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A vancomycin monitoring program at a community hospital.

BACKGROUND: Because of concern about patients' increased risk of developing resistance to vancomycin, a vancomycin monitoring program involving education, not restriction, on the prudent use of vancomycin was developed at the Barnes-Jewish Christian (BJC) North Region hospitals in St Louis. The program was spearheaded by the pharmacy department and monitored by interdisciplinary committees within the hospital. METHODS: An educational note based on a Centers for Disease Control and Prevention (CDC) guideline for prudent use of vancomycin was prepared and placed in patient charts by a designated pharmacist. This intervention was tracked along with the medical staff's response to the note. In a one-year period, the rate of appropriate use of vancomycin increased from 59% to 80% (p < 0.01), whereas the number of care interventions involving vancomycin usage decreased by approximately 75%. DISCUSSION: A community hospital can promote appropriate use of antibiotics, in this case vancomycin. The fact that the rate at which vancomycin was appropriately prescribed increased and the number of pharmacist interventions (notes) decreased suggests that the vancomycin note reminders and related educational material were successful. Although these numbers do not represent 100% compliance, treatment with vancomycin may have been clinically appropriate for some of the cases even if the situation was not listed as an appropriate use in the CDC guideline. CONCLUSION: The vancomycin monitoring program, which represents a simple means of intervening and maintaining continuous monitoring and quality improvement in a clinical area, continues at the BJC North Region hospitals.

Anti-Bacterial Agents↗

Control of vancomycin-resistant enterococcus in health care facilities in a region.

BACKGROUND: In late 1996, vancomycin-resistant enterococci were first detected in the Siouxland region of Iowa, Nebraska, and South Dakota. A task force was created, and in 1997 the assistance of the Centers for Disease Control and Prevention was sought in assessing the prevalence of vancomycin-resistant enterococci in the region's facilities and implementing recommendations for screening, infection control, and education at all 32 health care facilities in the region. METHODS: The infection-control intervention was evaluated in October 1998 and October 1999. We performed point-prevalence surveys, conducted a case-control study of gastrointestinal colonization with vancomycin-resistant enterococci, and compared infection-control practices and screening policies for vancomycin-resistant enterococci at the acute care and long-term care facilities in the Siouxland region. RESULTS: Perianal-swab samples were obtained from 1954 of 2196 eligible patients (89 percent) in 1998 and 1820 of 2049 eligible patients (89 percent) in 1999. The overall prevalence of vancomycin-resistant enterococci at 30 facilities that participated in all three years of the study decreased from 2.2 percent in 1997 to 1.4 percent in 1998 and to 0.5 percent in 1999 (P<0.001 by chi-square test for trend). The number of facilities that had had at least one patient with vancomycin-resistant enterococci declined from 15 in 1997 to 10 in 1998 to only 5 in 1999. At both acute care and long-term care facilities, the risk factors for colonization with vancomycin-resistant enterococci were prior hospitalization and treatment with antimicrobial agents. Most of the long-term care facilities screened for vancomycin-resistant enterococci (26 of 28 in 1998 [93 percent] and 23 of 25 in 1999 [92 percent]) and had infection-control policies to prevent the transmission of vancomycin-resistant enterococci (22 of 25 [88 percent] in 1999). All four acute care facilities had screening and infection-control policies for vancomycin-resistant enterococci in 1998 and 1999. CONCLUSIONS: An active infection-control intervention, which includes the obtaining of surveillance cultures and the isolation of infected patients, can reduce or eliminate the transmission of vancomycin-resistant enterococci in the health care facilities of a region.

Adult↗

The emergence of decreased susceptibility to vancomycin in Staphylococcus epidermidis.

