Decreased prevalence of Moraxella catarrhalis in addition to Streptococcus pneumoniae in children with upper respiratory tract infection after introduction of conjugated pneumococcal vaccine : a retrospective cohort study

Objectives: To study effects of the introduction of pneumococcal conjugate vaccines (PCV) on the interspecies dynamics of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis in preschool children with respiratory tract infection. Methods: Nasopharyngeal samples from children aged ≤6 years with upper respiratory tract infection (n = 14 473) in South Sweden were analysed during 14 consecutive years, 5 years before and 9 years after PCV introduction. The yearly prevalence was calculated, and multivariate count regressions between prevalence and estimated yearly proportions of vaccinated children were performed. Associations between pneumococcal serotypes and the other pathogens were assessed. Results: When comparing the prevaccine period with the years after introduction, the prevalence of S. pneumoniae decreased by 65.2% (16.4 to 5.7 per 1000 individuals; p < 0.001), whereas M. catarrhalis and H. influenzae decreased by 52.1% (21.5 to 10.3 per 1000 individuals; p < 0.001) and 46.6% (13.6 to 7.3 per 1000 individuals; p < 0.001), respectively. In multivariate negative binomial regressions adjusted for yearly numbers of samples taken, S. pneumoniae and M. catarrhalis were significantly negatively associated with increasing vaccine coverage proportions (adjusted prevalence ratio (aPR) = 0.17; p < 0.001 and aPR = 0.48; p < 0.001, respectively), whereas H. influenzae (aPR = 0.75; p = 0.17) was not. In addition, the proportion of cultures positive for S. pneumoniae as well as M. catarrhalis was significantly lower in the postvaccine period compared to the prevaccine period, while this was not the case for H. influenzae. A significant positive association between certain PCV serotypes and simultaneous growth with M. catarrhalis was observed. Conclusions: After introduction of PCV, the prevalence of M. catarrhalis in addition to S. pneumoniae in children with respiratory tract infection decreased; this was also the case after adjusting for reduced numbers of samples taken. This may partly be attributed to a positive association between PCV serotypes and M. catarrhalis

Ampicillin-resistant Haemophilus influenzae isolates in Geneva: serotype, antimicrobial susceptibility, and β-lactam resistance mechanisms

The purpose of this study was to analyze the molecular mechanisms of ampicillin-resistant Haemophilus influenzae isolated in Geneva, Switzerland. We investigated the association between specific patterns of amino acid substitutions in penicillin-binding protein 3 (with or without β-lactamase production) and β-lactam susceptibility. Another main focus for this study was to compare the accuracy of disk diffusion and Etest methods to detect resistance to ampicillin and amoxicillin/clavulanic acid. The antibiotic susceptibility to β-lactam antibiotics of 124 H. influenzae isolates was determined by disk diffusion and Etest methods, and interpreted by European Committee on Antimicrobial Susceptibility Testing (EUCAST) and Clinical and Laboratory Standards Institute (CLSI) breakpoints. Alterations in PBP3 were investigated by sequencing the ftsI gene. Of the 124 clinical isolates analyzed, ampicillin resistance was found in 36% (45 out of 124). The rate of resistance to amoxicillin/clavulanic acid was 9% and 0.8%, using EUCAST and CLSI breakpoints respectively. For the 78 β-lactamase negative ampicillin-susceptible (BLNAS) isolates for which the Etest method indicated a high degree of susceptibility (MIC ≤ 1 mg/L), the disk diffusion method revealed resistance to ampicillin and amoxicillin/clavulanic acid in 33 cases (42%). Most common amino acid substitutions were Asn526Lys and Val547Ile, followed by Asp569Ser, Ala502Val, Asp350Asn, Met377Ile, Ile449Val, and Arg517His. The patterns observed were classified into six groups (IIa, IIb, IIc, IId, III-like, and miscellaneous). Continued characterization of both invasive and respiratory H. influenzae isolates is necessary in order to observe changes in the microbiology and epidemiology of this pathogen that could lead to clinical failure when treated by empirical antibiotic therapy