Noa Eliakim-Raz

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

BACKGROUNDnCommunity-acquired pneumonia (CAP) is caused by various pathogens, traditionally divided into 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.nnnOBJECTIVESnThe main objective was to estimate the mortality and proportion with treatment failure using regimens containing atypical antibiotic coverage compared to those that had typical coverage only. Secondary objectives included the assessment of adverse events.nnnSEARCH METHODSnWe searched the Cochrane Central Register of Controlled Trials (CENTRAL) Issue 3, 2012 which includes the Acute Respiratory Infection Groups Specialized Register, MEDLINE (January 1966 to April week 1, 2012) and EMBASE (January 1980 to April 2012).nnnSELECTION CRITERIAnRandomized controlled trials (RCTs) of adult patients hospitalized due to CAP, comparing antibiotic regimens with atypical coverage (quinolones, macrolides, tetracyclines, chloramphenicol, streptogramins or ketolides) to a regimen without atypical antibiotic coverage.nnnDATA COLLECTION AND ANALYSISnTwo review authors independently assessed the risk of bias and extracted data from included trials. We estimated risk ratios (RRs) with 95% confidence intervals (CIs). We assessed heterogeneity using a Chi(2) test.nnnMAIN RESULTSnWe included 28 trials, encompassing 5939 randomized patients. The atypical antibiotic was administered as monotherapy in all but three studies. Only one study assessed a beta-lactam combined with a macrolide compared to the same beta-lactam. There was no difference in mortality between the atypical arm and the non-atypical arm (RR 1.14; 95% CI 0.84 to 1.55), RR < 1 favors the atypical arm. 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 less common in the atypical arm (RR 0.70; 95% CI 0.53 to 0.92). Although the trials assessed different antibiotics, no significant heterogeneity was detected in the analyses.nnnAUTHORS CONCLUSIONSnNo benefit of survival or clinical efficacy was shown with empirical atypical coverage in hospitalized patients with CAP. This conclusion relates mostly to the comparison of quinolone monotherapy to beta-lactams. Further trials, comparing beta-lactam monotherapy to the same combined with a macrolide, should be performed.

Influenza vaccines in immunosuppressed adults with cancer

BACKGROUNDnImmunosuppressed cancer patients are at increased risk of serious influenza-related complications. Guidelines, therefore, recommend influenza vaccination for these patients. However, data on vaccine effectiveness in this population is lacking, and the value of vaccination in this population remains unclear.nnnOBJECTIVESnTo assess the effectiveness of influenza vaccine in immunosuppressed adults with malignancies. The primary review outcome is all-cause mortality, preferably at the end of the influenza season. Influenza-like illness (ILI, a clinical definition), confirmed influenza, pneumonia, any hospitalization and influenza-related mortality were defined as secondary outcomes.nnnSEARCH METHODSnWe searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and LILACS databases up to August 2013. We searched the following conference proceedings: ICAAC, ECCMID, IDSA (infectious disease conferences), ASH, ASBMT, EBMT (hematological), and ASCO (oncological) between the years 2006 to 2010. In addition, we scanned the references of all identified studies and pertinent reviews. We searched the websites of the manufacturers of influenza vaccine. Finally, we searched for ongoing or unpublished trials in clinical trial registry databases using the website.nnnSELECTION CRITERIAnRandomized controlled trials (RCTs), prospective and retrospective cohort studies and case-control studies were considered, comparing inactivated influenza vaccines versus placebo, no vaccination or a different vaccine, in adults (16 years and over) with cancer. We considered solid malignancies treated with chemotherapy, haematological cancer patients treated or not treated with chemotherapy, cancer patients post-autologous (up to six months after transplantation) or allogeneic (at any time) hematopoietic stem cell transplantation.nnnDATA COLLECTION AND ANALYSISnTwo review authors independently assessed the risk of bias and extracted data from included studies adhering to Cochrane methodology. Meta-analysis could not be performed because of different outcome and denominator definitions in the included studies.nnnMAIN RESULTSnWe identified four studies: one RCT and three observational studies, including 2124 participants. One study reported results in person-years while the other three reported per person. The studies were performed between 1993 and 2012 and included adults with haematological diseases (two studies), patients following bone marrow transplantation (one study) and solid malignancies (three studies). Only two observational studies reported all-cause mortality; one showing an adjusted hazard ratio (HR) of 0.88 (95% CI 0.77 to 0.99) for death with vaccination and the other reporting an odds ratio (OR) of 0.43 (95% CI 0.26 to 0.71). The RCT reported a statistically significant reduction in ILI with vaccination, while no difference was observed in one observational study. Confirmed influenza rates were lower with vaccination in the three observational studies, the difference reaching statistical significance in one. Pneumonia was observed significantly less frequently with vaccination in one observational study, but no difference was detected in another or in the RCT. The RCT showed a reduction in hospitalizations following vaccination, while an observational study found no difference. No life-threatening or persistent adverse effects from vaccination were reported. The strength of evidence is limited by the low number of included studies and by their low methodological quality (high risk of bias).nnnAUTHORS CONCLUSIONSnObservational data suggests a lower mortality with influenza vaccination. Infection-related outcomes were lower or similar with influenza vaccination. The strength of evidence is limited by the small number of studies and by the fact that only one was a RCT. Influenza vaccination is safe and the evidence, although weak, is in favour of vaccinating adults with cancer receiving chemotherapy.

