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The optimal control group for case-control studies examining antibiotics as risk factors for the emergence of antimicrobial resistance is patients selected randomly from the total hospital population, while the selection of patients with a susceptible bacterium is deemed suboptimal. We sought to theoretically elaborate on potential parameters that introduce bias associated with the use of randomly selected control subjects, based on personal experience and data from the literature. In addition, we considered parameters that introduce potential bias associated with the definition of case patients. Parameters that may introduce potential bias associated with the randomly selected control subjects are use of antibiotics in the community (background exposure), availability of an antibiotic in a country, ability to purchase specific antibiotics or health care, the bacterial resistance pattern in the country, in vitro evaluation issues, source of admitting patients (nursing home or community), type of hospital to which patients are admitted (general or disease specific), and ward of hospital to which patients are admitted. Parameters that may introduce potential bias associated with the case definition are multidrug resistance versus resistance to only one antibiotic, resistance phenotype of the microbe, multistep versus one-step development of resistance, appropriateness versus adequacy of antibiotic treatment, antibiotic synergy, details regarding the daily dose and duration of administration of the specific antibiotic, and use of other antibiotics. In conclusion, selection of control subjects from the hospital population is also associated with bias. The most acceptable solutions to evaluate the risk factors for antimicrobial resistance are probably the case-control-control study design and the case-case-control study design.

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.

Summary Objective To evaluate whether the use of high doses of quinolones may reduce the development of antimicrobial resistance. Data sources Relevant studies were identified from PubMed and the Cochrane Central Register of Controlled Trials (until June 2006). Study selection and data extraction We performed a systematic review of the available data from comparative clinical studies reporting on the emergence of resistance when using different daily doses of quinolones. Data synthesis Twelve studies reported comparative data regarding the emergence of antimicrobial resistance. Development of resistance occurred in patients of 5/12 studies included in the review, with no statistical difference between the compared arms. Conclusions Although data from laboratory studies are indicative of a benefit from using high daily doses of quinolones in order to minimize the emergence of antimicrobial resistance, the data from the reviewed trials are limited and can neither support nor reject this finding. However, it seems that if a true benefit exists this is rather small and regards mainly isolates with initially high minimum inhibitory concentrations. Further comparative clinical studies focusing on this issue are justified.

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.

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.

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.

Summary Background Intra-abdominal infections result in substantial morbidity and mortality. Fluoroquinolones are among the various regimens that are used for the treatment of these infections. Aim To evaluate the available data from laboratory and clinical studies regarding the use of fluoroquinolones for the treatment of patients with intra-abdominal infections. Methods We searched for relevant laboratory and clinical studies in the PubMed and the Cochrane Library databases. Results Good pharmacokinetic and pharmacodynamic properties of fluoroquinolones in inflamed abdominal tissue are reported in several laboratory studies. In six prospective non-randomized clinical studies of patients with intra-abdominal infections, the clinical success achieved with the use of fluoroquinolones ranged from 77% to 94%. In 10 randomized-controlled trials fluoroquinolone-based regimens were compared with other commonly used (mainly β-lactam-based) regimens. Clinical success, bacterial eradication, withdrawal because of toxicity and mortality were similar between the compared treatment arms except from two randomized-controlled trials, in which clinical success was statistically higher in the fluoroquinolone treatment arm. Conclusions Fluoroquinolones seem to be an effective and relatively safe option for the treatment of patients with intra-abdominal infections.

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.

This chapter highlights urethritis. The term urethritis refers to inflammation of the urethra, which can be attributed both to infectious and noninfectious processes. The urethral canal essentially represents the first site of the body to be exposed to a variety of sexually transmitted pathogens, and the interaction of these pathogens with the epithelial cells of the urethra gives rise to the syndrome’s symptoms. Dysuria refers to the experience of pain or burning sensation or discomfort in urination, and is a subjective symptom related to varying pathology of the urinary tract. The urethra being the terminal pathway of urine flow, its inflammation most often accounts for experience of dysuria. Antibiotic treatment of urethritis should always follow the diagnosis to prevent complications and further transmission of the pathogen.

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.

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.

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.

The contributions of classical Greek culture to science, including medicine, were considerable. Happily, Greece is again becoming a force in modern biomedicine. Bibliometric analysis shows that, compared to the rest of the world, Greece has achieved a steady, gradual increase in research productivity during the last 10 years both in absolute and relative terms. However, that increase has come in selected fields and despite the fact that the proportion of the gross domestic product (GDP) devoted to research and development has been stable at around 0.6% (i.e., 3–5 times lower than that of the European Community, the United States of America, and Japan, where the relevant values are 1.9%, 2.7%, and 2.9%). In addition, there are serious problems related to the adequacy of the infrastructure that supports research in Greece. This article outlines the classical contributions to biomedical science in the cradle of Western civilization and the state of science in Greece today.

