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Treatment options for multidrug resistant Acinetobacter baumannii strains (MDR-AB) are limited. Minocycline has been used alone or in combination in the treatment of infections associated with AB. A systematic review of the clinical use of minocycline in nosocomial infections associated with MDR-AB was performed according to the PRISMA-P guidelines. PubMed-Medline, Scopus and Web of Science TM databases were searched from their inception until March 2019. Additional Google Scholar free searches were performed. Out of 2990 articles, 10 clinical studies (9 retrospective case series and 1 prospective single center trial) met the eligibility criteria. In total, 223 out of 268 (83.2%) evaluated patients received a minocycline-based regimen; and 200 out of 218 (91.7%) patients with available data received minocycline as part of a combination antimicrobial regimen (most frequently colistin or carbapenems). Pneumonia was the most common infection type in the 268 cases (80.6% with 50.4% ventilator-associated pneumonia). The clinical and microbiological success rates following minocycline treatment were 72.6% and 60.2%, respectively. Mortality was 20.9% among 167 patients with relevant data. In this systematic review, minocycline demonstrated promising activity against MDR-AB isolates. This review sets the ground for further studies exploring the role of minocycline in the treatment of MDR-AB associated infections.

International audience; Data regarding the epidemiology and diagnosis of invasive aspergillosis in the critically ill population are limited, with data regarding elderly patients (≥75 years old) even scarcer. We aimed to further compare the epidemiology, characteristics and outcome of elderly versus nonelderly critically ill patients with invasive aspergillosis (IA) Prospective, international, multicenter observational study (AspICU) including adult intensive care unit (ICU) patients, with a culture and/or direct examination and/or histopathological sample positive for Aspergillus spp. at any site. We compared clinical characteristics and outcome of IA in ICU patients using two different diagnostic algorithms. Elderly and nonelderly ICU patients with IA differed in a number of characteristics, including comorbidities, clinical features of the disease, mycology testing, and radiological findings. No difference regarding mortality was found. According to the clinical algorithm, elderly patients were more likely to be diagnosed with putative IA. Elderly patients had less diagnostic radiological findings and when these findings were present they were detected late in the disease course. The comparison between elderly survivors and nonsurvivors demonstrated differences in clinical characteristics of the disease, affected sites and supportive therapy needed. All patients who were diagnosed with proven IA died. Increased vigilance combined with active search for mycological laboratory evidence and radiological confirmation are necessary for the timely diagnosis of IA in the elderly patient subset. Although elderly state per se is not a particular risk factor for mortality, a high SOFA score and the decision not to administer antifungal therapy may have an impact on survival of elderly patients.

Background Clostridium difficile is one of the major causes of diarrhoea among critically ill patients and its prevalence increases exponentially in relation to the use of antibiotics and medical devices. We sought to investigate the incidence of C. difficile infection in Greek units, and identify potential risk factors related to C. difficile infection. Methods A prospective multicenter cohort analysis of critically ill patients (3 ICUs from 1/1/2014 to 31/12/2014). Results Among 970(100%) patients, 95(9.79%) with diarrhoea, were included. Their demographic, comorbidity and clinical characteristics were recorded on admission to the unit. The known predisposing factors for the infection were recorded and the diagnostic tests to confirm C. difficile were conducted, based on the current guidelines. The incidence of C. difficile infection was 1.3% (n = 13). All-cause mortality in patients with diarrhoea, C. difficile infection and attributable mortality in patients with C. difficile infection was 28%, 38.5% and 30.8% respectively. Sequential Organ Failure Assessment (SOFA) scores on admission were significantly lower and prior C. difficile infection was more common in patients with current C. difficile infection. Regarding other potential risk factors, no difference was found between groups. No factor was independently associated with C. difficile infection. Conclusions C. difficile infection is low in Greek intensive care units, but remains a serious problem among the critically-ill. Mortality was similar to reports from other countries. No factor was independently associated with C. difficile infection.

BACKGROUND Intra-abdominal candidiasis (IAC) has a considerable cost in terms of mortality and morbidity. We sought to study the epidemiology, characteristics and outcome of elderly (>75 years old) versus non-elderly patients with IAC and risk factors for mortality in elderly patients. METHODS Post-hoc analysis of a retrospective multinational cohort study over a 3-year period (2011-2013). RESULTS Of 482 patients, 124 (25.7%) were elderly and 358 (74.3%) were non-elderly. The mean age was 80.4±3.9 and 56.3±13.8 years, respectively. Fifty-four of 124 (43.5%) and 75/358 (20.9%) died until the end of observation. The majority of isolates were Candida albicans. Echinocandins were the most prescribed initial agent. Elderly patients were more likely to have a higher APACHE II Score, and to suffer from chronic obstructive pulmonary disease and heart disease. Non-elderly patients were more likely to be treated with immunosuppressants and steroids, and to have received solid organ transplantation. Mortality was significantly higher in the elderly group. Regarding risk factors for mortality in elderly patients, non-survivors were more likely to be males, reoperated, develop septic shock, receive vasopressors, suffer from end-stage renal disease (ESRD), and have inadequate abdominal source control within 48 hours. They had a higher APACHE II Score and a higher number of acquired organ dysfunction. ESRD and inadequate abdominal source control were significantly associated with mortality. CONCLUSIONS Factors independently predicting mortality in elderly patients with IAC were ESRD and inadequate abdominal source control. Elderlies were found to have more pulmonary and cardiac morbidities and had higher mortality than non-elderlies.

