Patients Recently Treated with Azithromycin Show Increased Resistance to Treatment for Neisseria gonorrhoeae

The bacterium Neisseria gonorrhoeae is the causative agent of gonorrhea, which is listed by the National Institute of Health (NIH), as the second most commonly reported infectious disease in the United States. Neisseria gonorrhoeae can infect the reproductive tract and fallopian tubes in women as well as the urethra, anus, mouth, throat, and eyes of both females and males. Untreated gonorrhea increases a patient’s risk of acquiring HIV and can lead to infertility as well as pelvic inflammatory disease. When passed from an infected mother to her child, gonorrhea can cause blindness or life-threatening complications in the child. This bacterium is particularly adept at developing new strategies to evade antibiotics, raising concerns that Neisseria gonorrhoeae may soon be resistant to all classes of currently available antibiotics.

Current clinical guidelines recommend the use of combination drug therapy to treat gonorrhea, consisting of the antibiotics ceftriaxone plus azithromycin. However, there have been increasing reports of azithromycin resistant strains reported. In a new study published in the journal, Clinical Infectious Diseases, principal investigator Henry JC. de Vries, MD, PhD, Professor of Skin Infections at the University of Amsterdam, and his colleagues examined the correlation between exposure to the drug azithromycin and decreased susceptibility of N. gonorrhoeae.

The authors conducted a retrospective study consisting of patients who visited a sexually transmitted infections (STI) outpatient clinic in Amsterdam between the years 1999 and 2013. For patients to be included in the study, they had to have a positive N. gonorrhoeae culture and had to have visited the STI clinic in the 60 days before being diagnosed with gonorrhea. In terms of exposure to azithromycin, the authors divided the patients into 3 groups, those unexposed to the drug in the 60 days preceding diagnosis, those exposed between 31 to 60 days before diagnosis, and those exposed in the 30 days prior to diagnosis. The authors sought to determine the relationship between exposure to azithromycin and the minimum inhibitory concentration (MIC).

After applying exclusion criteria, the study included 14 patients that were exposed to azithromycin in the 30 days before diagnosis with gonorrhea, 97 patients exposed between 31 and 60 days before diagnosis, and 212 patients were unexposed to the drug. The majority of patients were of Dutch descent and 73% of the 395 patients included in the study were men who have sex with men (MSM). After adjusting for age, ethnicity, year of infection, and anatomical site, the authors found a significant correlation between exposure and azithromycin MIC. Professor de Vries and his colleagues determined that patients exposed to azithromycin in the 30-day group had azithromycin MICs that were 2.7 times higher than the unexposed group. However, in the group exposed between 31 and 60 days prior to diagnosis, there was no significant association compared to the unexposed group.

In addition to MIC assays, the authors performed whole genome sequencing (WGS) to compare exposed and unexposed isolates in an effort to evaluate molecule resistance markers. The results indicated there were no shared molecular markers based on exposure to azithromycin. However, mutations in the gene mtrR were more common in isolates from patients exposed to azithromycin.

Overall, Professor de Vries and his colleagues demonstrated a significant correlation between higher azithromycin MICs and exposure to the azithromycin, suggesting that frequent use of the drug in high-risk patients can result in antibiotic resistance.

Samar Mahmoud graduated from Drew University in 2011 with a BA in Biochemistry and Molecular Biology. After two years of working in industry as a Quality Control Technician for a blood bank, she went back to school and graduated from Montclair State University in 2016 with an MS in Pharmaceutical Biochemistry. She is currently pursuing her PhD in Molecular and Cellular Biology at the University of Massachusetts at Amherst.