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PubMed2002

Emergence of vancomycin-resistant Enterococcus faecium at a tertiary care hospital in Karachi, Pakistan.

Vancomycin-resistant enterococcus (VRE) has not been reported previously in Pakistan. This is the first report where in vancomycin-resistant Enterococcus faecium was isolated from the clinical specimens of six patients admitted to the intensive care unit (ICU) and neonatal intensive care unit (NICU) of the Aga Khan University Hospital, Karachi. To identify the extent of the outbreak, rectal swabs were obtained from all the patients admitted to the ICU and NICU at that time. A total of 10 strains of vancomycin-resistant Enterococcus faecium were isolated. All the strains showed high-level resistance to both glycopeptides (vancomycin and teicoplanin) with a vancomycin minimum inhibitory concentration greater than 256 mg/L. All isolates had the vanA gene detected by polymerase chain reaction. The contour-clamped homogeneous electric field (CHEF) pattern demonstrated that all but one of the isolates were of a single clone, suggesting that they were derived from common source. Use of vancomycin and prolonged hospitalization were common features in all cases investigated.

Adult↗

PubMed1999

Emergence of vancomycin resistance in Staphylococcus aureus. Glycopeptide-Intermediate Staphylococcus aureus Working Group.

BACKGROUND: Since the emergence of methicillin-resistant Staphylococcus aureus, the glycopeptide vancomycin has been the only uniformly effective treatment for staphylococcal infections. In 1997, two infections due to S. aureus with reduced susceptibility to vancomycin were identified in the United States. METHODS: We investigated the two patients with infections due to S. aureus with intermediate resistance to glycopeptides, as defined by a minimal inhibitory concentration of vancomycin of 8 to 16 microg per milliliter. To assess the carriage and transmission of these strains of S. aureus, we cultured samples from the patients and their contacts and evaluated the isolates. RESULTS: The first patient was a 59-year-old man in Michigan with diabetes mellitus and chronic renal failure. Peritonitis due to S. aureus with intermediate resistance to glycopeptides developed after 18 weeks of vancomycin treatment for recurrent methicillin-resistant S. aureus peritonitis associated with dialysis. The removal of the peritoneal catheter plus treatment with rifampin and trimethoprim-sulfamethoxazole eradicated the infection. The second patient was a 66-year-old man with diabetes in New Jersey. A bloodstream infection due to S. aureus with intermediate resistance to glycopeptides developed after 18 weeks of vancomycin treatment for recurrent methicillin-resistant S. aureus bacteremia. This infection was eradicated with vancomycin, gentamicin, and rifampin. Both patients died. The glycopeptide-intermediate S. aureus isolates differed by two bands on pulsed-field gel electrophoresis. On electron microscopy, the isolates from the infected patients had thicker extracellular matrixes than control methicillin-resistant S. aureus isolates. No carriage was documented among 177 contacts of the two patients. CONCLUSIONS: The emergence of S. aureus with intermediate resistance to glycopeptides emphasizes the importance of the prudent use of antibiotics, the laboratory capacity to identify resistant strains, and the use of infection-control precautions to prevent transmission.

Aged↗

PubMed2000

Vancomycin population pharmacokinetics in neonates.

