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Across 20 vaccine breakthrough cases detected at our institution, all 20 (100%) infections were due to variants of concern (VOCs) and had a median Ct of 20.2 (IQR, 17.1–23.3). When compared with 5174 contemporaneous samples sequenced in our laboratory, VOCs were significantly enriched among breakthrough infections (P < .05).

Uncomplicated Enterobacteriaceae bacteremia is usually transient and may not require follow-up blood cultures (FUBC). This is a retrospective observational study conducted at a university-affiliated urban teaching hospital in Seattle, WA. All patients ≥ 18 years hospitalized between July 2014 and August 2019 with ≥ 1 positive blood culture for either Escherichia coli or Klebsiella species were included. The primary outcome was to determine the number and frequency of FUBC obtained, and the detection rate for positive FUBC. There were 335 episodes of E. coli and Klebsiella spp. bacteremia with genitourinary (54%) being the most common source. FUBC were sent in 299 (89.3%) patients, with a median of 3 (interquartile range (IQR): 2, 4) sets of FUBC drawn per patient. Persistent bacteremia occurred in 37 (12.4%) patients. In uncomplicated E. coli and Klebsiella spp. bacteremia, when the pre-test probability of persistent bacteremia is relatively low, FUBC may not be necessary in the absence of predisposing factors.

Background Following a meropenem shortage, we implemented a postprescription review with feedback (PPRF) in November 2015 with mandatory infectious disease (ID) consultation for all meropenem and imipenem courses > 72 hours. Providers were made aware of the policy via an electronic alert at the time of ordering. Methods A retrospective study was conducted at the University of Washington Medical Center (UWMC) and Harborview Medical Center (HMC) to evaluate the impact of the policy on antimicrobial consumption and clinical outcomes pre- and postintervention during a 6-year period. Antimicrobial use was tracked using days of therapy (DOT) per 1000 patient-days, and data were analyzed by an interrupted time series. Results There were 4066 and 2552 patients in the pre- and postintervention periods, respectively. Meropenem and imipenem use remained steady until the intervention, when a marked reduction in DOT/1000 patient-days occurred at both hospitals (UWMC: percentage change −72.1% (95% confidence interval [CI] −76.6, −66.9), P < .001; HMC: percentage change −43.6% (95% CI −59.9, −20.7), P = .001). Notably, although the intervention did not address antibiotic use until 72 hours after initiation, there was a significant decline in meropenem and imipenem initiation (“first starts”) in the postintervention period, with a 64.9% reduction (95% CI 58.7, 70.2; P < .001) at UWMC and 44.7% reduction (95% CI 28.1, 57.4; P < .001) at HMC. Conclusions PPRF and mandatory ID consultation for meropenem and imipenem use beyond 72 hours resulted in a significant and sustained reduction in the use of these antibiotics and notably impacted their up-front usage.

Gram-negative bacteremia secondary to focal infection such as skin and soft-tissue infection, pneumonia, pyelonephritis, or urinary tract infection is commonly encountered in hospital care. Current practice guidelines lack sufficient detail to inform evidence-based practices. Specifically, antimicrobial duration, criteria to transition from intravenous to oral step-down therapy, choice of oral antimicrobials, and reassessment of follow-up blood cultures are not addressed. The presence of bacteremia is often used as a justification for a prolonged course of antimicrobial therapy regardless of infection source or clinical response. Antimicrobials are lifesaving but not benign. Prolonged antimicrobial exposure is associated with adverse effects, increased rates of Clostridioides difficile infection, antimicrobial resistance, and longer hospital length of stay. Emerging evidence supports shorter overall duration of antimicrobial treatment and earlier transition to oral agents among patients with uncomplicated Enterobacteriaceae bacteremia who have achieved adequate source control and demonstrated clinical stability and improvement. After appropriate initial treatment with an intravenous antimicrobial, transition to highly bioavailable oral agents should be considered for total treatment duration of 7 days. Routine follow-up blood cultures are not cost-effective and may result in unnecessary healthcare resource utilization and inappropriate use of antimicrobials. Clinicians should incorporate these principles into the management of gram-negative bacteremia in the hospital.

