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Quinoline Antimalarials Increase the Antibacterial Activity of Ampicillin
Olajumoke A Olateju1, Chinedum P Babalola1,2, Olujide O Olubiyi3
1Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Ibadan, Ibadan, Nigeria.
Abstract:
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.
Insights
Quinine and chloroquine enhance ampicillin’s antibacterial effectiveness against common co-infections. This study investigated drug interactions, finding additive effects that may improve treatment outcomes for bacterial and malaria co-infections.
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- Bacterial and malaria co-infections are prevalent in malaria-endemic regions.
- Co-administration of antibiotics and antimalarials is clinically necessary.
- Anecdotal reports suggest interactions between penicillins and antimalarials, but mechanisms are unclear.
Purpose of the Study:
- To investigate the in vitro interaction between ampicillin and two quinoline antimalarials (chloroquine, quinine).
- To determine the effect of these antimalarials on ampicillin's antibacterial activity.
- To assess the impact of drug combinations on bacterial cell integrity.
Main Methods:
- Antimicrobial interaction testing: paper strip diffusion, modified disc diffusion, and checkerboard assays.
- Evaluation of ampicillin-antimalarial combinations against Gram-positive and Gram-negative bacteria.
- Measurement of potassium ion release to assess bacterial cell integrity.
Main Results:
- Antimalarials showed minimal intrinsic antibacterial activity, except quinine at high concentrations (bactericidal).
- Chloroquine and quinine significantly enhanced ampicillin's inhibitory effect, increasing inhibition zones.
- Interactions were predominantly additive, with Fractional Inhibitory Concentration Indices between 0.5 and 1.
Conclusions:
- Quinine and chloroquine potentiate the antibacterial activity of ampicillin.
- These findings have significant implications for the combined clinical use of ampicillin and antimalarials.
- Further research into ampicillin-antimalarial interactions may optimize treatment strategies for co-infections.
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