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October 16, 1996, Vol 276, No. 15 >
ARTICLE | October 16, 1996

A Multi-institutional Outbreak of Highly Drug-Resistant Tuberculosis: Title and subTitle BreakEpidemiology and Clinical Outcomes FREE

Thomas R. Frieden, MD, MPH; Lisa Fine Sherman, MPH; Khin Lay Maw, MBBS, MPH; Paula I. Fujiwara, MD, MPH; Jack T. Crawford, PhD; Beth Nivin, MPH; Victoria Sharp, MD; Dial Hewlett, Jr, MD; Karen Brudney, MD; David Alland, MD; Barry N. Kreiswirth, PhD
[+] Author Affiliations

Reprints: Thomas Frieden, MD, MPH, Director, Bureau of Tuberculosis Control, New York City Department of Health, 125 Worth St, Box 74, New York, NY 10013.


JAMA. 1996;276(15):1229-1235. doi:10.1001/jama.1996.03540150031027
Text Size: A A A
Published online
Article
References

Objective.  —To investigate a multi-institutional outbreak of highly resistant tuberculosis and evaluate patient outcome.

Design.  —Epidemiologic investigation of every tuberculosis case reported in New York City.

Setting.  —Patients cared for at all public and nonpublic institutions from January 1, 1990, to August 1, 1993 (43 months).

Patients.  —We reviewed medical and public health records and conducted clinical, epidemiologic, drug susceptibility, and restriction fragment length polymorphism (RFLP) analyses. A case was defined as tuberculosis in a patient with an isolate resistant to isoniazid, rifampin, ethambutol hydrochloride, and streptomycin (and rifabutin, if sensitivity testing included it), and, if RFLP testing was done, a pattern identical to or closely related to strain W.

Main Outcome Measures.  —Patient survival and the conversion of sputum cultures from positive to negative.

Results.  —Of the 357 patients who met the case definition, 267 had identical or nearly identical RFLP patterns; isolates from the other 90 patients were not available for RFLP testing. Among these 267 patients, 86% were human immunodeficiency virus (HIV)-infected, 7% were HIV-negative, and 7% had unknown HIV status. All-cause mortality was 83%. Epidemiologic linkages were identified for 70% of patients, of whom 96% likely had nosocomially acquired disease at 11 hospitals. Survival was prolonged among patients who recieved medications to which their isolate was susceptible, especially capreomycin sulfate, and among patients with a CD4+ T-lymphocyte count greater than 0.200×109/L (200/μL). Treatment with isoniazid and a fluoroquinolone antibiotic was also independently associated with longer survival.

Conclusions.  —This outbreak accounted for nearly one fourth of the cases of multidrug-resistant tuberculosis in the United States during a 43-month period. Most patients had nosocomially acquired disease, were infected with HIV, and unless promptly and appropriately treated, died rapidly. With appropriate directly observed treatment, especially combinations including an injectable medication, even severely immunocompromised patients had culture conversion and prolonged, tuberculosis-free survival.