The MITIGATE toolkit was developed to assist urgent care and emergency departments in the development of antimicrobial stewardship programs. At the University of Washington, we adopted the MITIGATE toolkit in 10 urgent care centers, 9 primary care clinics, and 1 emergency department. We encountered and overcame challenges: a complex data build, choosing feasible outcomes to measure, issues with accurate coding, and maintaining positive stewardship relationships. Herein, we discuss solutions to challenges we encountered to provide guidance for those considering using this toolkit.

On January 19, 2020, the first case of a patient with coronavirus disease 2019 (COVID-19) in the United States was reported in Washington State. On February 29, 2020, a patient infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) passed away in a hospital in Seattle-King County, the first reported COVID-19-related death in the United States. That same day, a skilled nursing and rehabilitation facility in the county reported that several of its residents tested positive for SARS-CoV-2 and that many staff had symptoms compatible with COVID-19. The University of Washington Medicine health system (UW Medicine), which is based in Seattle-King County and provides quaternary care for the region, was one of several health care organizations called upon to address this growing crisis. What ensued was a series of swiftly enacted decisions and activities at UW Medicine, in partnership with local, state, and national public health agencies, to respond to the COVID-19 pandemic. Tapping into the multipronged mission areas of academic medicine, UW Medicine worked to support the community, innovate in science and clinical practice; lead policy and practice guideline development; and adopt changes as the crisis unfolded. In doing so, health system leaders had to balance their commitments to students, residents and fellows, researchers, faculty, staff, and hospital and health center entities, while ensuring that patients continued to receive cutting-edge, high-quality, safe care. In this Invited Commentary, the authors highlight the work and challenges UW Medicine has faced in responding to the global COVID-19 pandemic.

Two near-identical clinical Streptococcus pyogenes isolates of emm subtype emm43.4 with a pbp2x missense mutation (T553K) were detected. Minimum inhibitory concentrations (MICs) for ampicillin and amoxicillin were 8-fold higher, and the MIC for cefotaxime was 3-fold higher than for near-isogenic control isolates, consistent with a first step in developing β-lactam resistance.

Background Between 15–50% of patients seen in ambulatory settings are prescribed an antibiotic. At least one third of this usage is considered unnecessary. In 2019, our institution implemented the MITIGATE Toolkit, endorsed by the Centers for Disease Control and Prevention to reduce inappropriate antibiotic prescribing for viral respiratory infections in emergency and urgent care settings. In February 2020 we identified our first hospitalized patient with SARS-CoV(2). In March, efforts to limit person-to-person contact led to shelter in place orders and substantial reorganization of our healthcare system. During this time we continued to track rates of unnecessary antibiotic prescribing. Methods This was a single center observational study. Electronic medical record data were accessed to determine antibiotic prescribing and diagnosis codes. We provided monthly individual feedback to urgent care prescribers, (Sep 2019-Mar 2020), primary care, and ED providers (Jan 2020 – Mar 2020) notifying them of their specific rate of unnecessary antibiotic prescribing and labeling them as a top performer or not a top performer compared to their peers. The primary outcome was rate of inappropriate antibiotic prescribing. Results Pre toolkit intervention, 14,398 patient visits met MITIGATE inclusion criteria and 12% received an antibiotic unnecessarily in Jan-April 2019. Post-toolkit intervention, 12,328 patient visits met inclusion criteria and 7% received an antibiotic unnecessarily in Jan-April 2020. In April 2020, patient visits dropped to 10–50% of what they were in March 2020 and April 2019. During this time the unnecessary antibiotic prescribing rate doubled in urgent care to 7.8% from 3.6% the previous month and stayed stable in primary care and the ED at 3.2% and 11.8% respectively in April compared to 4.6% and 10.4% in the previous month. Conclusion Rates of inappropriate antibiotic prescribing were reduced nearly in half from 2019 to 2020 across 3 ambulatory care settings. The increase in prescribing in April seen in urgent care and after providers stopped receiving their monthly feedback is concerning. Many factors may have contributed to this increase, but it raises concerns for increased inappropriate antibacterial usage as a side effect of the SARS-CoV(2) pandemic. Disclosures All Authors: No reported disclosures

Concerns about severe acute respiratory syndrome coronavirus 2 exposure in health care settings may cause patients to delay care. Among 2992 patients testing negative on admission to an academic, 3-hospital system, 8 tested positive during hospitalization or within 14 days postdischarge. Following adjudication of each instance, health care–associated infection incidence ranged from 0.8 to 5.0 cases per 10 000 patient-days.

