Distribution of 13-Valent pneumococcal conjugate vaccine serotype streptococcus pneumoniae in adults 50 Years and Older presenting with community-acquired pneumonia in Israel

Background: Community acquired pneumonia (CAP) is a major cause of morbidity and mortality worldwide, and is a leading cause of hospitalization in previously healthy individuals without predisposing risk factors or comorbidities. In this study we determined PCV13 serotype distribution in adults aged ≥50 years with radiographically confirmed CAP in Israel. Methods: Subjects aged ≥50 years were enrolled from one of three hospitals (Emek Medical Center, Meir Medical Center and Sheba Medical Center) from March 2014 to July 2015. Information was collected on subject demographics, comorbidities, risk factors, and pneumococcal vaccine immunization status. Subjects presented with suspected CAP supported by radiographic evidence, and provided a urine sample and informed consent. Subjects without radiographic confirmation of CAP or who received PPSV23 within 30 days of study enrollment were excluded from the final analysis. Serotype distribution was performed using the urinary antigen detection (UAD) assay and/or microbiological culture. Results: Overall, 498 subjects with radiographically confirmed CAP were enrolled in the study. Eighty subjects (16.1%) were positive for any S. pneumoniae serotype by ≥1 assay, and 38 (7.6%) were positive for PCV13 serotypes via the UAD. The overall 30-day mortality rate was 1.2%, though S. pneumoniae was not isolated from any case leading to death. Conclusion: Despite six years of high pneumococcal immunization coverage in children in Israel, we have shown that 7.6% of CAP cases among adults in Israel remain related to PCV13 serotypes; and that the burden of PCV13 may be as high as 47% of observed pneumococcal CAP

Invasive Fungal Diseases in Hospitalized Patients with COVID-19 in Israel: A Multicenter Cohort Study

Highly variable estimates of COVID-19-associated fungal diseases (IFDs) have been reported. We aimed to determine the incidence of clinically important fungal diseases in hospitalized COVID-19 patients during the first year of the pandemic. We performed a multicenter survey of IFDs among patients hospitalized with COVID-19 in 13 hospitals in Israel between February 2020 and May 2021. COVID-19-associated pulmonary mold disease (PMD) and invasive candidiasis (IC) were defined using ECMM/ISHAM and EORTC/MSG criteria, respectively. Overall rates of IC and PMD among patients with critical COVID-19 were 10.86 and 10.20 per 1000 admissions, respectively, with significant variability among medical centers. PMD rates were significantly lower in centers where galactomannan was a send-out test versus centers with on-site testing (p = 0.035). The 30-day mortality rate was 67.5% for IC and 57.5% for PMD. Treatment with an echinocandin for IC or an extended-spectrum azole for PMD was associated with significantly lower mortality rates (adjusted hazard ratio [95% confidence interval], 0.26 [0.07–0.91] and 0.23 [0.093–0.57], respectively). In this multicenter national survey, variable rates of PMD were associated with on-site galactomannan testing, suggesting under-detection in sites lacking this capacity. COVID-19-related IFDs were associated with high mortality rates, which were reduced with appropriate antifungal therapy

Correlates of protection for booster doses of the SARS-CoV-2 vaccine BNT162b2

Abstract Vaccination, especially with multiple doses, provides substantial population-level protection against COVID-19, but emerging variants of concern (VOC) and waning immunity represent significant risks at the individual level. Here we identify correlates of protection (COP) in a multicenter prospective study following 607 healthy individuals who received three doses of the Pfizer-BNT162b2 vaccine approximately six months prior to enrollment. We compared 242 individuals who received a fourth dose to 365 who did not. Within 90 days of enrollment, 239 individuals contracted COVID-19, 45% of the 3-dose group and 30% of the four-dose group. The fourth dose elicited a significant rise in antibody binding and neutralizing titers against multiple VOCs reducing the risk of symptomatic infection by 37% [95%CI, 15%-54%]. However, a group of individuals, characterized by low baseline titers of binding antibodies, remained susceptible to infection despite significantly increased neutralizing antibody titers upon boosting. A combination of reduced IgG levels to RBD mutants and reduced VOC-recognizing IgA antibodies represented the strongest COP in both the 3-dose group (HR = 6.34, p = 0.008) and four-dose group (HR = 8.14, p = 0.018). We validated our findings in an independent second cohort. In summary combination IgA and IgG baseline binding antibody levels may identify individuals most at risk from future infections

