Transcript Management of Drug Resistant TBH Patients

Management of Drug Resistant
Tuberculosis Patients,
Egypt experience
Study Objective
• To evaluate the so far effect of
treatment on the first treatment
cohort of MDR-TB patients and
analysing some factors that might
affect the interim outcome.
Materials & Methods
• The pilot program had the initial approval of the GLC/WHO
to treat 75 patients in the first DR-TB centre in Abbassia
chest hospital for inpatient care of patients with MDR-TB.
• One floor of 12 rooms was chosen and modified to apply
the necessary infection control procedures.
• Mission from the GLC in early 2003 before approval of the
program was issued.
• This centre was assigned for the inpatients treatment while
ambulatory treatment was conducted in TB units after the
working staff in these units received 3 days training on
management of those patients before they are discharged for
ambulatory treatment.
Materials & Methods
• The national reference laboratory was chosen to do the
initial culture and drug susceptibility testing (DST) to
determine the resistance pattern of the patient before
starting treatment.
• The first cohort of patients to be enrolled in the pilot
project consisted of chronic patients found in the TBMUs
and DSTs were done to all of them to confirm infection
with MDR-TB.
• The frequency of patient enrolment was determined by
the hospital capacity and availability of the drugs.
Patients were eligible for treatment if they were proved to
be MDR-TB with no absolute exclusion criteria.
Materials & Methods
• Patient with concomitant diseases or with poor general condition were
considered high risk group for close supervision and frequent evaluation.
• A formal written consent was taken from every patient before starting
treatment.
• The proved MDR-TB patients were put on a treatment regimen based on
the resistance profile of patients to first line anti-TB treatment and would
be modified according to treatment history of the patient.
• If the patient gave any history of previous use of the second line anti-TB
drugs, which are not available in the market in Egypt, except for Amikacin
and Flouroquinolones, the regimen would have been adjusted accordingly.
• DST for second line drugs was made for patients who gave history of
previous use of the previously mentioned second line anti-TB drugs or
showed potential failure to prepare the retreatment regimen. Accordingly,
the regimen used can be considered, more or less an individualized one.
Treatment regimens
• MDR-TB patients were started on a regimen consisting Kanamycin,
Ofloxacin, Ethionamide, p-aminosalicylic acid (PAS), Cycloserine.
• Patient received the injectable drug for nine months, the first three
months on daily basis, and then every other day. The treatment
duration was 21 months for patients who were enrolled and
completed treatment before the emergency update of the
programmatic management of DR-TB guidelines were issued with
recommendation of at least 18 months treatment after sputum
culture conversion.
• The duration of hospitalization was about 9 months, during the use
of an injectable drug and the clinical condition of the patient and
tolerability of the drugs. Patients were tested for HIV at the start of
treatment.
Treatment regimens
• Sputum smear and culture were conducted monthly, and, when
culture positive
• Chest radiographs were performed at enrolment, and every 6 months
thereafter
• Adverse events were managed rapidly and aggressively with the
ancillary drugs and with the help of specialists like a psychiatrist,
without permanent removal of a drug from the treatment regimen for
any patient of the study cohort.
• All treatment doses of drugs were directly observed during the
hospitalization period, and three times a week after discharge during
the ambulatory treatment period.
• Resection surgery was undertaken for one of the patients who
declared failed and he is now on retreatment as after failure of
second-line anti-TB treatment and not included in this analysis after
surgery
Laboratory testing
• Sputum smear microscopy, culture and were
conducted according to international standards in
Abbassia chest hospital laboratory but DST was
conducted only in the national reference laboratory.
Smears were assessed using direct microscopy and
culture using Lowenstein-Jensen media.
• DST was conducted for 4 first-line drugs (isoniazid,
rifampicin, ethambutol, streptomycin) and secondline drugs (Capreomycin, Kanamyin, Ofloxacin)
Data collection and analysis
• A computerized medical record system, Excel based,
was instituted from the start of the pilot program.
• This system was designed to record significantly
more information than that routinely collected in the
DOT program, where patient data from the entire
treatment course were recorded on a single, two-sided
treatment card.
• Analyses were performed using SPSS (SPSS version
16.0)
Results
- Description of the studied group: • Among the multi-drug resistant (MDR) patients (n=168) admitted to
Abbassia Chest Hospital till 30/6/2009 only 65 patients completed
their treatment course.
• Their age ranges from 17 to 76 years with the mean = 37.8 ± 12.4
years. Male to female ratio is 46 (70.8 %) to 19 (29.2 %). No
statistically significant difference between males and females as
regards their mean age (t-test = 1.2, p > 0.05)
• All of the patients were pulmonary tuberculosis except for 1 extrapulmonary (cervical Pott's); 3 (4.6 %) were new cases and 62 (95.4
%) retreated cases.
