Prevalence of Primary Multidrug Resistance to Anti-Tuberculosis Drugs in Pakistan

Prevalence of primary multidrug resistance to anti-tuberculosis drugs in Pakistan

A. Javaid,* R. Hasan,† A. Zafar,† A. Ghafoor,‡ A. J. Pathan,§ A. Rab,¶ A. Sadiq,# C. M. Akram,** I. Burki,†† K. Shah,‡‡ M. Ansari,§§ N. Rizvi,¶¶ S. U. Khan,## S. R. Awan,## Z. A. Syed,*** Z. H. Iqbal,††† Z. Shaheen,*** N. ur Rehman‡‡‡ * Department of Pulmonology, Postgraduate Medical Institute, Lady Reading Hospital Peshawar, † Department of Microbiology, Agha Khan University Hospital, Karachi, ‡ TB Control Programme, North West Frontier Province (NWFP), Peshawar, § Institute of Chest Diseases, Kotri, ¶ Department of Pulmonology, Ayub Teaching Hospital, Abbotabad, # Ojha Institute of Chest Diseases, Karachi, ** Gulab Devi Hospital, Lahore, †† Lyari General Hospital, Karachi, ‡‡ National TB Control Programme, Islamabad, §§ Liaqat National Hospital, Karachi, ¶¶ Jinnah Postgraduate Medical Centre, Karachi, ## King Edwards Medical University, Lahore, *** Nishtar Medical College, Multan, ††† Allama Iqbal Medical, Lahore, ‡‡‡ Wyeth (Pvt) Limited, Karachi, Pakistan

SUMMARY

SETTING: Pakistan ranks sixth in the world in terms of isoniazid (INH) (1 g/ml) in 51 (7.6%), rifampicin (RMP) tuberculosis (TB) burden, with a World Health Organiza- (5 g/ml) in 15 (2.2%), ethambutol (10 g/ml) in 12 tion estimated incidence of 181 per 100 000, or 286 000 (1.8%) and pyrazinamide in 22 (3.3%) samples. Forty- new cases annually. Hospital-based data indicate a sig- six (6.8%) of the isolates tested were resistant to a single nificant problem of multidrug-resistant TB (MDR-TB) drug, 10 (1.5%) to two drugs, 12 (1.8%) to three drugs, in the country and highlight the need to assess its extent and 6 (0.9%) to four drugs, while 2 (0.3%) isolates were at community level. In this cross-sectional study, sputum resistant to all five first-line agents. Primary MDR-TB samples from 742 untreated newly diagnosed pulmo- was 1.8% (n 12) (INH 1 g/ml, RMP 5 g/ml). nary TB patients from all over the country were used. CONCLUSION: The results of this study show a prevalence OBJECTIVE: To assess the prevalence of primary drug of primary MDR-TB in Pakistan of 2%, which needs resistance in Pakistan. to be addressed through an effective DOTS strategy. RESULTS: Of 672 culture-positive patients, 76 (11.3%) KEY WORDS: primary drug resistance; MDR-TB; showed resistance to one or more drugs. Resistance to Pakistan streptomycin (10 g/ml) was found in 36 (5.4%) patients,

WORLDWIDE EMERGENCE of multidrug-resistant TB incidence in Pakistan is estimated at 181 per tuberculosis (MDR-TB) has been reported in both in- 100 000 population; each year at least 286 000 new dustrialised and developing countries and poses a ma- TB cases are added to the existing patient population jor threat to the control of TB.1,2 Primary drug resis- of around 1.8 million.5 tance is deﬁned as resistance that develops in a person The level of drug resistance is known to provide an who has not been exposed to anti-tuberculosis treat- epidemiological indicator for assessing the extent of ment in the past, while acquired drug resistance occurs resistant bacterial transmission in the community as in patients previously treated with inadequate or irreg- well as the success or otherwise of the National Tuber- ular chemotherapy. The World Health Organization culosis Programme (NTP). High levels of resistance (WHO) International Union against Tuberculosis and have been reported in certain regions of the world, Lung Disease working group on global surveillance particularly in Asia and parts of Africa.6–12 The rec- for anti-tuberculosis drug resistance reported a prev- ommendation to use drug susceptibility testing (DST) alence of primary MDR of 1.4% and acquired resis- for monitoring and guiding NTPs was made many years tance of 13% in previously treated patients.3 A survey ago.13 In view of the practical difﬁculties of collecting of 48 geographic sites revealed that drug-resistant TB comparable data, the WHO proposed a programme of is ubiquitous, and that the median prevalence of pri- global surveillance of TB drug resistance through its mary resistance to at least one drug is around 10.7%, collaborating centres for TB bacteriology which would while that of primary MDR is only 1%.4 function as supranational reference laboratories (SRL)

