Synergistic combinations of polymyxins

Lenhard, Justin R.; Nation, Roger L.; Tsuji, Brian T.

doi:10.1016/j.ijantimicag.2016.09.014

Cited by 83 publications

(68 citation statements)

References 60 publications

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“…We confirmed the described multi-drug resistance of P. aeruginosa strains that were isolated in clinical 59 and municipal waste water, see IDs NCT01732250 and NCT01597973) (Lenhard et al, 2016). 67…”

supporting

confidence: 75%

Synergy pattern of short cationic antimicrobial peptides against multidrug-resistantPseudomonas aeruginosa

Ruden

Rieder

Mikut

et al. 2019

Preprint

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With the rise of various multi-drug resistance pathogenic bacteria, worldwide health care is under pressure to respond. Conventional antibiotics are failing and the development of novel classes or alternative strategies is a major priority. Antimicrobial peptides (AMPs) can not only kill multi-drug resistant bacteria, but also can be used synergistically with conventional antibiotics. We selected 30 short AMPs from different origins and measured their synergy in combination with Polymyxin B, Piperacillin, Ceftazidime, Cefepime, Meropenem, Imipenem, Tetracycline, Erythromycin, Kanamycin, Tobramycin, Amikacin, Gentamycin, and Ciprofloxacin. In total 403 unique combinations were tested against a multi-drug resistant Pseudomonas aeruginosa isolate (PA910). As a measure of the synergistic effects, fractional inhibitory concentrations (FICs) were determined using microdilution assays with FICs ranges between 0.25 and 2. A high number of combinations between peptides and Polymyxin B, Erythromycin and Tetracycline were found to be synergistic. Novel variants of Indolicidin also showed a high frequency in synergist interaction.

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supporting

confidence: 75%

Synergy pattern of short cationic antimicrobial peptides against multidrug-resistantPseudomonas aeruginosa

Ruden

Rieder

Mikut

et al. 2019

Preprint

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“…Additionally, the derivatives have very modest activity against K. pneumoniae strains that display high‐level resistance to polymyxins. A possible alternative approach would be to look for suitable partner antibiotics that show synergism with appropriate, well‐tolerated polymyxin derivatives against such polymyxin‐resistant strains, in analogy with what has already been done for polymyxin B and colistin, as recently reviewed by Lenhard et al …”

Section: Discussionmentioning

confidence: 99%

New polymyxin derivatives that display improved efficacy in animal infection models as compared to polymyxin B and colistin

Vaara

2018

Medicinal Research Reviews

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Polymyxin B and colistin (polymyxin E) are bactericidal pentacationic lipopeptides that act specifically on Gram-negative bacteria, first by disrupting their outermost permeability barrier, the outer membrane (OM), and then damaging the cytoplasmic membrane. The discovery of both polymyxin B and colistin was published independently by three laboratories as early as in 1947. They were subsequently used in intravenous therapy. Unfortunately, they also exhibit significant and dose-limiting nephrotoxicity. Therefore, polymyxins were reserved as agents of last-line defense. The emergence of extremely multiresistant strains has now forced clinicians to reinstate polymyxins in the therapy of severe infections. However, the current dosage regimens lead to insufficient drug concentrations in serum and clinicians have been advised to use larger doses, which further increases the risk of nephrotoxicity. Very recently, the interest in developing better tolerated and more effective polymyxins has grown. This review focuses on describing four development programs that have yielded novel derivatives that are more effective than the old polymyxins in animal infection models. Compounds from three programs are superior to the old polymyxins in the rodent lung infection model with Acinetobacter baumannii and/or Pseudomonas aeruginosa. One of them is also more effective than polymyxin B in A. baumannii mouse thigh infection. The fourth program includes compounds that are approximately tenfold more effective in Escherichia coli murine pyelonephritis than polymyxin B.

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“…The major threat is posed by gram negative bacteria which have not only become resistant to third generation cephalosporins, aminogycosides and fluroquinolones but also to carbapenems This situation has forced the clinicians to use colistin, tigecycline, fosfomycin in various combinations. 13 One of the major contributing factors towards resistance has been antibiotic use. 14 Antibiotic use has been seen to be high in India with one recent surveillance study indicating 40 per cent of patients in the community on antibiotics and an even higher rate of inappropriate use.…”

Section: Why Implement Antimicrobial Stewardship Programme?mentioning

confidence: 99%

Antimicrobial stewardship: need of the hour

Ahmad

Rehman

2018

Int J Basic Clin Pharmacol

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Efforts to tackle the global threat of Antimicrobial Resistance (AMR) have recently taken shape in a number of potentially far-reaching collaborative initiatives. When microbes become resistant to medicines, the options for treating the diseases they cause are reduced. This resistance to antimicrobial medicines is happening in all parts of the world for a broad range of microorganisms with an increasing prevalence that threatens human and animal health. The direct consequences of infection with resistant microorganisms can be severe, including longer illnesses, increased mortality, prolonged hospital stay, loss of protection for patients undergoing operations and other medical procedures, and increased costs. Antimicrobial resistance affects all areas of health, involves many sectors and has an impact on the whole of society. To overcome the threat of antimicrobial resistance, a three-pillar approach has been advocated i.e. Optimize the use of existing antimicrobial agents, prevent the transmission of drug-resistant organisms through infection control and Improve environmental decontamination. Antimicrobial stewardship [AMSP] is one of the key strategies to overcome resistance. It is an inter-professional effort, across the continuum of care, involves timely and optimal selection, dose and duration of an antimicrobial for the best clinical outcome for the treatment or prevention of infection with minimal toxicity to the patient and minimal impact on resistance and other ecological adverse events.

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Synergistic combinations of polymyxins

Cited by 83 publications

References 60 publications

Synergy pattern of short cationic antimicrobial peptides against multidrug-resistantPseudomonas aeruginosa

Synergy pattern of short cationic antimicrobial peptides against multidrug-resistantPseudomonas aeruginosa

New polymyxin derivatives that display improved efficacy in animal infection models as compared to polymyxin B and colistin

Antimicrobial stewardship: need of the hour

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