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PubMed1991

A targeted review of vancomycin use.

In recent years vancomycin usage at the Ottawa Civic Hospital has been steadily increasing. In an effort to determine the reason for this resurgence, and whether or not it is justified, a prospective assessment of vancomycin utilization was performed. All new orders for vancomycin received in the pharmacy in a two-month period were evaluated against predetermined criteria for appropriate use, which were developed in conjunction with Infectious Diseases and Cardiac Surgery. Of the 55 orders evaluated during the study period, 32 (58.2%) were considered inappropriate, translating to a cost of approximately $5,500.00 for the seven-week period. Use of vancomycin in penicillin-allergic patients without a confirmed history of IgE-mediated reaction, was responsible for the majority of vancomycin prescribed unnecessarily (-66%). As a result of the review's findings, the following actions were taken by the Pharmacy and Therapeutics Committee: (1) vancomycin was restricted to specific indications; (2) vancomycin will be prospectively monitored by the Pharmacy Department; (3) physician education on approved indications and dosing of vancomycin; and (4) development of guidelines for assessment and prescribing in penicillin-allergic patients.

Anti-Bacterial Agents↗

PubMed2001

Invasive infections due to vancomycin-resistant enterococci in adult patients.

Since 1990, vancomycin-resistant enterococci have emerged as important nosocomial pathogens. Invasive infections caused by these organisms have challenged most physicians because they are resistant to multiple antibiotics. We analyzed the clinical characteristics of adult patients with invasive vancomycin-resistant enterococci infections in the National Taiwan University Hospital from January 1993 through December 2000. A total of 11 adult patients were identified, 9 of whom had bacteremia (7 caused by vancomycin-resistant Enterococcus faecalis and 2 by vancomycin-resistant Enterococcus faecium) and one each had thoracic empyema (vancomycin-resistant E. faecium) and peritonitis (vancomycin-resistant E. faecium). Five patients had rectal swab cultures positive for vancomycin-resistant enterococci; 4 of them had underlying malignancies. The majority (91%) of these patients had prolonged hospitalization and prior long-term use of broad-spectrum cephalosporins (ceftriaxone, ceftazidime, or cefepime) or anti-anaerobic agents (clindamycin or metronidazole). The crude mortality rate was 64%. In conclusion, invasive infection caused by vancomycin-resistant enterococci is an emerging problem among hospitalized patients in Taiwan, particularly those with severe underlying diseases and exposure to multiple antibiotics.

Adult↗

PubMed2002

Phenotypes and genotypes of vancomycin-resistant enterococci isolated during long-term follow-up in a patient with recurrent bacteremia and colonization.

Twenty-seven isolates of vancomycin-resistant enterococci were obtained at monthly intervals from a bed-ridden man with hypoxic encephalopathy. During the 28-month period of the patient's hospitalization, 3 episodes of bacteremia and one episode of catheter-related infection caused by vancomycin-resistant enterococci occurred. Rectal swabs showed colonization of vancomycin-resistant enterococci for more than 2 years. Three months after termination of antimicrobial therapy, the rectal colonization for vancomycin-resistant enterococci was eradicated. Four species (Enterococcus faecium, Enterococcus gallinarum, Enterococcus faecalis, and Enterococcus casseliflavus) were identified among the 27 vancomycin-resistant enterococcus isolates. Three non-clonal related patterns were found among 17 strains of E. faecium by pulsed-field gel electrophoresis. All of the 3 E. faecalis isolates were of the VanB phenotype, but of the vanA genotype. Linezolid had the most potent in vitro activity against these vancomycin-resistant enterococcus isolates, with minimum inhibitory concentrations >2 microg/mL. Eighty-five percent of these vancomycin-resistant enterococcus isolates were susceptible to tetracycline and 66% were susceptible to quinupristin-dalfopristin. Although a high genetic correlation of E. faecium was identified in the patient with prolonged hospitalization, the isolation of 3 genetically unrelated colonized isolates suggested a lack of correlation between infection and colonization. Precautions against resistant organisms, adapted antibiotic policies, and elimination of patient carriage are useful for controlling the spread of vancomycin-resistant enterococci.

