Effective antibiotic stewardship in spinal cord injury: Challenges and a way forward

Context: Antibiotic stewardship, defined as a multidisciplinary program to reduce the misuse of antibiotics, and in turn, antibiotic resistance, is a high priority. Persons with spinal cord injury/disorder (SCI/D) are vulnerable to receiving multiple courses of antibiotics over their lifetime given frequent healthcare exposure, and have high rates of bacterial infection with multi-drug resistant organisms. Additional challenges to evaluating appropriate use of antibiotics in this population include bacterial colonization in the urine and the differences in the presenting signs and symptoms of infection. Therefore, Veterans Health Administration (VHA) facilities with SCI/D centers need effective antibiotic stewardship programs.

Results: We analyzed the results of a 2012 VHA-wide survey evaluating available antibiotic stewardship resources, and compared the resources present at facilities with SCI/D (n=23) versus non-SCI/D facilities (n=107). VHA facilities with SCI/D centers are more likely to have components of an antibiotic stewardship program that have led to reduced antibiotic use in previous studies. They are also more likely to have personnel with infectious diseases training.

Conclusion: VHA facilities with SCI/D centers have the resources needed for antibiotic stewardship. The next step will be to determine how to implement effective antibiotic stewardship tailored for this patient care setting.     

星点设计-效应面法优化丁香苦苷聚乳酸-羟基乙酸纳米粒的制备工艺

目的优化丁香苦苷聚乳酸(Syr)-羟基乙酸共聚物[poly(lactic-co-glycolic acid),PLGA]纳米粒(Syr-NPs)的处方。方法采用纳米沉淀法制备Syr-NPs,以包封率、载药量、平均粒径以及总评"归一值"为评价指标,采用星点设计-效应面法考察PLGA质量浓度(A)、丁香苦苷质量浓度(B)、水相与有机相比例(C)3因素考察对包封率、载药量、平均粒径以及总评归一值的影响,以星点设计-效应面法选取最佳处方条件进行预测分析。结果最优处方工艺为PLGA质量浓度为9.63 mg/mL,Syr质量浓度为12.88 mg/mL,有机相与水相的比例为1∶9.46,制得的Syr-NPs的包封率、载药量、平均粒径分别为(27.86±0.87)%、(7.02±0.15)%、(110.0±1.20)nm。结论该方法稳定可行,可用于优化包载Syr的PLGA纳米粒处方与制备工艺。     

肉毒毒素注射引起的不良反应

肉毒毒素注射引起的不良反应,是药物本身的组成成分引起的与用药目的无关的有害反应,与医生注射方式和注射技术无关。尽管肉毒毒素生产厂家的药品说明书上也有提示,但其所提供的信息不够全面,也未必能引起医生的足够重视。目前文献上多为散发病例。为此作者对过去20年有关肉毒毒素注射引起的过敏反应、肉瘤样肉芽肿、眼睑水肿、流感样症状等相关不良反应的临床表现、发病机制与治疗方法进行综述。     

西格列汀联合二甲双胍治疗肥胖型2型糖尿病的疗效及对体脂含量情况分析

目的研究肥胖型2型糖尿病患者联合采用西格列汀、二甲双胍治疗的临床效果。方法选择2018年10月—2020年4月该院100例肥胖型2型糖尿病患者为研究对象,采用随机数表法分成常规组和治疗组,每组50例。常规组予二甲双胍治疗,治疗组予二甲双胍+西格列汀治疗。比较两组治疗效果、血糖指标、体脂含量、胰岛功能指标及不良反应。。结果两组治疗效果比较,差异有统计学意义(P<0.05)。治疗后常规组血糖指标高于治疗组,差异有统计学意义(t=8.183、4.828、18.158,P<0.05)。治疗后常规组体脂含量高于治疗组,差异有统计学意义(t=5.993、7.657、4.420,P<0.05)。治疗后两组胰岛功能比较,差异有统计学意义(t=5.898、5.283、16.033,P<0.05)。常规组不良反应总发生率低于治疗组,但差异无统计学意义(χ²=0.136,P=0.712)。结论西格列汀、二甲双胍联合治疗肥胖型2型糖尿病效果确切。     

