Heterogeneous Vancomycin Resistance in Staphylococcus Aureus: A Review of Epidemiology,Diagnosis,and Clinical Significance

Abstract

Spanish

OBJECTIVE:

To provide an overview of heterogeneously glycopeptide intermediate Staphylococcus aureus, its epidemiology, methods of diagnosis, and clinical relevance.

DATA SOURCES:

Literature was retrieved in December 2009 through Academic Search Premier, Alt-Health Watch, MEDLINE, OVID, and PubMed, using the search terms heterogeneous glycopeptide-intermediate Staphylococcus aureus, hGISA, hVISA, vancomycin-intermediate Staphylococcus aureus, GISA, and VISA (from 2003 to December 2009). Additional references were obtained through review of publication citations.

STUDY SELECTION AND DATA EXTRACTION:

All articles retrieved through the literature search and reference review were evaluated for inclusion in this review.

DATA SYNTHESIS:

Heterogeneously glycopeptide-intermediate S. aureus (hGISA) has been shown to significantly complicate treatment for patients with bacteremia and often escapes detection in clinical laboratories. Population analysis profile area under the curve ratio (PAP-AUC) is considered to be the gold standard of hGISA detection; however, it is labor-intensive, expensive, and not feasible in a clinical setting. The Etest macromethod is a reasonable alternative to PAP, yielding high sensitivity and specificity, and has potential for routine use in clinical laboratories. Due to these difficulties in detection, an exact prevalence is difficult to obtain though, based on available data, it appears that approximately 5-15% of isolates display this phenotype. hGISA is associated with prolonged bacteremia, high bacterial load infections, prolonged antibiotic therapy, prolonged hospitalization, treatment failure, and potential for increased mortality.

CONCLUSIONS:

Overall, hGISA is associated with a poor clinical course in patients with bacteremia. Information is still lacking regarding the actual prevalence of hGISA as well as the extent of its clinical impact. A uniform method of diagnosis must be established in order to better account for all cases of hGISA. More studies must be conducted to assess clinical outcomes of hGISA.

Keywords

hGISA hVISA

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References

Howden

Stinear

Allen

Johnson

Ward

Davies

Genomic analysis reveals a point mutation in the two-component sensor gene graS that leads to intermediate vancomycin resistance in clinical Staphylococcus aureus. Antimicrob Agents Chemother 2008;52:3755–62.

Reduced susceptibility of Staphylococcus aureus to vancomycin—Japan, 1996. MMWR Morb Mortal Wkly Rep 1997;46:624–6.

Appelbaum

Reduced glycopeptide susceptibility in methicillin-resistant Staphylococcus aureus (MRSA). Int J Antimicrob Agents 2007;30: 398–408.

Maor

Hagin

Belausov

Keller

Ben-David

Rahav

Clinical features of heteroresistant vancomycin-intermediate Staphylococcus aureus bacteremia versus those of methicillin-resistant S. aureus bacteremia. J Infect Dis 2009;199:619–24.

Garnier

Chainier

Walsh

A 1 year surveillance study of glycopeptide-intermediate Staphylococcus aureus strains in a French hospital. J Antimicrob Chemother 2006;57:146–9.

Rybak

Leonard

Rossi

Cheung

Sader

Jones

Characterization of vancomycin-heteroresistant Staphylococcus aureus from the metropolitan area of Detroit, Michigan, over a 22-year period (1986 to 2007). J Clin Microbiol 2008;46:2950–4.

Moore

Perdreau-Remington

Chambers

Vancomycin treatment failure associated with heterogeneous vancomycin-intermediate Staphylococcus aureus in a patient with endocarditis and in the rabbit model of endocarditis. Antimicrob Agents Chemother 2003;47:1262–6.

Fridkin

Gaynes

Antimicrobial resistance in intensive care units. Clin Chest Med 1999;20:303–16, viii.

Staphylococcus aureus resistant to vancomycin—United States, 2002. MMWR Morb Mortal Wkly Rep 2002;51:565–7.

10.

MRSA with intermediate resistance to teicoplanin. Commun Dis Rep CDR Wkly 2000;10(11):99, 102.

11.

Hiramatsu

Hanaki

Ino

Yabuta

Oguri

Tenover

Methicillin-resistant Staphylococcus aureus clinical strain with reduced vancomycin susceptibility. J Antimicrob Chemother 1997;40:135–6.

12.

Clinical and Laboratories Standards Institute. Performance standards for antimicrobial susceptibility testing: eighteenth international supplement M100-S18. Wayne, PA: Clinical and Laboratory Standards Institute, 2008.

13.

Liu

Chambers

Staphylococcus aureus with heterogeneous resistance to vancomycin: epidemiology, clinical significance, and critical assessment of diagnostic methods. Antimicrob Agents Chemother 2003;47:3040–5.

14.

Cui

Iwamoto

Lian

Novel mechanism of antibiotic resistance originating in vancomycin-intermediate Staphylococcus aureus. Antimicrob Agents Chemother 2006;50:428–38.

