The global increase in tuberculosis which has occurred in the 1980s and 1990s, and the associated re-emergence of resistance to antituberculous drugs, has focused attention on recent trends in resistance in Europe and the United States.1–3 In the United Kingdom overall drug resistance levels have been low.4 A surveillance system, the UK Mycobacterial Resistance Network (MYCOBNET), was established in 1994 by the Public Health Laboratory Service to record drug resistance in laboratory isolates of tuberculosis. We used data from this network to examine resistance among people with newly diagnosed tuberculosis.
Subjects, methods, and results
We analysed the data on initial isolates of Mycobacterium tuberculosis complex referred to United Kingdom reference laboratories5 during 1994 to 1996. Initial isolates were defined as the first positive culture from a person from whom no positive culture had been recorded during the past 12 months. Since M bovis isolates are intrinsically resistant to pyrazinamide these were excluded from estimates of pyrazinamide resistance.
We calculated the resistance to each first line antibiotic and multidrug resistance (resistance to isoniazid and rifampicin with or without resistance to other antituberculous drugs) together with 95% confidence intervals. The incidence was assumed to follow the Poisson distribution. A χ2 test for trend was used to investigate changes in isoniazid and multidrug resistance over time.
Of 10 142 isolates recorded for 1994-6, 599 (5.9%; 95% confidence interval 5.5% to 6.4%) were resistant to isoniazid, 174 (1.7%; 1.5% to 2.0%) to rifampicin, 90/7494 (1.2%; 1.0% to 1.5%) to pyrazinamide; and 71 (0.7%; 0.6% to 0.9%) to ethambutol; 152 (1.5%; 1.3% to 1.8%) showed multidrug resistance.
The number and proportion of isolates resistant to isoniazid or with multidrug resistance increased from 1994 to 1996 (table). However, these increases were not significant (χ2=0.797, df =1, P=0.372 for isoniazid resistance; χ2 =1.253, df =1, P= 0.263 for multidrug resistance). People aged 15 to 44 had the highest percentage of initial isolates with isoniazid resistance (8.1%) and multidrug resistance (2.0%) (table). A slightly higher percentage of males than females showed isoniazid resistance (6.2% v 5.6%) and multidrug resistance (1.8% v 1.2%).
In all, 568 (5.6%) patients had a known history of tuberculosis. These patients had a higher percentage of isoniazid resistance (18.8% v 5.1%) and higher percentage of multidrug resistance (11.3% v 0.9%) than those with no known history (table).
Resistance was higher among patients resident in England than in the rest of the United Kingdom (6.2% v 3.8% for isoniazid resistance, and 1.6% v 0.9% for multidrug resistance). Furthermore, patients diagnosed in London were more likely to have isolates resistant to isoniazid (8.0% v 4.7%) or multidrug resistant (2.3% v 1.0%) than those diagnosed outside London.
Resistance to isoniazid and multidrug resistance were observed among 13.5% and 6.1% respectively of the 460 patients known to be infected with HIV compared with 5.5% and 1.3% among the combined group of six HIV negative and 9676 patients whose HIV status was unknown.
Comment
This preliminary analysis of resistance in laboratory isolates establishes the importance of drug resistance in the United Kingdom and the need for continuing surveillance. Although overall resistance is low and the small increase was not significant, resistance remains a concern and should be considered in all newly detected cases. Action to prevent the emergence of new resistance by the supervision and completion of treatment and to stop the spread of established resistance is essential.
Table.
