Rifamycins (rifampin, rifabutin, and rifapentine) play an essential role in the treatment of mycobacterial and some nonmycobacterial infections. They also induce the activity of various drug transporting and metabolizing enzymes, which can impact the concentrations and efficacy of substrates. Many anticoagulant and antiplatelet (AC/AP) agents are substrates of these enzymes and have narrow therapeutic indices, leading to risks of thrombosis or bleeding when coadministered with rifamycins. The objective of this systematic review was to evaluate the effects on AC/AP pharmacokinetics, laboratory markers, and clinical safety and efficacy of combined use with rifamycins. A systematic review following the Preferred Reporting Items for Systematic Reviews and Meta‐analyses guidance was performed. The PubMed, Embase, and Web of Science databases were queried for English‐language reports on combination use of rifamycins and AC/AP agents from database inception through August 2021. The 29 studies identified examined warfarin (n = 17), direct oral anticoagulants (DOACs) (n = 8), and antiplatelet agents (n = 4) combined with rifampin (n = 28) or rifabutin (n = 1). Eleven studies were case reports or small case series; 14 reported on pharmacokinetic or laboratory markers in healthy volunteers. Rifampin‐warfarin combinations led to reductions in warfarin area under the curve (AUC) of 15%–74%, with variability by warfarin isomer and study. Warfarin dose increases of up to 3–5 times prerifampin doses were required to maintain coagulation parameters in the therapeutic range. DOAC AUCs were decreased by 20%–67%, with variability by individual agent and with rifampin versus rifabutin. The active metabolite of clopidogrel increased substantially with rifampin coadministration, whereas prasugrel was largely unaffected and ticagrelor saw decreases. Our review suggests most combinations of AC/AP agents and rifampin are problematic. Further studies are required to determine whether rifabutin or rifapentine could be safe alternatives for coadministration with AC/AP drugs.

BackgroundRespiratory infection due to Achromobacter species has been increasingly more common, especially in patients with cystic fibrosis (CF). Recurrent infections in these patients contribute to significant morbidity and mortality as well as lead to repeated antibiotic exposures with subsequent development of multi-drug-resistant (MDR) pathogens. Several recently approved antimicrobials target MDR Gram-negative pathogens, but none are FDA approved for MDR Achromobacter respiratory infections and lack susceptibility breakpoint recommendations.MethodsThis retrospective analysis evaluated hospitalized patients with MDR Achromobacter respiratory infections from August 2017 to March 2019 at AdventHealth Orlando, a 2,885-bed healthcare system including 8 campuses across Central Florida. The purpose of this descriptive study was to examine novel therapeutic agents for the treatment of respiratory infections due to MDR Achromobacter.ResultsMDR Achromobacter was isolated in 36 respiratory cultures from 18 unique patients. A. xylosoxidans (61%) and A. denitrificans (22%) were the most frequently isolated species. Mean patient age was 40 years, 56% were female, and 67% had CF. Treatment indications included CF exacerbation (38%), pneumonia (35%), post-lung transplant infection (16%), and other (11%). Twenty-four infections were polymicrobial (67%) and 23 infections included MDR pathogens. Minimum inhibitory concentrations (MIC) of the antibiotics used for treatment were available for 70% of cases. Of the 18 patients with isolated MDR Achromobacter organisms, 72% had MIC changes with 69% exhibiting higher MICs on subsequent testing. Novel agents were used in 63% of cases (Table 1) for an average duration of 10 days. Eravacycline was the most frequently used monotherapy agent (5/6 cases) and the most utilized novel antibiotic (21%). All-cause readmission rates at 30 days was 33%; 92% was due to infection. Inpatient all-cause mortality was 11%.ConclusionAntibiotics available to treat MDR Achromobacter infections are limited and lack standard susceptibility breakpoint recommendations. Based on this evaluation, novel agents, such as eravacycline or meropenem/vaborbactam, may be viable treatment options for patients with MDR Achromobacter respiratory infections. Disclosures All authors: No reported disclosures.