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Assessment of the in vitro activity of azithromycin niosomes alone and in combination with levofloxacin on extensively drug-resistant Klebsiella pneumoniae clinical isolates

  • Clinical Microbiology - Research Paper
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Abstract

Background and aim

Extensively drug-resistant (XDR) Klebsiella pneumoniae represent a major threat in intensive care units. The aim of the current study was to formulate a niosomal form of azithromycin (AZM) and to evaluate its in vitro effect on XDR K. pneumoniae as a single agent or in combination with levofloxacin.

Material and methods

Forty XDR K. pneumoniae isolates (23 colistin-sensitive and 17 colistin-resistant) were included in the study. Formulation and characterization of AZM niosomes were performed. The in vitro effect of AZM solution/niosomes alone and in combination (with levofloxacin) was investigated using the checkerboard assay, confirmed with time-kill assay and post-antibiotic effect (PAE).

Results

The AZM niosome mean minimal inhibitory concentration (MIC) (187.4 ± 209.1 μg/mL) was significantly lower than that of the AZM solution (342.5 ± 343.4 μg/mL). AZM niosomes/levofloxacin revealed a 40% synergistic effect compared to 20% with AZM solution/levofloxacin. No antagonistic effect was detected. The mean MIC values of both AZM niosomes and AZM solution were lower in the colistin-resistant group than in the colistin-sensitive group. The mean PAE time of AZM niosomes (2.3 ± 1.09 h) was statistically significantly longer than that of the AZM solution (1.37 ± 0.5 h) (p = 0.023).

Conclusion

AZM niosomes were proved to be more effective than AZM solution against XDR K. pneumoniae, even colistin-resistant isolates.

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Authors and Affiliations

  1. Medical Microbiology and Immunology Department, Faculty of Medicine, Alexandria University, Khartoum Square, Azarita, Alexandria, 21512, Egypt

    Hoda Mohamed Owais, Manal Mohammad Baddour, Hala Abd El-Raouf El-Metwally & Marwa Ahmed Meheissen

  2. Pharmaceutics Department, Faculty of Pharmacy, Alexandria University, Alexandria, 21512, Egypt

    Heba Soliman Barakat

  3. Alexandria University Hospitals, Alexandria University, Alexandria, 21512, Egypt

    Nour Sherif Ammar

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Contributions

MMB and HAE were responsible for the idea, study design, and revision of the manuscript. HSB was responsible for the formulation and characterization of niosomes. NSA was responsible for the data collection. HAO was responsible for the laboratory work, data analysis, and drafting of the manuscript. MAM was responsible for the idea, study design, laboratory work supervision, data analysis and interpretation, and writing of the manuscript. All authors contributed to the interpretation of data and approved the final manuscript.

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Correspondence to Marwa Ahmed Meheissen.

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Owais, H.M., Baddour, M.M., El-Metwally, H.A.ER. et al. Assessment of the in vitro activity of azithromycin niosomes alone and in combination with levofloxacin on extensively drug-resistant Klebsiella pneumoniae clinical isolates. Braz J Microbiol 52, 597–606 (2021). https://doi.org/10.1007/s42770-021-00433-2

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