Antimicrobial Susceptibility StudiesSurrogate analysis of vancomycin to predict susceptible categorization of dalbavancin☆
Introduction
Dalbavancin is a recently approved lipoglycopeptide agent for the treatment of acute bacterial skin and skin structure infections (ABSSSIs) in adults, known or suspected to be caused by designated susceptible strains of Gram-positive pathogens (Billeter et al., 2008, Boucher et al., 2014, Chambers, 2014, Dalvance™, 2014, Jones et al., 2005, Streit et al., 2004, Zhanel et al., 2010). Pharmacokinetic/pharmacodynamic characteristics of dalbavancin (terminal half-life of 2 weeks, 93% protein binding) allow for a 2 intravenous dose regimen of 1000 mg followed 1 week later by 500 mg (Andes and Craig, 2007, Chambers, 2014, Dorr et al., 2005). Two ABSSSI trials (DISCOVER 1 and DISCOVER 2) comparing dalbavancin to a control regimen of vancomycin/linezolid showed that dalbavancin was noninferior to the comparators leading to approval by the USA Food and Drug Administration (USA-FDA) (Boucher et al., 2014) and confirming conclusions from earlier clinical trials (Jauregui et al., 2005, Seltzer et al., 2003).
Lipoglycopeptides (dalbavancin, oritavancin, and telavancin) have physiochemical features that can challenge the development of in vitro methods for susceptibility testing (Rennie et al., 2007, Zhanel et al., 2010). Early studies, particularly with dalbavancin, demonstrated that reference MIC (agar dilution and broth microdilution) and agar diffusion (disk tests) methods were flawed by high binding affinities of these drugs for media components and plastics as well as limited diffusion in agar due to the drug's high molecular size (Rennie et al., 2007). A reference broth microdilution method for all marketed lipoglycopeptides has been approved and published by the Clinical and Laboratory Standards Institute (CLSI) wherein a surfactant (polysorbate 80 at 0.002%) supplement was added to the Mueller–Hinton broth to minimize binding to the plastic trays and thus accurately measuring drug potency (Clinical and Laboratory Standards Institute (CLSI), 2012, Clinical and Laboratory Standards Institute (CLSI), 2014). Dalbavancin, among the clinically approved lipoglycopeptides, has been studied in resistance surveillance trials for over a decade (Biedenbach et al., 2009, Jones et al., 2005, Streit et al., 2004) and has a validated E-test (Fritsche et al., 2006) and a dry-form broth microdilution method (Jones et al., 2004), plus published quality control (QC) guidelines (Anderegg et al., 2003, Clinical and Laboratory Standards Institute (CLSI), 2014) to assure precise measures of it's activity.
However, like other newer antimicrobial agents at the time of USA-FDA approval (Jones et al., 2013b), commercial diagnostic devices for dalbavancin may not be available. In the interim, 1 possible strategy for dalbavancin in vitro testing would be to apply the results of a commonly tested chemically similar agent such as vancomycin for a surrogate marker of susceptibility (Clinical and Laboratory Standards Institute (CLSI), 2014, Jones and Pfaller, 2001, Jones et al., 2007). This type of analysis (cross-susceptibility) was initially reported for dalbavancin in 2006 (Jones et al., 2006) and showed diagnostic promise but did not use the recent regulatory-approved interpretive breakpoint criteria for this new agent (Dalvance™, 2014). We present here, an updated analysis of year 2011–2013 clinical strains of Gram-positive pathogens to establish vancomycin susceptibility results as a possible surrogate predictor of dalbavancin activity.
Section snippets
Organisms tested
Major Gram-positive pathogens collected by the SENTRY Antimicrobial Surveillance Program (64,815 strains) during 2011–2013 were used in this surrogate testing analysis. These organisms from USA and European medical centers included Staphylococcus aureus (33,688), coagulase-negative staphylococci (CoNS; 4576, including 5 major species with >200 isolates); enterococci (6515; mostly Enterococcus faecalis at 4126 isolates), β-hemolytic streptococci (5722, including 5 species or serogroups with >200
Results and discussion
Table 1 presents the most recent published spectrum and activity of dalbavancin tested in a resistance surveillance study (SENTRY Program, 2011–2012) for a collection of 3144 isolates of Gram-positive pathogens (Jones et al., 2013a, Jones et al., 2013c). Dalbavancin exhibits high potencies (MIC90, ≤0.06 μg/mL) for all tabulated species except S. agalactiae and the enterococci, and all MIC values were ≤0.25 μg/mL, except for 41.6% of Enterococcus spp. (vancomycin-resistant enterococci [VRE]
Acknowledgments
The research and publication process was supported by Durata Therapeutics.
JMI Laboratories has received research and educational grants in 2012–2014 from Achaogen, Actelion, Affinium, American Proficiency Institute, AmpliPhi Bio, Anacor, Astellas, AstraZeneca, Basilea, BioVersys, Cardeas, Cempra, Cerexa, Cubist, Daiichi, Dipexium, Durata, Fedora, Forest Research Institute, Furiex, Genentech, GlaxoSmithKline, Janssen, Johnson & Johnson, Medpace, Meiji Seika Kaisha, Melinta, Merck, Methylgene,
References (27)
- et al.
