Search

Objectives: Influenza is associated with significant morbidity and mortality, especially in older and immunocompromised patients. Few data are available on the clinical benefit of high dose trivalent influenza vaccine (TIV). We aimed to assess the clinical efficacy and safety of high dose TIV.Methods: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs), evaluating high dose versus standard dose TIV for prevention of seasonal influenza in adult population. Primary outcome was laboratory-confirmed influenza. Subgroups analyses included older adults and immunocompromised patients.Results: We included 16 trials, 47,857 patients; 10 included older adults and three immunocompromised patients. Laboratory confirmed influenza was significantly reduced with high dose TIV (relative risk 0.76, 95% confidence interval 0.64 to 0.9). This outcome stemmed mainly from one trial in older adults. Specifically, A(H3N2) laboratory confirmed influenza, but not A(H1N1) or B lineages, was reduced. No difference in mortality or hospitalizations was demonstrated. Immunological response was significantly higher with high dose vaccine. Serious adverse events were significantly less common in the high dose group.Conclusions: High dose TIV lowers the rates of laboratory confirmed influenza, mainly A (H3N2), in older adults vs. standard dose. Further studies should address immunocompromised patients and report clinical outcomes. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to evaluate different interventions to reduce multidrug-resistant Enterobacteriaceae (MDR-E) infection/colonization.Methods: A systematic review and meta-analysis evaluating interventions for prevention of MDR-E infection/colonization among hospitalized adult patients. The co-primary outcomes were mortality and MDR-E infections. PubMed, Cochrane library, and LILACS databases were searched up till December 2019, as well as grey literature sources. We included randomized controlled trials and observational studies. Infection/colonization/acquisition outcomes were reported per patient-days as pooled incidence ratios (IRs) with 95% confidence intervals (CIs). Interrupted time series (ITS) analysis studies were reported separately.Results: Sixty-three studies were included, 16 RCTs, 33 observational studies, and 14 ITS. For the intervention of antimicrobial stewardship program (ASP), 23 studies were included. No differences in mortality or MDR-E infections were observed with ASP, however, MDR-E colonization was significantly reduced (IR 0.69, 95% CI 0.57-0.82). Seventeen studies examined decolonization without significant difference in outcomes. Other interventions were scarcely represented. Among 14 ITS publications, most evaluating ASP, 11 showed benefit of the intervention.Conclusions: ASP is an effective measure in preventing MDR-E colonization. Decolonization did not show significant benefit in reducing infection or colonization. Studies are needed to evaluate the cost effectiveness of ASP and assess bundles of interventions. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 RT-PCR re-positivity SARS-CoV-2 RT-PCR re-positivity describes positive RT-PCR following negative tests in an asymptomatic patient up to 90 days from the first episode. Keywords: COVID-19; PCR re-positivity; Reinfection; Relapse EN COVID-19 PCR re-positivity Reinfection Relapse 315 318 4 03/03/21 20210301 NES 210301 Introduction Defining reinfection, relapsed infection and recurrence of positive (re-positive) nucleic acid detection might have clinical and epidemiological implications for treatment and infection control measures, respectively. (b) Proof of a reinfection with two positive SARS-CoV-2 RT-PCR tests with Ct < 35 (or proof of replicating virus by cell culture or detection of subgenomic RNA) at different time-points. COVID-19 reinfection In August 2020, To et al. described an asymptomatic patient from Hong Kong with a positive SARS-CoV-2 PCR test from a sample collected 142 days after a first symptomatic COVID-19 episode. [Extracted from the article]