BACKGROUND: Coagulase-negative staphylococci (CNS) are the major cause of nosocomial bloodstream infection. Emergence of vancomycin resistance among CNS is a serious public health concern, because CNS usually are multidrug-resistant, and glycopeptide antibiotics, among which only vancomycin is available in the United States, are the only remaining effective therapy. In this report, we describe the first bloodstream infection in the United States associated with a Staphylococcus epidermidis strain with decreased susceptibility to vancomycin. METHODS: We reviewed the hospital's microbiology records for all CNS strains, reviewed the patient's medical and laboratory records, and obtained all available CNS isolates with decreased susceptibility to vancomycin. Blood cultures were processed and CNS isolates identified by using standard methods; antimicrobial susceptibility was determined by using minimum inhibitory concentration (MIC) and disk-diffusion methods. Nares cultures were obtained from exposed healthcare workers (HCWs) to identify possible colonization by CNS with decreased susceptibility to vancomycin. RESULTS: The bloodstream infection by an S. epidermidis strain with decreased susceptibility to vancomycin occurred in a 49-year-old woman with carcinoma. She had two blood cultures positive for CNS; both isolates were S. epidermidis. Although susceptible to vancomycin by the disk-diffusion method (16-17 mm), the isolates were intermediate by MIC (8-6 microg/mL). The patient had received an extended course of vancomycin therapy; she died of her underlying disease. No HCW was colonized by CNS with decreased susceptibility to vancomycin. CONCLUSIONS: This is the first report in the United States of bloodstream infection due to S. epidermidis with decreased susceptibility to vancomycin. Contact precautions likely played a role in preventing nosocomial transmission of this strain, and disk-diffusion methods may be inadequate to detect CNS with decreased susceptibility to vancomycin.

Anti-Bacterial Agents↗

Effect of vancomycin therapy for osteomyelitis on colonization by methicillin-resistant Staphylococcus aureus: lack of emergence of glycopeptide resistance.

BACKGROUND: In treating orthopedic infections, the long-term impact of vancomycin therapy on colonization by methicillin-resistant Staphylococcus aureus (MRSA) and the emergence of vancomycin-intermediate S. aureus is unknown. DESIGN: Prospective surveillance of the effect of long-term vancomycin therapy on colonization by MRSA and the emergence of vancomycin-intermediate S. aureus. METHODS: Thirty-four patients with MRSA osteomyelitis that was microbiologically documented were longitudinally observed for the emergence of vancomycin-intermediate S. aureus at 3 body sites (wound, anterior nares, and groin) during the initial period of vancomycin therapy and at the 2-month follow-up. Twenty patients received the standard dose (20 mg/kg/d) for 34 +/- 6 days and 14 patients received a high dose (40 mg/kg/d) of vancomycin for 37 +/- 9 days. RESULTS: During vancomycin treatment, global MRSA carriage (all body sites) fell from 100% to 25% in the group of patients receiving the standard dose of vancomycin, and from 100% to 40% in the group receiving the high dose. During the 2-month follow-up period after vancomycin therapy, global MRSA carriage increased from 25% to 55% in the group receiving the standard dose and decreased from 43% to 36% in the group receiving the high dose. CONCLUSION: Therapy with a high dose of vancomycin contributes to the sustained eradication of MRSA carriage without promoting the emergence of glycopeptide resistance.

Adult↗

High vancomycin dosage regimens required by intensive care unit patients cotreated with drugs to improve haemodynamics following cardiac surgical procedures.

