Person:

Hooper, David

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.

ABSTRACT Staphylococcus aureus is a leading cause of both community- and hospital-acquired infections that are increasingly antibiotic resistant. The emergence of S. aureus resistance to even last-line antibiotics heightens the need for the development of new drugs with novel targets. We generated a highly saturated transposon insertion mutant library in the genome of S. aureus and used Tn-seq analysis to probe the entire genome, with unprecedented resolution and sensitivity, for genes of importance in infection. We further identified genes contributing to fitness in various infected compartments (blood and ocular fluids) and compared them to genes required for growth in rich medium. This resulted in the identification of 426 genes that were important for S. aureus fitness during growth in infection models, including 71 genes that could be considered essential for survival specifically during infection. These findings highlight novel as well as previously known genes encoding virulence traits and metabolic pathways important for S. aureus proliferation at sites of infection, which may represent new therapeutic targets.

Background: No published systematic reviews have assessed the natural history of colonization with methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant Enterococcus (VRE). Time to clearance of colonization has important implications for patient care and infection control policy. Methods: We performed parallel searches in OVID Medline for studies that reported the time to documented clearance of MRSA and VRE colonization in the absence of treatment, published between January 1990 and July 2012. Results: For MRSA, we screened 982 articles, identified 16 eligible studies (13 observational studies and 3 randomized controlled trials), for a total of 1,804 non-duplicated subjects. For VRE, we screened 284 articles, identified 13 eligible studies (12 observational studies and 1 randomized controlled trial), for a total of 1,936 non-duplicated subjects. Studies reported varying definitions of clearance of colonization; no study reported time of initial colonization. Studies varied in the frequency of sampling, assays used for sampling, and follow-up period. The median duration of total follow-up was 38 weeks for MRSA and 25 weeks for VRE. Based on pooled analyses, the model-estimated median time to clearance was 88 weeks after documented colonization for MRSA-colonized patients and 26 weeks for VRE-colonized patients. In a secondary analysis, clearance rates for MRSA and VRE were compared by restricting the duration of follow-up for the MRSA studies to the maximum observed time point for VRE studies (43 weeks). With this restriction, the model-fitted median time to documented clearance for MRSA would occur at 41 weeks after documented colonization, demonstrating the sensitivity of the pooled estimate to length of study follow-up. Conclusions: Few available studies report the natural history of MRSA and VRE colonization. Lack of a consistent definition of clearance, uncertainty regarding the time of initial colonization, variation in frequency of sampling for persistent colonization, assays employed and variation in duration of follow-up are limitations of the existing published literature. The heterogeneity of study characteristics limits interpretation of pooled estimates of time to clearance, however, studies included in this review suggest an increase in documented clearance over time, a result which is sensitive to duration of follow-up.

The quinolone class of antimicrobial agents is one of most widely used classes of antimicrobial agents in outpatient and inpatient treatment. However, quinolone resistance in gram-positive and gram-negative bacteria has emerged and increased globally. This resistance limits the usefulness of quinolones in clinical practice. The review summarizes mechanisms of quinolone resistance and its epidemiology and implications in the most common clinical settings, urinary tract infections, respiratory tract infections, intraabdominal infections, skin and skin structure infections, and sexually transmitted diseases.

