Publications by authors named "Ebbing Lautenbach"

227 Publications

Impact of donor multidrug-resistant organisms on solid organ transplant recipient outcomes.

Transpl Infect Dis 2021 Dec 30:e13783. Epub 2021 Dec 30.

Division of Infectious Diseases, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Background: The impact of donor colonization or infection with multidrug-resistant organisms (MDROs) on solid organ transplant (SOT) recipient outcomes remains uncertain. We thus evaluated the association between donor MDROs and risk of posttransplant infection, graft failure, and mortality.

Methods: A multicenter retrospective cohort study was performed. All SOT recipients with a local deceased donor were included. The cohort was divided into three exposure groups: recipients whose donors had (1) an MDRO, (2) a non-MDRO bacterial or candidal organism, or (3) no growth on cultures. The primary outcomes were (1) bacterial or invasive candidal infection within 3 months and (2) graft failure or death within 12 months posttransplant. Mixed effect multivariable frailty models were developed to evaluate each association.

Results: Of 658 total SOT recipients, 93 (14%) had a donor with an MDRO, 477 (73%) had a donor with a non-MDRO organism, and 88 (13%) had a donor with no organisms on culture. On multivariable analyses, donor MDROs were associated with a significantly increased hazard of infection compared to those with negative donor cultures (adjust hazard ratio [aHR] 1.63, 95% CI 1.01-2.62, p = .04) but were not associated with graft failure or death (aHR 0.45, 95% CI 0.15-1.36, p = .16).

Conclusions: MDROs on donor culture increase the risk of early posttransplant infection but do not appear to affect long-term graft or recipient survival, suggesting organ donors with MDROs on culture may be safely utilized. Future studies aimed at reducing early posttransplant infections associated with donor MDROs are needed.
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http://dx.doi.org/10.1111/tid.13783DOI Listing
December 2021

Spatial and temporal effects on severe acute respiratory coronavirus virus 2 (SARS-CoV-2) contamination of the healthcare environment.

Infect Control Hosp Epidemiol 2021 Dec 27:1-6. Epub 2021 Dec 27.

Division of Infectious Diseases, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.

Background: The spatial and temporal extent of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) environmental contamination has not been precisely defined. We sought to elucidate contamination of different surface types and how contamination changes over time.

Methods: We sampled surfaces longitudinally within COVID-19 patient rooms, performed quantitative RT-PCR for the detection of SARS-CoV-2 RNA, and modeled distance, time, and severity of illness on the probability of detecting SARS-CoV-2 using a mixed-effects binomial model.

Results: The probability of detecting SARS-CoV-2 RNA in a patient room did not vary with distance. However, we found that surface type predicted probability of detection, with floors and high-touch surfaces having the highest probability of detection: floors (odds ratio [OR], 67.8; 95% credible interval [CrI], 36.3-131) and high-touch elevated surfaces (OR, 7.39; 95% CrI, 4.31-13.1). Increased surface contamination was observed in room where patients required high-flow oxygen, positive airway pressure, or mechanical ventilation (OR, 1.6; 95% CrI, 1.03-2.53). The probability of elevated surface contamination decayed with prolonged hospitalization, but the probability of floor detection increased with the duration of the local pandemic wave.

Conclusions: Distance from a patient's bed did not predict SARS-CoV-2 RNA deposition in patient rooms, but surface type, severity of illness, and time from local pandemic wave predicted surface deposition.
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http://dx.doi.org/10.1017/ice.2021.530DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8755533PMC
December 2021

Severe acute respiratory coronavirus virus 2 (SARS-CoV-2) surface contamination in staff common areas and impact on healthcare worker infection: Prospective surveillance during the coronavirus disease 2019 (COVID-19) pandemic.

Infect Control Hosp Epidemiol 2021 Nov 15:1-4. Epub 2021 Nov 15.

Division of Infectious Diseases, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.

We prospectively surveyed SARS-CoV-2 RNA contamination in staff common areas within an acute-care hospital. An increasing prevalence of surface contamination was detected over time. Adjusting for patient census or community incidence of coronavirus disease 2019 (COVID-19), the proportion of contaminated surfaces did not predict healthcare worker COVID-19 infection on study units.
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http://dx.doi.org/10.1017/ice.2021.468DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8649357PMC
November 2021

Real-world clinical outcomes of meropenem/vaborbactam for treatment of carbapenem-resistant Enterobacterales infections.

J Glob Antimicrob Resist 2021 12 12;27:299-302. Epub 2021 Nov 12.

Division of Infectious Diseases, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA; Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.

Objectives: Real-world data regarding the effectiveness of meropenem/vaborbactam (MVB) in the treatment of carbapenem-resistant Enterobacterales (CRE) infections remain limited. In this retrospective case series, we describe the outcomes of patients who received MVB for serious CRE infections.

Methods: This study included adult patients with MVB-susceptible CRE infection who received ≥48 h of MVB. Clinical and microbiological outcomes were ascertained via chart review.

Results: Among 15 patients with CRE infection who were treated with MVB, 9 (60.0%) had a positive clinical response. Among five patients with CRE bone and joint infection, three (60.0%) experienced a positive clinical response. One patient developed a microbiologically confirmed recurrent CRE infection and one patient developed Clostridioides difficile infection.

Conclusion: MVB was well tolerated and effective for the majority of patients in this case series.
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http://dx.doi.org/10.1016/j.jgar.2021.09.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8712410PMC
December 2021

Healthcare microenvironments define multidrug-resistant organism persistence.

Infect Control Hosp Epidemiol 2021 Aug 24:1-7. Epub 2021 Aug 24.

Division of Infectious Diseases, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.

Background: Multidrug-resistant organisms (MDROs) colonizing the healthcare environment have been shown to contribute to risk for healthcare-associated infections (HAIs), with adverse effects on patient morbidity and mortality. We sought to determine how bacterial contamination and persistent MDRO colonization of the healthcare environment are related to the position of patients and wastewater sites.

