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. 2024 Sep 24;9(2):194-204.
doi: 10.20411/pai.v9i2.711. eCollection 2024.

Effect of Ceftaroline, Ceftazidime/Avibactam, Ceftolozane/Tazobactam, and Meropenem/Vaborbactam on Establishment of Colonization by Vancomycin-Resistant Enterococci and Klebsiella pneumoniae in Mice

Bryan S Hausman  1   2 , Samir Memic  2 , Jennifer L Cadnum  2 , Elizabeth G Zink  3 , Brigid M Wilson  1   3 , Curtis J Donskey  1   3
Affiliations

Effect of Ceftaroline, Ceftazidime/Avibactam, Ceftolozane/Tazobactam, and Meropenem/Vaborbactam on Establishment of Colonization by Vancomycin-Resistant Enterococci and Klebsiella pneumoniae in Mice

Bryan S Hausman et al. Pathog Immun. .

Abstract

Background: The potential for promotion of intestinal colonization with healthcare-associated pathogens by new antibiotics used to treat infections due to multidrug-resistant Gram-negative bacilli is unclear.

Methods: Mice treated for 3 days with daily subcutaneous phosphate-buffered saline (control), ceftazidime/avibactam, ceftolozane/tazobactam, ceftaroline, and meropenem/vaborbactam were challenged with 10,000 colony-forming units (CFU) of vancomycin-resistant Enterococcus (VRE) resistant to each of the antibioics or carbapenemase-producing Klebsiella pneumoniae 1 day after the final treatment dose. The concentrations of VRE or K. pneumoniae in stool were measured on days 1, 3, 6, and 15 after challenge.

Results: Control mice had transient low levels of VRE or K. pneumoniae (<3 log10 CFU/g) detected in stool with negative cultures on days 6 and 15 after challenge. In comparison to control mice, each of the antibiotics promoted establishment of high-density colonization with VRE (mean concentration, >8 log10 CFU/g of stool on day 1 after challenge) that persisted at >4 log10 CFU/g of stool through day 15 (P<0.01). In comparison to control mice, meropenem/vaborbactam and ceftaroline promoted high-density colonization with K. pneumoniae (peak concentration, >8 log10 CFU/g of stool) (P<0.01), ceftolozane/tazobactam promoted colonization to a lesser degree (peak concentration, >5 log10 CFU/g of stool), and ceftazidime/avibactam did not promote colonization (P>0.05).

Conclusions: Our results suggest that several beta-lactam antibiotics recently developed for treatment of infections with resistant Gram-negative bacilli have the potential to promote colonization by healthcare-associated pathogens. Additional studies are needed to examine the impact of these agents in patients.

Keywords: ceftaroline; ceftazidime/avibactam; ceftolozane/tazobactam; colonization resistance; meropenem/vaborbactam; vancomycin-resistant enterococci.

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Conflict of interest statement

The authors declare that no competing interests exist.

Figures

Figure 1.
Figure 1.
Mean +SE concentrations of vancomycin-resistant enterococci (VRE) (A) and Klebsiella pneumoniae VA367 (B) in stool of mice after orogastric gavage of 10,000 colony-forming units (CFU) of the test organisms 1 day after the final of 3 daily antibiotic doses. Error bars show the standard error.
Figure 2.
Figure 2.
Concentration (mg/kg) of antibiotics in stool of mice at 4, 8, and 24 hours after the final of 3 daily antibiotic doses. N.D., not detected.
See this image and copyright information in PMC

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