Sisomicin: An Aminoglycoside Antibiotic that is Highly Effective against Pseudomonas

Abstract

The in vitro activity of sisomicin against Pseudomonas is two- to eight-fold greater then gentamicin or amikacin, and similar to tobramycin. Minimal inhibitory concentrations of sisomicin are usually <1.0 μg/ml. Sisomicin interacts synergistically with a variety of penicillins against many Pseudomonas, including strains resistant to gentamicin. The degree of cross-resistance between sisomicin and other aminoglycosides varies depending upon mechanism. Many strains with inactivating enzymes are resistant to sisomicin, gentamicin and tobramycin. However, due to high intrinsic potency, sisomicin is active against many strains that are resistant to other aminoglycosides as a result of impermeability. Thus sisomicin is active against 4% to 66% of strains resistant to gentamicin, tobramycin or amikacin. The ability of sisomicin to protect animals from fatal Pseudomonas infections has been assessed in 29 paired tests with tobramycin and 36 paired tests with gentamicin. The dose of sisomicin in mg/kg required to protect 50% of animals from death is, on average, 1.5 times lower than tobramycin and 3.1 times lower than gentamicin. Sisomicin also interacts synergistically with carbenicillin or ticarcillin in treatment of experimental infections in animals. The human pharmacology of sisomicin is similar to gentamicin. Rates of adverse reactions to sisomicin are comparable to those seen with gentamicin or tobramycin. Clinical trials have shown sisomicin to be as effective, and in some instances more effective, than gentamicin, tobramycin, or amikacin. In several studies, the efficacy of sisomicin, administered in lower doses than gentamicin, was equal to or greater than gentamicin. Infections caused by gentamicin-resistant Pseudomonas have responded to sisomicin. Also, several patients who failed to respond to either gentamicin or tobramycin have been successfully treated with sisomicin. In view of its high intrinsic potency both in vitro and in vivo, sisomicin may become a preferred agent for treatment of serious Pseudomonas infections due to sensitive strains.

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References

Basker

M J

Comber

K E

Sutherland

(1978) Synergy between ticarcillin and aminoglycosides against Gram-negative bacilli in vitro and in vivo. In: Siegenthaler

Luthy

(Ed.). Current chemotherapy. Proceedings of the 10th International Congress of Chemotherapy, Zurich, September 18–23, 1977. American Society for Microbiology, Washington, D.C., p 425.

Braveny

Voecki

Machka

(1980) Antimicrobial activity of netilmicin in comparison with gentamicin, sisomicin, tobramycin, and amikacin and their resistance patterns. Arzneim-Forsch/Drug Res. 30, 491.

Cooper

D J

Jaret

R S

Reimann

(1971) Structure of sisomicin, a novel unsaturated aminoglycoside antibiotic from Micromonospora inyoensis. Chem. Commun. 7, 285.

Daschner

(1979) Synergistic effects of azlocillin and mezlocillin with the aminoglycosides in nosocomial infections. Infection 7, (Suppl. 3), S250.

Davies

Courvalin

(1977) Mechanisms of resistance to aminoglycosides. Am. J. Med. 62, 868.

Davies

Smith

D I

(1978) Plasmid-determined resistance to antimicrobial agents. Annual Rev. Microbiol. 32, 469.

Devaud

Kayser

F H

Huber

(1977) Resistance of bacteria to the newer aminoglycoside antibiotics: an epidemiological and enzymatic study. J. Antibiot. 30, 655.

Goering

R V

Sanders

C C

Sanders

W E

Jr (1978) Comparison of 5-episisomicin (Sch 22591), gentamicin, sisomicin and tobramycin in treatment of experimental pseudomonas infections in mice. Antimicrob. Agents Chemother. 14, 824.

Habwe

Shadomy

(1979) Comparative in vitro studies with netilmicin, amikacin, gentamicin, sisomicin, and tobramycin. J. Antimicrob. Chemother. 5, 73.

10.

Kabins

S A

Nathan

(1978) In vitro activity of 5-episisomicin in bacteria resistant to other aminoglycoside antibiotics. Antimicrob. Agents Chemother. 14, 391.

11.

Keating

M J

Bodey

G P

Valdivieso

Rodriquez

(1979) A randomized comparative trial of three aminoglycosides – comparison of continuous infusions of gentamicin, amikacin and sisomicin combined with carbenicillin in treatment of infections in neutropenic patients with malignancies. Medicine (Baltimore) 58, 159.

