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Korean J Intern Med > Volume 16(3); 2001 > Article
Lee and Chang: Drug-resistant tuberculosis in a tertiary referral teaching hospital of Korea

Abstract

Background :

Resistance of Mycobacterium tuberculosis strains is an increasing problem worldwide. Our purpose was to determine the prevalence of drug resistance (DR) and risk factors of DR in patients with tuberculosis and to assess the clinical characteristics and socioeconomic status of patients with drug-resistant tuberculosis.

Methods :

We retrospectively studied drug susceptibility tests and clinical and socioeconomic records for 308 cases of culture-positive Mycobacterium tuberculosis infection, diagnosed at Mokdong Hospital, Ewha Womans University from March, 1995 to February, 2000.

Results :

DR to at least one drug was identified in 75 (24.4%); the rate of primary DR, 18.7% and acquired DR, 39.3%. Multi-drug resistance (MDR) was identified in 31 (10.1%); primary MDR, 7.0% and acquired MDR, 21.4%. The risk factors of DR were previous TB treatment, pulmonary involvement and associated medical illness. DR group showed lesser adherence to treatment than the drug-sensitive group. DR group showed more frequent self-interruption of medication, lower completion rate of treatment and higher failure rate of follow-up than the drug-sensitive group. In previously treated tuberculosis patients, higher rate of overall DR and MDR, larger number of resistant drugs and more frequent self-interruption of medication were observed than newly diagnosed patients. Among DR group, acquired DR (ADR) group was older, less educated and treated for longer duration and had more advanced disease than primary DR group.

Conclusion :

Previously treated tuberculosis is a most important risk factor for DR. DR group, especially ADR, showed less compliance with treatment. More proper education and attention to prevent self-interruption should be given to a previously treated group. In TB prevalent areas, it should be considered to obtain initial drug susceptibility testing in high risk of DR.

INTRODUCTION

Tuberculosis (TB) is one of the major infectious diseases in severity and morbidity despite coverage of the National Tuberculosis Program and improved social and economic conditions1). Recently, epidemic of acquired immune deficiency syndromes, poor isolation of drug-resistant subjects and increased numbers of poor and crowded residences have caused increased proportion of drug resistance (DR), especially multi-drug resistance (MDR)27). In Korea, although the overall prevalence of tuberculosis diminished to less than 1.0%, the rate of drug resistance, especially MDR in previously treated groups was still high8, 9). It is important to define the risk factors, including the socioeconomic status of DR for the prompt isolation and proper management of drug-resistant tuberculosis. We examined current characteristics of DR in a university hospital setting and compared it to national studies.

MATERIALS AND METHODS

1. Study population

From March 1995 through February 2000, 308 patients with culture-positive Mycobacterium tuberculosis infection and their drug susceptibility testing were included. The medical records of these patients were reviewed and the following data were collected: age, sex, history of previous antituberculous treatment, familial history of TB, associated medical illness of diabetes mellitus, liver disease and malignancy, history of smoking and alcohol drinking, marital status, and employment status. Whether they graduated more than high school and had resided in their own houses were inquired of patients with drug resistant tuberculosis using interviews by letters or telephones.

2. Drug susceptibility test

The drug susceptibility testing against ten antituberculosis drugs was conducted by a laboratory certified under the Korean National Tuberculosis Association. The drug susceptibility of the M. tuberculosis isolates was determined by the absolute concentration method described in detail by Canetti et al10). The drugs and their critical concentrations for resistance are as follows: isoniazid 0.2 μg/mL; rifampin 40 μg/mL; ethambutol 2 μg/mL; streptomycin 10 μgg/mL; kanamycin 40 μg/mL; prothionamide 20 μg/mL; cycloserine 30 μg/mL; paraam-inosalicylic acid 1 μg/mL; ofloxacin 2 μg/mL. Pyrazinamide susceptibility was determined by pyrazinamidase test.

