A decision support model to predict the presence of an acute infiltrate on chest radiograph.

A chest infiltrate is needed to make a diagnosis of community-acquired pneumonia, but chest X-rays might be time consuming, entail radiation exposure, and demand resources that are not always available. We sought to derive a model to predict whether a patient will have an infiltrate on chest X-ray (CXR). This prospective observational study included patients visiting the Emergency Department of Beilinson Hospital in the years 2003-2004 (derivation cohort) and 2010-2011 (validation cohort), who had undergone a CXR, and were suspected of having a respiratory infection. We excluded all patients with possible healthcare associated infections. A logistic regression model was derived and applied to the validation cohort. A total of 1,555 patients met inclusion criteria: 993 in the derivation cohort and 562 in the validation cohort with 287 (29%) and 226 (40%) having an infiltrate, respectively. The derivation model area-under-the curve (AUC) was 0.79 (95% CI 0.76-0.82). We categorized the patients into three groups-presence or absence of infiltrate, or undetermined. In the validation cohort, 70 (12%) patients were classified as 'no infiltrate'; 3 (4%) of them had an infiltrate, 367 (65%) were classified as 'infiltrate'; 190 (52%) of them had an infiltrate on CXR, and 125 (46%) were classified as 'undetermined'; 33 (26%) of them with an infiltrate on CXR. Using this prediction model for the evaluation of patients with suspected respiratory infection in an ED setting may help avoid over 10% of CXRs.

Quantifying the associations between antibiotic exposure and resistance - a step towards personalised antibiograms.

Empirical antibiotic treatment is selected to target causative bacteria with antibiotics to which they are not resistant. We analysed the increase in bacterial resistance among individual patients associated with antibiotic exposure in the month prior to infection onset, compared to unexposed patients. From a series of prospective cohort studies in the period 2002-2011 at Beilinson Hospital, Israel, 4232 consecutive patients suspected of infection were included. We analysed resistance to antibiotics in bacterial isolates from patients with clinically significant and microbiologically documented infections, starting antibiotics after obtaining cultures (n = 775). In Gram-negative bacteria, significantly higher rates of resistance was associated with exposure to antibiotics, while no significant associations were found for Gram-positive bacteria. Significant odds ratios (ORs) for increased resistance to classes of antibiotics ranged from 2.1 to 3.3 in Gram-negative bacteria from patients exposed to any antibiotic(s), with quinolones having the highest OR, followed by aminoglycosides, penicillins with ß-lactamase inhibitor and cephalosporins. The majority of significant associations also had significant ORs after exposure to another class of antibiotics, indicating a substantial effect of cross-resistance. In conclusion, increased resistance was observed following exposure to antibiotics, both from the same class and from other classes. The results indicate a reason to adjust the expected coverage of empirical antibiotic treatments for patients recently exposed to antibiotics, with some antibiotics being more affected than others.

Risk factors for long-term mortality of Staphylococcus aureus bacteremia.

Staphylococcus aureus bacteremia (SAB) is a fatal disease. We aimed to describe risk factors for long-term mortality with SAB. We analyzed data from a retrospectively collected database including 1,692 patients with SAB. We considered variables of infection and background conditions for the analysis of long-term survival. The Kaplan-Meier procedure was used for analysis of long-term survival. Variables significantly associated with mortality were analyzed using a Cox regression model. We included 1,692 patients in the analysis. Patients were followed for up to 22 years. Within one year, 62% of patients died and within 5 years 72% died. A total of 82% of patients aged 65 years and older died within 5 years. Independent predictors of long-term mortality were older age (Hazard ratio 1.029, 95% confidence interval 1.022-1.036), female gender (HR 1.302, 95% CI 1.118-1.517), pneumonia or primary/ unknown source of infection (HR 1.441, 95% CI 1.230-1.689), dementia (HR 1.234, 95% CI 1.004-1.516), higher Charlson score (HR 1.155, 95% CI 1.115-1.196), shock at onset (HR 1.776, 95% CI 1.430-2.207) and arrival to hospitalization from an institution (HR 1.319, 95% CI 1.095-1.563). Long-term survival of patients older than 65 years and of women with SAB is severely curtailed.

