Association of ß-Lactam Allergy Documentation and Prophylactic Antibiotic Use in Surgery: A National Cross-Sectional Study of Hospitalized Patients.

Alternative antibiotics for surgical prophylaxis are associated with increased adverse events and surgical site infection compared to cefazolin. In a sample of perioperative inpatients from 100 hospitals in the United States, cefazolin was 9-fold less likely to be used in patients with a documented ß-lactam allergy whereas clindamycin was 45-fold more likely.

Penicillin Allergy Evaluation Access: A National Survey.

In a study of 121 hospitals from 38 US states, 44% had access to an allergist for inpatient consultations and 39% had access to inpatient penicillin skin testing, indicating that the majority of US hospitals lack sufficient resources to address inpatient penicillin allergies.

Vancomycin Area Under the Curve and Acute Kidney Injury: A Meta-analysis.

BACKGROUND: This study analyzed the relationship between vancomycin area under the concentration-time curve (AUC) and acute kidney injury (AKI) reported across recent studies. METHODS: A systematic review of PubMed, Medline, Scopus, and compiled references was conducted. We included randomized cohort and case-control studies that reported vancomycin AUCs and risk of AKI (from 1990 to 2018). The primary outcome was AKI, defined as an increase in serum creatinine of ≥0.5 mg/L or a 50% increase from baseline on ≥2 consecutive measurements. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Primary analyses compared the impact of AUC cutpoint (greater than ~650 mg × hour/L) and AKI. Additional analysis compared AUC vs trough-guided monitoring on AKI incidence. RESULTS: Eight observational studies met inclusion/exclusion criteria with data for 2491 patients. Five studies reported first-24-hour AUCs (AUC0-24) and AKI, 2 studies reported 24- to 48-hour AUCs (AUC24-48) and AKI, and 2 studies reported AKI associated with AUC- vs trough-guided monitoring. AUC less than approximately 650 mg × hour/L was associated with decreased AKI for AUC0-24 (OR, 0.36 [95% CI, .23-.56]) as well as AUC24-48 (OR, 0.45 [95% CI, .27-.75]). AKI associated with the AUC monitoring strategy was significantly lower than trough-guided monitoring (OR, 0.68 [95% CI, .46-.99]). CONCLUSIONS: AUCs measured in the first or second 24 hours and lower than approximately 650 mg × hour/L may result in a decreased risk of AKI. Vancomycin AUC monitoring strategy may result in less vancomycin-associated AKI. Additional investigations are warranted.

Understanding the Components, Calculation, and Impact of Monthly and Seasonal Variation of the Standardized Antimicrobial Utilization Ratio (SAAR).

This study sought to characterize the impact of 3 types of variation on the Standardized Antimicrobial Administration Ratio (SAAR) utilizing local National Healthcare Safety Network (NHSN) data. SAAR and antimicrobial days per 1,000 days present (AD/1000DP) were compiled monthly for Northwestern Memorial Hospital from 2014 to 2016. Antimicrobial consumption was aggregated into agent categories (via NHSN criteria). Month-to-month changes in SAAR and AD/1000DP were evaluated. Azithromycin and oseltamivir AD/1000DP from 2012 through 2017 were explored for seasonal variation. A sensitivity analysis was performed to explore the effect of seasonality and altered consumption at other hypothetical hospitals on the SAAR. Across agent categories for both the intensive care unit (n = 4) and general wards (n = 4), the average matched-month percent change in AD/1000DP was correlated with the corresponding change in SAAR (coefficient of determination of 0.99). The monthly mean ± standard deviation (SD) AD/1000DP was 235 (range, 47.2 to 661.5), and the mean ± SD SAAR was 1.09 ± 0.26 (range, 0.79 to 1.09) across the NHSN agent categories. Five seasons exhibited seasonal variation in AD/1000DP for azithromycin with a mean percent change of 26.76% (range, 22.27 to 30.69). Eight seasons exhibited seasonal variation in AD/1000DP for oseltamivir with a mean percent change of 129.1% (range, 32.01 to 352.74). The sensitivity analyses confirm that antimicrobial usage at comparator hospitals does not impact the local SAAR, and seasonal variation of antibiotics has the potential to impact SAAR. Month-to-month changes in the SAAR mirror monthly changes in an institution's AD/1000DP. Seasonal variation is an important variable for future SAAR consideration, and the variable antibiotic use at peer hospitals is not currently captured by the SAAR methodology.