Background Treatment options for multi-drug-resistant (including extensively and pandrug-resistant) Acinetobacter baumannii strains (herein MDR-AB) are limited. Minocycline, a synthetic tetracycline derivative, has been used alone or in combination in the treatment of infections associated with AB. We systematically reviewed the available clinical evidence regarding its role in the treatment of nosocomial infections caused by MDR-AB isolates in adult patients. Methods A systematic review of the published literature examining the clinical use of minocycline in nosocomial infections associated with MDR-AB isolates (defined according to ECDC guidance) was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Guidelines. PubMed, Scopus and Web of Sciences™ databases were searched from their inception until the March 20, 2018. Three researchers individually evaluated the available clinical studies according to predefined inclusion and exclusion criteria. No language restrictions were applied. Results Out of 2,576 articles, 9 clinical studies (8 retrospective case series and 1 prospective single-center trial) met the eligibility criteria. In total, 221 out of 265 (83.4%) evaluated adult patients received a minocycline-based antimicrobial regimen and 44 out of 265 (16.6%) received other antimicrobial agents (most frequently aminoglycocides); 198 out of 216 (91.7%) patients with available data, received minocycline as part of an antimicrobial combination regimen (most frequently colistin and carbapenems). Pneumonia was the most prevalent infection (81.5% with 50.4% ventilator associated pneumonias). Clinical and microbiological success rates in the minocycline group were 72.4% and 59.7%, respectively. Mortality rate was 21.2% among 165 patients with relevant data. In the non-minocycline group, clinical and microbiological cure rates were 45.5% and 18.2%, respectively. Conclusion In this systematic review, minocycline demonstrated promising activity against MDR-AB isolates. This study could set the grounds for further research with large randomized, controlled trials that would explore and establish the role of minocycline in the treatment of MDR-AB-associated infections. Disclosures All authors: No reported disclosures.

Background: We performed a systematic review and meta-analysis of short- vs long-duration antibiotic regimens for ventilator-associated pneumonia (VAP). Methods: We searched PubMed and Cochrane Central Registry of Controlled Trials. Four randomized controlled trials (RCTs) comparing short (7-8 days) with long (10-15 days) regimens were identifi ed. Primary outcomes included mortality, antibiotic-free days, and clinical and microbiologic relapses. Secondary outcomes included mechanical ventilation-free days, duration of mechanical ventilation, and length of ICU stay. Results: All RCTs included mortality data, whereas data on relapse and antibiotic-free days were provided in three and two out of four RCTs, respectively. No difference in mortality was found between the compared arms (fi xed effect model [FEM]: OR 5 1.20; 95% CI, 0.84-1.72; P 5 .32). There was an increase in antibiotic-free days in favor of the short-course treatment with a pooled weighted mean difference of 3.40 days (random effects model: 95% CI, 1.43-5.37; P , .001). There was no difference in relapses between the compared arms, although a strong trend to lower relapses in the long-course treatment was observed (FEM: OR 5 1.67; 95% CI, 0.99-2.83; P 5 .06). No difference was found between the two arms regarding the remaining outcomes. Sensitivity analyses yielded similar results. Conclusions: Short-course treatment of VAP was associated with more antibiotic-free days. No difference was found regarding mortality and relapses; however, a strong trend for fewer relapses was observed in favor of the long-course treatment, being mostly driven by one study in which the observed relapses were probably more microbiologic than clinical. Additional research is required to elucidate the issue.

Ventilator-associated pneumonia (VAP) is a major cause of morbidity and mortality in the critical care setting. It incurs great additional cost and the antibiotics prescribed for patients with VAP account for the majority of total antibiotic prescriptions. The increased cost of VAP as well as the emergence of antimicrobial resistance and the potential adverse events because of treatment indicate that the application of shorter antibiotic regimens for the treatment of VAP poses as a one-way choice.According to the findings of relevant randomized controlled trials, patients receiving short-course regimens for the treatment of VAP have significantly more antibiotic-free days without any negative impact on mortality. Additionally, no other differences were found regarding other secondary outcomes. However, there were higher relapse rates in patients with VAP because of nonfermenting Gram-negative bacilli and there was a lower emergence of multidrug-resistant pathogens.The shortening of the duration of treatment for VAP is promising, as long as a holistic approach that combines methods ensuring the adequate sterilization of septic foci, the optimization of antibiotic levels, the multifaceted delivery of antimicrobials in the lung and the usage of biomarkers that allow the monitoring of the disease course and the effectiveness of administered treatment are incorporated in clinical practice.

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

We evaluated the published data for the incidence, characteristics and outcomes of patients with community-acquired pneumonia (CAP) due to methicillin-resistant Staphylococcus aureus (MRSA). The estimated incidence of MRSA CAP is 0.51-0.64 cases per 100,000. We identified 74 articles reporting data on 114 patients. Influenza like symptoms was reported in 41% of patients. Pneumonia improved in 59 (54.1%) out of 109 patients; 49 (44.5%) out of 110 patients died. The duration of hospitalisation was 38.1+/-24.9 and 8.3+/-11.7 days, respectively. The duration of intensive care unit (ICU) stay was 18.9+/-13.6 and 6.8+/-9.7 days, respectively. 76 strains carried the Panton-Valentine leukocidin gene. The univariate analysis showed that multi-organ failure (p

