Rivera, Christina G.

Abstract Background Although trimethoprim-sulfamethoxazole (TMP-SMX) has consistently demonstrated significant interindividual variability, therapeutic drug monitoring is used to optimize dosing and avoid adverse reactions that may contribute to treatment interruption. While data exists on the use of SMX level monitoring in pneumocystis, there is a lack of data in SMX serum monitoring utility for invasive Nocardia infections. Methods We retrospectively reviewed adults who received TMP-SMX to treat nocardial brain abscess (BA) and underwent SMX testing level from January 2010 to December 2020. Results Overall, 24 patients had Nocardia spp. BA; Twenty-two (91.7%) were treated with TMP-SMX, and 16/22 (72.7%) had a documented SMX serum level. The median age was 64 (IQR 58-69) years, and the majority were males (77.3%). Compared to those who did not have a documented SMX serum level, patients with SMX levels had a higher prevalence of hemodialysis (HD, 42.9% vs. 33%; P=.99) and malignancy (50% vs. 33.3%; P=.65). The most common BA location was the frontal lobe (43.8% vs. 33.3%; P=.99), with a single (68.8% vs. 50%; P=.62) and smaller (1.3 vs. 1.9 cm; P=.58) brain fluid collection, and with fewer midline shift (6.3% vs. 16.7%; P=.48), respectively. The median TMP-SMX duration was 350 days (P=.31). The most common dosing was 2-double strength, three times a day (31.8%). The SMX median level was 158.5 (IQR 120-218) mcg/mL, collected at two hours (75%) post-administration in the induction phase (81.3%). The most common recommendation was to continue therapy based on the level results. Eleven (46%) patients had a level >150 mcg/mL, and 5 (45.5%) reported drug toxicity, including nausea in 3, acute kidney injury in 2, and thrombocytopenia in 2 patients. Ninety-four percent of the patients with SMX levels had surgical intervention for therapeutic purposes vs. 83% of those without it (P=.65). A total of 11 (50%) patients were cured, 3 (18.8%) relapsed, and 2 (12.5%) died. Conclusion Patients with SMX serum level monitoring are more likely to be on HD, during the induction phase and among those with higher and more frequent dosing. About half of patients with SMX levels >150 mcg/mL experienced drug toxicity; however, SMX levels did not impact patient outcome and length of treatment. Disclosures All Authors: No reported disclosures

AbstractHuman antimicrobial consumption largely occurs in the ambulatory setting, with inappropriate or unnecessary antimicrobial prescribing well documented in the literature. In 2020, The Joint Commission implemented a regulatory standard requiring the development and implementation of antimicrobial stewardship programs (ASP) in those institutions surveyed under the ambulatory accreditation standard. While experience with inpatient antimicrobial stewardship has continued to increase, ambulatory ASPs are programmatically distinct and can present unique challenges with regards to operationalizing regulatory components. Herein, we lay a framework for addressing the task of developing an ambulatory ASP for a large health system by reviewing the regulatory requirements, examining relevant recent publications, and describing our institutional experience.

Purpose of review To date, more than 30 antiretroviral drugs have been approved by the Food and Drug Administration for the treatment of HIV infection. As new drugs with better efficacy and safety profile become available for clinical practice, older drugs are either withdrawn from the market or become no longer actively prescribed. We review hepatotoxicity associated with contemporary antiretroviral drugs, with emphasis on data from the past 3 years. Recent findings Although less robust data exists for side effects of contemporary antiretroviral medications recently approved for the management of HIV (i.e., doravirine, ibalizumab, fostemsavir, cabotegravir), the risks of substantial hepatotoxicity appears to be minimal with these agents. Summary Although newer antiretroviral drugs are better tolerated than their earlier counterparts, they are not completely devoid of adverse drug reactions, including hepatotoxicity. Monitoring patients on antiretroviral therapy for treatment-emergent liver injury should continue to be part of routine clinical care.

AbstractOutpatient parenteral antimicrobial therapy (OPAT) is a well‐established mechanism to facilitate patient discharge, lower inpatient admission cost, and decrease the risk of health care–acquired infections. Although there are numerous benefits to patients and health care institutions, OPAT is complex and not without risks. Patients may be discharged on long courses of oral antimicrobials, known as complex outpatient antimicrobial therapy (COpAT), which also requires careful monitoring and oversight. This, coupled with the need for antimicrobial stewardship across the continuum of care, positions pharmacists with infectious diseases (ID) training as crucial leaders in the field of OPAT. The development, implementation, and maintenance of these services requires the careful attention of health care personnel in discharge antimicrobial selection, continuity of care at key care transitions, implementation of optimal care bundles, provision of thorough patient education throughout the OPAT process, coordination with a multidisciplinary team including home infusion and nursing, and monitoring of program metrics to determine successes and opportunities for improvement. Ongoing support for optimal delivery of patient care will be required as OPAT practice, and health care delivery at large, continues to evolve. This involves continued advocacy for collaborative practice development, optimizing payment for nondispensatory OPAT services, and integration of effective telehealth programs. This article summarizes the need for practice expansion of ID pharmacist specialists in OPAT/COpAT management across the care continuum and best practices for establishment of these services.

Red Man Syndrome is a term used for an adverse event attributed to vancomycin infusion. Based on the presentation within white patients, the term is imprecise at best and can lead to suboptimal classification and management. Recent calls have advocated for the discontinuation of the use of this terminology. Pharmacists should take the lead in advocating for this change.