Evaluation of the impact of the Accelerate Pheno™ system on time to result for differing antimicrobial stewardship intervention models in patients with gram-negative bloodstream infections.

BACKGROUND: Initiating early effective antimicrobial therapy is the most important intervention demonstrated to decrease mortality in patients with gram-negative bacteremia with sepsis. Rapid MIC-based susceptibility results make it possible to optimize antimicrobial use through both escalation and de-escalation. METHOD: We prospectively evaluated the performance of the Accelerate Pheno™ system (AXDX) for identification and susceptibility testing of gram-negative species and compared the time to result between AXDX and routine standard of care (SOC) using 82 patient samples and 18 challenge organisms with various confirmed resistance mechanisms. The potential impact of AXDX on time to antimicrobial optimization was investigated with various simulated antimicrobial stewardship (ASTEW) intervention models. RESULTS: The overall positive and negative percent agreement of AXDX for identification were 100 and 99.9%, respectively. Compared to VITEK® 2, the overall essential agreement was 96.1% and categorical agreement was 95.4%. No very major or major errors were detected. AXDX reduced the time to identification by an average of 11.8 h and time to susceptibility by an average of 36.7 h. In 27 patients evaluated for potential clinical impact of AXDX on antimicrobial optimization, 18 (67%) patients could potentially have had therapy optimized sooner with an average of 18.1 h reduction in time to optimal therapy. CONCLUSION: Utilization of AXDX coupled with simulated ASTEW intervention notification substantially shortened the time to potential antimicrobial optimization in this cohort of patients with gram-negative bacteremia. This improvement in time occurred when ASTEW support was limited to an 8-h coverage model.

Measuring the impact of varying denominator definitions on standardized antibiotic consumption rates: implications for antimicrobial stewardship programmes.

Objectives: To quantify the impact of varying the at-risk days definition on the overall report of at-risk days and on the calculated standardized consumption rates (SCRs) for piperacillin/tazobactam, amikacin, daptomycin and vancomycin. Methods: Data were evaluated for two system hospitals, an 894 bed academic centre and a 114 bed community hospital. Aggregate inpatient antibiotic administration and occupancy data were extracted from electronic databases at the facility-wide level. Occupancy data were reported from admission-discharge-transfer systems. At-risk days were defined as hospital days present (DP), patient days (PD), persons present (PP) and billing days (BD). Inpatient antimicrobial days of therapy (DOT) across four major antimicrobial agents were used to calculate facility-wide SCRs using each denominator and were evaluated by least-squares regression and R2 values. Results: Within the 894 bed academic hospital, the average monthly facility-wide days were 28 424, 22 198, 15 957 and 14 789 by the DP, PP, PD and BD definitions, respectively. Within the 114 bed community hospital, the average monthly facility-wide days were 5175, 3523 and 2816 by the DP, PP and PD definitions, respectively. Strong concordance was observed between facility-wide SCRs using the DP and PP definitions in both the academic (R2 = 0.99, y = 0.78x - 0.001) and community (R2 = 0.99, y = 0.68x - 0.03) centres across all four inpatient antibiotics evaluated. In an analysis of piperacillin/tazobactam SCRs, rates were over-predicted by 28%-93% at the facility-wide level across centres using alternative denominators. Conclusions: We found that data source and definitions of at-risk denominator days meaningfully impact antibiotic SCRs. Centres should carefully consider these potential sources of variation when setting consumption benchmarks and internally evaluating use.

Analysis of an Infectious Diseases Pharmacist on Call Pager Program to Inform Educational Efforts.

