RESUMO
Recent advances in antimicrobial resistance detection have spurred the development of multiple assays that can accurately detect the presence of bacterial resistance from positive blood cultures, resulting in faster institution of effective antimicrobial therapy. Despite these advances, there are limited data regarding the use of these assays in solid organ transplant (SOT) recipients and there is little guidance on how to select, implement, and interpret them in clinical practice. We describe a practical approach to the implementation and interpretation of these assays in SOT recipients using the best available data and expert opinion. These findings were part of a consensus conference sponsored by the American Society of Transplantation held on December 7, 2021 and represent the collaboration between experts in transplant infectious diseases, pharmacy, antimicrobial and diagnostic stewardship, and clinical microbiology. Areas of unmet need and recommendations for future investigation are also presented.
Assuntos
Anti-Infecciosos , Doenças Transmissíveis , Transplante de Órgãos , Sepse , Humanos , Antibacterianos/uso terapêutico , Transplante de Órgãos/efeitos adversos , Transplante de Órgãos/métodos , Farmacorresistência Bacteriana , Anti-Infecciosos/uso terapêutico , Transplantados , Sepse/tratamento farmacológicoRESUMO
The last decade has seen an explosion of advanced assays for the diagnosis of infectious diseases, yet evidence-based recommendations to inform their optimal use in the care of transplant recipients are lacking. A consensus conference sponsored by the American Society of Transplantation (AST) was convened on December 7, 2021, to define the utility of novel infectious disease diagnostics in organ transplant recipients. The conference represented a collaborative effort by experts in transplant infectious diseases, diagnostic stewardship, and clinical microbiology from centers across North America to evaluate current uses, unmet needs, and future directions for assays in 5 categories including (1) multiplex molecular assays, (2) rapid antimicrobial resistance detection methods, (3) pathogen-specific T-cell reactivity assays, (4) next-generation sequencing assays, and (5) mass spectrometry-based assays. Participants reviewed and appraised available literature, determined assay advantages and limitations, developed best practice guidance largely based on expert opinion for clinical use, and identified areas of future investigation in the setting of transplantation. In addition, attendees emphasized the need for well-designed studies to generate high-quality evidence needed to guide care, identified regulatory and financial barriers, and discussed the role of regulatory agencies in facilitating research and implementation of these assays. Findings and consensus statements are presented.
Assuntos
Transplante de Órgãos , Transplantes , Humanos , Transplantados , Consenso , Transplante de Órgãos/efeitos adversos , América do NorteRESUMO
As some of those who were lucky enough to have been mentored by Dr Francisco Marty in transplant infectious diseases, we stand with the larger medical community in mourning his untimely death and in commemorating him as a uniquely exceptional and talented physician, investigator, teacher, mentor, friend, artist, and human being.
Assuntos
Médicos , Humanos , MasculinoRESUMO
OBJECTIVES: To use a standardized tool for a multicenter assessment of antibiotic appropriateness in ICUs and identify local antibiotic stewardship improvement opportunities. DESIGN: Pilot point prevalence conducted on October 5, 2016; point prevalence survey conducted on March 1, 2017. SETTING: ICUs in 12 U.S. acute care hospitals with median bed size 563. PATIENTS: Receiving antibiotics on participating units on March 1, 2017. INTERVENTIONS: The Centers for Disease Control and Prevention tool for the Assessment of Appropriateness of Inpatient Antibiotics was made actionable by an expert antibiotic stewardship panel and implemented across hospitals. Data were collected by antibiotic stewardship program personnel at each hospital, deidentified and submitted in aggregate for benchmarking. hospital personnel identified most salient reasons for inappropriate use by category and agent. MEASUREMENTS AND MAIN RESULTS: Forty-seven ICUs participated. Most hospitals (83%) identified as teaching with median licensed ICU beds of 70. On March 1, 2017, 362 (54%) of 667 ICU patients were on antibiotics (range, 8-81 patients); of these, 112 (31%) were identified as inappropriate and administered greater than 72 hours among all 12 hospitals (range, 9-82%). Prophylactic antibiotic regimens and PICU patients demonstrated a statistically significant risk ratio of 1.76 and 1.90 for inappropriate treatment, respectively. Reasons for inappropriate use included unnecessarily broad spectrum (29%), no infection or nonbacterial syndrome (22%), and duration longer than necessary (21%). Of patients on inappropriate antibiotic therapy in surgical ICUs, a statistically significant risk ratio of 2.59 was calculated for noninfectious or nonbacterial reasons for inappropriate therapy. CONCLUSIONS: In this multicenter point prevalence study, 31% of ICU antibiotic regimens were inappropriate; prophylactic regimens were often inappropriate across different ICU types, particularly in surgical ICUs. Engaging intensivists in antibiotic stewardship program efforts is crucial to sustain the efficacy of antibiotics and quality of infectious diseases care in critical care settings. This study underscores the value of standardized assessment tools and benchmarking to be shared with local leaders for targeted antibiotic stewardship program interventions.
