Prolonged use of bedaquiline in two patients with pulmonary extensively drug-resistant tuberculosis: Two case reports

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.

Establishment of extensively drug-resistant Pseudomonas aeruginosa pneumonia model in rat

Objective:To establish extensively drug-resistant Pseudomonas aeruginosa(XDR-PA)infection-induced pneumonia model in rats.Methods:Twenty-four male SD rats were randomly divided into blank group,low bacterial group,medium bacterial group,and high bacterial group.The low,medium and high bacterial groups were given intratracheal instillation of 0.1 mL of bacterial suspension(bacterial concentration in turn is 7.5×10^(9),3×10^(10),6×10^(10)CFU/mL),while the blank group were given the same volume of sterile normal saline.After modeling,the general conditions of rats in each group were observed,including mental state,hair,respiration,activity,eating,weight,and the survival curve was drawn.The pathological characteristics of lung tissue and the infiltration of inflammatory cells were observed.Pathogenic identification of each group was carried out by bacterial culture of lung tissue homogenate.Results:The general state of the blank group was normal,and the rats in other groups showed signs of mental depression,bristling,shortness of breath,even oral and nasal bleeding,decreased food intake and activity,and significant weight loss,and different degrees of death within 48 hours,the difference was statistically significant(P<0.05).Pathological results showed that the alveolar structure of rats in the blank group was complete,and the alveolar space was clear without exudation.The lung tissue of the low and medium bacterial groups showed obvious inflammatory cell infiltration,alveolar structure destruction,alveolar septum thickening,interstitial edema,but the pathological damage of the medium group was more severe,with a mortality rate of up to 50%,and the mortality rate of the low bacterial group was 17%.In the high bacterial group,red blood cells,inflammatory cells and a large amount of fibrin-like exudation can be seen in the alveolar space,which has the pathological characteristics of acute respiratory failure,and the mortality rate is as high as 67%.The results of bacterial culture of lung tissue homogenate showed that the blank group had no bacterial colonies,while PA colony growth can be seen in low,medium and high bacterial groups.Conclusion:9 Intratracheal instillation of low bacterial count(0.1 mL of 7.5×10^(9) CFU/mL)XDR-PA bacterial suspension can successfully construct a rat pneumonia model of XDR-PA infection.

Clinical effects of detailed nursing management interventions on medication adherence and disease perception in patients with drugresistant tuberculosis

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.

Molecular Characterization of Drug-Resistant Beijing Family Isolates of Mycobacterium Tuberculosis from Tianjin,China

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.

Extensively drug-resistant bacteria are an independent predictive factor of mortality in 130 patients with spontaneous bacterial peritonitis or spontaneous bacteremia

AIM: To evaluate the epidemiology and outcomes of culture-positive spontaneous bacterial peritonitis (SBP) and spontaneous bacteremia (SB) in decompensated cirrhosis.METHODS: We prospectively collected clinical, laboratory characteristics, type of administered antibiotic, susceptibility and resistance of bacteria to antibiotics in one hundred thirty cases (68.5% males) with positive ascitic fluid and/or blood cultures during the period from January 1, 2012 to May 30, 2014. All patients with SBP had polymorphonuclear cell count in ascitic fluid > 250/mm3. In patients with SB a thorough study did not reveal any other cause of bacteremia. The patients were followed-up for a 30-d period following diagnosis of the infection. The final outcome of the patients was recorded in the end of follow-up and comparison among 3 groups of patients according to the pattern of drug resistance was performed.RESULTS: Gram-positive-cocci (GPC) were found in half of the cases. The most prevalent organisms in a descending order were Escherichia coli (33), Enterococcus spp (30), Streptococcus spp (25), Klebsiella pneumonia (16), S. aureus (8), Pseudomanas aeruginosa (5), other Gram-negative-bacteria (GNB) (11) and anaerobes (2). Overall, 20.8% of isolates were multidrug-resistant (MDR) and 10% extensively drug-resistant (XDR). Health-care-associated (HCA) and/or nosocomial infections were present in 100% of MDR/XDR and in 65.5% of non-DR cases. Meropenem was the empirically prescribed antibiotic in HCA/nosocomial infections showing a drug-resistance rate of 30.7% while third generation cephalosporins of 43.8%. Meropenem was ineffective on both XDR bacteria and Enterococcus faecium (E. faecium). All but one XDR were susceptible to colistin while all GPC (including E. faecium) and the 86% of GNB to tigecycline. Overall 30-d mortality was 37.7% (69.2% for XDR and 34.2% for the rest of the patients) (log rank, P = 0.015). In multivariate analysis, factors adversely affecting outcome included XDR infection (HR = 2.263, 95%CI: 1.005-5.095, P = 0.049), creatinine (HR = 1.125, 95%CI: 1.024-1.236, P = 0.015) and INR (HR =1.553, 95%CI: 1.106-2.180, P = 0.011).CONCLUSION: XDR bacteria are an independent life-threatening factor in SBP/SB. Strategies aiming at restricting antibiotic overuse and rapid identification of the responsible bacteria could help improve survival.

