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.

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.

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.

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.

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.

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.

Molecular Detection of Carbapenemase Genes in Extensive Drug Resistant Acinetobacter baumannii Clinical Isolates from ICU Patients, Khartoum

Background: The emergence of carbapenemase producing Acinetobacter baumannii is increasingly reported nowadays and constitutes a major problem to the intensive care unit (ICU) patients with notable extensive-drug resistance ability. The study investigates carbapenemase producing A. baumannii strains exhibiting an extensively drug-resistant (XDR) phenotype, isolated from ICU patients in Khartoum. Methods: A total of 100 nonduplicate Gram-negative coccobacilli strains were obtained from microbiology laboratory of ICU patients’ clinical isolates. Molecular identification of A. baumannii was performed by targeting 16S rRNA gene using specifically designed primers. Then, XDR strains were determined by susceptibility testing (disc diffusion). For detection of carbapenemase genes Polymerase chain reaction (PCR) was carried out. Result: Of 100 ICU clinical isolates, 38 (38.0%) was confirmed A. baumannii strains, those strains showed 100% carbapenem resistance and 60.5% extensive drug resistance to the antibiotics tested. The frequency of carbapenemase producer was 57.9% (22/38) of carbapenem resistance A. baumannii (CRAB). The most common carbapenemase associated with resistance was blaOXA gene followed by blaNDM and blaGES A. baumannii isolates. The co-occurrence of blaOXA-48-like and blaNDM, blaOXA-23-like and blaOXA-51, and blaNDM-1 and blaOXA-51 was detected in 22.7%, 18.2% strains and 4.5% respectively. A unique characteristic of our findings was the coharbouring of the genes blaNDM-1, blaOXA-23-like, blaOXA-51 and blaOXA-143 in 9.1% strains (2/22), and this was the first report in the Khartoum city, Sudan. Conclusion: We have demonstrated for the first time a high prevalence of XDR-carbapenemase producing A. baumannii clinical isolates from ICU patients in Khartoum. Also an emergent blaOXA-143 was reported as High-Risk Clones. This highlights the routine mentoring of XDR-carbapenemase producing A. baumannii to avoid clone dissemination in our region hospitals.

血清降钙素原联合皮特菌血症评分对泛耐药肺炎克雷伯菌血流感染患者生存状况的预测效果

目的 分析血清降钙素原(PCT)联合皮特菌血症评分(PBS)对泛耐药肺炎克雷伯菌(XDR-KP)血流感染患者生存状况的预测效果。方法 对2021年1月至2022年12月期间郑州市第一人民医院收治的162例XDR-KP血流感染患者展开回顾性分析,所有患者均随访1个月,依据其生存情况分为死亡组(n=99)和存活组(n=63)。比较两组患者的各项一般资料和临床资料,对有统计学意义的进一步行Logistic多因素分析明确XDR-KP血流感染患者死亡的危险因素,并绘制受试者工作特征(ROC)曲线分析PCT联合PBS评分对XDR-KP血流感染患者生存状况的预测效果。结果 死亡组患者PBS≥4分、急性生理与慢性健康(APACHEⅡ)评分≥15分、序贯器官衰竭(SOFA)评分≥5分、入院至血培养时间<30 d、机械通气、持续肾脏替代治疗、抗生素治疗、PCT≥5 ng/mL、感染性休克、入住重症监护室(ICU)的占比高于存活组,死亡组患者的白细胞计数(WBC)水平高于存活组,血小板计数(PLT)水平低于存活组,差异有统计学意义(P<0.05)。PCT≥5 ng/mL、PBS≥4分为XDR-KP血流感染患者死亡的危险因素(P<0.05)。PCT水平、PBS评分对XDR-KP血流感染患者生存状况均有一定的预测价值,且联合应用预测效果更佳。结论 PCT≥5 ng/mL、PBS≥4分为XDR-KP血流感染患者死亡的危险因素,且二者联合应用对患者死亡有较佳的预测价值。

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.

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.

Human mpox co-infection with advanced HIV-1 and XDR-TB in a MSM patient previously vaccinated against smallpox:A case report

Mpox is a zoonotic infectious disease caused by the mpox virus(MPXV).Historically,the majority of mpox cases have been documented in Central Africa.However,since May 2022,there has been a notable rise in reported cases from regions beyond Africa.Currently,over 110 countries spanning Europe,North America,South America,Asia,and other territories have reported mpox infections.This report details a case involving a patient who identifies as a man who has sex with men(MSM)and is concurrently infected with MPXV,human immunodeficiency virus type 1(HIV-1),Pneumocystis jiroveci,as well as extensively drug-resistant tuberculosis(XDR-TB).This patient had also received a vaccination for smallpox in the past.Additionally,we provide photographic documentation charting the progression of dermatological manifestations associated with mpox.This case highlights the significance of sexual intercourse as a crucial mode of transmission for mpox.The rapid and widespread dissemination of the MPXV across various regions,especially among MSM communities,underscores the importance of enhancing preventive education efforts targeted at high-risk populations.