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.

Brucellosis is a zoonotic disease with worldwide distribution that is endemic in the Mediterranean region, the Middle East, Central Asia, and parts of Africa and Latin America. Worldwide, brucellosis remains a major cause of morbidity in humans and domesticated animals. In animals, bovine brucellosis, caused mainly by Brucella abortus, is still the most widespread form. In humans, ovine/caprine brucellosis caused by Brucella melitensis is by far the most common type of disease. The disease has a wide spectrum of clinical manifestations and can affect a variety of organs and systems. Localized and complicated forms of brucellosis cause important morbidity and require prolonged medical treatment. Fortunately, mortality is relatively low and is related mainly to cardiovascular and central nervous system complications of the disease. Although several studies have been conducted over the past 2 decades, there is no conclusive evidence on the optimum antibiotic therapy for brucellosis. Disease relapse still represents one of the most important therapeutic problems. The last recommendation by the World Health Organization (WHO) for the treatment of acute brucellosis in adults was published in 1986 and suggested 600 to 900 mg rifampin and 200 mg doxycycline daily for a minimum of 6 weeks (8). Alternatively, the WHO suggested that rifampin could be replaced with 15 mg/kg of streptomycin, administered intramuscularly for only 2 weeks. However, a meta-analysis, as well as a prospective randomized trial, both performed by Solera et al., showed that the “good old” combination regimen of streptomycin with an oral tetracycline results in fewer relapses than the doxycycline-rifampin combination (57, 58). Controlled clinical trials with other antibiotics, including trimethoprim-sulfomethoxazole, new macrolides, and β-lactams, have shown inferior results or involved too few patients for a proper evaluation. Thus, the most widely used regimens are the two aforementioned combinations that were recommended by the WHO. In addition, rifampin monotherapy is the main option for brucellosis during pregnancy, whereas its combination with trimethoprim-sulfomethoxazole is the suggested treatment for childhood brucellosis (5, 34). Certain focal forms of brucellosis are difficult to treat, and surgery should be considered for patients with endocarditis or cerebral, epidural, splenic, or other abscesses (20, 41). Regarding medical treatment, although the antibiotics used are essentially the same, prolonged therapy, up to six or more months, may be needed for patients with osteoarticular forms of the disease, and especially spondylitis (18, 56, 65). Also, triple-antibiotic combinations were found to be of value in some case series of brucellar endocarditis, spondylitis, and meningitis (2, 41, 65). Relapse of the disease also represents a major therapeutic problem for its focal forms. Since the mid 1980s, laboratory researchers and clinicians have performed several microbiological and clinical studies of the possible use of quinolones in the treatment of human brucellosis. The activity against intracellular bacteria (23), reduced risk of nephrotoxicity, good pharmacokinetic characteristics, and lack of a requirement for drug level monitoring represent the main advantages of using quinolones in this setting. Moreover, the need for a regimen that would eliminate disease relapse further necessitated the use of quinolones. However, there is only one brief review focusing on the issue, published in 1992 (38). This study reviewed the available in vitro and clinical data at the time and examines the rationale, as well as the outcomes, of quinolone use for brucellosis.

Spondylodiscitis is a rare complication after facet joint steroid injection. This article presents a 78-y-old male with chronic back pain and facet joint arthritis who developed Pseudomonas aeruginosa L2-L3 and L3-L4 spondylodiscitis after computed tomography-guided facet joint steroid injection. Magnetic resonance imaging, fine needle aspiration and cultures confirmed the diagnosis. The patient was treated with intravenous administration of amikacin, and imipenem plus cilastatin for 4 weeks, followed by oral administration of ciprofloxacin for another 10 weeks. Sterile preparation prior to facet joint steroid injection should be stressed. To the best of our knowledge, this is the only reported case of iatrogenic spondylodiscitis after facet joint steroid injection. This iatrogenic complication should be considered in the risk-benefit analysis of facet joint diagnostic or therapeutic injections.

