How do you choose antibiotic treatment?Commentary: Resist jumping to conclusionsCommentary: A matter of good clinical practiceCommentary: Honesty is the best policy
BMJ 1999; 318 doi: https://doi.org/10.1136/bmj.318.7198.1614 (Published 12 June 1999) Cite this as: BMJ 1999;318:1614
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EDITOR - It is surprising that neither Leibovici et al.1 nor the
commentaries mention the issue of antibiotic induced Clostridium difficile
infection when discussing the appropriateness of antimicrobial treatment
of a severe urinary tract infection in a 83 year old male. Despite
evidence of under-reporting,2 notifications of C. difficile continue to
increase in England and Wales, with over 17000 predominantly hospital-
acquired cases reported to the Communicable Disease Surveillance Centre in
1998, 80% of which affect the elderly. Cephalosporins such as cefuroxime
and cefotaxime have been widely cited as predisposing to C. difficile
infection. Leibovici et al. consider cephalosporins but not
fluoroquinolones such as ciprofloxacin or ureidopenicillins including
piperacillin-tazobactam for the empirical treatment of severe sepsis.
There are data supporting a lower propensity of aminoglycosides,
fluoroquinolones and ureidopenicillins to induce C. difficile infection.3
A prospective, geriatric ward crossover study found that empirical
treatment with piperacillin-tazobactam was seven-fold less likely to
induce C. difficile infection than cefotaxime.4 Notably, the proportion
of UK hospitals reporting a change in antibiotic policies due to C.
difficile infection increased from 5% to 20% between 1993 and 1996.2
Elderly patients with nosocomial C. difficile infection stay a median of
three weeks longer in hospital, two weeks of which is spent in scarce
isolation facilities, and an excess cost of more than £4000 per case has
been documented in a case control study.5 Such costs dwarf those
associated with the acquisition costs of antibiotics and cannot be ignored
in cost-effectiveness analyses of antimicrobial treatment.
Care must be taken when extrapolating study average gains to specific
patient scenarios. Leibovici et al.1 refer to data derived from patients
with a median age of 72 years and hospital- or community-acquired
bacteraemia or fungaemia. Outcome in an 82 year old with community-
acquired urinary tract infection may well differ from the earlier
composite study findings. Also, Leibovici et al.1 give antibiotic
susceptibility rates for bacteraemic isolates, which include community and
hospital pathogens, thus biasing towards resistant strains. Presumably,
the figure of 77% susceptibility to gentamicin includes Gram-positive and
Gram-negative isolates; community-acquired Gram-negative isolates are
likely to be markedly more susceptible to gentamicin. Once-daily
gentamicin may be associated with lower nephrotoxicity and in combination
with ampicillin would be a potential therapeutic choice.
In short the choice of antibiotic therapy is a complex issue.
Workable antibiotic policies should aim to guide optimal therapy, but will
inevitably contain compromises and assumptions, not least because locally
applicable and patient specific data are rarely available. While
‘appropriate’ antimicrobial therapy is a laudable goal, side effects
cannot be relegated as secondary considerations.
Mark H Wilcox Senior Lecturer / Consultant
Jon Sandoe Specialist Registrar
Department of Microbiology, The General Infirmary and The University of
Leeds, Leeds LS1 3EX.
References
1 Leibovici L, Shraga I, Andreassen S. How do you choose antibiotic
treatment? BMJ 1999; 318:1614-8. (12 June).
2 Wilcox MH, Smyth ET. Incidence and impact of Clostridium difficile
infection in the UK, 1993-1996. J Hosp Infect 1998;39:181-7.
3 Anand A, Bashey B, Mir T, Glatt AE. Epidemiology, clinical
manifestations, and outcome of Clostridium difficile diarrhoea. Am J
Gastroenterol 1994;89:519-23.
4 Settle CD, Wilcox MH, Fawley WN, Corrado OJ, Hawkey PM.
Prospective study of the risk of Clostridium difficile diarrhoea in
elderly patients following treatment with cefotaxime or piperacillin-
tazobactam. Alimentary Pharmacology & Therapeutics 1998;12:1217-23.
5 Wilcox MH, Cunniffe JG, Trundle C, Redpath C. Financial burden of
hospital-acquired Clostridum difficile infection. J Hosp Infect
1996;34:23-30.
Competing interests: No competing interests
Dear Sir
I read with interest the articles and commentaries (1) on choosing
antibiotic treatment in an elderly patient admitted from the community
with a severe urinary tract infection. The clinical and public health
aspects are indeed important. However, epidemiological considerations
must also inform the individual's empirical therapeutic decision making
and this does not seem to have been considered in this case history.
These factors are also essential to inform the design of treatment
algorithms or cost-models.
We are not told whether the patient had a recent hospital admission,
if this was to the same hospital and which department. The occurrence of
resistance rates may vary within hospitals and certainly between
hospitals. A patient's previous hospitalisations can be complex. The
possible therapeutic consequences are well illustrated in a recent
incident where a patient from the community had a history of admission to
a hospital abroad. Subsequent inter-hospital transfers in the UK resulted
in the spread of a multiple antibiotic-resistant strain of Klebsiella
pneumoniae (2). Thinking globally during history taking can inform
individual patient empirical antimicrobial prescribing.
As importantly, we are not informed whether there were any urinary
tract manipulations, such as surgery or catheterisation. These will
provide additional opportunities for resistant organisms from other
patients to be transferred directly or indirectly via the faecal flora to
his urinary tract.
The development of new tools for modelling and informing prescribing
is much needed but will require these epidemiological data. It is perhaps
unfortunate that this opportunity was not taken to remind clinicians to
employ this approach in this otherwise very valuable exercise.