Anti-Bacterial Agents↗

PubMed1991

Vancomycin-induced thrombocytopenia.

Vancomycin-induced thrombocytopenia has only been reported once previously in the medical literature. We describe a patient in whom sudden severe reversible thrombocytopenia developed on two separate occasions after exposure to vancomycin hydrochloride. A 54-year-old man was admitted to the hospital for bilateral swelling and erythema of his extremities. At the time of admission he received 2 days of vancomycin therapy without incident. On day 14 he was reexposed to vancomycin and thrombocytopenia developed, with a nadir value of 17 x 10(9)/L. On day 30, a single dose of vancomycin was administered, and thrombocytopenia once again developed, with a nadir value of 11 x 10(9)/L. Hematologic cytopenias are infrequent adverse effects of vancomycin therapy. It is postulated that these effects may be due to an immunologically mediated mechanism. With the increasing use of vancomycin due to the emergence of methicillin-resistant Staphylococcus aureus, this case should alert clinicians to this rare but potentially lethal manifestation of vancomycin.

Humans↗

PubMed1990

Desensitization in the management of vancomycin hypersensitivity.

Vancomycin is the preferred antimicrobial agent in the treatment of methicillin-resistant staphylococcal infections. One of the well-known hypersensitivity reactions to this agent is the "red-man syndrome," which is believed to involve drug-induced histamine release in certain individuals. Although rate and/or dose reductions may be effective in some cases, some hypersensitivity reactions necessitate the discontinuation of vancomycin. In this article one patient is described who developed vancomycin-associated reactions consistent with the red-man syndrome despite having tolerated vancomycin administration previously. This case was managed by sequential increments in vancomycin administration over several days that allowed for therapeutic doses of the drug to be administered. Prior to desensitization, vancomycin administration at a lowered rate and dose was unsuccessfully attempted, despite the presence of combination antihistamine therapy. A loss of skin prick test reactivity to vancomycin was demonstrated after successful desensitization. This desensitization method may be useful in managing certain refractory cases of vancomycin hypersensitivity.

Adult↗

PubMed1989

Vancomycin pharmacokinetics in very low birth weight neonates.

The pharmacokinetics of vancomycin hydrochloride was studied in 12 very low birth weight infants. The gestational age (mean +/- SD) was 25.9 +/- 1.3 weeks and body weight was 769.2 +/- 151.5 g at the time of initiation of the study. Vancomycin was infused over a period of 60 minutes in a dosage of 14.2 +/- 3.2 mg/kg once daily in 10 patients, twice daily in 1 patient and every 36 hours in 1 patient for a mean of 10.5 +/- 4.9 days. Serial blood samples were obtained and the concentration time data were fitted to a one-compartment open model using the ADAPT computer program. A significant positive correlation was found between postconceptional age and vancomycin clearance (P less than 0.005) and between vancomycin elimination half-life and plasma creatinine (P less than 0.01). A negative correlation existed between plasma creatinine and vancomycin clearance (P less than 0.005), between postconceptional age and plasma creatinine (P less than 0.005) and between vancomycin half-life and postconceptional age (P less than 0.01). On the basis of these findings a vancomycin dosage of 15 mg/kg every 24 hours for infants less than 1000 g should yield concentrations within the accepted therapeutic range. This susceptible population requires frequent monitoring of vancomycin concentrations because of the high degree of interpatient variability and the continuous maturation of renal function.

Bacterial Infections↗

PubMed1988

Accuracy of delivery of cefazolin, chloramphenicol, and vancomycin by a controlled-release membrane infusion device.

