Whole-Genome Sequencing Surveillance and Machine Learning of the Electronic Health Record for Enhanced Healthcare Outbreak Detection.

BACKGROUND: Most hospitals use traditional infection prevention (IP) methods for outbreak detection. We developed the Enhanced Detection System for Healthcare-Associated Transmission (EDS-HAT), which combines whole-genome sequencing (WGS) surveillance and machine learning (ML) of the electronic health record (EHR) to identify undetected outbreaks and the responsible transmission routes, respectively. METHODS: We performed WGS surveillance of healthcare-associated bacterial pathogens from November 2016 to November 2018. EHR ML was used to identify the transmission routes for WGS-detected outbreaks, which were investigated by an IP expert. Potential infections prevented were estimated and compared with traditional IP practice during the same period. RESULTS: Of 3165 isolates, there were 2752 unique patient isolates in 99 clusters involving 297 (10.8%) patient isolates identified by WGS; clusters ranged from 2-14 patients. At least 1 transmission route was detected for 65.7% of clusters. During the same time, traditional IP investigation prompted WGS for 15 suspected outbreaks involving 133 patients, for which transmission events were identified for 5 (3.8%). If EDS-HAT had been running in real time, 25-63 transmissions could have been prevented. EDS-HAT was found to be cost-saving and more effective than traditional IP practice, with overall savings of $192 408-$692 532. CONCLUSIONS: EDS-HAT detected multiple outbreaks not identified using traditional IP methods, correctly identified the transmission routes for most outbreaks, and would save the hospital substantial costs. Traditional IP practice misidentified outbreaks for which transmission did not occur. WGS surveillance combined with EHR ML has the potential to save costs and enhance patient safety.

Ampicillin-Ceftriaxone vs Ampicillin-Gentamicin for Definitive Therapy of Enterococcus faecalis Infective Endocarditis: A Propensity Score-Matched, Retrospective Cohort Analysis.

BACKGROUND: Ampicillin-ceftriaxone (AC) has emerged as an alternative antibiotic regimen for enterococcal infective endocarditis (EIE) with reduced toxicity compared with ampicillin-gentamicin (AG), but evidence regarding its success in reducing EIE-associated death in the United States is limited. METHODS: We conducted a retrospective, propensity score-matched cohort analysis of EIE patients treated with AC or AG between 2010 and 2017 at 3 hospitals in Pittsburgh, Pennsylvania. We assessed all-cause 90-day mortality as the primary outcome and in-hospital mortality, length of hospital stay, hospital readmissions, adverse events, and relapse of bacteremia as the secondary outcomes. RESULTS: A total of 190 patients with EIE (100 treated with AC and 90 with AG) were included. Ninety-day mortality was significantly higher with AC than AG (21% vs 8%; P = .02). After propensity score matching, 56 patients in each group remained for the outcomes analysis. Documented aminoglycoside resistance, presence of annular or aortic abscess, and complete pacemaker removal were the significantly different variables between the 2 matched cohorts. We observed no statistically significant difference in 90-day mortality between the 2 treatment groups (11% vs 7%; P = .55). Adverse events were more common in patients treated with AG (25 vs 39; P = .0091), and more patients in the propensity score-matched AG cohort switched antibiotic regimens than in the AC group (10% vs 49%; P < .0001). CONCLUSIONS: Patients treated with AC demonstrate no significant differences in mortality, treatment failure, or bacteremia relapse compared with AG in a propensity score-matched EIE cohort.

Outbreak of Pseudomonas aeruginosa Infections from a Contaminated Gastroscope Detected by Whole Genome Sequencing Surveillance.

