(Chest. 2001;119:1730-1736.)
© 2001
American College of Chest Physicians
Treatment of Isoniazid-Resistant Tuberculosis in Southeastern Texas*
Patricio Escalante, MD;
Edward A. Graviss, PhD, MPH;
David E. Griffith, MD, FCCP;
James M. Musser, MD, PhD and
Robert J. Awe, MD, FCCP
*
From the Sections of Pulmonary and Critical Care (Drs. Escalante and Awe) and Infectious Diseases (Dr. Graviss), Institute for the Study of Human Bacterial Pathogenesis, Baylor College of Medicine, Houston, TX; the Center for Pulmonary and Infectious Disease Control (Dr. Griffith), University of Texas Health Center at Tyler, Tyler, TX; and the Laboratory of Human Bacterial Pathogenesis (Dr. Musser), Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT.
Correspondence to: Patricio Escalante, MD, Assistant Professor, Division of Pulmonary and Critical Care, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles County Medical Center, 1200 N. State St, GNH 11900, Los Angeles, CA 90033; e-mail: Patricioe{at}aol.com
 |
Abstract
|
|---|
Background: Isoniazid-resistant tuberculosis (INHr-TB)
can be treated successfully with several treatment regimens. However,
the optimal regimen and duration are unclear.
Study
objective: To analyze the efficacy of treatment regimens used for
INHr-TB in the southeastern Texas region.
Design:
Retrospective cohort study.
Setting: Health-care
facilities reporting tuberculosis (TB) patients in the Houston and
Tyler areas.
Subjects: All patients reported to have
INHr-TB from 1991 to 1998. Exclusion criteria included poor compliance,
additional first-line drug-resistance (except aminoglycosides), and
death before completion of 1 month of treatment.
Measurements and results: Main treatment outcomes
were treatment failure, relapse, and TB-related death. Fifty-three of
83 patients were included in the study; aminoglycoside resistance
coexisted in 37.5% of isolates. Seven types of treatment regimens were
identified. Eighteen patients (34%) received rifampin, pyrazinamide,
and ethambutol thrice weekly for 9 months. Four patients (7.5%) had a
total effective treatment duration of < 9 months. Thirty patients
(56.6%) and 16 patients (30.2%) received thrice-daily and daily
treatment regimens, respectively. Forty-nine patients achieved sputum
conversion. Treatment failure and death occurred in one patient
(1.9%). Three patients (5.7%) experienced relapses. There was a
significant difference in total effective treatment time between
patients with and without relapses (8.3 ± 1.1 months vs
11.1 ± 2.1 months; p < 0.02). Twice-weekly treatment regimens
were associated with relapse (p = 0.05).
Conclusions: Several treatment regimens were prescribed for
INHr-TB in southeastern Texas. INHr-TB treatment durations were > 7
months, and treatment regimen efficacy was adequate. Twice-weekly
treatment was associated with relapse, whereas thrice-weekly and daily
treatments performed similarly. A prospective study with different
treatment durations is needed to determine the optimal treatment
regimen for patients with INHr-TB.
Key Words: drug resistance • isoniazid • isoniazid resistance • relapse • treatment • tuberculosis
|
Introduction
|
|---|
Effective
short-course chemotherapy for tuberculosis (TB) has been available
worldwide for > 20 years.1
Despite this, drug-resistant
TB continues to threaten the efforts to control the disease in many
parts of the world. A recent global surveillance study2
assessing the resistance to first-line anti-TB agents depicted the
magnitude of the problem. In particular, primary and secondary
isoniazid-resistant TB (INHr-TB) strains were highly prevalent,
particularly in areas with a high incidence of TB.2
Some
developed countries, including the United States, have also shown high
rates of isoniazid (INH) resistance, especially in patients with a
history of prior TB.2
3
In addition to the INHr-TB
problem, a significant number of TB patients are unable to use INH in
their regimens. INH intolerance can be a significant problem,
especially in adult populations, and although INH treatment is
uncommonly associated with hepatitis, the use of this drug is
problematic in patients with chronic liver disease.4
5
Several regimens have been used successfully to treat patients with
INHr-TB in the past.6
Treatment failures are rare when
regimens containing rifampin (RIF) and two other first-line drugs for
6 months are used. A review6
of 12 controlled trials
conducted in Africa, Hong Kong, and Singapore described reduced relapse
rates with the use of four or five drug treatment regimens, including
RIF. Despite the numerous patients included in those studies, the
optimal treatment regimen and duration for INHr-TBhave
not been exclusively addressed in a prospective, randomized fashion.
