Time kill-assays of antibiotic combinations for multidrug resistant clinical isolates of OXA-48 carbapenemase producing Klebsiella pneumoniae

Creative Commons License

Erdem F., Diez-Aguilar M., Öksüz L., Kayacan C., Abulaila A., Öncül M. O., ...More

ACTA MICROBIOLOGICA ET IMMUNOLOGICA HUNGARICA, vol.69, no.3, pp.215-219, 2022 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 69 Issue: 3
  • Publication Date: 2022
  • Doi Number: 10.1556/030.2022.01785
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, CAB Abstracts, EMBASE, MEDLINE, Veterinary Science Database
  • Page Numbers: pp.215-219
  • Keywords: OXA-48 carbapenemase, MDR Klebsiella pneumoniae, time kill -assay, combination therapy, GRAM-NEGATIVE BACTERIA, INFECTIONS, AVIBACTAM, COLISTIN, THERAPY
  • Eskisehir Osmangazi University Affiliated: Yes


Treatment of infections caused by OXA-48 carbapenemase producing multidrug-resistant isolates often necessitates combination therapy. In vitro effect of different antibiotic combinations against multidrug-resistant (MDR) Klebsiella pneumoniae isolates were evaluated in this study.Meropenem-tobramycin (MER+TOB), meropenem-ciprofloxacin (MER+CIP), colistin-mer-openem (COL+MER), colistin-ciprofloxacin (COL+CIP) and colistin-tobramycin (COL+TOB) combinations were tested by time kill-assays. Each antibiotic alone and in combination at their Cmax values were tested against 4 clinical K. pneumoniae isolates at 1, 2, 4, 6, 8, 12 and 24 h. Effect of colistin and its associations were also assessed at 30 min. Bactericidal activity was defined as >= 3log10 CFU mL-1 decrease compared with initial inoculum. Synergy was defined as >= 2log10CFU mL-1 decrease by the combination compared with the most active single agent. Presence of blaOXA-48, blaNDM, blaVIM, blaIMP, blaKPC and blaCTX-M-1 genes was screened by PCR using specific primers.The blaOXA-48 gene was identified together with blaCTXM-1 group gene in all isolates. COL+MER demonstrated to be synergistic and bactericidal. MER+TOB showed synergistic and bactericidal effect on two strains although, regrowth was seen on other two strains at 24 h. MER+CIP exhibited indif-ferent effect on the strains.Combination therapy could be a potential alternative to treat MDR K. pneumoniae infections. This combination might prevent resistance development and secondary effects of colistin monotherapy. MER+TOB and MER+CIP might have an isolate-dependent effect, that may not always result in synergism.