BACKGROUND: Traditional methods of outbreak investigations utilize reactive whole genome sequencing (WGS) to confirm or refute the outbreak. We have implemented WGS surveillance and a machine learning (ML) algorithm for the electronic health record (EHR) to retrospectively detect previously unidentified outbreaks and to determine the responsible transmission routes. METHODS: We performed WGS surveillance to identify and characterize clusters of genetically-related Pseudomonas aeruginosa infections during a 24-month period. ML of the EHR was used to identify potential transmission routes. A manual review of the EHR was performed by an infection preventionist to determine the most likely route and results were compared to the ML algorithm. RESULTS: We identified a cluster of 6 genetically related P. aeruginosa cases that occurred during a 7-month period. The ML algorithm identified gastroscopy as a potential transmission route for 4 of the 6 patients. Manual EHR review confirmed gastroscopy as the most likely route for 5 patients. This transmission route was confirmed by identification of a genetically-related P. aeruginosa incidentally cultured from a gastroscope used on 4of the 5 patients. Three infections, 2 of which were blood stream infections, could have been prevented if the ML algorithm had been running in real-time. CONCLUSIONS: WGS surveillance combined with a ML algorithm of the EHR identified a previously undetected outbreak of gastroscope-associated P. aeruginosa infections. These results underscore the value of WGS surveillance and ML of the EHR for enhancing outbreak detection in hospitals and preventing serious infections.

Transmission Dynamics and Microevolution of Neisseria meningitidis During Carriage and Invasive Disease in High School Students in Georgia and Maryland, 2006-2007.

BACKGROUND: The mechanisms by which Neisseria meningitidis cause persistent human carriage and transition from carriage to invasive disease have not been fully elucidated. METHODS: Georgia and Maryland high school students were sampled for pharyngeal carriage of N. meningitidis during the 2006-2007 school year. A total of 321 isolates from 188 carriers and all 67 invasive disease isolates collected during the same time and from the same geographic region underwent whole-genome sequencing. Core-genome multilocus sequence typing was used to compare allelic profiles, and direct read mapping was used to study strain evolution. RESULTS: Among 188 N. meningitidis culture-positive students, 98 (52.1%) were N. meningitidis culture positive at 2 or 3 samplings. Most students who were positive at >1 sampling (98%) had persistence of a single strain. More than a third of students carried isolates that were highly genetically related to isolates from other students in the same school, and occasional transmission within the same county was also evident. The major pilin subunit gene, pilE, was the most variable gene, and no carrier had identical pilE sequences at different time points. CONCLUSION: We found strong evidence of local meningococcal transmission at both the school and county levels. Allelic variation within genes encoding bacterial surface structures, particularly pilE, was common.

Automated Multireplicate Quantification of Persistent HIV-1 Viremia in Individuals on Antiretroviral Therapy.

Clearance of low-level viremia that persists in most HIV-1-positive individuals on antiretroviral therapy (ART) is an important milestone for efforts to cure HIV-1 infection. The level of persistent viremia on ART is generally below the lower limit of quantification (LOQ) of current FDA-cleared plasma HIV-1 RNA assays (20 to 40 copies/ml) but can be quantified by reverse transcriptase PCR (RT-PCR) assays with single-copy sensitivity. Such assays require multistep manual methods, and their low throughput limits the capacity to monitor the effects of interventions on persistent viremia. Recently, S. Bakkour, X. Deng, P. Bacchetti, E. Grebe, et al. (J Clin Microbiol 58:e01400-20, 2020, https://doi.org/10.1128/JCM.01400-20), reported the use of multiple replicates and Poisson statistics to infer HIV-1 RNA concentrations below the commercial LOQ of an automated platform (Hologic Panther Aptima). Here, we evaluate the detection and quantitation of low-level viremia using the following two adaptions of the automated platform: a multireplicate strategy (9×) and a concentrated single-replicate strategy in which 5 ml of plasma is concentrated by centrifugation (1×, concentrated). We compare these new methods to a recently reported manual integrase-targeting single-copy assay version 2 (iSCA v2). Using laboratory-generated HIV-1 RNA plasma samples at known concentrations, all three methods had similar sensitivity for HIV-1 RNA detection, although iSCA v2 was most sensitive (95% LOD, 2.3 copies/ml), 9× was marginally less sensitive (95% LOD, 3.0 copies/ml), and 1×, concentrated was least sensitive (95% LOD, 3.9 copies/ml). In contrast, for clinical plasma samples, 9× had greater sensitivity than iSCA v2 (82% of samples were quantifiable compared with 62% of samples by iSCA v2). These results support 9× as an acceptable high-throughput alternative to iSCA v2 for quantifying low-level viremia in individuals on ART.

