OBJECTIVE: To evaluate trough serum vancomycin concentrations and identify their influencing factors in critically ill neurosurgical patients. METHODS: A retrospective study was conducted. Adult patients who received vancomycin with at least one appropriate monitoring of trough serum vancomycin concentration and admitted to neurosurgical intensive care unit (ICU) of the First Affiliated Hospital of Sun Yat-sen University from November 2017 to July 2019 were enrolled. General information including gender, age, comorbidities, etc., trough serum vancomycin concentrations, vancomycin dosage, duration of vancomycin therapy, urine output, serum creatinine (SCr), concurrent medications (including mannitol,diuretic, vasopressors, non-steroidal anti-inflammatory drugs, polymyxin, aminoglycosides and contrast medium, etc.) were collected for analysis. Trough serum vancomycin concentrations were evaluated and their influencing factors were analyzed by multiple linear regression method. RESULTS: In total, 81 trough serum vancomycin concentration data sets obtained from 28 patients were evaluated. (1) The initial daily dose of vancomycin was 2.00 (2.00, 2.00) g/d. After 4-6 doses, the trough serum vancomycin concentration obtained from initial blood draw was 10.99 (6.98, 16.25) mg/L, of which only 17.9% (5/28) achieving targeted concentrations (15-20 mg/L), 71.4% (20/28) subtherapeutic level and 10.7% (3/28) supratherapeutic level. (2) The duration of vancomycin therapy was 8.0 (6.0, 15.0) days. With average daily dose of 2.00 (1.75, 3.00) g/d, targeted trough vancomycin concentrations were achieved in only 30.9% (25/81) of all cases, subtherapeutic concentrations in 49.4% (40/81) and supratherapeutic concentrations in 19.7% (16/81). (3) There were significant differences in age, comorbidities, vancomycin dosage, diuretics use and mannitol dosage, etc. among different vancomycin concentration groups. Multiple linear regression analysis suggested that the trough serum vancomycin concentration increased by 0.14 mg/L [95% confidence interval (95%CI) was 0.06-0.22] for every 1 year increase in age, increased by 7.22 mg/L (95%CI was 2.08-12.36) in patients with multiple comorbidities (concomitant hypertension, diabetes and coronary heart disease) compared with those without comorbidities, increased by 2.78 mg/L (95%CI was 0.20-5.35) in patients treated with diuretics compared with those without diuretics. The effect of other variables was not statistically significant. It suggested that age, multiple comorbidities (concomitant hypertension, diabetes and coronary heart disease), and diuretic usage affected trough serum vancomycin concentrations. CONCLUSIONS Targeted trough serum vancomycin level is not often achieved in neurosurgical ICU patients following standard dosing. Younger patients are associated with lower trough serum vancomycin concentrations, while diuretic usage, combined with multiple comorbidities are associated with higher trough serum vancomycin concentrations.
Adult ; Anti-Bacterial Agents/blood* ; Critical Illness ; Humans ; Intensive Care Units ; Retrospective Studies ; Vancomycin/blood*

PURPOSE: With the increase in vancomycin use, adverse drug reactions (ADRs) associated with vancomycin have been reported increasingly more often. However, the characteristics of cutaneous ADRs with and without systemic reactions (SRs) have not been described. This study investigated the characteristics of spontaneously reported and assessed ADRs associated with vancomycin by a pharmacovigilance center. METHODS: ADRs (n=121) associated with vancomycin in 96 patients were collected from 2008 to 2009. Records from physician- and nurse-reported suspected cases of vancomycin ADRs, ADR type, latent period, and laboratory results were compared between cutaneous ADRs with and without SRs. RESULTS: The main vancomycin-related ADRs were skin rashes (47.9%), hematologic abnormalities (17.36%), fever (12.4%), and elevated serum creatinine (12.4%). Significant differences were observed in latent period (days) and the mean change in eosinophils (%) between cutaneous (9.21+/-9.71 and 1.4+/-3.4, respectively) and other ADRs (14.03+/-11.71 and -0.5+/-3.5, respectively). Twelve cases of cutaneous ADRs with SRs had been initially reported as cutaneous ADRs only. Mean changes in the eosinophil count were significantly higher for cutaneous ADRs with SRs compared to those without SRs. CONCLUSIONS: Skin rashes accompanied by peripheral eosinophilia, representing suspected immune-mediated delayed hypersensitivity reactions, are a common vancomycin ADR. For the early and exact detection of ADRs associated with vancomycin administration, close monitoring of laboratory tests, including complete blood counts with differential analysis, is recommended.
Blood Cell Count ; Creatinine ; Drug Toxicity ; Eosinophilia ; Eosinophils ; Exanthema ; Fever ; Humans ; Hypersensitivity, Delayed ; Pharmacovigilance ; Vancomycin