Background: An on call infectious diseases (ID) pharmacist may be used as a resource for physicians, pharmacists, and other health care providers to help answer questions regarding anti-infective agents. Objective: To assess type, requestor, resources dedicated, and temporal trends of questions received through an ID pharmacist on call pager program. A secondary objective was to gather insight as to how this information was utilized to inform educational initiatives. Methods: This was a retrospective study of questions received by the ID pharmacist on call via pager at a large academic medical center. Question data were documented in a central database and analyzed to assess temporal trends and question type, and qualitatively analyzed to determine areas for targeted educational efforts. Results: The ID pharmacist on call recorded 545 questions during the 1-year study period; questions were composed of various antimicrobial agent-related queries, including antibiotic spectrum and selection (n = 251, 46.1%), dosing of antimicrobials (n = 195, 35.8%), and drug monitoring (n = 26, 4.8%). Targeted educational initiatives secondary to questions received included pharmacist education regarding the use of polymyxin antibiotics and antibiotic dosing protocol updates. Conclusions: An ID pharmacist on call pager program was utilized to inquire about antibiotic spectrum and selection for the majority of questions. Records of questions received may be utilized to direct educational efforts and create or revise targeted resources for pharmacists and other clinicians.

Investigating the Extremes of Antibiotic Use with an Epidemiologic Framework.

Benchmarks for judicious use of antimicrobials are needed. Metrics such as defined daily doses (DDDs) and days of therapy (DOTs) quantify antimicrobial consumption. However, benchmarking with these metrics is complicated by interhospital variability. Thus, it is important for each hospital to monitor its own temporal consumption trends. Time series analyses allow trends to be detected; however, many of these methods are complex. We present simple regressive methods and caveats in using them to define potential antibiotic over- and underutilizations.

Use of electronic health records and clinical decision support systems for antimicrobial stewardship.

Electronic health records (EHRs) and clinical decision support systems (CDSSs) have the potential to enhance antimicrobial stewardship. Numerous EHRs and CDSSs are available and have the potential to enable all clinicians and antimicrobial stewardship programs (ASPs) to more efficiently review pharmacy, microbiology, and clinical data. Literature evaluating the impact of EHRs and CDSSs on patient outcomes is lacking, although EHRs with integrated CDSSs have demonstrated improvements in clinical and economic outcomes. Both technologies can be used to enhance existing ASPs and their implementation of core ASP strategies. Resolution of administrative, legal, and technical issues will enhance the acceptance and impact of these systems. EHR systems will increase in value when manufacturers include integrated ASP tools and CDSSs that do not require extensive commitment of information technology resources. Further research is needed to determine the true impact of current systems on ASP and the ultimate goal of improved patient outcomes through optimized antimicrobial use.

Bringing the "power" to Cerner's PowerChart for antimicrobial stewardship.

The electronic medical record (EMR) has huge potential for facilitating antimicrobial stewardship efforts by directing providers to preferred antimicrobials. Cerner PowerChart currently holds the number 2 position in the EMR market. Although PowerChart has limited "out of the box" functionalities to optimize stewardship efforts, there are many potential utilities that can be developed to assist in stewardship practice. However, to harness the stewardship potential of the EMR system, significant hospital information technology resources are needed. Herein we describe the experiences of 3 large healthcare systems utilizing Cerner to facilitate prior authorization of antimicrobials, prospective audit and feedback of antimicrobials, and supplemental stewardship strategies.

Use of a Clinical Decision Support System Alert to Prevent Supratherapeutic Vancomycin Concentrations.