Systematic detection of horizontal gene transfer across genera among multidrug-resistant bacteria in a single hospital.

Multidrug-resistant bacteria pose a serious health threat, especially in hospitals. Horizontal gene transfer (HGT) of mobile genetic elements (MGEs) facilitates the spread of antibiotic resistance, virulence, and environmental persistence genes between nosocomial pathogens. We screened the genomes of 2173 bacterial isolates from healthcare-associated infections from a single hospital over 18 months, and identified identical nucleotide regions in bacteria belonging to distinct genera. To further resolve these shared sequences, we performed long-read sequencing on a subset of isolates and generated highly contiguous genomes. We then tracked the appearance of ten different plasmids in all 2173 genomes, and found evidence of plasmid transfer independent from bacterial transmission. Finally, we identified two instances of likely plasmid transfer within individual patients, including one plasmid that likely transferred to a second patient. This work expands our understanding of HGT in healthcare settings, and can inform efforts to limit the spread of drug-resistant pathogens in hospitals.

Bacteria are able to pass each other genes that make them invulnerable to antibiotics. This exchange of genetic material, also called horizontal gene transfer, can turn otherwise harmless bacteria into drug-resistant 'superbugs'. This is particularly problematic in hospitals, where bacteria use horizontal gene transfer to become resistant to several antibiotics and disinfectants at once, leading to serious infections that are difficult to treat. How can scientists stop bacteria from sharing genes with one another? To answer this question, first it is important to understand how horizontal gene transfer happens in the bacteria that cause infections in hospitals. To this end, Evans et al. examined the genomes of over 2000 different bacteria, collected from a hospital over 18 months, for signs of horizontal transfer. First the experiments identified the genetic material that had potentially been transferred between bacteria, also known as 'mobile genetic elements'. Next, Evans et al. examined the data of patients who had been infected with the bacteria carrying these mobile genetic elements to see whether horizontal transfer might have happened in the hospital. By combining genomics with patient data, it was determined that many of the mobile genetic elements identified were likely being shared among hospital bacteria. One of the mobile genetic elements identified was able to provide resistance to several drugs, and appeared to have been horizontally transferred between bacteria infecting two separate patients. The findings of Evans et al. show that the horizontal transfer of mobile genetic elements in hospital settings is likely frequent, but complex and difficult to study with current methods. The results of this study show how these events can now be tracked and analyzed, which may lead to new strategies for controlling the spread of antibiotic resistance.

Long-Acting Rilpivirine (RPV) Preexposure Prophylaxis Does Not Inhibit Vaginal Transmission of RPV-Resistant HIV-1 or Select for High-Frequency Drug Resistance in Humanized Mice.

As a long-acting formulation of the nonnucleoside reverse transcriptase inhibitor rilpivirine (RPV LA) has been proposed for use as preexposure prophylaxis (PrEP) and the prevalence of transmitted RPV-resistant viruses can be relatively high, we evaluated the efficacy of RPV LA to inhibit vaginal transmission of RPV-resistant HIV-1 in humanized mice. Vaginal challenges of wild-type (WT), Y181C, and Y181V HIV-1 were performed in mice left untreated or after RPV PrEP. Plasma viremia was measured for 7 to 10 weeks, and single-genome sequencing was performed on plasma HIV-1 RNA in mice infected during PrEP. RPV LA significantly prevented vaginal transmission of WT HIV-1 and Y181C HIV-1, which is 3-fold resistant to RPV. However, it did not prevent transmission of Y181V HIV-1, which has 30-fold RPV resistance in the viruses used for this study. RPV LA did delay WT HIV-1 dissemination in infected animals until genital and plasma RPV concentrations waned. Animals that became infected despite RPV LA PrEP did not acquire new RPV-resistant mutations above frequencies in untreated mice or untreated people living with HIV-1, and the mutations detected conferred low-level resistance. These data suggest that high, sustained concentrations of RPV were required to inhibit vaginal transmission of HIV-1 with little or no resistance to RPV but could not inhibit virus with high resistance. HIV-1 did not develop high-level or high-frequency RPV resistance in the majority of mice infected after RPV LA treatment. However, the impact of low-frequency RPV resistance on virologic outcome during subsequent antiretroviral therapy still is unclear.IMPORTANCE The antiretroviral drug rilpivirine was developed into a long-acting formulation (RPV LA) to improve adherence for preexposure prophylaxis (PrEP) to prevent HIV-1 transmission. A concern is that RPV LA will not inhibit transmission of drug-resistant HIV-1 and may select for drug-resistant virus. In female humanized mice, we found that RPV LA inhibited vaginal transmission of WT or 3-fold RPV-resistant HIV-1 but not virus with 30-fold RPV resistance. In animals that became infected despite RPV LA PrEP, WT HIV-1 dissemination was delayed until genital and plasma RPV concentrations waned. RPV resistance was detected at similar low frequencies in untreated and PrEP-treated mice that became infected. These results indicate the importance of maintaining RPV at a sustained threshold after virus exposure to prevent dissemination of HIV-1 after vaginal infection and low-frequency resistance mutations conferred low-level resistance, suggesting that RPV resistance is difficult to develop after HIV-1 infection during RPV LA PrEP.

