Levofloxacin Treatment Failure in<i>Haemophilus influenzae</i>Pneumonia

Bastida, Teresa; Pérez-Vázquez, Marı́a; Campos, José; Cortés-Lletget, María Cristina; Román, Federico; Tubau, Fé; Campa, Adela G. de la; Alonso-Tarrés, Carles

doi:10.3201/eid0911.030176

Cited by 34 publications

(32 citation statements)

References 13 publications

(5 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Some specific mutations involved in FQ resistance in H. influenzae were originally described in 1996 (19). Subsequent studies have confirmed the mutations described by Georgiou et al and described new mutations involved in resistance (15,16,18,19,22,24,29,33,37,39). FQ resistance is acquired gradually with increasing numbers of mutations.…”

Section: Discussionsupporting

confidence: 67%

“…To the best of our knowledge, two reports of FQ treatment failure have been published to date (15,18). In 1999, Vila et al reported a case of FQ resistance after treatment with ofloxacin in a patient with recurrent respiratory infections (15), and in 2003, Bastida et al reported a case of LVX treatment failure in a patient with community-acquired pneumonia who had previously been treated with LVX and moxifloxacin (18). Some specific mutations involved in FQ resistance in H. influenzae were originally described in 1996 (19).…”

Section: Discussionmentioning

confidence: 99%

“…Since their first description in 1993, FQ-resistant H. influenzae isolates have been detected all over the world (7)(8)(9)(10)(11)(12)(13)(14)(15)(16). Although resistance in this bacterial pathogen remains low (8,17), treatment failure with ofloxacin or levofloxacin (LVX) has already been described (15,18). FQ resistance in H. influenzae is due mainly to chromosomal point mutations in the quinolone resistance-determining regions (QRDRs) of the genes encoding DNA gyrase (gyrA and gyrB) and topoisomerase IV (parC and parE) (19).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Molecular Characterization of Fluoroquinolone Resistance in Nontypeable Haemophilus influenzae Clinical Isolates

Puig

Tirado-Vélez

Calatayud

et al. 2015

Antimicrob Agents Chemother

Self Cite

View full text Add to dashboard Cite

Section: Discussionsupporting

confidence: 67%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Molecular Characterization of Fluoroquinolone Resistance in Nontypeable Haemophilus influenzae Clinical Isolates

Puig

Tirado-Vélez

Calatayud

et al. 2015

Antimicrob Agents Chemother

Self Cite

View full text Add to dashboard Cite

“…We and other authors have reported a high prevalence of hypermutable H. influenzae isolates causing respiratory infections (22,24). We also noticed a high rate of fluoroquinolone resistance in these isolates (22) and reported a therapeutic failure in a community-acquired pneumonia case due to levofloxacinresistant H. influenzae (2).…”

mentioning

confidence: 62%

Fluoroquinolone Resistance in Haemophilus influenzae Is Associated with Hypermutability

Pérez-Vázquez

Román

García-Cobos

et al. 2007

Antimicrob Agents Chemother

View full text Add to dashboard Cite

Forty-three percent (12/28) of ciprofloxacin (CIP)-nonsusceptible respiratory isolates of Haemophilus influenzae were hypermutable, compared with 8.5% (3/35) in the CIP-susceptible control group (P ‫؍‬ 0.002). CIP-nonsusceptible mutants were obtained with hypermutable strains only; these mutants developed three resistance mechanisms in a step-by-step process: target modifications, loss of a porin protein, and increased efflux.Fluoroquinolone-resistant Haemophilus influenzae isolates have been described in several countries (4,5,8,17,19). In general, hypermutable isolates contribute to the emergence of antibiotic resistance (3, 9). Fluoroquinolone resistance in Staphylococcus aureus is related to hypermutability (23). We and other authors have reported a high prevalence of hypermutable H. influenzae isolates causing respiratory infections (22,24). We also noticed a high rate of fluoroquinolone resistance in these isolates (22) and reported a therapeutic failure in a community-acquired pneumonia case due to levofloxacinresistant H. influenzae (2).The main mechanism of fluoroquinolone resistance in H. influenzae is amino acid changes in the quinolone resistance-determining region (QRDR) of the topoisomerase II and I genes (5, 8, 9). Although not reported in H. influenzae, mutations resulting in overexpression of efflux pumps and permeability defects can also affect quinolone susceptibility (12).In this study, we investigated the hypothesis that ciprofloxacin (CIP) resistance in H. influenzae occurs mainly in hypermutable clinical isolates. To test this hypothesis, first we made an observational study, and after that, we subjected CIP-susceptible hypermutable isolates to selective pressure with CIP. We also characterized other mechanisms of resistance in highly fluoroquinolone-resistant isogenic mutants as overexpression of efflux pumps and permeability defects.The CIP reduced-susceptibility study group included 28 clinical isolates (3 from the United States [1] and 25 from Spain) chosen because they had amino acid changes in GyrA of the QRDR (21) and corresponding MICs for CIP of 0.12 to 32 g/ml. The CIP-susceptible control group contained 35 clinical strains without amino acid changes and corresponding MICs for CIP of Ͻ0.12 g/ml. All strains were noncapsulated and were isolated from respiratory specimens of adult patients with chronic respiratory infections (19,21).The study of mutation frequencies in response to rifampin was done in triplicate as described previously (22). Isolates were considered hypermutable if their mutation frequency was 10 Ϫ7 CFU/ml or higher (22). Forty-three percent of the strains (12/28) in the study group were hypermutable, compared to 8.5% (3/35) in the control group (odds ratio, 8; P, 0.0024). The average mutation frequencies in the two groups (4 ϫ 10 Ϫ6 CFU/ml for the study group and 7 ϫ 10 Ϫ8 CFU/ml for the control group) differed significantly (P, 0.017; Mann-Whitney U test). The mutation frequency distributions are shown in Fig. 1. A positive correlation was found between mutation...