STUDY DESIGN Retrospective hospital-registry study. OBJECTIVE To characterize the microbial epidemiology of surgical site infection (SSI) in spinal fusion surgery and the burden of resistance to standard surgical antibiotic prophylaxis. SUMMARY OF BACKGROUND DATA SSI persists as a leading complication of spinal fusion surgery despite the growth of enhanced recovery programs and improvements in other measures of surgical quality. Improved understandings of SSI microbiology and common mechanisms of failure for current prevention strategies are required to inform the development of novel approaches to prevention relevant to modern surgical practice. METHODS Spinal fusion cases performed at a single referral center between January 2011 and June 2019 were reviewed and SSI cases meeting National Healthcare Safety Network criteria were identified. Using microbiologic and procedural data from each case, we analyzed the anatomic distribution of pathogens, their differential time to presentation, and correlation with methicillin-resistant Staphylococcus aureus screening results. Susceptibility of isolates cultured from each infection were compared with the spectrum of surgical antibiotic prophylaxis administered during the index procedure on a per-case basis. Susceptibility to alternate prophylactic agents was also modeled. RESULTS Among 6727 cases, 351 infections occurred within 90 days. An anatomic gradient in the microbiology of SSI was observed across the length of the back, transitioning from cutaneous (gram-positive) flora in the cervical spine to enteric (gram-negative/anaerobic) flora in the lumbosacral region (correlation coefficient 0.94, P

The emergence of coronavirus disease 2019 (COVID-19), caused by the SARS-CoV-2 (SC2) virus, in late December 2019 has placed an overwhelming strain on healthcare institutions nationwide. The modern healthcare system has never dealt with a pandemic of this magnitude, the ramifications of which will undoubtedly lead to lasting changes in policy and protocol development for viral testing guidelines, personal protective equipment (PPE), surgical scheduling, and residency education and training. The State of Washington (WA) had the first reported case and death related to COVID 19 in the United States (US). Oral and maxillofacial surgeons are at a unique risk of exposure to SC2 and developing COVID-19 due to our proximity of working in and around the oro- and nasopharynx. This article summarizes the evolution of COVID-19 guidelines in four key areas: 1. preoperative SARS-CoV-2 (SC2) testing, 2. personal protective equipment (PPE) stewardship, 3. surgical scheduling guidelines, and 4. resident education and training for oral and maxillofacial surgery (OMS) at the University of Washington, Seattle, WA.

Background Healthcare workers (HCWs) who serve on the front lines of the coronavirus disease 2019 (COVID-19) pandemic have been at increased risk for infection due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in some settings. Healthcare-acquired infection has been reported in similar epidemics, but there are limited data on the prevalence of COVID-19 among HCWs and their associated clinical outcomes in the United States. Methods We established 2 high-throughput employee testing centers in Seattle, Washington, with drive-through and walk-through options for symptomatic employees in the University of Washington Medicine system and its affiliated organizations. Using data from these testing centers, we report the prevalence of SARS-CoV-2 infection among symptomatic employees and describe the clinical characteristics and outcomes among employees with COVID-19. Results Between 12 March 2020 and 23 April 2020, 3477 symptomatic employees were tested for COVID-19 at 2 employee testing centers; 185 (5.3%) employees tested positive for COVID-19. The prevalence of SARS-CoV-2 was similar when comparing frontline HCWs (5.2%) with nonfrontline staff (5.5%). Among 174 positive employees reached for follow-up at least 14 days after diagnosis, 6 reported COVID-related hospitalization; all recovered. Conclusions During the study period, we observed that the prevalence of positive SARS-CoV-2 tests among symptomatic HCWs was comparable to that of symptomatic nonfrontline staff. Reliable and rapid access to testing for employees is essential to preserve the health, safety, and availability of the healthcare workforce during this pandemic and to facilitate the rapid return of SARS-CoV-2–negative employees to work.