Methods: We performed a prospective cohort study, enrolling 51 hospital rooms at the time of admitting a patient with an eligible MDRO in the prior 30 days. We performed systematic sampling and MDRO culture of rooms, as well as 16S rRNA sequencing to define the environmental microbiome in a subset of samples.

Results: The probability of detecting resistant gram-negative organisms, including Enterobacterales, Acinetobacter spp, and Pseudomonas spp, increased with distance from the patient. In contrast, Clostridioides difficile and methicillin-resistant Staphylococcus aureus were more likely to be detected close to the patient. Resistant Pseudomonas spp and S. aureus were enriched in these hot spots despite broad deposition of 16S rRNA gene sequences assigned to the same genera, suggesting modifiable factors that permit the persistence of these MDROs.

Conclusions: MDRO hot spots can be defined by distance from the patient and from wastewater reservoirs. Evaluating how MDROs are enriched relative to bacterial DNA deposition helps to identify healthcare micro-environments and suggests how targeted environmental cleaning or design approaches could prevent MDRO persistence and reduce infection risk.
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http://dx.doi.org/10.1017/ice.2021.323DOI Listing
August 2021

Respiratory microbiome disruption and risk for ventilator-associated lower respiratory tract infection.

Clin Infect Dis 2021 Aug 7. Epub 2021 Aug 7.

Division of Infectious Diseases, Department of Medicine; , Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Background: Ventilator-associated lower respiratory tract infection (VA-LRTI) is a common among critically ill patients and has been associated with increased morbidity and mortality. In acute critical illness, respiratory microbiome disruption indices (MDIs) have been shown to predict risk for VA-LRTI, but their utility beyond the first days of critical illness is unknown. We sought to characterize how MDIs previously shown to predict VA-LRTI at initiation of mechanical ventilation change with prolonged mechanical ventilation, and if they remain associated with VA-LRTI risk.

Methods: We developed a cohort of 83 subjects admitted to a long-term acute care hospital due to their prolonged dependence on mechanical ventilation; performed dense, longitudinal sampling of the lower respiratory tract, collecting 1066 specimens; and characterized the lower respiratory microbiome by 16S rRNA sequencing as well as total bacterial abundance by 16S rRNA qPCR.

Results: Cross-sectional MDIs, including low Shannon diversity and high total bacterial abundance, were associated with risk for VA-LRTI, but the associations had wide posterior credible intervals. Persistent lower respiratory microbiome disruption showed a more robust association with VA-LRTI risk, with each day of (base e) Shannon diversity < 2.0 associated with a VA-LRTI odds ratio of 1.36 (95% credible interval 1.10 to 1.72). The observed association was consistent across multiple clinical definitions of VA-LRTI.

Conclusions: Cross-sectional MDIs have limited ability to discriminate VA-LRTI risk during prolonged mechanical ventilation, but persistent lower respiratory tract microbiome disruption, best characterized by consecutive days with low Shannon diversity, may identify a population at high risk for infection and may help target infection prevention interventions.
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http://dx.doi.org/10.1093/cid/ciab678DOI Listing
August 2021

Advancing Diagnostic Stewardship for Healthcare Associated Infections, Antibiotic Resistance, and Sepsis.

Clin Infect Dis 2021 Aug 4. Epub 2021 Aug 4.

Division of Healthcare Quality Promotion, Centers for Disease Control and Prevention, Atlanta, GA.

Diagnostic stewardship means ordering the right tests, for the right patient at the right time to inform optimal clinical care. Diagnostic stewardship is an integral part of antibiotic stewardship efforts to optimize antibiotic use and improve patient outcomes, including reductions in antibiotic resistance, and treatment of sepsis. CDC's Division of Healthcare Quality Promotion (DHQP) hosted a meeting on improving patient safety through diagnostic stewardship with a focus on the use of the laboratory. The meeting identified emerging issues in the field of diagnostic stewardship, raised awareness of these issues among stakeholders, and discussed strategies and interventions to address the issues-all with an emphasis on improved outcomes and patient safety. This white paper summarizes the key takeaways of the meeting including needs for diagnostic stewardship implementation, promising future avenues for diagnostic stewardship implementation, and areas of needed research.
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http://dx.doi.org/10.1093/cid/ciab672DOI Listing
August 2021

Improving Outpatient Antibiotic Prescribing for Respiratory Tract Infections in Primary Care; a Stepped-Wedge Cluster Randomized Trial.

Clin Infect Dis 2021 Jul 2. Epub 2021 Jul 2.

Division of Infectious Diseases, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.

Background: Inappropriate antibiotic prescribing is common in primary care (PC), particularly for respiratory tract diagnoses (RTDs). However, the optimal approach for improving prescribing remains unknown.

Methods: We conducted a stepped-wedge study in PC practices within a health system to assess the impact of a provider-targeted intervention on antibiotic prescribing for RTDs. RTDs were grouped into tiers based on appropriateness of antibiotic prescribing: tier 1 (almost always indicated), tier 2 (may be indicated), and tier 3 (rarely indicated). Providers received education on appropriate RTD prescribing followed by monthly peer comparison feedback on antibiotic prescribing for (1) all tiers and (2) tier 3 RTDs. Chi-squared testing was used to compare the proportion of visits with antibiotic prescriptions before and during the intervention. Mixed-effects multivariable logistic regression analysis was performed to assess the association between the intervention and antibiotic prescribing.

Results: Across 30 PC practices and 185,755 total visits, overall antibiotic prescribing was reduced with the intervention, from 35.2% to 23.0% of visits (p<0.001). In multivariable analysis, the intervention was associated with a reduced odds of antibiotic prescription for tiers 2 (OR 0.57; 95% CI 0.52 - 0.62) and 3 (OR 0.57; 95% CI 0.53 - 0.61), but not for tier 1 (OR 0.98; 95% CI 0.83 - 1.16).

