Abstract

In this study, we evaluated the effect of proton pump inhibitors (PPIs) on in vitro antimicrobial activity of tigecycline against several species of clinical pathogens. Clinical non-duplicate isolates of Acinetobacter baumannii, Staphylococcus aureus, Enterococcus faecalis and three species of Enterobacteriaceae (Escherichia coli, Klebsiella pneumonia and Enterobacter cloacae) were collected from a tertiary hospital and their MICs of tigecycline alone and in combination with PPIs (omeprazole, lansoprazole and pantoprazole) were determined. With one randomly selected isolate of each bacterial species, an in vitro time–kill study was performed for the confirmation of the effect of PPIs on tigecycline activity. The MIC changes after PPIs addition correlated with the PPIs concentrations in the test media. Compared with tigecycline alone, the addition of 5 mg/L PPIs could increase the MICs of tigecycline by 0 to 2-fold and the addition of 50 mg/L PPIs could increase the MICs of tigecycline by 4 to >128-fold. The time–kill study confirmed that the addition of PPIs could affect the in vitro activity of tigecycline. Even at low concentration (5 mg/L) of omeprazole and pantoprazole, antagonistic effect could be observed in E. cloacae and E. faecalis strains. We conclude that In vitro activity of tigecycline can be influenced by the presence of PPIs in a concentration-dependent manner.

Highlights

  • [4] Werner et al and Yang and Chua showed that addition of omeprazole to test medium could lead to increased MIC of tigecycline in one E. faecalis strain and one A. baumannii strain respectively. [5,6] Whether these are accidental phenomena or the concomitant use of omeprazole could influence the activity of tigecycline is worthy of further investigation

  • Whether other commonly used proton pump inhibitors (PPIs) in clinical practice such as lansoprazole and pantoprazole could affect the MICs of tigecycline is unknown

  • MIC50 values doubled for E. coli, K. pneumoniae and E. faecalis at pantoprazole concentration of 5 mg/L

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Summary

Introduction

Tigecycline is the first commercially available member of glycylcyclines which are derived from minocycline. [1] It is a bacteriostatic agent with appealing in vitro activity against various multidrug-resistant pathogens such as vancomycin-resistant Enterococcus faecalis and Enterococcus faecium, methicillin-resistant Staphylococcus aureus, Acinetobacter spp., and Gram-negative bacteria producing extended-spectrum beta-lactamases. [2] since tigecycline has been widely prescribed to treat these organisms, resistant strains are increasingly reported around the world. [3] It’s worth noting that Cordina et al reported the emergence of tigecycline-resistant E. faecalis in a patient might be associated with prolonged use of omeprazole. [4] Werner et al and Yang and Chua showed that addition of omeprazole to test medium could lead to increased MIC of tigecycline in one E. faecalis strain and one A. baumannii strain respectively. [5,6] Whether these are accidental phenomena or the concomitant use of omeprazole could influence the activity of tigecycline is worthy of further investigation. [4] Werner et al and Yang and Chua showed that addition of omeprazole to test medium could lead to increased MIC of tigecycline in one E. faecalis strain and one A. baumannii strain respectively.

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Conclusion

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