The significance of persistent fever in the treatment of suspected bacterial infections among inpatients: a prospective cohort study.

Antibiotic escalations are frequently guided by fever persistence. Unnecessary antibiotic escalation is associated with resistance induction. We examined whether fever persistence is associated with adverse outcomes among medical inpatients with sepsis. In a single-center prospective cohort study, we included consecutive medical inpatients with suspected or documented bacterial infections. Data were collected on days 0, 2, 4, and 30 days from episode onset. We examined the association between fever persistence at 4 days and 30-day mortality on univariate and multivariate analysis. Inappropriate empirical antibiotic treatment (IAET) was defined for patients with microbiologically documented infections (MDIs). Odds ratios (ORs) are presented with 95% confidence intervals (CIs). A total of 1,621 patients were included. Among patients with MDIs, 38/206 (18.4%) given appropriate empiric therapy had continued fever on day 4, compared to 64/231 (27.7%) of patients receiving IAET, OR 0.59, 95% CI 0.37-0.93. Fever persistence was not associated with mortality after adjustment for other risk factors. Among patients with presumed sepsis who did not have MDIs, persistent fever was significantly associated with 30-day mortality on a multivariate analysis, adjusted OR 2.77 (95% CI 1.78-4.31). Other risk factors for mortality included older age, nosocomial infections, malignancy, dyspnea, shock, decreased albumin, and elevated creatinine. For patients with MDIs, fever persistence for up to 4 days is a marker of IAET, but is not associated with mortality, and should not, in itself, trigger antibiotic escalation. For patients without MDIs, fever persistence should trigger careful re-evaluation, as it is associated with mortality.

Assessment of bias in outcomes reported in trials on pneumonia: a systematic review.

Subjective outcomes may exaggerate intervention effects compared to objectively measured outcomes. We compared effect estimates for clinical failure and all-cause mortality clinical trials of antibiotic treatment for pneumonia. A systematic review of randomized controlled trials assessing adults with pneumonia, comparing different antibiotics, published between 2005 and 2012 was undertaken. We compared the intervention to the control arm. The all-cause mortality in the intention-to-treat population and clinical failure as defined by the study investigators for the primary analyzed population were the primary outcomes examined. Risk ratios (RRs) with 95 % confidence intervals (CIs) were pooled, using a fixed effect model. Meta-regression was used to examine the impact of clinical failure on the mortality effect size. Thirty-six trials were included, of which 30 were industry-sponsored and 30 were non-inferiority trials. There was no difference between the effect on mortality for intervention versus control (RR 1.02, 95 % CI 0.91-1.16) and clinical failure (RR 1.01, 95 % CI 0.93-1.10), without significant heterogeneity in both analyses. In double-blind trials with adequate sequence generation and concealment, there was a significant advantage to the intervention for clinical failure (RR 0.86, 95 % CI 0.76-0.98), but not for mortality (RR 0.96, 95 % CI 0.76-1.21). RRs for clinical failure did not explain the variability in the RRs for mortality significantly, with a meta-regression coefficient of 0.32 (95 % CI -0.21-0.85). In non-inferiority trials of antibiotic treatment for pneumonia, we did not find evidence for bias induced by the use of a subjective outcome overall. The small number of trials without sponsorship precludes an adequate assessment of sponsorship effects.

Consequences of treated versus untreated asymptomatic bacteriuria in the first year following kidney transplantation: retrospective observational study.

Asymptomatic bacteriuria (AB) is frequent among kidney transplant patients during the first year post transplantation. Currently, there are no clear guidelines for the antibiotic treatment of AB among these patients. We examined the outcomes of treatment versus no treatment of AB in kidney transplant patients during the first year post transplantation. A retrospective cohort study including adults >16 years of age transplanted in one center between 1/2004 and 12/2010 was undertaken. The primary outcome was a composite of hospitalization for symptomatic urinary tract infection (UTI) or more than 25 % reduction in the estimated glomerular filtration rate (eGFR) 30 days after the documentation of AB. Secondary outcomes included symptomatic UTIs following the episode of AB, persistent recurrent AB, total days in hospital, mortality, adverse events, and resistance development. A total of 112 patients with AB fulfilled the inclusion criteria. Twenty-two patients received antibiotic treatment (19.6 %), while 90 patients did not. The primary outcome occurred in 4/22 (18.2 %) of the treated patients versus 5/90 (5.6 %) of the untreated patients [odds ratio (OR) = 3.78, 95 % confidence interval (CI) 0.9-15]. The risk of developing symptomatic UTI after AB was almost three times higher (p < 0.05) and the total number of hospitalization days at 6 months post AB was also significantly higher (p < 0.026) in the treated group. No patient died during the study period. UTI caused by bacteria resistant to the antibiotic used for the treatment of AB occurred in 36 % of the treated patients. We observed no benefit for the antibiotic treatment of AB in the short- and long-term follow-up. A prospective observational study is needed.

