An assessment of nucleic acid amplification testing for active mycobacterial infection

Component	A Excellent	B Good	C Satisfactory
D Poor
Evidence-base^a	One or more level I studies with a low risk of bias or several level II studies with a low risk of bias
Consistency^b	All studies consistent
Clinical impact			Moderate
Generalisability			Population(s) studied in body of evidence differ to target population for guideline but it is clinically sensible to apply this evidence to target population
Applicability		Applicable to Australian healthcare context with few caveats

SR = systematic review; several = more than two studies

^a Level of evidence determined from the NHMRC evidence hierarchy (see Table ).

Source: Adapted from NHMRC (2009)

The review by Forget and Menzies (2006), assessed as medium quality, searched only one database (Medline) and in addition sought relevant articles from the authors’ files and pearled references. While the review did not meet all criteria that define an SR, it nevertheless provided the best identified evidence across a range of first-line drugs for prophylactic treatment in patients of all ages with active TB and. A second review of medium quality assessed the toxicity of first-line drugs and prophylactic treatment in children with TB through literature identified in PubMed, EMBASE and the Cochrane Library Reference (Frydenberg & Graham 2009). In addition, reference lists were hand-searched for relevant articles. The third relevant study identified assessed evidence of multidrug resistance following inappropriate TB treatment, and was of high quality (van der Werf et al. 2012). This study conducted a broad systematic literature search and used clearly defined criteria for appropriate treatment regimens and multidrug resistance.

Adverse reactions to first-line TB therapy (all ages)

Forget and Menzies (2006) reported on the serious adverse reactions associated with five first-line anti-TB drugs. Their results for isoniazid, rifampicin, pyrazinamide and ethambutol will be discussed here. The authors comment that the attribution of side effects to individual drugs is challenging as most patients are given multidrug regimens; however, if a temporal relationship between a drug and symptoms could be established, the symptoms were attributed to that drug. The authors of this review used the attribution made by the primary study authors. In some studies attribution of symptoms could only be made to the treatment regimen, and therefore the adverse reactions to multidrug TB regimens are also reported briefly here.

Isoniazid

Metabolism of isoniazid therapy is dependent on two pathways (direct and indirect) associated with different levels of activity in patients who have either high or low N-acetyltransferase activity (i.e. fast or slow acetylators). N-acetyltransferase activity is associated with race (90% of Asian, 45% of black, and 45% of white people are fast acetylators) and hepatic adverse reactions (Mitchell et al. 1975; Mitchell et al. 1976). A summary of hepatic adverse reactions reported in 10 studies that administered isoniazid as chemoprophylaxis against TB is tabulated in Table .

Table Summary of hepatic AEs to isoniazid from prospective and retrospective studies