BACKGROUND Tuberculosis(TB)is a chronic respiratory infectious disease that considerably jeopardizes human health,and there is no effective vaccine suitable for its prevention in the entire population.AIM To investiga...BACKGROUND Tuberculosis(TB)is a chronic respiratory infectious disease that considerably jeopardizes human health,and there is no effective vaccine suitable for its prevention in the entire population.AIM To investigate the promotion of medication adherence and disease cognition in patients with drug-resistant(DR-)TB using detailed nursing management.METHODS In total,114 patients with DR-TB who were diagnosed and treated at our hospital between January 2019 and January 2023 were included in this study.Patients in the control group(n=57)were managed with conventional nursing care,while those in the observation group(n=57)were managed with detailed nursing care.Medication adherence,disease awareness scores,medication safety,and nursing satisfaction were compared between the two groups after the intervention.RESULTS The post-intervention medication compliance rate was 91.23%in the observation group and 75.44%in the control group,with the former being 15.79%higher than the latter(P<0.05).There was no statistically significant difference in the disease awareness scores between the two groups before the intervention;the disease awareness scores of the observation group were significantly higher than those of the control group after the intervention(P<0.05).The incidence of gastrointestinal reactions,joint swelling and pain,hearing loss,electrolyte disorders,and liver and kidney function abnormalities were lower in the observation group than those in the control group.The total nursing satisfaction of the observation group was higher than that of the control group(P<0.05).CONCLUSION Implementation of detailed nursing management for patients with DR-TB can effectively improve medication adherence,enhance awareness of the disease,ensure safety of medication,and improve satisfaction with nursing care.展开更多
Introduction: Infections are additional factors of morbidity and mortality in multiple myeloma (MM), and the current recommendation is antibiotic prophylaxis. In sub-Saharan Africa, few data on infectious complication...Introduction: Infections are additional factors of morbidity and mortality in multiple myeloma (MM), and the current recommendation is antibiotic prophylaxis. In sub-Saharan Africa, few data on infectious complications of MM are available. We aim to describe the microbiological features of infections in MM, and their impact on survival in Senegalese patients. Methods: A retrospective (January 2005-January 2022), analytic, multicenter study on infections in patients followed for MM (IMWG criteria) in Senegalese clinical hematology services. The socio-epidemiological, diagnostic, microbiological, evolutionary and survival aspects were analyzed. Results: The study included 106 patients with multiple myeloma who had an infection at admission or during the treatment. Ten patients have the comorbidity (hypertension, lupus, type 2 diabetes). These patients had 136 infectious events identified at diagnosis (79.2%) or during chemotherapy (20.8%). The sites of infection are lung (42.6%), urinary (29.4%), dermatological (6.6%), digestive (5.2%), osteoarticular (4.4%), ear, nose and throat (3.7%), central nervous system (1.5%), or without site. We recorded 26.4% of patients with multi-site infections. The causal pathogens are bacteria (Gram-negative bacilli: 22.1%;Gram positive bacilli: 9.5%, Mycobacterium tuberculosis: 13.3%), parasitique (plasmodium falciparum 6.6%), viruses (SARS-COV2: 2.9%, VZV: 2.2%) and fungal (2.9%). Survival was reduced in patients who had an infection at the time of multiple myeloma diagnosis (p: 0.189) and those who had multiple infectious foci (p: 0.011). Conclusion: Infections in multiple myeloma are more frequent at diagnosis. The germs are varied and mostly bacteria, particularly gram-negative bacteria, and Kochs bacillus. Our study reveals that multiple infectious foci are a poor prognosis factor. It is necessary to evaluate the infectious risk early, and to adopt an antibiotic prophylaxis based on our tropical environment.展开更多
Objective Tuberculosis remains a severe public health issue, and the Beijing family of mycobacterium tuberculosis (M. tuberculosis) is widespread in East Asia, especially in some areas in China, like Beijing and Tia...Objective Tuberculosis remains a severe public health issue, and the Beijing family of mycobacterium tuberculosis (M. tuberculosis) is widespread in East Asia, especially in some areas in China, like Beijing and Tianjin. This study aimed at determining the mutation patterns of drug-resistant Beijing strains of M. tuberculosis isolated from Tianjin, China. Methods A total of 822 M. tuberculosis isolates were screened for drug resistance by an absolute concentration method and the genotype was identified by PCR. 169 drug-resistant isolates of the Beijing family were analyzed for the potential mutations in the rpoB, katG, inhA promoter region and in rpsL, rrs and embB genes, which are associated with resistance to rifampin (RFP), isoniazid (INH), streptomycin (SM) and ethambutol (EMB) respectively by PCR and DNA sequencing. Results Fifty-eight out of 63 RFP-resistant isolates were found to carry the mutations within the 81-bp RFP resistance determining region (RRDR) of the rpoB gene and the most frequent mutations occurred at codon 531 (44.4%), 526 (28.6%), and 516 (7.9%) respectively. 