Dalbavancin: A review for dermatologists
Published Web Locationhttps://doi.org/10.5070/D30wn7d4q9
Dalbavancin: A review for dermatologistsDepartment of Dermatology St Lukes Roosevelt Hospital, New York NY. Scheinfeld@earthlink.net
Noah Scheinfeld MD
Dermatology Online Journal 12 (4): 6
Most complicated skin and skin structure infections (cSSSI) are caused by Staphylococcus aurens (SA) and streptococcus (SC). More and more isolates of SA and SC are resistant to methicillin (MRSA) and there are concerns that SA will become resistant to vancomycin (VRSA), the current standard of treatment. Dalbavancin (BI397) is a novel semisynthetic lipoglycopeptide that was designed to improve uon the natural glycopeptides currently available, vancomycin and teicoplanin. Phase-III clinical trials comprising more than 1,500 patients evaluating once-weekly dalbavancin in skin and soft tissue infections (SSTIs) associated with Gram-positive bacteria met the primary endpoint of non-inferiority in patients whose clinical response was evaluated at 2 weeks following therapy when compared to linezolid, cefazolin, or vancomycin, the three most widely administered standard-of-care agents for SSTIs. The side effect profile of dalbavancin is mild, with headache and pyrexia being the most adverse effects. Once-a-week dosing with dalbavancin may obviate the need for the continued presence of IV lines in some patients, which could translate into fewer local infections and blood stream infections and which could facilitate transfer of the patients to skilled nursing facilities. Unlike other new antibiotics, such as oritavancin and tigecycline, dalbavancin is not active against vancomycin-resistant enterococcus or VRSA. Its approval by the FDA is expected soon. The extent to which dalbavancin will supplant vancomycin and whether it will be preferred other newer agents such as linezolid.
As the chronic diseases such as diabetes and invasive types of surgery such as joint replacement have been more prevalent, the number of complicated skin structure infections (cSSSIs) has increased. These cSSSI include infected ulcers, burns, major abscesses, infections of deeper soft tissues, and other skin structure infections requiring significant surgical intervention along with antimicrobial drug therapy.
Complicated skin structure infections are part of the approximately two million hospitalized patients in the United States are infected with bacterial that occur independent of the diseases for which they are hospitalized . Catheter-related bloodstream infections occur in 5 percent of the seven million procedures annually in the United States according to the Center for Disease Control and Prevention; they are a major cause of death when such infections occur. More than 70 percent of the bacteria associated with nosocomial infections are resistant to at least one of the drugs most commonly used to treat those infections, according to the CDC . Hospital-acquired infections kill some 90,000 people each year.
The most common pathogens involved in iatrogenic cSSSIs are group-A Streptococci (SC) and Staphylococcus aurens (SA). More and more isolates of SA are resistant to methicillin (MRSA) and there rare cases of MRSA resistant to vancomycin (MRSA). Streptococccus isolates and methicillin-resistant Staphylococcus epidermidis (MRSE) are also becoming resistant to existing antibiotics and increasing in incidence. To treat such infections new antibiotics have been introduced which include linezolid, the first oxazolidinone in clinical use, daptomycin, the first lipopeptide in clinical use, telithromycin, a ketolide that is derived from clarithromycin, and tigecycline, a broad-spectrum intravenous tetracycline Antibiotics in development or near to approval include: ceftobiprole, a broad-spectrum cephalosporin that has activity against methicillin-resistant staphylococci, DX-619 and WCK-771, which are potent quinolones that have activity against quinolone-resistant staphylococci, iclaprim, which is a diaminopyrimidine, and oritavancin and dalbavancin, both of which are new glycopeptides . This article will review data surrounding dalbavancin.
A number of reviews have noted that dalbacancin is a promising antibiotic for the treatment of complex skin infections [4, 5, 6, 7, 8, 9, 10, 11, 12]. As of June 30, 2005 dalbavancin has been evaluated with good results as follows:
- three Phase 3 clinical trials for the treatment of skin and soft tissue infections (completed and top-line data released)
- a Phase 2 clinical trial for the treatment of catheter-related blood stream infections (completed, top-line data released and published)
- a Phase 2 trial in skin and soft tissue infections (completed, top-line data released and published)
Phase III study design and results
In August 2004 Vicuron Pharmaceuticals announced results from pivotal Phase III clinical trials comprising more than 1,500 patients evaluating once-weekly dalbavancin in skin and soft tissue infections (SSTIs) caused by Gram-positive bacteria. All three studies met the primary endpoint of non-inferiority in evaluable patients' clinical response at 2 weeks following therapy when compared to linezolid, cefazolin or vancomycin, the three most widely administered standard-of-care agents for SSTIs . All studies also met the secondary endpoint of non-inferiority in clinical response for the intent-to-treat (ITT) patient population. It is effective against methicillin-resistant Staphylococcus aureus (MRSA) but is not effective against vancomycin-resistant enterococci (VRE). Phase III studies showed that dalbavancin was well tolerated.
