Comparative Efficacy of Amoxicillin-Clavulanate, Cloxacillin, and Vancomycin Against Methicillin-Sensitive and Methicillin-Resistant Staphylococcus aureus Endocarditis in Rats

372

203

The clinical courses of 13 consecutive intravenous drug users with Staphylococcus aureus endocarditis treated principally with vancomycin were reviewed. Two patients, one with only right-sided endocarditis and the other with tricuspid and mitral valve endocarditis, had recurrences of positive blood cultures 2 days after completing a 4-week course of vancomycin. Two patients, both of whom eventually were cured, had modifications of therapy because of bacteremia persisting 7 and 16 days into therapy. One patient required an operation for recurrent fevers, and the resected vegetation showed evidence of active infection. Time-kill studies performed with nafcillin and vancomycin for 10 isolates of S. aureus showed that vancomycin was less rapidly bactericidal than nafcillin. Although vancomycin is used as an alternative to penicillinase-resistant penicillins for treatment of staphylococcal endocarditis, these findings raise the question of whether it is equivalent to these drugs in efficacy.Staphylococcus aureus endocarditis in parenteral drug users is well characterized; complications and relapses are unusual. Overall cure rates of 95% are expected (3,6,17). This excellent cure rate partly is due to the fact that in three-quarters of cases the tricuspid valve, rather than aortic or mitral valves, is the site of infection. Bacteremia is rapidly cleared, lasting a mean of 3.4 days when nafcillin alone is used (17).Vancomycin is often considered equal in efficacy to penicillinase-resistant beta-lactam antibiotics. However, a review of our experience in treating S. aureus endocarditis in intravenous drug users with vancomycin revealed unsatisfactory or unexpectedly complicated clinical courses in 5 of 13 cases (38%). These cases are summarized and the current literature pertaining to the efficacy of vancomycin for S. aureus endocarditis is reviewed below. MATERIALS AND METHODSPatients. The names of all patients admitted to San Francisco General Hospital with blood cultures growing S. aureus were collected prospectively from records of the clinical microbiology laboratory. Intravenous drug users with community-acquired S. aureus bacteremia treated primarily with vancomycin were identified for July 1983 through July 1987.The medical records of these cases were reviewed to identify patients with endocarditis. Patients were considered to have endocarditis if they had (i) a temperature greater than 38.5°C, (ii) cardiac murmurs, (iii) at least two blood cultures growing only S. aureus without any obvious extracardiac source of bacteremia, and (iv) one or more of the following: physical findings of peripheral emboli, chest X rays consistent with septic pulmonary infiltrates, and valvular vegetations on echocardiograms. For cases in which auscultatory or echocardiographic findings did not identify the infected valves, the presence of pulmonary involvement or peripheral emboli was used to define right-or left-sided involvement, respectively.Drug users with S. aureus endocarditis whose primary * Corresponding author.antibiotic wa...

Section: Discussionmentioning

confidence: 90%

Vancomycin for Staphylococcus aureus endocarditis in intravenous drug users

Small

Chambers

1990

372

203

“…Multiple studies have demonstrated that the in vitro activities of j-lactam-p-lactamase inhibitor combinations against MRSA are within the range of the clinically achievable concentrations in serum (2,7,11,13,14,19,34). Also, the majority (7,14,34,40), but not all (10), of the animal model studies suggest that such combinations are effective in vivo.…”

Section: Discussionmentioning

confidence: 99%

“…Also, the majority (7,14,34,40), but not all (10), of the animal model studies suggest that such combinations are effective in vivo. Chambers et al (10) have suggested that the seemingly contradictory results among animal studies may be related to the number of bacteria present at the time that therapy is instituted.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of prophylaxis with beta-lactams and beta-lactam-beta-lactamase inhibitor combinations against wound infection by methicillin-resistant and borderline-susceptible Staphylococcus aureus in a guinea pig model