The aim of this study was to evaluate retrospectively the importance of a Bayesian pharmacokinetic approach for predicting vancomycin concentrations to individualize its dosing regimen in 18 critically ill patients admitted to intensive care units following cardiothoracic surgery. The possible influence of some coadministered drugs with important haemodynamic effects (dopamine, dobutamine, frusemide) on vancomycin pharmacokinetics was assessed. Vancomycin serum concentrations were measured by fluorescence polarization immunoassay. Vancomycin dosage regimens predicted by the Bayesian method (D(a)) were compared retrospectively with Moellering's nomogram-based dosages (D(M)) to assess possible major differences in vancomycin dosing. D(a) values were similar to D(M) in 10 patients (D(a) approximately D(M) group) (20.52 +/- 8.40 mg/kg/day versus 18.81 +/- 7.24 mg/kg; P = 0.15), whereas much higher dosages were required in the other eight patients (D(a) >> D(M) group) (26.78 +/- 3.01 mg/kg/day versus 18.95 +/- 3.41 mg/kg/day; P < 0.0001) despite no major difference in attained vancomycin steady-state trough concentration (C(min ss)) (9.22 +/- 1. 33 mg/L versus 8.99 +/- 1.26 mg/L; = 0.75) or estimated creatinine clearance (1.23 +/- 0.49 mL/min/kg versus 1.21 +/- 0.24 mL/min/kg; P = 0.95) being found between the two groups. The ratio between D(a) and D(M) was significantly higher in the D(a) >> D(M) group than in the D(a) approximately D(M) group (1.44 +/- 0.18 versus 1.10 +/- 0. 21; P < 0.01). In four D(a) >> D(M) patients the withdrawal of cotreatment with haemodynamically active drugs was followed by a sudden substantial increase in the vancomycin C(min ss) (13.30 +/- 1. 13 mg/L versus 8.79 +/- 0.87 mg/L; P < 0.01), despite no major change in bodyweight or estimated creatinine clearance being observed. We postulate that these drugs with important haemodynamic effects may enhance vancomycin clearance by inducing an improvement in cardiac output and/or renal blood flow, and/or by interacting with the renal anion transport system, and thus by causing an increased glomerular filtration rate and renal tubular secretion. Given the wide simultaneous use of vancomycin and dopamine and/or dobutamine and/or frusemide in patients admitted to intensive care units, clinicians must be aware of possible subtherapeutic serum vancomycin concentrations when these drugs are coadministered. Therefore, therapeutic drug monitoring (TDM) for the pharmacokinetic optimization of vancomycin therapy is strongly recommended in these situations.

Anti-Bacterial Agents↗

Vancomycin mass transfer characteristics of high-flux cellulosic dialysers.

BACKGROUND: In comparison to conventional haemodialysis membranes, highly permeable membranes allow a broader spectrum of solute removal, including enhanced elimination of vancomycin (1448 Daltons). However, the mass transfer characteristics of vancomycin removal by highly permeable membranes have not been adequately assessed. An understanding of vancomycin's predominant dialytic mass transfer mechanism under a given set of operating conditions, including dialyser type and flow rates, may permit more accurate dosing of the drug. METHODS: We performed a mass transfer analysis of vancomycin removal by a high-flux dialyser, cellulose triacetate (CT). In a cross-over fashion with a 3-week washout between treatments, eight subjects received vancomycin 1000 mg (1) during the last hour of CT haemodialysis; or (2) after dialysis. Serial urea and vancomycin serum concentrations were used to assess dialytic removal. RESULTS: Dialysis removed 26.2% (mean; range 16-44%) of the administered vancomycin dose. While vancomycin removal and (Kt/V)urea were directly correlated (r = 0.88; P < 0.005), no correlation was observed between vancomycin removal and weight-normalized ultrafiltration rate. CONCLUSIONS: These findings suggest that for the CT dialyser and dialysis operating conditions employed in this study, vancomycin clearance was primarily mediated by diffusion. As such, these data challenge the general concept that convection is primarily responsible for the removal of solutes in the same molecular weight class as vancomycin during high-flux dialysis.

Adult↗

Intraoperative and postoperative effects of vancomycin administration in cardiac surgery patients: a prospective, double-blind, randomized trial.

