Sequential intraventricular injection of tigecycline and polymyxin B in the treatment of intracranial Acinetobacter baumannii infection after trauma: a case report and review of the literature

Background:Intracranial infection after craniotomy is one of the most serious postoperative complications,especially multidrug-resistant(MDR)or extensively drug-resistant(XDR)bacterial meningitis,and strongly affects the prognosis of patients.Current treatment experience regarding these infections is scarce.Case presentation:We report a case of severe intracranial infection of XDR Acinetobacter baumannii(A.baumannii)that was treated by intravenous(IV)injection,sequential intraventricular(IVT)injection of tigecycline and polymyxin B,and other anti-infective drugs.Good results were obtained,and the patient was eventually discharged from the hospital.This case is characterized by intracranial infection.Conclusions:The polymyxin B IV+IVT pathway is an ideal treatment strategy for XDR A.baumannii.The tigecycline IVT pathway is also a safe treatment option.

Porphyromonas gingivalis Resistance to Polymyxin B Is Determined by the Lipid A 4’-Phosphatase, PGN_0524

Aim To elucidate the genetic basis for the pronounced resistance that the oral pathogen, Porphyromonas gingivalis （P. gingivalis）, exhibits towards the cationic antimicrobial peptide, polymyxin B. Methodology A genetic screen of P. gingivalis clones generated by a Tn4400-based random insertion mutagenesis strategy was performed to identify bacteria harboring novel genetic mutations that render P. gingivalis susceptible to killing by the cationic antimicrobial peptide, polymyxin B （PMB, 50μg·mL^-1）. Results P. gingivalis （ATCC 33277） is unusually resistant to the cationic antimicrobial peptide, PMB at relatively high concentrations （200μg·mL^-1）. Approximately 2,700 independent Tn4400 ＇-derived mutants ofP. gingivalis were examined for increased sensitivity to PMB killing at a relatively low dose （50 μg·mL^-1）. A single PMB-sensitive mutant was obtained in this phenotypic screen. We determined that the Tn4400＇ transposon was integrated into the gene encoding the lipid A 4＇-phosphatase, PGN 0524, demonstrating that this insertion event was responsible for its increased susceptibility of this clone to PMB-dependent killing. The resulting mutant strain, designated 0524-Tn4400＇, was highly sensitive to PMB killing relative to wild-type P. gingivalis, and exhibited the same sensitivity as the previously characterized strain, 0524KO, which bears a genetically engineered deletion in the PGN_0524 locus. Positive ion mass spectrometric structural （MALDI-TOF MS） analyses revealed that lipid A isolates from 0524-Tn4400＂ and 0524KO strains displayed strikingly similar MALDI-TOF MS spectra that were substantially different from the wildtype P gingivalis lipid A spectrum. Finally, intact 0524- Tn4400＇ and 0524KO mutant bacteria, as well as their corresponding LPS isolates, were significantly more potent in stimulating Toll-like receptor 4 （TLR4）-dependent E-selectin expression in human endothelial cells relative to intact wild-type P.. gingivalis or its corresponding LPS isolate. Conclusion The combined molecular evidence provided in this report suggests that PGN 0524, a lipid A 4＇-phosphatase, is the sole genetic element conferring the ability of the periodontopathogen, P. gingivalis, to evade the killing activity of cationic antimicrobial peptides, such as PMB. These data strongly implicate PGN_0524 as a critical virulence factor for the ability of P.. gingivalis to evade front-line host innate defenses that are dependent upon cationic antimicrobial peptide activity and TLR 4 sensing.