Successful treatment of pyogenic ventriculitis caused by extensively drug-resistant Acinetobacter baumannii with multi-route tigecycline: A case report

BACKGROUND Pyogenic ventriculitis caused by extensively drug-resistant Acinetobacter baumannii(A.baumannii)is one of the most severe complications associated with craniotomy.However,limited therapeutic options exist for the treatment of A.baumannii ventriculitis due to the poor penetration rate of most antibiotics through the blood-brain barrier.CASE SUMMARY A 68-year-old male patient with severe traumatic brain injury developed pyogenic ventriculitis on postoperative day 24 caused by extensively drug-resistant A.baumannii susceptible to tigecycline only.Successful treatment was accomplished through multi-route administration of tigecycline,including intravenous combined with continuous ventricular irrigation plus intraventricular administration.The pus was cleared on the 3rd day post-irrigation,and cerebrospinal fluid cultures were negative after 12 d.CONCLUSION Our findings suggest that multi-route administration of tigecycline can be a therapeutic option against pyogenic ventriculitis caused by extensively drugresistant A.baumannii.

Risk Factors for Drug-Resistant Tuberculosis

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.

Multidrug-Resistant Tuberculosis Disease in North-Kivu Province, Democratic Republic of Congo

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.

Identification, Synthesis, Isolation and Spectral Characterization of Multidrug-Resistant Tuberculosis (MDR-TB) Related Substances

Several related substances were detected at trace level in (2R)-2,3-dihydro-2-methyl-6-nitro-2-[[4-[4-[4-(trifluoromethoxy)phenoxy]-1-piperidinyl] phenoxy] methyl]imidazo[2, 1-b]oxazole drug substance by a newly developed high-performance liquid chromatography method. All related substances were characterized rapidly but some impurities were found to be intermediates. Proposed structures were further confirmed by characterization using NMR, FT-IR, and HRMS techniques. Based on the spectroscopic data;unknown related sub-stances were characterized as 1-(Methylsulfonyl)-4-[4-(trifluoromethoxy) phenoxy]piperidine;4-{4-[4-(Tri-fluoromethoxy)-phenoxy]piperidin-1-yl}phenol and 4-{4-[4-(trifluoromethoxy)phenoxy]piperidin-1-yl}phenyl methane sulfonate;4-Bromophenyl methane sulfonate, Ethyl 3,6-dihydro-1(2H)-pyridine carboxylate, (2S)-3-(4-Bromophenoxy)-2-hydroxy-2-methylpropyl methane sulfonate, (2S)-3-(4-Bromophenoxy)-2-methylpropane-1,2-diyldimethane-sulfonate, (2S)-2-Methyl-3-(4-{4-[4-(trifluoromethoxy) phenoxy]-piperidin-1-yl} phenoxy)-propane-1,2-diyldimethane sulfonate, (S)-3-(4-Bromophenoxy)-2-methyl-propane-1,2-diol and corresponding Enantiomer, (2R)-2-[(4-Bromo-phenoxy)methyl]-2-methyloxirane and (2R)-2-[(4-bromophenoxy)methyl]-2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b][1,3]oxazole. A possible mechanism for the formation of these related substances is also proposed.

The Role of Pyridoxine in the Prevention and Treatment of Neuropathy and Neurotoxicity Associated with Rifampicin-Resistant Tuberculosis Treatment Regimens: A Topic Review

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.

Molecular Characterization and Drug-resistance of Mycobacterium tuberculosis Strains in Xuzhou, China

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.

Transmission of extensively drug-resistant and multidrug resistant Mycobacterium tuberculosis in families identified by genotyping

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.

Activities of Biapenem against Mycobacterium tuberculosis in Macrophages and Mice

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.

Application of PCR-SSCP in detecting rpoB drug resistant gene polymorphism of M. tuberculosis L-form from pneumoconiosis patients with tuberculosis

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.

Detecting drug resistant genetic mutation among pneumoconiosis patients complicated with tuberculosis in Mycobacterium tuberculosis L-forms application of PCR-SSCP technique in Huainan mining district

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.

Global prevalence of drug-resistant tuberculosis: a systematic review and meta-analysis

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.

