RESUMEN
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.
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Antibacterianos , Vacunas contra la COVID-19 , COVID-19 , SARS-CoV-2 , Humanos , Anciano , Masculino , Femenino , Antibacterianos/uso terapéutico , Antibacterianos/administración & dosificación , COVID-19/prevención & control , Vacunas contra la COVID-19/administración & dosificación , Anciano de 80 o más Años , SARS-CoV-2/inmunología , Vacunación/estadística & datos numéricos , Pacientes Ambulatorios/estadística & datos numéricos , Prescripciones de Medicamentos/estadística & datos numéricos , Pautas de la Práctica en Medicina/estadística & datos numéricosRESUMEN
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.
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Regulación Emocional , Personal Militar , Estrés Psicológico , Humanos , Adolescente , Femenino , Masculino , Estrés Psicológico/psicología , Personal Militar/psicología , Emociones , Encuestas y Cuestionarios , Conducta Alimentaria/psicologíaRESUMEN
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.
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Disforia de Género , Pubertad , Humanos , Disforia de Género/psicología , Disforia de Género/terapia , Pubertad/psicología , Femenino , Niño , Masculino , Adolescente , Supresión de la PubertadRESUMEN
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.
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Lesión Renal Aguda , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Humanos , Vancomicina/efectos adversos , Antibacterianos/efectos adversos , beta-Lactamas/efectos adversos , Estudios Retrospectivos , Combinación Piperacilina y Tazobactam/efectos adversos , Tazobactam/efectos adversos , Piperacilina/efectos adversos , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/epidemiología , Lesión Renal Aguda/tratamiento farmacológico , Quimioterapia CombinadaRESUMEN
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.
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Infecciones por Virus Sincitial Respiratorio , Virus Sincitial Respiratorio Humano , Humanos , Recién Nacido , Lactante , Antivirales/uso terapéutico , Infecciones por Virus Sincitial Respiratorio/tratamiento farmacológico , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales Humanizados/farmacología , Anticuerpos Monoclonales Humanizados/uso terapéutico , Virus Sincitial Respiratorio Humano/genéticaRESUMEN
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.
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Emociones , Enfermedad Iatrogénica , Humanos , Identidad de GéneroRESUMEN
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.
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Disforia de Género , Personas Transgénero , Transexualidad , Humanos , Transexualidad/terapia , Identidad de Género , Incertidumbre , EmocionesRESUMEN
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.
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Lactancia Materna , Mujeres Embarazadas , Embarazo , Femenino , Humanos , Niño , Anciano , Ensayos Clínicos Controlados Aleatorios como Asunto , Periodo Posparto , Factores de TiempoRESUMEN
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.
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Adaptación Psicológica , Ansiedad , Trastornos de Alimentación y de la Ingestión de Alimentos , Familia Militar , Adolescente , Adulto , Femenino , Humanos , Masculino , Ansiedad/epidemiología , Actitud , Personal Militar , Aumento de Peso , Trastornos de Alimentación y de la Ingestión de Alimentos/psicología , Familia Militar/psicologíaRESUMEN
OBJECTIVES: Adolescent military-dependents experience distinct risk and protective factors, which may necessitate additional clinical considerations. In civilian youth, overweight/obesity is associated with eating, internalizing, and externalizing difficulties, with some studies reporting more difficulties among non-Hispanic White (vs. non-Hispanic Black) youth. It is unknown if these disparities exist among adolescent military-dependents, or between civilian and military-dependent youth. METHODS: Non-Hispanic Black (187 civilian, 38 military-dependent) and non-Hispanic White (205 civilian, 84 military-dependent) adolescents with overweight/obesity (14.7 ± 1.6 years; 73.9% girls; body mass index adjusted for age and sex 1.9 ± 0.5) completed a disordered-eating interview; parents completed a measure assessing their child's internalizing and externalizing difficulties. Multiple linear regressions examined parental military-status as a moderator of the relationship of participant race with eating, internalizing, and externalizing difficulties. RESULTS: White civilian youth with overweight/obesity reported significantly greater disordered-eating than their Black peers (p < .001); there were no other significant racial differences. In all regressions, parental military-status significantly moderated the association between race and each dependent variable (ps < .047). Black military-dependents (vs. civilians) reported more disordered-eating and internalizing difficulties (ps = .01). White military-dependents (vs. civilians) reported fewer externalizing difficulties (p = .01). CONCLUSIONS: Black adolescent military-dependents with overweight/obesity may experience more eating and internalizing difficulties (vs. civilians), a pattern not observed among White participants. Future work should examine if being a military-dependent and a historically marginalized racial group member accounts for these findings. Such data may inform providers of youth with intersecting minority identities.
