ArticleThe Journal of antimicrobial chemotherapy2015
Synergistic killing of NDM-producing MDR Klebsiella pneumoniae by two 'old' antibiotics-polymyxin B and chloramphenicol.
Article in The Journal of antimicrobial chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 81 citations in OpenAlex.
- Cefdinir reprograms Gram-positive bacteria to synergize with lysozyme against superbugs.mLife · 2026Article
- A mechanism-based pharmacokinetic/pharmacodynamic analysis of polymyxin B-based combination therapy against carbapenem-resistantAntimicrobial agents and chemotherapy · 2026Article
- Hyperforin potentiates polymyxin B against multidrug-resistant Gram-negative pathogens via membrane disruption, biofilm eradication, and oxidative stress.Antimicrobial agents and chemotherapy · 2025Article
- A novel role for colistin as an efflux pump inhibitor in multidrug-resistant Klebsiella pneumoniae.Scientific reports · 2025Article
- A strategy to re-sensitise drug-resistant Gram-positive bacteria to oxazolidinone-class antibiotics.EBioMedicine · 2025Article
- Impact of high frequency electromagnetic radiation on bacterial survival and antibiotic activity in exposed bacteria.Scientific reports · 2025Article
- Transcriptomic investigations of polymyxins and colistin/sulbactam combination against carbapenem-resistantComputational and structural biotechnology journal · 2024Article
- Metabolic profiling unveils enhanced antibacterial synergy of polymyxin B and teixobactin against multi-drug resistant Acinetobacter baumannii.Scientific reports · 2024Article
- Post Trauma Acinetobacter Baumanii Meningitis Treatment Approach.Ulusal travma ve acil cerrahi dergisi = Turkish journal of trauma & emergency surgery : TJTES · 2024Article
- CTX-M, TEM, and SHV Genes inInfection and drug resistance · 2024Article
- Unveiling synergism of polymyxin B with chloramphenicol derivatives against multidrug-resistant (MDR) Klebsiella pneumoniae.The Journal of antibiotics · 2023Article
- Model-informed dose optimisation of polymyxin-rifampicin combination therapy against multidrug-resistant Acinetobacter baumannii.International journal of antimicrobial agents · 2023Article
- Lipid A Modification and Metabolic Adaptation in Polymyxin-Resistant, New Delhi Metallo-β-Lactamase-Producing Klebsiella pneumoniae.Microbiology spectrum · 2023Article
- Proof-of-concept for incorporating mechanistic insights from multi-omics analyses of polymyxin B in combination with chloramphenicol against Klebsiella pneumoniae.CPT: pharmacometrics & systems pharmacology · 2023Article
- Synergistic effect and antibiofilm activity of the antimicrobial peptide K11 with conventional antibiotics against multidrug-resistant and extensively drug-resistantFrontiers in cellular and infection microbiology · 2023Article
- Synergistic Effects of Capric Acid and Colistin against Colistin-Susceptible and Colistin-ResistantAntibiotics (Basel, Switzerland) · 2022Article
- Apolipoprotein E mimetic peptide COG1410 combats pandrug-resistantFrontiers in microbiology · 2022Article
- Comparative metabolomics revealed key pathways associated with the synergistic killing of multidrug-resistantComputational and structural biotechnology journal · 2022Article
- Review
- Rescuing the Last-Line Polymyxins: Achievements and Challenges.Pharmacological reviews · 2021Review
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
Abstract
objectivesCombination therapy is an important option in the fight against Gram-negative 'superbugs'. This study systematically investigated bacterial killing and the emergence of polymyxin resistance with polymyxin B and chloramphenicol combinations used against New Delhi metallo-β-lactamase (NDM)-producing MDR Klebsiella pneumoniae.
methodsFour NDM-producing K. pneumoniae strains were employed. The presence of genes conferring resistance to chloramphenicol was examined by PCR. Time-kill studies (inocula ∼10(6) cfu/mL) were conducted using various clinically achievable concentrations of each antibiotic (range: polymyxin B, 0.5-2 mg/L; chloramphenicol, 4-32 mg/L), with real-time population analysis profiles documented at baseline and 24 h. The microbiological response was examined using the log change method and pharmacodynamic modelling in conjunction with scanning electron microscopy (SEM).
resultsMultiple genes coding for efflux pumps involved in chloramphenicol resistance were present in all strains. Polymyxin B monotherapy at all concentrations produced rapid bacterial killing followed by rapid regrowth with the emergence of polymyxin resistance; chloramphenicol monotherapy was largely ineffective. Combination therapy significantly delayed regrowth, with synergy observed in 25 out of 28 cases at both 6 and 24 h; at 24 h, no viable bacterial cells were detected in 15 out of 28 cases with various combinations across all strains. No polymyxin-resistant bacteria were detected with combination therapy. These results were supported by pharmacodynamic modelling. SEM revealed significant morphological changes following treatment with polymyxin B both alone and in combination.
conclusionsThe combination of polymyxin B and chloramphenicol used against NDM-producing MDR K. pneumoniae substantially enhanced bacterial killing and suppressed the emergence of polymyxin resistance.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.