3. Definitions

The term ‘previously treated TB patients’ refers to patients with verified TB with treatment of more than one month in the past. The term ‘drug resistance’ means resistance to at least one antituberculosis drug, ‘poly-drug resistance’ means resistance to more than any two drugs and ‘multi-drug resistance’ means resistance to at least isoniazid and rifampin. The term ‘primary DR’ refers to resistance occurred in a patient who has never received antituberculosis therapy and ‘acquired DR’ refers to resistance developed during or following chemotherapy of subjects who had previously been regarded as drug-susceptible tuberculosis.

4. Data analysis

The data were analyzed using SPSS software. The χ2 test and independent T test were applied to compare variables between the two groups. Multiple logistic regression analysis was used to define the strength of major risk factors to develop DR.

RESULTS

1. Rate of drug resistance

Among 308 culture-positive patients, 187 had newly diagnosed TB and 84 had previously treated TB, except for 37 cases with no available record of previous TB history. Resistance to at least one drug was found in 75 (24.4%) out of 308 cases and MDR in 31 (10.1%). Among antituberculosis drugs, resistance to isoniazid was the most common (19.5%), followed by resistance to rifampin (12.3%), ethambutol (8.8%) and streptomycin (5.8%). Primary DR was found in 35 (18.7%) out of 187 cases and primary MDR in 13 (7.0%). Primary DR to isoniazid was 13.4%; rifampin, 9.1%; ethambutol, 7.0% and streptomycin, 4.8%. Acquired DR was found in 33 (39.3%) out of 84 cases and acquired MDR in 18 (21.4%). Acquired DR to isoniazid was 35.7%; rifampin, 22.6%; ethambutol, 15.5% and streptomycin, 8.3%. Each of acquired DR and acquired MDR was significantly higher than each of primary DR and primary MDR (39.3% vs. 18.7%; p<0.001, 21.4% vs. 7.0%; p<0.01) (Table 1).

2. Comparison between drug-sensitive group and drug-resistant group

Drug-resistant group presented a history of previously treated TB (48.5% vs. 25.1%; p<0.001), pulmonary involvement of TB (92.6% vs. 80.1%; p<0.05) and associated medical illness more frequently than drug-sensitive group (29.4% vs. 19.5%; p<0.05). Drug-resistant group showed more frequent self-interruption of medication (38.8% vs. 13.4%; p<0.001), lower completion rate of treatment (39.7% vs. 58.4%; p<0.01) and higher failure rate of follow-up than drug-sensitive group (36.8% vs. 12.7%; p<0.001) (Table 2).

3. Risk factors of drug resistance

Multiple logistic regression analysis was applied to factors associated with DR and MDR. Previous treatment of TB was the strongest risk factor of DR (odds ratio, 2.67; p<0.01) and MDR (odds ratio, 3.69; p<0.01). Pulmonary involvement of TB (odds ratio, 3.27; p<0.05) and associated medical illness (odds ratio, 2.30; p<0.05) were also risk factors of DR, but not of MDR (Table 3).

4. Comparison between primary DR and acquired DR

Acquired DR group was older (48.2 ± 16.5years vs. 39.6 ± 16.3years; p<0.05) and lesser educated than primary DR group (11.1% vs. 38.9%; p<0.05). Acquired DR group also had higher rate of family history of TB (28.0% vs. 16.7%) and more lived in rented houses than primary DR group (30.8% vs. 22.2%), but it is not statistically significant (Table 4). Acquired DR group showed more involved lobes in chest X-ray (2.0 ± 0.8 vs. 1.4 ± 0.7; p<0.01) and longer duration of treatment than PDR group (18.3 ± 7.2 months vs. 10.6 ± 6.3 months; p<0.05) (Table 5).