The effects of flow rate and drug concentration on the accuracy of in vitro delivery of cefazolin, chloramphenicol, and vancomycin by a new controlled-release membrane infusion device, MICROS, were studied. Cefazolin, chloramphenicol, and vancomycin 1 g in sterile water for injection 10 mL were injected into the drug chamber of the device and delivered through an administration set with 0.9% sodium chloride injection from a primary line. Drug delivery was studied at four flow rates (0.5, 1.0, 1.5, and 2.0 mL/min). In addition, three concentrations of each drug (25, 50, and 100 mg/mL for cefazolin and vancomycin, and 50, 100, and 200 mg/mL for chloramphenicol) were studied at a fixed flow rate of 1 mL/min. Samples were collected in triplicate every 2.5-5.0 minutes using a fraction collector over a 90-minute period for cefazolin and a 120-minute period for chloramphenicol and vancomycin. The concentration of each drug was measured by high-performance liquid chromatography. At various flow rates, the time for delivery of greater than or equal to 95% of each dose ranged from 30 to 55 minutes for cefazolin, 45 to 70 minutes for chloramphenicol, and 50 to 65 minutes for vancomycin. At various concentrations, greater than or equal to 95% of each dose was delivered in 40 to 55 minutes for cefazolin, 40 to 70 minutes for chloramphenicol, and 50 to 60 minutes for vancomycin. The desired delivery times were 30-60 minutes for cefazolin and chloramphenicol and 50-70 minutes for vancomycin. Delivery of cefazolin and vancomycin by the MICROS membrane infusion system was accurate. Some delay was encountered in the delivery of chloramphenicol.(ABSTRACT TRUNCATED AT 250 WORDS)

Cefazolin↗

PubMedDate not supplied

Elimination of vancomycin by continuous arteriovenous hemofiltration.

Continuous arteriovenous hemofiltration (CAVH) is being used increasingly in pediatric patients with acute renal failure and/or other fluid and electrolyte imbalances. At times, vancomycin may be concurrently given for sepsis therapy. We evaluated the removal of vancomycin by CAVH in a 15-month-old male child with renal failure who was receiving the drug for suspected infection of an arterial catheter. Two separate CAVH treatments were performed with polysulfone membranes. Serum samples and ultrafiltrate outflow (n = 6) were collected over 79 h for vancomycin concentration determination. The mean vancomycin concentration in the ultrafiltrate was 90.4 +/- 5.4% of those of the serum. 0.53-1.11 mg of the drug was removed per hour by CAVH at serum concentrations of 12.4-25.4 mg/l. CAVH vancomycin clearance was 0.039-0.050 liter/h. The CAVH drug clearances accounted for 66.2% of the total vancomycin clearance. CAVH is thus a major route of vancomycin elimination. Dosage adjustment and serum concentration monitoring are necessary in patients undergoing CAVH while receiving vancomycin therapy.

Acute Kidney Injury↗

PubMedDate not supplied

Pharmacology and efficacy of vancomycin for staphylococcal infections in children.

Vancomycin is effective against most multiply resistant staphylococci, organisms that are becoming increasingly important in clinical medicine. Reported experience with vancomycin therapy in pediatric patients is limited. In this study vancomycin was administered intravenously to 33 patients whose ages ranged from one week to 16 years and who had suspected or proved infections caused by either Staphylococcus aureus or Staphylococcus epidermidis. The spectrum of staphylococcal infections included skin and soft-tissue infections and abscesses, osteomyelitis, pneumonia, shunt infections, endocarditis, and septicemia. All 29 patients with bacteriologically proved staphylococcal infections responded to vancomycin therapy. Peak and trough concentrations of vancomycin in serum produced satisfactory bacteriostatic and bactericidal titers against the infecting pathogens. In an anephric patient hemodialysis removed only negligible amounts of vancomycin. The amount of vancomycin that penetrated into ventricular fluid of 10 patients with shunt infections ranged from 7% to 37% (mean, 18%) of serum concentrations. One case of phlebitis and one case of transient elevation of serum levels of aspartate amino transferase were observed. No renal or otologic damage was detected in any patient. Adequate dilution of the drug, intravenous administration during 1 hr, and monitoring of the concentration in serum of patients undergoing long-term treatment and/or with impaired renal function minimize the likelihood of side effects. Vancomycin is an effective and safe agent for treatment of staphylococcal infections in pediatric patients.