REFERENCES

1 +
Frieden TR, Sterling T, Pablos-Méndez 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.
2 +
Bloch AB, Cauthen GM, Onorato IM, et al.  Nationwide survey of drug-resistant tuberculosis in the United States . JAMA . 1994;;271:665-671.
3 +
Centers for Disease Control.  Nosocomial transmission of multidrug-resistant tuberculosis among HIV-infected persons—Florida and New York, 1988-1991 . MMWR Morb Mortal Wkly Rep . 1991;;40:585-591.
4 +
Coronado VG, Beck-Sague CM, Hutton MD, et al.  Transmission of multidrug-resistant Mycobacterium tuberculosis among persons with human immunodeficiency virus infection in an urban hospital: epidemiologic and restriction fragment length polymorphism analysis . J Infect Dis . 1993;;168:1052-1055.
5 +
Small PM, Shafer RW, Hopewell PC, et al.  Exogenous reinfection with multidrug-resistant Mycobacterium tuberculosis in patients with advanced HIV infection . N Engl J Med . 1993;;328:1137-1144.
6 +
Pearson ML, Jereb JA, Frieden TR, et al.  Nosocomial transmission of multidrug-resistant Mycobacterium tuberculosis: a risk to patients and health care workers . Ann Intern Med . 1992;;117:191-196.
7 +
Valway SE, Greifinger RB, Papania M, et al.  Multidrug-resistant tuberculosis in the New York State prison system, 1990-1991 . J Infect Dis . 1994;;170:151-156.
8 +
Goble M.  Drug-resistant tuberculosis . Semin Respir Infect . 1986;;1:220-229.
9 +
Plikaytis BB, Marden JL, Crawford JT, Woodley CL, Butler WR, Shinnick TM.  Multiplex PCR assay specific for the multidrug-resistant strain W of Mycobacterium tuberculosis . J Clin Microbiol . 1994;;32:1542-1546.
10 +
Friedman CR, Stoeckle MY, Kreiswirth BN, et al.  Transmission of multidrug-resistant tuberculosis in a large urban setting . Am J Respir Crit Care Med . 1995;;152:355-358.
11 +
Bifani PJ, Plikaytis BB, Kapur V, et al.  Origin and interstate spread of a New York City multidrug-resistant Mycobacterium tuberculosis clone family . JAMA . 1996;;275:452-457.
12 +
Hewlett D Jr, Horn DL, Alfalla C.  Drug-resistant tuberculosis: inconsistent results of pyrazinamide susceptibility testing . JAMA . 1995;;273:916-917.
13 +
Frieden TR, Fujiwara PI, Washko RM, Hamburg MA.  Tuberculosis in New York City: turning the tide . N Engl J Med . 1995;;333:229-233.
14 +
Hermans PW, van Soolingen D, Dale JW, et al.  Insertion elements IS986 from Mycobacterium tuberculosis: a useful tool for diagnosis and epidemiology of tuberculosis . J Clin Microbiol . 1990;;28:2051-2058.
15 +
Cave MD, Eisenach KD, McDermott PF, Bates JH, Crawford JT.  IS6110: conservation of sequence in the Mycobacterium tuberculosis complex and its utilization in DNA fingerprinting . Mol Cell Probes . 1991;;5:73-80.
16 +
van Embden JDA, Cave MD, Crawford JT, et al.  Strain identification of Mycobacterium tuberculosis by DNA fingerprinting: recommendations for a standardized methodology . J Clin Microbiol . 1993;;31:406-409.
17 +
Dean AG, Dean JA, Coulombier D, et al. Epi Info, Version 6.03: A Word Processing, Database, and Statistics Program for Public Health on IBM-Compatible Microcomputers . Atlanta, Ga: Centers for Disease Control and Prevention; 1995;.
18 +
SAS Institute Inc. SAS/STAT Software: Syntax Version 6. Cary, NC: SAS Institute Inc; 1993.
19 +
Azmeh W, Ziegenfuss R, Lutfey M, et al.  Clinical, microbiologic, and epidemiologic evaluation of an outbreak of multi-drug resistant tuberculosis (MDR-TB) . In: Programs and abstracts of the 33rd Interscience Conference on Antimicrobial Agents and Chemotherapy ; October 17-20, 1993;; New Orleans, La. Abstract 604.
20 +
Alfalla C, Hewlett D, Horn D, et al.  An outbreak of multidrug resistant tuberculosis among 28 patients at a New York City hospital . In: Programs and abstracts of the 32nd Interscience Conference on Antimicrobial Agents and Chemotherapy ; October 11-14, 1992;; Anaheim, Calif. Abstract 551.
21 +