16 mutation pattems affecting 12 different codons around the RRDR of rpoB were found. Of 116 INH-resistant isolates, 56 (48.3%) had the mutation of katG 315 (AGC→ACC) (Ser→Thr), 3 (2.6%) carried S315N (AGC→AAC) and 27 (16.0%) had the mutation of inhA-15A→T. 84 out of 122 SM-resistant isolates (68.9%) displayed mutations at the codons 43 or 88 with AAG→AGG (Lys→Arg) of the rpsL gene and 22 (18.0%) with the mutations at positions 513A→C, 516C→T or 905 A→G in the rrs gene. Of 34 EMB-resistant isolates, 6 had mutation with M306V (ATG→GTG), 3 with M306I (ATG→ATT), 1 with M306I (ATG→ATA), 1 with D328Y (GAT→TAT), 1 with V348L (GTC→CTC), and 1 with G406S (GGC→AGC) in the embB gene. Conelusion These novel findings extended our understanding of resistance-related mutations in the Beijing strains of M. tuberculosis and may provide a scientific basis for development of new strategies for diagnosis and control of tuberculosis in China and other countries where Beijing strains are prevalent.展开更多
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
Objective: Drug resistance is considered one of the main threats for tuberculosis control. Our aim was to identify risk factors for drug resistance in tuberculosis patients in the Northern Portugal. Study Design and M...Objective: Drug resistance is considered one of the main threats for tuberculosis control. Our aim was to identify risk factors for drug resistance in tuberculosis patients in the Northern Portugal. Study Design and Methods: Retrospective case-control study. The medical records and drug susceptibility test data from TB patients diagnosed between 31 March 2009 and 1 April 2010 were examined. We enrolled 119 patients with any drug resistance to first line anti-TB drugs and 238 with drug-susceptible TB, matched by age group. Variables analyzed included: gender, country of origin, employment situation, site of disease, previous treatment, presence of diabetes mellitus, HIV infection, alcohol abuse, intravenous drug use, abuse of other drugs and smoking habits. Multivariate conditional logistic regression was used to identify independent predictors for drug-resistant TB. Results: Diabetes mellitus [adjusted odds ratio (OR): 3.54;95% CI: 1.45 - 8.66], intravenous drug use (OR: 4.77;95% CI: 1.24 - 18.32) and previous TB treatment (OR: 2.48;95% CI: 1.12 - 5.49) were found to be risk factors for drug-resistant disease development. Conclusions: Diabetes mellitus, prior tuberculosis treatment, and intravenous drug use were risk factors for drug-resistant disease. The association between diabetes and drug-resistant TB should be further explored. Identifying clinical predictors of drug resistance can allow prompt identification of patients at risk for drug-resistant TB.展开更多
Multiple abscesses of the costo-chondral junctions are very uncommon in practice.In this report we present the case of a 55 year old man who presented to us with chest pain and fever of few months duration.On imaging ...Multiple abscesses of the costo-chondral junctions are very uncommon in practice.In this report we present the case of a 55 year old man who presented to us with chest pain and fever of few months duration.On imaging with ultrasound and CECT we were able to demonstrate multiple abscesses of costo-chondral junctions bilaterally.We confirmed tuberculosis by FNAC and BACTEC cultures from abscesses.展开更多
Introduction: The emergency of Mycobacterium tuberculosis resistant to the first line drug reduced access possibility to second line drugs for appropriate treatment and required for urgent action especially in le Demo...Introduction: The emergency of Mycobacterium tuberculosis resistant to the first line drug reduced access possibility to second line drugs for appropriate treatment and required for urgent action especially in le Democratic Republic of Congo (DRC), which counts among the highest tuberculosis (TB) burden countries in Africa. Objective: To present prevalence and describe multidrug-resistant tuberculosis cases in North-Kivu Province identified by using Genexpert technology. Methods: We conducted an observational prospective study on multidrug-resistant tuberculosis (MDR-TB) cases in North-Kivu Province, DRC from 2017 to 2018. All cases of MDR-TB identified by Genexpert MTB/ RIB were included in this series. Result: Of 15,544 tuberculosis cases registered during the study period, 19 cases of MDR-TB were identified. 57.9% was male, 89.5% was retreatment cases and 5.3% was coinfection HIV/TB cases. Conclusion: This new molecular technology diagnostic facilitates multidrug-resistance tuberculosis detection and improves the reporting of data lack.展开更多
