Respiratory quinolones can eradicate amoxicillin-induced mature biofilms and nontypeable Haemophilus influenzae in biofilms

J Infect Chemother. 2022 Dec;28(12):1595-1604. doi: 10.1016/j.jiac.2022.07.019. Epub 2022 Aug 21.

Abstract

Objectives: Biofilm is thought to be involved in the persistent bacterial infections caused by nontypeable Haemophilus influenzae (NTHi). This study aims to evaluate the efficacy of antibiotics against NTHi biofilms.

Methods: A 96-wells pin replicator assay was applied for evaluation of antimicrobial efficacies against NTHi biofilms. The NTHi IH-202 strain for the standard and 10 clinical strains were evaluated, as well as the viability of NTHi in biofilms after antimicrobial exposures.

Results: Biofilms formed by IH-202 strain accumulated during incubation. AMPC if not high concentrations, neither reduce or inhibit biofilm formation, nor eradicate matured NTHi biofilms. The NTHi in matured biofilm were alive after exposure to amoxicillin (AMPC). Even high concentration of AMPC produced live NTHi after suspension of exposure, while tosufloxacin and garenoxacin inhibited biofilm formation of NTHi and eradicated matured biofilms. The respiratory quinolones, but not AMPC, killed NTHi in biofilms even at sub-MIC.

Conclusions: NTHi persists in biofilms, even after exposure to AMPC. These findings may eventually lead to a better understanding of effective use of antibiotics to eradicate NTHi growing as biofilms, or even to the development of novel therapeutic agents for treating patients with mucosal NTHi biofilm infections. Meanwhile, respiratory quinolones are attractive agents in reducing NTHi biofilm formation and destroying established biofilm.

Keywords: Amoxicillin; Biofilm; Nontypeable H. influenzae; Respiratory quinolones.

MeSH terms

  • Amoxicillin / pharmacology
  • Anti-Bacterial Agents / pharmacology
  • Anti-Infective Agents* / pharmacology
  • Biofilms
  • Haemophilus Infections* / drug therapy
  • Haemophilus Infections* / microbiology
  • Haemophilus influenzae
  • Humans
  • Quinolones* / pharmacology

Substances

  • Anti-Bacterial Agents
  • Anti-Infective Agents
  • Quinolones
  • Amoxicillin