Sathyakumar C, Palumbo LA, Ebrahimzadeh A, Reimer SM.  Time to detect growth of multidrug-resistant Mycobacterium tuberculosis . Presented at the 95th General Meeting of the American Society for Microbiology ; May 21-25, 1995;; Washington, DC. Abstract U-146.
22 +
Cohn ML, Kovitz C, Oda U, Middlebrook G:  Studies on isoniazid and tubercle bacilli, II: the growth requirements, catalase activities, and pathogenic properties of isoniazid-resistant mutant . Am Rev Tuberc . 1954;;70:641-644.
23 +
Ausina V, Riutort N, Viñado B, et al.  Prospective study of drug-resistant tuberculosis in a Spanish urban population including patients at risk for HIV infection . Eur J Clin Microbiol Infect Dis . 1995;;14:105-110.
24 +
Daley CL, Small PM, Schecter GF, et al.  An outbreak of tuberculosis with accelerated progression among persons infected with the human immunodeficiency virus: an analysis using restrictionfragment-length polymorphisms . N Engl J Med . 1992;;326:231-235.
25 +
Valway S, Greifinger R.  Risk of HIV-positive persons becoming infected and developing disease after exposure to multidrug-resistant tuberculosis , New York. In: Programs and abstracts of the 33rd Interscience Conference on Antimicrobial Agents and Chemotherapy ; October 17-20, 1993;; New Orleans, La. Abstract 607.
26 +
Centers for Disease Control.  Guidelines for preventing the transmission of tuberculosis in health-care settings, with special focus on HIV-related issues . MMWR Morb Mortal Wkly Rep . 1990;;39 (RR-17):1-27.
27 +
Wenger PN, Otten J, Breeden A, Orfas D, Beck-Sague CM, Jarvis WR.  Control of nosocomial transmission of multidrug-resistant Mycobacterium tuberculosis among health care workers and HIV-infected patients . Lancet . 1995;;345:235-240.
28 +
Maloney SA, Pearson ML, Gordon MT, Del Castillo R, Boyle JF, Jarvis WR.  Efficacy of control measures in preventing nosocomial transmission of multidrug-resistant tuberculosis to patients and health care workers . Ann Intern Med . 1995;;122:90-95.
29 +
Iseman MD.  Treatment of multidrug-resistant tuberculosis . N Engl J Med . 1993;;329:784-791.
30 +
Mitchison DA, Dickinson JM.  Laboratory aspects of intermittent drug therapy . Postgrad Med J . 1971;;47:737-741.
31 +
Comstock GW, Livesay VT, Ferebee Woolpert S.  The prognosis of a positive tuberculin reaction in childhood and adolescence . Am J Epidemiol . 1974;;99:131-138.
32 +
Villarino ME, Dooley SW Jr, Geiter LJ, Castro KG, Snider DE Jr.  Management of persons exposed to multidrug-resistant tuberculosis . MMWR Morb Mortal Wkly Rep . 1992;;41(RR-11):59-71.
33 +
Horn DL, Hewlett D, Alfalla C, et al.  Limited tolerance of ofloxacin and pyrazinamide prophylaxis in health care workers following exposure to rifampin-isoniazid-streptomycin-ethambutol-resistant tuberculosis . Infect Dis Clin Pract . 1995;;4: 219-225.
34 +
Centers for Disease Control.  Nosocomial transmission of multidrug-resistant tuberculosis to health-care workers and HIV-infected patients in an urban hospital—Florida . MMWR Morb Mortal Wkly Rep . 1989;;38:313-320, 325.
35 +
Centers for Disease Control and Prevention.  Guidelines for preventing the transmission of Mycobacterium tuberculosis in health care facilities . MMWR Morb Mortal Wkly Rep . 1994;;43(RR-13):1-132.
36 +
Telzak EE, Sepkowitz K, Alpert P, et al.  Multidrug-resistant tuberculosis in patients without HIV infection . N Engl J Med . 1995;;333:907-911.
37 +
Turett GS, Telzak EE, Torian LV, et al.  Improved outcomes for patients with multidrug-resistant tuberculosis . Clin Infect Dis . 1995;;21:1238-1244.
38 +
Saloman N, Perlman DC, Friedmann P, Buchstein S, Kreiswirth BN, Mildvan D.  Predictors and outcome of multidrug-resistant tuberculosis . Clin Infect Dis . 1995;;21:1245-1252.
39 +
Fischl MA, Daikos GL, Uttamchandani RB, et al.  Clinical presentation and outcome of patients with HIV infection and tuberculosis caused by multiple-drug-resistant bacilli . Ann Intern Med . 1992;;117:184-190.