Assuntos
Antibacterianos/uso terapêutico , Prescrição Inadequada/prevenção & controle , Unidades de Terapia Intensiva/estatística & dados numéricos , Gestão de Antimicrobianos/métodos , Gestão de Antimicrobianos/estatística & dados numéricos , Humanos , Prescrição Inadequada/estatística & dados numéricos , Projetos Piloto , Padrões de Prática Médica/estatística & dados numéricos , Melhoria de Qualidade , Estados UnidosRESUMO
BACKGROUND: Liver tumours observed in rats exposed to micafungin led to a black box warning upon approval in Europe in 2008. Micafungin's risk for liver carcinogenicity in humans has not been investigated. We sought to describe the risk of fatal hepatocellular carcinoma (HCC) among persons who received micafungin and other parenteral antifungals (PAFs) with up to 12 years of follow-up. METHODS: We assembled a US multicentre cohort of hospitalized patients who received micafungin or other PAFs between 2005 and 2012. We used propensity score (PS) matching on patient characteristics from electronic medical records to compare rates of HCC mortality identified through the National Death Index though to the end of December 2016. We computed HRs and 95% CIs. RESULTS: A total of 40110 patients who received a PAF were identified; 6903 micafungin recipients (87% of those identified) were successfully matched to 16317 comparator PAF users. Ten incident HCC deaths, one in the micafungin-exposed group and nine among comparator PAF users, occurred in 71285 person-years of follow-up. The HCC mortality rate was 0.05 per 1000 person-years in micafungin patients and 0.17 per 1000 person-years in comparator PAF patients. The PS-matched HR for micafungin versus comparator PAF was 0.29 (95% CI 0.04-2.24). CONCLUSIONS: Both micafungin and comparator PAFs were associated with HCC mortality rates of <0.2 per 1000 person-years. Given the very low event rates, any potential risk for HCC should not play a role in clinical decisions regarding treatment with micafungin or other PAFs investigated in this study.
