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PubMed1990

Pharmacokinetics and cerebrospinal fluid (CSF) concentrations of vancomycin in pediatric patients undergoing CSF shunt placement.

Staphylococcus epidermidis has been established as the common pathogen causing cerebrospinal fluid shunt infections. In addition, clinical isolates of S. epidermidis from infected shunts are typically resistant to methicillin. Vancomycin is often used for neurosurgical prophylaxis due to its excellent in vitro activity against methicillin-resistant staphylococci. Limited data are available about the pharmacokinetics and cerebrospinal fluid concentrations of vancomycin in pediatric patients intraoperatively. The objectives of this study were to characterize the pharmacokinetics and determine the cerebrospinal fluid concentrations of vancomycin. Eight patients (mean age 8.3 +/- 7.0 years) received three doses of intravenous vancomycin, 15 mg/kg every 6 h. The first dose was administered 1 h prior to surgery. Blood samples were collected at 0, 0.5, 1, 2, 4, and 5 h after the end of the infusion. A cerebrospinal fluid sample was collected at the time of shunt insertion. Urine samples were collected over a 24-hour period. Vancomycin was measured with a fluorescence polarization immunoassay. The peak serum concentrations ranged from 15.6 to 33.7 micrograms/ml; cerebrospinal fluid concentrations ranged from less than 0.6 to 0.8 microgram/ml. The mean total clearance, renal clearance, apparent volume of distribution, and elimination half-life were 0.11 +/- 0.05 l/h/kg, 0.07 +/- 0.02 l/h/kg, 0.54 +/- 0.15 l/kg, and 4.8 +/- 4.0 h, respectively. Approximately 70% of total vancomycin dose was excreted in the urine. A 2- to 5-fold variation in total clearance and a 2.5-fold variability in renal clearance were observed. Low cerebrospinal fluid concentrations of vancomycin were present at the time of shunt insertion in these pediatric patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMedDate not supplied

Conventional and nonconventional modes of vancomycin administration to decontaminate the internal surface of catheters colonized with coagulase-negative staphylococci.

Using a quantitative in vitro model simulating clinical conditions, we studied the efficacy of conventional and nonconventional 3-day therapies involving vancomycin for treating the internal surface of catheters colonized with a slime-producing strain of Staphylococcus epidermidis. When infused for 1 hr every 8 hr through the catheter at the daily dose recommended for a 10-kg child (450 mg), vancomycin alone reduced bacterial colonization but failed to sterilize the inserts. Vancomycin was more active in combination with netilmicin (25 mg for 1 hr every 8 hr), rifampin (150 mg for 90 min every 12 hr), or fosfomycin (500 mg for 4 hr every 6 hr), but the catheters were inconsistently decontaminated after 3 days of treatment. Two nonconventional modes of antibiotic administration were tested for their capacity to ensure high levels of vancomycin in the catheter lumen over a prolonged time. Vancomycin infused continuously through the catheter at a daily dose of 450 mg had the same poor sterilizing effect as vancomycin administered intermittently. On the contrary, catheters were totally decontaminated when 2.5 mg of vancomycin in a volume of 0.5 ml were injected twice daily into noninfused catheters, confirming that the antibiotic-lock technique is an approach of great interest to sterilize the internal surface of catheters colonized with staphylococci.

Catheters, Indwelling↗

PubMed1998

Vancomycin administration in continuous ambulatory peritoneal dialysis: the risk of ototoxicity.

