Resistance Profile of Neisseria gonorrhoeae in KwaZulu-Natal, South Africa Questioning the Effect of the Currently Advocated Dual Therapy

Abstract

Background We report on the antimicrobial resistance profile of Neisseria gonorrhoeae isolates and the distribution of tetM genes in isolates with high-level tetracycline resistance in KwaZulu-Natal, South Africa. Methods Male and female patients presenting with urethral and/or vaginal discharge were recruited into the study. Urethral and cervical secretions were cultured on New York City agar. Confirmatory tests for N. gonorrhoeae included Gram stain, catalase, oxidase, and carbohydrate utilization tests. Beta-lactamase was tested by means of the chromogenic cephalosporin test. Minimum inhibitory concentrations were determined using agar dilution with multipoint inoculation. Polymerase chain reaction with gel electrophoresis was used to detect the presence and type of the tetM gene. Results N. gonorrhoeae was isolated from the specimens of 319 (26%) of the 1220 recruited patients. Of these 319 isolates, 71% were resistant to 3 or more drugs. Resistance to azithromycin was found in 68% of the isolates. All isolates showed high-level tetracycline resistance with minimum inhibitory concentration values of 16 and 32 mg/mL. The tetM gene was present in 293 (92%). The American type was found in 264 (90%) and the Dutch type in 29 (10%). Twenty-six (8%) did not carry a tetM gene. Conclusions The current syndromic management with dual ceftriaxone and azithromycin is due to the high level of azithromycin resistance factually single-drug therapy. High-level tetracycline resistance based on a resistance mechanism other than ribosome protection by the tetM gene product is present in N. gonorrhoeae infecting South African patients.

Where have all the susceptible gonococci gone? A historical review of changes in MIC distribution over the past 75 years

“…MICs were tested using the agar dilution method. MICs tested via agar diffusion using Oxoid DST agar.[21]Ceftriaxone1995 & 1999In 1995, 61 isolates and in 1999 58 isolates from men with urethritis and women with vaginal discharge syndrome presenting to a single GUM clinic in Durban. MIC testing was performed with agar diffusion using Oxoid DST agar.[22]2013319 isolates from men with urethritis and women with vaginal discharge syndrome presenting to two GUM clinics in Durban and Pietermaritzburg.…”

“…MICs were tested using the agar dilution method. MICs tested via agar diffusion using Oxoid DST agar.[21]UKBenzylpenicillin1957Taken from a report produced by the Medical Research Council Working Party to Examine the Resistance of Gonococci to Benzylpenicillin. Results for 302 isolates taken in the London area in April to December 1957 are provided.…”

Where have all the susceptible gonococci gone? A historical review of changes in MIC distribution over the past 75 years

“…The earliest benzylpenicillin MIC distribution was from 1976 and was not dissimilar to the Denmark bimodal distribution in 1957 with peaks at 0.01 and 0.5 mg/L (range 0.006 to 1mg/L) [16]. By 2013, the bimodal MIC distribution was retained but right shifted with two peaks at 0.25 and 8 mg/L [17]. Only 1.6% of isolates in 2013 had a MIC £0.06 mg/L.…”

“…These data were obtained using same methodology testing patients attending the same clinics. By 2013 the proportion with MICs of £0.007 mg/L had decreased to 77% (Fig.3c) [17].…”

“…South Africa: The prevalence of azithromycin resistance increased from 5.4% to 68.0% between 1999 and 2013 in the same clinic in South Africa [17,24]. This was associated with a right shift of the entire MIC distribution.…”