• Oesophageal candidiasis is a common infection among immunocompromised patients. • Available guidelines recommend fluconazole as the preferred treatment. • Data regarding the effectiveness of fluconazole have not been compiled systematically in times of increased fluconazole resistance. • No difference in efficacy or safety was demonstrated between fluconazole and other azoles for the treatment of oesophageal candidiasis. • Use of echinocandins resulted in lower mycological cure rates and higher relapse rates. Oesophageal candidiasis is a common infection among individuals with immunosuppression, associated with significant morbidity. Available guidelines recommend fluconazole as the preferred treatment; however, data regarding its effectiveness in an era of increased fluconazole resistance has not been systematically compiled. A systematic review and meta-analysis of randomized controlled trials (RCTs) addressing systemic antifungal therapy for oesophageal candidiasis was undertaken. The primary outcome was clinical response. Subgroup analysis was planned based on immune status and Candida spp. Twelve RCTs were included, of which six compared fluconazole with other azoles, four compared fluconazole with echinocandins, and two compared amphotericin deoxycholate with echinocandins. Most RCTs mainly included human-immunodeficiency-virus-positive individuals. No significant differences were found between fluconazole and comparators for the outcomes of clinical response or combined clinical and endoscopic response [relative risk (RR) 1.02, 95% confidence interval (CI) 0.97–1.07 and RR 1.06, 95% CI 0.98–1.15, respectively]. No differences were found between fluconazole and other azoles for other outcomes; however, compared with echinocandins, fluconazole had significantly higher mycological response rates and lower early relapse rates (RR 1.09, 95% CI 1.02–1.17 and RR 0.42, 95% CI 0.26–0.68, respectively). No significant differences were demonstrated between fluconazole and comparators for overall or severe adverse events. Information required for the planned subgroup analyses was not available. No differences in efficacy or safety were found between fluconazole and other azoles for the treatment of candida oesophagitis. The use of echinocandins resulted in lower mycological cure rates and higher relapse rates. Additional RCTs should evaluate these interventions among broader patient populations and a wider spectrum of Candida spp. [ABSTRACT FROM AUTHOR]

Background: In patients with euvolemic and hypervolemic hyponatremia, the effect of vasopressin antagonists is yet undefined. Study Design: Systematic review and meta-analysis of randomized controlled trials (RCTs). Setting & Population: In- and outpatients with euvolemic or hypervolemic hyponatremia. Selection Criteria for Studies: We included all RCTs regardless of publication status or language. Intervention: Vasopressin antagonists with or without fluid restriction versus placebo or no treatment with or without fluid restriction. Outcomes: Response rate defined as normalization of serum sodium level or significant increase in serum sodium level at 3-7 days (primary) and later, change from baseline serum sodium level at 3-7 days and later, adverse events, rate of rapid sodium level correction, and rate of hypernatremia. Results: 15 RCTs were identified. Vasopressin antagonist treatment significantly increased response rate both early (RR, 3.15; 95% Cl, 2.27-4.37; 11 trials) and late (RR, 2.27; 95% Cl, 1.79-2.89; 4 trials). Response rates were high in trials assessing mostly euvolemic patients and those assessing mostly hypervolemic patients, with greater effect estimate in the former. Change from baseline serum sodium level was significantly increased both early (weighted mean difference, 5.27 mEq/L; 95% Cl, 4.27-6.26, 13 trials) and late (weighted mean difference, 3.49 mEq/L; 95% Cl, 2.56-4.41, 8 trials). Although there was an increased rate of rapid sodium correction (RR, 2.52; 95% Cl, 1.26-5.08, 8 trials) with vasopressin antagonists, hypernatremia rates were not significantly higher (AR, 2.21; 95% Cl, 0.61-7.96; 5 trials), adverse events were not increased, and there were no reports of osmotic demyelination syndrome. Limitations: Significant heterogeneity in the primary outcome. Conclusions: Vasopressin antagonists are effective for the treatment of hypervolemic and euvolemic hyponatremia. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: Antiviral prophylaxis is commonly prescribed to haematological cancer patients. We conducted a systematic review and meta-analysis to quantify its overall benefit in specific clinical scenarios. Methods: Randomised controlled trials assessing antiviral prophylaxis versus placebo, no treatment, pre-emptive treatment or another antiviral drug were included. Patients undergoing haematopoietic stem cell transplantation (HSCT) or intensive chemotherapy for acute leukaemia or high-grade lymphoma were included. No restrictions on language, year or publication status were applied. Overall mortality, herpes simplex virus (HSV) and cytomegalovirus (CMV) diseases were assessed as primary outcomes. Pooled relative risks (RRs) and numbers needed to treat (NNT) with 95% confidence intervals (CI) are reported. Results: HSCT was the condition assessed in 22 trials and intensive chemotherapy in 5 trials. In the pre-engraftment setting of autologous or allogeneic HSCT, antiviral prophylaxis (mainly acyclovir for HSV seropositive recipients) significantly reduced HSV (NNT 2, 2–2, control event rate (CER) 61.9%) and CMV disease, with no effect on overall mortality. In the allogeneic post-engraftment setting (mainly CMV-seropositive recipients/donors), antiviral prophylaxis resulted in a significant reduction in overall mortality, RR 0.79 (0.65–0.95), NNT 12 (7–50, CER 39.4%) and all viral-related outcomes. In this setting, acyclovir significantly reduced overall mortality (RR 0.71, 0.53–0.96, 4 trials) and ganciclovir/maribavir significantly reduced CMV disease (RR 0.26, 0.14–0.48, 5 trials). During chemotherapy, acyclovir significantly decreased HSV disease (NNT 3, 2–4, CER 37.4%) and infection rates, with no effect on mortality. Conclusions: Antiviral prophylaxis reduced mortality with a small NNT in the post-engraftment setting of allogeneic HSCT. In the pre-engraftment phase and during chemotherapy only viral-related morbidity was reduced. [Copyright &y& Elsevier]

