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Emergence of Extended-Spectrum β-Lactamase Urinary Tract Infections Among Hospitalized Emergency Department Patients in the United States

Talan, David A; Takhar, Sukhjit S; Krishnadasan, Anusha; Mower, William R; Pallin, Daniel J; Garg, Manish; Femling, Jon; Rothman, Richard E; Moore, Johanna C; Jones, Alan E; Lovecchio, Frank; Jui, Jonathan; Steele, Mark T; Stubbs, Amy M; Chiang, William K; Moran, Gregory J
STUDY OBJECTIVE/OBJECTIVE:Enterobacteriaceae resistant to ceftriaxone, mediated through extended-spectrum β-lactamases (ESBLs), commonly cause urinary tract infections worldwide, but have been less prevalent in North America. Current US rates are unknown. We determine Enterobacteriaceae antimicrobial resistance rates among US emergency department (ED) patients hospitalized for urinary tract infection. METHODS:We prospectively enrolled adults hospitalized for urinary tract infection from 11 geographically diverse university-affiliated hospital EDs during 2018 to 2019. Among participants with culture-confirmed infection, we evaluated prevalence of antimicrobial resistance, including that caused by ESBL-producing Enterobacteriaceae, resistance risk factors, and time to in vitro-active antibiotics. RESULTS:Of 527 total participants, 444 (84%) had cultures that grew Enterobacteriaceae; 89 of 435 participants (20.5%; 95% confidence interval 16.9% to 24.5%; 4.6% to 45.4% by site) whose isolates had confirmatory testing had bacteria that were ESBL producing. The overall prevalence of ESBL-producing Enterobacteriaceae infection among all participants with urinary tract infection was 17.2% (95% confidence interval 14.0% to 20.7%). ESBL-producing Enterobacteriaceae infection risk factors were hospital, long-term care, antibiotic exposure within 90 days, and a fluoroquinolone- or ceftriaxone-resistant isolate within 1 year. Enterobacteriaceae resistance rates for other antimicrobials were fluoroquinolone 32.3%, gentamicin 13.7%, amikacin 1.3%, and meropenem 0.3%. Ceftriaxone was the most common empirical antibiotic. In vitro-active antibiotics were not administered within 12 hours of presentation to 48 participants (53.9%) with ESBL-producing Enterobacteriaceae infection, including 17 (58.6%) with sepsis. Compared with other Enterobacteriaceae infections, ESBL infections were associated with longer time to in vitro-active treatment (17.3 versus 3.5 hours). CONCLUSION/CONCLUSIONS:Among adults hospitalized for urinary tract infection in many US locations, ESBL-producing Enterobacteriaceae have emerged as a common cause of infection that is often not initially treated with an in vitro-active antibiotic.
PMID: 33131912
ISSN: 1097-6760
CID: 4660402

Massive aripiprazole overdose in a toddler [Meeting Abstract]

Warstadt, Nicholus; Furlano, Emma; Mohan, Sanjay; Gibbs, Eric; Shenker, Jennifer; Howland, Mary Ann; Chiang, William; Smith, Silas
ISI:000708210400307
ISSN: 1556-3650
CID: 5303852

A Randomized Trial Comparing Antibiotics with Appendectomy for Appendicitis

Flum, David R; Davidson, Giana H; Monsell, Sarah E; Shapiro, Nathan I; Odom, Stephen R; Sanchez, Sabrina E; Drake, F Thurston; Fischkoff, Katherine; Johnson, Jeffrey; Patton, Joe H; Evans, Heather; Cuschieri, Joseph; Sabbatini, Amber K; Faine, Brett A; Skeete, Dionne A; Liang, Mike K; Sohn, Vance; McGrane, Karen; Kutcher, Matthew E; Chung, Bruce; Carter, Damien W; Ayoung-Chee, Patricia; Chiang, William; Rushing, Amy; Steinberg, Steven; Foster, Careen S; Schaetzel, Shaina M; Price, Thea P; Mandell, Katherine A; Ferrigno, Lisa; Salzberg, Matthew; DeUgarte, Daniel A; Kaji, Amy H; Moran, Gregory J; Saltzman, Darin; Alam, Hasan B; Park, Pauline K; Kao, Lillian S; Thompson, Callie M; Self, Wesley H; Yu, Julianna T; Wiebusch, Abigail; Winchell, Robert J; Clark, Sunday; Krishnadasan, Anusha; Fannon, Erin; Lavallee, Danielle C; Comstock, Bryan A; Bizzell, Bonnie; Heagerty, Patrick J; Kessler, Larry G; Talan, David A
BACKGROUND:Antibiotic therapy has been proposed as an alternative to surgery for the treatment of appendicitis. METHODS:We conducted a pragmatic, nonblinded, noninferiority, randomized trial comparing antibiotic therapy (10-day course) with appendectomy in patients with appendicitis at 25 U.S. centers. The primary outcome was 30-day health status, as assessed with the European Quality of Life-5 Dimensions (EQ-5D) questionnaire (scores range from 0 to 1, with higher scores indicating better health status; noninferiority margin, 0.05 points). Secondary outcomes included appendectomy in the antibiotics group and complications through 90 days; analyses were prespecified in subgroups defined according to the presence or absence of an appendicolith. RESULTS:In total, 1552 adults (414 with an appendicolith) underwent randomization; 776 were assigned to receive antibiotics (47% of whom were not hospitalized for the index treatment) and 776 to undergo appendectomy (96% of whom underwent a laparoscopic procedure). Antibiotics were noninferior to appendectomy on the basis of 30-day EQ-5D scores (mean difference, 0.01 points; 95% confidence interval [CI], -0.001 to 0.03). In the antibiotics group, 29% had undergone appendectomy by 90 days, including 41% of those with an appendicolith and 25% of those without an appendicolith. Complications were more common in the antibiotics group than in the appendectomy group (8.1 vs. 3.5 per 100 participants; rate ratio, 2.28; 95% CI, 1.30 to 3.98); the higher rate in the antibiotics group could be attributed to those with an appendicolith (20.2 vs. 3.6 per 100 participants; rate ratio, 5.69; 95% CI, 2.11 to 15.38) and not to those without an appendicolith (3.7 vs. 3.5 per 100 participants; rate ratio, 1.05; 95% CI, 0.45 to 2.43). The rate of serious adverse events was 4.0 per 100 participants in the antibiotics group and 3.0 per 100 participants in the appendectomy group (rate ratio, 1.29; 95% CI, 0.67 to 2.50). CONCLUSIONS:For the treatment of appendicitis, antibiotics were noninferior to appendectomy on the basis of results of a standard health-status measure. In the antibiotics group, nearly 3 in 10 participants had undergone appendectomy by 90 days. Participants with an appendicolith were at a higher risk for appendectomy and for complications than those without an appendicolith. (Funded by the Patient-Centered Outcomes Research Institute; CODA ClinicalTrials.gov number, NCT02800785.).
PMID: 33017106
ISSN: 1533-4406
CID: 4669442