Long COVID sexual dysfunction among both genders: Evaluation of a cohort of COVID-19 recoverees.

OBJECTIVES: We aimed to assess Long COVID sexual dysfunction among both sexes. PATIENTS AND METHODS: A cross-sectional study at a multidisciplinary COVID clinic. Consecutive patients answered a symptom-based questionnaire, which included sexual dysfunction. Individuals reporting any degree of sexual dysfunction were compared with those who denied. A multivariable logistic regression was conducted to identify risk factors. A principal component analysis was implemented to explore other symptoms associated with sexual dysfunction. RESULTS: All in all, 391 individuals recovering from COVID-19 completed the questionnaire, 211 women and 180 men. Mean age was 45.2 (SD 15.4) years. Most (280, 85.9%) had mild COVID-19, assessed at a median of 3.8 (IQR 2.0) months from diagnosis. Sexual dysfunction was reported by 55 (36%) of the men and 48 (28%) of the women. Increased age [per year; men OR 1.05 (95% CI 1.02-1.08)], long COVID cough [men 2.58 (1.05-6.32)], chest pain [women 3.54 (1.28-9.80)], irritability [women 3.45 (1.28-9.29)], paresthesia [men 4.23 (1.55-10.44); women 3.08 (1.14-8.32)], and emotional distress [men 3.26 (1.36-7.82); women 4.29 (1.65-11.18)] were significantly associated with sexual dysfunction. In women, sexual dysfunction was part of the emotional pattern, while among men, it was part of the emotional and pulmonary patterns. CONCLUSION: Sexual dysfunction is a common manifestation of long COVID in both men and women. Presence of other long COVID symptoms, and older age, are associated with this phenomenon. Further studies should explore the mechanisms for long COVID sexual dysfunction in both men and women, as well as strategies for prevention and treatment.

The effect of empiric antibiotic therapy on mortality in debilitated patients with dementia.

The purpose of this investigation was to assess the effect of empirical antibiotic treatment on 30-day mortality among debilitated inpatients with dementia and Gram-negative bacteremia. A retrospective cohort study in the years 2005-2007 was undertaken. Data were collected through patient chart review. The association between individual variables and 30-day mortality was assessed through univariate analysis. Variables significantly associated with mortality (p < 0.05) were entered into a logistic regression analysis. Adjusted odds ratios (ORs) for mortality with 95% confidence intervals (CIs) are shown. Subgroup analysis of patients with and without decubitus ulcers was performed. In our cohort of 378 patients with dementia and Gram-negative bacteremia, the 30-day mortality was 39% overall and 61% in the subgroup of patients with decubitus ulcers. Inappropriate empirical therapy was associated with higher mortality, although this effect was not statistically significant (OR 1.41, 95% CI 0.86-2.29). Inappropriate empirical therapy did not affect mortality in the subgroup of patients with decubitus ulcers (OR 0.37, 95% CI 0.11-1.28). Other factors found to independently affect mortality included age, co-morbidities, source of infection, sepsis severity, and hospital-acquired infection. Appropriate empirical antibiotic therapy for patients with dementia and severe bacterial infection did not have a clear advantage, especially in the sickest group of patients with decubitus ulcers.

Tocilizumab in the treatment of COVID-19-a meta-analysis.