Summary: Cefepime is a broad-spectrum cephalosporin with enhanced coverage against Gram-positive and Gram-negative bacteria. We did a systematic review of randomised trials that compared cefepime with another β-lactam antibiotic, alone or with the addition of a non-β-lactam antibiotic to both study groups. We searched Central, PubMed, Embase, Lilacs, new US Food and Drug Administration drug applications, conference proceedings, and references of the included studies. Two reviewers independently did the search and data extraction. 57 trials were included. All-cause mortality—the primary outcome—was higher with cefepime than other β-lactams (risk ratio [RR] 1·26 [95% CI 1·08–1·49]). Sensitivity analyses by the trials'' methodological quality revealed higher RRs for trials reporting adequate allocation-sequence generation (1·52 [1·20–1·92]) and allocation concealment (1·36 [1·09–1·70]). Baseline risk factors for mortality were similar. No significant differences between groups in treatment failure, superinfection, or adverse events were found. This Review provides evidence and offers possible explanations for increased mortality among patients treated with cefepime in randomised trials. [Copyright &y& Elsevier]

We aimed to evaluate the rates of antibody response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine among kidney transplant recipients, and to identify factors associated with reduced immunogenicity. This was a prospective cohort study including consecutive kidney transplant recipients in a single referral transplant centre. Participants were tested for anti-spike (anti-S) antibodies 2–4 weeks after a second vaccine dose. Primary outcome was rate of seropositivity. Univariate and multivariate analyses were conducted to identify factors associated with seropositivity. Of 308 kidney transplant recipients included, only 112 (36.4%) tested positive for anti-S antibodies 2–4 weeks after receiving the second dose of BNT162b2 vaccine. Median antibody titre was 15.5 AU/mL (interquartile range (IQR) 3.5–163.6). Factors associated with antibody response were higher estimated glomerular filtration rate (eGFR) (odds ratio (OR) 1.025 per mL/min/1.73 m2, 95% confidence interval (CI) 1.014–1.037, p < 0.001), lower mycophenolic acid dose (OR 2.347 per 360 mg decrease, 95%CI 1.782–3.089, p < 0.001), younger age (OR 1.032 per year decrease, 95%CI 1.015–1.05, p < 0.001) and lower calcineurin inhibitor (CNI) blood level (OR 1.987, 95%CI 1.146–3.443, p 0.014). No serious adverse events resulting from the vaccine were reported. Kidney transplant recipients demonstrated an inadequate antibody response to SARS-CoV-2 mRNA vaccination. Immunosuppression level was a significant factor in this response. Strategies to improve immunogenicity should be examined in future studies. [ABSTRACT FROM AUTHOR]

