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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.

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., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Rapid molecular blood culture Gram-positive (BC-GP) assay can promptly identify vancomycin-resistant enterococcal (VRE) bloodstream infections (BSIs). We sought to evaluate patients with VRE BSI following the pre (N = 44) and post (N = 20) implementation of Verigene BC-GP assay. The average time to detection of VRE was 25.9 ± 4.1h (95% confidence interval (CI): 17.6-34.1; P < 0.001) earlier with Verigene BC-GP assay. Compared to patients in the pre-Verigene BC-GP period, the mean adjusted difference in time to administration of anti-VRE therapy was 18.2 ± 7.8h (95% CI: 2.5-33.8; P = 0.024) earlier among patients in the post-Verigene BC-GP period., (Published by Elsevier Ltd.)

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.

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.

Retrospective study aimed to examine outcomes of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia in relationship to vancomycin minimum inhibitory concentration (VAN MIC) and serum trough concentrations among subjects who had ≥1 blood culture positive for MRSA between April 2008 and August 2009. Treatment failure occurred in 7/24 (29%) subjects with VAN MIC = 2 mg/L versus 20/94 (21%) subjects with VAN MIC ≤1.5 mg/L (adjusted OR 1.11, 95% confidence interval [CI] 0.24-5.14). Among subjects who had documented VAN serum trough concentrations, treatment failure occurred in 5/26 (19%) subjects with concentrations <15 mg/L versus 18/68 (27%) subjects with concentrations ≥15 mg/L (adjusted OR 0.91, 95% CI 0.21-3.84). In conclusion, treatment outcomes were similar regardless of VAN MIC, although there was a non-statistically significant trend towards decreased clinical efficacy among patients with VAN MIC = 2 mg/L. Optimization of VAN pharmacokinetic indices did not appear to correlate with clinical responses., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Vancomycin has been the treatment standard for methicillin-resistant Staphylococcus aureus (MRSA) infections, but clinical efficacy is limited. We report outcomes of a cohort with MRSA ventilator-associated pneumonia (VAP) treated with vancomycin vs linezolid., Methods: Retrospective analysis of 113 participants with MRSA VAP confirmed by bronchoscopy who have been initiated on therapy with either vancomycin or linezolid within 24 hours after bronchoscopy and completed ≥7 days of therapy during their hospitalization from July 2003 to June 2007. The primary endpoints were hospital survival and clinical cure, defined as resolution of signs and symptoms of VAP or microbiological eradication after completion of therapy along with clinical pulmonary infection score (CPIS) ≤6 at day 7 of therapy., Results: At hospital discharge, 23/27 (85.2%) of linezolid and 72/86 (83.7%) of vancomycin recipients had survived (P = .672). In comparison to linezolid recipients, the adjusted odds ratio (OR) for survival was 0.72 (95% confidence interval [CI]: 0.16-3.27) with vancomycin therapy. Clinical cure was achieved in 24/27 (88.9%) of linezolid and 63/86 (73.3%) of vancomycin recipients (P = .066). Compared to linezolid recipients, the adjusted OR for clinical cure was 0.24 (95% CI: 0.05-1.10) with vancomycin therapy. Survival and clinical cure did not differ significantly between vancomycin recipients with trough level ≥15 and <15 μg/mL, respectively., Conclusions: Our results suggested no survival benefit but a trend toward higher cure rate with linezolid therapy. The optimal treatment of MRSA VAP requires further study through randomized, controlled trials.

Objectives: Carbapenem-resistant (CR) Acinetobacter baumannii is an important pathogen in ventilator-associated pneumonia (VAP), but therapeutic options are limited. We describe the clinical outcomes of the largest case series of CR-Acinetobacter VAP reported to date., Methods: A retrospective analysis of 55 participants with CR-Acinetobacter VAP from July 2004 to December 2007 was undertaken. The primary endpoint was clinical response or microbiological eradication. Secondary endpoint was treatment-associated nephrotoxicity defined as ≥ 50% increase in serum creatinine or an increase of ≥ 0.5 mg/dL during therapy., Results: Forty-two (76.4%) participants achieved clinical response at the completion of therapy. Clinical responses were achieved in 60.0% of sulbactam-based, 66.7% of polymyxin-based, 77.8% of aminoglycoside-based, 80.6% of minocycline-based, and 90.0% of tigecycline-based regimens. Follow-up sputum cultures were available in 6 of 10 tigecycline-treated participants with 4 of 6 isolates developing intermediate resistance to tigecycline while on therapy. Ten (18.2%) participants without preexisting renal disease developed treatment-associated nephrotoxicity. Baseline serum creatinine was 0.9 ± 0.1 mg/dL (range: 0.6-1.0 mg/dL) at the start of therapy and peaked at 1.9 ± 0.5 mg/dL (range: 1.6-3.0 mg/dL) during therapy. After excluding other potential concomitant renal toxic agents, nephrotoxicity developed in 6 of 30 (20.0%) and 4 of 7 (57.1%) participants treated with an aminoglycoside-or polymyxin-based regimen, respectively., Conclusions: Our results demonstrated that CR-Acinetobacter VAP can be effectively treated with second-line agents. However, colistin-related nephrotoxicity was much higher than recently reported and decreased susceptibility to tigecycline emerged on therapy demonstrating the limitations of alternative regimens.

Objective: To describe the development of a guideline for the management of ventilator-associated pneumonia (VAP) based on local microbiologic findings and to evaluate the impact of the guideline on antimicrobial use practices., Design: Retrospective comparison of antimicrobial use practices before and after implementation of the guideline., Setting: Intensive care units at Harborview Medical Center, Seattle, Washington, a university-affiliated urban teaching hospital., Patients: A total of 819 patients who received mechanical ventilation and who underwent quantitative bronchoscopy between July 1, 2003, and June 30, 2005, for suspected VAP., Interventions: Implementation of an evidence-based VAP guideline that focused on the use of quantitative bronchoscopy for diagnosis, administration of empirical antimicrobial therapy based on local microbiologic findings and resistance patterns, tailoring definitive antimicrobial therapy on the basis of culture results, and appropriate duration of therapy., Results: During the baseline period, 168 (46.7%) of 360 patients had quantitative cultures that met the diagnostic criteria for VAP, compared with 216 (47.1%) of 459 patients in the period after the guideline was implemented. The pathogens responsible for VAP remained similar between the 2 periods, except that the prevalence of VAP due to carbapenem-resistant Acinetobacter species increased from 1.8% to 15.3% (P<.001), particularly in late-onset VAP. Compared with the baseline period, there was an improvement in antimicrobial use practices after implementation of the guideline: antimicrobial therapy was more frequently tailored on the basis of quantitative culture results (103 [61.3%] of 168 vs 150 [69.4%] of 216 patients; P = .034), there was an increase in the use of appropriate definitive therapy (135 [80.4%] of 168 vs 193 [89.4%] of 216 patients; P = .001), and there was a decrease in the mean duration of therapy (12.0 vs 10.7 days; P = .0014). The all-cause mortality rate was similar in the periods before and after the guideline was implemented (38 [22.6%] of 168 vs 46 [21.3%] of 216 patients; P = .756)., Conclusions: Implementation of a guideline for the management of VAP that incorporated the use of quantitative bronchoscopy, the use of empirical therapy based on local microbiologic findings, tailoring of therapy on the basis of culture results, and use of shortened durations of therapy led to significant improvements in antimicrobial use practices without adversely affecting the all-cause mortality rate.