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Letters to the Editor
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Trimethoprim
Will switching lead to increased resistance?
From Professor R. Finch, and others
The Advisory Committee on Antimicrobial Resistance and Healthcare Associated
Infection (ARHAI) has noted the recent reclassification
of trimethoprim and nitrofurantoin from POM to P (PJ, 19 April 2008, p459).
ARHAI welcomes the improved roles and responsibilities for pharmacists outlined
in the English White Paper for pharmacy. ARHAI and its predecessor — the
Specialist Advisory Committee on Antimicrobial Resistance — were instrumental
in the recognition of the important role that antimicrobial clinical pharmacists
can play in promoting the safe and optimal use of antimicrobials and has given
them active support.
However ARHAI considered the reclassification of antimicrobials from POM to
P could increase demand, promote the diffusion of prescribing of broad spectrum
antimicrobials and contribute to increases in resistance among target urinary
tract and other pathogens.1
If trimethoprim and nitrofurantoin both become pharmacy medicines this may
encourage other applications for POM to P shifts of other urinary tract infection
(UTI) agents, for example, pivmecillinam, cefaclor, fosfomycin, norfloxacin.
This has potential implications for prescribing in the community.
Nitrofurantoin is recommended for the treatment of lower UTIs due to extended
spectrum beta-lactamases (ESBLs). If nitrofurantoin is routinely used in pharmacies
this will remove this agent from second-line use by GPs. Indeed, nitrofurantoin
may be less satisfactory and may require longer courses of therapy, and thus
is considered to be an alternative, rather than a first-line, therapeutic agent
for this clinical syndrome.2
If nitrofurantoin and trimethoprim are routinely used in pharmacies GPs will
inevitably start to use more broad-spectrum antibiotics for UTIs, in the expectation
that patients will have already received trimethoprim and nitrofurantoin. This
would almost certainly include quinolones and cephalosporins, which are risk
factors for increasing community-associated meticillin-resistant Staphylococcus
aureus (MRSA), Clostridium difficile and ESBL.3–5
Since the first application for change of trimethoprim from POM to P use three
years ago, the prevalence of MRSA, C difficile and ESBLs has increased in the
community, making it even more important that use of antibiotic agents in the
community is suitably controlled and monitored by robust processes.3–5
We would welcome the views of pharmacy staff and, in particular, antimicrobial
clinical pharmacists in NHS hospitals who have to deal with targets to reduce
MRSA and C difficile infections, and pharmacy staff in primary care trusts
who are seeking to address GP prescribing (e-mail esmita.charani@hpa.org.uk).
Roger Finch
Chairman
Jonathan Cooke
Member
Esmita Charani
Pharmacist Lead
Advisory Committee on Antimicrobial Resistance and Healthcare Associated Infections
References
1. Hillier S, Roberts Z, Dunstan F, Butler C. Prior antibiotics and
risk of antibiotic-resistant community-acquired urinary tract infection:
a case-control
study. Journal of Antimicrobial Chemotherapy 2007;60:92–9
2. Garau J. Other antimicrobials of interest in the era of extended-spectrum
beta-lactamases: fosfomycin, nitrofurantoin and tigecycline. Clinical Microbiology
and Infection 2008;14(s1):198–202
3. Draft guidance on clostridium difficile (PDF 1.2MB)
(accessed 25 April
2008)
4. Nathwani D, Morgan M, Masterton RF, Dryden M, Cookson BD, French G et
al. Guidelines for UK practice for the diagnosis and management of methicillin-resistant
Staphylococcus aureus (MRSA) infections presenting in the community. Journal
of Antimicrobial Chemotherapy 2008;61:976–94
5. Howe R. Don’t include trimethoprim. BMJ 2008;336:787
Trimethoprim is not suitable for treatment in pharmacy
From Dr C. Edwards, MRPharmS, and Dr J. Sarma, MRCPath
We agree with Colette McCreedy (PJ, 19 April 2008, p459) that
changing trimethoprim from POM to P status may
not increase its usage, but there are other
reasons why trimethoprim may not be suitable to treat urinary tract infections
(UTIs) in community pharmacy, even at current levels of use.
We responded to the Medicines and Healthcare products Regulatory Agency consultation
document, which proposed the reclassification of trimethoprim, in August 2005
and the main points were re-emphasised
in a letter to you (PJ, 13 August 2005,
p193). We think that it is worth reminding supporters of this POM to P reclassification
of our main concerns:
• In our experience locally, the resistance of urinary coliforms to
trimethoprim from samples in primary care has been rising and is now
around 30 per cent. Such a significant degree of resistance makes one
question its efficacy as a first-line treatment, whether usage increases
or not. Although it may be argued that many urine samples sent to laboratories
are from a skewed sample of patients who have failed first-line treatment,
there are parallels with amoxicillin, which at one time was first-line
choice in the management of UTIs.
• About 50 per cent of urine samples have negative cultures and this throws
into question the appropriateness of antibiotic treatment for many patients.
• The MHRA consultation document quoted a report of a working party of the
British Society for Antimicrobial Chemotherapy that stated that antibiotics
could be suitable for self-medication for uncomplicated lower UTIs, provided
they are agents indicated only for UTI. Trimethoprim is not such a drug because,
as Robin Howe pointed out in his letter to the BMJ (12 April 2008, p787), trimethoprim
may be used to treat other infections, including MRSA. Nitrofurantoin would
be a more appropriate choice.
Locally, the level of resistance to nitrofurantoin is about 10 per cent.
We think this drug is a more suitable agent for OTC treatment of UTIs.
Clive Edwards
Newcastle upon Tyne
Jayanta Sarma
Consultant Microbiologist, Northumbria Healthcare
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