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Key Points Question Do patients with cancer develop adequate antibody responses to messenger RNA SARS-CoV-2 vaccines? Findings In this cohort study that included 102 patients with cancer who were receiving active treatment and 78 healthy controls, 92 patients with cancer (90%) and 100% of the controls were seropositive after the second messenger RNA BNT162b2 vaccine dose.. Meaning The findings of this study suggest that patients with cancer who are receiving active treatment and are at higher risk for severe COVID-19 disease respond well to messenger RNA SARS-CoV-2 vaccines and that vaccination of these patients should be seriously considered., Importance Patients with cancer undergoing treatment are at high risk of COVID-19 following SARS-CoV-2 infection; however, their ability to produce an adequate antibody response to messenger RNA SARS-CoV-2 vaccines is unclear. Objective To evaluate rates of antispike (anti-S) antibody response to a BNT162b2 vaccine in patients with cancer who are undergoing systemic treatment vs healthy controls. Design, Setting, and Participants This prospective cohort study included 102 adult patients with solid tumors undergoing active intravenous anticancer treatment and 78 controls who received the second dose of the BNT162b2 vaccine at least 12 days before enrollment. The controls were taken from a convenience sample of the patients’ family/caregivers who accompanied them to treatment. The study was conducted between February 22, 2021, and March 15, 2021 at Davidoff Cancer Center at Beilinson Hospital (Petah Tikva, Israel). Interventions Blood samples were drawn from the study participants. Serum samples were analyzed and the titers of the IgG antibodies against SARS-CoV-2 spike receptor–binding domain were determined using a commercially available immunoassay. Seropositivity was defined as 50 or greater AU/mL. Main Outcomes and Measures The primary outcome was the rate of seropositivity. Secondary outcomes included comparisons of IgG titers and identifying factors that were associated with seropositivity using univariate/multivariable analyses. Results The analysis included 180 participants, which comprised 102 patients with cancer (median [interquartile range (IQR)] age, 66 [56-72] years; 58 men [57%]) and 78 healthy controls (median [IQR] age, 62 [49-70] years; 25 men [32%]). The most common tumor type was gastrointestinal (29 [28%]). In the patient group, 92 (90%) were seropositive for SARS-CoV 2 antispike IgG antibodies after the second vaccine dose, whereas in the control group, all were seropositive. The median IgG titer in the patients with cancer was significantly lower than that in the controls (1931 [IQR, 509-4386] AU/mL vs 7160 [IQR, 3129-11 241] AU/mL; P, This cohort study evaluates rates of antispike antibody response to a messenger RNA SARS-CoV-2 vaccine in Israeli patients with cancer who are undergoing systemic treatment vs healthy controls.

Importance: Patients with cancer undergoing treatment are at high risk of COVID-19 following SARS-CoV-2 infection; however, their ability to produce an adequate antibody response to messenger RNA SARS-CoV-2 vaccines is unclear. Objective: To evaluate rates of antispike (anti-S) antibody response to a BNT162b2 vaccine in patients with cancer who are undergoing systemic treatment vs healthy controls. Design, Setting, and Participants: This prospective cohort study included 102 adult patients with solid tumors undergoing active intravenous anticancer treatment and 78 controls who received the second dose of the BNT162b2 vaccine at least 12 days before enrollment. The controls were taken from a convenience sample of the patients' family/caregivers who accompanied them to treatment. The study was conducted between February 22, 2021, and March 15, 2021 at Davidoff Cancer Center at Beilinson Hospital (Petah Tikva, Israel). Interventions: Blood samples were drawn from the study participants. Serum samples were analyzed and the titers of the IgG antibodies against SARS-CoV-2 spike receptor-binding domain were determined using a commercially available immunoassay. Seropositivity was defined as 50 or greater AU/mL. Main Outcomes and Measures: The primary outcome was the rate of seropositivity. Secondary outcomes included comparisons of IgG titers and identifying factors that were associated with seropositivity using univariate/multivariable analyses. Results: The analysis included 180 participants, which comprised 102 patients with cancer (median [interquartile range (IQR)] age, 66 [56-72] years; 58 men [57%]) and 78 healthy controls (median [IQR] age, 62 [49-70] years; 25 men [32%]). The most common tumor type was gastrointestinal (29 [28%]). In the patient group, 92 (90%) were seropositive for SARS-CoV 2 antispike IgG antibodies after the second vaccine dose, whereas in the control group, all were seropositive. The median IgG titer in the patients with cancer was significantly lower than that in the controls (1931 [IQR, 509-4386] AU/mL vs 7160 [IQR, 3129-11 241] AU/mL; P < .001). In a multivariable analysis, the only variable that was significantly associated with lower IgG titers was treatment with chemotherapy plus immunotherapy (s, -3.5; 95% CI, -5.6 to -1.5). Conclusions and Relevance: In this cohort study of patients with cancer who were receiving active systemic therapy, 90% of patients exhibited adequate antibody response to the BNT162b2 vaccine, although their antibody titers were significantly lower than those of healthy controls. Further research into the clinical relevance of lower titers and their durability is required. Nonetheless, the data support vaccinating patients with cancer as a high priority, even during therapy.

Changes in the epidemiology of Staphylococcus aureus bacteremia (SAB) have been described in recent decades. Decreased mortality has been reported over time, mostly from countries with low methicillin resistance rates. We aimed to describe time trends in SAB in a tertiary center with high methicillin resistance rates. We retrospectively analyzed 1692 patients with SAB, and compared between three time periods: 1988–1994 (342 patients), 1998–2004 (597 patients) and 2005–2010 (753 patients). In our cohort, 30 days mortality increased significantly with time, reaching 42.9 % during 2005–2010. The latter period was characterized by higher rates of older patients (35.1 % aged 80 years and older), with lower functional capacity (46.5 % bedridden) and higher rates of comorbidities (33.6 % renal disease, 24.8 % heart failure, 19.0 % dementia). These patients were more likely to be ventilated (18.7 %) and carry a urinary catheter at presentation (46.6 %); present with septic shock (15.9 %) and have pneumonia (20.5 %) or endocarditis (7.2 %) as source. Similar characteristics were found among patients younger than 50 years and with independent functional status. No significant increase in methicillin resistant Staph aureus (MRSA) rates or inappropriate empirical therapy was demonstrated during 2005–2010. In our cohort, increased mortality in recent years in patients with SAB can be explained by baseline condition of patients. MRSA or inappropriate empiric therapy did not explain the increase in mortality. The patients afflicted with SAB changed over time. Epidemiology and outcomes of SAB vary with time and according to geographical location. External validity of studies should be taken into consideration.

