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PubMed1992

Vancomycin-resistant Enterococcus faecium in hospitalized children.

OBJECTIVE: Determine the epidemiology and risk factors for colonization with vancomycin-resistant Enterococcus faecium. DESIGN: Survey; case-control study. SETTING: Children's hospital. PATIENTS: Pediatric oncology patients. INTERVENTION: Contact isolation, restriction of vancomycin prescribing. RESULTS: There was a high prevalence of colonization with vancomycin-resistant enterococci among pediatric oncology patients. The length of hospitalization and the administration of vancomycin and other intravenous antibiotics was associated with colonization. Prevention of colonization was associated with restriction of vancomycin use and contact isolation. CONCLUSIONS: Vancomycin use may predispose to colonization with vancomycin-resistant E faecium. Vancomycin-resistant E faecium may be nosocomially spread. Contact isolation and restriction of vancomycin use may prevent spread of vancomycin-resistant E faecium.

Bacterial Typing Techniques↗

PubMed1990

Nephrotoxicity of vancomycin, alone and with an aminoglycoside.

The incidence of nephrotoxicity in patients receiving vancomycin alone or in combination with an aminoglycoside was prospectively evaluated. A total of 231 courses of antibiotic therapy in 224 patients were consecutively monitored over 28-month period. One hundred and sixty-eight patients received vancomycin alone, 63 patients received vancomycin with an aminoglycoside, and 103 patients received gentamicin. Nephrotoxicity was defined as an increase in serum creatinine of 0.5 mg/dl or a 50% increase above baseline, whichever was greater. Eight patients (5%) receiving vancomycin alone, 14 patients (22%) receiving vancomycin with an aminoglycoside, and 11 patients (11%) receiving gentamicin alone were found to have nephrotoxicity. Factors found to be associated with increased risk of nephrotoxicity in patients receiving vancomycin were concurrent therapy with an aminoglycoside, length of treatment with vancomycin (greater than 21 days), and vancomycin trough serum concentration (greater than 10 mg/l). Although the incidence of vancomycin nephrotoxicity is low, patients receiving vancomycin therapy with the above risk factors should be closely monitored.

Adult↗

PubMed1993

In-vitro synergy and mechanism of interaction between vancomycin and ciprofloxacin against enterococcal isolates.

In-vitro synergy between vancomycin and ciprofloxacin against 44 enterococcal isolates was studied. Synergy occurred in chequerboard MIC determinations with six Enterococcus faecium strains resistant to both vancomycin and ciprofloxacin. The combination was additive for strains susceptible to one or both antibiotics. Time-kill studies involving selected strains with different susceptibility patterns confirmed the chequerboard results. The effect of ciprofloxacin on the induction of vancomycin resistance was compared in two vancomycin-resistant strains of E. faecium. Sub-inhibitory concentrations of ciprofloxacin prevented induction of vancomycin resistance in a ciprofloxacin-resistant strain, but not in a ciprofloxacin-susceptible strain. Membranes isolated from vancomycin-resistant ciprofloxacin-resistant cultures grown with vancomycin and ciprofloxacin at < or = 8 mg/L (0.125 x MIC) expressed a 39.5-kDa membrane protein involved in the expression of vancomycin resistance, but the protein was not detected in membranes from cultures grown in ciprofloxacin 16 mg/L. These findings indicated that a vancomycin-ciprofloxacin combination can be synergic against enterococci resistant to both vancomycin and ciprofloxacin, but would be unlikely to offer any advantage in the treatment of enterococcal infections because of the high concentrations required.

Bacterial Outer Membrane Proteins↗

PubMed2000

Pharmacodynamics of vancomycin and ampicillin alone and in combination with gentamicin once daily or thrice daily against Enterococcus faecalis in an in vitro infection model.

