The current CDC recommended therapy for the treatment of uncomplicated gonorrhea remains the dual combination therapy of 250 mg ceftriaxone delivered intramuscularly and 1 g of azithromycin taken orally.
The currently recommended therapy for gonorrhea is still effective; however, work is still needed that is mindful of mutations in antimicrobial genes that could ultimately result in resistance in strains identified in the future, according to a study presented at US Centers for Disease Control and Prevention’s (CDC) 2018 STD Prevention Conference, held August 27-30, 2018, in Washington, DC.
“The current CDC recommended therapy for the treatment of uncomplicated gonorrhea remains the dual combination therapy of 250 mg ceftriaxone delivered intramuscularly and 1 g of azithromycin taken oral,” lead author Jesse C. Thomas IV, PhD, MS, told Contagion® in an interview. “Although the findings from our study identified several isolates with elevated minimum inhibitory concentrations (MICs) [to azithromycin and a cephalosporin], none of them were linked to verified treatment failures.”
For the study, which characterized genomics of Neisseria gonorrhoeae strains with potential elevated MICS to azithromycin and extended-spectrum cephalosporins, the investigators selected isolates from the US Gonococcal Isolate Surveillance Project (GISP) that featured elevated MICs to azithromycin between 1993-2005 (MIC ≥1 μg/ml) and 2006-2016 (MIC ≥2 μg/ml). Additionally, isolates with either an elevated MIC to cefixime (MIC ≥0.25 μg/ml) or ceftriaxone (MIC ≥0.125 μg/ml) were selected. Characterization of the identified GISP isolates and 11 international isolates featuring comparable susceptibility patterns was performed using core genome phylogeny, multi-locus sequence typing (MLST), and mutational analysis.
“The GISP monitors antimicrobial resistance trends over time using data collected from routine antimicrobial susceptibility testing of specimens collected from patients diagnosed with urethral gonorrhea,” Dr. Thomas explained. “The program tests specimens against a variety of antibiotics (eg, fluoroquinolones, azithromycin, cephalosporins, etc). And so, the largest benefit, in my opinion, is in knowing the prevalence and incidence of antimicrobial resistance within the US population. These data aid in informing CDC’s treatment guidelines.”
Of 164,900 isolates identified in the GISP between 1993-2016, a total of 20 isolates featured elevated MICs to both azithromycin and a cephalosporin. Only 12 of these isolates are currently sequenced. Birmingham-2000 was the oldest isolate identified, and this isolate featured a unique MLST (ST10316) sequence type (ST). Baltimore isolates between 2001-2012 and Phoenix isolates in 2011 clustered together phylogenetically, yet showed different sequence types. A total of 7 isolates in each the GISP and international databases formed a single clade. Adenine deletion in mosaic penA, ponA L421P, and porB (A121K and A121N) mutations, as well as mtrR promotor, which the investigators cited, was a marker of elevated azithromycin MIC, were carried by all isolates with the exception of the Birmingham-2000.
According to Dr. Thomas, point-of-care testing may “be widely available that are able to assist physicians in determining what the Neisseria gonorrhoeae strain infecting their patient is resistant or susceptible to [the strain].” He added that an individualized therapeutic approach “could help physicians in prescribing the best treatment therapy for their patient, but we first need to understand antimicrobial resistance trends in circulating gonococcal strains. From that aspect, I think the kind of monitoring GISP does could help inform the development of POC tests.”
“The current study, as it was designed, does what it was intended to do, which was to characterize the genetics of GISP isolates between 1993 and 2016 on the basis of their antimicrobial resistance mutations, particularly to azithromycin and the cephalosporins, and to investigate relatedness with similar international strains,” Dr. Thomas concluded. “I do think it opens the door for larger retrospective studies. GISP has a large number of un-sequenced isolates, so it would interesting to look at the prevalence of antimicrobial resistance mutations over time. I think that is a logical next step, to have that historical genetic background, and to see how strains are evolving and developing resistance.”
Additionally, the investigators added that their findings highlight the overall need for continual international monitoring and collaboration of Neisseria gonorrhoeae isolates. “Mitigating the emergence and spread of resistant Neisseria gonorrhoeae supports the need for robust surveillance systems with the capacity to rapidly identify known resistant strains and novel resistance mechanisms as they arise,” they reported.
Jesse Thomas IV, Sandra Seby, Audrey Abrams, Matthew Schmerer, Cau Pham, Samera Sharpe, Kevin Pettus, Sancta St. Cyr, Elizabeth Torrone, Ellen Kersh, Kim Gernert. Genomic Characterization of Neisseria Gonorrhoeae Strains Displaying Elevated Minimum Inhibitor Concentrations (MICS) to Azithromycin and Extended-Spectrum Cephalosporins — United States, 1993—2016.