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Rifampin or multidrug-resistant tuberculosis (RR/MDR-TB) treatment has largely transitioned to regimens free of the injectable aminoglycoside component, despite the drug class' purported bactericidal activity early in treatment. We tested whether Mycobacterium tuberculosis killing rates measured by tuberculosis molecular bacterial load assay (TB-MBLA) in sputa correlate with composition of the RR/MDR-TB regimen. Serial sputa were collected from patients with RR/MDR- and drug-sensitive TB at days 0, 3, 7, and 14, and then monthly for 4 months of anti-TB treatment. TB-MBLA was used to quantify viable M. tuberculosis 16S rRNA in sputum for estimation of colony forming units per ml (eCFU/ml). M. tuberculosis killing rates were compared among regimens using nonlinear-mixed-effects modeling of repeated measures. Thirty-seven patients produced 296 serial sputa and received treatment as follows: 13 patients received an injectable bedaquiline-free reference regimen, 9 received an injectable bedaquiline-containing regimen, 8 received an all-oral bedaquiline-based regimen, and 7 patients were treated for drug-sensitive TB with conventional rifampin/isoniazid/pyrazinamide/ethambutol (RHZE). Compared to the adjusted M. tuberculosis killing of -0.17 (95% confidence interval [CI] -0.23 to -0.12) for the injectable bedaquiline-free reference regimen, the killing rates were -0.62 (95% CI -1.05 to -0.20) log10 eCFU/ml for the injectable bedaquiline-containing regimen (P = 0.019), -0.35 (95% CI -0.65 to -0.13) log10 eCFU/ml for the all-oral bedaquiline-based regimen (P = 0.054), and -0.29 (95% CI -0.78 to +0.22) log10 eCFU/ml for the RHZE regimen (P = 0.332). Thus, M. tuberculosis killing rates from sputa were higher among patients who received bedaquiline but were further improved with the addition of an injectable aminoglycoside.

Objectives: Differences among Mycobacterium tuberculosis complex (MTC) species may predict drug resistance or treatment success. Thus, we optimised and deployed the genotype MTBC assay (gMTBC) to identify MTC to the species level, and then performed comparative genotypic drug‐susceptibility testing to anti‐tuberculosis drugs from direct sputum of patients with presumed multidrug‐resistant tuberculosis (MDR‐TB) by the MTBDRplus/sl reference method. Methods: Patients with positive Xpert® MTB/RIF (Xpert) results were consented to provide early‐morning‐sputum for testing by the gMTBC and the reference MTBDRplus/sl. Chi‐square or Fisher's exact test compared proportions. Modified Poisson regression modelled detection of MTC by gMTBC. Results: Among 73 patients, 53 (73%) were male and had a mean age of 43 (95% CI; 40–45) years. In total, 34 (47%), 36 (49%) and 38 (55%) had positive gMTBC, culture and MTBDR respectively. Forty patients (55%) had low quantity MTC by Xpert, including 31 (78%) with a negative culture. gMTBC was more likely to be positive in patients with chest cavity 4.18 (1.31–13.32, P = 0.016), high‐quantity MTC by Xpert 3.03 (1.35–6.82, P = 0.007) and sputum smear positivity 1.93 (1.19–3.14, P = 0.008). The accuracy of gMTBC in detecting MTC was 95% (95% CI; 86–98; κ = 0.89) compared to MTBDRplus/sl. All M. tuberculosis/canettii identified by gMTB were susceptible to fluoroquinolone and aminoglycosides/capreomycin. Conclusions: The concordance between the gMTBC assay and MTBDRplus/sl in detecting MTC was high but lagged behind the yield of Xpert MTB/RIF. All M. tuberculosis/canettii were susceptible to fluoroquinolones, a core drug in MDR‐TB treatment regimens. [ABSTRACT FROM AUTHOR]