Surgical site infections following craniotomy focusing on possible post-operative acquisition of infection: prospective cohort study.

Neurosurgery is characterized by a prolonged risk period for surgical site infection (SSI), mainly related to the presence of cerebrospinal fluid (CSF) drains. We aimed to examine factors associated with post-neurosurgical SSIs, focusing on post-operative factors. A prospective cohort study was conducted in a single center over a period of 18xa0months in Israel. Included were adult patients undergoing clean or clean-contaminated craniotomy, including craniotomies with external CSF drainage or shunts. SSIs were defined by the Centers for Disease Control and Prevention (CDC) criteria for healthcare-associated infections. All patients were followed up for 90xa0days and those with foreign body insertion for 1xa0year. We compared patients with and without SSI. A multivariable regression analysis for SSI was conducted including uncorrelated variables significantly associated with SSI. A total of 502 patients were included, with 138 (27.5xa0%) undergoing emergent or urgent craniotomy. The overall SSI rate was 5.6xa0% (28 patients), of which 3.2xa0% (16 patients) were intracerebral. Non-elective surgery, external CSF drainage/monitoring devices, re-operation, and post-operative respiratory failure were independently associated with subsequent SSI. External CSF devices was the only significant risk factor for intracerebral SSIs (pu2009<u20090.001). Internal shunts or other foreign body insertions were not associated with SSIs. A phenotypically identical isolate to that causing the SSI was isolated from respiratory secretions prior to the SSI in 4/9 patients with microbiologically documented intracerebral SSIs. Patients with SSIs had longer hospital stay, poorer functional capacity on discharge, and higher 90-day mortality. We raise the possibility of post-operative infection acquisition through external CSF devices. Standard operating procedures for their maintenance are necessary.

Macrolides vs. quinolones for community-acquired pneumonia: meta-analysis of randomized controlled trials

The relative efficacy, safety and ecological implications of macrolides vs. quinolones in the treatment of community-acquired pneumonia (CAP) are debatable. We performed a systematic review and meta-analysis of randomized controlled trials comparing any macrolide vs. any quinolone for the treatment of CAP among adult inpatients or outpatients, as monotherapy or both in combination with a beta-lactam. We did not limit inclusion by pneumonia severity, publication status, language or date of publication. The primary outcomes assessed were 30-day all-cause mortality and treatment failure. Two authors independently extracted the data. Fixed effect meta-analysis of risk ratios (RRs) with 95% confidence intervals was performed. Sixteen trials (4989 patients) fulfilling inclusion criteria were identified, mostly assessing outpatients with mild to moderate CAP. All-cause mortality was not significantly different for macrolides vs. quinolones, RR 1.03 (0.63-1.68, seven trials), with a low event rate (2%). Treatment failure was significantly lower with quinolones, RR 0.78 (0.67-0.91, 16 trials). The definition of failure used in the primary studies was not clearly representative of patients benefit. Microbiological failure was lower with quinolones, RR 0.63 (0.49-0.81, 13 trials). All adverse events, adverse events requiring discontinuation and any premature antibiotic discontinuation were significantly more frequent with macrolides, mainly on account of gastrointestinal adverse events. Resistance development was not assessed in the trials. Randomized controlled trials show an advantage of quinolones in the treatment of CAP with regard to clinical cure without need for antibiotic modification at end of treatment and gastrointestinal adverse events. The clinical significance of this advantage is unclear.