Burkholderia cepacia complex (BCC) is an important group of pathogens affecting patients with cystic fibrosis and chronic granulomatous disease as well as immunocompromised and hospitalised patients. Therapeutic options are limited owing to high levels of resistance of the organism, either intrinsic or acquired, to many antimicrobial agents. Co-trimoxazole (trimethoprim/sulfamethoxazole) has been a drug of choice. However, in some cases it cannot be administered because of allergic or hypersensitivity reactions, intolerance or resistance. We systematically searched for relevant publications including clinical data in PubMed and Scopus. The search identified 48 relevant case reports (57 cases) and 8 cohort studies or trials. Nineteen (33.3%) of 57 patients included in the case reports received ceftazidime-based regimens, 14 (73.7%) of whom were cured. Meropenem was administered in seven patients (12.3%), one (14.3%) of whom improved and five (71.4%) were cured. Seven (12.3%) of 57 cases were treated with penicillins, four of which were piperacillin (all had a favourable outcome). Based on the data reported in the eight relevant cohort studies or trials identified, favourable outcomes were observed in 68.4% (26/38) to 100% (16/16) of cases treated with ceftazidime and 66.7% (6/9) of cases treated with meropenem. Also, 9/12 (75%) of patients receiving penicillins improved. Thus, Ceftazidime, meropenem and penicillins, mainly piperacillin, either alone or in combination with other antimicrobial agents, may be considered as alternative options for BCC infections, according to the in vitro antimicrobial susceptibility patterns and clinical results. However, the available clinical data are not sufficient and further clinical experience is required to clarify the appropriateness of these antibiotics for BCC infections.

Several types of infections involving the respiratory tract have a seasonal variation. We further examined whether lower urinary tract infections (UTIs) are associated with meteorological parameters. We retrospectively evaluated the correlation of the weekly percentage of house call visits for lower UTIs (relatively to all house call visits, excluding those for respiratory tract infections), performed by "SOS Doctors" specialized physicians in Attica, Greece (1/11/2000-18/1/2005), with the average weekly temperature and humidity, recorded at the same area, 3 days earlier. Three thousand two hundred and twenty-one visits for lower UTIs were recorded in patients of 62.9 +/- 21.0 years of age. House call visits for lower UTIs, as defined above, correlated with the average weekly temperature (Spearman's rho+0.468) and humidity (Spearman's rho -0.394); similarly, if respiratory tract infections were not excluded from the calculations (Spearman's rho +0.491 and -0.406, respectively); or if a 2-day lag between measurements was used (Spearman's rho +0.468 and -0.386, respectively). All the above findings were significant (p

Background: Despite the high incidence of acute pyelonephritis in the community setting, there is no consensus on the optimal duration of treatment. A potential reduction in the duration of the administered antibiotic regimens could contribute to avoiding further development of antimicrobial resistance. Objective: The aim of this meta-analysis was to compare short-course (7- to 14-day) with long-course (14- to 42-day) treatment with the same antibiotic regimens, in terms of the effectiveness and tolerability, in acute pyelonephritis. Methods: We searched PubMed, Cochrane Central Register of Controlled Trials, and SCOPUS (January 1966-March 2008) to identify and extract data from randomized controlled trials (RCTs) comparing the effectiveness and toxicity of short- versus long-course regimens. Additionally, references of studies were searched. A publication was included if: it was an RCT; involved adult and/or adolescent patients with acute pyelonephritis; compared regimens with the same antibiotic, at the same daily dosage, that were administered for differing durations (a short course and a long course lie, no absolute time cutoff (in days) was employed; rather, the duration of one regimen compared with another defined short- vs long-course]); and reported data regarding clinical success, bacteriologic efficacy, relapses, recurrences, and adverse events and/or patient withdrawals due to adverse events. Trials with a mixed population, including patients with acute pyelonephritis as a subset, were also included in the meta-analysis. Efficacy was assessed by evaluating clinical success , defined as resolution of symptoms and signs at the test-of-cure visit, and bacteriologic efficacy , defined as yielding sterile urine cultures or positive cultures with 3 colony-forming units per milliliter of urine at the test-of-cure visit. Tolerability was assessed by extracting data for adverse events. Results: According to our initial search, 205, 136, 179, and 73 potentially relevant articles were retrieved from PubMed, Cochrane Central Register of Controlled Trials, SCOPUS, and references of evaluable trials, respectively. Four RCTs were eligible for inclusion in the meta-analysis. Significant differences were not found between the short- and long-course treatment of acute pyclonephritis in terms of clinical success (odds ratio [OR], 1.27; 95% CI, 0.59-2.70), bacteriologic efficacy (OR, 0.80; 95% CI, 0.13-4.95), and relapse (OR, 0.65; 95% CI, 0.08-5.39). Also, significant differences were not found between the short- and long-course treatments regarding adverse events (OR, 0.64; 95% CI, 0.33-1.25), withdrawals due to adverse events (OR, 0.65; 95% CI, 0.28-1.55), and recurrences (OR, 1.39; 95% CI, 0.63-3.06). Conclusion: This meta-analysis failed to identify any significant differences, with regard to effectiveness and tolerability, between short- and long-course treatment with the same antibiotic.

In this investigation, we sought to investigate the characteristics of Citrobacter spp. infections. A retrospective cohort study in a 700-bed, tertiary care, university hospital was carried out during the period from June 1994 to January 2006. Seventy-eight patients (70 adults) with Citrobacter spp. isolates were identified. C. freundii was more common (71.8%), followed by C. koseri (23.1%) and C. braakii (3.8%). The most common associated clinical syndromes were urinary tract infections (52.6% of cases, including eight cases of asymptomatic bacteriuria), as well as intra-abdominal (14.1%), surgical site (7.7%), skin and soft tissue (6.4%), and respiratory tract infections (6.4%). In 29.5% of patients, Citrobacter spp. isolates were associated to polymicrobial infections, principally at sites other than the urinary tract. Antibiograms of 38 consecutive Citrobacter spp. isolates (29 C. freundii) were available. Most active agents were colistin (100%), fosfomycin (100%), imipenem (97.4%), gentamicin (89.5%), nitrofurantoin (89.5%), ciprofloxacin (80.6%), and cefepime (73.7%). Most patients (82.1%) had at least one underlying illness. Combination antimicrobial therapy was administered in 28.2% of cases. One patient died during hospitalization. The length of hospital stay was longer in patients with polymicrobial compared to monomicrobial infections (23 versus 13 days, respectively, p = 0.02). The isolation of Citrobacter species, although rather infrequent, was clinically relevant in the great majority of cases. Further attention should be paid to these pathogens.

