine identified relevant studies. RESULTS: The attributable mortalities, in the hospital and in the intensive care unit, of patients with A. baumannii infection in six matched case-control studies included in our review ranged from 7.8% to 23% and from 10% to 43%, respectively. In addition, a statistically significantly higher mortality was reported for patients with A. baumannii acquisition; that is, colonization or infection (cases) compared with controls without such an acquisition in all four reviewed studies that reported data on this comparison. CONCLUSION: Although definitive statements about the mortality attributable to the acquisition of A. baumannii cannot be made from the available studies because of their methodological heterogeneity, the reviewed data suggest that infection with or acquisition of A. baumannii seems to be associated with increased mortality.

Administration of antibiotics via the respiratory tract for the prevention of ICU-acquired pneumonia: a meta-analysis of comparative trials.

INTRODUCTION: The administration of prophylactic antibiotics via the respiratory tract is one of several strategies for the prevention of ICU-acquired pneumonia. We systematically examined the available evidence regarding the effect of prophylactic antibiotics administered via the respiratory tract on the development of ICU-acquired pneumonia, mortality, colonization of the respiratory tract, emergence of antimicrobial resistance, and toxicity. METHODS: We searched the PubMed database (1/1950 to 9/2005) and references from relevant articles to identify trials that provided comparative data regarding the above-mentioned outcomes. Two investigators independently performed the data extraction to calculate the effect of the studied intervention on clinically relevant outcomes. RESULTS: 8 comparative trials (5 randomized controlled trials (RCTs) and 3 non-randomized trials) studying gentamicin (3 trials) polymyxins (3 trials), tobramycin (1 trial), and ceftazidime (1 trial) that studied 1,877 patients were included in our meta-analysis. Our primary analysis that included the 5 RCTs, revealed that ICU-acquired pneumonia was less common in the group of patients that received the antibiotic prophylaxis (OR = 0.49, 95% CI 0.32-0.76). No difference in mortality was found between the compared groups (OR = 0.86, 95% CI 0.55-1.32). There were limited data to permit an analysis of colonization with Pseudomonas aeruginosa. A secondary analysis by adding the 3 non-randomized comparative trials did not reveal substantially different results regarding ICU-acquired pneumonia and mortality, while fewer patients were colonized with Pseudomonas aeruginosa in the group that received prophylaxis, compared to the group of patients that received no prophylaxis (OR = 0.51, 95% CI 0.30-0.86). No serious drug-related toxicity was noted. No meaningful systematic analysis of the evidence regarding the emergence of resistance could be performed in the studies included in our meta-analysis. CONCLUSIONS: The limited available evidence supports that prophylactic administration of antibiotics via the respiratory tract is associated with reduction of occurrence of ICU-acquired pneumonia. However, there is evidence from non-comparative studies that this preventive strategy may lead to an increase in the emergence of resistant bacteria. Thus, further investigation, at least in ICU patients at high risk for development of ICU-acquired pneumonia is warranted, including a more systematic evaluation of issues related to the emergence of resistance.