We aimed to examine the rate and characteristics of retracted articles in infectious diseases and clinical microbiology. Using the Retraction Watch Database, we conducted a cross-sectional study for retracted publications categorized as 'Infectious Disease' or 'Microbiology' until June 30 2022. We included publications for which citation information was available through the Web of Science database. Study characteristics, retraction trends and number of citations before and after the retraction year were analysed. Overall, 1004 retracted publications were included, retracted between August 1968 and June 2022. The number of retractions climbed through the years, peaking in 2020–2021. A total of 614 retractions originated from USA, China, and India, of total 183 736 PubMed publications from these countries. Overall, 378 (38%) were retracted because of errors; 182 (18%) because of plagiarism; and 142 (14%) because of falsification/fabrication. Specific reasons included 'concerns/issues about data' (158, 16%); 'duplication of image' (127, 13%); and 'unreliable results' (116, 12%). Of the 347 retractions during 2020 to June 2022, 91 (26%) were COVID-19 related. Fifty of 895 (5.6%) first authors had two retracted papers, and 14 (1.6%) had ≥2 retractions. Of 824 publications cited at least once, 466 (57%) were cited more often after retraction. Retractions of infectious diseases and clinical microbiology publications are increasing. Concerning reasons such as plagiarism, falsification/fabrication and errors are not uncommon. Nonetheless, these publications continue to be commonly cited after being retracted. [ABSTRACT FROM AUTHOR]

Long COVID-19 - it's not over until? Coronavirus disease 2019 survivors, Long COVID-19, Recovery, Severe acute respiratory syndrome coronavirus 2. [Extracted from the article]

Summary Background The 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. Methods A retrospective cohort of candidemic patients in IMWs, general surgery wards, and an ICU at Beilinson Hospital during the period 2007–2014 was analyzed. Results A 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 ( p < 0.01); these patients did not have central line catheters comparable to ICU and surgical patients ( p < 0.001). They were less likely to receive adequate antifungal therapy within 48 h, and this was the only significant predictor of survival in these patients ( p = 0.028): hazard ratio 3.7 (95% confidence interval 1.14–12.5) for therapy delayed to >48 h. Conclusions IMW candidemic patients account for a substantial proportion of candidemia cases and have unique characteristics and high mortality rates. [ABSTRACT FROM AUTHOR]

To identify predictors of 30-day survival in elderly patients with coronavirus disease 2019 (COVID-19). Retrospective cohort study including patients with COVID-19 aged ≥65 years hospitalized in six European sites (January 2020 to May 2021). Data on demographics, comorbidities, clinical characteristics, and outcomes were collected. A predictive score (FLAMINCOV) was developed using logistic regression. Regression coefficients were used to calculate the score. External validation was performed in a cohort including elderly patients from a major COVID-19 centre in Israel. Discrimination was evaluated using the area under the receiver operating characteristic curve (AUC) in the derivation and validation cohorts. Survival risk groups based on the score were derived and applied to the validation cohort. Among 3010 patients included in the derivation cohort, 30-day survival was 74.5% (2242/3010). The intensive care unit admission rate was 7.6% (228/3010). The model predicting survival included independent functional status (OR, 4.87; 95% CI, 3.93–6.03), a oxygen saturation to fraction of inspired oxygen (SpO 2 /FiO 2) ratio of >235 (OR, 3.75; 95% CI, 3.04–4.63), a C-reactive protein level of <14 mg/dL (OR, 2.41; 95% CI, 1.91–3.04), a creatinine level of <1.3 (OR, 2.02; 95% CI, 1.62–2.52) mg/dL, and absence of fever (OR, 1.34; 95% CI, 1.09–1.66). The score was validated in 1174 patients. The FLAMINCOV score ranges from 0 to 15 and showed good discrimination in the derivation (AUC, 0.79; 95% CI, 0.77–0.81; p < 0.001) and validation cohorts (AUC, 0.79; 95% CI, 0.76–0.81; p < 0.001). Thirty-day survival ranged from 39.4% (203/515) to 95.3% (634/665) across four risk groups according to score quartiles in the derivation cohort. Similar proportions were observed in the validation set. The FLAMINCOV score identifying elderly with higher or lower chances of survival may allow better triage and management, including intensive care unit admission/exclusion. [ABSTRACT FROM AUTHOR]