Clinical effectiveness of seasonal influenza vaccine among adult cancer patients.

Patients with cancer are at increased risk of developing complications of influenza. In this study, the authors assessed the effectiveness of influenza vaccination among cancer patients.

Factors associated with influenza vaccination among adult cancer patients: a case–control study

Influenza vaccination is recommended for cancer patients; however, adherence is low. We aimed to identify predictive factors for vaccination among cancer patients. We conducted a case-control analysis of a patient cohort in the 2010-2011 influenza season. We included adult cancer patients with solid malignancies undergoing chemotherapy, and haematological patients with active disease. Patients who died between October and November 2010 (N = 43) were excluded from analysis. Cases received the 2011 seasonal influenza vaccine, and controls did not. Data were obtained from patients records, and validated through personal interviews. We collected socio-demographic information, and data on the malignancy and co-morbidities and triggers for vaccination and non-vaccination. We performed bivariate and multivariable analyses, in which vaccination status was the dependent variable. Of 806 patients included in analysis, 387 (48%) were vaccinated. Variables associated with vaccination on bivariate analysis were older age, higher socio-economic status, lower crowding index, marital status (widowed > married > single), malignancy type (haematological > solid tumours) and time from diagnosis, low-risk malignancy, diabetes, past vaccination, country of birth (non-Russian origin), and physicians recommendations. Predictive factors found to be independently associated with vaccination on multivariable analysis were past vaccinations, low-risk malignancy, and country of birth. In the analysis conducted among interviewees (N = 561), recommendations from the oncologist (OR 10.7, 95% CI 5.4-21.2) and from the primary-care physician (OR 3.35, 95% CI 2.05-5.49) were strong predictors for vaccination. We conclude that habitual vaccinees continue influenza vaccinations when ill with cancer. Physicians recommendations, especially the oncologists, have a major influence on patients compliance with influenza vaccination.

Bloodstream infections in older patients.

ABSTRACT Bloodstream infections (BSIs) are both common and fatal in older patients. We describe data from studies evaluating older patients hospitalized with BSIs. Most older patients with BSIs present “typically” with either fever or leukocytosis. The most common source of BSI in older patients is the urinary tract, and accordingly, Gram-negative organisms predominate. A significant part of these BSIs may thus be preventable by removal of unnecessary urinary catheters. Increased long term mortality is reported following BSIs in older patients, however, data on other long-term outcomes, including functional capacity, cognitive decline and others are lacking. Management of BSIs may include less invasive procedures due to the fragility of older patients. This approach may delay the diagnosis and treatment in some cases. Older patients are probably under-represented in clinical trials assessing treatment of bacteremia. Physicians treating older patients should consider the relevance of these studies outcomes.

Risk Factors for Treatment Failure and Mortality among Hospitalised Patients with Complicated Urinary Tract Infection: A Multicentre Retrospective Cohort Study, RESCUING Study Group

BackgroundnComplicated urinary tract infections (cUTIs) are responsible for a major share of all antibiotic consumption in hospitals. We aim to describe risk factors for treatment failure and mortality among patients with cUTIs.nnnMethodsnA multinational, multicentre retrospective cohort study, conducted in 20 countries in Europe and the Middle East. Data were collected from patients files on hospitalised patients with a diagnosis of cUTI during 2013-2014. Primary outcome was treatment failure, secondary outcomes included 30 days all-cause mortality,among other outcomes. Multivariable analysis using a logistic model and the hospital as a random variable was performed to identify independent predictors for these outcomes.nnnResultsnA total of 981 patients with cUTI were included. Treatment failure was observed in 26.6% (261/981), all cause 30-day mortality rate was 8.7% (85/976), most of these in patients with catheter related UTI (CaUTI). Risk factors for treatment failure in multivariable analysis were ICU admission (OR 5.07, 95% CI 3.18-8.07), septic shock (OR 1.92, 95% CI 0.93-3.98), corticosteroid treatment (OR 1.92, 95% CI 1.12-3.54), bedridden (OR 2.11, 95%CI 1.4-3.18), older age (OR 1.02, 95% CI 1.0071.03-), metastatic cancer (OR 2.89, 95% CI 1.46-5.73) and CaUTI (OR 1.48, 95% CI 1.04-2.11). Management variables, such as inappropriate empirical antibiotic treatment or days to starting antibiotics were not associated with treatment failure or 30-day mortality. More patients with pyelonephritis were given appropriate empirical antibiotic therapy than other CaUTI [110/171; 64.3% vs. 116/270; 43%, p <0.005], nevertheless, this afforded no advantage in treatment failure rates nor mortality in these patients.nnnConclusionsnIn patients with cUTI we found no benefit of early appropriate empirical treatment on survival rates or other outcomes. Physicians might consider supportive treatment and watchful waiting in stable patients until the causative pathogen is defined.

