The Medicines and Healthcare Products Regulatory Agency (MHRA) moves to recommend, for the first time, that a systemic antibiotic (trimethoprim) should have its licence reclassified from prescription only medicine (POM) to pharmacy (P) availability.1 For systemic antibiotics particular concerns exist that do not apply to other medicines.
The use of antibiotics may have an adverse effect not only on the specific patient but also on the public health of the community. Quantifying the relation between antibiotic exposure and resistance is difficult, but a case-control study of risk of an antibiotic resistant Escherichia coli urinary tract infection found that the risk of a trimethoprim resistant infection was significantly associated with a trimethoprim prescription in the preceding month (odds ratio 13.91 (95% confidence interval 3.32 to 58.31) if the prescription was for ≥7 days, and 4.03 (1.69 to 9.59) if the prescription was for <7 days).2
Because resistance to multiple agents is often linked, the selective pressure of using one antibiotic will often select for resistance to other unrelated agents. Data from the Cardiff area show that trimethoprim resistant coliforms are significantly more resistant to second line treatments such as ciprofloxacin (see table). Thus trimethoprim use will select for ciprofloxacin resistance.
Resistance rates for community urinary coliform isolates from the Cardiff area
| % resistant | |||||
|---|---|---|---|---|---|
| Amoxicillin | Co-amoxiclav | Cefalexin | Nitrofurantoin | Ciprofloxacin | |
| All coliforms | 52.6 | 13.1 | 7.2 | 14.1 | 8.1 |
| Trimethoprim resistant coliforms | 81.1 | 23.5 | 23.5 | 21.8 | 22.0 |
There is also an issue of selecting resistance in organisms other than those targeted by treatment since most commensal flora will also be exposed to some degree to a systemic antibiotic. Trimethoprim is an oral option for treating various infections caused by meticillin resistant Staphylococcus aureus (MRSA).3 Although rates of resistance are significant (35%) in UK bacteraemia isolates,3 resistance among community isolates of MRSA in some areas (for example, south Wales) remains low at 12%. Increased trimethoprim use in the community is likely to select for resistance in MRSA and hence remove a valuable oral therapeutic option.
For these reasons, and for the growing concern about Clostridium difficile associated disease in the community, antibiotic use must be regulated to minimise inappropriate use. Restricting systemic antibacterial agents to prescription only has been recommended by the European Commission (2002/77/EC) and a House of Lords select committee.4
Given the ever-increasing restrictions on antibiotic use in hospitals that are being encouraged by the Department of Health in an effort to control resistance and C difficile, it seems paradoxical to reclassify trimethoprim.
Competing interests: None declared.
References
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