Vancomycin is a bacteriocidal antibiotic experiencing a resurgence of utility because of increasing clinical problems with methicillinresistant staphylcoccal infections. Vancomycin can cause two types of hypersensitivity reactions, the red man syndrome and anaphylaxis. There is a consensus that slow intravenous administration of vancomycin should minimize the risk of infusion related adverse effects. We report a case of vancomycin hypersensitivity reaction with slow infusion of vancomycin.
Administration, Intravenous ; Anaphylaxis ; Consensus ; Hypersensitivity ; Vancomycin

OBJECTIVE: To investigate the effectiveness and safety of clinical pharmacists-directed vancomycin dosing and therapeutic drug monitoring (TDM), and to promote the individualized medication of vancomycin. METHODS: Information of hospitalized patients treated by vancomycin admitted to Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2011 to October 2017 was collected retrospectively during study period, the patients were divided into pharmacists intervention and non-pharmacists intervention groups according to pharmacist-directed vancomycin dosing guideline or not. The individualized dosing regimen of vancomycin for the patients in pharmacists intervention group was guided by clinical pharmacists, this guideline was that pharmacists offered the TDM guidance, made the individualized dosage regimen of vancomycin, etc., which based on the patients' pathophysiology, condition, and the adjustments of increased dose or 24-hour continuous infusion vancomycin were made for patients if the steady-state trough concentrations fell below the target level. Vancomycin dosage was made for patients in the non-pharmacists intervention group by physicians only based on vancomycin instructions or clinical experience. The vancomycin dosing, TDM, microorganism culture, renal function, 30-day mortality rate, and length of hospital stay were recorded. The appropriateness of TDM for vancomycin was defined as a blood collection within 1 hour of the next scheduled dose after steady state achieved. The rationality of the initial dosing regimen was determined based on the vancomycin application guidelines issued by Infectious Diseases Society of America (IDSA) in 2009. RESULTS: A total of 258 patients were enrolled, and there were 158 patients in the non-pharmacists intervention group and 100 in pharmacists intervention group. The appropriateness of TDM for vancomycin in pharmacists intervention group was significantly improved as compared with that in non-pharmacists intervention group [87.0% (87/100) vs. 69.6% (110/158), P < 0.01], the percentage of first trough serum concentrations drawn on day 3 after steady state achieved was significantly increased [51.0% (51/100) vs. 37.3% (53/142), P < 0.05]. Compared with the non-pharmacists intervention group, the percentages of patients who received appropriate initial dosing and attained the initial target therapeutic range in pharmacists intervention group were significantly increased [87.4% (76/87) vs. 68.2% (75/110), 51.7% (45/87) vs. 30.9% (34/110), both P < 0.01], the percentage of patients whose vancomycin dosing regimen was adjusted based on TDM results was also significantly increased [54.0% (47/87) vs. 15.5% (17/110), P < 0.01], the rate of vancomycin serum concentrations reaching the standard was increased [70.1% (61/87) vs. 32.7% (36/110), P < 0.01], and a lower number of patients in sub- or supra-therapeutic range was observed in pharmacists intervention group [27.6% (24/87) vs. 46.4% (51/110), 2.3% (2/87) vs. 20.9% (23/110), both P < 0.01]. In addition, a lower incidence of vancomycin-induced acute kidney injury (AKI) was observed in pharmacists intervention group as compared with that in non-pharmacists intervention group [0 (0/87) vs. 6.4% (7/110), P < 0.01]. No significant difference was observed in the microorganism culture, 30-day mortality rate or length of hospital stay between the two groups. Among the 87 patients in pharmacists intervention group, the vancomycin dosing was adjusted for 42 patients who did not attain the target therapeutic range, increasing the dose of vancomycin was made for 22 patients, 24-hour continuous infusion was made for 20 patients. Compared with the only increasing vancomycin dose group, vancomycin continuous infusion for 24 hours could significantly increase the serum trough concentration (mg/L: 18.0±6.7 vs. 12.5±5.8, P < 0.05), and reduce daily dosage (mg/kg: 27.1±7.1 vs. 36.6±9.2, P < 0.01). CONCLUSIONS The implementation of a pharmacist-directed vancomycin dosing guideline based on TDM optimized vancomycin dosing regimen, improved the accuracy and timeliness of TDM for vancomycin, achieved a higher percentage of levels within the therapeutic range, and a lower incidence of vancomycin-induced AKI.
Anti-Bacterial Agents ; China ; Drug Monitoring ; Humans ; Pharmacists ; Retrospective Studies ; Vancomycin/administration & dosage*