Results
• The number of treatment courses taken before starting second-line
treatment ranged from 1 to more than 7 with the median = 3 and mode = 2
courses.
• As regards the resistance pattern: - 51 (78.5 %) patients were resistant to
the four first-line drugs hence, they received the treatment regimen I (36
males and 15 females). 13 (20.0 %) patients were resistant to three of them
and on treatment regimen II (9 males and 4 female). There is one (1.5 %)
male patient resistant to 2 drugs (RH) and on regimen III. Resistance
pattern was not significantly different between males and females (ChiSquare = 0.4, p>0.05).
• 12 (18.5 %) patients (10 males and 2 female) gave positive history of
receiving the second line anti-tuberculosis drugs (Ofloxacin and Amikacin
in addition to one Sudanese male patient received all second line drugs) and
53 (81.5 %) patients (36 male and 17 females) denied their use. The sex
difference was not statistically significant (Fisher’s Exact test, p>0.05).
Results
• The duration of TB illness before starting treatment with the
second line anti-tuberculosis drugs, it was found that the mean
duration = 7.3 ± 6.1 and the median = 6 years
• Co-morbidity: - 12 (18.5 %) patients were found to be diabetic
(6 males and 6 female) and only 2 (3.1 %) male patient was
HCV positive. No statistically significant sex differences were
observed for both variables (Fisher’s Exact test, p > 0.05).
• There were no HIV positive cases.
Distribution of patients according to the time
taken for sputum smear to be converted
negative
60%
50%
49.20%
40%
30%
24.60%
20%
10%
7.70%
4.60%
3.10%
0%
After 1 month
After 2 month
After 3 month
After 4 month
After 5 month
Distribution of patients according to the time
taken for sputum culture to be converted
negative
25%
20%
20%
15%
13%
11%
10%
10%
10%
5%
5%
2%
1%
0%
Reported side effects
90%
80%
80%
79%
75%
70%
60%
50%
40%
40%
30%
40%
39%
29%
25%
22%
20%
10%
0%
19%
17%
15%
14%
12%
11%
9%
8%
6%
5%
Treatment outcome of the studied
patients
80.00%
70.00%
67.70%
60.00%
50.00%
40.00%
30.00%
20.00%
16.90%
9.20%
10.00%
6.20%
0.00%
Treatment success
Defaulter
Failure
Died
• Some factors that might affect treatment outcome were
studied. Of them the following showed significant association
with successful treatment:
- young age of patients,
- non smoking,
- no past history of intake of the second-line anti-tuberculosis
drugs,
- the extension of lung tissue destruction on x-ray findings and
- the sputum culture conversion within 3 months of treatment.
more than half of the total patients and about 83% of those
achieved successful outcome were converted culture negative
within the first 3 months of treatment. These factors could be
taken as parameters to predict a successful outcome
• Alcoholism and smoking are among the factors that
might contribute to the development of drug
resistance and hence, the unsuccessful outcome. The
difference in the rate of treatment success was
significant with smoking but did not reach the
statistical significance among the alcohol or drug
users most probably because of the small number of
this group of patients.
• The clearly observed high mortality rate (about 17%)
could be due to that 52.3 % of the cases (34 patients
out of the 65) showed extensive unilateral or bilateral
lung tissue destruction, and of those who died this
proportion was 90.9% ,10 out of 11 patients.
Conclusion
• About 68 % treatment success is achieved with the
first group of MDR-TB cases admitted to Abbassia
chest hospital.
• The proportion of failures, defaulters and deaths were
9, 6, and 17% respectively. These rate that are
comparable with the average treatment success rate
reached within the GLC projects and with other
reported literatures.
• The high mortality rate (about 17%) highlighted the
importance of continuing the ongoing efforts for the
rapid diagnosis and treatment of MDR patients and
the urgency of applying the direct observation
throughout the whole treatment period.
• The significant risk factors for successful outcome
included young age of patients, non smoking, and the
factors related to treatment which are the most
important factors. These are negative history of intake
of 2nd line anti-tuberculosis drugs, no cavity in x-ray
findings and sputum culture conversion before 3
months of treatment.
Recommendations
• Decrease the inefficient and unnecessary use of the
second-line anti-TB drugs
(aminoglycosides&floroquinolones).
• Encouragement of the application of direct observation
for MDR TB patients throughout their treatment
period.
• Application of rapid diagnostic techniques for prompt
enrollment of patients in the correct treatment regimen.
• Strong patient support and follow up system is
mandatory to achieve better results especially with
MDR TB patients
Limitations
• The effect of surgical intervention on the
treatment outcome of MDR TB patients was
not investigated as this treatment modality was
not performed widely enough with our patients
to evaluate its role.
• More data from high risk patients is needed for
better evaluation of treatment especially those
with diabetes, HCV and HIV infections.