The phase III study involved complicated SSTIs and was a randomized, controlled, double-blind study of 854 patients versus linezolid . The primary endpoint was clinical response at the follow-up visit in the evaluable patient population. Evaluable patients taking dalbavancin demonstrated an 88.9 percent response versus 91.2 percent for linezolid patients (95 % confidence interval -7.3 ,2.9 ). In the ITT group, dalbavancin patients showed a 76.5 percent response versus 82.7 for linezolid (95 percent confidence interval -12.0, -0.3). Dalbavancin was well tolerated in the study.
The phase III study also involved uncomplicated SSTIs and was a randomized, controlled, double-blind study of 565 patients versus intravenous cefazolin followed by oral cephalexin. The primary endpoint was clinical response at the follow-up visit in the evaluable patient population. Evaluable patients taking dalbavancin demonstrated an 89.1 percent response versus 89.1 percent for cefazolin (95 percent confidence interval -6.8, 6.8). In the ITT group, dalbavancin patients showed a 76.0 percent response versus a 75.8 percent response for cefazolin (95 percent confidence interval -7.7, 8.2). Dalbavancin was well tolerated in the study.
The phase III study also involved SSTIs caused by MRSA and was a randomized, controlled, open-label study of 156 patients versus vancomycin in SSTIs suspected or confirmed to be caused by methicillin-resistant Staphylococcus aureus (MRSA). The primary endpoint was clinical response at the follow-up visit in the evaluable patient population. Evaluable patients taking dalbavancin demonstrated an 89.9 percent response versus 86.7 percent for vancomycin (95 percent confidence interval -13.0, 19.4). In the ITT group, dalbavancin patients showed an 86.0 percent response versus 65.3 percent for vancomycin (95 percent confidence interval 4.3, 37.0). Dalbavancin was well tolerated in the study. This study is not pivotal, but will be part of the NDA submission .
Prospects for approval of dalbavancin
On September 22, The Pink Sheet, a medical trade publication, reported the The US Food and Drug Administration (FDA) had said that Pfizer received an approvable letter from the FDA for dalbavancin. Such letters are not approvals but instead a kind of delay, saying that most of the data needed for approval are in but that additional steps need to be taken if the drug is to reach the market. Pfizer would say only that dalbavancin was still under FDA review. An FDA spokeswoman, Rae Jones, says the agency does not comment on regulatory communications .
Development of dalbavancin
Dalbavancin (BI397) is a novel semisynthetic lipoglycopeptide that was designed to improve upon the natural glycopeptides currently available, vancomycin and teicoplanin. Dalbavancin is a teicoplanin analog and is a dimethylaminepropyl amide derivative of the lipoglycopeptide A40926. Both dalbavancin and MDL-63246 are dimethylaminopropyl amide derivatives of A-40926; dalbavancin differs from MDL-63246 in its acylamino sugar, which consists of glucuronic acid in dalbavancin and glucosamine in MDL-63246. The development of MDL-63246 has been discontinued .
Another lipoglycopeptide is oritavancin (LY333328), which is the 4'-chlorobiphenylmethyl derivative of chloroeremomycin, an analogue to vancomycin. It is characterised by the following: i) a spectrum covering vancomycin-resistant enterococci (VRE), methicillin-resistant Staphylococcus aureus (MRSA) and to some extent glycopeptide-intermediate S. aureus (GISA); ii) rapid bactericidal activity including against the intracellular forms of enterococci and staphylococci; and iii) a prolonged half-life, allowing for daily administration .
Dalbavancin has a long half life in the body, about 200-300 hours. Dalbavancin is considered an advance on existing agents based on its patient-convenient once-weekly dosing regimen . A number of studies have found that dalbavancin is an effective medication when given once weekly [20, 21, 22].
