BACKGROUND Bedaquiline is among the prioritized drugs recommended by the World Health Organization for the treatment of extensively drug-resistant tuberculosis(XDRTB).Many patients have not achieved better clinical im...BACKGROUND Bedaquiline is among the prioritized drugs recommended by the World Health Organization for the treatment of extensively drug-resistant tuberculosis(XDRTB).Many patients have not achieved better clinical improvement after bedaquiline is stopped at 24 wk.However,there is no recommendation or guideline on bedaquiline administration beyond 24 wk,which is an important consideration when balancing the benefit of prognosis for XDR-TB against the uncertain safety concerning the newer antibiotics.CASE SUMMARY This paper reported 2 patients with XDR-TB(a female of 58 years of age and a female of 18 years of age)who received bedaquiline for 36 wk,as local experience to be shared.The 2 cases had negative cultures after 24 wk of treatment,but lung imaging was still positive.After discussion among experts,the consensus was made to bedaquiline prolongation by another 12 wk.The 36-wk prolonged use of bedaquiline in both cases achieved a favorable response without increasing the risk of cardiac events or new safety signals.CONCLUSION Longer regimen,including 36-wk bedaquiline treatment,might be an option for patients with XDR-TB.More studies are needed to explore the effectiveness and safety of prolonged use of bedaquiline for 36 wk vs standard 24 wk in the treatment of multidrug-resistant/XDR-TB or to investigate further the biomarkers and criteria indicative for extension of bedaquline to facilitate clinical use of thisnovel drug.展开更多
Background:Tuberculosis(TB),caused by Mycobacterium tuberculosis,remains the second leading cause of death from a single infectious disease globally and poses a significant economic and clinical burden in the world in...Background:Tuberculosis(TB),caused by Mycobacterium tuberculosis,remains the second leading cause of death from a single infectious disease globally and poses a significant economic and clinical burden in the world in 2022.Of particular concern is the emergence of drug-resistant TB,accounting for 15%-20%of TB deaths.It is imperative to delve into the global trends of incidence and death rate for multidrug-resistant tuberculosis(MDRTB)and extensively drug-resistant tuberculosis(XDR-TB),drawing upon the comprehensive Global Burden of Disease(GBD)2021 drug-resistant tuberculosis dataset.Methods:From the GBD 2021,data on incidence,prevalence,disability-adjusted life years(DALYs),and death of MDR-TB and XDR-TB from 1990 to 2021 were collected.We calculated the estimated annual percentage changes in age standardized incidence rate(ASIR)and age-standardized death rate(ASDR),segmented by age,sex,and socio-demographic index(SDI).The impacts of various risk factors on MDR-TB and XDR-TB were also analyzed.Results:In 2021,there were an estimated 443,680(95%uncertainty interval[UI]:259,196-766,545)incident cases of MDR-TB,and an estimated 106,818(95%UI:41,612-211,854)death cases of MDR-TB,while there were an estimated 24,036(95%UI:17,144-34,587)incident cases of XDR-TB and 7,946(95%UI:3,326-14,859)death cases of XDR-TB.The incidence and death cases of MDR-TB were lowest in high SDI regions,whereas the incidence rates of XDR-TB in high-middle SDI regions were higher than those in middle SDI and high SDI regions.Conclusion:This study reported the disease burden of drug-resistant TB from 1990 to 2021.Until 2021,drugresistant TB is still a serious problem in low SDI countries,especially for high-risk age populations with highrisk factors.Controlling drug-resistant TB requires effective control strategies and healthcare systems.展开更多