Ketorolac use and anastomotic leak in patients with esophageal cancer

ObjectivesRecent evidence has shown an association between postoperative ketorolac use and anastomotic leak in patients undergoing intestinal and colorectal operations, but this relationship has been minimally explored after esophagectomy. As the use of nonopioid pain control and enhanced recovery protocols is increasingly prioritized, determination of a possible correlation between perioperative ketorolac use and leak is essential.MethodsRecords of patients undergoing esophagectomy for adenocarcinoma at a single institution from 2006 to 2018 reviewed for occurrence of anastomotic leak. Institutional pharmacy records were queried for ketorolac administration during the surgical case through the time of discharge. Multivariable logistic regression was used to determine the relationship between ketorolac administration and anastomotic leak.ResultsA total of 1019 patients met inclusion criteria, the majority of whom were male (907, 89%) with a median age of 62 years. Patients predominantly presented with locoregionally advanced disease and were treated with initial chemoradiation. Ketorolac was administered to 686 patients (67%); use was observed to increase over the study period from 49% in 2006 to 92% in 2016. Conversely, anastomotic leak occurred in 87 patients (9%) overall and decreased over time from 15% (11/72) in 2006 to 2% (2/83) in 2018. Upon multivariable analysis, neither ketorolac administration evaluated as a categoric variable (odds ratio, 0.99; P = .958) or as a continuous variable using dose (odds ratio, 1.00; P = .843) demonstrated an association with anastomotic leak.ConclusionsKetorolac in the postoperative period after esophagectomy has become an integral component of enhanced recovery pathways and does not appear to be associated with anastomotic leak.     

Assessment of the Physical Compatibility of Eravacycline and Common Parenteral Drugs During Simulated Y-site Administration

PurposeEravacycline is a broad-spectrum, intravenous fluorocycline antibiotic approved for the treatment of complicated intra-abdominal infections in adults. A 60-minute infusion is recommended for each infused dose. Compatibility data that may allow convenient Y-site administration of eravacycline with other parenteral medications are unavailable. We aimed to determine the physical compatibility of eravacycline with other intravenous medications by simulated Y-site administration.MethodsEravacycline was reconstituted according to published prescribing information and diluted with 0.9% sodium chloride to a concentration of 0.6 mg/mL. Simulated Y-site administration was performed by mixing 5 mL of eravacycline with an equal volume of 51 other intravenous medications, including crystalloid and carbohydrate hydration fluids and 20 antimicrobials. Secondary medications were assessed at the upper range of concentrations considered standard for intravenous infusion. Mixtures underwent visual inspection and turbidity measurement immediately on mixture and at 3 subsequent time points (30, 60, and 120 minutes after admixture), and pH was measured at 60 minutes for comparison with the baseline value of the secondary medication.FindingsEravacycline was physically compatible with 41 parenteral drugs (80%) by simulated Y-site administration. Incompatibility was observed with albumin, amiodarone hydrochloride, ceftaroline fosamil, colistimethate sodium, furosemide, meropenem, meropenem/vaborbactam, micafungin sodium, propofol, and sodium bicarbonate.ImplicationsEravacycline for injection was physically compatible with most parenteral medications assessed. Pharmacists and nurses should be knowledgeable of the observed incompatibilities with eravacycline to prevent the unintentional mixing of incompatible intravenous medications.     

Sustainability and switching of biologics for psoriasis and psoriatic arthritis at Fukuoka University Psoriasis Registry

Biologics are efficacious for treating psoriasis vulgaris (PsV) and psoriatic arthritis (PsA), but sometimes must be terminated or changed for various reasons including ineffectiveness or adverse events. To find the optimal choice of biologics for treating psoriasis, we analyzed the real‐world data on drug survival and the reason for terminating or switching biologics. Medical records from patients with PsV or PsA, who visited the Department of Dermatology, Fukuoka University Hospital from 2010 to 2017, were analyzed. Two hundred and eleven patients received biologics, and 147 patients (69.7%) were treated with only one biologic, while 64 patients (30.3%) were switched to different products. Frequently used biologics in PsV were ustekinumab (UST), infliximab and adalimumab when calculated by patient‐year. Tumor necrosis factor inhibitor (TNFi) use decreased while UST and interleukin (IL)‐17 inhibitors increased in newly introduced patients. UST showed the highest survival rate as a first‐line drug, but the advantage was lost in the second reagent's group. The major reasons for terminating/switching biologics were as follows: primary ineffectiveness (26.4%), secondary loss of efficacy (36.5%), patient's preference, including referral to nearby hospital, or stopped visiting (22.6%), side‐effects (7.7%), comorbidities (3.4%) and economic burden (2.4%). In PsA patients, TNFi are more frequently employed than in PsV patients, although switching to UST or IL‐17 inhibitors showed an increasing trend. Biologic reagents were changed mostly because of primary or secondary loss of efficacy, which affected drug survival. Further research is needed to find the optimal choice of biologics with larger samples at multiple facilities.     

A graph model of combination therapies

The simultaneous use of multiple medications causes drug–drug interactions (DDI) that impact therapeutic efficacy. Here, we argue that graph theory, in conjunction with game theory and ecosystem theory, can address this issue. We treat the coexistence of multiple drugs as a system in which DDI is modeled by game theory. We develop an ordinary differential equation model to characterize how the concentration of a drug changes as a result of its independent capacity and the dependent influence of other drugs through the metabolic response of the host. We coalesce all drugs into personalized and context-specific networks, which can reveal key DDI determinants of therapeutical efficacy. Our model can quantify drug synergy and antagonism and test the translational success of combination therapies to the clinic.