Acetaminophen poisoning: reclaiming the definition of recovery [Letter]

DiSalvo, Philip C; Chiang, William K; Wang, Josh J
PMID: 32400217
ISSN: 1556-9519
CID: 4438102

Variations in the detection, reporting, and interpretation of low acetaminophen concentrations may lead to overtreatment [Meeting Abstract]

Disalvo, Philip C.; Backus, Timothy C.; Furlano, Emma R.; Ali, Khameinei; Chiang, William K.; Wang, Josh J.
ISI:000531053300222
ISSN: 1556-3650
CID: 4491782

Laboratory variability in reporting salicylate levels may limit high-quality poison center recommendations [Meeting Abstract]

Backus, Timothy C.; Disalvo, Philip C.; Furlano, Emma R.; Ali, Khameinei; Chiang, William K.; Wang, Josh J.
ISI:000531053300219
ISSN: 1556-3650
CID: 4491752

Valproic acid reporting cutoffs impact poison control recommendations [Meeting Abstract]

Furlano, Emma R.; Disalvo, Philip C.; Backus, Timothy C.; Ali, Khameinei; Chiang, William K.; Wang, Josh J.
ISI:000531053300220
ISSN: 1556-3650
CID: 4491762

Precise determination of phenobarbital concentrations may delay patient-centred care in severe poisoning [Meeting Abstract]

Backus, Timothy C.; Disalvo, Philip C.; Furlano, Emma R.; Ali, Khameinei; Chiang, William K.; Wang, Josh J.
ISI:000531053300221
ISSN: 1556-3650
CID: 4491772

Laboratory practice variations complicate poison centre recommendations for massive paracetamol overdose [Meeting Abstract]

Wang, Josh J.; Furlano, Emma R.; Disalvo, Philip C.; Backus, Timothy C.; Ali, Khameinei; Chiang, William K.
ISI:000531053300223
ISSN: 1556-3650
CID: 4491792

On the analytical characteristics of commercial acetaminophen assays in the united states between 1984 and 2019 [Meeting Abstract]

Ali, K; Chiang, W K; Wang, J J
Introduction: Management of acetaminophen (APAP) toxicity is heavily reliant on the plasma or serum concentration. We sought to determine the analytical characteristics of past and current commercial APAP assays in the United States.
Method(s): We systematically reviewed the analytical characteristics of APAP assays cleared by the Food and Drug Administration's (FDA) 510(k) premarket notification process by searching the Clinical Laboratory Improvement Amendments (CLIA) database. If no analytical data were available, we contacted the manufacturer directly and searched for peer reviewed reports. We excluded non-blood assays, qualitative assays, and assays for which precision data were not available. We collected the following data where available: test principle, precision near 10mg/L, precision near 150 mg/L, limits of detection, and limits of quantitation. Accuracy and specificity were not routinely reported and outside the scope of this study.
Result(s): From 212 search results, we identified 19 different assays derived from 15 parent devices (Figure 1). All extracted analytical characteristics are shown in Table 1. Twelve were enzymatic while 7 were immunoassays. For all assays, absolute analytical precision decreased as analyte concentration increased (Figure 1). Near [APAP]=10mg/L, the most precise assays had a standard deviation (SD) of 0.2 mg/L or coefficient of variation (CV=SD/mean) of 1% and the least precise assays had a SD of range of 1.8mg/L or a CV of 10%. Near [APAP]=150 mg/L, the most precise assay had a SD of 1.4 mg/L or CV of 0.9% and the least precise assays had a SD of 7.4mg/L or a CV of 4.9%. Some manufacturers failed to validate assay precision at or near clinically- relevant [APAP]: two assays did not have precision data for [APAP]<40 mg/L, eight assays did not have precision data for [APAP]>150mg/L. The limit of detection ranged from 0.1- 2.4mg/L. The lower limit of quantitation ranged from 0.6-10mg/ L. The upper limit of quantitation ranged from 200-380 mg/L, before dilution.
Conclusion(s): APAP assays uncovered by our search had good analytical precision with improvement over time. The failure of some manufacturers to validate precision near treatment thresholds is concerning. Newer APAP assays could quantify lower [APAP], raising the likelihood of overdiagnosis and subsequent overtreatment. The FDA CLIA database for 510(k) devices is limited by redundant entries and incomplete data but remains a freely accessible starting point for clinicians to learn about many toxicologic assays. These data are not a substitute for independent laboratory optimization and validation.
EMBASE:634337052
ISSN: 1556-9519
CID: 4805092