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PubMed2004

An in vitro study on the compatibility and precipitation of a combination of ciprofloxacin and vancomycin in human vitreous.

AIMS: To investigate the precipitation process of a mixture of vancomycin and ciprofloxacin by equilibrium dialysis and its subsequent effect on the level of available free antibiotics. METHODS: Concentrations of vancomycin and ciprofloxacin in an equilibrium dialysis chamber were measured during the equilibrium process by high performance liquid chromatography and fluorescence polarisation immunoassay. Normal saline (NS), balanced salt solution plus (BSS Plus), and vitreous were used separately as the medium of dialysis. RESULTS: Precipitation of ciprofloxacin occurred on incubation at 37 degrees C. It formed precipitate on its own or when mixed with vancomycin in all the three media of NS, BSS Plus, and vitreous. There was more precipitation at higher initial ciprofloxacin concentrations; at 25.0 mg/l about 75% free drug in BSS Plus was lost after 72 hours. The extent of precipitation was similar in both NS and BSS Plus. In the dialysis chambers, 20 mg/l ciprofloxacin dialysed against 125 mg/l vancomycin was reduced to a concentration about 5.0 mg/l after 168 hours. Precipitation of vancomycin was negligible. Ciprofloxacin precipitated in vitreous at body temperature, irrespective of the presence of vancomycin. Even after precipitation, the resultant concentration of ciprofloxacin was still higher than the MIC(90) of the drug against most Gram negative organisms. CONCLUSIONS: Based on this in vitro study, ciprofloxacin precipitated in vitreous at body temperature, irrespective of the presence of vancomycin or the medium for intravitreal injection. The resultant amount of ciprofloxacin was still higher than the MIC(90) of the drug against most Gram negative organisms after precipitation. The authors suggest ciprofloxacin in place of ceftazidime when used in combination with vancomycin for treatment of infective endophthalmitis.

Aged↗

PubMed2004

Human corneal stromal tissue concentration after consecutive doses of topically applied 3.3% vancomycin.

AIMS: To evaluate vancomycin penetration into human corneal stromal tissue in patients treated with topical vancomycin eyedrops before penetrating keratoplasty (PKP). METHODS: Twenty four patients who underwent PKP, seven patients with keratoconus (group 1) and 17 patients with corneal scar or corneal decompensation (group 2). All patients received topical application of vancomycin eyedrops (concentration: 33 mg/ml) 10, 3, 2, 1 hour, and 15 minutes before the operation. Corneal cumulative vancomycin levels were assessed by bioassay. RESULTS: Mean vancomycin corneal stromal tissue concentration was 46.7 (SE 4.11) microg/g tissue. This value was four to 20-fold in excess of the MIC90 of vancomycin in Staphylococcus aureus (2-10 microg/ml). CONCLUSIONS: Vancomycin reached high corneal tissue concentrations that significantly exceeded the MIC90 (2-10 microg/ml) for most key Gram positive corneal pathogens. The ratio of vancomycin stromal concentration to protein concentration was statistically higher in group 2 (non-keratoconus).

Adult↗

PubMed2002

Dose regimen for vancomycin not needing serum peak levels?

AIM: To determine the safety, efficacy, and need to measure peak serum vancomycin concentrations in a neonatal population using a standard vancomycin dosage regimen. METHOD: A total of 101 infants who were admitted to a regional neonatal intensive care unit and received vancomycin (15 mg/kg every 12 or 18 hours depending on postnatal age) were studied retrospectively. Infants who had been started on vancomycin before they were transferred to the unit were excluded. The proportion of infants was measured whose serum vancomycin concentrations were within a conservative therapeutic range of trough 5-10 mg/l, peak 20-40 mg/l, and a less conservative, but still safe, range of trough 5-12 mg/l, peak 15-60 mg/l. RESULTS: Trough concentrations of 5-10 mg/l were achieved by 46.5% of infants, and 5-12 mg/l by 55.4%. Peak concentrations of 20-40 mg/l were found in 83.2% of infants, and 15-60 mg/l in 99.0%. Highest peak concentration was 47.2 mg/l. Some 89.4% of infants with trough concentrations of 5-10 mg/l had a peak concentration of 20-40 mg/l. CONCLUSIONS: The vancomycin dosage regimen used in this study produces acceptable therapeutic serum vancomycin concentrations. Peak serum vancomycin concentrations do not need to be measured in neonates using this dosage regimen.

