In Vitro and in Vivo Studies of Three Antibiotic Combinations Against Gram-negative Bacteria and Staphylococcus Aureus

Overview

Journal Antimicrob Agents Chemother

Publisher American Society for Microbiology

Specialty Pharmacology

Date 1981 Oct 1

PMID 6282192

Citations 10

Authors

S H Zinner

J Klastersky

H Gaya

C Bernard

J C Ryff

Affiliations

Soon will be listed here.

Abstract

The activities of azlocillin, cefotaxime, and amikacin alone and in combination were evaluated in in vitro checkerboard studies, in infected neutropenic mice, and in human volunteers. The combination of cefotaxime plus amikacin was more synergistic in vitro than the others against the Enterobacteriaceae tested, and the combination of azlocillin plus amikacin was more synergistic against Pseudomonas aeruginosa and Staphylococcus aureus. Survival of neutropenic mice infected with Escherichia coli and Klebsiella pneumoniae, respectively, was greater with azlocillin plus amikacin (24 of 40 and 11 of 40) and with cefotaxime plus amikacin (21 of 40 and 17 of 40) than with azlocillin plus cefotaxime (22 of 40 and 3 of 40; P less than 0.05). Median serum bactericidal activity in volunteers receiving these antibiotics alone and in combination was greater than or equal to 1:8 with most agents and with all combinations tested against 10 strains each of E. coli, K. pneumoniae, P. aeruginosa, and S. aureus. These data suggest that clinical trials with combinations of azlocillin or cefotaxime plus amikacin deserve further study in febrile neutropenic patients.

Citing Articles

Therapy with antibiotics in leukemic patients.

Klastersky J Infection. 1983; 11 Suppl 2:S97-101.

PMID: 6671799 DOI: 10.1007/BF01645297.

Susceptibility and tolerance of beta-lactamase-producing, methicillin-sensitive strains of Staphylococcus aureus towards seven broad-spectrum penicillins.

Wehrli R, von Graevenitz A, Luthy R Infection. 1983; 11(6):322-5.

PMID: 6607889 DOI: 10.1007/BF01641357.

Comparative study of the serum bactericidal activity of cefoperazone alone and in combination with amikacin or mezlocillin against gram-negative bacilli and Staphylococcus aureus.

Lagast H, Klastersky J, Standiford H, Viollier A Infection. 1984; 12(3):190-3.

PMID: 6432702 DOI: 10.1007/BF01640897.

Cefotaxime. A review of its antibacterial activity, pharmacological properties and therapeutic use.

Carmine A, Brogden R, Heel R, Speight T, Avery G Drugs. 1983; 25(3):223-89.

PMID: 6303743 DOI: 10.2165/00003495-198325030-00001.

Cefotaxime plus amikacin as empiric therapy in the treatment of febrile episodes in neutropenic patients with hematologic malignancies.

Martino P, Venditti M, Petti M, Mandelli F, Serra P Infection. 1985; 13(3):125-9.

PMID: 3928495 DOI: 10.1007/BF01642871.

References

BERENBAUM M . A method for testing for synergy with any number of agents. J Infect Dis. 1978; 137(2):122-30. DOI: 10.1093/infdis/137.2.122. View

Gurwith M, Brunton J, Lank B, Ronald A, Harding G, McCullough D . Granulocytopenia in hospitalized patients. II. A prospective comparison of two antibiotic regimens in the empiric therapy of febrile patients. Am J Med. 1978; 64(1):127-32. DOI: 10.1016/0002-9343(78)90188-2. View

Wise R, Gillett A, Andrews J, Bedford K . Activity of azlocillin and mezlocillin against gram-negative organisms: comparison with other penicillins. Antimicrob Agents Chemother. 1978; 13(4):559-65. PMC: 352288. DOI: 10.1128/AAC.13.4.559. View

Sosna J, Murray P, Medoff G . Comparison of the in vitro activities of HR756 with cephalothin, cefoxitin, and cefamandole. Antimicrob Agents Chemother. 1978; 14(6):876-9. PMC: 352572. DOI: 10.1128/AAC.14.6.876. View