Ceftazidime, carbapenems, or piperacillin-tazobactam as single definitive therapy for Pseudomonas aeruginosa bloodstream infection: a multisite retrospective study

BACKGROUND: The optimal antibiotic regimen for Pseudomonas aeruginosa bacteremia is controversial. Although β-lactam monotherapy is common, data to guide the choice between antibiotics are scarce. We aimed to compare ceftazidime, carbapenems, and piperacillin-tazobactam as definitive monotherapy. METHODS: A multinational retrospective study (9 countries, 25 centers) including 767 hospitalized patients with P. aeruginosa bacteremia treated with β-lactam monotherapy during 2009-2015. The primary outcome was 30-day all-cause mortality. Univariate and multivariate, including propensity-adjusted, analyses were conducted introducing monotherapy type as an independent variable. RESULTS: Thirty-day mortality was 37/213 (17.4%), 42/210 (20%), and 55/344 (16%) in the ceftazidime, carbapenem, and piperacillin-tazobactam groups, respectively. Type of monotherapy was not significantly associated with mortality in either univariate, multivariate, or propensity-adjusted analyses (odds ratio [OR], 1.14; 95% confidence interval [CI], 0.52-2.46, for ceftazidime; OR, 1.3; 95% CI, 0.67-2.51, for piperacillin-tazobactam, with carbapenems as reference in propensity adjusted multivariate analysis; 542 patients). No significant difference between antibiotics was demonstrated for clinical failure, microbiological failure, or adverse events. Isolation of P. aeruginosa with new resistance to antipseudomonal drugs was significantly more frequent with carbapenems (36/206 [17.5%]) versus ceftazidime (25/201 [12.4%]) and piperacillin-tazobactam (28/332 [8.4%] (P = .007). CONCLUSIONS: No significant difference in mortality, clinical, and microbiological outcomes or adverse events was demonstrated between ceftazidime, carbapenems, and piperacillin-tazobactam as definitive treatment of P. aeruginosa bacteremia. Higher rates of resistant P. aeruginosa after patients were treated with carbapenems, along with the general preference for carbapenem-sparing regimens, suggests using ceftazidime or piperacillin-tazobactam for treating susceptible infection

Risk factors for mortality among patients with Pseudomonas aeruginosa bacteraemia: a retrospective multicentre study

This study aimed to evaluate risk factors for 30-day mortality among hospitalised patients with Pseudomonas aeruginosa bacteraemia, a highly fatal condition. A retrospective study was conducted between 1 January 2009 and 31 October 2015 in 25 centres (9 countries) including 2396 patients. Univariable and multivariable analyses of risk factors were conducted for the entire cohort and for patients surviving ≥48 h. A propensity score for predictors of appropriate empirical therapy was introduced into the analysis. Of the 2396 patients, 636 (26.5%) died within 30 days. Significant predictors (odds ratio and 95% confidence interval) of mortality in the multivariable analysis included patient-related factors: age (1.02, 1.01–1.03); female sex (1.34, 1.03–1.77); bedridden functional capacity (1.99, 1.24–3.21); recent hospitalisation (1.43, 1.07–1.92); concomitant corticosteroids (1.33, 1.02–1.73); and Charlson comorbidity index (1.05, 1.01–1.93). Infection-related factors were multidrug-resistant Pseudomonas (1.52, 1.15–2.1), non-urinary source (2.44, 1.54–3.85) and Sequential Organ Failure Assessment (SOFA) score (1.27, 1.18–1.36). Inappropriate empirical therapy was not associated with increased mortality (0.81, 0.49–1.33). Among 2135 patients surviving ≥48 h, hospital-acquired infection (1.59, 1.21–2.09), baseline endotracheal tube (1.63, 1.13–2.36) and ICU admission (1.53, 1.02–2.28) were additional risk factors. Risk factors for mortality among patients with P. aeruginosa were mostly irreversible. Early appropriate empirical therapy was not associated with reduced mortality. Further research should be conducted to explore subgroups that may not benefit from broad-spectrum antipseudomonal empirical therapy. Efforts should focus on prevention of infection, mainly hospital-acquired infection and multidrug-resistant pseudomonal infection

