IDSA’s Journal of Infectious Diseases provides a monthly roundup of JID papers with direct relevance to clinicians. Read on to learn more about zoliflodacin and gepotidacin cross-resistance and fitness in N. gonorrhoeae, the benefits of rifapentine- and rifabutin-based regimens for tuberculosis meningitis and other research ready to inform clinical practice. Two perspectives from this issue are also highlighted. (Titles and summaries are adapted from the July 2026 issue of JID.)
Perspectives
Why Americans Are Dying Younger? NIH Is Not the Problem. Our Broken Health Care Delivery Is
Major Articles and Brief Reports
Multidrug-resistant Neisseria gonorrhoeae has created an urgent need for new therapeutic options. Zoliflodacin and gepotidacin, two first-in-class topoisomerase inhibitors, are oral antibiotics recently approved by the Food and Drug Administration for gonorrhea treatment. Zoliflodacin resistance can occur through gyrBD429N and, in this in vitro study, gyrBD429N conferred cross-resistance to gepotidacin in three of nine clinical strains; parCD86N appeared to potentiate gyrBD429N cross-resistance to gepotidacin. These data reveal a potential cross-resistance pathway among new topoisomerase inhibitors, likely important to clinical care.
Due to increasing macrolide resistance, moxifloxacin-use for M. genitalium infections has risen over the past decade. Conversely, moxifloxacin-efficacy is in decline due to the emergence of key fluoroquinolone mutations such as ParC-S83I. In this study in Australia, moxifloxacin-efficacy decreased from 100% in 2015 to 79.3% in 2023 (ptrend = 0.007). With the use of the ParC-S83 assay, moxifloxacin-use decreased from 60.3% in 2023 to 49.2% in 2024 (p < 0.0001), and cure increased from 79.3% in 2023 to 89.2% in ParC-S83 wildtype infections. Introduction of a ParC-S831 resistance test enabled guidance for moxifloxacin use (wild-type ParC-S83) and alternative therapies for detection of ParC-S831.
TB meningitis carries high mortality and neurological sequelae, and current rifampin-based regimens are limited by poor central nervous system penetration. In a murine model, both rifapentine- and rifabutin-containing regimens demonstrated bactericidal activity in the brain, similar to or better than the standard rifampin-containing regimen, as well as reduced neuroinflammation and brain injury. Rifapentine- and rifabutin-based regimens offer pharmacokinetic advantages over rifampin, demonstrate excellent activity, supporting future evaluation for TB meningitis.
In an innovative case report, the authors report successful treatment of a recurrent C. difficile infection (12 episodes) in an individual with secondary hypogammaglobulinemia (recalcitrant to vancomycin, fidaxomicin, rifaximin, fecal microbiota transplantation and bezlotoxumab therapies) with use of an IgM/IgA-enriched immunoglobulin preparation (pentaglobin) given intravenously.