Anti-Bacterial Agents↗

PubMed1992

Vancomycin: its effect on intracranial pressure.

Vancomycin is a commonly used antibiotic in neurosurgical practice. It is, however, notorious for causing histamine release which has been associated experimentally with rises in intracranial pressure (ICP). The observation that patients receiving vancomycin had an elevation in ICP during vancomycin infusion over 1 h, and that this elevation persisted for the hour following infusion led to a more formal evaluation. Presented here are data obtained from 6 patients who received vancomycin while on external ventricular drainage for a variety of reasons. The mean ICP for the hour prior to, during and following vancomycin administration was 8 mm Hg (SD 5.6), 13.8 mm Hg (SD 4.9), and 12.6 mm Hg (SD 4.3), respectively. The data were analyzed using a repeated measures analysis of variance between the preadministration values, during-administration values and postadministration values. The p value was significant at < 0.0001. These observations led to experimentation in animals to further assess the effects of vancomycin on ICP. The mean ICP prior to, during and following vancomycin infusion was 1.95 mm Hg (SD 0.75), 8.4 mm Hg (SD 5.1) and 5.6 mm Hg (SD 2.5), respectively. The data were analyzed using a repeated measure analysis of variance for the preadministration, during-administration and postadministration values. The p value was significant at < 0.0001. Based on these data the use of vancomycin should be tempered in the setting of intracranial pathology.

Animals↗

PubMed1979

Peritoneal transport of vancomycin during peritoneal dialysis.

The peritoneal transport of vancomycin during peritoneal dialysis was studied in 11 uremic patients following intravenous and intraperitoneal administration of vancomycin. The half-life of vancomycin was about 18 h and the clearance of vancomycin 6.1 ml/min (range 4.2--9.8) during the period of dialysis. Following intraperitoneal administration of vancomycin 50 micrograms/ml of dialysate, serum concentrations from 5.1 to 21.5 micrograms/ml were obtained and 35% of the instilled amount of vancomycin was absorbed during 15 h of dialysis. The peritoneal transport of vancomycin indicates that the dosage should be increased during peritoneal dialysis. Peritonitis caused by Staphylococcus aureus may be treated by peritoneal dialysis with vancomycin added to the dialysate.

Adolescent↗

PubMed1993

Vancomycin therapeutic drug monitoring: is it necessary?

OBJECTIVE: To review the literature and assess the validity of obtaining vancomycin serum drug concentrations in patients. DATA SOURCES: A MEDLINE search of the English literature and a bibliographic review of articles pertaining to vancomycin serum concentrations, their use, and the rationale of cited therapeutic ranges. STUDY SELECTION AND DATA EXTRACTION: Studies pertaining to the use of vancomycin concentrations in the clinical setting, methods for predicting these concentrations, and studies that reported efficacy or toxicity associated with vancomycin use and possible correlation of serum concentrations. DATA SYNTHESIS: The usefulness of vancomycin serum concentrations, the determination of a therapeutic range of values, and their correlation to antibacterial efficacy and drug toxicity in the clinical setting are controversial. Old reports of toxicities need to be critically examined due to lack of information and the actual frequency of toxic reactions. The efficacy of vancomycin's antibacterial effect and its correlation with reported therapeutic ranges may advocate obtaining a vancomycin trough concentration in certain groups of patients. CONCLUSIONS: Determination of serum vancomycin concentrations in the clinical setting and their usefulness in patient care is questionable and unnecessary in the majority of patients.

Animals↗

PubMed1994

Possible red-man syndrome associated with systemic absorption of oral vancomycin in a child with normal renal function.

