Randomized study of vancomycin versus teicoplanin for the treatment of gram-positive bacterial infections in immunocompromised hosts

Abstract

Seventy-four immunocompromised patients with severe infection due to gram-positive organisms were randomized to receive either vancomycin or teicoplanin. Extensive cancer was present in 71 patients, of whom 47 died within a month. The types of infections were 46 bacteremias (39 associated with central catheters), 24 skin and soft tissue infections (3 with bacteremia), and 7 others (mainly bronchopneumonia). Gram-positive bacteria have recently become the leading pathogens in cancer patients whether granulocytopenic or not. Several factors may contribute to this situation in granulocytopenic patients (25). More aggressive anticancer treatments have been associated with an increased incidence and severity of mucositis; in addition, the recurrence of oral herpes simplex has increased and represents a risk factor for bacteremia due to oral streptococci (15). The widespread use of gut decontamination with antimicrobial agents which are preferentially active against gram-negative bacilli has been associated with a decrease in rapidly fatal gram-negative bacillus infections. In addition, the frequently used longterm intravascular accesses, including implantable catheters (Port-a-Cath, Hickman, Broviac), are major sources of infection caused by gram-positive cocci. Moreover, grampositive bacteria usually proliferate from endogenous sources and various potential sites have been recognized, such as the skin (and possibly the gut) for coagulase-negative staphylococci, the oral mucosa for viridans group streptococci, and the gut for enterococci and some Streptococcus anginosus strains. The widespread incidence of oxacillinresistant coagulase-negative staphylococci renders the empirical use of oxacillin obsolete for nosocomial infections; vancomycin seems to be as effective as oxacillin against oxacillin-susceptible Staphylococcus aureus (3). Therefore, in most situations vancomycin is now considered the drug of choice for the treatment of proven or suspected grampositive bacteremia. However, vancomycin is potentially nephrotoxic and drug monitoring of concentrations in serum is recommended. Vancomycin is rather poorly tolerated and needs to be administered by the intravenous (i.v.) route; tissue irritation does not allow intramuscular use. Teicoplanin is a glycopeptide closely related to vancomycin, with a similar spectrum of activity (24), which seems less toxic at * Corresponding author. daily doses of .800 mg (6 to 12 mg/kg of body weight) (1, 5,18,21,26). The optimal dosage of teicoplanin has been controversial for several years. During the first clinical studies with 200-mg daily doses (3 mg/kg) (1, 2, 5), failures (including persisting or breakthrough bacteremia) were attributed to suboptimal dosing and unpredictable concentrations in serum (2, 5). Our preliminary open study (5) showed encouraging data with teicoplanin; therefore, the purpose of the present study was to compare the clinical results of a prospective randomized comparative study of vancomycin versus teicoplanin for documented gram-positive bacterial inf...

Tests for bactericidal effects of antimicrobial agents: technical performance and clinical relevance

“…A current review by Korvick and Yu highlights the problem of interpreting in vitro susceptibility test results for this pathogen (60). Similar results were reported by Van der Auwera et al for immunocompromised patients infected with gram-positive bacteria and treated with vancomycin or teicoplanin (113). On the other hand, recognition of bacterial isolates resistant to antimicrobial agents is critical and a prime concern of the clinical laboratory.…”

Comparative Efficacy and Safety of Vancomycin versus Teicoplanin: Systematic Review and Meta-Analysis

“…1. The search yielded 269 publications, 61 of which were potentially eligible; and 24 individual randomized controlled trials comparing vancomycin versus teicoplanin fulfilled inclusion criteria (1,4,8,10,11,14,18,20,22,33,34,40,42,45,46,48,49,51,60,62,(71)(72)77).…”

“…Four trials were performed prior to Eli Lilly's launch of purified vancomycin in 1990 (8,11,62,72), and in one study the purified preparation was introduced during the trial (71). The standard dosing of teicoplanin for adults was 400 mg/day for adults and 10 to 12 mg/kg of body weight/day for children, following a loading dose (Table 1); lower doses (200 mg/day) were used for adults during the first part of the study in three trials (45,62,71).…”

Teicoplanin alone or combined with rifampin compared with vancomycin for prophylaxis and treatment of experimental foreign body infection by methicillin-resistant Staphylococcus aureus

“…Subsequent results from a number of additional open or comparative trials performed over the past decade (4,17,20,23,31,33,36,(46)(47)(48)50) combined with more accurate pharmacokinetic and protein binding estimates (2,10,29,43) have led to recommendations (15, 23) of higher daily doses of teicoplanin, ranging from 6 (15) to 12 (53) or 15 (23) mg/kg/ day. With the 15-mg/kg teicoplanin regimen, very high levels of drug in serum (>30 pug/ml), equivalent to 30 times the MICs of teicoplanin for susceptible isolates of S. aureus, were continuously present in patients (23) and could overcome protein binding by serum components.…”

“…Taken together, these different studies have led to discrepant results and controversial interpretations concerning teicoplanin safety and efficacy (see reviews in references 8, 15, and 16). The divergent results of these clinical studies may be explained by significant differences in their design, for example, the choice of open (4,22,23,31,33,36,47) versus comparative (7,17,20,46,48,50) trials, and by the wide range of dosage regimens, treatment durations, and antibiotic combinations used by the different investigators.…”