To understand the genetic diversity and drug resistance status of Mycobocterium tuberculosis (M. tuberculosis) circulating in Xuzhou of China, the spacer-oligonucleotide typing (Spoligotyping) and multi-loci VNTRs...To understand the genetic diversity and drug resistance status of Mycobocterium tuberculosis (M. tuberculosis) circulating in Xuzhou of China, the spacer-oligonucleotide typing (Spoligotyping) and multi-loci VNTRs (variable number tandem repeats) analysis (MLVA) were utilized for the genotyping of the isolates. Drug susceptibility test (DST) was performed by the proportion method on the Lowenstein-Jensen (L-J) medium using isoniazid, rifampicin, ethambutol, and streptomycin. By Spoligotyping, 287 M. tuberculosis isolates were differentiated into 14 clusters. Then with 15-1oci MLVA, these strains could be divided into 32 clusters, 228 genotypes. Of 15 VNTRs, 6 loci had the highly discriminatory powers, 6 loci presented moderate discrimination and 3 loci demonstrated less polymorphism. The DST results showed that 46 strains were resistant to at least one first-line anti-tuberculosis agent. There was a difference in the isoniazid resistance between Beijing and non-Beijing genotype strains. We concluded that the combination of Spoligotyping and 15 VNTR loci as the genotyping in our study was applicable for this region, the drug resistant isolates were identified, and the Beijing family was the most prevalent genotype in the rural counties of Xuzhou.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
Bedaquiline resistance is increasingly observed in the treatment of rifampicin-resistant tuberculosis(TB),yet standardized regimens for managing bedaquiline-resistant TB are lacking.Studies indicate a high proportion ...Bedaquiline resistance is increasingly observed in the treatment of rifampicin-resistant tuberculosis(TB),yet standardized regimens for managing bedaquiline-resistant TB are lacking.Studies indicate a high proportion of bedaquiline-resistant cases have previously been treated for TB,and often involve strains resistant to quinolones.Regular monitoring of the culture status in patients receiving bedaquiline resistance treatment is advised.Methods such as experimental evolution,protein modeling,genome sequencing,and phenotypic analysis have been instrumental in identifying the mechanisms of bedaquiline resistance.Specifically,variants in the Rv0678 transcriptional repressor of the MmpS5-MmpL5 efflux system are linked to this type of resistance.Bayesian probability estimates show promise in determining the genotypic–phenotypic association for bedaquiline resistance,suggesting potential utility in clinical practice.Future research should explore the practical application of Bayesian probabilities in managing bedaquiline resistance.Sequencing-based technologies are anticipated to play a vital role in the early detection and management of drug-resistant TB strains.展开更多
A fundamental goal in cellular signaling is to understand allosteric communication, the process by which sig-nals originating at one site in a protein propagate reliably to affect distant functional sites. The general...A fundamental goal in cellular signaling is to understand allosteric communication, the process by which sig-nals originating at one site in a protein propagate reliably to affect distant functional sites. The general principles of protein structure that underlie this process remain unknown. Statistical coupling analysis (SCA) is a statistical technique that uses evolutionary data of a protein family to measure correlation between distant functional sites and suggests allosteric communication. In proteins, very distant and small interactions between collections of amino acids provide the communication which can be important for signaling process. In this paper, we present the SCA of protein alignment of the esterase family (pfam ID: PF00756) containing the sequence of antigen 85C secreted by Mycobacterium tuberculosis to identify a subset of interacting residues. Clustering analysis of the pairwise correlation highlighted seven important residue positions in the esterase family alignments. These resi-dues were then mapped on the crystal structure of antigen 85C (PDB ID: 1DQZ). The mapping revealed corre-lation between 3 distant residues (Asp38, Leu123 and Met125) and suggests allosteric communication between them. This information can be used for a new drug against this fatal disease.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
Background:The detection of drug-resistant tuberculosis(DR-TB)is a major health concern in China.We aim to summarize interventions related to the screening and detection of DR-TB in Jiangsu Province,analyse their impa...Background:The detection of drug-resistant tuberculosis(DR-TB)is a major health concern in China.We aim to summarize interventions related to the screening and detection of DR-TB in Jiangsu Province,analyse their impact,and highlight policy implications for improving the prevention and control of DR-TB.Methods:We selected six prefectures from south,central and no「th Jiangsu Province.We reviewed policy documents between 2008 and 2019,and extracted routineTB patient registration data from theTB Information Management System(TBIMS)between 2013 and 2019.We used the High-quality Health System Framework to structure the analysis.We performed statistical analysis and logistic regression to assess the impact of different policy interventions on DR-TB detection.Results:Three prefectures in Jiangsu introduced DR-TB related interventions