Preliminary study on the safety and efficacy of a new polymyxin B-immoblized resin column in treatment of LPS-induced sepsis beagles

Background:This study aims to assess the safety and efficacy of direct hemoperfu-sion using a new polymyxin B-immobilized resin column(disposable endotoxin ad-sorber,KCEA)in an endotoxin/lipopolysaccharide(LPS)-induced sepsis model.Methods:Eighteen beagles were randomized into 1 intervention group(KCEA group,n=6)and 2 control groups(sham group and model group,n=6 each).Sepsis was in-duced by continuous intravenous application of 0.5 mg/kg body weight of endotoxin for 60 min.An extracorporeal hemoperfusion device made with KCEA for endotoxin adsorption was used.Model group beagles received standard treatment with fluids and vasoactive drugs,KCEA group beagles received standard treatment and direct hemoperfusion of KCEA for 2 h,and sham group beagles were treated with standard treatment and direct hemoperfusion of a sham column for 2 h.Results:Good blood compatibility of KCEA was confirmed by assessing clinical pa-rameters.Blood endotoxin peak levels in the KCEA group were significantly lower,resulting in a significant suppression of IL-6,TNF-αand procalcitonin,which improved mean arterial pressure and significantly lowered vasopressor demand,thereby pro-tecting organ function and improving survival time and rate.In the KCEA group,MAP was significantly higher over 6 h than those recorded both in the sham group and model group.The 7-day survival rates of the KCEA,sham and model groups were 50%,0%and 0%,respectively.Conclusion:KCEA hemoadsorption was effective at detoxifying circulatory endotoxin and inflammatory mediators and contributed to the decreased mortality rate in the sepsis beagles.

Nystatin-Neomycin-Polymyxin B Combination:Efficacy and Tolerance as 1st-Line Local Treatment of Infectious Vaginitis

Objective: To evaluate the efficacy and tolerance of a local treatment combining two antibacterials and one antifungal in patients with a clinical presentation suggesting infectious vaginitis. Patients and methods: 169 patients presenting with clinical criteria for vaginitis were included in an open, multicenter trial. Vaginal samples were taken for microbiological analyses and a triple-combination product of nystatin, neomycin and polymyxin B was then started as local treatment, without waiting for the test results. The treatment was continued with the usual dosage (1 vaginal capsule at bedtime for 12 days) for vaginal infections in the scope of the combination product with approved labeling. A second vaginal sample was performed at the end of the treatment. The main efficacy criterion was the clinical success rate (cure or improvement of the clinical signs and symptoms) according to the investigator.Results: 93 patients were included in the efficacy population. Non-exclusively fungal vaginitis (strictly bacterial or bacterial + fungal) represented 31.2% of the cases. The clinical success rate was 97.8% according to the investigator and 95.7% according to the patients. The microbiological success rate was 81.3%, with no differences between etiologies (Candida spp., bacteria or both). The combination product was well-tolerated, despite the local inflammation before treatment. Discussion and conclusion: Given the etiological diversity of vaginitis, this trial supports the efficacy of a triple-combination product (nystatin, neomycin, polymyxin B) as a first-line local treatment of Candida, bacterial or mixed vaginitis.

Polymyxin B hemoperfusion as a feasible therapy after source control in abdominal septic shock

BACKGROUND Polymyxin B hemoperfusion(PMX-HP)has been used as a treatment for intraabdominal septic shock by absorbing and removing endotoxins of gram-negative bacilli.AIM To investigate the clinical efficacy of PMX-HP in patients with gram-negative septic shock who underwent abdominal surgery.METHODS From January 2012 to December 2018,patients who had septic shock secondary to peritonitis were enrolled.They were classified into PMX-HP treated and control groups based on postopreative intervention using PMX-HP.The clinical outcomes were compared using 1:1 propensity score matching methods to balance the overall distribution between the two groups.RESULTS After propensity score matching,40 patients were analyzed(20 patients in the PMX group and 20 patients in the control group).The scores of total Sequential Organ Failure Assessment(SOFA)score,renal SOFA and coagulation SOFA were significantly improved in the PMX group but not in the control group.(from 11.2±5.8 to 4.7±3.5 in PMX group vs 10.0±4.0 to 8.7±7.3 in control group,P=0.047 from 2.6±1.0 to 0.7±1.0 in PMX group vs 2.6±1.5 to 2.8±1.6 in control group,P=0.000,from 1.6±1.5 to 1.3±1.3 in PMX group vs 1.2±1.2 to 2.8±1.8 in control group,P=0.014,respectively).Further,the length of intensive care unit(ICU)stay was significantly shorter in PMX group.However,no statistically significant difference was found in ICU mortality(50%in PMX group vs 50%in control group).CONCLUSION PMX-HP is a feasible adjunct treatment for peritonitis in ICU patients with peritonitis for improved organ impairment and to stabilize hemodynamics.It would be helpful to enhance clinical outcomes especially in patients with complete elimination of the source of gram-negative bacilli infection by surgical procedure accompanied with conventional treatment of sepsis.

