Postantibiotic effect of meropenem and ciprofloxacin in the presence of 5-fluorouracil.

BACKGROUND: The postantibiotic effect (PAE) of meropenem and ciprofloxacin was studied in the presence of the antineoplastic agent 5-fluorouracil (5-FU). The purpose of the study was to investigate whether the PAEs of the combinations differed from the PAEs of the antibiotics alone. METHODS: The PAEs of the combinations of 5-FU plus meropenem or ciprofloxacin were determined with viable counts against four reference strains of Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, Escherichia coli and two clinical isolates of S. epidermidis. The results were compared with the PAEs of the antibiotics drugs and 5-FU alone. The gram-positive strains were tested for slime production, both alone and in the presence of 5-FU. RESULTS: Against two of the three tested strains of S. epidermidis, the combination of ciprofloxacin and 5-FU gave a synergistic prolongation of the PAE in comparison with the PAEs induced by the drugs alone. The combinations showed indifference against the other bacteria. The combination of meropenem and 5-FU had a synergistic PAE against one of the three tested strains of S. epidermidis and an additive effect against E. coli but showed indifference against the rest of the strains. CONCLUSIONS: The presence of 5-FU did not influence the PAEs of the antibiotics against most of the tested strains, but caused a synergistic prolongation of the PAEs induced by ciprofloxacin and meropenem against some of the tested strains of S. epidermidis. 5-FU inhibited slime production in the same S. epidermidis strains, which might have contributed to the longer PAE.

Bactericidal effect of combinations of antibiotic and antineoplastic agents against Staphylococcus aureus and Escherichia coli.

BACKGROUND: The bactericidal effect of some antibiotic and antineoplastic agents commonly used in clinical practice was investigated to analyse whether the combinations act synergistically, have indifferent or antagonistic antibacterial effects compared to the effect of the antibiotics alone. METHODS: The rate of killing of meropenem, ceftazidime and tobramycin was studied against six different strains of Staphylococcus aureus and Escherichia coli, and the results were compared to the rate of killing of the antibiotics in combination with the cytostatic drugs doxorubicin, etoposide and 5-fluorouracil (5-FU). RESULTS: Tobramycin showed synergy against two strains of S. aureus after 3 h in the presence of 5-FU and against one strain of S. aureus in the presence of doxorubicin. Meropenem induced an antagonistic bactericidal effect against one isolate of S. aureus after 24 h. Ceftazidime expressed an indifferent bactericidal effect together with the cytostatic agents. The antineoplastic agents had no impact on the bacterial killing of any of the antibiotics against E. coli. CONCLUSIONS: Tobramycin expressed a significantly better bactericidal effect against S. aureus after 3 h in the presence of doxorubicin and 5-FU than tobramycin alone. Meropenem expressed antagonism against one clinical strain of S. aureus, but the cytostatic drugs did not affect the killing of other strains tested. Ceftazidime expressed indifferent bactericidal activity together with the antineoplastic agents.

Pharmacokinetics of ceftazidime in febrile neutropenic patients.

Eight patients with fever and neutropenia were given 2 g of ceftazidime i.v. as a bolus injection over the course of 3 min. The pharmacokinetic variables for ceftazidime were similar to those found previously in febrile, acutely ill, non-neutropenic patients. The area under the plasma-concentration-time curve was significantly smaller, and the terminal half-life (t1/2lambda(z)) significantly shorter, compared with elderly, healthy subjects (p < 0.005). Three patients survived long enough to be assayed after normalization of temperature and neutrophil counts. Glomerular filtration rates and clearances tended to be higher and the area under the curve and half-life lower on the day of fever and neutropenia. When considering our data in relation to known MIC values for common pathogens, ceftazidime administered intermittently every 6 h seems an appropriate regimen in patients with febrile neutropenia. Larger studies are needed to confirm this.

Gastrointestinal damage induced by cytostatic treatment does not affect the bioavailability of co-trimoxazole.

Twelve lymphoma patients received prophylaxis with co-trimoxazole during cytostatic treatment according to the MACOP-B regimen with cyclophosphamide, doxorubicin, vincristine, methotrexate, bleomycin, folinic acid and prednisone. Gastrointestinal mucosal damage from cytostatic treatment was estimated by WHO toxicity scores. No correlation was found between the degree of gastrointestinal damage and the presumed bioavailability of co-trimoxazole as estimated from serum levels of trimethoprim and sulphamethoxazole. The serum concentrations were above the minimum inhibitory concentration for Escherichia coli, Staphylococcus aureus and coagulase-negative staphylococci irrespective of the degree of toxicity. There is no apparent reason to change the dosing regimen of prophylactic co-trimoxazole when there is clinical evidence of damage to the gastrointestinal mucosa induced by chemotherapy.

Pharmacokinetics of meropenem in febrile neutropenic patients. Swedish study group.

To determine the impact of neutropenia on the pharmacokinetics of meropenem, 14 patients with fever and neutropenia were given 1 g of meropenem i.v. every 8 h as an infusion over 30 min. The volume of distribution (16.2 l/1.73 m2) and the nonrenal clearance [75 ml/(min x 1.73 m2)] in this group were significantly increased compared to healthy subjects studied previously with identical techniques. The kinetic study was repeated when the patients had a normal temperature and a raised neutrophil count; most kinetic variables did not differ from the findings on the first day of treatment. The pharmacokinetic profile of meropenem in febrile neutropenic patients differs from earlier findings in healthy subjects. Considering these data and known minimum inhibitory concentration values for common pathogens, meropenem administered every 6 to 8 h seems an appropriate regimen in patients with febrile neutropenia. The shorter time interval may be used for treatment of Pseudomonas infection.