OBJECTIVE To evaluate the effectiveness and safety of short-course antibiotic treatment of group A β-hemolytic streptococcal (GAS) tonsillopharyngitis. METHODS We performed a meta-analysis of randomized controlled trials (RCTs) retrieved from PubMed and the Cochrane Central Register of Controlled Trials using a structured search strategy. The last date either database was accessed was November 14, 2007. We included RCTs that involved patients of any age with GAS tonsillopharyngitis, comparing short-course (≤7 days) vs long-course (at least 2 days longer than short-course) treatment with the same antibiotics. The primary analysis compared 5 to 7 days with 10 days of treatment, using a random effects model. RESULTS Eleven RCTs comparing short-course vs long-course treatment (5 with penicillin V, 4 with oral cephalosporins, 1 with intramuscular ceftriaxone, and 1 with clindamycin; 6 of the 11 were open label) were included. In the primary analysis, microbiological eradication rates of GAS were inferior for short-course vs long-course treatment (8 RCTs, 1607 patients; odds ratio [OR], 0.49; 95% confidence interval [CI], 0.32-0.74). This association was noted with penicillin V treatment (3 RCTs, 500 patients; OR, 0.36; 95% CI, 0.13-0.99) but was nonsignificant with cephalosporin treatment (4 RCTs, 1018 patients; OR, 0.62; 95% CI, 0.38-1.03). Microbiological eradication was less likely with short-course treatment in trials involving primarily children and adolescents (aged CONCLUSION Short-course treatment for GAS tonsillopharyngitis, particularly with penicillin V, is associated with inferior bacteriological eradication rates.

Objectives: The aim of this study was to evaluate the comparative effectiveness and safety of short (5 days) and long (7 or 10 days) duration antimicrobial treatment of patients with acute exacerbations of chronic bronchitis (AECB). Methods: We performed a meta-analysis of randomized controlled trials (RCTs) comparing regimens of the same antibiotic (same dosage and same route of administration) administered for a different time period. We searched PubMed, the Cochrane Central Register of Controlled Trials and reference lists from publications, with no language restrictions. Results: Of the 1031 reports retrieved initially, seven RCTs, enrolling 3083 patients with AECB, met our inclusion criteria. The antimicrobials studied in these seven RCTs were quinolones, cefixime and clarithromycin. There was no difference between the short- and long-duration therapies with regard to treatment success in intention-to-treat [relative risk (RR) 5 0.99, 95% confidence interval (CI) 0.95‐1.03], clinically evaluable (RR 5 0.99, 95% CI 0.96‐1.02) or microbiologically evaluable (RR 5 0.98, 95% CI 0.93‐1.02) patients. Short-duration treatment, when compared with long, was associated with fewer adverse events (RR 5 0.84, 95% CI 0.72‐0.97). Conclusions: Short-duration treatment seems to be as effective as and safer than long-duration antimicrobial treatment of patients with AECB. Additional research is required to clarify the long-term outcomes (namely the exacerbation-free interval after the resolution of an initial episode) of the compared regimens.

Study design A meta-analysis of randomized control trials. Objective To compare fluoroquinolones to beta-lactams for the treatment of osteomyelitis. Summary of background data Treatment of osteomyelitis remains a real challenge in medicine necessitating the use of broad-spectrum antibiotics, because of the variety of the pathogens causing the infection and the fact that the infected bone may become necrotic and avascular, preventing systemic antibiotics from adequately penetrating to the infection site. Methods A literature search was performed by 2 reviewers independently (PubMed database and the Cochrane Central Register of Controlled Trials). Results We identified 7 studies eligible for inclusion in our meta-analysis; ciprofloxacin, ofloxacin, and pefloxacin were used in 3, 3, and 1 study, respectively, while various beta-lactams (mainly in the intravenous form) were used as comparators. There was no difference in treatment success for osteomyelitis between fluoroquinolones and beta-lactams [194 patients, fixed effect model (FEM), odds ratio (OR) = 0.99, 95% confidence interval (CI) 0.51-1.91], bacteriological success (201 isolates, FEM, OR = 0.88, 95% CI = 0.45-1.70), superinfections (173 patients, FEM, OR = 1.75, 95% CI = 0.63-4.90), relapses (153 patients, FEM, OR = 1.23, 95% CI = 0.46-3.31), or adverse events (170 patients, FEM, OR = 0.47, 95% CI = 0.21-1.06). Conclusion Fluoroquinolones are as effective as beta-lactams for the treatment of osteomyelitis and can be considered as a useful alternative in the physician's armamentarium. The value of fluoroquinolones for the treatment of osteomyelitis lies in the fact that they can be administered in an outpatient setting. However, they should be used with caution, so as to preserve their activity against increasingly resistant bacteria.