Polymyxin B-immobilized fiber columns:A column to breathe new life into the treatment of interstitial lung disease?

Acute exacerbations of idiopathic pulmonary fibrosis(IPF) is a severe respiratory condition with high mortality rate. Direct hemoperfusion with polymyxin B-immobilized fiber columns(PMX-DHP) was originally introduced for the treatment of septic shock. Application of PMX-DHP to the treatment of acute exacerbations of IPF may improve oxygenation and survival of the patients with the disease. In addition to acute exacerbations of IPF, PMXDHP has been applied to acute respiratory failure fromvarious causes; an amyopathic dermatomyositis patient who developed rapidly progressive interstitial lung disease(ILD) with elevated anti-CADM-140/MDA5 autoantibody and a patient with severe amiodarone pulmonary toxicity. It is also demonstrated that PMX-DHP performed on the first day of steroid pulse therapy may improve the prognosis of patients with rapidly progressive ILDs in a case-control setting. PMX treatment decreases not only various circulating molecules but also inflammatory cells, in particular activated monocytes, producing such mediators. Although the incidence of acute exacerbations of IPF is too low for proper randomization, in order to test the effects of PMX-DHP on the disease, a cohort or casecontrol analytic study needs to be conducted, preferably from more than one center or research group.

Differential Role of Two-Component Regulatory Systems (<i>phoPQ</i>and <i>pmrAB</i>) in Polymyxin B Susceptibility of <i>Pseudomonas aeruginosa</i>

Polymyxins are often considered as a last resort to treat multidrug resistant P. aeruginosa but polymyxin resistance has been increasingly reported worldwide in clinical isolates. Polymyxin resistance in P. aeruginosa is known to be associated with alterations in either PhoQ or PmrB. In this study, mutant strains of P. aeruginosa carrying amino acid substitution, a single and/or dual inactivation of PhoQ and PmrB were constructed to further understand the roles of PhoQ and PmrB in polymyxin susceptibility. Polymyxin B resistance was caused by both inactivation and/or amino acid substitutions in PhoQ but by only amino acid substitutions of PmrB. Alterations of both PhoQ and PmrB resulted in higher levels of polymyxin B resistance than alteration of either PhoQ or PmrB alone. These results were confirmed by time-killing assays suggesting that high-level polymyxin resistance in P. aeruginosa is caused by alterations of both PhoQ and PmrB.

Polymyxin B Alleviates Angiotensin II-Induced Stress Fiber Formation and Cellular Hypertrophy

Polymyxin B is widely used antibiotic in the clinic for resistant Gram-negative infections. In addition, polymyxin B-immobilized hemoperfusion cartridge has been used for endotoxin removal therapy in patients with septic shock. The aim of this study was to investigate the anti-fibrotic and anti-cellular hypertrophic effects of polymyxin B, and further to explore its possible mechanism. Polymyxin B (3, 10 μM) significantly inhibited stress fiber formation induced by angiotensin II (Ang II) in rat heart-derived H9c2 cells. Furthermore, polymyxin B (1 - 10 μM) showed a potent inhibitory effect on Ang II-induced cellular hypertrophy in H9c2 cells. Under the mechanism study, the inhibitory activities of polymyxin B against kinases involved in cellular hypertrophy such as AKT1, CAMK, GRK5, GSK3β, MLCK, PKC, PKD2, AMPK, ROCK2, p70S6K, SGK1were evaluated. Polymyxin B possesses a potent G protein related kinase 5 (GKR5) inhibitory activity with IC50 value of 1.1 μM, and has an ATP non-competitive inhibitory mode. Taken together, these results indicate that polymyxin B alleviates Ang II-induced stress fiber formation and cellular hypertrophy, and propose that one mechanism underlying these effects involves inhibition of the GRK5 pathway.

