The Effect of COVID-19 Vaccination on Outpatient Antibiotic Prescribing in Older Adults: A Self-Controlled Risk-Interval Study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) vaccination has been associated with reduced outpatient antibiotic prescribing among older adults with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We assessed the impact of COVID-19 vaccination on outpatient antibiotic prescribing in the broader population of older adults, regardless of SARS-CoV-2 infection status. METHODS: We included adults aged ≥65 years who received their first, second, and/or third COVID-19 vaccine dose from December 2020 to December 2022. We used a self-controlled risk-interval design and included cases who received an antibiotic prescription 2-6 weeks before vaccination (pre-vaccination or control interval) or after vaccination (post-vaccination or risk interval). We used conditional logistic regression to estimate the odds of being prescribed (1) any antibiotic, (2) a typical "respiratory" infection antibiotic, or (3) a typical "urinary tract" infection antibiotic (negative control) in the post-vaccination interval versus the pre-vaccination interval. We accounted for temporal changes in antibiotic prescribing using background monthly antibiotic prescribing counts. RESULTS: 469 923 vaccine doses met inclusion criteria. The odds of receiving any antibiotic or a respiratory antibiotic prescription were lower in the post-vaccination versus pre-vaccination interval (aOR, .973; 95% CI, .968-.978; aOR, .961; 95% CI, .953-.968, respectively). There was no association between vaccination and urinary antibiotic prescriptions (aOR, .996; 95% CI, .987-1.006). Periods with high (>10%) versus low (<5%) SARS-CoV-2 test positivity demonstrated greater reductions in antibiotic prescribing (aOR, .875; 95% CI, .845-.905; aOR, .996; 95% CI, .989-1.003, respectively). CONCLUSIONS: COVID-19 vaccination was associated with reduced outpatient antibiotic prescribing in older adults, especially during periods of high SARS-CoV-2 circulation.

Emotional dysregulation moderates the relation between perceived stress and emotional eating in adolescent military dependents.

OBJECTIVE: Adolescent children of US service members (i.e., military-dependent youth) face unique stressors that increase risk for various forms of disinhibited eating, including emotional eating. Difficulties with adaptively responding to stress and aversive emotions may play an important role in emotional eating. This study examined emotion dysregulation as a potential moderator of the association between perceived stress and emotional eating in adolescent military dependents. METHOD: Participants were military-dependent youth (N = 163, 57.7% female, Mage = 14.5 ± 1.6, MBMI-z = 1.9 ± 0.4) at risk for adult binge-eating disorder and high weight enrolled in a randomized controlled prevention trial. Prior to intervention, participants completed questionnaires assessing perceived stress and emotional eating. Parents completed a questionnaire assessing their adolescent's emotion dysregulation. Moderation analyses were conducted using the PROCESS macro in SPSS and adjusted for theoretically relevant sociodemographic covariates. RESULTS: The interaction between adolescent perceived stress and emotion dysregulation (parent-reported about the adolescent) in relation to adolescent emotional eating was found to be significant, such that higher emotion dysregulation magnified the association between perceived stress and emotional eating (p = .010). Examination of simple slopes indicated that associations between perceived stress and emotional eating were strongest for youth with above-average emotion dysregulation, and non-significant for youth with average or below-average emotion dysregulation. DISCUSSION: Findings suggest that greater emotion dysregulation may increase risk for emotional eating in response to stress among military-dependent youth at risk for binge-eating disorder or high weight. Improving emotion regulation skills may be a useful target for eating disorder prevention among youth who are at risk for emotional eating. PUBLIC SIGNIFICANCE: Prior research has shown that adolescent military dependents are at increased risk for eating disorders and high weight. The current study found that emotion dysregulation moderated the relationship between perceived stress and emotional eating among military-dependent youth. There may be clinical utility in intervening on emotion regulation for adolescent dependents at particular risk for emotional eating and subsequent eating disorders.

Puberty Suppression for Pediatric Gender Dysphoria and the Child's Right to an Open Future.

