The Time for Action Is Now: The Impact of Timing of Infectious Disease Consultation for Staphylococcus aureus Bacteremia.

This retrospective cohort study was performed to compare clinical outcomes between patients with Staphylococcus aureus bacteremia who received an early versus late infectious disease consultation. Early consultation resulted in significantly greater adherence to quality care indicators and shorter hospital stays.

Effectiveness and Safety of Beta-Lactam Antibiotics with and without Therapeutic Drug Monitoring in Patients with Pseudomonas aeruginosa Pneumonia or Bloodstream Infection.

This objective of this study was to compare clinical outcomes in hospitalized patients with Pseudomonas aeruginosa pneumonia (PNA) or bloodstream infection (BSI) receiving beta-lactam antibiotic (BLA) infusions with and without the guidance of therapeutic drug monitoring (TDM). A retrospective, parallel cohort study was conducted at two academic medical centers between December 2015 and January 2020, UF Shands Gainesville, which uses BLA TDM for select patients (BLA TDM), and UF Health Jacksonville, which does not use BLA TDM (No-BLA TDM). All hospitalized adult patients with respiratory or blood culture positive for P. aeruginosa who met diagnosis criteria for lower respiratory tract infection with a positive P. aeruginosa respiratory culture and who received ≥48 h of intravenous BLA with in vitro susceptibility within 72 h of positive culture collection were included. The primary outcome was a composite of presumed treatment failure defined as the presence of any of the following from index-positive P. aeruginosa culture collection to the end of BLA therapy: all-cause mortality, escalation of and/or additional antimicrobial therapy for P. aeruginosa infection after 48 h of treatment with susceptible BLA due to worsening clinical status, or transfer to a higher level of care (i.e., the intensive care unit [ICU]). Analyses were adjusted for possible confounding with inverse probability of treatment weighting (IPTW). Two-hundred patients were included (BLA TDM, n = 95; No-BLA TDM, n = 105). In IPTW-adjusted analysis of the primary composite endpoint, BLA TDM demonstrated a significant decrease in presumed treatment failure compared to No-BLA TDM (adjusted odds ratio [aOR] 0.037, 95% confidence interval [CI] [0.013 to 0.107]; P < 0.001). BLA TDM had more 30-, 60- and 90-day infection-related readmissions ([aOR], 11.301, 95% CI (3.595 to 35.516); aOR 10.389, 95% CI [2.496 to 43.239], and aOR 24.970, 95% CI [6.703 to 93.028]) in IPTW analyses. For both unadjusted and IPTW-adjusted cohorts, there was no significant difference in hospital and ICU length of stay, adverse effects while on BLA, or microbiological eradication between BLA TDM and No-BLA TDM. In hospitalized adult patients with P. aeruginosa PNA or BSI, the use of TDM-guided BLA infusions decreased the odds of presumed treatment failure compared to patients receiving BLA infusions without TDM guidance. Future studies should evaluate BLA TDM impact on readmission.

A Case Report of Melioidotic Prostatic Abscess in a Traveler.

A 48-year-old man who had returned from Panama 5 weeks prior presented with fever, dysuria, hematuria, flank pain, and suprapubic pain and was found to have a prostatic abscess. Abscess fluid obtained during transurethral drainage grew Burkholderia pseudomallei. Blood cultures remained negative, and imaging did not show any other visceral abscess. This presentation of primary prostatic melioidosis is extremely rare in this region.

Fungemia due to Aureobasidium pullulans.

Aureobasidium pullulans is a yeast-like dematiaceous fungus ubiquitous in nature. It is a rare cause of skin and soft tissue infection, peritonitis, and catheter-related fungemia in certain human hosts. We report a case of recurrent A. pullulans catheter-related fungemia that was successfully treated with caspofungin, posaconazole, and catheter removal.

Influence of Antimicrobial Stewardship and Molecular Rapid Diagnostic Tests on Antimicrobial Prescribing for Extended-Spectrum Beta-Lactamase- and Carbapenemase-Producing Escherichia coli and Klebsiella pneumoniae in Bloodstream Infection.