SUMMARY Background Ertapenem is a new member of the carbapenem class of antibiotics, with a favourable pharmacokinetic profile, but a narrower spectrum of antimicrobial activity, compared with older representatives of this class. Aim To evaluate the effectiveness and safety of ertapenem for treatment of complicated intra-abdominal infections. Methods We performed a meta-analysis of randomized-controlled trials identified in PubMed, Cochrane and Scopus that compared ertapenem with other antimicrobial regimens, in patients of all ages, with complicated intra-abdominal infections. The primary outcomes evaluated were clinical success (cure or improvement) in the modified intention-to-treat population and clinical adverse events. Results Six randomized-controlled trials involving patients with complicated intraabdominal infections, mainly of mild-to-moderate severity (three with a double-blind design; one performed in children) that compared ertapenem treatment (once daily) against piperacillin ⁄ tazobactam, ceftriaxone plus metronidazole and ticarcillin ⁄ clavulanic acid (in three, two and one randomizedcontrolled trials respectively) were included. No difference was found between adult patients with complicated intra-abdominal infections treated with ertapenem vs. comparators, regarding clinical success (five randomized-controlled trials, 2002 patients, fixed-effect model, odds ratio: 1.11, 95% confidence interval (CI): 0.89–1.39); clinical adverse events (four randomized-controlled trials, 1530 patients, fixed-effect model, OR: 0.86, 95% CI: 0.61–1.20); microbiological success; mortality and withdrawals because of adverse events. Ertapenem was associated with more laboratory adverse events (four randomized-controlled trials, 1530 patients, fixed-effect model, OR: 1.73, 95% CI: 1.14–2.61), but none was reported as serious. Conclusion This meta-analysis provides additional evidence that ertapenem can be used as effectively and safely, as other recommended antimicrobial regimens, for the treatment of complicated intra-abdominal infections, particularly of mild-tomoderate severity.

Statins are currently used for hyperlipidaemia control and considered useful for protection from cardiovascular events. In addition, there is increasing evidence for the potential use of statins in preventing and treating infections.We performed a systematic review of the literature that compared the outcome between statin and non-statin users among patients suffering from sepsis or other infections. The relevant studies were identified from searches of PubMed, Scopus and the Cochrane Library databases.Twenty studies were identified (13 of them were retrospective), out of which 9 examined the use of statins in patients with sepsis, bacteraemia or multiorgan dysfunction syndrome, 4 community-acquired pneumonia (CAP), 1 ICU infections, 2 other bacterial infections and 4 viral infections. Eleven studies had data regarding mortality as the main outcome: 8 showed decreased mortality in statin users (3 of them reported on patients with bacteraemia), 2 showed no difference in mortality and 1 reported an increased mortality in patients who received statins. Seven studies examined the risk of sepsis as the main outcome; six of these studies showed a decreased risk of sepsis in patients receiving statins, whereas one study found no difference.The majority of the studies suggest that statins may have a positive role in the treatment of patients with sepsis and infection. However, the majority of the reviewed studies have the inherent methodological limitations of retrospective studies. Conclusions regarding this important clinical question should wait for the results of ongoing relevant randomized controlled trials.

Summary Aim To compare the effectiveness and safety of clindamycin/aminoglycoside with broad-spectrum β-lactam monotherapy in patients with intra-abdominal infections by performing a meta-analysis of randomized controlled trials (RCTs). Methods The relevant 28 RCTS were retrieved from PubMed searches and reviewed by two reviewers independently. Results β-lactam monotherapy was more effective regarding cure of the infection than clindamycin/aminoglycoside (3177 clinically evaluable patients, fixed effects model, OR = 0.67, 95% CI: 0.55–0.81). The same result was found in several subset analyses. There was no difference in all-cause mortality and attributable-to-infection mortality [2382 intention-to-treat (ITT) patients, fixed effects model, OR = 1.25, 95% CI: 0.74–2.11 and 1976 ITT patients, OR = 1.19, 95% CI: 0.59–2.41, respectively]. There was no difference regarding overall adverse events and ototoxicity (1460 ITT patients, OR = 1.05, 95% CI: 0.80–1.37, and 1404 ITT patients, OR = 3.22, 95% CI: 0.72–14.45, respectively). However, treatment with clindamycin/aminoglycoside was more likely to be associated with nephrotoxicity compared to β-lactam (3065 ITT patients, OR = 3.7, 95% CI: 2.09–6.57). Clindamycin/aminoglycoside was less likely to be associated with antibiotic-associated diarrhoea compared to β-lactam (3050 ITT patients, OR = 0.68, 95% CI: 0.46–1.00). Conclusion The results of our meta-analysis suggest that β-lactams are more effective in the treatment of intra-abdominal infections compared with clindamycin/aminoglycoside.

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.

To the Editor, A report on the use of tigecycline for treatment of carbapenem-resistant Klebsiella pneumoniae (CRKp) infections in critically ill patients was recently published in this journal [1]...

Fungal infections represent a major burden in the critical care setting with increasing morbidity and mortality. Candidiasis is the leading cause of such infections, with C. albicans being the most common causative agent, followed by Aspergillosis and Mucormycosis. The diagnosis of such infections is cumbersome requiring increased clinical vigilance and extensive laboratory testing, including radiology, cultures, biopsies and other indirect methods. However, it is not uncommon for definitive evidence to be unavailable. Risk and host factors indicating the probability of infections may greatly help in the diagnostic approach. Timely and adequate intervention is important for their successful treatment. The available therapeutic armamentarium, although not very extensive, is effective with low resistance rates for the newer antifungal agents. However, timely and prudent use is necessary to maximize favorable outcomes.

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.