A prospective study was undertaken in 16 patients with chronic renal failure on continuous ambulatory peritoneal dialysis, with 22 episodes of peritonitis treated with vancomycin, a known ototoxic agent. Twelve patients had one episode each, and four had recurrent peritonitis. Each treatment course consisted of two infusions of vancomycin (30 mg/kg body weight) in 2 L of peritoneal dialysate administered at 6-day intervals. Serum vancomycin analyzed by enzyme immunoassay showed a mean trough level of 11.00 microg/ml on day 6 and mean serum levels of 33.8 and 38.6 microg/ml about 12 hours after administration on days 1 and 7, respectively. Similar levels, well within the therapeutic range, were encountered with repeated vancomycin therapy for recurrent episodes of peritonitis, suggesting that no changes occurred in the pharmacokinetic profile of the drug. Pure-tone audiometry, electronystagmography, and clinical assessment performed during each course of treatment showed no evidence of ototoxicity even on repeated courses of vancomycin therapy. The results suggest that vancomycin therapy when given in appropriate concentrations as a single therapeutic agent is both effective and safe. We believe, however, that vancomycin administered in combination with an aminoglycoside may produce ototoxic effects that may be greatly aggravated, possibly because of synergism.

Adult↗

PubMed1995

Changes in vancomycin pharmacokinetics in critically ill infants.

We aimed to assess the pharmacokinetics of vancomycin in critically ill infants, and to evaluate the standard recommended dose of 10 mg/kg 6 hourly. All infants admitted to the Baragwanath Hospital ICU who had arterial lines in situ, and for whom vancomycin 10 mg/kg 6 hourly was prescribed for an infective insult and who had parental consent, were included in the study. Vancomycin was infused over 60 minutes. Serum samples were taken immediately before the dose and at 30, 60, 120 and 300 minutes after the end of the vancomycin infusion, on days 2 and 8 of therapy. Extrapolated peak concentration (Cmax), trough concentration (Cmin), apparent volume of distribution (Vd), elimination half-life (t1/2el) and clearance (CL) were determined for each patient. Day 2 values were compared with those of day 8. Day 2 serum concentrations were assayed on 20 patients and day 8 concentrations in 15. The mean vancomycin Vd on day 2 (0.81 l/kg) was significantly (P = 0.007) larger than that on day 8 (0.44 l/kg). The change in Vd resulted in a significant change in mean Cmax (29.1 vs 35.5 micrograms/ml) (P = 0.02) and mean t1/2el (5.3 vs 3.4h) (P = 0.01) over the treatment period. Critically ill infants displayed a large initial volume of distribution which probably resulted from aggressive fluid resuscitation. This also results in a large variation in other pharmacokinetic parameters, namely Cmax and t1/2el. Although the routine monitoring of vancomycin serum concentrations remain controversial, we feel that in view of these large pharmacokinetic variations, the critically ill infant is a specific group where monitoring of vancomycin serum levels is indicated.

Anti-Bacterial Agents↗

PubMed1986

Monitoring vancomycin therapy.

Vancomycin is an effective and widely used antistaphylococcal antibiotic. Despite several decades of use, however, our knowledge of the toxicologic and pharmacokinetic properties of vancomycin remains incomplete. This review summarizes current information regarding the adverse reactions and pharmacokinetics of vancomycin. Although there have been reports of side effects with vancomycin, these effects tend to be infrequent, easily managed, and reversible. Several methods for adjustment of vancomycin therapy have been recommended. The relationship between serum concentrations of vancomycin and the occurrence of ototoxicity or nephrotoxicity has not been well established. However, because of large interpatient variations in pharmacokinetic parameters, it seems preferable to individualize vancomycin therapy based on serum concentration data.

Adult↗

PubMed1991

Oral vancomycin-induced rash: case report and review of the literature.

Disseminated rash and pruritus are described in an 82-year-old woman with chronic renal failure following administration of oral vancomycin hydrochloride 125 mg q6h for the treatment of Clostridium difficile colitis. Renal function was estimated to be 0.27 mL/s based on a serum creatinine of 177 mumol/L. After eight days of therapy, she developed a slightly raised maculopapular rash on her legs and torso, which spread to her abdomen and arms with continued treatment. Vancomycin was discontinued and the patient was treated symptomatically. The rash cleared and did not recur. Rechallenge with vancomycin was not initiated. No other changes in medications or initiations of new medications occurred during the time of treatment with vancomycin. The patient denied any previous immunologically mediated reactions to medications. Maculopapular rash is rare secondary to vancomycin administration, particularly after oral administration. Although clinically significant serum concentrations can be obtained in patients treated with oral vancomycin who have concomitant C. difficile colitis and renal failure, there has not been a clear correlation between these concentrations and any reported adverse sequelae. This case supports the possible occurrence of a true allergic reaction secondary to low-dose oral vancomycin administration.

