RESUMEN
INTRODUCTION: Multidrug-resistant (MDR) Gram-negative organisms cause life-threatening infections, and the incidence is rising globally. Timely therapy for these infections has a direct impact on patient survival. This study aimed to determine the impact of a multidisciplinary diagnostic and antimicrobial stewardship (AMS) workflow on time to appropriate therapy (TAP) for these infections using novel beta-lactam/beta-lactamase inhibitors. METHODS: This was a retrospective quasi-experimental study of adult patients with carbapenem-resistant Enterobacterales (CRE) and multidrug-resistant Pseudomonas (MDR PsA) infections at a 1500 bed university hospital. Included patients who received ≥ 72 hours of ceftazidime-avibactam (CZA) or ceftolozane-tazobactam (C/T) from December 2017 to December 2019. During the pre-intervention period (December 2017 to December 2018), additional susceptibilities (including CZA and C/T) were performed only upon providers' request. In 2019, reflex algorithms were implemented for faster identification and testing of all CRE/MDR PsA isolates. Results were communicated in real-time to the AMS team to tailor therapy. RESULTS: A total of 99 patients were included, with no between-group differences at baseline. The median age was 60 years and 56 (56.7%) were in intensive care at the time of culture collection. Identified organisms included 71 (71.7%) MDR PsA and 26 CRE, of which 18 were carbapenemase producers (Klebsiella-producing carbapenemase = 12, New Delhi metallo-ß-lactamase = 4, Verona integron-encoded metallo-ß-lactamase = 2). The most common infections were pneumonia (49.5%) and bacteraemia (30.3%). A decrease was found in median TAP (103 [IQR 76.0-156.0] vs. 75 [IQR 56-100] hours; P < 0.001). Median time from culture collection to final susceptibility results was shorter in the post-intervention group (123 vs. 93 hours; P < 0.001). CONCLUSION: This study identified improvement in TAP in MDR PsA and CRE infections with implementation of a reflex microbiology workflow and multidisciplinary antimicrobial stewardship initiatives.
Asunto(s)
Programas de Optimización del Uso de los Antimicrobianos , Artritis Psoriásica , Humanos , Persona de Mediana Edad , Antibacterianos/uso terapéutico , Antibacterianos/farmacología , Estudios Retrospectivos , Flujo de Trabajo , Artritis Psoriásica/tratamiento farmacológico , Ceftazidima/farmacología , Bacterias Gramnegativas , Inhibidores de beta-Lactamasas/uso terapéutico , Inhibidores de beta-Lactamasas/farmacología , beta-Lactamasas , Carbapenémicos/farmacología , Combinación de Medicamentos , Compuestos de Azabiciclo/farmacología , Pruebas de Sensibilidad Microbiana , Pseudomonas aeruginosaRESUMEN
BACKGROUND: Pseudomonas aeruginosa is a persistent and difficult-to-treat pathogen in many patients, especially those with Cystic Fibrosis (CF). Herein, we describe a longitudinal analysis of a series of multidrug resistant (MDR) P. aeruginosa isolates recovered in a 17-month period, from a young female CF patient who underwent double lung transplantation. Our goal was to understand the genetic basis of the observed resistance phenotypes, establish the genomic population diversity, and define the nature of sequence evolution over time. METHODS: Twenty-two sequential P. aeruginosa isolates were obtained within a 17-month period, before and after a double-lung transplant. At the end of the study period, antimicrobial susceptibility testing, whole genome sequencing (WGS), phylogenetic analyses and RNAseq were performed in order to understand the genetic basis of the observed resistance phenotypes, establish the genomic population diversity, and define the nature of sequence changes over time. RESULTS: The majority of isolates were resistant to almost all tested antibiotics. A phylogenetic reconstruction revealed 3 major clades representing a genotypically and phenotypically heterogeneous population. The pattern of mutation accumulation and variation of gene expression suggested that a group of closely related strains was present in the patient prior to transplantation and continued to change throughout the course of treatment. A trend toward accumulation of mutations over time was observed. Different mutations in the DNA mismatch repair gene mutL consistent with a hypermutator phenotype were observed in two clades. RNAseq performed on 12 representative isolates revealed substantial differences in the expression of genes associated with antibiotic resistance and virulence traits. CONCLUSIONS: The overwhelming current practice in the clinical laboratories setting relies on obtaining a pure culture and reporting the antibiogram from a few isolated colonies to inform therapy decisions. Our analyses revealed significant underlying genomic heterogeneity and unpredictable evolutionary patterns that were independent of prior antibiotic treatment, highlighting the need for comprehensive sampling and population-level analysis when gathering microbiological data in the context of CF P. aeruginosa chronic infection. Our findings challenge the applicability of antimicrobial stewardship programs based on single-isolate resistance profiles for the selection of antibiotic regimens in chronic infections such as CF.
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Fibrosis Quística , Infecciones por Pseudomonas , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Fibrosis Quística/complicaciones , Fibrosis Quística/tratamiento farmacológico , Fibrosis Quística/genética , Resistencia a Múltiples Medicamentos , Femenino , Humanos , Pruebas de Sensibilidad Microbiana , Filogenia , Infecciones por Pseudomonas/microbiología , Pseudomonas aeruginosaRESUMEN
Early detection of carbapenem resistance in Gram-negative (CRGN) infections can help tailor therapy sooner and prevent horizontal transmission more efficiently. This involves timely, multidisciplinary communication. To this aim, we describe our experience with implementing reflex testing algorithms for expanded antibiotic susceptibilities and molecular mechanisms of resistance in a large academic hospital.