between 2008 and 2010 in partnership with the Global Fund to Fight AIDS,Tuberculosis and Malaria(the Global Fund)and the Bill&Melinda Gates Foundation(Gates Foundation).By 2017,all prefectures in Jiangsu had implemented provincial level DR-TB policies,such as use of rapid molecular tests(RMT),and expanded drug susceptibility testing(DST)for populations at risk of DR-TB.The percentage of pulmonary TB cases con firmed by bacteriology in creased from 30.0%in 2013 to over 50.0%in all prefectures by 2019,indicating that the implementation of new diagnostics has provided more sensitive testing results than the traditional smear microscopy.At the same time,the proportion of bacteriologically confirmed cases tested for drug resistance has increased substantially,indicating that the intervention of expanding the coverage of DST has reached more of the population at risk of DR-TB.Prefectures that implemented interventions with support from the Global Fund and the Gates Foundation had better detection performance of DR-TB patiens compared to those did not receive external support.However,the disparities in DR-TB detection across prefectures significantly narrowed after the implementation of provincial DR-TB polices.Con elusions:The introduction of new diagnostics,including RMT,have improved the detection of DR-TB.Prefectures that received support from the Global Fund and the Gates Foundation had better detection of DR-TB.Additionally,the implementation of provincial DR-TB polices led to improvements in the detection of DR-TB across all prefectures.展开更多
Objective: To study the relationship between the polymorphism of drug resistant gene rpoB and drug resistance against rifampicin(RFP) of M. tuberculosis L-forms, and to evaluate its clinical application. Methods: A to...Objective: To study the relationship between the polymorphism of drug resistant gene rpoB and drug resistance against rifampicin(RFP) of M. tuberculosis L-forms, and to evaluate its clinical application. Methods: A total of 52 clinical isolated strains of M. tuberculosis L-forms were collected. rpoB gene polymorphism was analyzed by polymerase chain reaction and single-strand conformation polymorphism (PCR-SSCP) and conventional antimicrobial susceptibility test (AST). Their results were compared. Results: AST results showed that 38 of 52 clinical isolated strains were drug resistance (73.08%),while PCR-SSCP indicated 65.38% (32/52) rpoB gene polymorphism. There was no statistic significance(χ2= 2.4914) between the 2 methods. Conclusion:Combined the application of PCR-SSCP with AST in detecting rpoB drug resistant gene polymorphism of M. tuberculosis L-form from pneumoconiosis patients with tuberculosis may have advantages at earlier diagnosis and guidance of clinical medications.展开更多
Objective: To study the relationship between drug resistant genetic mutation and drug resistance in Mycobacterium tuberculosis L-form, discuss the internal relationship between drug resistances and drug-resistant rel...Objective: To study the relationship between drug resistant genetic mutation and drug resistance in Mycobacterium tuberculosis L-form, discuss the internal relationship between drug resistances and drug-resistant related genes and explore the value of PCR- SSCP to clinical application. Methods: A total of 52 clinically isolated strains of tuberculosis L-form were collected among 97 pneumoconiosis patients complicated with tuberculosis. The gene mutations of katG, rpoB and rpsL were detected by PCR-SSCP, and the results were compared with those analyzed by traditional antimicrobial susceptibility test(AST). Results: The gene muta- tion rates of katG, rpoB and rpsL by PCR-SSCP were respectively 57.70% (30/52), 65.38% (32/52) and 40.38% (21/52). The rate of reversion was 78.85%(41/52) and the result of drag-resistant genes was invariable. The results of AST showed that there were 40 (76.92%) multi-drug resistant strains in 52 clinically isolated strains. The number for three-drug resistant strain was 21 (40.38%) and that of two-drug resistant was 19(36.54%), but only 12(23.08%) strains were one drug resistant. The rate of total drug-resistance was 100%, but there were 15 strains of allied mutation of three genes, 16 of two mutations and 6 of only one by PCR-SSCP. The coincidences were respectively 71.43%, 84.12% and 50.00%. Then there was no significant difference between the allied mutations of multi-drug resistant gene and the mutations of only one drug resistant gene (P 〉 0.05). Conclusion: PCR-SSCP technique has a higher sensibility and specificity to detect the genes of katG, rpoB and rpsL in tuberculosis L-form among pneumoconiosis complicated with tuberculosis,and the detecting rate of two drug resistant strains and three drug resistant strains was higher. The combined application of PCR-SSCP and AST has advantages at earlier diagnosis and guidance of clinical medications.展开更多
