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

INTRODUCTION: Recent 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 ß-lactams (VA therapy). METHODS: The present study, performed at Tsuyama Chuo Hospital between June 2012 and December 2018, included adult patients who received VCM and ß-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. RESULTS: We 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). CONCLUSION: VP therapy was associated with an increased risk of AKI compared to that with VA therapy among the Japanese population.

Effects of pharmacist intervention in Vancomycin treatment for patients with bacteremia due to Methicillin-resistant Staphylococcus aureus.

OBJECTIVE: We conducted a retrospective study based on composite endpoints for treatment failure to evaluate the effect of pharmacist-led VCM initial dose planning for Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia patients. METHODS: A retrospective cohort study was performed between pharmacist intervention and non-intervention groups. In this study, four types of failure were defined as the composite endpoint. When any one of the following failures occurred: 1) Death within 30 days from the start of VCM therapy, 2) Positive blood culture 7 days after the start of VCM therapy, 3) Change of VCM to another anti-MRSA agent, and 4) Development of nephrotoxicity, we considered that VCM treatment had failed. Survival time analysis was conducted with the Kaplan-Meier method and Cox's proportional hazard model that included seven predefined parameters: pharmacist intervention, age, sex, weight, baseline VCM trough concentration, Charlson Comorbidity Index (CCI), and Pitt Bacteremia score (PBS). The effect of pharmacist intervention was studied as the survival probability estimated from the period of time from the start of VCM administration to the earliest failure. RESULTS: The survival rate at 30 days after starting VCM therapy, at the end of follow-up, was 53.1 and 82.1% in the non-intervention and intervention groups, respectively. A significant survival time prolongation was noted in the intervention group (p = 0.011, log rank test). Among the seven parameters, only pharmacist intervention was significantly different and its hazard ratio was 0.26 (p = 0.014). The survival probability of the intervention group was higher than that of the non-intervention group for the time to each failure. In subgroup analyses, a significant difference was noted in male patients between the intervention and non-intervention groups (p = 0.005). Age was categorized into those under and over 65 years old. For those over 65 years old, a significant difference was shown between the groups (p = 0.018). CONCLUSION: To our knowledge, this is the first study to evaluate the failure of VCM treatment based on the composite endpoint. Pharmacist intervention through the initial VCM dose planning could maintain a balance between the efficacy and safety of VCM treatment and might avoid treatment failure for patients with MRSA bacteremia. Further investigations with large sample sizes are required to confirm our findings.

Clinical characteristics and outcome of critically ill patients with bacteremia caused by extended-spectrum ß-lactamase-producing and non-producing Escherichia coli.

The number of patients infected with extended-spectrum beta-lactamase (ESBL)-producing organisms has increased dramatically worldwide, and high mortality rates are seen in severely ill patients. This study retrospectively compared the clinical characteristics and outcomes of critically ill patients in an intensive care unit (ICU) at the Tsuyama Chuo Hospital (Okayama, Japan) who were hospitalized for bacteremia caused by ESBL-producing Escherichia coli (ESBL-EC) or non-ESBL-producing E. coli (non-ESBL-EC) between January 2006 and December 2016 (11 years). We analyzed the patients' age, sex, underlying disease(s), sequential organ failure assessment scores, primary focus of bacteremia, empiric antibiotics, rate of appropriateness of empiric antibiotics, and treatment duration, with 28-day mortality being the primary outcome. The study included 24 patients with ESBL-EC bacteremia and 77 with non-ESBL-EC bacteremia. The rate of appropriate initial antibiotic treatment was significantly lower (54.2% vs. 96.1%, respectively; P < 0.01) and the mortality due to bacteremia significantly higher (37.5% vs. 15.6%, respectively; P = 0.04) in the ESBL-EC than in the non-ESBL-EC bacteremia group. A subgroup analysis focusing on patients who were administered appropriate empiric antibiotics showed that the 28-day mortality rate did not differ significantly between the two groups (P = 0.23). To our knowledge, this is the first study to compare the outcomes of patients with ESBL-EC and non-ESBL-EC bacteremia in a Japanese ICU setting. Initial empiric antibiotic therapy covering ESBL-producing pathogens should be considered for critically ill patients in the ICU.

Risk factors for Propionibacterium acnes infection after neurosurgery: A case-control study.

Propionibacterium acnes is increasingly known as a causative organism for post-neurosurgical infection; however, no clinical studies have examined the risk factors associated with P. acnes infections. Clinical data obtained from 14 cases of P. acnes infection and 28 controls infected with other pathogens were analyzed. Craniotomy, malignancy, and prolonged duration of operation were significantly associated with the onset of P. acnes infection. No fatal cases were reported.

Pyogenic Spondylitis and Diskitis Caused by Helicobacter cinaedi in an Immunocompetent Adult Patient.

We herein describe the first reported case of pyogenic spondylitis and diskitis caused by Helicobacter cinaedi. The results of magnetic resonance imaging and the histology of biopsied tissue were suggestive of acute infection at the lumbar spine. The pathogen was obtained by a blood culture examination and identified by 16S rRNA analysis. Eight weeks of antibiotics therapy resulted in a good clinical course. H. cinaedi infections have been increasingly reported in recent years, but the pathogen's epidemiological and pathological characteristics are still unclear. One of the difficulties in understanding the pathogenesis of H. cinaedi has been the challenges in cultivating the pathogen. Novel strategies for the diagnosis of H. cinaedi must be developed.