The only exception is a clinical trial conducted in
Kenya.7
This study compared 6-month and 9-month regimens
of daily direct observed therapy (DOT) with RIF plus ethambutol (EMB),
including an initial 8-week daily treatment regimen of pyrazinamide
(PZA) and streptomycin (SM). Treatment failures were low (< 1%).
However, the relapse rates were relatively high (up to 21%) when the
isolates were INH resistant and SM resistant, and/or the treatment was
given for only 6 months.7
A joint statement of the
American Thoracic Society (ATS) and the Centers for Disease Control and
Prevention (CDC) has recommended the use of a "6-month four-drug"
treatment regimen as an effective regimen for INHr-TB,8
based on a randomized trial performed in Singapore.9
This
clinical trial, performed about 20 years ago, included 33 patients with
INHr-TB (with or without coexistence of SM-resistant TB) and had only 6
months of follow-up. The ATS/CDC statement also recommends the
discontinuation of INH treatment, and the use of PZA for the entire 6
months of treatment. In cases in which PZA is not used, the treatment
duration is extended to 9 months. When RIF and EMB are used solely, a
12-month regimen is recommended. Although the efficacy of intermittent
short-course treatment has been well established for the treatment of
pansensitive Mycobacterium tuberculosis,10
11
12
the optimal treatment dose frequency for INHr-TB has not been
elucidated at the present time.8
The main aims of our
study are to retrospectively describe and to attempt to evaluate the
efficacy of the different treatment regimens used for INHr-TB in the
southeastern Texas region.
|
Materials and Methods
|
|---|
Patients
The study included all known patients who were reported to have
INHr-TB isolates from different health facilities and clinics located
in southeastern Texas to the health departments of the Houston and
Tyler areas between 1991 and 1998. Additional INHr-TB patients were
prospectively included from referrals to the Chest Clinics at Ben Taub
General Hospital and the University of Texas Health Center at Tyler
(referral centers for cases of drug-resistant TB in the southeastern
Texas region) since early 1997. In addition, the existing patient
information was complemented by the use of a comprehensive database
from the Houston TB Initiative. The Houston TB Initiative is an
ongoing, population-based, active surveillance and molecular
epidemiology project encompassing all known reported cases of TB
(approximately 2,580 cases up to January 1999) in Harris County, Texas
since 1995. Treatment and follow-up information was gathered from the
local TB control program records, patient charts, patient interviews,
and telephone calls.
Exclusion Criteria
Exclusion criteria were as follows: inadequate clinical
information, evidence of poor compliance during INHr-TB treatment
course, uncompleted treatment, coexistence of resistance to other
first-line drugs (excluding aminoglycosides), coinfection with
mycobacteria other than tuberculosis, silicotuberculosis, and
death after < 1 month of treatment. Inadequate clinical information
was defined as insufficient patient data after searching all possible
sources of case information related to patient TB-focus, clinical
history, bacteriology, treatment, and posttreatment patient
information.
Specimen Processing and Drug-Susceptibility Testing
All clinical specimens were processed similarly in all locations
of the study according to the procedure manual of the Texas Health
Department. Briefly, smear specimens were decontaminated with 4% NaOH
solution and processed using the Truant’s staining for fluorescent
microscopic acid-fast bacilli determination.13
All
positive smear results were confirmed by overstaining with
Ziehl-Neelsen stain unless oil was placed on the smear.14
Primary isolation was performed using the BACTEC 460 instrument
technique (Becton Dickinson Microbiology Systems; Sparks, MD)
and culture in Middlebrook 7H10 or Lowenstein-Jensen
media.13
15
All isolates were niacin positive and nitrate
reductase positive, as well as AccuProbe (GenProbe; San Diego, CA)
positive.