Assuntos
Antifúngicos/efeitos adversos , Carcinoma Hepatocelular/mortalidade , Fungemia/tratamento farmacológico , Neoplasias Hepáticas/mortalidade , Micafungina/efeitos adversos , Adulto , Idoso , Carcinoma Hepatocelular/microbiologia , Registros Eletrônicos de Saúde , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Infusões Parenterais , Neoplasias Hepáticas/microbiologia , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Estudos Retrospectivos , Fatores de Risco , Fatores de TempoAssuntos
Infecções por Citomegalovirus/diagnóstico , Dermatomiosite/complicações , Pulmão/patologia , Pneumonia Viral/diagnóstico , Anti-Inflamatórios/efeitos adversos , Infecções por Citomegalovirus/complicações , Dermatomiosite/diagnóstico , Dermatomiosite/tratamento farmacológico , Diagnóstico Diferencial , Dispneia/etiologia , Feminino , Febre/etiologia , Humanos , Hipotensão/etiologia , Hipóxia/etiologia , Hospedeiro Imunocomprometido , Pulmão/diagnóstico por imagem , Pneumopatias/diagnóstico , Pessoa de Meia-Idade , Debilidade Muscular/etiologia , Pneumonia Viral/complicações , Tomografia Computadorizada por Raios X , Tuberculose Pulmonar/diagnósticoAssuntos
Arteriopatias Oclusivas/diagnóstico por imagem , Artéria Subclávia/diagnóstico por imagem , Arterite de Takayasu/diagnóstico , Adulto , Anemia/etiologia , Arteriopatias Oclusivas/etiologia , Diagnóstico Diferencial , Eritema/etiologia , Feminino , Humanos , Infecções/diagnóstico , Angiografia por Ressonância Magnética , Dermatopatias/etiologia , Artéria Subclávia/patologia , Arterite de Takayasu/complicações , Trombocitose/etiologia , Tomografia Computadorizada por Raios X , ViagemAssuntos
Corioamnionite/microbiologia , Listeria monocytogenes/isolamento & purificação , Listeriose/diagnóstico , Complicações Infecciosas na Gravidez/diagnóstico , Adulto , Colestase/complicações , Corioamnionite/diagnóstico , Diagnóstico Diferencial , Feminino , Febre/etiologia , Humanos , Listeriose/complicações , Pulmão/diagnóstico por imagem , Pulmão/patologia , Mialgia/etiologia , Náusea/etiologia , Gravidez , Complicações Infecciosas na Gravidez/microbiologia , Terceiro Trimestre da Gravidez , Gravidez de Gêmeos , RadiografiaAssuntos
Mama/patologia , Histoplasmose/diagnóstico , Neoplasias da Mama/diagnóstico , Diagnóstico Diferencial , Feminino , Histoplasmose/complicações , Histoplasmose/patologia , Humanos , Hospedeiro Imunocomprometido , Lúpus Eritematoso Sistêmico/complicações , Mamografia , Pessoa de Meia-Idade , Nefrite/complicações , Infecções Oportunistas/diagnóstico , Dor/etiologiaRESUMO
PURPOSE OF REVIEW: Novel treatment modalities for previously fatal diseases, including newer chemotherapeutic and biologic agents and the expansion of the indications for solid organ and stem cell transplantation, have resulted in prolonged patient survival and a significant increase in the population of immunocompromised hosts (ICHs). RECENT FINDINGS: This review discusses the increasing spectrum of opportunistic infections in the ICH, the general approach for early diagnosis and treatment of pulmonary infections in this population, and the current and novel diagnostic modalities available to establish a rapid and specific microbiologic diagnosis, focusing on recent controversies and advances. SUMMARY: Early diagnosis and prompt initiation of effective therapy for infection help reduce morbidity in ICHs. Advances in diagnostic assays using nonculture-based methods, such as nucleic acid amplification, may allow for earlier targeted therapy. Invasive procedures including bronchoscopy and biopsy remain essential and should be vigorously pursued in ICHs given the broad differential diagnosis of possible pulmonary pathogens in this population, and the need to establish a specific diagnosis to allow accurate targeted therapy.