Conclusion: A provider-focused intervention reduced overall antibiotic prescribing for RTDs without affecting prescribing for infections that likely require antibiotics. Future research should examine the sustainability of such interventions, potential unintended adverse effects on patient health or satisfaction, and provider perceptions and acceptability.
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http://dx.doi.org/10.1093/cid/ciab602DOI Listing
July 2021

Quantifying the Impact of Nasopharyngeal Specimen Quality on Severe Acute Respiratory Syndrome Coronavirus 2 Test Performance.

Open Forum Infect Dis 2021 Jun 12;8(6):ofab235. Epub 2021 May 12.

Division of Infectious Diseases, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse-transcription polymerase chain reaction (RT-PCR) cycle threshold (Ct) has been used to estimate quantitative viral load, with the goal of targeting isolation precautions for individuals with coronavirus disease 2019 (COVID-19) and guiding public health interventions. However, variability in specimen quality can alter the Ct values obtained from SARS-CoV-2 clinical assays. We sought to define how variable nasopharyngeal (NP) swab quality impacts clinical SARS-CoV-2 test sensitivity.

Methods: We performed amplification of a human gene target (β-actin) in parallel with a clinical RT-PCR targeting the SARS-CoV-2 gene for 1282 NP specimens collected from patients with clinical concern for COVID-19. We evaluated the relationship between NP specimen quality, characterized by late Ct values for the human gene target β-actin Ct, and the probability of SARS-CoV-2 detection via logistic regression, as well as the linear relationship between SARS-CoV-2 and β-actin Ct.

Results: Low-quality NP swabs are less likely to detect SARS-CoV-2 (odds ratio, 0.607 [95% credible interval {CrI}, .487-.753]). We observed a positive linear relationship between SARS-CoV-2 and β-actin Ct values (slope, 0.181 [95% CrI, .097-.264]), consistent with a reduction in detection of 0.181 cycles for each additional cycle of the β-actin target. COVID-19 disease severity was not associated with β-actin Ct values.

Conclusions: Variability in NP specimen quality significantly impacts the performance of clinical SARS-CoV-2 assays, and caution should be taken when interpreting quantitative SARS-CoV-2 Ct results. If unrecognized, low-quality NP specimens, which are characterized by a low level of amplifiable human DNA target, may limit the successful application of SARS-CoV-2 Ct values to direct infection control and public health interventions.
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http://dx.doi.org/10.1093/ofid/ofab235DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8136075PMC
June 2021

Development and validation of antibiotic stewardship metrics for outpatient respiratory tract diagnoses and association of provider characteristics with inappropriate prescribing.

Infect Control Hosp Epidemiol 2022 Jan 2;43(1):56-63. Epub 2021 Jun 2.

Division of Infectious Diseases, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania.

Objective: To determine metrics and provider characteristics associated with inappropriate antibiotic prescribing for respiratory tract diagnoses (RTDs).

Design: Retrospective cohort study.

Setting: Primary care practices in a university health system.

Participants: Patients seen by an attending physician or advanced practice provider (APP) at their primary care office visit with International Classification of Disease, Tenth Revision, Clinical Modification (ICD-10-CM)-coded RTDs.

Methods: Medical records were reviewed for 1,200 randomly selected office visits in which an antibiotic was prescribed to determine appropriateness. Based on this gold standard, metrics and provider characteristics associated with inappropriate antibiotic prescribing were determined.

Results: Overall, 69% of antibiotics were inappropriate. Metrics utilizing prespecified RTDs most strongly associated with inappropriate prescribing were (1) proportion prescribing for RTDs for which antibiotics are almost never required (eg, bronchitis) and (2) proportion prescribing for any RTD. Provider characteristics associated with inappropriate antibiotic prescribing were APP versus physician (72% vs 58%; P = .02), family medicine versus internal medicine (76% vs 63%; P = .01), board certification 1997 or later versus board certification before 1997 (75% vs 63%; P = .02), nonteaching versus teaching practice (73% vs 51%; P < .01), and nonurban vs urban practice (77% vs 57%; P < .01).

Conclusions: Metrics utilizing proportion prescribing for RTDs for which antibiotics are almost never required and proportion prescribing for any RTD were most strongly associated with inappropriate prescribing. APPs and clinicians with family medicine training, with board certification 1997 or later, and who worked in nonteaching or nonurban practices had higher proportions of inappropriate prescribing. These findings could inform design of interventions to improve prescribing and could represent an efficient way to track inappropriate prescribing.
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http://dx.doi.org/10.1017/ice.2021.44DOI Listing
January 2022

Antibiotic Utilization in Deceased Organ Donors.

Clin Infect Dis 2021 10;73(7):1284-1287

Division of Infectious Diseases, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Antibiotic use in deceased organ donors has not been previously described. In a retrospective cohort of 440 donors, we found 427 (97%) received at least one antibiotic course, 312 (71%) received broad-spectrum antibiotics, and 61 (14%) received potentially redundant antibiotics during their terminal hospitalization, suggesting a need for stewardship.
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http://dx.doi.org/10.1093/cid/ciab463DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8561239PMC
October 2021

Patient and Microbial Genomic Factors Associated with Carbapenem-Resistant Klebsiella pneumoniae Extraintestinal Colonization and Infection.

mSystems 2021 Mar 16;6(2). Epub 2021 Mar 16.