BackgroundSARS-CoV-2 reverse transcriptase polymerase chain reaction (RT-PCR) testing remains the cornerstone of laboratory-based identification of patients with COVID-19. As the availability and speed of SARS-CoV-2 testing platforms improve, results are increasingly relied upon to inform critical decisions related to therapy, use of personal protective equipment, and workforce readiness. However, early reports of RT-PCR test performance have left clinicians and the public with concerns regarding the reliability of this predominant testing modality and the interpretation of negative results. In this work, two independent research teams report the frequency of discordant SARS-CoV-2 test results among initially negative, repeatedly tested patients in regions of the United States with early community transmission and access to testing.MethodsAll patients at the University of Washington (UW) and Stanford Health Care undergoing initial testing by nasopharyngeal (NP) swab between March 2nd and April 7th, 2020 were included. SARS-CoV-2 RT-PCR was performed targeting the N, RdRp, S, and E genes and ORF1ab, using a combination of Emergency Use Authorization laboratory-developed tests and commercial assays. Results through April 14th were extracted to allow for a complete 7-day observation period and an additional day for reporting.ResultsA total of 23,126 SARS-CoV-2 RT-PCR tests (10,583 UW, 12,543 Stanford) were performed in 20,912 eligible patients (8,977 UW, 11,935 Stanford) undergoing initial testing by NP swab; 626 initially test-negative patients were re-tested within 7 days. Among this group, repeat testing within 7 days yielded a positive result in 3.5% (4.3% UW, 2.8% Stanford) of cases, suggesting an initial false negative RT-PCR result; the majority (96.5%) of patients with an initial negative result who warranted reevaluation for any reason remained negative on all subsequent tests performed within this window.ConclusionsTwo independent research teams report the similar finding that, among initially negative patients subjected to repeat SARS-CoV-2 RT-PCR testing, the occurrence of a newly positive result within 7 days is uncommon. These observations suggest that false negative results at the time of initial presentation do occur, but potentially at a lower frequency than is currently believed. Although it is not possible to infer the clinical sensitivity of NP SARS-CoV-2 RT-PCR testing using these data, they may be used in combination with other reports to guide the use and interpretation of this common testing modality.

Background β-Hemolytic streptococci are frequently implicated in necrotizing soft-tissue infections (NSTIs). Clindamycin administration may improve outcomes in patients with serious streptococcal infections. However, clindamycin resistance is growing worldwide, and resistance patterns in NSTIs and their impact on outcomes are unknown. Methods Between 2015 and 2018, patients with NSTI at a quaternary referral center were followed up for the outcomes of death, limb loss, and streptococcal toxic shock syndrome. Surgical wound cultures and resistance data were obtained within 48 hours of admission as part of routine care. Risk ratios for the association between these outcomes and the presence of β-hemolytic streptococci or clindamycin-resistant β-hemolytic streptococci were calculated using log-binomial regression, controlling for age, transfer status, and injection drug use–related etiology. Results Of 445 NSTIs identified, 85% had surgical wound cultures within 48 hours of admission. β-Hemolytic streptococci grew in 31%, and clindamycin resistance was observed in 31% of cultures. The presence of β-hemolytic streptococci was associated with greater risk of amputation (risk ratio, 1.80; 95% confidence interval, 1.07–3.01), as was the presence of clindamycin resistance among β-hemolytic streptococci infections (1.86; 1.10–3.16). Conclusions β-Hemolytic streptococci are highly prevalent in NSTIs, and in our population clindamycin resistance was more common than previously described. Greater risk of limb loss among patients with β-hemolytic streptococci—particularly clindamycin-resistant strains—may portend a more locally aggressive disease process or may represent preexisting patient characteristics that predispose to both infection and limb loss. Regardless, these findings may inform antibiotic selection and surgical management to maximize the potential for limb salvage.

We retrospectively evaluated off-label use of dalbavancin as secondary therapy in 32 patients with serious Staphylococcus aureus infections (endocarditis, osteomyelitis, septic thrombophlebitis, epidural infection) who were also persons who use drugs. The majority of patients (56%) had a clinical response to treatment. Only 1 patient who completed the intended dalbavancin course experienced a treatment failure.