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Trastornos de Alimentación y de la Ingestión de Alimentos , Personal Militar , Adolescente , Índice de Masa Corporal , Niño , Femenino , Humanos , Masculino , Obesidad , Sobrepeso , PadresRESUMEN
Myeloproliferative Neoplasms (MPNs) constitute a group of rare blood cancers that are characterized by mutations in bone marrow stem cells leading to the overproduction of erythrocytes, leukocytes, and thrombocytes. Mutations in calreticulin (CRT) genes may initiate MPNs, causing a novel variable polybasic stretch terminating in a common C-terminal sequence in the frameshifted CRT (CRTfs) proteins. Peptide antibodies to the mutated C-terminal are important reagents for research in the molecular mechanisms of MPNs and for the development of new diagnostic assays and therapies. In this study, eight peptide antibodies targeting the C-terminal of CRTfs were produced and characterised by modified enzyme-linked immunosorbent assays using resin-bound peptides. The antibodies reacted to two epitopes: CREACLQGWTE for SSI-HYB 385-01, 385-02, 385-03, 385-04, 385-07, 385-08, and 385-09 and CLQGWT for SSI-HYB 385-06. For the majority of antibodies, the residues Cys1, Trp9, and Glu11 were essential for reactivity. SSI-HYB 385-06, with the highest affinity, recognised recombinant CRTfs produced in yeast and the MARIMO cell line expressing CRTfs when examined in Western immunoblotting. Moreover, SSI-HYB 385-06 occasionally reacted to CRTfs from MPN patients when analysed by flow cytometry. The characterized antibodies may be used to understand the role of CRTfs in the pathogenesis of MPNs and to design and develop new diagnostic assays and therapeutic targets.
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Calreticulina , Trastornos Mieloproliferativos , Anticuerpos/metabolismo , Calreticulina/genética , Calreticulina/metabolismo , Humanos , Mutación , Trastornos Mieloproliferativos/genética , Péptidos/genética , Péptidos/metabolismoRESUMEN
PURPOSE: Evidence suggests that difficulties identifying and describing one's feelings, core components of alexithymia, are associated with attitudinal and behavioral symptoms of disordered eating; depressive symptoms also may underlie these associations. Specifically, research indicates that alexithymia is positively related to depressive symptoms, which in turn may promote both disordered-eating attitudes and certain disinhibited-eating behaviors (e.g., emotional eating). Findings also suggest that military-dependent youth with high weight may exhibit elevated depressive symptoms and disordered eating. As such, understanding associations among alexithymia, depressive symptoms, and disordered eating is particularly relevant for this vulnerable population. METHODS: We examined 149 adolescent military dependents (14.4 ± 1.6y; 55.0% female; 20.0% non-Hispanic Black; BMIz: 1.9 ± 0.4) at high risk for binge-eating disorder and obesity in adulthood. Participants completed questionnaires assessing two components of alexithymia (difficulty identifying feelings [DIF] and difficulty describing feelings [DDF]), depressive symptoms, emotional eating, and trait anxiety; disordered-eating attitudes were assessed via semi-structured interview. RESULTS: A series of regression-based models examined indirect relationships of DIF and DDF with disordered-eating attitudes and emotional eating through depressive symptoms. Bootstrapped 95% confidence intervals revealed a significant indirect path from each of the alexithymia components to disordered-eating attitudes via depressive symptoms; indirect paths to emotional eating were non-significant. CONCLUSION: Results support the salience of depressive symptoms in the relationship between alexithymia and disordered-eating attitudes. Future research should utilize prospective designs and explore direct and indirect associations of alexithymia with other disordered-eating behaviors. LEVEL OF EVIDENCE: Level III, evidence obtained from a well-designed cohort study.