Background Tuberculosis is a bacterial infectious disease,which affects different parts of a human body,mainly lungs and can lead to the patient’s death.The aim of this study is to investigate the global prevalence o...Background Tuberculosis is a bacterial infectious disease,which affects different parts of a human body,mainly lungs and can lead to the patient’s death.The aim of this study is to investigate the global prevalence of drug-resistant tuberculosis using a systematic review and meta-analysis.Methods In this study,the PubMed,Scopus,Web of Science,Embase,ScienceDirect and Google Scholar repositories were systematically searched to find studies reporting the global prevalence of drug-resistant tuberculosis.The search did not entail a lower time limit,and articles published up until August 2022 were considered.Random effects model was used to perform the analysis.The heterogeneity of the studies was examined with the I^(2) test.Data analysis was conducted within the Comprehensive Meta-Analysis software.Results In the review of 148 studies with a sample size of 318,430 people,the I^(2) index showed high heterogeneity(I^(2)=99.6),and accordingly random effects method was used to analyze the results.Publication bias was also examined using the Begg and Mazumdar correlation test which indicated the existence of publication bias in the studies(P=0.008).According to our meta-analysis,the global pooled prevalence of multi-drug resistant TB is 11.6%(95%CI:9.1–14.5%).Conclusions The global prevalence of drug-resistant tuberculosis was found to be very high,thus health authorities should consider ways to control and manage the disease to prevent a wider spread of tuberculosis and potentially subsequent deaths.展开更多
文摘BACKGROUND Tuberculosis(TB)is a chronic respiratory infectious disease that considerably jeopardizes human health,and there is no effective vaccine suitable for its prevention in the entire population.AIM To investigate the promotion of medication adherence and disease cognition in patients with drug-resistant(DR-)TB using detailed nursing management.METHODS In total,114 patients with DR-TB who were diagnosed and treated at our hospital between January 2019 and January 2023 were included in this study.Patients in the control group(n=57)were managed with conventional nursing care,while those in the observation group(n=57)were managed with detailed nursing care.Medication adherence,disease awareness scores,medication safety,and nursing satisfaction were compared between the two groups after the intervention.RESULTS The post-intervention medication compliance rate was 91.23%in the observation group and 75.44%in the control group,with the former being 15.79%higher than the latter(P<0.05).There was no statistically significant difference in the disease awareness scores between the two groups before the intervention;the disease awareness scores of the observation group were significantly higher than those of the control group after the intervention(P<0.05).The incidence of gastrointestinal reactions,joint swelling and pain,hearing loss,electrolyte disorders,and liver and kidney function abnormalities were lower in the observation group than those in the control group.The total nursing satisfaction of the observation group was higher than that of the control group(P<0.05).CONCLUSION Implementation of detailed nursing management for patients with DR-TB can effectively improve medication adherence,enhance awareness of the disease,ensure safety of medication,and improve satisfaction with nursing care.
文摘Introduction: Infections are additional factors of morbidity and mortality in multiple myeloma (MM), and the current recommendation is antibiotic prophylaxis. In sub-Saharan Africa, few data on infectious complications of MM are available. We aim to describe the microbiological features of infections in MM, and their impact on survival in Senegalese patients. Methods: A retrospective (January 2005-January 2022), analytic, multicenter study on infections in patients followed for MM (IMWG criteria) in Senegalese clinical hematology services. The socio-epidemiological, diagnostic, microbiological, evolutionary and survival aspects were analyzed. Results: The study included 106 patients with multiple myeloma who had an infection at admission or during the treatment. Ten patients have the comorbidity (hypertension, lupus, type 2 diabetes). These patients had 136 infectious events identified at diagnosis (79.2%) or during chemotherapy (20.8%). The sites of infection are lung (42.6%), urinary (29.4%), dermatological (6.6%), digestive (5.2%), osteoarticular (4.4%), ear, nose and throat (3.7%), central nervous system (1.5%), or without site. We recorded 26.4% of patients with multi-site infections. The causal pathogens are bacteria (Gram-negative bacilli: 22.1%;Gram positive bacilli: 9.5%, Mycobacterium tuberculosis: 13.3%), parasitique (plasmodium falciparum 6.6%), viruses (SARS-COV2: 2.9%, VZV: 2.2%) and fungal (2.9%). Survival was reduced in patients who had an infection at the time of multiple myeloma diagnosis (p: 0.189) and those who had multiple infectious foci (p: 0.011). Conclusion: Infections in multiple myeloma are more frequent at diagnosis. The germs are varied and mostly bacteria, particularly gram-negative bacteria, and Kochs bacillus. Our study reveals that multiple infectious foci are a poor prognosis factor. It is necessary to evaluate the infectious risk early, and to adopt an antibiotic prophylaxis based on our tropical environment.
基金supported by National Science Key Grant(2008ZX10003-009).
