Treatment of infections by staphylococci and other Gram-positive bacteria with teicoplanin: an open study

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...

Section: Discussioncontrasting

confidence: 45%

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

Auwera

Aoun

Meunier

1991

“…This study confirms that teicoplanin in combination with another antibiotic, usually an aminoglycoside, is effective for (9,12). This cure rate was not different from the reported 15 to 25% mortality rate for bacterial endocarditis (21).…”

Section: Discussionsupporting

confidence: 81%

Evaluation of teicoplanin for treatment of endocarditis caused by gram-positive cocci in 20 patients

Leport

Perronne

Massip

et al. 1989

(85%), and a favorable clinical outcome had occurred in 14 of 17 evaluable patients (82%). Of these 14 patients, one relapsed 4 months after the end of treatment. Thus, teicoplanin was effective in 13 of 17 patients (76%). Mean peak levels of teicoplanin in serum were lower, 23.1 ± 2.9 ,g/ml, in patients who failed than in those who were cured (45.8 8.4 ,ug/ml). Side effects occurred in 7 of 20 patients (35%), and required premature discontinuation of teicoplanin in 3 patients. These side effects were fever in three patients, rash in three patients, hearing loss in two patients, and increased serum transaminase levels in two patients. This study demonstrates the efficacy of teicoplanin in the treatment of endocarditis and the need for achieving peak levels in serum close to 40 ,ug/ml. Teicoplanin should now be further evaluated in endocarditis caused by gram-positive cocci by means of a controlled comparative study with standard therapy.

“…All (1). In the present study, on the basis of SBA level monitoring, teicoplanin was administered at daily dosages at least twice as high as those previously used (1,8,11,14,25). In the present series, five patients with staphylococcal endocarditis were treated with teicoplanin alone, three had right-side endocarditis, and two were treated with teicoplanin plus surgery.…”

Section: Methodsmentioning

confidence: 90%

“…However, it has a longer elimination half-life, which allows once-a-day administration, and appears to be well tolerated (8,14,23). Although studies with animal models suggested good results with teicoplanin, alone or in combination with other antibiotics, for the treatment of infective endocarditis and other life-threatening infections (3,5,20), the results of recent clinical trials are somewhat conflicting (1,8,11,14,25). Moreover, only a few gram-positive-bacterial endocarditis cases were included in the above studies.…”

mentioning

confidence: 99%

Teicoplanin in the treatment of gram-positive-bacterial endocarditis

Martino

Venditti

Micozzi

et al. 1989

Intravenous teicoplanin has been used to treat 23 cases of gram-positive-bacterial endocarditis, usually with 3 to 7 mg/kg every 12 h on the first day, followed by 3 to 7 mg/kg every 24 h. For some cases (staphylococcal and enterococcal endocarditis), the dosage was 8 to 14.4 mg/kg per day and/or other antibiotics were given. The mean duration was 48.2 days (range, 23 to 130 days). Of 23 patients, 21 (91.3%) had negative cultures or were cured. A total of 18 patients were treated with teicoplanin alone; of these, 4 had surgery, and all (except 2 who relapsed) were cured. Teicoplanin was combined with one or more antibiotics in five cases; in all cases appropriate cultures were negative, but three patients died during therapy or follow-up. Mild renal impairment was seen in two patients; both were receiving teicoplanin in combination with an aminoglycoside. We conclude that intravenous teicoplanin administered once a day at doses of 7 to 14 mg/kg per day is well tolerated, easy to administer, and may represent an efficacious therapy for gram-positive-bacterial endocarditis.Gram-positive microorganisms still are the most frequent cause of infective endocarditis (6, 24). Moreover, new species which are resistant to several antibiotics (i.e., JK corynebacteria) are emerging (10,16,19). Teicoplanin is a glycopeptide antibiotic with an antibacterial spectrum similar to that of vancomycin which is active against multipleantibiotic-resistant, gram-positive bacteria (4, 9, 13, 22). However, it has a longer elimination half-life, which allows once-a-day administration, and appears to be well tolerated (8,14,23). Although studies with animal models suggested good results with teicoplanin, alone or in combination with other antibiotics, for the treatment of infective endocarditis and other life-threatening infections (3,5,20), the results of recent clinical trials are somewhat conflicting (1,8,11,14,25). Moreover, only a few gram-positive-bacterial endocarditis cases were included in the above studies. The majority of these cases were caused by Staphylococcus species and were treated with a standard dose of 400 mg on the first day followed by 200 mg/day afterwards. Such a schedule of teicoplanin administration proved to be inadequate for the therapy of severe staphylococcal infections in a recent clinical trial (1). We report here our 3 years of experience with 23 cases of gram-positive-bacterial endocarditis, most of which were treated with doses of teicoplanin higher than those previously used. MATERIALS AND METHODSPatients. All subjects were inpatients in various divisions of the Policlinico Umberto I, University of Rome. They were initially considered eligible for the study if they had clinical syndromes consistent with gram-positive-bacterial endocarditis. Only those cases fitting recently recommended strict case definitions were included in the analysis of the results (15, 24). For almost all patients two-dimensional echocardiography was performed, and specific attention was paid not only to the valvular structures but...