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Background The variant of concern Omicron has become the sole circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant for the past several months. Omicron subvariants BA.1, BA.2, BA.3, BA.4, and BA.5 evolved over the time, with BA.1 causing the largest wave of infections globally in December 2021–January 2022. This study compared the clinical outcomes in patients infected with different Omicron subvariants and the relative viral loads and recovery of infectious virus from upper respiratory specimens. Methods SARS-CoV-2–positive remnant clinical specimens, diagnosed at the Johns Hopkins Microbiology Laboratory between December 2021 and July 2022, were used for whole-genome sequencing. The clinical outcomes of infections with Omicron subvariants were compared with infections with BA.1. Cycle threshold (Ct) values and the recovery of infectious virus on the VeroTMPRSS2 cell line from clinical specimens were compared. Results BA.1 was associated with the largest increase in SARS-CoV-2 positivity rate and coronavirus disease 2019 (COVID-19)–related hospitalizations at the Johns Hopkins system. After a peak in January, cases decreased in the spring, but the emergence of BA.2.12.1 followed by BA.5 in May 2022 led to an increase in case positivity and admissions. BA.1 infections had a lower mean Ct value when compared with other Omicron subvariants. BA.5 samples had a greater likelihood of having infectious virus at Ct values <20. Conclusions Omicron subvariants continue to be associated with a relatively high rate of polymerase chain reaction (PCR) positivity and hospital admissions. The BA.5 infections are more while BA.2 infections are less likely to have infectious virus, suggesting potential differences in infectibility during the Omicron waves. [ABSTRACT FROM AUTHOR]

Background Prompt initiation of antibiotic therapy improves the survival of patients with bloodstream infections (BSIs). We sought to determine if the sequence of administration of the first dose of antibiotic therapy (ie, β-lactam or vancomycin, if both are deemed necessary and cannot be administered simultaneously) impacts early mortality for patients with BSI. Methods We conducted a multicenter, observational study of patients ≥13 years with BSIs to evaluate the association of the sequence of antibiotic administration with 7-day mortality using inverse probability of treatment weighting (IPTW) incorporating propensity scores. Propensity scores were generated based on demographics, Pitt bacteremia score, intensive care unit status, highest lactate, highest white blood cell count, Charlson comorbidity index, severe immunocompromise, administration of active empiric therapy, combination therapy, and time from emergency department arrival to first antibiotic dose. Results Of 3376 eligible patients, 2685 (79.5%) received a β-lactam and 691 (20.5%) received vancomycin as their initial antibiotic. In the IPTW cohort, exposed and unexposed patients were similar on all baseline variables. Administration of a β-lactam agent prior to vancomycin protected against 7-day mortality (adjusted odds ratio [aOR], 0.48 [95% confidence interval {CI},.33–.69]). Similar results were observed when evaluating 48-hour mortality (aOR, 0.45 [95% CI,.24–.83]). Administration of vancomycin prior to a β-lactam was not associated with improved survival in the subgroup of 524 patients with methicillin-resistant Staphylococcus aureus BSI (aOR, 0.93 [95% CI,.33–2.63]). Conclusions For ill-appearing patients likely to be experiencing a BSI, prioritizing administration of a β-lactam over vancomycin may reduce early mortality, underscoring the significant impact of a relatively simple practice change on improving patient survival. [ABSTRACT FROM AUTHOR]

Background The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant of concern (VOC) B.1.617.2 (Delta) displaced B.1.1.7 (Alpha) and is associated with increases in coronavirus disease 2019 (COVID-19) cases, greater transmissibility, and higher viral RNA loads, but data are lacking regarding the infectious virus load and antiviral antibody levels in the nasal tract. Methods Whole genome sequencing, cycle threshold (Ct) values, infectious virus, anti-SARS-CoV-2 immunoglobulin G (IgG) levels, and clinical chart reviews were combined to characterize SARS-CoV-2 lineages circulating in the National Capital Region between January and September 2021 and differentiate infections in vaccinated and unvaccinated individuals by the Delta, Alpha, and B.1.2 (the predominant lineage prior to Alpha) variants. Results The Delta variant displaced the Alpha variant to constitute 99% of the circulating lineages in the National Capital Region by August 2021. In Delta infections, 28.5% were breakthrough cases in fully vaccinated individuals compared to 4% in the Alpha infected cohort. Breakthrough infections in both cohorts were associated with comorbidities, but only Delta infections were associated with a significant increase in the median days after vaccination. More than 74% of Delta samples had infectious virus compared to <30% from the Alpha cohort. The recovery of infectious virus with both variants was associated with low levels of local SARS-CoV-2 IgG. Conclusions Infection with the Delta variant was associated with more frequent recovery of infectious virus in vaccinated and unvaccinated individuals compared to the Alpha variant but was not associated with an increase in disease severity in fully vaccinated individuals. Infectious virus was correlated with the presence of low amounts of antiviral IgG in the nasal specimens. [ABSTRACT FROM AUTHOR]