Correspondence to: Arshad Javaid, Hayatabad Medical Complex, Peshawar, NWFP, Pakistan. Tel: (92) 91 921 7188, Mobile: (92) 300 594 9509. e-mail: [email protected] Article submitted 29 June 2007. Final version accepted 9 November 2007. Primary M. tuberculosis drug resistance in Pakistan 327 for the various regions. The proposed programme was centres to ensure good coordination and close liaison based on random sampling of patients reporting to with the central laboratory. clinics for TB treatment. DST was to be performed by the reference laboratories based on a common proto- Preparatory phase col, including uniform laboratory methods. As a first In the preparatory phase, coordinators and investiga- step, a regional survey was carried out in 10 Latin tors jointly assessed study requirements, infrastruc- American countries.14 The overall experience gained ture and procedures. The investigators were trained in Latin America suggested that a sample survey of in all aspects of the study including case selection, col- drug resistance with high failure rates of 5% may lection of sputum samples, entries to be made in the indicate inadequate routine treatment and high levels relevant forms and dispatch of specimens to the col- of initial resistance, making drug resistance surveil- lection centres of the central laboratory. lance a priority.14 Several countries in Asia and Africa undertook na- Data analysis tional surveys in accordance with the protocol. Coun- Sampling tries such as Tanzania,15 South Africa16 and India17 This was a cross-sectional prevalence study to estimate established systematic national surveillance pro- the prevalence of drug resistance among newly diag- grammes. No such national level survey has ever been nosed TB patients with no prior exposure to TB drugs, carried out in Pakistan. In a country that ranks sixth using a non-probability convenience sampling meth- in the world in terms of TB disease burden and with odology. The sample size was calculated taking into 45% of the TB disease burden of the Eastern Mediter- consideration the total population of each province of ranean region, a country wide resistance surveillance Pakistan and the WHO-estimated incidence of smear- study was badly needed to determine the prevalence, positive TB in the country. According to these calcula- pattern and trends of anti-tuberculosis drug resistance tions, a sample size of at least 500 was needed for the in the country. study. Keeping in mind the expected 60% positive culture yield of smear-positive specimens, it was decided to collect 750 specimens. Respectively 430, 140, 122 STUDY POPULATION AND METHODS and 50 samples were collected over the 8-month study Organisational and survey outline period in the provinces of Punjab, Sindh, the North Survey area West Frontier Province (NWFP) and Baluchistan. Spu- tum specimens were sent in the containers provided The entire country of Pakistan constituted the survey by the central laboratory along with individual forms area. The study was designed to determine the resis- filled out by the investigator at the diagnostic centre, tance of Mycobacterium tuberculosis isolates from including a declaration by the investigator that the pa- sputum cultures of newly diagnosed smear-positive tient had never taken anti-tuberculosis drugs in the past. TB patients collected from various cities in Pakistan. Patients were given information leaflets and asked for Ethical approval informed consent. In the case of illiterate subjects, the information was read and explained to them and their The study was approved by the Research and Ethics oral consent to participate in the trial was requested. Committee of the Postgraduate Medical Institute, Peshawar, NWFP, Pakistan. Inclusion criteria The following inclusion criteria were used in the study: Diagnostic centres The centres in the different cities where the 15 inves- • new smear-positive pulmonary TB patients tigators worked formed the diagnostic centres. These • any sex and age included TB hospitals, teaching hospitals, NTP Cen- • Pakistani residents tres and private clinics. A total of 29 centres partici- • no prior anti-tuberculosis medication (treatment- pated in the study. They included three TB hospi- naïve patients) tals, six teaching hospitals, eight NTP Centres and • sputum collected for culture before start of 13 private clinics. Sputum smear examination was per- treatment. formed at the diagnostic centres where TB suspects Central laboratory were screened. Only smear-positive specimens were The Department of Microbiology Laboratory at the sent to the central laboratory for culture and DST, pro- Aga Khan University Hospital was used as the central vided the patient had not been given anti-tuberculosis laboratory for culture and DST. treatment in the past. Microbiology method Supervision A central coordinator and a team of two doctors Sputum specimen collection for culture and DST closely supervised all the investigators and diagnostic Patients were given the following instructions: 328 The International Journal of Tuberculosis and Lung Disease