白细胞减少的准广泛耐药肺结核患者使用康替唑胺的临床实践分析

目的:分析1例白细胞减少的准广泛耐药(pre-extensively drug-resistant,pre-XDR)肺结核患者使用康替唑胺的临床实践过程,为类似耐药结核病患者探索有效的抗结核治疗方案提供参考。方法与结果:患者4个月前被确诊为pre-XDR肺结核,并予贝达喹啉+利奈唑胺+氯法齐明+环丝氨酸+丙硫异烟胺抗结核治疗;治疗20 d后,反复出现头晕、多梦、易醒等症状;1 d前,再次出现难以入睡症状并伴烦热感和右膝关节疼痛,遂入院治疗;住院期间,患者多次出现白细胞减少情况,考虑为利奈唑胺骨髓抑制所致,服用利可君片亦不能改善,临床在斟酌后决定停用利奈唑胺,改用康替唑胺,之后白细胞水平果然明显恢复;此外,患者反复出现的难以入睡症状考虑为环丝氨酸的中枢神经毒性反应,而住院期间出现的Q-T间期延长则考虑是贝达喹啉所致,遂决定停用此二药;最后,患者的抗结核方案被调整为康替唑胺+氯法齐明+阿米卡星+乙胺丁醇+丙硫异烟胺,之后患者未再出现不适症状和指标异常。结论:pre-XDR肺结核属于较为难治的疾病,治疗时用药较多且复杂,很容易发生药物不良反应,并且部分药物不良反应可能会导致严重不良后果;对此,临床应采取积极干预措施,并及时调整抗结核治疗方案,以保证患者的用药安全和治疗效果。

肺结核患者氟喹诺酮类耐药影响因素预测模型的构建与验证:基于LASSO-Logistic回归模型

背景利福平耐药/耐多药结核病(RR/MDR-TB)治疗困难,治愈率低,且传染性强,氟喹诺酮类(FQs)作为治疗RR/MDR-TB的核心药物,耐药趋势严峻,对FQs影响因素进行分析有助于提高RR/MDR-TB的治愈率,并控制准广泛耐药(pre-XDR)和广泛耐药结核病的发生。目的分析住院肺结核患者FQs耐药情况及影响因素,构建FQs耐药危险因素的列线图(Nomogram)预测模型并进行验证。方法回顾性选取于2021年1月—2022年2月在贵阳市公共卫生救治中心住院且有药物敏感试验结果的583例肺结核患者为研究对象。根据治疗史将患者分为初治组(296例)和复治组(287例);根据FQs耐药情况将患者分为FQs耐药组(63例)和FQs敏感组(520例)。分析患者对13种抗结核药物总耐药分布情况,比较FQs耐药组与FQs敏感组肺结核患者的基线特征。采用LASSO回归模型筛选特征变量后,行多因素Logistic回归分析FQs耐药的独立危险因素,并构建Nomogram预测模型;采用受试者工作特征(ROC)曲线下面积(AUC)、校准曲线对其进行验证。结果583例患者中FQs敏感520例,耐药63例,耐药率为10.81%,仅次于一线抗结核药异烟肼、利福平、链霉素、乙胺丁醇总耐药率(36.36%、32.76%、21.61%、12.86%)。复治组患者利福平、异烟肼、乙胺丁醇、链霉素、左氧氟沙星、莫西沙星、利福平耐药(RR)、耐多药(MDR)、pre-XDR耐药率高于初治组(P<0.05)。FQs耐药组患者其他民族、复治、艾滋病、吸毒史、空洞、咯血、不规则抗结核史、MDR占比高于FQs敏感组(P<0.05)。LASSO回归筛选出6个变量:民族、治疗史、艾滋病、吸毒史、咯血、MDR;多因素Logistic回归分析结果显示,其他民族(OR=2.313,95%CI=1.153~4.640,P=0.018)、复治(OR=1.892,95%CI=1.005~3.560,P=0.048)、咯血(OR=1.941,95%CI=1.087~3.465,P=0.025)、MDR(OR=3.342,95%CI=2.398~7.862,P<0.001)是肺结核患者FQs耐药的独立危险因素;Logistic回归方程Logit(P)=-3.571+0.838×民族+0.638×治疗史+0.663×咯血+1.468×MDR,基于此构建风险Nomogram预测模型,AUC为0.796(95%CI=0.717~0.876),Bootstrap法验证平均绝对误差为0.015,通过Hosmer-Lemeshow拟合优度检验,预测模型有较好的校准能力(χ^(2)=3.426,P=0.489)。结论肺结核患者FQs耐药率较高,其他民族、复治、咯血、MDR是肺结核患者FQs耐药的独立危险因素,构建Nomogram预测模型对于肺结核患者FQs耐药具有较好的预测价值,能够为临床诊断耐药结核病及为RR/MDR-TB制订合理治疗方案提供新思路。

