Contribution of the patient microbiome to surgical site infection and antibiotic prophylaxis failure in spine surgery.

Despite modern antiseptic techniques, surgical site infection (SSI) remains a leading complication of surgery. However, the origins of SSI and the high rates of antimicrobial resistance observed in these infections are poorly understood. Using instrumented spine surgery as a model of clean (class I) skin incision, we prospectively sampled preoperative microbiomes and postoperative SSI isolates in a cohort of 204 patients. Combining multiple forms of genomic analysis, we correlated the identity, anatomic distribution, and antimicrobial resistance profiles of SSI pathogens with those of preoperative strains obtained from the patient skin microbiome. We found that 86% of SSIs, comprising a broad range of bacterial species, originated endogenously from preoperative strains, with no evidence of common source infection among a superset of 1610 patients. Most SSI isolates (59%) were resistant to the prophylactic antibiotic administered during surgery, and their resistance phenotypes correlated with the patient's preoperative resistome (P = 0.0002). These findings indicate the need for SSI prevention strategies tailored to the preoperative microbiome and resistome present in individual patients.

Asymptomatic bacteriuria in critical-access hospitals: Prevalence and patient characteristics driving treatment.

We evaluated the prevalence and treatment of asymptomatic bacteriuria (ASB) in 17 critical-access hospitals. Among 891 patients with urine cultures from September 2021 to June 2022, 170 (35%) had ASB. Also, 76% of patients with ASB received antibiotics for a median duration of 7 days, demonstrating opportunities for antimicrobial stewardship.

How to disagree better: utilizing advocacy-inquiry techniques to improve communication and spur behavior change.

The ability to provide feedback to a colleague is a key skill required for professional growth and patient safety. However, these conversations are limited by time constraints, differences in values, and a culture of "noninterference." This advocacy-inquiry-identify-teach framework creates an organized approach to initiating successful "challenging" conversations with peers.

Defining the Optimal Antibiotic Duration in Necrotizing Skin and Soft Tissue Infections: Clinical Experience from a Quaternary Referral Center.

Background: Early initiation of broad-spectrum antibiotic agents is a cornerstone of the care of necrotizing skin and soft tissue infections (NSTI). However, the optimal duration of antibiotic agents is unclear. We sought to characterize antibiotic prescribing patterns for patients with NSTI, as well as associated complications. Patients and Methods: Using an NSTI registry, we characterized antibiotic use at a quaternary referral center. Kaplan-Meier analyses were used to describe overall antibiotic duration and relative to operative source control, stratified by presence of other infections that independently influenced antibiotic duration. Factors associated with successful antibiotic discontinuation were identified using logistic regression. Results: Between 2015 and 2018, 441 patients received antibiotic agents for NSTI with 18% experiencing a complicating secondary infection. Among those without a complicating infection, the median duration of antibiotic administration was 9.8 days (95% confidence interval [CI], 9.2-10.5) overall, and 7.0 days after the final debridement. Perineal NSTI received fewer days of antibiotic agents (8.3 vs. 10.6) compared with NSTI without perineal involvement. White blood cell (WBC) count and fever were not associated with failure of antibiotic discontinuation, however, a chronic wound as the underlying infection etiology was associated with greater odds of antibiotic discontinuation failure (odds ratio [OR], 4.33; 95% CI, 1.24-15.1). Conclusions: A seven-day course of antibiotic agents after final operative debridement may be sufficient for NSTI without any secondary complicating infections, because clinical characteristics do not appear to be associated with differences in successful antibiotic discontinuation.

Antibiotic prescribing patterns for bacterial superinfection of mpox: A retrospective cohort study in an urban center.

Bacterial superinfection and antibiotic prescribing in the setting of the current mpox outbreak are not well described in the literature. This retrospective observational study revealed low prevalence (11%) of outpatient antibiotic prescribing for bacterial superinfection of mpox lesions; at least 3 prescriptions (23%) were unnecessary.

Rapid molecular severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing in hospital employees with mild, nonspecific respiratory symptoms facilitates expedient return to work.