Drug-susceptibility testing was performed locally twice and routinely
repeated at the Texas Health Department for all patients reported as
having smear-positive and/or culture-positive disease. Susceptibility
testing was performed using the direct and indirect BACTEC methods
(Becton Dickinson Microbiology Systems) and by an indirect method using
Middlebrook 7H10 agar. The drugs (and breakpoint concentrations) tested
by the BACTEC method included INH (0.4 µg/mL), RIF (2.0 µg/mL), EMB
(2.5 µg/mL), SM (2.0 µg/mL), and PZA (50 µg/mL) in acidic
media.15
The agents (and breakpoint concentrations) tested
using Middlebrook 7H10 agar included INH (1.0 µg/mL), RIF (1.0
µg/mL), EMB (5.0 µg/mL), SM (2.0 µg/mL), kanamycin (5.0 µg/mL
and 6.0 µg/mL), ethionamide (5.0 µg/mL), rifabutin (2.0 µg/mL),
capreomycin (10.0 µg/mL), and ciprofloxacin (2.0 µg/mL). No INH
dilution was performed with the liquid media. Drug-susceptibility
testing was conducted by laboratories certified under the Federal
Clinical Laboratory Improvement Act.13
Drug resistance was
defined as any degree of resistance reported to the local public health
authorities according to the Texas Department of Health laboratory
retesting results described above.
Clinical Outcomes and Definitions
All available clinical patient information was recorded,
including patient demographics, clinical symptoms, medical history,
comorbidities (including HIV status), social history, bacteriologic
information, radiologic data, detailed treatment information, side
effects, treatment outcomes, and posttreatment follow-up information.
Failure during treatment was defined in bacteriologic terms as the
presence of at least two positive culture findings obtained during the
last part of the patient treatment or after 4 months of adequate
treatment. One positive culture finding associated with worsening of
the patient’s symptoms or TB-related death during treatment was also
included in the definition of treatment failure. Relapse after stopping
treatment was defined as the presence of at least two positive culture
findings obtained in different months in any consecutive 3-month
period. Relapse was also considered by the presence of one positive
culture finding associated with recurrent patient symptoms after
completing treatment. Adequate treatment was defined by a minimum of 6
months of DOT, the use of one of the currently ATS/CDC recommended
regimens8
for treatments started after 1994 when the
statement was published, and the opinion of the patient’s responsible
physician attesting to appropriately completed treatment. Adherence to
treatment was assessed by comparing the number of administered
treatment doses against the number of treatment doses scheduled each
month. Although there are no specific guidelines to define poor
adherence in retrospective treatment studies in TB, poor compliance
with treatment was defined as consistently missing 35% of monthly
scheduled doses of medication in 2 months of treatment. Other end
points measured, based on available information, included death during
treatment, bacteriologic response assessed by routine monthly
sputum/specimen smear for acid-fast bacilli and culture as described
above, radiologic response based on available chest radiograph reports,
and the presence of side effects to treatment. Sputum conversion was
defined as the first negative follow-up sputum culture finding.
The efficacy of the various anti-TB regimens was assessed based on (1)
the prevention of emergence of drug resistance, treatment failure, and
death, and (2) sterilization of the lesions, measured as the proportion
of patients with (a) sputum conversion and maintenance as such, and (b)
the prevention of relapse.
Statistics
Relevant patient clinical data including treatment regimen
characteristics were analyzed against described clinical end points.
Statistical significance was tested using either a
2 or Fisher’s Exact Test according rules for
parametric data.16
Data were analyzed using software (SAS
version 6.12; SAS Institute; Cary, NC).
|
Results
|
|---|
Fifty-three of 83 patients (64%) reported to have INHr-TB were
included in the study. The main reasons for patient exclusion are
described in Table 1
. Baseline patient characteristics are listed in Table 2
. SM resistance coexisted with INH resistance in 20 patients (37.5% of
isolates). There was a great variation between treatment regimens
prescribed for INHr-TB patients in the study population, especially
with regard to anti-TB drug regimen composition, frequency of
administration, dosage, and length of treatment. Although the treatment
regimens in general were different between patients, we attempted to
group them arbitrarily into seven types according to drug regimen
composition, dose frequency, and frequency of utilization (Table 3
). Eighteen patients (34%) received RIF, PZA, and EMB thrice weekly for
at least 9 months. Thirty-six patients (67.9%) had a duration of
specific treatment, after INH-resistant determination, of 9 months.