Department of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, USA

Carbapenem-resistant (CRKP) is a critical-priority antibiotic resistance threat that has emerged over the past several decades, spread across the globe, and accumulated resistance to last-line antibiotic agents. While CRKP infections are associated with high mortality, only a subset of patients acquiring CRKP extraintestinal colonization will develop clinical infection. Here, we sought to ascertain the relative importance of patient characteristics and CRKP genetic background in determining patient risk of infection. Machine learning models classifying colonization versus infection were built using whole-genome sequences and clinical metadata from a comprehensive set of 331 CRKP extraintestinal isolates collected across 21 long-term acute-care hospitals over the course of a year. Model performance was evaluated based on area under the receiver operating characteristic curve (AUROC) on held-out test data. We found that patient and genomic features were predictive of clinical CRKP infection to similar extents (AUROC interquartile ranges [IQRs]: patient = 0.59 to 0.68, genomic = 0.55 to 0.61, combined = 0.62 to 0.68). Patient predictors of infection included the presence of indwelling devices, kidney disease, and length of stay. Genomic predictors of infection included presence of the ICEKp10 mobile genetic element carrying the yersiniabactin iron acquisition system and disruption of an O-antigen biosynthetic gene in a sublineage of the epidemic ST258 clone. Altered O-antigen biosynthesis increased association with the respiratory tract, and subsequent ICEKp10 acquisition was associated with increased virulence. These results highlight the potential of integrated models including both patient and microbial features to provide a more holistic understanding of patient clinical trajectories and ongoing within-lineage pathogen adaptation. Multidrug-resistant organisms, such as carbapenem-resistant (CRKP), colonize alarmingly large fractions of patients in regions of endemicity, but only a subset of patients develop life-threatening infections. While patient characteristics influence risk for infection, the relative contribution of microbial genetic background to patient risk remains unclear. We used machine learning to determine whether patient and/or microbial characteristics can discriminate between CRKP extraintestinal colonization and infection across multiple health care facilities and found that both patient and microbial factors were predictive. Examination of informative microbial genetic features revealed variation within the ST258 epidemic lineage that was associated with respiratory tract colonization and increased rates of infection. These findings indicate that circulating genetic variation within a highly prevalent epidemic lineage of CRKP influences patient clinical trajectories. In addition, this work supports the need for future studies examining the microbial genetic determinants of clinical outcomes in human populations, as well as epidemiologic and experimental follow-ups of identified features to discern generalizability and biological mechanisms.
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http://dx.doi.org/10.1128/mSystems.00177-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8546970PMC
March 2021

Clinical prediction tool for extended-spectrum beta-lactamase-producing enterobacterales as the etiology of a bloodstream infection in solid organ transplant recipients.

Transpl Infect Dis 2021 Aug 25;23(4):e13599. Epub 2021 Mar 25.

Division of Infectious Diseases, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.

Background: Multidrug-resistant Gram-negative bacterial infections are increasingly common among solid organ transplant (SOT) recipients, leading to challenges in the selection of empiric antimicrobial therapy. We sought to develop a clinical tool to predict which SOT recipients are at high risk for extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales (EB) bloodstream infection (BSI).

Methods: A multicenter case-control study was performed. The source population included SOT recipients with an EB BSI between 2005 and 2018. Cases were those with ESBL-EB BSI; controls were those with non-ESBL EB BSI. The population was subdivided into derivation and validation cohorts based on study site. The predictive tool was developed in the derivation cohort through iterative multivariable logistic regression analyses that maximized the area under the receiver-operating curve (AUC). External validity was assessed using the validation cohort.

Results: A total of 897 SOT recipients with an EB BSI were included, of which 539 were assigned to the derivation cohort (135, 25% ESBL-EB) and 358 to the validation cohort (221, 62% ESBL-EB). Using multivariable analyses, the most parsimonious model that was predictive of ESBL-EB BSI consisted of 10 variables, which fell into four clinical categories: prior colonization or infection with EB organisms, recent antimicrobial exposures, severity of preceding illness, and immunosuppressive regimen. This model achieved an AUC of 0.81 in the derivation cohort and 0.68 in the validation cohort.

Conclusions: Though further refinements are needed in additional populations, this tool shows promise for guiding empiric therapy for SOT recipients with EB BSI.
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http://dx.doi.org/10.1111/tid.13599DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8443704PMC
August 2021

Attributable Cost of Healthcare-Associated Methicillin-Resistant Staphylococcus aureus Infection in a Long-term Care Center.

Clin Infect Dis 2021 01;72(Suppl 1):S27-S33

IDEAS Center, Veterans Affairs Salt Lake City Health Care System, Salt Lake City, Utah USA.

Background: Studies have shown that healthcare-associated infections (HAIs) due to methicillin-resistant Staphylococcus aureus (MRSA) can lead to substantial healthcare costs in acute care settings. However, little is known regarding the consequences of these infections on patients in long-term care centers (LTCCs). The purpose of this study was to estimate the attributable cost of MRSA HAIs in LTCCs within the Department of Veterans Affairs (VA).

Methods: We performed a retrospective cohort study of patients admitted to VA LTCCs between 1 January 2009 and 30 September 2015. MRSA HAIs were defined as a positive clinical culture at least 48 hours after LTCC admission so as to exclude community-acquired infections. Positive cultures were further classified by site (sterile or nonsterile). We used multivariable generalized linear models and 2-part models to compare the LTCC and acute care costs between patients with and without an MRSA HAI.

Results: In our primary analysis, there was no difference in LTCC costs between patients with and without a MRSA HAI. There was, however, a significant increase in the odds of being transferred to an acute care facility (odds ratio, 4.40 [95% confidence interval {CI}, 3.40-5.67]) and in acute care costs ($9711 [95% CI, $6961-$12 462]).

Conclusions: Our findings of high cost and increased risk of transfer from LTCC to acute care are important because they highlight the substantial clinical and economic impact of MRSA infections in this population.
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http://dx.doi.org/10.1093/cid/ciaa1582DOI Listing
January 2021

Impact of Nasopharyngeal Specimen Quality on SARS-CoV-2 Test Sensitivity.

medRxiv 2020 Dec 11. Epub 2020 Dec 11.

Background: The SARS-CoV-2 reverse-transcription polymerase chain reaction (RT-PCR) cycle of threshold (Ct) has been used to estimate quantitative viral load, with the goal of targeting isolation precautions for individuals with COVID-19 and guiding public health interventions. However, variability in specimen quality can alter the Ct values obtained from SARS-CoV-2 clinical assays. We sought to define how variable nasopharyngeal (NP) swab quality impacts clinical SARS-CoV-2 test sensitivity.