OBJECTIVES: In response to an increased frequency of Staphylococcus epidermidis infections in postoperative cardiac surgery patients, antibiotic prophylaxis was changed to include both vancomycin and cefazolin pre- and intraoperatively. Subsequent to the addition of vancomycin prophylaxis, clinical impression and retrospective analysis supported a correlation between vancomycin administration and post-cardiopulmonary bypass norepinephrine use. DESIGN: A prospective, double-blind, randomized study. SETTING: Tertiary care center in a university hospital. PATIENTS: A total of 58 patients undergoing elective coronary artery bypass surgery under high-dose fentanyl anesthesia. INTERVENTIONS: Patients were randomized to receive cefazolin and either vancomycin or normal saline pre-, intra-, and postoperatively in a double-blinded protocol. MEASUREMENTS AND MAIN RESULTS: Hemodynamic profiles and doses of administered vasoactive agents were calculated and recorded for all patients for both intra- and postoperative time periods. Hypotension consistent with vasodilation was treated with a norepinephrine infusion. The rate and frequency of norepinephrine infusions were tabulated for both groups. Hemodynamic profiles that were obtained after the administration of the initial dose of vancomycin or normal saline and before the induction of general anesthesia and those profiles obtained after the induction of general anesthesia until the initiation of cardiopulmonary bypass showed no difference between groups and no evidence of vasodilation secondary to vancomycin administration. However, subsequent doses of vancomycin in the intra- and postoperative periods were associated with a significantly greater frequency of norepinephrine infusions to maintain normal hemodynamic indices. In the vancomycin group, 50% of patients received a norepinephrine infusion in the intra- and/or postoperative period as compared with 14% in the normal saline group (p < .01). Furthermore, the group of patients who received vancomycin and subsequently required a norepinephrine infusion had significantly lower mean systolic arterial pressure, mean arterial pressure, and systemic vascular resistance as compared with all other groups. There were no differences between groups in the use of vasopressors (other than norepinephrine) or fluid balance. CONCLUSIONS: The results show that a significantly greater number of patients who received vancomycin required a norepinephrine infusion and that, despite norepinephrine infusion therapy, systemic vascular resistance was not normalized in this group of patients. The study supports the conclusion that perioperative administration of vancomycin in cardiac surgery patients may result in hypotension requiring the use of a vasopressor in an attempt to normalize hemodynamic indices.

Aged↗

Vancomycin pharmacokinetics in critically ill patients receiving continuous venovenous haemodiafiltration.

AIMS: To investigate the pharmacokinetics of vancomycin in critically ill patients on continuous venovenous haemodiafiltration (CVVHDF), a continuous renal replacement therapy (CRRT) and to see if routine measures approximate vancomycin clearance. METHODS: Pharmacokinetic profiles (15) of initial and steady-state doses of 750 mg twice daily intravenous vancomycin were obtained from blood and ultrafiltrate samples from 10 critically ill patients in the intensive care unit, with acute renal failure on CVVHDF (1 l h(-1) dialysate plus 2 l h(-1) filtration solution; 3 l h(-1) effluent; extracorporeal blood flow 200 ml min(-1)). RESULTS: CVVHDF clearance of vancomycin was 1.8 +/- 0.4 l h(-1) (30 +/- 6.7 ml min(-1)). This was 1.3-7.2 times that reported previously for vancomycin using other forms of CRRT. Total vancomycin body clearance was 2.5 +/- 0.7 l h(-1) (41.7 +/- 11.7 ml min(-1)). The clearance of vancomycin by CVVHDF was 76 +/- 16.5% of the total body clearance. CVVHDF removed approximately half the vancomycin dose during the 12-h period (A(CVVHDF) = 413 mg). The fraction eliminated by all routes was 60%. The sieving coefficient for vancomycin was 0.7 +/- 0.1 and for urea was 0.8 +/- 0.06. CONCLUSIONS: Vancomycin is cleared effectively by CVVHDF. Clearance was faster than other forms of CRRT, therefore doses need to be relatively high. Urea clearance slightly overestimates vancomycin clearance. The administered doses of 750 mg every 12 h were too high and accumulation occurred, as only approximately 60% of a dose was cleared over this period. The maintenance dose required to achieve a target average steady-state plasma concentration of 15 mg l(-1) can be calculated as 450 mg every 12 h.

Adult↗

Susceptibility to vancomycin of methicillin-resistant Staphylococcus aureus isolated in a university hospital in Japan.