• To collect an early morning specimen: on an empty Microscopy stomach, rinse the mouth with water, go to the open Smears for microscopy were screened using auramine- air away from others, take a deep breath, cough and rhodamine staining. Positive slides were further con- spit out 3–5 ml sputum, not saliva, into the culture firmed by staining with Kinyoun modification of Ziehl- tube (a sterile screw-capped graduated 50 ml plastic Neelsen stain. culture tube provided by the central laboratory) • take the sputum sample to the specimen collection Isolation of M. tuberculosis centre. Mycobacterial cultures were performed on both liq- Patients were advised on the safe transportation uid and solid media. Sediments were cultured at 37 C of the sample (treat with care, and transport only in using Löwenstein-Jensen (LJ) medium and the Myco- the upright position). bacteria Growth Indicator Tube (Becton Dickinson Health workers handling the sputum samples for Diagnostic Instruments Systems, Sparks, MD, USA). culture were instructed to follow the following steps: For the LJ slant, 0.1 ml of concentrated specimen was inoculated and incubated for 8 weeks. MGIT vials • clean the external surface of the tube with 5% phe- were inoculated with 0.5 ml of specimen and incu- nol solution bated at 37C after supplementation of the medium • check the quality and quantity of the specimen with oleic acid-albumin-dextrose-catalase and PANTA • fill out all information necessary for the precise (polymyxin B, amphotericin B, nalidixic acid, trimetho- identification of the patient in the TB culture/ prim and azlocillin). Growth from the positive LJ slant smear test request/report form and MGIT vials were first stained with Kinyoun. • register the specimen in the Primary Study Designed M. tuberculosis was then identified using the BACTEC Laboratory Register and indicate the specimen NAP TB differentiation test (Becton Dickinson). identification number on the outside of the sputum container (not on the lid) Drug susceptibility testing • keep the specimen under refrigeration, preferably DST was performed using the standard agar propor- at 4C, until shipment. tion method on enriched Middlebrook 7H10 medium Samples were shipped at 4C in accordance with (BBL, Beckton Dickinson) at the following drug con- international regulations. centrations: rifampicin (RMP) 1 and 5 g/ml, isoniazid (INH) 0.2 and 1 g/ml, streptomycin (SM) 2 g and TB reference laboratory 10 g/ml and ethambutol (EMB) 5 and 10 g/ml.18,19 To ensure selection of high-level resistance strains for Quality check of the specimen the purposes of this paper, however, only the higher Before processing of the sputum specimen received concentrations were reported. Disc elution suscepti- for culture, it was checked for: bility plates were prepared using paper susceptibility • leakage discs (BBL). McFarland No. 1 standard suspension of • quality and quantity isolates was made from growth on LJ slant and di- 2 4 • date of collection luted to 10 and 10 . The inoculated plates were in- • serial numbers of specimens matching the dispatch cubated at 35 C and examined for growth each week list. for 8 weeks. M. tuberculosis was considered resistant to a given drug when growth of 1% above the drug- Recording free control was observed in the drug-containing area. Complete information on all samples that met the in- Pyrazinamide (PZA) sensitivity was carried out using clusion criteria were noted in full in the TB culture BACTEC 7H12 medium pH6.0 at 100 g/ml (BACTEC register. Each sample was assigned a serial number to PZA test medium, Becton Dickinson, Sparks, MD, permit proper identification of the specimen obtained USA) in accordance with the manufacturer’s instruc- from the diagnostic centre and to facilitate feedback tions. M. tuberculosis H37Rv was used as a control of the culture result. with each batch of DST.

