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Amikacin for the treatment of carbapenem-resistant Klebsiella pneumoniae infections: clinical efficacy and toxicity

  • Clinical Microbiology - Research Paper
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Abstract

Infections by carbapenem-resistant Klebsiella pneumoniae (CRKp) are an increasing global threat with limited therapeutic options. Our objective was to evaluate clinical and microbiological outcomes of patients treated with amikacin for CRKp infections. We did a retrospective cohort of patients > 18 years old, with CRKp infections treated with amikacin in two tertiary care hospitals in Porto Alegre, Brazil. The impact of clinical factors, antibiotic treatment, and amikacin minimum inhibitory concentration (MIC) on patients’ 30-day mortality was assessed. Microbiological clearance and nephrotoxicity (assessed by RIFLE score) were evaluated as secondary outcomes. A Cox regression analysis was done for mortality. We included 84 patients for analysis. Twenty-nine (34.5%) patients died in 30 days. Amikacin MIC values ranged from 0.125 to 8 μg/mL and did not influence on mortality, regardless of the prescribed dose of this antibiotic (P = 0.24). Bacterial clearance occurred in 17 (58.6%) of 29 patients who collected subsequent cultures. Two (16.6%) of the 12 persistently positive cultures changed the amikacin susceptibility profile from susceptible to intermediate. Twenty-nine (37.2%) patients developed acute kidney injury (AKI): risk 13, injury 11, and failure 5. Risk factors for AKI were higher baseline eGFR (P < 0.01) and combination therapy with colistin (P = 0.02). Comparing patients who received combination with colistin vs polymyxin B, AKI occurred in 60.0% vs 20.6%, respectively, P < 0.01. Fifteen of the 16 (16.6%) patients who developed renal injury or failure were receiving colistin. In conclusion, amikacin was an effective treatment for CRKp infections. Within susceptible range, amikacin MIC values did not influence on clinical outcomes. Combination therapy of amikacin and colistin was highly nephrotoxic and should be used with caution.

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The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

This study was funded by Fundo de Incentivo à Pesquisa (FIPE) do Hospital de Clínicas de Porto Alegre. APZ is a research fellow of the National Council for Scientific and Technological Development (CNPq), Ministry of Science and Technology, Brazil.

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Authors and Affiliations

  1. Medical Sciences Post-Graduation Program, Universidade Federal Do Rio Grande Do Sul, Porto Alegre, Brazil

    Diógenes Rodrigues, Alexandre P. Zavascki & Maria Helena Rigatto

  2. Infectious Diseases Service, Hospital São Lucas da PUCRS, Porto Alegre, Brazil

    Maria Helena Rigatto

  3. Medical School, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil

    Douglas Mathos & Alexandre P. Zavascki

  4. Infectious Diseases Service, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil

    Alexandre P. Zavascki & Maria Helena Rigatto

  5. Pontifícia Universidade Católica Do Rio Grande Do Sul Medical School, Porto Alegre, Brazil

    Giulia Soska Baldissera, Aline Sartori & Maria Helena Rigatto

Authors
  1. Diógenes Rodrigues
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  2. Giulia Soska Baldissera
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  3. Douglas Mathos
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  4. Aline Sartori
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  5. Alexandre P. Zavascki
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  6. Maria Helena Rigatto
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Contributions

Diógenes Rodrigues performed research, analyzed data, and wrote the paper; Giulia Soska Baldissera, Douglas Mathos, and Aline Sartori collected and analyzed data; Alexandre P. Zavascki analyzed data and wrote the paper; Maria Helena Rigatto conceived the study, performed research, analyzed data, and wrote the paper.

Corresponding author

Correspondence to Maria Helena Rigatto.

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Ethics approval

The project was carried out after its approval by the institution’s Research Ethics Committee number 2.687.149 and 2.476.428.

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As this was a retrospective study, the ethics committee waived the need for informed consent.

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All authors agree on the publication of this manuscript.

Competing interests

Alexandre P Zavascki receives research grants from Pfizer. The other authors declare no competing interests.

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Cite this article

Rodrigues, D., Baldissera, G.S., Mathos, D. et al. Amikacin for the treatment of carbapenem-resistant Klebsiella pneumoniae infections: clinical efficacy and toxicity. Braz J Microbiol 52, 1913–1919 (2021). https://doi.org/10.1007/s42770-021-00551-x

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  • DOI: https://doi.org/10.1007/s42770-021-00551-x

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