Background: Alerts issued by clinical decision support systems (CDSS) may be useful to identify and prevent the occurrence of acute kidney injury among patients on nephrotoxic drugs, particularly vancomycin. Objective: The purpose of this instructive study was to determine the effectiveness of using a pharmacist-run CDSS alert of early serum creatinine increases in patients receiving intravenous vancomycin to decrease the proportion of severely elevated vancomycin concentrations. Methods: This was a retrospective study of a prospectively reviewed CDSS alert that triggered in patients with an increase in serum creatinine by 25% from baseline within 24 hours. Severely elevated vancomycin concentrations were divided into a control group (before alert implementation) and a study group (after alert implementation) and considered for study inclusion. The proportion of severely elevated vancomycin concentrations (ie, >30 mg/L) were collected in the control and study groups. Results: There were 1290 and 1501 vancomycin concentrations in the control group and the study group, respectively. A total of 696 CDSS alerts triggered during the study period. The proportion of severely elevated vancomycin troughs decreased from 5.3% (n = 68, median = 36.6 mg/L, interquartile range = 33.75-43.2 mg/L) in the control group to 3.7% (n = 55, median = 34.7 mg/L, interquartile range = 31.3-39.3 mg/L) in the study group. This reflects a statistically significant decrease in the proportion of severely elevated vancomycin concentrations (P = .04). Conclusion: Overall, this instructive analysis on a novel use of CDSS software suggests that the implementation of an alert based on early detection of serum creatinine changes led to a significant decrease in the proportion of severely elevated serum vancomycin concentrations.

Diagnostic testing and antibiotic utilization among inpatients evaluated for coronavirus disease 2019 (COVID-19) pneumonia.

We evaluated diagnostic test and antibiotic utilization among 252 patients from 11 US hospitals who were evaluated for coronavirus disease 2019 (COVID-19) pneumonia during the severe acute respiratory coronavirus virus 2 (SARS-CoV-2) omicron variant pandemic wave. In our cohort, antibiotic use remained high (62%) among SARS-CoV-2-positive patients and even higher among those who underwent procalcitonin testing (68%).

Clinical implications of antiretroviral drug interactions with warfarin: a case-control study.

OBJECTIVES: Warfarin, a frequently prescribed anticoagulant with a narrow therapeutic index, is susceptible to drug-drug interactions with antiretroviral therapy (ART). This study compared the warfarin maintenance dose (WMD) between patients receiving and not receiving ART and evaluated predictors of warfarin dosage among those on ART. METHODS: This was a case-control (1:2) study. Cases were HIV-infected patients receiving warfarin and protease inhibitor (PI)- and/or non-nucleoside reverse transcriptase inhibitor (NNRTI)-based ART. Controls were randomly selected HIV-uninfected patients receiving warfarin. The WMD was compared between cases and controls and between cases on varying ART regimens. Bivariate comparisons were performed and a linear regression model was developed to identify predictors of WMD. RESULTS: We identified 18 case and 36 control patients eligible for inclusion. Cases were younger than controls (mean age: 45.8 versus 63.1 years, P < 0.01), more often male (72.2% versus 36.1%, P=0.02) and more likely to be African American (50.0% versus 22.2%, P=0.04). ART was classified as PI-based (n=9), NNRTI-based (n=7) and PI + NNRTI-based (n=2). The WMD (mean ±â€ŠSD) differed between cases and controls (8.6  ±  3.4 mg versus 5.1 ±â€Š1.5 mg, P < 0.01), but not ART regimens (PI: 8.8  ±  4.5 mg; NNRTI: 8.6   ±â€Š1.8 mg; PI + NNRTI: 7.3  ±  3.3 mg; P = 0.86). Race and ritonavir dose were independent predictors of WMD, predicting an increase of 3.9 mg (95% CI: 0.88-6.98, P = 0.02) if a patient was African American or 3.7 mg (95% CI: 0.53-6.89, P = 0.03) if the total daily ritonavir dose was 200 mg. CONCLUSIONS: The required WMD was significantly higher in patients receiving ART. Prompt dose titration to achieve a higher WMD with vigilant monitoring may be required due to these drug-drug interactions.

The impact of anti-infective drug shortages on hospitals in the United States: trends and causes.

Anti-infective shortages pose significant logistical and clinical challenges to hospitals and may be considered a public health emergency. Anti-infectives often represent irreplaceable life-saving treatments. Furthermore, few new agents are available to treat increasingly prevalent multidrug-resistant pathogens. Frequent anti-infective shortages have substantially altered patient care and may lead to inferior patient outcomes. Because many of the shortages stem from problems with manufacturing and distribution, federal legislation has been introduced but not yet enacted to provide oversight for the adequate supply of critical medications. At the local level, hospitals should develop strategies to anticipate the impact and extent of shortages, to identify therapeutic alternatives, and to mitigate potential adverse outcomes. Here we describe the scope of recent anti-infective shortages in the United States and explore the reasons for inadequate drug supply.

