Addition of Rifampin to Vancomycin for Methicillin-Resistant Staphylococcus aureus Infections: What Is the Evidence?

Abstract

Spanish

French

OBJECTIVE

To evaluate evidence supporting efficacy and safety of the combination of vancomycin and rifampin for treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections.

DATA SOURCES

MEDLINE (1946-February 2013), EMBASE (1974-February 2013) and Cochrane Database of Systematic Reviews were searched.

STUDY SELECTION

All human prospective trials and retrospective studies evaluating clinical outcomes of vancomycin-rifampin combinations were included. Case reports, case series, and in vitro or animal data were excluded.

DATA EXTRACTION

Full-text articles were included and abstracts excluded; 43 of 421 references were reviewed. Five articles met inclusion and were evaluated.

DATA SYNTHESIS

A nonrandomized prospective trial reported complete clearance of MRSA bacteremia at 24 hours in all 14 burn patients receiving vancomycin-rifampin therapy. In a case-control study of 42 patients with MRSA endocarditis, adding rifampin prolonged bacteremia (5.2 vs 2.1 days, p < 0.001), decreased survival rates (79% vs 95%, p = 0.048), resulted in drug interactions (52% of cases), and increased hepatic transaminases (21% vs 2%, p = 0.014). In a retrospective analysis of 28 patients with persistent MRSA bacteremia requiring salvage therapy, switching from vancomycin-based to linezolid-based treatment was associated with better salvage success than adding rifampin (88% vs 0%, p < 0.001). In a randomized open-label trial of 42 patients with MRSA endocarditis, addition of rifampin to vancomycin did not affect cure rates (90% combination vs 82% monotherapy, p > 0.20), but increased duration of bacteremia (9 vs 7 days, p > 0.20) compared with vancomycin monotherapy. Another randomized open-label trial of combination versus monotherapy for MRSA pneumonia in 93 intensive care unit patients reported higher clinical successes (53.7% vs 31.0%, p = 0.047), similar 30-day mortality rates, and more adverse events with combination therapy (11 vs 6).

CONCLUSIONS

Limited evidence exists to support the adjunctive use of rifampin to treat MRSA infections. The combination may increase drug interactions, adverse effects, and rifampin resistance. Further studies are needed to define the role of rifampin adjunct therapy.

Get full access to this article

View all access options for this article.

References

1. Liu

, Bayer

, Cosgrove

, Clinical practice guidelines by the infectious diseases society of america for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis 2011; 52: e18–55. DOI: 10.1093/cid/ciq146

2. Schilling

, Neuner

, Rehm

. Vancomycin: a 50-something-year-old antibiotic we still don't understand. Cleve Clin J Med 2011; 78: 465–71. DOI: 10.3949/ccjm.78a.10168

3. Deresinski

. Vancomycin in combination with other antibiotics for the treatment of serious methicillin-resistant Staphylococcus aureus infections. Clin Infect Dis 2009; 49: 1072–9. DOI: 10.1086/605572

4. Gould

, Cauda

, Esposito

, Gudiol

, Mazzei

, Garau

. Management of serious meticillin-resistant Staphylococcus aureus infections: what are the limits? Int J Antimicrob Agents 2011; 37: 202–9. DOI: 10.1016/j.ijantimicag.2010.10.030

5. van Hal

, Lodise

, Paterson

. The clinical significance of vancomycin minimum inhibitory concentration in Staphylococcus aureus infections: a systematic review and meta-analysis. Clin Infect Dis 2012; 54: 755–71. DOI: 10.1093/cid/cir935

6. Brink

. Does resistance in severe infections caused by methicillin-resistant Staphylococcus aureus give you the ‘creeps’? Curr Opin Crit Care 2012; 18: 451–9 doi: 10.1097/MCC.0b013e3283578968

7. Rybak

, Lomaestro

, Rotschafer

, Therapeutic monitoring of vancomycin in adult patients: a consensus review of the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Diseases Pharmacists. Am J Health Syst Pharm 2009; 66: 82–98.

8. Johnson

. Methicillin-resistant Staphylococcus aureus: the European landscape. J Antimicrob Chemother 2011; 66 (suppl 4): iv43–8. DOI: 10.1093/jac/dkr076

9. Nichol

, Adam

, Hussain

, Comparison of community-associated and health care-associated methicillin-resistant Staphylococcus aureus in Canada: results of the CANWARD 2007–2009 study. Diagn Microbiol Infect Dis 2011; 69: 320–5. DOI: 10.1016/j.diagmicrobio.2010.10.028

10.

10. Pallin

, Egan

, Pelletier

, Espinola

, Hooper

, Camargo

Jr . Increased US emergency department visits for skin and soft tissue infections, and changes in antibiotic choices, during the emergence of community-associated methicillin-resistant Staphylococcus aureus . Ann Emerg Med 2008; 51: 291–8. DOI: 10.1016/j.annemergmed.2007.12.004

11.

