Carbapenem-resistant Enterobacterales in Children at 18 US Health Care System Study Sites: Clinical and Molecular Epidemiology From a Prospective Multicenter Cohort Study.

Background: Carbapenem-resistant Enterobacterales (CRE) are an urgent public health threat in the United States. Objective: Describe the clinical and molecular epidemiology of CRE in a multicenter pediatric cohort. Methods: CRACKLE-1 and CRACKLE-2 are prospective cohort studies with consecutive enrollment of hospitalized patients with CRE infection or colonization between 24 December 2011 and 31 August 2017. Patients younger than age 18 years and enrolled in the CRACKLE studies were included in this analysis. Clinical data were obtained from the electronic health record. Carbapenemase genes were detected using polymerase chain reaction and whole-genome sequencing. Results: Fifty-one children were identified at 18 healthcare system study sites representing all U.S. census regions. The median age was 8 months, with 67% younger than age 2 years. Median number of days from admission to culture collection was 11. Seventy-three percent of patients had required intensive care and 41% had a history of mechanical ventilation. More than half of children had no documented comorbidities (Q1, Q3 0, 2). Sixty-seven percent previously received antibiotics during their hospitalization. The most common species isolated were Enterobacter species (41%), Klebsiella pneumoniae (27%), and Escherichia coli (20%). Carbapenemase genes were detected in 29% of isolates tested, which was lower than previously described in adults from this cohort (61%). Thirty-four patients were empirically treated on the date of culture collection, but only 6 received an antibiotic to which the CRE isolate was confirmed susceptible in vitro. Thirty-day mortality was 13.7%. Conclusions: CRE infection or colonization in U.S. children was geographically widespread, predominantly affected children younger than age 2 years, associated with significant mortality, and less commonly caused by carbapenemase-producing strains than in adults.

Accessory Genomes Drive Independent Spread of Carbapenem-Resistant Klebsiella pneumoniae Clonal Groups 258 and 307 in Houston, TX.

Carbapenem-resistant Klebsiella pneumoniae (CRKp) is an urgent public health threat. Worldwide dissemination of CRKp has been largely attributed to clonal group (CG) 258. However, recent evidence indicates the global emergence of a CRKp CG307 lineage. Houston, TX, is the first large city in the United States with detected cocirculation of both CRKp CG307 and CG258. We sought to characterize the genomic and clinical factors contributing to the parallel endemic spread of CG258 and CG307. CRKp isolates were collected as part of the prospective, Consortium on Resistance against Carbapenems in Klebsiella and other Enterobacterales 2 (CRACKLE-2) study. Hybrid short-read and long-read genome assemblies were generated from 119 CRKp isolates (95 originated from Houston hospitals). A comprehensive characterization of phylogenies, gene transfer, and plasmid content with pan-genome analysis was performed on all CRKp isolates. Plasmid mating experiments were performed with CG307 and CG258 isolates of interest. Dissection of the accessory genomes suggested independent evolution and limited horizontal gene transfer between CG307 and CG258 lineages. CG307 contained a diverse repertoire of mobile genetic elements, which were shared with other non-CG258 K. pneumoniae isolates. Three unique clades of Houston CG307 isolates clustered distinctly from other global CG307 isolates, indicating potential selective adaptation of particular CG307 lineages to their respective geographical niches. CG307 strains were often isolated from the urine of hospitalized patients, likely serving as important reservoirs for genes encoding carbapenemases and extended-spectrum ß-lactamases. Our findings suggest parallel cocirculation of high-risk lineages with potentially divergent evolution. IMPORTANCE The prevalence of carbapenem-resistant Klebsiella pneumoniae (CRKp) infections in nosocomial settings remains a public health challenge. High-risk clones such as clonal group 258 (CG258) are particularly concerning due to their association with blaKPC carriage, which can severely complicate antimicrobial treatments. There is a recent emergence of clonal group 307 (CG307) worldwide with little understanding of how this successful clone has been able to adapt while cocirculating with CG258. We provide the first evidence of potentially divergent evolution between CG258 and CG307 with limited sharing of adaptive genes. Houston, TX, is home to the largest medical center in the world, with a large influx of domestic and international patients. Thus, our unique geographical setting, where two pandemic strains of CRKp are circulating, provides an indication of how differential accessory genome content can drive stable, endemic populations of CRKp. Pan-genomic analyses such as these can reveal unique signatures of successful CRKp dissemination, such as the CG307-associated plasmid (pCG307_HTX), and provide invaluable insights into the surveillance of local carbapenem-resistant Enterobacterales (CRE) epidemiology.

Point-Counterpoint: Should Clinical Microbiology Laboratories Report Vancomycin MICs?

INTRODUCTIONWith numerous reported challenges to reporting MICs for vancomycin, clinical laboratories are attempting to identify accurate methods for MIC testing. However, the issues of poor reproducibility, accuracy, and clinical utility remain a challenge. In this Point-Counterpoint, Dr. Sara Revolinski discusses the pros of reporting MICs for vancomycin, while Dr. Christopher Doern argues for the use of caution.