We aimed to assess whether there is an association between the proportion of female editors-in-chief and members of editorial boards in infectious disease (ID) and microbiology journals. Our cross-sectional observational study included ID or microbiology journals according to the 2019 Clarivate Journal Citation Reports. Journals' Q ranking, open-access status, and number and gender of editors-in-chief and editorial board members were collected from the journals' official websites. We conducted a binary gender assignment for each editor using names, pictures, and other online descriptors. Journals with over 100 editorial board members and those with over 25% of board members for whom we could not determine gender were excluded. Editorial teams with >50% women were considered women dominant. Univariate and multivariable analyses for female editor dominance were performed. Overall, 167 journals were included, with total 6057 editorial members, 1655 (27.3%) of whom were women. Of 214 editors-in-chief, 48 (22%) were women, and only 25% (40 of 162) of journals had female editor-in-chief dominance. Factors associated with female dominance in the editor-in-chief role in univariate analysis were higher quartile rank, higher impact factor, and open access. Open-access journals remined significant in multivariable analysis (odds ratio (OR) 2.521; 95% CI, 1.140–5.576, p = 0.022). Larger editorial boards were less likely to have female dominance. Female editor-in-chief dominance was significantly associated with women-dominant editorial boards. ID and microbiology journals have significantly few women as editors-in-chief and editorial board members. Understanding the reasons for this inequality is required as an important step to confront and resolve it. [ABSTRACT FROM AUTHOR]

The aim of these guidelines is to provide evidence-based recommendations for the assessment and management of individuals with persistent symptoms after acute COVID-19 infection and to provide a definition for this entity, termed 'long COVID'. We performed a search of the literature on studies addressing epidemiology, symptoms, assessment, and treatment of long COVID. The recommendations were grouped by these headings and by organ systems for assessment and treatment. An expert opinion definition of long COVID is provided. Symptoms were reviewed by a search of the available literature. For assessment recommendations, we aimed to perform a diagnostic meta-analysis, but no studies provided relevant results. For treatment recommendations we performed a systematic review of the literature in accordance with the PRISMA statement. We aimed to evaluate patient-related outcomes, including quality of life, return to baseline physical activity, and return to work. Quality assessment of studies included in the systematic review is provided according to study design. Evidence was insufficient to provide any recommendation other than conditional guidance. The panel recommends considering routine blood tests, chest imaging, and pulmonary functions tests for patients with persistent respiratory symptoms at 3 months. Other tests should be performed mainly to exclude other conditions according to symptoms. For management, no evidence-based recommendations could be provided. Physical and respiratory rehabilitation should be considered. On the basis of limited evidence, the panel suggests designing high-quality prospective clinical studies/trials, including a control group, to further evaluate the assessment and management of individuals with persistent symptoms of COVID-19. [ABSTRACT FROM AUTHOR]

• In the current outbreak, monkeypox might get easily overlooked outside of endemic areas. • Monkeypox might be misdiagnosed as other sexually transmitted diseases. • Misdiagnosis leads to delayed isolation and administration of inappropriate treatment. The aim of this study was to characterize overlooked cases of patients with monkeypox infection in the 2022 outbreak. Clinical characteristics of 26 patients who were misdiagnosed with other diseases were described. Of the 26 patients who were misdiagnosed, six (23%) were given a diagnosis of bacterial tonsillitis, six (23%) were diagnosed with primary syphilis, five (19.2%) with oral or genital herpes, and four (15.3%) with bacterial proctitis or anal abscess. The average time interval between missed and right diagnosis was 4.4 days. There was no difference in the missed cases between the early and the later month of the outbreak. Monkeypox might still be commonly overlooked, especially in patients presenting with fever and sore throat or solitary ulcer as sole manifestations. [ABSTRACT FROM AUTHOR]