Keating M, Bodey G, Valdivieso M, Rodriguez V . A randomized comparative trial of three aminoglycosides--comparison of continuous infusions of gentamicin, amikacin and sisomicin combined with carbenicillin in the treatment of infections in neutropenic patients with malignancies. Medicine (Baltimore). 1979; 58(2):159-70. DOI: 10.1097/00005792-197903000-00004. View

Winston D, Sidell J, Hairston J, Young L . Antimicrobial therapy of septicemia due to Klebsiella pneumoniae in neutropenic rats. J Infect Dis. 1979; 139(4):377-88. DOI: 10.1093/infdis/139.4.377. View

Moellering Jr R . Antimicrobial synergism--an elusive concept. J Infect Dis. 1979; 140(4):639-41. DOI: 10.1093/infdis/140.4.639. View

Love L, Schimpff S, Schiffer C, Wiernik P . Improved prognosis for granulocytopenic patients with gram-negative bacteremia. Am J Med. 1980; 68(5):643-8. DOI: 10.1016/0002-9343(80)90243-0. View

Bennett J, BRODIE J, BENNER E, KIRBY W . Simplified, accurate method for antibiotic assay of clinical specimens. Appl Microbiol. 1966; 14(2):170-7. PMC: 546645. DOI: 10.1128/am.14.2.170-177.1966. View

10.

Schimpff S, Satterlee W, YOUNG V, Serpick A . Empiric therapy with carbenicillin and gentamicin for febrile patients with cancer and granulocytopenia. N Engl J Med. 1971; 284(19):1061-5. DOI: 10.1056/NEJM197105132841904. View

11.

Klastersky J, Cappel R, Daneau D . Therapy with carbenicillin and gentamicin for patients with cancer and severe infections caused by gram-negative rods. Cancer. 1973; 31(2):331-6. DOI: 10.1002/1097-0142(197302)31:2<331::aid-cncr2820310210>3.0.co;2-s. View

12.

Klastersky J, Daneau D, Swings G, Weerts D . Antibacterial activity in serum and urine as a therapeutic guide in bacterial infections. J Infect Dis. 1974; 129(2):187-93. DOI: 10.1093/infdis/129.2.187. View

13.

Klastersky J, Cappel R, Daneau D . Clinical significance of in vitro synergism between antibiotics in gram-negative infections. Antimicrob Agents Chemother. 1972; 2(6):470-5. PMC: 444341. DOI: 10.1128/AAC.2.6.470. View

14.

Acar J, Sabath L, Ruch P . Antagonism of the antibacterial action of some penicillins by other penicillins and cephalosporins. J Clin Invest. 1975; 55(3):446-53. PMC: 301771. DOI: 10.1172/JCI107950. View

15.

Scott R, Robson H . Synergistic activity of carbenicillin and gentamicin in experimental Pseudomonas bacteremia in neutropenic rats. Antimicrob Agents Chemother. 1976; 10(4):646-51. PMC: 429808. DOI: 10.1128/AAC.10.4.646. View

16.

Sande M, Courtney K . Nafcillin-gentamicin synergism in experimental staphylococcal endocarditis. J Lab Clin Med. 1976; 88(1):118-24. View

17.

Kelly M, Matsen J . In vitro activity, synergism, and testing parameters of amikacin, with comparisons to other aminoglycoside antibiotics. Antimicrob Agents Chemother. 1976; 9(3):440-7. PMC: 429549. DOI: 10.1128/AAC.9.3.440. View

18.

Ekwo E, Peter G . Effect of clindamycin on aminoglycoside activity in a murine model of invasive Escherichia coli infection. Antimicrob Agents Chemother. 1976; 10(6):893-8. PMC: 429861. DOI: 10.1128/AAC.10.6.893. View

19.

Klastersky J, Prevost J . Significance of antimicrobial synergism for the outcome of gram negative sepsis. Am J Med Sci. 1977; 273(2):157-67. DOI: 10.1097/00000441-197703000-00005. View

20.

Lau W, Young L, Black R, Winston D, Linne S, Weinstein R . Comparative efficacy and toxicity of amikacin/carbenicillin versus gentamicin/carbenicillin in leukopenic patients: a randomized prospective trail. Am J Med. 1977; 62(6):959-66. DOI: 10.1016/0002-9343(77)90669-6. View