In this essay, we consider the clinical and ethical implications of puberty blockers for pediatric gender dysphoria through the lens of "the child's right to an open future," which refers to rights that children do not have the capacity to exercise as minors, but that must be protected, so they can exercise them in the future as autonomous adults. We contrast the open future principle with the beliefs underpinning the gender affirming care model and discuss implications for consent. We evaluate claims that puberty blockers are reversible, discuss the scientific uncertainty about long-term benefits and harms, summarize international developments, and examine how suicide has been used to frame puberty suppression as a medically necessary, lifesaving treatment. In discussing these issues, we include relevant empirical evidence and raise questions for clinicians and researchers. We conclude that treatment pathways that delay decisions about medical transition until the child has had the chance to grow and mature into an autonomous adulthood would be most consistent with the open future principle.

The impact of the COVID-19 pandemic on blood culture practices and bloodstream infections.

IMPORTANCE: Bacterial infections are a significant cause of morbidity and mortality worldwide. In the wake of the COVID-19 pandemic, previous studies have demonstrated pandemic-related shifts in the epidemiology of bacterial bloodstream infections (BSIs) in the general population and in specific hospital systems. Our study uses a large, comprehensive data set stratified by setting [community, long-term care (LTC), and hospital] to uniquely demonstrate how the effect of the COVID-19 pandemic on BSIs and testing practices varies by healthcare setting. We showed that, while the number of false-positive blood culture results generally increased during the pandemic, this effect did not apply to hospitalized patients. We also found that many infections were likely under-recognized in patients in the community and in LTC, demonstrating the importance of maintaining healthcare for these groups during crises. Last, we found a decrease in infections caused by certain pathogens in the community, suggesting some secondary benefits of pandemic-related public health measures.

Newborn and Early Infant Outcomes Following Maternal COVID-19 Vaccination During Pregnancy.

Importance: The study team previously showed that maternal mRNA COVID-19 vaccination during pregnancy confers protection against SARS-CoV-2 infection and COVID-19-related hospital admission in newborns and young infants. In this study, the study team evaluated newborn and early infant safety outcomes following maternal messenger RNA (mRNA) COVID-19 vaccination during pregnancy, for which there is limited comparative epidemiological evidence. Objective: To determine if maternal mRNA COVID-19 vaccination during pregnancy is associated with adverse newborn and early infant outcomes. Design, Setting, and Participants: This population-based retrospective cohort study took place in Ontario, Canada, using multiple linked health administrative databases. Singleton live births with an expected delivery date between May 1, 2021, and September 2, 2022, were included. Data were analyzed from January 2023 through March 2023. Exposure: Maternal mRNA COVID-19 vaccination (1 or more doses) during pregnancy. Main Outcomes and Measures: Severe neonatal morbidity (SNM), neonatal death, neonatal intensive care unit (NICU) admission, neonatal readmission, and hospital admission up to 6 months of age. The study team calculated inverse probability of treatment weighted risk ratios (RRs) and fit weighted Cox proportional hazards regression models comparing outcomes in infants of mothers who received COVID-19 vaccination during pregnancy with those who received no COVID-19 vaccine doses before delivery. Results: In total, 142 006 infants (72 595 male [51%]; mean [SD] gestational age at birth, 38.7 [1.7] weeks) were included; 85 670 were exposed to 1 or more COVID-19 vaccine doses in utero (60%). Infants of vaccinated mothers had lower risks of SNM (vaccine exposed 7.3% vs vaccine unexposed 8.3%; adjusted RR [aRR], 0.86; 95% CI, 0.83-0.90), neonatal death (0.09% vs 0.16%; aRR, 0.47; 95% CI, 0.33-0.65), and NICU admission (11.4% vs 13.1%; aRR, 0.86; 95% CI, 0.83-0.89). There was no association between maternal vaccination during pregnancy and neonatal readmission (5.5% vs 5.1%; adjusted hazard ratio, 1.03; 95% CI, 0.98-1.09) or 6-month hospital admission (8.4% vs 8.1%; adjusted hazard ratio, 1.01; 95% CI, 0.96-1.05). Conclusions and Relevance: In this population-based cohort study in Ontario, Canada, maternal mRNA COVID-19 vaccination during pregnancy was associated with lower risks of SNM, neonatal death, and NICU admission. In addition, neonatal and 6-month readmissions were not increased in infants of mothers vaccinated during pregnancy.