Adolescent↗

PubMed1995

Recommendations for preventing the spread of vancomycin resistance. Recommendations of the Hospital Infection Control Practices Advisory Committee (HICPAC).

Since 1989, a rapid increase in the incidence of infection and colonization with vancomycin-resistant enterococci (VRE) has been reported by U.S. hospitals. This increase poses important problems, including a) the lack of available antimicrobial therapy for VRE infections, because most VRE are also resistant to drugs previously used to treat such infections (e.g., aminoglycosides and ampicillin), and b) the possibility that the vancomycin-resistant genes present in VRE can be transferred to other gram-positive microorganisms (e.g., Staphylococcus aureus). An increased risk for VRE infection and colonization has been associated with previous vancomycin and/or multiantimicrobial therapy, severe underlying disease or immunosuppression, and intraabdominal surgery. Because enterococci can be found in the normal gastrointestinal and female genital tracts, most enterococcal infections have been attributed to endogenous sources within the individual patient. However, recent reports of outbreaks and endemic infections caused by enterococci, including VRE, have indicated that patient-to-patient transmission of the microorganisms can occur either through direct contact or through indirect contact via a) the hands of personnel or b) contaminated patient-care equipment or environmental surfaces. This report presents recommendations of the Hospital Infection Control Practices Advisory Committee for preventing and controlling the spread of vancomycin resistance, with a special focus on VRE. Preventing and controlling the spread of vancomycin resistance will require coordinated, concerted efforts from all involved hospital departments and can be achieved only if each of the following elements is addressed: a) prudent vancomycin use by clinicians, b) education of hospital staff regarding the problem of vancomycin resistance, c) early detection and prompt reporting of vancomycin resistance in enterococci and other gram-positive microorganisms by the hospital microbiology laboratory, and d) immediate implementation of appropriate infection-control measures to prevent person-to-person transmission of VRE.

Anti-Bacterial Agents↗

PubMed1993

Safety of vancomycin with or without gentamicin in neonates.

Short- and long-term side effects of vancomycin, or the combination of vancomycin and gentamicin, were retrospectively evaluated for 65 treatment courses in 47 premature infants who were exposed to high vancomycin serum concentrations. Thirty-five treatment courses involved treatment with the combination; 30 courses involved treatment with vancomycin alone. No immediate side effects were noted. Nephrotoxicity, defined as an increase in serum creatinine 0.5 mg/dl or more above baseline, was found in only 1 patient receiving vancomycin as the only antibiotic; that patient had pre-existing renal dysfunction. Three treatment courses involving the vancomycin-gentamicin combination resulted in nephrotoxicity; renal function returned to normal by 14 days after treatment. Thrombocytopenia was noted in 5 patients, but none exhibited clinical bleeding. Low platelet counts persisted throughout treatment, but by two weeks after treatment, this was resolved. In conclusion, the use of vancomycin or the combination of vancomycin and gentamicin in seriously ill premature infants is usually safe. The adverse effects noted were reversible, and monitoring creatinine and platelet counts during treatment is recommended.

Drug Monitoring↗

PubMed1994

Vancomycin dosing in neonatal patients: the controversy continues.

During the past decade, an increasing incidence of staphylococcus organisms resistant to penicillinase-resistant penicillins has necessitated the use of vancomycin. This increased utilization has revitalized research concerning efficacious vancomycin dosing regimens for premature neonates, infants, and children. Vancomycin dosing in neonates is variable because this patient population has decreased renal clearance and a larger volume of distribution than infants, children, or adults. The observation of the variability in vancomycin clearance and volume of distribution in infants with the same postconceptional age (PCA) but different gestational age (GA) suggests that the rates of maturation both extrauterine and intrauterine for disposition mechanisms of vancomycin are similar when PCAs are equal. Conditions such as patent ductus arteriosus, respiratory distress syndrome, sepsis, and asphyxia may further complicate the renal maturation process. Few investigations suggest vancomycin dosing regimens. Most of these studies propose dosing regimens based on retrospective analysis of vancomycin pharmacokinetics obtained from regimens based on physician discretion. To ensure efficacious and rational vancomycin dosing for premature neonates and infants, regimens should consider PCA as well as body weight.