The objective of this study was to evaluate whether the addition of the Verigene BC-GN molecular rapid diagnostic test to standard antimicrobial stewardship practices (mRDT + ASP) decreased the time to optimal and effective antimicrobial therapy for patients with extended-spectrum beta-lactamase (ESBL)- and carbapenemase-producing Escherichia coli and Klebsiella pneumoniae bloodstream infections (BSI) compared to conventional microbiological methods with ASP (CONV + ASP). This was a multicenter, retrospective cohort study evaluating the time to optimal antimicrobial therapy in 5 years of patients with E. coli or K. pneumoniae BSI determined to be ESBL- or carbapenemase-producing by mRDT and/or CONV. Of the 378 patients included (mRDT + ASP, n = 164; CONV + ASP, n = 214), 339 received optimal antimicrobial therapy (mRDT + ASP, n = 161; CONV + ASP, n = 178), and 360 (mRDT + ASP, n = 163; CONV + ASP, n = 197) received effective antimicrobial therapy. The mRDT + ASP demonstrated a statistically significant decrease in the time to optimal antimicrobial therapy (20.5 h [interquartile range (IQR), 17.0 to 42.2 h] versus 50.1 h [IQR, 27.6 to 77.9 h]; P < 0.001) and the time to effective antimicrobial therapy (15.9 h [IQR, 1.9 to 25.7 h] versus 28.0 h [IQR, 9.5 to 56.7 h]; P < 0.001) compared to CONV + ASP, respectively. IMPORTANCE Our study supports the additional benefit of molecular rapid diagnostic test in combination with timely antimicrobial stewardship program (ASP) intervention on shortening the time to both optimal and effective antimicrobial therapy in patients with ESBL- or carbapenemase-producing Escherichia coli and Klebsiella pneumoniae bloodstream infections, compared to conventional microbiological methods and ASP. Gram-negative infections are associated with significant morbidity and mortality, often resulting in life-threatening organ dysfunction. Both resistance phenotypes confer resistance to many of our first-line antimicrobial agents with carbapenemase-producing Enterobacterales requiring novel beta-lactam and beta-lactamase inhibitor combinations or other susceptible non-beta-lactam antibiotics for treatment. National resistance trends in a cohort of hospitalized patients at U.S. hospitals during our study period demonstrate the increasing incidence of both resistance phenotypes, reinforcing the generalizability and timeliness of such analysis.

Comparison of acute kidney injury in patients prescribed vancomycin in combination with piperacillin-tazobactam or cefepime for diabetic foot infections.

Concomitant therapy with vancomycin (VAN) and piperacillin-tazobactam (PTZ) has been associated with acute kidney injury (AKI). Diabetic patients may be more susceptible to AKI due to various factors. In an observational, retrospective, cohort study of adults treated for diabetic foot infections (DFIs), rates of AKI were compared between groups receiving VAN+PTZ versus VAN+cefepime (CFP). Among 356 patients screened for inclusion, 210 were analyzed. Forty-nine of 140 patients (35%) in the VAN+PTZ group and 5 of 70 patients (7%) in the VAN+CFP group developed AKI according to the Acute Kidney Injury Network criteria (OR 7.00 (95% CI 2.64 to 18.53), p<0.001). After adjusting for baseline differences, VAN+PTZ was an independent predictor of AKI (OR 6.21 (95% CI 2.30 to 16.72), p<0.001). Time to AKI was 102.1 hours (IQR 47-152.7) in the VAN+PTZ group versus 78.3 hours (IQR 39.8-100.6) in the VAN+CFP group (p>0.999). Median length of stay was significantly higher in the VAN+PTZ group at 11.9 days (IQR 7.9-17.8) versus 7.8 days (IQR 4.9-12.1) in the VAN+CFP group (p<0.001). VAN+PTZ was also associated with higher total hospital charges at US$99,742.83 (IQR US$69,342.50-US$165,549.59) compared with US$74,260.25 (IQR US$48,446.88-US$107,396.99) in the VAN+CFP arm (p<0.001). In conclusion, VAN+CFP should be the preferred empiric regimen in patients with severe DFI.

Preanalytical Challenges During Capillary Fingerstick Sampling Preclude Its Widespread Use in Adult Hospitalized Patients.

