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.

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.

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.

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.

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.

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.

Hospital Length of Stay Among Patients Receiving Intermittent Versus Prolonged Piperacillin/Tazobactam Infusion in the Intensive Care Units.

OBJECTIVES: We sought to evaluate clinical outcomes of intensive care unit (ICU) patients following a hospital-wide initiative of prolonged piperacillin/tazobactam (PIP/TAZ) infusion. METHODS: Retrospective observational study of patients >18 years old who was hospitalized in the ICU receiving PIP/TAZ for >72 hours during the preimplementation (June 1, 2010 to May 31, 2011) and postimplementation (July 7, 2011 to June 30, 2014) periods. RESULTS: There were 124 and 429 patients who met inclusion criteria with average age of 54.3 and 56.9 years, and average duration of PIP/TAZ therapy was 6.1 ± 2.8 days and 5.9 ± 3.4 days in the pre- and postimplementation period, respectively. Intensive care unit and hospital length of stay (LOS) following initiation of PIP/TAZ were 8.0 ± 8.4 days versus 6.4 ± 6.8 days and 26.3 ± 22.8 days versus 20.4 ± 16.1 days among patients in the pre- and postimplementation periods, respectively. Compared to patients who received intermittent PIP/TAZ infusion, the adjusted difference in ICU and hospital LOS was 0.6 ± 0.8 days (95% confidence interval [CI]: -0.9 to 2.1 days) and 5.6 ± 2.1 days (95% CI: 1.4 - 9.7 days) shorter among patients who received prolonged PIP/TAZ infusion. At hospital discharge, 19 (15.3%) intermittent infusion and 74 (17.2%) prolonged infusion recipients had died. In comparison to intermittent infusion recipients, the adjusted odds ratio for mortality was 1.17 (95% CI: 0.65-2.1) with prolonged infusion. CONCLUSION: Our study demonstrated a reduction in hospital LOS with prolonged PIP/TAZ infusion among critically ill patients. Randomized trials are needed to further validate these findings.

Epidemiology and Microbiology of Sepsis Syndromes in a University-Affiliated Urban Teaching Hospital and Level-1 Trauma and Burn Center.

PURPOSE: To use the 2010 to 2011 data collected by structured chart review to provide a detailed up-to-date description of the epidemiology and microbiology of the sepsis syndromes. METHODS: Prospective observational study conducted at a university-affiliated urban teaching hospital and level-1 trauma and burn center. All adult patients who triggered a Code Sepsis in the emergency department (ED) between January 2010 and December 2011 were included. RESULTS: One hundred eighty four patients presented with a verified sepsis syndrome and triggered a Code Sepsis in the ED during the studied time period. The mean hospital and intensive care unit length of stays (LOSs) were 15.4 (interquartile range [IQR] = 14) and 6.7 (IQR = 5) days, respectively. The total inpatient mortality was 19% (n = 35). Patients with an unspecified source of infection and those without an isolated pathogen had the highest inpatient mortality, 42.1% (n = 8) and 23.3% (n = 10), respectively. CONCLUSION: Hospital mortality and hospital LOS of sepsis are similar to those reported in other observational studies. Our study confirms a decline in the mortality of sepsis predicted by earlier longitudinal studies and should prompt a resurgence of epidemiological research of the sepsis syndromes in the United States.

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.

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.

A prospective cohort study comparing the effect of single-dose 2 g metronidazole on Trichomonas vaginalis infection in HIV-seropositive versus HIV-seronegative women.

