Evaluation of Timing of Antimicrobial Surgical Prophylaxis on Rates of Surgical Site Infections.

Background: Surgical site infections (SSIs) are common healthcare-associated infections, and national guidelines recommend that antimicrobial prophylaxis (AP) be administered 60 min prior to incision. However, there are limited data regarding the "most optimal" time for administration within the 60-min window. Patients and Methods: This was a multicenter, retrospective study of adult (≥18-year-old) patients that underwent an abdominal hysterectomy, colorectal surgery, or craniotomy and received AP within 60 min of incision. Incidence of SSI was compared between patients who received AP 0-30 versus 31-60 min of incision. In addition, a predefined subgroup analysis evaluated incidence of SSI for 15-min intervals within the 60-min timeframe. Results: Of the 277 patients included in the primary analysis, 233 (84.1%) and 44 (15.9%) received AP 0-30 min and 31-60 min prior to incision, respectively. SSIs were documented in 6.0% (14/233) versus 4.5% (2/44) of patients in the primary analysis (p = 0.703). In the secondary analysis, 137 (49.5%), 95 (34.3%), 34 (12.3%), and 11 (4.0%) patients received AP 0-15, 16-30, 31-45, and 46-60 min prior to incision, respectively. There was no difference in incidence of SSIs among the 15-min intervals (4.4% vs. 8.4% vs. 2.9% vs. 9.1%, p = 0.487). Of the 16 patients in this study that incurred a SSI, 5 patients had positive cultures, of which 3 contained bacteria that proved to be resistant to the antibiotic used for AP. Conclusions: The results of our analysis support current national guidelines. Future investigation of different intervals (e.g., AP 15-45 min prior to incision) may be beneficial on the basis of pharmacokinetics of routinely prescribed AP.

A Retrospective Case Series of Concomitant Carbapenem and Valproic Acid Use: Are Best Practice Advisories Working?

Background: A Best Practice Advisory (BPA) warns clinicians of an interaction between carbapenems and valproic acid (VPA) that can cause significant declines in VPA levels leading to serious consequences for patients treated for seizure disorder and unknown implications for alternative indications. Objective: The goal of this study was to assess BPA efficacy in avoiding concomitant VPA/carbapenems, and to characterize use of these agents, clinical implications, and potential alternative therapeutic options. Methods: Retrospective chart review was performed on all patients over the course of 1 year who were concomitantly prescribed a carbapenem and VPA at Hartford Hospital, Hartford, CT. Data collected included: level of care, duration of concomitant therapy, indications, VPA levels during or surrounding overlap, documentation of the interaction, and therapeutic implications. Results: Carbapenems and VPA were administered to 591 and 625 patients, respectively; the BPA fired 126 times in 24 patients, and 15 patients were initiated on these agents concomitantly. Eight (53%) patients received VPA for seizures. The remaining seven (47%) received VPA for alternative indications. Eight of nine VPA levels were sub-therapeutic during carbapenem therapy and polypharmacy was administered in all patients receiving VPA for non-convulsive indications. Conclusion: Co-prescribing of these drugs was rare; however, the BPA was ineffective in 63% of instances. Reductions in VPA efficacy for any indication should be expected with concomitant carbapenem administration. Antibiotics other than carbapenems should be considered when coverage of multidrug resistant Gram-negative pathogens is required in patients whose VPA treatment cannot be interrupted or switched to a therapeutic alternative.

Impact of a Pharmacist-Managed Procalcitonin Program on COVID-19 Respiratory Tract Infection Outcomes and Health Care Resource Utilization.