BACKGROUND: Recently the value of vancomycin therapeutic drug monitoring, as well as the required therapeutic range, has been subject of debate, resulting in new recommendations. This study was performed to incorporate these new insights in an up-to-date dosing scheme for neonates of various gestational ages. METHODS: In this retrospective study with prospective validation, 108 newborns with suspected central line-related septicemia during the first month of life received 30 mg/kg/day vancomycin divided into two doses regardless of gestational or postconceptional age. Trough and peak vancomycin serum concentrations were determined before and after the third dose. Vancomycin data were analyzed according to a one-compartment open model with use of NONMEM population pharmacokinetic software. Model parameters were evaluated and then used to simulate vancomycin dosing for different dose and dose interval combinations. Targets were a trough concentration between 5 and 15 mg/L and a peak below 40 mg/L. In the prospective study, the optimal scheme was tested in 22 patients. RESULTS: Of the 108 patients, 34.3% of measured trough concentrations and 17.6% of peak concentrations were outside the desired therapeutic range. The model that best fitted the data included clearance and volume per kilogram and was independent of gestational age. Simulation of various dosing schemes showed that a dosing schedule of 30 mg/kg/day, irrespective of gestational age, in three doses was optimal, and this scheme was prospectively tested. Mean trough concentrations before the second dose were 8.2 +/- 2.2 mg/L versus a predicted trough of 8.9 +/- 2.5 mg/L. No peak levels higher than 40 mg/L were found. CONCLUSIONS: The use of the proposed schedule leads to adequate vancomycin trough serum concentrations, and there is no need for routine monitoring of peak serum concentrations.

Analysis of Variance↗

PubMed2000

Risk factors for acquisition of vancomycin-resistant enterococci among patients on a renal ward during a community hospital outbreak.

BACKGROUND: During an outbreak of vancomycin-resistant enterococcal (VRE) infection and colonization at a community hospital in Indianapolis, Indiana, we performed a case-control study of patients on the hospital's renal unit to determine risk factors for acquisition of VRE among this potentially high-risk patient population. METHODS: Twenty-four renal patients with VRE colonization/infection (ie, case-patients) were compared by univariate and multivariate analyses with 29 renal patients with nosocomially acquired vancomycin-susceptible enterococcal infection and colonization (ie, controls). RESULTS: Age and length of hospitalization were similar between the VRE case-patients and the vancomycin-susceptible enterococcal control-patients, but case-patients had higher Acute Physiology and Chronic Health Evaluation II scores and received significantly greater numbers of antimicrobials and significantly more days of antimicrobials during the 60 days preceding the first positive enterococcal culture. In an assessment of the appropriateness of vancomycin use, one third of vancomycin orders were found to be inappropriate in both patient groups. CONCLUSIONS: Our data show that among renal patients, those who are severely ill and receive multiple and prolonged courses of antimicrobials are at greatest risk for acquiring VRE infection or colonization. The Centers for Disease Control and Prevention recommends that hospitals develop a comprehensive plan to prevent and control infection and colonization of patients with VRE. This plan should include prompt identification of affected patients, initiation of isolation precautions to prevent patient-to-patient transmission of VRE, and prudent use of antimicrobials, including vancomycin.

APACHE↗

PubMed2002

Vancomycin versus cefazolin prophylaxis for cardiac surgery in the setting of a high prevalence of methicillin-resistant staphylococcal infections.

OBJECTIVE: This study was undertaken to compare the efficacy of vancomycin prophylaxis with that of cefazolin in preventing surgical site infections in a tertiary medical center with a high prevalence of methicillin-resistant staphylococcal infections. METHODS: All adult patients (> or = 18 years) scheduled for cardiac surgery requiring sternotomy were randomly assigned to receive vancomycin (1 g every 12 hours) or cefazolin (1 g every 8 hours). Prophylaxis was started during the induction of anesthesia and continued for only 24 hours. Patients were followed up for at least 30 days (1 year for those receiving a cardiac implant). Surgical site infections were stratified according to the National Nosocomial Infections Surveillance System risk index. RESULTS: Of the 885 patients included in the study, 452 received vancomycin and 433 received cefazolin. The overall surgical site infection rates were similar in the two groups (43 cases in the vancomycin group, 9.5%, vs 39 cases in the cefazolin group, 9.0%, P =.8). Superficial and deep incisional surgical site infection rates were also similar in the two groups. There was a trend toward more frequent organ-space infections and infections with beta-lactam-resistant organisms among patients receiving cefazolin, but this trend did not reach statistical significance. In contrast, surgical site infections caused by methicillin-susceptible staphylococci were significantly more common in the vancomycin group (17 cases, 3.7%, vs 6 cases, 1.3%, P =.04). The durations of postoperative hospitalization and the mortalities were similar in the two groups. CONCLUSIONS: This trial suggests that vancomycin and cefazolin have similar efficacy in preventing surgical site infections in cardiac surgery.