OBJECTIVES: Patient compliance with laboratory testing is one of the most underrecognized challenges in developing a treatment plan for acute and chronically ill patients. The ability to offer alternatives to standard venipuncture blood draws would greatly increase a laboratory's ability to provide testing to patients and health care providers. METHODS: We performed a prospective observational study on paired venous and fingerstick capillary blood samples from admitted patients undergoing vancomycin therapy. Paired specimens were analyzed for vancomycin and a basic metabolic panel (BMP: calcium, carbon dioxide, chloride, potassium, sodium, creatinine, glucose, serum urea nitrogen) on the core laboratory's automated chemistry and immunochemistry platforms. RESULTS: A total of 59 paired fingerstick and venous blood specimens from 56 unique inpatients were analyzed. Paired samples were comparable for all the analytes tested with the exception of bicarbonate and potassium, which were significantly different among the capillary sample group. Patients required multiple fingers be lanced in 15% of cases to obtain sufficient blood to carry out the testing. Capillary sample rejection rates due to insufficient volumes were as high as 30% in the initial 30 patients enrolled in the study. CONCLUSIONS: Vancomycin and the BMP, with the exception of potassium and bicarbonate, were determined to be analytically comparable. However, significant preanalytical issues should preclude laboratories and providers from more widespread adoption of fingerstick-derived capillary blood as an alternative sampling method except in the most extenuating of circumstances.

Clinical impact of a pharmacist-led antimicrobial stewardship initiative evaluating patients with Clostridioides difficile colitis.

Clostridioides difficile is the most common cause of healthcare-associated infection and gastroenteritis-associated death in the USA. Adherence to guideline recommendations for treatment of severe C. difficile infection (CDI) is associated with improved clinical success and reduced mortality. The purpose of this study was to determine whether implementation of a pharmacist-led antimicrobial stewardship program (ASP) CDI initiative improved adherence to CDI treatment guidelines and clinical outcomes. This was a single-center, retrospective, quasi-experimental study evaluating patients with CDI before and after implementation of an ASP initiative involving prospective audit and feedback in which guideline-driven treatment recommendations were communicated to treatment teams and documented in the electronic health record via pharmacy progress notes for all patients diagnosed with CDI. The primary endpoint was the proportion of patients treated with guideline adherent definitive regimens within 72 hours of CDI diagnosis. Secondary objectives were to evaluate the impact on clinical outcomes, including length of stay (LOS), infection-related LOS, 30-day readmission rates, and all-cause, in-hospital mortality. A total of 233 patients were evaluated. The proportion of patients on guideline adherent definitive CDI treatment regimen within 72 hours of diagnosis was significantly higher in the post-interventional group (pre: 42% vs post: 58%, p=0.02). No differences were observed in clinical outcomes or proportions of patients receiving laxatives, promotility agents, or proton pump inhibitors within 72 hours of diagnosis. Our findings demonstrate that a pharmacist-led stewardship initiative improved adherence to evidence-based practice guidelines for CDI treatment.

Clinical utility of methicillin-resistant Staphylococcus aureus nasal polymerase chain reaction assay in critically ill patients with nosocomial pneumonia.

PURPOSE: This study investigated the diagnostic performance characteristics of a methicillin-resistant Staphylococcus aureus (MRSA) nasal polymerase chain reaction (PCR) assay in critically ill patients with nosocomial pneumonia. MATERIALS AND METHODS: This retrospective, single-center study included adult patients admitted to an intensive care unit with suspected nosocomial pneumonia. Patients must have received an MRSA nasal PCR assay and respiratory culture within predetermined time intervals. The primary outcome included the diagnostic performance characteristics of the assay. Secondary outcomes included the change in negative predictive value (NPV) over time, rate of acute kidney injury, and cost avoidance associated with vancomycin and monitoring. RESULTS: In 400 patients meeting inclusion criteria, the prevalence of culture confirmed MRSA pneumonia was 9.3%. When compared to initial cultures, the PCR assay demonstrated 91.89% sensitivity and 84.3% specificity with a positive predictive value and NPV of 37.36% and 99.03%. The NPV decreased to 87.5% at 21.9 days. No difference was found in rates of acute kidney injury. A cost avoidance of $108 per patient was estimated in patients de-escalated based on negative results. CONCLUSION: In critically ill patients, an MRSA nasal PCR assay has a high NPV for nosocomial pneumonia and can be used to guide vancomycin de-escalation.

