Concomitant vancomycin and piperacillin/tazobactam treatment is associated with an increased risk of acute kidney injury in Japanese patients

IntroductionRecent studies have corroborated that the co-administration of vancomycin (VCM) and piperacillin/tazobactam (PT) is correlated with an increased incidence of acute kidney injury (AKI). However, evidence directed at the Japanese population is scarce. Therefore, we conducted a retrospective study to compare the occurrence of AKI among Japanese patients who received VCM with PT (VP therapy) and VCM with another β-lactams (VA therapy).MethodsThe present study, performed at Tsuyama Chuo Hospital between June 2012 and December 2018, included adult patients who received VCM and β-lactam antibiotics for ≥48 h. We defined the primary outcome as the incidence of AKI based on the risk, injury, failure, loss, and end-stage kidney disease criteria. Patients' clinical characteristics and outcomes were reviewed and compared between the two groups with univariate and multivariate logistic regression analyses. Subgroup analysis was conducted by stratifying the patients’ baseline hospital admittance status, as intensive care unit or general wards.ResultsWe analyzed 272 patients (92 V P therapy and 180 VA therapy). Univariate analysis revealed a significant difference in AKI development between VP and VA therapy (25.0% vs 12.2%; p < 0.01). A multivariate analysis demonstrated that VP therapy and VCM initial trough levels ≥15 μg/mL were associated with an incidence of AKI. Patients at general wards, rather than those admitted at an intensive care unit, developed AKI with VP therapy (p = 0.02).ConclusionVP therapy was associated with an increased risk of AKI compared to that with VA therapy among the Japanese population.     

反复粪便培养金黄色葡萄球菌阳性老年患者口服万古霉素效果评价

目的 通过探讨肠道非急性感染期反复粪便培养金黄色葡萄球菌阳性的老年患者口服万古霉素的效果，为此类患者提供一种潜在的治疗方案。方法 前瞻性分析吉林大学第一医院干部病房2015 年9 月～2018 年12 月收治的186 例肠道非急性感染期反复粪便培养金黄色葡萄球菌阳性的老年患者。根据是否口服万古霉素治疗分为万古组和对照组。收集两组患者的一般临床资料，比较两组患者试验前后万古霉素血药浓度、血常规、降钙素原（PCT）、C 反应蛋白（CRP），试验期间粪便培养结果、体温、抗生素使用情况。结果 试验治疗期间，万古组便培养转阴率高于对照组，差异有统计学意义（P＜0.05）；万古组发热率（29.75%）低于对照组的34.77%，差异有高度统计学意义（P＜0.01）；万古组抗生素使用率（4.49%）低于对照组的19.23%，差异有高度统计学意义（P＜0.01）。试验前两组白细胞、中性粒细胞计数、中性粒细胞比例、PCT、CRP 比较，差异无统计学意义（P＞0.05）；试验后万古组白细胞、中性粒细胞计数、中性粒细胞比例、CRP 低于对照组，差异有高度统计学意义（P＜0.01）。试验后万古组白细胞、中性粒细胞计数、中性粒细胞比例、CRP 低于试验前，差异有高度统计学意义（P＜0.01）。结论 口服万古霉素可能提高肠道非急性感染期反复粪便培养金黄色葡萄球菌阳性的老年患者粪便转阴率，减少发热及抗生素的应用，降低炎症细胞水平，可能是此类患者一种潜在的临床治疗方案。     

万古霉素与利奈唑胺治疗老年人MRSA肺炎的疗效与安全性分析

目的：比较利奈唑胺与万古霉素治疗老年人医院获得性耐甲氧西林金黄色葡萄球菌（MRSA）肺炎的疗效和安全性。方法57例老年医院获得性MRSA肺炎患者随机分成利奈唑胺组（29例）与万古霉素组（28例），疗程结束后比较两组临床有效率、细菌学清除率及不良反应情况。结果利奈唑胺组临床有效率75.9%，万古霉素组67.9%，两组差异无统计学意义（P＞0.05）。利奈唑胺组血小板减少发生率20.7%，用药前后的差异有统计学意义（P＜0.05）；万古霉素组肾功能损害发生率14.2%。结论利奈唑胺治疗老年人医院获得性肺炎临床疗效与万古霉素相仿，但其不良反应相对轻微。     