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Antibacterianos/farmacología , Carbapenémicos/farmacología , Bacterias Gramnegativas/efectos de los fármacos , Infecciones por Bacterias Gramnegativas/diagnóstico , Algoritmos , Antibacterianos/uso terapéutico , Programas de Optimización del Uso de los Antimicrobianos , Carbapenémicos/uso terapéutico , Técnicas de Laboratorio Clínico , Farmacorresistencia Bacteriana/efectos de los fármacos , Farmacorresistencia Bacteriana/genética , Enterobacteriaceae/efectos de los fármacos , Enterobacteriaceae/genética , Enterobacteriaceae/aislamiento & purificación , Bacterias Gramnegativas/genética , Bacterias Gramnegativas/aislamiento & purificación , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Infecciones por Bacterias Gramnegativas/prevención & control , Humanos , Persona de Mediana Edad , Pseudomonas aeruginosa/efectos de los fármacos , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/aislamiento & purificaciónRESUMEN
BACKGROUND: Carbapenem-resistant Enterobacteriaceae (CRE) is an urgent public health threat globally. Limited data are available regarding the epidemiology of CRE in South Florida. We describe the epidemiology of CRE within a large public healthcare system in Miami, FL, the experience with an internal registry, active surveillance testing, and the impact of infection prevention practices. METHODS: Retrospective cohort study in 4 hospitals from a large healthcare system in Miami-Dade County, FL from 2012 to 2016. The internal registry included all CRE cases from active surveillance testing from rectal and/or tracheal screening occurring in the intensive care units of 2 of the hospitals and clinical cultures across the healthcare system. All CRE cases were tagged in the electronic medical record and automatically entered into a platform for automatic infection control surveillance. The system alerted about new cases, readmissions, and transfers. RESULTS: A total of 371 CRE cases were identified. The overall prevalence was 0.077 cases per 100 patient-admissions; the admission prevalence was 0.019 per 100 patient-admissions, and the incidence density was 1.46 cases per 10,000 patient-days. Rates increased during the first 3 years of the study and declined later to a lower level than at the beginning of study period. CONCLUSIONS: Active surveillance testing and the use of an internal registry facilitated prompt identification of cases contributing to control increasing rates of CRE by rapid implementation of infection prevention strategies.
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Enterobacteriaceae Resistentes a los Carbapenémicos , Infección Hospitalaria , Infecciones por Enterobacteriaceae , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Carbapenémicos/farmacología , Infección Hospitalaria/tratamiento farmacológico , Infección Hospitalaria/epidemiología , Atención a la Salud , Enterobacteriaceae , Infecciones por Enterobacteriaceae/tratamiento farmacológico , Infecciones por Enterobacteriaceae/epidemiología , Florida/epidemiología , Hospitales , Humanos , Sistema de Registros , Estudios Retrospectivos , beta-LactamasasRESUMEN
Infections with carbapenemase-producing carbapenem-resistant Enterobacteriaceae represent an emergent problem worldwide. Treatment of infections caused by New Delhi metallo-beta-lactamase (NDM)-harboring Enterobacteriaceae is particularly challenging as it frequently involves the use of nephrotoxic agents, which is problematic in kidney transplant recipients and non-renal transplant patients with marginal kidney function. We present two cases of urinary tract infections caused by NDM-harboring Enterobacteriaceae successfully treated with a combination of "double carbapenem" and oral fosfomycin.
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Carbapenémicos/uso terapéutico , Infecciones por Enterobacteriaceae/tratamiento farmacológico , Enterobacteriaceae/efectos de los fármacos , Fosfomicina/uso terapéutico , Trasplante de Riñón/efectos adversos , Infecciones Urinarias/tratamiento farmacológico , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Carbapenémicos/administración & dosificación , Enterobacteriaceae/enzimología , Infecciones por Enterobacteriaceae/etiología , Infecciones por Enterobacteriaceae/microbiología , Fosfomicina/administración & dosificación , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Resultado del Tratamiento , Infecciones Urinarias/complicaciones , Infecciones Urinarias/microbiología , beta-Lactamasas/biosíntesis , beta-Lactamasas/efectos de los fármacosAsunto(s)
Antibacterianos/uso terapéutico , Farmacorresistencia Bacteriana Múltiple , Intestinos/trasplante , Trasplante de Riñón , Infecciones por Klebsiella/tratamiento farmacológico , Klebsiella pneumoniae/genética , Medicina de Precisión , Adulto , Antibacterianos/farmacología , Profilaxis Antibiótica , Carbapenémicos/uso terapéutico , Farmacorresistencia Bacteriana Múltiple/genética , Ertapenem/uso terapéutico , Femenino , Fosfomicina/uso terapéutico , Humanos , Infecciones por Klebsiella/microbiología , Klebsiella pneumoniae/efectos de los fármacos , Meropenem/uso terapéutico , Complicaciones Posoperatorias/tratamiento farmacológico , Complicaciones Posoperatorias/microbiologíaRESUMEN
New antibiotic options are urgently needed for the treatment of carbapenem-resistant Enterobacteriaceae infections. We report a 64-year-old female with prolonged hospitalization following an intestinal transplant who developed refractory bacteremia due to a serine carbapenemase-producing pandrug-resistant isolate of Klebsiella pneumoniae. After failing multiple antimicrobial regimens, the patient was successfully treated.