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BackgroundAlthough chronic infections by typhoidal Salmonella are well-known, prolonged human infections by nontyphoidal Salmonella (NTS) are poorly characterized.MethodsWe retrospectively analyzed 48 345 culture-confirmed NTS infections that occurred in Israel 1995-2012. A case-control study was performed to identify risk factors associated with persistent infections. Whole-genome-sequencing, pulsed-field gel electrophoresis (PFGE), and a mouse infection model were used to study genetic and phenotypic differences between same-patient persistent, recurring isolates.ResultsIn total, 1047 cases of persistent NTS infections, comprising 2.2% of all reported cases of salmonellosis, were identified. The persistence periods ranged between 30 days to 8.3 years. The majority (93%) of the persistently infected patients were immunocompetent, and 65% were symptomatic with relapsing diarrhea, indicating a distinct clinical manifestation from the asymptomatic carriage of typhoidal Salmonella. Four NTS serovars (Mbandaka, Bredeney, Infantis and Virchow) were found to be significantly more frequently associated with persistence than others. Comparative genomics between early and later isolates obtained from the same patients confirmed clonal infection and showed 0 to 10 SNPs between persistent isolates. A different composition of mobile genetic elements (plasmids and phages) or amino acid substitutions in global regulators was identified in multiple cases. These changes resulted in differences in phenotype and virulence between early and later same-patient isolates.ConclusionsThese results illuminate the overlooked clinical manifestation of persistent salmonellosis that can serve as a human reservoir for NTS infections. Additionally, we demonstrate mechanisms of in-host microevolution and exhibit their potential to shape Salmonella pathogenicity, antimicrobial resistance and host-pathogen interactions.

Background Waning immunity and an increased incidence of coronavirus disease 2019 (COVID-19) during the Omicron outbreak led the Israeli Ministry of Health to recommend a fourth vaccine dose for high-risk individuals. In this study, we assessed its effect for hospitalized patients with severe breakthrough COVID-19. Methods In this multicenter cohort study of hospitalized adults with severe COVID-19 in Israel, from 15 to 31 January 2022, cases were divided according to the number of vaccinations received. Poor outcome was defined as mechanical ventilation or in-hospital death and was compared between 3- and 4-dose vaccinees using logistic regression. Results Included were 1049 patients, median age 80 years. Among them, 394 were unvaccinated, 386 and 88 had received 3 or 4 doses, respectively. The 3-dose group was older, included more males, and immunosuppressed patients but with similar outcomes, 49% vs 51% compared with unvaccinated patients (P =.72). Patients who received 4 doses were similarly older and immunosuppressed but had better outcomes compared with unvaccinated patients, 34% vs 51% (P <.01). We examined independent predictors for poor outcome in patients who received either 3 or 4 doses a median of 161 days or 14 days before diagnosis, respectively. Receipt of the fourth dose was associated with protection (odds ratio, 0.51; 95% confidence interval,.3–.87), as was remdesivir. Male sex, chronic renal failure, and dementia were associated with poor outcomes. Conclusions Among hospitalized patients with severe breakthrough COVID-19, a recent fourth dose was associated with significant protection against mechanical ventilation or death compared with 3 doses. [ABSTRACT FROM AUTHOR]