Only four patients (7.5%) had a total effective treatment duration of
< 9 months. However, no patient had a total effective treatment
duration of < 7 months, except one patient who died after 1 month of
treatment. Thirty patients (56.6%) and 16 patients (30.2%) received
thrice-weekly and daily treatments, respectively.
All 49 patients who had pulmonary TB involvement and documented sputum
acid-fast bacilli smear achieved sputum conversion (Table 4 ). Treatment failure occurred in one patient (1.9%) who died and did
not achieve a sputum-negative culture finding. This patient had AIDS
with a CD4 count of 72, and received treatment with daily INH, RIF,
PZA, and EMB for 1 month in the hospital. The patient died of
respiratory insufficiency due to a combination of TB, aspiration
pneumonia, and sepsis. Three patients (5.7%) experienced relapses: one
patient had 7 months of treatment of undetermined dose frequency, and
the other two patients had 11 months and 14 months of treatment,
respectively, administered twice weekly. In the first case, the patient
received PZA for the first 2 months, in addition to RIF and EMB for a
total of 7 months, 5 months of which the patient received treatment in
a chest hospital and the last 2 months by DOT. The second patient
initially received twice-weekly treatment with INH, RIF, and PZA for 2
months followed by twice-weekly treatment with RIF, PZA, and EMB by DOT
for the next 9 months, in addition to SM for the first 2 months of the
9 months. Except for missing 35% of the doses in his fourth month of
treatment, his overall compliance was good. The third patient was
initially treated in 1991 with INH, RIF, and PZA twice weekly for 5
months, followed by 3 months of treatment with RIF, PZA, and EMB twice
weekly, and 6 additional months of twice-weekly RIF and EMB treatment.
This third patient had virtually no missing scheduled doses of
treatment. All patients with relapses were HIV-negative. Their
adherence to treatment did not meet the definition of poor compliance
according to the study exclusion criteria. The first two patients
developed RIF resistance in addition to the original INH resistance.
Follow-up time posttreatment ranged from 0 to 51.75 months with a mean
of 7.21 months. Six patients (11%) developed side effects during
treatment, four of which were attributed to PZA. In three of these
patients, PZA treatment was discontinued.
Analysis of relevant patient clinical data, including treatment
characteristics, against main clinical end points showed a statistical
difference between total effective treatment time in patients with and
without relapses (8.33 ± 1.15 months vs 11.06 ± 2.08 months,
p < 0.02; Fig 1
). Twice-weekly treatment was associated with relapse (p = 0.05; Table 5
). The likelihood of relapse was not associated with any demographic
feature, history of prior TB, lack of treatment before availability of
drug susceptibility results (pretreatment period), HIV status,
comorbidities, alcohol abuse, bacteriologic or radiologic feature, or
other treatment characteristics. Treatment failure was not associated
with any clinical or bacteriologic end point. No other clinically
relevant and/or statistically significant association was found.
|
Discussion
|
|---|
Despite the introduction of modern chemotherapy decades ago, TB
continues to be a global public health problem. Moreover, primary and
secondary INH resistance has became a significant issue that appears to
be worsening in different parts of the world.2
In
addition, INH intolerance is not an uncommon challenge facing
physicians who treat patients with TB. These problems emphasize the
need to define a standard, cost-effective, and well-proven regimen for
the majority of INH-resistant and INH-intolerant patients.
Extensive and extraordinary clinical work has been done led mainly by
the British Medical Research Council (BMRC) TB and Chest Disease Unit
and collaborators in East Africa, Hong Kong, and Singapore, which
sustains the foundation of our modern short-course TB therapy. Yet, the
optimal treatment for INHr-TB patients is unclear and has not been
exclusively evaluated in a prospective, randomized, and controlled
fashion. Nevertheless, different treatment regimens for INHr-TB have
been shown to be effective (by having reasonable low failure and
relapse rates) according to data from INHr-TB patients from these
trials and the prospective trial from Kenya.6
7
However, a
post hoc analysis from the BMRC trials included mostly
primary INHr-TB patients, and the Kenya trial included only secondary
INHr-TB patients. Both studies included patients treated under ideal
protocol conditions, and excluded patients who had poor compliance or
side effects that precluded protocol continuation without alterations
in their treatment regimens. In addition, none of these studies has
addressed the impact of the frequency of treatment dose in their
analysis.