Controversies in Antimicrobial Stewardship: Focus on New Rapid Diagnostic Technologies and Antimicrobials.

Antimicrobial stewardship programs (ASPs) are challenged with ensuring appropriate antimicrobial use while minimizing expenditures. ASPs have consistently demonstrated improved patient outcomes and significant cost reductions but are continually required to justify the costs of their existence and interventions due to the silo mentality often adopted by hospital administrators. As new technologies and antimicrobials emerge, ASPs are in a constant tug-of-war between providing optimal clinical outcomes and ensuring cost containment. Additionally, robust data on cost-effectiveness of new rapid diagnostic technologies and antimicrobials with subsequent ASP interventions to provide justification are lacking. As the implementation of an ASP will soon be mandatory for acute care hospitals in the United States, ASPs must find ways to justify novel interventions to align themselves with healthcare administrators. This review provides a framework for the justification of implementing a rapid diagnostic test or adding a new antimicrobial to formulary with ASP intervention, reviews approaches to demonstrating cost-effectiveness, and proposes methods for which ASPs may reduce healthcare expenditures via alternative tactics.

Impact of an antimicrobial stewardship initiative to evaluate ß-lactam allergy in patients ordered aztreonam.

PURPOSE: An evaluation of the clinical and economic impact of an antimicrobial stewardship quality initiative (ASQI) focusing on allergy assessment in patients with a documented ß-lactam allergy prescribed aztreonam was conducted. METHODS: This retrospective study was executed at a hospital with an interdisciplinary antimicrobial stewardship program (ASP). A total of 186 patients with self-reported ß-lactam allergies who were prescribed aztreonam while admitted during a 36-month time period surrounding the ASQI implementation were included. The primary study outcome was median time in hours to aztreonam discontinuation among nonanaphylactic patients. RESULTS: After implementation of the ASQI, the percentage of patients continued on aztreonam for the duration of therapy was nearly cut in half, and a greater percentage of patients were switched to ß-lactam antibiotics. No adverse effects associated with ß-lactam therapy were observed in any study patient. Antimicrobial cost savings was not associated with any difference in clinical outcomes. Overall, hospitalwide aztreonam prescribing and aztreonam use declined. Institutional aztreonam orders per 1000 patient-days decreased from 1.5 to 1 after implementation of the ASQI. Additionally, hospitalwide aztreonam days of therapy per 1000 patient-days was reduced from 3.6 in the pre-ASQI period to 1.8 in the post-ASQI period. CONCLUSION: An ASQI that included critical evaluation of patient-reported ß-lactam allergies led to decreased aztreonam use, reduced antimicrobial expenditure, and similar clinical outcomes to those observed before implementation.

A Stewardship Approach To Optimize Antimicrobial Therapy through Use of a Rapid Microarray Assay on Blood Cultures Positive for Gram-Negative Bacteria.

A Gram-negative (GN) blood culture microarray assay with an antimicrobial stewardship program (ASP) intervention was evaluated in 126 patients with GN bacteremia. The median time to optimal therapy was shorter in the postintervention group than in the preintervention group (49.3 h versus 38.5 h, respectively; P = 0.0199). ASP can utilize microarray technology to decrease the time to optimal antimicrobial therapy.

Short-course of ranolazine prevents postoperative atrial fibrillation following coronary artery bypass grafting and valve surgeries.

BACKGROUND: Postoperative atrial fibrillation (POAF) is a common complication arising after coronary artery bypass grafting (CABG) and valve replacement or repair surgeries. POAF has been associated with increased mortality, morbidity and cost. METHODS: The study was conducted to evaluate the incidence of POAF following CABG, valve or combination surgeries when perioperative ranolazine (1,000 mg preoperatively, then 1,000 mg twice daily for 7 days or until discharge) was or was not added to standard therapy. RESULTS: A total of 205 patients were evaluated for POAF after CABG, valve or combination surgeries. POAF occurred less frequently in the ranolazine group compared with the non-ranolazine group in unmatched analysis (10.1 vs. 41.9 %, p < 0.0001). After adjusting for potential sources of bias through propensity-score matched-pair analysis and conditional logistic regression, ranolazine was an independent predictor of preventing POAF (p < 0.0001). There were no differences in bradycardia, new renal failure or neurological events between the two groups. Early, symptomatic hypotension occurred more frequently in the ranolazine group (p = 0.0004) although this difference did not persist after 72 h. No significant difference was found in the length of stay in the intensive care unit following cardiac surgery. While a significant difference was found in the hospital readmission rate for a cardiac cause within 30 days in the unmatched analysis (p = 0.046), this difference was nonexistent after matching (p = 0.39). No difference was found in 30-day cardiovascular mortality. CONCLUSION: Adding ranolazine to standard therapy was independently associated with a significant decrease in POAF development after CABG, valve or combination surgeries.