文摘Objective Tuberculosis remains a severe public health issue, and the Beijing family of mycobacterium tuberculosis (M. tuberculosis) is widespread in East Asia, especially in some areas in China, like Beijing and Tianjin. This study aimed at determining the mutation patterns of drug-resistant Beijing strains of M. tuberculosis isolated from Tianjin, China. Methods A total of 822 M. tuberculosis isolates were screened for drug resistance by an absolute concentration method and the genotype was identified by PCR. 169 drug-resistant isolates of the Beijing family were analyzed for the potential mutations in the rpoB, katG, inhA promoter region and in rpsL, rrs and embB genes, which are associated with resistance to rifampin (RFP), isoniazid (INH), streptomycin (SM) and ethambutol (EMB) respectively by PCR and DNA sequencing. Results Fifty-eight out of 63 RFP-resistant isolates were found to carry the mutations within the 81-bp RFP resistance determining region (RRDR) of the rpoB gene and the most frequent mutations occurred at codon 531 (44.4%), 526 (28.6%), and 516 (7.9%) respectively. 16 mutation pattems affecting 12 different codons around the RRDR of rpoB were found. Of 116 INH-resistant isolates, 56 (48.3%) had the mutation of katG 315 (AGC→ACC) (Ser→Thr), 3 (2.6%) carried S315N (AGC→AAC) and 27 (16.0%) had the mutation of inhA-15A→T. 84 out of 122 SM-resistant isolates (68.9%) displayed mutations at the codons 43 or 88 with AAG→AGG (Lys→Arg) of the rpsL gene and 22 (18.0%) with the mutations at positions 513A→C, 516C→T or 905 A→G in the rrs gene. Of 34 EMB-resistant isolates, 6 had mutation with M306V (ATG→GTG), 3 with M306I (ATG→ATT), 1 with M306I (ATG→ATA), 1 with D328Y (GAT→TAT), 1 with V348L (GTC→CTC), and 1 with G406S (GGC→AGC) in the embB gene. Conelusion These novel findings extended our understanding of resistance-related mutations in the Beijing strains of M. tuberculosis and may provide a scientific basis for development of new strategies for diagnosis and control of tuberculosis in China and other countries where Beijing strains are prevalent.
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.
文摘Objective: Drug resistance is considered one of the main threats for tuberculosis control. Our aim was to identify risk factors for drug resistance in tuberculosis patients in the Northern Portugal. Study Design and Methods: Retrospective case-control study. The medical records and drug susceptibility test data from TB patients diagnosed between 31 March 2009 and 1 April 2010 were examined. We enrolled 119 patients with any drug resistance to first line anti-TB drugs and 238 with drug-susceptible TB, matched by age group. Variables analyzed included: gender, country of origin, employment situation, site of disease, previous treatment, presence of diabetes mellitus, HIV infection, alcohol abuse, intravenous drug use, abuse of other drugs and smoking habits. Multivariate conditional logistic regression was used to identify independent predictors for drug-resistant TB. Results: Diabetes mellitus [adjusted odds ratio (OR): 3.54;95% CI: 1.45 - 8.66], intravenous drug use (OR: 4.77;95% CI: 1.24 - 18.32) and previous TB treatment (OR: 2.48;95% CI: 1.12 - 5.49) were found to be risk factors for drug-resistant disease development. Conclusions: Diabetes mellitus, prior tuberculosis treatment, and intravenous drug use were risk factors for drug-resistant disease. The association between diabetes and drug-resistant TB should be further explored. Identifying clinical predictors of drug resistance can allow prompt identification of patients at risk for drug-resistant TB.
文摘Multiple abscesses of the costo-chondral junctions are very uncommon in practice.In this report we present the case of a 55 year old man who presented to us with chest pain and fever of few months duration.On imaging with ultrasound and CECT we were able to demonstrate multiple abscesses of costo-chondral junctions bilaterally.We confirmed tuberculosis by FNAC and BACTEC cultures from abscesses.
文摘Introduction: The emergency of Mycobacterium tuberculosis resistant to the first line drug reduced access possibility to second line drugs for appropriate treatment and required for urgent action especially in le Democratic Republic of Congo (DRC), which counts among the highest tuberculosis (TB) burden countries in Africa. Objective: To present prevalence and describe multidrug-resistant tuberculosis cases in North-Kivu Province identified by using Genexpert technology. Methods: We conducted an observational prospective study on multidrug-resistant tuberculosis (MDR-TB) cases in North-Kivu Province, DRC from 2017 to 2018. All cases of MDR-TB identified by Genexpert MTB/ RIB were included in this series. Result: Of 15,544 tuberculosis cases registered during the study period, 19 cases of MDR-TB were identified. 57.9% was male, 89.5% was retreatment cases and 5.3% was coinfection HIV/TB cases. Conclusion: This new molecular technology diagnostic facilitates multidrug-resistance tuberculosis detection and improves the reporting of data lack.
