title: Ampicillin resistance of invasive Haemophilus influenzae isolates in Germany 2009-2012.
abstract: In this retrospective study covering a four-year observation period (2009-2012) the prevalence of aminopenicillin resistance of invasive Haemophilus influenzae (Hi) in Germany was analyzed. The main resistance mechanism against aminopenicillins is conferred by β-lactamase production, which can be inhibited by clavulanate or sulbactam. Apart from that, β-lactamase negative ampicillin resistance (BLNAR) has been reported due to mutations in the penicillin-binding protein PBP3. The prevalence of BLNAR varies considerably in different countries. Representative data from Germany have not been reported. We analyzed 704 culture positive cases with bacteraemia or detection of Hi in cerebrospinal fluid; 82 isolates (11.6%) were phenotypically resistant to ampicillin. Among these isolates, 65 (79.3%) showed β-lactamase production, and 17 isolates (20.7%) were phenotypic BLNAR Hi. The proportion of ampicillin resistant isolates remained stable over the observation period. Analysis of the PBP3 sequences of 133 isolates with different susceptibility phenotypes including susceptible, BLNAR, and β-lactamase positive isolates, revealed a high genetic diversity. Previously described PBP3 mutations were associated to elevated MIC values, albeit not exclusively, since few highly susceptible strains were found to be positive for the mutations. Furthermore, since ampicillin susceptible strains with elevated MIC values frequently harboured these mutations, prediction of the resistance phenotype using ftsI sequencing appears to be impossible.
authors: Institute for Hygiene and Microbiology, National Reference Centre for Meningococci and Haemophilus influenzae, University of Würzburg, Josef-Schneider-Str. 2 (E1), 97080 Würzburg, Germany. Electronic address: ttlam@hygiene.uni-wuerzburg.de.
authors: Thiên-Trí
authors: TT
authors: Lâm
authors: Institute for Hygiene and Microbiology, National Reference Centre for Meningococci and Haemophilus influenzae, University of Würzburg, Josef-Schneider-Str. 2 (E1), 97080 Würzburg, Germany.
authors: Heike
authors: H
authors: Claus
authors: Institute for Hygiene and Microbiology, National Reference Centre for Meningococci and Haemophilus influenzae, University of Würzburg, Josef-Schneider-Str. 2 (E1), 97080 Würzburg, Germany.
authors: Johannes
authors: J
authors: Elias
authors: Institute for Hygiene and Microbiology, National Reference Centre for Meningococci and Haemophilus influenzae, University of Würzburg, Josef-Schneider-Str. 2 (E1), 97080 Würzburg, Germany.
authors: Matthias
authors: M
authors: Frosch
authors: Institute for Hygiene and Microbiology, National Reference Centre for Meningococci and Haemophilus influenzae, University of Würzburg, Josef-Schneider-Str. 2 (E1), 97080 Würzburg, Germany.
authors: Ulrich
authors: U
authors: Vogel
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000667:Ampicillin / Q000494:pharmacology*; D000668:Ampicillin Resistance; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D016470:Bacteremia / Q000453:epidemiology / Q000382:microbiology; D002648:Child; D002675:Child, Preschool; D005260:Female; D005838:Genotype; D005858:Germany / Q000453:epidemiology; D006192:Haemophilus Infections / Q000453:epidemiology / Q000382:microbiology*; D006193:Haemophilus influenzae / Q000187:drug effects* / Q000302:isolation & purification; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D016920:Meningitis, Bacterial / Q000453:epidemiology / Q000382:microbiology; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D046915:Penicillin-Binding Proteins / Q000235:genetics; D015995:Prevalence; D012189:Retrospective Studies; D055815:Young Adult; D001618:beta-Lactamases / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D046915:Penicillin-Binding Proteins; D000667:Ampicillin; D001618:beta-Lactamases
keywords: BLNAR; Beta-lactamase; Epidemiology; Invasive infection; Laboratory surveillance; ftsI