Animal models also have shown that once weekly dosing of dalbavancin is effective. For the treatment of rabbit endocarditis, dalbavancin given once daily (10 mg/kg of body weight for 4 days) or as a single 40-mg/kg dose was active against Staphylococcus aureus with or without reduced susceptibility to glycopeptides, as expected from its good in vitro activity, even in broth supplemented with 90 percent serum and given its prolonged elimination half-life . Dalbavancin has a long t½ (approximately 8 days) in the rat and distributes widely throughout the body, and it is not selectively retained in any single organ, tissue or blood component and is completely eliminated by both renal and non-renal routes in rats .
Dalbavancin has dual routes of elimination, with around two-thirds of the excreted drug-derived radioactivity being found in the urine and around one-third in the feces. In patients with mild or moderate hepatic impairment there is no impact on the half-life of dalbavancin (Fig. 1); the half-life is shown to be greater than 300 hours in these patients, buttressing the usefulness of dalbavancin as a once-a-week drug for the treatment of serious staphylococcal infections .
Dalbavancin is generally more potent than vancomycin, teicoplanin and other agents
Dalbavancin, has better activity, in vitro and in animal infection models, than vancomycin and teicoplanin. This is facilitated by its long half life. In particular, dalbavancin has excellent activity against staphylococci, including coagulase-negatives . It has good activity against staphylococci and streptococci . Dalbavancin is bactericidal for staphylococci, and resistance to this semi-synthetic glycopeptide is not readily developed in vitro .
Studies show that dalbavancin is generally more potent than vancomycin or teicoplanin. In a study involving 375 antimicrobial-resistant Gram-positive pathogens collected worldwide during 2001-2003, dalbavancin was highly active against penicillin- and ceftriaxone-resistant Streptococcus pneumoniae strains (MIC(90), ≤ 0.016 mug/mL); dalbavancin was also very active against teicoplanin-nonsusceptible coagulase-negative staphylococci (CoNS; MIC range, 0.03-0.25 mug/mL), but dalbavancin MIC results were slightly elevated compared with wild type strains. Dalbavancin inhibited vanB enterococci (MIC range, 0.03-0.12 mug/mL) and was active against other resistant, non-vanA enterococcal species; however, vanA enterococcal strains were not as susceptible to dalbavancin (MIC(50), 16 mug/mL .
In comparison with other antibacterial agents (e.g., vancomycin, teicoplanin) against 1229 Gram-positive organisms collected from medical centres in Latin America, dalbavancin was the most potent compound tested against isolates of Staphylococcus aureus (MIC(50), 0.06 mg/L) and coagulase-negative staphylococci (MIC(50), 0.03 mg/L), independently of methicillin susceptibility. Dalbavancin inhibited all Streptococcus pneumoniae isolates at ≤ 0.06 mg/L. Dalbavancin also demonstrated excellent activity against β-hemolytic (MIC(50), </= 0.008 mg/L) and viridans group (MIC(50), 0.016 mg/L) streptococci. All vancomycin-susceptible Enterococcus spp. isolates were inhibited by dalbavancin at ≤ 0.25 mg/L, but some vancomycin-resistant Enterococcus spp. isolates were only inhibited by dalbavancin levels of ≥ 8 mg/L (4) dalbavancin exhibited excellent activity against isolates of Corynebacterium spp. and Listeria spp. .
In a study in which dalbavancin was tested against 146 staphylococci isolates, it was more potent than other drugs tested, with an MIC at which 50 percent of staphylococci were inhibited of 0.03 µg/ml and an MIC at which 90 percent of staphylococci were inhibited of 0.06 µg/ml by microdilution demonstrating it was bactericidal at four times the MIC against all six strains tested; for all strains, MICs of vancomycin, linezolid, ranbezolid, oritavancin, daptomycin, and quinupristin-dalfopristin were ≤ 4.0 µg/ml .
Streit tested dalbavancin and selected comparators against 6,339 clinical isolates in 2002 from the Americas and Europe using reference susceptibility testing methods . The general characteristics of this Gram-positive organism collection were as follows: oxacillin (OXA)-resistant Staphylococcus aureus (ORSA) at 39 percent of strains; vancomycin-resistant enterococci (VRE) at 10 percent ; and penicillin-nonsusceptible pneumococci at 28 percent . The overall distribution of dalbavancin minimum inhibitory concentration (MIC) values ranged from ≤ 0.015 to > 32 µg/ml, but > 99 percent of MIC results were at ≤ µg/ml. S. aureus and coagulase-negative staphylococci were extremely susceptible to dalbavancin (MIC90, 0.06 µg/ml) despite resistance patterns to other agents. Dalbavancin was the most potent compound (by weight) against vancomycin-susceptible Enterococcus faecalis and E. faecium (MIC90, 0.06 and 0.12 µg/ml, respectively); however, VRE strains showed decreased dalbavancin susceptibility (MIC50, 4 or 8 µg/ml). All streptococcal isolates were inhibited at ≤ .25 µg/ml of dalbavancin. This reported dalbavancin activity indicates that the new glycopeptide has significant activity, superior to available agents in the class, and a potency that was uniform across geographically sampled organisms. Some VRE were inhibited by very low dalbavancin concentrations (≤ 1 µg/ml; Van B phenotypes).
