An Update on Technical, Interpretative and Clinical Relevance of Antimicrobial Synergy Testing Methodologies

Laishram, Shakti; Pragasam, Agila Kumari; Bakthavatchalam, Yamuna Devi; Veeraraghavan, Balaji

doi:10.4103/ijmm.ijmm_17_189

Cited by 50 publications

(49 citation statements)

References 111 publications

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“…These CA results are used to classify the combination in one of three categories: synergy, indifference or antagonism [4]. Another more time-consuming method is to carry out static time-kill studies (sTKS) in which constant concentrations of drugs are used to monitor the kinetics of bacterial killing over time [5–8]. sTKS is a more quantitative approach than CA as the bacterial counts during exposure to the drugs alone or in combination are compared over 24 h. However, although both CA and sTKS assays are inexpensive and quite easy to perform, their limitations include short duration of the assay and the exposure to constant concentrations of drugs.…”

Section: Introductionmentioning

confidence: 99%

Comparison of in vitro static and dynamic assays to evaluate the efficacy of an antimicrobial drug combination against Staphylococcus aureus

Broussou

Toutain

Woehrle³

et al. 2019

PLoS ONE

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An easily implementable strategy to reduce treatment failures in severe bacterial infections is to combine already available antibiotics. However, most in vitro combination assays are performed by exposing standard bacterial inocula to constant concentrations of antibiotics over less than 24h, which can be poorly representative of clinical situations. The aim of this study was to assess the ability of static and dynamic in vitro Time-Kill Studies (TKS) to identify the potential benefits of an antibiotic combination (here, amikacin and vancomycin) on two different inoculum sizes of two S. aureus strains. In the static TKS (sTKS), performed by exposing both strains over 24h to constant antibiotic concentrations, the activity of the two drugs combined was not significantly different the better drug used alone. However, the dynamic TKS (dTKS) performed over 5 days by exposing one strain to fluctuating concentrations representative of those observed in patients showed that, with the large inoculum, the activities of the drugs, used alone or in combination, significantly differed over time. Vancomycin did not kill bacteria, amikacin led to bacterial regrowth whereas the combination progressively decreased the bacterial load. Thus, dTKS revealed an enhanced effect of the combination on a large inoculum not observed in sTKS. The discrepancy between the sTKS and dTKS results highlights that the assessment of the efficacy of a combination for severe infections associated with a high bacterial load could be demanding. These situations probably require the implementation of dynamic assays over the entire expected treatment duration rather than the sole static assays performed with steady drug concentrations over 24h.

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Section: Introductionmentioning

confidence: 99%

Comparison of in vitro static and dynamic assays to evaluate the efficacy of an antimicrobial drug combination against Staphylococcus aureus

Broussou

Toutain

Woehrle³

et al. 2019

PLoS ONE

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“…Synergic activity was evaluated using the checkerboard assay ( Garcia, 2010 ; Laishram et al, 2017 ). Wells containing 50 μl of each antimicrobial agent received 100 μl of overnight Salmonella culture diluted to 5 × 10 5 CFU/ml.…”

Section: Methodsmentioning

confidence: 99%

Inhibitory Activity of Natural Synergetic Antimicrobial Consortia Against Salmonella enterica on Broiler Chicken Carcasses