International consensus recommendations for the use of prolonged-infusion beta-lactam antibiotics: Endorsed by the American College of Clinical Pharmacy, British Society for Antimicrobial Chemotherapy, Cystic Fibrosis Foundation, European Society of Clinical Microbiology and Infectious Diseases, Infectious Diseases Society of America, Society of Critical Care Medicine, and Society of Infectious Diseases Pharmacists: An executive summary.

Intravenous ß-lactam antibiotics remain a cornerstone in the management of bacterial infections due to their broad spectrum of activity and excellent tolerability. ß-lactams are well established to display time-dependent bactericidal activity, where reductions in bacterial burden are directly associated with the time that free drug concentrations remain above the minimum inhibitory concentration (MIC) of the pathogen during the dosing interval. In an effort to take advantage of these bactericidal characteristics, prolonged (extended and continuous) infusions (PI) can be applied during the administration of intravenous ß-lactams to increase time above the MIC. PI dosing regimens have been implemented worldwide, but implementation is inconsistent. We report consensus therapeutic recommendations for the use of ß-lactam PI developed by an expert international panel with representation from clinical pharmacy and medicine. This consensus guideline provides recommendations regarding pharmacokinetic and pharmacodynamic targets, therapeutic drug monitoring considerations, and the use of PI ß-lactam therapy in the following patient populations: severely ill and nonseverely ill adult patients, pediatric patients, and obese patients. These recommendations provide the first consensus guidance for the use of ß-lactam therapy administered as PIs and have been reviewed and endorsed by the American College of Clinical Pharmacy (ACCP), the British Society for Antimicrobial Chemotherapy (BSAC), the Cystic Fibrosis Foundation (CFF), the European Society of Clinical Microbiology and Infectious Diseases (ESCMID), the Infectious Diseases Society of America (IDSA), the Society of Critical Care Medicine (SCCM), and the Society of Infectious Diseases Pharmacists (SIDP).

International consensus recommendations for the use of prolonged-infusion beta-lactam antibiotics: Endorsed by the American College of Clinical Pharmacy, British Society for Antimicrobial Chemotherapy, Cystic Fibrosis Foundation, European Society of Clinical Microbiology and Infectious Diseases, Infectious Diseases Society of America, Society of Critical Care Medicine, and Society of Infectious Diseases Pharmacists.

Intravenous ß-lactam antibiotics remain a cornerstone in the management of bacterial infections due to their broad spectrum of activity and excellent tolerability. ß-lactams are well established to display time-dependent bactericidal activity, where reductions in bacterial burden are directly associated with the time that free drug concentrations remain above the minimum inhibitory concentration (MIC) of the pathogen during the dosing interval. In an effort to take advantage of these bactericidal characteristics, prolonged (extended and continuous) infusions (PIs) can be applied during the administration of intravenous ß-lactams to increase time above the MIC. PI dosing regimens have been implemented worldwide, but implementation is inconsistent. We report consensus therapeutic recommendations for the use of PI ß-lactams developed by an expert international panel with representation from clinical pharmacy and medicine. This consensus guideline provides recommendations regarding pharmacokinetic and pharmacodynamic targets, therapeutic drug-monitoring considerations, and the use of PI ß-lactam therapy in the following patient populations: severely ill and nonseverely ill adult patients, pediatric patients, and obese patients. These recommendations provide the first consensus guidance for the use of ß-lactam therapy administered as PIs and have been reviewed and endorsed by the American College of Clinical Pharmacy (ACCP), the British Society for Antimicrobial Chemotherapy (BSAC), the Cystic Fibrosis Foundation (CFF), the European Society of Clinical Microbiology and Infectious Diseases (ESCMID), the Infectious Diseases Society of America (IDSA), the Society of Critical Care Medicine (SCCM), and the Society of Infectious Diseases Pharmacists (SIDP).