Kernodle

Kaiser

1993

Although some j-lactams and K1-lactam-13-lactamase inhibitor combinations exhibit activity against methicillin-resistant Staphylococcus aureus, there remains the concern that therapeutic failures may result from the selection of resistant subpopulations. The prophylactic use of these antibiotics in clean surgery, however, may prove adequate since wound infections arise from the inoculation of small numbers of bacteria. In (4,28,41).The detection of resistance in MRSA and ,B-lactamaseproducing S. aureus, including BSSA, is inoculum size dependent (6,8,15,22,35,36). Although small numbers of bacteria may appear to be susceptible to ,B-lactam antibiotics in vitro, the testing of large inocula facilitates the recognition of resistance. The clinical implications of this observation are that the use of any ,-lactam cannot be recommended as therapy against infection by MRSA, and vancomycin is the preferred treatment (1,15,39). Similarly, although 1-lactamase-susceptible antibiotics such as penicillin G exhibit marked in vitro activity against small numbers of P-lactamase-producing S. aureus (36), penicillin G is ineffective in * Corresponding author. treating infections caused by these strains (3, 6). The penicillinase-resistant antistaphylococcal penicillins are the therapy of choice for serious infections caused by such strains (39).Since wound infections that complicate clean surgical procedures are believed to originate with the inoculation of small numbers of bacteria into the surgical field (12,16,17), the prophylactic use of ,-lactams, including relatively ,-lactamase-labile antibiotics, may prove to be effective in preventing these infections. In this clinical setting, heterogeneity in the phenotypic expression of 1-lactam resistance among MRSA may permit in vivo antibiotic efficacy. Similarly, the amount of preformed and induced P-lactamase accompanying 3-lactamase-producing S. aureus within the wound site may be insufficient to protect the strain against antibiotics in the serum and tissues. To test this hypothesis, we determined the prophylactic efficacies of ampicillin and cefazolin, alone and in combination with ,-lactamase inhibitors, against two MRSA strains and one BSSA strain using a low-inoculum guinea pig model of wound infection. MATERIALS AND METHODS

“…Tazobactam and sulbactam are closely related, and sulbactam has been shown to exert synergy with 3-lactam antibiotic independently of any ,3-lactamase inhibition (,3-lactamase-negative strains). With the exception of methicillin-resistant S. aureus (4,15), similar findings with clavulanate have not been reported.…”

Section: * Corresponding Authormentioning

confidence: 70%

Ex vivo pharmacodynamic study of piperacillin alone and in combination with tazobactam, compared with ticarcillin plus clavulanic acid

Auwera

Duchateau

Lambert

et al. 1993

Ten volunteers received piperacillin (4 g), piperacillin (4 g) plus tazobactam (0.5 g) (Tazocin), and ticarcillin (3 g) plus clavulanic acid (0.2 g) (Timentin) intravenously over 30 min in a cross-over blinded scheme. Blood samples were obtained 0.5 and 3 h after the end of infusion to measure by (high-pressure liquid chromatography) the concentration and bactericidal titers against 70 gram-negative bacilli. Serum time-kill curves were done against 35 strains to measure killing rates and area under the time-kill curve. Using the measure of serum bactericidal activity, ticarcillin-clavulanic acid and piperacillin-tazobactam were equally effective against Pseudomonas aeruginosa, Escherichia coli, Enterobacter cloacae, Serratia marcescens, and Bacteroidesfragilis. Piperacillin-tazobactam was superior to ticarcillin-clavulanic acid against piperacillin-resistant Kiebsiella pneumoniae (4 to 16 times) and S. marcescens (2 to 4 times). By using the area under the time-kill curve, piperacillin-tazobactam was equivalent to ticarcillin-clavulanic acid against piperacillin-susceptible strains; piperacillin-tazobactam was significantly more active than piperacillin against piperacillin-resistant strains and was more active than ticarcillin-clavulanic acid when the sample obtained 3 h after the end of infusion to volunteers was considered. Serum piperacillin concentrations (mean standard error of the mean; in mg/liter) were 115 + 13 at 0.5 h and 7.4 + 1.4 at 3 h after the administration of piperacillin alone and 105.5 12.6 (0.5 h) and 7.7 + 1.6 after the administration of piperacillin-tazobactam. Serum tazobactam concentrations (in milligrams per liter) were 13.1 1.4 at 0.5 h and 1.2 + 0.2 at 3 h. The piperacillin-tazobactam ratio was 8 0.3 at 0.5 h and 6.2 0.5 at 3 h. Piperacillin-tazobactam appears promising against ,3-lactamase-producing gram-negative bacilli.Infections by gram-negative organisms are still a major cause of morbidity in patients with cancer, especially when they are neutropenic (19). Treatment of these infections often consists of the administration of a broad-spectrum ,-lactam antibiotic in combination with an aminoglycoside, although the use of monotherapy with a broad-spectrum cephalosporin or imipenem has been advocated. The increasing incidence of gram-negative bacilli with broad-spectrum ,3-lactamases has caused the empiric use of monotherapy to be questioned. One way to overcome this problem is use of the combination of a broad-spectrum penicillin with an effective ,-lactamase inhibitor. Piperacillin is a broadspectrum penicillin which has a high level of in vitro activity against members of the family Enterobacteriaceae and Pseudomonas aeruginosa. Tazobactam is an effective inhibitor of various types of 3-lactamases, especially the penicillinase type of Staphylococcus aureus, the TEM types, and the cephalosporinase of Bacteroides fragilis (2,3,(8)(9)(10)14). In particular, tazobactam is a better inhibitor of the chromosomal cephalosporinases of members of the family Enterobactenaceae (Enterobacter,...