Impact of an Antimicrobial Stewardship Program Pharmacist During Microbiology Rounds.

OBJECTIVES: The purpose of this study is to describe and evaluate the impact of the participation of an antimicrobial stewardship program (ASP) pharmacist in microbiology rounds at our institution. METHODS: This single-center retrospective descriptive study included inpatient and ambulatory adults (≥18 years) with a susceptibility request reviewed during microbiology rounds between October 2018 and March 2019. In October 2018, multidisciplinary telephone microbiology rounds were initiated with the medical directors of the clinical microbiology laboratory and ASP pharmacist to review susceptibility requests. Numbers and types of interventions made by an ASP pharmacist and potential benefits were recorded and analyzed. RESULTS: Sixty-seven susceptibility requests were reviewed by an ASP pharmacist, of which 83.6% were inpatient. An ASP pharmacist completed chart reviews for 92.5% of requests and contacted the requester or primary team 74.6% of the time. About half (47.8%) of susceptibility requests were approved, and only 65.2% of requests from an infectious diseases provider were approved (P = .039). The most frequent potential benefits of the intervention included preventing unnecessary susceptibility testing (47.8%), improving clinician understanding (40.3%), and preventing treatment of a culture result deemed as a contaminant (19.4%). CONCLUSIONS: ASP pharmacists are uniquely accessible and able to assist with preventing unnecessary susceptibility testing, optimizing antimicrobial therapy, and providing education to other health care professionals.

Assessing Pharmacy Students' and Preceptors' Understanding of and Exposure to Antimicrobial Stewardship Practices on Introductory Pharmacy Practice Experiences.

Antimicrobial stewardship (AMS) is commonly employed, and may be required, in multiple healthcare settings, with pharmacists playing an integral role in developing and conducting AMS techniques. Despite its prevalence, AMS is minimally taught in pharmacy school curricula. In order to increase student and preceptor understanding and application of AMS techniques, the Medical College of Wisconsin School of Pharmacy required introductory pharmacy practice students to complete three checklists and reflections of AMS techniques observed at three different practice settings: inpatient, ambulatory, and community (retail) pharmacy. Student and preceptor understanding and application of AMS techniques were then assessed via voluntary survey. Survey response rates were 43% for pharmacy students, while preceptor response rates were 27%. Student understanding and application of AMS techniques increased after completion of the AMS checklist, with the largest magnitude of change seen with antibiotic selection recommendations and guideline and policy development. Preceptor understanding was minimally impacted by the activity; however, an increase in understanding was seen for allergy assessments, antibiotic time-outs, and vaccine assessments and recommendations. AMS is an important component of pharmacy practice today. Implementation of a checklist and reflection activity within experiential education increases perceived student understanding and application of relevant AMS techniques.

Antibiotic Duration and Outcome Complications for Surgical Site Infection Prevention in Traumatic Mandible Fracture.

BACKGROUND: The appropriate duration of antibiotic therapy for surgical site infection (SSI) prevention in traumatic mandibular fracture repair is unknown, and practices vary significantly. The objective of this study was to characterize antibiotic duration and outcomes after surgical repair of traumatic mandibular fracture. METHODS: A single-center, retrospective analysis of all adult patients who underwent surgical fixation of a mandible fracture between January 2014 and December 2016 was performed. Operative service was categorized between otolaryngology (ear, nose, and throat surgery), plastic and reconstructive surgery, and oral and maxillofacial services. Primary outcomes were SSI and operative complications (including osteomyelitis, nonunion, malocclusion, and hardware infections). Differences in antibiotic prescription pattern were analyzed using analysis of variance test and Pearson chi-squared test. RESULTS: A total of 75 patients were included in the study with 33 (44.0%), 26 (34.7%), and 16 (21.3%) managed by plastic and reconstructive surgery, ear, nose, and throat surgery, and oral and maxillofacial services, respectively. Median age was 30.0 y. Median injury severity score was 4.0. There was no significant difference in hospital length of stay (P = 0.44), intensive care unit length of stay (P = 0.53), or postoperative complications (P = 0.15). None of our patients developed an SSI or postantibiotics complications. Although the total inpatient duration of antibiotics was not significantly different among services (P = 0.37), there were significant differences in outpatient duration of antibiotics (P = 0.007) and total duration of antibiotics (P = 0.003). CONCLUSIONS: Duration of antibiotics is not associated with postoperative SSI or antibiotics-related complications. The wide variation in prescribing practices and lack of any clear benefit for prolonged antibiotics provides an opportunity to explore the benefits of a standardized short course of antibiotics. LEVEL OF EVIDENCE: Therapeutic study, III.

Clostridioides difficile in transplant patients: early diagnosis, treatment, and prevention.