Vancomycin Therapeutic Drug Monitoring: A Cross-Sectional Survey of Canadian Hospitals.

Background: Little is known about the current landscape of vancomycin therapeutic drug monitoring (TDM) in Canadian hospitals, which operate within publicly funded health care systems. Objectives: To determine current TDM practices for vancomycin and associated challenges and to gather perceptions about TDM based on area under the concentration-time curve (AUC) in Canadian hospitals. Methods: An electronic survey was distributed to hospital pharmacists in spring 2021 through multiple national and provincial antimicrobial stewardship, public health, and pharmacy organizations. The survey gathered data about hospital characteristics, TDM methods, inclusion criteria for patient selection, pharmacokinetic and pharmacodynamic targets, vancomycin susceptibility testing and reporting, and perceived barriers and challenges. Results: In total, 120 pharmacists from 10 of the 13 provincial and territorial jurisdictions in Canada, representing 12.5% of Canadian acute care hospitals (n = 962), completed at least 90% of survey questions. The predominant TDM method was trough-based (107/119, 89.9%); another 10.1% of respondents (12/119) reported performing AUC-based TDM (with or without trough-based TDM), and 17.9% (19/106) of those not already using AUC-based TDM were considering implementing it within 1 to 2 years. Among hospitals performing trough-based TDM, 60.5% (66/109) targeted trough levels between 15 and 20 mg/L for serious infections with methicillin-resistant Staphylococcus aureus. One-quarter of the respondents using this method (27/109, 24.8%) agreed that trough-based TDM was of uncertain benefit, and about one-third (33/109, 30.3%) were neutral on this question. Multiple challenges were identified for trough-based TDM, including sub- or supra-therapeutic concentrations and collection of specimens at inappropriate times. Overall, 40.5% (47/116) of respondents agreed that AUC-based TDM was likely safer than trough-based TDM, whereas 23.3% (27/116) agreed that AUC-based TDM was likely more effective. Conclusions: This survey represents a first step in developing evidence-based, standardized best practices for vancomycin TDM that are uniquely suited to the Canadian health care system.

Contexte: On connaît peu de choses sur le paysage actuel du suivi thérapeutique pharmacologique (STP) de la vancomycine dans les hôpitaux canadiens, dont les activités s'inscrivent dans le cadre des systèmes de soins de santé financés par les deniers publics. Objectifs: Déterminer les pratiques actuelles de STP de la vancomycine et les défis associés et recueillir les perceptions concernant le STP sur la base de l'aire sous la courbe de la concentration en fonction du temps (ASC) dans les hôpitaux canadiens. Méthodes: Un sondage a été distribué électroniquement aux pharmaciens d'hôpitaux au printemps 2021 par plusieurs organismes nationaux et provinciaux de gestion de l'utilisation des antimicrobiens, de santé publique et de pharmacie. Le sondage a permis de rassembler des données concernant les caractéristiques des hôpitaux, les méthodes de STP, les critères d'inclusion pour la sélection des patients, les objectifs pharmacocinétiques et pharmacodynamiques, les tests de sensibilité à la vancomycine et les rapports des résultats, ainsi que les obstacles et les défis perçus. Résultats: Au total, 120 pharmaciens de 10 des 13 provinces et territoires du Canada, représentant 12,5 % des hôpitaux canadiens de soins actifs (n = 962), ont répondu à au moins 90 % des questions du sondage. La méthode de STP prédominante utilisée était celle de la concentration minimale (107/119, 89,9 %); un autre 10,1 % des répondants (12/119) ont déclaré effectuer un STP basé sur l'ASC (avec ou sans STP basé sur la concentration minimale), et 17,9 % (19/106) de ceux qui n'effectuaient pas déjà le STP basé sur l'ASC envisageaient de le mettre en œuvre d'ici 1 à 2 ans. Parmi les hôpitaux pratiquant le STP basé sur la concentration minimale, 60,5 % (66/109) ciblaient des concentrations minimales entre 15 et 20 mg/L pour les infections graves à Staphylococcus aureus résistant à la méthicilline. Un quart des répondants qui utilisaient cette méthode (27/109, 24,8 %) convenaient que les avantages du STP basé sur la concentration minimale étaient incertains, et environ un tiers (33/109, 30,3 %) étaient neutres. De multiples défis ont été identifiés pour le STP basé sur la concentration minimale, notamment des concentrations sous-ou supra-thérapeutiques et la collecte d'échantillons à des moments inappropriés. Dans l'ensemble, 40,5 % (47/116) des répondants convenaient que le STP basé sur l'ASC était probablement plus sûr que le STP basé sur la concentration minimale, tandis que 23,3 % (27/116) convenaient que le STP basé sur l'ASC était probablement plus efficace. Conclusions: Ce sondage représente une première étape dans l'élaboration de pratiques exemplaires normalisées et fondées sur des données probantes pour le STP de la vancomycine qui sont particulièrement adaptées au système de santé canadien.

