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Impact of Antimicrobial Treatment for Acute Otitis Media on Carriage Dynamics of Penicillin-Susceptible and Penicillin-Nonsusceptible Streptococcus pneumoniae.

ABSTRACT: Background:Despite concerns that antimicrobial treatment of prevalent infections may select for drug-resistant bacteria, the effects of antimicrobial treatment on colonization dynamics have not been well quantified. Methods:We measured impacts of antimicrobial treatment on nasopharyngeal carriage of penicillin-susceptible Streptococcus pneumoniae (PSSP) and penicillin-nonsusceptible (PNSP) lineages at the end of treatment and 15, 30, and 60 days after treatment in a previously conducted randomized, double-blinded, placebo-controlled trial of amoxicillin-clavulanate for stringently defined acute otitis media. Results:In intention-to-treat analyses, immediate treatment with amoxicillin-clavulanate reduced PSSP carriage prevalence by 88% (95% confidence interval [CI], 76%-96%) at the end of treatment and by 27% (-3%-49%) after 60 days but did not alter PNSP carriage prevalence. By the end of treatment, 7% of children who carried PSSP at enrollment remained colonized in the amoxicillin-clavulanate arm, compared with 61% of PSSP carriers who received placebo; impacts of amoxicillin-clavulanate persisted at least 60 days after treatment among children who carried PSSP at enrollment. Amoxicillin-clavulanate therapy reduced PSSP acquisition by >80% over 15 days. Among children who carried PNSP at enrollment, no impacts on carriage prevalence of S. pneumoniae, PSSP, or PNSP were evident at follow-up visits. Conclusions:Although the absolute risk of carrying PNSP was unaffected by treatment, antimicrobial therapy conferred a selective impact on colonizing pneumococci by accelerating clearance and delaying acquisition of PSSP.

SUBMITTER: Lewnard JA

PROVIDER: S-EPMC6151080 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Impact of Antimicrobial Treatment for Acute Otitis Media on Carriage Dynamics of Penicillin-Susceptible and Penicillin-Nonsusceptible Streptococcus pneumoniae.

Lewnard Joseph A JA Tähtinen Paula A PA Laine Miia K MK Lindholm Laura L Jalava Jari J Huovinen Pentti P Lipsitch Marc M Ruohola Aino A

The Journal of infectious diseases 20180901 9

<h4>Background</h4>Despite concerns that antimicrobial treatment of prevalent infections may select for drug-resistant bacteria, the effects of antimicrobial treatment on colonization dynamics have not been well quantified.<h4>Methods</h4>We measured impacts of antimicrobial treatment on nasopharyngeal carriage of penicillin-susceptible Streptococcus pneumoniae (PSSP) and penicillin-nonsusceptible (PNSP) lineages at the end of treatment and 15, 30, and 60 days after treatment in a previously con ...[more]

PMID: 29873739

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Project description:Acute otitis media (AOM) is the most common childhood bacterial infectious disease requiring antimicrobial therapy. Most cases of AOM are caused by translocation of Streptococcus pneumoniae or Haemophilus influenzae from the nasopharynx to the middle ear during an upper respiratory tract infection (URI). Ongoing genomic surveillance of these pathogens is important for vaccine design and tracking of emerging variants, as well as for monitoring patterns of antibiotic resistance to inform treatment strategies and stewardship.In this work, we examined the ability of a genomics-based workflow to determine microbiological and clinically relevant information from cultured bacterial isolates obtained from patients with AOM or an URI. We performed whole genome sequencing (WGS) and analysis of 148 bacterial isolates cultured from the nasopharynx (N = 124, 94 AOM and 30 URI) and ear (N = 24, all AOM) of 101 children aged 6-35 months presenting with AOM or an URI. We then performed WGS-based sequence typing and antimicrobial resistance profiling of each strain and compared results to those obtained from traditional microbiological phenotyping.WGS of clinical isolates resulted in 71 S. pneumoniae genomes and 76 H. influenzae genomes. Multilocus sequencing typing (MSLT) identified 33 sequence types for S. pneumoniae and 19 predicted serotypes including the most frequent serotypes 35B and 3. Genome analysis predicted 30% of S. pneumoniae isolates to have complete or intermediate penicillin resistance. AMR predictions for S. pneumoniae isolates had strong agreement with clinical susceptibility testing results for beta-lactam and non beta-lactam antibiotics, with a mean sensitivity of 93% (86-100%) and a mean specificity of 98% (94-100%). MLST identified 29 H. influenzae sequence types. Genome analysis identified beta-lactamase genes in 30% of H. influenzae strains, which was 100% in agreement with clinical beta-lactamase testing. We also identified a divergent highly antibiotic-resistant strain of S. pneumoniae, and found its closest sequenced strains, also isolated from nasopharyngeal samples from over 15 years ago.Ultimately, our work provides the groundwork for clinical WGS-based workflows to aid in detection and analysis of H. influenzae and S. pneumoniae isolates.

Dataset Information

Impact of Antimicrobial Treatment for Acute Otitis Media on Carriage Dynamics of Penicillin-Susceptible and Penicillin-Nonsusceptible Streptococcus pneumoniae.

Publications

Impact of Antimicrobial Treatment for Acute Otitis Media on Carriage Dynamics of Penicillin-Susceptible and Penicillin-Nonsusceptible Streptococcus pneumoniae.

Similar Datasets

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