The purpose of the study was to explore the effect of 2 hour infusion of vancomycin(1g) in 200ml of isotonic saline every 12 hour on the frequency of "red man syndrome", phlebitis and length of peripheral catheter placement of infected patients, in order to provide safe infusion method for reducing vancomycin-induced RMS and phlebitis. The subjects of the study consisted of 16 hospitalized patients; 3 oncology and gastro-intestinal patients, 1 neurological patient, 6 thoracic surgical patients and 6 orthopedic patients, who had received vancomycin from July to October in 1999 at S-hospital. The dependent variables were the incidence of RMS, phlebitis and the length of peripheral catheter placement. The incidence of RMS was checked by an inspector at the first night whenever the infusion method of vancomycin was changed. RMS was observed every 15 minutes during an hour for symptoms of RMS such as itching, erythema, chest pain and systolic blood pressure. Incidence of phlebitis was assessed by inspector twice a day from the insertion of peripheral catheter to the removal of the catheter. The data were analyzed by percentage, mean, X2-test, t-test, repeated ANOVA, and logistic regression analysis using the SPSSWIN program. The results are summarized as follows; 1. No significant difference was identified in frequency of RMS between the experimental group and control group. 2. There was no significant difference in the change of systolic blood pressure as the time goes on between the experimental group and control group. 3. The incidence of phlebitis was significantly lower in the experimental group than in the control group. 4. The length of peripheral catheter placement was significantly longer in the experimental group than in the control group. 5. Other drugs administrated with vancomycin didn't influence the occurrence of phlebitis. However, the infusion method of vancomycin influenced the occurrence of phlebitis. The results suggest that 2 hour infusion of vancomycin(1g) in 200ml of isotonic saline every 12 hours may decrease the incidence of phlebitis and increase the length of peripheral catheter placement compared to 1 hour infusion of vancomycin(1g) in 100ml of isotonic saline every 12 hours. However, it does not reduce the incidence of RMS.
Blood Pressure ; Catheters* ; Chest Pain ; Erythema ; Humans ; Incidence* ; Logistic Models ; Orthopedics ; Phlebitis ; Pruritus ; Vancomycin*

STUDY DESIGN: Retrospective study. PURPOSE: To evaluate the effect of intraoperative wound application of vancomycin on preventing surgical wound contamination during instrumented lumbar spinal surgery. OVERVIEW OF LITERATURE: Postoperative infection is the one of the most devastating complications of lumbar surgery. There are a few reports showing the benefits of intraoperative wound application of vancomycin during spinal surgery. However, there is no report about the effectiveness of local vancomycin instillation in prevention of surgical wound contamination. METHODS: Eighty-six patients underwent instrumented lumbar spinal surgery. Mean patient age was 65.19 years (range, 23-83 years). There were 67 females and 19 males. During surgery, vancomycin powder was applied into the surgical site before closure in 43 patients (antibiotic group) and vancomycin powder was not applied into the surgical site before closure in 43 patients (control group). The tip of the surgical drain was cultured to evaluate surgical wound contamination. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were measured on the first, third, seventh, and fourteenth day after the operation. RESULTS: We found two patients with a positive culture from the tip of surgical drains in the antibiotic group, and one patient with a positive culture from the tip of the surgical drain in the control group. Postoperative ESR and CRP levels did not show significant differences between the two groups. On the third postoperative day, ESR in patients of the antibiotic group was more significantly decreased than that in patients of the control group, while CRP level did not show a significant difference between the two groups. CONCLUSIONS: There was no evidence to suggest that intraoperative vancomycin application is effective in decreasing the risk of postoperative wound infection after instrumented posterior lumbar fusion surgery.
Anti-Bacterial Agents* ; Blood Sedimentation ; C-Reactive Protein ; Female ; Humans ; Male ; Retrospective Studies ; Surgical Wound Infection ; Vancomycin ; Wounds and Injuries

OBJECTIVETo analyze serum vancomycin concentration after administration of different therapeutic doses in children with Staphylococcus aureus pneumonia (SAP) in order to determine the appropriate dose of vancomycin in clinical administration.

METHODSThe clinical data of 35 children who were diagnosed with SAP and treated with vancomycin from January 2008 to December 2013 were retrospectively analyzed.