Methods: We performed amplification of a human gene target (β-actin) in parallel with a clinical RT-PCR targeting the SARS-CoV-2 gene for 1311 NP specimens collected from patients with clinical concern for COVID-19. We evaluated the relationship between NP specimen quality, characterized by high Ct values for the human gene target β-actin Ct, and the probability of SARS-CoV-2 detection via logistic regression, as well as the linear relationship between SARS-CoV-2 and β-actin Ct.

Results: Low quality NP swabs are less likely to detect SARS-CoV-2 (odds ratio 0.654, 95%CI 0.523 to 0.802). We observed a positive linear relationship between SARS-CoV-2 and β-actin Ct values (slope 0.169, 95%CI 0.092 to 0.247). COVID-19 disease severity was not associated with β-actin Ct values.

Conclusions: Variability in NP specimen quality accounts for significant differences in the sensitivity of clinical SARS-CoV-2 assays. If unrecognized, low quality NP specimens, which are characterized by a low level of amplifiable human DNA target, may limit the application of SARS-CoV-2 Ct values to direct infection control and public health interventions.
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http://dx.doi.org/10.1101/2020.12.09.20246520DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7743104PMC
December 2020

Leveraging Existing and Soon-to-Be-Available Novel Diagnostics for Optimizing Outpatient Antibiotic Stewardship in Patients With Respiratory Tract Infections.

Clin Infect Dis 2021 06;72(12):e1115-e1121

Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Respiratory tract infections (RTIs) drive many outpatient encounters and, despite being predominantly viral, are associated with high rates of antibiotic prescriptions. With rising antibacterial resistance, optimization of prescribing of antibiotics in outpatients with RTIs is a critical need. Fortunately, this challenge arises at a time of increasing availability of novel RTI diagnostics to help discern which patients have bacterial infections warranting treatment. Effective implementation of antibiotic stewardship is needed, but optimal approaches for ambulatory settings are unknown. Future research needs are reviewed in this summary of a research summit convened by the Infectious Diseases Society of America in the fall of 2019.
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http://dx.doi.org/10.1093/cid/ciaa1815DOI Listing
June 2021

Pediatric research priorities in healthcare-associated infections and antimicrobial stewardship.

Infect Control Hosp Epidemiol 2021 05 26;42(5):519-522. Epub 2020 Nov 26.

Division of Infectious Diseases and Center for Pediatric Clinical Effectiveness, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.

Objective: To develop a pediatric research agenda focused on pediatric healthcare-associated infections and antimicrobial stewardship topics that will yield the highest impact on child health.

Participants: The study included 26 geographically diverse adult and pediatric infectious diseases clinicians with expertise in healthcare-associated infection prevention and/or antimicrobial stewardship (topic identification and ranking of priorities), as well as members of the Division of Healthcare Quality and Promotion at the Centers for Disease Control and Prevention (topic identification).

Methods: Using a modified Delphi approach, expert recommendations were generated through an iterative process for identifying pediatric research priorities in healthcare associated infection prevention and antimicrobial stewardship. The multistep, 7-month process included a literature review, interactive teleconferences, web-based surveys, and 2 in-person meetings.

Results: A final list of 12 high-priority research topics were generated in the 2 domains. High-priority healthcare-associated infection topics included judicious testing for Clostridioides difficile infection, chlorhexidine (CHG) bathing, measuring and preventing hospital-onset bloodstream infection rates, surgical site infection prevention, surveillance and prevention of multidrug resistant gram-negative rod infections. Antimicrobial stewardship topics included β-lactam allergy de-labeling, judicious use of perioperative antibiotics, intravenous to oral conversion of antimicrobial therapy, developing a patient-level "harm index" for antibiotic exposure, and benchmarking and or peer comparison of antibiotic use for common inpatient conditions.

Conclusions: We identified 6 healthcare-associated infection topics and 6 antimicrobial stewardship topics as potentially high-impact targets for pediatric research.
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http://dx.doi.org/10.1017/ice.2020.1267DOI Listing
May 2021

Impact of rapid diagnostics with antimicrobial stewardship support for children with positive blood cultures: A quasi-experimental study with time trend analysis.

Infect Control Hosp Epidemiol 2020 08 23;41(8):883-890. Epub 2020 Jun 23.

Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.

Objective: Evaluate the clinical impact of the implementation of VERIGENE gram-positive blood culture testing (BC-GP) coupled with antimicrobial stewardship result notification for children with positive blood cultures.

Design: Quasi-experimental study.

Setting: Quaternary children's hospital.

Patients: Hospitalized children aged 0-21 years with positive blood culture events 1 year before and 1 year after implementation of BC-GP testing.

Methods: The primary outcome was time to optimal antibiotic therapy for positive blood cultures, defined as receiving definitive therapy without unnecessary antibiotics (pathogens) or no antibiotics (contaminants). Secondary outcomes were time to effective therapy, time to definitive therapy, and time to stopping vancomycin, length of stay, and 30-day mortality. Time-to-therapy outcomes before and after the intervention were compared using Cox regression models and interrupted time series analyses, adjusting for patient characteristics and trends over time. Gram-negative events were included as a nonequivalent dependent variable.

Results: We included 264 preintervention events (191 gram-positive, 73 gram-negative) and 257 postintervention events (168 gram-positive, 89 gram-negative). The median age was 2.9 years (interquartile range, 0.3-10.1), and 418 pediatric patients (80.2%) had ≥1 complex chronic condition. For gram-positive isolates, implementation of BC-GP testing was associated with an immediate reduction in time to optimal therapy and time to stopping vancomycin for both analyses. BC-GP testing was associated with decreased time to definitive therapy in interrupted time series analysis but not Cox modeling. No such changes were observed for gram-negative isolates. No changes in time to effective therapy, length of stay, or mortality were associated with BC-GP.

Conclusions: The implementation of BC-GP testing coupled with antimicrobial stewardship result notification was associated with decreased time to optimal therapy and time to stopping vancomycin for hospitalized children with gram-positive blood culture isolates.
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http://dx.doi.org/10.1017/ice.2020.191DOI Listing
August 2020

Prescriber perceptions of fluoroquinolones, extended-spectrum cephalosporins, and infection.