DISCUSSION

This study presented findings related to drug resistance in a TB endemic country not associated with HIV epidemic. The drug resistance in TB is one of the most important problems in the world and a major cause of morbidity and mortality2). TB was one of the most common 10 causes of Korean adults’ deaths until 19968). DR and severity of infection are important factors determining the mortality in TB patients. The national goal of TB control is closely related to control of DR. According to a national TB survey of Korea, the rate of DR was the highest in 1980 and then it tended to decline8, 9).
The rate of isoniazid-resistant TB was the highest among the antituberculous drugs throughout the world and the rate of rifampin-resistant TB was high in an endemic area5,1114). This study showed that nearly 20 percent of the patients with active TB could transmit isoniazid-resistant organisms. The use of rifampin with or without pyrazinamide in chemoprophylaxis for the case contact in a prevalent area of isoniazid-resistant TB is issued15). The increasing resistance to rifampin is particularly troubling, since rifampin is essential to short-course antituberculosis therapy16). In this study, 10 percent of the total cases could transmit organisms resistant to both isoniazid and rifampin. Consensus on preventive therapy for MDR TB was not reached and the current recommendation was a regimen of pyrazinamide and fluoroquinolone for 4 months17).
Because previous use of antituberculous medication was the most important risk factor of DR4,6,13,14,18,19) as shown in this study, and accompanied medical illness due to decreased immunity was high risk group of DR3, 20, 21), DR should be suspected in cases of delayed response to therapy or continued positive AFB smear despite treatment. The ability to complete antituberculosis therapy can be affected by housing status, employment status, level of literacy and psychological aspects2225). In this study, alcohol abuse, marital status or employment status did not influence the development of DR. Because patients with DR are usually treated with 2nd line antituberculosis drugs for a long duration, which are more toxic and costlier than first line drugs, they are apt to have poor adherence to medication compared with drug-sensitive patients. The other factors to develop DR are drug intolerance during therapy25), contact with DR TB26), birth and residence in an endemic area5,6,13,14,19), HIV infection6, 13) and cavitary pulmonary tuberculosis18, 19).
The first large scale sample survey in Korea in 1994, cooperation with WHO and IUATLD9, 11), presented lower rates in overall DR and primary DR and higher rate in acquired DR compared with this study (Table 6). The discrepancies between this study and the nationwide study could originate from differences in the size and nature of the study population, study period and study area. The population of previous treated TB cases out of all cases in this study was higher than that in the national study (84 of 308 cases, 27.3% vs. 189 of 2675 cases, 7.1%). This could contribute to raise the overall rate of DR in this study. Although the rate of acquired DR was lower in this study than the national survey of 1994, the rate of MDR is about 3 times that of the national survey of 1994. The population of this study was derived mainly from residents in Seoul. Residents in other areas were only 52 (13.6%) out of 308 patients. Therefore, this study could represent drug resistance in Seoul as an urban area. Generally, an urban community is more crowded and has more chance to transmit an infectious disease than a rural community. As another reason to be considered, more advanced cases among newly diagnosed subjects might prefer to be treated in 3rd referral hospitals rather than in a public TB care center as in rural areas. Actually, in this study, patients with primary DR showed a higher rate of hospitalization despite a younger age than those with acquired DR, and the rate of primary MDR in this study was far higher than that in the national survey of 1994. Our data had comparable results with the report from Chungnam University of Korea27).
In this study, patients with acquired DR showed chronic reluctant course, low education level and low economic status compared with those with primary DR. Traditionally, patients with DR TB are classified as having acquired DR or primary DR on the basis of a history of previous TB treatment28, 29). Only cases of primary DR are assumed to be due to transmission of DR strains. Recent studies based on restriction-fragment length polymorphisms, useful in distinguishing different strains of M. tuberculosis, revealed that recent transmission as well as true acquisition of DR during therapy was an important cause of DR, especially MDR, even in previously treated cases in certain urban populations30, 31). Therefore, traditional clinical classification based on a history of previous treatment may result in misinterpretation and the underestimation of transmission. Improper isolation and poor ventilation due to crowding are important reasons for spread of TB particularly in the low socioeconomic status of urban areas. The resistant cases, especially previously treated, remain sources of infection for prolonged periods and they are likely to infect others3135). Finally, the high rate of DR and MDR in acquired cases contribute to increasing rates of DR and MDR in primary cases.
When dealing with a patient who has resistant TB, it is very important that the physician evaluate the situation fully. When seeing a patient who has already been treated for TB, susceptibility tests should be ordered. The only way to ensure that patients take their medication properly is to give it to them, i.e. direct observed therapy (DOT)34). Although routine DOT can not be afforded in many countries with a high prevalence of MDR TB, application of DOT is requisite in drug resistant TB, especially for poor adherence to treatment, to prevent the development of further drug resistance36).
Previously treated tuberculosis is a most important risk factor for DR. DR group, especially ADR, showed less compliance with treatment. More proper education and attention to prevent self-interruption should be given to a previously treated group. This study showed a higher rate of primary DR and primary MDR compared to the national study, suggesting more severe cases among newly diagnosed patients treated in tertiary referral hospitals rather than public TB care centers. High rate of acquired DR contributes to increasing the rate of primary DR. Initial drug susceptibility testing is necessary to guide optimal treatment to a culture positive case with the high risk of DR, especially in TB prevalent areas.