A polymyxin B loaded hypoxia-responsive liposome with improved biosafety for efficient eradication of bacterial biofilms

Biofilm-associated bacterial infection brings serious threats to global public health owing to serious antibiotic resistance.It is urgently needed to develop innovative strategies to combat biofilm-associated bacterial infections.Polymyxins stand out as the last line of defense against Gram-negative bacteria.However,serious nephrotoxicity of polymyxins severely limits their clinical utility.Herein,a hypoxia-responsive liposome is designed as the nanocarrier of polymyxin B(PMB)to combat biofilms developed by Gram-negative bacteria.A metronidazole modified lipid(hypoxia-responsive lipid(HRLipid))is synthesized to fabricate hypoxia-responsive liposomes(HRLip).PMB loaded hypoxia-responsive liposomes(HRL-PMB)is then prepared to mitigate the nephrotoxicity of PMB while preserving its excellent bactericidal activity.HRL-PMB shows very low hemolysis and cytotoxicity due to liposomal encapsulation of PMB.PMB can be readily released from HRL-PMB in response to hypoxic biofilm microenvironment,exerting its bactericidal activity to realize biofilm eradication.The excellent in vivo antibiofilm ability of HRL-PMB is confirmed by a Pseudomonas aeruginosa infected zebrafish model and a P.aeruginosa pneumonia infection model.Meanwhile,HRL-PMB can greatly reduce the nephrotoxicity of PMB after intravenous injection.The hypoxia-sensitive liposomes held great promise to improve the biosafety of highly toxic antibiotics while preserving their intrinsic bactericidal ability,which may provide an innovative strategy for combating biofilm-associated infections.

Chinese consensus guidelines for therapeutic drug monitoring of polymyxin B,endorsed by the Infection and Chemotherapy Committee of the Shanghai Medical Association and the Therapeutic Drug Monitoring Committee of the Chinese Pharmacological Society

Polymyxin B,which is a last-line antibiotic for extensively drug-resistant Gram-negative bacterial infections,became available in China in Dec.2017.As dose adjustments are based solely on clinical experience of risk toxicity,treatment failure,and emergence of resistance,there is an urgent clinical need to perform therapeutic drug monitoring(TDM)to optimize the use of polymyxin B.It is thus necessary to standardize operating procedures to ensure the accuracy of TDM and provide evidence for their rational use.We report a consensus on TDM guidelines for polymyxin B,as endorsed by the Infection and Chemotherapy Committee of the Shanghai Medical Association and the Therapeutic Drug Monitoring Committee of the Chinese Pharmacological Society.The consensus panel was composed of clinicians,pharmacists,and microbiologists from different provinces in China and Australia who made recommendations regarding target concentrations,sample collection,reporting,and explanation of TDM results.The guidelines provide the first-ever consensus on conducting TDM of polymyxin B,and are intended to guide optimal clinical use.

多黏菌素B治疗危重症儿童多重耐药革兰阴性菌感染的疗效观察

目的:评估多黏菌素B治疗危重症儿童多重耐药革兰阴性菌感染的疗效,并探讨其影响多黏菌素B疗效的可能因素。方法:选取某院重症监护室2020年2月~2022年6月诊治的26例危重症多重耐药革兰阴性菌感染患儿,根据患者的疗效分为临床有效组(n=14)和临床无效组(n=12)。比较两组患者的性别、年龄、小儿危重病例评分、合并疾病、病原菌、治疗时间、机械通气情况以及与其他抗菌药物联用情况。对其中有意义的变量进行多因素Logistic回归分析,探讨影响多黏菌素B疗效的可能因素。结果:临床有效组与无效组的性别、年龄、小儿危重病例评分、合并疾病、病原菌以及与其他抗菌药物联用情况比较均无统计学差异(P>0.05)。临床有效组的多黏菌素B使用时间较无效组更长(P=0.000),临床无效组有更多的患儿应用机械通气(P=0.034)。Logistic回归分析果结提示治疗时间(OR:2.606,95%CI:1.346~5.046,P=0.004)是影响多黏菌素B治疗危重症儿童多重耐药革兰阴性菌感染临床疗效的可能因素。结论:多黏菌素B治疗危重症儿童多重耐药革兰阴性菌感染具有较好的治疗效果,治疗时间是影响多黏菌素临床疗效的可能因素。