Background Diagnosis and appropriate treatment of multidrug-resistant tuberculosis （MDR-TB） remain major challenges. We sought to elucidate that persons who share a household with drug resistance tuberculosis patien...Background Diagnosis and appropriate treatment of multidrug-resistant tuberculosis （MDR-TB） remain major challenges. We sought to elucidate that persons who share a household with drug resistance tuberculosis patients are at high risk for primary drug resistance tuberculosis and how to prevent these outbreaks. Methods We used 12-locus mycobactedal interspersed repetitive unit and 7-locus variable-number tandem repeat to identify household transmission of extensively drug resistant and multiple drug resistant Mycobacterium tuberculosis in three families admitted in Shanghai Pulmonary Hospital affiliated with Tongji University. Drug susceptibility tests were done by the modified proportion method in the MGIT 960 system in the same time. Clinical data were also obtained from the subjects＇ medical records. Results All of the six strains were defined as Beijing genotype by the deletion-targeted multiplex PCR （DTM-PCR） identification on the genomic deletion RD105. Strains from family-1 had the same minisatellite interspersed repetitive unit （MIRU） pattern （232225172531） and the same MIRU pattern （3677235）. Strains from family-2 had the same MIRU pattern （2212261553323） and the same MIRU pattern （3685134）. Strains from family-3 did not have the same MIRU pattern and they differed at only one locus （223326173533, 223325173533）, and did not have the same VNTR pattern with two locus differed （3667233, 3677234）. Conclusions Household transmission exists in the three families. A clear chain of tuberculosis transmission within family exists. Tuberculosis susceptibility should be considered when there is more than one tuberculosis patients in a familv. Household tuberculosis transmission could be prevented with adequate treatment of source Patients.展开更多
Objective To assess the activities of biapenem against multidrug-resistant and extensively drug-resistant Mycobacterium tuberculosis. Methods Biapenem/clavulanate(BP/CL) was evaluated for in vitro activity against Myc...Objective To assess the activities of biapenem against multidrug-resistant and extensively drug-resistant Mycobacterium tuberculosis. Methods Biapenem/clavulanate(BP/CL) was evaluated for in vitro activity against Mycobacterium tuberculosis(Mtb) multidrug-resistant(MDR) isolates, extensively drug-resistant(XDR) isolates, and the H37 RV strain. BP/CL activity against the H37 Rv strain was assessed in liquid cultures, in macrophages, and in mice. Results BP/CL exhibited activity against MDR and XDR Mtb isolates in liquid cultures. BP/CL treatment significantly reduced the number of colony forming units(CFU) of Mtb within macrophages compared with control untreated infected macrophages. Notably, BP/CL synergized in pairwise combinations with protionamide, aminosalicylate, and capreomycin to achieve a fractional inhibitory concentration for each pairing of 0.375 in vitro. In a mouse tuberculosis infection model, the efficacy of a cocktail of levofloxacin + pyrazinamide + protionamide + aminosalicylate against Mtb increased when the cocktail was combined with BP/CL, achieving efficacy similar to that of the positive control treatment(isoniazid + rifampin + pyrazinamide) after 2 months of treatment. Conclusion BP/CL may provide a new option to clinically treat MDR tuberculosis.展开更多
Rifampicin-resistant tuberculosis (RR-TB) is a global public health problem caused by mycobacterium tuberculosis resistant to Rifampicin. Drug-induced peripheral neuropathy and neurotoxicity are well-known adverse eff...Rifampicin-resistant tuberculosis (RR-TB) is a global public health problem caused by mycobacterium tuberculosis resistant to Rifampicin. Drug-induced peripheral neuropathy and neurotoxicity are well-known adverse effects of treatment regimens that cause significant morbidity. Pyridoxine is often added to treatment regimens for the prevention and/or treatment of these side effects. The basis and effectiveness of this practice are unclear. We conducted a systematic review to evaluate the effectiveness of pyridoxine in preventing and/or treating neuropathy and neurotoxicity associated with RR-TB treatment. We included studies with patients with RR-TB who experienced neuropathy or neurotoxicity attributed to RR-TB regimens and were given pyridoxine. Our