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BackgroundCarbapenem-resistant Enterobacterales (CRE) are an urgent global health threat. Inferring the dynamics of local CRE dissemination is currently limited by our inability to confidently trace the spread of resistance determinants to unrelated bacterial hosts. Whole-genome sequence comparison is useful for identifying CRE clonal transmission and outbreaks, but high-frequency horizontal gene transfer (HGT) of carbapenem resistance genes and subsequent genome rearrangement complicate tracing the local persistence and mobilization of these genes across organisms.MethodsTo overcome this limitation, we developed a new approach to identify recent HGT of large, near-identical plasmid segments across species boundaries, which also allowed us to overcome technical challenges with genome assembly. We applied this to complete and near-complete genome assemblies to examine the local spread of CRE in a systematic, prospective collection of all CRE, as well as time- and species-matched carbapenem-susceptible Enterobacterales, isolated from patients from four US hospitals over nearly 5 years.ResultsOur CRE collection comprised a diverse range of species, lineages, and carbapenem resistance mechanisms, many of which were encoded on a variety of promiscuous plasmid types. We found and quantified rearrangement, persistence, and repeated transfer of plasmid segments, including those harboring carbapenemases, between organisms over multiple years. Some plasmid segments were found to be strongly associated with specific locales, thus representing geographic signatures that make it possible to trace recent and localized HGT events. Functional analysis of these signatures revealed genes commonly found in plasmids of nosocomial pathogens, such as functions required for plasmid retention and spread, as well survival against a variety of antibiotic and antiseptics common to the hospital environment.ConclusionsCollectively, the framework we developed provides a clearer, high-resolution picture of the epidemiology of antibiotic resistance importation, spread, and persistence in patients and healthcare networks.

Background For persons with suspected pulmonary tuberculosis, the guidelines of the Centers for Disease Control and Prevention recommend collecting 3 respiratory specimens 8 to 24 hours apart for acid-fast bacilli (AFB) smear and culture, in addition to 1 nucleic acid amplification test (NAAT). However, data supporting this approach are limited. Our objective was to estimate the performance of 1, 2, or 3 AFB smears with or without NAATs to detect pulmonary tuberculosis in a low-prevalence setting. Methods We conducted a retrospective study of hospitalized persons at 8 Massachusetts acute care facilities who underwent mycobacterial culture on 1 or more respiratory specimens between July 2016 and December 2022. We evaluated percentage positivity and yield on serial AFB smears and NAATs among people with growth of Mycobacterium tuberculosis on mycobacterial cultures. Results Among 104 participants with culture-confirmed pulmonary tuberculosis, the first AFB smear was positive in 41 cases (39%). A second AFB smear was positive in 11 (22%) of the 49 cases in which it was performed. No third AFB smears were positive following 2 initial negative smears. Of 52 smear-negative cases, 36 had a NAAT performed, leading to 23 additional diagnoses. Overall sensitivity to detect tuberculosis prior to culture positivity was higher in any strategy involving 1 or 2 NAATs (74%–79%), even without AFB smears, as compared with 3 smears alone (60%). Conclusions Tuberculosis diagnostic testing with 2 AFB smears offered the same yield as 3 AFB smears while potentially reducing laboratory burden and duration of airborne infection isolation. Use of 1 or 2 NAATs increased sensitivity to detect culture-positive pulmonary tuberculosis when added to AFB smear–based diagnostic testing alone. [ABSTRACT FROM AUTHOR]

Carbapenem-resistant Enterobacteriaceae (CRE) are among the most severe threats to the antibiotic era. Multiple different species can exhibit resistance due to many different mechanisms, and many different mobile elements are capable of transferring resistance between lineages. We prospectively sampled CRE from hospitalized patients from three Boston-area hospitals, together with a collection of CRE from a single California hospital, to define the frequency and characteristics of outbreaks and determine whether there is evidence for transfer of strains within and between hospitals and the frequency with which resistance is transferred between lineages or species. We found eight species exhibiting resistance, with the majority of our sample being the sequence type 258 (ST258) lineage of Klebsiella pneumoniae There was very little evidence of extensive hospital outbreaks, but a great deal of variation in resistance mechanisms and the genomic backgrounds carrying these mechanisms. Local transmission was evident in clear phylogeographic structure between the samples from the two coasts. The most common resistance mechanisms were KPC (K. pneumoniae carbapenemases) beta-lactamases encoded by blaKPC2, blaKPC3, and blaKPC4, which were transferred between strains and species by seven distinct subgroups of the Tn4401 element. We also found evidence for previously unrecognized resistance mechanisms that produced resistance when transformed into a susceptible genomic background. The extensive variation, together with evidence of transmission beyond limited clonal outbreaks, points to multiple unsampled transmission chains throughout the continuum of care, including asymptomatic carriage and transmission of CRE. This finding suggests that to control this threat, we need an aggressive approach to surveillance and isolation.