头孢他啶阿维巴坦与多黏菌素B治疗耐碳青霉烯类铜绿假单胞菌感染疗效比较

目的比较头孢他啶阿维巴坦(CAZ/AVI)与多黏菌素B(PMB)治疗耐碳青霉烯类铜绿假单胞菌(CRPA)感染的临床疗效。方法回顾性分析医院2019年1月至2022年12月收治的CRPA感染患者75例,按治疗方案的不同分为CAZ/AVI组(48例)和PMB组(27例),分别静脉滴注CAZ/AVI和PMB。结果CAZ/AVI组患者的临床治愈率、细菌清除率均显著高于PMB组(54.17%比29.63%,66.67%比37.04%,P<0.05),但皮肤色素沉着发生率显著低于PMB组(0比48.15%,P<0.001)。两组患者疗程、联合治疗及30 d死亡率均无显著差异(P>0.05)。结论CAZ/AVI治疗CRPA感染的临床疗效和细菌清除率均较PMB更高,且不良反应更少。

ICU患者多黏菌素B血药浓度及不良反应分析

目的 探讨重症监护室(ICU)患者多黏菌素B血药浓度达标情况及不良反应,为临床合理用药提供参考。方法 回顾性分析61例ICU患者使用多黏菌素B治疗后的稳态24 h浓度-时间曲线下面积(AUC_(ss,24h))达标情况、影响因素及不良反应。结果 61例患者多黏菌素B AUC_(ss,24h)达标率为37.70%(23/61)。肌酐清除率与谷浓度(C_(min))及AUC_(ss,24h)差异有统计学意义(P<0.05),肌酐清除率与C_(min)(r=-0.45)及AUC_(ss,24h)均为负相关(r=-0.34)。单因素和多因素分析显示,AUC_(ss,24h)与滴注时间显著相关(P<0.05),输注时间>1小时组AUC_(ss,24h)达标率高于1小时组。虽然AUC_(ss,24h)与年龄及肾功能差异无统计学意义(P>0.05),但是年龄增大或中重度肾功能不全,AUC_(ss,24h)达标率降低。多黏菌素B相关肾损伤发生率为45.24%(19/42),肾损伤组AUC_(ss,24h)>100 (mg·h)/L比例较高。结论 多黏菌素B AUC_(ss,24h)可能与年龄、输注时间及肾功能有关,多黏菌素B相关肾损伤与AUC_(ss,24h)>100(mg·h)/L有关,临床需根据患者情况进行血药浓度监测和个体化给药。

硫酸多黏菌素B在两种溶媒中的含量稳定性

目的考察硫酸多黏菌素B在成品输液及高浓度储备液中的含量稳定性,为临床给药提供依据。方法建立测定硫酸多黏菌素B含量的高效液相色谱方法,将硫酸多黏菌素B分别溶于0.9%氯化钠注射液及5%葡萄糖注射液,配成0.5、1 mg·mL^(-1)成品输液及5 mg·mL^(-1)储备液,并在4和25℃储存条件下于0、2、4、6、8、12、16、20及24 h测定多黏菌素B含量。结果4和25℃储存条件下,0.5、1 mg·mL^(-1)硫酸多黏菌素B成品输液和5 mg·mL^(-1)硫酸多黏菌素B储备液均稳定,多黏菌素B1和多黏菌素B2含量和0 h(以100%计)比较,分别在97.23%~102.63%和97.30%~102.63%范围内。结论硫酸多黏菌素B溶于0.9%氯化钠注射液及5%葡萄糖注射液,0.5、1和5 mg·mL^(-1)溶液在4和25℃储存,24 h内稳定性良好。

