Measuring empiric antibiotic spectrum-A journey through space and time.

OBJECTIVES: The typical 5-day work week affects healthcare outcomes. Structured work hours have also been implicated in antimicrobial prescribing choice. We developed a visualization tool to aid in evaluating breadth of antibiotic use in various time (day of week and hour of day) and space (patient location) combinations. METHODS: We evaluated antibiotic administration data from a tertiary-care academic medical center between July 1, 2018, and July 1, 2020. We calculated a cumulative empiric antibiotic spectrum score by adapting a previously validated antibiotic spectrum index (ASI) and applying that score to empiric antibiotic use. We visualized these data as a heat map based on various day-of-week-time combinations and then compared the distribution of scores between weekday nights, weekend days, and weekend nights to the typical workweek hours (weekday days, weekday days) using the Mann-Whitney U nonparametric test with a Bonferroni correction. RESULTS: The analysis included 76,535 antibiotic starts across 53,900 unique patient admissions over 2 years. The mean cumulative ASI was higher in all 3 night and weekend combinations (weekday nights, 7.3; weekend days, 7.6; weekend nights, 7.5) compared to the weekday daytime hours (weekday days, 7.1) and the distribution of scores was different in all groups compared to the weekday daytime reference. The cumulative ASI was also higher in intensive care units. CONCLUSIONS: Empiric antibiotic prescribing patterns differed across space and time; broader antibiotic choices occurred in the intensive care units and on nights and weekends. Visualization of these patterns aids in antimicrobial prescribing pattern recognition and may assist in finding opportunities for additional antimicrobial stewardship interventions.

Comparison of Open-Access, Trough-Only Online Calculators Versus Trapezoidal Method for Calculation of Vancomycin Area Under the Curve (AUC).

BACKGROUND: Vancomycin area-under-the-curve (AUC) monitoring is associated with reduced nephrotoxicity but may increase cost and workload for personnel compared to trough monitoring. OBJECTIVE: The purpose of this study was to compare the accuracy of vancomycin AUC calculated by open-access, online, trough-only calculators to AUCs calculated by the trapezoidal method (TM) using peak and trough concentrations. METHODS: This retrospective, multi-center study included adults ≥18 years old with stable renal function who received vancomycin with steady-state peak and trough concentrations. Areas under the curve calculated by TM were compared to AUCs calculated by 3 online calculators using trough-only options for calculation: ClinCalc, VancoVanco, and VancoPK. The primary outcome was actual difference in AUC between TM and the online calculators. Secondary outcomes were percent difference in AUC and clinical alignment in dose adjustments between methods. RESULTS: Seventy patients were included for analysis. There was a statistically significant difference in AUC between TM and ClinCalc (median actual difference: -52, P < 0.001) and VancoVanco (median actual difference: 95, P < 0.001), whereas there was no significant difference between TM and VancoPK (median actual difference: -0.8, P = 0.827). Discordant dose adjustments were indicated when comparing ClinCalc, VancoVanco, and VancoPK to TM in 28%, 36%, and 12% of cases, respectively. CONCLUSION: The AUC calculator most closely aligned with TM was VancoPK, whereas other included calculators were statistically different. Owing to the cost and complexity of obtaining multiple levels, our findings support using a single steady-state trough using VancoPK as an alternative to TM for calculation of vancomycin AUC.

Evaluation of an Opt-Out Protocol for Antibiotic De-Escalation in Patients With Suspected Sepsis: A Multicenter, Randomized, Controlled Trial.