Summary Objective To study the characteristics, risk factors and outcomes of intensive care unit (ICU) patients with carbapenem-resistant (CRKp) and carbapenem-susceptible (CSKp) Klebsiella pneumoniae infections. Methods A retrospective cohort of patients with K. pneumoniae infections in an eight-bed ICU between January 2006 and October 2009. Results During the study period, 104 patients were diagnosed with K. pneumoniae infection (80 CRKp and 24 CSKp). Isolation of CRKp increased gradually during the study period, while isolation of CSKp remained constant. The mean age of patients was 66.3 ± 14.3 years. The mean APACHE II score was 17.9 ± 6.9. The median duration of ICU stay until the infection was 15 days. Thirty five patients (33.7%) had primary and 30 (28.8%) had secondary bacteremia. Seventy-two patients (69.2%) died in the ICU. No independent risk factors for development of CRKp infections were identified in the multivariate analysis. Treatment failure ( p = 0.001) was the only independent predictor of mortality in the multivariate analysis (APACHE II, shock, multi-organ failure, respiratory failure, acute renal failure, acidosis and extensive-drug resistance were included in the model). No difference in mortality was found between patients with CRKp and CSKp isolates. Conclusions Infection due to K. pneumoniae in the ICU was associated with high mortality. Control of the infection was the most important determinant of the outcome of critically ill patients.

We present a case of a 29-y-old woman with rectocele, cystocele, and uterine prolapse who developed a vaginal infection after the placement of a macroporous polypropylene vaginal mesh. Bacteroides melaninogenicus was isolated from the area of the infection. The exposed parts of the mesh were removed and she received treatment with metronidazole and doxycycline. No recurrence of the infection was noted during 12 months of follow-up. However, the patient continued to avoid intercourse due to severe dyspareunia. Vaginal mesh-related infections represent an emerging type of infection that may complicate reconstructive surgery in patients with pelvic organ prolapse.

We performed a systematic review and meta-analysis of short- vs long-duration antibiotic regimens for ventilator-associated pneumonia (VAP).We searched PubMed and Cochrane Central Registry of Controlled Trials. Four randomized controlled trials (RCTs) comparing short (7-8 days) with long (10-15 days) regimens were identified. Primary outcomes included mortality, antibiotic-free days, and clinical and microbiologic relapses. Secondary outcomes included mechanical ventilation-free days, duration of mechanical ventilation, and length of ICU stay.All RCTs included mortality data, whereas data on relapse and antibiotic-free days were provided in three and two out of four RCTs, respectively. No difference in mortality was found between the compared arms (fixed effect model [FEM]: OR = 1.20; 95% CI, 0.84-1.72; P = .32). There was an increase in antibiotic-free days in favor of the short-course treatment with a pooled weighted mean difference of 3.40 days (random effects model: 95% CI, 1.43-5.37; Plt; .001). There was no difference in relapses between the compared arms, although a strong trend to lower relapses in the long-course treatment was observed (FEM: OR = 1.67; 95% CI, 0.99-2.83; P = .06). No difference was found between the two arms regarding the remaining outcomes. Sensitivity analyses yielded similar results.Short-course treatment of VAP was associated with more antibiotic-free days. No difference was found regarding mortality and relapses; however, a strong trend for fewer relapses was observed in favor of the long-course treatment, being mostly driven by one study in which the observed relapses were probably more microbiologic than clinical. Additional research is required to elucidate the issue.

We aimed to describe various parameters of critically ill patients who developed VAP and correlate them with its outcome.

We sought to perform a systematic review and meta-analysis of procalcitonin(PCT)-guided antibiotic therapy algorithms for critically ill adult patients. We performed a search in PubMed and in the Cochrane Central Register of Controlled Trials. Seven evaluable randomised clinical trials (RCTs) were identified and analysed. Primary outcomes included the duration of antibiotic therapy for the first episode of infection and 28-day mortality. Secondary outcomes included length of ICU stay, length of hospitalisation, antibiotic-free days within the first 28 days of hospitalisation, recurrences, and superinfections. Data on the duration of antibiotic therapy for the first episode of infection were provided in five out of seven included RCTs, while data on 28-day mortality were provided in all of the included RCTs. Duration of antibiotic therapy for the first episode of infection was reduced in favour of PCT-guided treatment [pooled weighted mean difference (WMD) = −3.15 days, random effects model, 95 % confidence interval (CI) −4.36 to −1.95, P

It is unclear whether the effectiveness of polymyxins depends on the site of infection, the responsible pathogen, dosage, and monotherapy vs. combination therapy. We investigated colistin therapy in a large, retrospective, single-centre, cohort study. Primary analysis outcomes were infection outcome, survival and nephrotoxicity. Over a 7-year period (October 2000 to October 2007), 258 patients received intravenous (i.v.) colistin for at least 72h for microbiologically documented multidrug-resistant Gram-negative bacterial infections, comprising 170 (65.9%) Acinetobacter baumannii , 68 (26.4%) Pseudomonas aeruginosa , 18 (7.0%) Klebsiella pneumoniae , 1 (0.4%) Stenotrophomonas maltophilia and 1 (0.4%) Enterobacter cloacae . Cure of infection occurred in 79.1% of patients, nephrotoxicity in 10% and hospital survival in 65.1%. In the multivariate analysis, independent predictors of survival were colistin average daily dose [adjusted odds ratio (aOR)=1.22, 95% confidence interval (CI) 1.05–1.42] and cure of infection (aOR=9, 95% CI 3.6–23.1), whilst the proportion of creatinine change (aOR=0.21, 95% CI 0.1–0.45), Acute Physiology and Chronic Health Evaluation (APACHE) II score (aOR=0.89, 95% CI 0.84–0.95) and haematological disease (aOR=0.23, 95% CI 0.08–0.66) were associated with mortality. Effectiveness of colistin was not dependent on the type of pathogen. No independent predictors for nephrotoxicity were observed. The findings of the largest cohort study to date on i.v. colistin show that colistin is a valuable antibiotic with acceptable nephrotoxicity and considerable effectiveness that depends on the daily dosage and infection site.