ResumoPeriaortite crônica (PC) é um termo genérico usado para descrever um grupo de condições nosologicamente ligadas que incluem a fibrose idiopática retroperitoneal (doença de Ormond), o aneurisma da aorta abdominal inflamatório e a fibrose retroperitoneal perianeurismática. O termo fibrose retroperitoneal engloba uma gama de doenças que se caracterizam pela presença de um tecido fibroinflamatório que geralmente envolve a aorta abdominal e as artérias ilíacas, se estende ao retroperitôneo e envolve estruturas ureterais vizinhas. A fibrose retroperitoneal geralmente é idiopática, mas pode também ser secundária ao uso de determinados fármacos, doenças malignas, infecções e cirurgia. Este estudo descreve o seguimento por cinco anos (2006‐2011) de cinco pacientes internados em nosso hospital que apresentavam sintomas e achados laboratoriais, de imagem e patológicos compatíveis com a fibrose retroperitoneal. Revisou‐se a evolução clínica dos pacientes, que foi comparada com os achados da literatura.AbstractChronic periaortitis (CP) is an umbrella term used to describe a group of nosologically allied conditions that include idiopathic retroperitoneal fibrosis (Ormond's disease), inflammatory abdominal aortic aneurysm, and perianeurysmal retroperitoneal fibrosis. Retroperitoneal fibrosis encompasses a range of diseases characterized by the presence of a fibro‐inflammatory tissue, which usually surrounds the abdominal aorta and the iliac arteries and extends into the retroperitoneum to envelop neighboring structures‐ureters. Retroperitoneal fibrosis is generally idiopathic, but can also be secondary to the use of certain drugs, malignant diseases, infections, and surgery. Here we describe a 5 years follow up (2006‐2011) of 5 patients admitted to our hospital with symptoms, laboratory, imaging and pathologic finding compatible with retroperitoneal fibrosis. We review our clinical course of our patient with respect to the literature.

Several studies have shown an association between exposure to statins and favorable clinical outcomes for various types of infections. We aimed to assess the impact of statin use on mortality, disease severity and complications among hospitalized patients with Clostridium difficile infection (CDI). Data were analyzed from a retrospectively collected database of 499 patients diagnosed with CDI during 2009–2014. We compared infection outcomes between 178 statin (36 %) users and 321 (64 %) non-users. On multivariate analysis, we found that statin use did not have a significant impact on 30-day mortality (OR = 1.54; 95 % CI, 0.85-2.79; p = 0.15) or any significant effect on CDI severity and complication. Concomitant statin use has no significant impact on short-term mortality or effect on CDI severity and complications among hospitalized patients with CDI. However, patients in the statin group were older and had higher Charlson score compared with the non-statin group. Whether these factors affected a possible impact of statins on the disease course remains to be investigated. • Clostridium difficile is the most common cause of infectious nosocomial diarrhea among hospitalized adult patients in the developed countries. • There is an increasing morbidity and mortality of CDI patients due to the emergence of new strains of high virulence. • Recent studies demonstrated that prior statin use has protective and ameliorating effects on morbidity and mortality among CDI patients. • Our study showed that concomitant statin use has no significant impact on short-term mortality, CDI severity and its complications.

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.

INTRODUCTION Risk factors for candidemia in the internal medicine wards (IMW) are poorly characterized. Their elucidation might assist in early diagnosis and treatment. OBJECTIVES We aimed to elucidate predictors of candidemia in the IMWs comparing them to patients with gram-negative bacteremia (GNB). METHODS A retrospective study of consecutive patients with candidemia in IMWs in Beilinson hospital (2007-2016) was performed. Patient demographics, comorbidities, and clinical characteristics were documented. The comparator group was GNB patients. RESULTS Sixty-two patients with candidemia were compared with 178 patients with GNB. Candidemic patients were younger and with less body mass index > 20 kg/m2 (73 ± 15 vs. 78 ± 10, P = 0.01; 44% vs. 60%, P =

Background Bloodstream infections (BSIs) are an important cause of hospitalizations and mortality among hemodialysis (HD) patients. Epidemiology of these infections is changing, with increasing rates of Gram-negative pathogens, including resistant ones. Few studies have focused on the characteristics and outcomes of these infections. Objective We aimed to document the causative pathogens of BSIs in HD patients and their clinical outcomes during 2008 - 2015, and to compare risk factors, clinical features, appropriateness of therapy, and outcomes between patients with Gram-negative vs. Gram-positive BSIs. Materials and methods A single-center retrospective cohort study. Charts of 120 HD patients hospitalized with first BSI were reviewed. Results A total of 120 patients were included, 61 episodes of Gram-negative (51.8%) and 59 episodes of Gram-positive bacteria (49.2%). Source of infection was significantly more likely to be urinary or abdominal among patients with Gram-negative infection. Otherwise, no statistically significant differences were documented between groups in terms of baseline characteristics, presentation of infection and outcomes. Most Gram-negative BSIs were caused by enterobacteriaceae, followed by Pseudomonas spp. Previous clinical or surveillance cultures added little to accurate prediction of the causative organism. Conclusion In a cohort of HD patients with BSI, no significant differences were found between Gram-negative and Gram-positive BSIs, besides source of infection. A urinary or abdominal source strongly suggests a Gram-negative pathogen. Otherwise, patient's characteristics, clinical presentation, and previous cultures, all cannot accurately predict the causative pathogen of BSI, and broad-spectrum antibiotics should be used empirically. .

Clostridium difficile infection (CDI) is the most common infectious disease cause of nosocomial diarrhea in adults in developed countries. Judging from the clinical trials on drugs used in CDIs, no approved treatment for recurrences exists, possibly indicating that a combination of treatment approaches are mandatory especially in severe infections, with current studies not being fully representative. Among the new strategies researched intensively fidaxomicin is presented, which demonstrates reduced CDI recurrences. Moreover, biotherapeutic strategies, mainly fecal microbiota transplantation but also competitive inhibition with non-toxigenic strains of C. difficile, and finally monoclonal antibodies against C. difficile toxins which offer protection against recurrences. Careful interpretation of the results based on lessons learned from previous trials conducted seems crucial. Questions are raised regarding how the results of future studies regarding new strategies researched will be managed and interpreted especially with regard to recurrence management as relevant data must be monitored for at least 30 days after end of treatment.

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.

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To evaluate the clinical effect of statins for the treatment of sepsis in RCTs.

Background Empirical colistin should be avoided. We aimed to evaluate the association between covering empirical antibiotics (EAT) and mortality for infections caused by carbapenem-resistant gram-negative bacteria (CRGNB). Methods This was a secondary analysis of a randomized controlled trial, including adults with bloodstream infections, pneumonia, or urosepsis caused by CRGNB. All patients received EAT followed by covering targeted therapy. The exposure variable was covering EAT in the first 48 hours. The outcome was 28-day mortality. We adjusted the analyses by multivariable regression analysis and propensity score matching. Results The study included 406 inpatients with severe CRGNB infections, mostly Acinetobacter baumannii (312/406 [77%]). Covering EAT was given to 209 (51.5%) patients, mostly colistin (n = 200). Patients receiving noncovering EAT were older, more frequently unconscious and dependent, carrying catheters, and mechanically ventilated with pneumonia. Mortality was 84 of 197 (42.6%) with noncovering vs 96 of 209 (45.9%) with covering EAT (P = .504). Covering EAT was not associated with survival in the adjusted analysis; rather, there was a weak association with mortality (odds ratio [OR], 1.37; 95% confidence interval [CI], 1.02-1.84). Results were similar for colistin monotherapy and colistin-carbapenem combination EAT. In the propensity score-matched cohort (n = 338) covering antibiotics were not significantly associated with mortality (OR, 1.42; 95% CI, .91-2.22). Similar results were obtained in an analysis of 14-day mortality. Conclusions Empirical use of colistin before pathogen identification, with or without a carbapenem, was not associated with survival following severe infections caused by CRGNBs, mainly A. baumannii.

