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Published on: February 23, 2014
Emergence of a multidrug-resistant Haemophilus influenzae strain causing chronic pneumonia in a patient with common
Yvonne Pfeifer1, Ines Meisinger, Klaus Brechtel
1Robert-Koch-Institute, FG13 Nosocomial Infections, Wernigerode, Germany.
Abstract:
We report the emergence of a multidrug-resistant Haemophilus influenzae strain in a patient with common variable immunodeficiency suffering from recurrent bronchopneumonia caused by H. influenzae. After the patient had received several antibiotic therapies, a strain was isolated showing resistance to ampicillin, ampicillin/sulbactam, cefazolin, cefuroxime, ciprofloxacin, and clarithromycin. Polymerase chain reaction analyses and sequencing revealed the presence of the beta-lactamase gene bla(TEM-1), two mutations (A502T and R517H) in the ftsI gene encoding the transpeptidase region of the penicillin-binding protein 3, and one mutation in the ribosomal protein gene L4 (G65D) conferring resistance to beta-lactams and macrolides, respectively. Additionally, the plasmid-encoded aac(6')-Ib-cr gene mediating slightly reduced susceptibility to quinolones and two mutations in the DNA gyrase gene gyrA and one mutation in the topoisomerase IV gene parC were identified leading to a high-level fluoroquinolone-resistant phenotype. In conclusion, the treatment of H. influenzae infections accompanied by high bacterial loads such as bronchopneumonia can be complicated by the selection of multidrug-resistant strains. Moreover, the emergence of aac(6')-Ib-cr in H. influenzae causing low fluoroquinolone resistance levels might have contributed to the selection of DNA gyrase and topoisomerase IV mutants.
Insights
A multidrug-resistant Haemophilus influenzae strain emerged in an immunodeficient patient with recurrent pneumonia. Genetic analysis revealed resistance mechanisms to beta-lactams, macrolides, and fluoroquinolones.
Area of Science:
- Medical Microbiology
- Genetics
- Immunology
Background:
- Common variable immunodeficiency (CVID) predisposes patients to recurrent infections.
- Haemophilus influenzae is a significant cause of respiratory tract infections, particularly in immunocompromised individuals.
Observation:
- A patient with CVID developed recurrent bronchopneumonia due to H. influenzae.
- Following multiple antibiotic treatments, an H. influenzae strain exhibited resistance to ampicillin, beta-lactam/beta-lactamase inhibitor combinations, cephalosporins, and macrolides.
Findings:
- Genetic analysis identified the bla(TEM-1) gene conferring beta-lactam resistance.
- Mutations in ftsI (A502T, R517H) and ribosomal protein L4 (G65D) conferred resistance to beta-lactams and macrolides, respectively.
- The plasmid-borne aac(6')-Ib-cr gene and mutations in gyrA and parC genes resulted in high-level fluoroquinolone resistance.
Implications:
- Treatment of H. influenzae infections with high bacterial loads can lead to the selection of multidrug-resistant strains.
- The emergence of aac(6')-Ib-cr may contribute to the selection of fluoroquinolone resistance in H. influenzae.
- Understanding these resistance mechanisms is crucial for managing infections in immunocompromised patients.
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