A Systematic Review of Implications, Mechanisms, and Stability of In Vivo Emergent Resistance to Colistin and Tigecycline in <em>Acinetobacter baumannii</em>

Abstract

The potential of A. baumannii for acquired resistance to last resort antibiotics (colistin and tigecycline) during treatment has important clinical implications, especially when dealing with patients failing to improve despite treatment with an active antimicrobial. However, the relevant literature remains scattered. Therefore, a systematic search was conducted in PubMed and Scopus. Several studies reported emergence of resistance to colistin or tigecycline during treatment, in most cases (86%) resulting in persistent or recurrent infections, especially in cases of emergent resistance without fitness cost. Lipopolysaccharide modification in the case of colistin and overexpression of efflux pumps in the case of tigecycline were the main mechanisms of resistance. Emergent colistin resistance is often associated with fitness cost resulting in re-emergence of the fitter and more virulent colistin susceptible strain after cessation of antibiotic pressure. Prospective studies are needed to determine the frequency of emergent resistance during treatment and its impact on patient outcomes.

The prevalence, presentation and outcome of colistin susceptible-only Acinetobacter Baumannii-associated pneumonia in intensive care unit: a multicenter observational study

“…Furthermore, pandrug-resistance (PDR) A. baumannii is another issue worthy to be concerned. PDR A. baumannii has been increasingly reported worldwide 26 , which could be, at least in part, associated with the high prevalence (33%) of colistin heteroresistance 27 and the emergence of colistin resistance during treatment for A. baumannii infection 28 . The treatment options for PDR A. baumannii are limited and undetermined, that were primarily relied on the synergistic combination of antimicrobial agents [29][30][31] .…”

Systematic review and meta-analysis of the proportion and associated mortality of polymicrobial (vs monomicrobial) pulmonary and bloodstream infections by Acinetobacter baumannii complex

“…Therefore, it is possible that a subset of patients with polymicrobial ABC infections may not require antimicrobial coverage of ABC. This has important antimicrobial stewardship implications, especially considering the potential of ABC for in-vivo emergence of resistance during treatment with last resort agents [9,10]. An alternative explanation for the lower mortality in polymicrobial infections, especially relevant to bloodstream infections, is that polymicrobial cultures may be more likely to represent colonization/contamination rather than infection, or may be associated with easier to treat sources of infection (e.g.…”

“…Differentiating infection from colonization has important antimicrobial stewardship implications. Overtreatment due to misclassification of colonization as infection can fuel the emergence of extensively-/pan-drug-resistant A. baumannii [9][10][11][12], for which treatment options are limited [13]. Reducing unnecessary use of last resort antibiotics may allow outcompeting of extensively-/pan-drug-resistant A. baumannii by more susceptible strains [9,12].…”

“…Overtreatment due to misclassification of colonization as infection can fuel the emergence of extensively-/pan-drug-resistant A. baumannii [9][10][11][12], for which treatment options are limited [13]. Reducing unnecessary use of last resort antibiotics may allow outcompeting of extensively-/pan-drug-resistant A. baumannii by more susceptible strains [9,12]. Furthermore, clarifying the role of A. baumannii in polymicrobial infections (pathogen vs bystander) and whether polymicrobial infection is an independent predictor of patient outcome has implications for the design and analysis of studies assessing intervention or treatment effects.…”

Antibiotic therapy for pan-drug-resistant infections

“…Tigecycline also was authorized for the therapy of complicated skin and gastrointestinal infections caused by susceptible microorganisms [32]. Treatment with tigecycline alone or in simultaneous consumption with other antibacterial substances including imipenem, colestimethate, amikacin, and ampicillin-sulbactam are impressive in treating PDR infection [33]. Another effective synergy was seen in the utilization of imipenem-colestimethate and tigecycline-imipenem combinations.…”