We attempted to retrospectively describe the treatment regimen
characteristics and to analyze the efficacy of these schemes in normal
working conditions in southeastern Texas. Houston, the largest
metropolitan area in the study region, has a large Mexican, Central
American, and Asian immigrant population. These immigrant groups have
the highest prevalence rates of INHr-TB in the United
States.3
This may explain the high proportion of Hispanic
and Asian persons found in the study sample (75%). Although a
substantial amount of information was obtained retrospectively, a
considerable portion, especially regarding treatment outcome and
follow-up data, was obtained prospectively. Nevertheless, the sample
size is similar to the extracted number of INHr-TB patients (with or
without SM resistance) from each of the BMRC trials, which ranged from
14 to 86 patients.6
9
11
Notably, 5 of 30 patients who
were excluded from the study died, 3 of them before achieving 1 month
of treatment. However, it is unclear whether TB was the main cause of
death, and no further information was available to elucidate this
issue.
Despite the aforementioned limitations, the relative heterogeneity of
the treatment regimens, and the usual shortcomings of a descriptive
retrospective cohort study, the study sample has shown an overall
adequate treatment efficacy measured by the sputum conversion rate at 2
months (64.6%), treatment failure (1.9%), and relapse rate (5.7%).
These rates are similar to those in the post hoc BMRC trials
study that extracted patients with INHr-TB and/or SM resistance (86%,
4%, and 7%, respectively) and in which patients received at least
four drugs including RIF (with or without PZA) for a minimum of 6
months of treatment.6
The difference in sputum conversion
at 2 months may be due to the probably greater number of patients with
secondary INHr-TB (approximately 20%) and cavitary disease (45%) in
our study population. Therefore, the slightly diminished sputum
conversion rate in our study may be due to a slower treatment response
in more chronic and extensive disease forms, compared to the population
of the BMRC trials. Otherwise, the final sputum conversion rate was
close to 100%.
In spite of the adequate treatment efficacy of the study population
overall, there was great variation in the composition, duration, and
dose frequency of the study treatment regimens. Therefore, it is
virtually impossible to identify superior or inferior regimens given
the type of study and the sample size. Nevertheless, almost 90% of
treatment regimens included at least three drugs, such as RIF, PZA and
EMB, that were administered under DOT for at least 9 months. However,
no treatment regimen was given for < 7 months despite the extensive
evidence of short-course treatment efficacy in pansensitive TB and the
ATS/CDC recommendations.8
Almost 87% of patients in the
study received mostly thrice-weekly or daily treatment regimens. None
of the patients who received daily and thrice-weekly RIF, PZA, and EMB
in their treatment regimens for at least 9 months (30 of 53 patients)
had negative outcomes.
Remarkably, two of four patients who received treatment twice weekly
experienced relapses. A comparison with all other treatment dose
frequencies yielded statistically significant association between
relapse and twice-weekly treatment. If we eliminate the relapsing case
of unknown treatment regimen from the analysis, the p value became 0.02
(Table 5)
. Thrice-weekly and daily treatment regimens were not
associated with relapse. Although there were some compliance issues in
one of these patients with a relapse, and treatment in the third
patient with a relapse did not follow completely the ATS/CDC
recommendations (his treatment was initiated 3 years before those were
published), these shortcomings were not believed to be severe enough
for exclusion from the study. Nevertheless, the twice-weekly treatment
results and the association with relapse should be interpreted
cautiously, given the type of study and the shortcomings presented.
