Why tuberculosis is never fought with a single drug
A patient with extensive lung tuberculosis may carry around a trillion bacteria, enough that a few will already resist any one antibiotic. Hit them with several drugs at once and the odds of a microbe resisting all of them become vanishingly small. That simple probability is why TB treatment has combined drugs for over fifty years.
The standard course for active TB lasts about six months. For the first two, patients take four drugs together: isoniazid, rifampicin, pyrazinamide and ethambutol, remembered in the US by the mnemonic RIPE. Isoniazid comes with pyridoxal phosphate to prevent nerve damage in the limbs. For the remaining four months only isoniazid and rifampicin continue, and miliary tuberculosis may need longer. Latent infection, which carries no symptoms but can turn active, is treated with isoniazid alone for three to nine months, or with isoniazid and rifampicin for three to four, which lowers the risk of liver damage.
The arithmetic behind combinations comes from known mutation rates. Resistance to each drug arises spontaneously and independently, so the chance that one bacterium resists both isoniazid and rifampicin is the product of two tiny odds, roughly one in a billion billion. The drugs also work differently: isoniazid kills multiplying bacteria, rifampicin kills and sterilises, and pyrazinamide excels against bacteria hiding in acidic pockets or inside immune cells.
Names vary by country. The WHO system writes the same four drugs as RHZE, and the codes stack into shorthand, with a number in front giving months and a slash separating the intensive phase from the continuation phase. American guidelines drop streptomycin from the first line because resistance to it is common; WHO makes no such call. Second-line drugs such as amikacin and moxifloxacin are held back for multidrug-resistant disease because they are weaker, more toxic, or both. Rifabutin works but is too costly for most developing countries to make the WHO list.
Treatment used to take far longer. Until rifampicin, every regimen ran 18 months or more; rifampicin entered TB care in 1968, and a British Thoracic Society study in 1984 found a six-month plan left fewer than 3 per cent relapsing after two years. Some combinations do carry a raised risk of drug-induced liver injury.
Source: Management of tuberculosis