Administration, Oral↗

PubMedDate not supplied

Vancomycin administration into the cerebrospinal fluid: a review.

OBJECTIVE: To discuss administering vancomycin directly into the cerebrospinal fluid (CSF) to treat serious central nervous system (CNS) infections. DATA SOURCES: References were obtained through an online search of MEDLINE, limited to material published in English. In addition, information was extracted from clinical trials, review articles, abstracts, and textbooks. STUDY SELECTION: Systematic evaluation of this topic in humans has not been done in a prospective manner. Related research articles describing the pathophysiology of CNS infections, intrathecal drug administration, and case reports of CSF vancomycin administration were reviewed. DATA EXTRACTION: Case reports regarding CSF vancomycin dosing were evaluated and included: drug dosing, infecting organism, infectious disease state, infectious outcome, CSF dynamics/flow abnormalities, methods of drug administration, drug monitoring, and toxicities. DATA SYNTHESIS: The results of this review are based on qualitative evaluations of anecdotal case reports and a basic understanding of intrathecal and intraventricular drug dosing principles. CSF administration of vancomycin is an effective means of bypassing the blood-brain barrier to achieve greater drug concentrations within the CSF. Current limitations to the CSF administration of vancomycin include a lack of data describing its safety, efficacy, and pharmacokinetics. CONCLUSIONS: CNS infections may require the CSF administration of vancomycin for successful eradication. Recommendations for dosing in the literature vary. Because of the potential toxicities associated with elevated CSF concentrations of vancomycin, dosing should be conservative.

Central Nervous System Diseases↗

PubMed1994

Stability of ceftazidime and vancomycin alone and in combination in heparinized and nonheparinized peritoneal dialysis solution.

OBJECTIVE: To examine the stability of ceftazidime, vancomycin, and heparin, alone and in combination, in dialysis solution over six days at three temperatures. DESIGN: Nine 250-mL Dianeal PD-2 dextrose 1.5% bags were prepared with ceftazidime, vancomycin, and heparin alone and in combination at set concentrations of 100 micrograms/mL, 50 micrograms/mL, and 1 unit/mL, respectively. Three bags of each mixture were stored at 4, 25, and 37 degrees C. Duplicate samples for analysis were removed from each bag at the following time points: premix, 0, 12, 24, 48, 72, 96, 120, and 144 hours. MAIN OUTCOME MEASURES: Each sample was examined visually for signs of cloudiness and precipitation. Each sample was analyzed by stability-indicating HPLC assay for ceftazidime and vancomycin, with stability defined as less than 10 percent degradation of drug over time. RESULTS: No color change or precipitation was observed in any bag. Vancomycin with or without heparin was stable for 5-6 days at 4, 25, and 37 degrees C. Ceftazidime with and without heparin was stable for 6 days at 4 degrees C, 4 days at 25 degrees C, and less than 12 hours at 37 degrees C. Vancomycin plus ceftazidime with and without heparin was stable for 6 days at 4 degrees C and 25 degrees C, and 4-5 days at 37 degrees C. Ceftazidime plus vancomycin with or without heparin was stable for 6 days at 4 degrees C, 2-3 days at 25 degrees C, and 12 hours at 37 degrees C. CONCLUSIONS: Bulk preparations of ceftazidime and vancomycin, alone and in combination and with or without heparin in Dianeal PD dextrose 1.5% solution, are sufficiently stable for use up to 6 days under refrigeration or 48 hours at room temperature.

