Antipseudomonal effects of selected dithiocarbamates alone and in combination with gentamicin or aztreonam.
The antipseudomonal effects conferred by combinations of substituted dithiocarbamates, gentamicin or aztreonam (Azactam) were measured and compared to those produced by single agents alone in female BALB/C mice bearing overwhelming Pseudomonas aeruginosa infections. Dimethyldithiocarbamate (DMDTC), diethyldithiocarbamate (DEDTC), and sodium N-methyl-D-glucamine dithiocarbamate (NMGDTC) were chosen as representative substituted dithiocarbamates. All three dithiocarbamates rescued some cisplatin-immunosuppressed mice from pseudomonal infections but DMDTC and NMGDTC produced better results than DEDTC. Single daily injections of DMDTC at doses of 5 mg/kg/day or higher for a total of 7 days rescued 14 of 18 mice given 10(6) viable Pseudomonas aeruginosa by tail vein inoculation. Similar dose regimens of 10 mg/kg/day or higher NMGDTC for a total of 7 days rescued 15 of 18 mice. DEDTC at doses of 5 mg/kg/day or higher for 7 days rescued 7 of 18 mice. Combinations of DMDTC or NMGDTC with gentamicin failed to produce better results than each agent alone in mice immunosuppressed with methyl-prednisolone (Solumedrol) at the dose range evaluated in mice inoculated with 10(6) viable organisms via tail veins. Combinations of DMDTC and aztreonam were effective in mice immunosuppressed with methylprednisolone and given overwhelming numbers of viable Pseudomonas aeruginosa (10(7) or more, ip). Combinations of 6 mg/kg/day or higher of each agent with multiple daily injections rescued 11 of 18 mice. The results yielded by either agent alone were not impressive. Similar results were obtained when mice immunosuppressed with cisplatin were given ip injections of 10(8) or more viable bacteria. No mice were rescued by the use of DMDTC, NMGDTC, aztreonam or gentamicin only. Combinations of DMDTC (6 mg/kg) and aztreonam (6 mg/kg) with multiple daily injections for seven days rescued 11 of 20 infected mice while combinations of NMGDTC with aztreonam were less effective (3 of 20 rescued). The concurrent administration of DMDTC and aztreonam offers considerable promise in the treatment of overwhelming pseudomonal infections in mice and may prove to be of value in human patients as well.
Walker
E M
EM
John L. McClellan Memorial Veterans Hospital, Little Rock, AR 72205.
Hardin
H F
HF
Gale
G R
GR
Reifsteck
M E
ME
Cannon
D J
DJ
Jones
M M
MM
D000818:Animals; D001398:Aztreonam / Q000008:administration & dosage*; D004125:Dimethyldithiocarbamate / Q000008:administration & dosage / Q000494:pharmacology*; D004050:Ditiocarb / Q000008:administration & dosage / Q000494:pharmacology*; D004359:Drug Therapy, Combination / Q000494:pharmacology; D005260:Female; D005839:Gentamicins / Q000008:administration & dosage*; D051379:Mice; D008807:Mice, Inbred BALB C; D011552:Pseudomonas Infections / Q000188:drug therapy; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D013012:Sorbitol / Q000031:analogs & derivatives*; D013113:Spin Labels; D013859:Thiocarbamates / Q000008:administration & dosage / Q000494:pharmacology*
D004125:Dimethyldithiocarbamate; D005839:Gentamicins; D013113:Spin Labels; D013859:Thiocarbamates; D013012:Sorbitol; C041262:N-methyl-D-glucamine dithiocarbamate; D004050:Ditiocarb; D001398:Aztreonam