Iatrogenic Harm in Gender Medicine.

Although transition regret and detransition are often dismissed as rare, the increasing number of young detransitioners who have come forward in recent years to publicly share their experiences suggests that there are cracks in the gender-affirmation model of care that can no longer be ignored. In this commentary, I argue that the medical community must find ways to have more open discussions and commit to research and clinical collaboration so that regret and detransition really are vanishingly rare outcomes. Moving forward, we must recognize detransitioners as survivors of iatrogenic harm and provide them with the personalized medicine and supports they require.

Transition Regret and Detransition: Meanings and Uncertainties.

Gender transition is undertaken to improve the well-being of people suffering from gender dysphoria. However, some have argued that the evidence supporting medical interventions for gender transition (e.g., hormonal therapies and surgery) is weak and inconclusive, and an increasing number of people have come forward recently to share their experiences of transition regret and detransition. In this essay, I discuss emerging clinical and research issues related to transition regret and detransition with the aim of arming clinicians with the latest information so they can support patients navigating the challenges of regret and detransition. I begin by describing recent changes in the epidemiology of gender dysphoria, conceptualization of transgender identification, and models of care. I then discuss the potential impact of these changes on regret and detransition; the prevalence of desistance, regret, and detransition; reasons for detransition; and medical and mental healthcare needs of detransitioners. Although recent data have shed light on a complex range of experiences that lead people to detransition, research remains very much in its infancy. Little is known about the medical and mental healthcare needs of these patients, and there is currently no guidance on best practices for clinicians involved in their care. Moreover, the term detransition can hold a wide array of possible meanings for transgender-identifying people, detransitioners, and researchers, leading to inconsistences in its usage. Moving forward, minimizing harm will require conducting robust research, challenging fundamental assumptions, scrutinizing of practice patterns, and embracing debate.

Current therapies and challenges for the treatment of Staphylococcus aureus biofilm-related infections.

Staphylococcus aureus is a major cause of nosocomial and community-acquired infections and contributes to significant increase in morbidity and mortality especially when associated with medical devices and in biofilm form. Biofilm structure provides a pathway for the enrichment of resistant and persistent phenotypes of S. aureus leading to relapse and recurrence of infection. Minimal diffusion of antibiotics inside biofilm structure leads to heterogeneity and distinct physiological activity. Additionally, horizontal gene transfer between cells in proximity adds to the challenges associated with eradication of biofilms. This narrative review focuses on biofilm-associated infections caused by S. aureus, the impact of environmental conditions on biofilm formation, interactions inside biofilm communities, and the clinical challenges that they present. Conclusively, potential solutions, novel treatment strategies, combination therapies, and reported alternatives are discussed.

Eligibility and enrollment of pregnant and breastfeeding women in psychiatry randomized controlled trials.