Mortality among patients with carbapenem-resistant Acinetobacter baumannii (CRAB) infections varies between studies. We examined whether in vivo fitness of CRAB strains is associated with clinical outcomes in patients with CRAB infections. Isolates were collected from patients enrolled in the AIDA trial with hospital-acquired pneumonia, bloodstream infections and/or urinary tract infections caused by CRAB. The primary outcome was 14-day clinical failure, defined as failure to meet all criteria: alive; haemodynamically stable; improved or stable Sequential Organ Failure Assessment (SOFA) score; improved or stable oxygenation; and microbiological cure of bacteraemia. The secondary outcome was 14-day mortality. We tested in vivo growth using a neutropenic murine thigh infection model. Fitness was defined based on the CFU count 24 hours after injection of an inoculum of 105 CFU. We used mixed-effects logistic regression to test the association between fitness and the two outcomes. The sample included 266 patients; 215 (80.8%) experienced clinical failure. CRAB fitness ranged from 5.23 to 10.08 log CFU/g. The odds of clinical failure increased by 62% for every 1-log CFU/g increase in fitness (OR 1.62, 95% CI 1.04–2.52). After adjusting for age, Charlson score, SOFA score and acquisition in the intensive care unit, fitness remained significant (adjusted OR 1.63, 95% CI 1.03–2.59). CRAB fitness had a similar effect on 14-day mortailty, although the association was not statistically significant (OR 1.56, 95% CI 0.95–2.57). It became significant after adjusting for age, Charlson score, SOFA score and recent surgery (adjusted OR 1.88, 95% CI 1.09–3.25). In vivo CRAB fitness was associated with clinical failure in patients with CRAB infection. [ABSTRACT FROM AUTHOR]

Nocardiosis is a rare infection that is often difficult to treat and may be life-threatening. There is no consensus on its management. Our aim was to provide the current evidence for the diagnosis and management of individuals with nocardiosis, and to propose a management approach for this uncommon infection. We systematically searched the medical literature on nocardiosis for studies published between 2010 and 2020 and describing ten or more individuals. Nocardiosis, a primarily opportunistic infection which may occur in immunocompetent persons, most commonly involves the lungs and frequently disseminates to other sites including the central nervous system. The reference standard for Nocardia species identification is molecular biology, and the preferred method for antibiotic susceptibility testing (AST) is broth microdilution. Monotherapy seems appropriate for patients with primary skin nocardiosis or non-severe pulmonary disease; we reserve a multidrug regimen for more severe infections. Species identification and AST results are often missing at initiation of antibiotics. Trimethoprim-sulfamethoxazole is the preferred agent for initial therapy, because Nocardia is very often susceptible to this agent, and because it has been the keystone of nocardiosis treatment for years. Linezolid, to which Nocardia is almost always susceptible, may be an alternative. When combination therapy is required, the repertoire of companion drugs includes third-generation cephalosporins, amikacin and imipenem. Therapeutic modifications should take into account clinical response to initial therapy and AST results. Treatment duration of 6 months is appropriate for most situations, but longer durations are preferred for disseminated nocardiosis and shorter durations are reasonable in low-risk situations. Secondary prophylaxis may be considered in selected individuals with permanent immunosuppression. We hereby provide the clinician with an easy-to-use algorithm for the management of individuals with nocardiosis. We also illuminate gaps in evidence and suggest future research directions. [ABSTRACT FROM AUTHOR]