We compared the pharmacodynamic activities of vancomycin and ampicillin with or without gentamicin once daily or thrice daily in an in vitro infection model with fibrin-platelet clots (FPCs) infected with Enterococcus faecalis. Antibiotics were administered as a bolus to simulate human pharmacokinetics with regimens consisting of vancomycin 1 g q12h, ampicillin 2 g q6h and gentamicin 1.3 mg/kg q8h and 5 mg/kg qd. Model experiments were performed in duplicate over 72 h. FPCs were removed from the models in triplicate at 0, 8, 24, 32, 48 and 72 h, weighed, homogenized, diluted and plated to determine colony counts. Additional FPCs were removed at over 72 h post-antibiotic dose to determine antibiotic concentrations. The inoculum density at 72 h was used to compare bactericidal activity between the regimens. Overall, all antibiotic regimens containing either ampicillin or vancomycin significantly (P < 0.01) decreased the bacterial load at 72 h compared with the growth control although monotherapy regimens with either vancomycin or gentamicin had little impact. Ampicillin was superior to vancomycin with or without the addition of gentamicin (P < 0.01). There were no significant differences in reduction of bacterial density at 72 h between the combination of ampicillin or vancomycin plus gentamicin q8h and ampicillin or vancomycin plus gentamicin once daily. This was despite achieving unmeasurable FPC gentamicin concentrations after the 8 h time point during the once-daily aminoglycoside regimen. Vancomycin plus gentamicin either every 8 h or once daily was significantly (P < 0.01) better than vancomycin alone. Ampicillin plus either of the two gentamicin regimens was also better than ampicillin alone but this did not reach statistical significance. Our data suggest that once-daily gentamicin in combination with ampicillin or vancomycin demonstrates equivalent bacterial reductions to combination therapy with thrice-daily gentamicin. Once-daily aminoglycoside combination therapy for the treatment of enterococcal endocarditis warrants further investigation.

Ampicillin↗

PubMed2005

Methicillin-resistant Staphylococcus aureus heterogeneously resistant to vancomycin in a Turkish university hospital.

OBJECTIVES: We investigated vancomycin-intermediate Staphylococcus aureus (VISA) and heterogeneously vancomycin-intermediate S. aureus (hetero-VISA) isolates from clinical specimens of hospitalized patients at Hacettepe University over a 4 year period. METHODS: Strains were screened for VISA and hetero-VISA by using brain heart infusion agar containing 4 mg/L vancomycin (BHI-V4) and macro Etest. Confirmation of the isolates that were found to have intermediate susceptibility to vancomycin with either of the methods was done by population analysis of subpopulations with reduced susceptibility to vancomycin. The MIC of vancomycin for the isolates grown on BHI-V4 was determined by the microdilution method. RESULTS: Among 256 methicillin-resistant S. aureus (MRSA) isolates, 145 grew on BHI-V4. Forty-six of these were also found to be heterogeneously vancomycin-intermediate strains when screened with the macro Etest. There were no VISA among 256 MRSA tested but 46 (17.97%) S. aureus strains with reduced susceptibility to vancomycin were identified by population analysis. Vancomycin MIC values for all isolates with reduced susceptibility were between <or=0.125 and 4 mg/L. Twelve of the 46 patients with hetero-VISA had a history of previously being treated with vancomycin or teicoplanin. CONCLUSIONS: To our knowledge, this study is the first publication showing the presence of hetero-VISA in Turkey. In order to understand the epidemiological relationship between our isolates, molecular typing methods are needed.

Anti-Bacterial Agents↗

PubMed2005

Evaluation of ceftriaxone, vancomycin and rifampicin alone and combined in an experimental model of meningitis caused by highly cephalosporin-resistant Streptococcus pneumoniae ATCC 51916.

OBJECTIVES: The aim of the study was to assess the in vitro and in vivo efficacy of ceftriaxone, vancomycin and rifampicin alone and combined against Streptococcus pneumoniae ATCC 51916 (MIC of ceftriaxone: 32 mg/L). METHODS: In vitro killing curves were performed with clinically achievable CSF antibiotic concentrations. In the rabbit model of pneumococcal meningitis, we studied the efficacy of and effects on inflammation of treatment with ceftriaxone 100 mg/kg/day, vancomycin 30 mg/kg/day and rifampicin 15 mg/kg/day, alone and combined, over a 26 h period. RESULTS: Time-kill curves showed that vancomycin was bactericidal, and ceftriaxone and rifampicin produced a bacteriostatic effect. An additive effect was observed when combinations of ceftriaxone plus vancomycin were studied at subinhibitory concentrations. Emergence of resistance to rifampicin was detected both when rifampicin was studied alone and when combined with ceftriaxone or vancomycin. In the rabbit meningitis model, ceftriaxone was bacteriostatic, whereas rifampicin and vancomycin were bactericidal at 24 h. Although not synergistic, the combinations of ceftriaxone plus vancomycin or rifampicin, and vancomycin plus rifampicin, improved the efficacy of any antibiotic tested alone--all combinations were bactericidal from 6 h--and significantly decreased inflammatory parameters in CSF compared with control and ceftriaxone groups. CONCLUSION: Ceftriaxone plus vancomycin, and vancomycin plus rifampicin appeared to be effective in the therapy of experimental pneumococcal meningitis caused by highly cephalosporin-resistant strains such as ATCC 51916. Our results provide an experimental basis for using these combinations as empirical therapy for pneumococcal meningitis, regardless of the degree of cephalosporin resistance of the causative strain.