To describe the eligibility and enrollment of pregnant and breastfeeding women in psychiatry randomized controlled trials (RCTs). We screened citations published 2017-2019 in the three highest impact psychiatry and five highest impact general medicine journals. We excluded male, pediatric, geriatric, and postmenopausal-focused RCTs and publications reporting subgroup, pooled, or secondary analyses of RCTs. We reviewed appendices, protocols, and registries for additional data. In total 108 RCTs were included. Three (2.8%) permitted enrollment of pregnant women; 59/108 (55%) and 46/108 (43%) explicitly excluded pregnant women or did not report pregnancy inclusion criteria, respectively. All RCTs including pregnant women evaluated non-pharmacological interventions for depression during pregnancy or postpartum. Among RCTs excluding pregnant women, 5/59 (8.5%) provided a rationale for exclusion. Contraception and/or negative pregnancy testing were required for women with reproductive capacity in 31/59 (53%). Three (2.8%) RCTs permitted enrollment of breastfeeding women and 3/41 (7.3%) RCTs excluding breastfeeding women provided a rationale for exclusion. This study demonstrates a major gap in psychiatry research involving pregnant and breastfeeding women. A shift from exclusion by default to inclusion and integration of this population into the clinical research agenda is needed to ensure they receive evidence-based care for mental illness.

The Relationship Between Anxiety, Coping, and Disordered-Eating Attitudes in Adolescent Military-Dependents at High-Risk for Excess Weight Gain.

Adolescent military-dependents are an understudied population who face unique stressors due to their parents' careers. Research suggests that adolescent military-dependents report more anxiety and disordered-eating than their civilian counterparts. While anxiety symptoms predict the onset and worsening of disordered-eating attitudes, the mechanisms underlying this relationship remain unclear. One factor that may underlie this relationship, and be particularly relevant for military-dependent youth, is coping. Therefore, we examined adolescent military-dependents (N=136; 14.5±1.5 years; 59.6% female; BMI-z: 1.9±0.4) who were at-risk for adult obesity and binge-eating disorder due to an age- and sex-adjusted BMI ≥ 85th percentile and loss-of-control eating and/or elevated anxiety. Participants completed an interview assessing disordered-eating attitudes and questionnaires on anxiety symptoms and coping strategies at a single time point. Bootstrapping models were conducted to examine the indirect paths between anxiety symptoms and disordered-eating attitudes through five coping subscales (aggression, distraction, endurance, self-distraction, and stress-recognition). Adjusting for relevant covariates, no significant indirect paths through the coping subscales (ps > .05) were found in any models. General coping, non-specific to eating, may not be a pathway between anxiety symptoms and disordered-eating attitudes among adolescents. Future research should examine other potential mediators of this relationship.

Nirsevimab: review of pharmacology, antiviral activity and emerging clinical experience for respiratory syncytial virus infection in infants.

Respiratory syncytial virus (RSV) is a leading cause of hospitalization and infant mortality worldwide. There are currently no approved vaccines against RSV, and immunoprophylaxis with the mAb palivizumab is limited to extremely vulnerable infants in resource-rich settings due to its high cost and the need for monthly injections throughout the RSV season. Nirsevimab (formerly MEDI8897) is a highly potent, long-acting, human, recombinant mAb that received approval for the prevention of RSV infection in newborns and infants during their first RSV season from the EMA and the UK's Medicines and Healthcare products Regulatory Agency in November 2022 based on positive results in Phase 2b and 3 clinical trials. Nirsevimab targets the highly conserved site Ø of the prefusion conformation of the RSV fusion (F) protein and contains a triple amino acid substitution in the Fc domain that extends its half-life, allowing for a single dose to cover a typical RSV season in regions with temperate climates. In this article I review key attributes of nirsevimab with an emphasis on pharmacology, pharmacokinetics, antiviral activity, and the potential for resistance and escape variants. I also summarize current progress in clinical trials and consider future research priorities.

Estimated Effectiveness of Postpartum Maternal Messenger RNA COVID-19 Vaccination Against Delta and Omicron SARS-CoV-2 Infection and Hospitalization in Infants Younger Than 6 Months.

This case-control study estimates the effectiveness of maternal postpartum messenger RNA (mRNA) COVID-19 vaccination against Delta and Omicron SARS-CoV-2 infection and hospitalization in infants younger than 6 months.