11. Cosgrove

, Sakoulas

, Perencevich

, Schwaber

, Karchmer

, Carmeli

. Comparison of mortality associated with methicillin-resistant and methicillin-susceptible Staphylococcus aureus bacteremia: a meta-analysis. Clin Infect Dis 2003; 36: 53–9. DOI: 10.1086/345476

12.

12. Hanberger

, Walther

, Leone

, Increased mortality associated with methicillin-resistant Staphylococcus aureus (MRSA) infection in the intensive care unit: results from the EPIC II study. Int J Antimicrob Agents 2011; 38: 331–5. DOI: 10.1016/j.ijantimicag.2011.05.013

13.

13. Perlroth

, Kuo

, Tan

, Bayer

, Miller

. Adjunctive use of rifampin for the treatment of Staphylococcus aureus infections: a systematic review of the literature. Arch Intern Med 2008; 168: 805–19. DOI: 10.1001/archinte.168.8.805

14.

14. Rifampin. Tuberculosis (Edinb) 2008; 88: 151–4. DOI: 10.1016/s1472-9792(08)70024-6

15.

15. Yamaoka

. The bactericidal effects of anti-MRSA agents with rifampicin and sulfamethoxazole-trimethoprim against intracellular phagocytized MRSA. J Infect Chemother 2007; 13: 141–6. DOI: 10.1007/s10156-007-0521-z

16.

16. Shelburne

, Musher

, Hulten

, In vitro killing of community-associated methicillin-resistant Staphylococcus aureus with drug combinations. Antimicrob Agents Chemother 2004; 48: 4016–9. DOI: 10.1128/AAC.48.10.4016-4019.2004

17.

17. Salem

, Elkhatib

, Noreddin

. Pharmacodynamic assessment of vancomycin-rifampicin combination against methicillin resistant Staphylococcus aureus biofilm: a parametric response surface analysis. J Pharm Pharmacol 2011; 63: 73–9. 10.1111/j.2042-7158.2010.01183.x

18.

18. Rose

, Poppens

. Impact of biofilm on the in vitro activity of vancomycin alone and in combination with tigecycline and rifampicin against Staphylococcus aureus . J Antimicrob Chemother 2009; 63: 485–8. DOI: 10.1093/jac/dkn513

19.

19. Zimmerli

, Widmer

, Blatter

, Frei

, Ochsner

. Role of rifampin for treatment of orthopedic implant-related staphylococcal infections: a randomized controlled trial. Foreign-body infection (FBI) study group. JAMA 1998; 279: 1537–41. DOI: 10.1001/jama.279.19.1537

20.

20. Van der Auwera

, Meunier-Carpentier

, Klastersky

. Clinical study of combination therapy with oxacillin and rifampin for staphylococcal infections. Rev Infect Dis 1983; 5 (suppl 3): S515–22.

21.

21. Van der Auwera

, Klastersky

, Thys

, Meunier-Carpentier

, Legrand

. Double-blind, placebo-controlled study of oxacillin combined with rifampin in the treatment of staphylococcal infections. Antimicrob Agents Chemother 1985; 28: 467–72. DOI: 10.1128/aac.28.4.467

22.

22. Ju

, Woolley

, Gordon

. Emergence and spread of rifampicin-resistant, methicillin-resistant Staphylococcus aureus during vancomycin-rifampicin combination therapy in an intensive care unit. Eur J Clin Microbiol Infect Dis 2006; 25: 61–2. DOI: 10.1007/s10096-005-0063-1

23.

23. Jung

, Koh

, Hong

, Effect of vancomycin plus rifampicin in the treatment of nosocomial methicillin-resistant Staphylococcus aureus pneumonia. Crit Care Med 2010; 38: 175–80.

24.

24. Gang

, Sanyal

, Mokaddas

, Lari

. Rifampicin as an adjunct to vancomycin therapy in MRSA septicaemia in burns. Burns 1999; 25: 640–4. DOI: 10.1016/s0305-4179(99)00045-5

25.

25. Riedel

, Weekes

, Forrest

. Addition of rifampin to standard therapy for treatment of native valve infective endocarditis caused by Staphylococcus aureus . Antimicrob Agents Chemother 2008; 52: 2463–7. DOI: 10.1128/AAC.00300-08

26.

26. Jang

, Kim

, Salvage treatment for persistent methicillin-resistant Staphylococcus aureus bacteremia: efficacy of linezolid with or without carbapenem. Clin Infect Dis 2009; 49: 395–401. DOI: 10.1086/600295

27.

27. Levine

, Fromm

, Reddy

. Slow response to vancomycin or vancomycin plus rifampin in methicillin-resistant Staphylococcus aureus endocarditis. Ann Intern Med 1991; 115: 674–80.

28.

28. Tsuji

, Rybak

. Short-course gentamicin in combination with daptomycin or vancomycin against Staphylococcus aureus in an in vitro pharmacodynamic model with simulated endocardial vegetations. Antimicrob Agents Chemother 2005; 49: 2735–45. DOI: 10.1128/aac.49.7.2735-2745.2005

29.

29. CLSI. 2007. Performance standards for antimicrobial susceptibility testing. CLSI approved standard M100-S17. Clinical and Laboratory Standards Institute, Wayne, PA.