Table 1.
Resistance to antituberculosis drugs in culture-positive tuberculosis cases.
Type of drug resistance All patients (n=308) No previous treatment n=187) Previous treatment (n=84)

N % N % N %
Any drug 75 24.4 35 18.7 33 39.3
Single drug resistance 32 10.4 17 9.1 12 14.3
Poly-drug resistance 43 14.0 18 9.6 21 25.0
Multi-drug resistance 31 10.1 13 7.0 18 21.4
Isoniazid 60 19.5 25 13.4 30 35.7
Rifampin 38 12.3 17 9.1 19 22.6
Ethambutol 27 8.8 13 7.0 13 15.5*
Streptomycin 18 5.8 9 4.8 7 8.3
Pyrazinamide 13 4.2 5 2.7 7 8.3*
Paraminosalicylic acid 13 4.2 5 2.7 7 8.3*
Prothionamide 6 1.9 1 0.5 4 4.8*
Kanamycin 5 1.6 2 1.1 3 3.6
Ofloxacin 4 1.3 3 1.6 1 1.2
Cycloserine 0 0.0 0 0.0 0 0.0

* p<0.05,

p<0.01,

p<0.001 vs. no previous treatment

Table 2.
Characteristics of patients with culture-documented tuberculosis.
Variables Drug-sensitive group (n=233) Drug-resistant group (n=75)
Age (year) 43.0 ± 18.9 43.5 ± 16.8
Body mass index (kg/m2) 19.6 ± 3.1 20.2 ± 2.0
Male sex 58.4% 53.3%
Previously treated tuberculosis 25.1% 48.5%
Family history of tuberculosis 22.7% 21.8%
Site of disease
  Pulmonary only 80.1% 92.6%*
  Pulmonary & extrapulmonary 15.8% 7.4%
  Extrapulmonary only 4.1% 0.0%
Cavitary disease in chest X-ray 19.5% 29.4%
Associated medical illness 12.7% 25.4%*
  Diabetes mellitus 8.1% 16.4%*
  Liver disease 3.6% 6.0%
  Malignancy 1.8% 3.0%
History of smoking 52.1% 51.7%
History of alcohol abuse 6.3% 7.1%
Single 37.3% 29.1%
Unemployed 31.7% 21.3%
Self-interruption of regular medication 13.4% 38.8%
Process of treatment
  Completion of treatment 58.4% 39.7%
  Failure to follow-up 12.7% 36.8%

Data are mean ± SD.