Maternal mRNA covid-19 vaccination during pregnancy and delta or omicron infection or hospital admission in infants: test negative design study.

OBJECTIVE: To estimate the effectiveness of maternal mRNA covid-19 vaccination during pregnancy against delta and omicron severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and hospital admission in infants. DESIGN: Test negative design study. SETTING: Community and hospital testing in Ontario, Canada. PARTICIPANTS: Infants younger than six months of age, born between 7 May 2021 and 31 March 2022, who were tested for SARS-CoV-2 between 7 May 2021 and 5 September 2022. INTERVENTION: Maternal mRNA covid-19 vaccination during pregnancy. MAIN OUTCOME MEASURES: Laboratory confirmed delta or omicron infection or hospital admission of the infant. Multivariable logistic regression estimated vaccine effectiveness, with adjustments for clinical and sociodemographic characteristics associated with vaccination and infection. RESULTS: 8809 infants met eligibility criteria, including 99 delta cases (4365 controls) and 1501 omicron cases (4847 controls). Infant vaccine effectiveness from two maternal doses was 95% (95% confidence interval 88% to 98%) against delta infection and 97% (73% to 100%) against infant hospital admission due to delta and 45% (37% to 53%) against omicron infection and 53% (39% to 64%) against hospital admission due to omicron. Vaccine effectiveness for three doses was 73% (61% to 80%) against omicron infection and 80% (64% to 89%) against hospital admission due to omicron. Vaccine effectiveness for two doses against infant omicron infection was highest with the second dose in the third trimester (53% (42% to 62%)) compared with the first (47% (31% to 59%)) or second (37% (24% to 47%)) trimesters. Vaccine effectiveness for two doses against infant omicron infection decreased from 57% (44% to 66%) between birth and eight weeks to 40% (21% to 54%) after 16 weeks of age. CONCLUSIONS: Maternal covid-19 vaccination with a second dose during pregnancy was highly effective against delta and moderately effective against omicron infection and hospital admission in infants during the first six months of life. A third vaccine dose bolstered protection against omicron. Effectiveness for two doses was highest with maternal vaccination in the third trimester, and effectiveness decreased in infants beyond eight weeks of age.

Nephrotoxicity of Vancomycin in Combination With Beta-Lactam Agents: Ceftolozane-Tazobactam vs Piperacillin-Tazobactam.

BACKGROUND: Vancomycin (VAN)-associated acute kidney injury (AKI) is increased when VAN is combined with certain beta-lactams (BLs) such as piperacillin-tazobactam (TZP) but has not been evaluated with ceftolozane-tazobactam (C/T). Our aim was to investigate the AKI incidence of VAN in combination with C/T (VAN/C/T) compared with VAN in combination to TZP (VAN-TZP). METHODS: We conducted a multicenter, observational, comparative study across the United States. The primary analysis was a composite outcome of AKI and risk, injury, failure, loss, end stage renal disease; Acute Kidney Injury Network; or VAN-induced nephrotoxicity according to the consensus guidelines. Multivariable logistic regression analysis was conducted to adjust for confounding variables and stratified Kaplan-Meir analysis to assess the time to nephrotoxicity between the 2 groups. RESULTS: We included VAN/C/T (n = 90) and VAN-TZP (n = 284) at an enrollment ratio of 3:1. The primary outcome occurred in 12.2% vs 25.0% in the VAN-C/T and VAN-TZP groups, respectively (P = .011). After adjusting for confounding variables, VAN-TZP was associated with increased odds of AKI compared with VAN-C/T; with an adjusted odds ratio of 3.308 (95% confidence interval, 1.560-6.993). Results of the stratified Kaplan-Meir analysis with log-rank time-to-nephrotoxicity analysis indicate that time to AKI was significantly shorter among patients who received VAN-TZP (P = .004). Cox proportional hazards analysis demonstrated that TZP was consistent with the primary analysis (P = .001). CONCLUSIONS: Collectively, our results suggest that the AKI is not likely to be related to tazobactam but rather to piperacillin, which is a component in VAN-TZP but not in VAN-C/T.