BACKGROUND: Interleukin-6 inhibitors showed promising results in observational trials of patients with coronavirus disease 2019 (COVID-19). AIM: To evaluate whether interleukin-6 inhibitor tocilizumab (TCZ) reduces mortality among hospitalized COVID-19 patients. DESIGN: A systematic review and meta-analysis. METHODS: Systematic review and meta-analysis of randomized controlled trials (RCTs) comparing TCZ vs. placebo/control, for treatment of adults with COVID-19. Primary outcome was 28-30 days all-cause mortality. Search was conducted up to 1 April 2021. Two independent reviewers screened citations, extracted data and assessed risk of bias. Relative risk (RR) with 95% confidence intervals (CI) were pooled. We performed subgroup analysis for patients with critical illness and sensitivity analyses. RESULTS: Eight RCTs were included, assessing 6481 patients with mostly severe non-critical COVID-19 infection. TCZ was associated with a reduction in all-cause 28-30-day mortality compared to placebo/control (RR = 0.89, 95% CI 0.82-0.96). Among the subgroup of critically ill patients no reduced mortality was demonstrated (RR = 0.94, 95% CI 0.74-1.19). No mortality benefit with TCZ was demonstrated in trials that used steroids for >80% of patients. TCZ was associated with significantly reduced risk for mechanical ventilation (MV); for combined endpoint of death or MV and for intensive care unit (ICU) admission. No significant difference in adverse events was demonstrated. Risk of serious superinfection was significantly lower with TCZ (RR = 0.57, 95% CI 0.35-0.93). CONCLUSION: The treatment with TCZ reduces 28-30 days all-cause mortality, ICU admission, superinfections, MV and the combined endpoint of death or MV. Among critically ill patients, and when steroids were used for most patients, no mortality benefit was demonstrated. Additional research should further define sub-groups that would benefit most and preferred timing of administration of TCZ in severe COVID-19.

Nucleoside reverse transcriptase inhibitors in combination therapy for HIV patients: systematic review and meta-analysis.

Treatment guidelines recommend dual nucleoside reverse transcriptase inhibitors (NRTI ) as a part of combination antiretroviral therapy. The objective of this study was to assess the relative efficacy and toxicity of the dual NRTI part of the regimen in antiretroviral-naïve HIV-1-infected adults. A systematic review and meta-analysis of randomized controlled trials assessing highly active antiretroviral therapy (HAART) for treatment-naïve HIV-infected adults with a 48-week follow-up were done. We searched the PubMed, CENTRAL, and EMBASE electronic databases up to April 2009. Proceedings from conferences were reviewed. Data were extracted independently by two reviewers. Primary outcome was viral suppression at 48 weeks. The odds ratio (OR) is reported with its corresponding 95% confidence interval (CI). Twenty-two randomized controlled trials, including 8,184 HIV-treatment-naïve patients, were included. The combination didanosine + lamivudine/emtricitabine (four trials, 1,148 patients) was more effective (OR 0.53, 95% CI 0.41-0.68) for viral load (VL) >50 copies/ml and less toxic (OR 0.52, 95% CI 0.36-0.76) for discontinuation due to adverse events (AE) than its comparators. The combination tenofovir + lamivudine/emtricitabine was more effective and less toxic (OR 0.75, 95% CI 0.58-0.96) only in the 144-week follow-up data (two trials, 1,119 patients). Abacavir + lamivudine had similar efficacy to its comparators (OR 0.81, 95% CI 0.8-1.1), but more AIDS-defining events (OR 3.22, 95% CI 1.24, 8.40). The once-daily combination didanosine + lamivudine/emtricitabine was found to be effective and tolerable. This combination, soon to be generic, should be compared to the current standard of care in a large randomized trial. An effective, safe, and inexpensive alternative to current options is needed.

Population pharmacokinetics of colistin and the relation to survival in critically ill patients infected with colistin susceptible and carbapenem-resistant bacteria.