• Respiratory syncytial virus (RSV) is considered a major pathogen that causes acute influenza-like illness. • Pneumonia was more common in RSV patients than in influenza patients. • RSV was found to be a predictor of respiratory illness and complications. Respiratory syncytial virus (RSV) is considered a major pathogen that causes acute influenza-like illness. The objective of this study was to compare the clinical outcomes of patients with laboratory-confirmed RSV and patients with influenza infection. Adults hospitalized in Beilinson Hospital (October 2017–April 2018) with laboratory-confirmed RSV or influenza were included. The primary outcome was the composite of RSV/influenza complications: 30-day mortality, pneumonia, mechanical ventilation, vasopressor support, intensive care unit admission, and myocarditis/encephalitis. Secondary outcomes were individual components of the primary outcome, 90-day mortality, 90-day readmission, and length of hospital stay. A total of 639 patients with RSV (n = 113) and influenza (n = 526) were included. The composite primary outcome was 21.4% (136/633), and was higher in RSV patients (30% (34/113) vs 19% (102/526), p = 0.002). Pneumonia was more common in RSV patients (21.2% (24/113) vs 9.1% (48/526), p = 0.001). On multivariable analysis, hypoalbuminemia (odds ratio (OR) 3.3, 95% confidence interval (CI) 2.1–5.3, p < 0.001), reduced room-air saturation (OR 1.1, 95% CI 1.02–1.1, p = 0.001), and infection with RSV (OR 1.67, 95% CI 1.01–2.76, p = 0.046) were predictors of complications. RSV infection in hospitalized adults resulted in serious respiratory illness with complications that are comparable to those caused by influenza. [ABSTRACT FROM AUTHOR]

In vitro models showing synergism between polymyxins and carbapenems support combination treatment for carbapenem-resistant Gram-negative (CRGN) infections. We tested the association between the presence of in vitro synergism and clinical outcomes in patients treated with colistin plus meropenem. This was a secondary analysis of AIDA, a randomized controlled trial comparing colistin with colistin–meropenem for severe CRGN infections. We tested in vitro synergism using a checkerboard assay. Based on the fractional inhibitory concentration (ΣFIC) index for each colistin–meropenem combination, we categorized results as synergistic, antagonistic or additive/indifferent. The primary outcome was clinical failure at 14 days. Secondary outcomes were 14- and 28-day mortality and microbiological failure. The sample included 171 patients with infections caused by carbapenem-resistant Acinetobacter baumannii (n = 131), Enterobacteriaceae (n = 37) and Pseudomonas aeuruginosa (n = 3). In vitro testing showed synergism for 73 isolates, antagonism for 20 and additivism/indifference for 78. In patients who received any colistin plus meropenem, clinical failure at 14 days was 59/78 (75.6%) in the additivism/indifference group (reference category), 54/73 (74.0%) in the synergism group (adjusted odds ratio (aOR) 0.76, 95% CI 0.31–1.83), and 11/20 (55%) in the antagonism group (aOR 0.77, 95% CI 0.22–2.73). There was no significant difference between groups for any secondary outcome. Comparing the synergism group to patients treated with colistin monotherapy, synergism was not protective against 14-day clinical failure (aOR 0.52, 95% CI 0.26–1.04) or 14-day mortality (aOR1.09, 95% CI 0.60–1.96). In vitro synergism between colistin and meropenem via checkerboard method did not translate into clinical benefit. [ABSTRACT FROM AUTHOR]

Abstract Use of GeneXpert MRSA/SA in diagnostic algorithms of Staphylococcus aureus bacteremia may influence both patients' clinical outcomes and antibiotic stewardship. We evaluated these outcomes in a retrospective cohort before (1/6/2015–31/5/2016) and after (1/6/2016–31/8/2017) the introduction of the test in adult patients with Gram-positive cocci in clusters in blood cultures. We included 254 patients (125 preintervention, 129 postintervention). No significant difference in 30-day mortality or clinical success was demonstrated between periods. Appropriate antibiotic therapy rates were significantly higher in the postintervention group, and vancomycin use was significantly reduced (80.6% vs 53.6%, P < 0.01; 2.3±0.38 vs 2.98±1.02 defined daily doses/100 patient days, P = 0.026, respectively). Appropriate beta-lactam use was also significantly higher (56.7% postintervention vs 23.1% preintervention, P < 0.01). Use of GeneXpert MRSA/SA test has a positive effect on antibiotic stewardship measures, though it has no significant effect on clinical outcomes including mortality in this fatal infection. Highlights • GeneXpert MRSA/SA test was introduced to diagnose staphylococcal bacteremia. • Introduction of the test significantly improved appropriate antibiotic therapy. • Vancomycin use was significantly reduced following the test introduction. • Clinical outcomes, including mortality, were not significantly affected. [ABSTRACT FROM AUTHOR]

