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CIDRAP Stewardship/Resistance Scan - Solithromycin failure vs gonorrhea; Amoxicillin Rx and resistance

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  • CIDRAP Stewardship/Resistance Scan - Solithromycin failure vs gonorrhea; Amoxicillin Rx and resistance


    Stewardship / Resistance Scan for Jun 11, 2019
    Solithromycin failure vs gonorrhea; Amoxicillin Rx and resistance

    Filed Under:
    Gonorrhea; Antimicrobial Stewardship

    Study: Standard gonorrhea treatment superior to solithromycin

    Solithromycin, a novel fourth-generation macrolide, isn't a suitable alternative to standard therapy of ceftriaxone plus azithromycin for treating gonorrhea, according to a study yesterday by researchers from Australia and the United States in The Lancet Infectious Diseases.
    Given growing concerns about antibiotic-resistant Neisseria gonorrhoeae, scientists are looking for new therapies. The study took place at two sites in Australia and one in the United States from September 2014 through August 2015. Patients with gonorrhea ages 15 and older were randomly assigned to receive a single 1,000-milligram (mg) dose of solithromycin or a 500-mg intramuscular dose of ceftriaxone plus a 1,000-mg dose of azithromycin. Of 261 participants, 130 were in the solithromycin group and 131 were in the standard-treatment group. Researchers also obtained Neisseria gonorrhoeae cultures at baseline and test day of cure.
    Of patients in the solithromycin group, 80% showed evidence of cure on follow-up testing, compared with 84% of the standard-treatment group, suggesting that solithromycin did not show non-inferiority at the preset -10% criterion.
    A secondary analysis limited to patients who had follow-up testing found that the eradication rate for solithromycin was 92%, compared with 100% for standard therapy. Also, the team found that adverse events such as diarrhea and nausea were higher in the solithromycin group.
    The authors concluded that the solithromycin dose tested isn't a suitable alternative first-line treatment, and further trials of longer dosing will need to consider potential side-effect risks.
    In a related commentary in the same issue, two infectious disease specialists from Amsterdam said the ceftriaxone cure rate for gonorrhea is still about 95%, but the number of N gonorrhoeae with decreased susceptibility is increasing, and alternative antibiotics are urgently needed. The authors are Henry de Vries, MD, PhD, and Maarten Schim-van der Loeff, MD, PhD.
    They note that the study found that solithromycin treatment failures weren't due to reinfection, hinting that a single dose might not be sufficient. They wrote that more study is needed on the pharmacodynamics of solithromycin. They add that the novel drug's use might be threatened by emerging azithromycin-resistant gonorrhea strains and that future trials involving the drug should include azithromycin-resistant gonorrhea strains.
    Jun 10 Lancet Infect Dis abstract
    Jun 10 Lancet Infect Dis commentary

    Amoxicillin prescribing tied to amoxicillin and ciprofloxacin resistance

    An analysis of UK national data has found that amoxicillin prescribing was not only associated with amoxicillin resistance but ciprofloxacin resistance, as well, whereas nitrofurantoin prescribing was associated with lower levels of resistance to amoxicillin, according to a study yesterday in PLOS One.
    The authors used primary care prescribing data from the National Health Service and records of 888,207 urine samples collected from April 2014 through January 2016 that were positive for Escherichia coli.
    The researchers determined that amoxicillin prescribing, measured in defined daily doses per 1,000 inhabitants per day, was positively associated with amoxicillin resistance (relative risk [RR], 1.03; 95% confidence interval [CI], 1.01-1.04) and ciprofloxacin (RR, 1.09; 95% CI 1.04-1.17) resistance. In contrast to those findings, nitrofurantoin prescribing was associated with lower levels of resistance to amoxicillin (RR, 0.92; 95% CI 0.84-0.97). Clinical practices with higher levels of trimethoprim prescribing also had higher levels of ciprofloxacin resistance (RR, 1.34; 95% CI, 1.10-1.59).
    The authors conclude, "Amoxicillin, which is mainly (and often unnecessarily) prescribed for respiratory tract infections is associated with increased resistance against various antibiotics among E. coli causing urinary tract infections. Our findings suggest that when predicting the potential impact of interventions on antibiotic resistances it is important to account for use of other antibiotics, including those typically used for other indications."
    Jun 10 PLOS One study