Methicillin-resistant Staphylococcus aureus (MRSA) is a growing infectious concern, mainly in the context of its rapid adaptation to novel antibiotic options for its treatment and the growing morbidity, mortality, and healthcare costs associated with its emergence. the authors sought to investigate whether an older antibiotic, such as trimethoprim-sulfamethoxazole (SXT), may have a role in treating MRSA-related infections, according to the available literature on the subject. The authors reviewed literature data on: resistance of MRSA to SXT worldwide in recent years, efficacy of SXT for MRSA decolonization or prophylaxis from MRSA infections, and clinical therapeutic efficacy of SXT in treating mild or severe community-acquired or hospital-acquired MRSA infections. Resistance varies worldwide, in general being low in the industrialized world and higher in developing countries. SXT is one of the numerous understudied options for MRSA decolonization and is growingly recognized as potentially effective in preventing MRSA infections in certain settings. Limited data on its therapeutic efficacy are encouraging, at least for mild, community-acquired infections. SXT may represent a cost-effective alternative weapon against MRSA. Its utility against this increasingly threatening pathogen need clarification through further clinical trials.

Surgical infections include surgical site infections and other infections requiring surgical intervention to resolve along with antibiotic treatment. The authors sought to conduct a review focusing on the application of the technique of meta-analyses in the study of surgical infections. Ninety meta-analyses were included in the review, which mainly focus on the use of antimicrobial prophylaxis and on the comparison of different techniques and procedures or therapeutic regimens for the treatment of surgical infections. The majority concern surgical infections in the field of abdominal surgery. Although surgical site infection rates or clinical efficacy are reported in all meta-analyses, mortality is reported as primary outcome in only a few. Meta-analyses focusing exclusively on surgical infections, reporting data on mortality as a primary outcome, and comparing different antibiotic regimens for the treatment of surgical infections may help the clinician with decision making.

Treatment guidelines generally support that a 10-14-day antibiotic regimen should be administered to uncomplicated acute bacterial sinusitis patients. However, the level of evidence for such a recommendation is rather weak. Treatment of such duration may have disadvantages compared with a shorter duration but equally effective regimen, including the promotion of bacterial drug resistance, poorest patient compliance, higher toxicity, and a greater overall economic burden.The findings of this meta-analysis suggest that short-course antibiotic treatment has similar effectiveness to longer-course treatment for patients with acute uncomplicated bacterial sinusitis, when treatment is warranted. However, we should underscore the importance of the clinician's own assessment, so that antimicrobial therapy should not inappropriately be curtailed in a patient not adequately responding to the regimen administered. We sought to evaluate the effectiveness and safety of short-course antibiotic treatment for acute bacterial sinusitis (ABS) compared with longer duration treatment. We performed a meta-analysis of randomized controlled trials (RCTs), identified by searching PubMed and the Cochrane Central Register of Controlled Trials. We included RCTs that compared short-course (up to 7 days) vs. long-course therapy (or =2 days longer than short-course), with the same antimicrobial agent, in the same daily dosage, for patients with ABS. Twelve RCTs (10 double-blinded) involving adult patients with radiologically confirmed ABS were included. There was no difference in the comparison of short-course (3-7 days) with long-course treatment (6-10 days) regarding clinical success [12 RCTs, 4430 patients, fixed effect model (FEM), odds ratio (OR) 0.95, 95% confidence interval (CI) 0.81, 1.12]; microbiological efficacy; relapses; adverse events (10 RCTs, 4172 patients, random effects model, OR 0.88, 95% CI 0.71, 1.09); or withdrawals due to adverse events. In the sensitivity analysis comparing 5- vs. 10-day regimens, clinical success was similar, although adverse events were fewer with short-course treatment (5 RCTs, 2151 patients, FEM, OR 0.79, 95% CI 0.63, 0.98). Although antibiotics for acute sinusitis should be reserved for select patients with substantial probability of bacterial disease, accurate clinical diagnosis is often difficult to attain. Short-course antibiotic treatment had comparable effectiveness to a longer course of therapy for ABS. Shortened treatment, particularly for patients without severe disease and complicating factors, might lead to fewer adverse events, better patient compliance, lower rates of resistance development and fewer costs.

To evaluate the effectiveness and safety of short-course antibiotic treatment of group A beta-hemolytic streptococcal (GAS) tonsillopharyngitis.We performed a meta-analysis of randomized controlled trials (RCTs) retrieved from PubMed and the Cochrane Central Register of Controlled Trials using a structured search strategy. The last date either database was accessed was November 14, 2007. We included RCTs that involved patients of any age with GAS tonsillopharyngitis, comparing short-course (or =7 days) vs long-course (at least 2 days longer than short-course) treatment with the same antibiotics. The primary analysis compared 5 to 7 days with 10 days of treatment, using a random effects model.Eleven RCTs comparing short-course vs long-course treatment (5 with penicillin V, 4 with oral cephalosporins, 1 with intramuscular ceftriaxone, and 1 with clindamycin; 6 of the 11 were open label) were included. In the primary analysis, microbiological eradication rates of GAS were inferior for short-course vs long-course treatment (8 RCTs, 1607 patients; odds ratio [OR], 0.49; 95% confidence interval [CI], 0.32-0.74). This association was noted with penicillin V treatment (3 RCTs, 500 patients; OR, 0.36; 95% CI, 0.13-0.99) but was nonsignificant with cephalosporin treatment (4 RCTs, 1018 patients; OR, 0.62; 95% CI, 0.38-1.03). Microbiological eradication was less likely with short-course treatment in trials involving primarily children and adolescents (aged18 years) (6 RCTs, 1258 patients; OR, 0.63; 95% CI, 0.40-0.98). Clinical success was inferior in patients who received short-course treatment (5 RCTs, 1217 patients; OR, 0.49; 95% CI, 0.25-0.96). Adverse events did not differ between compared groups. The above associations were consistent in the analyses involving all included RCTs.Short-course treatment for GAS tonsillopharyngitis, particularly with penicillin V, is associated with inferior bacteriological eradication rates.