[Investigation of Intravenous Azithromycin Treatment Safety When Reducing Solvent for Intensive Care Unit Patients].

Intravenous azithromycin (AZM) was approved for use in December 2011 in Japan. In general, intravenous AZM injections are diluted to 1 mg/mL, with a total infusion volume of 500 mL to avoid phlebitis. Patients in intensive care units (ICUs) require small infusion volumes. We retrospectively evaluated the total AZM infusion volume in 65 ICU patients receiving AZM treatment from December 2011 to August 2014. Thirteen patients (20.0%) received a reduced volume [100 mL (5 mg/mL) or 250 mL (2 mg/mL)] using an infusion pump over 2 h. No peripheral phlebitis was observed in any patient. Based on this result, it is assumed that AZM can be safely administered to ICU patients even though the volume of solvent is reduced. AZM is widely recommended for the treatment of community-acquired respiratory infections and is used in patients with severe infections. Further investigation is required in additional patients to understand the effects of AZM volume reduction in greater detail.

Impact of pharmacist intervention on preventing nephrotoxicity from vancomycin.

OBJECTIVES: To evaluate the impact of pharmacist interventions on preventing nephrotoxicity from vancomycin. METHODS: A pre- to postpharmacist intervention study was performed in the Tsuyama Central Hospital. 508 Patients admitted from May 2007 to May 2012 served as the non-pharmacist intervention group, while 102 patients admitted from June 2012 to November 2013 formed the pharmacist intervention group. Pharmacist interventions were mainly performed for the initial dosage planning, controlling vancomycin prescriptions, and real-time monitoring of medical records before routine therapeutic drug monitoring. The non- and pharmacist intervention groups were compared to evaluate the outcomes of pharmacist interventions. RESULTS: By pharmacist interventions, initial trough concentration of vancomycin promptly tightened within the 10 - 20 µg/mL therapeutic trough concentration range (p < 0.001), and reaching an ineffective or risky trough concentration was avoided. Also, the mean vancomycin trough concentrations of patients with and without nephrotoxicity were 23.9 and 13.9 µg/mL, respectively. Furthermore, by multivariate logistic regression analysis, significant increased risks of nephrotoxicity in baseline creatinine clearance, and 15 - 20 and over 20 µg/mL of initial vancomycin trough concentration were observed. Significant decreased risk of nephrotoxicity was gender (male). Although pharmacist intervention showed a trend of 45% decrease in the incidence of nephrotoxicity, there was no significant difference between the pharmacist intervention and non-intervention groups. CONCLUSION: Pharmacist intervention may have an impact on vancomycin therapy from the standpoint of balancing a higher vancomycin trough concentration with risk of nephrotoxicity.

Clinical characteristics of Raoultella ornithinolytica bacteremia: a case series and literature review.

Raoultella ornithinolytica is a rare pathogen in human infection and bacteremic cases had been scarcely reported. For further comprehension of the rare infection, we summarized clinical characteristics of 6 cases that were detected at our medical facility and 5 cases from previous literature. The most common infectious focus was biliary infection and elderly patients with a history of any biliary intervention or malignancy were considered to be at a great risk for the infection. The prognosis of the patients was quite satisfactory. Bacterial identification in this report was performed on the basis of biochemical tests alone, and further investigations by molecular analysis are required to confirm our findings.

Lafutidine facilitates calcitonin gene-related peptide (CGRP) nerve-mediated vasodilation via vanilloid-1 receptors in rat mesenteric resistance arteries.

Lafutidine is a histamine H(2)-receptor antagonist with gastric antisecretory and gastroprotective activity associated with activation of capsaicin-sensitive nerves. The present study examined the effect of lafutidine on neurotransmission of capsaicin-sensitive calcitonin gene-related peptide (CGRP)-containing vasodilator nerves (CGRPergic nerves) in rat mesenteric resistance arteries. Rat mesenteric vascular beds were perfused with Krebs solution and vascular endothelium was removed by 30-s perfusion with sodium deoxycholate. In preparations preconstricted by continuous perfusion of methoxamine (alpha(1) adrenoceptor agonist), perfusion of lafutidine (0.1 - 10 microM) concentration-dependently augmented vasodilation induced by the periarterial nerve stimulation (PNS, 1 Hz) without affecting vasodilation induced by exogenous CGRP (10 pmol) injection. Perfusion of famotidine (H(2)-receptor antagonist, 1 - 100 microM) had no effect on either PNS-induced or CGRP-induced vasodilation. Perfusion of lafutidine concentration-dependently augmented vasodilation induced by a bolus injection of capsaicin (vanilloid-1 receptor agonist, 30 pmol). The presence of a vanilloid-1 receptor antagonist, ruthenium red (10 microM) or capsazepine (5 microM), abolished capsaicin-induced vasodilation and significantly decreased the PNS-induced vasodilation. The decreased PNS-induced vasodilation by ruthenium red or capsazepine was not affected by perfusion of lafutidine. These results suggest that lafutidine facilitates CGRP nerve-mediated vasodilation by modulating the function of presynaptic vanilloid-1 receptors located in CGRPergic nerves.