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Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature

Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal

1 +
Frieden TR, Sterling T, Pablos-Méndez 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.
2 +
Bloch AB, Cauthen GM, Onorato IM, et al.  Nationwide survey of drug-resistant tuberculosis in the United States . JAMA . 1994;;271:665-671.
3 +
Centers for Disease Control.  Nosocomial transmission of multidrug-resistant tuberculosis among HIV-infected persons—Florida and New York, 1988-1991 . MMWR Morb Mortal Wkly Rep . 1991;;40:585-591.
4 +
Coronado VG, Beck-Sague CM, Hutton MD, et al.  Transmission of multidrug-resistant Mycobacterium tuberculosis among persons with human immunodeficiency virus infection in an urban hospital: epidemiologic and restriction fragment length polymorphism analysis . J Infect Dis . 1993;;168:1052-1055.
5 +
Small PM, Shafer RW, Hopewell PC, et al.  Exogenous reinfection with multidrug-resistant Mycobacterium tuberculosis in patients with advanced HIV infection . N Engl J Med . 1993;;328:1137-1144.
6 +
Pearson ML, Jereb JA, Frieden TR, et al.  Nosocomial transmission of multidrug-resistant Mycobacterium tuberculosis: a risk to patients and health care workers . Ann Intern Med . 1992;;117:191-196.
7 +
Valway SE, Greifinger RB, Papania M, et al.  Multidrug-resistant tuberculosis in the New York State prison system, 1990-1991 . J Infect Dis . 1994;;170:151-156.
8 +
Goble M.  Drug-resistant tuberculosis . Semin Respir Infect . 1986;;1:220-229.
9 +
Plikaytis BB, Marden JL, Crawford JT, Woodley CL, Butler WR, Shinnick TM.  Multiplex PCR assay specific for the multidrug-resistant strain W of Mycobacterium tuberculosis . J Clin Microbiol . 1994;;32:1542-1546.
10 +
Friedman CR, Stoeckle MY, Kreiswirth BN, et al.  Transmission of multidrug-resistant tuberculosis in a large urban setting . Am J Respir Crit Care Med . 1995;;152:355-358.
11 +
Bifani PJ, Plikaytis BB, Kapur V, et al.  Origin and interstate spread of a New York City multidrug-resistant Mycobacterium tuberculosis clone family . JAMA . 1996;;275:452-457.
12 +
Hewlett D Jr, Horn DL, Alfalla C.  Drug-resistant tuberculosis: inconsistent results of pyrazinamide susceptibility testing . JAMA . 1995;;273:916-917.
13 +
Frieden TR, Fujiwara PI, Washko RM, Hamburg MA.  Tuberculosis in New York City: turning the tide . N Engl J Med . 1995;;333:229-233.
14 +
Hermans PW, van Soolingen D, Dale JW, et al.  Insertion elements IS986 from Mycobacterium tuberculosis: a useful tool for diagnosis and epidemiology of tuberculosis . J Clin Microbiol . 1990;;28:2051-2058.
15 +
Cave MD, Eisenach KD, McDermott PF, Bates JH, Crawford JT.  IS6110: conservation of sequence in the Mycobacterium tuberculosis complex and its utilization in DNA fingerprinting . Mol Cell Probes . 1991;;5:73-80.
16 +
van Embden JDA, Cave MD, Crawford JT, et al.  Strain identification of Mycobacterium tuberculosis by DNA fingerprinting: recommendations for a standardized methodology . J Clin Microbiol . 1993;;31:406-409.
17 +
Dean AG, Dean JA, Coulombier D, et al. Epi Info, Version 6.03: A Word Processing, Database, and Statistics Program for Public Health on IBM-Compatible Microcomputers . Atlanta, Ga: Centers for Disease Control and Prevention; 1995;.
18 +
SAS Institute Inc. SAS/STAT Software: Syntax Version 6. Cary, NC: SAS Institute Inc; 1993.
19 +
Azmeh W, Ziegenfuss R, Lutfey M, et al.  Clinical, microbiologic, and epidemiologic evaluation of an outbreak of multi-drug resistant tuberculosis (MDR-TB) . In: Programs and abstracts of the 33rd Interscience Conference on Antimicrobial Agents and Chemotherapy ; October 17-20, 1993;; New Orleans, La. Abstract 604.
20 +
Alfalla C, Hewlett D, Horn D, et al.  An outbreak of multidrug resistant tuberculosis among 28 patients at a New York City hospital . In: Programs and abstracts of the 32nd Interscience Conference on Antimicrobial Agents and Chemotherapy ; October 11-14, 1992;; Anaheim, Calif. Abstract 551.
