Clonal spread of β-lactamase-producing amoxicillin–clavulanate-resistant (BLPACR) strains of non-typeable Haemophilus influenzae among young children attending a day care in Japan

Abstract

Objective: Resistant strains of non-typeable Haemophilus influenzae (NTHi) are one of the principal causes of recurrent acute otitis media (otitis prone), rhinosinusitis, and pneumonia in young children. β-lactamase-nonproducing ampicillin-resistant (BLNAR) strains are particularly common in Japan, and β-lactamase-producing amoxicillin-clavulanate resistant (BLPACR) strains are now emerging. We investigated the nasopharyngeal carriage status of these resistant strains among children attending a same day care center during a 10-year period. Methods:From 1999 to 2008, we obtained nasopharyngeal swab specimens from young children attending a same day care center and examined the incidence of resistant strains of NTHi.Antimicrobial resistance of NTHi was identified based on PCR analysis of mutation of the penicillin binding protein (PBP) genes. Pulsed-field gel electrophoresis (PFGE) was performed to examine the clonal relationship of each resistant strain. Results:The prevalence of resistant strains of NTHi among the children attending this day care has significantly increased during the past 10 years and most of this day care children recently have resistant strains with PBP gene mutations in their nasopharynx. Genetically BLPACR (gBLPACR) strains have rapidly increased since 2007 and PFGE analysis demonstrated that all gBLPACR were clonally identical. This is the first report of apparent clonal dissemination of gBLPACR strains of NTHi occurring in a certain environment such as day care. Conclusions:The rapidly increasing prevalence of resistant strains, in particular gBLPACR, in this day care center may predict a high incidence of these resistant bacteria from clinical isolates in the near future and potential serious medical problems worldwide.

Oropharyngeal Colonization by NontypeableHaemophilus influenzaeAmong Healthy Children Attending Day Care Centers

“…The prevalence of H. influenzae was similar or lower than other colonization studies conducted on worldwide centers. 2,7,10,13,14,19,20 Recently, Carvalho et al 7 reported NTHi colonization in 32% of the children from DCCs in a large Brazilian city with a frequent antibiotic use (> 80%) within the studied population, 7 while studies in the United States showed a carriage rate of 64%. 2,10 Antimicrobial susceptibility was high probably due to the low range of antimicrobial agents given to treat infections in children.…”

“…16 Although NTHi is considered less virulent than Hib, it can be responsible for severe diseases, especially among children with previous comorbidities. 11 Several studies have been performed to establish the H. influenzae carriage rate after vaccine introduction, 2,7,10,[12][13][14][19][20][21] although to our knowledge, no studies have been reported from Spain. Longitudinal studies performed on one or two selected DCCs give information about the dynamics of colonization, but fail to give an overall view of the situation in similar centers of the same geographical area.…”

Vaccines for Nontypeable Haemophilus influenzae: the Future Is Now

“…Otitis media is the most common reason for children in industrialized countries to receive antimicrobial therapy, and children play an important role in transmission of resistant isolates into the community (40). Infections in COPD are one of the most common indications for antimicrobial therapy in adults.…”

Documento de consenso sobre etiología, diagnóstico y tratamiento de la otitis media aguda

“…Sin embargo, en los últimos años, desde la introducción de las vacunas antineumocócicas conjugadas, H. influenzae no tipificable productor de betalactamasas tiene cada vez más relevancia, sobre todo en las OMA recurrentes o persistentes 43 . Además, se calcula que una de cada 8 o 9 otitis producidas por esta bacteria no responde a la amoxicilina 44,45 .…”