Global response to antimicrobial resistance
Editor - In a recent issue of the Bulletin, Smith & Coast (1) succinctly reviewed the emerging global scourge of antimicrobial resistance (AMR). Nevertheless, their strategies for containment of the emergence and dissemination of AMR in Table 1 do not include an evaluation of the potency and bio-availability of antibiotics, probiotics or vaccines being offered to the public worldwide. Plausible host factors or pharmacokinetics of drugs have also been ignored.
Antimicrobial agents require constant storage within a controlled temperature range: from either subzero to 2-8 oC, or 15 to 25-30 oC (2). Inadvertent exposure to extremes of temperature or humidity would alter their potency. This was evident during a Nigerian field trial when the active ingredients in 48% of the samples of common medicines were found to be outside the limits specified by the British Pharmacopoeia (3). Identical scenarios may occur with antimicrobial formulations elsewhere. Such formulations would be ineffective against microbial replication and, being lower than the required antibiotic quantum, encourage selection and dissemination of resistant microbes.
Obviously, any response at local, national, regional or global levels to manage AMR will not be effective unless losses in potency and bioavailability of antimicrobial agents are monitored regularly, including during their administration. Simple assay formats that could accomplish qualitative and quantitative analysis of antimicrobial agents in the clinical and household setting should be standardized. Recently, Green et al. (4) proposed a quick and simple field test requiring few chemicals and no sophisticated equipment to identify artesenuate, an antimalarial drug. Identical tests for frequently used antimicrobial agents would confirm the quality of the antibiotics or probiotics being consumed.
The addition of chemical stabilizers may well help retain the potency of antibiotics and probiotics in adverse environments. The least stable of the common childhood vaccines, oral polio vaccine is stabilized by the addition of pirodavir and deuterium oxide (5). Pre-stabilization of therapeutics would not only prevent emergence and dissemination of AMR, but be cost-effective.
Host-induced factors could alter the efficacy of therapeutic agents offered against microbial infection. For example, any concurrent formulations of antacid containing magnesium hydroxide or aluminium hydroxide alter the efficacy of orally administered therapeutic agents. The bioavalibility of ciprofloxacin would be reduced drastically with a concurrent administration of milk (6). Such eventualities cannot be ignored and should be eliminated by assaying the maximum drug plasma concentration, including the area under the assay curve. Undoubtedly, simpler tests to measure drug concentration in saliva or urine, rather than in blood, could be employed. These tests would be important assets for the global effort to tackle AMR (1). n
Subhash C. Arya4
Conflicts of interest: none declared.
1. Smith RD, Coast J. Antimicrobial resistance: a global response. Bulletin of the World Health Organization 2002;80:126-33.
2. Physicians' desk reference. 55th edition. Medical Economics Company. Montvale, 2001.
3. Taylor RB, Shakoor O, Behrens RH, et al. Pharmacopoeial quality of drugs supplied by Nigerian pharmacies. Lancet 2001;357:1933-6.
4. Green MD, Mount DL, Wirtz RA, White NJ. A colorimetric field method to assess authenticity of drugs sold as the antimalarial artesenuate. Journal of Pharmaceutical and Biomedical Analysis 2000;24:65-70.
5. Verheyden B, Andrus K, Rombart B. Capsid and RNA stabilization of oral poliovaccine. Vaccine 2001; 9:1899-905.subhashji@vsnl.net).
6. Hoogkarmer JFW, Kleinbloesem CH. The effect of milk consumption on the pharmakinetics of fleroxin and ciprofloxacin. Drugs 1995;49 (Suppl 2):346-8.
4 Research Physician, Centre for Logistical Research and Innovation, M-122 Greater Kailash - Part 2, New Delhi 110048, India (email: subhashii@vsnl.net).