Isoniazid and multidrug resistance in isolates from patients with newly diagnosed tuberculosis in United Kingdom, 1994-6
| All Isolates | Isoniazid resistant
|
Multidrug resistant
|
||||
|---|---|---|---|---|---|---|
| No (%) | 95% CI | No (%) | 95% CI | |||
| All 1994-6 | 10 142 | 599 (5.9) | 5.5 to 6.4 | 152 (1.5) | 1.3 to 1.8 | |
| Year: | ||||||
| 1994 | 3 253 | 181 (5.6) | 4.8 to 6.4 | 43 (1.3) | 1.0 to 1.8 | |
| 1995 | 3 254 | 197 (6.1) | 5.3 to 7.0 | 49 (1.5) | 1.1 to 2.0 | |
| 1996 | 3 635 | 221 (6.1) | 5.3 to 6.9 | 60 (1.7) | 1.3 to 2.1 | |
| Age (years): | ||||||
| 0-14 | 185 | 8 (4.3) | 2.2 to 8.6 | 2 (1.1) | 0.3 to 4.3 | |
| 15-44 | 4 792 | 389 (8.1) | 7.3 to 9.0 | 95 (2.0) | 1.6 to 2.4 | |
| 45-64 | 2 224 | 119 (5.4) | 4.5 to 6.4 | 33 (1.5) | 1.1 to 2.1 | |
| ⩾65 | 2 492 | 58 (2.3) | 1.8 to 3.0 | 17 (0.7) | 0.4 to 1.1 | |
| Unknown | 449 | 25 (5.6) | 3.8 to 8.2 | 5 (1.1) | 0.5 to 2.7 | |
| Sex: | ||||||
| Male | 5 780 | 361 (6.2) | 5.6 to 6.9 | 105 (1.8) | 1.5 to 2.2 | |
| Female | 3 983 | 224 (5.6) | 4.9 to 6.4 | 46 (1.2) | 0.9 to 1.5 | |
| Sex unknown | 379 | 14 (3.7) | 2.2 to 6.2 | 1 (0.3) | 0.0 to 1.9 | |
| History of tuberculosis: | ||||||
| Previous tuberculosis | 568 | 107 (18.8) | 14.8 to 21.6 | 64 (11.3) | 8.4 to 13.7 | |
| No known previous tuberculosis | 9 574 | 492 (5.1) | 4.7 to 5.6 | 88 (0.9) | 0.7 to 1.1 | |
| Country in which diagnosed: | ||||||
| England | 8 731 | 546 (6.3) | 5.8 to 6.8 | 140 (1.6) | 1.4 to 1.9 | |
| Northern Ireland | 170 | 6 (3.5) | 1.6 to 7.9 | 1 (0.6) | 0.1 to 4.2 | |
| Scotland | 930 | 33 (3.5) | 2.5 to 5.0 | 8 (0.9) | 0.4 to 1.7 | |
| Wales | 311 | 14 (4.5) | 2.7 to 7.6 | 3 (1.0) | 0.3 to 3.0 | |
| Place of diagnosis: | ||||||
| London | 3 731 | 299 (8.0) | 7.2 to 9.0 | 85 (2.3) | 1.8 to 2.8 | |
| Outside London | 6 411 | 300 (4.7) | 4.2 to 5.2 | 67 (1.0) | 0.8 to 1.3 | |
| HIV infection: | ||||||
| Positive | 460 | 62 (13.5) | 10.5 to 17.3 | 28 (6.1) | 4.2 to 8.8 | |
| Negative or unknown | 9 682 | 537 (5.5) | 5.1 to 6.0 | 124 (1.3) | 1.1 to 1.5 | |
Acknowledgments
We thank the following for contributing to data collection, and to developing the surveillance system: B Bannister, S Bex, M Cocksedge, M Connolly, I Farrell, W Ferguson, J Grace-Parker, G Gleissberg, G Harris, A Hayward, E Hemingway, R Henry, D Howitt, P Jenkins, E Kazcmarski, J Leat, R Mallard, F Marais, A Middleton, J Mobray, P Morrell, C Newman, P Ormerod, R Poll, G Ratcliffe, A Rayner, M Roberts, R Schofield, R Shaw, G Stewart, D Tompkins, T Turner, T Wilson, and M Yates.
Footnotes
Funding: Public Health Laboratory Service.
Competing interests: None declared.
References
- 1.Raviglione MC, Snider DE, Kochi A. Global epidemiology of tuberculosis. JAMA. 1996;273:220–226. [PubMed] [Google Scholar]
- 2.Hayward AC, Watson JM. Tuberculosis in England and Wales 1982-1993: notifications exceeded predictions. Commun Dis Rep. 1995;5:R29–R33. [PubMed] [Google Scholar]
- 3.Frieden TR, Sterling T, Pablos-Mendez A, Kilburn JO, Cauthen GM, Dooley SW. The emergence of drug-resistant tuberculosis in New York city. N Engl J Med. 1993;328:521–526. doi: 10.1056/NEJM199302253280801. [DOI] [PubMed] [Google Scholar]
- 4.Warburton ARE, Jenkins PA, Waight PA, Watson JM. Drug resistance in initial isolates of Mycobacterium tuberculosis in England and Wales, 1982-1991. Commun Dis Rep CDR Rev. 1993;3:R175–R179. [PubMed] [Google Scholar]
- 5.Drobniewski FA, Magee JG, Smith EG, Williams R. PHLS mycobacteriology reference services in England and Wales. Commun Dis Rep. 1997;7:R106–R109. [PubMed] [Google Scholar]