Background Hematopoietic-cell transplant (HCT) recipients are at risk for severe respiratory syncytial virus (RSV) infection. We evaluated the RSV fusion inhibitor presatovir in a randomized, double-blind, Phase II trial in HCT recipients with RSV upper respiratory tract infections. Methods Patients were stratified by lymphopenia (<200/µL) and ribavirin use; were randomized, stratified by lymphopenia (<200/μL) and ribavirin use, to receive oral presatovir at 200 mg or a placebo on Days 1, 5, 9, 13, and 17, and were followed through Day 28. The coprimary efficacy endpoints were the time-weighted average change in the nasal RSV viral load between Days 1 and 9 and the proportion of patients developing lower respiratory tract complications (LRTCs) through Day 28. Results From 23 January 2015 to 16 June 2017, 189 patients were randomly assigned to treatment (96 to presatovir and 93 to the placebo). Presatovir treatment, compared with the placebo treatment, did not significantly affect (prespecified α = 0.01) a time-weighted average decline in the RSV viral load from Day 1 to 9 (treatment difference, −0.33 log10 copies/mL; 95% confidence interval [CI] −.64 to −.02 log10 copies/mL; P =.040) or the progression to LRTC (11.2% vs 19.5%, respectively; odds ratio, 0.50; 95% CI,.22–1.18; P =.11). In a post hoc analysis among patients with lymphopenia, presatovir decreased LRTC development by Day 28 (2/15 [13.3%] vs 9/14 [64.3%], respectively; P =.008), compared with the placebo. Adverse events were similar for patients receiving presatovir and the placebo. Conclusions Presatovir had a favorable safety profile in adult HCT recipients with RSV but did not achieve the coprimary endpoints. Exploratory analyses suggest an antiviral effect among patients with lymphopenia. Clinical Trials Registration NCT02254408; EUDRA-CT#2014-002474-36. [ABSTRACT FROM AUTHOR]

Background Isavuconazole was compared to caspofungin followed by oral voriconazole in a Phase 3, randomized, double-blind, multinational clinical trial for the primary treatment of patients with candidemia or invasive candidiasis. Methods Adult patients were randomized 1:1 to isavuconazole (200 mg intravenous [IV] three-times-daily [TID] for 2 days, followed by 200 mg IV once-daily [OD]) or caspofungin (70 mg IV OD on day 1, followed by 50 mg IV OD [70 mg in patients > 80 kg]) for a maximum of 56 days. After day 10, patients could switch to oral isavuconazole (isavuconazole arm) or voriconazole (caspofungin arm). Primary efficacy endpoint was successful overall response at the end of IV therapy (EOIVT) in patients with proven infections who received ≥1 dose of study drug (modified-intent-to-treat [mITT] population). The pre-specified noninferiority margin was 15%. Secondary outcomes in the mITT population were successful overall response at 2 weeks after the end of treatment, all-cause mortality at days 14 and 56, and safety. Results Of 450 patients randomized, 400 comprised the mITT population. Baseline characteristics were balanced between groups. Successful overall response at EOIVT was observed in 60.3% of patients in the isavuconazole arm and 71.1% in the caspofungin arm (adjusted difference -10.8, 95% confidence interval -19.9–-1.8). The secondary endpoints, all-cause mortality, and safety were similar between arms. Median time to clearance of the bloodstream was comparable between groups. Conclusions This study did not demonstrate non-inferiority of isavuconazole to caspofungin for primary treatment of invasive candidiasis. Secondary endpoints were similar between both groups. Clinical Trials Registration NCT00413218. [ABSTRACT FROM AUTHOR]

Background. Telavancin is a lipoglycopeptide bactericidal against gram-positive pathogens.Methods. Two methodologically identical, double-blind studies (0015 and 0019) were conducted involving patients with hospital-acquired pneumonia (HAP) due to gram-positive pathogens, particularly methicillin-resistant Staphylococcus aureus (MRSA). Patients were randomized 1:1 to telavancin (10 mg/kg every 24 h) or vancomycin (1 g every 12 h) for 7–21 days. The primary end point was clinical response at follow-up/test-of-cure visit.Results. A total of 1503 patients were randomized and received study medication (the all-treated population). In the pooled all-treated population, cure rates with telavancin versus vancomycin were 58.9% versus 59.5% (95% confidence interval [CI] for the difference, –5.6% to 4.3%). In the pooled clinically evaluable population (n = 654), cure rates were 82.4% with telavancin and 80.7% with vancomycin (95% CI for the difference, –4.3% to 7.7%). Treatment with telavancin achieved higher cure rates in patients with monomicrobial S. aureus infection and comparable cure rates in patients with MRSA infection; in patients with mixed gram-positive/gram-negative infections, cure rates were higher in the vancomycin group. Incidence and types of adverse events were comparable between the treatment groups. Mortality rates for telavancin-treated versus vancomycin-treated patients were 21.5% versus 16.6% (95% CI for the difference, –0.7% to 10.6%) for study 0015 and 18.5% versus 20.6% (95% CI for the difference, –7.8% to 3.5%) for study 0019. Increases in serum creatinine level were more common in the telavancin group (16% vs 10%).Conclusions. The primary end point of the studies was met, indicating that telavancin is noninferior to vancomycin on the basis of clinical response in the treatment of HAP due to gram-positive pathogens. [ABSTRACT FROM AUTHOR]