Outbreak of Vancomycin-resistant Enterococcus faecium in Interventional Radiology: Detection Through Whole-genome Sequencing-based Surveillance.

BACKGROUND: Vancomycin-resistant enterococci (VRE) are a major cause of hospital-acquired infections. The risk of infection from interventional radiology (IR) procedures is not well documented. Whole-genome sequencing (WGS) surveillance of clinical bacterial isolates among hospitalized patients can identify previously unrecognized outbreaks. METHODS: We analyzed WGS surveillance data from November 2016 to November 2017 for evidence of VRE transmission. A previously unrecognized cluster of 10 genetically related VRE (Enterococcus faecium) infections was discovered. Electronic health record review identified IR procedures as a potential source. An outbreak investigation was conducted. RESULTS: Of the 10 outbreak patients, 9 had undergone an IR procedure with intravenous (IV) contrast ≤22 days before infection. In a matched case-control study, preceding IR procedure and IR procedure with contrast were associated with VRE infection (matched odds ratio [MOR], 16.72; 95% confidence interval [CI], 2.01 to 138.73; P = .009 and MOR, 39.35; 95% CI, 7.85 to infinity; P < .001, respectively). Investigation of IR practices and review of the manufacturer's training video revealed sterility breaches in contrast preparation. Our investigation also supported possible transmission from an IR technician. Infection prevention interventions were implemented, and no further IR-associated VRE transmissions have been observed. CONCLUSIONS: A prolonged outbreak of VRE infections related to IR procedures with IV contrast resulted from nonsterile preparation of injectable contrast. The fact that our VRE outbreak was discovered through WGS surveillance and the manufacturer's training video that demonstrated nonsterile technique raise the possibility that infections following invasive IR procedures may be more common than previously recognized.

Evolution of Outbreak-Causing Carbapenem-Resistant Klebsiella pneumoniae ST258 at a Tertiary Care Hospital over 8 Years.

Carbapenem-resistant Klebsiella pneumoniae (CRKP) strains belonging to sequence type 258 (ST258) are frequent causes of hospital-associated outbreaks and are a major contributor to the spread of carbapenemases. This genetic lineage emerged several decades ago and remains a major global health care challenge. In this study, genomic epidemiology was used to investigate the emergence, evolution, and persistence of ST258 carbapenem-resistant K. pneumoniae outbreak-causing lineages at a large tertiary care hospital over 8 years. A time-based phylogenetic analysis of 136 ST258 isolates demonstrated the succession of multiple genetically distinct ST258 sublineages over the 8-year period. Ongoing genomic surveillance identified the emergence and persistence of several distinct clonal ST258 populations. Patterns of multidrug resistance determinants and plasmid replicons were consistent with continued evolution and persistence of these populations. Five ST258 outbreaks were documented, including three that were caused by the same clonal lineage. Mutations in genes encoding effectors of biofilm production and iron acquisition were identified among persistent clones. Two emergent lineages bearing K. pneumoniae integrative conjugative element 10 (ICEKp10) and harboring yersiniabactin and colibactin virulence factors were identified. The results show how distinct ST258 subpopulations have evolved and persisted within the same hospital over nearly a decade.IMPORTANCE The carbapenem class of antibiotics is invaluable for the treatment of selected multidrug-resistant Gram-negative pathogens. The continued transmission of carbapenem-resistant bacteria such as ST258 K. pneumoniae is of serious global public health concern, as treatment options for these infections are limited. This genomic epidemiologic investigation traced the natural history of ST258 K. pneumoniae in a single health care setting over nearly a decade. We found that distinct ST258 subpopulations have caused both device-associated and ward-associated outbreaks, and some of these populations remain endemic within our hospital to the present day. The finding of virulence determinants among emergent ST258 clones supports the idea of convergent evolution of drug-resistant and virulent CRKP strains and highlights the need for continued surveillance, prevention, and control efforts to address emergent and evolving ST258 populations in the health care setting.