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Trastorno por Atracón , Trastornos de Alimentación y de la Ingestión de Alimentos , Personal Militar , Adulto , Humanos , Adolescente , Femenino , Masculino , Trastorno por Atracón/complicaciones , Síntomas Afectivos/complicaciones , Síntomas Afectivos/diagnóstico , Depresión/complicaciones , Depresión/psicología , Estudios de Cohortes , Obesidad/epidemiología , Trastornos de Alimentación y de la Ingestión de Alimentos/complicacionesRESUMEN
In this counterpoint we critically appraise the evidence supporting therapeutic drug monitoring based on the vancomycin 24-hour area under the concentration-time curve (AUC24) for serious methicillin-resistant Staphylococcus aureus infections. We reveal methodologically weaknesses and inconsistencies in the data and suggest that, in the absence of clear and convincing evidence of benefit compared with modestly reducing trough targets, alternative strategies are more likely to result in superior safety and efficacy. These include focusing on fundamental antibiotic stewardship to limit vancomycin exposure overall, achieving earlier and more complete source control, and establishing alternative therapeutic options to vancomycin. Implementation of AUC24-based therapeutic drug monitoring will take resources away from these more promising, alternative solutions.
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Staphylococcus aureus Resistente a Meticilina , Infecciones Estafilocócicas , Adulto , Antibacterianos/uso terapéutico , Área Bajo la Curva , Niño , Monitoreo de Drogas , Humanos , Pruebas de Sensibilidad Microbiana , Infecciones Estafilocócicas/tratamiento farmacológico , Vancomicina/uso terapéuticoRESUMEN
Mounting evidence suggests that pregnant people have an elevated risk of severe COVID-19-related complications compared with their non-pregnant counterparts, underscoring the need for effective prevention and treatment strategies. However, despite progress in innovative and flexible trial designs during the COVID-19 pandemic, regressive policies excluding pregnant and breastfeeding people from biomedical research persist. Remdesivir, a broad-spectrum antiviral, was the first drug licensed for the treatment of COVID-19, based on data showing it reduced the time to recovery in hospitalized patients. Pregnant and breastfeeding people were specifically excluded from all clinical trials of remdesivir in COVID-19, but data are accumulating from post-marketing registries, compassionate use programmes and case series/reports. In this review we synthesize these data and highlight key knowledge gaps to help inform clinical decision-making about its use in pregnancy and lactation.
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Tratamiento Farmacológico de COVID-19 , Complicaciones Infecciosas del Embarazo , Adenosina Monofosfato/análogos & derivados , Alanina/análogos & derivados , Alanina/uso terapéutico , Antivirales/uso terapéutico , Lactancia Materna , Femenino , Humanos , Lactancia , Pandemias , Embarazo , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , SARS-CoV-2RESUMEN
In the modern era of rapid advances in the field of antimicrobial 'precision dosing' through therapeutic drug monitoring (TDM), there is growing pressure to adopt new technologies and expand the number of antimicrobials managed with TDM and/or the complexity of TDM methods. For many clinicians, it may seem inevitable that TDM must improve patient outcomes. However, based on the evidence to date, this concept remains largely a hypothesis. Conversely, it is plausible that focusing on TDM may distract from careful clinical monitoring of the patient for efficacy and drug-related toxicities and shift finite resources from other valuable interventions. In this article we make the case for embracing critical appraisal of precision dosing, remaining skeptical until persuaded by compelling evidence, and adopting new technologies only when they have proven their value over competing priorities; that is, we make the case for using 'conservative pharmacotherapy'.