PROCESSING OF SPUTUM SPECIMENS RESULTS Microbiological methods A total of 742 samples were found to be evaluable; of these, 675 (90%) were culture-positive. Of the Specimen processing culture-positive patients, 365 (54%) were males and All samples were decontaminated with N-acetyl-L- 306 (45.3%) females, with a M:F ratio of 1.2:1; 405 cysteine (NALC) sodium hydroxide according to the (60%) patients were aged between 15 and 35 years, standard protocol. All specimens were concentrated 238 (35.2%) were aged 35 years, and 29 (4.27%) by centrifugation for 30 min and sediments were used were aged 15 years. The M:F ratio of the 67 culture- for acid-fast bacilli microscopy and culture. negative patients was 1.3:1; 52% were aged between Primary M. tuberculosis drug resistance in Pakistan 329

Table 1 Collection of samples by province Table 3 Resistance pattern (n 76)

Culture- n (%) Serial Samples Samples positive no. Province allotted collected samples Total culture-positive 672 (100) Fully sensitive 596 (88.7) 1 Sind 178 140 131 2 Punjab 422 430 387 Any resistance 76 (11.3) 3 NWFP 106 122 118 Resistance to 4 Baluchistan 44 50 36 Only H 22 (3.2) Total Pakistan 750 742 672 Only R 2 (0.3) Only E 4 (0.6) NWFP North West Frontier Province. Only S 18 (2.7) Only Z 0 HE 5 (0.7) HS 3 (0.4) 15 and 35 years and 41% were aged 35 years. The dis- HZ 2 (0.3) tribution of the samples by province is shown in Table 1. HRZ 4 (0.6) HSZ 7 (1) Smear RSZ 1 (0.15) HREZ 1 (0.15) On smear examination, 44 (6.5%) of the 675 speci- HRSZ 5 (0.7) mens collected from diagnostic centres from across HRSEZ 2 (0.3) the country were found to be smear-negative at the Any H resistance 55 (7.6) reference laboratory. Any R resistance 18 (2.2) Any HR resistance 12 (1.8) Culture H isoniazid; R rifampicin; E ethambutol; S streptomycin; Z DST was conducted on 742 patients, of whom 675 pyrazinamide. were culture-positive. Three samples grew mycobac- teria other than tuberculosis (MOTT) and were ex- cluded from further analysis. Of the remaining 672 2–41), while the overall median prevalence of pri- patients, isolates from 596 (88.7%) were fully suscep- mary MDR-TB was 1.4% (range 0–10). Among the tible to all the first-line drugs tested, while 76 (11.3%) South-East Asian Region (SEAR) countries, the prev- showed resistance to one or more drugs. Resistance to alence of primary resistance is readily available only INH alone or in combination with other drugs was for Nepal and Thailand, as they participated in the observed in 51 (7.6%) patients. Resistance to SM, WHO supported Global Project on Anti-tuberculosis RMP, EMB and PZA was seen in respectively 36 Drug Resistance Surveillance in 1994–1997. The me- (5.4%), 15 (2.2%), 12 (1.8%) and 22 (3.3%) isolates dian prevalence of acquired resistance to any drug (Table 2). was recorded as 23.2% (range 9.8–36.6). The median Resistance to one drug was seen in 46 patients, two prevalence of primary MDR-TB was 2.5%, which is in 10 patients, three in 12 patients, four in six patients significantly higher than the global mean of 1.4%.3 and all five drugs in two patients (Table 3). MDR was However, such information based on standardised pro- found in 12 patients (1.8%). Of the 12 MDR cases, tocols and methods is not available for other SEAR three were from NWFP, four were from Sindh, and countries. three from the province of Punjab. Although drug-resistant TB has frequently been en- countered in Pakistan, no comprehensive reports have been published, mainly due to the limited facilities DISCUSSION available for culture and DST across the country. The The WHO/IUATLD Global Project on Anti-tuberculosis present study on drug resistance in Pakistan, using in- Drug Resistance Surveillance recorded considerable ternationally acceptable guidelines and a standardised variations in the prevalence of drug resistance among methodology, gives reliable baseline information. 