Aina Gomila,1,2 JCarratalà,1–3 N Eliakim-Raz,4 E Shaw,1,2 I Wiegand,5 LVallejo-Torres,6 A Gorostiza,2 JM Vigo,7 S Morris,6 M Stoddart,8 S Grier,8 C Vank,5 N Cuperus,9 L Van den Heuvel,9 C Vuong,5 A MacGowan,8 L Leibovici,4 I Addy,5 M Pujol1,2 On behalf of COMBACTE MAGNET WP5 RESCUING Study Group and Study Sites 1Department of Infectious Diseases, Hospital Universitari de Bellvitge, Institut Català de la Salut (ICS-HUB), Spanish Network for Research in Infectious Diseases (REIPI RD12/0015), Instituto de Salud Carlos III (ISCIII), Madrid, Spain; 2Institut d’Investigació Biomèdica de Bellvitge (IDIBELL), Barcelona, Spain; 3Infectious Diseases Department, University of Barcelona, Barcelona, Spain; 4Department of Medicine E, Beilinson Hospital, Rabin Medical Center, Petah-Tiqva and Sackler Faculty of Medicine, Tel Aviv University, Israel; 5AiCuris Anti-infective Cures, Wuppertal, Germany; 6UCL Department of Applied Health Research, University College London, London, UK; 7Informatics Unit, Fundació Institut Català de Farmacologia, Barcelona, Spain; 8Department of Medical Microbiology, Southmead Hospital, North Bristol NHS Trust, Bristol, UK; 9Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands 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. Keywords: health care-associated infections, complicated urinary tract infections, Pseudomonas aeruginosa, multidrug-resistance

Objective Complicated urinary tract infections (cUTIs) impose a high burden on healthcare systems and are a frequent cause of hospitalisation. The aims of this paper are to estimate the cost per episode of patients hospitalised due to cUTI and to explore the factors associated with cUTI-related healthcare costs in eight countries with high prevalence of multidrug resistance (MDR). Design This is a multinational observational, retrospective study. The mean cost per episode was computed by multiplying the volume of healthcare use for each patient by the unit cost of each item of care and summing across all components. Costs were measured from the hospital perspective. Patient-level regression analyses were used to identify the factors explaining variation in cUTI-related costs. Setting The study was conducted in 20 hospitals in eight countries with high prevalence of multidrug resistant Gram-negative bacteria (Bulgaria, Greece, Hungary, Israel, Italy, Romania, Spain and Turkey). Participants Data were obtained from 644 episodes of patients hospitalised due to cUTI. Results The mean cost per case was €5700, with considerable variation between countries (largest value €7740 in Turkey; lowest value €4028 in Israel), mainly due to differences in length of hospital stay. Factors associated with higher costs per patient were: type of admission, infection source, infection severity, the Charlson comorbidity index and presence of MDR. Conclusions The mean cost per hospitalised case of cUTI was substantial and varied significantly between countries. A better knowledge of the reasons for variations in length of stays could facilitate a better standardised quality of care for patients with cUTI and allow a more efficient allocation of healthcare resources. Urgent admissions, infections due to an indwelling urinary catheterisation, resulting in septic shock or severe sepsis, in patients with comorbidities and presenting MDR were related to a higher cost.

Elevated blood pressure (BP) is a known factor that affects the structure of the left ventricle. The association between left ventricular hypertrophy (LVH) and BP in normotensive individuals is poorly understood. All individuals who underwent routine echocardiography and BP measurements as aircrew candidates for the Israeli Air Force in the years 2006 to 2012 were identified. Participants with normal values were included. Associations between echocardiographic characteristics and BP were studied. A total of 2386 participants were included. Mean systolic BP was 125.31±11.18 mm Hg and mean diastolic BP was 68.69±9.02 mm Hg. Interventricular septal (IVS) thickness was positively correlated with systolic BP (P

Recent Infectious Diseases Society of America guidelines for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections recommend maintaining vancomycin trough concentrations of 15-20 mg/L for serious infections. We conducted a systematic review and meta-analysis of all studies assessing the impact of low (

Bacteraemia is associated with high mortality. Although many models for predicting bacteraemia have been developed, not all have been validated, and even when they were, the validation processes varied. We identified validated models that have been developed; asked whether they were successful in defining groups with a very low or high prevalence of bacteraemia; and whether they were used in clinical practice. Electronic databases were searched to identify studies that underwent validation on prediction of bacteraemia in adults. We included only studies that were able to define groups with low or high probabilities for bacteraemia (arbitrarily defined as below 3% or above 30%). Fifteen publications fulfilled inclusion criteria, including 59 276 patients. Eleven were prospective and four retrospective. Study populations and the parameters included in the different models were heterogeneous. Ten studies underwent internal validation; the model performed well in all of them. Twelve performed external validation. Of the latter, seven models were validated in a different hospital, using a new independent database. In five of these, the model performed well. After contacting authors, we found that none of the models was implemented in clinical practice. We conclude that heterogeneous studies have been conducted in different defined groups of patients with limited external validation. Significant savings to the system and the individual patient can be gained by refraining from performing blood cultures in groups of patients in which the probability of true bacteraemia is very low, while the probability of contamination is constant. Clinical trials of existing or new models should be done to examine whether models are helpful and safe in clinical use, preferably multicentre in order to secure utility and safety in diverse clinical settings.

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.

The objective of this study was to explore whether the percentage of inappropriate empirical antibiotic treatment in patients with bacteremia changed over time and to understand the factors that brought on the change. Three prospective cohorts of patients with bacteremia in three different periods (January 1st, 1988 to December 31st, 1989; May 1st, 2004 to November 30, 2004; May 1st, 2010 to April 30, 2011) were compared. Analysis was performed on a total of 811 patients. In 2010–2011, 55.9% (76/136) of patients with bacteremia received inappropriate empirical treatment, compared with 34.5% (170/493) and 33.5% (55/164) in the first and second periods, respectively, in a significant upward trend (p = 0.001). Resistance to antibiotics increased significantly during the study period. The following variables were included in the multivariate analysis assessing risk factors for inappropriate empirical treatment: study period (third period) [odds ratio, OR = 2.766 (95% confidence interval, CI, 1.655–4.625)], gender (male) [OR = 1.511 (1.014–2.253)], pathogen carrying extended-spectrum beta-lactamases [OR = 10.426 (4.688–23.187)], multidrug-resistant Acinetobacter baumannii [OR = 5.428 (2.181–13.513)], and skin/soft infections [OR = 3.23 (1.148–9.084)]. A model excluding microbiological data included: gender (male) [OR = 1.648 (1.216–2.234)], study period (third period) [OR = 2.446 (1.653–3.620)], hospital-acquired infection [OR = 1.551 (1.060–2.270)], previous use of antibiotics [OR = 1.815 (1.247–2.642)], bedridden patient [OR = 2.019 (1.114–3.658)], and diabetes mellitus [OR = 1.620 (1.154–2.274)]. We have observed a worrisome increase in the rate of inappropriate empirical treatment of bacteremia. We need tools that will allow us better prediction of the pathogen and its susceptibilities during the first hours of managing a patient suspected of a severe bacterial infection.

