sf-2052 and Bacterial-Infections

A reproducible experimental model of intra-abdominal infections in rats has been developed in order to simulate intra-abdominal sepsis in patients. A 1-cm segment of ileum was isolated on its vascular pedicle. The intestine was then divided at each end of the segment and intestinal continuity was re-established by an end-to-end anastomosis. Dactimicin is a new aminoglycoside antibiotic with a broad antibacterial spectrum including both aerobic Gram-positive and Gram-negative bacteria. The experimental model was used to compare the efficacy of dactimicin in combination with clindamycin with the combination gentamicin/clindamycin in the treatment of intra-abdominal infections. Of the untreated animals, 70% died within two days. Animals treated with dactimicin plus clindamycin or gentamicin plus clindamycin exhibited significantly decreased mortality and increased cure rates during the experimental period. Only 5% of these animals died. Thus the combination dactimicin/clindamycin seems to be useful in the treatment of intra-abdominal infections.

Topics: Abdomen; Aminoglycosides; Animals; Anti-Bacterial Agents; Ascitic Fluid; Bacteria; Bacterial Infections; Clindamycin; Drug Therapy, Combination; Gentamicins; Male; Microbial Sensitivity Tests; Rats; Rats, Inbred Strains

Topics: Amikacin; Aminoglycosides; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Drug Combinations; Humans; Microbial Sensitivity Tests

Antimicrobial activity of dactimicin, a pseudo-disaccharide aminoglycoside antibiotic, was compared with those of dibekacin, netilmicin, sisomicin and micronomicin using clinical isolates of four Gram-positive and sixteen Gram-negative bacteria. Dactimicin was more active than the reference amino-glycosides against Serratia marcescens, especially gentamicin-resistant Serratia sp., Proteus vulgaris, P. rettgeri and Klebsiella oxytoca, but less active against Pseudomonas aeruginosa and P. mirabilis. Dactimicin was equally active as the references excepting netilmicin against Gram-positive bacteria and some Gram-negative bacteria including Escherichia coli, K. pneumoniae, Morganella morganii, Haemophilus influenzae, Citrobacter freundii, Enterobacter aerogens, E. cloacae, Acinetobacter calcoaceticus and Campylobacter jejunii. Dactimicin was active against resistant strains possessing various aminoglycoside-modifying enzymes including AAC(3)-1, by which dactimicin was acetylated.

Topics: Aminoglycosides; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Dibekacin; Drug Resistance, Microbial; Gentamicins; Microbial Sensitivity Tests; Netilmicin; Sisomicin

Dactimicin is a new aminoglycoside and its in vitro activity has been compared with that of gentamicin against 100 recent clinical isolates. The minimum inhibitory concentrations were determined by agar dilution. Dactimicin was generally one two-fold dilution step less active or as equally active as gentamicin against enterobacteria and pseudomonas. Dactimicin was several times more active than gentamicin against Acinetobacter and staphylococci. Both compounds share poor activity against enterococci and have a variable effect on other streptococci. They are highly active against serogroup A streptococci and pneumococci.

Topics: Aminoglycosides; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Enterobacteriaceae; Gentamicins; Humans; Microbial Sensitivity Tests

The in vitro antimicrobial activity of dactimicin against aerobic and anaerobic bacteria isolated from intra-abdominal infections was compared to those of gentamicin and metronidazole. The data obtained show that dactimicin is a promising new aminoglycoside covering aerobic bacteria and that it may be used together with an antianaerobic agent in the treatment of these infections.

Topics: Abdomen; Aminoglycosides; Anti-Bacterial Agents; Bacteria, Aerobic; Bacteria, Anaerobic; Bacterial Infections; Gentamicins; Humans; Metronidazole

A reproducible experimental model of intra-abdominal infections in rats has been worked out in order to simulate intra-abdominal sepsis in patients. A 1-cm segment of ileum was isolated on its vascular pedicle. The intestine was then divided at each end of the segment and intestinal continuity was reestablished by an end-to-end anastomosis. Dactimicin is a new aminoglycoside antibiotic and has a broad antibacterial spectrum including both Gram-positive and Gram-negative aerobic bacteria. The experimental model was used to compare the efficacy of dactimicin alone and in combination with metronidazole with the combination gentamicin and metronidazole in the treatment of intra-abdominal infections. Many of the untreated animals (70%) died within 2 days. Within 7 days 40% of the animals receiving dactimicin died. Animals treated with dactimicin plus metronidazole or gentamicin plus metronidazole had a significantly decreased mortality and increased cure rates during the experimental period. Only 5% of these animals died. Thus the combination dactimicin and metronidazole seems to be useful in the treatment of intra-abdominal infections.

Topics: Abdomen; Aminoglycosides; Animals; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Gentamicins; Metronidazole; Microbial Sensitivity Tests; Rats; Rats, Inbred Strains

The stability of dactimycin to aminoglycoside-modifying enzymes produced by 341 bacterial clinical isolates has been studied. Enzymatic activities were measured by the phosphocellulose binding assay. The results demonstrated that dactimicin was stable to the following enzymes: (i) AAC(3)-II,-III,-IV and -V. (ii) AAC(2'); (iii)AAC(6')-I and -II;(iv) ANT(2"); (v)ANT(4'); (vi) APH(3')-I,-II,-III and -IV. In contrast, dactimicin was only inactivated by two enzymes, AAC(3)-I and the bifunctional AAC(6')/APH(2"). This staphylococcal enzyme modified and inactivated dactimicin by acetylation but not by phosphorylation, suggesting the possibility of a second target amino group, such as 6'-NH2, in addition to the C4 amino group, which is the target for AAC(3)-I.

Topics: Acetyltransferases; Aminoglycosides; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Microbial Sensitivity Tests