Infect Control Hosp Epidemiol 2020 08 29;41(8):914-920. Epub 2020 May 29.

Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.

Background: Fluoroquinolones (FQs) and extended-spectrum cephalosporins (ESCs) are associated with higher risk of Clostridioides difficile infection (CDI). Decreasing the unnecessary use of FQs and ESCs is a goal of antimicrobial stewardship. Understanding how prescribers perceive the risks and benefits of FQs and ESCs is needed.

Methods: We conducted interviews with clinicians from 4 hospitals. Interviews elicited respondent perceptions about the risk of ESCs, FQs, and CDI. Interviews were audio recorded, transcribed, and analyzed using a flexible coding approach.

Results: Interviews were conducted with 64 respondents (38 physicians, 7 nurses, 6 advance practice providers, and 13 pharmacists). ESCs and FQs were perceived to have many benefits, including infrequent dosing, breadth of coverage, and greater patient adherence after hospital discharge. Prescribers stated that it was easy to make decisions about these drugs, so they were especially appealing to use in the context of time pressures. They described having difficulty discontinuing these drugs when prescribed by others due to inertia and fear. Prescribers were skeptical about targeting specific drugs as a stewardship approach and felt that the risk of a negative outcome from under treatment of a suspected bacterial infection was a higher priority than the prevention of CDI.

Conclusions: Prescribers in this study perceived many advantages to using ESCs and FQs, especially under conditions of time pressure and uncertainty. In making decisions about these drugs, prescribers balance risk and benefit, and they believed that the risk of CDI was acceptable in compared with the risk of undertreatment.
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http://dx.doi.org/10.1017/ice.2020.183DOI Listing
August 2020

Assessing an intervention to improve the safety of automatic stop orders for inpatient antimicrobials.

Infect Prev Pract 2020 Jun 30;2(2):100062. Epub 2020 Apr 30.

Division of Infectious Diseases, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.

Background: Automatic stop orders (ASOs) for antimicrobials have been recommended as a component of antimicrobial stewardship programs, but may result in unintentional treatment interruption due to failure of providers to re-order an antimicrobial medication. We examined the impact of a multifaceted intervention designed to reduce the potential harms of interrupting antimicrobial treatment due to ASOs.

Methods: An intervention was implemented that included pharmacist review of expiring antimicrobials as well as provider education to encourage use of a long-term antimicrobial order set for commonly used prophylactic antimicrobials. Pharmacist interventions and antimicrobial re-ordering was recorded. Percent of missed doses of a commonly used prophylactic antimicrobial, single strength co-trimoxazole, was compared pre- and post-intervention using a chi-squared test.

Results: From November 1, 2015 to November 30, 2016, there were 401 individual pharmacist interventions for antimicrobial ASOs, resulting in 295 instances of antimicrobial re-ordering. The total percent of presumed missed single strength co-trimoxazole doses was reduced from 8.4% to 6.2% post-intervention (<0.001).

Conclusions: This study found that a targeted intervention was associated with a reduction in unintended antimicrobial treatment interruption related to ASOs.
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http://dx.doi.org/10.1016/j.infpip.2020.100062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8336312PMC
June 2020

Risk Factors for Extended-Spectrum β-lactamase-Producing Enterobacterales Bloodstream Infection Among Solid-Organ Transplant Recipients.

Clin Infect Dis 2021 03;72(6):953-960

GlaxoSmithKline, Rockville, Maryland, USA.

Background: Approximately 40% of all Enterobacterales (EB) bloodstream infections (BSIs) among solid organ transplant recipients (SOTRs) are due to extended-spectrum β-lactamase (ESBL)-producing organisms, but risk factors for such infections remain ill defined in this population. We sought to determine the risk factors for ESBL-EB BSIs among SOTRs.

Methods: A multicenter case-control study was performed. All SOTRs with an EB BSI at the Hospital of the University of Pennsylvania and University of Maryland Medical Center between 1 January 2007 and 30 June 2018 and at The Johns Hopkins Hospital between 1 January 2005 and 31 December 2015 were included. Cases were those with an ESBL-EB BSI. Controls were those with a non-ESBL-EB BSI. Multivariable logistic regression was performed to determine risk factors for ESBL-EB BSI.

Results: There were 988 episodes of EB BSI, of which 395 (40%) were due to an ESBL-EB. On multivariable analysis, the independent risk factors for ESBL-EB BSI included: ESBL-EB on prior culture (aOR, 12.75; 95% CI, 3.23-50.33; P < .001), a corticosteroid-containing immunosuppression regimen (aOR 1.30; 95% CI 1.03-1.65; P = .030), acute rejection treated with corticosteroids (aOR 1.18; 95% CI 1.16-1.19; P < .001), and exposure to third-generation cephalosporins (aOR 1.95; 95% CI 1.48-2.57; P < .001), echinocandins (aOR 1.61; 95% CI 1.08-2.40; P = .020), and trimethoprim-sulfamethoxazole (aOR 1.35; 95% CI 1.10-1.64; P = .003).

Conclusions: We identified several novel risk factors that are uniquely important to the SOTR population, including exposure to trimethoprim-sulfamethoxazole and corticosteroid-containing immunosuppressive regimens. Further studies exploring these associations and testing interventions aimed at these modifiable risk factors among SOTRs are needed.
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http://dx.doi.org/10.1093/cid/ciaa190DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7958726PMC
March 2021

Impact of deceased donor multidrug-resistant bacterial organisms on organ utilization.

Am J Transplant 2020 09 12;20(9):2559-2566. Epub 2020 Mar 12.