To compare the effectiveness and toxicity of ciprofloxacin vs an aminoglycoside, both in combination with a beta-lactam, for the treatment of febrile neutropenia in the inpatient setting.For this meta-analysis of randomized controlled trials (RCTs) that compared the ciprofloxacin/beta-lactam combination vs an aminoglycoside/beta-lactam combination for the treatment of febrile neutropenia and reported data on effectiveness, mortality, and/or toxicity, we searched PubMed (1950-2004), Current Contents, Cochrane Central Register of Controlled Trials, and reference lists of retrieved articles, including review articles, as well as abstracts presented at international conferences. Data for 3 primary and 2 secondary outcomes were extracted by 2 investigators.Eight RCTs were included in the analysis. Comparable or better outcomes were observed with the ciprofloxacin/beta-lactam combination vs an aminoglycoside/beta-lactam combination: clinical cure without modification of the initial regimen (odds ratio [OR], 1.32; 95% confidence interval [CI], 1.00-1.74; P=.05), clinical cure in the subset of patients with documented Infections (OR, 1.56; 95% CI, 1.05-2.31; P=.03), all-cause mortality (OR, 0.85; 95% CI, 0.54-1.35; P=.49), withdrawal of the study drugs due to toxicity (OR, 0.87; 95% CI, 0.57-1.32; P-.51), and nephrotoxicity (OR, 0.30; 95% CI, 0.16-0.59; P.001). The ciprofloxacin/beta-lactam combination was also associated with better clinical cure compared to the aminoglycoside/beta-actam combination in the subset of RCTs with non-low-risk patients (OR, 1.38; 95% CI, 1.01-1.88; P=-.04), as well as in the subset of studies that included the same beta-lactam in both treatment arms (OR, 1.47; 95% CI, 1.06-2.05; P=.02).The combination of ciprofloxacin with a beta-actam antibiotic should be considered an important therapeutic option in hospitalized febrile neutropenic patients who have not received a quinolone for prevention of infections and in settings in which quinolone resistance is not common.

We present our experience with a 56-year-old man who complained for generalized dermatopathy, manifested by skin lesions with diameter from 0.5 to 5cm. The lesions did not respond to a 20-day systemic steroid regimen. The results of biopsies of three excised lesions, in combination with the clinical manifestations, led to the diagnosis of subcorneal pustular dermatosis type of IgA pemphigus. An unexpected improvement was noted after treatment with azithromycin (which was provided for management of concurrent non-specific urethritis) and local non-potent steroid plus keratolytic agent ointment

In order to expand upon the limited literature estimating the quantity and quality of worldwide research production in the field of microbiology, a bibliometric analysis was conducted for the period 1995-2003 using the PubMed and Journal Citation Reports databases. By searching the "microbiology" category of the Journal Citation Reports database, a total of 74 journals were identified that were also included in PubMed. From these journals, a total of 89,527 articles were identified for analysis, and data on the country in which the research originated was available for 88,456 (98.8%) of them. The individual countries were separated into nine world regions. In terms of research production for the period studied, Western Europe exceeded all other world regions, with the USA ranking second. The mean impact factor was highest for the USA at 3.4, while it was 2.8 for Western Europe and 2.4 for the rest of the world combined. The research productivity per unit of expenditure for research and development was higher for Canada and Western Europe than for the USA. The three regions in which research productivity increased the most were Asia, Latin America, and Eastern Europe.

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.

The use of a mesh has been an advance in hernia repair and subsequently has become prevalent worldwide. However, the use of mesh may be associated with both non-infectious and infectious complications. We present here a representative case of a mesh-related infection due to Staphylococcus aureus and review the available data about the incidence, etiology, clinical manifestations, diagnosis, management, and prevention of this emerging type of foreign body infections.

The objective of this review was to compare the effectiveness and safety of β-lactam combined with aminoglycoside or fluoroquinolone with that of β-lactam monotherapy for the treatment of Pseudomonas aeruginosa infections. We searched Scopus and PubMed databases and synthesised the outcomes of the individual studies in a meta-analysis. Both non-randomised studies and randomised controlled trials (RCTs) that evaluated outcomes of patients with P. aeruginosa infections receiving treatment with β-lactams alone or in combination with an aminoglycoside or a fluoroquinolone were included. Studies including patients with cystic fibrosis were excluded. Nineteen articles (eight RCTs) were included (1721 patients with P. aeruginosa infections). Patients receiving combination therapy had no difference in mortality compared with patients receiving β-lactam monotherapy either as definitive (risk ratio=0.97, 95% confidence interval 0.77-1.22) or as empirical treatment (1.02, 0.78-1.34). In the definitive treatment group, no difference in mortality was found between combination therapy and monotherapy for patients with bacteraemia (0.95, 0.67-1.34) or severe infections (0.96, 0.75-1.24). Patients receiving definitive combination therapy had non-significantly higher clinical cure compared with patients receiving β-lactam monotherapy (1.36, 0.99-1.86). A higher clinical cure rate was observed for patients receiving empirical treatment with combination therapy (1.23, 1.05-1.43). There was no difference in clinical cure either for RCTs (1.29, 0.91-1.83) or for non-randomised studies (1.18, 0.97-1.45). In conclusion, no benefit in mortality was observed in patients receiving combination therapy for P. aeruginosa infections. A well-designed multicentre RCT is warranted to address this important issue.