Ceftazidime↗

PubMed2004

Fluctuations in vancomycin CNS tissue concentrations following intermittent and continuous infusions in the rat.

The purpose of this investigation was to compare the variability of vancomycin concentrations in the serum and CNS when administered continuously or as intermittent intravenous infusions in the rat. The hypothesis for this investigation was that the magnitude of change in serum vancomycin concentrations directly relates to the extent of vancomycin concentration fluctuations in the CNS. Microdialysis and serum sampling techniques were employed and biologic samples were analysed for vancomycin using HPLC. Over the dosing interval, the mean changes in concentrations were 71.8 +/- 9.8% and 13.6 +/- 9.3% for serum and 61.7 +/- 7.8% and 6.8 +/- 3.5% for brain extracellular fluid in the intermittent and continuously infused groups, respectively. Accordingly, the relative changes in vancomycin concentrations in brain extracellular fluid were closely associated with corresponding changes in serum concentrations (R2=0.94). Thus, continuous intravenous administration of vancomycin results in minimal serum and CNS tissue concentration changes as compared to traditional intermittent dosing methods and allows for more consistent vancomycin concentrations in the CNS.

Animals↗

PubMed2000

Comparison of efficacy and safety of teicoplanin and vancomycin in children with antineoplastic therapy-associated febrile neutropenia and gram-positive bacteremia.

To compare their efficacy and safety, teicoplanin and vancomycin were randomly administered to 32 children for 52 gram-positive bacteremias during malignancy-associated neutropenia (<1000/microl). Patients mainly suffered from hematological malignancies. Twenty-five episodes were treated with teicoplanin (10 mg x kg(-1) x d(-1)) and 21 with vancomycin (40 mg x kg(-1) x d(-1)) plus ceftazidime and netilmicin. Six episodes were treated with teicoplanin because of previous "red man" reaction to vancomycin. Staphylococci (12% Staphylococcus aureus) were isolated from 50 episodes and viridans streptococci from 2. Defervescence on 3rd-4th day occurred in 29/31 (93.5%) teicoplanin-treated and 18/21 (85.7%) vancomycin-treated episodes. All 12 teicoplanin-treated and 13/13 vancomycin-treated episodes with repeat blood cultures on 3rd-4th day showed microbiological response. Two teicoplanin-treated and 3 vancomycin-treated patients required antifungals. Mild renal insufficiency appeared in 5 vancomycin-treated patients that was corrected without drug discontinuation. While both glycopeptides exhibit equal clinical and microbiological efficacy, teicoplanin is less likely to induce allergic reactions or nephrotoxicity in children.

Anti-Bacterial Agents↗

PubMed2006

Appropriateness of empiric gentamicin and vancomycin therapy for bacteremias in chronic dialysis outpatient units in the era of antibiotic resistance.

Bacteremias in inpatient chronic HD units have been described, but there is little information on bacteremias in ambulatory HD units. To determine the frequency of bacteremia and pathogen distribution in ambulatory chronic HD units, we retrospectively reviewed our experience with 107 bacteremias in 5 chronic ambulatory HD units over a 3 year period. The object of the study was twofold. The first objective was to determine if bacteremias in ambulatory HD setting were substantially different in frequency or type than in the inpatient HD setting. Secondly, febrile patients suspected of having bacteremia in chronic HD patients are often empirically treated with vancomycin and gentamicin. Chronic HD patients require repeated and frequent venous access for HD. Bacteremias are common in chronic HD patients and may be primary or secondary and are often related to venous access site infections. The distributions of bacteremia pathogens in chronic HD patients are predominantly reflective of skin flora, i.e., staphylococci and to lesser extent aerobic Gram-negative bacilli. After S. aureus (MSRA/MSSA) and coagulase-negative staphylococcus (CoNS), enterococci are the next most important Gram-positive pathogens in bacteremic HD patients. Most strains of E. faecalis are sensitive to vancomycin and for practical purposes should be considered as vancomycin sensitive enterococci (VSE). In contrast, most strains of E. faecium are resistant to vancomycin and should be considered as vancomycin resistant enterococci (VRE). We retrospectively reviewed 107 patients on chronic ambulatory HD to determine the adequacy of empiric vancomycin and gentamicin prophylaxis. We found amikacin is preferred to gentamicin and that meropenem is an effective alternate substitution for gentamicin and vancomycin combination therapy.