We assessed temporal changes in the household secondary attack rate of severe acute respiratory syndrome coronavirus 2 and identified risk factors for transmission in vulnerable Latino households of Baltimore, Maryland. The household secondary attack rate was 45.8%, and it appeared to increase as the alpha variant spread, highlighting the magnified risk of spread in unvaccinated populations. [ABSTRACT FROM AUTHOR]

Background The threat posed by antibiotic resistance is of increasing concern in low- and middle-income countries (LMICs) as their rates of antibiotic use increase. However, an understanding of the burden of resistance is lacking in LMICs, particularly for multidrug-resistant (MDR) pathogens. Methods We conducted a retrospective, 10-hospital study of the relationship between MDR pathogens and mortality in India. Patient-level antimicrobial susceptibility test (AST) results for Enterococcus spp. Escherichia coli , Staphylococcus aureus , Klebsiella pneumoniae , Acinetobacter baumannii , Pseudomonas aeruginosa , and Enterobacter spp. were analyzed for their association with patient mortality outcomes. Results We analyzed data on 5103 AST results from 10 hospitals. The overall mortality rate of patients was 13.1% (n = 581), and there was a significant relationship between MDR and mortality. Infections with MDR and extensively drug resistant (XDR) E. coli , XDR K. pneumoniae , and MDR A. baumannii were associated with 2–3 times higher mortality. Mortality due to methicillin-resistant S. aureus (MRSA) was significantly higher than susceptible strains when the MRSA isolate was resistant to aminoglycosides. Conclusions This is one of the largest studies undertaken in an LMIC to measure the burden of antibiotic resistance. We found that MDR bacterial infections pose a significant risk to patients. While consistent with prior studies, the variations in drug resistance and associated mortality outcomes by pathogen are different from those observed in high-income countries and provide a baseline for studies in other LMICs. Future research should aim to elucidate the burden of resistance and the differential transmission mechanisms that drive this public health crisis. [ABSTRACT FROM AUTHOR]

Background Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) have been associated with worse patient outcomes and higher costs of care than methicillin-susceptible (MSSA) infections. However, since prior studies found these differences, the healthcare landscape has changed, including widespread dissemination of community-associated strains of MRSA. We sought to provide updated estimates of the excess costs of MRSA infections. Methods We conducted a retrospective analysis using data from the National Inpatient Sample from the Agency for Healthcare Research and Quality for the years 2010–2014. We calculated costs for hospitalizations, including MRSA- and MSSA-related septicemia and pneumonia infections, as well as MRSA- and MSSA-related infections from conditions classified elsewhere and of an unspecified site ("other infections"). Differences in the costs of hospitalization were estimated using propensity score–adjusted mortality outcomes for 2010–2014. Results In 2014, estimated costs were highest for pneumonia and sepsis-related hospitalizations. Propensity score–adjusted costs were significantly higher for MSSA-related pneumonia ($40725 vs $38561; P =.045) and other hospitalizations ($15578 vs $14792; P <.001) than for MRSA-related hospitalizations. Similar patterns were observed from 2010 to 2013, although crude cost differences between MSSA- and MRSA-related pneumonia hospitalizations rose from 25.8% in 2010 to 31.0% in 2014. Compared with MSSA-related hospitalizations, MRSA-related hospitalizations had a higher adjusted mortality rate. Conclusions Although MRSA infections had been previously associated with higher hospitalization costs, our results suggest that, in recent years, costs associated with MSSA-related infections have converged with and may surpass costs of similar MRSA-related hospitalizations. [ABSTRACT FROM AUTHOR]