Antibiotic resistance among Neisseria meningitidis isolates in England, Wales and Northern Ireland (July 2010 - August 2019)

Willerton, Laura Jane (2021) Antibiotic resistance among Neisseria meningitidis isolates in England, Wales and Northern Ireland (July 2010 - August 2019). Masters by Research thesis (MSc), Manchester Metropolitan University.

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Abstract

Invasive meningococcal disease (IMD), caused by Neisseria meningitidis, has a fatality rate as high as 10%, even with appropriate treatment. In the UK, penicillin is administered to patients in primary care whilst cefotaxime and ceftriaxone are administered in secondary care. The first-choice antibiotic for chemoprophylaxis of close contacts is ciprofloxacin, followed by rifampicin. IMD caused by non-groupable (NG) meningococci affects mainly immunocompromised individuals, who are recommended antibiotic chemoprophylaxis due to a greater risk of IMD development. Resistance to antibiotics among meningococci is relatively rare, however reduced susceptibility and resistance to penicillin is increasing globally. Limited data exist regarding the prevalence of antibiotic resistance among meningococci in the UK. The Public Health England Meningococcal Reference Unit receives all isolates from IMD cases in England, Wales and Northern Ireland. The aims of this project were to i) investigate the distribution of antibiotic resistance to penicillin, rifampicin, ciprofloxacin and cefotaxime among IMD isolates from 2010/11-2018/19 (n=4,122), ii) investigate a recent outbreak of IMD in England caused by a ciprofloxacin-resistant NG meningococcal strain and iii) investigate increasing levels of penicillin resistance among serogroup W ST-11 clonal complex isolates in England. Out of the 4,122 IMD isolates, 113 were penicillin-resistant, two were rifampicin-resistant, five were ciprofloxacin-resistant and one was cefotaxime-resistant. Penicillin resistance was mainly due to altered penA alleles. Rifampicin and ciprofloxacin resistance were due to altered rpoB and gyrA alleles, respectively. Cefotaxime resistance was observed in an isolate with an altered penA allele containing additional mutations to those harboured by penicillin-resistant isolates. A ciprofloxacin-resistant strain of the ST-175 CC with an apparent propensity for reduced susceptibility to penicillin was identified and found to be of concern among immunocompromised individuals. An increase in penicillin-resistant English serogroup W ST-11 CC isolates was due to several strains; in particular, a strain first identified in Australia in 2016. This research highlights the need for continued surveillance of antibiotic resistance among meningococci and the need for vigilance among immunocompromised patients to maintain successful chemoprophylaxis regimes.