Nonspecific respiratory symptoms overlap with coronavirus disease 2019 (COVID-19). Prompt diagnosis of COVID-19 in hospital employees is crucial to prevent nosocomial transmission. Rapid molecular SARS-CoV-2 testing was performed for 115 symptomatic employees. The case positivity rate was 2.6%. Employees with negative tests returned to work after 80 (±28) minutes.

Prevalence and treatment of asymptomatic bacteriuria at academic and critical-access hospitals-Opportunities for stewardship efforts.

Asymptomatic bacteriuria (ASB) is common among hospitalized patients and often leads to inappropriate antimicrobial use. Data from critical-access hospitals are underrepresented. To target antimicrobial stewardship efforts, we measured the point prevalence of ASB and detected a high frequency of ASB overtreatment across academic, community, and critical-access hospitals.

Doing More With Less: Pragmatic Implementation of Vancomycin Area-Under-the-Curve (AUC) Monitoring.

Universal area-under-the-curve (AUC) guided vancomycin therapeutic drug monitoring (TDM) is resource-intensive, cost-prohibitive, and presents a paradigm shift that leaves institutions with the quandary of defining the preferred and most practical method for TDM. We report a step-by-step quality improvement process using 4 plan-do-study-act (PDSA) cycles to provide a framework for development of a hybrid model of trough and AUC-based vancomycin monitoring. We found trough-based monitoring a pragmatic strategy as a first-tier approach when anticipated use is short-term. AUC-guided monitoring was most impactful and cost-effective when reserved for patients with high-risk for nephrotoxicity. We encourage others to consider quality improvement tools to locally adopt AUC-based monitoring.

Characterization of Secondary Bacterial Infections and Antibiotic Use in Mechanically Ventilated Patients With COVID-19 Induced Acute Respiratory Distress Syndrome.

BACKGROUND: COVID-19 has a widely variable clinical syndrome that is difficult to distinguish from bacterial sepsis, leading to high rates of antibiotic use. Early studies indicate low rates of secondary bacterial infections (SBIs) but have included heterogeneous patient populations. Here, we catalogue all SBIs and antibiotic prescription practices in a population of mechanically ventilated patients with COVID-19 induced acute respiratory distress syndrome (ARDS). METHODS: This was a retrospective cohort study of all patients with COVID-19 ARDS requiring mechanical ventilation from 3 Seattle, Washington hospitals in 2020. Data were obtained via electronic and manual review of the electronic medical record. We report the incidence and site of SBIs, mortality, and antibiotics per day using descriptive statistics. RESULTS: We identified 126 patients with COVID-19 induced ARDS during the study period. Of these patients, 61% developed clinical infection confirmed by bacterial culture. Ventilator associated pneumonia was confirmed in 55% of patients, bacteremia in 20%, and urinary tract infection (UTI) in 17%. Staphylococcus aureus was the most commonly isolated bacterial species. A total of 97% of patients received antibiotics during their hospitalization, and patients received nearly one antibiotic per day during their hospital stay. CONCLUSIONS: Mechanically ventilated patients with COVID-19 induced ARDS are at high risk for secondary bacterial infections and have extensive antibiotic exposure.

Finding the path of least resistance: Locally adapting the MITIGATE toolkit in emergency departments and urgent care centers.

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.

Follow-up blood cultures in E. coli and Klebsiella spp. bacteremia-opportunities for diagnostic and antimicrobial stewardship.

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.

2021 Young Investigator Award Winner: Anatomic Gradients in the Microbiology of Spinal Fusion Surgical Site Infection and Resistance to Surgical Antimicrobial Prophylaxis.

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 < 0.001). The majority (57.5%) of infections were resistant to the prophylaxis administered during the procedure. Cephalosporin-resistant gram-negative infection was common at lumbosacral levels and undetected methicillin-resistance was common at cervical levels. CONCLUSION: Individualized infection prevention strategies tailored to operative level are needed in spine surgery. Endogenous wound contamination with enteric flora may be a common mechanism of infection in lumbosacral fusion. Novel approaches to prophylaxis and prevention should be prioritized in this population.Level of Evidence: 3.

Postprescription Review With Threat of Infectious Disease Consultation and Sustained Reduction in Meropenem Use Over Four Years.

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.

Tocilizumab in hospitalized patients with COVID-19: Clinical outcomes, inflammatory marker kinetics, and safety.

