Xpert MTB/RIF Ultra on contaminated liquid cultures for tuberculosis and rifampicin-resistance detection: a diagnostic accuracy evaluation.

BACKGROUND: Xpert MTB/RIF Ultra (Ultra) is a widely used rapid front-line tuberculosis and rifampicin-susceptibility testing. Mycobacterium Growth Indicator Tube (MGIT) 960 liquid culture is used as an adjunct but is vulnerable to contamination. We aimed to assess whether Ultra can be used on to-be-discarded contaminated cultures. METHODS: We stored contaminated MGIT960 tubes (growth-positive, acid-fast bacilli [AFB]-negative) originally inoculated at a high-volume laboratory in Cape Town, South Africa, to diagnose patients with presumptive pulmonary tuberculosis. Patients who had no positive tuberculosis results (smear, Ultra, or culture) at contamination detection and had another, later specimen submitted within 3 months of the contaminated specimen were selected. We evaluated the sensitivity and specificity of Ultra on contaminated growth from the first culture for tuberculosis (next-available non-contaminated culture result reference standard) and rifampicin resistance (vs MTBDRplus on a later isolate). We calculated potential time-to-diagnosis improvements and also evaluated the immunochromatographic MPT64 TBc assay. FINDINGS: Between June 1 and Aug 31, 2019, 36 684 specimens from 26 929 patients were processed for diagnostic culture. 2402 (7%) cultures from 2186 patients were contaminated. 1068 (49%) of 2186 patients had no other specimen submitted. After 319 exclusions, there were 799 people with at least one repeat specimen submitted; of these, we included in our study 246 patients (31%) with a culture-positive repeat specimen and 429 patients (54%) with a culture-negative repeat specimen. 124 patients (16%) with a culture-contaminated repeat specimen were excluded. When Ultra was done on the initial contaminated growth, sensitivity was 89% (95% CI 84-94) for tuberculosis and 95% (75-100) for rifampicin-resistance detection, and specificity was 95% (90-98) for tuberculosis and 98% (93-100) for rifampicin-resistance detection. If our approach were used the day after contamination detection, the time to tuberculosis detection would improve by a median of 23 days (IQR 13-45) and provide a result in many patients who had none. MPT64 TBc had a sensitivity of 5% (95% CI 0-25). INTERPRETATION: Ultra on AFB-negative growth from contaminated MGIT960 tubes had high sensitivity and specificity, approximating WHO criteria for sputum test target product performance and exceeding drug susceptibility testing. Our approach could mitigate negative effects of culture contamination, especially when repeat specimens are not submitted. FUNDING: The European & Developing Countries Clinical Trials Partnership, National Institutes of Health.

Intensive Care Unit Sluice Room Sinks as Reservoirs and Sources of Potential Transmission of Carbapenem-Resistant Bacteria in a South African Tertiary Care Hospital.

Purpose: Carbapenem-resistant bacteria (CRB) pose a major health risk to patients in intensive care units (ICU) across African hospitals. There are hardly any data about the role of hospital sinks as reservoirs of CRB in resource-poor African settings. Furthermore, the specific within-sink location of the highest concentration of pathogens and the role of splash back as a transmission mechanism remains poorly clarified. Methods: We swabbed ICU sluice room sinks in a tertiary hospital in Cape Town, South Africa. Swabs were taken from four different parts of the sluice room sinks (tap-opening, trap, below the trap, and u-bend). Dilutions were prepared and plated on carbapenem-infused agar. Colonies were identified and drug resistance profiles were determined using a biochemical analyser. To evaluate the potential transmission from the sink, similar plates were placed at fixed distances from the sink when the tap was turned on and off. Results: CRB were isolated from the trap, water interface below the trap, and the u-bend (the latter harboured the highest density of CRB species). Five CRB, resistant to at least 7 antibiotic classes, were isolated including Pseudomonas, Klebsiella, Citrobacter, Serratia, and Providencia. CRB could be cultured from droplets that fell on agar-containing plates placed at a varying distance from the trap. Conclusion: There is a higher density of CRB in the u-bend of ICU sluice room sinks which can act as a potential source of transmission. The data inform targeted CRB transmission-interruption strategies in resource-poor settings.