Use of online tools for antimicrobial resistance prediction by whole-genome sequencing in methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE).

OBJECTIVES: The antimicrobial resistance (AMR) crisis represents a serious threat to public health and has resulted in concentrated efforts to accelerate development of rapid molecular diagnostics for AMR. In combination with publicly available web-based AMR databases, whole-genome sequencing (WGS) offers the capacity for rapid detection of AMR genes. Here we studied the concordance between WGS-based resistance prediction and phenotypic susceptibility test results for methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) clinical isolates using publicly available tools and databases. METHODS: Clinical isolates prospectively collected at the University of Pittsburgh Medical Center between December 2016 and December 2017 underwent WGS. The AMR gene content was assessed from assembled genomes by BLASTn search of online databases. Concordance between the WGS-predicted resistance profile and phenotypic susceptibility as well as the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated for each antibiotic/organism combination, using the phenotypic results as gold standard. RESULTS: Phenotypic susceptibility testing and WGS results were available for 1242 isolate/antibiotic combinations. Overall concordance was 99.3%, with a sensitivity, specificity, PPV and NPV of 98.7% (95% CI 97.2-99.5%), 99.6% (95% CI 98.8-99.9%), 99.3% (95% CI 98.0-99.8%) and 99.2% (95% CI 98.3-99.7%), respectively. Additional identification of point mutations in housekeeping genes increased the concordance to 99.4%, sensitivity to 99.3% (95% CI 98.2-99.8%) and NPV to 99.4% (95% CI 98.4-99.8%). CONCLUSION: WGS can be used as a reliable predicator of phenotypic resistance both for MRSA and VRE using readily available online tools.

Automated data mining of the electronic health record for investigation of healthcare-associated outbreaks.

BACKGROUND: Identifying routes of transmission among hospitalized patients during a healthcare-associated outbreak can be tedious, particularly among patients with complex hospital stays and multiple exposures. Data mining of the electronic health record (EHR) has the potential to rapidly identify common exposures among patients suspected of being part of an outbreak. METHODS: We retrospectively analyzed 9 hospital outbreaks that occurred during 2011-2016 and that had previously been characterized both according to transmission route and by molecular characterization of the bacterial isolates. We determined (1) the ability of data mining of the EHR to identify the correct route of transmission, (2) how early the correct route was identified during the timeline of the outbreak, and (3) how many cases in the outbreaks could have been prevented had the system been running in real time. RESULTS: Correct routes were identified for all outbreaks at the second patient, except for one outbreak involving >1 transmission route that was detected at the eighth patient. Up to 40 or 34 infections (78% or 66% of possible preventable infections, respectively) could have been prevented if data mining had been implemented in real time, assuming the initiation of an effective intervention within 7 or 14 days of identification of the transmission route, respectively. CONCLUSIONS: Data mining of the EHR was accurate for identifying routes of transmission among patients who were part of the outbreak. Prospective validation of this approach using routine whole-genome sequencing and data mining of the EHR for both outbreak detection and route attribution is ongoing.

Statistical outbreak detection by joining medical records and pathogen similarity.

We present a statistical inference model for the detection and characterization of outbreaks of hospital associated infection. The approach combines patient exposures, determined from electronic medical records, and pathogen similarity, determined by whole-genome sequencing, to simultaneously identify probable outbreaks and their root-causes. We show how our model can be used to target isolates for whole-genome sequencing, improving outbreak detection and characterization even without comprehensive sequencing. Additionally, we demonstrate how to learn model parameters from reference data of known outbreaks. We demonstrate model performance using semi-synthetic experiments.