Evaluation of clinical outcomes in patients with bloodstream infections due to Gram-negative bacteria according to carbapenem MIC stratification.

Predictive modeling suggests that actual carbapenem MIC results are more predictive of clinical patient outcomes than categorical classification of the MIC as susceptible, intermediate, or resistant. Some have speculated that current CLSI guidelines' suggested thresholds are too high and that clinical success is more likely if the MIC value is ≤1 mg/liter for certain organisms. Patients treated with carbapenems and with positive blood cultures for Pseudomonas aeruginosa, Acinetobacter baumannii, or extended-spectrum beta-lactamase (ESBL)-producing Gram-negative bacteria were considered for evaluation in this clinical retrospective cohort study. Relevant patient demographics and microbiologic variables were collected, including carbapenem MIC. The primary objective was to define a risk-adjusted all-cause hospital mortality breakpoint for carbapenem MICs. Secondarily, we sought to determine if a similar breakpoint existed for indirect outcomes (e.g., time to mortality and length of stay [LOS] postinfection for survivors). Seventy-one patients met the criteria for study inclusion. Overall, 52 patients survived, and 19 died. Classification and regression tree (CART) analysis determined a split of organism MIC between 2 and 4 mg/liter and predicted differences in mortality (16.1% versus 76.9%; P < 0.01). Logistic regression controlling for confounders identified each imipenem MIC doubling dilution as increasing the probability of death 2-fold (adjusted odds ratio [aOR] 2.0; 95% confidence interval [CI], 1.3 to 3.2). Secondary outcomes were similar between groups. This study revealed that patients with organisms that had a MIC of ≥4 mg/liter had worse outcomes than patients whose isolates had a MIC of ≤2 mg/liter, even after adjustment for confounding variables. We recommend additional clinical studies to better understand the susceptibility breakpoint for carbapenems.

Successful treatment of extensively drug-resistant Acinetobacter baumannii peritoneal dialysis peritonitis with intraperitoneal polymyxin B and ampicillin-sulbactam.

OBJECTIVE: To describe a case of extensively drug-resistant (XDR) Acinetobacter baumannii peritoneal dialysis (PD)-associated peritonitis successfully treated with combination antibiotics, including intraperitoneal polymyxin B, with retention of the catheter. CASE SUMMARY: A 54-year-old woman with end-stage renal disease receiving chronic PD and recent antibiotic and hospital exposure presented with abdominal pain, nausea, and vomiting. She was found to have XDR A. baumannii PD peritonitis. Treatment was initiated with intravenous and intraperitoneal ampicillin-sulbactam, followed by the addition of intraperitoneal polymyxin B based on susceptibilities. The patient recovered without the need for catheter removal or switch to hemodialysis. DISCUSSION: The frequency of XDR A. baumannii as a nosocomial pathogen is increasing, and polymyxins are being used more often as part of combination therapy for infections caused by this organism. Neither XDR A. baumannii PD peritonitis nor the use of intraperitoneal polymyxin B has been well described. In our patient, intraperitoneal dosing of polymyxin B was determined based on limited published pharmacokinetic and pharmacodynamic data. CONCLUSIONS: A case of XDR A. baumannii PD peritonitis was successfully treated with combination antibiotic therapy, including intraperitoneal polymyxin B, without major complications.

Decreasing incidence of Acinetobacter baumannii pneumonia and trends in antibiotic consumption: A single-center retrospective observational study.