OBJECTIVE: To report possible red-man syndrome (RMS) associated with oral administration of vancomycin. CASE SUMMARY: A 23-month-old child with acute myeloblastic leukemia developed symptoms compatible with RMS while receiving oral vancomycin for suspected Clostridium difficile colitis. Serum concentrations of vancomycin, measured at the time of the clinical episode, demonstrated significant oral absorption of the drug. Serum concentrations of vancomycin decreased later, implying a possible decrease in absorption, after the patient's neutrophil count returned to normal. The child later experienced another clinical episode compatible with RMS while vancomycin was being administered intravenously for suspected sepsis. DISCUSSION: There is no published report of RMS following oral administration of vancomycin. The reaction described took place while the child was neutropenic. Because of the absence of any significant renal function alteration that could explain the importance of the serum concentrations observed, we assume that C. difficile, neutropenia-, and chemotherapy-associated colitis may have resulted in extensive intestinal lesions, leading to an increased amount of vancomycin being systemically absorbed. This increased absorption during profound neutropenia may have been sufficient to exceed a purported threshold, leading to RMS. CONCLUSIONS: This case demonstrates that significant absorption of vancomycin may occur in neutropenic patients with normal renal function, and that it may be accompanied by RMS, usually associated with rapid infusions or large parenteral doses of the drug.

Administration, Oral↗

PubMed2000

Histamine release induced by antimicrobial agents and effects of antimicrobial agents on vancomycin-induced histamine release from rat peritoneal mast cells.

Vancomycin and certain fungicides may cause anaphylactoid reactions. We investigated the effects of vancomycin, miconazole and fluconazole on histamine release in rat peritoneal mast cells. Vancomycin and miconazole provoked histamine release in a dose-dependent manner. In contrast, fluconazole did not provoke histamine release at concentrations of 3 x 10(-6)-3 x 10(-3) M. Vancomycin is efficacious in the treatment of gram-positive bacterial infections; patients presenting themselves with mixed infections require concomitant therapy with a second antimicrobial agent. We investigated the effect of fosfomycin sodium, cilastatin sodium or fluconazole on vancomycin-induced histamine release. Fosfomycin sodium inhibited vancomycin-induced histamine release but neither cilastatin sodium nor fluconazole inhibited it in the mole ratios of daily doses used in humans. These results suggest that vancomycin and miconazole provoke histamine release in rat mast cells, but that fluconazole probably does not, while fosfomycin sodium may inhibit vancomycin-induced histamine release.

Animals↗

PubMed1990

Hemodynamic effects of rapid vancomycin infusion in critically ill patients.

The rapid infusion of vancomycin produces histamine release resulting in rash ("red-man's" syndrome) and hypotension. Because this phenomenon has been described primarily in healthy subjects, we prospectively studied the rapid infusion of vancomycin in 16 critically ill patients after open heart surgery in an attempt to document histamine release with resulting hemodynamic changes, and to see if there is any correlation with vancomycin levels. After establishing baseline hemodynamic stability and histamine levels, 1 g vancomycin diluted in 50 mL of 5% dextrose was infused over 30 min. Cardiac index, heart rate, blood pressure, pulmonary venous pressures, and systemic and pulmonary vascular resistances remained unchanged during the infusion. Although the mean plasma vancomycin level increased to a peak of 69 +/- 20 micrograms/mL after 20 min of the infusion before declining, mean plasma histamine levels in 15 of the 16 patients remained within the normal range during the infusion. In one patient a baseline histamine level (2.8 ng/mL) more than three times the normal before the vancomycin infusion increased further during the infusion (3.0, 4.9, and 5.0 ng/mL at t = 10, 20, and 30 min, respectively), and remained elevated (2.9 ng/mL) 30 min after the infusion. This patient developed the red-man's syndrome, although there were no hemodynamic changes. There was no evidence of myocardial depression in any of the patients. In conclusion, we safely infused a concentrated solution of vancomycin into critically ill patients over 30 min without any adverse hemodynamic changes. One patient developed the red-man's syndrome. There was no correlation between peak vancomycin levels and the release of histamine in this patient population.

Adult↗

PubMed1992

Intraventricular vancomycin-induced cerebrospinal fluid eosinophilia: report of two patients.