30.

30. Henry

, Rouse

, Whitesell

, McConnell

, Wilson

. Treatment of methicillin-resistant Staphylococcus aureus experimental osteomyelitis with ciprofloxacin or vancomycin alone or in combination with rifampin. Am J Med 1987; 82: 73–5.

31.

31. Eng

SSMTMCC. Rifampin resistance: development during the therapy of methicillin-resistant Staphylococcus aureus infection. Arch Intern Med 1985; 145: 146–8. 10.1001/archinte.1985.00360010188034

32.

32. Stein

, Wells

. The importance of tissue penetration in achieving successful antimicrobial treatment of nosocomial pneumonia and complicated skin and soft-tissue infections caused by methicillin-resistant Staphylococcus aureus: vancomycin and linezolid. Curr Med Res Opin 2010; 26: 571–88. DOI: 10.1185/03007990903512057

33.

33. Skhirtladze

, Hutschala

, Fleck

, Impaired target site penetration of vancomycin in diabetic patients following cardiac surgery. Antimicrob Agents Chemother 2006; 50: 1372–5. DOI: 10.1128/aac.50.4.1372-1375.2006

34.

34. Kropec

, Daschner

. Penetration into tissues of various drugs active against gram-positive bacteria. J Antimicrob Chemother 1991; 27: 9–15. DOI: 10.1093/jac/27.suppl_B.9

35.

35. Mindermann

, Zimmerli

, Gratzl

. Rifampin concentrations in various compartments of the human brain: a novel method for determining drug levels in the cerebral extracellular space. Antimicrob Agents Chemother 1998; 42: 2626–9.

36.

36. Walkey

, O'Donnell

, Wiener

. Linezolid vs glycopeptide antibiotics for the treatment of suspected methicillin-resistant Staphylococcus aureus nosocomial pneumonia. Chest 2011; 139: 1148–55. DOI: 10.1378/chest.10-1556

37.

37. Kalil

, Murthy

, Hermsen

, Neto

, Sun

, Rupp

. Linezolid versus vancomycin or teicoplanin for nosocomial pneumonia: a systematic review and meta-analysis. Crit Care Med 2010; 38: 1802–8. DOI: 10.1097/CCM.0b013e3181eb3b96

38.

38. Wunderink

, Niederman

, Kollef

, Linezolid in methicillin-resistant Staphylococcus aureus nosocomial pneumonia: a randomized, controlled study. Clin Infect Dis 2012; 54: 621–9. DOI: 10.1093/cid/cir895

39.

39. Prasad

, Sun

, Danner

, Natanson

. Excess deaths associated with tigecycline after approval based on noninferiority trials. Clin Infect Dis 2012; 54: 1699–709. DOI: 10.1093/cid/cis270

40.

40. Corey

, Wilcox

, Talbot

, Integrated analysis of CANVAS 1 and 2: phase 3, multicenter, randomized, double-blind studies to evaluate the safety and efficacy of ceftaroline versus vancomycin plus aztreonam in complicated skin and skin-structure infection. Clin Infect Dis 2010; 51: 641–50. DOI: 10.1086/655827

41.

41. Knudsen

, Fuursted

, Espersen

, Frimodt-Moller

. Activities of vancomycin and teicoplanin against penicillin-resistant pneumococci in vitro and in vivo and correlation to pharmacokinetic parameters in the mouse peritonitis model. Antimicrob Agents Chemother 1997; 41: 1910–5.

42.

42. Wong-Beringer

, Joo

, Tse

, Beringer

. Vancomycin-associated nephrotoxicity: a critical appraisal of risk with high-dose therapy. Int J Antimicrob Agents 2011; 37: 95–101. DOI: 10.1016/j.ijantimicag.2010.10.013

43.

43. Kullar

, Davis

, Taylor

, Kaye

, Rybak

. Effects of targeting higher vancomycin trough levels on clinical outcomes and costs in a matched patient cohort. Pharmacotherapy 2012; 32: 195–201. DOI: 10.1002/j.1875-9114.2011.01017.x

44.

44. Lwdin

, Odenholt

, Cars

. In vitro studies of pharmacodynamic properties of vancomycin against Staphylococcus aureus and staphylococcus epidermidis . Antimicrob Agents Chemother 1998; 42: 2739–44.

45.

45. Gould

. Clinical activity of anti-gram-positive agents against methicillin-resistant Staphylococcus aureus . J Antimicrob Chemother 2011; 66 (suppl 4): iv17–21. DOI: 10.1093/jac/dkr073

46.

46. Baciewicz

, Chrisman

, Finch

, Self

. Update on rifampin and rifabutin drug interactions. Am J Med Sci 2008; 335: 126–36. DOI: 10.1097/MAJ.0b013e31814a586a

47.

47. Eng

RHK

, M-Smith

, Buccini

, Cherabin

. Differences in ability of cell-wall antibiotics to suppress emergence of rifampicin resistance in Staphylococcus aureus . J Antimicrob Chemother 1985; 15: 201–7. DOI: 10.1093/jac/15.2.201