Adult↗

PubMed2003

High level oxacillin and vancomycin resistance and altered cell wall composition in Staphylococcus aureus carrying the staphylococcal mecA and the enterococcal vanA gene complex.

Recently, for the first time in the history of this bacterial species, methicillin-resistant Staphylococcus aureus (MRSA) carrying the enterococcal vanA gene complex and expressing high level resistance to vancomycin was identified in clinical specimens (CDC (2002) MMWR 51, 565-567). The purpose of our studies was to understand how vanA is expressed in the heterologous background of S. aureus and how it interacts with the mecA-based resistance mechanism, which is also present in these strains and is targeted on cell wall biosynthesis. The vanA-containing staphylococcal plasmid was transferred from the clinical vancomycin-resistant S. aureus (VRSA) strain HIP11714 (CDC (2002) MMWR 51, 565-567) to the methicillin-resistant S. aureus (MRSA) strain COL for which extensive genetic and biochemical information is available on staphylococcal cell wall biochemistry and drug resistance mechanisms. The transconjugant named COLVA showed high and homogeneous resistance to both oxacillin and vancomycin. COLVA grown in vancomycin-containing medium produced an abnormal peptidoglycan: all pentapeptides were replaced by tetrapeptides, and the peptidoglycan contained at least 22 novel muropeptide species that frequently showed a deficit or complete absence of pentaglycine branches. The UDP-MurNAc-pentapeptide, the major component of the cell wall precursor pool in vancomycin-sensitive cells was replaced by UDP-MurNAc-depsipeptide and UDP-MurNAc-tetrapeptide. Transposon inactivation of the beta-lactam resistance gene mecA caused complete loss of beta-lactam resistance but had no effect on the expression of vancomycin resistance. The two major antibiotic resistance mechanisms encoded by mecA and vanA residing in the same S. aureus appear to use different sets of enzymes for the assembly of cell walls.

Anti-Bacterial Agents↗

PubMed2006

Moxifloxacin superior to vancomycin for treatment of bone infections--a study in rats.

BACKGROUND: Increasing resistance rates towards conventional antibiotics necessitate investigations of the efficacy of newly developed antibiotics. Thus, in a rat study, we compared the efficacy of moxifloxacin and vancomycin in the treatment of a local Staphylococcus aureus bone infection. METHOD: The femoral medullary cavities of 36 Wistar rats were contaminated with 100 muL of an oxacillin-sensitive Staphylococcus aureus strain (ATCC 29213) at 10(8) cfu/mL. On the seventh day, antibiotic treatment with moxifloxacin (10 mg/kg twice daily i.p.) or vancomycin (15 mg/kg twice daily i.p.) was commenced in 12 animals each. 12 control animals were left untreated. After 21 days, the infected femurs were explanted and the bacterial counts (cfu/g) were determined. RESULTS: In the control group, a median of 3.42 x 10(6) cfu/g (LQ/UQ 1.09 x 10(6)/ 1.55 x 10(7)) was cultured, with a median of 2.53 x 10(6) cfu/g (LQ/UQ 1.95 x 10(6)/ 4.25 x 10(6)) in the vancomycin group and a median of 2.49 x 10(5) cfu/g (LQ/UQ 2.84 x 10(4)/ 3.75 x 10(5)) in the moxifloxacin group. The bacterial count was reduced by treatment with moxifloxacin both in comparison with the control group (p < 0.001), and in comparison with treatment with vancomycin (p < 0.001). There was no statistically significant difference between the vancomycin group and the control group (p = 0.53). INTERPRETATION: In contrast to vancomycin, moxifloxacin proved to be an effective antibiotic for the treatment of bone infections due to Staphylococcus aureus in our animal model.

Animals↗

PubMed2004

Tolerance to vancomycin in pneumococci: detection with a molecular marker and assessment of clinical impact.