Barry Cookson
1 Leibovici L, Shraga H., Andreassen S. How do you choose antibiotic
treatment? BMJ 1999; 18:1614-18
2 Cookson B, Johnson AP, Azadian B, Paul J et al, International inter-
and intrahospital patient spread of a multiple antibiotic-resistant strain
of Klebsiella pneumoniae. J Infect Dis 1995;171:511-513.
Competing interests: No competing interests
This excellent discussion about the prescription of antimicrobials
makes a fundamental point - the right antibiotic at the right time saves
lives - and we should not forget it! Yet as the various commentators point
out it is not always easy to chose the right antimicrobial since we know
that all drugs have side effects, some are expensive and some are more
poisonous than others.
In the setting of intensive care, many of our patients have septic
shock as the presentation of their infection and we usually only get "one
bite" at that particular cherry. I try to teach our residents a few of the
"see-saw" principles of antimicrobial prescribing that I have learnt along
the way.
Firstly, as I have said before and wish to ephasise again, the right
drug in the right dose (big) at the right time does save lives.
Surprisingly to some, antibiotics do actually work and you need to get it
right from the start. Secondly, there is not much point in saving your
"best" antibiotic for the post-mortem room - it does not work very well
down there. Next, we treat patients - we do not treat fevers, white cell
counts, chest-X rays nor cultures! But on the other hand, just because the
laboratory cannot grow some thing does not mean that there are no germs
there causing trouble! And it does not mean that you should not consult
them. You should. Finally, try and avoid poisoning the patient but always
remember (and keep telling the managers) that saving lives costs money.
There is nothing cheaper than a quick death!
I gratefully acknowledge my fine teachers at Guy's and St. Thomas's
Hospitals - Norman Simmons, Susan Ewkyn and Ron Bradley - who drummed
these principles into my head.
David Bihari
Competing interests: No competing interests
How do you choose antibiotic treatment? Consider the risks of Clostridium difficile in the elderly.
Clostridium difficile in the elderly
Leibovici et al, in their recent article on choosing an antibiotic,
state that this "entails analysing the benefits and detriments associated
with each drug and balancing each one against the other".1
They outline the case of an 83 year old man with urosepsis admitted
at night and consider four therapeutic agents; ampicillin, gentamicin, a
third generation cephalosporin and imipenem. The junior doctor caring for
the patient opts for the cephalosporin and Leibovici et al support this.
In the article and following commentary no reference is made to the
risk of Clostridium difficile infection. This is an emergent nosocomial
infection in UK hospitals and over 80% of cases occur in those over 65
years old.2
While C. difficile infection is related to a number of factors, prior
antibiotic use is a recurrent association, especially clindamycin and
injectable cephalosporin.3 In addition, it has been shown that removal of
cephalosporins, such as cefuroxime, from medical ward treatment guidelines
can reduce the incidence of C. difficile infection in both epidemic and
endemic environments.4 Furthermore, a prospective crossover study carried
out on two well matched Care of the Elderly wards showed a marked decrease
in C. difficile colonisation and infection in those treated with
piperacillin/tazobactam compared to cefotaxime.5 Substitution of
cephalosporins by combinations of antibiotics including gentamicin,
trimethoprim, benzylpenicillin and ciprofloxacin, while reducing C.
difficile acquisition does not seem to affect mortality or length of stay,
indicating no penalty in terms of reduced clinical efficacy.4,5
Sadly Leibovici et al did not consider the possibility of use of
trimethoprim or quinolones in this clinical case. The use of both these
agents in urosepsis is more common than carbapenems in the UK.
We believe that the widespread promotion of intravenous
cephalosporins to treat infection is the elderly will only result in
excess acquisition of C. difficile infection, with resultant mortality,
morbidity and increased hospital costs which have been calculated at over
£4,000 per case.6 Promotion and policing of antimicrobial guidelines are
essential to ensure the rational use of antibiotics which includes the
risk of short term detrimental effects such as acquisition of C. difficile
infection as well as longer term ones such a emergence of resistance.
Yours sincerely
CLIODNA A M McNULTY
PHLS Primary Care Co-ordinator
ALASDAIR P MACGOWAN
Consultant Medical Microbiologist, North Bristol NHS Trust,
Southmead Hospital
References
1. Leibovici L, Shraga I and Andreassen S. How do you choose
antibiotic treatment? BMJ 1999;318:1614-6.
2. Djuretic T, Ryan MJ, Fleming DM, Wall PG. Infectious intestinal
disease in elderly people. Communicable Disease Report Weekly 1996;6:R107-
R112.
3. MacGowan AP, Feeney R, Brown I. McCulloch SY, Reeves DS and
Lovering AM. Healthcare resource utilisation and antimicrobial use in the
elderly patients with community-acquired lower respiratory tract infection
who develop Clostridium difficile-associated diarrhoea. Journal of
Antimicrobial Chemotherapy 1997;39:537-41.
4. McNulty CAM, Logan ML, Donald IP, Ennis D, Taylor D, Baldwin RN,
Bannerjee M, Cartwright KAV. Successful control of Clostridium difficile
infection in an elderly care unit through use of a restrictive antibiotic
policy. Journal of Antimicrobial Chemotherapy 1997;40:707-11.
5. Settle CD, Wilcox MH. Fawley WN, Corrado OJ and Hawkey PM.
Prospective study of the risk of Clostridium difficile diarrhoea in
elderly patients following treatment with cefotaxime or piperacillin-
tazobactam. Alimentary Pharmacology and Therapeutics 1998;12:1217-23.
6. Wilcox MH, Cunniffe JG, Trundle C and Redpath C. Financial burden
of hospital-acquired Clostridium difficile infection. Journal of Hospital
Infection 1996;34:23-30.
Competing interests: No competing interests