title: Fluoroquinolone, Macrolide, and Ketolide Resistance in Haemophilus parainfluenzae from South Africa.
abstract: Fluoroquinolones and ketolides are among the drugs of choice for the treatment of Haemophilus parainfluenzae infections. There has been a report of an emerging fluoroquinolone and telithromycin resistance in H. parainfluenzae isolates from the private sector of KwaZulu-Natal Province of South Africa that necessitates molecular investigation. The aim of this study is to characterize these resistance delineating mutations in genes commonly associated with reduced susceptibility. Ten H. parainfluenzae isolates retrieved from the sputum of 10 patients with H. parainfluenzae pneumonia were subjected to sensitivity testing by the disc diffusion and CLSI broth microdilution methods, polymerase chain reaction (PCR) and DNA sequencing of selected genes associated with resistance were carried out, while repetitive extragenic palindromic PCR (REP-PCR) was used to ascertain clonality. Fluoroquinolone resistance was attributed to the following amino acid substitutions: S84F, D88Y in GyrA, and S84Y/L, S138T, and M198 L change in ParC of the isolates. The plasmid-mediated quinolone resistance gene aac-(6')-Ib-cr was detected for the first time in four isolates of H. parainfluenzae and D420 N change was observed in ParE in one isolate. Macrolide and ketolide resistance were ascribed to the resistance genes mef (A), msr (D), and erm (B) detected in the isolates. REP-PCR analysis showed that the isolates were not clonal. All the observed resistance mechanisms are first reports in Africa. There is an emerging fluoroquinolone and macrolide resistance in H. parainfluenzae in South Africa that is attributable to known/novel resistance mechanisms, necessitating the monitoring of this pathogen as a potential opportunistic pathogen in a country with a high HIV and AIDS prevalence.
authors.affiliation: 1 Antimicrobial Research Unit, School of Health Sciences, University of KwaZulu-Natal , Durban, South Africa .|2 Department of Pharmaceutical Microbiology, School of Pharmacy, University of Health and Allied Sciences, Ho, Ghana .
authors.forename: Regina Esinam
authors.initials: RE
authors.lastname: Abotsi
authors.affiliation: 1 Antimicrobial Research Unit, School of Health Sciences, University of KwaZulu-Natal , Durban, South Africa .
authors.forename: Usha
authors.initials: U
authors.lastname: Govinden
authors.affiliation: 3 Lancet Laboratories , Durban, South Africa .
authors.forename: Krishnee
authors.initials: K
authors.lastname: Moodley
authors.affiliation: 1 Antimicrobial Research Unit, School of Health Sciences, University of KwaZulu-Natal , Durban, South Africa .
authors.forename: Sabiha
authors.initials: S
authors.lastname: Essack
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics; D005260:Female; D024841:Fluoroquinolones / Q000627:therapeutic use*; D044135:Haemophilus parainfluenzae / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D048628:Ketolides / Q000627:therapeutic use*; D018942:Macrolides / Q000627:therapeutic use*; D008297:Male; D008826:Microbial Sensitivity Tests / Q000379:methods; D008875:Middle Aged; D013019:South Africa; D013183:Sputum / Q000382:microbiology
chemical_list: D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D048628:Ketolides; D018942:Macrolides
keywords: aac-(6′)-Ib-cr; erm (B); mef (A); msr (D); parE; telithromycin