A Simpler and More Sensitive Single-Copy HIV-1 RNA Assay for Quantification of Persistent HIV-1 Viremia in Individuals on Suppressive Antiretroviral Therapy.

A real-time quantitative reverse transcriptase PCR assay with single-copy sensitivity targeting the integrase region of HIV-1 (integrase single-copy assay [iSCA] v1.0) has been widely used to quantify plasma viremia in individuals on antiretroviral therapy (ART). iSCA v1.0 requires the use of an ultracentrifuge, and only about half of the nucleic acid extracted from plasma is assayed for HIV-1 RNA. We sought to simplify sample processing using microcentrifugation and improve assay sensitivity by testing more than 75% of the total extracted nucleic acid for HIV-1 RNA (iSCA v2.0). We evaluated the limit of detection (LoD) of iSCA v2.0 by testing replicates of low-copy plasma HIV-1 RNA standards. By probit analysis, the 95% LoD was 1 copy of HIV-1 RNA per milliliter for a 5-ml plasma sample. To compare the sensitivity of iSCA v1.0 and v2.0, we tested plasma samples with both assays from 60 participants on ART with HIV-1 RNA below 20 cps/ml. Of the 31 samples that had no detectable HIV-1 RNA by iSCA v1.0, 17 (55%) were detectable by v2.0 with an HIV-1 RNA mean value of 3.5 cps/ml. Twenty-nine samples were detectable with both assay versions, but average values of HIV-1 RNA cps/ml were 2.7-fold higher for v2.0 than v1.0. These results support the adoption of a new, more sensitive and simpler single-copy HIV-1 RNA assay (iSCA v2.0) to quantify residual viremia on ART and to assess the impact of experimental interventions designed to decrease HIV-1 reservoirs.

Obesity, Diabetes, and the Risk of Invasive Group B Streptococcal Disease in Nonpregnant Adults in the United States.

BACKGROUND: Rates of invasive group B Streptococcus (GBS) disease, obesity, and diabetes have increased in US adults. We hypothesized that obesity would be independently associated with an increased risk of invasive GBS disease. METHODS: We identified adults with invasive GBS disease within Active Bacterial Core surveillance during 2010-2012 and used population estimates from the Behavioral Risk Factor Surveillance System to calculate invasive GBS incidence rates. We estimated relative risks (RRs) of invasive GBS using Poisson analysis with offset denominators, with obesity categorized as class I/II (body mass index [BMI] = 30-39.9 kg/m2) and class III (BMI ≥ 40.0 kg/m2). RESULTS: In multivariable analysis of 4281 cases, the adjusted RRs of invasive GBS disease were increased for obesity (class I/II: RR, 1.52; 95% confidence interval [CI], 1.14-2.02; and class III: RR, 4.87; 95% CI, 3.50-6.77; reference overweight) and diabetes (RR, 6.04; 95% CI, 4.77-7.65). The adjusted RR associated with class III obesity was 3-fold among persons with diabetes (95% CI, 1.38-6.61) and nearly 9-fold among persons without diabetes (95% CI, 6.41-12.46), compared with overweight. The adjusted RRs associated with diabetes varied by age and BMI, with the highest RR in young populations without obesity. Population attributable risks of invasive GBS disease were 27.2% for obesity and 40.1% for diabetes. CONCLUSIONS: Obesity and diabetes were associated with substantially increased risk of infection from invasive GBS. Given the population attributable risks of obesity and diabetes, interventions that reduce the prevalence of these conditions would likely reduce the burden of invasive GBS infection.

Can improving patient hand hygiene impact Clostridium difficile infection events at an academic medical center?