ObjectiveTo evaluate the use of routinely collected electronic health data in Medicare claims to identify surgical site infections (SSIs) following hip arthroplasty, knee arthroplasty, and vascular surgery.DesignRetrospective cohort study.SettingFour academic hospitals that perform prospective SSI surveillance.MethodsWe developed lists of International Classification of Diseases, Ninth Revision, and Current Procedural Terminology diagnosis and procedure codes to identify potential SSIs. We then screened for these codes in Medicare claims submitted by each hospital on patients older than 65 years of age who had undergone 1 of the study procedures during 2007. Each site reviewed medical records of patients identified by either claims codes or traditional infection control surveillance to confirm SSI using Centers for Disease Control and Prevention/National Healthcare Safety Network criteria. We assessed the performance of both methods against all chart-confirmed SSIs identified by either method.ResultsClaims-based surveillance detected 1.8-4.7-fold more SSIs than traditional surveillance, including detection of all previously identified cases. For hip and vascular surgery, there was a 5-fold and 1.6-fold increase in detection of deep and organ/space infections, respectively, with no increased detection of deep and organ/space infections following knee surgery. Use of claims to trigger chart review led to confirmation of SSI in 1 out of 3 charts for hip arthroplasty, 1 out of 5 charts for knee arthroplasty, and 1 out of 2 charts for vascular surgery.ConclusionClaims-based SSI surveillance markedly increased the number of SSIs detected following hip arthroplasty, knee arthroplasty, and vascular surgery. It deserves consideration as a more effective approach to target chart reviews for identifying SSIs.

We evaluated antimicrobial exposure, discharge diagnoses, or both to identify surgical site infections (SSI). This retrospective cohort study in 13 hospitals involved weighted, random samples of records from 8,739 coronary artery bypass graft (CABG) procedures, 7,399 cesarean deliveries, and 6,175 breast procedures. We compared routine surveillance to detection through inpatient antimicrobial exposure (> 9 days for CABG, > 2 days for cesareans, and > 6 days for breast procedures), discharge diagnoses, or both. Together, all methods identified SSI after 7.4% of CABG, 5.0% of cesareans, and 2.0% of breast procedures. Antimicrobial exposure had the highest sensitivity, 88%-91%, compared with routine surveillance, 38%-64%. Diagnosis codes improved sensitivity of detection of antimicrobial exposure after cesareans. Record review confirmed SSI after 31% to 38% of procedures that met antimicrobial surveillance criteria. Sufficient antimicrobial exposure days, together with diagnosis codes for cesareans, identified more postoperative SSI than routine surveillance methods. This screening method was efficient, readily standardized, and suitable for most hospitals.

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection is poorly understood, partly because few studies have systematically applied genomic analysis to distinguish reinfection from persistent RNA detection related to initial infection. We aimed to evaluate the characteristics of SARS-CoV-2 reinfection and persistent RNA detection using independent genomic, clinical, and laboratory assessments. Methods All individuals at a large academic medical center who underwent a SARS-CoV-2 nucleic acid amplification test (NAAT) ≥45 days after an initial positive test, with both tests between 14 March and 30 December 2020, were analyzed for potential reinfection. Inclusion criteria required having ≥2 positive NAATs collected ≥45 days apart with a cycle threshold (Ct) value <35 at repeat testing. For each included subject, likelihood of reinfection was assessed by viral genomic analysis of all available specimens with a Ct value <35, structured Ct trajectory criteria, and case-by-case review by infectious diseases physicians. Results Among 1569 individuals with repeat SARS-CoV-2 testing ≥45 days after an initial positive NAAT, 65 (4%) met cohort inclusion criteria. Viral genomic analysis characterized mutations present and was successful for 14/65 (22%) subjects. Six subjects had genomically supported reinfection, and 8 subjects had genomically supported persistent RNA detection. Compared to viral genomic analysis, clinical and laboratory assessments correctly distinguished reinfection from persistent RNA detection in 12/14 (86%) subjects but missed 2/6 (33%) genomically supported reinfections. Conclusions Despite good overall concordance with viral genomic analysis, clinical and Ct value-based assessments failed to identify 33% of genomically supported reinfections. Scaling-up genomic analysis for clinical use would improve detection of SARS-CoV-2 reinfections. [ABSTRACT FROM AUTHOR]