RESULTSAmong the 35 SAP cases with vancomycin therapy, 22 cases (63%) had serum vancomycin trough concentration monitored. The numbers of cases with vancomycin at 10, 12.5, and 15 mg/(kg·dose) × every 6 hours (q6h) were 11, 4 and 7, respectively. The mean serum trough concentration of vancomycin in the 15 mg/(kg·dose) group was 14.98 mg/L, which was significantly higher than in the 10 mg/(kg·dose) and 12.5 mg/(kg·dose) groups (4.97 and 8.00 mg/L respectively; P<0.05). The percentage of cases that reached the expected trough concentration in the 15 mg/(kg·dose) group (71%) was significantly higher than that in the 10 mg/(kg·dose) group (9%), but there was no significant difference in this percentage between the 15 mg/(kg·dose) and 12.5 mg/(kg·dose) groups (71% vs 25%).

CONCLUSIONSThe reasonable dosage of vancomycin for the treatment of pediatric SAP is 15 mg/(kg·dose) × q6h or 60 mg/(kg·d).

Adolescent ; Anti-Bacterial Agents ; blood ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Male ; Pneumonia, Staphylococcal ; blood ; drug therapy ; Vancomycin ; adverse effects ; blood

Insertion of indwelling arterial catheter has become a valuable procedure for blood pressure monitoring and for measurement of blood gas tension during anesthesia. A 34-year-old man with chronic alcoholism and diabetes mellitus was admitted to the hospital because of hyperosm-olar coma. On the first hospital day, percutaneous left radial artery cannulation was carried out for hemodynamic monitoring and arterial blood gas analysis after a modified Allen's test appear-ed to be positive. On the eleventh hospital day, the catheter was removed because of fever and sign of infection at the insertion site. Treatment with vancomycin by sensitivity test was begun on day 13, after continued for 2 weeks. On day 34 a pulsatile mass was noted at the insertion site. During surgery, a pseudoaneurysm of 1X1.2 cm size was found, and liquified hematoma and necrotic material were noted. The aneurysm was removed and end to end anastomosis was successfully completed. We suggest that risk factors for pseudoaneurysm may include abnormal state of vessel wall, multiple attempts at cannulation, increased duration of catheterization, adva-nced age, prolonged hospitalization, hematoma and infection at cannulation site.
Adult ; Alcoholism ; Anesthesia ; Aneurysm ; Aneurysm, False* ; Blood Gas Analysis ; Blood Pressure Monitors ; Catheterization* ; Catheters ; Coma ; Diabetes Mellitus* ; Fever ; Hematoma ; Hemodynamics ; Hospitalization ; Humans ; Radial Artery* ; Risk Factors ; Vancomycin

We developed a population pharmacokinetic model of vancomycin by integrating the effects of cystatin C and other demographic factors in a large population of Korean patients with normal serum creatinine concentrations to elucidate the precise role of serum cystatin C concentrations in the prediction of vancomycin clearance. A population pharmacokinetic model of vancomycin was developed using NONMEM software from a total of 1,373 vancomycin concentration measurements in 678 patients whose serum creatinine concentrations were lower than 1.2 mg/dL. Covariate selection revealed that cystatin C was the most influential factor and had negative influence (-0.78) in the relationship. Total body weight, sex, age, and serum creatinine were also significantly correlated with the clearance. The estimated intersubject variabilities of clearance and volume of distribution were 24.7% and 25.1%, respectively. A 14-fold difference in predicted trough concentrations was observed according to only cystatin C concentrations in a population of simulated individuals with median demographic characteristics. The use of serum cystatin C as marker of vancomycin clearance for more accurate predictions of serum vancomycin concentrations could be useful, particularly among patients with normal serum creatinine concentrations.
Adolescent ; Adult ; Age Factors ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents/blood/*pharmacokinetics ; Biological Markers/blood ; Body Weight ; Creatinine/*blood ; Cystatin C/*blood ; Demography ; Female ; Humans ; Male ; Middle Aged ; Models, Statistical ; Sex Factors ; *Software ; Vancomycin/blood/*pharmacokinetics ; Young Adult