Pharmacokinetic parameters can be significantly altered for acute kidney injury (AKI), extracorporeal membrane oxygenation (ECMO) and continuous veno-venous hemofiltration therapy (CVVH). Here we reported a case of individualized vancomycin dosing for a patient diagnosed as severe acute pancreatitis treated with concurrent ECMO and CVVH. A 65 kg 32-year-old woman was admitted to hospital presented with severe acute pancreatitis (SAP), respiratory failure, metabotropic acidosis and hyperkalemia. She was admitted to intensive care unit (ICU) on hospital day 1 and was initiated on CVVH. She progressed to multiple organ dysfunction syndrome (MODS) and acute respiratory distress syndrome (ARDS) on ICU day 2, and veno-venous ECMO was instituted. Several catheters were inserted into the body to support ECMO, CVVH and pulse indicator continuous cardiac output (PiCCO), so vancomycin was prescribed empirically on ICU day 3 for prevention of catheter-related infection. Given the residual renal function and continuous hemofiltration intensity on day 3, vancomycin bolus of 1 000 mg was prescribed, followed by a maintenance dose of 500 mg every 8 hours. On ICU day 4, a vancomycin trough serum concentration of 14.1 mg/L was obtained before the fourth dose, which was within the target range of 10-20 mg/L. By ICU day 7, vancomycin dosage was elevated to 1.0 g every 12 hours because of aggravated infection and improved kidney function. On ICU day 14, a vancomycin trough serum concentration of 17 mg/L was obtained. Her white blood cell (WBC) and neutrophil percentage (Neut%) dropped to the normal level by ICU day 19. This vancomycin regimen was successful in providing a target attainment of trough serum concentration ranging from 10-20 mg/L quickly and in controlling infection-related symptoms and signs properly. With the help of this case report we want to call attention to the clinically significant alteration in vancomycin pharmacokinetics among critically ill patients. Individualized vancomycin dosing regimens and therapeutic drug monitoring are necessary for critically ill patients receiving CVVH and ECMO to ensure that the target serum vancomycin levels are reached to adequately treat the infection and avoid nephrotoxicity.
Adult ; Anti-Bacterial Agents/administration & dosage* ; Critical Illness ; Extracorporeal Membrane Oxygenation ; Female ; Hemofiltration ; Humans ; Pancreatitis/drug therapy* ; Vancomycin/administration & dosage*

OBJECTIVE: To explore the impact of augmented renal clearance (ARC) on vancomycin pharmacokinetic target attainment in severe infective patients, and to analyze the initial dose of vancomycin based on the measured 12-hour urinary creatinine clearance (12 h-CL_CR). METHODS: A retrospective observational study was conducted. The patients with severe infection, who receiving vancomycin empiric or targeted therapy, admitted to intensive care unit (ICU) of the Affiliated Drum Tower Hospital of Nanjing University Medical School from February 2013 to December 2017 were enrolled. All patients were treated with vancomycin intravenously by intermittent bolus every 6-12 hours. After four or five doses, blood samples were drawn before the next dosage for serum trough vancomycin concentration (Cmin), and target concentration was defined between 15 mg/L and 20 mg/L. The urine creatinine (UCr) was measured, and CL_CR was calculated. ARC was defined as 12 h-CL_CR > 130 mL×min^-1×1.73 m^-2. According to 12 h-CL_CR before treatment, the patients were divided into ARC group and non-ARC group. The basic renal function of the patients was monitored, and the dosage of vancomycin and the dosage of vancomycin when the blood concentration reached the target were recorded. The correlations between 12 h-CL_CR and the dosage of vancomycin when the blood concentration reached the target as well as the blood concentration of vancomycin were analyzed by Spearman correlation analysis. Dosage stratification analysis was carried out according to different 12 h-CL_CR. The predictive value of 12 h-CL_CR for vancomycin dosage when the blood concentration reached the target was evaluated by using the receiver operator characteristic curve (ROC). RESULTS: Data was provided from a total of 135 patients with severe infection, in which 102 patients met the inclusion criteria. The patients with vancomycin treatment duration less than 72 hours, chronic kidney disease V phase, vancomycin treatment before entering ICU and those with incomplete data were excluded. The mean 12 h-CL_CR was (114.31±73.38) mL×min^-1×1.73 m^-2. The 12 h-CL_CR in ARC group (n = 44, 43.14%) was significantly higher than that in non-ARC group (n = 58, 56.86%) (mL×min^-1×1.73 m^-2: 179.37±59.04 vs. 65.95±35.71, P < 0.01). Target Cmin of vancomycin was achieved in 50.98% of patients (52/102), the target rate in ARC group was significantly lower than that in non-ARC group [29.55% (13/44) vs. 67.24% (39/58), P < 0.01], and the Cmin of vancomycin in ARC group was significantly lower than that in non-ARC group (mg/L: 10.98±6.09 vs. 14.67±6.20, P < 0.01). Spearman correlation analysis showed that there was a significantly negative correlation between 12 h-CL_CR and initial Cmin of vancomycin (n = 102, r = -0.436, P < 0.001), but a positive correlation was found between 12 h-CL_CR and vancomycin dosage when the blood concentration reached the target (n = 52, r = 0.275, P = 0.048). The patients with ARC need higher dosage for blood concentration reaching the target than those without ARC (mg×kg^-1×d^-1: 42.47±13.17 vs. 31.53±14.43, P < 0.01). According to 12 h-CL_CR, the patients with initial treatment reaching the target were divided into five subgroups, < 40, 40-70, 71-100, 101-130 and > 130 mL×min^-1×1.73 m^-2. The results showed that as 12 h-CL_CR increased, the attained dosage of vancomycin was also increased correspondingly. ROC curve analysis showed that when 12 h-CL_CR≥69.83 mL×min^-1×1.73 m^-2, the attained dose of vancomycin when the blood concentration reached the target was greater than conventional dosage of 30 mg×kg^-1×d^-1. CONCLUSIONS Patients with ARC have low concentrations of vancomycin and often fail to achieve therapeutic target. The initial dose of vancomycin can be selected according to 12 h-CL_CR, the higher the 12 h-CL_CR, the more the dosage of vancomycin is. When 12 h-CL_CR is greater than or equal to 69.83 mL×min^-1×1.73 m^-2, the dosage of vancomycin should be higher than the conventional dosage.
Anti-Bacterial Agents ; Creatinine ; Humans ; Infections ; Intensive Care Units ; Kidney Function Tests ; Retrospective Studies ; Vancomycin/administration & dosage*