Clinical analysis of colistin sulfate in the treatment of pneumonia caused by carbapenem-resistant Gram-negative bacteria

BACKGROUND Multidrug-resistant Gram-negative bacteria,exacerbated by excessive use of antimicrobials and immunosuppressants,are a major health threat.AIM To study the clinical efficacy and safety of colistin sulfate in the treatment of carbapenem-resistant Gram-negative bacilli-induced pneumonia,and to provide theoretical reference for clinical diagnosis and treatment.METHODS This retrospective analysis involved 54 patients with Gram-negative bacilli pneumonia admitted to intensive care unit of The General Hospital of the Northern Theater Command of the People's Liberation Army of China from August 2020 to June 2022.After bacteriological culture,the patients'airway secretions were collected to confirm the presence of Gram-negative bacilli.The patients were divided into the experimental and control groups according to the medication used.The research group consisted of 28 patients who received polymyxin sulfate combined with other drugs through intravenous,nebulization,or intravenous combined with nebulization,with a daily dosage of 1.5–3.0 million units.The control group consisted of 26 patients who received standard dosages of other antibiotics(including sulbactam sodium for injection,cefoperazone sodium sulbactam for injection,tigecycline,meropenem,or vaborbactam).RESULTS Of the 28 patients included in the research group,26 patients showed improvement,treatment was ineffective for two patients,and one patient died,with the treatment efficacy rate of 92.82%.Of the 26 patients in the control group,18 patients improved,treatment was ineffective for eight patients,and two patients died,with the treatment efficacy rate of 54.9%;significant difference was observed between the two groups(P<0.05).The levels of white blood cell(WBC),procalcitonin(PCT),and C-reactive protein(CRP)in both groups were significantly lower after treatment than before treatment(P<0.05),and the levels of WBC,PCT,and CRP in the research group were significantly lower than those in the control group(P<0.05).Compared with before treatment,there were no significant changes in aspartate aminotransferase,creatinine,and glomerular filtration rate in both groups,while total bilirubin and alanine aminotransferase decreased after treatment(P<0.05)with no difference between the groups.In patients with good clinical outcomes,the sequential organ failure assessment(SOFA)score was low when treated with inhaled polymyxin sulfate,and specific antibiotic treatment did not improve the outcome.Sepsis and septic shock as well as a low SOFA score were independent factors associated with good clinical outcomes.CONCLUSION Polymyxin sulfate has a significant effect on the treatment of patients with multiple drug-resistant Gram-negative bacilli pneumonia and other infections in the lungs and is safe and reliable.Moreover,the administration route of low-dose intravenous injection combined with nebulization shows better therapeutic effects and lower adverse reactions,providing new ideas for clinical administration.

内蒙古地区结核病的耐药现状及影响因素研究

目的了解内蒙古地区结核病的耐药现状及影响因素,为耐药结核精准防控提供参考依据。方法采用随机抽样法,分析内蒙古地区结核定点诊治医院就诊的符合纳入标准的结核患者的临床资料,对耐药菌株进行鉴定和表型药敏检测,计算耐药谱和耐药率,并采用Logistic回归模型分析结核病患者耐药的影响因素。结果一共纳入1321株结核患者,男性936例,女性385例,平均年龄(52.65±18.09)岁;单耐药、耐多药、多耐药及总耐药率分别为19.00%、11.58%、11.66%、42.24%,耐药率较高的是链霉素(7.27%)、异烟肼(4.69%)和异烟肼+链霉素(4.47%),耐药谱呈现多样性和复杂性;相较于女性,男性患者耐药比例较高(P<0.001);抗结核药物敏感患者比例随着年龄的增加而增加(P<0.05);20~40岁、40~60岁、60岁及以上耐多药患者比例均高于0~20岁(P<0.05),而20~40岁以及40~60岁耐多药患者比例高于60岁及以上(P<0.05);复治患者的耐多药、多耐药比例均高于初治患者(P<0.001);多因素Logistic回归分析显示,男性(OR=1.48,95%CI:1.02~2.14)、20~40岁(OR=2.64,95%CI:1.05~6.60)、复治(OR=2.34,95%CI:1.70~3.22)、门诊随访患者(OR=1.56,95%CI:1.05~2.33)是耐药结核发生的危险因素。结论内蒙古地区结核患者耐多药及总耐药率较高,耐药谱呈现多样性以及复杂性,男性、20~40岁、复治、门诊随访是结核耐药发生的独立危险因素。应当进一步完善临床诊疗工作,合理使用抗结核一线药物、注重个体化治疗,加强健康教育、完善医保制度和患者管理模式,以提高患者的依从性。