OBJECTIVE: To describe the epidemiology of Acinetobacter baumannnii (AB) pneumonia at our center, including the antibiotic exposure patterns of individual AB pneumonia cases and to investigate whether hospital-wide antibiotic consumption trends were associated with trends in AB pneumonia incidence. DESIGN: Single-center retrospective study with case-control and ecological components. SETTING: US private tertiary-care hospital. PARTICIPANTS AND METHODS: All hospitalized patients with AB infection from 2008 to 2019 were identified through laboratory records; for those with AB pneumonia, medical records were queried for detailed characteristics and antibiotic exposures in the 30 days preceding pneumonia diagnosis. Hospital-wide antibiotic consumption data from 2015 through 2019 were obtained through pharmacy records. RESULTS: Incidence of both pneumonia and nonrespiratory AB infections decreased from 2008 to 2019. Among the 175 patients with AB pneumonia, the most frequent antibiotic exposure was vancomycin (101 patients). During the 2015-2019 period when hospital-wide antibiotic consumption data were available, carbapenem consumption increased, and trends negatively correlated with those of AB pneumonia (r = -0.48; P = .031) and AB infection at any site (r = -0.63; P = .003). Conversely, the decline in AB infection at any site correlated positively with concurrent declines in vancomycin (r = 0.55; P = .012) and quinolone consumption (r = 0.51; P = .022). CONCLUSIONS: We observed decreasing incidence of AB infection despite concurrently increasing carbapenem consumption, possibly associated with declining vancomycin and quinolone consumption. Future research should evaluate a potential role for glycopeptide and quinolone exposure in the pathogenesis of AB infection.

Impact of early antimicrobial stewardship intervention in patients with positive blood cultures: results from a randomized comparative study.

BACKGROUND: Antimicrobial stewardship intervention (ASI) appears to be necessary to realize the full benefits of rapid diagnostic technologies in clinical practice. This study aimed to compare clinical outcomes between early ASI paired with matrix-associated laser desorption ionization-time of flight mass spectrometry (MALDI-TOF) compared with MALDI-TOF with standard of care (SOC) reporting in patients with positive blood cultures. METHODS: Adult patients with positive blood cultures and organism speciation via MALDI-TOF admitted between February 2015 and September 2015 were randomized to ASI or SOC in a 1:1 fashion. Patients admitted for at least 48 h following positive culture were included in analyses. ASI was defined as a clinical assessment by a stewardship team member with non-binding treatment recommendations offered to the primary team. The primary outcome was time to definitive therapy. Secondary outcomes included post-culture length of stay (LOS), time to first change in antibiotics, and in-hospital mortality. RESULTS: In total, 149 patients were included in the analyses (76 in the ASI group and 73 in the SOC group). ASI and SOC arms did not differ according to age, sex, comorbidities or severity of illness. Gram-positive organisms were common in both SOC and ASI arms (74.0 vs. 61.8%, P=0.11). Time to definitive therapy was reduced, on average, by 30.3 h in the ASI group (71.6 vs. 41.3 h, P=0.01). Hospital LOS following the first positive blood culture was significantly shorter in the ASI group (8.7 vs. 11.2 days, P=0.049). CONCLUSIONS: ASI combined with MALDI-TOF reduced the time to definitive therapy and time to first change in antibiotics, and was associated with a shorter post-culture LOS.

The impact of coronavirus disease 2019 (COVID-19) on the antimicrobial stewardship pharmacist workforce: A multicenter survey.

Objective: The coronavirus disease 2019 (COVID-19) pandemic has required healthcare systems and hospitals to rapidly modify standard practice, including antimicrobial stewardship services. Our study examines the impact of COVID-19 on the antimicrobial stewardship pharmacist. Design: A survey was distributed nationally to all healthcare improvement company members. Participants: Pharmacist participants were mostly leaders of antimicrobial stewardship programs distributed evenly across the United States and representing urban, suburban, and rural health-system practice sites. Results: Participants reported relative increases in time spent completing tasks related to medication access and preauthorization (300%; P = .018) and administrative meeting time (34%; P = .067) during the COVID-19 pandemic compared to before the pandemic. Time spent rounding, making interventions, performing pharmacokinetic services, and medication reconciliation decreased. Conclusion: A shift away from clinical activities may negatively affect the utilization of antimicrobials.