Oct 15, 1991 - 1]) was cured after a 6-week treatment with teicoplanin, which was combined with netilmicin during the last 5 weeks of therapy. A third protocol ...
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Apr. 1992, p. 723-726 0066-4804/92/040723-04$02.00/0 Copyright C) 1992, American Society for Microbiology
Vol. 36, No. 4
4-Week Treatment of Streptococcal Native Valve Endocarditis with High-Dose Teicoplanin MARIO VENDIThl,1'2 VINCENZO GELFUSA,"12 PIETRO SERRA,' CAMILLO BRANDIMARTE,' ALESSANDRA MICOZZI,3 AND PIETRO MARTINO3* Patologia Medica IIP and Servizio di Consulenze Infettivologiche,2 Istituto di Clinica Medica VI, and Ematologia, Dipartimento di Biopatologia Umana,3 Universita "La Sapienza " di Roma, 00161 Rome, Italy Received 15 October 1991/Accepted 30 January 1992
The efficacy and safety of a 4-week course of intravenous teicoplanin (500 mg every 12 h for the first 2 days and 10 mg/kg of body weight every 24 h thereafter) in the treatment of streptococcal native valve endocarditis in 20 patients were evaluated. All blood isolates were inhibited by a concentration of 0.12 ,ug of teicoplanin per ml. Serum bactericidal activity levels were measured 1/2 and 24 h after antibiotic infusion on days 5 to 7 of therapy in 19 patients, and titers of .1:32 and .1:8, respectively, were obtained with 17 patients (89%). On the other hand, for two patients who were infected with teicoplanin-tolerant Streptococcus bovis, serum bactericidal activity levels of < 1:2 were found. Of 20 patients, 4 were excluded from further analysis because of protocol violation or prosthetic valve infection. Of the remaining 16 patients, 6 did not complete teicoplanin therapy because of early death (1 patient) or drug fever (5 patients). Among patients who developed drug fever, three who discontinued teicoplanin by day 15 were switched to penicillin therapy, whereas the remaining two, who discontinued teicoplanin on day 22 and 25, respectively, did not receive any further therapy and have shown no relapse during the follow-up. Of 10 patients who completed trial therapy, 9 were cured and 1 relapsed. It is concluded that a 4-week course of high-dose teicoplanin may be a useful regimen for home treatment of selected cases of streptococcal native valve endocarditis. However, drug fever and infection with teicoplanin-tolerant S. bovis may be factors of concern with this therapeutic approach.
Viridans group Streptococcus species still represent a major cause of native valve endocarditis (9, 13). On the other hand, Streptococcus bovis, a group D species, is an emerging etiological agent, in particular in elderly patients with colonic neoplasms (9). These organisms are still highly susceptible to penicillin, which remains the first-choice antibiotic for streptococcal endocarditis (9). However, penicillin therapy requires frequent daily administrations or continuous infusion, which may discomfort patients or limit the feasibility of domiciliary treatment of selected cases (7). Teicoplanin is a glycopeptide antibiotic with a potent antistreptococcal activity and a prolonged serum half-life, which allows single-daily-dose treatment (11, 12). Preliminary studies, which used dosages of 3 to 6 mg/kg of body weight per day for 6 weeks and combined aminoglycoside therapy, showed encouraging results (3, 4). The aim of the present study was to evaluate the efficacy and safety of high once-a-day doses of intravenous teicoplanin for 4 weeks in the treatment of streptococcal native valve endocarditis to allow home antibiotic therapy of uncomplicated cases (10).
starting protocol therapy. As shown in Table 1, there were three definite, eight probable, and nine possible endocarditis cases at a final assessment, and vegetative lesions could be detected by two-dimensional echocardiography in 18 patients. No vegetations were demonstrated in two patients (cases 3 and 11) who had a possible endocarditis defined by the presence of both persistent Streptococcus bacteremia and an underlying predisposing heart disease. Microbiology studies. Aerobic and anaerobic blood cultures were obtained daily from each patient before and after (until day 4) initiation of therapy. Streptococcal isolates were identified to species level with API 20 Strept (Bio Merieux, Lyon, France). MICs of teicoplanin (Lepetit, Gerenzano, Italy), penicillin (E.R. Squibb & Sons, Princeton, N.J.), and gentamicin (Schering Corp., Bloomfield, N.J.) were determined by a macrodilution method in cationsupplemented Mueller-Hinton broth with 5% horse blood lysed with saponin (5). A sample (0.5 ml) of organisms from an overnight broth culture was added to each series of tubes containing equal volumes of twofold dilutions of antibiotics to yield a final inoculum of approximately 5 x 105 organisms per ml. For each test, the inoculum size was measured by counting CFU. Tests for which the inoculum size was later found to be less than 5 x 105 CFU/ml were repeated. The MIC was defined as the lowest concentration of antibiotic that completely inhibited growth after 24 h of incubation at 35°C. The MBCs were determined by subculturing 0.01 ml of a broth culture to antibiotic-free sheep blood tryptic soy agar plates. The MBC was defined as the lowest concentration of antibiotic that exhibited 99.9% killing of the original inoculum after 48 h of incubation. The 95% confidence limit of the 99.9% killing endpoint was calculated as suggested by Pearson et al. (6). After 5 to 7 days of therapy, serum bactericidal activity (SBA) titers were measured at 1/2 and 24 h after intravenous infusion of teicoplanin by a standardized macro-
MATERLALS AND METHODS Patients. Inpatients observed in various divisions of the university hospital Policlinico Umberto I who met strict case definition criteria for the diagnosis of endocarditis (13) were enrolled in the study. On the basis of this protocol, 20 patients were initially included in the study and received at least 1 week of teicoplanin therapy according to the schedule described below. At the time of enrollment, 8 patients had probable endocarditis and 12 had possible endocarditis. All patients had had blood cultures that were persistently positive for Streptococcus species for at least 3 days before *
Corresponding author. 723
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VENDIM ET AL.
ANTIMICROB. AGENTs CHEMOTHER.
TABLE 1. Teicoplanin therapy of viridans group Streptococcus and S. bovis endocarditis: relationship among in vitro susceptibility of the pathogen, SBA levels, and clinical outcome Case no. and Streptococcus species
Endocarditis definition
MIC (p.g/ml) of: Site(s) of a tvegetations Teicoplanin Penicillin Gentamicin
S. sanguis I S. mutans S. salivanius S. sanguis I 5. S. sanguis I 6. S. sanguis I 7. S. sanguis II 8. S. morbillorum 9. S. mutans 10. S. bovis 11. S. mutans 12. S. agalactiae 13. S. mitis
Possible Possible Possible Probable Possible Possible Probable Possible Probable Probable Possible Definite Definite
M VSD
c0.03 0.06 .0.03
A M M, A M, A M M A
.0.03
.0.03 .0.03
