Failure of treatment with teicoplanin at 6 milligrams/kilogram/day in patients with Staphylococcus aureus intravascular infection. The Infectious Diseases Consortium of Oregon

Abstract

Patients with blood cultures positive for gram-positive cocci were enrolled in a prospective randomized double-blind comparative trial of vancomycin at 15 mg/kg every 12 h versus teicoplanin at 6 mg/kg every 12 h for three doses and then 6 mg/kg every 24 h. A total of 54 patients were randomized, and 40 were evaluable. Of the 40, 9 had infection of indwelling vascular catheters. Four infections were due to Staphylococcus aureus, and five were due to Staphylococcus epidermidis. In concert with catheter removal, all patients were treated successfully, regardless of which drug they were taking. Of 31 patients without an indwelling catheter, 19 were infected with S. aureus, and 12 of the 19 had either endocarditis or mycotic aneurysm. Six of eight patients given teicoplanin failed treatment, as opposed to one of four patients given vancomycin (P = 0.14). Of greater concern, four of four patients with left-sided endocarditis or mycotic aneurysm failed to recover when given teicoplanin, as opposed to one of three patients given vancomycin (P = 0.07). Although not quite statistically significant, the unexpectedly high number of treatment failures with teicoplanin resulted in a decision to discontinue patient enrollment. It is suggested that future trials explore the efficacy of larger doses of teicoplanin.Teicoplanin is a new glycopeptide antibiotic chemically related to the vancomycin-ristocetin group of antibiotics (10, 25). The teicoplanin MIC for 90% of strains of methicillinsusceptible Staphylococcus aureus is 0.4 pug/ml (19), and the serum half-life ranges from 40 to 100 h (10, 25). The long serum half-life and the low MIC for 90% of strains suggest that teicoplanin would be effective in a once-daily dosage regimen against serious infections due to methicillin-susceptible S. aureus.The average peak concentration in serum after a 3-mg/kg (of body weight) dose of teicoplanin is 7 ,ug/ml, with a trough concentration some 23 h later of 2 ,ug/ml (23). On the basis of these levels and the in vitro MICs for 90% of strains, the initial clinical trials were conducted with a teicoplanin loading dose of 6 mg/kg and then a once-daily dose of 3 mg/kg. This regimen proved inadequate for severe S. aureus infections (3, 12

Meta-analysis of Randomized Controlled Trials of Vancomycin for the Treatment of Patients With Gram-Positive Infections: Focus on the Study Design

“…a These numbers correspond to 2 different randomized controlled trials that were published as one in Clinical Infectious Diseases. 50 45 2005 Corey et al, 39 2010 D'Antonio et al, 55 2004 Florescu et al, 44 2008 Gilbert et al, 72 1991 Jaksic et al, 32 2006 Kureishi et al, 69 1991 Lin et al, 27 2008 Noel et al, 43 2008 Noel et al, 42 2008 Rolston et al, 66 1994 Rolston et al, 58 1999 Rubinstein et al, 38 2001 Rubinstein et al, 50 2011 (0015) …”

Bactericidal activities of teicoplanin, vancomycin, and gentamicin alone and in combination against Staphylococcus aureus in an in vitro pharmacodynamic model of endocarditis

“…38,1994 on April 27, 2019 by guest http://aac.asm.org/ Downloaded from vegetation, decreased antibiotic activity under anaerobic and acidic conditions, impaired host defenses at the site of infection, the high degree of virulence of some infecting pathogens, and the development of resistance (4,14,28). These problems have been highlighted with the recent failure of teicoplanin for the treatment of endocarditis caused by susceptible strains of S. aureus (10,22).…”

“…Furthermore, autoradiographic studies have evaluated the diffusion of antibiotics into rabbit endocardial vegetations (15,16 (10,22).…”

“…Infective endocarditis continues to be a difficult therapeutic problem because of the poor penetration of antibiotics, large inoculum size, the development of resistance, and the lack of host defense at the infection site (4,10,14,22,28,33). In the case of endocarditis caused by Staphylococcus aureus, the treatment choices remain extremely limited.…”

Pharmacokinetic and pharmacodynamic requirements for antibiotic therapy of experimental endocarditis

“…Although most organisms are highly susceptible to many antibiotics, therapy must be maintained for weeks in order to eradicate the infection. Moreover, recent clinical observations with teicoplanin have reemphasized that treatment failure can occur, even with very susceptible organisms, after conventional durations of therapy (35). The difficulty encountered in sterilizing vegetations is usually explained by (i) the poor penetration of antibiotics into infected vegetations, (ii) the altered metabolic state of the organisms within the vegetation, and (iii) the absence of a host defense cellular response inside the vegetation which could cooperate with the antibiotic action.…”