Vancomycin serum concentration monitoring

Vancomycin serum concentration monitoring can either be minimized or avoided entirely for many patients who are treated with this antimicrobial. 

Initial antibiotic choice should always cover gram-positive organisms (e.g., vancomycin 20 mg/kg intravenously with serum concentration monitoring or cefazolin 20 mg/kg intravenously 3 times... 

In clinical practice, serum concentration monitoring is routinely performed on patients receiving aminoglycosides. Despite the lack of supporting evidence for its usefulness or need, serum vancomycin concentration monitoring is also widespread. Flucytosine serum concentration monitoring has been shown to reduce toxicity when doses are adjusted to maintain peak concentrations below 100 mcg/mL. 

In a randomized, prospective, cost-effectiveness study both teicoplanin and vancomycin were assessed as second-line therapy in 66 neutropenic patients after the failure of empirical treatment with a combination of piperacillin -I- tazobactam and amikacin (10). The primary success of second-line therapy was equivalent, and the direct total costs were similar. Acquisition costs per dose were in favor of vancomycin, but costs derived from administering vancomycin and serum concentration monitoring led to similar costs for both regimens. With the exception of the red man syndrome, which occurred in 10% of vancomycin-treated patients but none of the tei-coplanin-treated patients, toxicity (renal, liver, and ear toxicity, diarrhea, phlebitis) was also similar. 

Due to the risks of serious adverse events such as nephrotoxicity and ototoxicity observed when systemic vancomycin was first used, therapeutic drug monitoring programs (TDM) for vancomycin were developed. To amehorate the risk of toxicity, clinicians have historically targeted a peak vancomycin serum concentration of 30 to 40 mg/L and a trough serum concentration of 5 to 10 mg/L. However, there is a notable lack of... 

The clinician should have an understanding of in vivo antimicrobial agent disposition in order to select the most appropriate therapy for a given infection and to help monitor for clinical or bacteri-ologic efficacy. Serum concentration monitoring is the most common method used to attempt to maximize efficacy and minimize toxicity of antimicrobials. Since most antimicrobials are well tolerated at their usual doses, only a select few agents (e.g., aminoglycosides, chloramphenicol, and vancomycin) are monitored routinely in the current clinical environment. There are a number of direct and indirect methods that are used to quantify the concentration of antimicrobial in an experimental sample. 

The aminoglycosides (i.e., amikacin, gentamicin, and tobramycin) and vancomycin remain the most common agents for which serum concentrations are monitored. A summary of the recommendations for serum concentration monitoring of these agents is shown in Table 103-2. 

Monitoring vancomycin serum concentrations is not cost-effective in preventing vancomydn-induced nephrotoxicity in patients with normal renal function, since the correlation between serum levels and antibacterial efficacy or toxicity remains controversial [185, 186, 182]. Serum level determination may be helpful in patients with increased volume of distribution, in patients with decreased renal function, in children or neonates, and in the elderly [165]. 

Historically, vancomycin serum concentrations have been monitored and adjusted using first-order pharmacokinetic calculations (see aminoglycosides). However, difficulty obtaining a reliable peak concentration because of the initial distribution phase and lack of correlation between serum concentrations and efficacy and toxicity have led to a reappraisal of the value of pharmacokinetic monitoring with vancomycin. 

Gentamicin is an aminoglycoside. All aminoglycosides tend to be nephrotoxic and ototoxic. The dose must be reduced and serum concentrations must be monitored in patients with impaired renal function. Concomitant administration of aminoglycosides and other nephrotoxic drugs, such as certain diuretics, ciclosporin, teicoplanin and vancomycin should be avoided. 

Monitoring Perform auditory function serial tests and monitor serum levels. When monitoring vancomycin serum levels, draw a peak concentration 1.5 to 2.5 hours after the completion of a 1-hour infusion and a trough concentration within 1 hour of the next scheduled dose. Peak levels are generally expected to be in the 30 to 40 mg/mL range and trough levels in the 10 to 15 mg/mL range. 