Pediatric neurosurgeons commonly instill vancomycin into the ventricles to treat shunt infections. This use for vancomycin, however, has not been studied in the laboratory to evaluate possible toxicities and side effects. We report two cases of cerebrospinal fluid eosinophilia (CSFE) secondary to the intraventricular administration of vancomycin. Two other cases of shunt infection during the same time period were treated for only 2 days with intraventricular vancomycin and did not manifest CSFE. We address the clinical problems and possible detrimental effects of CSFE in the setting of shunt infection. We propose a mechanism of vancomycin-induced mast cell degranulation and subsequent release of eosinophil chemotactic factor as a cause of CSFE. An initial dose of intraventricular vancomycin should take into account volume of distribution (ventricular size) to obtain a peak cerebrospinal fluid concentration of 20 to 30 micrograms/mL. We recommend following daily cell counts and vancomycin peak and trough levels to calculate the amount and frequency of intraventricular vancomycin required to maintain safe and effective concentrations and to monitor for CSFE.

Ceftazidime↗

PubMed1999

Life-threatening reaction to vancomycin given for noninfectious fever.

OBJECTIVE: To report a case of vancomycin-induced anaphylaxis (or anaphylactoid reaction) in a patient with a fever of unrecognized noninfectious origin. CASE SUMMARY: An 83-year-old white man, who was a patient of the Veterans Affairs Medical Center, developed a serious anaphylactic (or anaphylactoid) reaction while receiving intravenous vancomycin as empiric therapy for a nosocomial fever of unknown origin. The fever was subsequently proved to have been due to acute polyarticular gout rather than an infection. DISCUSSION: This patient developed respiratory distress and an increased serum troponin concentration, suggestive of a myocardial enzymatic leak as a result of vancomycin therapy. Vancomycin was given before the noninfectious cause of his fever was recognized. CONCLUSIONS: Even with cautious slow infusion, intravenous vancomycin can precipitate life-threatening infusion-related reactions in some patients. Because of this, and to reduce selective pressure for vancomycin resistance, sources of fever that do not require treatment with vancomycin should be diligently investigated prior to the institution of empiric vancomycin therapy in febrile patients, particularly when the past medical history is suggestive of an alternative diagnosis.

Aged↗

PubMed1999

Accuracy of measured vancomycin serum concentrations in patients with end-stage renal disease.

OBJECTIVE: To review information related to the accuracy of vancomycin serum drug concentrations in patients with end-stage renal disease, focusing on available assays and mechanisms of cross-reactivity. DATA SOURCES: Primary and review articles identified from a MEDLINE search (January 1980-June 1999) and through secondary sources. STUDY SELECTION AND DATA EXTRACTION: All articles identified were evaluated, and all relevant information was included in this review. DATA SYNTHESIS: Falsely elevated vancomycin serum concentrations may occur in patients with renal dysfunction. The underlying mechanism is due to the formation and accumulation of a pseudo-metabolite, the vancomycin crystalline degradation product (CDP). Vancomycin is converted to CDP when exposed to heat, including normal body temperature. Because the molecular structures of CDP and vancomycin are similar, both molecules are detected by polyclonal immunoassay systems used in clinical laboratories. This cross-reactivity leads to falsely elevated serum vancomycin concentrations in excess of 50-70%. Such large assay inaccuracies may result in improper dosage adjustments and therapeutic failures. A monoclonal immunoassay system has been developed that does not significantly cross-react with CDP. CONCLUSIONS: To appropriately interpret laboratory results, it is essential for clinicians to be aware of the vancomycin-CDP cross-reactivity problem and to be familiar with the specific assay used to measure vancomycin concentrations in patients with renal dysfunction.

Animals↗

PubMed2004

Vancomycin ointment for MRSA infection at a cranioplasty site.