Summary Background Necrotizing fasciitis (NF) is a life-threatening soft tissue infection. It is usually caused by Streptococcus pyogenes and other Gram-positive bacteria. Several reports, however, emphasize the importance of Gram-negative rods in this infection. Methods We retrospectively studied all cases of monomicrobial necrotizing fasciitis hospitalized in our center during the years 2002–2012. We compared clinical characteristics and outcomes of patients with Gram-negative versus Gram-positive infection. Results Forty-five cases were reviewed, 19 caused by Gram-negative organisms, 10 of them Escherichia coli , and 26 caused by Gram-positive organisms, 10 of them S. pyogenes . Compared to Gram-positive infections, patients with Gram-negative infections were more likely to have a baseline malignancy (9/19, 47.4%) or to have undergone recent surgery (4/19, 42.3%). The 30-day mortality was higher among Gram-negative infected patients (8/19, 42.1% vs. 8/26, 30.8%). Creatine phosphokinase (CPK) was elevated in a minority of patients with Gram-negative necrotizing fasciitis, and its absolute value was lower than in Gram-positive necrotizing fasciitis. Conclusions In our center, 42% of monomicrobial necrotizing fasciitis cases were found to be caused by Gram-negative organisms, mostly E. coli . These infections usually appeared in immunocompromised or postoperative patients, often presented with normal CPK levels, and were associated with high mortality rates.

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 oncologist's, have a major influence on patients' compliance with influenza vaccination.

Polymicrobial endocarditis is uncommon. We present a case of polymicrobial endocarditis caused by Enterococcus faecalis and Coxiella burnetii and review previous cases of polymicrobial endocarditis involving Coxiella burnetii. Testing for Q fever should be considered in any patient with endocarditis living in an endemic area.

BACKGROUND 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. METHODS A prospective, noninterventional cohort study was conducted during the 2010 to 2011 influenza season. The cohort included adult cancer patients with solid malignancies who were receiving chemotherapy and hematologic patients who had active disease. Patients who died between October and November 2010 (N = 43) were excluded. A comparison was made between patients who received the 2011 seasonal influenza vaccine with those who did not. The primary outcome was a composite of hospitalizations for fever or acute respiratory infections, pneumonia, and/or infection-related chemotherapy interruptions. All-cause mortality was a secondary outcome. A propensity-matched analysis was conducted based on the propensity for vaccination. RESULTS Of 806 patients who were included, 387 (48%) were vaccinated. Factors that were associated independently with vaccination included past influenza vaccination, past pneumococcal vaccination, >6 months since cancer diagnosis, country of birth, and cancer type/status. The primary outcome occurred in 111 of 387 (28.7%) vaccinated patients versus 112 of 419 (26.7%) unvaccinated patients (P = .54). No association was observed between vaccination and the primary outcome in a propensity-matched analysis (N = 436) or during peak influenza activity. The mortality rate was 11.9% (46 of 387 patients) in vaccinated patients versus 19.1% (80 of 419 patients) in unvaccinated patients (P = .005). Vaccination retained a significant association with mortality on multivariable analysis (odds ratio, 2.31; 95% confidence interval, 1.4-3.79) and in a propensity-matched analysis (odds ratio, 2.39; 95% confidence interval, 1.32-4.32). CONCLUSIONS Influenza vaccination was associated with lower mortality among cancer patients, although an association with infection-related complications could not be demonstrated. The current results support efforts to promote influenza vaccination in patients with cancer. Cancer 2013;119:4028–4035. © 2013 American Cancer Society.

The gap between the emergence of antibiotic resistance and new antibiotic development has drawn attention to old antibiotics whose spectrum of coverage frequently comprises highly resistant bacteria. However, these antibiotics have frequently not undergone the structured process of antibiotic development of modern antibiotics, from pharmacokinetic/pharmacodynamic (PK/PD) studies establishing safe and effective dosing, establishment of susceptibility breakpoints, to clinical trials establishing clinical safety and effectiveness. In this review, we highlight the gaps for which we need old antibiotics in community- and hospital-acquired infections. Reviewing recently published and ongoing randomised controlled trials (RCTs) shows advances in our understanding of the efficacy and effectiveness of oral fosfomycin, mecillinam and nitrofurantoin for cystitis, and of trimethoprim/sulfamethoxazole for complicated skin infections caused by methicillin-resistant Staphylococcus aureus (MRSA) in the community. Summarising older evidence shows the inferiority of chloramphenicol versus modern antibiotics for severe infections. We lack studies on severe infections caused by carbapenem-resistant Gram-negative bacteria and other multidrug-resistant (MDR) bacteria in hospitalised and critically ill patients; ongoing studies assessing colistin and intravenous fosfomycin might fill in some gaps. In the re-development process of old antibiotics, we mandate modern PK/PD studies comprising special populations as well as RCTs addressing the target population of patients in need of these antibiotics powered to examine patient-relevant outcomes. Structured antibiotic re-development from the laboratory to evidence-based treatment recommendations requires public funding, multidisciplinary collaboration, international co-ordination, and methods to streamline the recruitment of critically ill patients infected by MDR bacteria.

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: The primary objective is to compare the effects of pneumococcal conjugated vaccines (PCV) alone or added to a pneumococcal polysaccharide vaccine (PPSV) versus PPSV alone for the prevention of any pneumonia. Secondary objectives are: 1. to compare the effect of PCV versus PPSV vaccine on any IPD and IPD caused by VT serotypes; 2. to compare the effect of PCV versus PPSV vaccine on VT pneumonia and any pneumonia requiring hospitalisation; 3. to examine the effects of PCV versus PPSV on immunological outcomes (antibodies level; opsonophagocytic activity); 4. to compare the effect of PCV versus PPSV on serotype replacement; and 5. to compare the adverse events caused by PCV to the adverse events caused by PPSV.

