ArticleThe Journal of antimicrobial chemotherapy2017
Polymyxin-resistant, carbapenem-resistant Acinetobacter baumannii is eradicated by a triple combination of agents that lack individual activity.
Article in The Journal of antimicrobial chemotherapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 2 of them syntheses that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
32 citing papers in PubMed, 2 syntheses or guidelines pooled it, 56 citations in OpenAlex.
- In search for a synergistic combination against pandrug-resistant A. baumannii; methodological considerations.Infection · 2022Pooled it
- Guideline
- Residual confounding and outcome definition in observational comparisons of PDR-Antimicrobial agents and chemotherapy · 2026Article
- Breaking the Phalanx: Overcoming Bacterial Drug Resistance with Quorum Sensing Inhibitors that Enhance Therapeutic Activity of Antibiotics.bioRxiv : the preprint server for biology · 2025Article
- Biomarker-Driven Pharmacokinetics and Efficacy of Polymyxin B in Critically Ill Patients with XDR-GN Pneumonia.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Integrative review on Acinetobacter baumannii as a multidrug-resistant pathogen: resistance mechanisms and therapeutic perspectives in the context of nosocomial infections.Revista da Sociedade Brasileira de Medicina Tropical · 2025Review
- Polymyxin B in The Treatment of Infections Caused by Multidrug-Resistant Gram-Negative Bacteria in Children: A Retrospective Case Series and A Literature Review.Infection and drug resistance · 2025Article
- Optimizing Treatment for Carbapenem-ResistantInfection & chemotherapy · 2024Review
- Early initiation of three-drug combinations for the treatment of carbapenem-resistant A. baumannii among COVID-19 patients.The Journal of antimicrobial chemotherapy · 2023Article
- Prediction of Tissue Exposures of Meropenem, Colistin, and Sulbactam in Pediatrics Using Physiologically Based Pharmacokinetic Modeling.Clinical pharmacokinetics · 2022Article
- The combination effect of meropenem/sulbactam/polymyxin-B on the pharmacodynamic parameters for mutant selection windows against carbapenem-resistantFrontiers in microbiology · 2022Article
- SPR741, Double- or Triple-Combined With Erythromycin and Clarithromycin, Combats Drug-ResistantFrontiers in cellular and infection microbiology · 2022Article
- Systematic Review of Antimicrobial Combination Options for Pandrug-ResistantAntibiotics (Basel, Switzerland) · 2021Review
- Virulence Potential and Treatment Options of Multidrug-Resistant (MDR)Microorganisms · 2021Review
- Polymyxin B Pharmacodynamics in the Hollow-Fiber Infection Model: What You See May Not Be What You Get.Antimicrobial agents and chemotherapy · 2021Article
- Pharmacodynamic evaluation of suppression of in vitro resistance in Acinetobacter baumannii strains using polymyxin B-based combination therapy.Scientific reports · 2021Article
- Cefiderocol-Based Combination Therapy for "Difficult-to-Treat" Gram-Negative Severe Infections: Real-Life Case Series and Future Perspectives.Antibiotics (Basel, Switzerland) · 2021Article
- Losing the Battle but Winning the War: Can Defeated Antibacterials Form Alliances to Combat Drug-Resistant Pathogens?Antibiotics (Basel, Switzerland) · 2021Review
- Rescuing the Last-Line Polymyxins: Achievements and Challenges.Pharmacological reviews · 2021Review
- Review
Corrections and comments
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Authors and funding
12 authors at 9 institutions in 4 countries.
Funding
Abstract
Objectives: The emergence of polymyxin resistance threatens to leave clinicians with few options for combatting drug-resistant Acinetobacter baumannii . The objectives of the current investigation were to define the in vitro emergence of polymyxin resistance and identify a combination regimen capable of eradicating A. baumannii with no apparent drug susceptibilities. Methods: Two clonally related, paired, A. baumannii isolates collected from a critically ill patient who developed colistin resistance while receiving colistin methanesulfonate in a clinical population pharmacokinetic study were evaluated: an A. baumannii isolate collected before (03-149.1, polymyxin-susceptible, MIC 0.5 mg/L) and an isolate collected after (03-149.2, polymyxin-resistant, MIC 32 mg/L, carbapenem-resistant, ampicillin/sulbactam-resistant). Using the patient's unique pharmacokinetics, the patient's actual regimen received in the clinic was recreated in a hollow-fibre infection model (HFIM) to track the emergence of polymyxin resistance against 03-149.1. A subsequent HFIM challenged the pan-resistant 03-149.2 isolate against polymyxin B, meropenem and ampicillin/sulbactam alone and in two-drug and three-drug combinations. Results: Despite achieving colistin steady-state targets of an AUC 0-24 >60 mg·h/L and C avg of >2.5 mg/L, colistin population analysis profiles confirmed the clinical development of polymyxin resistance. During the simulation of the patient's colistin regimen in the HFIM, no killing was achieved in the HFIM and amplification of polymyxin resistance was observed by 96 h. Against the polymyxin-resistant isolate, the triple combination of polymyxin B, meropenem and ampicillin/sulbactam eradicated the A. baumannii by 96 h in the HFIM, whereas monotherapies and double combinations resulted in regrowth. Conclusions: To combat polymyxin-resistant A. baumannii , the triple combination of polymyxin B, meropenem and ampicillin/sulbactam holds great promise.
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Registered trials
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