MALDI-TOF-MS在耐碳青霉烯肠杆菌多黏菌素B快速药敏试验中的应用

目的构建一种耐碳青霉烯类肠杆菌科细菌(CRE)多黏菌素B的快速药敏试验方法,为临床抗生素的选择和精准调整提供依据。方法采用WHONET 5.6软件对分离自西安市第一医院2023年3月至2024年3月的108株CRE菌株信息进行筛选,以肉汤稀释法为参比方法,采用基质辅助激光解吸/电离飞行时间质谱仪(MALDI-TOF-MS)进行多黏菌素B快速药敏测定。结果108株CRE分离株以肺炎克雷伯菌为主(48.14%),其次是产气肠杆菌和奇异变形杆菌(各占13.89%)。标本来源以痰液为主(65.74%),其次尿液(18.52%)和血液(8.33%)。临床科室分布以神经外科为主(48.15%),其次为重症医学科(18.52%)和呼吸内科(14.81%)。CRE分离株对大部分药物呈现高度耐药,对常见β内酰胺类、喹诺酮类、氨基糖苷类、β内酰胺复合药物耐药率分别超过70%,80%,50%和75%。与肉汤稀释法相比,MALDI-TOF-MS法测定CRE对多黏菌素B药敏结果的分类一致率(CA)为98.1%,重大误差(ME)为1.85%,未出现非常重大误差(VME),均在可允许范围之内。结论本院分离的CRE对多种抗菌药物广泛耐药,基于MALDI-TOF-MS的快速药敏试验方法准确可靠,可用来评价CRE对多黏菌素B的敏感性,便于临床及时调整泛耐药细菌治疗方案。

替加环素和多黏菌素B治疗重症患者耐碳青霉烯类肠杆菌科细菌肺炎的疗效和安全性分析

目的:比较替加环素和多黏菌素B治疗重症患者耐碳青霉烯类肠杆菌科细菌(CRE)肺炎的疗效和安全性。方法:回顾性分析2018年1月1日至2023年6月30日于我院重症医学科(ICU)接受替加环素或多黏菌素B治疗的CRE肺炎患者的临床资料。主要结局包括28 d全因病死率和28 d临床治愈率。次要结局包括ICU病死率、住院病死率、住院时间、ICU住院时间、微生物清除率、机械通气时间。采用Cox回归分析检验影响28 d临床治愈率的独立预测因素。结果:倾向性评分匹配后纳入83名患者,其中替加环素组54例,多黏菌素B组29例。替加环素组28 d全因病死率为31.5%(17/54),多黏菌素B组为37.9%(11/29),差异无统计学意义(P=0.554);替加环素组28 d临床治愈率为63%(34/54),显著高于多黏菌素B组的34.5%(10/29)(P=0.013)。两组的次要结局指标均无统计学差异。多因素回归分析发现,使用替加环素是28 d临床治疗有效的独立预测因素(HR:2.083,95%CI 1.018-4.263,P=0.045)。但替加环素组用药后活化部分凝血活酶时间、凝血酶原时间较多黏菌素B组显著延长(P=0.047;P=0.027),纤维蛋白原显著下降(P<0.001)。结论:替加环素组和多黏菌素组28 d全因病死率无显著差异;与多黏菌素B相比,替加环素可能与更高的28 d临床治愈率相关。同时需注意,替加环素可能增加凝血功能异常的风险。

复方多黏菌素B软膏治疗寻常痤疮的效果观察

分析复方多黏菌素B软膏治疗寻常痤疮的效果.选取滨州市中心医院2022年1月-2023年3月收治的100例寻常痤疮患者为研究对象,采用随机抽签法将患者分为对照组和观察组,每组各50例.对照组患者接受裸花紫珠胶囊治疗,观察组患者在对照组治疗基础上接受复方多黏菌素B软膏治疗,比较两组患者治疗效果.结果显示,观察组患者治疗总有效率高于对照组(P<0.05);观察组患者丘疹、粉刺、脓包个数均少于对照组(P<0.05);两组患者不良反应总发生率比较,无统计学差异(P>0.05);治疗后,观察组角质层含水量大于对照组,面部溢脂量、炎性皮损指标均低于对照组(P<0.05).研究发现,复方多黏菌素B软膏治疗寻常痤疮的效果明显,可提高患者的治疗总有效率,减少皮损数量和不良反应,改善患者的生活质量,治疗安全性较高.