Chronic periaortitis (CP) is an umbrella term used to describe a group of nosologically allied conditions that include idiopathic retroperitoneal fibrosis (Ormond's disease), inflammatory abdominal aortic aneurysm, and perianeurysmal retroperitoneal fibrosis. Retroperitoneal fibrosis encompasses a range of diseases characterized by the presence of a fibro-inflammatory tissue, which usually surrounds the abdominal aorta and the iliac arteries and extends into the retroperitoneum to envelop neighboring structures-ureters. Retroperitoneal fibrosis is generally idiopathic, but can also be secondary to the use of certain drugs, malignant diseases, infections, and surgery. Here we describe a 5 years follow up (2006-2011) of 5 patients admitted to our hospital with symptoms, laboratory, imaging and pathologic finding compatible with retroperitoneal fibrosis. We review our clinical course of our patient with respect to the literature. RESUMO Periaortite crônica (PC) é um termo genérico usado para descrever um grupo de condições nosologicamente ligadas que incluem a fibrose idiopática retroperitoneal (doença de Ormond), o aneurisma da aorta abdominal inflamatório e a fibrose retroperitoneal perianeurismática. O termo fibrose retroperitoneal engloba uma gama de doenças que se caracterizam pela presença de um tecido fibroinflamatório que geralmente envolve a aorta abdominal e as artérias ilíacas, se estende ao retroperitôneo e envolve estruturas ureterais vizinhas. A fibrose retroperitoneal geralmente é idiopática, mas pode também ser secundária ao uso de determinados fármacos, doenças malignas, infecções e cirurgia. Este estudo descreve o seguimento por cinco anos (2006-2011) de cinco pacientes internados em nosso hospital que apresentavam sintomas e achados laboratoriais, de imagem e patológicos compatíveis com a fibrose retroperitoneal. Revisou-se a evolução clínica dos pacientes, que foi comparada com os achados da literatura.

Most cases of Clostridium difficile infections (CDI) occur in patients aged 65 years and older. Older age is associated with increased mortality. Risk factors for mortality in patients aged 80 years and older are not well recognized.We analyzed retrospective data including 184 patients aged 80 years and older hospitalized with CDI during 2009-2014. We aimed to delineate risk factors for short- and long-term mortality.The 30-day mortality was 33.2%; 1-year mortality was 64.7%. Median survival was 110 days (interquartile range 24-655 days). All four patients who underwent colectomy died. Risk factors for 30-day mortality in multivariate analysis were diabetes mellitus, low albumin and therapy other than metronidazole monotherapy, the latter probably reflecting higher severity of disease rather than a true predictor of mortality. Risk factors for long-term mortality analyzed in Cox regression were albumin ≤2.5 g/dL (HR 0.58, 95% CI 0.395-0.850), presentation with sepsis (HR 0.597, 95% CI 0.408-0.873), a non-independent activities of daily living baseline status (HR 0.460, 95% CI 0.236--0.897) and Charlson score (HR 0.867, 95% CI 0.801-0.938). None of the traditional severity indices for CDI (such as leukocytosis or creatinine increase) proved to be predictors of mortality over the age of 80 years.The prognosis of old patients with CDI is dismal. Considering the high mortality, efforts to prevent CDI should be first priority in patients aged 80 years and older. Assessment of albumin levels should be part of the evaluation at presentation and considered when choosing treatment, rather than standard severity indexes for CDI. Geriatr Gerontol Int 2017; 17: 1378-1383.

Aim Most cases of Clostridium difficile infections (CDI) occur in patients aged 65 years and older. Older age is associated with increased mortality. Risk factors for mortality in patients aged 80 years and older are not well recognized. Methods We analyzed retrospective data including 184 patients aged 80 years and older hospitalized with CDI during 2009–2014. We aimed to delineate risk factors for short- and long-term mortality. Results The 30-day mortality was 33.2%; 1-year mortality was 64.7%. Median survival was 110 days (interquartile range 24–655 days). All four patients who underwent colectomy died. Risk factors for 30-day mortality in multivariate analysis were diabetes mellitus, low albumin and therapy other than metronidazole monotherapy, the latter probably reflecting higher severity of disease rather than a true predictor of mortality. Risk factors for long-term mortality analyzed in Cox regression were albumin ≤2.5 g/dL (HR 0.58, 95% CI 0.395–0.850), presentation with sepsis (HR 0.597, 95% CI 0.408–0.873), a non-independent activities of daily living baseline status (HR 0.460, 95% CI 0.236–-0.897) and Charlson score (HR 0.867, 95% CI 0.801–0.938). None of the traditional severity indices for CDI (such as leukocytosis or creatinine increase) proved to be predictors of mortality over the age of 80 years. Conclusions The prognosis of old patients with CDI is dismal. Considering the high mortality, efforts to prevent CDI should be first priority in patients aged 80 years and older. Assessment of albumin levels should be part of the evaluation at presentation and considered when choosing treatment, rather than standard severity indexes for CDI. Geriatr Gerontol Int 2016; ••: ••–••.

Importance The use of nitrofurantoin and fosfomycin has increased since guidelines began recommending them as first-line therapy for lower urinary tract infection (UTI). Objective To compare the clinical and microbiologic efficacy of nitrofurantoin and fosfomycin in women with uncomplicated cystitis. Design, Setting, and Participants Multinational, open-label, analyst-blinded, randomized clinical trial including 513 nonpregnant women aged 18 years and older with symptoms of lower UTI (dysuria, urgency, frequency, or suprapubic tenderness), a positive urine dipstick result (with detection of nitrites or leukocyte esterase), and no known colonization or previous infection with uropathogens resistant to the study antibiotics. Recruitment took place from October 2013 through April 2017 at hospital units and outpatient clinics in Geneva, Switzerland; Lodz, Poland; and Petah-Tiqva, Israel. Interventions Participants were randomized in a 1:1 ratio to oral nitrofurantoin, 100 mg 3 times a day for 5 days (n = 255), or a single 3-g dose of oral fosfomycin (n = 258). They returned 14 and 28 days after therapy completion for clinical evaluation and urine culture collection. Main Outcomes and Measures The primary outcome was clinical response in the 28 days following therapy completion, defined as clinical resolution (complete resolution of symptoms and signs of UTI without prior failure), failure (need for additional or change in antibiotic treatment due to UTI or discontinuation due to lack of efficacy), or indeterminate (persistence of symptoms without objective evidence of infection). Secondary outcomes included bacteriologic response and incidence of adverse events. Results Among 513 patients who were randomized (median age, 44 years [interquartile range, 31-64]), 475 (93%) completed the trial and 377 (73%) had a confirmed positive baseline culture. Clinical resolution through day 28 was achieved in 171 of 244 patients (70%) receiving nitrofurantoin vs 139 of 241 patients (58%) receiving fosfomycin (difference, 12% [95% CI, 4%-21%]; P = .004). Microbiologic resolution occurred in 129 of 175 (74%) vs 103 of 163 (63%), respectively (difference, 11% [95% CI, 1%-20%]; P = .04). Adverse events were few and primarily gastrointestinal; the most common were nausea and diarrhea (7/248 [3%] and 3/248 [1%] in the nitrofurantoin group vs 5/247 [2%] and 5/247 [1%] in the fosfomycin group, respectively). Conclusions and Relevance Among women with uncomplicated UTI, 5-day nitrofurantoin, compared with single-dose fosfomycin, resulted in a significantly greater likelihood of clinical and microbiologic resolution at 28 days after therapy completion. Trial Registration ClinicalTrials.gov Identifier:NCT01966653