Division of Infectious Diseases, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

The extent to which donor multidrug-resistant organisms (MDROs) affect organ utilization remains unclear. We performed a retrospective cohort study at 4 transplant centers between 2015 and 2016 to evaluate this question. All deceased donors who donated at least one organ were included. Exposed donors had at least one MDRO on culture. Unexposed donors had no MDRO-positive cultures. Only cultures obtained during the donor's terminal hospitalization were evaluated. Multivariable regression was used to determine the association between donor MDRO and (1) number of organs transplanted per donor and (2) the match run at which each organ was accepted. Subsequently, we restricted the analysis to donors with MDR-Gram-negative (GN) organisms. Of 440 total donors, 29 (7%) donors grew MDROs and 7 (2%) grew MDR-GNs. There was no significant association between donor MDRO and either measure of organ utilization. However, donor MDR-GNs were associated with a significant reduction in the number of organs transplanted per donor (incidence rate ratio 0.43, 95% confidence interval [CI] 0.39-0.48, P < .01), and organs were accepted significantly further down the match list (relative count 5.08, 95% CI 1.64-15.68, P = .01). Though donor MDR-GNs were infrequent in our study, their growing prevalence could meaningfully reduce the donor pool over time.
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http://dx.doi.org/10.1111/ajt.15830DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7483863PMC
September 2020

Comparing Propensity Score Methods Versus Traditional Regression Analysis for the Evaluation of Observational Data: A Case Study Evaluating the Treatment of Gram-Negative Bloodstream Infections.

Clin Infect Dis 2020 12;71(9):e497-e505

The Johns Hopkins University School of Medicine, Department of Pediatrics, Baltimore, Maryland, USA.

Background: Propensity score methods are increasingly being used in the infectious diseases literature to estimate causal effects from observational data. However, there remains a general gap in understanding among clinicians on how to critically review observational studies that have incorporated these analytic techniques.

Methods: Using a cohort of 4967 unique patients with Enterobacterales bloodstream infections, we sought to answer the question "Does transitioning patients with gram-negative bloodstream infections from intravenous to oral therapy impact 30-day mortality?" We conducted separate analyses using traditional multivariable logistic regression, propensity score matching, propensity score inverse probability of treatment weighting, and propensity score stratification using this clinical question as a case study to guide the reader through (1) the pros and cons of each approach, (2) the general steps of each approach, and (3) the interpretation of the results of each approach.

Results: 2161 patients met eligibility criteria with 876 (41%) transitioned to oral therapy while 1285 (59%) remained on intravenous therapy. After repeating the analysis using the 4 aforementioned methods, we found that the odds ratios were broadly similar, ranging from 0.84-0.95. However, there were some relevant differences between the interpretations of the findings of each approach.

Conclusions: Propensity score analysis is overall a more favorable approach than traditional regression analysis when estimating causal effects using observational data. However, as with all analytic methods using observational data, residual confounding will remain; only variables that are measured can be accounted for. Moreover, propensity score analysis does not compensate for poor study design or questionable data accuracy.
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http://dx.doi.org/10.1093/cid/ciaa169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7713675PMC
December 2020

Gene Expression Profiles in Children With Suspected Sepsis.

Ann Emerg Med 2020 06 23;75(6):744-754. Epub 2020 Jan 23.

Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania, Philadelphia, PA.

Study Objective: Sepsis recognition is a clinical challenge in children. We aim to determine whether peripheral blood gene expression profiles are associated with pathogen type and sepsis severity in children with suspected sepsis.

Methods: This was a prospective pilot observational study in a tertiary pediatric emergency department with a convenience sample of children enrolled. Participants were older than 56 days and younger than 18 years, had suspected sepsis, and had not received broad-spectrum antibiotics in the previous 4 hours. Primary outcome was source pathogen, defined as confirmed bacterial source from sterile body fluid or confirmed viral source. Secondary outcome was sepsis severity, defined as maximum therapy required for shock reversal in the first 3 hospital days. We drew peripheral blood for ribonucleic acid isolation at the sepsis protocol activation, obtained gene expression measures with the GeneChip Human Gene 2.0 ST Array, and conducted differential expression analysis.

Results: We collected ribonucleic acid samples from a convenience sample of 122 children with suspected sepsis and 12 healthy controls. We compared the 66 children (54%) with confirmed bacterial or viral infection and found 558 differentially expressed genes, many related to interferon signaling or viral immunity. We did not find statistically significant gene expression differences in patients according to sepsis severity.

Conclusion: The study demonstrates feasibility of evaluating gene expression profiling data in children evaluated for sepsis in the pediatric emergency department setting. Our results suggest that gene expression profiling may facilitate identification of source pathogen in children with suspected sepsis, which could ultimately lead to improved tailoring of sepsis treatment and antimicrobial stewardship.
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http://dx.doi.org/10.1016/j.annemergmed.2019.09.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7261647PMC
June 2020

Pet Ownership Protects Against Recurrence of Infection.

Open Forum Infect Dis 2020 Jan 18;7(1):ofz541. Epub 2020 Jan 18.

Divisions of Infectious Diseases and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Background: infection (CDI) is the leading cause of antibiotic-associated and health care-associated diarrhea in humans. Recurrent CDI (R-CDI) occurs in ~20%-30% of patients with CDI and results in increased morbidity, mortality, and hospital costs. Genomic analyses have shown overlap of isolates from animals and people, suggesting that a zoonotic reservoir may contribute to recurrence. The objective of this study was to determine whether pet ownership is a risk factor for recurrence of CDI.

Methods: We conducted a case-control study among patients with recurrent CDI (cases; n = 86) and patients with nonrecurrent CDI (controls; n = 146). Multivariable logistic regression modeling was used to determine the association between recurrence of CDI and pet ownership while accounting for patient-level risk factors.

Results: Pet ownership was not significantly associated with recurrence of CDI (odds ratio [OR], 1.02; 95% confidence interval [CI], 0.38-2.72;  = 0.965) among all patients (n = 232). However, among the subset of patients with community-associated or community-onset health care facility-acquired CDI (n = 127), increasing contact with pets was increasingly protective against recurrence: for every point increase in a pet contact score (out of 7 possible points), the odds of recurrence decreased by 14% (OR, 0.86; 95% CI, 0.74-1.00;  = 0.051).

