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Azithromycin Pharmacodynamics against Persistent Haemophilus influenzae in Chronic Obstructive Pulmonary Disease

Brian T Tsuji1, James Fisher1,2, Raheal Boadi-Yeboah1

  • 1Laboratory for Antimicrobial Pharmacodynamics, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, the State University of New York, Buffalo, New York, USA.

Antimicrobial Agents and Chemotherapy
|November 29, 2017
PubMed

Insights

Azithromycin effectiveness decreased against persistent nontypeable Haemophilus influenzae (NTHi) strains in chronic obstructive pulmonary disease (COPD) patients. NTHi viability persisted despite simulated azithromycin treatment regimens.

Area of Science:

  • Pharmacodynamics
  • Microbiology
  • Pulmonary Medicine

Background:

  • Nontypeable Haemophilus influenzae (NTHi) is a significant pathogen in chronic obstructive pulmonary disease (COPD) exacerbations.
  • Persistent NTHi strains can develop reduced susceptibility to antibiotics, complicating treatment.
  • Azithromycin is frequently used for its immunomodulatory and antimicrobial effects in COPD.

Purpose of the Study:

  • To characterize the pharmacodynamic profile of azithromycin against persistent NTHi strains.
  • To evaluate azithromycin's efficacy against NTHi isolated from COPD patients over extended periods.

Main Methods:

  • Pharmacodynamic profiling of azithromycin against NTHi strains.
  • Comparison of azithromycin susceptibility between early and late NTHi isolates from the same patient.
  • Utilized a hollow-fiber infection model to simulate azithromycin treatment regimens.

Main Results:

  • Azithromycin demonstrated concentration-dependent activity against NTHi (R² ≥ 0.988).
  • A significant attenuation in pharmacodynamic response was observed, with EC50 increasing over 50-fold for late-emergent strains compared to early strains (0.0821 mg/L vs. 4.23 mg/L).
  • NTHi viability was maintained throughout 10-day simulated azithromycin (Zithromax Z-Pak) regimens in the hollow-fiber model.

Conclusions:

  • Persistent NTHi strains in COPD patients can develop significantly reduced susceptibility to azithromycin.
  • Standard azithromycin regimens may be insufficient to eradicate long-term NTHi airway colonization.
  • Further investigation into alternative or combination therapies is warranted for persistent NTHi infections in COPD.
Keywords:
azithromycinmacrolide-lincosamide-streptogramin Bnontypeable H. influenzae

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