Although to our knowledge there is no prospective study comparing the
efficacy of twice-weekly vs thrice-weekly treatment in INHr-TB,
virtually all treatment regimens that included RIF (with or without
PZA) for 4 months in all the BMRC-sponsored trials received daily
and/or thrice-weekly treatment.6
Those treatment regimens
had the smallest treatment failure and relapse rates for INHr-TB with
or without SM resistance. When RIF was given for 2 months and the
continuation phase was given twice weekly, such as in two arms of the
second BMRC/Hong Kong trial, then the relapse rate increased up to 11%
and 36% with the use of PZA and EMB, respectively, in conjunction with
SM and INH.17
Even though relatively weaker regimens did
not include RIF in the continuation phase, the findings may still
suggest that twice-weekly treatment may not be as effective as daily
and thrice-weekly treatments for INHr-TB. This is not the case for
pansensitive TB patients treated with twice-weekly regimens, which have
been shown to be at least as effective as the daily
regimens.10
Interestingly, there was a statistical difference between total
effective treatment time in patients with and without relapses (Fig 1)
.
This result should be interpreted with caution because of the sample
size effect, the shortcomings of a retrospective study, and the
heterogeneity of the treatment regimens as a confounding factor in our
study. Nevertheless, it is reasonable to postulate that a shorter
duration of treatment may increase the chances of relapse in INHr-TB
patients if the treatment regimen associated with relapse is not highly
effective. To our knowledge, the Kenya trial was the only prospective
study that compared treatment times in patients with INHr-TB. This
trial, which included 226 patients with only INHr-TB with or without
additional SM resistance, may support the hypothesis of treatment for
> 6 months.7
If we rearrange the Kenya trial data to
group all the patients who received 4-month RIF and EMB treatment
(n = 86) and 7-month RIF and EMB treatment (n = 92) in the
continuation phase mixing INHr-TB patients and SM-resistant TB
patients, then the resulting new proportions of relapse cases are 6 of
86 patients (6.9%) and 2 of 92 patients (2.1%) for the 6-month and
9-month treatment periods, respectively (p < 0.05). However, the
third Hong Kong study included 78 patients with INHr-TB with or without
SM resistance.11
The trial tested five treatment regimens:
INH-RIF-SM-PZA-EMB (thrice weekly), INH-RIF-SM-PZA (thrice weekly),
INH-RIF-SM-EMB (thrice weekly), INH-RIF-PZA-EMB (thrice weekly), and
INH-RIF-PZA-EMB (daily), all for 6 months. The only regimen that showed
a higher relapse rate compared to all the others was the one using INH,
RIF, SM, and EMB thrice weekly (4 of 21 patients; 21%). These findings
also suggest that using less effective regimens such as RIF and EMB
thrice weekly as the only effective treatment for INHr-TB for < 6
months is inadequate. In addition, the same study points out the
importance of receiving PZA, in addition to RIF, throughout the
treatment,11
or at minimum during the intensive phase, as
shown by others.6
Finally, the overall rate of side effects (11.4%) was within the
expected number, compared to similar values reported in the third
(6-month thrice-weekly and daily) Hong Kong/BMRC trial.11
Interestingly, in our study as well as in the BMRC trial, PZA was the
drug most frequently associated with interruption of treatment and
termination of the drug treatment from the regimen. However, the rate
of side effects related to PZA was not high enough to preclude the use
of this important drug.
|
Conclusion
|
|---|
Several types of treatment regimens for INHr-TB have been used in
southeastern Texas since 1992. INHr-TB treatment regimens have for the
most part been for > 6 months, and the overall treatment efficacy was
adequate. Both twice-weekly and once-daily treatments had similar
treatment outcomes. A prospective study with different treatment
durations and comparing twice-weekly against thrice-weekly and/or
once-daily dose frequency is needed to determine the optimal treatment
for INHr-TB patients.
|
Acknowledgements
|
|---|
We thank all personnel at the Ben Taub General
Hospital and at the University of Texas at Tyler Chest clinic for their
kind and helpful collaboration. We also kindly acknowledge the
assistance of the workers at the Tuberculosis Control Unit of the City
of Houston, the Houston TB Initiative, and the Texas Department of
Health laboratory personnel.
|
Footnotes
|
|---|
Abbreviations:
ATS = American Thoracic Society; BMRC = British Medical Research
Council; CDC = Centers for Disease Control and Prevention;
DOT = directly observed therapy; EMB = ethambutol;
INH = isoniazid; INHr-TB = isoniazid-resistant tuberculosis;
PZA = pyrazinamide; RIF = rifampin; SM = streptomycin;
TB = tuberculosis
Support was provided by US Public Health Services Grant DA-09238 (to
J.M.M.).