Abstract Background: Criteria defining Ventilator Associated Events (VAEs) are objective and often available in the electronic health record (EHR) data. The use of ventilation data extracted directly from the patient’s bedside monitor to allow for real-time surveillance, however, has not been previously incorporated into electronic surveillance approaches. Here we describe validation of a system that can detect and report on VAEs hospital-wide autonomously and in real-time. Methods: We developed a secure informatics hardware and software platform to identify VAEs autonomously using streaming data. The automated process included 1) archiving and analysis of bedside physiologic monitor data to detect increases in positive end-expiratory pressure (PEEP) or FiO2 settings; 2) real-time querying of EHR data for leukopenia or leukocytosis and concurrent antibiotic initiation; and 3) retrieval and interpretation of microbiology reports for the presence of respiratory pathogens. The algorithm was validated on two 3-month periods in 2015 and 2016 as follows: 1) autonomous surveillance (AS) generated detections of three VAE subclasses: VAC, IVAC, and PVAP; 2) manual surveillance (MS) by Infection Control (IC) staff independently performed standard surveillance based on chart review, 3) senior IC staff adjudicated the gold standard for cases of AS-MS discordance. The sensitivity (Se), specificity (Sp), and positive predictive value (PPV) of the algorithm are reported. Results: The number of ventilated patients, ventilator days, and events were: 1,591/9,407/3,014. In cases with complete data, AS detected 66 VAE events identified by MS; AS detected 32 VAEs missed by MS; no MS-identified events were missed by AS. The Se, Sp, and PPV of AS and MS were: 91%/100%/100%, and 61%/100%/83%, respectively. Clinical surveillance case reports generated by AS enabled visual interpretation (figure). Conclusion: We developed a surveillance tool directly streaming bedside physiologic monitor and EHR data including ventilator settings, laboratory results, and microbiology reports, to apply the CDC’s VAE definitions on source data. This resulted in an accurate, objective, and efficient method for real-time hospital-wide surveillance. Disclosures All authors: No reported disclosures.

Abstract Background: Discordance between in vitro susceptibility and empiric antibiotic therapy is inextricably linked to antibiotic resistance and decreased survival in bloodstream infections (BSI). However, its prevalence, patient- and hospital-level risk factors, and impact on outcome in a large cohort and across different pathogens remain unclear. Methods: We examined in vitro susceptibility interpretations for bacterial BSI and corresponding antibiotic therapy among inpatient encounters across 156 hospitals from 2000 to 2014 in the Cerner Healthfacts database. Discordance was defined as nonsusceptibility to initial therapy administered from 2 days before pathogen isolation to 1 day before final susceptibility reporting. Discordance prevalence was compared across taxa; risk factors and its association with in-hospital mortality were evaluated by logistic regression. Adjusted odds ratios (aOR) were estimated for pathogen-, patient- and facility-level factors. Results: Of 33,161 unique encounters with BSIs, 4,219 (13%) at 123 hospitals met criteria for discordant antibiotic therapy, ranging from 3% for pneumococci to 55% for E. faecium. Discordance was higher in recent years (2010–2014 vs. 2005–2009) and was associated with older age, lower baseline SOFA score, urinary (vs. abdominal) source and hospital-onset BSI, as well as ≥500-bed, Midwestern, non-teaching, and rural hospitals. Discordant antibiotic therapy increased the risk of death [aOR = 1.3 [95% CI 1.1–1.4]). Among Gram-negative taxa, discordant therapy increased risk of mortality associated with Enterobacteriaceae (aOR = 1.3 [1.0–1.6]) and non-fermenters (aOR = 1.7 [1.1–2.5]). Among Gram-positive taxa, risk of mortality from discordant therapy was significantly higher for S. aureus (aOR = 1.3 [1.1–1.6]) but unchanged for streptococcal or enterococcal BSIs. Conclusion: The prevalence of discordant antibiotic therapy displayed extensive taxon-level variability and was associated with patient and institutional factors. Discordance detrimentally impacted survival in Gram-negative and S. aureus BSIs. Understanding reasons behind observed differences in discordance risk and their impact on outcomes could inform stewardship efforts and guidelines for empiric therapy in sepsis. Disclosures All authors: No reported disclosures.

The global spread and continued evolution of SARS-CoV-2 has driven an unprecedented surge in viral genomic surveillance. Amplicon-based sequencing methods provide a sensitive, low-cost and rapid approach but suffer a high potential for contamination, which can undermine laboratory processes and results. This challenge will only increase with expanding global production of sequences by diverse laboratories for epidemiological and clinical interpretation, as well in genomic surveillance in future outbreaks. We present SDSI+AmpSeq, an approach which uses synthetic DNA spike-ins (SDSIs) to track samples and detect inter-sample contamination through the sequencing workflow. Applying SDSIs to the ARTIC Consortium’s amplicon design, we demonstrate their utility and efficiency in a real-time investigation of a suspected hospital cluster of SARS-CoV-2 cases and across thousands of diagnostic samples at multiple laboratories. We establish that SDSI+AmpSeq provides increased confidence in genomic data by detecting and in some cases correcting for relatively common, yet previously unobserved modes of error without impacting genome recovery.