15.

Howden

Johnson

Ward

Stinear

Davies

Isolates with low-level vancomycin resistance associated with persistent methicillin-resistant Staphylococcus aureus bacteremia. Antimicrob Agents Chemother 2006;50:3039–47.

16.

Sieradzki

Tomasz

Alterations of cell wall structure and metabolism accompany reduced susceptibility to vancomycin in an isogenic series of clinical isolates of Staphylococcus aureus. J Bacteriol 2003;185:7103–10.

17.

Deresinski

Vancomycin heteroresistance and methicillin-resistant Staphylococcus aureus. J Infect Dis 2009;199:605–9.

18.

Sakoulas

Moellering

Jr Eliopoulos

Adaptation of methicillin-resistant Staphylococcus aureus in the face of vancomycin therapy. Clin Infect Dis 2006;42(suppl 1):S40–50.

19.

Meehl

Herbert

Gotz

Cheung

Interaction of the GraRS two-component system with the VraFG ABC transporter to support vancomycin-intermediate resistance in Staphylococcus aureus. Antimicrob Agents Chemother 2007;51:2679–89.

20.

Howden

Smith

Mansell

Different bacterial gene expression patterns and attenuated host immune responses are associated with the evolution of low-level vancomycin resistance during persistent methicillin-resistant Staphylococcus aureus bacteraemia. BMC Microbiol 2008;8:39.

21.

Maor

Rahav

Belausov

Ben-David

Smollan

Keller

Prevalence and characteristics of heteroresistant vancomycin-intermediate Staphylococcus aureus bacteremia in a tertiary care center. J Clin Microbiol 2007;45:1511–4.

22.

Ariza

Pujol

Cabo

Vancomycin in surgical infections due to methicillin-resistant Staphylococcus aureus with heterogeneous resistance to vancomycin. Lancet 1999;353:1587–8.

23.

Sun

Chen

Liu

Prevalence and characterization of heterogeneous vancomycin-intermediate Staphylococcus aureus isolates from 14 cities in China. Antimicrob Agents Chemother 2009;53:3642–9.

24.

de Lassence

Hidri

Timsit

Control and outcome of a large outbreak of colonization and infection with glycopeptide-intermediate Staphylococcus aureus in an intensive care unit. Clin Infect Dis 2006; 42:170–8.

25.

Walsh

Howe

The prevalence and mechanisms of vancomycin resistance in Staphylococcus aureus. Annu Rev Microbiol 2002;56:657–75.

26.

Fridkin

Vancomycin-intermediate and -resistant Staphylococcus aureus: what the infectious disease specialist needs to know. Clin Infect Dis 2001;32:108–15.

27.

Voss

Mouton

van Elzakker

A multi-center blinded study on the efficiency of phenotypic screening methods to detect glycopeptide intermediately susceptible Staphylococcus aureus (GISA) and heterogeneous GISA (h-GISA). Ann Clin Microbiol Antimicrob 2007;6:9.

28.

Walsh

Bolmstrom

Qwarnstrom

Evaluation of current methods for detection of staphylococci with reduced susceptibility to glycopeptides. J Clin Microbiol 2001;39:2439–44.

29.

Wootton

MacGowan

Walsh

Howe

A multicenter study evaluating the current strategies for isolating Staphylococcus aureus strains with reduced susceptibility to glycopeptides. J Clin Microbiol 2007;45:329–32.

30.

Yusof

Engelhardt

Karlsson

Evaluation of a new Etest vancomycin-teicoplanin strip for detection of glycopeptide-intermediate Staphylococcus aureus (GISA), in particular, heterogeneous GISA. J Clin Microbiol 2008;46:3042–7.

31.

Leonard

Rossi

Newton

Rybak

Evaluation of the Etest GRD for the detection of Staphylococcus aureus with reduced susceptibility to glycopeptides. J Antimicrob Chemother 2009;63:489–92.

32.

Plipat

Livni

Bertram

Thomson

Jr.

Unstable vancomycin heteroresistance is common among clinical isolates of methicilliin-resistant Staphylococcus aureus. J Clin Microbiol 2005;43:2494–6.

33.

Moise

Schentag

Vancomycin treatment failures in Staphylococcus aureus lower respiratory tract infections. Int J Antimicrob Agents 2000;16(suppl 1):S31–4.

34.

Fong

Low

Koh

Kurup

Clinical features and treatment outcomes of vancomycin-intermediate Staphylococcus aureus (VISA) and heteroresistant vancomycin-intermediate Staphylococcus aureus (hVISA) in a tertiary care institution in Singapore. Eur J Clin Microbiol Infect Dis 2009;28:983–7.

35.

Howden

Ward

Charles

Treatment outcomes for serious infections caused by methicillin-resistant Staphylococcus aureus with reduced vancomycin susceptibility. Clin Infect Dis 2004;38:521–8.

36.