Received for publication March 23, 2000.
Accepted for publication January 10, 2001.
|
References
|
|---|
-
Iseman, MD, Sbarbaro, JA (1991) Short-course chemotherapy of tuberculosis: hail Britannia (and friends) [editorial]! Am Rev Respir Dis 143,697-698[Medline]
-
Pablos-Mendez, A, Raviglione, MC, Laszlo, A, et al (1998) Global surveillance for antituberculosis-drug resistance, 1994–1997. N Engl J Med 338,1641-1649[Abstract/Free Full Text]
-
Moore, M, Onorato, IM, McCray, E, et al (1997) Trends in drug-resistant tuberculosis in the United States, 1993–1996. JAMA 278,833-837[Abstract]
-
Molding, TS, Redeker, AG, Kanel, GC (1989) Twenty isoniazid-associated deaths in one state. Am Rev Respir Dis 140,700-705[ISI][Medline]
-
Ormerod, LP, Horsfield, N (1996) Frequency and type of reaction to antituberculosis drugs: observation in routine treatment Tubercle Lung Dis 77,37-42[CrossRef][ISI][Medline]
-
Mitchison, DA, Nunn, AJ (1986) Influence of initial drug resistance to short-course chemotherapy of pulmonary tuberculosis. Am Rev Respir Dis 133,423-430[ISI][Medline]
-
Babu Swai, O, Aluoch, JA, Githui, WA, et al (1988) Controlled clinical trial of a regimen of two durations for the treatment of isoniazid resistant pulmonary tuberculosis. Tubercle 69,5-14[CrossRef][Medline]
-
. American Thoracic Society (1994) Treatment of tuberculosis and tuberculosis infection in adults and children Am J Respir Crit Care Med 149,1359-1374[Abstract]
-
. Singapore Tuberculosis Service/British Medical Research Council (1979) Clinical trial of six-month and four-month regimens of chemotherapy in the treatment of pulmonary tuberculosis Am Rev Respir Dis 119,579-585[Medline]
-
Castelo, A, Jardim, JRB, Goihman, S, et al (1989) Comparison of daily and twice-weekly regimens to treat pulmonary tuberculosis. Lancet 2,1173-1176[Medline]
-
. Hong Kong Chest Service/British Medical Research Council (1981) Controlled trial of four thrice-weekly regimens and a daily regimen all given for 6 months for pulmonary tuberculosis Lancet 1,171-174[CrossRef][Medline]
-
. Hong Kong Chest Service/British Medical Research Council (1977) Controlled trial of 6-month and 9-month regimens of daily and intermittent streptomycin plus isoniazid plus pyrazinamide for pulmonary tuberculosis in Hong Kong: the results up to 30 months Am Rev Respir Dis 115,727-735[ISI][Medline]
-
. Centers for Disease Control and Prevention (1995) Laboratory practices for diagnosis of tuberculosis-United States, 1994 MMWR Morb Mortal Wkly Rep 44,587-591[Medline]
-
Truant, JP, Brett, WA, Thomas, W, Jr (1962) Fluorescence microscopy of tuberculosis bacilli stained with auramine and rhodamine. Henry Ford Hosp Med Bull 10,287-296
-
Heifets, LB, Good, RC (1994) Current laboratory methods for the diagnosis of tuberculosis. Bloom, BR eds. Tuberculosis: pathogenesis, protection, and control ,85-109 ASM Press Washington, DC.
-
Dawson-Saunders, B, Trapp, RG (1994) Basic clinical biostatistics 2nd ed. ,143-161 Appleton & Lange Norwalk, CT.
-
. Hong Kong Chest Service/British Medical Research Council (1979) Controlled trial of 6-month and 8-month regimens in the treatment of pulmonary tuberculosis: the results up to 24 months Tubercle 60,201-210[CrossRef][ISI][Medline]
TOP
Abstract
Introduction