Background: Colistin-carbapenem combinations are synergistic in vitro against carbapenem-resistant Gram-negative bacteria. We aimed to test whether combination therapy improves clinical outcomes for adults with infections caused by carbapenem-resistant or carbapenemase-producing Gram-negative bacteria.Methods: A randomised controlled superiority trial was done in six hospitals in Israel, Greece, and Italy. We included adults with bacteraemia, ventilator-associated pneumonia, hospital-acquired pneumonia, or urosepsis caused by carbapenem-non-susceptible Gram-negative bacteria. Patients were randomly assigned (1:1) centrally, by computer-generated permuted blocks stratified by centre, to intravenous colistin (9-million unit loading dose, followed by 4·5 million units twice per day) or colistin with meropenem (2-g prolonged infusion three times per day). The trial was open-label, with blinded outcome assessment. Treatment success was defined as survival, haemodynamic stability, improved or stable Sequential Organ Failure Assessment score, stable or improved ratio of partial pressure of arterial oxygen to fraction of expired oxygen for patients with pneumonia, and microbiological cure for patients with bacteraemia. The primary outcome was clinical failure, defined as not meeting all success criteria by intention-to-treat analysis, at 14 days after randomisation. This trial is registered at ClinicalTrials.gov, number NCT01732250, and is closed to accrual.Findings: Between Oct 1, 2013, and Dec 31, 2016, we randomly assigned 406 patients to the two treatment groups. Most patients had pneumonia or bacteraemia (355/406, 87%), and most infections were caused by Acinetobacter baumannii (312/406, 77%). No significant difference between colistin monotherapy (156/198, 79%) and combination therapy (152/208, 73%) was observed for clinical failure at 14 days after randomisation (risk difference -5·7%, 95% CI -13·9 to 2·4; risk ratio [RR] 0·93, 95% CI 0·83-1·03). Results were similar among patients with A baumannii infections (RR 0·97, 95% CI 0·87-1·09). Combination therapy increased the incidence of diarrhoea (56 [27%] vs 32 [16%] patients) and decreased the incidence of mild renal failure (37 [30%] of 124 vs 25 [20%] of 125 patients at risk of or with kidney injury).Interpretation: Combination therapy was not superior to monotherapy. The addition of meropenem to colistin did not improve clinical failure in severe A baumannii infections. The trial was unpowered to specifically address other bacteria.Funding: EU AIDA grant Health-F3-2011-278348. [ABSTRACT FROM AUTHOR]

To assess the humoral immune response to the BNT162b2 vaccine after allogeneic haematopoietic cell transplantation (HCT). This is a prospective cohort study. The SARS-CoV-2 IgGII Quant (Abbott©) assay was performed 4–6 weeks after the second BNT162b2 vaccine for quantitative measurement of anti-spike antibodies. The cohort included 106 adult patients. Median time from HCT to vaccination was 42 (range 4–439) months. Overall, 15/106 (14%, 95% confidence interval (CI) 7–21%) were seronegative despite vaccination, 14/52 patients on immunosuppression (27%, 95%CI 19–35%) compared to only 1/54 patients off immunosuppression (1.8%, 95%CI 1–4%) (p 0.0002). The proportion of seronegative patients declined with time; it was 46% (6/13) during the first year, 12.5% (3/24) during the second year and 9% (6/69) beyond 2 years from transplant. Patients with acute graft-versus-host disease (GVHD) (odds ratio (OR) 3.3, 95%CI 0.97–11.1, p 0.06) and moderate to severe chronic GVHD (OR 5.9, 95%CI 1.2–29, p 0.03) were more likely to remain seronegative. Vaccination was well tolerated by most patients. However, 7% (7/106) reported that GVHD-related symptoms worsened within days following vaccination. A significant proportion of allogeneic HCT recipients receiving immunosuppression demonstrated an inadequate humoral response to the BNT162b2 vaccine. These patients should be recognized and instructed to take appropriate precautions. Recipients who were off immunosuppression had a humoral response that was comparable to that of the general population. [ABSTRACT FROM AUTHOR]