BACKGROUND: Sepsis guidelines recommend daily review to de-escalate or stop antibiotics in appropriate patients. This randomized, controlled trial evaluated an opt-out protocol to decrease unnecessary antibiotics in patients with suspected sepsis. METHODS: We evaluated non-intensive care adults on broad-spectrum antibiotics despite negative blood cultures at 10 US hospitals from September 2018 through May 2020. A 23-item safety check excluded patients with ongoing signs of systemic infection, concerning or inadequate microbiologic data, or high-risk conditions. Eligible patients were randomized to the opt-out protocol vs usual care. Primary outcome was post-enrollment antibacterial days of therapy (DOT). Clinicians caring for intervention patients were contacted to encourage antibiotic discontinuation using opt-out language. If continued, clinicians discussed the rationale for continuing antibiotics and de-escalation plans. To evaluate those with zero post-enrollment DOT, hurdle models provided 2 measures: odds ratio of antibiotic continuation and ratio of mean DOT among those who continued antibiotics. RESULTS: Among 9606 patients screened, 767 (8%) were enrolled. Intervention patients had 32% lower odds of antibiotic continuation (79% vs 84%; odds ratio, 0.68; 95% confidence interval [CI], .47-.98). DOT among those who continued antibiotics were similar (ratio of means, 1.06; 95% CI, .88-1.26). Fewer intervention patients were exposed to extended-spectrum antibiotics (36% vs 44%). Common reasons for continuing antibiotics were treatment of localized infection (76%) and belief that stopping antibiotics was unsafe (31%). Thirty-day safety events were similar. CONCLUSIONS: An antibiotic opt-out protocol that targeted patients with suspected sepsis resulted in more antibiotic discontinuations, similar DOT when antibiotics were continued, and no evidence of harm. CLINICAL TRIALS REGISTRATION: NCT03517007.

Impact of COVID-19 pandemic on pharmacist-led allergy assessments and penicillin skin testing.

Allergy assessments and penicillin skin testing are associated with reductions in high-Clostridioides difficile infection (CDI)-risk antibiotic use and lower hospital-acquired CDI rates; however, these activities require substantial personnel and resource allocation. Recently, many antimicrobial stewardship programs' (ASPs) focus shifted towards supporting the COVID-19 pandemic response. We evaluated the impact of the COVID-19 pandemic on a pharmacist-led allergy assessment and penicillin skin testing program. Patients undergoing allergy assessment and/or penicillin skin testing (PST) from 1 January 2017 through 30 April 2021 were included for review. Monthly PST and allergy assessment rates were calculated and defined as the number of PSTs or allergy assessments per 1000 unique patient encounters for each month, respectively. The study used interrupted time series regression to assess potential level and slope changes in allergy assessments and PSTs during the pandemic. 200 058 total inpatient encounters by 188 867 unique patients occurred during the study period. ASP performed 918 allergy assessments and 204 PSTs. The local onset of the SARS-CoV-2 pandemic during March 2020 was associated with significant level reductions in allergy assessments and PSTs. Additional responsibilities added to the ASP team during the COVID-19 pandemic limited the ability to perform core antimicrobial stewardship activities with proven patient care benefits.

Characterization of Isavuconazole serum concentrations after enteral feeding tube administration in a hospitalized cohort: A case series.

WHAT IS KNOWN AND OBJECTIVE: Invasive fungal infections often occur in patients with comorbidities that complicate oral administration. Serum concentrations of isavuconazole were characterized after enteral tube administration. CASE DESCRIPTION: Thirteen of 14 isavuconazole concentrations were >1 mg/dl (median 1.6 mg/dl) among those receiving enteral tube administration, which was comparable to intravenous (median 1.9 mg/dl). Higher concentrations were observed during oral administration (median 3 mg/dl). WHAT IS NEW AND CONCLUSION: Administration of isavuconazole via tube resulted in concentrations comparable to FDA-approved routes of administration. This route may be feasible and appropriate for select patients.

Ceftolozane-tazobactam: A new-generation cephalosporin.