OBJECTIVE Studies have shown that ambulatory blood pressure (BP) is more closely related to preclinical target organ damage than office measurements. A review and meta-analysis of studies investigating the association of home BP measurements with target organ damage was performed. METHODS A PubMed and Cochrane Library search (1950-2011) revealed 23 studies reporting comparative data of home BP versus ambulatory and/or office measurements in terms of their association with several indices of target organ damage. Correlation coefficients were pooled by random-effects model meta-analysis. RESULTS Fourteen studies (n = 2485) assessing echocardiographic left ventricular mass index (LVMI) showed similar correlations with home (coefficients r = 0.46/0.28, systolic/diastolic) as with ambulatory BP (0.37/0.26, P = NS for difference versus home BP), and superior to office measurements (r = 0.23/0.19, P < 0.001/0.009 for difference versus home BP). Four methodologically heterogeneous studies assessing the glomerular filtration rate (n = 609) could not be pooled or lead to a concrete result. Four studies assessing carotid intima-media thickness (n = 1222), three assessing pulse wave velocity (n = 720) and two assessing urinary protein excretion (n = 156) showed no difference in pooled correlation coefficients with home versus office BP measurements. With all the measurement methods SBP was more closely associated with target organ damage than DBP. CONCLUSION These data suggest that home BP is as good as ambulatory monitoring and superior to office measurements in regard to their association with preclinical organ damage assessed by echocardiographic LVMI. More research is required to evaluate the relationship of home BP with other indices of target organ damage.

Background It is recognized that for the reliable assessment of blood pressure (BP) and the accurate diagnosis of hypertension, out-of-office BP measurement with ambulatory (ABPM) or home BP monitoring (HBPM) is often required. The clinical usefulness of ABPM is well established. However, despite the wide use of HBPM, only in the last decade convincing evidence on its usefulness has accumulated. Methods Systematic review of the evidence on applying HBPM in the diagnosis and treatment of hypertension (PubMed, Cochrane Library, 1970-2010). Results Sixteen studies in untreated and treated subjects assessed the diagnostic ability of HBPM by taking ABPM as reference. Seven randomized studies compared HBPM vs. office measurements or ABPM for treatment adjustment, whereas many studies compared HBPM with office measurements in assessing the antihypertensive drug effects. Several studies with different design investigated the role of HBPM vs. office measurements in improving patients' compliance with treatment and hypertension control rates. The evidence on the cost-effectiveness of HBPM is limited. The studies reviewed consistently showed moderate diagnostic agreement between HBPM and ABPM, and superiority of HBPM compared to office measurements in diagnosing uncontrolled hypertension, assessing antihypertensive drug effects and improving patients' compliance and hypertension control. Preliminary evidence suggests that HBPM has the potential for cost savings. Conclusions There is conclusive evidence that HBPM is useful for the initial diagnosis and the long-term follow-up of treated hypertension. These data are useful for the optimal application of HBPM, which is widely used in clinical practice. More studies on the cost-effectiveness of HBPM are needed.

We reviewed the records of 313 diabetic patients attending a diabetes clinic for at least two years. Despite improvements in the control rates of cardiovascular risk factors, only 8.9% of the patients reached all the metabolic target goals simultaneously at the end, indicating a gap between guidelines and clinical practice.

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.

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.

There is still controversy regarding the appropriate management of diverticulitis of the colon in cases when both surgical and conservative treatment may be an option. We performed a systematic review of the available evidence regarding the outcomes after medical and surgical treatment of diverticulitis from studies published after 1980 and indexed in the PubMed database. We included original studies that reported comparative data for at least one outcome in medically- and surgically-treated patients with transverse or left colon diverticulitis. The main outcomes of interest were mortality, morbidity, and recurrence of diverticulitis after medical or surgical treatment. There were 21 studies fulfilling our inclusion criteria out of 1360 initially identified as possibly relevant. More patients were treated conservatively in the included studies compared to emergency surgery (24 862 vs 6504). Emergency surgery was the main option for patients with severe complications of diverticular disease, including peritonitis. In most studies, in-hospital mortality for patients treated surgically was generally higher than that of patients treated medically, whereas there were insufficient comparative data regarding mortality during follow up. However, readmission to the hospital due to diverticular disease during follow up was more common in the group of patients treated conservatively compared to those treated surgically (4358/23 446 [18.6%]vs 22/359 [6.1%]). Conservatively-treated patients, with a first or second episode of diverticulitis, required surgery for recurrent disease during follow up in a maximum of 45% of cases, with larger studies reporting percentages lower than 11%. It should be emphasized that medical and surgical treatments have not ever been compared in a randomized controlled trial in patients with diverticulitis (without generalized peritonitis that is a surgical emergency). Although medical treatment results in more readmissions due to recurrence, it may be reasonable to avoid surgical therapy in the vast majority of patients with acute diverticulitis. It is unclear what the best treatment option is for younger patients (

