Diversity of ampicillin-resistance genes in Haemophilus influenzae in Japan and the United States.

Abstract

Clinical isolates of Haemophilus influenzae from Japan (n = 296) and the United States (n = 100) were tested by the microdilution method for susceptibility in vitro to 10 beta-lactam antibiotics and molecular mechanisms of beta-lactam resistance. For all isolates, PCR was used to identify six elements, including beta-lactamase-producing ampicillin (AMP)-resistance (BLPAR) and beta-lactamase-nonproducing AMP-resistance (BLNAR) genes as follows: (1) TEM-1 type beta-lactamase gene, (2) ROB-1 type beta-lactamase gene, (3) part of normal ftsI gene encoding PBP3, which is involved in septal peptidoglycan synthesis, (4) a portion of the ftsI gene possessing some amino acid substitutions commonly detected in BLNAR strains, (5) p6 gene encoding P6 membrane proteins specific to H. influenzae, and (6) serotype b capsule gene. In Japanese and U.S. isolates, respective prevalences of each resistance class in Japan and the United States were 55.1% and 46% for beta-lactamase-nonproducing, AMP-susceptible (BLNAS); 3.0% and 26% for the TEM-1 type beta-lactamase gene; 0% and 10% for the ROB-1 type; 26.4% and 13% for low-BLNAR with a low degree of AMP resistance; and 13.2% and 0% for BLNAR strains. A few remaining isolates were beta-lactamase-producing strains with a mutation in the ftsI gene. MICs of all beta-lactam agents against low-BLNAR strains were 2-8 times higher than against BLNAS. MICs of cephalosporin antibiotics against BLNAR strains were 16-32 times higher than against BLNAS. The rank order of beta-lactam MIC90 values against BLNAR strains was piperacillin = ceftriaxone = cefditoren (0.25 microg/ml), meropenem (0.5), cefotaxime (1), AMP = cefpodoxime (8), cefdinir (16), amoxicillin (16), and cefaclor (64). Serotype b isolates were few in both countries (2.4% in Japan, 3% in the United States). Differences in proportions of respective AMP-resistant genes in H. influenzae isolates between the two countries might reflect differences in antibiotic agents ordinarily given to outpatients with community-acquired bacterial infections.

• Authors: Keiko Hasegawa, Kentarou Yamamoto, Naoko Chiba, Reiko Kobayashi, Kensuke Nagai, Michael R Jacobs, Peter C Appelbaum, Keisuke Sunakawa, Kimiko Ubukata
• Journal: Microbial drug resistance (Larchmont, N.Y.) (Microb Drug Resist) Vol. 9 Issue 1 Pg. 39-46 ( 2003) ISSN: 1076-6294 [Print] United States
• PMID: 12705682 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Bacterial Agents
• beta-Lactams
• beta-Lactamases

Topics

• Ampicillin Resistance (genetics)
• Anti-Bacterial Agents (pharmacology)
• DNA Fingerprinting
• Haemophilus influenzae (drug effects, genetics, isolation & purification)
• Japan
• Microbial Sensitivity Tests
• Polymerase Chain Reaction
• United States
• beta-Lactamases (biosynthesis, genetics)
• beta-Lactams