Horne

Howden

Grabsch

Prospective comparison of the clinical impacts of heterogeneous vancomycin-intermediate methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-susceptible MRSA. Antimicrob Agents Chemother 2009;53:3447–52.

37.

Bobin-Dubreux

Reverdy

Nervi

Clinical isolate of vancomycin-heterointermediate Staphylococcus aureus susceptible to methicillin and in vitro selection of a vancomycin-resistant derivative. Antimicrob Agents Chemother 2001;45:349–52.

38.

Charles

Ward

Johnson

Howden

Grayson

Clinical features associated with bacteremia due to heterogeneous vancomycin-intermediate Staphylococcus aureus. Clin Infect Dis 2004;38:448–51.

39.

Eng

Smith

Buccini

Cherubin

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

40.

Lalani

Federspiel

Boucher

Associations between the genotypes of Staphylococcus aureus bloodstream isolates and clinical characteristics and outcomes of bacteremic patients. J Clin Microbiol 2008;46:2890–6.

41.

Van Griethuysen

Van 't Veen

Buiting

Walsh

Kluytmans

High percentage of methicillin-resistant Staphylococcus aureus isolates with reduced susceptibility to glycopeptides in the Netherlands. J Clin Microbiol 2003;41:2487–91.

42.

Szabo

hVISA/VISA: diagnostic and therapeutic problems. Expert Rev Anti Infect Ther 2009;7:1–3.

43.

Climo

Patron

Archer

Combinations of vancomycin and beta-lactams are synergistic against staphylococci with reduced susceptibilities to vancomycin. Antimicrob Agents Chemother 1999;43:1747–53.

44.

Leonard

Vidaillac

Rybak

Activity of telavancin against Staphylococcus aureus strains with various vancomycin susceptibilities in an in vitro pharmacokinetic/pharmacodynamic model with simulated endocardial vegetations. Antimicrob Agents Chemother 2009;53:2928–33.

45.

Wootton

MacGowan

Walsh

Comparative bactericidal activities of daptomycin and vancomycin against glycopeptide-intermediate Staphylococcus aureus (GISA) and heterogeneous GISA isolates. Antimicrob Agents Chemother 2006;50:4195–7.

46.

Leonard

Rybak

Evaluation of vancomycin and daptomycin against methicillin-resistant Staphylococcus aureus and heterogeneously vancomycin-intermediate S. aureus in an in vitro pharmacokinetic/pharmacodynamic model with simulated endocardial vegetations. J Antimicrob Chemother 2009;63:155–60.

47.

Patel

Jevitt

Hageman

McDonald

Tenover

An association between reduced susceptibility to daptomycin and reduced susceptibility to vancomycin in Staphylococcus aureus. Clin Infect Dis 2006;42:1652–3.

48.

Rybak

Lomaestro

Rotscahfer

Vancomycin therapeutic guidelines: a summary of consensus recommendations from the Infectious Diseases Society of America, the American Society of Health-System Pharmacists, and the Society of Infectious Diseases Pharmacists. Clin Infect Dis 2009;49:325–7.

49.

Lodise

Lomaestro

Graves

Drusano

Larger vancomycin doses (at least four grams per day) are associated with an increased incidence of nephrotoxicity. Antimicrob Agents Chemother 2008;52:1330–6.

50.

Higgins

Chang

Debabov

Telavancin, a multifunctional lipoglycopeptide, disrupts both cell wall synthesis and cell membrane integrity in methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother 2005;49:1127–34.

51.

Hegde

Difuntorum

Skinner

Trumbull

Krause

Efficacy of telavancin against glycopeptide-intermediate Staphylococcus aureus in the neutropenic mouse bacteraemia model. J Antimicrob Chemother 2009;63:763–6.

52.

Stryjewski

Graham

Wilson

Telavancin versus vancomycin for the treatment of complicated skin and skin-structure infections caused by gram-positive organisms. Clin Infect Dis 2008;46:1683–93.

53.

Lin

Appelbaum

Activity of ceftobiprole compared with those of other agents against Staphylococcus aureus strains with different resisto-types by time-kill analysis. Diagn Microbiol Infect Dis 2008;60:233–5.

54.

Bogdanovich

Ednie

Shapiro

Appelbaum

Antistaphylococcal activity of ceftobiprole, a new broad-spectrum cephalosporin. Antimicrob Agents Chemother 2005;49:4210–9.

55.

Vidaillac

Leonard

Rybak

In vitro activity of ceftaroline against methicillin-resistant Staphylococcus aureus and heterogeneous vancomycin-intermediate S. aureus in a hollow fiber model. Antimicrob Agents Chemother 2009;53:4712–7.

56.

Hebeisen

Heinze-Krauss

Angehrn

Hohl

Page

Then

In vitro and in vivo properties of Ro 63-9141, a novel broad-spectrum cephalosporin with activity against methicillin-resistant staphylococci. Antimicrob Agents Chemother 2001;45:825–36.