We reviewed the bibliographic evidence from comparative trials regarding the role of rifampin as adjuvant treatment in the treatment of Gram-positive infections [PubMed (1/1950–7/2006)]. Only studies reporting comparative outcome data in patients treated with an antibiotic regimen with the addition or not of rifampin were included. Eight comparative studies were identified [all were randomized controlled trials (RCTs)], five reporting on infections caused by staphylococci (S. aureus in 97% of patients) and three by streptococci. There was no statistically significant difference in mortality between the treatment arms (with and without rifampin) in any of the included studies. Clinical cure was achieved more commonly (p

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.

The use of antimicrobial-impregnated central venous catheters (CVCs) for the prevention of CVC microbial colonization and catheter-related bloodstream infection (CRBSI) remains controversial.We performed a meta-analysis of randomized controlled trials (RCTs) evaluating CRBSI and colonization of CVCs impregnated with rifampicin-based antimicrobial combinations. Our main analysis compared the occurrence of CRBSI with rifampicin/minocycline-impregnated CVCs with that of non-rifampicin-impregnated CVCs. The PubMed and Cochrane Central Register of Controlled Trials databases were searched (until October 2006).Eight RCTs were included in the analysis. The main analysis (seven RCTs) demonstrated that rifampicin/minocycline-impregnated CVCs were associated with fewer CRBSIs compared with catheters not impregnated with rifampicin/minocycline (OR 0.23, 95% CI 0.14-0.40). The same was true regarding colonization (OR 0.46, 95% CI 0.31-0.69). Further analysis, comparing rifampicin-based CVCs with non-rifampicin-impregnated CVCs, demonstrated superiority of rifampicin-based CVCs in reducing colonization (OR 0.38, 95% CI 0.24-0.62) and CRBSI (OR 0.24, 95% CI 0.14-0.40). Similar results, suggesting superiority of rifampicin/minocycline-impregnated CVCs, were noted in a subgroup analysis of colonization and CRBSIs in which rifampicin/minocycline-impregnated CVCs were compared with simple, non-tunnelled, non-antimicrobially impregnated CVCs, a subgroup analysis that was performed by excluding low quality RCTs, and a subgroup analysis for colonization comprising studies in which the sonication technique was used. No serious adverse events and no difference in mortality between the two treatment groups were reported. No clear conclusions can be made regarding the impact of the use of rifampicin/minocycline-impregnated CVCs on the development of antimicrobial resistance based on the available data.The available evidence suggests that rifampicin/minocycline-impregnated CVCs are safe and effective in reducing the rate of catheter colonization and CRBSI. Further research should focus on the possible development of resistance and on pharmacoeconomic issues related to the use of rifampicin/minocycline-impregnated CVCs.

OBJECTIVE To systematically examine the available evidence regarding the effect of initial discordant therapy with β-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) β-lactam monotherapy with discordant (inactive in vitro) monotherapy with the same β-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 β-lactam 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 β-lactam antibiotics was not associated with a statistically significant increase in mortality or clinical or bacteriological failure of therapy for pneumococcal pneumonia.

Background. Rifampin has been studied as prophylaxis against Staphylococcus aureus-related infections in patients on dialysis. Methods. We performed a meta-analysis of randomized controlled trials (RCTs) that compared the effectiveness and safety of oral rifampin with another regimen or no therapy in reducing S. aureus-related infections in dialysis patients. Results. Four RCTs evaluated oral rifampin (administered for 5 days every 3 months, or for 5 days once) as prophylaxis in dialysis patients. Oral rifampin with or without bacitracin was associated with less accesssite infections with S. aureus compared with no treatment (odds ratio ¼ 0.16, 95% confidence intervals: 0.06–0.44, 3 RCTs). There was no difference between prophylaxis with oral rifampin and topical mupirocin applied at the catheter site, for all studied outcomes, in the RCT comparing these regimens. Withdrawal from the study due to drug-related toxicity occurred in 7/107 (6.6%) of the studied patients with renal failure. Development of resistance of S. aureus to rifampin ranged from 0 to 18.2% (reported in three out of four included RCTs). Conclusion. Prophylactic use of oral rifampin reduces access-site infections with S. aureus in patients with renal failure undergoing dialysis. However, development of toxicity and antimicrobial resistance during the treatment with rifampin occur in considerable proportions of patients, limiting its use and supporting the guidelines that recommend the use of local antibiotics at the exit site, such as mupirocin, for these indications. The available data are rather limited and more studies should be performed to examine this important clinical question.

