Pharmacodynamics of tigecycline alone and in combination with colistin against clinical isolates of multidrug-resistant Acinetobacter baumannii in an in vitro pharmacodynamic model

Cai, Xuejiu; Yang, Zhen; Dai, Jianqiang; Chen, Kun; Zhang, Liangda; Ni, Wentao; Wei, Chuanqi; Cui, Jiayue

doi:10.1016/j.ijantimicag.2017.01.007

Cited by 30 publications

(21 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Consequently, there was a compelling reason to use colistin and tigecycline in combination. Colistin and tigecycline combination therapy against CRE infection had varying outcomes from synergy to indifference (Bercot et al, 2011;Karaoglan et al, 2013;Rao et al, 2016;Cai et al, 2017;Ku et al, 2017). In this study, combination of clinically achievable concentration of colistin and tigecycline produced a synergistic activity in vitro against E. coli harboring bla NDM-5 and mcr-1, resulting in a >4.0-log 10 cfu/mL reduction by 48 h. An additional in vivo synergistic effect was indeed observed in the murine thigh model, at both low and high inoculums.…”

Section: Discussionsupporting

confidence: 51%

“…Data from previous case reports also showed beneficial activity of tigecycline and colistin combination therapy against K. pneumoniae bacteremia (Cobo et al, 2008). Interestingly, the higher dose of tigecycline has been shown to be associated with better synergistic outcomes against multidrug-resistant CRE, compared with the conventional dosing regimen (De Pascale et al, 2014;Cai et al, 2017). In contrast, a potential trend toward antagonism was observed at lower tigecycline concentrations (Albur et al, 2012).…”

Section: Discussionmentioning

confidence: 87%

“…The clinical impact of infections due to colistin-resistant NDM-5-producing E. coli is currently unknown, but our findings provide an alternative approach to combat such resistant strains. In support of this view, a recent report indicated that colistin and tigecycline combination was able to prevent the emergence of high-level resistance to these antibiotics (Cai et al, 2017).…”

Section: Discussionmentioning

confidence: 90%

See 2 more Smart Citations

Colistin Combined With Tigecycline: A Promising Alternative Strategy to Combat Escherichia coli Harboring blaNDM–5 and mcr-1

et al. 2020

View full text Add to dashboard Cite

Infections due to carbapenem-resistant NDM-producing Escherichia coli represent a major therapeutic challenge, especially in situations of pre-existing colistin resistance. The aim of this study was to investigate combinatorial pharmacodynamics of colistin and tigecycline against E. coli harboring bla NDM-5 and mcr-1, with possible mechanisms explored as well. Colistin disrupted the bacterial outer-membrane and facilitated tigecycline uptake largely independent of mcr-1 expression, which allowed a potentiation of the tigecycline-colistin combination. A concentration-dependent decrease in colistin MIC and EC 50 was observed with increasing tigecycline levels. Clinically relevant concentrations of colistin and tigecycline combination significantly decreased bacterial density of colistin-resistant E. coli by 3.9 to 6.1-log 10 cfu/mL over 48 h at both inoculums of 10 6 and 10 8 cfu/mL, and were more active than each drug alone (P < 0.01). Importantly, colistin and tigecycline combination therapy was efficacious in the murine thigh infection model at clinically relevant doses, resulting in >2.0log 10 cfu/thigh reduction in bacterial density compared to each monotherapy. These data suggest that the use of colistin and tigecycline combination can provide a therapeutic alternative for infection caused by multidrug-resistant E. coli that harbored both bla NDM-5 and mcr-1.

show abstract

Section: Discussionsupporting

confidence: 51%

Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 90%

See 1 more Smart Citation

Colistin Combined With Tigecycline: A Promising Alternative Strategy to Combat Escherichia coli Harboring blaNDM–5 and mcr-1

et al. 2020

View full text Add to dashboard Cite

show abstract

“…As the MSWs of one antimicrobial agent can be narrowed to some extent by combining with another whether it is synergistic or not, many combinations had enough potential to prevent resistance 14 , 17 , 25 , 28 , and which mainly depended on their dose administrated and the change of their MSWs in a combination. Even, these could partly interpret why the susceptibility of one antimicrobial agent might be enhanced by another in an antagonistic combination 29 .…”

Section: Discussionmentioning

confidence: 99%

Synergistic combination of two antimicrobial agents closing each other’s mutant selection windows to prevent antimicrobial resistance