Contemporary antiretroviral agents afford enhanced potency and safety for patients living with HIV. Newer antiretroviral drugs are often better tolerated than those initially approved in the early stages of the HIV epidemic. While the safety profile has improved, adverse drug reactions still occur. We have segregated the antiretroviral agents used in contemporary practice into class groupings based on their mechanism of antiviral activity (non-nucleoside reverse transcriptase inhibitors, nucleoside reverse transcriptase inhibitors, integrase inhibitors, protease inhibitors, and entry inhibitors) while providing a review and discussion of the hepatoxicity seen in the most relevant clinical literature published to date. Clinical literature for individual agents is discussed and agent comparisons afforded within each group in tabular format. Our review will provide a summative overview of the incidence and medications associated with hepatic adverse reactions linked to the use of contemporary antiretroviral drugs.

Abstract Purpose To identify risk factors that may predispose patients to rifampin- and cefazolin-induced coagulopathy. Summary An 86-year-old man with a history of rheumatoid arthritis on chronic prednisone and stage 3 chronic kidney disease, notably not on warfarin, presented to the hospital with a 10-day history of right hip pain, swelling, and drainage after a recent right total-hip arthroplasty. The patient underwent a combination of surgical intervention and medication therapy with rifampin and ceftriaxone. After discharge and at postoperative day 9, ceftriaxone was changed to cefazolin due to increasing alkaline phosphatase levels. Four weeks after the initial debridement, antibiotics, and implant retention, the patient underwent a second irrigation and debridement due to persistent infection. Cefazolin and rifampin therapy was extended. Three days later, the patient presented to the emergency room with significant bleeding at the surgical site and a profoundly elevated prothrombin time and international normalized ratio (INR). No potential contributors were identified. The Naranjo adverse drug reaction probability scale identified cefazolin and rifampin as the probable cause of elevated INR. The Liverpool adverse drug reaction avoidability assessment tool classified this adverse event as “definitely avoidable.” Conclusion Rifampin-containing regimens are often recommended to treat staphylococcal prosthetic joint infections when the implant is retained. In methicillin-susceptible staphylococcal infections, cefazolin is routinely employed as the β-lactam backbone of definitive antimicrobial regimens. Although rifampin- and cefazolin-induced hypoprothrombinemia seems to be rare, adverse consequences of its occurrence may be prevented with appropriate monitoring.

Abstract Background Fluoroquinolones (FQs) are known to be accompanied by significant risks. However, the incidence of adverse events (ADEs) resulting in unplanned drug discontinuation when used for periprosthetic joint infections (PJIs) is currently unknown. Methods This study included 156 patients over the age of 18 treated for staphylococcal PJI with debridement, antibiotics, and implant retention between 1 January 2007 and 21 November 2019. Of the 156 patients, 64 had total hip arthroplasty (THA) and 92 had total knee arthroplasty (TKA) infections. The primary outcome was rate of unplanned drug discontinuation. Secondary outcomes included incidence of severe ADEs, unplanned rifamycin discontinuation, mean time to unplanned regimen discontinuation, and all-cause mortality. Results Overall, unplanned drug discontinuation occurred in 35.6% of patients in the FQ group and 3% of patients in the non-FQ group. The rate of unplanned discontinuation of FQ regimens as compared with non-FQ regimens was 27.5% vs 4.2% (P = .021) in THA infections and 42% vs 2.4% (P < .001) in TKA infections. There was no significant difference in severe ADEs between FQ and non-FQ regimens in both THA and TKA infections. The overall rate of nonsevere ADEs in FQ compared with non-FQ regimens was 43.3% vs 6.1% (P < .001). FQs were associated with tendinopathy, myalgia, arthralgia, and nausea. Conclusions A significantly higher rate of unplanned drug discontinuation was associated with FQ as compared with non-FQ regimens. This provides a real-world view of the implications of FQ-related ADEs on unplanned discontinuation when used in prolonged durations for the management of staphylococcal PJIs.

AbstractIn an effort to “flatten the curve” of SARS-CoV-2, society is urged to practice social distancing. However, the management of other disease states may require some patients to undergo outpatient parenteral antimicrobial therapy (OPAT). Practical considerations for OPAT management during an infectious pandemic are reviewed. These include shortening durations of therapy, utilizing the oral route, avoiding medications requiring therapeutic drug monitoring, selecting antimicrobials with long durations, decreasing frequency of laboratory blood draws, and performing tele-health visits.

Abstract Background Owing to patient intolerance or drug interactions, alternative agents to rifampin are needed for management of staphylococcal periprosthetic joint infection. In the current study, we evaluated rifabutin, rifapentine and rifampin, with and without vancomycin, in a rat model of foreign body osteomyelitis. Methods Proximal tibiae were inoculated with methicillin-resistant Staphylococcus aureus (MRSA) and a Kirschner wire (K-wire) implanted in each. After 4 weeks of infection, rifampin, rifabutin, or rifapentine were administered, alone or with vancomycin. Tibiae and K-wires were cultured, and medians were reported as log10 colony-forming units (CFUs) per gram of bone or log10 CFUs per K-wire, respectively. Results Rifampin, rifabutin or rifapentine administered with vancomycin yielded less MRSA from bones (0.10, 3.02, and 0.10 log10 CFUs/g, respectively) than did no treatment (4.36 log10 CFUs/g) or vancomycin alone (4.64 log10 CFUs/g) (both P ≤ .02). The K-wires of animals receiving no treatment or vancomycin monotherapy recovered medians of 1.76 and 2.91 log10 CFUs/g per K-wire, respectively. In contrast, rifampin, rifabutin and rifapentine administered with vancomycin yielded medians of 0.1 log10 CFUs per K-wire, respectively. Rifampin resistance was detected in a single animal in the rifampin monotherapy group. Conclusions Rifabutin or rifapentine with vancomycin were as active as rifampin with vancomycin against MRSA in rat foreign body osteomyelitis, suggesting that rifabutin and/or rifapentine may be alternatives to rifampin in the clinical management of staphylococcal periprosthetic joint infections.