基金funded by the projects 2013ZX10003002-001 of Chinese National Key Program of Mega Infectious Disease of the National 12th Five-Year Planthe Science and Technology Innovation Team Support project CX201412 of Changzhi Medical College
文摘To understand the genetic diversity and drug resistance status of Mycobocterium tuberculosis (M. tuberculosis) circulating in Xuzhou of China, the spacer-oligonucleotide typing (Spoligotyping) and multi-loci VNTRs (variable number tandem repeats) analysis (MLVA) were utilized for the genotyping of the isolates. Drug susceptibility test (DST) was performed by the proportion method on the Lowenstein-Jensen (L-J) medium using isoniazid, rifampicin, ethambutol, and streptomycin. By Spoligotyping, 287 M. tuberculosis isolates were differentiated into 14 clusters. Then with 15-1oci MLVA, these strains could be divided into 32 clusters, 228 genotypes. Of 15 VNTRs, 6 loci had the highly discriminatory powers, 6 loci presented moderate discrimination and 3 loci demonstrated less polymorphism. The DST results showed that 46 strains were resistant to at least one first-line anti-tuberculosis agent. There was a difference in the isoniazid resistance between Beijing and non-Beijing genotype strains. We concluded that the combination of Spoligotyping and 15 VNTR loci as the genotyping in our study was applicable for this region, the drug resistant isolates were identified, and the Beijing family was the most prevalent genotype in the rural counties of Xuzhou.
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.
文摘Bedaquiline resistance is increasingly observed in the treatment of rifampicin-resistant tuberculosis(TB),yet standardized regimens for managing bedaquiline-resistant TB are lacking.Studies indicate a high proportion of bedaquiline-resistant cases have previously been treated for TB,and often involve strains resistant to quinolones.Regular monitoring of the culture status in patients receiving bedaquiline resistance treatment is advised.Methods such as experimental evolution,protein modeling,genome sequencing,and phenotypic analysis have been instrumental in identifying the mechanisms of bedaquiline resistance.Specifically,variants in the Rv0678 transcriptional repressor of the MmpS5-MmpL5 efflux system are linked to this type of resistance.Bayesian probability estimates show promise in determining the genotypic–phenotypic association for bedaquiline resistance,suggesting potential utility in clinical practice.Future research should explore the practical application of Bayesian probabilities in managing bedaquiline resistance.Sequencing-based technologies are anticipated to play a vital role in the early detection and management of drug-resistant TB strains.
文摘A fundamental goal in cellular signaling is to understand allosteric communication, the process by which sig-nals originating at one site in a protein propagate reliably to affect distant functional sites. The general principles of protein structure that underlie this process remain unknown. Statistical coupling analysis (SCA) is a statistical technique that uses evolutionary data of a protein family to measure correlation between distant functional sites and suggests allosteric communication. In proteins, very distant and small interactions between collections of amino acids provide the communication which can be important for signaling process. In this paper, we present the SCA of protein alignment of the esterase family (pfam ID: PF00756) containing the sequence of antigen 85C secreted by Mycobacterium tuberculosis to identify a subset of interacting residues. Clustering analysis of the pairwise correlation highlighted seven important residue positions in the esterase family alignments. These resi-dues were then mapped on the crystal structure of antigen 85C (PDB ID: 1DQZ). The mapping revealed corre-lation between 3 distant residues (Asp38, Leu123 and Met125) and suggests allosteric communication between them. This information can be used for a new drug against this fatal disease.
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.
基金The study was partially funded by a research grant from Jiangsu Provincial Health Commissi on to support the tale nted researchers in the health sector.Dr.Xiao-Yan Ding,supported by the Jiangsu Health International Exchange Program,was a visiting fellow at Duke Global Health Institute,when she was working on this manuscript.
文摘Background:The detection of drug-resistant tuberculosis(DR-TB)is a major health concern in China.We aim to summarize interventions related to the screening and detection of DR-TB in Jiangsu Province,analyse their impact,and highlight policy implications for improving the prevention and control of DR-TB.Methods:We selected six prefectures from south,central and no「th Jiangsu Province.We reviewed policy documents between 2008 and 2019,and extracted routineTB patient registration data from theTB Information Management System(TBIMS)between 2013 and 2019.We used the High-quality Health System Framework to structure the analysis.We performed statistical analysis and logistic regression to assess the impact of different policy interventions on DR-TB detection.Results:Three prefectures in Jiangsu introduced DR-TB related interventions between 2008 and 2010 in partnership with the Global Fund to Fight AIDS,Tuberculosis and Malaria(the Global Fund)and the Bill&Melinda Gates Foundation(Gates Foundation).By 2017,all prefectures in Jiangsu had implemented provincial level DR-TB policies,such as use of rapid molecular tests(RMT),and expanded drug susceptibility testing(DST)for populations at risk of DR-TB.The percentage of pulmonary TB cases con firmed by bacteriology in creased from 30.0%in 2013 to over 50.0%in all prefectures by 2019,indicating that the implementation of new diagnostics has provided more sensitive testing results than the traditional smear microscopy.At the same time,the proportion of bacteriologically confirmed cases tested for drug resistance has increased substantially,indicating that the intervention of expanding the coverage of DST has reached more of the population at risk of DR-TB.Prefectures that implemented interventions with support from the Global Fund and the Gates Foundation had better detection performance of DR-TB patiens compared to those did not receive external support.However,the disparities in DR-TB detection across prefectures significantly narrowed after the implementation of provincial DR-TB polices.Con elusions:The introduction of new diagnostics,including RMT,have improved the detection of DR-TB.Prefectures that received support from the Global Fund and the Gates Foundation had better detection of DR-TB.Additionally,the implementation of provincial DR-TB polices led to improvements in the detection of DR-TB across all prefectures.
