Factors Influencing Broth Microdilution Antimicrobial Susceptibility Test Results for Dalbavancin, a New Glycopeptide Agent

Rennie, Robert; Koeth, Laura; Jones, Ronald N.; Fritsche, Thomas R.; Knapp, C C; Killian, S. B.; Goldstein, Beth P.

doi:10.1128/jcm.02411-06

Cited by 39 publications

(30 citation statements)

References 10 publications

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“…The loss of dalbavancin activity following exposure of the stock solution to plastic and without the addition of P-80 has been well documented 7 . In 2 additional studies, the addition of P-80 to the initial and intermediate stock solutions (Table 6) and the use of glass or plastic tubes for the preparation of the initial and intermediate stock solutions (Table 7) did not have an effect on the dalbavancin MIC results.…”

Section: Representative Resultsmentioning

confidence: 98%

“…The presence of lysed horse blood in the broth media for testing of streptococci has been shown to have a surfactant-like activity, comparable to P-80 7,8 . The dalbavancin reference method for streptococcus does include both P-80 and lysed horse blood, however, unlike staphylococci and enterococci, dalbavancin MIC results for streptococci are similar (within +/-1 dilution) with and without the addition of P-80.…”

Section: Representative Resultsmentioning

confidence: 99%

“…A slight variation in MIC results due to method difference, in addition to the inherent BMD variation of ± one dilution, could potentially have a significant impact on the susceptibility rates. 6 Similar to other lipoglycopeptide agents, dalbavancin susceptibility testing can be challenging as a result of solubility and the relatively large size of the molecule and its binding properties 7,8,9 . The reference BMD method described here includes two specific steps that are unique to insoluble agents and/or lipoglycopeptide agents: (1) the use of DMSO for preparation of stock solutions and (2) addition of 0.002% P-80 in the final MIC panel dilutions.…”

Section: Introductionmentioning

confidence: 99%

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A Reference Broth Microdilution Method for Dalbavancin <em>In Vitro</em> Susceptibility Testing of Bacteria that Grow Aerobically

Koeth¹,

DiFranco-Fisher²,

McCurdy

2015

JoVE

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Antimicrobial susceptibility testing (AST) is performed to assess the in vitro activity of antimicrobial agents against various bacteria. The AST results, which are expressed as minimum inhibitory concentrations (MICs) are used in research for antimicrobial development and monitoring of resistance development and in the clinical setting for antimicrobial therapy guidance. Dalbavancin is a semi-synthetic lipoglycopeptide antimicrobial agent that was approved in May 2014 by the Food and Drug Administration (FDA) for the treatment of acute bacterial skin and skin structure infections caused by Gram-positive organisms. The advantage of dalbavancin over current anti-staphylococcal therapies is its long half-life, which allows for once-weekly dosing. Dalbavancin has activity against Staphylococcus aureus (including both methicillin-susceptible S. aureus [MSSA] and methicillin-resistant S. aureus [MRSA]), coagulase-negative staphylococci, Streptococcus pneumoniae, Streptococcus anginosus group, β-hemolytic streptococci and vancomycin susceptible enterococci. Similar to other recent lipoglycopeptide agents, optimization of CLSI and ISO broth susceptibility test methods includes the use of dimethyl sulfoxide (DMSO) as a solvent when preparing stock solutions and polysorbate 80 (P80) to alleviate adherence of the agent to plastic. Prior to the clinical studies and during the initial development of dalbavancin, susceptibility studies were not performed with the use of P-80 and MIC results tended to be 2-4 fold higher and similarly higher MIC results were obtained with the agar dilution susceptibility method. Dalbavancin was first included in CLSI broth microdilution methodology tables in 2005 and amended in 2006 to clarify use of DMSO and P-80. The broth microdilution (BMD) procedure shown here is specific to dalbavancin and is in accordance with the CLSI and ISO methods, with step-by-step detail and focus on the critical steps added for clarity.

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Section: Representative Resultsmentioning

confidence: 98%

Section: Representative Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A Reference Broth Microdilution Method for Dalbavancin <em>In Vitro</em> Susceptibility Testing of Bacteria that Grow Aerobically

Koeth¹,

DiFranco-Fisher²,

McCurdy

2015

JoVE

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“…A large number of studies have examined the in vitro activity of these compounds against [17], which leads, by steric hindrance, to an inhibition of the glycan chain extension and, to a lesser extent, of crosslinking between peptidic stems. Oritavancin has additional interactions with the pentaglycyl bridge and the D-iso-glutamine residue in position 2 of the pentapeptide terminus of lipid II (zone highlighted in orange) [37], which allow it to be a stronger inhibitor of transpeptidases [38] collections of Gram-positive clinical isolates, yet many of these studies were performed using broth that was not supplemented by polysorbate-80, which is needed to prevent the adsorption of the drugs to the plastic [40][41][42]. Table 1 therefore focuses on recent studies that have used the standard procedure currently recommended by the Clinical Laboratory Standards Institute (CLSI), i.e., 0.002 % polysorbate-80 added to the culture medium [43].…”