Morganella morganii is a commensal Gram-negative bacillus of the intestinal tract of humans and other mammals and reptiles. Few reports exist in the literature regarding infections caused by this organism. A retrospective study at the 650-bed University Hospital of Heraklion, Crete, Greece was performed during a 4-year period (2001–2004) to identify and analyze infections caused by M. morganii. Twenty-four patients had M. morganii isolated from clinical specimens during the study period. Thirteen patients (54%) suffered from skin and soft tissue infections, five from pyelonephritis, three from female genital tract infections, one from pneumonia, one from gangrenous appendicitis, and one from tonsillitis. M. morganii was a constituent of polymicrobial infections in 14 patients (58%). The patients received various antibiotics, i.e., six patients received ciprofloxacin, four piperacillin/tazobactam, two amoxicillin/clavulanic acid, one ticarcillin/clavulanic acid, one ceftriaxone, one imipenem, and one cefuroxime monotherapy, whereas the remaining eight received antibiotic combinations. Two (both debilitated) of 24 patients (8%) died, despite antibiotic treatment. Skin and soft tissue infection was the commonest type of infection due to M. morganii in our series. M. morganii is commonly a part of polymicrobial infections and can rarely cause fatalities in debilitated patients.

Background The addition of an aminoglycoside to a beta-lactam for the treatment of patients with infective endocarditis has been supported by data from laboratory and animal studies. Purpose We sought to review the evidence from the available comparative clinical trials regarding the role of aminoglycosides in combination with a beta-lactam for the treatment of bacterial endocarditis caused by Gram-positive cocci. Data sources The studies for our meta-analysis were retrieved from searches of the PubMed and Cochrane Central Register of Controlled Trials databases, as well as from the references cited in relevant articles. No limits were set regarding the language and date of publication of the studies. Study selection Included studies were prospective studies that provided comparative data regarding the effectiveness of the treatment and/or mortality in patients receiving monotherapy with a beta-lactam or beta-lactam/aminoglycoside combination therapy. Data extraction Two independent reviewers performed the literature search, study selection and extraction of data from relevant studies. Data synthesis No clinical trial comparing beta-lactam monotherapy with beta-lactam/aminoglycoside combination therapy for the treatment of enterococcal endocarditis was found. We performed a meta-analysis of five available comparative trials [four randomized controlled trials (RCTs) and one comparative prospective trial], which included 261 patients with bacterial endocarditis in native valves due to Staphylococcus aureus (four studies) or streptococci of the viridans group (one study). There was no statistically significant difference between beta-lactam monotherapy and beta-lactam/aminoglycoside combination therapy regarding mortality [odds ratio (OR) = 0.59, 95% confidence interval (95% CI) = 0.21-1.66], treatment success (OR = 1.25, 95% CI = 0.49-3.05), treatment success without surgery (OR = 1.66, 95% CI = 0.64-4.30) or relapse of endocarditis (OR = 0.79, 95% CI = 0.15-4.29). Nephrotoxicity was less common in the beta-lactam monotherapy arm than in the beta-lactam/aminoglycoside combination therapy arm (OR = 0.38, 95% CI = 0.16-0.88, P = 0.024). No difference between the two treatment arms was found in subanalyses of the four studies that included only patients with staphylococcal infections in terms of mortality (OR = 0.69, 95% CI = 0.26-1.86, fixed effects model), treatment success (OR = 1.27, 95% CI = 0.47-3.43, fixed effects model) or relapse (OR = 0.76, 95% CI = 0.12-4.92, fixed effects model). Limitations The relatively small number of available comparative trials was the major limitation of this meta-analysis. Conclusions The limited evidence from the available prospective comparative studies does not offer support for the addition of an aminoglycoside to beta-lactam treatment of patients with endocarditis caused by Gram-positive cocci. A large multicentre RCT is necessary to reach a definitive conclusion on this issue.

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.

