No abstract

Objective: To provide an overview of pathophysiological changes to the pancreas during infected necrotizing pancreatitis (INP), optimal drug properties needed to penetrate the pancreas, human and animal studies supporting the use of antimicrobials, and carbapenem-sparing strategies in INP. Data Sources: A literature analysis of PubMed/MEDLINE was performed (from 1960 to September 2020) using the following key terms: infected necrotizing pancreatitis, necrotizing acute pancreatitis, and infected pancreatitis antimicrobial concentration. Individual antimicrobials were investigated with these search terms. Study Selection and Data Extraction: All relevant studies describing the management of INP, and human and animal pharmacokinetic (PK) data supporting antimicrobial use in the pancreas were reviewed for possible inclusion regardless of sample size or study design. Data Synthesis: Piperacillin/tazobactam and cefepime achieve adequate pancreatic tissue concentrations in INP studies. A majority of the literature supporting carbapenem use in INP involves imipenem, and meropenem Monte Carlo simulations suggest that standard dosing regimens of meropenem may not achieve PK targets to eradicate Pseudomonas aeruginosa. Relevance to Patient Care and Clinical Practice: Carbapenems are often utilized for INP treatment based on guideline recommendations. This review discusses PK data, the history of carbapenem use in INP, and the pathophysiology of pancreatitis to suggest carbapenem-sparing strategies and provides stewardship tactics such as when to start antimicrobials, which empirical antimicrobial to use, and when to discontinue antimicrobials in the INP setting. Conclusions: Noncarbapenem antipseudomonals, such as piperacillin/tazobactam and cefepime, are appropriate carbapenem-sparing options in INP, based on PK data, spectrum of activity, and risk of collateral damage.

Background Tocilizumab (TCZ) was approved by the Food and Drug Administration under emergency use authorization for treatment of COVID-19 in patients requiring supplemental oxygen, non-invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation. Despite multiple clinical trials, there remain unanswered questions surrounding TCZ use. Methods This multi-hospital retrospective cohort study included patients who received TCZ for COVID-19 between January 29th, 2021 and June 30th, 2021 at five University of Pennsylvania Health System (UPHS) hospitals. Patients were eligible for TCZ per UPHS criteria if they scored ≥ 5 on the World Health Organization (WHO) ordinal scale for ≤ 24 hours and experienced < 14 days of acute COVID-19 symptoms. Descriptive statistics were performed to characterize usage within the health system. Results This study evaluated 134 patients who received TCZ for the treatment of COVID-19. TCZ was ordered a median of 22 hours (interquartile range [IQR], 13.2 – 41.5) after hospital admission. A majority of patients (76.1%) were admitted to the intensive care unit and a small portion (12.7%) had a WHO ordinal scale that was >5 at time of TCZ order entry. All patients received concomitant dexamethasone therapy at a total prednisone equivalent of 400 mg (IQR, 335.6 – 480). Overall 33.6% of patients experienced an adverse event (ADE) within 30 days of TCZ administration (Table 1). Most common ADEs included bacterial infection (29.9%), hepatitis (6.7%), and fungal infection (3%); other etiologies of ADEs were not accounted for. All-cause mortality (Table 2) at day 30 occurred in 20.9% of patients and median time from TCZ administration to mortality was 12.5 days (IQR 5 – 18.3). Ninety-six patients in the cohort (71.6%) were discharged by day 30. Of the subgroup discharged by day 30, the majority (70.8%) were discharged to home. Conclusion Patients who received TCZ for severe COVID-19 experienced 20.9% mortality; mortality was higher among those with higher ordinal scale at the time of TCZ dosing. A large portion of patients (70.8%) were discharged to home within 30 days. One third of patients experienced an adverse event, primarily bacterial or fungal infection. Our experience may be useful in counseling patients about anticipated effects of TCZ. Disclosures George L Anesi, MD, MSCE, AHRQ, NHLBI, UpToDate: Advisor/Consultant|AHRQ, NHLBI, UpToDate: Grant/Research Support Kathleen Degnan, MD, Gilead: Grant/Research Support.

