Combination Therapy for Treatment of Infections with Gram-Negative Bacteria

Tamma, Pranita D.; Cosgrove, Sara E.; Maragakis, Lisa L.

doi:10.1128/cmr.05041-11

Cited by 681 publications

(581 citation statements)

References 255 publications

(304 reference statements)

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“…Similar discrepancies were also seen in a previous study that employed the G. mellonella infection model [15]. There are many examples where combinations of antibiotics are shown to have enhanced activity in vitro but offer no therapeutic benefit when tested in vivo (reviewed in [21]). Thus, screening for novel antibiotic treatments in vitro is not a good predictor of in vivo efficacy and instead should be performed in rapid, tractable in vivo infection models such as G. melonella larvae to ensure a greater chance of success when these treatments are tested in subsequent mammalian infection models.…”

Section: Discussionsupporting

confidence: 45%

Enhancement of Antibiotic Efficacy against Multi-drug Resistant Pseudomonas Aeruginosa Infections via Combination with Curcumin and 1-(1-Naphthylmethyl)-Piperazine

Ballard¹,

Coote²

2016

J Antimicro

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Objective: The aim of this study was to determine if the plant phenolic curcumin (CUR) and the arylpiperazine 1-(1-naphthylmethyl)-piperazine (NMP) could restore antibiotic efficacy versus MDR P. aeruginosa infection. Methods:The MICs of piperacillin, meropenem and levofloxacin in the presence or absence of CUR or NMP against a MDR strain that over-expresses the MexAB-OprM efflux-pump and the isogenic parent strain were compared. The efficacy of the same combination treatments was also tested in a Galleria mellonella in vivo infection model and larval survival and bacterial burden compared. Results:In vitro, CUR restored the activity of piperacillin, meropenem and levofloxacin versus the MDR strain of P. aeruginosa only weakly. There was no evidence in vitro of a similar effect with NMP. In vivo, treatment of G. mellonella larvae infected with the MDR strain with a combination of NMP or CUR plus levofloxacin, and piperacillin plus CUR, resulted in enhanced therapeutic benefit compared to the monotherapies. When compared with monotherapies, the enhanced efficacy of the combination treatments correlated with reduced bacterial burden.Conclusion: CUR and NMP restored the efficacy of antibiotic therapy in vivo versus MDR P. aeruginosa infection.

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Section: Discussionsupporting

confidence: 45%

Enhancement of Antibiotic Efficacy against Multi-drug Resistant Pseudomonas Aeruginosa Infections via Combination with Curcumin and 1-(1-Naphthylmethyl)-Piperazine

Ballard¹,

Coote²

2016

J Antimicro

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“…Disadvantages associated with Combination therapy [5]: There are certain disadvantages of antibiotic combination therapy.…”

Section: Introductionmentioning

confidence: 99%

Burden of Antibiotic Resistance in Common Infectious Diseases: Role of Antibiotic Combination Therapy

Mehta¹

2014

JCDR

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“…Employing two or more therapeutic agents to treat a disease has shown promise for certain cancers [42], bacterial diseases [43] and HIV [44] (see also examples in [45]). The basis is two-fold.…”

Section: Combination Therapiesmentioning

confidence: 99%

Six wedges to curing disease

Hochberg

2017

Preprint

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Abstract.One of the great challenges in ecology and evolutionary biology is to explain disease, whether caused by infectious agents such as parasites and pathogens, or by the deterioration or transformation of cellular behavior and function, a prime example of the latter being cancer. Decades of observation and research suggest that successfully treating disease requires insights into how the environment mediates the interactions between disease causing agents (DCAs) and diseased individuals. A major finding is that single factor, targeted therapies are not only likely to fail in controlling or eradicating many DCAs, but are also likely to select for resistance, reducing options for subsequent treatment attempts, and in cases of infectious DCAs, rendering therapeutic agents (e.g., antibiotics) obsolete.I argue that meeting the growing challenge of treating disease in agriculture and animal husbandry, in protected and domesticated species, wildlife, and in the human population will require a fundamental understanding of ecological interactions at sites of infection or disease. I discuss different ways in which components of such disease ecosystems mediate DCA and therapeutic dynamics and resistance evolution, and derive a very simple mathematical criterion for therapeutic success. I then touch on how fundamental insights as revealed by the processes of evolutionary rescue and competitive release can help understand why therapies succeed or fail. Finally, I present six "wedges" that can each contribute alone, or as part of multi-pronged approaches to successfully treating disease. The Magic BulletDespite remarkable progress in prevention and treatment, the impacts of diseases in agriculture and animal husbandry, and on protected and domesticated species, wildlife, and human health are likely to intensify into the 21 st century. Humans in particular are increasingly in contact with each other and with wildlife, treated with drug regimens that select for resistance, and adopt life-styles or are exposed to environments that render them more susceptible to infectious diseases and more likely to get cellular diseases such as cancers.For many clinicians the Holy Grail is to discover the Ehrlichian "Magic Bullet"-a drug that will target the disease-causing agents (DCAs) and cure disease. Intuitively, the most effective way to reduce DCAs is to "hit hard and fast". That is, more drug means more kill within the tolerance limits of the patient. Rapid administration of the drug means forestalling further DCA growth and associated symptoms, but also reducing the probability of the appearance of resistant mutant strains. Despite decades of research on pest and disease control (much of it with an ecological basis) this approach and the many alternatives described below remain highly controversial (e.g., [1]).The Magic Bullet may be shortsighted for another reason. What will cure most patients may not be optimal for the general population in which resistant variants may emerge and spread 1 . This problem is in many ways similar...

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Combination Therapy for Treatment of Infections with Gram-Negative Bacteria

Cited by 681 publications

References 255 publications

Enhancement of Antibiotic Efficacy against Multi-drug Resistant Pseudomonas Aeruginosa Infections via Combination with Curcumin and 1-(1-Naphthylmethyl)-Piperazine

Enhancement of Antibiotic Efficacy against Multi-drug Resistant Pseudomonas Aeruginosa Infections via Combination with Curcumin and 1-(1-Naphthylmethyl)-Piperazine

Burden of Antibiotic Resistance in Common Infectious Diseases: Role of Antibiotic Combination Therapy

Six wedges to curing disease

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