Little is known regarding the utilization of services of a hospital-based employee health clinic (EHC).We evaluated the utilization of services of the EHC of a tertiary hospital in Greece. Demographic and clinical data were prospectively collected and analyzed for all employees who visited the EHC during a 24-month period (01/06/2003-31/05/2005).A total of 939 primary and 55 follow-up visits were recorded. Of all 994 visits, 419 were made by nurses (42%), 270 by administrative staff (27%), and only 15 visits by physicians (1%). Only 5.6% of physicians used the EHC during the study period (14 out of 252 doctors) whereas 35.4% of the nurses (218 out of 615) visited the EHC at least once (p0.001). Three hundred and one of the rest 544 employees (55.3%) visited the EHC, significantly more than physicians (p0.001) and nurses (p0.001). The majority of employees who visited the clinic were females (78%), while the most common reason for consultation was periodic evaluation accounting for 108 visits (11%), followed by abdominal pain (99 visits, 10%), dizziness (48 visits, 5%), and respiratory tract infections (44 visits, 5%). A significant reduction in the number of visits was observed after the 9(th) month of the study, coinciding with a change in the worker's health insurance policy (p0.001).Periodic evaluations, abdominal pain, dizziness, respiratory tract infections, and weakness/malaise cover the bulk of consultation visits of a hospital-based EHC. Physicians were the group of employees that visited the EHC less often.

The use of aortic allografts has emerged as a management option in patients with aortic graft infections. We present a patient with a history of Takayasu's disease whose aortic graft infection was controlled with replacement of the excised infected aortic graft with an allograft. However, the patient died 9 months later after the rupture of a large anastomotic aortic aneurysm. Our report emphasizes the limitations in the management of aortic graft infections in patients with extensive vascular disease such as Takayasu's disease. This is the result of difficulties in performing extra-anatomical bypass as well as a possibly increased risk of formation of anastomotic aneurysms in these patients.

Summary We did a meta-analysis of randomised controlled trials studying glycopeptides as part of the initial empirical treatment of febrile neutropenic patients with a beta-lactam and with or without an aminoglycoside. 14 randomised controlled trials that studied 2413 patients were included in the analysis. A better outcome regarding treatment success, without modification of the initial regimen, was accomplished with the inclusion of a glycopeptide in the empirical therapy; this better outcome applied to the full set of studied patients (OR=1·63, 95% CI 1·17–2·28), as well as in three important subsets of patients—those with microbiologically documented infections (2·03, 1·39–2·97), patients with bacteraemia (1·80, 1·23–2·63), and patients with severe neutropenia, defined as a white blood cell count below 100 cells/μL (2·24, 1·15–4·39). However, mortality was not different in the compared groups (0·67, 0·42–1·05). Overall treatment success was not different if a glycopeptide was added to the antimicrobial regimen in the case of continuation of fever 72 hours or more after the start of treatment (1·02, 0·68–1·52). Also, the inclusion of a glycopeptide in the empirical regimen did not lead to a difference regarding time to defervesence. Adverse effects (4·98, 2·91–8·55), including nephrotoxicity (2·10, 1·12–3·95), were more common in the group receiving a glycopeptide as part of the empirical treatment. In conclusion, our meta-analysis suggests that there are good reasons why glycopeptides should not be routinely used as part of the initial empirical treatment of febrile neutropenic patients.

The quantity and quality of published research in the field of Virology by different world regions was estimated in this study. Using the PubMed database, articles from journals included in the "Virology" category of the "Journal Citation Reports" database of the Institute for Scientific Information for the period 1995-2003 were retrieved. The world was divided into nine regions based on geographic, economic, and scientific criteria. Data on the country of origin of the research was available for 33,425 out of 33,712 articles (99.2% of all articles from the included journals). USA exceeds all other world regions in research production for the period studied (42% of total articles), with Western Europe ranking second (35.7%). The mean impact factor in articles published in Virology journals was highest for the USA (4.60), while it was 3.90 for Western Europe and 3.22 for the rest of the world (seven regions combined). USA and Canada ranked first in research productivity when both gross national income per capita (GNIPC) and population were taken into account. The results of this analysis show a distressing fact; the absolute and relative production of research in the field of Virology by the developing regions is very low, although viral diseases cause considerable morbidity and mortality in these areas. It is evident from this study that developing regions need more help from the developed regions to enhance research infrastructure.

