Effect of Reduced Fluoroquinolone Use on Cephalosporin Use, Susceptibilities and Clostridioides difficile Infections.

Background: Overuse of fluoroquinolones has led to concerning rates of resistance, particularly among Gram-negative organisms. They are also highly implicated as a risk factor for Clostridioides difficile infection, and reports of other serious adverse events led to recommendations to restrict their use. Our health system began targeting the reduction in unnecessary fluoroquinolone prescribing in 2018, aiming to promote their safe and effective use. Broad-spectrum cephalosporins are often used as an alternative to fluoroquinolones. We sought to evaluate whether decreased fluoroquinolone use was associated with increased third- and fourth-generation cephalosporin use and whether these changes in utilization impacted other outcomes, including C. difficile infection (CDI) rates and susceptibilities among Gram-negative organisms. Methods: This retrospective descriptive analysis included adult patients who received a fluoroquinolone or broad-spectrum cephalosporin in a three-year time period across a large healthcare system. The primary objective was to evaluate the change in days of therapy (DOT) of fluoroquinolones and third- and fourth-generation cephalosporins. Secondary objectives included rates of resistance among common Gram-negative organisms, CDI, and analyses stratified by antibiotic indication. Results: Cephalosporin use increased by an average of 1.70 DOT/1000 PD per month (p < 0.001). Additionally, fluoroquinolone use decreased by an average of 1.18 DOT/1000 PD per month (p < 0.001). C. difficile infections decreased by 0.37 infections/10,000 patient-days per month (p < 0.001). Resistance to fluoroquinolones remained stable from 2018 to 2020, and a declining trend was observed in 2021. Conclusion: This study demonstrated that reduced fluoroquinolone use in a large healthcare system was associated with increased usage of broad-spectrum cephalosporins, decreased CDI and improvements in resistance patterns.

Process analysis of procalcitonin monitoring within community hospitals.

PURPOSE: Monitoring of procalcitonin (PCT) levels may support appropriate antibiotic discontinuation. The purpose of this study was to determine the current state of PCT monitoring at community hospitals across the United States. METHODS: Data from adult patients who were admitted to community hospitals affiliated with a large healthcare system between August 1, 2016, and July 31, 2017, and who received antibiotics were evaluated for the number of PCT levels drawn and the timing between multiple levels. Data from eligible patients were evaluated for the discontinuation of antibiotics after meeting prespecified PCT thresholds for discontinuation of therapy, namely, a PCT measurement of <0.5 µg/L or a decrease of ≥80% from a previous peak value. RESULTS: PCT levels were evaluated for 103,913 patient data sets collected from 136 hospitals. Of these, 70% of the data sets showed a single PCT level drawn, and approximately 30% (30,887) of the data sets showed multiple levels drawn. The first PCT measurement was drawn within 36 hours of antibiotic initiation in 96% of the patients. Of those with multiple levels, 23% (7,089) had levels drawn 24 to 72 hours apart. A small proportion (20% [6,127]) of the patients with multiple levels were eligible for evaluation of appropriate antibiotic discontinuation. Of these, 1,973 (32.2%) patients had antibiotics discontinued within 36 hours of meeting the prespecified PCT thresholds; these patients had a mean duration of antibiotic therapy of 6.1 days with a median of 4.7. CONCLUSION: Additional standardization of ongoing PCT monitoring and education regarding the appropriate discontinuation of antibiotics when thresholds are reached could aid in the use of this biomarker in support of antibiotic and laboratory stewardship.

Doripenem (Doribax): the newest addition to the carbapenems.

Carbapenems are a class of antimicrobials structurally related to penicillin. Doripenem, the newest agent in this class, was recently approved by the Food and Drug Administration for the treatment of complicated intra-abdominal infections and complicated urinary tract infections. Its spectrum of activity is similar to that of meropenem and imipenem/cilastatin. Some studies indicate that approximately 29% of carbapenem-resistant Pseudomonas aeruginosa isolates may remain sensitive to doripenem, although the clinical relevance of that finding has not been determined. Clinical studies, which have been published only in abstract form to date, have found doripenem to be similar to comparator agents. The most common adverse effects related to doripenem therapy were headache, nausea, diarrhea, rash, and phlebitis. Doripenem, like the other carbapenems, may also cause seizures. Because of the lack of published data, the lack of clear advantages over meropenem, and the increased cost compared with meropenem, doripenem will not be available for use at Baylor University Medical Center except by infectious diseases specialists.

Posaconazole (Noxafil): a new triazole antifungal agent.

Posaconazole is the newest triazole antifungal agent. It is structurally related to itraconazole and has activity against Candida species, Aspergillus species, Cryptococcus neoformans, the zygomycetes, and other filamentous fungi. Randomized, double-blind trials have shown posaconazole to be at least as efficacious as fluconazole for the prevention of invasive fungal infections in immunocompromised patients. It has also shown promising results in the treatment of various fungal infections refractory to other antifungal therapy. The dose of posaconazole is 200 mg orally three times daily for the prevention of invasive fungal infections and 800 mg daily in two to four divided doses for the treatment of invasive fungal infections refractory to other antifungal treatment. All posaconazole doses should be given with food or a nutritional supplement to enhance absorption. The most common adverse effects reported with posaconazole therapy were fever, diarrhea, nausea, vomiting, and headache. Instances of elevated liver enzyme levels, hyperbilirubinemia, and hepatocellular damage were also noted in clinical trials, and these laboratory values should be monitored during treatment with posaconazole.