BACKGROUND: Hand hygiene plays an important role in the prevention of Clostridium difficile (CD) infection (CDI). Patient hand hygiene (PHH) may be a potentially underused preventative measure for CDI. Patient mobility and acuity along with a lack of education present obstacles to PHH for the hospitalized patient. Surveys of patients at our institution showed a need for increased PHH opportunities. The objective of this study was to increase PHH and to examine if PHH affected CDI at our hospital. METHODS: A biphasic, quasi-experimental study was performed to increase PHH through education for staff and to provide education, assistance, and opportunities to the patient for hand cleaning. PHH practice was assessed by patient surveys and analyzed by χ2 test. PHH effect on CDI was determined by following health care facility-onset CD laboratory-identified events data analyzed by National Healthcare Safety Network standardized infection ratios (SIRs). RESULTS: PHH opportunities improved significantly (P < .0001) after staff and patient education. CD SIRs deceased significantly for 6 months (P ≤ .05) after the PHH intervention. CONCLUSIONS: PHH opportunities can be increased by providing education and opportunities for patients to clean their hands. PHH should be considered a relevant preventative measure for CDI in hospitalized patients.

Risk Factors for Surgical Site Infections Following Neurosurgical Spinal Fusion Operations: A Case Control Study.

OBJECTIVE To determine risk factors for the development of surgical site infections (SSIs) in neurosurgery patients undergoing spinal fusion. DESIGN Retrospective case-control study. SETTING Large, academic, quaternary care center. PATIENTS The study population included all neurosurgery patients who underwent spinal fusion between August 1, 2009, and August 31, 2013. Cases were defined as patients in the study cohort who developed an SSI. Controls were patients in the study cohort who did not develop an SSI. METHODS To achieve 80% power with an ability to detect an odds ratio (OR) of 2, we performed an unmatched case-control study with equal numbers of cases and controls. RESULTS During the study period, 5,473 spinal fusion procedures were performed by neurosurgeons in our hospital. With 161 SSIs recorded during the study period, the incidence of SSIs associated with these procedures was 2.94%. While anterior surgical approach was found to be a protective factor (OR, 0.20; 95% confidence interval [CI], 0.08-0.52), duration of procedure (OR, 1.58; 95% CI, 1.29-1.93), American Society of Anesthesiologists score of 3 or 4 (OR, 1.79; 95% CI, 1.00-3.18), and hospitalization within the prior 30 days (OR, 5.8; 95% CI, 1.37-24.57) were found in multivariate analysis to be independent predictors of SSI following spinal fusion. Prior methicillin-resistant Staphylococcus aureus (MRSA) nares colonization was highly associated with odds 20 times higher of SSI following spinal fusion (OR, 20.30; 95% CI, 4.64-8.78). CONCLUSIONS In additional to nonmodifiable risk factors, prior colonization with MRSA is a modifiable risk factor very strongly associated with development of SSI following spinal fusion. Infect Control Hosp Epidemiol 2017;38:348-352.

Safety and utilization of peripherally inserted central catheters versus midline catheters at a large academic medical center.

BACKGROUND: Peripherally inserted central catheters (PICCs) are a commonly used central intravenous (IV) access device, which can be associated with significant complications. Midline catheters (MCs) are peripheral IV access devices that may reduce the need for central lines and hence decrease central line-associated bloodstream infections. The objective of this study is to compare the utilization and safety of PICCs and MCs. METHODS: This was a retrospective study comparing the use and outcomes of PICCs and MCs at a large academic medical center between January and May 2015. Data were collected using electronic medical records and IV team insertion data. Statistical software was used for analysis. RESULTS: A total of 206 PICCs and 200 MCs were inserted in 367 patients within the study duration. Patients with MCs were more likely to have complications than those with PICCs (19.5% vs 5.8%, P < .0001). CONCLUSIONS: MCs were associated with a higher risk of non-life-threatening complications versus PICCs, which showed fewer but more serious complications, including bacteremia. The decision to move toward more use of MCs is not without risk. Institutions should continue to review the utilization and safety data of IV catheter use to determine the most appropriate use of these devices.

Infection and readmission rate of cardiac implantable electronic device insertions: An observational single center study.