Stenotrophomonas maltophilia has emerged as an important opportunistic pathogen, causing infections whose management is often problematic due to its inherent resistance to many antibiotics, making co-trimoxazole the main therapeutic option. However, there are cases in which either due to antimicrobial resistance or allergic reactions and intolerance to co-trimoxazole this antibiotic cannot be administered. We sought to evaluate the available clinical evidence regarding potentially effective alternative antibiotics for the treatment of S. maltophilia infections.The literature search was performed in the PubMed and Scopus databases. The search string used was 'Stenotrophomonas maltophilia OR Xanthomonas maltophilia'.Thirty-one case reports and 5 case series were retrieved including a total of 49 patients with a variety of infections. Twenty of 49 cases (40.8%) were treated with ciprofloxacin as monotherapy or in combination with other antibiotics; 12 of 49 cases (24.5%) were treated with ceftriaxone- or ceftazidime-based regimens; and 6 of 49 cases (12.2%) were treated with ticarcillin- or ticarcillin/clavulanate-based regimens. The cure or improvement rates were 18 cases (90%), 8 (75%) and 4 (66.7%), respectively. The remaining 11 patients received various antimicrobials including aminoglycoside-based regimens, carbapenems, levofloxacin, chloramphenicol, aztreonam, minocycline and other beta-lactams.The limited available data suggest that ciprofloxacin, ceftazidime or ceftriaxone, and ticarcillin/clavulanate, alone or in combination with other antibiotics, may be considered as alternative options beyond co-trimoxazole.

The emergence of multidrug-resistant gram-negative bacteria has led to the re-use of colistin, but resistance to this agent has already been reported. We aimed to investigate the potential risk factors for the isolation of colistin-resistant Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa from hospitalized patients.Matched case-control study.Tertiary care hospital in Athens, Greece.Case patients were those who had provided a clinical specimen from which a colistin-resistant K. pneumoniae, A. baumannii, or P. aeruginosa was isolated. Controls were selected from a pool of patients who had susceptible to colistin isolates and were matched (1:1) to cases for species of microorganism and site of isolation. Susceptibility to colistin was determined with the Etest.None.Data regarding patient demographics, comorbidities, admission to the intensive care unit, prior antibiotic use, and invasive procedures performed were analyzed as risk factors in a matched bivariable model. Variables significantly associated with colistin-resistant isolates (p.05) were entered in a backward multivariable logistic regression model. Forty-one colistin-resistant unique patient isolates were identified from January 1, 2006, until March 31, 2007. These isolates represented infection in 35 of 41 patients. Risk factors significantly associated with the isolation of colistin-resistant isolates were age, duration of intensive care unit stay, [corrected] surgical procedures, use of colistin, use of monobactams, duration of use of colistin and duration of use of antifungal agents [corrected] In the multivariable model, use of colistin was identified as the only independent risk factor (adjusted odds ratio = 7.78, p = .002).Colistin-resistant K. pneumoniae, A. baumannii, and P. aeruginosa pathogens may be encountered in clinical practice, in association with inappropriate colistin use. To prevent this phenomenon, colistin should be used judiciously, given that treatment options for colistin-resistant gram-negative bacteria are limited.

Recent studies have focused on issues related to heteroresistance, including its definition, methods of detection and frequency. Most such studies have reported data concerning infections caused by Staphylococcus aureus, but the clinical significance of heteroresistance is unclear. Six studies have described infections caused by S. aureus strains that were heteroresistant to vancomycin, with two suggesting an association between the emergence of heteroresistance and treatment failure or mortality, and four suggesting no such association. Further studies are required to evaluate the clinical implications of heteroresistance in an era in which rates of antimicrobial resistance are increasing alarmingly worldwide.

The administration of angiotensin-converting enzyme (ACE) inhibitors has been suggested as an alternative strategy for lowering the risk of community-acquired pneumonia (CAP) in the elderly, especially in patients with neurological and cerebrovascular comorbidity. We critically examined the relevant data from studies regarding the impact of ACE inhibitors in lowering the risk of CAP and/or mortality due to CAP in the elderly. We searched PubMed, Cochrane Database, and references of initially retrieved articles, and http://clinicaltrials.gov for ongoing trials. We identified 285 evaluable studies. Fourteen studies met the inclusion criteria and were evaluated further, of which seven were prospective studies, two randomized controlled trials, and five retrospective studies. Eight of ten studies including patients of Asian origin demonstrated a statistical significance in favor of ACE inhibitors. On the contrary, only one of five studies including patients of non-Asian origin demonstrated results in favor of ACE inhibitors. The available data suggest that ACE inhibitors may contribute to the reduction of the risk of CAP. Nevertheless, clinical data are scarce and mainly comprise studies including patients of Asian origin. As there seem to be differences regarding the genetic polymorphism of ACE among patients of different origins, future studies are needed that incorporate relevant genetics data that may help clarify the role, if any, of ACE inhibitors in preventing CAP.