OBJECTIVE: To report a case illustrating therapeutic success with long-term topical application of aseptic vancomycin ointment to treat methicillin-resistant Staphylococcus aureus (MRSA) infection at a cranioplasty site. CASE SUMMARY: A 63-year-old Japanese woman underwent evacuation of a subdural hematoma complicated by subarachnoid hemorrhage. Subsequent craniotomy for clipping and external decompression of an aneurysm of the neck was followed by cranioplasty using an autologous bone graft. The graft became infected with MRSA, which responded to intravenously infused vancomycin. The graft was then replaced with a ceramic implant. The implant site became reinfected with MRSA. Vancomycin infusion failed on this occasion, despite a favorable in vitro sensitivity test. After obtaining patient consent, investigative treatment was begun using long-term aseptic application of vancomycin 2.5% ointment, resulting in control of the infection and negative cultures. DISCUSSION: The care of an infection at the site of cranioplasty with a ceramic artificial bone implant is difficult. Our patient's infection resolved with the use of vancomycin ointment. In this case, blood concentrations of vancomycin remained below detectable levels, and no adverse effects resulted from application of vancomycin ointment. CONCLUSIONS: Topical administration of vancomycin was more effective than systemic administration in the treatment of our patient's MRSA skull implant infection. No adverse effects from topical treatment were encountered over 3 years.

Administration, Topical↗

PubMed2006

Vancomycin-induced elevation of liver enzyme levels.

OBJECTIVE: To report a case of oral vancomycin-induced elevation of liver enzyme levels. CASE SUMMARY: A 57-year-old man with multiple medical conditions requiring systemic antibiotic therapy developed numerous Clostridium difficile-associated enterocolitis episodes. The patient did not respond adequately to oral metronidazole, as evidenced by his continuing diarrhea. He was treated with oral vancomycin on 5 separate occasions (with doses from 125 to 500 mg/day), each of which resulted in significant elevations in alanine aminotransferase (to 371 U/L) and aspartate aminotransferase (to 203 U/L) levels. The elevations resolved on each occasion with discontinuation of vancomycin. DISCUSSION: Vancomycin, a glycopeptide antibiotic, has primary activity against gram-positive bacteria. Oral vancomycin can be used for the treatment of C. difficile-associated enterocolitis in patients who fail to respond to or are intolerant to metronidazole therapy. Oral vancomycin has very poor bioavailability and, as of May 4, 2006, has not been associated with hepatic toxicity. Inflammatory bowel disease processes can result in increased absorption of oral vancomycin. CONCLUSIONS: This is the first reported case of oral vancomycin-induced elevation of hepatic enzyme levels. Use of the Naranjo probability scale indicated that this was a probable adverse drug-associated event.

Alanine Transaminase↗

PubMed1999

Implications of vancomycin degradation products on therapeutic drug monitoring in patients with end-stage renal disease.

In renally impaired patients, vancomycin concentrations typically are maintained at body temperature for extended periods of time due to the drug's prolonged half-life. Both time and increased temperature potentiate production of vancomycin crystalline degradation products (CDP-1). Commercially available vancomycin assays, such as fluorescence polarization immunoassay (FPI) and radioimmunoassay, cross-react with CDP-1 isomers. Overestimation of vancomycin concentrations by 40-53% due to cross-reactivity of CDP-1 with active factor B vancomycin occurs with FPI. As FPI is the most common method of analyzing serum vancomycin, clinicians must be aware of its potential shortcomings and be prepared to alter vancomycin dosages in renally impaired patients. The possibility of adverse affects due to elevated concentrations of CDP-1 or therapeutic failures due to subtherapeutic levels of factor B vancomycin cannot be excluded.

Anti-Bacterial Agents↗

PubMed2006

Predictability of vancomycin trough concentrations using seven approaches for estimating pharmacokinetic parameters.