et al. 2021

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The currently most utilized antimicrobial agent in poultry processing facilities is peracetic acid, a chemical increasingly recognized as hazardous to human health. We evaluated the efficacy of mixtures of natural antimicrobial compounds, namely reuterin, microcin J25, and lactic acid, for reducing the viability of Salmonella enterica and total aerobes on broiler chicken carcasses. The compounds were compared singly and in combination with water and 0.1% peracetic acid. The minimum inhibitory concentrations of reuterin, lactic acid, and microcin J25 against S. enterica serovar Enteritidis were respectively 2 mM, 0.31%, and 0.03 μM. In vitro, the combinations of reuterin + lactic acid and reuterin + microcin J25 were synergic, making these compounds effective at four times lower concentrations than those used alone. Salmonella viable counts fell to zero within 10 min of contact with reuterin + lactic acid at 10 times the concentrations used in combination, compared to 18 h in the case of reuterin + microcin J25. Sprayed onto chilled chicken carcasses, this reuterin + lactic acid mixture reduced Salmonella spp. counts by 2.02 Log CFU/g, whereas reuterin + microcin J25 and peracetic acid reduced them by respectively 0.83 and 1.13 Log CFU/g. The synergy of reuterin with lactic acid or microcin J25 as inhibitors of bacterial growth was significant. Applied as post-chill spray, these mixtures could contribute to food safety by decreasing Salmonella counts on chicken carcasses.

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“…Commercially procured trimethoprim and sulfamethoxazole discs (Oxoid) arranged as strips in the T-conformation was used as a positive control for synergism (Bushby and Hitchings, 1968;Bernstein, 1982) and similarly placed ampicillin and trimethoprim disc combinations were used as a "no-interaction" control. The pattern of growth of test organisms was interpreted as follows: broadening of the zones of inhibition at adjoining ends depicts synergism, depression or narrowing of the zones indicates antagonism while no effect on the zones of inhibition indicate indifference (Laishram et al, 2017).…”

Section: Paper Strip Diffusion Testmentioning

confidence: 99%

“…In this method, disc diffusion tests are performed after incorporation of an agent in the agar medium to determine the nature of interactions between the agent in the medium and that in the disc (Amin et al, 2015;de Ruyck et al, 2016;Laishram et al, 2017). Doubling dilutions of the antimalarials (62.5-1,000 µg/mL) were made in molten Muller Hinton agar, which was then poured and set in plates aseptically.…”

Section: Modified Disc Diffusion (Mdd) Assaymentioning

confidence: 99%

Quinoline Antimalarials Increase the Antibacterial Activity of Ampicillin

et al. 2021

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Bacterial and malaria co-infections are common in malaria endemic countries and thus necessitate co-administration of antibiotics and antimalarials. There have long been anecdotal clinical reports of interactions between penicillins and antimalarial agents, but the nature and mechanisms of these interactions remain to be investigated. In this study, we employed antimicrobial interaction testing methods to study the effect of two antimalarials on the antibacterial activity of ampicillin in vitro. Paper strip diffusion, a modified disc diffusion and checkerboard methods were used to determine the nature of interactions between ampicillin and quinoline antimalarials, chloroquine and quinine, against Gram-positive and Gram-negative bacteria. The impact of antimalarials and ampicillin-antimalarial drug combinations on cell integrity of test bacteria were determined by measuring potassium release. The tested antimalarials did not show substantial antibacterial activity but quinine was bactericidal at high concentrations. Chloroquine and quinine increased ampicillin activity, with increasing concentrations extending the antibacterial’s inhibition zones by 2.7-4.4 mm and from 1.1 to over 60 mm, respectively. Observed interactions were largely additive with Fractional Inhibitory Concentration Indices of >0.5-1 for all ampicillin-antimalarial combinations. Quinine and, to a lesser extent, chloroquine increase the activity of ampicillin and potentially other β-lactams, which has implications for combined clinical use.

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An Update on Technical, Interpretative and Clinical Relevance of Antimicrobial Synergy Testing Methodologies

Cited by 50 publications

References 111 publications

Comparison of in vitro static and dynamic assays to evaluate the efficacy of an antimicrobial drug combination against Staphylococcus aureus

Comparison of in vitro static and dynamic assays to evaluate the efficacy of an antimicrobial drug combination against Staphylococcus aureus

Inhibitory Activity of Natural Synergetic Antimicrobial Consortia Against Salmonella enterica on Broiler Chicken Carcasses

Quinoline Antimalarials Increase the Antibacterial Activity of Ampicillin

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