* p<0.05,

p<0.01,

p<0.001 vs. drug- sensitive group

Table 3.
Factors associated with resistance to antituberculosis drugs
Factor Drug resistance Multi-drug resistance

Odds ratio (95% CI) P value Odds ratio (95% CI) P value
Previous treatment of TB 2.67 (1.48–4.31) <0.01 3.69 (1.67–8.13) <0.01
Pulmonary involvement of TB 3.27 (1.21–8.34) <0.05 - 0.34
Associated medical illness 2.30 (1.12–4.75) <0.05 - 0.16

CI, confidence interval

Table 4.
Demographic and social status of drug-resistant tuberculosis
Variables Primary drug resistance (n=35) Acquired drug resistance (n=33)
Age (years) 39.6 ± 16.3 48.2 ± 16.5*
Body mass index (kg/m2) 20.2 ± 2.2 20.1 ± 1.8
Male sex 46.2% 53.8%
Family history of tuberculosis 16.7% 28.0%
History of smoking in male 76.5% 72.2%
History of alcohol abuse 6.7% 7.7%
Single 26.7% 32.0%
Unemployed 20.0% 22.7%
Highly educated 38.9% 11.1%*
Living in a rented house 22.2% 30.8%

Data are mean ± SD.

*: p<0.05 vs. primary drug resistance

Table 5.
Clinical characteristics of drug-resistant tuberculosis
Variables Primary drug resistance (n=35) Acquired drug resistance (n=33)
Number of resistant drugs 2.3 ± 1.6 2.8 ± 1.9
Site of disease
  Pulmonary only 94.3% 90.9%
  Pulmonary & extrapulmonary 5.7% 9.1%
Lesion of chest X-ray
  Cavitary disease 31.4% 27.3%
  Number of involved lobes 1.4 ± 0.7 2.0 ± 0.8
Hospitalization 60.0% 48.5%
Associated medical illness 41.2% 58.8%
  Diabetes mellitus 14.7% 18.2%
  Liver disease 5.9% 6.1%
  Malignancy 0.0% 3.0%
Self-interruption of regular medication 31.5% 46.9%
Process of treatment
  Completion of treatment 37.1% 42.4%
  Failure to follow-up 34.3% 39.4%
Duration of treatment (months) 10.6 ± 6.3 18.3 ± 7.2*

Data are mean ± SD.

* p<0.05,

p<0.01 vs. primary drug resistance

Table 6.
Drug resistance among Korean patients with tuberculosis in our study and other reports
Study group Ewha Womans University Mokdong Hospital Korea, Global Surveillance by WHO/ IUATLD9 Chungnam National University Hospital27

Period 1995.3–1999.12 1994.7–1994. 9 1995.1–1996.6
Number of patients n=308
P=187
R=84
n=2675
P=2486
R=189
n=92
P=66
R=26
Overall drug resistance (%) 24.4 14.4 26.0
Poly-drug resistance (%) 14.0 7.1 -
Primary drug resistance (%) 18.7 11.3 16.7
Acquired drug resistance (%) 39.3 54.0 50.0
Multi-drug resistance (%) 10.1 3.4 8.6
Primary MDR (%) 7.0 1.6 3.0
Acquired MDR (%) 21.4 27.5 23.0
Isoniazid (%) 19.5 10.4 19.5
Rifampin (%) 12.3 4.3 9.7
Ethambutol (%) 8.8 4.5 9.7
Streptomycin (%) 5.8 3.6 11.9
Pyrazinamide (%) 4.2 1.8 5.4

P, number of new cases; R, number of retreatment cases.