Objectives Chloramphenicol is an old broad-spectrum antibiotic. We assessed its efficacy and safety. Methods This was a systematic review and meta-analysis. Electronic databases were searched to identify randomized controlled trials (RCTs) that assessed patients, of any age, with systemic bacterial infections that can cause sepsis and compared chloramphenicol alone versus other antibiotics. No restrictions on the date of publication, language or publication status were applied. The primary outcome assessed was overall mortality. Results Sixty-six RCTs fulfilled the inclusion criteria, and these included 9711 patients. We found a higher mortality with chloramphenicol for respiratory tract infections [risk ratio (RR) 1.40, 95% CI 1.00–1.97] and meningitis (RR 1.27, 95% CI 1.00–1.60), both without heterogeneity. The point estimate was similar for enteric fever, without statistical significance. No statistically significant difference was found between chloramphenicol and other antibiotics regarding treatment failure, except for enteric fever (RR 1.46, 95% CI 1.07–2.00, without heterogeneity). This difference derived mainly from studies comparing chloramphenicol with fluoroquinolones (RR 1.85, 95% CI 1.07–3.2). There were no statistically significant differences between chloramphenicol and other antibiotics in terms of adverse events, including haematological events, except for anaemia, which occurred more frequently with chloramphenicol (RR 2.80, 95% CI 1.65–4.75, I2 = 0%), and gastrointestinal side effects, which were less frequent with chloramphenicol (RR 0.67, 95% CI 0.46–0.99, I2 = 0%). Many of the studies included were sponsored by pharmaceutical companies marketing the comparator drug to chloramphenicol, and this might have influenced the results. Conclusions Chloramphenicol cannot be recommended as a first-line treatment for respiratory tract infections, meningitis or enteric fever as alternatives are probably more effective. Chloramphenicol is as safe as treatment alternatives for short antibiotic courses. RCTs are needed to test this treatment against MDR organisms when better alternatives do not exist.

Data on risk factors for Clostridium difficile infection (CDI) in diabetic patients are scarce. Recently, it has been shown that metformin increases the Bacteroidetes/Firmicutes ratio; therefore, it may yield a protective effect against CDI. We aimed to assess risk factors for CDI in diabetic patients beyond antibiotic treatment, and to determine the impact of metformin therapy on the development of CDI in these patients. In this retrospective, case–control study, all consecutive CDI diabetic patients, from January 2009 to December 2013, were included and compared to consecutive diabetic patients without CDI, hospitalized during the same period and in the same departments. Of 7,670 patients tested for C. difficile toxins, 486 were diabetics. Of them, 150 (30.8 %) were positive for C. difficile toxins and 336 (69.1 %) were negative. On multivariate analysis, metformin treatment was associated with a significant reduction in CDI [odds ratio (OR) = 0.58; 95 % confidence interval (CI), 0.37–0.93; p = 0.023], while heart failure was associated with significantly higher rates of CDI (OR = 1.654; 95 % CI, 1.007–2.716; p = 0.047), together with poor functional status, previous hospitalization, and abdominal surgery. Our findings suggest that, in diabetic patients, in addition to the well-recognized risk factors, heart failure is an additional risk factor for CDI, while metformin treatment seems to have a protective effect against the development of CDI. The exact mechanisms underlying this protective effect remain to be fully understood.

BACKGROUND: This is an update of the Cochrane review published in 2013, Issue 10. Immunosuppressed 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 are lacking, and the value of vaccination in this population remains unclear. OBJECTIVES: To 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 hospitalisations, influenza‐related mortality and immunogenicity were defined as secondary outcomes. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and LILACS databases up to May 2017. We searched the following conference proceedings: ICAAC, ECCMID, IDSA (infectious disease conferences), ASH, ASBMT, EBMT (haematological), and ASCO (oncological) between the years 2006 to 2017. 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. SELECTION CRITERIA: Randomised 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) haematopoietic stem cell transplantation (HSCT). DATA COLLECTION AND ANALYSIS: Two 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. MAIN RESULTS: We identified six studies with a total of 2275 participants: five studies comparing vaccination with no vaccination, and one comparing adjuvanted vaccine with non‐adjuvanted vaccine. Three studies were RCTs, one was a prospective observational cohort study and two were retrospective cohort studies. For the comparison of vaccination with no vaccination we included two RCTs and three observational studies, including 2202 participants. One study reported results in person‐years while the others reported results per person. The five studies were performed between 1993 and 2015 and included adults with haematological diseases (three studies), patients following bone marrow transplantation (BMT) (two studies) and solid malignancies (three studies). One RCT and two observational studies reported all‐cause mortality; the RCT showed similar mortality rates in both arms (odds ratio (OR) 1.25 (95% CI 0.43 to 3.62; 1 study, 78 participants, low‐certainty evidence)); and the observational studies demonstrated a significant association between vaccine receipt and lower risk of death, adjusted hazard ratio 0.88 (95% CI 0.78 to 1; 1 study, 1577 participants, very low‐certainty evidence) in one study and OR 0.42 (95% CI 0.24 to 0.75; 1 study, 806 participants, very low‐certainty evidence) in the other. One RCT reported a reduction in ILI with vaccination, while no difference was observed in one observational study. Confirmed influenza rates were lower with vaccination in one RCT and 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. One RCT showed a reduction in hospitalisations following vaccination, while an observational study found no difference. No life‐threatening or persistent adverse effects from vaccination were reported. The strength of evidence was limited by the low number of included studies and by their low methodological quality and the certainty of the evidence for the mortality outcome according to GRADE was low to very low. For the comparison of adjuvanted vaccine with non‐adjuvanted vaccine, we identified one RCT, including 73 patients. No differences were found for the primary and all secondary outcomes assessed. Mortality risk ratio was 0.54 (95% CI 0.05 to 5.73; low‐certainty evidence) in the adjuvanted vaccine group. The quality of evidence was low due to the small sample size and the large confidence intervals for all outcomes. AUTHORS' CONCLUSIONS: Observational data suggest lower mortality and infection‐related outcomes with influenza vaccination. The strength of evidence is limited by the small number of studies and low grade of evidence. It seems that the evidence, although weak, shows that the benefits overweigh the potential risks when vaccinating adults with cancer against influenza. However, additional placebo or no‐treatment controlled RCTs of influenza vaccination among adults with cancer is ethically questionable.There is no conclusive evidence regarding the use of adjuvanted versus non‐adjuvanted influenza vaccine in this population.

Summary Objectives Adherence to scheduled chemotherapy is important for optimal outcomes of cancer patients. We examined causes for delay or cancellation of planned chemotherapy, focusing on mild respiratory infections during the winter. Methods Prospective cohort study. We included all adults with solid or hematologic cancer receiving active chemotherapy treatment during the winter of 2010–2011 in a cancer center. We compared baseline characteristics and outcomes between patients with and without chemotherapy delays, cancellations, or dose-reductions ("chemotherapy delay"). Results We included 547 patients receiving chemotherapy during the winter of 2011. Of these, 213 (38.9%) patients experienced 306 episodes of chemotherapy delays. The main documented reasons for the chemotherapy delay were neutropenia (84/306, 27.4%), fever or infection (73/306, 23.9%) and thrombocytopenia (26/306, 8.5%). Independent risk factors for chemotherapy delays were upper respiratory infections (OR 1.87, 95% CI 1.27–2.76), lymphopenia, prior hospitalization, peripheral vascular disease and colon cancer relative to hematologic cancer. In the adjusted analysis focusing on chemotherapy delays due to infection alone, upper respiratory infections (OR 5.25, 95% I 2.81–9.84) and age were significant independent risk factors. Discussion Mild respiratory infections were associated with chemotherapy delays. Our results should encourage modalities to prevent influenza and other upper respiratory infections among cancer patients.