Background Antimicrobial resistance is a rapidly emerging threat and antibiograms are a key component in guiding empiric antimicrobial selection. Patients admitted from post-acute care facilities (PACF) are at a heightened risk for infections from multi-drug resistant organisms, posing a challenge for clinicians selecting empiric therapy. It is uncommon for antibiograms to differentiate between sources of admission. This study aimed to characterize culture proven infections and the appropriateness of empiric antimicrobial regimens for patients admitted from PACF in the Philadelphia region. Methods This was a retrospective quality improvement study that included patients admitted from Philadelphia PACF from August 2020 to June 2021. Patients were included if they had at least one positive culture within 72 hours of admission. Appropriate therapy was determined based on a comparison of empiric antimicrobial selection and susceptibilities that resulted from collected cultures. Descriptive statistics were employed for data analysis. Results A total of 106 patients and 154 cultures were evaluated during the study period. The majority of patients received initial empiric coverage for Pseudomonas aeruginosa (79%) and methicillin-resistant Staphylococcus aureus (59%). Over 50% of all cultures had been obtained from urinary sources. Enterococcus spp. were the most commonly isolated gram positive organism (61%) and Escherichia coli was the most common gram negative organism (33%). A portion of patients (32.7%) did not receive appropriate empiric therapy. Discrepancies in susceptibility patterns between our internal antibiogram and PACF patients were most notable for gram negative organisms including decreased levofloxacin susceptibilities to P. mirabilis isolates (89% vs 45%). Other notable discrepancies include decreased meropenem susceptibilities to P. aeruginosa isolates (88% vs 65%). Select susceptibility patterns are reported in Figure 1. Conclusion Antimicrobial susceptibility was discordant amongst patients admitted from PACF in the Philadelphia region compared to our general antibiogram. The increased resistance identified supports a need to re-evaluate empiric prescribing guidelines for this specific population. Disclosures All Authors: No reported disclosures.

Background The reliability of piperacillin-tazobactam (TZP) and cefepime (FEP) breakpoints for extended spectrum β-lactamase Enterobacterales (ESBL-E) isolates remains controversial. The Infectious Diseases Society of America recommends against the use of TZP and FEP for the treatment of bloodstream infections (BSIs) caused by ESBL-E, even when in-vitro susceptibility is demonstrated. The University of Pennsylvania Health System microbiology laboratory suppresses TZP susceptibilities on Escherichia coli and Klebsiella pneumoniae blood isolates nonsusceptible to ceftriaxone (CRO) or ceftazidime (CAZ) and specifies the presence of a multidrug resistant organism. However, FEP susceptibilities are reported. The objective of this study was to assess appropriate antimicrobial prescribing for the treatment of FEP-susceptible ESBL-E BSIs with our institution’s current susceptibility reporting practices. Methods This multicenter retrospective observational study included patients with blood cultures positive for E. coli, K. oxytoca, K. pneumoniae, and Proteus mirabilis nonsusceptible to CRO or CAZ but susceptible to FEP from August 1, 2018 through August 1, 2021. Patients with a concominant gram-negative infection or true beta-lactam allergy were excluded. Patients were assessed for appropriate therapy (demonstrated susceptibility to and administration of carbapenems fluoroquinolones, novel beta-lactam/beta-lactamase inhibitors, or sulfamethoxazole-trimethoprim) within 24 h following the availability of susceptibility results. Results During the study period 38 patients were included. Of the 38 patients, 52.6% (n=20) received appropriate therapy with an average time to appropriate therapy of 3.7 (SD 2.1) h. Among patients receiving inappropriate therapy (n=18), 50% (n=9) were changed to appropriate therapy >24 h after susceptibility results, with an average time to appropriate therapy of 46.5 (SD 44.4) h. The remaining 9 patients (23.7%) did not receive appropriate therapy beyond 24 h. Conclusion Reporting FEP susceptibility results on ESBL-E blood isolates may contribute to the prescribing of FEP for the treatment of ESBL-E BSIs and delay appropriate antimicrobial therapy. Given these findings, cefepime will now be suppressed on ESBL-E blood isolates. Disclosures All Authors: No reported disclosures.