Patients hospitalized with coronavirus disease 2019 (COVID-19) often receive empiric antibiotic coverage. Procalcitonin (PCT) is a biomarker with Food and Drug Administration-approved guidance cutoffs for antibiotic use in lower respiratory tract infections. Herein we describe the implementation and impact of a pharmacist-managed PCT monitoring program in hospitalized patients with COVID-19. In this quasi-experimental, single-center, retrospective study of a prospective antimicrobial stewardship pharmacist-managed program, inpatients who were severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction positive were reviewed during weekday working hours and evaluated for appropriateness of antibiotic treatment by utilizing the PCT biomarker. As needed, the infectious diseases pharmacist offered feedback around antibiotic discontinuation in patients with PCT values ≤0.25 ng/mL. Adherence to PCT cutoffs, clinical outcomes, and utilization of health care resources were quantified and compared with a time frame immediately preceding the program's implementation. A total of 772 patients hospitalized with COVID-19 were analyzed. The pre-intervention cohort was comprised of 519 patients, and 253 patients were included after program implementation. Antibiotics were prescribed within 72 hours of admission to 232 (44.7%) and 108 (42.7%) patients during the control and intervention phases, respectively. There was no difference in the primary outcome of percentage of patients who received >1 day of antibiotic therapy (23.5% vs 21.7%; P = .849) or in any secondary outcome including hospital length of stay, 30-day readmission rates, or discharge disposition. In a hospital where the majority of COVID-19 patients did not receive empiric antibiotics, the implementation of a pharmacist-managed PCT monitoring program did not significantly decrease antibiotic use or health care resource utilization.

Antimicrobial Stewardship at Transitions of Care to Outpatient Settings: Synopsis and Strategies.

Inappropriate antibiotic use and associated consequences, including pathogen resistance and Clostridioides difficile infection, continue to serve as significant threats in the United States, with increasing incidence in the community setting. While much attention has been granted towards antimicrobial stewardship in acute care settings, the transition to the outpatient setting represents a significant yet overlooked area to target optimized antimicrobial utilization. In this article, we highlight notable areas for improved practices and present an interventional approach to stewardship tactics with a framework of disease, drug, dose, and duration. In doing so, we review current evidence regarding stewardship strategies at transitional settings, including diagnostic guidance, technological clinical support, and behavioral and educational approaches for both providers and patients.

Impact of Order-Set Modifications and Provider Education Following Guideline Updates on Broad-Spectrum Antibiotic Use in Patients Admitted With Community Acquired Pneumonia.

Purpose: Following updates to the Infectious Diseases Society of America (IDSA) practice guidelines for the Diagnosis and Treatment of Adults with Community-acquired Pneumonia in 2019, Hartford HealthCare implemented changes to the community acquired pneumonia (CAP) order-set in August 2020 to reflect criteria for the prescribing of broad-spectrum antimicrobial therapy. The objective of the study was to evaluate changes in broad-spectrum antibiotic days of therapy (DOT) following these order-set updates with accompanying provider education. Methods: This was a multi-center, quasi-experimental, retrospective study of patients with a diagnosis of CAP from September 1, 2019 to October 31, 2019 (pre-intervention) and September 1, 2020 to October 31, 2020 (post-intervention). Patients were identified using ICD-10 codes (A48.1, J10.00-J18.9) indicating lower respiratory tract infection. Data collected included demographics, labs and vitals, radiographic, microbiological, and antibiotic data. The primary outcome was change in broad-spectrum antibiotic DOT, specifically anti-pseudomonal ß-lactams and anti-MRSA antibiotics. Secondary outcomes included guideline-concordance of initial antibiotics, utilization of an order-set to prescribe antibiotics, and length of stay (LOS). Results: A total of 331 and 352 patients were included in the pre- and post-intervention cohorts, respectively. There were no differences in order-set usage (10% vs 11.3%, P = .642) between the pre- and post-intervention cohort, respectively. The overall duration of broad-spectrum therapy was a median of 2 days (IQR 0-8 days) in the pre-intervention period and 0 days (IQR 0-4 days) in the post-intervention period (P < .001). Patients in whom the order-set was used in the post-intervention period were more likely to have guideline-concordant regimens ([36/40] 90% vs [190/312] 60.9%; P = .003). Hospital LOS was shorter in the post-intervention cohort (4.8 days [2.9-7.2 days] vs 5.3 days [IQR 3.5-8.5 days], P = .002). Conclusion: Implementation of an updated CAP order-set with accompanying provider education was associated with reduced use of broad-spectrum antibiotics. Opportunities to improve compliance and thus further increase guideline-concordant therapy require investigation.

Cefiderocol for the Treatment of Adult and Pediatric Patients With Cystic Fibrosis and Achromobacter xylosoxidans Infections.

