9.4 Assessment of patients when treatment failure is suspected

Any patient not clinically responding to therapy after several weeks should be considered as being at risk for failure. In particular, patients should be considered as being at high risk for treatment failure if they had at least 3 months of full adherence to what was deemed to be an effective treatment regimen with quality-assured drugs, but show evidence of active disease – either clinical, radiographic or bacteriological (DST or culture) – or reappearance of disease. The following steps are recommended in such a situation.]

Confirm treatment

The treatment card should be reviewed to confirm that the patient has fully adhered to treatment.

Look for undetected comorbidities

Some undetected comorbidities mimic treatment failure through clinical and chest radiographic deterioration that occurs simultaneously with repeated culture-negative and smear-negative results. These comorbidities (e.g. NTMs, fungal infections, lung infections or a pulmonary malignancy) should be diagnosed and treated appropriately. Illnesses that may decrease absorption of medicines (e.g. chronic diarrhoea) or may result in immune suppression (e.g. HIV infection) should also be excluded.

Review the bacteriological data

A single positive culture in the presence of an otherwise good clinical response can be caused by a laboratory contaminant or error. In such cases, subsequent cultures that are negative help to prove that the apparently positive result did not reflect treatment failure. Positive smears with negative cultures may be caused by the presence of dead bacilli and thus do not necessarily indicate treatment failure.

Review the DST

If there is evidence of acquired resistance to any drug, treatment failure is likely and a new regimen for DR-TB may need to be started promptly

Review CXR

If comparison of CXR at baseline and at the current time shows no improvement or deterioration of the CXR image, this may indicate failure of TB treatment.

Review treatment regimen

The treatment regimen should be reviewed in relation to medical history, contacts and all DST reports. If any resistance appears that was not present or evident previously, the patients should be managed as DR-TB or MDR-TB with a new regimen, and rapid action should be taken to ensure that adequate infection control measures are implemented.

Consider malabsorption

In rare cases, genetic reasons mean that one or more drugs are not well absorbed, leading to suboptimal blood levels, suboptimal effect of the drug and potential development of drug-resistance. Therapeutic drug monitoring, based on collection of a dried drop of blood (which can be easily sent by normal mail to one of the laboratories performing the test), makes it possible to evaluate the drug level in the blood and, eventually, to adjust the dose. Although not yet recommended by WHO, other clinical guidelines do recommend this test in specific cases (43).

Absorption of drugs is reduced in severely ill patients admitted to the critical care department with conditions such as central nervous system TB or acute respiratory distress syndrome (ARDS). In such cases, intravenous anti-TB treatment should be considered until the situation improves and a nasogastric tube can be used.

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