Assuntos
Hospedeiro Imunocomprometido/imunologia , Pneumopatias Fúngicas/imunologia , Infecções Oportunistas/imunologia , Pneumonia/imunologia , Transplante de Medula Óssea , Diagnóstico Diferencial , Diagnóstico Precoce , Feminino , Humanos , Pneumopatias Fúngicas/diagnóstico , Pneumopatias Fúngicas/tratamento farmacológico , Masculino , Infecções Oportunistas/diagnóstico , Infecções Oportunistas/tratamento farmacológico , Transplante de Órgãos , Seleção de Pacientes , Pneumonia/diagnóstico , Pneumonia/tratamento farmacológico , Medição de RiscoRESUMO
Objective: Screening for asymptomatic bacteriuria (ASB) is not recommended outside of patients undergoing invasive urological procedures and during pregnancy. Despite national guidelines recommending against screening for ASB, this practice is prevalent. We present outcomes from a quality-improvement intervention targeting patients undergoing cardiac artery bypass grafting surgery (CABG) at Massachusetts General Hospital, a tertiary-care hospital in Boston, Massachusetts, where preoperative testing checklists were modified to remove routine urinalysis and urine culture. This was a before-and-after intervention study. Methods: Prior to the intervention, screening for ASB was included in the preoperative check list for all patients undergoing CABG. We assessed the proportion of patients undergoing screening for ASB in the 6 months prior to and after the intervention. We estimated cost savings from averted laboratory analyses, and we evaluated changes in antibiotic prescriptions. We additionally examined the incidence of postoperative surgical-site infections (SSIs), central-line-associated bloodstream infections (CLABSIs), catheter-associated urinary tract infections (CAUTIs) and Clostridioides difficile infections (CDIs). Results: Comparing the pre- and postintervention periods, urinalyses decreased by 76.5% and urine cultures decreased by 87.0%, with an estimated cost savings of $8,090.38. There were 50% fewer antibiotic prescriptions for bacteriuria after the intervention. Conclusions: Removal of urinalysis and urine culture from preoperative checklists for cardiac surgery led to a statistically significant decrease in testing without an increase in SSIs, CLABSIs, CAUTIs, or CDI. Challenges identified included persistence of checklists in templated order sets in the electronic health record.
RESUMO
PURPOSE: Coronavirus disease-2019 (COVID-19) is associated with a wide spectrum of clinical symptoms including acute respiratory failure. Biomarkers that can predict outcomes in patients with COVID-19 can assist with patient management. The aim of this study is to evaluate whether procalcitonin (PCT) can predict clinical outcome and bacterial superinfection in patients infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). METHODS: Adult patients diagnosed with SARS-CoV-2 by nasopharyngeal PCR who were admitted to a tertiary care center in Boston, MA with SARS-CoV-2 infection between March 17 and April 30, 2020 with a baseline PCT value were studied. Patients who were presumed positive for SARS-CoV-2, who lacked PCT levels, or who had a positive urinalysis with negative cultures were excluded. Demographics, clinical and laboratory data were extracted from the electronic medical records. RESULTS: 324 patient charts were reviewed and grouped by clinical and microbiologic outcomes by day 28. Baseline PCT levels were significantly higher for patients who were treated for true bacteremia (p = 0.0005) and bacterial pneumonia (p = 0.00077) compared with the non-bacterial infection group. Baseline PCT positively correlated with the NIAID ordinal scale and survival over time. When compared to other inflammatory biomarkers, PCT showed superiority in predicting bacteremia. CONCLUSIONS: Baseline PCT levels are associated with outcome and bacterial superinfection in patients hospitalized with SARS-CoV-2.
Assuntos
Infecções Bacterianas/metabolismo , COVID-19/metabolismo , Pró-Calcitonina/metabolismo , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/metabolismo , Boston , Estudos de Casos e Controles , Feminino , Humanos , Inflamação/metabolismo , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , SARS-CoV-2/patogenicidadeRESUMO
BACKGROUND: In fall 2020, the Food and Drug Administration issued emergency use authorization for monoclonal antibody (mAb) therapies for outpatients with COVID-19. The Commonwealth of Massachusetts issued guidance outlining the use of a reserve system with a lottery for allocation of mAbs in the event of scarcity that would prioritize socially vulnerable patients for 20% of the infusion slots. The Mass General Brigham health system subsequently implemented such a reserve system. RESEARCH QUESTION: Can a reserve system be deployed successfully in a large health system in a way that promotes equitable access to mAb therapy among socially vulnerable patients with COVID-19? STUDY DESIGN AND METHODS: We conducted a retrospective review of the operation of the reserve system for allocation of mAb therapies to identify how referrals moved through the allocation process and what proportion of patients who were offered and received mAb therapies were socially vulnerable. RESULTS: Notwithstanding multiple operational challenges, the reserve system for allocation of mAb therapy worked as intended to enhance the number of socially vulnerable patients who were offered and received mAb therapy. A significantly higher proportion of patients offered mAb therapy were socially vulnerable (27.0%) than would have been the case if the infusion appointments had been allocated using a pure lottery system without a vulnerable reserve (19.8%), and a significantly higher proportion of patient who received infusions were socially vulnerable (25.3%) than would have been the case if the infusion appointments had been allocated using a pure lottery system (17.6%) INTERPRETATION: Our health system experience demonstrates that a reserve system with a lottery for tiebreaking is a viable way to distribute scarce therapeutics when enhancing access for certain groups is desirable.
Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Neutralizantes/uso terapêutico , Antivirais/uso terapêutico , Tratamento Farmacológico da COVID-19 , Acessibilidade aos Serviços de Saúde , Combinação de Medicamentos , Feminino , Humanos , Masculino , Massachusetts , Pessoa de Meia-Idade , Seleção de Pacientes , Encaminhamento e Consulta , Estudos RetrospectivosRESUMO
BACKGROUND: Remdesivir (RDV) was approved for treatment of coronavirus disease 2019 (COVID-19), in May 2020 under US Food and Drug Administration emergency use authorization (EUA). Clinical outcomes related to RDV use in hospitalized patients during the EUA period are not well described. METHODS: We conducted a retrospective study of patients who received RDV under EUA. The primary outcome was clinical recovery by day 14 as determined by an eight-category ordinal scale. Secondary outcomes included recovery and survival to day 28, and adverse events. Recovery and survival were calculated using a stratified log-rank Kaplan-Meier estimator and a Cox proportional hazards model. RESULTS: Overall, 164 patients received RDV between May and October 2020, and 153 (93.3%) had evaluable data. Most (77.1%) were hospitalized within 10 days of symptom onset, and 79.7% started RDV within 48 hours. By days 14 and 28, 96 (62.7%) and 117 patients (76.5%) met the definition of clinical recovery, respectively. Median time to recovery was 6 days [interquartile range (IQR) 4-12]. Mortality rates were 6.5% and 11.8% by days 14 and 28, respectively. Age and time to start of RDV after hospital admission were predictive of recovery and 28-day mortality. CONCLUSIONS: In this real-world experience, outcomes after 5 days of RDV therapy were comparable to those of clinical trials. Disease severity, age, and dexamethasone use influenced clinical outcomes. Time to RDV initiation appeared to affect recovery and 28-day mortality, a finding that should be explored further. Mortality rate decreased over the analysis period, which could be related to dexamethasone use and improved management of COVID-19.
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Immunomodulating therapies for COVID-19 may carry risks of reactivating latent infections in foreign-born people. We conducted a rapid review of infection-related complications of immunomodulatory therapies for COVID-19. We convened a committee of specialists to formulate a screening and management strategy for latent infections in our setting. Dexamethasone, used in severe COVID-19, is associated with reactivation of latent tuberculosis, hepatitis B, and dissemination/hyperinfection of Strongyloides species and should prompt screening and/ or empiric treatment in appropriate epidemiologic contexts. Other immunomodulators used in COVID-19 may also increase risk, including interleukin-6 receptor antagonist (e.g., tocilizumab) and kinase inhibitors. People with specific risk factors should also be screened for HIV, Chagas disease, and endemic mycoses. Racial and ethnic minorities in North America, including foreign-born persons, who receive immunomodulating agents for COVID-19 may be at risk for reactivation of latent infections. We develop a screening and management pathway for such patients.
