Molecular Characterization of Fluoroquinolone-Resistant<i>Haemophilus parainfluenzae</i>Clinical Isolates in Spain

López-Hernández, Inmaculada; Machuca, Jesús; Alba, Paula Díaz de; Sarvisé, Carolina; Gómez, Frederic; Rodríguez-Martínez, José Manuel; Pascual, Álvaro

doi:10.1089/mdr.2016.0186

Cited by 4 publications

(1 citation statement)

References 16 publications

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“…Interestingly, for the isolates with a Ͼ4-fold increase in fluoroquinolone MIC values from both arms, 3 out of the 4 isolates were genetically unrelated. Previous studies from Spain and South Africa reported fluoroquinolone resistance arising from mutations in the QRDR as well as plasmid-mediated resistance (9,10). The mutations observed in H. parainfluenzae in this study were also observed in isolates reported in the Spanish and South African studies.…”

Section: Discussionsupporting

confidence: 75%

Efficacy of Delafloxacin versus Moxifloxacin against Bacterial Respiratory Pathogens in Adults with Community-Acquired Bacterial Pneumonia (CABP): Microbiology Results from the Delafloxacin Phase 3 CABP Trial

McCurdy

Keedy

Lawrence

et al. 2020

Antimicrob Agents Chemother

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Delafloxacin is a novel fluoroquinolone with activity against Grampositive, Gram-negative, and atypical pathogens, including fluoroquinolone-nonsusceptible methicillin-resistant Staphylococcus aureus (MRSA). The microbiological results of a phase 3 clinical trial in adults with community-acquired pneumonia (CAP) comparing delafloxacin (300 mg intravenously [i.v.] with the option to switch to 450 mg orally every 12 h) to moxifloxacin (400 mg i.v. with the option to switch to 400 mg orally once a day [QD]) were determined. Patients from 4 continents, predominately Europe but also South America and Asia, were enrolled. The microbiological intent-to-treat (MITT) population included 520 patients, and 60.5% of these patients had a bacterial pathogen identified. Multiple diagnostic methods were employed, including culture, serology, PCR, and urinary antigen tests. Based on baseline MIC 90 values, delafloxacin exhibited at least 16-fold greater activity than moxifloxacin for Gram-positive and fastidious Gram-negative pathogens. Delafloxacin retained activity against resistant phenotypes found in Streptococcus pneumoniae (penicillin-, macrolide-, and multiple-drug resistant), Haemophilus species (␤-lactamase producing and macrolide nonsusceptible), and S. aureus (MRSA and fluoroquinolonenonsusceptible methicillin-susceptible S. aureus [MSSA]). The microbiological success rates were 92.7% for S. pneumoniae (87.5% for penicillin-resistant S. pneumoniae [PRSP]), 92.6% for S. aureus (100% for MRSA), 100% for Escherichia coli, 82.4% for Klebsiella pneumoniae, 100% for Klebsiella oxytoca, 100% for Moraxella catarrhalis, 91.7% for Haemophilus influenzae, 88.6% for Haemophilus parainfluenzae, 96.7% for Mycoplasma pneumoniae, 93.1% for Legionella pneumophila, and 100% for Chlamydia pneumoniae. There was little correlation between MICs and outcomes, with a high proportion of favorable outcomes observed across all delafloxacin baseline MIC values. Delafloxacin may be considered a treatment option as monotherapy for CAP in adults, where broad-spectrum coverage including MRSA activity is desirable.

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Section: Discussionsupporting

confidence: 75%

Efficacy of Delafloxacin versus Moxifloxacin against Bacterial Respiratory Pathogens in Adults with Community-Acquired Bacterial Pneumonia (CABP): Microbiology Results from the Delafloxacin Phase 3 CABP Trial

McCurdy

Keedy

Lawrence

et al. 2020

Antimicrob Agents Chemother

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Emergence of multidrug resistance among Haemophilus parainfluenzae from respiratory and urogenital samples in Barcelona, Spain

Sierra

González-Díaz

Tubau

et al. 2019

Eur J Clin Microbiol Infect Dis

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Genome-wide analysis of urogenital and respiratory multidrug-resistant Haemophilus parainfluenzae

Sierra

González-Díaz

Carrera-Salinas

et al. 2021

Journal of Antimicrobial Chemotherapy

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Objectives To characterize the mechanisms of antimicrobial resistance and the prevalence of the polysaccharide capsule among urogenital and respiratory Haemophilus parainfluenzae isolates. Methods Antimicrobial susceptibility was tested by microdilution. Fifty-five MDR strains were subjected to WGS and were phylogenetically compared with all the available H. parainfluenzae genomes from the NCBI database. The identification of the capsular bexA gene was performed by PCR in 266 non-MDR strains. Results In 31 of the 42 ampicillin-resistant strains, blaTEM-1 located within Tn3 was identified. β-Lactamase-negative cefuroxime-resistant strains (n = 12) presented PBP3 substitutions. The catS gene (n = 14), the tet(M)-MEGA element (n = 18) and FolA substitutions (I95L and F154V/S) (n = 41) were associated with resistance to chloramphenicol, tetracycline plus macrolides, and co-trimoxazole, respectively. Thirty-seven isolates had a Tn10 harbouring tet(B)/(C)/(D)/(R) genes with (n = 15) or without (n = 22) catA2. Putative transposons (Tn7076–Tn7079), including aminoglycoside and co-trimoxazole resistance genes, were identified in 10 strains (18.2%). These transposons were integrated into three new integrative and conjugative elements (ICEs), which also included the resistance-associated transposons Tn3 and Tn10. The capsular operon was found only in the urogenital isolates (18/154, 11.7%), but no phylogenetic clustering was observed. The capsular operons identified were similar to those of Haemophilus influenzae serotype c and Haemophilus sputorum type 2. Conclusions The identification of ICEs with up to three resistance-associated transposons suggests that these transferable elements play an important role in the acquisition of multidrug resistance in H. parainfluenzae. Moreover, the presence of polysaccharide capsules in some of these urogenital isolates is a cause for concern.

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Molecular Characterization of Fluoroquinolone-ResistantHaemophilus parainfluenzaeClinical Isolates in Spain

Cited by 4 publications

References 16 publications

Efficacy of Delafloxacin versus Moxifloxacin against Bacterial Respiratory Pathogens in Adults with Community-Acquired Bacterial Pneumonia (CABP): Microbiology Results from the Delafloxacin Phase 3 CABP Trial

Efficacy of Delafloxacin versus Moxifloxacin against Bacterial Respiratory Pathogens in Adults with Community-Acquired Bacterial Pneumonia (CABP): Microbiology Results from the Delafloxacin Phase 3 CABP Trial

Emergence of multidrug resistance among Haemophilus parainfluenzae from respiratory and urogenital samples in Barcelona, Spain

Genome-wide analysis of urogenital and respiratory multidrug-resistant Haemophilus parainfluenzae

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