DIARRHOEA, stomach cramps and ruptured bowels were among the surprises that
lay in store for patients staying in the orthopaedic ward at the Royal Devon and
Exeter Hospital in July 1999. These abdominal horrors struck 65 people who were
in for routine operations. The culprit was Clostridium difficile, a
potentially fatal infection that rapidly spread from one patient to another.
Ironically, these patients were susceptible to the bug because of an
antibiotic they were taking to protect their wounds from infection after
surgery. The drug was cefuroxime鈥攁 common choice in these circumstances.
But as well as preventing wound infections, cefuroxime wipes out most of the
bacteria in the gut. These 鈥渇riendly鈥� organisms normally have a protective
effect, stopping harmful bugs from taking hold. Their absence gave
C. difficile the perfect opportunity to take over.
Staff at the hospital tackled the problem in two ways. They tried to improve
hygiene on the ward. And they stopped giving everyone cefuroxime. In its place,
patients were given the antibiotic vancomycin, which doesn鈥檛 wipe out gut
bacteria the way cefuroxime does. Patients became less susceptible to C.
difficile diarrhoea, and by November the outbreak was over. Almost a year
later, the doctors in Exeter are still giving vancomycin to every patient they
operate on, and C. difficile has not returned.
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Last resort
It sounds like a success story. The patients and their doctors are happy, as
are the hospital鈥檚 financial administrators, since each case of
C. difficile costs 拢4000 to treat.
But many public health experts are worried, because vancomycin is one of the
few weapons left against 鈥渟uperbugs鈥� such as methicillin-resistant
Staphylococcus aureus(MRSA), which most antibiotics can鈥檛 touch. 鈥淚t鈥檚 a
drug of last resort,鈥� says Richard Wise, president of the British Society for
Antimicrobial Chemotherapy (BSAC).
If superbugs become resistant to vancomycin as well, we may face untreatable
life-threatening infections. Vancomycin-resistant strains of
Enterococcus bacteria (VRE) are becoming increasingly common. Three years
ago MRSA bugs partly resistant to vancomycin emerged in Japan
(快猫短视频, 3 May 1997, p 5).
Such strains have since appeared in the US and
Europe, including two cases in Glasgow last year.
David Jenkins, a clinical microbiologist at Leicester Public Health
Laboratory, says vancomycin is being routinely used for prophylaxis in many
hospitals. 鈥淓xeter is certainly not an exception.鈥� But he notes the exact scale
of the practice is unknown because little information is gathered routinely.
Any use of antibiotics increases the risk that resistant bacteria will
emerge. And using drugs prophylactically means giving them not just to people
who are ill but to every patient who is at risk of infection. So why use this
precious drug for this way?
鈥淰ancomycin is of benefit to the patients, with only a small theoretical risk
of resistance,鈥� says Terry Riordan from the Public Health Laboratory in Exeter,
a member of the team that made the decision. He says vancomycin resistance is
only likely to arise where patients are given prolonged courses of the drug. 鈥淲e
are giving a single dose, and patients have a relatively short hospital
蝉迟补测.鈥�
Consultant epidemiologist Richard Mayon-White from Oxfordshire Health
Authority is far from reassured. 鈥淚t is perfectly reasonable to argue that
single-dose antibiotics are less likely to encourage resistance,鈥� he says. 鈥淏ut
using it in more people increases the likelihood of giving the antibiotic to
somebody who is carrying an organism poised to become vancomycin resistant . . .
if you are giving it to large numbers of patients, the single doses add up.鈥�
Both Mayon-White and Wise say that vancomycin should only be used to prevent
life-threatening MRSA infections, not C. difficile.
Pharmacoeconomist Peter Davey of the Medicines Monitoring Unit at Dundee
University thinks the events in Exeter highlight a wider problem. Doctors are
worried that the bugs threatening their patients might be antibiotic resistant,
he says. So they go straight to drugs which they are confident will work first
time.
But Davey says that there鈥檚 no evidence that vancomycin is better than other
drugs at preventing infections. 鈥淭he trials that have been done that you would
have thought would show an advantage for vancomycin鈥攈aven鈥檛. Anybody who
is saying `I want to do the best for the patient鈥� can鈥檛 produce a shred of
evidence to say that vancomycin is better.鈥�
There are also signs that doctors are prescribing longer courses of
antibiotics than are necessary for prophylaxis, just to make sure. 鈥淭he evidence
is that one dose is enough,鈥� says Jenkins. 鈥淏ut it is hard to convince the
surgeons. In the hospital here, [Leicester Royal Infirmary] antibiotics are
often given for 48 hours following cardiac surgery. When something is working,
they don鈥檛 want to change.鈥� In an audit in Aberdeen, 62 per cent of patients
undergoing general or orthopaedic surgery were given three doses or more.
The longer courses increase the risk of resistance.
There is also concern that doctors鈥� enthusiasm for drugs such as vancomycin
could be masking a hygiene crisis in our hospitals. 鈥淪ometimes antibiotic
prophylaxis is seen as an alternative to hygiene,鈥� says Jenkins.
Another problem is a lack of coherent advice about what drugs to use for
prophylaxis, and when. 鈥淲e don鈥檛 issue any national guidelines,鈥� says a
spokeswoman for the Department of Health. 鈥淭he situation concerning antibiotic
resistance can vary from hospital to hospital, so it makes sense for the people
working at the hospital to make the decision.鈥�
That sounds fine in theory. But in a survey of hospitals鈥� antibiotic control
measures published in 1994 only 51 per cent of them had a policy for surgical
prophylaxis. Of these, only half monitored compliance.
The dilemma over how and when to use vancomycin isn鈥檛 confined to Britain.
American hospitals also take a pragmatic approach. Pamela Lipsett, director of
surgical intensive care at Johns Hopkins Hospital in Baltimore, describes the
prophylactic use of vancomycin as 鈥渧ery limited and in general strongly and
officially discouraged by the federal Centers for Disease Control and
Prevention鈥�. Nonetheless, she adds, there may be clinical circumstances in which
the use of vancomycin is reasonable. 鈥淭his might include a hospital with a high
baseline rate of MRSA infection.鈥�
There are plenty of those. Around 14,000 people a year die from infections
acquired in US hospitals. The World Health Organization in its annual report on
infectious diseases notes this year that 鈥減articularly in the US most
Staphylococcusand Enterococcusinfections are increasingly
颈苍迟谤补肠迟补产濒别.鈥�
Jenkins suggests we need to change how we think about preventing infection.
鈥淭he priority should be to reduce antibiotic resistance so that we can still
treat the infections that occur, rather than trying to prevent every single
one,鈥� he says.
But the picture looks rather different if you happen to be one of the unlucky
ones with an infection that could have been prevented with more aggressive use
of antibiotics. 鈥淎 physician鈥檚 first duty is to his patient,鈥� says Alan Johnson
from the Public Health Laboratory Service in London. 鈥淚f in specific
circumstances that means going against the guidelines, then one has to do that.鈥�
Riordan agrees. 鈥淥ur first priority is to have effective prophylaxis for the
prevention of joint infection. Our second priority is to minimise the risk of
C. difficile infection.鈥� Preventing antibiotic resistance comes low on
the list.
Wise insists there should be a wider debate. 鈥淚s prescribing drugs for the
betterment of a large number of people more important for society than the needs
of one individual patient?鈥� he asks. 鈥淭hese are matters that society has got to
take choices on.鈥�
With WHO experts warning that the rise of antibiotic resistance threatens to
undermine even the most routine surgery, a decision needs to be made.