Importance Identifying infectious causes of subacute or chronic meningitis can be challenging. Enhanced, unbiased diagnostic approaches are needed. Objective To present a case series of patients with diagnostically challenging subacute or chronic meningitis using metagenomic next-generation sequencing (mNGS) of cerebrospinal fluid (CSF) supported by a statistical framework generated from mNGS of control samples from the environment and from patients who were noninfectious. Design, Setting, and Participants In this case series, mNGS data obtained from the CSF of 94 patients with noninfectious neuroinflammatory disorders and from 24 water and reagent control samples were used to develop and implement a weighted scoring metric based onzscores at the species and genus levels for both nucleotide and protein alignments to prioritize and rank the mNGS results. Total RNA was extracted for mNGS from the CSF of 7 participants with subacute or chronic meningitis who were recruited between September 2013 and March 2017 as part of a multicenter study of mNGS pathogen discovery among patients with suspected neuroinflammatory conditions. The neurologic infections identified by mNGS in these 7 participants represented a diverse array of pathogens. The patients were referred from the University of California, San Francisco Medical Center (n = 2), Zuckerberg San Francisco General Hospital and Trauma Center (n = 2), Cleveland Clinic (n = 1), University of Washington (n = 1), and Kaiser Permanente (n = 1). A weightedzscore was used to filter out environmental contaminants and facilitate efficient data triage and analysis. Main Outcomes and Measures Pathogens identified by mNGS and the ability of a statistical model to prioritize, rank, and simplify mNGS results. Results The 7 participants ranged in age from 10 to 55 years, and 3 (43%) were female. A parasitic worm (Taenia solium, in 2 participants), a virus (HIV-1), and 4 fungi (Cryptococcus neoformans,Aspergillus oryzae,Histoplasma capsulatum, andCandida dubliniensis) were identified among the 7 participants by using mNGS. Evaluating mNGS data with a weightedzscore–based scoring algorithm reduced the reported microbial taxa by a mean of 87% (range, 41%-99%) when taxa with a combined score of 0 or less were removed, effectively separating bona fide pathogen sequences from spurious environmental sequences so that, in each case, the causative pathogen was found within the top 2 scoring microbes identified using the algorithm. Conclusions and Relevance Diverse microbial pathogens were identified by mNGS in the CSF of patients with diagnostically challenging subacute or chronic meningitis, including a case of subarachnoid neurocysticercosis that defied diagnosis for 1 year, the first reported case of CNS vasculitis caused byAspergillus oryzae, and the fourth reported case ofC dubliniensismeningitis. Prioritizing metagenomic data with a scoring algorithm greatly clarified data interpretation and highlighted the problem of attributing biological significance to organisms present in control samples used for metagenomic sequencing studies.

Cause-of-death data for many developing countries are not available. Information on deaths in hospital by cause is available in many low- and middle-income countries but is not a representative sample of deaths in the population. We propose a method to estimate population cause-specific mortality fractions (CSMFs) using data already collected in many middle-income and some low-income developing nations, yet rarely used: in-hospital death records.For a given cause of death, a community's hospital deaths are equal to total community deaths multiplied by the proportion of deaths occurring in hospital. If we can estimate the proportion dying in hospital, we can estimate the proportion dying in the population using deaths in hospital. We propose to estimate the proportion of deaths for an age, sex, and cause group that die in hospital from the subset of the population where vital registration systems function or from another population. We evaluated our method using nearly complete vital registration (VR) data from Mexico 1998-2005, which records whether a death occurred in a hospital. In this validation test, we used 45 disease categories. We validated our method in two ways: nationally and between communities. First, we investigated how the method's accuracy changes as we decrease the amount of Mexican VR used to estimate the proportion of each age, sex, and cause group dying in hospital. Decreasing VR data used for this first step from 100% to 9% produces only a 12% maximum relative error between estimated and true CSMFs. Even if Mexico collected full VR information only in its capital city with 9% of its population, our estimation method would produce an average relative error in CSMFs across the 45 causes of just over 10%. Second, we used VR data for the capital zone (Distrito Federal and Estado de Mexico) and estimated CSMFs for the three lowest-development states. Our estimation method gave an average relative error of 20%, 23%, and 31% for Guerrero, Chiapas, and Oaxaca, respectively.Where accurate International Classification of Diseases (ICD)-coded cause-of-death data are available for deaths in hospital and for VR covering a subset of the population, we demonstrated that population CSMFs can be estimated with low average error. In addition, we showed in the case of Mexico that this method can substantially reduce error from biased hospital data, even when applied to areas with widely different levels of development. For countries with ICD-coded deaths in hospital, this method potentially allows the use of existing data to inform health policy.