Successful treatment of meningitis due to multiply resistant Enterococcus faecium with a combination of intrathecal teicoplanin and intravenous antimicrobial agents.

Following neurosurgery necessitated by intractable seizures, Enterococcus faecium meningitis that was resistant to ampicillin, a high-level aminoglycoside (MIC, > 2,000 micrograms/mL), and vancomycin developed in a 6-year-old boy. Treatment with intrathecal teicoplanin in combination with intravenous clindamycin, rifampin, and ampicillin was successful. The role of intravenous and intrathecal antibiotics in treatment of this infection is discussed. This case is illustrative of the safety and potential usefulness of intrathecally administered teicoplanin.

Bioassay of teicoplanin in serum containing rifampin or a beta-lactam antibiotic.

The purpose of this study was to develop bioassays for the measurement of teicoplanin in serum containing rifampin or a beta-lactam antibiotic. Use of rifampin-resistant Bacillus subtilis as indicator organism or pretreatment of the serum sample with Bacillus cereus penicillinase Type I (nafcillin, ticarcillin, mezlocillin) or Type II (cefazolin, cefuroxime, ceftazidime, ceftriaxone) effectively eliminated assay interference. Validation bioassays performed on two separate days utilizing triplicate coded serum samples containing 0 to 200 micrograms teicoplanin in combination with 40 micrograms/ml rifampin or 200 to 500 micrograms/ml beta-lactam showed no significant differences (p greater than 0.05, two-way analysis of variance) in analyte recovery between assay days. Regression analysis of each teicoplanin/rifampin or teicoplanin/beta-lactam data set yielded slope values of 0.92 to 1.01, intercept values of -0.45 to 0.84 and correlation coefficients of 0.9925 to 0.9990. Thus, serum teicoplanin can be quantitated accurately, precisely, and reproducibly in patients receiving concomitant rifampin or beta-lactam chemotherapy.

A sensitive bioassay for teicoplanin in serum in the presence or absence of other antibiotics.

A teicoplanin bioassay has been developed that is accurate, sensitive, and reliable. A linear relationship is obtained between the diameter of the zone of inhibition and log10 teicoplanin concentration in human serum over the range of 0.15 or 1.25 to 96 micrograms/ml using wells or paper filter disks, respectively. The assay medium devised consists of 50 g BBL Mueller-Hinton II Agar, 30 g NaCl, 8 g CaCl2, and 1.0 g citric acid (monohydrate) per liter of deionized water (resulting pH 5.1 +/- 0.1) and the assay organism Bacillus subtilis ATCC 6633. This system allows the assay of teicoplanin in the presence of commonly used aminoglycosides and in the presence of beta-lactams after inactivation by beta-lactamase. Additionally, it has the potential to be used in the presence of rifampin by using a rifampin-resistant strain of B. subtilis.

In vitro and in vivo evaluation of MDL 19,592, an oral cephalosporin.

MDL 19,592 is a new semisynthetic cephalosporin with a good therapeutic potential against Gram-positive bacterial infections when administered orally or parenterally. In the oral treatment of benzylpenicillin-resistant Staphylococcus aureus infections in mice, MDL 19,592 was superior to cephalexin, cephradine, cefaclor, cefadroxil and cefroxadine. These in vivo results reflect the in vitro superiority expressed by MDL 19,592 over the other oral cephalosporins against staphylococci. Additionally, MDL 19,592 orally was superior to cefazolin and cephalothin administered subcutaneously and to a number of penicillinase-resistant penicillins given orally or subcutaneously in the treatment of S. aureus mouse infections. MDL 19,592 killed S. aureus cells at the same or faster rate than did cephalexin or cephradine. As compared to cephalexin, MDL 19,592 was marginally superior in vitro against Streptococcus pyogenes and Streptococcus pneumoniae. In vivo, MDL 19,592 was significantly the more effective of the two against S. pyogenes and marginally more effective against S. pneumoniae. Against Gram-negative organisms, with the exception of Haemophilus influenzae, cephalexin was the more potent of the two antibiotics both in vitro and in vivo. Administered orally to mice, MDL 19,592 was absorbed as rapidly as cephalexin with both drugs attaining similar concentrations in the blood. MDL 19,592, like cephalexin, was minimally bound by mouse serum.