Deviations from the standard regimen::Tuberculosis management


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Deviations from the standard regimen There is evidence supporting some deviations from the standard regimen when treating pulmonary TB. Sputum culture positive patients who are smear negative at the start of treatment do well with only 4 months of treatment (this has not been validated for HIV-positive patients); and sputum culture negative patients do well on only 3 months of treatment (possibly because some of these patients never had TB at all).<ref>{{#invoke:Citation/CS1|citation |CitationClass=journal }}</ref> It is unwise to treat patients for only three or four months, but all TB physicians will have patients who stop their treatment early (for whatever reason), and it can be re-assuring to know that sometimes retreatment is unnecessary. Elderly patients who are already taking a large number of tablets may be offered 9HR, omitting PZA which is the bulkiest part of the regimen.

It may not always be necessary to treat with four drugs from the beginning. An example might be a close contact of a patient known to have a fully sensitive strain of tuberculosis: in this case, it is acceptable to use 2HRZ/4HR (omitting EMB and STM) in the expectation that their strain will be INH susceptible also. Indeed, this was previously the recommended standard regimen in many countries until the early 1990s, when isoniazid-resistance rates increased.

TB involving the brain or spinal cord (meningitis, encephalitis, etc.) is currently treated with 2HREZ/10HR (12 months of treatment in total), but there is no evidence to say that this is superior to 2HREZ/4HR, it is merely that no-one has been brave enough to do the clinic trial that answers the question if the short course is equivalent.

Regimens omitting isoniazid

Isoniazid resistance accounts 6.9% of isolates in the UK (2010).<ref name="HPA2010">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> Worldwide, it is the most common type of resistance encountered, hence the current recommendation of using HREZ at the beginning of treatment until sensitivities are known. It is useful to know of current reported outbreaks (like the current outbreak of INH-resistant TB in London).

If patients are discovered to be infected with an isoniazid-resistant strain of TB having completed 2 months of HREZ, then they should be changed to RE for a further 10 months, and the same thing if the patient is intolerant to isoniazid (although 2REZ/7RE may be acceptable if the patient is well supervised). The US recommendation is 6RZE with the option of adding a quinolone such as moxifloxacin. The level of evidence for all these regimens is poor, and there is little to recommend one over the other.

Regimens omitting rifampicin

The UK prevalence of rifampicin (RMP) resistance is 1.4%.<ref name="HPA2010"/> It is rare for TB strains to be resistant to RMP without also being resistant to INH,<ref name="PLOS2008">{{#invoke:Citation/CS1|citation |CitationClass=journal }}</ref> which means that rifampicin-resistance usually means resistance to INH as well (that is, MDR-TB). However, RMP intolerance is not uncommon (hepatitis or thrombocytopaenia being the most common reasons for stopping rifampicin). Of the first-line drugs, rifampicin is also the most expensive, and in the poorest countries, regimens omitting rifampicin are therefore often used. Rifampicin is the most potent sterilising drug available for the treatment of tuberculosis and all treatment regimens that omit rifampicin are significantly longer than the standard regimen.

The UK recommendation is 18HE or 12HEZ. The US recommendation is 9 to 12HEZ, with the option of adding a quinolone (for example, MXF).

Regimens omitting pyrazinamide

PZA is a common cause of rash, hepatitis and of painful arthralgia in the HREZ regimen, and can be safely stopped in those patients who are intolerant to it. Isolated PZA resistance is uncommon in M. tuberculosis, but M. bovis is innately resistant to PZA. PZA is not crucial to the treatment of fully sensitive TB, and its main value is in shortening the total treatment duration from nine months to six.

An alternative regimen is 2HRE/7HR, for which there is excellent clinical trial evidence.<ref>{{#invoke:Citation/CS1|citation |CitationClass=journal }}</ref><ref name="BTS2">{{#invoke:Citation/CS1|citation |CitationClass=journal }}</ref><ref>{{#invoke:Citation/CS1|citation |CitationClass=journal }}</ref><ref name="Slutkin1988">{{#invoke:Citation/CS1|citation |CitationClass=journal }}</ref> The 1994 US CDC guidelines for tuberculosis<ref>{{#invoke:Citation/CS1|citation |CitationClass=journal }}</ref> erroneously cite Slutkin<ref name="Slutkin1988"/> as evidence that a nine-month regimen using only isoniazid and rifampicin is acceptable, but almost all of the patients in that study received ethambutol for the first two to three months (although this is not obvious from the abstract of that article). This mistake was rectified in the 2003 guidelines.<ref>{{#invoke:Citation/CS1|citation |CitationClass=journal }}</ref>

This regimen (2HRE/7HR) is the first-line regimen used to treat M. bovis, since M. bovis is intrinsically resistant to pyrazinamide.

Regimens omitting ethambutol

EMB intolerance or resistance is rare. If a patient is truly intolerant or is infected with TB that is resistant to EMB, then 2HRZ/4HR is an acceptable regimen.<ref name="Combs1990">{{#invoke:Citation/CS1|citation |CitationClass=journal }}</ref> The main motivator for including EMB in the initial two months is because of increasing rates of INH resistance.

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Deviations from the standard regimen
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