35 countries in five continents.14 The median preva- Although one of the criteria for inclusion of pa- lence of primary drug resistance was 9.9% (range tients in this study was a smear-positive test at the diagnostic centres, 6.5% of all smear-tested specimens were negative by microscopy at the reference labora- Table 2 Susceptibility patterns (n 672) tory. Nevertheless, the agreement of 93.5% shows that sputum microscopy at the diagnostic centres, with Resistant to Isolates, n (%) minimal infrastructure, was at an acceptable standard. Streptomycin 10 g 36 (5.4) Furthermore, 90% of all the smear-positive patients Isoniazid 1 g 51 (7.6) Rifampicin 5 g 15 (2.2) were culture-positive, confirming that the reference Ethambutol 10 g 12 (1.8) laboratory at the Aga Khan University was function- Pyrazinamide 100 g 22 (3.3) ing at an acceptable level. MDR 12 (1.8) The observed level of INH resistance (7.6%), RMP MDR multidrug-resistant. resistance (2.2%), and MDR (1.8%) in previously 330 The International Journal of Tuberculosis and Lung Disease untreated cases is not as high as expected, given that 2 World Health Organization, Communicable Diseases. Global Pakistan has just recently reached the WHO target of tuberculosis control. WHO report 2001. WHO/CDS/TB/2001. 100% DOTS coverage. These values are comparable 287. Geneva, Switzerland: WHO, 2001. 3 Pablos Mendez A, Raviglione M C, Laszlo A, et al. Global sur- with resistance studies in the other developing coun- veillance for anti-tuberculosis drug resistance 1994–1997. World tries. However, the results of this study are different Health Organization–International Union Against Tuberculosis from other surveys conducted in Pakistan. In a study and Lung Disease Working Group on Anti-Tuberculosis Drug by Khan et al., primary resistance to INH and RMP Resistance Surveillance. N Engl J Med 1998; 338: 1641–1649. was respectively 11% and 15%,20 while in another 4 Espinal M A, Laszlo A, Simonsen L, et al. Global trends in resistance to anti-tuberculosis drugs. World Health Organization– study, resistance was found to be even higher (INH International Union Against Tuberculosis and Lung Disease 25%, RMP 15%, EMB 12% and SM 19%).21 This Working Group on Anti-Tuberculosis Drug Resistance Surveil- relatively high level of resistance to individual drugs lance. N Engl J Med 2001; 344: 1294–1303. in the above-mentioned studies was perhaps due to 5 World Health Organization. Global tuberculosis control— faulty patient selection, and it appears that efforts were surveillance, planning, financing. WHO report 2007. WHO/ HTM/TB/2007.376. Geneva, Switzerland: WHO, 2007. not made to separate primary drug resistance from ini- 6 Kochi A, Vareldzis B, Styblo K. Multidrug-resistant tuberculo- tial or acquired resistance. There was therefore a clear sis and its control. Res Microbiol 1993; 144: 104–110. need to evaluate primary resistance to anti-tuberculo- 7 Kim S J, Hong Y F. Drug resistance of Mycobacterium tuber- sis drugs in Pakistan in a nationwide study. culosis in Korea. Tubercle Lung Dis 1992; 73: 219–224. There may have been a gradual increase in primary 8 Chandrasekaran S, Jagota P, Chaudhury K, et al. Initial drug resistance to anti-tuberculosis drugs in urban and rural districts drug resistance over the years. This could be over- tuberculosis programme. Indian J Tuberc 1992; 39: 