Who benefits from antimicrobial combination therapy?

Pletz, Mathias W.; Hagel, Stefan; Forstner, Christina

doi:10.1016/s1473-3099(17)30233-5

Cited by 30 publications

(25 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Taken together, we do not think that the INCREMENT-CPE score is useful as a bedside tool due to its complicated construction including other scores. 3 Furthermore, we do not agree with the authors´ conclusion, that combination therapy should be used based on the INCREMENT-CPE score. Pending further data from other cohorts or randomised trials the use of monotherapy or combination therapy will remain a clinical expert decision.…”

Section: Combination Therapy For Bloodstream Infections With Carbapencontrasting

confidence: 60%

“…Along with many other countries worldwide, we have recently been involved in investigating an outbreak of invasive Mycobacterium chimaera infections linked with surgery conducted on cardiopulmonary bypass. 3 Evidence to date, including whole genome sequencing analysis, strongly implicates aerosol dispersal of contaminated water from heater-cooler units used for cardiopulmonary bypass as the source of this outbreak. 3,4 A key question in identifying measures to potentially mitigate against this risk of aerosol dispersal, given that these machines cannot be readily taken out service without substantial disruption to life-saving cardiothoracic surgery, is whether laminar flow might offer a means to prevent contaminated aerosol entering the surgical field.…”

Section: Evidence That Mycobacterium Chimaera Aerosols Penetrate Lamimentioning

confidence: 99%

“…3 Evidence to date, including whole genome sequencing analysis, strongly implicates aerosol dispersal of contaminated water from heater-cooler units used for cardiopulmonary bypass as the source of this outbreak. 3,4 A key question in identifying measures to potentially mitigate against this risk of aerosol dispersal, given that these machines cannot be readily taken out service without substantial disruption to life-saving cardiothoracic surgery, is whether laminar flow might offer a means to prevent contaminated aerosol entering the surgical field. Sommerstein and colleagues 5 investigated the dispersal of M chimera from a heater-cooler unit in a fully functional cardiac theatre fitted with an ultraclean air ventilation system validated to ISO EN 14644-3 :2005.…”

Section: Evidence That Mycobacterium Chimaera Aerosols Penetrate Lamimentioning

confidence: 99%

“…2 Indeed, several previous randomised trials predominantly involving patients undergoing general surgical procedures revealed that chlorhexidine-based antiseptic agents were more effective than iodine-based antiseptic agents for the prevention of SSI. Although most trials compared a chlorhexidine-alcohol combination with iodine alone, a study 3 for preoperative skin preparation showed that the risk of SSI after caesarean delivery was significantly lower when chlorhexidine-alcohol was used than when iodine-alcohol was used. Furthermore, switching from iodine to chlorhexidine resulted in a net cost savings of US$16 to $26 per surgical case and $349 904 to $568 594 per year in the USA, and the cost-effectiveness is not negligible.…”

Section: Timing Of Surgical Antimicrobial Prophylaxismentioning

confidence: 99%

See 3 more Smart Citations

Timing of surgical antimicrobial prophylaxis

Kanemoto

Tanimoto

Maeda

et al. 2017

The Lancet Infectious Diseases

View full text Add to dashboard Cite

Section: Combination Therapy For Bloodstream Infections With Carbapencontrasting

confidence: 60%

Section: Evidence That Mycobacterium Chimaera Aerosols Penetrate Lamimentioning

confidence: 99%

Section: Evidence That Mycobacterium Chimaera Aerosols Penetrate Lamimentioning

confidence: 99%

Section: Timing Of Surgical Antimicrobial Prophylaxismentioning

confidence: 99%

See 2 more Smart Citations

Timing of surgical antimicrobial prophylaxis

Kanemoto

Tanimoto

Maeda

et al. 2017

The Lancet Infectious Diseases

View full text Add to dashboard Cite

“…One of the primary motivations for the use of combination antibiotic therapy is reducing the probability of resistance evolution (P letz et al , 2017). Here, we study the evolution of multi-resistance evolution to two antibiotics under single-drug and combination treatments.…”