Antibiotic Prophylaxis↗

PubMed1986

Pharmacokinetics of intraventricular vancomycin in hydrocephalic rats.

An animal model was developed for studying the pharmacokinetics of antibiotics administered intraventricularly in hydrocephalus. Obstructive hydrocephalus was consistently produced in craniectomized adult rats by injecting kaolin into the cisterna magna. After induction of hydrocephalus, vancomycin was injected into the right lateral ventricle of each rat. Bilateral ventricular cerebrospinal fluid (CSF) and brain parenchymal samples were obtained at 0.5, 1, 2, 4, 8, and 12 hours and the concentration of vancomycin in these samples was determined. Brain tissue was also analyzed histologically. The results show: (a) vancomycin is rapidly distributed within the CSF, including the contralateral ventricle, within 30 minutes; (b) vancomycin concentrations were nearly identical in both ventricles at all time points; (c) mean peak CSF vancomycin concentrations occurred at 2 hours and were 23.8 and 21.3 micrograms/ml for the left and right lateral ventricles, respectively; (d) elimination from CSF was slow (T1/2 beta = 2.22 hours, T1/2 gamma = 19.65 hours); (e) no vancomycin was detected (less than or equal to 2 micrograms/g) in the samples of periventricular white matter; (f) histological changes observed were consistent with untreated obstructive hydrocephalus and did not seem to be related to vancomycin treatment. The clinical significance of these results and the usefulness of the experimental model are discussed.

Animals↗

PubMed2004

Topical vancomycin for chronic suppurative otitis media with methicillin-resistant Staphylococcus aureus otorrhoea.

There has been a steady increase in the number of cases of methicillin-resistant Staphylococcus aureus (MRSA) otorrhoea; this is a growing concern. The purpose of this study was to evaluate the efficacy of topical vancomycin treatment in patients with MRSA otorrhoea. Fifty-five patients with MRSA otorrhoea were prospectively enrolled into the study. Thirty-five patients were treated with vancomycin eardrops as outpatients. The concentration of the locally prepared vancomycin solution was 25 mg/ml. The dose of vancomycin was two drops three times daily for 10 days. As a control group, 20 patients were treated with gentamicin 0.3% solution. Data were analysed by the Mann-Whitney U test to compare the efficacy of vancomycin eardrops and gentamicin eardrops. In the vancomycin group, the otorrhoea was significantly reduced in 33 ears (94%); in the gentamicin group, in four ears (20 per cent); this reduction was statistically significant (P < 0.03). The use of topical vancomycin treatment was effective for patients with MRSA otorrhoea refractory to conventional antibiotic treatment.

Administration, Topical↗

PubMed1998

Vancomycin-induced acute interstitial nephritis.

OBJECTIVE: To report a case of acute interstitial nephritis (AIN) related to administration of vancomycin for the treatment of Staphylococcus aureus sternal wound infection, osteomyelitis, and infective endocarditis. CASE SUMMARY: Reports in the literature regarding vancomycin-induced AIN are scarce. We describe the fifth known case of AIN, in a 64-year-old white man who developed fever, maculopapular rash, acute renal failure, eosinophilia, and eosinophiluria after approximately 1 month of vancomycin treatment. The results of the renal biopsy were consistent with an allergic drug reaction. Four months after his initial episode of AIN, the patient was rechallenged with vancomycin for the treatment of S. aureus septic arthritis. One day after initiation of vancomycin, serum eosinophils started to rise, his urine tested positive for eosinophils, but his serum creatinine remained stable. CONCLUSIONS: Our case report and others from the literature suggest vancomycin causes allergic AIN. Clinicians should be aware of this adverse effect in an era of increasing use of vancomycin for treatment of resistant gram-positive organisms.

