Mycobacterium tuberculosis complex drug resistance in Italy.To the Editor: The reemergence of tuberculosis (TB) as a global health problem over the past 2 decades, accompanied by increased drug resistance, which represents a serious problem both in terms of TB control and clinical management (1), prompted Western European countries to develop comprehensive national surveillance systems to monitor trends in TB drug resistance. Moreover, the World Health Organization (WHO) and the international Union Against Tuberculosis and Lung Disease lung disease Pulmonary disease Pulmonology Any condition causing or indicating impaired lung function Types of LD Obstructive lung disease–↓ in air flow caused by a narrowing or blockage of airways–eg, asthma, emphysema, chronic bronchitis; (IUATLD IUATLD International Union Against Tuberculosis and Lung Disease ) launched the Global Project on Anti-Tuberculosis Drug Resistance Surveillance to measure the prevalence of drug resistance by using standardized methods and assess its correlation with indicators of TB control (2,3). Since comprehensive data on resistance to firstline drugs were not available in Italy, a network of 20 regional laboratories was established to participate in this project. The Department of Bacteriology bacteriology
Study of bacteria. Modern understanding of bacterial forms dates from Ferdinand Cohn's classifications. Other researchers, such as Louis Pasteur, established the connection between bacteria and fermentation and disease. and Medical Mycology of Istituto Superiore di Sanita in Rome and the Mycobacteriology Unit of Istituto Villa Marelli in Milan (appointed respectively as Supranational Supranational
An international organization, or union, whereby member states transcend national boundaries
or interests to share in the decision-making and vote on issues pertaining to the wider grouping. Reference Laboratory and National Reference Laboratory) supervised and controlled the network of regional laboratories. The combination of reference laboratories in the network and associated clinical units, which covered 30% of definite cases reported each year (4), was known as SMIRA (Italian Multicentre Study on Resistance to Anti-Tuberculosis Drugs). The WHO/IUATLD coordinating center in Ottawa, Canada, provided a batch of 20 Mycobacterium tuberculosis Mycobacterium tuberculosis
Mycobacterium tuberculosis strains to set up proficiency testing to check drug susceptibility procedures in all SMIRA laboratories (5). We summarize the nature and extent of TB drug resistance in Italy between 1998 and 2001.
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 stratified /strat·i·fied/ (strat´i-fid) formed or arranged in layers.
Arranged in the form of layers or strata. by the following categories: any resistance, monoresistance, resistance to both isoniazid isoniazid (ī'sōnī`əzĭd), drug used to treat tuberculosis. Also known as isonicotinic acid hydrazide, isoniazid is the most effective antituberculosis drug currently available. and rifampicin rifampicin /rif·am·pi·cin/ (rif´am-pi-sin) rifampin.
a derivative of rifamycin; an antibacterial and antifungal agent used in the treatment of mycobacterial infections, actinomycosis and histoplasmosis. (known as rifampin rifampin (rĭfăm`pĭn), antibiotic used in the treatment of tuberculosis. It is also used to eliminate the meningococcus microorganism from carriers and to treat leprosy, or Hansen's disease. 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 Lowenstein-Jensen medium
one containing eggs for the cultivation of mycobacteria. while others used liquid nonradiometric media (8). Each of the 20 M. tuberculosis M. tuberculosis,
n the bacterium responsible for tuberculosis, generally a respiratory infection in man; nonrespiratory tuberculosis is considered an indicator disease for AIDS. See also 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 ethambutol /etham·bu·tol/ (e-tham´bu-tol) an antibacterial, specifically effective against Mycobacterium; used with one or more other antituberculous drugs in the treatment of pulmonary tuberculosis, administered as the , and streptomycin streptomycin (strĕp'tōmī`sĭn), antibiotic produced by soil bacteria of the genus Streptomyces and active against both gram-positive and gram-negative bacteria (see Gram's stain), including species resistant to other was 3.5%, 0.8%, 0.5%, and 4.3%, respectively, while prevalence of multidrug resistance multidrug resistance,
n the adaptation of tumor cells or infectious agents to resist chemotherapeutic agents. (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 HIV (Human Immunodeficiency Virus), either of two closely related retroviruses that invade T-helper lymphocytes and are responsible for AIDS. There are two types of HIV: HIV-1 and HIV-2. HIV-1 is responsible for the vast majority of AIDS in the United States. 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 immigration, entrance of a person (an alien) into a new country for the purpose of establishing permanent residence. Motives for immigration, like those for migration generally, are often economic, although religious or political factors may be very important. 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 (TBC tbc abbr (= to be confirmed) → por confirmar
tbc abbr (= to be confirmed) → noch zu bestätigen
tbc abbr 1) from the Associazione Italiana Pneumologi Ospedalieri (AIPO AIPO Asociación Interacción Persona-Ordenador
AIPO Associazione Italiana Pneumologi Ospedalieri
AIPO Asean Inter-Parliamentary Organization
AIPO Arizona Immunization Program Office
AIPO Asian Inter-Parliamentary Organization
AIPO Artificial Intelligence Project Office ).
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Geneva (jənē`və), Fr. Genève, canton (1990 pop. 373,019), 109 sq mi (282 sq km), SW Switzerland, surrounding the southwest tip of the Lake of Geneva. , 1997. WHO/TB/97.229:1-227.
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members of the genus Mycobacterium.
see opportunist (atypical) mycobacteria (below).
see opportunist (atypical) mycobacteria (below). and drug susceptibility testing of Mycobacterium tuberculosis from acid-fast smear-positive specimens. J Clinic Microbiol 1983;18:689-96.
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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 rosella
a type of Australian parrot Centis, * Lanfranco Fattorini, * Giorgio Besozzi, * Cesare Saltini, * Claudio Scarparo, * Daniela Cirillo, * Andrea Gori Gori (gô`rē), city (1989 pop. 68,924), central Georgia. It has food processing plants. Mentioned in the 7th cent. as Tontio, it was later named after a fortress. Gori passed to Russia in 1801. Stalin was born in the city. , * Antonio Cassone cassone (käs-sô`nā), the Italian term for chest or coffer, usually a bridal or dower chest, highly ornate and given prominence in the home. , * and Claudio Piersimoni *
* SMIRA (Italian Multicentre Study on Resistance to Antituberculosis Drugs) Coordinating Committee