PURPOSE: The chemistry, pharmacokinetic and pharmacodynamic properties, efficacy, and safety of the recently introduced combination antimicrobial agent ceftolozane-tazobactam are reviewed. SUMMARY: Ceftolozane-tazobactam (Zerbaxa, Cubist Pharmaceuticals) is a cephalosporin ß-lactam and ß-lactamase inhibitor marketed as a fixed-dose combination agent for the treatment of complicated urinary tract and intraabdominal infections. Its dosing and chemistry provide expansive antimicrobial coverage of gram-negative organisms, including Pseudomonas aeruginosa, and stable activity against many ß-lactamases, as well as coverage of most extended-spectrum ß-lactamase-producing organisms and some anaerobes. Ceftolozane-tazobactam is susceptible to hydrolysis by carbapenemase enzymes but is not affected by other resistance mechanisms such as efflux pumps and porin loss. Clinical trials demonstrated that combination treatment with ceftolozane-tazobactam plus metronidazole had efficacy comparable to that of levofloxacin in patients with complicated urinary tract infections, including pyelonephritis, and comparable to that of meropenem against complicated intraabdominal infections. A Phase III trial of ceftolozane-tazobactam versus meropenem for treatment of bacterial pneumonia, including ventilator-associated pneumonia, is underway. Adverse effects reported with ceftolozane-tazobactam use are comparable to those seen with other ß-lactams (e.g., hypersensitivity, nausea, diarrhea, headache). Initially, ceftolozane-tazobactam may be reserved for targeted therapy against multidrug-resistant pathogens. CONCLUSION: Ceftolozane-tazobactam is a new cephalosporin with enhanced activity against multidrug-resistant P. aeruginosa and other gram-negative pathogens.

Clinical and economic outcomes associated with medication errors in kidney transplantation.

BACKGROUND AND OBJECTIVES: Modern immunosuppressant regimens have significantly decreased acute rejection rates, but may have increased the risk of graft loss driven by adverse drug reactions (ADRs) and medication errors (MEs). The objectives of this study were to determine the incidence and risk factors for MEs and ADRs and determine the association between transplant outcomes and these events. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This was a post hoc analysis of a prospective, randomized trial that included patients aged>18 years that received a solitary renal transplant at an academic medical center recruited between March 2009 and July 2011. Patients were divided into groups based on developing a clinical significant ME (CSME), defined as a significant ME that contributed to a hospital admission. RESULTS: The mean study follow-up was 2.5 ± 0.7 years. There were a total of 233 MEs and 327 ADRs in the 200 patients included in the analysis, with 64% of the cohort experiencing at least one ME and 87% experiencing an ADR; 23 patients (12%) experienced a CSME. Patients that experienced CSMEs had a trend toward more post-transplant readmissions (median 1 [interquartile range (IQR), 0-5] versus 0 [0-2]; P=0.06), higher costs for readmissions (median $18,091 [IQR, $3023-$56,268] versus $0 [$0-$15,991]; P<0.01), and overall length of stay (median 5.0 days [IQR, 2.0-14.0] versus 0.0 days [IQR, 0.0-5.5]; P<0.01) after the CSME event. CSME patients were also more likely to experience graft failure (22% versus 10%; P=0.05). CONCLUSIONS: Significant MEs commonly occur in renal transplant recipients and are associated with an increased risk of deleterious clinical outcomes, including subsequent hospital days, costs, and graft loss.

Bullous pemphigoid: corticosteroid treatment and adverse effects in long-term care patients.

Bullous pemphigoid (BP) is the most common autoimmune bullous disease. It primarily presents in elderly patients older than 70 years of age. The presentation can vary with localized or generalized disease that variably affects mucosal tissue. Therapy primarily consists of administration of topical and systemic corticosteroids. Topical corticosteroids are effective with less adverse effects compared with systemic steroids. Other therapies, such as steroid-sparing agents and plasma exchanges, have been recommended and studied to some degree, but these require more evidence before they can be routinely recommended. A 68-year-old African-American female resident of a nursing facility develops a rash and is evaluated at a dermatology clinic. Since the resident has many medications and concomitant diseases, the physician at first suspected a drug rash. On subsequent visits, the resident undergoes multiple punch biopsies and is diagnosed with BP. Treatment is initiated with topical steroids, systemic steroids, and oral minocycline. On a follow-up visit, the resident is showing improvement of her BP. However, the resident's hypertension and hyperglycemia are now uncontrolled as a result of the discontinuation of hydrochlorothiazide and the initiation of steroid therapy. This case highlights the dangers of corticosteroids in patients, especially the elderly, who have multiple comorbidities.