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

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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.

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Acknowledgements

We thank our collaborator, Dr. Young-min Yang (experiments support and collecting samples). This data was previously published in cross-resistance and the mechanisms of cephalosporine-resistant urinary tract infection (UTI)-causative bacteria isolated in Indonesia. Shigemura K, Kitagawa K, Shirakawa T, Fujisawa M. European Urology Supplements. 2019.Volume 18, Issue 1, Page e546.

Funding

This study was supported by following Grants: Japan Initiative for Global Research Network on Infectious Diseases (J-GRID) from the Ministry of Education, Culture, Sport, Science and Technology in Japan [Grant No. 18fm0108004h0004]; Japan Agency for Medical Research and Development (AMED) [Grant No. JP18fk0108019]; JSPS KAKENHI [Grant No. 18K10045 and 19K09670]; Tahir Professorship from the University of Airlangga, Surabaya, Indonesia; The Institute of Tropical Disease, University of Airlangga, Surabaya, Indonesia; and Indonesia-Japan Collaborative Research Center for Emerging and Re-emerging Infectious Diseases.

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Authors and Affiliations

  1. Department of Public Health, Kobe University Graduate School of Health Sciences, Kobe, Japan

    Aya Ishii, Katsumi Shigemura, Koichi Kitagawa & Toshiro Shirakawa

  2. Department of Urology, Kobe University Graduate School of Medicine, Kobe, Japan

    Katsumi Shigemura & Masato Fujisawa

  3. Department of Infection Control, Kobe University Graduate School of Medicine, Kobe, Japan

    Katsumi Shigemura

  4. Department of Advanced Medical Science, Kobe University Graduate School of Science, Technology and Innovation, Kobe, Japan

    Koichi Kitagawa & Toshiro Shirakawa

  5. Central Laboratory Department, Local Independent Administrative Agency, Rinkuu General Medical Center, Osaka, Japan

    Mizuki Harada

  6. Department of Medical Technology, School of Medicine Faculty of Health Sciences, Kobe University, Kobe, Japan

    Yuki Kan & Fuka Hayashi

  7. Department of Medical Technology, Kobe Tokiwa University, Kobe, Japan

    Kayo Osawa

  8. Department of Microbiology, Faculty of Medicine, Airlangga University, Surabaya, Indonesia

    K. Kuntaman

Authors
  1. Aya Ishii
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  2. Katsumi Shigemura
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  10. Masato Fujisawa
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Contributions

KS, KO and TS contributed to conception and design of the study, project administration, and critical revision for important intellectual content. AI, KK, MH, YK, FH and KK were involved in sample collection, acquisition of data, and laboratory analysis. AI, KS, and KK contributed to writing—original draft, and writing—review and editing. MF was involved in supervision. All authors contributed to analysis and interpretation of data and final approval of the submitted version.

Corresponding author

Correspondence to Katsumi Shigemura.

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We have no conflict of interest to declare.

Research Involving Human Participants

This study was approved by the ethical committee on health research of the Kobe University Graduate School of Health Sciences and Dr. Soetomo’s hospital in Surabaya. All experiments were carried out in compliance with the relevant laws and guidelines in accordance with the ethical standards of the Declaration of Helsinki.

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Written informed consent was obtained from all subjects.

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Ishii, A., Shigemura, K., Kitagawa, K. et al. Cross-Resistance and the Mechanisms of Cephalosporin-Resistant Bacteria in Urinary Tract Infections Isolated in Indonesia. Curr Microbiol 78, 1771–1777 (2021). https://doi.org/10.1007/s00284-021-02415-x

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  • DOI: https://doi.org/10.1007/s00284-021-02415-x

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