Animals↗

PubMed1998

An investigation of vancomycin-resistant Enterococcus faecium within the pediatric service of a large urban medical center.

BACKGROUND: Between 1990 to 1992 and 1993 to 1995 there was a >5-fold increase (16.7% to 89.8%) in vancomycin-resistant Enterococcus faecium isolates as a percentage of all isolates of vancomycin-resistant enterococci on the pediatric units of The New York Hospital-Cornell Medical Center (NYH-CMC). A molecular epidemiologic investigation was undertaken to determine the extent to which this increase was associated with the spread of a vanA-containing clone of vancomycin-resistant E. faecium that had been previously defined in adults hospitalized at NYH-CMC or with the spread of another vanA clone that had been defined in children hospitalized on the pediatric service at Memorial Sloan-Kettering Cancer Center, which shares a common pediatric intensive care unit and pediatric house staff with NYH-CMC. METHODS: Molecular genotyping of vancomycin-resistant E. faecium isolates obtained from pediatric patients from 1993 to 1995 was performed by pulsed field gel electrophoresis of chromosomal SmaI digests. Southern hybridization was performed using vanA- and vanB-specific probes. Medical records of patients were reviewed for pertinent clinical and demographic information. RESULTS: A single vanB clone of vancomycin-resistant E. faecium was responsible for 17 (77.3%) of 22 isolates in the neonatal intensive care unit (NICU) of NYH-CMC. Two other vanB strains of vancomycin-resistant E. faecium and 2 vanA strains were identified among the 5 remaining NICU isolates. Vancomycin-resistant E. faecium isolates from the other pediatric units represented a heterogeneous population of primarily vanA strains, but vanA clonal strains previously identified from patients on adult services at NYH-CMC and from children hospitalized at Memorial Sloan-Kettering Cancer Center were not detected. CONCLUSION: A newly identified vanB clone was responsible for the increase in vancomycin-resistant E. faecium isolates in the NICU of NYH-CMC. The increase of vancomycin-resistant E. faecium among children hospitalized at NYH-CMC was unrelated to the spread of vancomycin-resistant E. faecium among adults in the same hospital or among children at an affiliated facility cared for by the same house staff and sharing a common pediatric intensive care unit.

Adolescent↗

PubMed2005

The fixed combination of fortified vancomycin and amikacin ophthalmic solution--VA solution: in vitro study of the potency and stability.

PURPOSE: We compared the in vitro potency and stability of a fixed combination of vancomycin and amikacin solution (VA solution) with amikacin or vancomycin solution. METHODS: Solutions of 2% amikacin (20 mg/mL) and of 5% vancomycin (50 mg/mL) and VA solution (each 1 mL contained 20 mg of amikacin and 50 mg of vancomycin) were prepared from parenteral antibiotics by reconstituting them with sterile injection water and refrigerated (4 degrees C) in the dark. Triplicate 5-mL portions of each solution were tested before storage and 7 and 14 days after preparation for potency of antimicrobial activity by the disk diffusion method and for stability. RESULTS: There were no significant differences in the diameter of zones of inhibition of VA solution compared with amikacin or vancomycin solution within a 2-week period. Visual inspection revealed that all solutions remained clear, colorless, and particle-free at 4 degrees C throughout the study period. For osmolarity, the VA solution was much higher than that of either amikacin or vancomycin solution at all tested times and more near the well-tolerated range of human eyes. There were no significant differences at days 0, 7, or 14 for either vancomycin, amikacin, or VA solution. For pH, the VA solution was higher than that of vancomycin solution (nearly equal to that of amikacin solution) at each time and more near the level of normal tear film. The pH did not differ significantly for either vancomycin, amikacin, or VA solution at all tested times. CONCLUSIONS: The vancomycin and amikacin ophthalmic solutions can be mixed together with the same potency and stable physical properties. It may be useful in the treatment of bacterial keratitis pending clinical trials to determine its effectiveness and safety.

