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01-01-2011 | Original Research Article

Risk of Hepatic Events in Patients Treated with Vancomycin in Clinical Studies

A Systematic Review and Meta-Analysis

Authors: Dr Yan Chen, Xiao Yan Yang, Michael Zeckel, Chris Killian, Kenneth Hornbuckle, Arie Regev, Simon Voss

Published in: Drug Safety | Issue 1/2011

Abstract

Background: Routine surveillance of spontaneous reporting data and subsequent disproportionality analyses have indicated that the use of vancomycin might be associated with an increased risk of hepatic events.

Objective: To conduct a meta-analysis of published randomized controlled clinical trials (RCTs) to better understand if the use of vancomycin is potentially associated with an increased risk of hepatic events.

Data Sources: A comprehensive search and review of published clinical studies indexed in MEDLINE, PubMed, International Pharmaceutical Abstracts and the Cochrane Library from 1950 to June 2010 was conducted.

Study Selection: The inclusion criteria consisted of (i) published RCTs comparing vancomycin with/without other additional treatments to other comparators; and (ii) studies that reported hepatic events.

Data Extraction: The data related to any hepatic events reported in RCTs were extracted and examined. The quality of selected studies was assessed based on the Jadad scale. The effect size was presented as a risk ratio (RR) with a 95% CI and number needed to harm. The pooled RRs were calculated by using both fixed-effects and random-effects models. The impact of publication bias was assessed by funnel plot and the Egger’s test.

Data Synthesis: A total of 20 RCTs, including 7419 patients, met the study inclusion criteria and were selected. An increased incidence of hepatic events, specifically elevated serum aminotransferase levels, was observed in patients receiving vancomycin, when compared with other comparators (pooled RR= 1.95; 95% CI 1.62, 2.36; ps< 0.001), but the majority of the events were mild to moderate in nature. No evidence is currently available suggesting that the use of vancomcycin confers a risk of progressive or severe drug-induced liver injury.

Conclusions: Continuous monitoring of hepatic events on a routine basis among patients with the use of vancomycin is suggested.

Griffith RS. Introduction to vancomycin. Rev Infect Dis 1981; 3: 200–4CrossRef

Anderson RCGR, Higgins Jr HM, Pettinga CD. Symposium: how a drug is born. Cincinnati J Med 1961; 42: 49–60

Moellering RC. Vancomycin: a 50-year reassessment. Clin Infec Dis 2006; 42 Suppl. 1: 3–4CrossRef

Farber BF, Moellering Jr RC. Retrospective study of the toxicity of preparations of vancomycin from 1974 to 1981. Antimicrob Agents Chemother 1983; 23: 138–41PubMedCrossRef

Elting LS, Rubenstein EB, Kurtin D, et al. Mississippi mud in the 1990s: risks and outcomes of vancomycin-associated toxicity in general oncology practice. Cancer 1998; 83: 2597–607PubMedCrossRef

Chen Y, Guo JJ, Steinbuch M, et al. Comparisons of data mining algorithms for signal detection: an empirical study based on the Adverse Event Reporting System of the Food and Drug Administration. Pharmaceut Med 2008; 22(6): 359–69CrossRef

Chen Y, Guo JJ, Healy DP, et al. The risk of hepatotoxicity associated with the use of Ketek: signal detection based upon FDA Spontaneous Reporting System. Ann Pharmacother 2008;42(12): 1791–6PubMedCrossRef

Cadle RM, Mansouri MD, Darouiche RO. Vancomycin-induced elevation of liver enzyme levels. Ann Pharma-cother 2006; 40: 1186–9CrossRef

Sikuler E, Guetta V, Keynan A, et al. Abnormalities in bilirubin and liver enzyme levels in adult patients with bacteremia: a prospective study. Arch Intern Med 1989; 149: 2246–8PubMedCrossRef

10.

Jaded AR, Moore RA, Carroll D, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 1996; 17: 1–12CrossRef

11.