BACKGROUND: Vancomycin is often added to therapy for meningitis caused by Streptococcus pneumoniae. Tolerant bacteria without classic resistance that escape killing by multiple antibiotics have been reported sporadically. We determined the prevalence of tolerance to vancomycin in pneumococci and its effect on the outcome of meningitis. METHODS: Archival samples of 215 nasopharyngeal (NP) and 113 meningitis isolates were tested for the killing efficacy of vancomycin. Specific DNA sequence changes in a transporter locus were identified for tolerant isolates. Similar tests were conducted prospectively on 517 NP isolates from healthy children. RESULTS: In archival isolates, tolerance to vancomycin was detected in 3.7% of NP and 10.6% of invasive isolates. Patients with meningitis caused by tolerant isolates had a worse estimated 30-day survival than did patients with meningitis caused by nontolerant isolates (49% vs. 86%; P = .048); 62.5% of tolerant archival NP isolates harbored a specific sequence change for pep27 and vex2 (P = .021). Prospective analysis of 517 carriage isolates indicated that 8.1% were tolerant to vancomycin and that 82.1% of tolerant isolates harbored the specified marker gene sequences (P = .001). CONCLUSIONS: Tolerance to vancomycin exists in the population of pneumococci. Tolerant isolates are associated with meningitis of increased mortality, and these isolates can be tracked by specific marker sequences in 2 genes.

Alleles↗

PubMed2005

Impact of vancomycin resistance on mortality among patients with neutropenia and enterococcal bloodstream infection.

We performed a retrospective cohort study to measure the impact of vancomycin resistance on clinical outcome for 83 episodes of enterococcal bloodstream infection (BSI; 22 with vancomycin-resistant enterococci [VRE] and 61 with vancomycin-susceptible enterococci [VSE]) in 77 patients with neutropenia. Cox proportional hazards models showed that vancomycin resistance was an independent predictor of mortality, after controlling for severity of illness, enterococcal species, gram-negative copathogens, sex, race, duration of neutropenia before bacteremia, and early administration of active antibiotics. This effect was evident only > or =10 days after the onset of bacteremia (P=.0263; hazard ratio [HR], 4.969) but not after adjustment for duration of bacteremia. The median duration of bacteremia was 4.5 days for VRE BSI and <1 day for VSE BSI (P=.0001). The only independent predictor of bacteremia duration was vancomycin resistance (P=.0284; HR, 3.863). Vancomycin resistance is associated with increased mortality in patients with neutropenia, possibly because of prolonged duration of bacteremia.

Adolescent↗

PubMed2005

Low colonization prevalence of Staphylococcus aureus with reduced vancomycin susceptibility among patients undergoing hemodialysis in the San Francisco Bay area.

BACKGROUND: Staphylococcus aureus exhibits varying degrees of reduced vancomycin susceptibility, and strains with intermediate levels of resistance are thought to emerge by antibiotic selection of subpopulations in heterogeneously resistant precursor strains exposed to this antibiotic. We sought to determine the prevalence of and risk factors for carriage of potential heterogeneous vancomycin-intermediate S. aureus (hVISA). METHODS: We prospectively observed a cohort of 211 patients undergoing hemodialysis and performed quarterly surveillance cultures for up to 2 years. We screened for reduced vancomycin susceptibility using brain-heart infusion agar with 4 microg/mL vancomycin. RESULTS: We identified 10 colonizing potential hVISA isolates recovered from 7 patients among both methicillin-susceptible and methicillin-resistant S. aureus strains. No confirmed hVISA isolates were identified; we can be 95% certain that the prevalence of confirmed hVISA carriage does not exceed 1.4%. When compared with noncolonized hemodialysis patients, neither vancomycin exposure, duration of hospitalization, nor any baseline clinical or demographic factor was found to predict colonization with potential hVISA on univariate analyses; increased number of months receiving hemodialysis was associated with potential hVISA colonization on multivariate analysis. CONCLUSIONS: Despite numerous published reports of S. aureus with reduced vancomycin susceptibility, carriage of these isolates remains a rare phenomenon. Given the unclear clinical significance of potential hVISA, it is not clear whether clinical laboratories should identify such strains, or how they should do so.