Amikacin↗

PubMed2005

An antibiotic order form intervention does not improve or reduce vancomycin use.

OBJECTIVES: To determine whether a paper-based antibiotic ordering system is an effective antibiotic stewardship measure. METHODS: An antibiotic order form (AOF) was introduced in July 2001 at a pediatric tertiary care hospital. Vancomycin courses prescribed before and after the AOF introduction were retrospectively reviewed based on Hospital Infection Control Practices Advisory Committee guidelines. The impact of the AOF on the appropriateness of vancomycin prescribing was evaluated in univariate and multivariable analyses that adjusted for other factors associated with appropriateness of vancomycin use. The density of vancomycin use after introduction of the AOF was also assessed. RESULTS: Compliance with the AOF was poor (<50%) during the planned study period; therefore an additional 2 months of improved compliance (70-80%) were included. Rates of inappropriate vancomycin use increased during the study periods: 35% before AOF; 39% post-AOF; and 51% during the improved compliance period. On adjusted analysis, vancomycin utilization was significantly more inappropriate after introduction of the AOF. Vancomycin doses per 1000 patient days increased after introduction of the AOF. CONCLUSIONS: Inappropriate vancomycin use and vancomycin use overall increased after the introduction of an AOF. An AOF intervention did not have its intended effect of improving and reducing vancomycin use.

Anti-Bacterial Agents↗

PubMed1994

Effects of teicoplanin and those of vancomycin in initial empirical antibiotic regimen for febrile, neutropenic patients with hematologic malignancies. Gimema Infection Program.

The efficacy and toxicity of teicoplanin and vancomycin in the initial empirical antibiotic regimen in febrile, neutropenic patients with hematologic malignancies were compared in a prospective, randomized, unblinded, multicenter trial in the setting of 29 hematologic units in tertiary-care or university hospitals. A total of 635 consecutive febrile patients with hematologic malignancies and chemotherapy-induced neutropenia were randomly assigned to receive intravenously amikacin plus ceftazidime plus either teicoplanin at 6 mg/kg of body weight once daily or vancomycin at 1 g twice daily. An efficacy analysis was done for 527 evaluable patients: 275 treated with teicoplanin and 252 treated with vancomycin. Overall, successful outcomes were recorded for 78% of patients who received teicoplanin and 75% of those who were randomized to vancomycin (difference, 3%; 95% confidence interval [CI], -10 to 4%; P = 0.33). A total of 102 patients presented with primary, single-agent, gram-positive bacteremia. Coagulase-negative staphylococci accounted for 42%, Staphylococcus aureus accounted for 27%, and streptococci accounted for 21% of all gram-positive blood isolates. The overall responses to therapy of gram-positive bacteremias were 92 and 87% for teicoplanin and vancomycin, respectively (difference, 5%; CI, -17 to 6%; P = 0.22). Side effects, mainly represented by skin rash, occurred in 3.2 and 8% of teicoplanin- and vancomycin-treated patients, respectively (difference, -4.8%; CI, 0.7 to 8%; P = 0.03); the rate of nephrotoxicity was 1.4 and 0.8% for the teicoplanin and vancomycin groups, respectively (difference, 0.6%; CI, -2 to 1%; P = 0.68). Further infections were caused by gram-positive organisms in two patients (0.7%) treated with teicoplanin and one patient (0.4%) who received vancomycin (difference, 0.3%; CI, -0.9 to 1.0%; P = 0.53). Overall mortalities were 8.5 and 11% for teicoplanin- and vancomycin-treated patients, respectively (difference, -2.5%; CI, - 2 to 7%; P = 0.43); death was caused by primary gram-positive infections in three patients (1%) in each treatment group. When used for initial empirical antibiotic therapy in febrile, neutropenic patients, teicoplanin was at least as efficacious as vancomycin, but it was associated with fewer side effects.