Conclusions: Close interactions with pets appear protective against the recurrence of community-acquired CDI. A potential mechanism may involve beneficial contributions to the microbiota of pet owners afflicted with CDI, as has been observed for other conditions such as atopy, obesity, and food allergies. However, more research is needed to understand the interactions between pets, owners, and their microbiota.
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http://dx.doi.org/10.1093/ofid/ofz541DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6969483PMC
January 2020

Whole-Genome Sequencing To Identify Drivers of Carbapenem-Resistant Klebsiella pneumoniae Transmission within and between Regional Long-Term Acute-Care Hospitals.

Antimicrob Agents Chemother 2019 11 22;63(11). Epub 2019 Oct 22.

Department of Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, Michigan, USA

Carbapenem-resistant (CRKP) is an antibiotic resistance threat of the highest priority. Given the limited treatment options for this multidrug-resistant organism (MDRO), there is an urgent need for targeted strategies to prevent transmission. Here, we applied whole-genome sequencing to a comprehensive collection of clinical isolates to reconstruct regional transmission pathways and analyzed this transmission network in the context of statewide patient transfer data and patient-level clinical data to identify drivers of regional transmission. We found that high regional CRKP burdens were due to a small number of regional introductions, with subsequent regional proliferation occurring via patient transfers among health care facilities. While CRKP was predicted to have been imported into each facility multiple times, there was substantial variation in the ratio of intrafacility transmission events per importation, indicating that amplification occurs unevenly across regional facilities. While myriad factors likely influence intrafacility transmission rates, an understudied one is the potential for clinical characteristics of colonized and infected patients to influence their propensity for transmission. Supporting the contribution of high-risk patients to elevated transmission rates, we observed that patients colonized and infected with CRKP in high-transmission facilities had higher rates of carbapenem use, malnutrition, and dialysis and were older. This report highlights the potential for regional infection prevention efforts that are grounded in genomic epidemiology to identify the patients and facilities that make the greatest contribution to regional MDRO prevalence, thereby facilitating the design of precision interventions of maximal impact.
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http://dx.doi.org/10.1128/AAC.01622-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6811406PMC
November 2019

Risk factors for multidrug-resistant organisms among deceased organ donors.

Am J Transplant 2019 09 26;19(9):2468-2478. Epub 2019 Jun 26.

Division of Infectious Diseases, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.

Donor infection or colonization with a multidrug-resistant organism (MDRO) affects organ utilization and recipient antibiotic management. Approaches to identifying donors at risk of carrying MDROs are unknown. We sought to determine the risk factors for MDROs among transplant donors. A multicenter retrospective cohort study was conducted at four transplant centers between 2015 and 2016. All deceased donors who donated at least one organ were included. Cultures obtained during the donor's terminal hospitalization and organ procurement were evaluated. The primary outcome was isolation of an MDRO on culture. Multivariable Cox regression was used to determine risk factors associated with time to donor MDRO. Of 440 total donors, 64 (15%) donors grew an MDRO on culture. Predictors of an MDRO on donor culture included hepatitis C viremia (hazard ratio [HR] 4.09, 95% confidence interval [CI] 1.71-9.78, P = .002), need for dialysis (HR 4.59, 95% CI 1.09-19.21, P = .037), prior hematopoietic cell transplant (HR 7.57, 95% CI 1.03-55.75, P = .047), and exposure to antibiotics with a narrow gram-negative spectrum (HR 1.13, 95% CI 1.00-1.27, P = .045). This is the first study to determine risk factors for MDROs among deceased donors and will be important for risk stratifying potential donors and informing transplant recipient prophylaxis.
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http://dx.doi.org/10.1111/ajt.15488DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6711782PMC
September 2019

A Deeper Dive: Implications of Identifying More of the Carbapenem-Resistant Enterobacteriaceae Iceberg.

J Infect Dis 2020 05;221(11):1743-1745

Division of Infectious Diseases, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia.

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http://dx.doi.org/10.1093/infdis/jiz290DOI Listing
May 2020

A Clinical Prediction Tool for Extended-Spectrum Cephalosporin Resistance in Community-Onset Enterobacterales Urinary Tract Infection.

Open Forum Infect Dis 2019 Apr 14;6(4):ofz164. Epub 2019 Mar 14.

Division of Infectious Diseases, Department of Medicine.

Background: Bacterial resistance to first line antibiotics used to treat community-onset urinary tract infections (UTIs) continues to increase. We sought to create a clinical prediction tool for community-onset UTIs due to extended-spectrum cephalosporin-resistant (ESC-R) Enterobacterales (formerly Enterobacteriaceae, EB).

Methods: A case-control study was performed. The source population included patients presenting to an emergency department (ED) or outpatient practice with an EB UTI between 2010 and 2013. Case patients had ESC-R EB UTIs. Control patients had ESC-susceptible EB UTIs and were matched to cases 1:1 on study year. Multivariable conditional logistic regression was performed to develop the predictive model by maximizing the area under the receiver-operating curve (AUC). Internal validation was performed via bootstrapping.

Results: A total of 302 patients with a community-onset EB UTI were included, with 151 cases and 151 controls. After multivariable analysis, we found that presentation with an ESC-R EB community-onset UTI could be predicted by the following: (1) a history of malignancy; (2) a history of diabetes; (3) recent skilled nursing facility or hospital stay; (4) recent trimethoprim-sulfamethoxazole exposure; and (5) pyelonephritis at the time of presentation (AUC 0.73, Hosmer-Lemeshow goodness-of-fit value 0.23). With this model, each covariate confers a single point, and a patient with ≥ 2 points is considered high risk for ESC-R EB (sensitivity 80%, specificity 54%). The adjusted AUC after bootstrapping was 0.71.

Conclusions: Community-onset ESC-R EB UTI can be predicted using the proposed scoring system, which can help guide diagnostic and therapeutic interventions.
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http://dx.doi.org/10.1093/ofid/ofz164DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6483753PMC
April 2019
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