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Cross-Resistance and the Mechanisms of Cephalosporin-Resistant Bacteria in Urinary Tract Infections Isolated in Indonesia.

Abstract
Urinary tract infection (UTI) by antibiotic-resistant strains has become increasingly problematic, with trends that differ from country to country. This study examined cross-resistance and the mechanisms of cephalosporin resistance in UTI-causative bacteria isolated in Indonesia. Antibiotic susceptibility tests based on Clinical Laboratory Standards Institute (CLSI) standards were done for UTI-causative strains (n = 50) isolated from patients in Indonesia in 2015-2016 and showed resistance against the third-generation cephalosporin. Mechanistic studies were carried out to confirm the presence of extended-spectrum β-lactamase (ESBL) genes, carbapenemase-related genes, the fosA3 gene related to fosfomycin resistance, and mutations of quinolone-resistance-related genes. Isolated UTI-causative bacteria included Escherichia coli (64.0%), Pseudomonas aeruginosa (16.0%), Klebsiella pneumoniae (10.0%), and others (10.0%). These strains showed 96.0% susceptibility to amikacin, 76.0% to fosfomycin, 90.0% to imipenem, 28.0% to levofloxacin, 92.0% to meropenem, and 74.0% to tazobactam/piperacillin. ESBL was produced by 68.0% of these strains. Mechanistic studies found no strains with carbapenemase genes but 6.0% of strains had the fosA3 gene. Seventy-two % of the strains had mutations in the gyrA gene and 74.0% in the parC gene. Most E. coli strains (87.5%) had Ser-83 → Leu and Asp-87 → Asn in gyrA and 93.8% of E. coli had Ser-80 → Ile in parC. There were significant correlations among mutations in gyrA and parC, and fosA3 gene detection (P < 0.05), respectively. To our knowledge, this is the first mechanistic study of antibiotic-cross-resistant UTI-causative bacteria in Indonesia. Further studies with a longer period of observation are necessary, especially for changes in carbapenem resistance without carbapenemase-related genes.
AuthorsAya Ishii, Katsumi Shigemura, Koichi Kitagawa, Mizuki Harada, Yuki Kan, Fuka Hayashi, Kayo Osawa, K Kuntaman, Toshiro Shirakawa, Masato Fujisawa
JournalCurrent microbiology (Curr Microbiol) Vol. 78 Issue 5 Pg. 1771-1777 (May 2021) ISSN: 1432-0991 [Electronic] United States
PMID33713209 (Publication Type: Journal Article)
Chemical References
  • Anti-Bacterial Agents
  • Cephalosporins
  • beta-Lactamases
Topics
  • Anti-Bacterial Agents (pharmacology, therapeutic use)
  • Cephalosporins (pharmacology)
  • Escherichia coli (genetics)
  • Escherichia coli Infections (drug therapy)
  • Humans
  • Indonesia
  • Microbial Sensitivity Tests
  • Urinary Tract Infections
  • beta-Lactamases (genetics)

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