Comparison of acute kidney injury during treatment with vancomycin in combination with piperacillin-tazobactam or cefepime.

STUDY OBJECTIVE: To evaluate the observed incidence of acute kidney injury (AKI) in adult patients receiving either piperacillin-tazobactam and vancomycin or cefepime-vancomycin for more than 48 hours. DESIGN: Retrospective matched cohort. SETTING: Large academic medical center. PATIENTS: Adult patients without preexisting renal dysfunction admitted over an 8-month time period who received either the combination of piperacillin-tazobactam and vancomycin or cefepime-vancomycin for more than 48 hours were evaluated for AKI, defined by the Acute Kidney Injury Network criteria. MEASUREMENTS AND MAIN RESULTS: A total of 224 patients receiving either antimicrobial combination were evaluated for AKI. The incidence of AKI was significantly higher in the piperacillin-tazobactam and vancomycin group (34.8%) compared with the cefepime-vancomycin group (12.5%) in the unmatched analysis (p<0.0001). After adjusting for potential sources of bias through propensity score matched pairs and conditional logistic regression, piperacillin-tazobactam and vancomycin combination therapy (p=0.003) was an independent predictor of AKI. There were no significant differences in time to AKI or hospital length of stay between groups. CONCLUSIONS: The results of this study suggest that there may be an association between piperacillin-tazobactam and vancomycin combination therapy and increased incidence of AKI.

Evaluation of an antimicrobial stewardship approach to minimize overuse of antibiotics in patients with asymptomatic bacteriuria.

An antimicrobial stewardship educational initiative provided to physicians and pharmacists was evaluated at an academic medical center to minimize inappropriate treatment of asymptomatic bacteriuria (ASB). A significant decrease in empirical antimicrobial use for ASB was observed after education. Multifaceted educational initiatives can reduce inappropriate antimicrobial treatment of ASB.

Stewardship approach for optimizing antimicrobial therapy through use of a rapid microarray assay on blood cultures positive for Enterococcus species.

Enterococci are a major cause of bloodstream infections in hospitalized patients and have limited antimicrobial treatment options due to their many resistance mechanisms. Molecular technologies have significantly shortened the time to enterococcal isolate identification compared with conventional methods. We evaluated the impact of rapid organism identification and resistance detection with the Verigene Gram-positive blood culture microarray assay on clinical and economic outcomes for patients with enterococcal bacteremia. A single-center preintervention/postintervention quasiexperimental study compared inpatients with enterococcal bacteremia from 1 February 2012 to 9 September 2012 (preintervention period) and 10 September 2012 to 28 February 2013 (postintervention period). An infectious disease and/or critical care pharmacist was contacted with the microarray assay results, and effective antibiotics were recommended. The clinical and economic outcomes for 74 patients were assessed. The mean time to appropriate antimicrobial therapy was 23.4 h longer in the preintervention group than in the postintervention group (P = 0.0054). A nonsignificant decrease in the mean time to appropriate antimicrobial therapy was seen for patients infected with vancomycin-susceptible Enterococcus isolates (P = 0.1145). For patients with vancomycin-resistant Enterococcus bacteremia, the mean time to appropriate antimicrobial therapy was 31.1 h longer in the preintervention group than in the postintervention group (P < 0.0001). In the postintervention group, the hospital length of stay was significantly 21.7 days shorter (P = 0.0484) and mean hospital costs were $60,729 lower (P = 0.02) than in the preintervention group. The rates of attributed deaths in the two groups were not statistically different. Microarray technology, supported by pharmacy and microbiology departments, can decrease the time to appropriate antimicrobial therapy, the hospital length of stay, and health care costs.