Evaluation of ceftazidime, ampicillin and chloramphenicol in experimental Haemophilus influenzae type b meningitis.

In an infant rat model of Haemophilus influenzae, type b meningitis, where treatment was given 24 and 48 h after infection, the dose of ceftazidime required to eradicate the infection from the CSF of half the animals (CD50) ranged from less than 0.15-1.5 mg/kg/dose. The accompanying blood infections were marginally less responsive to therapy with CD50 values ranging from 0.5-3.9 mg/kg/dose. Comparable data for ampicillin were 12.5-40 mg/kg/dose and 20- greater than 200 mg/kg/dose for the CSF and blood infections while those for chloramphenicol were 18- greater than 100 mg/kg/dose and 22- greater than 100 mg/kg/dose for the CSF and blood infections respectively. Investigation of the relative rates of kill in vivo showed that all three drugs rapidly reduced the bacterial numbers to minimal levels. However, whereas ceftazidime completely eradicated the infection, chloramphenicol, and to a lesser extent, ampicillin-treated rats experienced substantial relapsing. Ceftazidime penetrated into the CSF of infected and uninfected rats slightly better than ampicillin--7.3% compared to 4.0% of the corresponding blood levels respectively. These results indicate that ceftazidime is significantly more active in the infant rat model of H. influenzae, type b meningitis than ampicillin or chloramphenicol.

The in-vivo antibacterial activity of ceftazidime (Gr 20263)--a comparison with other new beta-lactam antibiotics and gentamicin.

Ceftazidime was compared with cefotaxime, ceftizoxime, cefmenoxime, cefotiam, cefoperazone, moxalactam, piperacillin, carbenicillin, mezlocillin, cefsulodin and the aminoglycoside antibiotic gentamicin in a series of mouse protection tests. Ceftazidime, together with the other cephalosporin antibiotics and moxalactam were equally effective against infections caused by Staphylococcus aureus with ED50 values ranging from 3.5 to 25 mg/kg. Gentamicin was the most active antibiotic with ED50 values of 0.4 and 1.6 mg/kg. Ceftazidime showed excellent activity against Enterobacteriaceae with ED50 values ranging from 0.2-0.9 mg/kg for Escherichia coli strains, 1.1-13.8 mg/kg for indole positive and negative Proteus spp, and 0.1-25 for Enterobacter cloacae, Klebsiella pneumoniae and Serratia spp. Similar activity against many of the test strains of Enterobacteriaceae was found for gentamicin, cefotaxime, ceftizoxime, cefmenoxime and moxalactam, although cefotiam and cefoperazone were significantly less active than ceftazidime. Ceftazidime was significantly more active than the other beta-lactam antibiotics tested against Pseudomonas aeruginosa infections with ED50 values ranging from 02-108 mg/kg. Only the aminoglycoside antibiotic gentamicin, with ED(50,S) 0.6-6.3 mg/kg, was as effective as ceftazidime. Very poor activity was found for moxalactam, cefoperazone, piperacillin, carbenicillin and mezlocillin against the majority of the test strains of Pseudomonas. The results of these in-vivo indicate that ceftazidime is a promising potential alternative to aminoglycoside antibiotics.

G1549, a new cyclic hydroxamic acid antibiotic, isolated from culture broth of Pseudomonas alcaligenes.

Antibiotic G1549, isolated from culture broth of Pseudomonas alcaligenes, is a new cyclic hydroxamic acid with a 1-hydroxy-2(1H)-pyridinone structure that complexes with metals. The structure of G1549 is suggested to be 1-hydroxy-5-methoxy-6-methyl-2(1H)-pyridinone. In vitro, G1549 and its copper and ferric complexes show moderate activity against Gram-positive bacteria, fungi and Trichomonas vaginalis. Topical application of G1549 and its copper and ferric complexes protect guinea pigs against cutaneous infection with Microsporum canis. The compounds, however, have some systemic toxicity in mice.