Sierra F. Evidence-based medicine (EBM) in practice: applying number needed to treat and number needed to harm. Am J Gastroenterol 2005; 100: 1661–3PubMedCrossRef

12.

RevMan 4.2 user guide. Oxford: The Cochrane Collaboration, 2004; 82–4

13.

Cochran WG. The combination of estimates from different experiments. Biometrics 1954; 10: 101–29CrossRef

14.

Egger M, Smith GD, Schneider M, et al. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997; 315: 629–34PubMedCrossRef

15.

Shenep JL, Hughes WT, Roberson PK, et al. Vancomycin, ticarcillin, and amikacin compared with ticarcillin-clavulanate and amikacin in the empirical treatment of febrile, neutropenic children with cancer. N Engl J Med 1988; 319(16): 1053–8PubMedCrossRef

16.

Calandra T, Zinner SH, Glauser MP, et al. Vancomycin added to empirical combination antibiotic therapy for fever in granulocytopenic cancer patients. European Organization for Research and Treatment of Cancer (EORTC). J Infect Dis 1991; 163(5): 951–8CrossRef

17.

Wilson AP, Gruneberg RN, Neu H. A critical review of the dosage of teicoplanin in Europe and the USA. Int J Anti-microb Agents 1994; 4 Suppl. 1: 1–40CrossRef

18.

Breedt J, Teras J, Gardovskis J, et al. Safety and efficacy of tigecycline in treatment of skin and skin structure infections: results of a double-blind phase III comparison study with vancomycin-aztreonam. Tigecycline 305 cSSSI Study Group. Antimicrob Agents Chemother 2005; 49(11): 4658–66PubMedCrossRef

19.

Sacchidanand S, Penn RL, Embil JM, et al. Efficacy and safety of tigecycline monotherapy compared with vancomycin plus aztreonam in patients with complicated skin and skin structure infections: results from a phase III, randomized, double-blind trial. Int J Infect Dis 2005; 9(5): 251–61PubMedCrossRef

20.

Stryjewski ME, Graham DR, Wilson SE, et al. Telavancin versus vancomycin for the treatment of complicated skin and skin-structure infections caused by gram-positive organisms. Clin Infect Dis 2008; 46: 1683–93PubMedCrossRef

21.

Stryjewski ME, Chu VH, O’Riordan WD, et al. Telavancin versus standard therapy for treatment of complicated skin and skin structure infections caused by gram-positive bacteria: FAST 2 study. Antimicrob Agents Chemother 2006; 50(3): 862–7PubMedCrossRef

22.

Stryjewski ME, O’Riordan WD, Lau WK, et al. Telavancin versus standard therapy for treatment of complicated skin and soft-tissue infections due to gram-positive bacteria. Clin Infect Dis 2005; 40(11): 1601–7PubMedCrossRef

23.

Arbeit RD, Maki D, Tally FP, et al. The safety and efficacy of daptomycin for the treatment of complicated skin and skin-structure infections. Clin Infect Dis 2004; 38(12): 1673–81PubMedCrossRef

24.

Lin DF, Zhang YY, Wu JF, et al. Linezolid for the treatment of infections caused by Gram-positive pathogens in China. Int J Antimicrob Agents 2008; 32(3): 241–9PubMedCrossRef

25.

Jantausch BA, Deville J, Adler S, et al. Linezolid for the treatment of children with bacteremia or nosocomial pneumonia caused by resistant gram-positive bacterial pathogens. Pediatr Infect Dis J 2003; 22 (9 Suppl.): 164–71

26.

Deville JG, Adler S, Azimi PH, et al. Linezolid versus vancomycin in the treatment of known or suspected resistant gram-positive infections in neonates. Pediatr Infect Dis J 2003; 22 (9 Suppl.): 158–63CrossRef

27.

Kaplan SL, Deville JG, Yogev R, et al. Linezolid versus vancomycin for treatment of resistant Gram-positive infections in children. Linezolid Pediatric Study Group. Pediatr Infect Dis J 2003; 22(8): 677–86PubMedCrossRef

28.

