Epidemiology and evolution of antibiotic resistance of Haemophilus influenzae in children 5 years of age or less in France, 2001–2008: a retrospective database analysis

Abstract

Trends in the evolution of antimicrobial resistance and mechanisms of resistance of Haemophilus influenzae to β-lactam antibiotics in France were assessed through a retrospective database review. The antimicrobial resistance of 2,206 H. influenzae strains from children aged ≤5 years was studied between 2001 and 2008. Strains were isolated from blood or cerebrospinal fluid (n = 170), bronchial secretions (n = 188), middle ear fluid, and nasopharynx or conjunctiva (n = 1,848). A proportion of 95.1 % (n = 2,097) were non-typeable H. influenzae (NTHi). β-lactamase production was identified in 27.5 % of NTHi isolates (all TEM-1), while β-lactamase-negative ampicillin resistance and β-lactamase-negative amoxicillin-clavulanate resistance among NTHi was 16.9 and 6.4 %, respectively. Over time, a statistically significant decrease in β-lactamase-producing strain prevalence (p < 0.0001) and a statistically significant increase in β-lactamase-negative ampicillin-resistant (BLNAR) strains (p < 0.0001) were observed in NTHi isolates from 2001 to 2008. The largest changes coincided with a campaign to reduce antibiotic use in France. An increasing diversity of amino acid substitution patterns was observed, with the emergence of group III/'III-like' patterns linked to high-level resistance. In France, amino acid substitution patterns are increasingly diverse, and strains with high-level antibiotic resistance are emerging. This study highlights the complexity of resistance dynamics within a given country. These results have implications on antibiotic guidelines and illustrate the importance of continued surveillance.

Molecular Epidemiology of Ampicillin-resistant Haemophilus influenzae Causing Acute Otitis Media in Japanese Infants and Young Children

“…4,5,7 In a number of European countries and the US, BLNAR isolates are less common and most strains with PBP3 substitutions are group I or II. 6,22,23,26,27 In contrast, BLNAR isolates in Japan tend to be group III strains that mainly have PBP3 substitutions. 5,28,29 In fact, 88.7% of gBLNAR strains were classified as group III in this study.…”

“…Reduced susceptibility to ampicillin was found in 68.8% of the isolates (26.7% were low-BLNAR, 33.8% were BLNAR, 4.5% were BLPAR and 3.8% were BLPACR), which is similar to the findings of a recent Japanese study performed in pediatric patients by Hoshino et al 8 In Japan, the prevalence of β-lactamase-producing isolates is lower and that of BLNAR isolates is higher compared with other countries because the percentage of β-lactamase-positive/BLNAR (including low-BLNAR) isolates in the US, France and Korea was reported to be 28.3/0.7, 27.3/16.9 and 52.4/6.1 %, respectively. [22][23][24] This study showed that amino acid substitutions of PBP3 were the most prevalent mechanism of ampicillin resistance for H. influenzae. According to the PCR-based genotyping of H. influenzae demonstrated that all of the BLNAR strains had amino acid substitutions related to ampicillin resistance (gBLNAR).…”

Adhesin genes and serum resistance in Haemophilus influenzae type f isolates

“…An obvious limitation of this method is the inability to detect b-lactamase-negative ampicillin-resistant (BLNAR) isolates encoding altered penicillin-binding proteins through mutation in the ftsI gene conferring resistance (Ubukata et al, 2001). A review of the literature failed to find reports of BLNAR isolates among Hif isolates, and the BLNAR phenotype is rare in North America in general, but evidence does suggest that, in areas of Europe and Asia, there is increasing prevalence of BLNAR isolates among non-typable and serotype b isolates, suggesting that future studies on antimicrobial susceptibility patterns should include methods to capture these strains as well (Hasegawa et al, 2006;Dabernat & Delmas, 2012).…”

Multilocus sequence typing and ftsI sequencing: a powerful tool for surveillance of penicillin-binding protein 3-mediated beta-lactam resistance in nontypeable Haemophilus influenzae

“…Isolates with high-level resistance (high-rPBP3) are a major clinical problem in Japan and South Korea [15-17] whereas low-level resistant (low-rPBP3) isolates so far predominate in the rest of the world [4,11,12,14,18-21]. Group II isolates with a characteristic substitution pattern, PBP3 type A (D350N, M377I, A502V, N526K, V547I and N569S) [11], and compatible patterns (identical to PBP3 type A as far as comparison is possible) are particularly common [3,4,9,11,12,16,18,20],[22-25].…”