OBJECTIVES: The aim was to analyse the population pharmacokinetics of colistin and to explore the relationship between colistin exposure and time to death. METHODS: Patients included in the AIDA randomized controlled trial were treated with colistin for severe infections caused by carbapenem-resistant Gram-negative bacteria. All subjects received a 9 million units (MU) loading dose, followed by a 4.5 MU twice daily maintenance dose, with dose reduction if creatinine clearance (CrCL) < 50 mL/min. Individual colistin exposures were estimated from the developed population pharmacokinetic model and an optimized two-sample per patient sampling design. Time to death was evaluated in a parametric survival analysis. RESULTS: Out of 406 randomized patients, 349 contributed pharmacokinetic data. The median (90% range) colistin plasma concentration was 0.44 (0.14-1.59) mg/L at 15 minutes after the end of first infusion. In samples drawn 10 hr after a maintenance dose, concentrations were >2 mg/L in 94% (195/208) and 44% (38/87) of patients with CrCL ≤120 mL/min, and >120 mL/min, respectively. Colistin methanesulfonate sodium (CMS) and colistin clearances were strongly dependent on CrCL. High colistin exposure to MIC ratio was associated with increased hazard of death in the multivariate analysis (adjusted hazard ratio (95% CI): 1.07 (1.03-1.12)). Other significant predictors included SOFA score at baseline (HR 1.24 (1.19-1.30) per score increase), age and Acinetobacter or Pseudomonas as index pathogen. DISCUSSION: The population pharmacokinetic model predicted that >90% of the patients had colistin concentrations >2 mg/L at steady state, but only 66% at 4 hr after start of treatment. High colistin exposure was associated with poor kidney function, and was not related to a prolonged survival.

Hydroxymethylglutaryl-CoA reductase inhibitors (statins) for the treatment of sepsis in adults - A systematic review and meta-analysis.

OBJECTIVES: The pleiotropic effect of hydroxymethylglutaryl-CoA reductase inhibitors (statins) might have a beneficial effect in sepsis through several mechanisms. The aim was to assess the efficacy and safety of statins, compared with placebo, for the treatment of sepsis in adults. METHODS: We searched the following databases: the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, 2017, Issue 12), OVID MEDLINE (from 1966 to January 2018), Embase (Ovid SP, from 1974 to January 2018), and LILACS (from 1986 to January 2018). We also searched the trial registries ISRCTN and ClinicalTrials.gov to January 2018. The eligibility criteria were randomized controlled trials comparing the treatment of statins versus placebo in adult patients who were hospitalized due to sepsis. Participants were adults (16 years and older) hospitalized because of sepsis or who developed sepsis during admission. Interventions were treatment with hydroxymethylglutaryl-CoA reductase inhibitors (statins) versus no treatment or placebo. We performed a systematic review of all randomized controlled trials published until January 2018, assessing the efficacy and safety of statins in sepsis treatment. Two primary outcomes were assessed: 30-day overall mortality and deterioration to severe sepsis during management. Secondary outcomes were hospital mortality, need for mechanical ventilation and drug related adverse events. RESULTS: Fourteen trials evaluating 2628 patients were included. Statins did not reduce 30-day all-cause mortality neither in all patients (risk ratio (RR) 0.96, 95% confidence interval (CI) 0.83-1.10), nor in a subgroup of patients with severe sepsis (RR 0.97, 95% CI 0.84-1.12). The certainty of evidence for both outcomes was high. There was no change in the rate of adverse events between study arms (RR 1.24, 95% CI 0.94 to 1.63). The certainty of evidence for this outcome was high. CONCLUSIONS: The use of statin therapy in adults for the indication of sepsis is not recommended.

Empiric antibiotic coverage of atypical pathogens for community acquired pneumonia in hospitalized adults.