Aging↗

PubMed1977

Vancomycin.

Vancomycin, a useful bactericidal antibiotic for selective clinical infections, is the therapy of choice for serious staphylococcal infections when the penicillins and cephalosporins cannot be used. The antibacterial spectrum of vancomycin also covers other gram-positive cocci and bacteria and gram-negative cocci. Vancomycin is given intravenously in most cases, usually in a dose of 1 g every 12 hours in patients who have normal renal function. The indications for vancomycin therapy are as follows. 1. Serious staphylococcal infections in patients who are intolerant to the penicillins and cephalosporins or when the organism is resistant to the commonly used bactericidal agents. 2. Streptococcal endocarditis in patients intolerant to penicillin G; in enterococcal infections, it is used with an associated aminoglycoside. Vancomycin is not used alone in enterococcal endocarditis. In nonenterococcal (Streptococcus bovis) and viridans streptococcal endocarditis, vancomycin may be used alone if the minimum bactericidal concentration is less than or equal to 10 microgram/ml; otherwise, it is combined with an aminoglycoside. 3. Other serious infections caused by organisms resistant to the commonly used agents such as corynebacterial endocarditis. 4. Acute staphylococcal ileocolitis, for which vancomycin is given orally or orally and intravenously if indicated. Vancomycin is relatively nontoxic; the predominant toxic response is neurotoxicity, but this is rarely seen if the serum levels are 30 microgram/ml or less.

Acute Disease↗

PubMed1998

[Increase of non-amidated muropeptides in the cell wall of vancomycin-resistant Staphylococcus aureus (VRSA) strain Mu50].

The mechanism of resistance was studied with vancomycin-resistant Staphylococcus aureus (VRSA) strain Mu50. It was demonstrated that the incorporation of 14C-N-acetylglucosamine into the cell wall of Mu50 was not suppressed in the presence of 8 microliters/ml of vacomycin, whereas it was completely suppressed in vancomycin-susceptible strains FDA209P and H-1. Increased binding of vancomycin to the wall of Mu50 was observed compared to the control strains: 1.7 x 10(16) (Mu50), 6.1 x 10(15) (209P), and 6.7 x 10(15) (H-1) vancomycin molecules/mg cell wall, respectively. Remarkable proportion of the cell-wall component muropeptides were non-amidated in the cell wall of Mu50. In concordance with this phenomena, peptidoglycan cross-linkage decreased strikingly in the Mu50 strain. Free D-Ala-D-Ala residues at the end of muropeptides in the pre-existing cell wall generated by decreased cross-linkage seems to account for increased vancomycin binding. The increase of vancomycin-resistance level is presumably caused by sequestration of vancomycin molecules from primary target point on cell membrane. It was considered that at least two phenotypic changes are required for the vancomycin resistance in the Mu50 strain. First, as we have described previously, is the activated cell wall synthesis, and second, the reduction of cross-linkage of peptidoglycan by production of non-amidated muropeptide precursors.

Acetylglucosamine↗

PubMed2003

Antimicrobial resistance patterns of vancomycin-resistant Streptococcus equinus isolated from animal foods and epidemiological typing of resistant S. equinus by microbial uniprimer kit.

Raw milk samples, and cow and chicken intestines were tested to isolate vancomycin-resistant, gram-positive bacteria. From these samples, we isolated seven vancomycin-resistant Streptococcus equinus, two vancomycin-resistant viridans Streptococcus and two vancomycin-resistant Enterococcus faecium. The MICs of several antibiotics, including vancomycin, against these strains were tested. Seven isolates of S. equinus showed high level resistance to vancomycin and teicoplanin (>100 microg/mL). The cell wall thickness of these strains was compared with that of the sensitive strain by TEM and no differences were obserbed between these strains. We compared the strains of vancomycin-resistant Streptococcus equinus using PCR with Microbial Uniprimer Kit. We concluded that it is necessary to combine other methods in order to cluster and identify all isolates of S. equinus.