Goldstein compared dalbavancin in vitro activities and those of nine comparator agents, including daptomycin, vancomycin, linezolid, and quinupristin-dalfopristin, against 290 recent Gram-positive clinical isolates strains, as determined by the NCCLS agar dilution method. The MICs of dalbavancin at which 90 percent of various isolates tested were inhibited were as follows: Actinomyces spp., 0.5 µg/ml; Clostridium clostridioforme, 8 µg/ml; C. difficile, 0.25 µg/ml; C. innocuum, 0.25 µg/ml; C. perfringens, 0.12 5 µg/ml; C. ramosum, 1 µg/ml; Eubacterium spp., 1 µg/ml; Lactobacillus spp., > 32 µg/ml, Propionibacterium spp., 0.5 µg/ml; and Peptostreptococcus spp., 0.25. µg/ml. Dalbavancin was 1 to 3 dilutions more active than vancomycin against most strains .
Jones investigated the activity of dalbavancin against 7,771 isolates in europe and north america . In vitro, its activity is excellent against Staph aureus, in this slide showing an MIC-50 and 90 of .03 and .06, in strains isolated both in Europe and North America (Fig. 2). Similar MICs, identical MICs, against coagulase-negative staphylococci, comparing favorably to many of the comparative antibiotics here (Fig. 3). Against enterococci, if they are ampicillin susceptible, dalbavancin is an excellent choice; however, it is limited against vancomycin-resistant enterococci (Fig. 4).
Device related infections
Dalbavancin is a promising agent in the prevention and treatment of device-related infection . This has been shown in the Phase III trial results discussed above and has been found in other studies. Vancomycin displays a poor activity against organisms embedded within the biofilm surrounding implanted devices. In a study in which twelve rabbits were randomized (three groups of four each) to receive intravenous injections of dalbavancin, vancomycin or normal saline (control). Eight polyurethane catheter segments were subcutaneously implanted in the back of each rabbit, then inoculated with S. aureus. Rabbits were sacrificed a week later and explanted devices were cultured. The rates of device colonization were comparable in the vancomycin (53 %) and control (47 %) groups, whereas only 28 percent of devices in the dalbavancin group became colonized. There was a trend (although not statistically significant) toward a lower rate of device colonization following receipt of dalbavancin vs. vancomycin (p = 0.07) or saline (p = 0.02).
A phase 2, open-label, randomized, controlled, multicenter study of 75 adult patients with catheter-related bloodstream infections (CR-BSIs) compared treatment with intravenous dalbavancin, administered as a single 1000-mg dose followed by a 500-mg dose 1 week later, with intravenous vancomycin, administered twice daily for 14 days. Gram-positive bacteria isolated in this study included coagulase-negative staphylococci (CoNS) and Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA). Infected patients who received weekly dalbavancin (n = 33) had an overall success rate (87.0 percent ; 95 percent confidence interval [CI], 73.2-100.0 percent ) that was significantly higher than that of those who received vancomycin (n=34) (50.0 percent ; 95 percent CI, 31.5-68.5 percent ). Adverse events and laboratory abnormalities were generally mild and were comparable for the two drugs .
Fifty-two healthy adult male and female volunteers in this double-blind study of dalbavancin found that its adverse effects (AEs) were mild . There were no serious AEs or deaths reported in this study. No dose effects were seen for AEs or laboratory values. Sixty-seven percent of the subjects reported at least one treatment-emergent AE. Most AEs were mild in severity, and none met the criteria for dose-limiting toxicity. The most common AEs in both the single- and multiple-dose groups were pyrexia (50 %), headache (25 %), and nausea (6 %). Subjects receiving placebo also reported pyrexia (38 percent ) and headache (31 percent ). Pyrexia was defined, in accordance with World Health Organization toxicity grading criteria, as any oral temperature of > 37.1 ° C; no subject had a temperature exceeding 37.5 °C at any time during the study. There were no clinically significant changes from the baseline regarding laboratory findings, vital signs, physical examinations, or ECGs. Mild (less than five times the upper limit of normal), transient, asymptomatic elevations in alanine aminotransferase and aspartate aminotransferase were observed in one subject who received 350 mg of dalbavancin and in no subjects who received higher doses. One dalbavancin-treated subject experienced a transient hyperglycemia (blood glucose level of 160 mg/dl) that was considered mild, and one subject in the placebo group also experienced mild hyperglycemia (135 mg of glucose/dl). In a study, Campbell found no subjects demonstrated ototoxic change after receiving dalbavancin, nor were any false-positive results obtained .