Adolescent↗

PubMed1996

Pharmacokinetics of vancomycin in critically ill infants undergoing extracorporeal membrane oxygenation.

Extracorporeal membrane oxygenation (ECMO) is a widely used therapy for neonates with respiratory failure. Because of sepsis, many of these infants require antibiotics like vancomycin during ECMO treatment. ECMO transiently alters renal function and increases the circulating blood volume by 75%. Initial vancomycin pharmacokinetics were determined in 12 infants undergoing ECMO to determine an adequate drug administration regimen. Vancomycin dosage was based on current recommendations for weight and gestational age. Pharmacokinetic parameters were determined by fitting the data to a two compartment model. This study yielded a mean steady-state volume of distribution of 1.1 +/- 0.5 (range, 0.6 to 2.1) liters/kg and a mean vancomycin clearance of 0.78 +/- 0.19 (range, 0.49 to 1.07) ml/min/kg. The mean vancomycin half-life was 16.9 +/- 9.5 (range, 8.8 to 42.9) h. Nomogram-calculated creatinine clearance was a significant predictor of vancomycin terminal rate constant and clearance. These data suggest alterations in the pharmacokinetics of vancomycin in infants on ECMO. With the goal of achieving vancomycin concentrations in serum above the MIC for the offending pathogen while using the least amount of the drug necessary, new administration guidelines for term infants without renal impairment undergoing ECMO should be 20 mg of vancomycin per kg at an interval of 24 h. With significant renal impairment, the interval should be extended on the basis of concentrations in serum. In comparison with previously published data, the neonates undergoing ECMO in our study demonstrated a much larger volume of distribution, a lower clearance, and consequently a longer vancomycin half-life.

Anti-Bacterial Agents↗

PubMed1999

Vancomycin-dependent Enterococcus faecalis clinical isolates and revertant mutants.

Three vancomycin-dependent clinical isolates of Enterococcus faecalis of the VanB type were studied by determining (i) the sequence of the ddl gene encoding the host D-Ala:D-Ala ligase and the vanSB-vanRB genes specifying the two-component regulatory system that activates transcription of the vanB operon, (ii) the level of expression of resistance genes by using DD-dipeptidase activity as a reporter, and (iii) the proportions of the peptidoglycan precursors synthesized. Each strain had a mutation in ddl leading to an amino acid substitution (D295 to V; T316 to I) or deletion (DAK251-253 to E) at invariant positions in D-Ala:D-Ala, D-Ala:D-Lac, and D-Ala:D-Ser ligases. These mutations resulted in impaired host D-Ala:D-Ala ligases since only precursors terminating in D-Ala-D-Lac were synthesized under vancomycin-inducing conditions. Two types of vancomycin-independent revertants of one isolate were obtained in vitro after growth in the absence of vancomycin: (i) vancomycin-resistant, teicoplanin-susceptible mutants had a 6-bp insertion in the host ddl gene, causing the E251-to-EYK change that restored D-Ala:D-Ala ligase activity, (ii) constitutive vancomycin-resistant, teicoplanin-resistant mutants had substitutions (S232 to F or E247 to K) in the vicinity of the autophosphorylation site of the VanSB sensor and produced exclusively precursors ending in D-Ala-D-Lac. Vancomycin- and teicoplanin-dependent mutants obtained by growth in the presence of teicoplanin had an 18-bp deletion in VanSB, affecting residues 402 to 407 and overlapping the G2 ATP binding domain. The rapid emergence of vancomycin-independent revertants in vitro suggests that interruption of vancomycin therapy may not be sufficient to cure patients infected with vancomycin-dependent enterococci.

Anti-Bacterial Agents↗

PubMed2001

Role of penicillin-binding protein 4 in expression of vancomycin resistance among clinical isolates of oxacillin-resistant Staphylococcus aureus.

