MANAGEMENT OF MULTIDRUG RESISTANCE TB

Hadiarto Mangunnegoro

Dept of Respiratory Medicine

Faculty of Medicine UI

MDR-TB will become a serious problem to maintain the sustainable success of National TB Program (NTP) in declining TB prevalence in Indonesia. Since the main cause of MDR due to inappropriate medication or treatment failure, obviously the most important strategy for controlling MDR-TB only by curing each TB patients on the first place, because to treat MDR TB patients will be extremely expensive far beyond the patient affordability as well as government capability.

WHO (2003) declared the increasing incidence of MDR TB gradually by 2% per year.

MDR-TB prevalence in developing countries are predicted between 4.6% to 22.2% .

Preliminary data from the first drug-resistance survey in Java suggests low rates of MDR-TB in new cases (1-2%), but elevated rates of MDR-TB in NTP patients reporting previous treatment (15%). Limited and unrepresentative hospital data (2006) show the reality of MDR-TB and XDR-TB, with one third of MDR-TB cases resistant to Ofloxacin and one documented XDR-TB case (among 24 MDR-TB cases). MDR-TB cases in Indonesia do not yet have access to adequate treatment of MDR-TB, as not all relevant drugs are available in the country.

From 2005 to 2007, 3727 total number TB patients in Persahabatan Hospital 554 (15%) patients confirmed as MDR-TB by culture.

The biggest problems lies in private sectors that is private practicing physicians  and most hospitals which are not covered NTP.

Past and current use of second line drugs.

Currently there only two categories of second line drugs avalailable in Indonesia: Kanamycin (KM) and Fluoroquinolones (FQ). Kanamycin is almost exclusively used for TB and short treatment of STI.

The other four categories of second line drugs: Capreomycin, Ethionamide Prothionamid and PAS are not registered in Indonesia. Cycloserine is registered but not avalailable in the market.

Kanamycin and streptomycin were widely used exclusively for treating TB patients before the era of short course therapy Rifampicin containing regiment.

FQs are regarded as the most cost effective drugs for the treatment of MDR-TB, unfortunately the FQs are already being widely used for almost all kind infectious diseases mainly respiratory infections regardless of true or false infections, bringing this class of drugs to rapid resistance including to M tuberculosis in the near future, furthermore it also known to be highly cross resistance with other FQs.

Our previous study (1997) with FQ namely Ofloxacin for the treatment of MDR-TB (58 pts) showed promising even with lower than recommended dosage(400 mg/day) in combination with Pyrazinamide, Ethambutol and Streptomycin for 9-12 months plus 12 months follow up period  with smear conversion up to 72% at the end of therapy, relapse rate 11.2% on 12 months follow up. Those who were resistance with only two drugs (RH) and duration of resistance less than 3 years showed better cure rate (90%) and lower relapse rate than those who were more than two drug resistance (8%) and more than 3 years duration of resistance. The resistance pattern of Oflo for Mtb in that study showed 20% (MIC>2mcg), clearly it should be higher rate by now.

Yew WW et al in retrospective comparison study  effectiveness of Ofloxacin versus Levofloxacin in patients wih  MDR-TB showed that Levo was more effective than oflo by 90 to 79% respectively

Limitation towards successful treatment of MDR-TB patients includes: substandard diagnostics and drug therapy, high cost of therapy, no government support, long duration (24 months), adverse reactions.

Current management of MDR-TB patients will be following WHO Guidelines os DOTS Plus Program.

Conclusions.

The top priority is not how to manage  MDR-TB, but how to prevent MDR-TB.