Acute Disease↗

PubMed2006

Using vancomycin concentrations for dosing daptomycin in a morbidly obese patient with renal insufficiency.

OBJECTIVE: To report a case in which vancomycin clearance was used to determine the daptomycin dosing interval in a morbidly obese patient with renal impairment. CASE SUMMARY: A 46-year-old man (209 kg; 178 cm) failed a 42 day course of vancomycin therapy for treatment of a methicillin-resistant Staphylococcus aureus-infected wound and cellulitis. The median trough vancomycin concentration was 12.6 microg/mL (range 7.3-24.1) through his course of therapy. Estimation of creatinine clearance (Cl(cr)) was confounded in this clinical scenario, given the patient's weight and a lack of valid equations in this patient population. Daptomycin was administered empirically at 6 mg/kg dosed every 48 hours based on estimated clearance from measured vancomycin concentrations. Steady-state plasma concentrations of daptomycin were determined, and the daptomycin half-life in this patient was more accurately estimated using vancomycin clearance as a surrogate. In addition, a 4 mg/kg dose of daptomycin would have been sufficient based on plasma concentrations. The patient demonstrated rapid clinical improvement and remained free of cellulitis for 6 months after completion of daptomycin and a 12 week course of trimethoprim/sulfamethoxazole. DISCUSSION: The dosing interval of daptomycin is adjusted based on Cl(cr). However, estimation of Cl(cr) is difficult in morbidly obese patients with renal impairment, given a lack of valid equations. In this clinical scenario, vancomycin concentrations were used to estimate Cl(cr) and served as a surrogate measure to determine the daptomycin dosing interval. Measured daptomycin concentrations validated this approach and confirmed the inadequacy of commonly used Cl(cr) equations. CONCLUSIONS: In this clinical scenario, vancomycin concentrations more accurately estimated Cl(cr), thereby facilitating determination of the daptomycin dosing interval.

Anti-Bacterial Agents↗

PubMed2003

Vancomycin-induced thrombocytopenia: a case proven with rechallenge.

In a rare case of vancomycin-induced thrombocytopenia, a 50-year-old man with culture-negative subacute bacterial endocarditis underwent mitral valve replacement surgery and was treated with vancomycin. His platelet count dropped from 346 x 10(3)/mm3 to 13 x 10(3)/mm3 on postoperative day 4, and a differential diagnosis of heparin- versus drug-induced thrombocytopenia was considered. Antiheparin antibodies were detected in the patient's serum on day 5. He showed no signs of bleeding. His platelet count remained below 5 x 10(3)/mm3 despite two platelet transfusions on day 5. A hemorrhagic pericardial effusion with tamponade developed, requiring drainage. A trial with intravenous immunoglobulin led to fever and chills, and the infusion was not completed. Vancomycin was changed to clindamycin on day 9, and methylprednisolone therapy was started on day 11. On day 12, the patient's clinical condition improved, and his platelet count increased from 3 x 10(3)/mm3 to 32 x 10(3)/mm3 with no bleeding. On day 18, his platelet count was 424 x 10(3)/mm3, and he was scheduled for discharge with vancomycin therapy for a total of 6 weeks. He received a single dose of intravenous vancomycin 1 g at the hospital; his platelet count dropped to 160 x 10(3)/mm3 1 hour after the infusion and to 58 x 10(3)/mm3 12 hours later. Vancomycin was discontinued and clindamycin and prednisone were restarted. On day 20, the patient's platelet count increased to 105 x 10(3)/mm3 and he was discharged with warfarin, prednisone, and clindamycin therapy. We suspect that our patient's thrombocytopenia was due to vancomycin.