findings showed contradicting evidence on the use of pyridoxine for preventing or treating neurotoxicity due to cycloserine in the treatment of RR-TB. Moreover, pyridoxine did not have a protective effect against neuropathy and/or neurotoxicity caused by other RR-TB regimens that do not contain isoniazid. In conclusion, we found that withdrawing or withholding medications such as linezolid, cycloserine, thioamides, fluoroquinolones, and ethambutol, implicated in causing neuropathy or neurotoxicity was more effective than using pyridoxine to stop the progression of symptoms, and in some instances, led to their reversal over time.展开更多
文摘BACKGROUND Bedaquiline is among the prioritized drugs recommended by the World Health Organization for the treatment of extensively drug-resistant tuberculosis(XDRTB).Many patients have not achieved better clinical improvement after bedaquiline is stopped at 24 wk.However,there is no recommendation or guideline on bedaquiline administration beyond 24 wk,which is an important consideration when balancing the benefit of prognosis for XDR-TB against the uncertain safety concerning the newer antibiotics.CASE SUMMARY This paper reported 2 patients with XDR-TB(a female of 58 years of age and a female of 18 years of age)who received bedaquiline for 36 wk,as local experience to be shared.The 2 cases had negative cultures after 24 wk of treatment,but lung imaging was still positive.After discussion among experts,the consensus was made to bedaquiline prolongation by another 12 wk.The 36-wk prolonged use of bedaquiline in both cases achieved a favorable response without increasing the risk of cardiac events or new safety signals.CONCLUSION Longer regimen,including 36-wk bedaquiline treatment,might be an option for patients with XDR-TB.More studies are needed to explore the effectiveness and safety of prolonged use of bedaquiline for 36 wk vs standard 24 wk in the treatment of multidrug-resistant/XDR-TB or to investigate further the biomarkers and criteria indicative for extension of bedaquline to facilitate clinical use of thisnovel drug.
基金supported by International Joint Laboratory on Tropical Diseases Control in Greater Mekong Subregion(grant number 21410750200)from Shanghai Municipality Government.
文摘Background:Tuberculosis(TB),caused by Mycobacterium tuberculosis,remains the second leading cause of death from a single infectious disease globally and poses a significant economic and clinical burden in the world in 2022.Of particular concern is the emergence of drug-resistant TB,accounting for 15%-20%of TB deaths.It is imperative to delve into the global trends of incidence and death rate for multidrug-resistant tuberculosis(MDRTB)and extensively drug-resistant tuberculosis(XDR-TB),drawing upon the comprehensive Global Burden of Disease(GBD)2021 drug-resistant tuberculosis dataset.Methods:From the GBD 2021,data on incidence,prevalence,disability-adjusted life years(DALYs),and death of MDR-TB and XDR-TB from 1990 to 2021 were collected.We calculated the estimated annual percentage changes in age standardized incidence rate(ASIR)and age-standardized death rate(ASDR),segmented by age,sex,and socio-demographic index(SDI).The impacts of various risk factors on MDR-TB and XDR-TB were also analyzed.Results:In 2021,there were an estimated 443,680(95%uncertainty interval[UI]:259,196-766,545)incident cases of MDR-TB,and an estimated 106,818(95%UI:41,612-211,854)death cases of MDR-TB,while there were an estimated 24,036(95%UI:17,144-34,587)incident cases of XDR-TB and 7,946(95%UI:3,326-14,859)death cases of XDR-TB.The incidence and death cases of MDR-TB were lowest in high SDI regions,whereas the incidence rates of XDR-TB in high-middle SDI regions were higher than those in middle SDI and high SDI regions.Conclusion:This study reported the disease burden of drug-resistant TB from 1990 to 2021.Until 2021,drugresistant TB is still a serious problem in low SDI countries,especially for high-risk age populations with highrisk factors.Controlling drug-resistant TB requires effective control strategies and healthcare systems.
