Colistin versus meropenem in the empirical treatment of ventilator-associated pneumonia (Magic Bullet study): an investigator-driven, open-label, randomized, noninferiority controlled trial.

BACKGROUND: Colistin is recommended in the empirical treatment of ventilator-associated pneumonia (VAP) with a high prevalence of carbapenem-resistant gram-negative bacilli (CR-GNB). However, the efficacy and safety of colistin are not well defined. METHODS: A multicenter prospective randomized trial conducted in 32 European centers compared the efficacy and safety of colistin (4.5 million unit loading dose followed by a maintenance dose of 3 million units every 8 h) versus meropenem (2 g every 8 h), both in combination with levofloxacin (500 mg every 12 h) for 7-14 days in patients with late VAP. Between May 2012 and October 2015, 232 patients were randomly assigned to the 2 treatment groups. The primary endpoint was mortality at 28 days after randomization in the microbiologically modified intention-to-treat (mMITT) population. Secondary outcomes included clinical and microbiological cure, renal function at the end of the treatment, and serious adverse events. The study was interrupted after the interim analysis due to excessive nephrotoxicity in the colistin group; therefore, the sample size was not achieved. RESULTS: A total of 157 (67.7%) patients were included in the mMITT population, 36 of whom (22.9%) had VAP caused by CR-GNB. In the mMITT population, no significant difference in mortality between the colistin group (19/82, 23.2%) and the meropenem group (19/75, 25.3%) was observed, with a risk difference of - 2.16 (- 15.59 to 11.26, p = 0.377); the noninferiority of colistin was not demonstrated due to early termination and limited number of patients infected by carbapenem-resistant pathogens. Colistin plus levofloxacin increased the incidence of renal failure (40/120, 33.3%, versus 21/112, 18.8%; p = 0.012) and renal replacement therapy (11/120, 9.1%, versus 2/112, 1.8%; p = 0.015). CONCLUSIONS: This study did not demonstrate the noninferiority of colistin compared with meropenem, both combined with levofloxacin, in terms of efficacy in the empirical treatment of late VAP but demonstrated the greater nephrotoxicity of colistin. These findings do not support the empirical use of colistin for the treatment of late VAP due to early termination. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01292031. Registered 9 February 2011.

Duration of therapy of ventilator-associated pneumonia.

PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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. SUMMARY: 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.

How to treat fungal infections in ICU patients.

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.

Upraising Stenotrophomonas maltophilia in Critically Ill Patients: A New Enemy?

Stenotrophomonas maltophilia (S. maltophilia), an important pathogen in immuno-compromised patients, has recently gained attention in patients admitted in intensive care units (ICU). We sought to investigate clinical features of infections caused by S. maltophilia in ICU patients and identify risk factors for mortality. We conducted a retrospective study in two multivalent non-COVID-19 ICUs of tertiary-teaching hospitals in Greece and Spain, including patients with isolated S. maltophilia from at least one clinical specimen along with clinical signs of infection. A total of 103 patients (66% male) were analyzed. Median age was 65.5 (54-73.3) years and mean APACHE II and SOFA scores upon ICU admission were 18.36 (±7.22) and 18.17 (±6.95), respectively. Pneumonia was the predominant clinical syndrome (72.8%), while 22% of cases were among hemato/oncology patients. Crude 28-day mortality rate was 54.8%, even though, 14-day clinical and microbiological response was 96%. Age, APACHE II on ICU admission, hemato-oncologic disease, and multi-organ failure were initially identified as potential predictors of mortality. In the multivariable analysis, only increasing age and hemato-oncologic disease were shown to be independent risk factors for 28-day mortality. High all-cause mortality was observed in critically ill patients with predominantly respiratory infections by S. maltophilia, despite initial clinical and laboratory response after targeted treatment. The study elucidates a potentially worrisome emerging pathogen in the ICU.

Resistance to polymyxins: Mechanisms, frequency and treatment options.

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

Effectiveness and safety of short vs. long duration of antibiotic therapy for acute bacterial sinusitis: a meta-analysis of randomized trials.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: 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. WHAT THIS STUDY ADDS: 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.