REFERENCES

1. Kent JH. The epidemiology of muitidrug-resistant tuberculosis in the United States. Med Clin North Am 77:1391–14091993.
crossref pmid
2. Rusch-Gerdes S. Epidemiology of resistant tuberculosis in Europe. Infection 27:S17–181999.
crossref pmid
3. Barnes PF, Bloch AB, Davidson PT, Snider DE Jr. Tuberculosis in patients with human immunodeficiency virus infection. N Engl J Med 324:1644–16501991.
crossref pmid
4. Frieden TR, Sterling T, Pablos-Mendes A, Kilburn JO, Cauthen GM, Dooley SW. The emergence of drug-resistant tuberculosis in New York city. N Engl J Med 328:521–5261993.
crossref pmid
5. Hersi A, Elwood K, Cowie R, Kunimoto D, Long R. Muitidrug-resistant tuberculosis in Alberta and British Columbia, 1989 to 1998. Can Respir J 6:155–1601999.
crossref pmid pdf
6. Chawla PK, Klapper PJ, Kamholz SL, Pollack AH, Heurich AE. Drug-resistant tuberculosis in urban population including patients at risk for human immunodeficiency virus infection. Am Rev Respir Dis 146:280–2841992.
crossref pmid
7. Telzak EE, Sepkowitz K, Alpert P, Mannheimer S, Medard F, El-Sadr W, Brum S, Gagliardi A, Salomon N, Turett G. Multidrug-resistant tuberculosis in patients without HIV infection. N Engl J Med 333:907–9111995.
crossref pmid
8. Ministry of Health and Welfare Korean Nation Tuberculosis Association. Report on the 7th tuberculosis prevalence survey in Korea. 1–180Seoul: 1996.