Treatment options for Achromobacter xylosoxidans are limited. Eight cystic fibrosis patients with A. xylosoxidans were treated with 12 cefiderocol courses. Pretreatment in vitro resistance was seen in 3 of 8 cases. Clinical response occurred after 11 of 12 treatment courses. However, microbiologic relapse was observed after 11 of 12 treatment courses, notably without emergence of resistance.

Plazomicin: an intravenous aminoglycoside antibacterial for the treatment of complicated urinary tract infections.

INTRODUCTION: Antimicrobial resistance continues to be a major public health concern due to the emergence and spread of multi-drug resistant (MDR) organisms, including extended spectrum ß-lactamase (ESBL) and carbapenemase producing Enterobacterales. Plazomicin is a novel aminoglycoside that demonstrates activity against MDR gram-negatives, including those producing ESBLs and most carbapenemases, and retains activity against aminoglycoside modifying enzymes as a result of structural modifications. The information discussed is meant to assist in identifying plazomicin's place in therapy and to expand the clinician's armamentarium. AREAS COVERED: Herein, we review the pharmacology, microbiology, clinical efficacy, and safety of plazomicin. To gather relevant information, a literature search was performed using PubMed, Ovid, and Google Scholar electronic databases. Search terms used include plazomicin, ACHN-490, extended spectrum ß-lactamase, ESBL, CRE, aminoglycoside modifying enzymes, and AME. Additional information was obtained from FDA review documents and research abstracts presented at international conferences. EXPERT OPINION: Plazomicin is a promising carbapenem or ß-lactam/ß-lactamase inhibitor-sparing alternative for the treatment of complicated urinary tract infections caused by MDR Enterobacterales. Although robust data for bloodstream infections and bacterial pneumonias are lacking, plazomicin may be considered in individual clinical scenarios if combination therapy is warranted provided supportive microbiological data and therapeutic drug monitoring are available.

Predicting and preventing antimicrobial resistance utilizing pharmacodynamics: part II Gram-negative bacteria.

INTRODUCTION: Antimicrobial resistance is a serious health threat worldwide. Better understanding of exposure targets that could suppress resistance amplification is necessary to guide the dosing of currently available agents as well as new therapies in the drug development process. Areas covered: This review will discuss studies that focused on predicting development of resistance using the pharmacokinetic-pharmacodynamic approach and how to design dosing regimens that can successfully suppress resistance emergence in Gram-negative bacteria. Expert opinion: Pharmacokinetic-pharmacodynamic targets could provide useful insights to guide antimicrobial dosing to prevent resistance emergence. Exposure targets required for resistance suppression are higher than those for efficacy and might not be clinically feasible. Combination therapy is a possible approach to improve the efficacy and minimize the resistance emergence for difficult-to-treat infections.

Epidemiology, treatment, and economics of patients presenting to the emergency department for skin and soft tissue infections.

OBJECTIVES: Skin and soft tissue infections (SSTIs) are among the most common bacterial diseases and represent a significant disease burden. The purpose of this study was to describe the real-world management of patients with SSTIs presenting to the emergency department (ED). METHODS: This is a retrospective cohort study. Adult patients identified with a primary diagnosis of SSTI determined by ICD-9 codes were assessed from index presentation for up to 30 days. Records were reviewed 30 days prior to inclusion to ensure index hospitalization was captured. For recurrent visits, a similar strategy was implemented 30 days afterward. RESULTS: Of 446 encounters screened, 357 were included; 106 (29.7%) were admitted to the hospital and 251 (70.3%) were treated outpatient. Of patients with a Charlson Comorbidity Index (CCI) score two or greater, 60.9% were treated as inpatients, whereas admission rates were 30.1% and 14.1% for patients with a CCI score of one and zero, respectively. Inpatients had an average length of stay (LOS) of 7.3 ± 7.1 days. No difference was detected in overall re-presentation to the facility 22.6% and 28.3% (p > 0.05) or in SSTI related re-presentation 10.4% and 15.1% (p > 0.05) between inpatient and outpatients. The most common gram-positive organisms identified on wound/abscess culture were MSSA (37.1% inpatients) and MRSA (66.7% outpatients). Mean total cost of care was $13,313 for inpatients and $413 for outpatients. CONCLUSION: This analysis identifies opportunities to improve processes of care for SSTIs with the aim of decreasing LOS, reducing readmissions, and ultimately decreasing burden on the healthcare system.

