Detection of multidrug-resistant gonorrhoea in the Gauteng province

Abstract

Two cefpodoxime-resistant Neisseria gonorrhoeae isolates were identified with high minimum inhibitory concentrations (MIC) for oral cephalosporins. The ceftriaxone MICs for both isolates were still in the susceptible range, although raised at 0.064 mg/l. Both isolates were cultured from urethral specimens that were collected from male patients who had presented to their general practitioners with urethral discharge. Patient 1 was treated empirically with azithromycin. Patient 2, who reported having had sex with other men, was given intravenous ceftriaxone as he had recently failed two courses of oral cefixime. Both isolates were also highly resistant to ciprofloxacin, resistant to penicillin (ß-lactamase negative) and resistant to tetracycline (and thus doxycycline), and exhibited decreased susceptibility to both azithromycin and gentamicin. On molecular testing, both isolates were found to have mosaic penA genes, which encode for penicillin-binding protein 2. Mosaic penA gene formation is the most common genetic mechanism that is associated with decreased susceptibility to oral cephalosporins. The isolates were typed using the highly discriminatory N. gonorrhoeae multiantigen sequence typing scheme and were found to have identical sequence types. This indicates that it is likely that there has been transmission of a single strain within Gauteng. It is probable that the two cases may be part of the same sexual network. Case histories Recently, a local Ampath laboratory identified two cefpodox-ime-resistant Neisseria gonorrhoeae isolates that were confirmed to exhibit high minimum inhibitory concentrations (MIC) to oral cephalosporins at the Centre for HIV and STIs [National Institute of Communicable Diseases (NICD), National Health Laboratory Services (NHLS)]. Both isolates were cultured from urethral specimens collected from male patients who had presented to their general practitioners with a typical gonococcal urethral discharge. Clinical details are lacking for the first patient, who presented in May 2012 and was treated empirically with single-dose oral azithromycin. The second patient presented in July 2012 and provided a history of persistent urethral gonorrhoea that commenced after sexual intercourse with another man. His urethral discharge had not responded to two courses of a 400-mg single dose of oral cefixime, the recommended first-line treatment for gonorrhoea in South Africa. Patient 2 was treated with a 2-g intravenous dose of ceftriaxone. It is not known whether either patient had asymptomatic gonorrhoea at other anatomical sites, i.e. the pharynx or anorectum, at the time that their urethral infection was treated. To date, neither patient has returned for follow-up. Both general practitioners are actively trying to recall their patients to ensure that they have been treated successfully. Laboratory testing Both gonococcal strains exhibited decreased susceptibility to cefixime (MIC 0.125 mg/l) and cefpodoxime (patient 1's isolate, MIC 0.75 mg/l; patient 2's isolate, MIC 1 mg/l) using Etest methodology. Both isolates were also highly resistant to ciprofloxacin and chromosomally resistant to penicillin (ß-lactamase negative). Further testing of patient 1's isolate demonstrated chromosomal resistance to tetracycline (and thus doxycycline) and decreased susceptibility to both azithromycin and gentamicin. The ceftriaxone MIC for both isolates was 0.064 mg/l, which, while still in the susceptible range, is elevated compared to the usual MIC range that is seen when testing South African gonococcal isolates (0.001-0.004 mg/l). Both isolates were found to have mosaic penA genes, which encode penicillin-binding protein 2, which is the most common genetic mechanism associated with decreased susceptibility to oral cephalosporins. The isolates were typed using the highly discriminatory N. gonorrhoeae multiantigen sequence typing scheme and were found to have identical sequence types. This indicates that it is likely that there has been transmission of a single strain within Gauteng.