Characteristics, risk factors and outcomes of Clostridium difficile infections in Greek Intensive Care Units.

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.

The Role of Minocycline in the Treatment of Nosocomial Infections Caused by Multidrug, Extensively Drug and Pandrug Resistant Acinetobacter baumannii: A Systematic Review of Clinical Evidence.

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.

Risk factors associated with the isolation of colistin-resistant gram-negative bacteria: a matched case-control study.

OBJECTIVE: 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. DESIGN: Matched case-control study. SETTING: Tertiary care hospital in Athens, Greece. PATIENTS: 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. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: 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). CONCLUSIONS: 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.

Statins for infection and sepsis: a systematic review of the clinical evidence.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Therapeutic options for Stenotrophomonas maltophilia infections beyond co-trimoxazole: a systematic review.

BACKGROUND: 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. METHODS: The literature search was performed in the PubMed and Scopus databases. The search string used was 'Stenotrophomonas maltophilia OR Xanthomonas maltophilia'. RESULTS: 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. CONCLUSIONS: 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.

Short- versus long-duration antimicrobial treatment for exacerbations of chronic bronchitis: a meta-analysis.

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) = 0.99, 95% confidence interval (CI) 0.95-1.03], clinically evaluable (RR = 0.99, 95% CI 0.96-1.02) or microbiologically evaluable (RR = 0.98, 95% CI 0.93-1.02) patients. Short-duration treatment, when compared with long, was associated with fewer adverse events (RR = 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.

Short- versus long-course antibacterial therapy for community-acquired pneumonia : a meta-analysis.

BACKGROUND: The evidence for traditionally recommended 7- to 14-day duration of antibacterial therapy for community-acquired pneumonia (CAP) is not well established. OBJECTIVES: We endeavoured to assess the effectiveness and safety of shorter than traditionally recommended antibacterial therapy for CAP. METHODS: We performed a meta-analysis of randomized controlled trials (RCTs) comparing short- (< or = 7 days) versus long- (> or = 2 days difference) course therapy for CAP with the same antibacterial regimens, in the same daily dosages. RESULTS: Five RCTs involving adults (including outpatients and inpatients who did not require intensive care) and two RCTs involving children (aged 2-59 months, residing in developing countries) were included. All RCTs were double-blind and assessed patients with CAP of mild to moderate severity. No differences were found between short- (adults 3-7 days; children 3 days) and long- (adults 7-10 days; children 5 days) course regimens (adults - amoxicillin, cefuroxime, ceftriaxone, telithromycin and gemifloxacin; children - amoxicillin) regarding clinical success at end-of-therapy (six RCTs; 5107 patients [1095 adults, 4012 children]; fixed-effect model [FEM]; odds ratio [OR] = 0.89; 95% CI 0.74, 1.07), clinical success at late follow-up, microbiological success, relapses, mortality (seven RCTs; 5438 patients; FEM; OR = 0.57; 95% CI 0.23, 1.43), adverse events (five RCTs; 3214 patients; FEM; OR = 0. 90; 95% CI 0.72, 1.13) or withdrawals as a result of adverse events. No differences were found in subset analyses of adults or children, and of patients treated with no more than 5-day short-course regimens versus at least 7-day long-course regimens. CONCLUSION: No difference was found in the effectiveness and safety of short- versus long-course antimicrobial treatment of adult and paediatric patients with CAP of mild to moderate severity.

Pandrug-resistant Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii infections: characteristics and outcome in a series of 28 patients.