PURPOSE OF REVIEW: Clostridioides difficile infection is common in solid organ transplant and hematopoietic stem-cell transplant recipients and is associated with significant morbidity and mortality. These populations are also underrepresented in clinical trials, making optimal management difficult. Because of this, management of these populations follows national guideline recommendations. This review aims to summarize the recent relevant literature pertaining to the clinical management of C. difficile infection in transplant patients, with a particular focus on diagnosis, treatment, and prevention. RECENT FINDINGS: Early diagnosis of C. difficile colonization may mitigate both horizontal and vertical transmission (progression from colonization to colitis) of infection. Once diagnosed, recent literature suggests antibiotic treatment should align with that recommended by national guidelines. Fecal microbiota transplant is an emerging therapy for recurrent C. difficile infection, and recent data have demonstrated safety and efficacy. Prevention strategies including antimicrobial stewardship, probiotic administration, antibiotic administration, and bezlotoxumab may be beneficial in transplant populations, but more data are needed to confirm recent findings. SUMMARY: Studies evaluating C. difficile infection in transplant patients are only recently starting to emerge. Further research is needed to identify optimal treatment and prevention strategies, and to examine novel strategies such as microbiome manipulation.

Clostridium difficile in Immunocompromised Hosts: A Review of Epidemiology, Risk Factors, Treatment, and Prevention.

Clostridium difficile is a significant pathogen in healthcare today, impacting both hospitalized and community-based patients. Immunocompromised patients experience a high incidence of C. difficile infection, ranging from 6% to 33% in the hematology-oncology population and up to 23% among lung transplant recipients, and have a rate of 7.1-8.3 cases per 1000 patient-years in patients with human immunodeficiency virus (HIV). Recurrence of C. difficile infections among immunocompromised patients is also high, with rates up to 40% in both the hematology-oncology population and solid organ transplant recipients. This higher incidence of C. difficile infection and recurrence is believed to be secondary to frequent antimicrobial use, suppressed immune function, increased exposure to healthcare settings, and higher prevalence of C. difficile colonization. This review summarizes published data describing the epidemiology, risk factors for acquisition and infection, treatment, and prevention of C. difficile in hematology-oncology, solid organ transplant, and HIV-infected patients.

Clostridium difficile Exposures, Colonization, and the Microbiome: Implications for Prevention.

New studies have been published regarding the epidemiology of Clostridium difficile in topics such as asymptomatic C. difficile colonization, community-associated C. difficile infection, environmental contamination outside healthcare settings, animal colonization, and the interactions between C. difficile and the gut microbiome. In addition to summarizing these findings, this review offers a perspective on the potential impact of high-throughput sequencing and other potential techniques on the prevention of C. difficile.Infect Control Hosp Epidemiol 2018;39:596-602.

A multicentre stewardship initiative to decrease excessive duration of antibiotic therapy for the treatment of community-acquired pneumonia.

Background: The increased emphasis on pneumonia-related performance measures and patient outcomes has led hospitals to implement multifaceted approaches to quickly identify patients with community-acquired pneumonia (CAP), start timely therapy and reduce readmission. However, there has been minimal focus on duration of therapy (DOT) and patients often receive prolonged antibiotic courses. The IDSA and American Thoracic Society (IDSA/ATS) CAP guidelines recommend 5 days of therapy for clinically stable patients that quickly defervesce and stewardship teams are well positioned to influence prescribing practices. Objectives: Determine the impact of a prospective stewardship intervention on total antibiotic DOT and associated clinical outcomes in hospitalized patients with CAP. Methods: This multicentre, quasi-experimental study evaluated three concurrent interventions over a 6 month period to promote appropriate DOT. All centres updated institutional CAP guidelines to promote IDSA/ATS-concordant DOT, provided education and conducted daily audit and feedback with intervention to provide patient-specific DOT recommendations. Results: A total of 600 patients with CAP were included (307 in the historical control group and 293 in the stewardship intervention group). The stewardship intervention increased compliance with DOT recommendations (42% versus 5.6%, P < 0.001) and reduced the median DOT per patient (6 versus 9 days, P < 0.001). Clinical outcomes, including mortality, readmission with pneumonia, presentation to the emergency centre/clinic with pneumonia and incidence of Clostridium difficile infection within 30 days of discharge, were not different between groups. Conclusions: This multicentre evaluation of a stewardship intervention in hospitalized CAP patients reduced the total antibiotic DOT and increased guideline-concordant DOT without adversely affecting patient outcomes.

Implementation of a Clinical Decision Support Alert for the Management of Clostridium difficile Infection.

Clostridium difficile infections are common in hospitalized patients and can result in significant morbidity and mortality. It is imperative to optimize the management of C. difficile infections to help minimize disease complications. Antimicrobial stewardship techniques including guidelines, order sets and other clinical decision support functionalities may be utilized to assist with therapy optimization. We implemented a novel alert within our electronic medical record to direct providers to the C. difficile order set in order to assist with initiating therapy consistent with institutional guideline recommendations. The alert succeeded in significantly increasing order set utilization, but guideline compliance was unchanged.