Changes in pharmacokinetics were studied in male Wistar rats when intravenous vancomycin 100 mg/kg and levofloxacin 20 mg/kg were administered together (124). There was an increase in the AUC and half-hfe of vancomycin. There was also an increase in the AUC and a delay in the t ax of levofloxacin, but no effect on Cmaxi these data suggested delayed absorption of levofloxacin. Concomitant administration had no effect on the correlation between serum and hepatic tissue concentrations of levofloxacin, but it markedly reduced the correlation between the serum and renal tissue concentrations of vancomycin. Vancomycin increased serum creatinine concentrations 8 hours after administration. However, there was no difference in animals who received monotherapy compared with animals who received combined therapy. The authors suggested the cautious use of a combination of levofloxacin and vancomycin and advised monitoring blood concentrations of vancomycin in such cases. 

De Gatta, del M.F. Calvo, V. Hernandez, J.M. Caballero, 48. D. San Miguel, J.F. Dominguez-Gil, A. Cost-effectiveness analysis of serum vancomycin concentration monitoring in patients with hematologic malignancies. Clin. Pharmacol. Ther. 1996, 60 (3), 332-340. 

Routine monitoring of serum concentrations is currently used for a select few antimicrobials (e.g., aminoglycosides, chloramphenicol, and vancomycin) in an attempt to minimize toxicity and maximize efficacy. 

Vancomycin hydrochloride 30 mg/kg per 24 h IV in two equally divided doses, not to exceed 2 g/24 h unless serum levels are monitored 4 Vancomycin therapy is recommended for patients allergic to yfi-lactams (see text regarding drug levels) according to the guidelines, serum concentrations of vancomycin should be obtained 1 h after completion of the infusion and should be in the range of 30-45 mcg/mL for twice-daily dosing... 

THERAPEUTIC USES Vancomycin (vancocin, others) is marketed for intravenous use as a sterile powder. It should be diluted and infused over at least 60 minutes to avoid infusion-related adverse reactions. The usual dose of vancomycin for adults is 30 mg/kg/day in 2-3 divided doses. A trough serum concentration of 5-15 (Xg/mL (10-20 (Xg/mL for serious infections such as endocarditis or meningitis) is recommended. Doses above 30 mg/kg/day may be required to achieve these trough concentrations, and up to 60 mg/kg/day has been suggested for meningitis. The peak concentration is not monitored routinely but should generally remain below 60 (Xg/mL to avoid ototoxicity. 

Thomas MP, Steele RW. Monitoring serum vancomycin concentrations in children is it necessary Pediatr Infect Dis J 1998 17(4) 351-3. 

Vancomycin exhibits predictable pharmacokinetic properties and its clinical use has been guided by the pharmacokinetic monitoring of serum levels to determine the dose and frequency of administration. Pharmacokinetic monitoring of vancomycin, however, has become increasingly controversial given the improved safety of this antibiotic and the lack of data to support what are considered the therapeutic and toxic serum levels. Historically, the most severe toxicities of vancomycin were ototoxicity and nephrotoxicity. The incidence of nephrotoxicity has declined since its introduction possibly due to the availability of purer forms of the antibiotic. Ototoxicity has always been a rare adverse event of vancomycin, but it has been observed with excessively high concentrations of the drug in plasma [170-172]. The purpose of this section is to describe the nephrotoxicity associated with the clinical use of vancomycin. 

Serum drug concentrations should be monitored for drugs with narrow therapeutic indices and ehminated largely by the kidney (e.g., aminoglycosides and vancomycin) to optimize therapy in pediatric patients with renal dysfunction. For drugs with wide therapeutic ranges (e.g., penicillins and cephalosporins), dosage adjustment may be necessary only in moderate to severe renal failure. 

Peak and/or trough concentrations are monitored rontinely for only a select few antimicrobials (e.g., aminoglycosides and vancomycin) during the contemporary management of infections. It is crucial for the health care team to ensure that the antimicrobiars administration time and serum sample time(s) are meticulously recorded because even small errors in recording these (e.g., 1 hour) may have a substantial impact on the calcnlation of pharmacokinetics for antibiotics such as the aminoglycosides, which have relatively short elimination half-lives. 

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