Section: Spectrum Of Activitymentioning

confidence: 99%

Lipoglycopeptide Antibacterial Agents in Gram-Positive Infections: A Comparative Review

Bambeke

2015

Drugs

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Oritavancin, telavancin, and dalbavancin are recently marketed lipoglycopeptides that exhibit remarkable differences to conventional molecules. While dalbavancin inhibits the late stages of peptidoglycan synthesis by mainly impairing transglycosylase activity, oritavancin and telavancin anchor in the bacterial membrane by the lipophilic side chain linked to their disaccharidic moiety, disrupting membrane integrity and causing bacteriolysis. Oritavancin keeps activity against vancomycin-resistant enterocococci, being a stronger inhibitor of transpeptidase than of transglycosylase activity. These molecules have potent activity against Grampositive organisms, most notably staphylococci (including methicillin-resistant Staphylococcus aureus and to some extent vancomycin-intermediate S. aureus), streptococci (including multidrug-resistant pneumococci), and Clostridia. All agents are indicated for the treatment of acute bacterial skin and skin structure infections, and telavancin, for hospitalacquired and ventilator-associated bacterial pneumonia. While telavancin is administered daily at 10 mg/kg, the remarkably long half-lives of oritavancin and dalbavancin allow for infrequent dosing (single dose of 1200 mg for oritavancin and 1000 mg at day 1 followed by 500 mg at day 8 for dalbavancin), which could be exploited in the future for outpatient therapy. Among possible safety issues evidenced during clinical development were an increased risk of developing osteomyelitis with oritavancin; taste disturbance, nephrotoxicity, and risk of corrected QT interval prolongation (especially in the presence of at-risk co-medications) with telavancin; and elevation of hepatic enzymes with dalbavancin. Interference with coagulation tests has been reported with oritavancin and telavancin. These drugs proved non-inferior to conventional treatments in clinical trials but their advantages may be better evidenced upon future evaluation in more severe infections. Key PointsNew lipoglycopeptides (telavancin, oritavancin, dalbavancin) differ from vancomycin by the presence of a lipophilic side chain, which profoundly modifies their pharmacokinetic and/or pharmacodynamic profile.Among these agents, telavancin and oritavancin have multiple modes of action and are highly bactericidal.Oritavancin and dalbavancin have prolonged halflives, allowing for their use a single-dose or twodose (once-a-week) regimen, respectively. These three drugs are indicated for the treatment of acute bacterial skin and skin structure infections, and telavancin is indicated for hospital-acquired and ventilator-associated bacterial pneumonia.

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“…The data was documented and analysed for the completion of this study. A reference strain S. aureus ATCC 25923 was used for the standardization of antibiotic susceptibility testing [20,21].…”

Section: Methodsmentioning

confidence: 99%

Conquering methicillin resistant Staphylococcus aureus: perspectives and treatment options

Rashid

Qureshi

et al. 2015

Int Arch Med

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Exploring optimal cure of Methicillin Resistant Staphylococcus aureus (MRSA), has been consistently challenged by clinical physicians and microbiologist. The fatal bacterial infection, Methicillin Resistant Staphylococcus aureus (MRSA), shows unique resistance; when selected drugs are tested on human patients. If holistic approach is overlooked, less possibilities are left for medication to curtail this lethal toxicity. If single range of drug treatment is exercised only, the associated complications and consequences of infections may proliferate beyond threshold levels. The research article is an outcome from primary microbial data collection (from urine and blood) in hospital. The focus of experiment is to scrutinize the highest risk vulnerable hospital area including sampled fluid. The preventive and therapeutic measures are discussed along with multiple substitutes of medication with prudent selection to achieve targeted and optimum outcome.

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Factors Influencing Broth Microdilution Antimicrobial Susceptibility Test Results for Dalbavancin, a New Glycopeptide Agent

Cited by 39 publications

References 10 publications

A Reference Broth Microdilution Method for Dalbavancin <em>In Vitro</em> Susceptibility Testing of Bacteria that Grow Aerobically

A Reference Broth Microdilution Method for Dalbavancin <em>In Vitro</em> Susceptibility Testing of Bacteria that Grow Aerobically

Lipoglycopeptide Antibacterial Agents in Gram-Positive Infections: A Comparative Review

Conquering methicillin resistant Staphylococcus aureus: perspectives and treatment options

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