Section: Discussionmentioning

confidence: 99%

Mutators drive evolution of multi-resistance to antibiotics

Gifford¹,

Berríos-Caro

Joerres³

et al. 2019

Preprint

View full text Add to dashboard Cite

Combination therapy aims to prevent growth of organisms not resistant to all component drugs, making it an obvious strategy for countering the global rise of multi-drug resistance. However, success relies on preventing resistance from arising to all component drugs before full inhibition is reached during treatment. Here, we investigated whether bacterial populations can overcome combination therapy by evolving 'multi-resistance', i.e. independent resistance mutations to multiple drugs, during single-drug and combination antibiotic treatment. Using both experimental evolution and in silico stochastic simulations, we studied resistance evolution in a common laboratory strain of bacteria (Escherichia coli K-12 BW25113). Populations were exposed to either single-drug or combination treatments involving rifampicin and nalidixic acid, with concentrations increasing through time. For wild-type populations, multi-resistance was not detected in any of the experimental populations, and simulations predict its evolution should be rare.However, populations comprising mixtures of wild-type and 'mutator' strains were readily capable of evolving multi-resistance. Increasing the initial frequency of mutators resulted in a higher proportion of populations evolving multi-resistance. Experiments and simulations produced the same qualitative-and in many cases, quantitative-insights about the association between resistance, mutators and antibiotic treatment. In particular, both approaches demonstrated that multi-resistance can arise through sequential acquisition of independent resistance mutations, without a need to invoke multi-drug resistance mechanisms. Crucially, we found multi-resistance evolved even when not directly favoured by natural selection, i.e. under single-drug treatments. Simulations revealed this resulted from elevated mutation supply caused by genetic hitch-hiking of the mutator allele on single-drug resistant backgrounds. Our results suggest that combination therapy does not necessarily prevent sequential acquisition of multiple drug resistances via spontaneous mutation when mutators are present. Indeed both combination and single-drug treatments actively promoted multi-resistance, meaning that combination therapy will not be a panacea for the antibiotic resistance crisis. inference, stochastic simulations, individual-based model, Markov chains W , K. B., 2016 Pairwise interactions and the battle against combinatorics in multidrug therapies.

show abstract

Simultaneous delivery of several antimicrobial drugs from multi‐compartment glycerol‐silicone membranes

Mazurek

Yuusuf

Silau

et al. 2021

J of Applied Polymer Sci

View full text Add to dashboard Cite

Combining drugs is an efficient tool in fighting bacterial infections. It has been proven to enable an increased antimicrobial activity compared to mono‐drug therapies. Current commercial dressings for treatment of infected wounds provide delivery of one drug only. Therefore, there is an obvious need to develop a technology enabling incorporation and release of two and more actives. Ideally, such technology should prevent potential cross‐reactions between the drugs during long‐term storage. Here, a concept of drug compartmentalization within distinct glycerol domains of glycerol‐silicone elastomer membranes is presented. Multiple drugs are encapsulated within different types of glycerol domains hampering any cross‐reactions. The drugs are simultaneously released upon contact with aqueous media and the release kinetics can be precisely adjusted by tuning various material parameters, such as glycerol content and membrane thickness. Ultimately, the drug release capabilities and the antimicrobial potential are evaluated against a variety of bacteria in an agar diffusion assay. The membranes are proven effective against different bacterial species, which confirms the efficiency of release even at minimum moisture levels. The glycerol‐silicone platform technology enables delivery of virtually unlimited combinations of drugs from different drug families (e.g., antimicrobial, anti‐inflammatory, and pain relief agents) facilitating new ways of treating wound disorders.

show abstract

Who benefits from antimicrobial combination therapy?

Cited by 30 publications

References 10 publications

Timing of surgical antimicrobial prophylaxis

Timing of surgical antimicrobial prophylaxis

Mutators drive evolution of multi-resistance to antibiotics

Simultaneous delivery of several antimicrobial drugs from multi‐compartment glycerol‐silicone membranes

Contact Info

Product

Resources

About