Adult↗

PubMed2006

The role of vancomycin in the treatment paradigm.

Vancomycin was introduced in the United States in 1956 as a possible treatment for infections due to penicillin-resistant Staphylococcus aureus, but it was not used widely because of toxicity and the nearly simultaneous development of semisynthetic antibiotics and cephalosporins. Thus, its main indication was the treatment of serious gram-positive infections in penicillin-allergic patients. For susceptible strains of S. aureus, vancomycin was more rapidly bactericidal than penicillin, nafcillin, or cefazolin, and, in a rabbit model of S. aureus endocarditis, sterilization of vegetations was more rapid with vancomycin. In clinical practice, however, nafcillin remained the treatment of choice for staphylococcal bacteremia, largely because it had failure rates of only 4%. With the appearance of methicillin-resistant S. aureus and coagulase-negative staphylococci, vancomycin became the drug of choice for these infections. Recently, the efficacy of vancomycin has been questioned because of vancomycin's increasing minimum inhibitory concentrations among staphylococci, poor tissue penetration, and apparently slower bacterial killing than previously was recognized.

Anti-Bacterial Agents↗

PubMed2006

Efficacy and safety of linezolid compared with vancomycin in a randomized, double-blind study of febrile neutropenic patients with cancer.

BACKGROUND: Gram-positive pathogens can cause serious infections in neutropenic patients with cancer, and vancomycin therapy is often initiated empirically. Linezolid may offer an option for these patients. METHODS: To compare the safety and efficacy of linezolid and vancomycin in febrile, neutropenic patients with cancer, we conducted a double-blind, multicenter equivalence study. Eligible patients with proven or suspected infection due to a gram-positive pathogen were randomized to receive linezolid or vancomycin. RESULTS: Clinical success rates 7 days after completion of therapy (primary end point) were equivalent between groups in the intent-to-treat (ITT) analysis (linezolid, 219 [87.3%] of 251 patients; vancomycin, 202 [85.2%] of 237 patients; 95% CI, -4.1 to 8.1; P=.52), modified ITT analysis, clinically evaluable analysis, and microbiologically evaluable analysis, as well as between subsets analyzed by malignancy and infection type. Mean time to defervescence was shorter for linezolid than vancomycin in the modified ITT (6.6 vs. 8.5 days; P=.04) and microbiologically evaluable subsets (5.9 vs. 9.1 days; P=.01), although post hoc analyses revealed delayed recovery of absolute neutrophil counts for linezolid in these subsets (P<.05). There were no between-group differences in microbiologic success rates in the modified ITT subset (41 [57.7%] of 71 patients vs. 29 [50.0%] of 58 patients; P=.38) and microbiologically evaluable subsets, as well as in mortality rates in the ITT subset (17 [5.6%] of 304 patients vs. 23 [7.6%] of 301 patients; P=.31) and all subsets. Distribution of adverse events, including reported hematologic events, was similar between groups, except that linezolid was associated with fewer drug-related adverse events (52 [17.2%] of 303 patients vs. 72 [24.0%] of 300 patients; P=.04) and fewer cases of drug-related renal failure (1 [0.3%] of 303 patients vs. 7 [2.3%] of patients; P=.04). CONCLUSIONS: Linezolid demonstrated efficacy and similar safety outcomes equivalent to those for vancomycin in febrile neutropenic patients with cancer.

Acetamides↗

PubMed2003

Effect of nosocomial vancomycin-resistant enterococcal bacteremia on mortality, length of stay, and costs.

