Rational use of Xpert testing in patients with presumptive TB: clinicians should be encouraged to use the test-treat threshold

Abstract

BackgroundA recently published Ugandan study on tuberculosis (TB) diagnosis in HIV-positive patients with presumptive smear-negative TB, which showed that out of 90 patients who started TB treatment, 20% (18/90) had a positive Xpert MTB/RIF (Xpert) test, 24% (22/90) had a negative Xpert test, and 56% (50/90) were started without Xpert testing. Although Xpert testing was available, clinicians did not use it systematically. Here we aim to show more objectively the process of clinical decision-making.First, we estimated that pre-test probability of TB, or the prevalence of TB in smear-negative HIV infected patients with signs of presumptive TB in Uganda, was 17%. Second, we argue that the treatment threshold, the probability of disease at which the utility of treating and not treating is the same, and above which treatment should be started, should be determined. In Uganda, the treatment threshold was not yet formally established. In Rwanda, the calculated treatment threshold was 12%. Hence, one could argue that the threshold was reached without even considering additional tests. Still, Xpert testing can be useful when the probability of disease is above the treatment threshold, but only when a negative Xpert result can lower the probability of disease enough to cross the treatment threshold. This occurs when the pre-test probability is lower than the test-treat threshold, the probability of disease at which the utility of testing and the utility of treating without testing is the same. We estimated that the test-treatment threshold was 28%. Finally, to show the effect of the presence or absence of arguments on the probability of TB, we use confirming and excluding power, and a log10 odds scale to combine arguments.ConclusionIf the pre-test probability is above the test-treat threshold, empirical treatment is justified, because even a negative Xpert will not lower the post-test probability below the treatment threshold. However, Xpert testing for the diagnosis of TB should be performed in patients for whom the probability of TB was lower than the test-treat threshold. Especially in resource constrained settings clinicians should be encouraged to take clinical decisions and use scarce resources rationally.

Case Report: Therapeutic Threshold for Rifampicin-Resistant Tuberculosis in a Patient from Maputo, Mozambique

“…Excluding and confirming powers are not directly influenced by disease prevalence. 12 excluding power ¼ specificity 1 À sensitivity confirming power ¼ sensitivity 1 À specificity :…”

“…Excluding and confirming powers are not directly influenced by disease prevalence. 12 The estimated probability of RR-TB in Mozambique was converted to odds and multiplied by the LRs of confirming arguments before testing. That result was multiplied with the excluding power of Xpert MTB+/RIF−.…”

The Value of Lateral Flow Urine Lipoarabinomannan Assay and Empirical Treatment in the Xpert MTB/RIF Ultra Era: a Prospective Cohort Study

“…Even when the Xpert MTB/RIF assay is available, empirical treatment remains highly prevalent in high TB burden countries [6]. The use of empirical treatment can be justi ed in these settings given the suboptimal performance of the Xpert assay, especially among smear negative individuals (sensitivity of 67%) and in people living with HIV (sensitivity of 80%) [7,8].…”

“…Furthermore, we found that empiric treatment of Xpert Ultra patients did not increase the odds of survival, as survival was similar between those who did and did not receive empiric TB treatment (OR 1.28, 95% CI: 0.3-5.3). These results suggest that the recommendation by Kendall et al and by Decroo et al, that clinicians should continue to prescribe TB treatment for Xpert MTB/RIF-negative patients whose clinical presentations strongly suggest pulmonary in order to minimize a risk of TB related mortality[6,7] may no longer hold in the Xpert Ultra era. All participants in whom the clinician started empiric TB treatment had been assessed by chest radiography and had received a 'trial' of antibiotics (ceftriaxone and azithromycin, amoxicillin or vancomycin and doxycycline) to which they had not responded favorably.…”

Role of empiric treatment in hospitalized patients with Xpert MTB/RIF-negative presumptive pulmonary tuberculosis: A prospective cohort study

“…Because the sensitivity of the 1st generation Xpert assay is still suboptimal in smear-negative sputum samples (Churchyard et al, 2015;Decroo et al, 2017) the 2018 Ethiopian TB treatment guideline recommends that an antibiotic trial is performed when a TB diagnosis is in doubt. A course of broad-spectrum antibiotics with negligible Mtb activity is given to symptomatic Xpertnegative patients.…”