Sodium Zirconium Cyclosilicate (ZS-9): A Novel Agent for the Treatment of Hyperkalemia.

Hyperkalemia is a potentially life-threatening electrolyte abnormality that may be caused by select medications, underlying organ dysfunction, or alterations in potassium homeostasis. Treatment for this condition has remained largely unchanged since the release of sodium polystyrene sulfonate (SPS) in 1958. Despite its widespread use, the safety and efficacy of SPS remains controversial. Two novel potassium-binding resins have emerged in recent years. Patiromer was the first of these to receive U.S. Food and Drug Administration approval for the treatment of hyperkalemia in October 2015. A second potassium-binding resin, a zirconium cyclosilicate currently known as ZS-9, may provide yet another alternative to the archetypal treatment with SPS. ZS-9 is an orally administered nonabsorbed inorganic compound that selectively binds potassium ions in vivo. Two phase III multicenter, randomized, placebo-controlled, double-blind trials have evaluated ZS-9 for the treatment of acute hyperkalemia. In this review, we discuss the pharmacology, clinical efficacy, safety, and potential place in therapy of ZS-9 for the enhanced elimination of potassium in the setting of hyperkalemia.

Evaluation of Posttransplantation Diabetes Mellitus After Liver Transplantation: Assessment of Insulin Administration as a Risk Factor.

BACKGROUND: Impaired glucose regulation posttransplantation can affect allograft survival and may lead to the development of posttransplant diabetes mellitus (PTDM). OBJECTIVES: The primary purpose of this study is to assess the difference in insulin burden between liver transplant patients who develop PTDM and patients who do not. METHODS: This was a single-center, retrospective study. Adult liver transplant recipients transplanted between January 1, 2005, and August 1, 2013, were included. PTDM was defined as: (1) use of an oral antihyperglycemic agent for ≥30 consecutive days after transplant, (2) use of insulin ≥30 consecutive days after transplant, or (3) hemoglobin A1C≥6.5 any time after transplant. RESULTS: Of the 114 patients included, 48 (42%) developed PTDM. The average 24-hour insulin requirement on the medical floors was 17.2 ± 14.5 units in the PTDM group and 11.3 ± 12.2 units in the PTDM-free group;P= 0.02. The average blood glucose level on the medical floor was 184.7 ± 31.5 mg/dL in the PTDM group and 169.3 ± 31.4 mg/dL in the PTDM-free group;P= 0.013. Multivariate analysis revealed that experiencing rejection was positively associated with the development of PTDM: adjusted odds ratio (AOR) = 3.237; 95% CI = 1.214-8.633. Basiliximab was negatively associated with the development of PTDM: AOR = 0.182; 95% CI = 0.040-0.836. CONCLUSION: Univariate analyses suggest that insulin burden is a positive risk factor for the development of PTDM; this association is lost in multivariate analyses. Rejection was a positive predictor, and use of basiliximab was a negative predictor for the development of PTDM.

Predicting and preventing antimicrobial resistance utilizing pharmacodynamics: Part I gram positive bacteria.

INTRODUCTION: Antimicrobial resistance is a potentially inevitable consequence of widespread use of antibiotics in the healthcare system. An enhanced understanding of pharmacodynamic (PD) targets that prevent antimicrobial resistance development will improve currently availably therapies and help to guide future drug development strategies. Current in vitro methods to predict bacterial resistance to antimicrobials consist of serial dilution experiments, determination of the mutant prevention concentration (MPC), mutant selection window (MSW), and human simulated pharmacodynamics studies. Clinical trial data and real -world surveillance studies can help validate or disprove in vitro modeling. AREAS COVERED: This review will discuss methods of predicting development of resistance and how the use of pharmacodynamics can reduce or eliminate the emergence of resistance among Staphylococcus aureus, Streptococcus pneumoniae, and Enterococcus species. EXPERT OPINION: Pharmacodynamic targets can be used successfully to guide antimicrobial therapy to prevent resistance development. Currently, PD targets do not take into consideration horizontal resistance gene transfer and various factors may lead to different PD targets based on sites of infection. Further research is necessary to guide future drug development strategies and optimize new drug therapies.