Combination versus monotherapy as definitive treatment for Pseudomonas aeruginosa bacteraemia: a multicentre retrospective observational cohort study

International audienceAbstract Background Pseudomonas aeruginosa bacteraemia is a common and serious infection. No consensus exists regarding whether definitive combination therapy is superior to monotherapy. We aimed to evaluate the impact of combination therapy on mortality. Methods This was a multicentre retrospective study (nine countries, 25 centres), including 1277 patients with P. aeruginosa bacteraemia during 2009–15. We evaluated the association between β-lactam plus aminoglycoside or quinolone combination therapy versus β-lactam monotherapy and mortality. The primary outcome was 30 day all-cause mortality. Univariate and multivariate Cox regression analyses were conducted, introducing combination as a time-dependent variable. Propensity score was conducted to adjust for confounding for choosing combination therapy over monotherapy. Results Of 1119 patients included, 843 received definitive monotherapy and 276 received combination therapy (59% aminoglycoside and 41% quinolone). Mortality at 30 days was 16.9% (189/1119) and was similar between combination (45/276; 16.3%) and monotherapy (144/843; 17.1%) groups (P = 0.765). In multivariate Cox regression, combination therapy was not associated with reduced mortality (HR 0.98, 95% CI 0.64–1.53). No advantage in terms of clinical failure, microbiological failure or recurrent/persistent bacteraemia was demonstrated using combination therapy. Likewise, adverse events and resistance development were similar for the two regimens. Conclusions In this retrospective cohort, no mortality advantage was demonstrated using combination therapy over monotherapy for P. aeruginosa bacteraemia. Combination therapy did not improve clinical or microbiological failure rates, nor affect adverse events or resistance development. Our finding of no benefit with combination therapy needs confirmation in well-designed randomized controlled trials

Risk factors for mortality among patients with Pseudomonas aeruginosa bacteraemia: a retrospective multicentre study

This study aimed to evaluate risk factors for 30-day mortality among hospitalised patients with Pseudomonas aeruginosa bacteraemia, a highly fatal condition. A retrospective study was conducted between 1 January 2009 and 31 October 2015 in 25 centres (9 countries) including 2396 patients. Univariable and multivariable analyses of risk factors were conducted for the entire cohort and for patients surviving ≥48 h. A propensity score for predictors of appropriate empirical therapy was introduced into the analysis. Of the 2396 patients, 636 (26.5%) died within 30 days. Significant predictors (odds ratio and 95% confidence interval) of mortality in the multivariable analysis included patient-related factors: age (1.02, 1.01–1.03); female sex (1.34, 1.03–1.77); bedridden functional capacity (1.99, 1.24–3.21); recent hospitalisation (1.43, 1.07–1.92); concomitant corticosteroids (1.33, 1.02–1.73); and Charlson comorbidity index (1.05, 1.01–1.93). Infection-related factors were multidrug-resistant Pseudomonas (1.52, 1.15–2.1), non-urinary source (2.44, 1.54–3.85) and Sequential Organ Failure Assessment (SOFA) score (1.27, 1.18–1.36). Inappropriate empirical therapy was not associated with increased mortality (0.81, 0.49–1.33). Among 2135 patients surviving ≥48 h, hospital-acquired infection (1.59, 1.21–2.09), baseline endotracheal tube (1.63, 1.13–2.36) and ICU admission (1.53, 1.02–2.28) were additional risk factors. Risk factors for mortality among patients with P. aeruginosa were mostly irreversible. Early appropriate empirical therapy was not associated with reduced mortality. Further research should be conducted to explore subgroups that may not benefit from broad-spectrum antipseudomonal empirical therapy. Efforts should focus on prevention of infection, mainly hospital-acquired infection and multidrug-resistant pseudomonal infection