D. H. Ho

Pharmacokinetics of cefoperazone in patients with neoplastic disease.

The pharmacokinetics of cefoperazone, a new semisynthetic cephalosporin, were studied in 34 patients with neoplastic disease. This compound was administered in a variety of doses and schedules without observable toxicity in any patient. The mean peak serum concentration after a 15-min intravenous infusion of 2 g was 264 microgram/ml after the first dose; the serum half-life was 2.1 h. There was no significant change in half-life or serum concentrations after 4 or 7 days of therapy. The mean peak serum concentration after infusion of 1 g over 15 min was 133 microgram/ml, with a mean of 10.7 microgram/ml at 6 h. The serum half-life was 2 h. The mean peak serum concentration after infusion of 1 g over 0.5 h was 101 microgram/ml. When 8 g was subsequently administered daily by a continuous infusion schedule, levels were maintained at 80 microgram/ml. When the dose was increased to 16 g daily, serum concentrations were maintained at an average of 153 microgram/ml. Only 37% of cefoperazone was recovered in the urine in a 12-h period after the initial dose, suggesting the importance of other mechanisms of excretion; however, serum concentrations in one patient with renal insufficiency were significantly higher than serum concentrations in patients with normal renal function.

In vitro activity of Ro 23-9424, a dual-action antibacterial agent, against bacterial isolates from cancer patients compared with those of other agents.

The in vitro activity of Ro 23-9424 against bacterial isolates from patients with cancer was compared with those of fleroxacin, ciprofloxacin, cefoperazone, and ceftazidime. Ro 23-9424 inhibited the majority of the members of the family Enterobacteriaceae and all Aeromonas isolates at a concentration of less than or equal to 1.0 micrograms/ml. It was also active against Acinetobacter spp. and Haemophilus influenzae, including beta-lactamase-producing strains. The MIC for 90% of isolates (MIC90) of Pseudomonas aeruginosa was 16.0 micrograms/ml. All group A and B streptococci were inhibited by less than or equal to 0.25 micrograms/ml, and 90% of group G streptococci and Streptococcus pneumoniae were inhibited by 1.0 micrograms/ml. All methicillin-susceptible strains of Staphylococcus aureus and 60% of methicillin-resistant strains were susceptible to 2.0 micrograms of Ro 23-9424 per ml, whereas the MIC90 for Staphylococcus epidermidis and Staphylococcus hominis isolates was 4.0 micrograms/ml. Staphylococcus haemolyticus and Enterococcus spp. were less susceptible; MIC90s for them were 16.0 and 32.0 micrograms/ml. Ro 23-9424 has a broad antibacterial spectrum and potential utility for therapy of infections in cancer patients.

Comparative in vitro activity of the new erythromycin derivative dirithromycin against gram-positive bacteria isolated from cancer patients

The in vitro activity of dirithromycin (LY-237216), a new macrolide erythromycin derivative, was compared to that of four other agents (clarithromycin, erythromycin, roxithromycin, clindamycin) against 334 gram-positive isolates obtained from cancer patients. Dirithromycin was similar in potency and antimicrobial spectrum to the other agents tested. It was very active against beta-haemolytic streptococci andStreptococcus pneumoniae, and moderately active against penicillin and methicillin susceptibleStaphylococcus aureus, Bacillus spp.,Listeria monocytogenes andCorynebacterium jeikeium. Erythromycin resistant organisms were also resistant to dirithromycin.

In vitro activity of FK-037, a novel parenteral cephalosporin, against bacterial isolates from neutropenic cancer patients

The in vitro activity of FK-037, a novel parenteral cephalosporin, was compared to that of ceftazidime, aztreonam and piperacillin (agents often used in empiric regimens in cancer patients) against recent bacterial isolates from patients with cancer. FK-037 was either equal to or 2 to 16-fold more active than the comparative agents against members of theEnterobacteriaceae. It was also active againstAcinetobacter spp.,Aeromonas spp.,Pseudomonas aeruginosa, and otherPseudomonas spp.Xanthomonas maltophilia andAlcaligenes denitrificans were relatively resistant to all four agents. FK-037 was also 4 to 16-fold more active against most gram-positive organisms (including some methicillin-resistant staphylococci) than was ceftazidime.Enterococcus spp.,Listeria monocytogenes andStaphylococcus haemolyticus were relatively resistant to FK-037 and ceftazidime. Overall, FK-037 has a broad antimicrobial spectrum that includes the majority of gram-positive and gram-negative isolates.

In vitro activity of cefpodoxime against bacterial isolates obtained from patients with cancer

The in vitro activity of cefpodoxime, an oral cephalosporin ester, against 792 bacterial isolates representing 36 species was evaluated in comparison to that of ciprofloxacin and trimethoprim/sulfamethoxazole (TMP/SMX). Cefpodoxime inhibited the majority ofStreptococcus spp.,Haemophilus influenzae andProteus mirabilis at a concentration of ≤0.12 µg/ml. It was also active againstCitrobacter diversus, Escherichia coli, Klebsiella spp.,Proteus vulgaris, Serratia marcescens and methicillin-susceptibleStaphylococcus aureus isolates. Overall, cefpodoxime appeared to be less active than ciprofloxacin and TMP/SMX against many pathogens common in cancer patients.

In vitro activity of PD127,391, a new quinolone against bacterial isolates from cancer patients.

The in vitro activity of PD127,391, a new 4-quinolone, was compared to that of ciprofloxacin against common clinical bacterial isolates from patients with cancer. PD127,391 was found to have a broad antimicrobial spectrum with excellent activity against gram-positive isolates (including multidrug-resistant organism such as Corynebacterium jeikeium, Enterococcus faecalis, Enterococcus faecium, methicillin-resistant Staphylococcus aureus and coagulase-negative Staphylococcus spp.). It was also extremely active against gram-negative bacilli including Pseudomonas aeruginosa. Against organisms such as Achromobacter xylosoxidans, Acinetobacter spp. and Xanthomonas maltophilia, which are frequently resistant to a variety of antimicrobial agents, PD127,391 exhibited good activity, inhibiting all such isolates at a concentration of 0.5 micrograms/ml. Overall, PD127,391 was far more potent than ciprofloxacin against gram-positive isolates and slightly more active against gram-negative isolates. No bacterium that we examined needed more than 2 micrograms/ml of PD127,391 for inhibition.

In vitro activity of trospectomycin (U-63366F), a novel spectinomycin analog, against gram-positive isolates from cancer patients

The in vitro activity of trospectomycin was compared to that of amikacin, cephalothin and vancomycin against gram-positive organisms, mostly isolated from cancer patients. Trospectomycin was considerably more active than amikacin against most isolates tested, particularly species ofStaphylococcus andStreptococcus. Overall, vancomycin was the most active agent tested.