万古霉素联合自体微小颗粒骨植骨治疗感染性骨缺损的临床研究

目的：探讨感染性骨缺损患者行万古霉素联合自体微小颗粒骨植骨治疗的临床疗效。方法方便选取该院2014年12月-2015年12月接收的120例感染性骨缺损患者，随机分为观察组与对照组各60例，对照组行自体微小颗粒骨植骨治疗，观察组在对照组基础上施加万古霉素治疗，对比两组治疗1周、5周、8周以及10周后的感染控制率与感染指标控制情况和两组治疗效果。结果两组经治疗1周、5周、8周以及10周后，对照组的感染控制率分别以6.7%、13.3%、23.3%、33.3%明显低于观察组的13.3%、26.7%、36.7%、50.0%(P<0.05)；观察组感染相关指标明显优于对照组(P<0.05)；治疗后两组X线片积分对比差异无统计学意义(P>0.05)。结论感染性骨缺损患者行万古霉素联合自体微小颗粒骨植骨治疗的效果显著，具推广价值。     

Vancomycin-related convulsion in a pediatric patient with neuroblastoma: A case report and review of the literature

BACKGROUNDVancomycin is often used as an anti-infective drug in patients receiving anti-tumor chemotherapy. There are concerns about its adverse drug reactions during treatment, such as nephrotoxicity, ototoxicity, hypersensitivity reactions, etc. However, potential convulsion related to high plasma concentrations of vancomycin in children receiving chemotherapy has not been reported.CASE SUMMARYA 3.9-year-old pediatric patient with neuroblastoma receiving vancomycin to treat post-chemotherapy infection developed an unexpected convulsion. No other potential disease conditions could explain the occurrence of the convulsion. The subsequently measured overly high plasma concentrations of vancomycin could possibly provide a clue to the occurrence of this convulsion. The peak and trough plasma concentrations of vancomycin were 59.5 mg/L and 38.6 mg/L, respectively, which were much higher than the safe range. Simulation with the Bayesian approach using MwPharm software showed that the area under the concentration-time curve over 24 h was 1086.6 mg· h/L. Therefore, vancomycin was immediately stopped and teicoplanin was administered instead combined with meropenem and fluconazole as the anti-infective treatment strategy.CONCLUSIONUnexpected convulsion occurring in a patient after chemotherapy is probably due to toxicity caused by abnormal pharmacokinetics of vancomycin. Overall evaluation and close therapeutic drug monitoring should be conducted to determine the underlying etiology and to take the necessary action as soon as possible.     

Detection of vancomycin variable enterococci (VVE) among clinical isolates of Enterococcus faecium collected across India-first report from the subcontinent

PurposeEmergence of vancomycin variable enterococci (VVE) poses a challenge to empiric vancomycin therapy. Vancomycin-variable enterococci (VVE) are vanA-positive, yet phenotypically vancomycin-susceptible enterococci that can switch to a vancomycin-resistant phenotype when exposed to vancomycin. The aim of the present study was to determine the prevalence of VVE in India.MethodsIsolates of phenotypically vancomycin susceptible Enterococcus faecium from 20 tertiary care hospitals across India were collected and tested for the presence of vanA, vanR, vanS, vanB and vanC genes by conventional PCR using previously published primers. Isolates positive for vanA gene were considered as VVE.ResultsThe prevalence of VVE was 1.5% (5/340). Only one VVE isolate was positive for vanR and vanS, and all the isolates were negative for vanB and vanC.ConclusionsAlthough the prevalence is low, our finding emphasizes the importance of routinely screening for van genes in enterococci that are phenotypically susceptible. Silenced vanA able to escape detection and revert to resistance during vancomycin therapy represents a new challenge in clinical settings.     

