Comparison of 5-episisomicin (Sch 22591), gentamicin, sisomicin, and tobramycin in treatment of experimental Pseudomonas infections in mice

Richard V. Goering, C. C. Sanders, W. E. Sanders

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Abstract

Sch 22591 (5-episisomicin), gentamicin, sisomicin, and tobramycin were compared for their ability to protect mice from lethal intraperitoneal challenge with 12 Pseudomonas strains, all susceptible to each of the aminoglycosides (minimal inhibitory concentrations and minimal bactericidal concentrations were ≤ 6.2 μg/ml). Median 50% protective doses were 5.8, 6.4, 7.7 and 17.8 mg/kg for Sch 22591, tobramycin, sisomicin, and gentamicin, respectively. Those for Sch 22591 were significantly lower than gentamicin in five protection tests and significantly lower than both gentamicin and tobramycin one test. Microbial analysis of the therapeutic effect indicated that protection from lethality by each of the four aminoglycosides was associated with either a complete eradication or a reduction in the number of challenge bacteria in both the heart blood and peritoneum. In rare instances, challenge isolates exhibiting decreased susceptibility to one or more of the aminoglycosides were recovered from animals. However, this in vivo selection of resistance did not appear related to either the aminoglycoside used in therapy or the outcome of therapy, and resistant isoltes were recovered as frequently from untreated animals as from those recieving one of the four aminoglycosides.

Original languageEnglish
Pages (from-to)824-828
Number of pages5
JournalAntimicrobial Agents and Chemotherapy
Volume14
Issue number6
StatePublished - 1978

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Sisomicin
Pseudomonas Infections
Tobramycin
Aminoglycosides
Gentamicins
Peritoneum
Therapeutic Uses
Pseudomonas
pentisomicin
Bacteria
Therapeutics

All Science Journal Classification (ASJC) codes

  • Pharmacology (medical)

Cite this

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title = "Comparison of 5-episisomicin (Sch 22591), gentamicin, sisomicin, and tobramycin in treatment of experimental Pseudomonas infections in mice",
abstract = "Sch 22591 (5-episisomicin), gentamicin, sisomicin, and tobramycin were compared for their ability to protect mice from lethal intraperitoneal challenge with 12 Pseudomonas strains, all susceptible to each of the aminoglycosides (minimal inhibitory concentrations and minimal bactericidal concentrations were ≤ 6.2 μg/ml). Median 50{\%} protective doses were 5.8, 6.4, 7.7 and 17.8 mg/kg for Sch 22591, tobramycin, sisomicin, and gentamicin, respectively. Those for Sch 22591 were significantly lower than gentamicin in five protection tests and significantly lower than both gentamicin and tobramycin one test. Microbial analysis of the therapeutic effect indicated that protection from lethality by each of the four aminoglycosides was associated with either a complete eradication or a reduction in the number of challenge bacteria in both the heart blood and peritoneum. In rare instances, challenge isolates exhibiting decreased susceptibility to one or more of the aminoglycosides were recovered from animals. However, this in vivo selection of resistance did not appear related to either the aminoglycoside used in therapy or the outcome of therapy, and resistant isoltes were recovered as frequently from untreated animals as from those recieving one of the four aminoglycosides.",
author = "Goering, {Richard V.} and Sanders, {C. C.} and Sanders, {W. E.}",
year = "1978",
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journal = "Antimicrobial Agents and Chemotherapy",
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T1 - Comparison of 5-episisomicin (Sch 22591), gentamicin, sisomicin, and tobramycin in treatment of experimental Pseudomonas infections in mice

AU - Goering, Richard V.

AU - Sanders, C. C.

AU - Sanders, W. E.

PY - 1978

Y1 - 1978

N2 - Sch 22591 (5-episisomicin), gentamicin, sisomicin, and tobramycin were compared for their ability to protect mice from lethal intraperitoneal challenge with 12 Pseudomonas strains, all susceptible to each of the aminoglycosides (minimal inhibitory concentrations and minimal bactericidal concentrations were ≤ 6.2 μg/ml). Median 50% protective doses were 5.8, 6.4, 7.7 and 17.8 mg/kg for Sch 22591, tobramycin, sisomicin, and gentamicin, respectively. Those for Sch 22591 were significantly lower than gentamicin in five protection tests and significantly lower than both gentamicin and tobramycin one test. Microbial analysis of the therapeutic effect indicated that protection from lethality by each of the four aminoglycosides was associated with either a complete eradication or a reduction in the number of challenge bacteria in both the heart blood and peritoneum. In rare instances, challenge isolates exhibiting decreased susceptibility to one or more of the aminoglycosides were recovered from animals. However, this in vivo selection of resistance did not appear related to either the aminoglycoside used in therapy or the outcome of therapy, and resistant isoltes were recovered as frequently from untreated animals as from those recieving one of the four aminoglycosides.

AB - Sch 22591 (5-episisomicin), gentamicin, sisomicin, and tobramycin were compared for their ability to protect mice from lethal intraperitoneal challenge with 12 Pseudomonas strains, all susceptible to each of the aminoglycosides (minimal inhibitory concentrations and minimal bactericidal concentrations were ≤ 6.2 μg/ml). Median 50% protective doses were 5.8, 6.4, 7.7 and 17.8 mg/kg for Sch 22591, tobramycin, sisomicin, and gentamicin, respectively. Those for Sch 22591 were significantly lower than gentamicin in five protection tests and significantly lower than both gentamicin and tobramycin one test. Microbial analysis of the therapeutic effect indicated that protection from lethality by each of the four aminoglycosides was associated with either a complete eradication or a reduction in the number of challenge bacteria in both the heart blood and peritoneum. In rare instances, challenge isolates exhibiting decreased susceptibility to one or more of the aminoglycosides were recovered from animals. However, this in vivo selection of resistance did not appear related to either the aminoglycoside used in therapy or the outcome of therapy, and resistant isoltes were recovered as frequently from untreated animals as from those recieving one of the four aminoglycosides.

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