BACKGROUND: Community acquired pneumonia (CAP) is caused by various pathogens, traditionally divided to 'typical' and 'atypical'. Initial antibiotic treatment of CAP is usually empirical, customarily covering both typical and atypical pathogens. To date, no sufficient evidence exists to support this broad coverage, while limiting coverage is bound to reduce toxicity, resistance and expense. OBJECTIVES: To assess the efficacy and need of adding antibiotic coverage for atypical pathogens in hospitalized patients with CAP, in terms of mortality and successful treatment. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2007, Issue 1) which includes the Acute Respiratory Infection Group's specialized register; MEDLINE (January 1966 to March 2007); and EMBASE (January 1980 to January 2007). SELECTION CRITERIA: Randomized trials of adult patients hospitalized due to CAP, comparing antibiotic regimens with atypical antibiotic coverage to a regimen without atypical antibiotic coverage. DATA COLLECTION AND ANALYSIS: Two review authors independently appraised the quality of each trial and extracted the data from included trials. Relative risks (RR) with 95% confidence intervals (CI) were estimated, assuming an intention-to-treat (ITT) basis for the outcome measures. MAIN RESULTS: Twenty five trials were included, encompassing 5244 randomized patients. There was no difference in mortality between the atypical arm and the non-atypical arm (RR 1.15; 95% CI 0.85 to 1.56). The atypical arm showed an insignificant trend toward clinical success and a significant advantage to bacteriological eradication, which disappeared when evaluating methodologically high-quality studies alone. Clinical success for the atypical arm was significantly higher for Legionella pneumophilae (L. pneumophilae) and non-significantly lower for pneumococcal pneumonia. There was no significant difference between the groups in the frequency of (total) adverse events, or those requiring discontinuation of treatment. However, gastrointestinal events were more common in the non-atypical arm (RR 0.73, 95% CI 0.54 to 0.99). All but two included trials compared a single atypical antibiotic to a beta-lactam, while no trials assessing the addition of an atypical antibiotic to a beta-lactam were identified. AUTHORS' CONCLUSIONS: No benefit of survival or clinical efficacy was shown to empirical atypical coverage in hospitalized patients with CAP. This conclusion relates mostly to the comparison of quinolone monotherapy to beta-lactams (BL) or cephalosporins. Further trials, comparing BL or cephalosporins therapy to BL or cephalosporins combined with a macrolide in this population, using mortality as its primary outcome, should be performed.

Colistin exposure as a risk factor for infections caused by inherently colistin resistant Enterobacteriaceae-a case-control study.

OBJECTIVES: Epidemiological studies have suggested an association between increased colistin use and selection for inherently colistin-resistant Enterobacteriaceae (ICRE). We aimed to evaluate whether colistin exposure is a risk factor for ICRE infection. METHODS: A matched 1:1 case-control study including patients recently hospitalized for ≥14 days with ICRE infection as cases matched with similar patients with a clinical isolate of a colistin-susceptible Enterobacteriaceae as controls was performed. Univariate analysis using McNemar test and multivariate analysis were conducted to explore risk factors for ICRE isolation, including colistin exposure 90 days before the positive culture. RESULTS: We included 446 patients, 223 cases and 223 controls matched for gender, age, department, year, source of culture and duration of hospitalization before positive culture. Colistin exposure was significantly associated with ICRE isolation in both univariate (14/223, 6.3% of cases versus 4/223, 1.8% of controls, p 0.031) and multivariate analyses (odds ratio 4.415, 95% CI 1.078-18.082). Curtailed functional capacity was a significant risk factor for ICRE as well. Exposure to other broad-spectrum antibiotics was associated with isolation of a colistin-susceptible pathogen. CONCLUSIONS: Exposure to colistin is associated with an increased risk of isolating an inherently colistin-resistant Enterobacteriaceae in patients with prolonged hospitalization. This should be taken into account while considering empirical therapy for such patients. Use of colistin should be judicious. The correlation between duration and magnitude of exposure and ICRE infection should be investigated in further studies.

Risk factors and prognosis of complicated urinary tract infections caused by Pseudomonas aeruginosa in hospitalized patients: a retrospective multicenter cohort study.