The control of infectious diseases is badly endangered by the rise in the number of microorganisms that are resistant to antimicrobial agents. This is because infections caused by resistant microorganisms often fail to respond to conventional treatment, resulting in prolonged illness and greater risk of death. Antimicrobial-resistant bacteria are also present in various water sources. This study therefore sought to document the microbiological quality and antibiograms of bacterial isolates (E. coli strains) from six different water sources in order to determine their safety for human consumption and to provide updated antibiotic data for pragmatic treatment of patients. Bacteria isolation and identification was done using API and conventional methods. Antibiotic susceptibility testing was conducted using the Kirby–Bauer method. Results obtained indicated that all the water sources tested were of poor quality. Bacteria isolated included E. coli, Enterobacter spp., Klebsiella spp., Salmonella typhi, Streptococcus spp., Proteus vulgaris, Vibrio cholera, Shigella spp., Pseudomonas aeruginosa, and Enterococcus faecalis. The prevalence of multidrug-resistant E. coli was 49.48%. E. coli isolates showed high resistance patterns to the tested antibiotics. They were most resistant to penicillin (32.99%), cefuroxime (28.87%), erythromycin (23.71%), and tetracycline (21.45%). In contrast, they were susceptible to nitrofurantoin (93.8%), cefotaxime and amikacin (91.75%), gentamicin (90.7%), nalidixic acid (89.65%), ciprofloxacin (74.2%), chloramphenicol (69.07%), pipemidic acid (65.97%), and cefuroxime (52.58%). Sixty-three percent (63%) of the multidrug-resistant E. coli strains recorded a multiple antibiotic resistance (MAR) index value >0.2. The susceptible antibiotics, especially the nitrofurantoin, are hence recommended in the practical treatment of waterborne bacterial diseases. [ABSTRACT FROM AUTHOR]

Background The novel Fujifilm SILVAMP TB-LAM (FujiLAM) assay detects mycobacterial lipoarabinomannan in urine and has demonstrated superior sensitivity to the Alere Determine TB-LAM Ag (AlereLAM) assay for detection of tuberculosis among hospitalized people with human immunodeficiency virus (PWH). This is the first study to evaluate the assay among a broad population referred for antiretroviral therapy including both outpatients (mainly) and inpatients. Methods We assessed diagnostic accuracy of FujiLAM and AlereLAM assays in biobanked urine samples from a cohort of adults referred for antiretroviral therapy in Ghana against a microbiological and a composite (including clinical judgement) reference standard, and we assessed the association of FujiLAM test positivity with mortality. Results We evaluated urine samples from 532 PWH (462 outpatients, 70 inpatients). Against a microbiological reference standard, the sensitivity of FujiLAM was 74.2% (95% confidence interval [CI], 62.0–84.2) compared to 53.0% (95% CI, 40.3–65.4) for AlereLAM, a difference of 21.2% (CI, 13.1–32.5). Specificity was 89.3% (95% CI, 85.8–92.2) versus 95.6% (95% CI, 93.0–97.4) for FujiLAM and AlereLAM, a difference of −6.3% (95% CI −9.6 to −3.3). Specificity estimates for FujiLAM increased markedly to 98.8% (95% CI, 96.6–99.8) in patients with CD4 >100 cells/µL and when using a composite reference standard. FujiLAM test positivity was associated with increased cumulative risk of mortality at 6 months (hazard ratio, 4.80; 95% CI, 3.01–7.64). Conclusions FujiLAM offers significantly increased diagnostic sensitivity in comparison to AlereLAM. Specificity estimates for FujiLAM were lower than for AlereLAM but were affected by the limited ability of the reference standard to correctly diagnose tuberculosis in individuals with low CD4 counts. [ABSTRACT FROM AUTHOR]

Early and accurate diagnosis and rigorous clinical and microbiological monitoring of multidrug-resistant tuberculosis (MDR-TB) treatment can curb morbidity and mortality. While others are still under evaluation, the World Health Organization has recommended few novel molecular methods for MDR-TB diagnosis only. We present current molecular methods for diagnosis and monitoring of MDR-TB treatment in TB-endemic settings. A systematic meta-narrative review was conducted according to the RAMESES recommendations. Electronic databases were searched for relevant articles published in English language from January 2013 to June 2018. Based on predefined criteria, two independent reviewers extracted the key messages from relevant articles. Disagreement between them was resolved through discussion and the involvement of a third reviewer, if needed. Key messages were synthesized to create the meta-narratives for method's accuracy, drug-susceptibility capability, and laboratory infrastructure required. We included 33 articles out of 1213 records retrieved, of which 16 (48%) and 12 (36%) were conducted in high- and low-TB-endemic settings, respectively. Xpert ® MTB/RIF, GenoType MTBDRplus, GenoType MTBDRsl, FlouroType™ MTBDR, TB TaqMan ® array card, and DNA sequencers can accurately guide effective treatment regimens. Molecular bacterial load assay quantifies mycobactericidal impact of these regimens. Although they present inherent advantages compared to the current standard of care, they carry important limitations to implementation and/or scale-up. Therefore, considerable effort must now be directed to implementation and health systems research to maximize these forecasted benefits for individual patient's health outcomes., Competing Interests: None