Background The intravenous use of polymyxins has been considered to be associated with considerable nephrotoxicity and neurotoxicity. For this reason, the systemic administration of polymyxins had been abandoned for about 20 years in most areas of the world. However, the problem of infections due to multidrug-resistant (MDR) Gram-negative bacteria such us Pseudomonas aeruginosa and Acinetobacter baumanniii has led to the re-use of polymyxins. Our objective was to study the toxicity of prolonged intravenous administration of colistin (polymyxin E). Methods An observational study of a retrospective cohort at "Henry Dunant" Hospital, a 450-bed tertiary care center in Athens, Greece, was undertaken. Patients who received intravenous colistin for more than 4 weeks for the treatment of multidrug resistant Gram-negative infections were included in the study. Serum creatinine, blood urea, liver function tests, symptoms and signs of neurotoxicity were the main outcomes studied. Results We analyzed data for 19 courses of prolonged intravenous colistin [mean duration of administration (± SD) 43.4 (± 14.6) days, mean daily dosage (± SD) 4.4 (± 2.1) million IU, mean cumulative dosage (± SD) 190.4 (± 91.0) million IU] in 17 patients. The median creatinine value increased by 0.25 mg/dl during the treatment compared to the baseline (p < 0.001) but returned close to the baseline at the end of treatment (higher by 0.1 mg/dl, p = 0.67). No apnea or other evidence of neuromuscular blockade was noted in any of these patients who received prolonged treatment with colistin. Conclusions No serious toxicity was observed in this group of patients who received prolonged intravenous colistin. Colistin should be considered as a therapeutic option in patients with infections due to multidrug resistant Gram-negative bacteria.

The addition of an aminoglycoside to a beta -lactam therapy regimen has been suggested to have a beneficial effect in delaying or preventing the development of antimicrobial resistance. We studied the effect of aminoglycoside/ beta -lactam combination therapy versus beta-lactam monotherapy on the emergence of resistance.We performed a meta-analysis of randomized, controlled trials (RCTs) that compared aminoglycoside/ beta-lactam combination therapy with beta-lactam monotherapy and that reported data regarding the emergence of resistance (primary outcome) and/or development of superinfection, treatment failure, treatment failure attributable to emergence of resistance, treatment failure attributable to superinfection, all-cause mortality during treatment, and mortality due to infection. Data for this meta-analysis were identified from the PubMed database, Current Contents database, Cochrane central register of controlled trials, and references in relevant articles.A total of 8 RCTs were included in the analysis. Beta -lactam monotherapy was not associated with a greater emergence of resistance than was the aminoglycoside/ beta-lactam combination (odds ratio [OR], 0.90; 95% confidence interval [CI], 0.56-1.47). Actually, beta -lactam monotherapy was associated with fewer superinfections (OR, 0.62; 95% CI, 0.42-0.93) and fewer treatment failures (OR, 0.62; 95% CI, 0.38-1.01). Rates of treatment failure attributable to emergence of resistance (OR, 3.09; 95% CI, 0.75-12.82), treatment failure attributable to superinfection (OR, 0.60; 95% CI, 0.33-1.10), all-cause mortality during treatment (OR, 0.70; 95% CI, 0.40-1.25), and mortality due to infection (OR, 0.74; 95% CI, 0.46-1.21) did not differ significantly between the 2 regimens.Compared with beta-lactam monotherapy, the aminoglycoside/ beta-lactam combination was not associated with a beneficial effect on the development of antimicrobial resistance among initially antimicrobial-susceptible isolates.

Background Trying to confront with the widespread burden of infectious diseases, the society worldwide invests considerably on research. We evaluated the contribution of different world regions in research production in Infectious Diseases. Methods Using the online Pubmed database we retrieved articles from 38 journals included in the "Infectious Diseases" category of the "Journal Citation Reports" database of the Institute for Scientific Information for the period 1995–2002. The world was divided into 9 regions based on geographic, economic and scientific criteria. Using an elaborate retrieval system we obtained data on published articles from different world regions. In our evaluation we introduced an estimate of both quantity and quality of research produced from each world region per year using: (1) the total number of publications, (2) the mean impact factor of publications, and (3) the product of the above two parameters. Results Data on the country of origin of the research was available for 45,232 out of 45,922 retrieved articles (98.5 %). USA and Western Europe are by far the most productive regions concerning publications of research articles. However, the rate of increase in the production of articles was higher in Eastern Europe, Africa, Latin America and the Caribbean, and Asia during the study period. The mean impact factor is highest for articles originating in the USA (3.42), while it was 2.82 for Western Europe and 2.73 for the rest of the world (7 regions combined). Conclusion USA and Western Europe make up a striking 80% of the world's research production in Infectious Diseases in terms of both quantity and quality. However, all world regions achieved a gradual increase in the production of Infectious Diseases articles, with the regions ranking lower at present displaying the highest rate of increase.

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.