PURPOSE: Complicated urinary tract infections (cUTIs) are among the most frequent health-care-associated infections. In patients with cUTI, Pseudomonas aeruginosa deserves special attention, since it can affect patients with serious underlying conditions. Our aim was to gain insight into the risk factors and prognosis of P. aeruginosa cUTIs in a scenario of increasing multidrug resistance (MDR). METHODS: This was a multinational, retrospective, observational study at 20 hospitals in south and southeastern Europe, Turkey, and Israel including consecutive patients with cUTI hospitalized between January 2013 and December 2014. A mixed-effect logistic regression model was performed to assess risk factors for P. aeruginosa and MDR P. aeruginosa cUTI. RESULTS: Of 1,007 episodes of cUTI, 97 (9.6%) were due to P. aeruginosa. Resistance rates of P. aeruginosa were: antipseudomonal cephalosporins 35 of 97 (36.1%), aminoglycosides 30 of 97 (30.9%), piperacillin-tazobactam 21 of 97 (21.6%), fluoroquinolones 43 of 97 (44.3%), and carbapenems 28 of 97 (28.8%). The MDR rate was 28 of 97 (28.8%). Independent risk factors for P. aeruginosa cUTI were male sex (OR 2.61, 95% CI 1.60-4.27), steroid therapy (OR 2.40, 95% CI 1.10-5.27), bedridden functional status (OR 1.79, 95% CI 0.99-3.25), antibiotic treatment within the previous 30 days (OR 2.34, 95% CI 1.38-3.94), indwelling urinary catheter (OR 2.41, 95% CI 1.43-4.08), and procedures that anatomically modified the urinary tract (OR 2.01, 95% CI 1.04-3.87). Independent risk factors for MDR P. aeruginosa cUTI were age (OR 0.96, 95% CI 0.93-0.99) and anatomical urinary tract modification (OR 4.75, 95% CI 1.06-21.26). Readmission was higher in P. aeruginosa cUTI patients than in other etiologies (23 of 97 [23.7%] vs 144 of 910 [15.8%], P=0.04), while 30-day mortality was not significantly different (seven of 97 [7.2%] vs 77 of 910 [8.5%], P=0.6). CONCLUSION: Patients with P. aeruginosa cUTI had characteristically a serious baseline condition and manipulation of the urinary tract, although their mortality was not higher than that of patients with cUTI caused by other etiologies.

Relative tachycardia in patients with sepsis: an independent risk factor for mortality.

BACKGROUND: Excess activation of the sympathetic nervous system may be a risk factor for mortality in patients with the systemic inflammatory response syndrome (SIRS) or sepsis. AIM: To examine whether excessive tachycardia, relative to the degree of fever is an independent risk factor for death in patients with SIRS. DESIGN: Prospective observational study. SETTING: Departments of medicine in three university hospitals in Israel, Germany and Italy. METHODS: We collected data for 3382 patients with SIRS, whether community- or hospital-acquired, 91% with sepsis, as part of an ongoing trial. RESULTS: Overall 30-day mortality was 12% (408/3382). The pulse/temperature ratio was significantly higher in patients who died than in survivors: mean +/- SD 2.55 +/- 0.57 vs. 2.40 +/- 0.48 bpm/ degrees C (p < 0.0001). Excessive tachycardia was significantly associated with a mortality in a logistic model accounting for other strong predictors of mortality (OR 1.54, 95%CI 1.10-2.17). Patients with septic shock were the only group for whom this association did not hold. DISCUSSION: Our data are compatible with the hypothesis that some patients with sepsis experience an excess activation of the sympathetic nervous system, leading to a fatal outcome.

Prophylaxis for Pneumocystis pneumonia (PCP) in non-HIV immunocompromised patients.

BACKGROUND: Pneumocystis pneumonia (PCP) is a disease affecting immunocompromised patients. PCP among these patients is associated with significant morbidity and mortality. OBJECTIVES: To assess the effectiveness of PCP prophylaxis among non-HIV immunocompromised patients. To define the type of immunocompromised patients for whom evidence suggests a benefit for PCP prophylaxis. SEARCH STRATEGY: Electronic searches of The Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library Issue 1, 2007), PubMed (March 2007), LILACS (March 2007), relevant conference proceedings; references of identified trials; the first author of each included trial was contacted. SELECTION CRITERIA: RCTs or quasi- RCTs comparing prophylaxis with an antibiotic effective against Pneumocystis versus placebo, no intervention, an antibiotic/s with no activity against Pneumocystis or another antibiotic effective against Pneumocystis for immune-compromised non-HIV patients. Only trials pre-defining Pneumocystis infections as an outcome were included. DATA COLLECTION AND ANALYSIS: Two authors independently appraised the quality of each trial and extracted data from included trials. Relative risks (RR), with 95% confidence intervals (CI) were estimated and pooled using the random effects model. MAIN RESULTS: Eleven trials including 1155 patients (520 children), performed between the years 1974 and 1997, were included. Compared to no treatment or treatment with fluoroquinolones (inactive against Pneumocystis), there was a 91% reduction in the occurrence of PCP in patients receiving prophylaxis with trimethoprim/sulfamethoxazole, RR 0.09 (95% CI 0.02 to 0.32), eight trials, 821 patients. No significant difference was encountered in all cause mortality, RR 0.81 (95% CI 0.27 to 2.37), five trials, 509 patients, while PCP-related mortality was significantly reduced, RR 0.17 (95% CI 0.03 to 0.94), seven trials, 701 patients. Occurrence of leukopenia, neutropenia and their duration were not reported consistently. No significant difference in any adverse event was seen comparing trimethoprim/sulfamethoxazole to no treatment/ placebo (four trials, 470 patients). No differences between once daily versus thrice weekly trimethoprim/sulfamethoxazole were seen (two trials, 207 patients). AUTHORS' CONCLUSIONS: Given an event rate of 7.5% as in included trials' control group, prophylaxis for PCP using TMP/SMX is highly effective among non-HIV patients, with a number needed to treat of 15 patients (95% CI 13 to 20). Prophylaxis should be considered for the types of patients with hematological malignancies, bone marrow transplantation and solid organ transplantation included in these trials.