The reported side effects of dalbavancin are very mild. However, as it is related to vancomycin and teicoplanin, it would not be surprising if its side effects as the medication is used widely will resemble those of the medications to which it is related.
Dalbavancin has advantages over existing antibiotics in the treatment of cSSSI . Dermatologists must be aware of its existence because it will likely become a mainstay of treatment for cSSSIs. Marketed and investigational antibiotics for SA and other serious Gram-positive hospital infections generally require single or multiple doses administered through intravenous (IV) lines daily over a treatment course. Once-a-week dosing with dalbavancin may obviate the need for the continued presence of IV lines in some patients, which could translate into fewer local infections and blood stream infections. This could also lead to pharmacoeconomic benefits, such as shorter hospital stays, decreased administration and monitoring costs, less need for follow. However, unlike other new antibiotics such as oritavancin and tigecycline it is not active against VRE. Time will tell whether it will replace the antibiotics (vancomycin and tecoplanin) from which it is derived and whether it will be preferred other newer agents.
Figures courtesy of Princeton Media Associates .
References1. http://www.shareholder.com/vicuron/downloads/ Vicuron2003AnnualReport.pdf
2. http://www.uspharmacist.com/index.asp? show=article&page=8_1094.htm
3. Appelbaum PC, Jacobs MR. Recently approved and investigational antibiotics for treatment of severe infections caused by Gram-positive bacteria. Curr Opin Microbiol. 2005 Aug 9;
4. Hoffman-Roberts HL, C Babcock E, Mitropoulos IF. Investigational new drugs for the treatment of resistant pneumococcal infections. Expert Opin Investig Drugs. 2005;14:973-95.
5. Shah PM. The need for new therapeutic agents: what is the pipeline? Clin Microbiol Infect. 2005;11 Suppl 3:36-42.
6. Padmanabhan RA, Larosa SP, Tomecki KJ. What's new in antibiotics? Dermatol Clin. 2005;23:301-12.
7. Bradley JS. Newer antistaphylococcal agents. Curr Opin Pediatr. 2005;17:71-7.
8. Anstead GM, Owens AD. Recent advances in the treatment of infections due to resistant Staphylococcus aureus. Curr Opin Infect Dis. 2004;17:549-55.
9. Torres-Viera C, Dembry LM. Approaches to vancomycin-resistant enterococci. Curr Opin Infect Dis. 2004;17:541-7.
10. Bozdogan B, Ednie L, Credito K, Kosowska K, Appelbaum PC. Derivatives of a vancomycin-resistant Staphylococcus aureus strain isolated at Hershey Medical Center. Antimicrob Agents Chemother. 2004;48:4762-5.
11. Van Bambeke F. Glycopeptides in clinical development: pharmacological profile and clinical perspectives. Curr Opin Pharmacol. 2004;4:471-8.
12. Raghavan M, Linden PK. Newer treatment options for skin and soft tissue infections. Drugs. 2004;64:1621-42.
13. Anderegg TR, Biedenbach DJ, Jones RN; Quality Control Working Group. Initial quality control evaluations for susceptibility testing of Dalbavancin (BI397), an investigational glycopeptide with potent gram-positive activity. J Clin Microbiol. 2003;41:2795-6.
16. http://www.forbes.com/home_europe/sciencesandmedicine/ 2005/10/03/pfizer-drug-fda-cx_mh_1004pfizer.html
17. Steiert M, Schmitz FJ. Dalbavancin (Biosearch Italia/Versicor). Curr Opin Investig Drugs. 2002;3:229-33.
18. Van Bambeke F, Van Laethem Y, Courvalin P, Tulkens PM. Glycopeptide antibiotics: from conventional molecules to new derivatives. Drugs. 2004;64:913-36.