Background Fever occurring in a neutropenic patient remains a common life-threatening complication of cancer chemotherapy. The common practice is to admit the patient to hospital and treat him or her empirically with intravenous broad-spectrum antibiotics. Oral therapy could be an alternative approach for selected patients. Objectives To compare the efficacy of oral antibiotics versus intravenous (IV) antibiotic therapy in febrile neutropenic cancer patients. Search methods The Cochrane Central Register of Controlled Trials (CENTRAL) (2013, Issue 1) in The Cochrane Library, MEDLINE (1966 to January week 4, 2013), EMBASE (1980 to 2013 week 4) and LILACS (1982 to 2007). We searched several databases for ongoing trials. We checked the conference proceedings of the Interscience Conference of Antimicrobial Agents and Chemotherapy (ICAAC) (1995 to 2007), and all references of included studies and major reviews were scanned. Selection criteria Randomised controlled trials (RCTs) comparing oral antibiotic(s) to intravenous antibiotic(s) for the treatment of neutropenic cancer patients with fever. The comparison between the two could be started initially (initial oral) or following an initial course of intravenous antibiotic treatment (sequential). Data collection and analysis Two review authors independently assessed trial eligibility and methodological quality and extracted data. Data concerning mortality, treatment failures and adverse events were extracted from the included studies assuming an 'intention-to-treat' basis for the outcome measures whenever possible. Risk ratios (RR) with 95% confidence intervals (CI) were estimated for dichotomous data. Risk of bias assessment was also made in line with methodology of The Cochrane Collaboration. Main results Twenty-two trials (3142 episodes in 2372 patients) were included in the analyses. The mortality rate was similar when comparing oral to intravenous antibiotic treatment (RR 0.95, 95% CI 0.54 to 1.68, 9 trials, 1392 patients, median mortality 0, range 0% to 8.8%). Treatment failure rates were also similar (RR 0.96, 95% CI 0.86 to 1.06, all trials). No significant heterogeneity was shown for all comparisons but adverse events. The effect was stable in a wide range of patients. Quinolones alone or combined with another antibiotic were used with comparable results. Adverse reactions, mostly gastrointestinal, were more common with oral antibiotics. Authors' conclusions Based on the present data, oral treatment is an acceptable alternative to intravenous antibiotic treatment in febrile neutropenic cancer patients (excluding patients with acute leukaemia) who are haemodynamically stable, without organ failure, and do not have pneumonia, infection of a central line or a severe soft-tissue infection. The wide CI for mortality allows the present use of oral treatment in groups of patients with an expected low risk for mortality, and further research should be aimed at clarifying the definition of low risk 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.A prospective, noninterventional cohort study was conducted during the 2010 to 2011 influenza season. The cohort included adult cancer patients with solid malignancies who were receiving chemotherapy and hematologic patients who had active disease. Patients who died between October and November 2010 (N = 43) were excluded. A comparison was made between patients who received the 2011 seasonal influenza vaccine with those who did not. The primary outcome was a composite of hospitalizations for fever or acute respiratory infections, pneumonia, and/or infection-related chemotherapy interruptions. All-cause mortality was a secondary outcome. A propensity-matched analysis was conducted based on the propensity for vaccination.Of 806 patients who were included, 387 (48%) were vaccinated. Factors that were associated independently with vaccination included past influenza vaccination, past pneumococcal vaccination,6 months since cancer diagnosis, country of birth, and cancer type/status. The primary outcome occurred in 111 of 387 (28.7%) vaccinated patients versus 112 of 419 (26.7%) unvaccinated patients (P = .54). No association was observed between vaccination and the primary outcome in a propensity-matched analysis (N = 436) or during peak influenza activity. The mortality rate was 11.9% (46 of 387 patients) in vaccinated patients versus 19.1% (80 of 419 patients) in unvaccinated patients (P = .005). Vaccination retained a significant association with mortality on multivariable analysis (odds ratio, 2.31; 95% confidence interval, 1.4-3.79) and in a propensity-matched analysis (odds ratio, 2.39; 95% confidence interval, 1.32-4.32).Influenza vaccination was associated with lower mortality among cancer patients, although an association with infection-related complications could not be demonstrated. The current results support efforts to promote influenza vaccination in patients with cancer.

Background: Acute pyelonephritis is a frequent cause of morbidity, with a wide variation in duration of therapy. We performed a systematic review of all randomized controlled trials (RCTs) comparing ≤7 days treatment with a longer course. Methods: Electronic databases were searched to identify RCTs that assessed adults treated for pyelonephritis, comparing a 7 day or shorter versus longer therapy. Primary outcome was clinical failure at the end of the long treatment arm (EOT). Secondary outcomes included clinical failure at the end of follow-up (EOF), microbiological failure, all-cause mortality, the development of resistance and adverse events. Results: Clinical failure at EOT did not significantly differ between the two treatment arms [relative risk (RR) 0.63, 95% CI 0.33-1.18, I(2) = 41%]. Results did not differ when including studies comparing only fluoroquinolones, reducing the heterogeneity (RR 0.76, 95% CI 0.49-1.17, I(2) = 0%). We found no difference between the short and long treatment arms regarding clinical failure at EOF, even in a small subgroup of bacteraemic patients. No difference was found between the arms regarding microbiological failure at EOF, except in a subgroup of studies with a high percentage of patients with urogenital abnormalities, where microbiological failure at EOF was significantly higher in the short treatment arm (RR 1.78, 95% CI 1.02-3.10, I(2) = 21%). Adverse events were similar between the arms. Conclusions: Seven days of treatment for acute pyelonephritis is equivalent to longer treatment in terms of clinical failure and microbiological failure, including in bacteraemic patients. In patients with urogenital abnormalities, the evidence, although weak, suggests that longer treatment is required.

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 18 months 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 90 days and those with foreign body insertion for 1 year. 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 (27.5%) undergoing emergent or urgent craniotomy. The overall SSI rate was 5.6% (28 patients), of which 3.2% (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 (p < 0.001). 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.

Introduction The emergence of multidrug resistant (MDR) Gram-negative bacteria (GNB), including carbapenemase-producing strains, has become a major therapeutic challenge. These MDR isolates are often involved in complicated urinary tract infection (cUTI), and are associated with poor clinical outcomes. The study has been designed to gain insight into the epidemiology, clinical management, outcome and healthcare cost of patients with cUTI, especially in countries with high prevalence of MDR GNB. Methods and analysis This multinational and multicentre observational, retrospective study will identify cases from 1 January 2013 to 31 December 2014 in order to collect data on patients with cUTI as a cause of hospital admission, and patients who develop cUTI during their hospital stay. The primary end point will be treatment failure defined as the presence of any of the following criteria: (1) signs or symptoms of cUTI present at diagnosis that have not improved by days 5–7 with appropriate antibiotic therapy, (2) new cUTI-related symptoms that have developed within 30 days of diagnosis, (3) urine culture taken within 30 days of diagnosis, either during or after completion of therapy, that grows ≥104 colony-forming unit/mL of the original pathogen and (4) death irrespective of cause within 30 days of the cUTI diagnosis. Sample size 1000 patients afford a power of 0.83 (α=0.05) to detect an absolute difference of 10% in the treatment failure rate between MDR bacteria and other pathogens. This should allow for the introduction of about 20 independent risk factors (or their interaction) in a logistic regression model looking at risk factors for failure. Ethics and dissemination Approval will be sought from all relevant Research Ethics Committees. Publication of this study will be considered as a joint publication by the participating investigator leads, and will follow the recommendations of the International Committee of Medical Journal Editors (ICMJE). Trial registration number NCT02641015; Pre-results.