皮特菌血症评分对泛耐药肺炎克雷伯菌血流感染患者预后的评估价值

目的探讨皮特菌血症评分(Pitt bacteremia score,PBS)对泛耐药肺炎克雷伯菌(extensively drug-resistant Klebsiella pneumonia,XDR-KP)血流感染患者28 d死亡风险的预测价值。方法采用回顾性队列研究方法,分析2018年1月至2021年12月收住南京大学医学院附属鼓楼医院急诊重症监护室诊断为XDR-KP血流感染患者临床特征资料,根据28 d生存情况将患者纳入存活组和死亡组。采用多因素Logistic回归分析明确XDR-KP血流感染患者28 d死亡的高危因素;绘制受试者工作特征曲线(receiver operator characteristic curve,ROC)评估PBS评分对XDRKP血流感染患者28 d死亡风险的预测价值。采用Pearson分析探讨PBS评分与急性生理学及慢性健康状况评分系统Ⅱ(acute physiology and chronic health evaluation Ⅱ,APACHE Ⅱ)和序贯器官衰竭评估系统(sequential organ failure assessment,SOFA)之间的相关性。并以PBS评分最佳截断值为界点分组,比较不同组患者APACHEⅡ和SOFA评分之间的差异;采用Kaplan-Meier法对XDR-KP血流感染患者的预后进行生存分析。结果共纳入118例XDR-KP血流感染患者,年龄(65.98±15.16)岁,其中男性82例,女性36例;患者28 d病死率为61.02%,PBS评分为(4.43±1.53)分,死亡组患者的PBS评分显著高于存活组[(5.68±1.86)vs.(2.48±1.02),(P=0.011)]。多因素Logistic回归分析提示PBS评分(OR=4.940,95%CI:2.720~8.968,P=0.008)、APACHEⅡ评分(OR=1.630,95%CI:1.361~1.952,P=0.010)及SOFA评分(OR=1.879,95%CI:1.451~2.422,P=0.009)是患者28 d死亡的独立危险因素。与APACHEⅡ评分和SOFA评分相比较,PBS评分对患者28 d死亡风险具有更好的预测价值,其ROC下面积为0.970(95%CI:0.945~0.995,P<0.001),最佳截断值为3.5分。PBS评分与APACHEⅡ评分(r=0.916,P<0.001)和SOFA评分(r=0.829,P<0.001)呈高度相关。Kaplan-Meier生存曲线提示PBS评分<3.5的患者28 d生存率显著高于PBS评分>3.5的患者(P=0.001)。结论PBS评分对XDR-KP血流感染患者28 d死亡风险具有良好的预测价值。

泛耐药鲍曼不动杆菌菌血症的临床特点及预后

目的对重症监护病房泛耐药鲍曼不动杆菌菌血症的临床特点及预后进行总结。方法回顾性研究2012年1月至2015年12月31日北京大学第一院呼吸监护室的鲍曼不动杆菌菌血症患者,收集患者人口学特点、临床资料、3d及14 d的预后。结果纳入8例患者,平均年龄(62.4±18.0)岁,男3例,女5例。所有患者均患有基础疾病,6例为免疫抑制患者,7例患者发病前2周内接受含有β内酰胺酶抑制剂的复合制剂或碳青霉烯类抗菌药物,6例接受机械通气,肺脏是主要病源。菌种鉴定均为泛耐药鲍曼不动杆菌。患病48h内平均急性生理与慢性健康状况Ⅱ(APACHEⅡ)评分为(28.3±7.5)分,C反应蛋白(18.2~231.0mg/L)和降钙素原(0.1~25.0ng/ml)个体差异较大。3d死亡率为4/8,均为入APACHEⅡ>25分的患者;14d死亡率为6/8,PCT>0.5ng/ml的患者均死亡。结论泛耐药鲍曼不动杆菌菌血症患者14d的预后和疾病严重程度及降钙素原升高有关。对于APACHEⅡ>25分、降钙素原升高、之前接受机械通气的高度可疑患者应考虑在血培养结果回报前抢先治疗。

替加环素联合治疗泛耐药肺炎克雷伯菌菌血症病例分析

目的探讨替加环素治疗泛耐药肺炎克雷伯菌所致菌血症的临床疗效。方法对1例使用替加环素治疗泛耐药肺炎克雷伯菌菌血症的病例进行分析。结果和结论替加环素是联合治疗泛耐药肺炎克雷伯菌菌血症的一种选择。