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Antiinfecciosos , Monitoreo de Drogas , Antibacterianos/uso terapéutico , HumanosRESUMEN
The revised vancomycin guidelines recommend implementing AUC24-based therapeutic drug monitoring (TDM) using Bayesian methods in both adults and paediatrics. The motivation for this change was accumulating evidence showing aggressive dosing to achieve high troughs, as recommended in the first guidelines for adults and extrapolated to paediatrics, is associated with increased nephrotoxicity without improving clinical outcomes. AUC24-based TDM requires substantial resources that may need to be diverted from other valuable interventions. It can therefore be justified only after certain assumptions are shown to be true: (i) there is a clear relationship between vancomycin efficacy and/or toxicity and the proposed therapeutic range; and (ii) maintaining exposure within the target range with AUC24-based TDM improves clinical outcomes and/or decreases toxicity. In this review, we critically appraise the scientific basis for these assumptions. We find studies evaluating the relationship between vancomycin AUC24/MIC and efficacy in adults and children do not offer strong support for the recommended lower limit of the proposed therapeutic range (i.e. AUC24/MIC ≥400). Nephrotoxicity in children increases in a stepwise manner along the vancomycin exposure continuum but it is unclear if one parameter (AUC24 versus trough) is a superior predictor. Overall, evidence in children suggests good-to-excellent correlation between AUC24 and trough. Most importantly, there is no convincing evidence that the method of vancomycin TDM has a causal role in improving efficacy or reducing toxicity. These findings question the need to transition to resource-intensive AUC24-based TDM over retaining trough-based TDM with lower targets to minimize nephrotoxicity in paediatrics.
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Pediatría , Vancomicina , Adulto , Antibacterianos/efectos adversos , Área Bajo la Curva , Teorema de Bayes , Niño , Monitoreo de Drogas , Humanos , Pruebas de Sensibilidad Microbiana , Vancomicina/efectos adversosRESUMEN
BACKGROUND: Mounting evidence suggests the addition of a ß-lactam (BL) to daptomycin (DAP) results in synergistic in vitro activity against methicillin-resistant Staphylococcus aureus (MRSA) and bolsters the innate immune response to infection. This study's objective was to provide clinical translation to these experimental data and determine if DAP+BL combination therapy results in improved clinical outcomes compared with treatment with DAP alone in patients with MRSA bloodstream infections (BSIs). METHODS: This was a retrospective, comparative cohort study conducted at 2 academic medical centers between 2008 and 2018. Adults with MRSA BSI treated with DAP for ≥72 hours and initiated ≤5 days of culture collection were included. Patients who received a BL for ≥24 hours and initiated ≤24 hours of DAP comprised the DAP+BL group. The primary outcome was composite clinical failure (60-day all-cause mortality and/or 60-day recurrence). Analyses were adjusted for confounding using inverse probability of treatment weighting (IPTW). RESULTS: A total of 229 patients were included (72 DAP+BL and 157 DAP). In unadjusted and IPTW-adjusted analyses, DAP+BL was associated with significantly reduced odds of clinical failure (odds ratio [OR], 0.362; 95% confidence interval [CI], .164-.801; adjusted OR, 0.386; 95% CI, .175-.853). Adjusted analyses restricted to prespecified subgroups based on infection complexity and baseline health status were consistent with the main analysis. CONCLUSIONS: The addition of a BL to DAP was associated with improved clinical outcomes in patients with MRSA BSI. This study provides support to ongoing and future studies evaluating the impact of combination therapy for invasive MRSA infections.Patients treated with daptomycin plus a ß-lactam for MRSA bloodstream infection had lower odds of composite clinical failure defined as 60-day all-cause mortality and/or 60-day recurrence compared with patients treated with daptomycin monotherapy after adjusting for confounding variables using inverse probability of treatment weighting.