12.

Klastersky

Nyamubeya

Vandenborre

(1974) Antimicrobial effectiveness of kanamycin, aminosidin, BBK-8, sisomicin, gentamicin, and tobramycin combined with carbenicillin or cephalothin against Gram-negative rods. J. Med. Microbiol. 7, 465.

13.

Lee

B K

Condon

R G

Munayyer

Weinstein

M J

(1978) Uptake of (methyl-14C)-sisomicin and (methyl-14C)-gentamicin into bacterial cells. J. Antibiot. (Tokyo) 31, 141.

14.

Liss

R H

Letourneau

R J

Ifrim

Goldmann

D A

(1979) Radio-chemical and ultra-structural studies of sisomicin and gentamicin uptake by bacterial cells (abstract No. 884). In: Proceedings and abstracts of the 19th Interscience Conference of Antimicrobial Agents and Chemotherapy, Boston, October 1–5. 1979. American Society for Microbiology, Washington, D.C.

15.

Maki

D G

Craig

W A

Agger

W A

(1979) A comparative clinical trial of sisomicin and gentamicin in major Gram-negative infections. Infection 7, (Suppl. 3), S298.

16.

Marks

M I

Hammerberg

Greenstone

Silver

(1976) Activity of newer aminoglycosides and carbenicillin, alone and in combination, against gentamicin-resistant Pseudomonas aeruginosa. Antimicrob. Agents Chemother. 10, 399.

17.

Meyers

B R

Hirschman

S Z

(1976) Comparison of activity of sisomicin and gentamicin in mouse protection tests with Gram-negative bacilli. Antimicrob. Agents Chemother. 10, 384.

18.

Noone

Perera

Amirak

I D

(1979) Sisomicin in serious Gram-negative sepsis (abstract No. 369). In: Proceedings and abstracts of the 19th Interscience Conference on Antimicrobial Agents and Chemotherapy, Boston, October 1–5, 1979. American Society for Microbiology, Washington, D.C..

19.

Norden

C W

Keleti

(1980) Experimental osteomyelitis caused by Pseudomonas aeruginosa. J. Infect. Dis. 141, 71.

20.

Phillips

King

B A

Shannon

K P

(1978) The mechanisms of resistance to aminoglycosides in the genus Pseudomonas. J. Antimicrob. Chemother., 4, 121.

21.

del Rosal

P L

del Rosal

L L

Carrasco

A G R

Rascon

(1980) Comparison of sisomicin and gentamicin in the treatment of serious systemic infections. Curr. Med. Res. Op., 6, 663.

22.

Rýc

Trojanová

Jedlicková

Výmola

(1978) Ultra-structural changes in Pseudomonas aeruginosa cells caused by amikacin, gentamicin and sisomicin. In: Siegenthaler

Luthy

(Ed.). Current chemotherapy. Proceedings of the 10th International Congress of Chemotherapy, Zurich, September 18–23. 1977. American Society of Microbiology, Washington, D.C. p 457.

23.

Sanders

W E

Jr Sanders

C C

(1980) Sisomicin: A review of eight years' experience. Revs. Infect. Dis., 2, 182.

24.

Schassan

H H

(1978) Comparative activity of mezlocillin, carbenicillin, and combinations of mezlocillin with aminoglycosides against Gram-negative bacteria. In: Siegenthaler

Luthy

(ed.). Current chemotherapy. Proceedings of the 10th International Congress of Chemotherapy, Zurich, September 18–23, 1977. American Society for Microbiology, Washington, D.C., p 428.

25.

Schering Corporation, data on file. Van Wingerden

G I

Lolans

Jackson

G G

(1974) Experimental pseudomonas osteomyelitis. Treatment with sisomicin and carbenicillin. J. Bone Joint Surg., 56-A (7), 1452.

26.

Waitz

J A

Miller

G H

(1979) Activity of sisomicin in experimental infections. Infection 7, (Suppl 3), S259.

27.

Waitz

A J

Miller

G H

(1980) Evaluation of the in vitro and in vivo potency of sisomicin. The Royal Society of Medicine. Int. Congress and Symposium series, No 35.

28.

Young

L S

Hewitt

W L

(1973) Activity of five aminoglycoside antibiotics in vitro against Gram-negative bacilli and Staphylococcus aureus. Antimicrob. Agents Chemother. 4, 617.