文摘Background Diagnosis and appropriate treatment of multidrug-resistant tuberculosis （MDR-TB） remain major challenges. We sought to elucidate that persons who share a household with drug resistance tuberculosis patients are at high risk for primary drug resistance tuberculosis and how to prevent these outbreaks. Methods We used 12-locus mycobactedal interspersed repetitive unit and 7-locus variable-number tandem repeat to identify household transmission of extensively drug resistant and multiple drug resistant Mycobacterium tuberculosis in three families admitted in Shanghai Pulmonary Hospital affiliated with Tongji University. Drug susceptibility tests were done by the modified proportion method in the MGIT 960 system in the same time. Clinical data were also obtained from the subjects＇ medical records. Results All of the six strains were defined as Beijing genotype by the deletion-targeted multiplex PCR （DTM-PCR） identification on the genomic deletion RD105. Strains from family-1 had the same minisatellite interspersed repetitive unit （MIRU） pattern （232225172531） and the same MIRU pattern （3677235）. Strains from family-2 had the same MIRU pattern （2212261553323） and the same MIRU pattern （3685134）. Strains from family-3 did not have the same MIRU pattern and they differed at only one locus （223326173533, 223325173533）, and did not have the same VNTR pattern with two locus differed （3667233, 3677234）. Conclusions Household transmission exists in the three families. A clear chain of tuberculosis transmission within family exists. Tuberculosis susceptibility should be considered when there is more than one tuberculosis patients in a familv. Household tuberculosis transmission could be prevented with adequate treatment of source Patients.
基金supported by the Beijing Medical Award Foundation [YJHYXKYJJ-104]
文摘Objective To assess the activities of biapenem against multidrug-resistant and extensively drug-resistant Mycobacterium tuberculosis. Methods Biapenem/clavulanate(BP/CL) was evaluated for in vitro activity against Mycobacterium tuberculosis(Mtb) multidrug-resistant(MDR) isolates, extensively drug-resistant(XDR) isolates, and the H37 RV strain. BP/CL activity against the H37 Rv strain was assessed in liquid cultures, in macrophages, and in mice. Results BP/CL exhibited activity against MDR and XDR Mtb isolates in liquid cultures. BP/CL treatment significantly reduced the number of colony forming units(CFU) of Mtb within macrophages compared with control untreated infected macrophages. Notably, BP/CL synergized in pairwise combinations with protionamide, aminosalicylate, and capreomycin to achieve a fractional inhibitory concentration for each pairing of 0.375 in vitro. In a mouse tuberculosis infection model, the efficacy of a cocktail of levofloxacin + pyrazinamide + protionamide + aminosalicylate against Mtb increased when the cocktail was combined with BP/CL, achieving efficacy similar to that of the positive control treatment(isoniazid + rifampin + pyrazinamide) after 2 months of treatment. Conclusion BP/CL may provide a new option to clinically treat MDR tuberculosis.
文摘Rifampicin-resistant tuberculosis (RR-TB) is a global public health problem caused by mycobacterium tuberculosis resistant to Rifampicin. Drug-induced peripheral neuropathy and neurotoxicity are well-known adverse effects of treatment regimens that cause significant morbidity. Pyridoxine is often added to treatment regimens for the prevention and/or treatment of these side effects. The basis and effectiveness of this practice are unclear. We conducted a systematic review to evaluate the effectiveness of pyridoxine in preventing and/or treating neuropathy and neurotoxicity associated with RR-TB treatment. We included studies with patients with RR-TB who experienced neuropathy or neurotoxicity attributed to RR-TB regimens and were given pyridoxine. Our findings showed contradicting evidence on the use of pyridoxine for preventing or treating neurotoxicity due to cycloserine in the treatment of RR-TB. Moreover, pyridoxine did not have a protective effect against neuropathy and/or neurotoxicity caused by other RR-TB regimens that do not contain isoniazid. In conclusion, we found that withdrawing or withholding medications such as linezolid, cycloserine, thioamides, fluoroquinolones, and ethambutol, implicated in causing neuropathy or neurotoxicity was more effective than using pyridoxine to stop the progression of symptoms, and in some instances, led to their reversal over time.