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Bacteriemia , Daptomicina , Staphylococcus aureus Resistente a Meticilina , Infecciones Estafilocócicas , Adulto , Antibacterianos/uso terapéutico , Bacteriemia/tratamiento farmacológico , Estudios de Cohortes , Daptomicina/uso terapéutico , Humanos , Estudios Retrospectivos , Infecciones Estafilocócicas/tratamiento farmacológico , Vancomicina , beta-Lactamas/uso terapéuticoRESUMEN
Our objective was to describe the prescribing practices, clinical characteristics, and outcomes of patients treated with ceftolozane-tazobactam (C/T) for multidrug-resistant (MDR) Gram-negative infections. This was a multicenter, retrospective, cohort study at eight U.S. medical centers (2015 to 2019). Inclusion criteria were age ≥18 years and receipt of C/T (≥72 hours) for suspected or confirmed MDR Gram-negative infection. The primary efficacy outcome, evaluated among patients with MDR Pseudomonas aeruginosa infections, was composite clinical failure, namely, 30-day all-cause mortality, 30-day recurrence, and/or failure to resolve or improve infection signs or symptoms after C/T treatment. In total, 259 patients were included, and P. aeruginosa was isolated in 236 (91.1%). The MDR and extremely drug-resistant phenotypes were detected in 95.8% and 37.7% of P. aeruginosa isolates, respectively. The most common infection source was the respiratory tract (62.9%). High-dose C/T was used in 71.2% of patients with a respiratory tract infection (RTI) overall but in only 39.6% of patients with an RTI who required C/T renal dose adjustment. In the primary efficacy population (n = 226), clinical failure and 30-day mortality occurred in 85 (37.6%) and 39 (17.3%) patients, respectively. New C/T MDR P. aeruginosa resistance was detected in 3 of 31 patients (9.7%) with follow-up cultures. Hospital-acquired infection and Acute Physiological and Chronic Health Evaluation II (APACHE II) score were independently associated with clinical failure (adjusted odds ratio [aOR], 2.472 and 95% confidence interval [CI], 1.322 to 4.625; and aOR, 1.068 and 95% CI, 1.031 to 1.106, respectively). Twenty-five (9.7%) patients experienced ≥1 adverse effect (9 acute kidney injury, 13 Clostridioides difficile infection, 1 hepatotoxicity, 2 encephalopathy, and 2 gastrointestinal intolerance). C/T addresses an unmet medical need in patients with MDR Gram-negative infections.
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Cefalosporinas/uso terapéutico , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Infecciones por Bacterias Gramnegativas/microbiología , Tazobactam/uso terapéutico , Anciano , Bacteriemia/tratamiento farmacológico , Bacteriemia/microbiología , Técnicas Bacteriológicas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neumonía Asociada al Ventilador/tratamiento farmacológico , Neumonía Asociada al Ventilador/microbiología , Pseudomonas aeruginosa/efectos de los fármacos , Pseudomonas aeruginosa/aislamiento & purificación , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Infecciones del Sistema Respiratorio/microbiología , Estudios Retrospectivos , Enfermedades Cutáneas Bacterianas/tratamiento farmacológico , Resultado del Tratamiento , Estados UnidosRESUMEN
OBJECTIVE: Parental military deployment can lead to stress in the family system due to concerns about the deployed service-member's safety and increased responsibilities for those not deployed. Parent-related stress can impact adolescent disordered eating. Given the important role that stress plays in disordered eating and obesity, it is crucial to understand the impacts of unique stressors to which vulnerable populations are exposed. METHOD: We studied 126 adolescent (14.3 ± 1.6 years; 59.5% girls; 44.4% non-Hispanic White; BMI-z, 1.91 ± .39) military dependents prior to entering an obesity and binge-eating disorder prevention trial. The Eating Disorder Examination was used to assess adolescent disordered eating. Parents self-reported their own distress and family deployment history that occurred during the adolescent's lifetime. RESULTS: Parental distress interacted with frequency of parental deployments such that for those with high parental distress, more frequent deployment was associated with greater adolescent shape and weight concerns (ß = .21, p = .012) and global eating pathology (ß = .18, p = .024). DISCUSSION: In this hypothesis-generating study, the combination of number of deployments and parental distress may be associated with disordered eating among adolescent military dependents seeking prevention of binge-eating disorder and adult obesity. If these preliminary findings are supported longitudinally, interventions to reduce parental stress related to deployment may be warranted to reduce disordered eating in adolescent dependents.