Animals↗

PubMedDate not supplied

In vitro activity of LY333328, a new glycopeptide, against extracellular and intracellular vancomycin-resistant enterococci.

The objectives of the study were to observe the activity of LY333328, a new semisynthetic glycopeptide, compared to that of vancomycin against six strains of Enterococcus faecium and Enterococcus faecalis, including four vancomycin-resistant strains. Bacteria ingested by polymorphonuclear leukocytes (PMN) as well as extracellular bacteria were studied using a colony count method. The activity against intracellular bacteria was tested with the drugs present in the extracellular medium, as well as after preincubating the PMN and removal of the drugs. LY333328 is active against the tested enterococci, regardless of their susceptibility to vancomycin, with MICs of 1-2 mg/l. It is bacteriostatic against extracellular enterococci at concentrations of 2 microg/ml and above regardless of their resistance to vancomycin. After 4 h incubation at 10 MIC, vancomycin-resistant strains of E. faecium and E. faecalis located intracellularly were reduced by 55% and 90%, respectively. Even after preincubation and removal of the drug, LY333328 had an effect at 10 MIC with a 20-30% reduction in the inoculum. The results suggest that in contrast to vancomycin, LY333328 is active against intracellular vancomycin-resistant enterococci, particularly E. faecalis, even after removal of the extracellular drug.

Anti-Bacterial Agents↗

PubMed2001

Low-level resistance to glycopeptides amongst staphylococcus species: surveillance in a university hospital and evaluation of a vancomycin screening agar.

The prevalence of low-level resistance to glycopeptides (teicoplanin MIC > or = 8 microg/mL and vancomycin MIC > or = 4 microg/mL) among staphylococci was investigated over a 15 month period. A total of 2,279 isolates (1,519 S. aureus, 760 coagulase-negative staphylococcus (CNS)) were screened using inoculum of 10(6) CFU/mL and Mueller-Hinton agars supplemented with 8 microg/mL of teicoplanin. Of these, 218 isolates (136 S. aureus and 82 CNS) grew on the screening agar. For these isolates, teicoplanin and vancomycin MICs were determined by agar dilution method and a vancomycin agar screening method was evaluated. The prevalence of low-level resistance to teicoplanin and vancomycin was 7.8% and 0.1% for S. aureus and 8.8% and 0.8% for CNS, respectively. The brain heart infusion agar containing 4 microg/mL of vancomycin failed to detect two out of eight staphylococcal isolates with vancomycin MICs of 4 microg/mL. Furthermore, the method appeared to lack reproducibility. Considering the increasing incidence of vancomycin treatment failure in staphylococcal infection, a more reliable screening method is required.

Agar↗

PubMed2000

Vancomycin treatment failures in Staphylococcus aureus lower respiratory tract infections.

We reviewed all patients with Staphylococcus aureus lower respiratory tract infections treated with vancomycin at our institution in 1998, to see how this antimicrobial is performing. We found that approximately 40% of evaluable patients were considered treatment failures, even though the S. aureus was still reported as being susceptible to vancomycin. We report in detail two example patients that failed to respond clinically to vancomycin and summarize the clinical characteristics of the 23 additional patients that failed. The first case was treated four times in the intensive care unit with vancomycin. Each course, after approximately 14 days therapy, the vancomycin was discontinued and his infection relapsed soon thereafter. The second was treated with vancomycin for 10 days initially. She relapsed, was restarted on vancomycin once more, but her condition deteriorated, and she died of refractory sepsis 20 days after admission. The cost of care for each patient ranged from $50,000 to over $100,000. With trends such as these, alternative therapies are needed to control resistant Gram-positive infections.

Aged↗