Can antimicrobial susceptibility testing results for ciprofloxacin or levofloxacin predict susceptibility to a newer fluoroquinolone, gatifloxacin? Report from The SENTRY Antimicrobial Surveillance Program (1997–1999)
Diagn Microbiol Infect Dis
(2001) - et al.
Validation of commercial dry-form broth microdilution panels and test reproducibility for susceptibility testing of dalbavancin, a new very long-acting glycopeptide
Int J Antimicrob Agents
(2004) - et al.
Selection of a surrogate beta-lactam testing agent for initial susceptibility testing of doripenem, a new carbapenem
Diagn Microbiol Infect Dis
(2007) - et al.
Surveillance of dalbavancin potency and spectrum in the United States (2012)
Diagn Microbiol Infect Dis
(2013) - et al.
Interim susceptibility testing for ceftaroline, a new MRSA-active cephalosporin: selecting potent surrogate β-lactam markers to predict ceftaroline activity against clinically-indicated species
Diagn Microbiol Infect Dis
(2013) - et al.
Update of dalbavancin spectrum and potency in the USA; report from the SENTRY Antimicrobial Surveillance Program (2011)
Diagn Microbiol Infect Dis
(2013) - et al.
Worldwide assessment of dalbavancin activity and spectrum against over 6,000 clinical isolates
Diagn Microbiol Infect Dis
(2004) - et al.
Statistical characterisation of bacterial wild-type MIC value distributions and the determination of epidemiological cut-off values
Clin Microbiol Infect
(2006) - et al.
Initial quality control evaluations for susceptibility testing of dalbavancin (BI397), an investigational glycopeptide with potent gram-positive activity
J Clin Microbiol
(2003) - et al.
In vivo pharmacodynamic activity of the glycopeptide dalbavancin
Antimicrob Agents Chemother
(2007)
Activities of dalbavancin against a worldwide collection of 81,673 gram-positive bacterial isolates
Antimicrob Agents Chemother
Dalbavancin: a novel once-weekly lipoglycopeptide antibiotic
Clin Infect Dis
Once-weekly dalbavancin versus daily conventional therapy for skin infection
N Engl J Med
Cited by (31)
Glycopeptide and Lipoglycopeptide Antibiotics
2022, Comprehensive PharmacologyCurrent trends in the real-life use of dalbavancin: report of a study panel
2020, International Journal of Antimicrobial AgentsCitation Excerpt :Dalbavancin MICs must be determined in the presence of polysorbate 80 (0.002% in the medium for broth dilution methods; agar dilution methods have not yet been validated). However, in microbiology practice, S. aureus, MRSA, streptococci groups A, B, C and G, and S. anginosus isolates susceptible to vancomycin can be reported as also susceptible to dalbavancin [7]. In contrast, whenever the strain is resistant in vitro to vancomycin, dalbavancin should not be used.
Dalbavancin and telavancin in the treatment of infective endocarditis: a literature review
2020, International Journal of Antimicrobial AgentsCitation Excerpt :No adverse effects were reported whilst receiving dalbavancin. In terms of use of vancomycin as a surrogate marker for dalbavancin susceptibility, a cross-susceptibility study of >58,000 clinical isolates (including S. aureus, beta-haemolytic streptococci, viridans group streptococci, CoNS and enterococci) reported susceptibility concordance rates of 97.7–100% for vancomycin and dalbavancin across the various species (based on an established dalbavancin susceptibility breakpoint ≤0.12 mg/L) [25]. Telavancin is a parenterally administered, once-daily, semisynthetic lipoglycopeptide antibiotic active against Gram-positive bacteria with demonstrable potent in-vitro activity against MSSA and MRSA [26].
Emergence of dalbavancin non-susceptible, vancomycin-intermediate Staphylococcus aureus (VISA) after treatment of MRSA central line-associated bloodstream infection with a dalbavancin- and vancomycin-containing regimen
2018, Clinical Microbiology and InfectionCitation Excerpt :Dalbavancin was chosen to avoid additional line placement and because of a lack of insurance coverage for home infusion services. Given the absence of commercially available methods for determining in vitro susceptibility to dalbavancin, vancomycin was used as a surrogate for inferring dalbavancin susceptibility according to current recommendations [6]. Twelve days after his dose of dalbavancin the patient returned with a severe drug reaction related to allopurinol.
Reproducibility of dalbavancin MIC test results and an updated surrogate accuracy analysis of vancomycin MIC values to infer dalbavancin susceptibility (2014)
2016, Diagnostic Microbiology and Infectious Disease
- ☆
Note: These data were presented in part as a late breaker abstract at the 54th ICAAC, Washington, DC, September 6–9, 2014. Abstract No. D-875b.