Mycobacterium tuberculosis complex drug resistance in Italy.
Isolates from all consecutive, definite cases diagnosed in TB units during 1998 through 2001 were included. When a patient's previous treatment status was unknown or dubious, the case was excluded. Resistant cases from patients with and without history of previous treatment were stratified by the following categories: any resistance, monoresistance, resistance to both isoniazid and rifampicin (known as rifampin in the United States), or resistance to three or more drugs. Confidence intervals were also calculated. Participating laboratories were allowed to use the WHO-recommended drug susceptibility method with which they were most familiar: absolute concentration method, resistance ratio method, proportion method and its variants, or BACTEC 460 radiometric method (Becton Dickinson, Towson, MD) (6,7). Among the laboratories reporting results by the proportion method, the majority used Lowenstein-Jensen medium while others used liquid nonradiometric media (8). Each of the 20 M. tuberculosis strains was tested against firstline drugs by the Italian Reference Laboratories in Rome and Milan and classified as resistant or susceptible. Results were compared to the standard criterion, represented by the judicial results of the WHO/IUATLD Global Network of Supranational Laboratories (9). Each network laboratory was validated for each firstline drug when no more than two results were different from the standard criterion.
The prevalence of drug resistance detected during the period 1998-2001 is summarized in the Table. Among previously untreated cases, the prevalence of resistance to isoniazid, rifampicin, ethambutol, and streptomycin was 3.5%, 0.8%, 0.5%, and 4.3%, respectively, while prevalence of multidrug resistance (resistance to at least isoniazid and rifampicin) and polyresistanee (resistance to two or more drugs, but not both isoniazid and rifampicin) was 1.1% and 2.4%, respectively. No difference was found by stratifying prevalence data by age, sex, or HIV status. In isolates from patients with previous treatment, drug resistance was found to be almost four times higher than in those from patients with no history of treatment. However, the prevalence of monoresistant strains was low (5.3%, 4.3%, 0.3%, and 4.3% for isoniazid, rifampicin, ethambutol, and streptomycin, respectively) compared with the prevalence of multidrug-resistant strains whose rate reached a peak of 30.4%.
Drug-resistant TB in countries with good national control programs, such as in Western Europe, is not commonly a major health problem, although increasing immigration prompts public health authorities to maintain vigilant surveillance systems. The results of our study indicate that throughout Italy, prevalence of resistance to firstline drugs and multidrug resistance among isolates from new cases was consistently low over the 4-year survey period. Prevalence of multidrug resistance among isolates from previously treated patients was high, although a downward trend could be demonstrated during the last 2 years. Since almost 2 out of 10 isolates resistant to rifampicin were multidrug resistant, using rapid molecular methods to identify rifampicin resistance in questionable cases appears cost-effective to facilitate early detection and control of multidrug-resistant TB (10). Resistance to isoniazid is associated with immigration from countries where isoniazid was used extensively in the past. This information is a useful tool for clinicians, as isoniazid resistance may be suspected early in the disease and properly treated. Finally, the finding of substantial multidrug resistance among isolates from previously treated patients, combined with the evidence that immigrants from areas where isoniazid resistance is endemic contribute substantially to the number of new TB cases in Italy every year, strongly suggests that public health action is needed to improve treatment outcomes.
Table. Pattern of drug resistance among strains from tuberculosis patients with and without a history of treatment, Italy 1998-2001 (a) No history of previous treatment Tested MTB strains No. % 95% CI Total tested 2,117 100 -- Fully sensitive 1,847 87.2 85.8 to 88.6 Any drug 270 12.7 11.4 to 14.2 INH 75 3.5 2.8 to 4.4 RMP 17 0.8 0.5 to 1.3 EMB 10 0.5 0.2 to 0.8 SM 93 4.3 3.6 to 5.3 Resistant to both INH and RMP 8 0.40 0.8 to 0.7 Resistant to INH, RMP, EMB 2 0.10 0.01 to 0.3 Resistant to INH, RMP, SM 6 0.30 0.1 to 0.6 Resistant to INH, RMP, EMB, SM 7 0.30 0.1 to 0.6 History of previous treatment Tested MTB strains No. % 95% CI Total tested 322 100 -- Fully sensitive 155 48.1 42.7 to 53.6 Any drug 167 51.8 46.4 to 57.3 INH 17 5.3 3.2 to 8.2 RMP 14 4.3 2.5 to 7.0 EMB 1 0.3 0.02 to 1.5 SM 14 4.3 2.5 to 7.0 Resistant to both INH and RMP 24 7.5 4.9 to 10.7 Resistant to INH, RMP, EMB 19 6.0 3.7 to 8.9 Resistant to INH, RMP, SM 23 7.1 4.7 to 10.4 Resistant to INH, RMP, EMB, SM 32 9.9 7.0 to 13.5 (a) MTB, Mycobacterium tuberculosis complex; CI, confidence interval; INH, isoniazid; RMP, rifampicin; EMB, ethambutol; SM, streptomycin.
This work was funded independently by the Istituto Superiore di Sanita-Rome (National TB Project) and the World Health Organization. It was also supported by a grant (TBC1) from the Associazione Italiana Pneumologi Ospedalieri (AIPO).
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Address for correspondence: Claudio Piersimoni, Department of Clinical Microbiology, General Hospital "Umberto I," Via Conca, I-60020, Ancona, Italy; fax: 39-071-596-4184; email: email@example.com
Giovanni B. Migliori, * Rosella Centis, * Lanfranco Fattorini, * Giorgio Besozzi, * Cesare Saltini, * Claudio Scarparo, * Daniela Cirillo, * Andrea Gori, * Antonio Cassone, * and Claudio Piersimoni *
* SMIRA (Italian Multicentre Study on Resistance to Antituberculosis Drugs) Coordinating Committee
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|Publication:||Emerging Infectious Diseases|
|Article Type:||Letter to the Editor|
|Date:||Apr 1, 2004|
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