Antibiotic resistant organisms in respiratory disease. 98/1
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Introduction
Antibiotic resistance is an important consideration when treating
bacterial infections and there is some evidence that resistance
is becoming more widespread. Bacterial antibiotic resistance can
either be intrinsic or acquired. For example, some bacterial species,
such as mycoplasmas, are intrinsically not sensitive to penicillin.
The second phenomenon, where a normally sensitive organism acquires
resistance for some reason, has long been recognised. The acquisition
and rapid spread of resistance to commonly used antibiotics in
common respiratory pathogens has become a widespread problem in
recent years. There are three main settings where this phenomenon
has been observed (figure 1).
Figure 1:The main types of antibiotic
resistant bacteria
Epidemiology
Streptococcus pneumoniae and Haemophilus influenzae
are the two most important bacterial causes of respiratory infection.
Penicillins and macrolides are the antibiotics most commonly used
to treat such infections.
Figure 2:Trends in the prevalence
of antibiotic resistance of pneumococci
S. pneumoniae
Penicillin resistance in S. pneumoniae was first observed
in New Guinea in 1967 and was subsequently found to be common
in South Africa and Spain. It is now a global phenomenon and all
countries which have been monitoring S. pneumoniae resistance
have found a steady rise in its frequency. In the UK, levels of
such resistance have generally been lower than in most other countries,
but even here this is increasing (figure 2). Penicillin resistant
pneumococci (PRP) are found more commonly in children and in hospital-acquired
infections. Macrolide resistance in S. pneumoniae has received
less attention than penicillin resistance but also appears to
be increasing and in the UK is over twice as common as penicillin
resistance.
H. influenzae
Aminopenicillin resistance in H. influenzae is also rising
and shows wide geographic variation. One study showed resistance
rates of 6.3% in Germany, 9.7% in the UK, 19.3% in France and
32.2% in Spain.
Causation
Figure 3:Annual ß-lactam prescriptions
Figure 4:Annual macrolide prescriptions
The root cause of acquired resistance is exposure to antibiotics
and these figures show how use of most antibiotics is steadily
rising. About half of all antibiotic use is in veterinary work.
By suppressing the growth of sensitive strains, antibiotic use
favours the development of a resistant strain which may then spread
between individuals, from country to country and continent to
continent by commensal organisms, as has been clearly documented
for penicillin resistant pneumococci.
The actual mechanism of resistance varies from antibiotic to
antibiotic and organism to organism. For example, penicillin resistance
in pneumococci occurs through changes in the penicillin binding
proteins in the cell wall. In contrast, aminopenicillin resistance
in H. influenzae is predominantly caused by b-lactamase production.
Clinical relevance
Penicillin resistance is a graded phenomenon and the effectiveness
of an antibiotic depends on the concentration at the site of the
bacteria being above the level which inhibits bacterial growth.
This means that an alternative antibiotic will be required for
organisms with borderline resistance isolated from a site where
penicillins penetrate poorly, such as the central nervous system.
For the same organism at a site where penicillins penetrate well,
such as the lung, penicillins can still be effective.
Most PRP isolates are of only intermediate resistance, and so
penicillins in high dose are still effective treatment in most
pneumococcal respiratory infections. Little clinical experience
has been gained with highly resistant PRP, but it is likely that
alternative antibiotics should be used in these cases.
Macrolide resistant pneumococci should not be treated with erythromycin.
It is not known whether the newer macrolides, which have better
tissue penetration, remain effective. Aminopenicillin resistant
H. influenzae should be treated with alternative antibiotics.
Since most patients are treated without knowledge of the causative
pathogen, let alone its antibiotic sensitivities, information
on the prevalence of resistance in the local population is important
for guiding empirical therapy. While it is not clear at what level
changes should be made, continued surveillance is an important
tool in the management of the problem and the patient.
Sources
Johnson AP, Speller DCE et al.
Brit Med J 1996; 312:1454-6
Baquero F. J Antimicrob Chemother
1996;38 Suppl A:117-32
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