Intravenous vancomycin was approved in 1991 in Japan and has been widely used for treatment of infections caused by methicillin-resistant Staphylococcus aureus (MRSA). Consequently, ever since the initial discovery of vancomycin intermediate-resistant S. aureus in Japan, the vancomycin resistance of this organism has been a great concern in clinical settings. We investigated whether vancomycin resistance had emerged in MRSA isolated in our hospital since the approval of the use of intravenous vancomycin. Vancomycin susceptibility was evaluated on the basis of minimum inhibitory concentrations determined by the agar dilution method and a heterogeneous resistance examination. The median minimum inhibitory concentration of the 69 MRSA strains isolated in 1988 and the 74 isolated in 1998 was 0.75 microgram/ml and 1.0 microgram/ml, respectively (p < 0.001), however, all of the strains were classified in the susceptible group. None of them was an MRSA heterogeneously resistant to vancomycin (hetero-VRSA), which has been defined as a strain having a 1/10(6) or greater heterogeneously resistant subpopulation to vancomycin. In another set of investigations, no hetero-VRSA were found among 12 other MRSA strains isolated after intravenous administration of vancomycin for 14 or more days (range: 14 to 77 days). We conclude that while the use of intravenous vancomycin may have slightly lowered the vancomycin susceptibility of MRSA in our hospital, the decrease in so small that it may not be significant clinically. In addition, no hetero-VRSA were found in our hospial.

Aged↗

Double-blind comparison of teicoplanin versus vancomycin in febrile neutropenic patients receiving concomitant tobramycin and piperacillin: effect on cyclosporin A-associated nephrotoxicity.

A prospective, randomized, and double-blind study comparing teicoplanin with vancomycin in the initial management of febrile neutropenic patients was conducted. Teicoplanin was administered at 6 mg per kg of body weight every 24 h (q24h) intravenously (i.v.) after initial loading at 6 mg/kg q12h for three doses. Vancomycin was administered at 15 mg/kg q12h i.v. Patients also received piperacillin (3 g q4h i.v.) and tobramycin (1.5 to 2.0 mg/kg q8h i.v.). Of 53 patients enrolled, 50 were judged to be evaluable. Among these, 25 received teicoplanin and 25 received vancomycin. At enrollment, both groups were comparable in age, sex, renal function, underlying hematologic condition, and concurrent therapy. Both groups had similar sites of infection and microbial pathogens. Empirical antimicrobial therapy resulted in the cure of or improvement in 23 (92%) teicoplanin patients and 21 (84%) vancomycin patients (P = 0.67). Failures occurred with two vancomycin patients but no teicoplanin patients. Clinical response was indeterminate for two patients in each group. Adverse reactions occurred significantly more often in the vancomycin group than in the teicoplanin group (P = 0.01), and these reactions required the termination of the study regimens of 6 vancomycin versus 0 teicoplanin patients (P = 0.02). Nephrotoxicity was observed more frequently in the vancomycin group (10 versus 2 patients; P = 0.02). Subgroup analysis revealed a significant deterioration of renal function when vancomycin and cyclosporin A, but not teicoplanin and cyclosporin A, were used concurrently (P = 0.02). Among patients who received vancomycin and amphotericin B or teicoplanin and amphotericin B concurrently, deterioration in renal function was equivalent in both groups. Teicoplanin in the dosage employed was tolerated better than vancomycin in the empirical treatment of fever and neutropenia in our patient population.

Adult↗

Effects of intravitreal dexamethasone on concentration of intravitreal vancomycin in experimental methicillin-resistant Staphylococcus epidermidis endophthalmitis.