We describe the characteristics and outcome of pandrug-resistant (PDR) Gram-negative bacterial infections (23 Klebsiella pneumoniae isolates, 3 Pseudomonas aeruginosa and 3 Acinetobacter baumannii) of hospitalised patients at a tertiary-care centre (1 January 2006-31 May 2007). The site of infection was central venous catheter-related in 5 of 24 patients with clinical infection, bacteraemia in 5, the respiratory system in 5, surgical site in 5, the urinary system in 2, the ascitic fluid in 1 and the central nervous system in one. Twenty of 24 patients with infection received an antibiotic regimen containing colistin (in combination with meropenem in 8 patients). The overall in-hospital mortality was 41.7% (10/24); 8 patients died because of the PDR infection (infection-related mortality 33.3%). Significant co-morbidity was present not only in the patients who died but also in survivors. PDR Gram-negative bacterial infections are associated with considerable mortality, although not as high as expected given the fact that the isolates were resistant to all tested antibiotics, including polymyxins. Antibiotics that are ineffective in vitro may prove life-saving for some of these patients, especially combination regimens containing colistin.

Inhaled Antimicrobials for Ventilator-Associated Pneumonia: Practical Aspects.

Positive experience with inhaled antibiotics in pulmonary infections of patients with cystic fibrosis has paved the way for their utilization in mechanically ventilated, critically ill patients with lower respiratory tract infections. A successful antibiotic delivery depends upon the size of the generated particle and the elimination of drug impaction in the large airways and the ventilator circuit. Generated droplet size is mainly affected by the type of the nebulizer employed. Currently, jet, ultrasonic, and vibrating mesh nebulizers are marketed; the latter can deliver optimal antibiotic particle size. Promising novel drug-device combinations are able to release drug concentrations of 25- to 300-fold the minimum inhibitory concentration of the targeted pathogens into the pulmonary alveoli. The most important practical steps of nebulization include pre-assessment and preparation of the patient (suctioning, sedation, possible bronchodilation, adjustment of necessary ventilator settings); adherence to the procedure (drug preparation, avoidance of unnecessary tubing connections, interruption of heated humidification, removal of heat-moisture exchanger); inspection of the procedure (check for residual in drug chamber, change of expiratory filter, return sedation, and ventilator settings to previous status); and surveillance of the patient for adverse events (close monitoring of the patient and particularly of peak airway pressure and bronchoconstriction). Practical aspects of nebulization are very important to ensure optimal drug delivery and safe procedure for the patient. Therefore, the development of an operational checklist is a priority for every department adopting this modality.

Elderly versus non-elderly patients with intra-abdominal candidiasis in the ICU.

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.

Fluoroquinolones vs beta-lactams for empirical treatment of immunocompetent patients with skin and soft tissue infections: a meta-analysis of randomized controlled trials.

OBJECTIVE: To compare the effectiveness and safety of fluoroquinolones with beta-lactams in the treatment of patients with skin and soft tissue infections (SSTIs). METHODS: We searched the PubMed database, Cochrane Database of Controlled Trials, and references of relevant articles for study reports published between January 1980 and February 2006. RESULTS: Twenty randomized controlled trials that enrolled 4817 patients were included in the analysis. Fluoroquinolones as empirical treatment of patients with SSTIs were more effective than beta-lactams for the clinically evaluable patients (90.4% vs 88.2%; odds ratio [OR], 1.29; 95% confidence interval [CI], 1.00-1.66). This was also true in subset analyses of randomized controlled trials that studied ciprofloxacin (OR, 2.49; 95% CI, 1.45-4.26) and for patients with mild to moderate infections (OR, 1.83; 95% CI, 1.13-2.96). In contrast, no difference was found between the compared regimens for patients with moderate to severe infections (OR, 1.12; 95% CI, 0.80-1.55), for patients who did not receive third-generation cephalosporins as the comparator antibiotic (OR, 0.99; 95% CI, 0.73-1.34), or for the microbiologically evaluable patients (OR, 1.19; 95% CI, 0.89-1.59). Fluoroquinolones were also associated with more adverse effects (19.2% vs 15.2%; OR, 1.33; 95% CI, 1.13-1.57). CONCLUSION: The high proportion of successfully treated patients in the compared groups of antibiotics and the development of more adverse effects associated with fluoroquinolone use suggest that these antibiotics do not have substantial advantages compared with beta-lactams for empirical treatment of patients with SSTIs.

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

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

Characteristics, risk factors and outcomes of carbapenem-resistant Klebsiella pneumoniae infections in the intensive care unit.

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.