Yuan

et al. 2018

Sci Rep

116

196

View full text Add to dashboard Cite

Antimicrobial resistance seriously threatened human health. Combination therapy is generally an effective strategy to fight resistance, while some data on its effects are conflicting. To explore the reasons, the fractional inhibitory concentration indexes (FICIs) of three designed combinations against methicillin-resistant Staphylococcus aureus (MRSA) were determined using checkerboard method, and their minimal concentrations inhibiting colony formation by 99% (MIC99%s) and mutant prevention concentrations (MPCs) alone or in combinations including different proportions were first determined using agar plates. The results indicated that different proportions of a combination had presented different MPCs and mutant selection window (MSWs), and also showed that the smaller the FICIs of two agents in combinations were, the more probable their MSWs were to close each other. As two agents of a combination had different pharmacokinetic characters, the ratios of two agents in blood and infectious sites were likely different even though a specific proportion was administrated, which would lead to different effects preventing resistance. Thereby, these experimental results theoretically indicated that synergistic combination closing each other’s MSWs had a great potency to prevent resistance according to the hypotheses of MSW and MPC, and deduced that in vivo synergistic validity of a combination was likely a key to prevent resistance. Moreover, a synergistic combination of roxithromycin/doxycycline with the FICIs of 0.26–0.50 and 0.28–0.38 respectively against MRSA 01 and 02 was obtained, and the MSWs of these two agents could be simultaneously closed each other in a certain range of proportions, but for others. Meanwhile, its effect preventing resistance needs to be further verified.

show abstract

“…Our study demonstrated that the number of planktonic and biofilm cells in clinical isolates of MDRA were significantly decreased by MIN and TGC at sub-MICs in a dose-dependent manner in contrast to the treatment of CST and PMB at sub-MICs, indicating that both bacterial growth and biofilm formation are inhibited in the presence of MIN and TGC at sub-MICs. Previous studies suggest that a combination of TGC with CST, LVX, amikacin, and IPM may be an effective therapy to synergistically prevent the emergence of resistance during treatment of MDRA infections [ 37 , 38 ]. Presumably, although the treatment of polymyxins or LVX alone can induce biofilm formation and confer bacteria with resistance against antibiotics ([ 25 ], in this study), the combination of TGC with polymyxins or LVX shows more favorable therapeutic outcomes against MDRA infections.…”

Section: Discussionmentioning

confidence: 99%

Sub-minimum inhibitory concentrations of colistin and polymyxin B promote Acinetobacter baumannii biofilm formation

et al. 2018

View full text Add to dashboard Cite

We investigated the numbers of planktonic and biofilm cells and the expression levels of genes encoding efflux pumps and biofilm-related proteins in 10 clinical isolates of multi-drug resistant Acinetobacter baumannii (MDRA) as well as in its standard strain ATCC 19606 in the presence of colistin (CST), polymyxin B (PMB), minomycin (MIN), and tigecycline (TGC) at their respective sub-MICs. The number of planktonic and biofilm cells of ATCC 19606 decreased in the presence of all aforementioned antibiotics in a dose-dependent manner. Cell number also decreased in two representative MDRA strains, R2 and R3, in the presence of MIN and TGC in a dose-dependent manner. In contrast, the number of biofilm cells in these two strains increased in the presence of CST, while they increased significantly in the presence of PMB in R2 only. Pearson correlation analysis revealed that the number of biofilm cells was positively and significantly correlated with the mRNA levels of genes encoding efflux pumps (adeB and adeG) and autoinducer synthase (abaI) in strain R2 and adeB, adeG, adeJ, poly-acetyl-glucosamine-porin (pgaA), and abaI in strain R3 in the presence of CST. It was positively and significantly correlated with the mRNA levels of genes encoding adeB in strain R2 and an outer membrane protein A (ompA) and biofilm-associated protein (bap) in strain R3 in the presence of PMB. These results provide valuable insights into the biofilm formation potency of clinical isolates of MDRA that depends on efflux pumps and biofilm-related genes and its regulation by antibiotics.

show abstract

Pharmacodynamics of tigecycline alone and in combination with colistin against clinical isolates of multidrug-resistant Acinetobacter baumannii in an in vitro pharmacodynamic model

Cited by 30 publications

References 33 publications

Colistin Combined With Tigecycline: A Promising Alternative Strategy to Combat Escherichia coli Harboring blaNDM–5 and mcr-1

Colistin Combined With Tigecycline: A Promising Alternative Strategy to Combat Escherichia coli Harboring blaNDM–5 and mcr-1

Synergistic combination of two antimicrobial agents closing each other’s mutant selection windows to prevent antimicrobial resistance

Sub-minimum inhibitory concentrations of colistin and polymyxin B promote Acinetobacter baumannii biofilm formation

Contact Info

Product

Resources

About