基于VOSviewer的多黏菌素B研究进展分析

目的基于Web of Science,PubMed数据库,分析多黏菌素B的研究热点和发展趋势。方法以“polymyxin B,Aerosporin”为检索词在Web of Science核心数据集和PubMed中检索近5年的英文文献。用VOS viewer作关键词和研究热点分析,总结多黏菌素B的抗菌机制、耐药性机制与检测方法、药代动力学及其临床应用情况。结果共纳入分析英文文献2012篇(2019年1月1日-2023年12月8日),发文量整体呈上升趋势。澳大利亚莫纳什大学发文量最多,学者Li Jian被收录的文献最多。中国发文量最高,美国总被引频次最高。结论多黏菌素B的耐药性机制、药代动力学和联合治疗方案优化是目前的研究热点。其中脓毒症是近年来多黏菌素B的关注焦点。

多黏菌素B致药品不良反应的循证评价

目的:探讨多黏菌素B(PMB)所致药品不良反应(ADR)的发生情况和临床特征,为临床合理用药提供参考。方法:计算机检索中国知网、万方数据库、维普数据库、中国生物医学文献数据库、PubMed、Web of Science、Scopus、the Cochrane Library和Embase数据库中临床注射应用PMB治疗后发生ADR的病例报告或病例系列,检索时限为建库至2023年10月31日。利用澳大利亚乔安娜布里格斯研究所(JBI)循证卫生保健中心的质量评价工具对纳入文献进行评价。采用百分比、汇总表等方式统计结果并进行描述性分析。结果:共纳入37篇注射应用PMB治疗后发生ADR的相关文献,包括51例患者,其中男性患者35例(占68.63%),女性患者16例(占31.37%),年龄为14~86岁。PMB引起的ADR有皮肤色素沉着/过敏(28例)、神经毒性(18例)、肾功能损害(5例)、横纹肌溶解(1例);ADR的发生时间为开始给药后5 min至用药30 d后,12例(占23.53%)患者首次用药后即发生ADR;32例(占62.75%)患者经停药或对症处理后症状有所改善或恢复。结论:临床需加强对PMB导致ADR的认识和监测,及时诊断与治疗,确保临床用药安全。

多黏菌素B治疗耐碳青霉烯类革兰阴性菌感染患者的全因死亡危险因素分析

目的回顾性分析多黏菌素B治疗耐碳青霉烯类革兰阴性菌感染患者的临床特征和全因死亡的危险因素。方法收集2017年6月1日—2020年5月1日温州医科大学附属第一医院和浙江省台州医院两家医院住院期间在肺部或血流感染耐碳青霉烯类革兰阴性菌(CR-GNB)且接受多黏菌素B治疗至少48 h的患者的相关临床资料,通过SPSS 25.0软件比较生存组和死亡组的临床特征差异,并用多因素Logistic回归分析这些患者住院全因死亡的危险因素。结果共80例患者纳入研究,基于logistic回归分析,这些患者住院死亡的相关危险因素包括:多黏菌素B用药疗程<7 d[OR=6.03,95%CI(1.28,28.41),P=0.023],从感染到使用多黏菌素B的时间越长[OR=1.08,95%CI(1.00,1.16),P=0.047]、Charlson共病指数[OR=1.41,95%CI(1.09,1.81),P=0.009]和血管活性药物的使用[OR=3.60,95%CI(1.01,28.41),P=0.047]。结论足疗程和早期给予多黏菌素B治疗可降低CR-GNB感染患者的死亡率。