文摘Objective: To study the relationship between the polymorphism of drug resistant gene rpoB and drug resistance against rifampicin(RFP) of M. tuberculosis L-forms, and to evaluate its clinical application. Methods: A total of 52 clinical isolated strains of M. tuberculosis L-forms were collected. rpoB gene polymorphism was analyzed by polymerase chain reaction and single-strand conformation polymorphism (PCR-SSCP) and conventional antimicrobial susceptibility test (AST). Their results were compared. Results: AST results showed that 38 of 52 clinical isolated strains were drug resistance (73.08%),while PCR-SSCP indicated 65.38% (32/52) rpoB gene polymorphism. There was no statistic significance(χ2= 2.4914) between the 2 methods. Conclusion:Combined the application of PCR-SSCP with AST in detecting rpoB drug resistant gene polymorphism of M. tuberculosis L-form from pneumoconiosis patients with tuberculosis may have advantages at earlier diagnosis and guidance of clinical medications.
基金This work was supported by the Youth Natural Science Foundation of Anhui University of Science & Technology(200537)
文摘Objective: To study the relationship between drug resistant genetic mutation and drug resistance in Mycobacterium tuberculosis L-form, discuss the internal relationship between drug resistances and drug-resistant related genes and explore the value of PCR- SSCP to clinical application. Methods: A total of 52 clinically isolated strains of tuberculosis L-form were collected among 97 pneumoconiosis patients complicated with tuberculosis. The gene mutations of katG, rpoB and rpsL were detected by PCR-SSCP, and the results were compared with those analyzed by traditional antimicrobial susceptibility test(AST). Results: The gene muta- tion rates of katG, rpoB and rpsL by PCR-SSCP were respectively 57.70% (30/52), 65.38% (32/52) and 40.38% (21/52). The rate of reversion was 78.85%(41/52) and the result of drag-resistant genes was invariable. The results of AST showed that there were 40 (76.92%) multi-drug resistant strains in 52 clinically isolated strains. The number for three-drug resistant strain was 21 (40.38%) and that of two-drug resistant was 19(36.54%), but only 12(23.08%) strains were one drug resistant. The rate of total drug-resistance was 100%, but there were 15 strains of allied mutation of three genes, 16 of two mutations and 6 of only one by PCR-SSCP. The coincidences were respectively 71.43%, 84.12% and 50.00%. Then there was no significant difference between the allied mutations of multi-drug resistant gene and the mutations of only one drug resistant gene (P 〉 0.05). Conclusion: PCR-SSCP technique has a higher sensibility and specificity to detect the genes of katG, rpoB and rpsL in tuberculosis L-form among pneumoconiosis complicated with tuberculosis,and the detecting rate of two drug resistant strains and three drug resistant strains was higher. The combined application of PCR-SSCP and AST has advantages at earlier diagnosis and guidance of clinical medications.
基金By Deputy for Research and Technology,Kermanshah University of Medical Sciences(IR)(50002460).
文摘Background Tuberculosis is a bacterial infectious disease,which affects different parts of a human body,mainly lungs and can lead to the patient’s death.The aim of this study is to investigate the global prevalence of drug-resistant tuberculosis using a systematic review and meta-analysis.Methods In this study,the PubMed,Scopus,Web of Science,Embase,ScienceDirect and Google Scholar repositories were systematically searched to find studies reporting the global prevalence of drug-resistant tuberculosis.The search did not entail a lower time limit,and articles published up until August 2022 were considered.Random effects model was used to perform the analysis.The heterogeneity of the studies was examined with the I^(2) test.Data analysis was conducted within the Comprehensive Meta-Analysis software.Results In the review of 148 studies with a sample size of 318,430 people,the I^(2) index showed high heterogeneity(I^(2)=99.6),and accordingly random effects method was used to analyze the results.Publication bias was also examined using the Begg and Mazumdar correlation test which indicated the existence of publication bias in the studies(P=0.008).According to our meta-analysis,the global pooled prevalence of multi-drug resistant TB is 11.6%(95%CI:9.1–14.5%).Conclusions The global prevalence of drug-resistant tuberculosis was found to be very high,thus health authorities should consider ways to control and manage the disease to prevent a wider spread of tuberculosis and potentially subsequent deaths.