This study was undertaken to evaluate the in vitro activities of arbekacin-based combination regimens against vancomycin hetero-intermediate Staphylococcus aureus (hetero-VISA). Combinations of arbekacin with vancomycin, rifampin, ampicillin-sulbactam, teicoplanin, or quinipristin-dalfopristin against seven hetero-VISA strains and two methicillin-resistant S. aureus strains were evaluated by the time-kill assay. The combinations of arbekacin with vancomycin, teicoplanin, or ampicillinsulbactam showed the synergistic interaction against hetero-VISA strains. Data suggest that these arbekacin-based combination regimens may be useful candidates for treatment options of hetero-VISA infections.
Virginiamycin/administration & dosage ; Vancomycin/*administration & dosage ; Teicoplanin/administration & dosage ; Sulbactam/administration & dosage ; Staphylococcus aureus/*drug effects/isolation & purification ; Staphylococcal Infections/drug therapy/microbiology ; Microbial Sensitivity Tests ; Methicillin Resistance ; Humans ; Drug Synergism ; Drug Resistance, Bacterial ; Dibekacin/administration & dosage/*analogs & derivatives ; Anti-Bacterial Agents/*administration & dosage ; Ampicillin/administration & dosage ; Aminoglycosides/*administration & dosage

This study aimed to develop a guideline for therapeutic drug monitoring (TDM) of vancomycin. We adopted the new guideline definition from the Institute of Medicine (IOM), adhered closely to the six domains of the Appraisal of Guidelines for Research & Evaluation II (AGREE II), and made recommendations based on systematic reviews. We established a Guideline Steering Group and a Guideline Development Group, formulated 12 questions in the form of Population, Intervention, Comparison, Outcome (PICO) and completed a literature search. As far as we know, we will develop the first evidenced-based guideline for vancomycin TDM under the framework of the Grade of Recommendations Assessment, Development and Evaluation (GRADE).
Anti-Bacterial Agents ; administration & dosage ; economics ; pharmacokinetics ; China ; Drug Administration Schedule ; Drug Monitoring ; methods ; Evidence-Based Medicine ; Humans ; Methicillin-Resistant Staphylococcus aureus ; drug effects ; growth & development ; pathogenicity ; Staphylococcal Infections ; drug therapy ; microbiology ; pathology ; Vancomycin ; administration & dosage ; economics ; pharmacokinetics

The two-stage exchange arthroplasty (one- or two-stage) is believed to be the gold standard for the management of infections following total knee arthroplasty. We herein report a novel two-stage exchange arthroplasty technique using an antibiotic-impregnated cement intramedullary nail, which can be easily prepared during surgery using a straight thoracic tube and a Steinmann pin, and may provide additional stability to the knee to maintain normal mechanical axis. In addition, there is less pain between the period of prosthesis removal and subsequent reimplantation. Less soft tissue contracture, less scar adhesion, easy removal of the cement intramedullary nail, and successful infection control are the advantages of this technique.
Aged ; Anti-Bacterial Agents/*administration & dosage ; *Arthroplasty, Replacement, Knee ; *Bone Cements ; *Bone Nails ; *Device Removal ; Female ; Gentamicins/administration & dosage ; Humans ; Knee Prosthesis/*adverse effects ; Orthopedic Procedures/methods ; Prosthesis-Related Infections/*therapy ; Reoperation ; Vancomycin/administration & dosage

OBJECTIVETo test the survival of Staphylococcus aureus (S. aureus) inside lymphocyte that contributes to the pathogenesis of infection and possible anti-inflammatory and antioxidative effect of nanoconjugated vancomycin against in vivo S. aureus infection in a dose and duration dependent manner.