OBJECTIVE: To determine the impact of vancomycin-resistant enterococcal bacteremia on patient outcomes and costs by assessing mortality, excess length of stay, and charges attributable to it. DESIGN: A population-based, matched, historical cohort study. SETTING: A 1,025-bed, university-based teaching facility and referral hospital. PATIENTS: Two hundred seventy-seven vancomycin-resistant enterococcal bacteremia case-patients and 277 matched control-patients identified between 1993 and 2000. RESULTS: The crude mortality rate was 50.2% and 19.9% for case-patients and control-patients, respectively, yielding a mortality rate of 30.3% attributable to vancomycin-resistant enterococcal bacteremia. The excess length of hospital stay attributable to vancomycin-resistant enterococcal bacteremia was 17 days, of which 12 days were spent in intensive care units. On average, dollars 77,558 in extra charges was attributable to each vancomycin-resistant enterococcal bacteremia. To adjust for severity of illness, 159 pairs of case-patients and control-patients, who had the same severity of illness (All Patient Refined-Diagnosis Related Group complexity level), were further analyzed. When patients were stratified by severity of illness, the crude mortality rate was 50.3% among case-patients compared with 27.7% among control-patients, accounting for an attributable mortality rate of 22.6%. Attributable excess length of stay and charges were 17 days and dollars 81,208, respectively. CONCLUSION: Vancomycin-resistant enterococcal bacteremia contributes significantly to excess mortality and economic loss, once severity of illness is considered. Efforts to prevent these infections will likely be cost-effective.

Adolescent↗

PubMed2006

Use of vancomycin-containing lock or flush solutions for prevention of bloodstream infection associated with central venous access devices: a meta-analysis of prospective, randomized trials.

BACKGROUND: Prolonged exposure to central venous access devices carries significant risk of device-associated bloodstream infection (BSI), which is associated with morbidity, added health care costs, and attributable mortality. We aimed to determine the efficacy of vancomycin-heparin lock or flush solution in preventing BSI in patients being treated with long-term central venous intravascular devices (IVDs). METHODS: We collected data from January 1966 to January 2006 from multiple computerized databases and compiled reference lists of identified articles. We identified prospective, randomized controlled trials comparing a vancomycin-heparin lock or flush solution with heparin alone for prevention of BSI associated with long-term central venous IVDs. Using a standardized form, we abstracted data regarding study quality, patient characteristics, and incidence of BSI. RESULTS: Seven randomized, controlled trials involving a total of 463 patients being treated with IVDs met the inclusion criteria; 5 studies were conducted among patients with cancer, 1 among a critically ill neonatal population, and 1 among patients with cancer or who required parenteral nutrition. We could not detect publication bias. The summary risk ratio with a vancomycin heparin-lock solution for IVD-associated BSI was 0.49 (95% confidence interval [CI], 0.26-0.95; P = .03). Results of the test for heterogeneity were statistically significant; however, when a single study was removed from the analysis, heterogeneity was no longer present. Use of vancomycin as a true lock solution--instilling it for a defined period, rather than simply flushing it directly through the device--conferred a much greater benefit, with a risk ratio of 0.34 (95% CI, 0.12-0.98; P = .04). The 2 studies that performed prospective surveillance cultures to identify colonization or infection by vancomycin-resistant organisms did not find an increased risk. CONCLUSIONS: Use of a vancomycin lock solution in high-risk patient populations being treated with long-term central IVDs reduces the risk of BSI. The use of an anti-infective lock solution warrants consideration for patients who require central access but who are at high risk of BSI, such as patients with malignancy or low-birthweight neonates.

Adult↗

PubMed1997

Cerebrospinal fluid (CSF) pharmacokinetics of intraventricular vancomycin in patients with staphylococcal ventriculitis associated with external CSF drainage.

We studied the efficacy and pharmacokinetics of intraventricularly administered vancomycin in three patients with shunt-associated staphylococcal ventriculitis. We instilled 10 mg of the drug intraventricularly every 24 hours. Cerebrospinal fluid (CSF) levels were measured 1 hour after instillation and then every 2 hours. Peak vancomycin levels reached a mean of 292.9 microg/mL. The mean trough levels, measured immediately before readministration of vancomycin, were 7.6 microg/mL; this level has proved to be sufficient for maintaining the necessary steady-state serum concentration of vancomycin. All three patients were cured clinically and bacteriologically, and CSF parameters returned to normal within 5-13 days. No side effects were observed. Our results suggest that intraventricularly administered vancomycin is a valuable therapeutic strategy for treating shunt-associated staphylococcal ventriculitis. In addition, we provide evidence that 10 mg of vancomycin, administered intraventricularly every 24 hours, allows maintenance of therapeutic drug levels in the CSF for at least 24 hours.