171–175. come by a strong NTP using the DOTS strategy to re- 9 Frieden T R, Sterling T, Pablos-Mendez A, et al. The emergence duce the emergence of drug resistance in the commu- of drug-resistant tuberculosis in New York City. N Engl J Med nity. As no new drugs for TB are likely to become 1993; 328: 521–526. available in the near future, the only options left for 10 Van der Werf T S, Groothuis D G, van Klingeren B. High initial the prevention of drug resistance are effective case drug resistance in pulmonary tuberculosis in Ghana. Tubercle 1989; 70: 249–255. finding, prompt and correct diagnosis and successful 11 Braun M M, Kilburn J O, Smithwick R W, et at. HIV infection treatment of patients. Apart from a strong NTP, contin- and primary resistance to anti-tuberculosis drugs in Abidjan, uous surveillance of drug resistance will provide infor- Cote d’ Ivoire. AIDS 1992; 6: 1327. mation that will serve as a useful parameter in the eval- 12 Paramasivan C N. An overview of drug resistant tuberculosis uation of NTPs. in India. Indian J Tuberc 1998; 45: 73. 13 World Health Organization. Surveillance of drug resistance in tuberculosis: a global random sample survey of initial and CONCLUSION acquired resistance. WHO/TB. Geneva, Switzerland: WHO, 1984; 143: 1. A poorly functioning programme can create MDR- 14 World Health Organization. Anti-tuberculosis drug resistance TB much faster than it can be treated, even if unlim- in the world (WHO/IUATLD global project on anti-tuberculosis drug resistance surveillance—1994–1997). WHO/TB/97-229. ited resources are available. There is no single pre- Geneva, Switzerland: WHO, 1997. scription for controlling MDR-TB, but the various 15 Chonde T M. The role of bacteriological surveys in the Na- tools available should be applied wisely. Adoption of tional Tuberculosis and Leprosy Programme in Tanzania. Bull the DOTS strategy to prevent the generation of resis- Int Union Tuberc Lung Dis 1989; 64: 37–39. tant strains and careful introduction of second-line 16 Weyer K, Kleeberg H H. Primary and acquired drug resistance in adult black patients with tuberculosis in South Africa: re- drugs to treat patients with MDR are the top priorities sults of continuous drug resistance surveillance programme infor the proper control and containment of MDR-TB. volvement. Tubercle Lung Dis 1992; 73: 106–112. 17 Paramasivan C N, Bhaskaraia K, Venkartaraman P, Chan- Acknowledgements drasekaran V, Narayanan P R. Surveillance of drug resistance in tuberculosis in the state of Tamil Nadu. Indian J Tuberc 2000; The study was financed by the Wyeth Pharmaceutical (Pvt) Ltd. 47: 27–32. The sponsor had no role in data collection, data analysis, data 18 Isenberg H D. Clinical microbiology procedure handbook. 2nd interpretation or writing of the report. The corresponding author ed. Vol. 2. Washington, DC, USA: ASM Press, 2004: pp 7821– had access to all data in the study and had final responsibility for 7823. the decision to submit for publication. 19 Wayne L G, Krasnow I. Preparation of tuberculosis susceptibility testing mediums by impregnated discs. Am J Public Health 1966; 45: 769–771. References 20 Khan J. Drug resistance of Mycobacterium tuberculosis in 1 Dye C, Scheel S, Dolin P, et al. Consensus statement. Global Karachi. Trop Doct 1993; 23: 13–14. burden of tuberculosis: estimated incidence, prevalence and 21 Haq M, Awan S R. Sensitivity pattern of M. tuberculosis in mortality by country. WHO Global Surveillance Monitoring Lahore, Pakistan. Annals King Edward Medical Coll 2002; 8: Project. JAMA 1999; 282: 677–686. 190–193. Primary M. tuberculosis drug resistance in Pakistan 331