9. Kim SJ, Bai GH, Hong YP. Drug-resistant tuberculosis in Korea, 1994. Int J Tuberc Lung Dis 1:302–3081997.
pmid
10. Canetti G, Fox W, Khomenko A, Mahler HT, Menon NK, Mitchison DA, Rist N, Smelev NA. Advances in techniques of testing mycobacterial drug sensitivity and the use of sensitivity tests in tuberculosis control programmes. Bull World Health Organ 41:21–431969.
pmid pmc
11. Pablos-Mendez A, Raviglione MC, Laszlo A, Binkin N, Rieder HL, Bustreo F, Cohn DL, Lambretgts-van Weezenbeek CSB, Kin SJ, Chaulet P, Nunn P. Global surveillance for antituberculosis-drug resistance, 1994–1997. N Engl J Med 338:1641–16491998.
crossref pmid
12. Moore M, Onorato IM, McCray E, Castro KG. Trends in drug-resistant tuberculosis in the United States, 1993–1996. JAMA 278:833–8371997.
crossref pmid
13. Fujiwara PI, Cook SV, Rutherfold CM, Crawford JT, Glickman SE, Kreiwirth BN, Sachdev PS, Osahan SS, Ebrahimzadeh A, Frieden TR. A continuing survey of drug-resistant tuberculosis, New York City, April 1994. Arch Intern Med 157:531–5361997.
crossref pmid
14. Schaberg T, Gloger G, Reichert B, Mauch H, Lode H. Drug-resistant pulmonary tuberculosis in Berlin, Germany, 1987–1993. Eur Respir J 8:278–2841995.
crossref pmid
15. Livengood JR, Sigler TG, Foster LR, Bobst G, Snider DE Jr. Isoniazid-resistant tuberculosis. A community outbreak and report of a rifampin prophylaxis failure. JAMA 253:847–28491985.
crossref
16. Mitchison DA, Nunn AJ. Influence of initial drug resistance on the response to short-course chemotherapy of pulmonary tuberculosis. Am Rev Respir Dis 133:423–4301986.
pmid
17. Passannante MR, Gallagher CT, Reichman LB. Preventive therapy for contacts of multidrug resistant tuberculosis : a Delphi survey. Chest 106:431–4341994.
crossref pmid
18. al Jarad N, Parastatides S, Paul EA, Sheldon CD, Gaya H, Rudd RM, Empey DW. Characteristics of patients with drug resistant and drug sensitive tuberculosis in East London between 1984 and 1992. Thorax 49:808–8101994.
crossref pmid pmc
19. Riley LW, Arathoon E, Loverde VD. The epidemiologic patterns of drug-resistant Mycobacterium tuberculosis infections: a community-based study. Am Rev Respir Dis 139:1282–12851989.
crossref pmid
20. Kim SJ, Hong YP, Lew WJ, Yang SC, Lee EG. Incidence of pulmonary tuberculosis among diabetes. Tuber Lung Dis 76:529–5331995.
crossref pmid
21. Kaplan M, Armstrong D, Rosen P. Tuberculosis complicating neoplastic disease. A review of 201 cases. Cancer 33:850–8581974.
crossref pmid
22. Barnes PF, el-Hajj H, Preston-Martin S, Cave MD, Jones BE, Otaya M, Pogoda J, Eisenach KD. Transmission of tuberculosis among the urban homeless. JAMA 275:305–3071996.
crossref pmid
23. Horwitz O. Tuberculosis risk and marital status. Am Rev Respir Dis 104:22–311971.
pmid
24. Lerner BH. Can stress cause disease? Revisiting the tuberculosis research of Thomas Holmes, 1949–1961. Ann Intern Med 124:673–6801996.
crossref pmid
25. Addington WW. Patient compliance: the most serious remaining problem in the control of tuberculosis in the United States. Chest 76:S741–7431979.
crossref
26. Pearson ML, Jereb JA, Frieden TR, Crawford JT, Davis BJ, Dooley SW, Jarvis WR. Nosocomial transmission of multidrug-resistant Mycobacterium tuberculosis. A risk to patients and health care workers. Ann Intern Med 117:191–1961992.
crossref pmid
27. Kim SY, Jeong SS, Kim KW, Shin KS, Park SG, Kim AK, Cho HJ, Kim JO. Drug-resistant pulmonary tuberculosis in a tertiary referral hospital in Korea. Korean J Intern Med 14:27–311999.
crossref pmid pmc
28. WHO/IUATLD Global Working Group on Antituberculosis Drug Resistance Surveillance. Guidelines for surveillance of drug resistance in tuberculosis. WHO Geneva/IUATLD Paris. Int J Tuberc Lung Dis 2:72–891998.
pmid
29. Cohn DL, Bustreo F, Raviglione MC. Drug-resistant tuberculosis: review of the worldwide situation and the WHO/IUATLD global surveillance project. Clin Infect Dis 24(S1):121–1301997.
crossref
30. Alland D, Kalkut GE, Moss AR, McAdam RA, Hahn JA, Bosworth W, Druckor E, Bloom BR. Transmission of tuberculosis in New York City: an analysis by DNA fingerprinting and conventional epidemiologic methods. N Engl J Med 330:1710–17161994.
crossref pmid
31. Van Rie A, Warren R, Richardson M, Gie RP, Enarson DA, Beyers N, Van Helden PD. Classification of drug-resistant tuberculosis in an epidemic area. Lancet 356:22–252000.
crossref pmid
32. Salomon N, Perlman DC, Friedmann P, Buchstein S, Kreiswirth BN, Mildvan D. Predictors and outcome of multidrug-resistant tuberculosis. Clin Infect Dis 21:1245–12521995.
crossref pmid
33. Sinkowitz RL, Fridkin SK, Manangan L, Wenger PN, Jarvis WR. Status of tuberculosis infection control programs at United States hospitals, 1989 to 1992. Am J Infect Control 24:226–2341996.
crossref pmid
34. Reichman LB. Multidrug Resistance in the world: the present situation. Chemotherapy 42:S2–91996.
crossref
35. Flament-Saillour M, Robert J, Jarlier V, Grosset J. Outcome of multi-drug-resistant tuberculosis in France. Am J Respir Crit Care Med 160:587–5931999.
crossref pmid
36. Espinai MA, Kim SJ, Suarez PG, Kam KM, Khomenko AG, Migliori GB, Baez J, Kochi A, Dye C, Raviglione MC. Standard short-course chemotherapy for drug-resistant tuberculosis. JAMA 283:2537–25452000.
crossref pmid
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