19. Guay DR. Dalbavancin: an investigational glycopeptide. Expert Rev Anti Infect Ther. 2004;2:845-52.
20. Dorr MB, Jabes D, Cavaleri M, Dowell J, Mosconi G, Malabarba A, White RJ, Henkel TJ. Human pharmacokinetics and rationale for once-weekly dosing of dalbavancin, a semi-synthetic glycopeptide. J Antimicrob Chemother. 2005;55 Suppl 2:ii25-30.
21. Jabes D, Candiani G, Romano G, Brunati C, Riva S, Cavaleri M. Efficacy of dalbavancin against methicillin-resistant Staphylococcus aureus in the rat granuloma pouch infection model. Antimicrob Agents Chemother. 2004;48:1118-23.
22. Seltzer E, Dorr MB, Goldstein BP, Perry M, Dowell JA, Henkel T; Dalbavancin Skin and Soft-Tissue Infection Study Group. Once-weekly dalbavancin versus standard-of-care antimicrobial regimens for treatment of skin and soft-tissue infections. Clin Infect Dis. 2003;37:1298-303.
23. Lefort A, Pavie J, Garry L, Chau F, Fantin B. Activities of dalbavancin in vitro and in a rabbit model of experimental endocarditis due to Staphylococcus aureus with or without reduced susceptibility to vancomycin and teicoplanin. Antimicrob Agents Chemother. 2004;48:1061-4.
24. Cavaleri M, Riva S, Valagussa A, Guanci M, Colombo L, Dowell J, Stogniew M. Pharmacokinetics and excretion of dalbavancin in the rat. J Antimicrob Chemother. 2005;55 Suppl 2:ii31-5.
26. Malabarba A, Goldstein BP. Origin, structure, and activity in vitro and in vivo of dalbavancin. J Antimicrob Chemother. 2005;55 Suppl 2:ii15-20.
27. Mushtaq S, Warner M, Johnson AP, Livermore DM. Activity of dalbavancin against staphylococci and streptococci, assessed by BSAC and NCCLS agar dilution methods. J Antimicrob Chemother. 2004;54:617-20.
28. Lopez S, Hackbarth C, Romano G, Trias J, Jabes D, Goldstein BP. In vitro antistaphylococcal activity of dalbavancin, a novel glycopeptide. J Antimicrob Chemother. 2005;55 Suppl 2:ii21-4.
29. Streit JM, Sader HS, Fritsche TR, Jones RN. Dalbavancin activity against selected populations of antimicrobial-resistant Gram-positive pathogens. Diagn Microbiol Infect Dis. 2005 May 25;
30. Gales AC, Sader HS, Jones RN. Antimicrobial activity of dalbavancin tested against Gram-positive clinical isolates from Latin American medical centres. Clin Microbiol Infect. 2005;11:95-100.
31. Lin G, Credito K, Ednie LM, Appelbaum PC. Antistaphylococcal activity of dalbavancin, an experimental glycopeptide. Antimicrob Agents Chemother. 2005;49:770-2.
32. Streit JM, Fritsche TR, Sader HS, Jones RN. Worldwide assessment of dalbavancin activity and spectrum against over 6,000 clinical isolates. Diagn Microbiol Infect Dis. 2004;48:137-43.
33. Goldstein EJ, Citron DM, Merriam CV, Warren Y, Tyrrell K, Fernandez HT. In vitro activities of dalbavancin and nine comparator agents against anaerobic gram-positive species and corynebacteria. Antimicrob Agents Chemother. 2003;47:1968-71.
35. Darouiche RO, Mansouri MD. Dalbavancin compared with vancomycin for prevention of Staphylococcus aureus colonization of devices in vivo. J Infect. 2005;50:206-9.
36. Raad I, Darouiche R, Vazquez J, Lentnek A, Hachem R, Hanna H, Goldstein B, Henkel T, Seltzer E. Efficacy and safety of weekly dalbavancin therapy for catheter-related bloodstream infection caused by gram-positive pathogens. Clin Infect Dis. 2005;40:374-80.
37. Leighton A, Gottlieb AB, Dorr MB, Jabes D, Mosconi G, VanSaders C, Mroszczak EJ, Campbell KC, Kelly E. Tolerability, pharmacokinetics, and serum bactericidal activity of intravenous dalbavancin in healthy volunteers. Antimicrob Agents Chemother. 2004;48:940-5.
38. Campbell KC, Kelly E, Targovnik N, Hughes L, Van Saders C, Gottlieb AB, Dorr MB, Leighton A. Audiologic monitoring for potential ototoxicity in a phase I clinical trial of a new glycopeptide antibiotic. J Am Acad Audiol. 2003;14:157-68; quiz 170-1.
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