Brain Injuries↗

PubMed1998

Comparison of vancomycin and cefuroxime for infection prophylaxis in coronary artery bypass surgery.

OBJECTIVE: To investigate clinically significant differences between vancomycin and cefuroxime for perioperative infection prophylaxis in coronary artery bypass surgery. DESIGN: A total of 884 patients were randomized prospectively to receive either cefuroxime (444) or vancomycin (440) and were assessed for infectious complications during hospitalization and 1 month postoperatively. SETTING: A university hospital. RESULTS: The overall immediate surgical-site infection rate was 3.2% in the cefuroxime group and 3.5% in the vancomycin group (difference, -0.3; 95% confidence interval, -2.6-2.1). CONCLUSIONS: The data suggest that vancomycin has no clinically significant advantages over cephalosporin in terms of antimicrobial prophylaxis. We suggest that cefuroxime (or first-generation cephalosporins, which were not studied here) is a good choice for infection prophylaxis in connection with coronary artery bypass surgery in institutions without methicillin-resistant Staphylococcus aureus problems. In addition to the increasing vancomycin-resistant enterococci problem, the easier administration and usually lower price of cefuroxime make it preferable to vancomycin.

Aged↗

PubMed2000

Pharmacokinetics of 0.5 mg of a single and a multiple dose of intravitreal vancomycin in infected rabbit eyes.

The purpose of this study was to determine the pharmacokinetics governing distribution and elimination of 0.5 mg of intravitreal vancomycin in a single dose and in a multiple therapeutic regime in infected rabbit eyes. A total of 96 rabbits was injected with approximately 200 CFU of S. aureus intravitreally. Four days later, a single dose of 0.5 mg of vancomycin was administered to Group I (n=36). Group II (n=60) was injected with a maximum of 4 doses of 0.5 mg every 36 hr. Four animals were sacrificed at different time points in each group. Samples of vitreous, aqueous and blood were taken from each animal for analyses by HPLC. These results were evaluated using the RSTRIP program. High vancomycin concentrations were demonstrated in the vitreous of Group I, with a calculated half-life of 12 hr. In Group II, vancomycin levels were within the therapeutic range during the entire experiment. There was minimal accumulation of the drug, and the half-life did not seem to be longer with multiple doses. In conclusion, the pharmacokinetics do not change significantly when a multidose regime is used compared with a single dose. Therapeutic intravitreal concentrations of vancomycin can be achieved by using repeated doses of 0.5 mg of vancomycin.

Animals↗

PubMed1980

Binding of Clostridium difficile cytotoxin and vancomycin by anion-exchange resins.

Cholestyramine and colestipol were tested for binding of Clostridium difficile cytotoxin with use of batch absorption and column chromatography. The toxin was bound by both resins and could not be eluted from cholestyramine with either an ionic of a pH gradient. Vancomycin bound to cholestyramine more strongly than to colestipol. Cholestyramine and vancomycin were also tested for therapeutic efficacy in the hamster model of clindamycin-induced cecitis. Both compounds delayed death and reduced levels of cytotoxin in stool; these effects were greatest for vancomycin. Use of the two compounds in combination reduced concentrations of biologically active vancomycin in stool, but the levels still exceeded the minimum inhibitory concentration for C. difficile. These data suggest that the therapeutic benefit of cholestyramine in some patients with antibiotic-associated pseudomembranous colitis is due to its binding of the C. difficile cytotoxin. Since anion-exchange resins also bind vancomycin, caution is necessary if resins are used concurrently with vancomycin for therapy.

Absorption↗