BACKGROUND: Concerns regarding increasing microbial resistance to vancomycin have resulted in recommendations for a higher trough serum vancomycin concentration. This study aimed to assess the dosage guidelines targeting vancomycin trough concentrations of 15-20 mg/L. METHODS: About 216 adult patients (age, >60 yr) were treated with intravenous vancomycin. The patients were divided into 2 groups according to their target vancomycin trough concentrations: the previous guideline group (n=108) treated with targeted vancomycin trough concentrations of 5-15 mg/L from Jan 2009 through April 2011 and the new guideline group (n=108) treated with targeted concentrations of 15-20 mg/L from November 2011 through July 2012. RESULTS: The 2 groups were not significantly different with respect to age, weight, initial serum creatinine, initial creatinine clearance, predictive trough levels, doses, serum drug concentrations, and area under the curve/minimal inhibitory concentrations. Regarding the proportions of vancomycin trough concentrations, the target range was achieved in 50% in the previous guideline group and in 16% in the new guideline group. In the previous and new guideline groups, the trough concentrations of 10-20 mg/dL were observed in 32.4% and 52.8% patients, respectively, and those of <10 mg/L were observed in 45.4% and 29.6%, respectively. CONCLUSIONS: Compared to the previous guideline group, the new guideline group showed higher proportions in the therapeutic range of 10-20 mg/L and lower proportions in trough concentrations <10 mg/L. The strictly managed vancomycin therapeutic drug monitoring in the new guideline group was assessed as more effective.
Aged ; *Drug Monitoring ; Female ; Gram-Positive Bacterial Infections/drug therapy ; Guidelines as Topic ; Half-Life ; Humans ; Injections, Intravenous ; Male ; Middle Aged ; Vancomycin/*blood/pharmacokinetics/therapeutic use

Human infection by Rhodococcus species is rare and mostly limited to immunocompromised hosts such as patients infected with the human immunodeficiency virus (HIV) or organ transplant recipients. The most common strain is R. equi, and the most common clinical presentation is pulmonary infection, reported in 80% of Rhodococcus spp. infections. The central nervous system is an uncommon infection site. We report a case of a patient with pneumonia, brain abscess, and recurrent meningitis caused by Rhodococcus spp. He initially presented with pneumonia with necrosis, which progressed to brain abscess and recurrent meningitis. Rhodococcus spp. was identified from the cerobrospinal fluid (CSF) collected during his fourth hospital admission. Despite prolonged treatment with appropriate antibiotics, meningitis recurred three times. Finally, in order to administer antibiotics directly into the CSF and bypass the blood-brain barrier, an Ommaya reservoir was inserted for administration of 90 days of intrathecal vancomycin and amikacin in conjunction with intravenous and oral antibiotics; the patient was finally cured with this treatment regimen.
Amikacin ; Anti-Bacterial Agents ; Blood-Brain Barrier ; Brain Abscess ; Central Nervous System ; HIV ; Humans ; Immunocompromised Host ; Injections, Spinal* ; Meningitis* ; Necrosis ; Pneumonia ; Rhodococcus* ; Transplants ; Vancomycin*

OBJECTIVETo summarize the clinical features of Enterococcus faecium meningitis in children.

METHODSThe clinical data of nine children with Enterococcus faecium meningitis were analyzed.

RESULTSIn all the nine children, Enterococcus faecium was isolated from blood, cerebrospinal fluid, or peripherally inserted central catheters; 6 (67%) patients were neonates, 2 (22%) patients were younger than 6 months, and 1 (11%) patient was three years and four months of age. In those patients, 56% had high-risk factors before onset, which included intestinal infection, resettlement of drainage tube after surgery for hydrocephalus, skull fracture, perinatal maternal infection history, and catheter-related infection. The main symptoms were fever and poor response. In those patients, 22% had seizures; no child had meningeal irritation sign or disturbance of consciousness. The white blood cell count and level of C-reactive protein were normal or increased; the nucleated cell count in cerebrospinal fluid was normal or mildly elevated; the protein level was substantially elevated; the glucose level was decreased. The drug sensitivity test showed that bacteria were all sensitive to vancomycin and the vancomycin treatment was effective. Only one child had the complication of hydrocephalus.

CONCLUSIONSEnterococcus faecium meningitis occurs mainly in neonates and infants. The patients have atypical clinical features. A high proportion of patients with Enterococcus faecium meningitis have high-risk factors. Enterococcus faecium is sensitive to vancomycin.

C-Reactive Protein ; analysis ; Enterococcus faecium ; drug effects ; Female ; Gram-Positive Bacterial Infections ; blood ; diagnosis ; drug therapy ; etiology ; Humans ; Infant ; Infant, Newborn ; Male ; Meningitis, Bacterial ; blood ; diagnosis ; drug therapy ; etiology ; Vancomycin ; pharmacology