How to optimize the evaluation and use of antibiotics in neonates

Early and late-onset neonatal sepsis has specific pathogen distribution and infection rates in neonates with different gestational and postnatal ages. Despite the fact that early-onset sepsis is relatively rare (<1% of total deliveries), it is a major cause of mortality and morbidity. The known immunological immaturity of the neonate combined with non-specific clinical symptoms of infection has resulted in the frequent overuse of antibiotics in neonatal intensive care units (NICUs). In addition to this overuse there is a huge variability in the choice of antibacterial agents and dosing regimens used in NICUs across the world. Therefore, a more rational approach in the neonatal use of antibiotics is needed because of two major reasons: the emergence of multi-resistant bacteria in NICUs, and short- and long-term side effects of frequently used antibacterial agents in the neonatal population. This paper will focus on the optimal use of aminoglycosides (both used in early and late onset sepsis) and vancomycin (primarily used in late onset infections) in NICUs, and will underscore the need for specialists in neonatal medicine and pediatric pharmacology to work closely together to reach the most effective and safe way of using medicines in the NICU.     

Adjunctive Hyperbaric Oxygen Therapy or Alone Antibiotherapy? Methicillin Resistant Staphylococcus aureus Mediastinitis in a Rat Model

OBJECTIVE

In the post-sternotomy mediastinitis patients, Staphylococcus aureus is the pathogenic microorganism encountered most often. In our study, we aimed to determine the efficacy of antibiotic treatment with vancomycin and tigecycline, alone or in combination with hyperbaric oxygen treatment, on bacterial elimination in experimental S. aureus mediastinitis.

METHODS

Forty-nine adult female Wistar rats were used. They were randomly divided into seven groups, as follows: non-contaminated, contaminated control, vancomycin, tigecycline, hyperbaric oxygen, hyperbaric oxygen + vancomycin and hyperbaric oxygen + tigecycline. The vancomycin rat group received 10 mg/kg/day of vancomycin twice a day through intramuscular injection. The tigecycline group rats received 7 mg/kg/day of tigecycline twice a day through intraperitoneal injection. The hyperbaric oxygen group underwent 90 min sessions of 100% oxygen at 2.5 atm pressure. Treatment continued for 7 days. Twelve hours after the end of treatment, tissue samples were obtained from the upper part of the sternum for bacterial count assessment.

RESULTS

When the quantitative bacterial counts of the untreated contaminated group were compared with those of the treated groups, a significant decrease was observed. However, comparing the antibiotic groups with the same antibiotic combined with hyperbaric oxygen, there was a significant reduction in microorganisms identified (P<0.05). Comparing hyperbaric oxygen used alone with the vancomycin and tigecycline groups, it was seen that the effect was not significant (P<0.05).

CONCLUSION

We believe that the combination of hyperbaric oxygen with antibiotics had a significant effect on mediastinitis resulting from methicillin-resistant Staphylococcus aureus. Methicillin-resistant Staphylococcus aureus mediastinitis can be treated without requiring a multidrug combination, thereby reducing the medication dose and concomitantly decreasing the side effects.     

不同剂量万古霉素治疗儿童金黄色葡萄球菌肺炎的血药浓度分析

目的 分析不同剂量万古霉素治疗儿童金黄色葡萄球菌肺炎（Staphylococcus aureus pneumonia,SAP）的血药浓度,探讨适宜的治疗剂量,为临床用药提供参考。方法 回顾性分析2008 年1 月至2013 年12月35 例使用万古霉素治疗的SAP 患儿临床资料。结果 35 例使用万古霉素治疗的SAP 患儿中,22 例（63%）进行了血药谷浓度监测,治疗剂量为10、12.5 和15 mg/（kg · 次）×q6h 者分别有11、4 和7 例。15 mg/（kg · 次）组平均谷浓度为14.98 mg/L（中位数）,显著高于剂量为10 mg/（kg · 次）和12.5 mg/（kg · 次）组患儿（分别为4.97和8.00 mg/L,P<0.05）;15 mg/（kg · 次）组达到万古霉素预计谷浓度的比例（71%）显著高于10 mg/（kg · 次）组（9%）,与12.5 mg/（kg · 次）组（25%）比较差异无统计学意义。结论 儿科临床治疗SAP 使用万古霉素的剂量可能以15 mg/（kg · 次）×q6h ,即60 mg/（kg · d）,较为合理。