Intravitreal corticosteroids in the treatment of bacterial endophthalmitis remain controversial. We utilized an experimental rabbit model of methicillin-resistant Staphylococcus epidermidis endophthalmitis (i) to calculate the intravitreal vancomycin concentration in rabbit eyes receiving intravitreal vancomycin alone or in combination with intravitreal dexamethasone and (ii) to determine whether an intravitreal steroid has any effect on intravitreal vancomycin levels. All right eyes were infected and all left eyes were uninfected. The rabbits were divided into two treatment groups: (i) 32 eyes (group I) were injected with intravitreal vancomycin, 1.0 mg (0.1 ml); (ii) 32 additional eyes (group II) were injected with intravitreal dexamethasone, 400 micrograms (0.1 ml), in addition to vancomycin. Measurement of intravitreal vancomycin concentration was performed following sacrifice, utilizing a microbiologic agar diffusion assay. Analyses of intravitreal vancomycin concentrations were performed by using model-independent parameters, with area under the concentration-time curves derived by trapezoidal approximation. The intravitreal vancomycin concentration was significantly lower in both uninfected and infected group II eyes (P less than 0.002). Analysis of intravitreal vancomycin concentration-time relationships was performed by using a nonlinear least-squares regression program; data best fit a one-compartment model. In addition, no vancomycin-dexamethasone interaction could be demonstrated. The reduced level of intravitreal vancomycin in the presence of intravitreal dexamethasone may have important clinical implications.

Animals↗

Vancomycin skin tests and prediction of "red man syndrome" in healthy volunteers.

The purpose of the present study was to assess the cutaneous response to intradermally administered vancomycin in healthy adults and to determine whether the magnitude of the cutaneous response correlated to the severity of "red man syndrome" (RMS) following intravenous administration of vancomycin to the same subjects. Eleven healthy males were skin tested with intradermally administered histamine and saline controls and intradermally administered vancomycin at different concentrations. Vancomycin caused a dose-dependent area of flare in all subjects. The sigmoidal maximal flare model was used to fit each dose-response curve, and cutaneous responsiveness to vancomycin was quantified by various methods, including the flare area at each dose, maximum flare area (maximal flare), dose required to produce 50% of maximum flare, dose required to produce a flare area of 400 mm2, and the slope of the dose-response curve. One week after skin testing, subjects received an infusion of vancomycin, 15 mg/kg of body weight over 60 min. For the assessment of the severity of RMS, we used previously described methods. Although all subjects experienced erythema from the intravenously administered vancomycin and 10 subjects had pruritus, there was no significant correlation between vancomycin skin test results and the severity of RMS. We conclude that vancomycin skin tests do not predict the severity of RMS. In addition, vancomycin skin tests may be of no benefit for assessing immunoglobulin E-mediated allergy to vancomycin, since all subjects had a positive reaction at concentrations of > or = 10 micrograms/ml.

Adult↗

Potentiation of vancomycin-induced histamine release by muscle relaxants and morphine in rats.

The intravenous injection of vancomycin sometimes causes anaphylactoid reactions, in which histamine release may play a major role. These reactions are more frequently manifested when vancomycin is injected into anesthetized patients. We examined the vancomycin-induced histamine release and the interaction of vancomycin with muscle relaxants or opioid in rats. In an in vitro study with rat peritoneal mast cells, treatment with vancomycin at concentrations of greater than 1.25 mM produced significant histamine release. Tubocurarine, vecuronium, pancuronium, succinylcholine, and morphine up to concentrations of 0.25, 1, 5, 30, and 5 mM, respectively, produced no significant histamine release. However, the nonsignificant histamine release induced by 0.5 mM vancomycin was clearly enhanced by combining vancomycin with any of these agents. In the in vivo study, the intravenous injection of vancomycin significantly increased the plasma histamine levels in rats when vancomycin was injected at 200 mg/kg of body weight (63.2 +/- 34.0 ng/ml [mean +/- standard deviation]) but not when it was injected at 100 mg/kg (30.8 +/- 20.2 ng/ml) compared with that in the saline-treated rats (22.5 +/- 11.4 ng/ml). Although the subcutaneous administration of morphine (10 mg/kg) never increased the plasma histamine levels, the intravenous injection of vancomycin (100 mg/kg) 30 min after this morphine treatment markedly increased the plasma histamine levels (56.0 +/- 26.9 ng/ml). These findings provide experimental evidence that the combination of muscle relaxants or an opioid with vancomycin may increase the risk of anaphylactoid reactions by enhancing the release of histamine.

