Summary—What is the diagnostic accuracy of NAAT versus culture in the diagnosis of NTM?
Diagnostic accuracy meta-analyses were conducted for multiple comparisons and the results are summarised below.
Culture as the reference standard
It should be noted that culture is an imperfect reference standard. When compared with a clinical reference standard, only 46% (95%CI 27, 66) of those clinically diagnosed were culture-positive and only 31% (95%CI 4, 58) were AFB-positive.
The median sensitivity of NTM-NAAT versus clinical diagnosis was 99% (range 98–99; k=2), indicating that many patients who are NTM-NAAT-positive and culture-negative would be diagnosed with clinical disease.
NAAT compared with culture
Meta-analysis was performed comparing two different NAATs with culture. NTM-NAAT detects NTMs in general by targeting either the 16S-23S rRNA sequence (k=3) or the gene encoding the 65-kDa heat shock protein (k=2); and MAC-NAAT specifically detects MAC strains (k=5).
The pooled sensitivity for NTM-NAAT compared with culture was 84% (95%CI 49, 97) and the specificity was 90% (95%CI 46, 99):
16% of patients had false-negative results and 10% of patients had false-positive results.
The pooled sensitivity for MAC-NAAT compared with culture was 59% (95%CI 35, 79) and the specificity was 100% (95%CI 99, 100):
41% of patients had false-negative results and no culture-negative patients had false-positive results.
The summary LR+ and LR– values for the ability of NAAT to correctly diagnose the presence or absence of NTM infections in patients when compared with culture suggest that:
Patients with a positive MAC-NAAT result most likely had a culture-positive MAC infection, and patients with a negative result may or may not have had a culture-positive MAC infection.
Patients with a positive NTM-NAAT were more likely to have an infection than not, and patients with a negative result were more likely to not have an NTM infection than to be falsely negative.
The SROC curve shows some threshold effect, suggesting that MAC-NAAT may be more sensitive and less specific than NTM-NAAT when compared with culture:
The AUC indicated that both NTM- and MAC-NAAT perform well in predicting culture positivity.
Overall, NAAT appears to be able to identify a larger proportion of patients with an NTM infection than either AFB microscopy or culture. However, only NTM-NAAT may be of any use in identifying those patients who do not have an NTM infection. Furthermore, these results should be viewed with caution due to the small number of studies included and the wide 95%CIs for many of the analyses.
Studies were included to assess the accuracy of NAAT according to criteria outlined in Box .
Box PICO criteria for direct evidence in patients with tissue biopsy consistent with NTM infection