Assuntos
COVID-19 , Tuberculose Latente , Humanos , Imunomodulação , Programas de Rastreamento , SARS-CoV-2RESUMO
BACKGROUND: Antifungal prophylaxis during induction for acute myeloid leukemia (AML) varies according to local rates of invasive fungal infections (IFIs). We evaluated fluconazole prophylaxis and no antifungal prophylaxis, as a natural interrupted time-series study to assess survival and infection complications. PATIENTS AND METHODS: We identified patients with AML ≥ 18 years old undergoing induction chemotherapy during 2 time periods: period 1, fluconazole prophylaxis from August 1, 2013 to September 30, 2015, and period 2, no prophylaxis from October 1, 2015 to December 31, 2017. The primary outcome was incidence of proven or probable IFI. Secondary outcomes included types of IFIs and 60-day overall survival (OS). IFI was defined by the 2002 European Organization for Research and Treatment of Cancer/Mycoses Study Group Consensus criteria. RESULTS: One hundred forty-four patients received induction chemotherapy over the 2 time periods. In the prophylaxis versus no-prophylaxis groups, the rate of proven or probable IFIs was 4 (5%) of 87 versus 12 (21%) of 57 (P = .01). The total number of proven IFIs was 3 (3%) of 87 versus 4 (7%) of 57 (P = .44), whereas probable IFIs were 1 (1%) of 87 versus 8 (14%) of 57 (P < .01). No difference was observed in fungemia. Incidence of IFIs was too low to detect resistance patterns. OS at 60 days was improved in with fluconazole prophylaxis compared with no prophylaxis (hazard ratio, 0.329; 95% confidence interval, 0.12-0.89; P = .028). CONCLUSION: Observed rates of proven or probable IFI were lower in the fluconazole prophylaxis group versus the no-prophylaxis group. Sixty-day OS was higher with fluconazole prophylaxis. Further study is required to evaluate how fluconazole may impart the differences in survival seen in this analysis.
Assuntos
Antifúngicos/uso terapêutico , Infecções Fúngicas Invasivas/etiologia , Leucemia Mieloide Aguda/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Incidência , Infecções Fúngicas Invasivas/patologia , Leucemia Mieloide Aguda/patologia , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
OBJECTIVE: To assess the utility of an automated, statistically-based outbreak detection system to identify clusters of hospital-acquired microorganisms. DESIGN: Multicenter retrospective cohort study. SETTING: The study included 43 hospitals using a common infection prevention surveillance system. METHODS: A space-time permutation scan statistic was applied to hospital microbiology, admission, discharge, and transfer data to identify clustering of microorganisms within hospital locations and services. Infection preventionists were asked to rate the importance of each cluster. A convenience sample of 10 hospitals also provided information about clusters previously identified through their usual surveillance methods. RESULTS: We identified 230 clusters in 43 hospitals involving Gram-positive and -negative bacteria and fungi. Half of the clusters progressed after initial detection, suggesting that early detection could trigger interventions to curtail further spread. Infection preventionists reported that they would have wanted to be alerted about 81% of these clusters. Factors associated with clusters judged to be moderately or highly concerning included high statistical significance, large size, and clusters involving Clostridioides difficile or multidrug-resistant organisms. Based on comparison data provided by the convenience sample of hospitals, only 9 (18%) of 51 clusters detected by usual surveillance met statistical significance, and of the 70 clusters not previously detected, 58 (83%) involved organisms not routinely targeted by the hospitals' surveillance programs. All infection prevention programs felt that an automated outbreak detection tool would improve their ability to detect outbreaks and streamline their work. CONCLUSIONS: Automated, statistically-based outbreak detection can increase the consistency, scope, and comprehensiveness of detecting hospital-associated transmission.
Assuntos
Infecção Hospitalar , Surtos de Doenças , Análise por Conglomerados , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/prevenção & controle , Hospitais , Humanos , Controle de Infecções , Estudos RetrospectivosAssuntos
Ceftriaxona , Sepse , Humanos , Cefepima/farmacologia , Ceftriaxona/farmacologia , Ceftriaxona/uso terapêutico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Cefalosporinas/farmacologia , Cefalosporinas/uso terapêutico , Sepse/tratamento farmacológico , Testes de Sensibilidade Microbiana , beta-LactamasesAssuntos
Antibacterianos/uso terapêutico , Economia Comportamental , Prescrição Inadequada/prevenção & controle , Pacientes Ambulatoriais/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos , Antibacterianos/efeitos adversos , Tomada de Decisão Clínica , Humanos , Prescrição Inadequada/economia , Padrões de Prática Médica/economiaRESUMO
Timely identification of outbreaks of hospital-associated infections is needed to implement control measures and minimize impact. Survey results from 33 hospitals indicated that most hospitals lacked a formal cluster definition and all targeted a very limited group of prespecified pathogens. Standardized, statistically based outbreak detection could greatly improve current practice.