a Infection and Immunodeficiency Unit, Tayside University Hospitals NHS Trust, Kings Cross Hospital; b Medical Medicines Monitoring Unit, Department of Clinical Pharmacology and Therapeutics, Faculty of Medicine, University of Dundee; c Department of Microbiology, Tayside University Hospitals NHS Trust, Ninewells Hospital, Scotland, UK
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Abstract |
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Introduction |
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As with other bacterial species there is concern over the increasing prevalence of antibiotic resistance in isolates of H. influenzae. The major mechanism for antibiotic resistance is ß-lactamase production, which usually occurs as a result of plasmid-mediated TEM-1 ß-lactamase production. Less frequently, resistance occurs as a result of a chromosomal mutation leading to reduced affinity of penicillin-binding proteins (PBPs) or a combination of altered permeability and reduced affinity of PBPs.2,3
In the UK, surveillance for resistance in H. influenzae in clinical isolates has been carried out since the 1970s: in surveys of 17 UK laboratories in 1977 and 1981 there was an increase in ampicillin resistance from 1.6% to 6.6%.4 More recently, in the 19951996 cold season ß-lactamase production was found in 15.1% of UK isolates.5
In this study we investigated potential risk factors for the emergence of amoxycillin resistance in respiratory isolates of H. influenzae in adults, using computerized data linkage between the microbiology laboratory, hospital admission records and community antibiotic prescribing data.
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Materials and methods |
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Consecutive isolates of H. influenzae cultured from clinical specimens received between 1 March 1993 and 31 December 1995 were identified from the Tayside University Hospitals NHS Trust Department of Microbiology database. Both hospital and community specimens were included. Age and gender of patients and source (community or hospital) were recorded. For each adult only the first (incident) isolate received was included. Non-respiratory tract isolates were excluded.
Sensitivities to amoxycillin were determined by the standard Stokes' disc diffusion method using 2 and 3 µg discs on chocolate blood agar (Columbia base, Oxoid, Basingstoke, UK) incubated in CO2. Hospitalization and community prescribing of antibiotics in the 3 months before the isolation of H. influenzae was determined. Hospitalization and prescription of antibiotics in the 3 days before H. influenzae isolation were ignored as this period corresponds to the current clinical episode. Community prescribing was determined from the Medicines Monitoring Unit.6 Antibiotics were then classified as ß-lactams (e.g. penicillins or cephalosporins) or other. Hospitalization was determined through the Scottish Morbidity and Mortality Record database. Data were linked with individual microbiology records by a unique 10-digit patient identification number used both in hospital and community medical records. Community prescribing and hospitalization were investigated as risk factors for amoxycillin resistance.
Data were analysed using the epi-info 5 statistical calculator. Odds ratios (with 95% confidence intervals) were calculated using the 2 test with the Yates correction. Adjusted odds ratios were calculated by controlling for hospitalization and community prescribing of antibiotics. P values were calculated and regarded as significant if <0.05.
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Results |
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Discussion |
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In the present study the majority of the cohort were in hospital care (in-patient or out-patient) and therefore not representative of the general adult population. By inference it is likely that the proportion of patients with COPD would be higher than in the general population. The population was not a sample as in other studies7,8 but represented the cohort of adult patients with H. influenzae isolation. Children were excluded as the majority of isolates were from infants. The interactions between mother, antibiotics, hospitalization and infant raised concerns over the introduction of unnecessary bias into the study.
Recent hospitalization and the community prescription of antibiotics have been identified as risk factors for amoxycillin resistance in H. influenzae. Data on sampling rates within the community are not currently available although it is possible that general practitioners sample sputa after first-line antibiotics have failed. It is likely that hospitalized patients received antibiotics during their admission, although acquisition of ß-lactamase via plasmids from other Gram-negative organisms in the hospital may also be a factor. Whether isolates were pathogenic in the patients studied is uncertain. In many cases it is possible that the isolation of H. influenzae simply reflects carriage. Carriage of penicillin-resistant pneumococci in children in Iceland has recently been demonstrated to correlate with individual consumption of antimicrobials.9 The clinical importance of penicillin-resistant pneumococci in pneumonia has recently been questioned.10 There are currently few data on the outcome of amoxycillin-resistant H. influenzae infections.8
This study adds further evidence of the importance of community antibiotic prescribing in the genesis of antimicrobial resistance. Control measures to reduce the inappropriate use of antimicrobials in the community (as well as in the hospital) need to be reinforced.
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Notes |
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References |
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2 . van Klingeren, B., van Embden, J. D. A. & Dessens-Kroon, M. (1977). Plasmid-mediated chloramphenicol resistance in Haemophilus influenzae. Antimicrobial Agents and Chemotherapy 11, 3837.[ISI][Medline]
3 . Parr, T. R. & Bryan, L. E. (1984). Mechanism of resistance of an ampicillin-resistant ß-lactamase negative clinical isolate of Haemophilus influenzae type B to ß-lactam antibiotics. Antimicrobial Agents and Chemotherapy 25, 74753.[ISI][Medline]
4 . Philpott-Howard, J. & Williams, J. D. (1982). Increase in antibiotic resistance in Haemophilus influenzae in the United Kingdom since 1977: report of study group. British Medical Journal 284, 15979.[ISI][Medline]
5 . Felmingham, D., Robbins, M. J., Tesfaslasie, Y., Harding, I., Shrimpton, S. & Gruneberg, R. N. (1998). Antimicrobial susceptibility of community-acquired lower respiratory tract bacterial pathogens isolated in the UK during the 19951996 cold season. Journal of Antimicrobial Chemotherapy 41, 4115.[Abstract]
6 . MacDonald, T. M. & McDevitt, D. G. (1994). The Tayside Medicines Monitoring Unit (MEMO). In Pharmacoepidemiology, 2nd edn, (Strom, B. L., Ed.), pp. 24555. Wiley, Chichester.
7 . Sportel, J. H., Koeter, G. H., van Altena, R., Lowenberg, A. & Boersma, W. G. (1995). Relation between ß-lactamase producing bacteria and patient characteristics in chronic obstructive pulmonary disease (COPD). Thorax 50, 24953.[Abstract]
8 . Johnson, S. R., Thompson, R. C. F., Humphreys, H. & Macfarlane, J. T. (1996). Clinical features of patients with ß-lactamase-producing Haemophilus influenzae isolated from sputum. Journal of Antimicrobial Chemotherapy 38, 8814.[Abstract]
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Arason, V. A., Kristinsson, K. G., Sigurdsson, J. A., Stefansdottir, G., Molstad, S. & Gudmundsson, S. (1996). Do antimicrobials increase the carriage rate of penicillin resistant pneumococci in children? Cross sectional prevalence study. British Medical Journal 313, 38791.
10 . Einarsson, S., Kristjansson, M., Kristinsson, K. G., Kjartansson, G. & Jonsson, S. (1998). Pneumonia caused by penicillin-nonsusceptible and penicillin-susceptible pneumococci in adults: a casecontrol study. Scandinavian Journal of Infectious Diseases 30, 2536.[ISI][Medline]
Received 22 November 1999; returned 22 February 2000; revised 3 March 2000; accepted 3 April 2000