RÉSUMÉ

CADRE : Le Pakistan occupe la sixième place au monde d’un ou de plusieurs médicaments. On a observé une ré- en termes de fardeau de la tuberculose (TB), l’incidence sistance à la streptomycine (10 g/ml) chez 36 (5,4%), à estimée par l’Organisation Mondial de la Santé étant de l’isoniazide (INH) (1 g/ml) chez 51 (7,6%), à la 181 pour 100 000, soit 286 000 nouveaux cas par an. rifampicine (RMP) (5 g/ml) chez 15 (2,2%), à l’étham- Les données basées sur les hôpitaux montrent l’énormité butol (10 g/ml) chez 12 (1,8%) et au pyrazinamide du problème de la multirésistance (MDR) dans le pays et chez 22 (3,3%) échantillons. Sur les isolats testés, 46 renforce la nécessité d’évaluer son étendue au niveau de (6,8%) étaient résistants à un seul médicament, 10 la collectivité. Dans cette étude transversale des échantil- (1,5%) à 2, 12 (1,8%) à 3, 6 (0,9%) à 4 et 2 (0,3%) ré- lons de crachats ont été obtenus en provenance de 742 sistants à l’ensemble des cinq agents de première ligne. patients récemment diagnostiqués comme TB pulmonaire La MDR primaire s’est élevée à 1,8% (n 12) (INH 1 g/ non traités dans l’ensemble du pays. ml, RMP 5 g/ml). OBJECTIF : Evaluer la prévalence de la résistance pri- CONCLUSION : Cette étude suggère que la prévalence de maire aux médicaments au Pakistan. la MDR primaire au Pakistan est 2% et devrait être RÉSULTATS : Sur 672 patients à culture positive, 76 maîtrisée grâce à une stratégie efficiente de DOTS. (11,3%) étaient porteurs de germes résistants à l’égard

RESUMEN

MARCO DE REFERENCIA : Pakistán ocupa el sexto lugar tivo, 76 (11,3%) exhibieron resistencia a uno o varios en el mundo en términos de carga de morbilidad por medicamentos. Se observó resistencia a estreptomicina tuberculosis (TB), con una incidencia estimada por la (10 g/ml) en 36 muestras (5,4%), a isoniazida (INH) Organización Mundial de la Salud en 181 casos por (1 g/ml) en 51 (7,6%), a rifampicina (RMP) (5 g/ml) 100 000 habitantes o 286 000 casos nuevos anuales. en 15 (2,2%), a etambutol (10 g/ml) en 12 (1,8%) y a Las bases de datos hospitalarios indican la existencia pirazinamida en 22 muestras (3,3%). Cuarenta y seis de un problema considerable de multidrogorresistencia (6,8%) de los aislados analizados fueron resistentes a un (MDR) en el país, con lo cual se valida la necesidad de solo medicamento ; 10 (1,5%) a 2 medicamentos ; 12 evaluar la amplitud del problema a escala comunitaria. (1,8%) a 3 ; 6 (0,9%) a 4 y 2 (0,3%) aislados fueron re- En el presente estudio transversal se obtuvieron mues- sistentes a los cinco medicamentos. La MDR primaria fue tras de esputo de 742 pacientes provenientes de todo el de 1,8% (n 12) (INH 1 g/ml, RMP 5 g/ml). país con diagnóstico reciente de TB pulmonar y sin trata- CONCLUSIÓN : En el presente estudio se encuentra que la miento previo. prevalencia de MDR primaria en Pakistán está 2% y OBJETIVO : Evaluar la prevalencia de farmacorresisten- se debe combatir con una estrategia eficaz de trata- cia primaria en Pakistán. miento corto directamente observado. RESULTADOS : De los 672 pacientes con cultivo posi-