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Phenotypic detection of clinical isolates of Haemophilus influenzae with altered penicillin-binding protein 3

A Aguirre-Quiñonero1,2, I C Pérez Del Molino3, C García de la Fuente3

  • 1Service of Microbiology, University Hospital Marqués de Valdecilla-IDIVAL, Avenida de Valdecilla s/n, 39008, Santander, Spain. amayiaguirre@gmail.com.

European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology
|May 15, 2018
PubMed

Insights

Mutations in the ftsI gene (PBP3) of Haemophilus influenzae correlate with aminopenicillin resistance. Current EUCAST guidelines may not reliably identify resistant strains, necessitating improved diagnostic approaches for ampicillin resistance.

Area of Science:

  • Microbiology
  • Genetics
  • Pharmacology

Background:

  • Aminopenicillin resistance in Haemophilus influenzae is a growing concern.
  • Mutations in the ftsI gene, encoding penicillin-binding protein 3 (PBP3), are a primary mechanism of resistance.
  • Accurate susceptibility testing is crucial for effective treatment of H. influenzae infections.

Purpose of the Study:

  • To investigate the correlation between ftsI gene mutations and aminopenicillin resistance in H. influenzae.
  • To evaluate the performance of current European Committee for Antibiotic Susceptibility Testing (EUCAST) guidelines for categorizing ampicillin, amoxicillin, and amoxicillin-clavulanate resistance.
  • To assess the utility of benzylpenicillin screening (BP1) for detecting resistant strains.

Main Methods:

  • Genetic characterization of 91 H. influenzae isolates by sequencing the ftsI gene.
  • Phenotypic testing including screening with benzylpenicillin 1U (BP1) and determination of minimum inhibitory concentrations (MICs) for ampicillin, amoxicillin, and amoxicillin-clavulanate.
  • Interpretation of MICs according to EUCAST recommendations.

Main Results:

  • Fourteen distinct amino acid substitutions in PBP3 were identified.
  • Common substitution patterns were observed in both bla-positive and bla-negative resistant PBP3 (rPBP3) strains.
  • Benzylpenicillin screening (BP1) correctly categorized most strains, but only 29% of bla-negative rPBP3 strains had ampicillin MICs above the EUCAST resistant breakpoint.
  • Current EUCAST breakpoints for ampicillin may not reliably identify bla-negative rPBP3 strains.

Conclusions:

  • The study confirms the association between ftsI mutations and aminopenicillin resistance in H. influenzae.
  • Existing EUCAST breakpoints for ampicillin may underestimate resistance in certain H. influenzae strains with mutated PBP3.
  • Further refinement of susceptibility testing guidelines is needed for accurate clinical categorization of ampicillin resistance.
Keywords:
EUCASTHaemophilus influenzaeftsIrPBP3β-lactam resistance

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