Community-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.The 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.We searched the Cochrane Central Register of Controlled Trials (CENTRAL) Issue 3, 2012 which includes the Acute Respiratory Infection Group's Specialized Register, MEDLINE (January 1966 to April week 1, 2012) and EMBASE (January 1980 to April 2012).Randomized 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.Two 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.We 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), RR1 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.No 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.

The aim of this study wasto determinethe effectof b-glycosphingolipids on intra-hepatic natural killer T (NKT) lymphocyte regulatory function and on lymphocyte trapping via alteration of cell membrane lipid rafts. Immune-mediated colitis was induced by intracolonic instillation of trinitroben- zene sulfonic acid. Mice were treated with b-lactosylceramide (LC), b-glucosylceramide (GC), b-galactosylceramide, cer- amide, or a combination of both GC and LC (IGL), or solvent alone. Lipid rafts were investigated by fluorescence-activated cell sorting analysis of ganglioside-GM1 and fluorescence microscopy of structure. Administration of b-glycosphingo- lipids resulted in an increased intrahepatic/peripheral NKT ratio, increased intrahepatic CD81 lymphocyte trapping, decreased serum interferon-g (IFN-g) levels and decreased serum IFN-g/interleukin-10 ratio. Administration of GC, LC, or IGL significantly altered the levels of GM1, a key marker of lipid rafts, on NKT regulatory lymphocytes. The immune modulatory effect of b-glycosphingolipids was associated with increased survival and significant alleviation of colitis as determined by improvement in both the macroscopic and microscopic scores. In conclusion, administration of b-glycosphingolipids increased NKT regulatory lymphocyte redistribution andintrahepatic CD8 1 T lymphocyte trapping, resulting in alleviation of immune-mediated colitis. The ef- fectsofthesenaturallyoccurringcompoundswereassociated with modification of the T lymphocyte lipid raft structure, which is a site for immune modulation.—Lalazar, G., A. Ben Yaʼacov, N. Eliakim-Raz, D. M. Livovsky, O. Pappo, S. Preston, L. Zolotarov, and Y. Ilan. b-Glycosphingolipids-mediated lipid raft alteration is associated with redistribution of NKT cells and increased intrahepatic CD8 1 T lymphocyte trapping. J. Lipid Res. 2008. 49: 1884-1893.

Psoriasis is a common immune-mediated disease which affects 1–3% of the population. The etiology of psoriasis is unknown. Idiopathic dilated cardiomyopathy is probably the end result of a variety of toxic, metabolic or infectious agents. During a computerized search for cardiomyopathy among all patients hospitalized with psoriasis in the Hadassah University Hospital since 1980 we found an increased prevalence of cardiomyopathy, and specifically dilated cardiomyopathy. We present 4 patients who suffer from both conditions. In accordance with previous data, an association between preexisting psoriasis and dilated cardiomyopathy is suggested. We suggest that the genetic risk factors of dilated cardiomyopathy are shared by psoriasis, and more specifically psoriatic arthritis. Alternatively, the immune reaction that is triggered in dilated cardiomyopathy leading to the progression of the disease might be enhanced in patients with psoriasis or psoriatic arthritis. Chronic inflammation and persistent secretion of proinflammatory cytokines may be considered a potential pathway, triggering the initiation and progression of dilated cardiomyopathy in psoriatic patients. Further investigation of the genetic and immune risk factors involved in dilated cardiomyopathy and in psoriasis may lead to a better understanding of the pathogenesis and treatment of dilated cardiomyopathy.

Source Citation Parekh TM, Raji M, Lin YL, et al. Hypoglycemia after antimicrobial drug prescription for older patients using sulfonylureas. JAMA Intern Med. 2014;174:1605-12. 25179404

AIM: To evaluate the impact of antiviral treatment on cytomegalovirus (CMV)-positive ulcerative colitis patients. METHODS: We performed a systematic review and meta-analysis (MA) of comparative cohort and case-control studies published between January 1966 and March 2013. Studies focusing on colectomy series and studies including only less than 3 patients in the treated or non-treated arm were excluded. The primary outcome was colectomy within 30 d of diagnosis. Secondary outcomes included colectomy during the follow-up period Subgroup analyses by method of detection of CMV, study design, risk of bias and country of origin were performed. Quality of studies was evaluated according to modified New-Castle Ottawa Scale. RESULTS: After full-text review, nine studies with a total of 176 patients were included in our MA. All the included studies were of low to moderate quality. Patients who have received antiviral treatment had a higher risk of 30-d colectomy (OR = 2.40; 95%CI: 1.05-5.50; I2 = 37.2%). A subgroup analysis including only patients in whom CMV diagnosis was based did not demonstrate a significant difference between the groups (OR = 3.41; 95%CI: 0.39-29.83; I2 = 56.9%). Analysis of long-term colectomy rates was possible for 6 studies including 110 patients. No statistically significant difference was found between the treated and untreated groups (OR = 1.71; 95%CI: 0.71-4.13; 6 studies, I2 = 0%). Analysis of mortality rate was not possible due to a very limited number of cases. Stratification of the outcomes by disease severity was not possible. CONCLUSION: No positive association between antiviral treatment and a favorable outcome was demonstrated. These findings should be interpreted cautiously due to primary studies’ quality and potential biases.

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.

SummaryBackgroundThe clinical characteristics of internal medicine ward (IMW) patients with candidemia are unclear. The aim of this study was to define the clinical characteristics of candidemic IMW patients and to study the incidence, species distribution, and outcomes of these patients compared to surgical and intensive care unit (ICU) candidemic patients.MethodsA retrospective cohort of candidemic patients in IMWs, general surgery wards, and an ICU at Beilinson Hospital during the period 2007–2014 was analyzed.ResultsA total of 118 patients with candidemia were identified in six IMWs, two general surgery wards, and one ICU in the hospital. Candida albicans was the leading causative agent (41.1%). Higher proportions of Candida parapsilosis and Candida tropicalis isolates were observed in the IMW patients. IMW patients were significantly older, with poorer functional capacity, and had more frequently been exposed to antibiotic therapy within 90 days, in particular β-lactam–β-lactamase inhibitor combinations and cephalosporins. At onset of candidemia, a significantly lower number of IMW patients were mechanically ventilated (p48h.ConclusionsIMW candidemic patients account for a substantial proportion of candidemia cases and have unique characteristics and high mortality rates.