PURPOSE: Seven methods for estimating vancomycin pharmacokinetic parameters were studied to determine which method best predicted measured concentrations for patients at a community teaching hospital. METHODS: Data from adult patients who were given vancomycin and had at least one steady-state trough concentration measured were retrospectively reviewed. Data analyzed included laboratory test values, concomitant medications, weight, height, sex, age, laboratory cultures, medical procedures performed, vancomycin dose and interval, measured vancomycin concentrations, and time of measurement. Relevant data were used in seven predictor methods that estimate volume of distribution, vancomycin clearance, and elimination rate constant to determine which yielded the best predictions of actual measured concentrations in the patient population. RESULTS: Data from 189 patients were included in the analyses. The coefficients of determination for the methods ranged from 0.114 to 0.234. Bias ranged from -5.90 to 0.69 mg/L, and precision ranged from 6.05 to 8.08. The Matzke method had the best combination of the least bias and best precision. Predictions were within 2.5 and 5 mg/L of measured concentrations 18.0-43.9% and 43.4-66.1% of the time, respectively. The percentage of predictions within 25% and 50% of measured concentrations ranged from 7.9% to 31.2% and from 18.0% to 48.1%, respectively. Ten (5.3%) patients had trough concentrations exceeding 20 mg/L, and 11 (5.8%) had trough concentrations of < or = 3 mg/L. CONCLUSION: The seven methods studied for estimating vancomycin pharmacokinetic parameters varied widely in predicting vancomycin trough concentrations compared with measured serum concentrations and were not sufficiently reliable to replace therapeutic monitoring of vancomycin serum concentrations.

Anti-Bacterial Agents↗

PubMed1989

Synthesis and antibacterial evaluation of N-alkyl vancomycins.

Over eighty N-alkyl vancomycins were synthesized by reductive alkylation of vancomycin with the appropriate aldehydes. The N-alkyl vancomycins exhibit greater antibacterial activity than the corresponding N-acyl vancomycins and the parent antibiotic. Some of these semisynthetic vancomycins are five times more active than vancomycin. The N-alkyl vancomycins also show longer elimination half-lives in rats than vancomycin.

Animals↗

PubMed2001

Determinants of vancomycin resistance and mortality rates in enterococcal bacteremia. a prospective multicenter study.

BACKGROUND: Enterococcus species are major nosocomial pathogens and are exhibiting vancomycin resistance with increasing frequency. Previous studies have not resolved whether vancomycin resistance is an independent risk factor for death in patients with invasive disease due to Enterococcus species or whether antibiotic therapy alters the outcome of enterococcal bacteremia. OBJECTIVE: To determine whether vancomycin resistance is an independent predictor of death in patients with enterococcal bacteremia and whether appropriate antimicrobial therapy influences outcome. DESIGN: Prospective observational study. SETTING: Four academic medical centers and a community hospital. PATIENTS: All patients with enterococcal bacteremia. MEASUREMENTS: Demographic characteristics; underlying disease; Acute Physiology and Chronic Health Evaluation (APACHE) II scores; antibiotic therapy, immunosuppression, and procedures before onset; and antibiotic therapy during the ensuing 6 weeks. The major end point was 14-day survival. RESULTS: Of 398 episodes, 60% were caused by E. faecalis and 37% were caused by E. faecium. Thirty-seven percent of isolates exhibited resistance or intermediate susceptibility to vancomycin. Twenty-two percent of E. faecium isolates showed reduced susceptibility to quinupristin-dalfopristin. Previous vancomycin use (odds ratio [OR], 5.82 [95% CI, 3.20 to 10.58]; P < 0.001), previous corticosteroid use (OR, 2.43 [CI, 1.22 to 4.86]; P = 0.01), and total APACHE II score (OR, 1.06 per unit change [CI, 1.02 to 1.10 per unit change]; P = 0.003) were associated with vancomycin-resistant enterococcal bacteremia. The mortality rate was 19% at 14 days. Hematologic malignancy (OR, 3.83 [CI, 1.56 to 9.39]; P = 0.003), vancomycin resistance (OR, 2.10 [CI, 1.14 to 3.88]; P = 0.02), and APACHE II score (OR, 1.10 per unit change [CI, 1.05 to 1.14 per unit change]; P < 0.001) were associated with 14-day mortality. Among patients with monomicrobial enterococcal bacteremia, receipt of effective antimicrobial therapy within 48 hours independently predicted survival (OR for death, 0.21 [CI, 0.06 to 0.80]; P = 0.02). CONCLUSIONS: Vancomycin resistance is an independent predictor of death from enterococcal bacteremia. Early, effective antimicrobial therapy is associated with a significant improvement in survival.

APACHE↗