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. 2019 Dec;7(23):779.
doi: 10.21037/atm.2019.11.33.

The in vitro activity of polymyxin B and tigecycline alone and combination with other antibiotics against carbapenem-resistant Enterobacter cloacae complex isolates, including high-risk clones

Yongxin Zhao  1   2 , Chunjiang Li  3 , Jisheng Zhang  1   2 , Yanjun Fu  2 , Kewang Hu  2 , Shanshan Su  2   4 , Yong Wang  2 , Huiling Li  2 , Xiaoli Zhang  1   2
Affiliations

The in vitro activity of polymyxin B and tigecycline alone and combination with other antibiotics against carbapenem-resistant Enterobacter cloacae complex isolates, including high-risk clones

Yongxin Zhao et al. Ann Transl Med. 2019 Dec.

Abstract

Background: The emergence of carbapenem-resistant Enterobacteriaceae (CRE) has become a significant problem for global public health. Currently, treatments program is minimal. This study aimed to evaluate the molecular mechanisms of carbapenem-resistant Enterobacter cloacae complex isolates (CREC) infections. Methods: Resistance genes were detected using PCR with specific primers. Multilocus sequence typing (MLST) was also performed. Furthermore, we evaluated the effects of polymyxin B (PMB) and tigecycline (TGC) antibiotics (Abs) alone and in combination with meropenem (MEM), amikacin (AMK), and levofloxacin (LEV) against CREC isolates. The results were then compared with in vitro synergy testing results obtained from time-kill assays (TKAs), and the microdilution checkerboard method.

Results: The synergistic efficiency of PMB + TGC was also evaluated. Abs use clinically achievable concentrations to determine the antibacterial effects of the Ab. Similar sequence type (ST) classifications had a comparably resistant phenotype; PMB-based combination therapy is better than TGC-based combination therapy.

Conclusions: we found that the combination of PMB + AMK is promising for the treatment of AMK-sensitive CREC. The high-risk ST93 carrying the bla KPC-2 gene should be monitored.

Keywords: Enterobacter cloacae complex (ECC); ST93; Synergism; carbapenemases; polymyxin B (PMB); tigecycline (TGC).

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Conflict of interest statement

Conflicts of Interest: The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Genetic resistance determinants in Enterobacter Cloacae complex isolates from Jiamusi, Heilongjiang, China, January 12, 2014–December 31, 2015. The isolates were classified according to the content in resistance determinants by using a binary distance matrix and UPGMA clustering method. Scale bar shows the dissimilarity in resistance gene content. ST, sequence type.
Figure 2
Figure 2
24-hour change in colony count for polymyxin B (PMB); tigecycline (TGC); meropenem (MEM); amikacin (AMK) and levofloxacin (LEV) against CREC isolates. Data are differences of geometric means at time points 0 and 24 h, experiment repeated twice (n=2) PMB or TGC (0.25 and 1 µg/mL); MEM (4 and 16 µg/mL); and AMK (8 and 16 µg/mL) and LEV 6.8 µg/mL. CREC, carbapenem-resistant Enterobacter cloacae.
Figure 3
Figure 3
Time kill curves of polymyxin B and tigecycline combination with meropenem; amikacin and levofloxacin against CREC isolates. Data points are geometric means of replicate experiments (n=2). Antibiotic concentrations were PMB or TGC (0.25 and 1 µg/mL); MEM (4 and 16 µg/mL); and AMK (8 and 16 µg/mL) and LEV 6.8 µg/mL. (A,B,C,D) Represents CREC4; (E,F,G,H) represents CREC5; (I,J,K,L) represents CREC7. The legend of (A) is consistent with (E,I); the legend of (B) is consistent with (F,J); the legend of (C) is consistent with (G,K); The legend of (D) is consistent with (H,L). CREC, carbapenem-resistant Enterobacter cloacae; PMB, polymyxin B; TGC, tigecycline; MEM, meropenem; AMK, amikacin; LEV, levofloxacin.
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