It has been reported that penicillin-binding protein 4 (PBP4) activity decreases when a vancomycin-susceptible Staphylococcus aureus isolate is passaged in vitro to vancomycin resistance. We analyzed the PBP profiles of four vancomycin intermediately susceptible S. aureus (VISA) clinical isolates and found that PBP4 was undetectable in three isolates (HIP 5827, HIP 5836, and HIP 6297) and markedly reduced in a fourth (Mu50). PBP4 was readily visible in five vancomycin-susceptible, oxacillin-resistant S. aureus (ORSA) isolates. The nucleotide sequences of the pbp4 structural gene and flanking sequences did not different between the VISA and vancomycin-susceptible isolates. Overproduction of PBP4 on a high-copy-number plasmid in the VISA isolates produced a two- to threefold decrease in vancomycin MICs. Inactivation of pbp4 by allelic replacement mutagenesis in three vancomycin-susceptible ORSA strains (COL, RN450M, and N315) led to a decrease in vancomycin susceptibility, an increase in highly vancomycin-resistant subpopulations, and decreased cell wall cross-linking by high-performance liquid chromatography analysis. Complementation of the COL mutant with plasmid-encoded pbp4 restored the vancomycin MIC and increased cell wall cross-linking. These data suggest that alterations in PBP4 expression are at least partially responsible for the VISA phenotype.

Bacterial Proteins↗

PubMed1996

Selective isolation of vancomycin-resistant enterococci.

Broth formulations of two media selective for enterococci, Enterococcel, M-Enterococcosel broths were supplemented with 6 micrograms of vancomycin per ml and evaluated for isolation of vancomycin-resistant enterococci (VRE). Each broth was challenged with various concentrations of Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and vancomycin-susceptible and vancomycin-resistant enterococci and with 193 perianal specimens obtained from patients at risk in our institution for VRE colonization. Both the Enterococcosel and M-Enterococcus broths with vancomycin detected as few as 1 to 9 CFU of VRE while inhibiting growth of the other organisms tested. Enterococcus faecium organisms (MIC, > 256 micrograms/ml) were recovered from 66 perianal swab cultures in the enterococcosel-vancomycin broth, and VRE were recovered from 62 perianal swab cultures in the M-Enterococcus-vancomycin broth. Enterococcosel-vancomycin broth detected VRE in perianal specimens 48 h earlier than did M-Enterococcus-vancomycin broth. Enterococcosel broth with 6 micrograms of vancomycin per ml can be used for the rapid and selective isolation of VRE from surveillance specimens.

Anti-Bacterial Agents↗

PubMedDate not supplied

Reducing vancomycin use utilizing a computer guideline: results of a randomized controlled trial.

BACKGROUND: Vancomycin-resistant enterococci represent an increasingly important cause of nosocomial infections. Minimizing vancomycin use represents a key strategy in preventing the spread of these infections. OBJECTIVE: To determine whether a structured ordering intervention using computerized physician order entry that requires use of a guideline could reduce intravenous vancomycin use. DESIGN: Randomized controlled trial assessing frequency and duration of vancomycin therapy by physicians. PARTICIPANTS AND SETTING: Three hundred ninety-six physicians and 1,798 patients in a tertiary-care teaching hospital. INTERVENTION: Computer screen displaying, at the time of physician order entry, an adaptation of the Centers for Disease Control and Prevention guidelines for appropriate vancomycin use. MAIN OUTCOME MEASURES: The frequency of initiation and renewal of vancomycin therapy as well the duration of therapy prescribed on a per prescriber basis. RESULTS: Compared with the control group, intervention physicians wrote 32 percent fewer orders (11.3 versus 16.7 orders per physician; P = 0.04) and had 28 percent fewer patients for whom they either initiated or renewed an order for vancomycin (7.4 versus 10.3 orders per physician; P = 0.02). In addition, the duration of vancomycin therapy attributable to physicians in the intervention group was 36 percent lower than the duration of therapy prescribed by control physicians (26.5 versus 41.2 days; P = 0.05). Analysis of pharmacy data confirmed a decrease in the overall hospital use of intravenous vancomycin during the study period. CONCLUSION: Implementation of a computerized guideline using physician order entry decreased vancomycin use. Computerized guidelines represent a promising tool for changing prescribing practices.

Drug Prescriptions↗

PubMed1993

Overestimation of serum vancomycin concentrations using a fluorescence polarization immunoassay (Tdx) in preterm neonates.