BACKGROUND: This analysis compared the frequency of persistent Trichomonas vaginalis (TV) among HIV-seropositive and HIV-seronegative women. METHODS: Data were obtained from women enrolled in an open cohort study of sex workers in Kenya. Participants were examined monthly, and those diagnosed as having TV by saline microscopy were treated with single-dose 2 g oral metronidazole. All women on antiretroviral therapy (ART) used nevirapine-based regimens. Generalized estimating equations with a logit link were used to compare the frequency of persistent TV (defined as the presence of motile trichomonads by saline microscopy at the next examination visit within 60 days) by HIV status. RESULTS: Three-hundred sixty participants contributed 570 infections to the analysis (282 HIV-seropositive and 288 HIV-seronegative). There were 42 (15%) persistent infections among HIV-seropositive participants versus 35 (12%) among HIV-seronegative participants (adjusted odds ratio, 1.14; 95% confidence interval [CI], 0.70-1.87). Persistent TV was highest among HIV-seropositive women using ART (21/64 [33%]) compared with HIV-seropositive women not using ART (21/217 [10%]). Concurrent bacterial vaginosis (BV) at TV diagnosis was associated with an increased likelihood of persistent TV (adjusted odds ratio, 1.90; 95% confidence interval, 1.16-3.09). CONCLUSIONS: The frequency of persistent TV infection after treatment with single-dose 2 g oral metronidazole was similar by HIV status. Alternative regimens including multiday antibiotic treatment may be necessary to improve cure rates for women using nevirapine-based ART and women with TV and concurrent BV.

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.

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.

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.

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.

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.

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.

Active surveillance cultures of methicillin-resistant Staphylococcus aureus as a tool to predict methicillin-resistant S. aureus ventilator-associated pneumonia.

OBJECTIVE: Ventilator-associated pneumonia is one of the most common infections in the intensive care unit and methicillin-resistant Staphylococcus aureus has emerged as a common cause of ventilator-associated pneumonia. We sought to study the performance characteristics of once weekly active surveillance culture of methicillin-resistant S. aureus colonization in predicting the development of methicillin-resistant S. aureus ventilator-associated pneumonia. DESIGN: Prospective observational study. SETTING: Eighty-nine-bed surgical and medical intensive care units in a university-affiliated urban teaching hospital and level I trauma and burn center. PATIENTS: All patients≥16 yrs old admitted to the intensive care unit on mechanical ventilation≥48 hrs who met diagnostic criteria for ventilator-associated pneumonia by quantitative lower respiratory tract cultures obtained through bronchoscopic alveolar lavage or brush specimen between January 2008 and October 2010 were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Nine hundred twenty-four episodes of suspected ventilator-associated pneumonia were evaluated, and 388 patients with bronchoalveolar lavage-confirmed ventilator-associated pneumonia were included. Surveillance cultures were taken from the nares, oropharynx or trachea, and any open wound routinely on admission to the intensive care unit, every 7 days afterward, and at intensive care unit discharge. Of the 388 patients, 37 (9.5%) had methicillin-resistant S. aureus ventilator-associated pneumonia and 54 (13.9%) had methicillin-resistant S. aureus colonization documented by active surveillance culture before the development of ventilator-associated pneumonia. The sensitivity and specificity of prior methicillin-resistant S. aureus colonization as a predictor for methicillin-resistant S. aureus ventilator-associated pneumonia are 70.3% (95% confidence interval [CI] 52.8-83.6) and 92.0% (95% CI 88.5-94.5), respectively. The positive and negative predictive values are 48.1% (95% CI 34.5- 62.0) and 96.7% (95% CI 94.0-98.3). CONCLUSIONS: In our study, prior methicillin-resistant S. aureus colonization as ascertained by once-weekly active surveillance culture yielded high specificity and negative predictive value, suggesting that negative active surveillance culture can accurately exclude methicillin-resistant S. aureus as an etiology in most patients with ventilator-associated pneumonia and may decrease the need for empirical methicillin-resistant S. aureus coverage in patients with suspected ventilator-associated pneumonia.

Infection control for critically ill trauma patients: a systematic approach to prevention, detection, and provider feedback.

Critically ill patients are particularly at risk for developing hospital-acquired infections. An understanding of the predisposing factors, the epidemiology of disease, and guidelines to treat and to prevent hospital-acquired infections is necessary to incorporate infection control into the daily care of the critically ill trauma patient. Although it remains a challenge, infection control programs have moved from providing surveillance data and guidelines recommendations to implementation and engagement programs aimed at a shared responsibility for hospital-acquired infections prevention. We describe a multidisciplinary approach to infection control in the critically ill trauma patient with a special focus on ventilator-associated pneumonia at a level 1 trauma and burn center.