Talbot GH, Thye D, Das A, et al. Phase 2 study of ceftaroline versus standard therapy in treatment of complicated skin and skin structure infections. Antimicrob Agents Chemother 2007; 51(10): 3612–6PubMedCrossRef

29.

Vazquez L, Encinas MP, Morin LS, et al. Randomized prospective study comparing cost-effectiveness of teicoplanin and vancomycin as second-line empiric therapy for infection in neutropenic patients. Haematologica 1999; 84(3): 231–6PubMed

30.

Rubinstein E, Cammarata S, Oliphant T, et al. Linezolid (PNU-100766) versus vancomycin in the treatment of hospitalized patients with nosocomial pneumonia: a randomized, double-blind, multicenter study. Linezolid Nosocomial Pneumonia Study Group. Clin Infect Dis 2001; 32(3): 402–12PubMedCrossRef

31.

Florescu I, Beuran M, Dimov R, et al. Efficacy and safety of tigecycline compared with vancomyin or linezolid for treatments of serious infections with methicillin-resistant staphylococcus aureus or vancomycin-resistant enterococci: a phase 3, multicentre, double-blind, randomized study. J Antimicrob Chemother 2008; 62 Suppl.: i17–28PubMedCrossRef

32.

Lv YH, Zhou QY, Li XH, et al. Clinical evaluation of vancomycin in treatment of neonatal infection pneumonia in NICU. Chin J Birth Health Hered 2004; 12: 95–6

33.

Neville LO, Brumfitt W, Hamilton-Miller JMT, et al. Teicoplanin vs. vancomycin for the treatment of serious infections: a randomized trial. Int J Antimicrob Agents 1995; 5: 187–93PubMedCrossRef

34.

Kohno S, Yamaguchi K, Aikawa N, et al. Linezolid versus vancomycin for the treatment of infections caused by methicillin-resistant Staphylococcus aureus in Japan. J Antimicrob Chemother 2007; 60: 1361–9PubMedCrossRef

35.

FDA. Guidance for industry. Drug-induced liver injury: premarketing clinical evaluation [online]. Available from URL: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM174090.pdf [Accessed 2009 Aug 7]

36.

Larrey D. Epidemiology and individual susceptibility to adverse drug reactions affecting the liver. Semin Liver Dis 2002; 22: 145–55PubMedCrossRef

37.

Holt MP, Ju C. Mechanisms of drug-induced liver injury. AAPS J 2006; 8: E48–54PubMedCrossRef

38.

Blazka ME, Wilmer JL, Holladay SD, et al. Role of proinflammatory cytokines in acetaminophen hepatotoxicity. Toxicol Appl Pharmacol 1995; 133: 43–52PubMedCrossRef

39.

Naisbitt DJ, Farrell J, Wong G, et al. Characterization of drug specific T cells in lamotrigine hypersensitivity. J Allergy Clin Immunol 2003; 111: 1393–403PubMedCrossRef

40.

Hamilton JR, Sass-Kortsak A. Jaundice associated with severe bacterial infection in young infacts. J Pediatr 1963; 63: 121–32PubMedCrossRef

41.

Rosner B. The binomial distribution. In: Rosner B. Fundamentals of biostatistics. Belmont (CA): Duxbury Press, 1995: 82–5

Title: Risk of Hepatic Events in Patients Treated with Vancomycin in Clinical Studies
A Systematic Review and Meta-Analysis
Authors: Dr Yan Chen
Xiao Yan Yang
Michael Zeckel
Chris Killian
Kenneth Hornbuckle
Arie Regev
Simon Voss
Publication date: 01-01-2011
Publisher: Springer International Publishing
Published in: Drug Safety / Issue 1/2011
Print ISSN: 0114-5916
Electronic ISSN: 1179-1942
DOI: https://doi.org/10.2165/11539560-000000000-00000

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Risk of Hepatic Events in Patients Treated with Vancomycin in Clinical Studies

A Systematic Review and Meta-Analysis

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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