Background. Surgical wound infections caused by rapidly growing mycobacteria developed in 15 women after insertion of breast implants from August to November 2003 at a single medical center. Methods. A case-control study was conducted that included the identified patients, as well as women who underwent breast operations at the same center who did not develop infections. The study was accompanied by an extensive environmental investigation. Isolates were identified by standard bacteriological methods and by comparison of their 16S rRNA, HSP65, RPOB, SODA, and RECA gene sequences. Isolates were compared by random amplified polymorphic DNA analysis and by pulsed-field gel electrophoresis. Results. The risk factors for infection included surgery performed by 1 specific surgeon (odds ratio, 21.3; 95% confidence interval, 3.64–125.6). Identical strains of mycobacteria were isolated from the infected wounds of the patients; from the eyebrows, hair, face, nose, ears, and groin of this particular surgeon; and from this surgeon's outdoor whirlpool. The isolates exhibited a biochemical profile overlapping that of Mycobacterium wolinskyi, but their sequences of 16S rRNA and HSP65, RPOB, SODA, and RECA genes differed. We propose the name ဘMycobacterium jacuzzii’ for this new species. DNA fingerprints of cultured isolates from the surgical wounds, areas of the surgeon's body that grow hair, and the surgeon's whirlpool were identical. When the surgeon discontinued his use of the whirlpool and began cleaning the hairy areas of his body with a shampoo containing triclosan, the outbreak ended. Conclusions. This outbreak brings to light the possibility of the colonization of human skin and human-tohuman transmission of environmental mycobacteria during surgery that involves implant insertion. [ABSTRACT FROM AUTHOR]

During 10 months at our hospital, 413 patients underwent extracorporeal shock-wave lithotripsy (ESWL). The occurrence of complications was examined in the 126 (30.5%) of these patients who had sterile urine before the procedure and who had neither indwelling catheters nor stents. No patient received prophylactic antibiotics. After ESWL, nine patients (7%) developed bacteriuria, which was usually transient and required no therapy. Seven of the nine cases developed within 2 weeks of ESWL. In no case did other complications follow bacteriuria. Patients in whom bacteriuria was suspected because of fever all proved to have sterile urine. Our results indicate that patients whose urine is sterile before ESWL do not need antimicrobial prophylaxis. [ABSTRACT FROM PUBLISHER]

Streptococcus pyogenes bacteremia occurred in 104 patients over a 6-year period, during which time the annual incidence remained constant. The clinical and epidemiologic characteristics are described for 90 of these patients. Of the 90 patients, 90% had community-acquired infection, and 77% had an underlying illness predisposing them to infection. Skin infection was the cause of bacteremia in 615r% of the cases. Septic shock developed in 13 patients. The overall mortality rate was 15%. An increased likelihood of death was associated with septic shock and diabetes mellitus. [ABSTRACT FROM PUBLISHER]

We describe a case of a young adult who had chronic recurrent multifocal osteomyelitis that was diagnosed by exclusion and review the distinct clinical course of this disease. It is important to make a correct diagnosis so that unnecessary repeated invasive diagnostic procedures and prolonged use of antibiotics, steroids, or other chemotherapeutic agents can be avoided. [ABSTRACT FROM PUBLISHER]