METHODS5×10(6) CFU/mL vancomycin-sensitive S. aureus (VSSA) and vancomycin-resistive S. aureus (VRSA) were challenged in Swiss male mice for 3 days, 5 days, 10 days and 15 days, respectively. Bacteremia and inflammatory parameters were observed to evaluate the duration for development of VSSA and VRSA infection. 100 mg/kg bw/day and 500 mg/kg bw/day nanoconjugated vancomycin were administrated to VSSA and VRSA infected group for 5 days. Bacteremia, inflammatory parameters and oxidative stress related parameters were tested to observe the effective dose of nanoconjugated vancomycin against VSSA and VRSA infection. Nanoconjugated vancomycin was treated at a dose of 100 mg/kg bw/day and 500 mg/kg bw/day, respectively, to VSSA and VRSA infected group for successive 5 days, 10 days and 15 days. Bacteremia, inflammatory parameters and oxidative stress related parameters were observed to assess the effective duration of nanoconjugated vancomycin against VSSA and VRSA infection.

RESULTSThe result revealed that in vivo VSSA and VRSA infection developed after 5 days of challenge by elevating the NO generation in lymphocyte and serum inflammatory markers. Administration with nanoconjugated vancomycin to VSSA and VRSA infected group at a dose of 100 mg/kg bw/day and 500 mg/kg bw/day, respectively, for successive 10 days eliminated bacterimia, decreased NO generation in lymphocyte, serum inflammatory markers and increased antioxidant enzyme status.

CONCLUSIONSThese findings suggest, in vivo challenge of VSSA and VRSA for 5 days can produce the highest degree of damage in lymphocyte which can be ameliorated by treatment with nanoconjugated vancomycin for 10 successive days.

Animals ; Anti-Bacterial Agents ; administration & dosage ; chemistry ; Bacteremia ; drug therapy ; immunology ; microbiology ; Drug Delivery Systems ; Humans ; Male ; Mice ; Nanoparticles ; chemistry ; Nitric Oxide ; immunology ; Staphylococcal Infections ; drug therapy ; immunology ; microbiology ; Staphylococcus aureus ; drug effects ; pathogenicity ; physiology ; Vancomycin ; administration & dosage ; chemistry ; Vancomycin Resistance

Adolescent ; Adult ; Aged ; Agranulocytosis ; complications ; drug therapy ; Anti-Bacterial Agents ; administration & dosage ; therapeutic use ; Child ; Female ; Humans ; Leukemia ; complications ; drug therapy ; Male ; Middle Aged ; Treatment Outcome ; Vancomycin ; administration & dosage ; therapeutic use ; Young Adult

OBJECTIVETo analyze the use of antibiotics and the drug resistance of Pseudomonas aeruginosa in the burn ward of our hospital in the past 11 years, so as to optimize the use of antibiotics in the future.

METHODSBacterial epidemiology during 1991-2001 in our burn ward was investigated. The change of the drug resistance of Pseudomonas aeruginosa was observed by defined daily dose (DDD) of antibiotics in adult patients and by the ranking of antibiotic administration days.

RESULTS(1) Staphylococcus aureus (10.53%-34.40%) and Pseudomonas aeruginosa (75.66%-11.47%) were dominant in our burn ward. (2) Predominant antibiotics used included Penicillin, Amikacin, Vancomycin, Imipenem and Ceftazidime. (3) There was increasing drug resistance of Pseudomonas aeruginosa to the following antibiotics ranking in following order: Piperacillin (41.57%-100.00%), Imipenem (36.36%-98.46%), Ceftazidime (23.46%-97.85%), Amikacin (13.16%-100.00%) and ciprofloxacin (6.90%-100.00%).

CONCLUSIONThere was increasing drug resistance of Pseudomonas aeruginosa to all antibiotics, which might be related to antibiotic abuse.

Amikacin ; therapeutic use ; Anti-Bacterial Agents ; therapeutic use ; Burn Units ; Ceftazidime ; therapeutic use ; Drug Administration Schedule ; Drug Resistance, Bacterial ; drug effects ; Humans ; Imipenem ; therapeutic use ; Penicillins ; therapeutic use ; Pseudomonas aeruginosa ; drug effects ; Vancomycin ; therapeutic use