Coronavirus disease 2019 (COVID-19) due to infection with severe acute respiratory syndrome coronavirus 2 causes substantial morbidity. Tocilizumab, an interleukin-6 receptor antagonist, might improve outcomes by mitigating inflammation. We conducted a retrospective study of patients admitted to the University of Washington Hospital system with COVID-19 and requiring supplemental oxygen. Outcomes included clinical improvement, defined as a two-point reduction in severity on a six-point ordinal scale or discharge, and mortality within 28 days. We used Cox proportional-hazards models with propensity score inverse probability weighting to compare outcomes in patients who did and did not receive tocilizumab. We evaluated 43 patients who received tocilizumab and 45 who did not. Patients receiving tocilizumab were younger with fewer comorbidities but higher baseline oxygen requirements. Tocilizumab treatment was associated with reduced C-reactive protein, fibrinogen, and temperature, but there were no meaningful differences in time to clinical improvement (adjusted hazard ratio [aHR], 0.92; 95% confidence interval [CI], 0.38-2.22) or mortality (aHR, 0.57; 95% CI, 0.21-1.52). A numerically higher proportion of tocilizumab-treated patients had subsequent infections, transaminitis, and cytopenias. Tocilizumab did not improve outcomes in hospitalized patients with COVID-19. However, this study was not powered to detect small differences, and there remains the possibility for a survival benefit.

Outcomes of ß-Hemolytic Streptococcal Necrotizing Skin and Soft-tissue Infections and the Impact of Clindamycin Resistance.

BACKGROUND: ß-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 ß-hemolytic streptococci or clindamycin-resistant ß-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. ß-Hemolytic streptococci grew in 31%, and clindamycin resistance was observed in 31% of cultures. The presence of ß-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 ß-hemolytic streptococci infections (1.86; 1.10-3.16). CONCLUSIONS: ß-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 ß-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.

Improving Appropriate Diagnosis of Clostridioides difficile Infection Through an Enteric Pathogen Order Set With Computerized Clinical Decision Support: An Interrupted Time Series Analysis.

BACKGROUND: Inappropriate testing for Clostridioides difficile leads to overdiagnosis of C difficile infection (CDI). We determined the effect of a computerized clinical decision support (CCDS) order set on C difficile polymerase chain reaction (PCR) test utilization and clinical outcomes. METHODS: This study is an interrupted time series analysis comparing C difficile PCR test utilization, hospital-onset CDI (HO-CDI) rates, and clinical outcomes before and after implementation of a CCDS order set at 2 academic medical centers: University of Washington Medical Center (UWMC) and Harborview Medical Center (HMC). RESULTS: Compared with the 20-month preintervention period, during the 12-month postimplementation of the CCDS order set, there was an immediate and sustained reduction in C difficile PCR test utilization rates at both hospitals (HMC, -28.2% [95% confidence interval {CI}, -43.0% to -9.4%], P = .005; UWMC, -27.4%, [95% CI, -37.5% to -15.6%], P < .001). There was a significant reduction in rates of C difficile tests ordered in the setting of laxatives (HMC, -60.8% [95% CI, -74.3% to -40.1%], P < .001; UWMC, -37.3%, [95% CI, -58.2% to -5.9%], P = .02). The intervention was associated with an increase in the C difficile test positivity rate at HMC (P = .01). There were no significant differences in HO-CDI rates or in the proportion of patients with HO-CDI who developed severe CDI or CDI-associated complications including intensive care unit transfer, extended length of stay, 30-day mortality, and toxic megacolon. CONCLUSIONS: Computerized clinical decision support tools can improve C difficile diagnostic test stewardship without causing harm. Additional studies are needed to identify key elements of CCDS tools to further optimize C difficile testing and assess their effect on adverse clinical outcomes.

The Changing Landscape of Uncomplicated Gram-Negative Bacteremia: A Narrative Review to Guide Inpatient Management.

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.

Graded Dalbavancin Challenge in a Patient With Severe Vancomycin Hypersensitivity Reaction.

Cross-reactivity should be considered when treating patients with a previous hypersensitivity reaction within the same class of antibiotics that share similar chemical structures. This case report describes a patient with severe hypersensitivity reaction to vancomycin who successfully tolerated a dalbavancin graded challenge.