BACKGROUND: Infection is one of the most serious complications following surgical placement of cardiac implantable electronic devices (CIEDs). Infection prevention efforts are necessary in reducing CIED infectious outcomes. These devices, however, are commonly inserted in higher risk patients, which may explain the ongoing risk of surgical site infection (SSI) in this population. The rates of CIED infection and utilization vary widely in the literature. The definitions of infection may also vary between clinical definitions and the National Healthcare Safety Network (NHSN) criteria. METHODS: The primary objective of this study was to review patient data to identify risk factors for infection and readmission after CIED placement at an academic medical center. The secondary objectives were to compare the rates of SSI identified by NHSN criteria compared to that obtained by applying clinical infection definitions. RESULTS: The overall rate of infection (SSI) was 1.9%, which was identical in both the clinical definition and NHSN reported data. The 30 day readmission rate and the 90 day readmission rate were 12.7% and 25.6% respectively with the most readmissions related to the patients' underlying medical conditions. A lower ejection fraction (EF) was identified as an independent risk factor for readmission, inpatient procedures, smoking and device infection were also significantly associated with readmission after CIED insertion.

Genomic Epidemiology of an Endoscope-Associated Outbreak of Klebsiella pneumoniae Carbapenemase (KPC)-Producing K. pneumoniae.

Increased incidence of infections due to Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae (KPC-Kp) was noted among patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) at a single hospital. An epidemiologic investigation identified KPC-Kp and non-KPC-producing, extended-spectrum ß-lactamase (ESBL)-producing Kp in cultures from 2 endoscopes. Genotyping was performed on patient and endoscope isolates to characterize the microbial genomics of the outbreak. Genetic similarity of 51 Kp isolates from 37 patients and 3 endoscopes was assessed by pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST). Five patient and 2 endoscope isolates underwent whole genome sequencing (WGS). Two KPC-encoding plasmids were characterized by single molecule, real-time sequencing. Plasmid diversity was assessed by endonuclease digestion. Genomic and epidemiologic data were used in conjunction to investigate the outbreak source. Two clusters of Kp patient isolates were genetically related to endoscope isolates by PFGE. A subset of patient isolates were collected post-ERCP, suggesting ERCP endoscopes as a possible source. A phylogeny of 7 Kp genomes from patient and endoscope isolates supported ERCP as a potential source of transmission. Differences in gene content defined 5 ST258 subclades and identified 2 of the subclades as outbreak-associated. A novel KPC-encoding plasmid, pKp28 helped define and track one endoscope-associated ST258 subclade. WGS demonstrated high genetic relatedness of patient and ERCP endoscope isolates suggesting ERCP-associated transmission of ST258 KPC-Kp. Gene and plasmid content discriminated the outbreak from endemic ST258 populations and assisted with the molecular epidemiologic investigation of an extended KPC-Kp outbreak.

Clinical Appraisal of Fosfomycin in the Era of Antimicrobial Resistance.

Fosfomycin is recommended as one of the first-line agents for treatment of urinary tract infections (UTIs) in the latest guidelines endorsed by the Infectious Diseases Society of America (IDSA) and the European Society for Clinical Microbiology and Infectious Diseases (ESCMID). We evaluated the use of fosfomycin among inpatients at a tertiary care hospital between 2009 and 2013. UTI cases were defined using physician diagnosis and the National Healthcare Safety Network (NHSN) surveillance definitions. The number of patients treated with fosfomycin increased from none in 2009 to 391 in 2013. Among 537 patients who received fosfomycin for any indication during this period, UTI was the most common indication (74%), followed by asymptomatic bacteriuria (10%). All except 19 patients received a single dose of fosfomycin. Escherichia coli was the most common organism involved (52%). For 119 patients with UTIs, after exclusion of those with negative urine culture results, negative urinalysis results, receipt of additional agents, or indeterminate clinical outcomes, the clinical success rate at 48 h was 74.8%. Of 89 patients who met the criteria for NHSN-defined UTIs, 89.9% had successful outcomes. Recurrent infections occurred in 4.3% of cases, and mild adverse events were observed in 2.0%. All 100 randomly selected extended-spectrum ß-lactamase (ESBL)-producing E. coli clinical isolates from this period were susceptible to fosfomycin. In conclusion, the use of fosfomycin has increased substantially since implementation of the updated guidelines at this hospital. Fosfomycin was used mainly for the treatment of physician-diagnosed UTIs, and the clinical outcomes were generally favorable. Fosfomycin maintained activity against E. coli despite the increased use of the agent.