Serum vancomycin concentrations determined by fluorescence polarization immunoassay (FPIA) with a specific high-performance liquid chromatography (HPLC) method in preterm neonates were compared. Preterm neonates (< 38 weeks gestational age) requiring vancomycin therapy and serum vancomycin concentration monitoring were enrolled. Peak serum vancomycin concentration samples were collected and independently analyzed by FPIA and HPLC. Multivariate and stratified data analysis was done with mean absolute error and mean percent error as dependent variables and independent variables as postconceptional age, postnatal age, gestational age, weight, and duration of therapy to characterize the findings. A total of 15 paired vancomycin concentrations were analyzed from neonates with a mean gestational age of 30 +/- 4 weeks. The mean percentage error of FPIA versus HPLC vancomycin concentrations was 18.1 +/- 11.1% and the mean absolute error was 3.7 +/- 2.0 mg/l. Postconceptional age, weight, and time from initiation of therapy to sample collection were independent variables which best characterized the overestimation of FPIA vancomycin concentrations. The FPIA vancomycin assay method overestimated actual vancomycin concentrations in preterm neonates. Preterm neonates less than 30 weeks postconceptional age, less than 1,200 g body weight, and duration of therapy greater than 48 h prior to concentration determination had the greatest difference in FPIA and HPLC results. Significant error in pharmacokinetic parameter estimations and dosage adjustments is possible when vancomycin concentrations are determined by FPIA.

Chromatography, High Pressure Liquid↗

PubMed1981

Vancomycin prophylaxis of experimental Streptococcus sanguis. Inhibition of bacterial adherence rather than bacterial killing.

Using a strain of Streptococcus sanguis tolerant to vancomycin to infect aortic vegetations in rats, we found that prophylactic intravenous vancomycin given 30 min before bacterial challenge decreased the incidence of endocarditis from 88 to 8% (P less than 10(-5)). Because peak vancomycin serum levels were below the minimal bactericidal concentration, mechanisms of protection other than bacterial killing were investigated. S. sanguis were incubated with inhibitory concentration of vancomycin (50 microgram/ml) for 10 h and washed. 85% of rats (73/86) inoculated with control bacteria developed endocarditis, whereas only 42% (33/78) of those inoculated with vancomycin-exposed bacteria did so (P less than 10(-5)). When rats were killed 30 min after bacterial challenge, S. sanguis were detected by culture of the vegetations in 44% of rats injected with control bacteria, but in only 13% of those challenged with vancomycin-exposed bacteria (P less than 0.03). Enhanced clearance of vancomycin-exposed streptococci was not responsible for this protection because blood cultures showed no difference in the level and duration of bacteremia after injection of control or vancomycin-exposed S. sanguis. Moreover, this protection was not abolished in neutropenic rats injected with vancomycin-exposed bacteria, despite more prolonged bacteremia. These results suggest that vancomycin exerted its protection by lowering adherence of tolerant S. sanguis to vegetations rather than through bactericidal activity or enhanced clearance of bacteria by phagocytic cells. In the choice of antibiotics for prophylaxis of endocarditis, reduction of bacterial adhesion may be a criterion as important as bacterial killing.

Animals↗

PubMed2001

Vancomycin removal during a plasma exchange transfusion.

OBJECTIVE: To report a case of clinically significant removal of vancomycin during a plasma exchange transfusion in a patient with sickle-cell anemia. CASE SUMMARY: A 46-year-old African American woman with sickle-cell disease was admitted on three separate occasions and treated with vancomycin. Vancomycin serum drug concentrations were obtained on all three admissions. During one of the admissions, a plasma exchange transfusion was performed the same day vancomycin concentrations were obtained. The vancomycin serum drug concentrations were considerably lower than predicted, resulting in potentially subtherapeutic vancomycin concentrations. Bayesian pharmacokinetic forecasting was used in interpreting the vancomycin concentrations. DISCUSSION: Searches from MEDLINE (1966-September 2000) and Drugs and Pharmacology (1990-September 2000) were performed to obtain pertinent published literature. CONCLUSIONS: Plasma exchange transfusions may result in clinically significant removal of vancomycin from the plasma. The potential exists of underdosing vancomycin in patients who are receiving frequent plasma exchange transfusions. Further research may be warranted to determine whether these patients may be candidates for more frequent and vigilant monitoring of vancomycin concentrations.

Anemia, Sickle Cell↗