show abstract

“…However, the pharmacokinetic and pharmacodynamic properties of these compounds cast doubt on their clinical efficacy against H. influenzae (18), and our group recently reported a macrolide efflux mechanism in baseline strains with MICs in the "susceptible" category (29). At present, most clinical strains of H. influenzae are quinolone susceptible (17); however, quinolone resistance has been described for both laboratory and clinical settings (2,10,26).…”

mentioning

confidence: 99%

Activity of LBM415 Compared to Those of 11 Other Agents against Haemophilus Species

Bogdanovich

Smith

Clark

et al. 2006

Antimicrob Agents Chemother

View full text Add to dashboard Cite

When tested against 254 Haemophilus influenzae strains, LBM415, a peptide deformylase inhibitor, gave MIC 50 and MIC 90 values of 2.0 g/ml and 8.0 g/ml, respectively. The MICs were independent of ␤-lactam or quinolone susceptibility and the presence or absence of macrolide efflux or ribosomal protein mutations. The MICs of LBM415 against 23 H. parainfluenzae strains were similar to those against H. influenzae. In contrast, erythromycin, azithromycin, and clarithromycin gave unimodal MIC distributions, and apart from ␤-lactamase-negative, ampicillin-resistant strains, all strains were susceptible to the ␤-lactams tested. Apart from selected quinolone-resistant strains, all strains were susceptible to ciprofloxacin, levofloxacin, gatifloxacin, moxifloxacin, and gemifloxacin. Resistance to trimethoprim-sulfamethoxazole was common. The potencies of all drugs against 23 H. parainfluenzae strains were similar to those against H. influenzae. Time-kill studies with 10 Haemophilus strains showed LBM415 to be bactericidal at 2؋ the MIC against 8 of 10 strains after 24 h. For comparison, the macrolides and ␤-lactams were bactericidal against 8 to 10 strains each at 2؋ the MIC after 24 h. Quinolones were bactericidal against all 10 strains tested at 2؋ the MIC after 24 h. Against six H. influenzae strains, postantibiotic effects for LBM415 lasted between 0.8 and 2.2 h. In multistep resistance selection studies, LBM415 produced resistant clones in 7 of the 10 strains tested, with MICs ranging from 4 to 64 g/ml. No mutations in deformylase (def) and formyltransferase (fmt) genes were detected in any of the LBM415-resistant mutants.Haemophilus influenzae is an important pathogen responsible for community-acquired respiratory tract infections in children and adults, including pneumonia, acute exacerbations of chronic bronchitis, sinusitis, and otitis media (9, 23). In countries such as the United States, where the H. influenzae type b vaccine is widely used, type b has been replaced by untypeable H. influenzae strains. Haemophilus parainfluenzae strains may also play a role in the pathogenesis of acute exacerbations of chronic bronchitis (S. Sethi, personal communication).Antimicrobials used for the empirical treatment of Haemophilus infections include ␤-lactams, macrolides, and (in adults) fluoroquinolones. The major resistance mechanism in H. influenzae in the United States and Europe is the production of ␤-lactamase (encoded by bla TEM-1 and, rarely, bla ROB-1 ), which is present in over 41% of H. influenzae strains in the United States (17,24,27,30). Although less common, resistance to ␤-lactams in the absence of ␤-lactamase production (␤-lactamase-negative ampicillin resistance [BLNAR]) is caused by alterations (mutations) in penicillin-binding protein 3 (8, 31). Strains producing ␤-lactamases remain susceptible to amoxicillin-clavulanate; however, clavulanate is not active against BLNAR strains. In addition, very rare H. influenzae strains producing ␤-lactamase have been found to be resistant to amoxicillin-clavulanate (8...

show abstract

Levofloxacin Treatment Failure inHaemophilus influenzaePneumonia

Cited by 34 publications

References 13 publications

Molecular Characterization of Fluoroquinolone Resistance in Nontypeable Haemophilus influenzae Clinical Isolates

Molecular Characterization of Fluoroquinolone Resistance in Nontypeable Haemophilus influenzae Clinical Isolates

Fluoroquinolone Resistance in Haemophilus influenzae Is Associated with Hypermutability

Activity of LBM415 Compared to Those of 11 Other Agents against Haemophilus Species

Contact Info

Product

Resources

About