Drug Hypersensitivity↗

PubMed2003

Mississippi mud no more: cost-effectiveness of pharmacokinetic dosage adjustment of vancomycin to prevent nephrotoxicity.

OBJECTIVE: To determine the cost-effectiveness of pharmacokinetic dosage adjustment of vancomycin to prevent nephrotoxicity. An analysis was performed for subpopulations of patients receiving nephrotoxic agents (aminoglycosides, amphotericin, and acyclovir), those in the intensive care unit, and those on the oncology service. METHODS: Decision analysis was used to model the cost-effectiveness of pharmacokinetic dosage adjustment of vancomycin. The reference case was determined, in part, by a retrospective review of 200 patients randomly selected from our clinical pharmacology consultation service. Patients were aged 18 years or older and had received intravenous vancomycin for at least 48 hours, with at least two--one peak and one trough--vancomycin serum concentrations obtained during therapy. Results of published clinical trials were used to determine the probability of vancomycin-induced nephrotoxicity. RESULTS: The mean cost of treating nephrotoxicity was 11,233 dollars at our institution. The mean cost for all patients was 25,166 dollars (sensitivity analysis 15,000-27,500 dollars)/nephrotoxic episode prevented. The subgroup analysis revealed a cost of 8,363 dollars (sensitivity analysis 4,368-10,500 dollars)/nephrotoxic episode prevented in intensive care patients, 5,000 dollars (sensitivity analysis 1,687-13,250 dollars ) in oncology patients, and a dominant strategy showing a cost savings of 5,564 dollars (sensitivity analysis 2,724-12,428 dollars) in those receiving concomitant nephrotoxins. CONCLUSION: Although pharmacokinetic monitoring and dosage adjustment are effective methods for reducing the toxicity of many drugs, controversy exists regarding the necessity of such monitoring with vancomycin. Evaluation by decision analysis over a range of assumptions, varying probabilities, and costs reveals that pharmacokinetic monitoring and vancomycin dosage adjustment to prevent nephrotoxicity are not cost-effective for all patients. However, such dosage adjustment demonstrates cost-effectiveness for patients receiving concomitant nephrotoxins, intensive care patients, and probably oncology patients.

Adult↗

PubMed2004

Vancomycin: pharmacokinetics and administration regimens in neonates.

This review describes the use of vancomycin in neonates over the last three decades. Given the relation of late-onset neonatal septicaemia to outcome and the increase in coagulase-negative staphylococcal infection as causative organism, vancomycin remains an important antibacterial in the neonatal intensive care unit. The pharmacokinetic behaviour of vancomycin in neonates can be adequately described by a one- or two-compartment model and is mainly determined by postconceptional age and renal function. In neonates, a patent ductus arteriosus as well as treatment with indomethacin or extracorporeal membrane oxygenation (ECMO) leads to an increase in volume of distribution and a decrease in clearance. Microbiological studies in vitro have shown that an increase in vancomycin concentrations above the minimum inhibitory concentration does not result in more effective killing. The microbiological and clinical efficacy of vancomycin in neonates has only been studied explicitly in a restricted number of patients. There are no definitive data relating serum concentrations to effect in this patient group. Vancomycin-related nephrotoxicity and ototoxicity in neonates is rare, and no clear relation to serum concentrations has been demonstrated. Based on the pharmacokinetic profile of vancomycin in neonates, several administration regimens have been constructed. Recent guidelines have suggested that dosage can be independent of gestational age or postconceptional age in neonates without renal failure. In patients with renal failure, therapy can be adequately tailored by using a regimen based on serum creatinine. The usefulness of routine monitoring of peak serum concentrations is doubtful based on the current literature. Recent research demonstrates a shift towards taking only routine trough serum concentrations in order to optimise efficacy. Patients with renal failure and other special subpopulations, such as patients exposed to ECMO or indomethacin, need to be monitored more closely.

Adult↗