Clinical Studies Are Needed to Determine the Efficacy of Ceftriaxone and Other Interventions in Addressing Resistant Neisseria gonorrhoeae Infection
Year: 2024
Type: article
Abstract: Dear editor We read with great interest the article by Lucente et al.,1 which detailed the 10-year trend in antimicrobial resistance among Neisseria gonorrhoeae isolates from Italy. With a continued rise globally in the prevalence of infection and antimicrobial resistance,2 the World Health Organization and United States Centers for Disease Control and Prevention have classified N. gonorrhoeae as a high-priority organism.3,4 We, therefore, commend the authors for their important contribution to antimicrobial susceptibility monitoring. However, the authors concluded that their results confirm both the efficacy of the primary regimen and the benefits of dual therapy, which were not supported by the data presented. Fundamentally, the low prevalence of strains with decreased ceftriaxone susceptibility does not confirm that ceftriaxone is efficacious. Only a well-performed clinical trial can do that. Unfortunately, there are no clinical outcome data to support current laboratory-defined microbiological minimum inhibitory concentration (MIC) cutoffs for ceftriaxone and N. gonorrhoeae infection. Further, treatment efficacy may differ by anatomic site of infection; in pharyngeal infections, salivary and tonsillar drug levels do not reflect serum levels, and nearly 90% of cephalosporin antibiotics may be protein-bound in tonsillar tissue.5 Thus, the relationship between serum drug levels and clinical outcomes is uncertain. The pharmacokinetic challenges of treating pharyngeal infections are further compounded in cases of N. gonorrhoeae infection with elevated ceftriaxone MICs. Efficient killing of strains with a ceftriaxone MIC of 2 mg/L may require free plasma concentrations of ceftriaxone between 2 and 3 mg/L for more than 24 hours,6 whereas a 1 g dose results in a free plasma concentration of 0.7 mg/L after 24 hours.7 Notably, the majority of urogenital cases with ceftriaxone-resistant N. gonorrhoeae infection have been successfully treated with standard ceftriaxone regimens,8 possibly due to higher concentrations of ceftriaxone in the urine; yet, the majority of cases failing therapy have involved the pharynx.9 Thus, the efficacy of ceftriaxone among isolates with reduced susceptibility remains unknown, particularly in the treatment of pharyngeal infections. Similarly, while modeling studies support the idea that combination therapy slows the emergence of resistance,10 no clinical data exist, and such a strategy is limited by rising rates of azithromycin resistance. Treatment diversification using novel antimicrobials in late-stage development and new diagnostics that enable resistance-guided therapy might decrease the selective pressure for ceftriaxone resistance; however, empirical evidence is still needed. Prospective or cross-sectional population-level studies with a comparison group can correlate changes in the prevalence of antimicrobial resistance to treatment diversification (or dual therapy). Antimicrobial surveillance data, as described by Lucente et al., have utility for resistance monitoring, but not determining the impact of treatment or other interventions. Ultimately, clinical or population-level trials are needed. Lao-Tzu Allan-BlitzDivision of Global Health Equity: Department of MedicineBrigham and Women's HospitalBoston, MA[email protected]Jeffrey D. KlausnerDepartment of Population and Public Health SciencesKeck School of MedicineUniversity of Southern CaliforniaLos Angeles, CA
Source: Sexually Transmitted Diseases
Authors: Lao-Tzu Allan-Blitz, Jeffrey D. Klausner
Language: English
Subfield: Microbiology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W4402207430