Animals↗

In vitro assessment of vancomycin HCl compatibility after coinfusion with a specialized amino acid formulation.

Vancomycin usage at British Columbia's Children's Hospital has increased substantially in the Special Care Nursery as a consequence of a study demonstrating a reduced morbidity and mortality in neonates with necrotizing enterocolitis when treated with vancomycin and cefotaxime. The inability to place more than one peripheral intravenous access necessitates interruption of parenteral nutrition to infuse vancomycin, resulting in a reduction of the planned daily intake of these neonates. This is clinically significant with the administration of vancomycin because of the long administration period required for this drug (60 minutes). This study was designed to assess the physical and chemical stability of vancomycin with a standard neonatal parenteral nutrition solution, Vamin A, when coadministered through the same intravenous line. To simulate the actual clinical setting, the dose of vancomycin and the infusion rate of Vamin A were chosen to represent those commonly used in a 1-kg neonate. Physical compatibility was assessed using effluent obtained after coinfusion of vancomycin with parenteral nutrition solution. Duplicate samples were visually checked for color changes and precipitate. High-pressure liquid chromatography (HPLC) and pH testing were used to assess chemical compatibility of vancomycin. The results of physical compatibility revealed no color change or precipitate. No changes in pH were observed. HPLC determination confirmed that there were no significant time-dependent changes in vancomycin stability. The samples were studied over 24 hours to determine the rate of degradation of vancomycin, if any, under various temperature conditions. The concentrations were not significantly different from each other at the different temperatures studied. Thus, there was no apparent change in the concentration of vancomycin in the presence of Vamin A.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗

Control of imported and acquired methicillin-resistant Staphylococcus aureus (MRSA) in mechanically ventilated patients: a dose-response study of enteral vancomycin to reduce absolute carriage and infection.

This study aimed to quantify the animate source provided by the patients using the concept of "absolute carriage" by multiplying the carrier rate by the level of carriage; and to compare the impact of a low and high dose of an oropharyngeal vancomycin gel on the absolute MRSA carriage and infection. In all, 265 patients were included, 126 were MRSA positive. Fifty-five patients received 2% vancomycin gel during the first year whilst 4% vancomycin gel was given to 50 patients during the second year. Surveillance swabs of throat and rectum were obtained from all eligible patients on admission and then twice weekly. The vancomycin protocol was started as soon as the surveillance cultures were positive for MRSA. Those patients received one gram of enteral vancomycin daily, divided into four doses. During the first year 2% vancomycin gel 4 ml (80 mg) was applied in the oropharynx in four doses in addition to the enteral solution (Group A). During the second year 4% vancomycin gel 4 ml (160 mg) was used (Group B). The absolute carriage was high during both periods: 3.6 for Group A, and 3.2 for Group B. The 4% vancomycin protocol significantly reduced the absolute carriage, compared to the 2% vancomycin protocol: 2.6 versus 1.5 (P < 0.01). Significant reduction in secondary endogenous infections was found in the second year: seven versus 15 patients (P < 0.05). A total of 3,588 microbiological samples were processed. Neither Staphylococcus aureus with intermediate sensitivity to vancomycin (VISA) nor vancomycin-resistant enterococci (VRE) were detected.

Administration, Rectal↗

Correlation of aminoglycoside and vancomycin pharmacokinetic parameters.