Early double J stent removal in renal transplant patients to prevent urinary tract infection – systematic review and meta-analysis of randomized controlled trials

Ureteral stents are routinely used in renal transplant and are associated with reduced urological complications but increased urinary tract infections (UTIs). There is no agreement on the preferred time to removal of stents after transplantation. We performed a systematic review and meta-analysis of all randomized controlled trials (RCTs) comparing stent duration of <14xa0days vsu2009>u2009=14xa0days. Electronic databases were searched to identify RCTs that compared early vs late stent removal. Primary outcome was urinary tract infections. Secondary outcomes included various urological complications. No significant difference in UTI rates was demonstrated between short and long stent duration (relative risk (RR) 0.85, 95% confidence interval (CI) 0.44–1.64), with significant heterogeneity (I2u2009=u200986%). Sensitivity analysis evaluating studies with low risk of bias for allocation concealment demonstrated statistically significant lower rates of UTI with short stent duration (RR 0.48, 95% CI 0.32–0.71) with no heterogeneity. No significant difference was demonstrated for the outcome of major urological complications (RR 0.72, 95% CI 0.50–1.05), without heterogeneity. Ureteral stenosis rates were significantly lower in the short duration arm (RR 0.42, 95% CI 0.18–0.98). Early removal of ureteral stents after renal transplant may be associated with reduced rates of UTI and ureteral stenosis. Additional RCTs are needed.

Predictive factors for multidrug-resistant gram-negative bacteria among hospitalised patients with complicated urinary tract infections

BackgroundPatients with complicated urinary tract infections (cUTIs) frequently receive broad-spectrum antibiotics. We aimed to determine the prevalence and predictive factors of multidrug-resistant gram-negative bacteria in patients with cUTI.MethodsThis is a multicenter, retrospective cohort study in south and eastern Europe, Turkey and Israel including consecutive patients with cUTIs hospitalised between January 2013 and December 2014. Multidrug-resistance was defined as non-susceptibility to at least one agent in three or more antimicrobial categories. A mixed-effects logistic regression model was used to determine predictive factors of multidrug-resistant gram-negative bacteria cUTI.ResultsFrom 948 patients and 1074 microbiological isolates, Escherichia coli was the most frequent microorganism (559/1074), showing a 14.5% multidrug-resistance rate. Klebsiella pneumoniae was second (168/1074) and exhibited the highest multidrug-resistance rate (54.2%), followed by Pseudomonas aeruginosa (97/1074) with a 38.1% multidrug-resistance rate. Predictors of multidrug-resistant gram-negative bacteria were male gender (odds ratio [OR], 1.66; 95% confidence interval [CI], 1.20–2.29), acquisition of cUTI in a medical care facility (OR, 2.59; 95%CI, 1.80–3.71), presence of indwelling urinary catheter (OR, 1.44; 95%CI, 0.99–2.10), having had urinary tract infection within the previous year (OR, 1.89; 95%CI, 1.28–2.79) and antibiotic treatment within the previous 30xa0days (OR, 1.68; 95%CI, 1.13–2.50).ConclusionsThe current high rate of multidrug-resistant gram-negative bacteria infections among hospitalised patients with cUTIs in the studied area is alarming. Our predictive model could be useful to avoid inappropriate antibiotic treatment and implement antibiotic stewardship policies that enhance the use of carbapenem-sparing regimens in patients at low risk of multidrug-resistance.