f Fluoroquinolones are the core drugs for the management of multidrug-resistant tuberculosis (MDR-TB). Molecular drug susceptibility testing methods provide considerable advantages for scaling up programmatic management and surveillance of drugresistant TB. We describe here the misidentification of fluoroquinolone resistance by the GenoType MTBDRsl (MTBDRsl) (Hain Lifescience GmbH, Nehren, Germany) line probe assay (LPA) encountered during a feasibility and validation study for the introduction of this rapid drug susceptibility test in Kinshasa, Democratic Republic of Congo. The double gyrA mutation 80Ala and 90Gly represented 57% of all fluoroquinolone mutations identified from MDR-TB patient sputum samples, as confirmed by DNA sequencing. This double mutation was previously found to be associated with susceptibility to fluoroquinolones, yet it leads to absent hybridization of a wild-type band in the MTBDRsl and is thus falsely scored as resistance. Our findings suggest that MTBDRsl results must be interpreted with caution when the interpretation is based solely on the absence of a wild-type band without confirmation by visualization of a mutant band. Performance of the MTBDRsl LPA might be improved by replacing the gyrA wild-type probes by additional probes specific for well-documented gyrA mutations that confer clinically relevant resistance.
In part due to a restrictive algorithm, Xpert as follow-on to smear microscopy did not increase the overall number of TB notifications, nor the number of bacteriologically positive cases.
In this manuscript the authors have studied the first two patients who were successfully treated with the treatment regimen containing Bedaquiline as second-line drug. The patients were diagnosed with pre-extensively drug-resistant tuberculosis (preXDR TB) whose prognosis was fatal in Democratic Republic of Congo (DRC). Bedaquiline is arguably one of the molecules of the future in the management of ultra-resistant tuberculosis. However, a larger cohort study may help to establish its effectiveness. Case report: Patients 1, 29 years old, with a history of multidrug-resistant TB (MDR-TB) one year previously. He showed signs of TB impregnation again 6 months after the last treatment. Bascilloscopy was positive again. The pre-extensively tuberculosis (pre-XDR TB) diagnosis was made by the Hain test (GenoType® MTBDRsl, Hain Lifescience). Patient 2, brother of the first patient, with a history of MDR TB a year before. He had low back pain with right parietal dorso swelling four months after the last treatment. The x-ray of the column showed L4-L5 disc disease. Parietal ultrasound showed a parietal abscess to the right of thoracic vertebrae with fistulization. Surgical biopsy and pus culture confirmed the diagnosis of Pre-XDR Extrapulmonary TB. The treatment regimen was the same for both patients: 6 months with Amikacin (Am) Bedaquiline (Bdq) Prothionamide (Pto) Paraamino Salicylic acid (PAS) Linezolid (Lzd) Cycloserine (Cs) Pyrazinamide (Z) and 14 months with PAS Lzd Cs Z. The side effects were minor. Bacteriological controls (smears and cultures) after 20 months of treatment are negative to date.
Background: A short treatment course for multidrug-resistant tuberculosis (MR-TB) is not yet well codified in children in the Democratic Republic of Congo (DRC). The objective of this study was to evaluate a short MR-TB treatment course in children. Methods: A prospective study was performed from April 2015 (corresponding to the inclusion) through April 2017 (and the later initiation time point was April 2016) in the University Clinics of Kinshasa. Enrolled children were aged 0 to 15 years. The treatment duration was in general for 9 months, with 4 months of intensive phase treatment with Kanamycin, Levofloxacin, Isoniazid, Pyrazinamide, Prothionamide, Clofazimine and Ethambutol, and 5 months of continuous phase treatment with Levofloxacin, Pyrazinamide, Clofazimine and Ethambutol. Frequencies were reported for significant results. Results: A total of 21 children had MDR-TB (11 males and 10 females). Fifteen (71.43%) were bacteriological confirmed cases (by Xpert/MTB), and 6 (28.57%) were clinically diagnosed (MDR-TB contact with suggestive radiologic lesions); 2 patients were coinfected with HIV, 15 cases had pulmonary TB, and 6 had extrapulmonary TB. The main radiologic findings included TB cavity (3 cases), pleural effusion (5 cases), alveolar syndrome (8 cases), adenopathy (7 cases), and interstitial infiltration, fibrosis and miliary (2 cases each). The Ziehl control was negative before 4 months of treatment in the majority of the cases. Overall, 11 patients were cured, 7 completed the treatment, 2 died and 1 was lost to follow up. Conclusions: MDR-TB remains a challenge in children. A more comfortable, short treatment course is feasible in children in the DRC. It is necessary to verify this observation with a larger cohort of MDR-TB patients in pediatrics.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.