OBJECTIVE: To investigate a correlation between the elimination rate constants (Ke) of aminoglycosides (AG) and vancomycin; to investigate the correlation between actual Ke and creatinine clearance (Clcr) for AG versus vancomycin; to investigate the calculated versus actual Ke for AG and vancomycin; and to investigate a correlation between volumes of distribution (Vd) between AG and vancomycin. DESIGN: Retrospective data collection. METHODS: Patients in our institution who received AGs or vancomycin concomitantly or within six weeks of each other were identified retrospectively. Patient subpopulations were identified and analyzed collectively as well as individually. Steady-state serum concentrations of AG and vancomycin (more than four half-lives) were obtained and kinetic parameters (Ke, Vd) were calculated using first-order pharmacokinetic equations. Linear regression was used to determine correlation coefficients. RESULTS: In the total population and all subpopulations, the correlation between Ke of AG and vancomycin was superior to the correlation between Ke and Clcr. The correlations (r2) between Ke for AG and vancomycin in the total, general medicine, oncology, and intensive care units (ICU) populations were 0.572, 0.878, 0.349, and 0.561, respectively. The correlations (r2) between Ke and Clcr for AG in the total, general medicine, oncology, and ICU populations were 0.235, 0.430, 0.005, and 0.238, respectively. The correlations (r2) between Ke and Clcr for vancomycin in the total, general medicine, oncology, and ICU populations were 0.300, 0.407, 0.055, and 0.309, respectively. CONCLUSIONS: The correlation between Ke of AG and vancomycin may be beneficial for predicting Ke of vancomycin when AG concentrations have already been obtained or vice versa, and may give more accurate estimations of dosing intervals and require less time adjusting, ordering, and interpreting concentrations and dosages.

Adult↗

Vancomycin-induced neutropenia during treatment of endocarditis in a pediatric patient.

OBJECTIVE: To report a case of reversible vancomycin-associated neutropenia occurring during long-term therapy with vancomycin using weight and age-adjusted dosing. CASE SUMMARY: A 2-year-old boy was started on vancomycin therapy for presumed endocarditis resulting from his ventriculoseptal defect. After 18 days of treatment, neutropenia with an absolute neutrophil count (ANC) of 990 x 10(6) cells/L was noted. The neutropenia progressed over the next 3 days and reached a nadir concentration of 459 x 10(6) cells/L. Vancomycin therapy was discontinued after 17 days (antibiotic day 20). A rise in the ANC occurred within 2 days of discontinuation. An improved ANC of 1672 x 10(6) cells/L occurred within 5 days. Vancomycin serum concentrations remained within an acceptable range: a peak of 30 micrograms/mL and a trough of 9 micrograms/mL. DISCUSSION: Case reports in the literature of vancomycin-associated neutropenia in adults were briefly reviewed and compared. The onset and resolution and mechanism of vancomycin-induced neutropenia were studied. The potential relationship between vancomycin, weight-, and age-adjusted dosing and the occurrence of neutropenia in our pediatric patient was postulated. CONCLUSIONS: Vancomycin is identified as a possible cause of drug-induced neutropenia. More data are needed that clearly indicate vancomycin as the offending agent in children. The vancomycin-induced neutropenia is believed to be immunologically based and independent of drug concentrations.

Child, Preschool↗

Prevention of MRSA pneumonia by oral vancomycin decontamination: a randomised trial.

This study was undertaken to assess whether oropharyngeal vancomycin may control oropharyngeal carriage and lower airway infection due to methicillin-resistant Staphylococcus aureus (MRSA) acquired in the intensive care unit (ICU). Secondary endpoints were the emergence of vancomycin-resistant enterococci, vancomycin-intermediate S. aureus and vancomycin consumption. A total of 84 patients, admitted to a medical/surgical ICU and mechanically ventilated for >72 h, were randomly assigned to control (n=42) or test (n=42) group. Both groups received the protocol of selective decontamination of the digestive tract, including polymyxin E, tobramycin and amphotericin B. Patients in the test group received 0.5 g of a 4% vancomycin gel at 6-h intervals in the oropharynx. Lower airway infections due to MRSA acquired on the ICU were reduced in the test group, as was oropharyngeal carriage. Neither vancomycin-resistant enterococci nor vancomycin-intermediate S. aureus were isolated from either surveillance or diagnostic samples during the study period. The vancomycin costs were lower in the test group. This study demonstrates that oropharyngeal vancomycin, which controls intensive care unit-acquired lower airway infections and secondary carriage due to methicillin-resistant Staphylococcus aureus, is cost-effective and safe in terms of vancomycin-resistant enterococci and vancomycin-intermediate Staphylococcus aureus.

Administration, Oral↗