Vaccines for preventing typhoid fever.

BACKGROUND: Two typhoid vaccines are commercially available, Ty21a (oral) and Vi polysaccharide (parenteral), but neither is used routinely. Other vaccines, such as a new modified, conjugated Vi vaccine called Vi-rEPA, are in development. OBJECTIVES: To evaluate vaccines for preventing typhoid fever. SEARCH STRATEGY: In December 2006, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (The Cochrane Library 2006, Issue 3), MEDLINE, EMBASE, LILACS, and mRCT. We also searched relevant conference proceedings up to 2004 and scanned the reference lists of all included trials. SELECTION CRITERIA: Randomized and quasi-randomized controlled trials (RCTs) comparing typhoid fever vaccines with other typhoid fever vaccines or an inactive agent (placebo or vaccine for a different disease). DATA COLLECTION AND ANALYSIS: Two authors independently applied inclusion criteria and extracted data. We computed vaccine efficacy per year of follow up and cumulative three-year efficacy, stratifying for vaccine type and dose. We calculated relative risks (RR) and efficacy (1-RR as a percentage) with 95% confidence intervals (CI). MAIN RESULTS: Of the 17 included RCTs, 10 evaluated efficacy (Ty21a: 5 trials; Vi polysaccharide: 4 trials, Vi-rEPA: 1 trial), and 11 reported on adverse events.Ty21a vaccine (3 doses). According to one trial (20,543 participants), this vaccine provided statistically significant protection in each of the first three years (one: 35%, 95% CI 8% to 54%; two: 58%, 95% CI 40% to 71%; three: 46%, 95% CI -6% to 72%), and the cumulative efficacy for 2.5 to 3 years was 48% (95% CI 34% to 58%). Four cluster-RCTs that did not adjust for clustering were not included in the meta-analyses. Compared with placebo, this vaccine was not associated with an increased rate of fever, vomiting, diarrhoea, nausea or abdominal pain, headache, or rash.Vi polysaccharide vaccine (1 dose). This vaccine provided protection in year one (68%, 95% CI 50% to 80%; 99,979 participants, 3 trials) and year two (60%, 95% CI 31% to 76%; 142,555 participants, 2 trials), but not in year three (11,384 participants, 1 trial). The three-year cumulative efficacy was 55% (95% CI 30% to 70%; 11,384 participants, 1 trial). Compared with placebo, there was no statistically significant difference in the incidence of fever or erythema, but local swelling was more common with the vaccine.Vi-rEPA vaccine (2 doses). In one trial of 12,008 participants, this vaccine provided protection in year one (94%, 95% CI 75% to 99%) and year two (87%, 95% CI 56% to 96%). Cumulative efficacy at 46 months (3.8 years) was 89% (95% CI 76% to 97%). No swelling or erythema occurred in the vaccine or placebo group; fever was more frequent in the vaccine group. AUTHORS' CONCLUSIONS: The licensed Ty21a and Vi polysaccharide vaccines are efficacious. The new and unlicensed Vi-rEPA vaccine is as efficacious and may confer longer immunity.