21 +
Sathyakumar C, Palumbo LA, Ebrahimzadeh A, Reimer SM.  Time to detect growth of multidrug-resistant Mycobacterium tuberculosis . Presented at the 95th General Meeting of the American Society for Microbiology ; May 21-25, 1995;; Washington, DC. Abstract U-146.
22 +
Cohn ML, Kovitz C, Oda U, Middlebrook G:  Studies on isoniazid and tubercle bacilli, II: the growth requirements, catalase activities, and pathogenic properties of isoniazid-resistant mutant . Am Rev Tuberc . 1954;;70:641-644.
23 +
Ausina V, Riutort N, Viñado B, et al.  Prospective study of drug-resistant tuberculosis in a Spanish urban population including patients at risk for HIV infection . Eur J Clin Microbiol Infect Dis . 1995;;14:105-110.
24 +
Daley CL, Small PM, Schecter GF, et al.  An outbreak of tuberculosis with accelerated progression among persons infected with the human immunodeficiency virus: an analysis using restrictionfragment-length polymorphisms . N Engl J Med . 1992;;326:231-235.
25 +
Valway S, Greifinger R.  Risk of HIV-positive persons becoming infected and developing disease after exposure to multidrug-resistant tuberculosis , New York. In: Programs and abstracts of the 33rd Interscience Conference on Antimicrobial Agents and Chemotherapy ; October 17-20, 1993;; New Orleans, La. Abstract 607.
26 +
Centers for Disease Control.  Guidelines for preventing the transmission of tuberculosis in health-care settings, with special focus on HIV-related issues . MMWR Morb Mortal Wkly Rep . 1990;;39 (RR-17):1-27.
27 +
Wenger PN, Otten J, Breeden A, Orfas D, Beck-Sague CM, Jarvis WR.  Control of nosocomial transmission of multidrug-resistant Mycobacterium tuberculosis among health care workers and HIV-infected patients . Lancet . 1995;;345:235-240.
28 +
Maloney SA, Pearson ML, Gordon MT, Del Castillo R, Boyle JF, Jarvis WR.  Efficacy of control measures in preventing nosocomial transmission of multidrug-resistant tuberculosis to patients and health care workers . Ann Intern Med . 1995;;122:90-95.
29 +
Iseman MD.  Treatment of multidrug-resistant tuberculosis . N Engl J Med . 1993;;329:784-791.
30 +
Mitchison DA, Dickinson JM.  Laboratory aspects of intermittent drug therapy . Postgrad Med J . 1971;;47:737-741.
31 +
Comstock GW, Livesay VT, Ferebee Woolpert S.  The prognosis of a positive tuberculin reaction in childhood and adolescence . Am J Epidemiol . 1974;;99:131-138.
32 +
Villarino ME, Dooley SW Jr, Geiter LJ, Castro KG, Snider DE Jr.  Management of persons exposed to multidrug-resistant tuberculosis . MMWR Morb Mortal Wkly Rep . 1992;;41(RR-11):59-71.
33 +
Horn DL, Hewlett D, Alfalla C, et al.  Limited tolerance of ofloxacin and pyrazinamide prophylaxis in health care workers following exposure to rifampin-isoniazid-streptomycin-ethambutol-resistant tuberculosis . Infect Dis Clin Pract . 1995;;4: 219-225.
34 +
Centers for Disease Control.  Nosocomial transmission of multidrug-resistant tuberculosis to health-care workers and HIV-infected patients in an urban hospital—Florida . MMWR Morb Mortal Wkly Rep . 1989;;38:313-320, 325.
35 +
Centers for Disease Control and Prevention.  Guidelines for preventing the transmission of Mycobacterium tuberculosis in health care facilities . MMWR Morb Mortal Wkly Rep . 1994;;43(RR-13):1-132.
36 +
Telzak EE, Sepkowitz K, Alpert P, et al.  Multidrug-resistant tuberculosis in patients without HIV infection . N Engl J Med . 1995;;333:907-911.
37 +
Turett GS, Telzak EE, Torian LV, et al.  Improved outcomes for patients with multidrug-resistant tuberculosis . Clin Infect Dis . 1995;;21:1238-1244.
38 +
Saloman N, Perlman DC, Friedmann P, Buchstein S, Kreiswirth BN, Mildvan D.  Predictors and outcome of multidrug-resistant tuberculosis . Clin Infect Dis . 1995;;21:1245-1252.
39 +
Fischl MA, Daikos GL, Uttamchandani RB, et al.  Clinical presentation and outcome of patients with HIV infection and tuberculosis caused by multiple-drug-resistant bacilli . Ann Intern Med . 1992;;117:184-190.

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