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Antibiotic susceptibility and characteristics of Neisseria meningitidis isolates from the African meningitis belt, 2000 to 2006: phenotypic and genotypic perspectives
Örebro University, School of Health and Medical Sciences.
Örebro University, School of Health and Medical Sciences.
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2009 (English)In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 53, no 4, p. 1561-1566Article in journal (Refereed) Published
Abstract [en]

Up-to-date information regarding the antibiotic susceptibility of Neisseria meningitidis strains from African countries is highly limited. Our aim was to comprehensively describe the antibiotic susceptibilities of a selection of N. meningitidis isolates recovered between 2000 and 2006 from 18 African countries, mainly those within the meningitis belt. Susceptibilities to 11 antibiotics were determined using Etest for 137 N. meningitidis isolates (stringently selected from 693 available isolates). The isolates were also characterized by serogrouping, multilocus sequence typing, genosubtyping, and penA allele identification. All N. meningitidis isolates were susceptible to ceftriaxone, chloramphenicol, and ciprofloxacin. No isolate produced beta-lactamase. Only three isolates (2%) displayed reduced susceptibility to penicillin G. The two isolates with the highest penicillin G MICs were the only isolates showing reduced susceptibility to ampicillin and cefuroxime. One of these isolates was also resistant to penicillin V. One percent of isolates displayed reduced susceptibility to rifampin, while 52% of the isolates were resistant to tetracycline, 74% were resistant to erythromycin, and 94% were resistant to sulfadiazine. The MICs of rifampin and tetracycline seemed to be associated with the serogroup of the isolates. In total, 18 sequence types (STs), 10 genosubtypes, and 8 different penA alleles were identified; the most common were ST-7, P1.20,9,35-1, and penA4, respectively. A high level of correlation was found between ST, genosubtype, and penA allele. In conclusion, N. meningitidis isolates from the African meningitis belt remain highly susceptible to the antibiotics used. Regarding beta-lactam antibiotics, rare isolates showed a reduced susceptibility to penicillins, but the expanded-spectrum cephalosporins are not affected at present.

Place, publisher, year, edition, pages
2009. Vol. 53, no 4, p. 1561-1566
National Category
Medical and Health Sciences Microbiology in the medical area
Research subject
Microbiology; Physiology; Biomedicine
Identifiers
URN: urn:nbn:se:oru:diva-8630DOI: 10.1128/AAC.00994-08PubMedID: 19188396OAI: oai:DiVA.org:oru-8630DiVA, id: diva2:278244
Available from: 2009-11-25 Created: 2009-11-23 Last updated: 2018-01-12Bibliographically approved
In thesis
1. Antibiotic susceptibility and resistance in Neisseria meningitidis: phenotypic and genotypic characteristics
Open this publication in new window or tab >>Antibiotic susceptibility and resistance in Neisseria meningitidis: phenotypic and genotypic characteristics
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Neisseria meningitidis, also known as the meningococcus, is a globally spread obligate human bacterium causing meningitis and/or septicaemia. It is responsible for epidemics in both developed and developing countries. Untreated invasive meningococcal disease is often fatal, and despite modern intensive care units, the mortality is still remarkably high (approximately 10%). The continuously increasing antibiotic resistance in many bacterial pathogens is a serious public health threat worldwide and there have been numerous reports of emerging resistance in meningococci during the past decades.

In paper I, the gene linked to reduced susceptibility to penicillins, the penA gene, was examined. The totally reported variation in all published penA genes was described. The penA gene was highly variable (in total 130 variants were identified). By examination of clinical meningococcal isolates, the association between penA gene sequences and penicillin susceptibility could be determined. Isolates with reduced susceptibility displayed mosaic structures in the penA gene. Two closely positioned nucleotide polymorphisms were identified in all isolates with reduced penicillin susceptibility and mosaic structured penA genes. These alterations were absent in all susceptible isolates and were successfully used to detect reduced penicillin susceptibility by real-time PCR and pyrosequencing in paper II. In papers III and IV, antibiotic susceptibility and characteristics of Swedish and African meningitis belt meningococcal isolates were comprehensively described. Although both populations were mainly susceptible to the antibiotics used for treatment and prophylaxis, the proportion of meningococci with reduced penicillin susceptibility was slightly higher in Sweden. A large proportion of the African isolates was resistant to tetracycline and erythromycin. In paper V, the gene linked to rifampicin resistance, the rpoB gene, was examined in meningococci from 12 mainly European countries. Alterations of three amino acids in the RpoB protein were found to always and directly lead to rifampicin resistance. A new breakpoint for rifampicin resistance in meningococci was suggested. The biological cost of the RpoB alterations was investigated in mice. The pathogenicity/virulence was significantly lower in rifampicin resistant mutants as compared with susceptible wild-type bacteria.

Place, publisher, year, edition, pages
Örebro: Örebro universitet, 2009. p. 94
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 38
Keywords
Neisseria meningitidis, meningococcal disease, antibiotic resistance, antibiotic susceptbility, biological cost, PCR, sequencing
National Category
Cell and Molecular Biology Microbiology in the medical area Microbiology in the medical area Microbiology in the medical area
Research subject
Biomedicine; Medicine
Identifiers
urn:nbn:se:oru:diva-8652 (URN)978-91-7668-702-4 (ISBN)
Public defence
2009-12-18, Wilandersalen, Universitetssjukhuset Örebro, Örebro, 09:00 (English)
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Available from: 2009-11-25 Created: 2009-11-25 Last updated: 2018-01-12Bibliographically approved

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Hedberg, Sara ThulinFredlund, HansUnemo, Magnus

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