Comparison Between Agar and Broth Minimum Inhibitory Concentrations of Cefamandole, Cefoxitin, and Cefuroxime

The activity of norfloxacin was studied in vivo with steel net cages implanted subcutaneously in rabbits. Four weeks after implantation, two of four cages in each animal were inoculated with a strain of Escherichia coli (seven animals) or Klebsiella pneumoniae (six animals). Four animals in each group received oral treatment with norfloxacin for 7 days. Treatment was started 18 h after inoculation of the cages. Peak concentrations above the in vitro minimal inhibitory concentrations for the strains used were achieved in the fluid of 14 of 16 of the infected cages after the first norfloxacin dose. The penetration of norfloxacin into both infected and uninfected tissue cage fluid was significantly higher on treatment days 3 and 7 than on treatment day 1. No difference was observed between the concentrations in uninfected and infected cage fluids or between cage fluids infected with different organisms. The viable counts of E. coli and K. pneumoniae decreased from 2 X 10(3) to 2 X 10(8) CFU/ml of cage fluid to less than 10 CFU/ml in 10 of the infected cage fluids 12 h after the last dose of norfloxacin. Fluid from four cages still containing low numbers of viable bacteria at that time became free from bacteria (less than 10 CFU/ml) 1 to 4 days later. No regrowth was found in any cage fluid 7 days after the treatment period. The viable counts of E. coli or K. pneumoniae in five untreated control animals did not decrease during 8 to 14 days after inoculation of cage fluid. In comparison with cephalosporins and aminoglycosides studied previously with the same experimental method, norfloxacin penetrated better into cage fluid and more effectively reduced the viable counts of the organisms.

Section: Discussionmentioning

confidence: 99%

Norfloxacin penetration into subcutaneous tissue cage fluid in rabbits and efficacy in vivo

Rylander¹,

Norrby²

1983

“…The clinical importance of such discrepancy also has been emphasized for cefamandole against Enterobacter cloacae (17,24). Rylander et al have demonstrated superior predictability of outcome for certain organisms in experimental infections by broth dilution MIC compared with agar dilution susceptibility testing (23).…”

mentioning

confidence: 99%

“…Although the mechanism(s) responsible for the discrepancies between disk diffusion and broth susceptibility testing was not systematically evaluated, one explanation may be the lower number of organisms tested in agar tests (9,23,25), with less opportunity for expression of resistant variants. Reports indicating superior activity of ticarcillinclavulanate against ticarcillin-resistant P. aeruginosa have been based on disk diffusion (Fosse et al, 14th ICC) or agar dilution susceptibility testing (14; Morisset et al, Proc.…”

mentioning

confidence: 99%

Discrepancies between disk diffusion and broth susceptibility studies of the activity of ticarcillin plus clavulanic acid against ticarcillin-resistant Pseudomonas aeruginosa

Manian¹,

Alford²

1986

Ticarcillin and clavulanic acid in combination were tested against 40 Pseudomonas aeruginosa isolates resistant to ticarcillin by disk diffusion. A total of 21 isolates (53%) were susceptible to ticarcillin-clavulanate by disk diffusion, under currently recommended criteria for ticarcilin susceptibility. Macro-broth dilution tests (ticarcillin plus clavulanic acid, 2 ,ug/ml) confirmed susceptibility (MIC <64 4g/ml) of only 8 (38%) of 21 isolates. Time-kill studies of disk diffusion susceptible isolates indicated 2 log10 or greater killing of most isolates at 6 h in broth containing ticarcillin (64 ,ig/ml) combined with clavulanic acid (1, 2, 5, or 10 ,ug/ml). After 6 h, regrowth was common in all concentrations of clavulanic acid except 10 ,ug/ml. Regrowth populations were resistant to ticarcillin-clavulanate by MIC determination. Poor bactericidal activity of ticarcillin-clavulanate against ticarcillin-resistant P. aeruginosa was confirmed, as most isolates did not undergo 99.9% or greater killing at 24 h in all concentrations of clavulanic acid. Serotype 0-11 was our most common serotype and was associated with disk diffusion "pseudosusceptibility." Concomitant disk diffusion testing of ticarcillinclavulanate and ticarcillin is recommended for testing the susceptibility of P. aeruginosa to ticarcillinclavulanate by disk diffusion. P. aeruginosa isolates resistant to ticarcillin should as a rule be considered also resistant to ticarcillin-clavulanate, despite apparent susceptibility by disk diffusion.Clavulanic acid, by virtue of its irreversible inhibition of Richmond type II, III, IV, and V P-lactamases (18,22), has broadened the spectrum of activity of ticarcillin to include many otherwise resistant strains of Staphylococcus aureus, the family Enterobacteriaceae, and Bacteroides spp. (2, 6-8, 11, 15, 19). Against ticarcillin-susceptible Pseudomonas aeruginosa, ticarcillin-clavulanate in combination has activity in vitro like that of ticarcillin alone (2,6,8,11,15).

“…Cefamandole is reported to be active against fl-lac' strains when tested by the agar dilution technique, inhibiting such strains at concentrations of 2 ug/ml or less (11), and has been suggested as a possible altemative in the treatment of infections caused by f,-lac+ H. influenzae. Rylander et al observed that for some organisms, the MIC of cefamandole, as determined by the broth dilution technique, is substantially higher than the MIC determined by agar dilution (18). Although Bergeron et al observed no difference between cefamandole MICs for fi-lac' H. influenzae in broth and agar, they noted that cefamandole was much less active against fl-lac' than against f,-lac-strains (4).…”

Section: Resutltsmentioning

confidence: 92%

Susceptibility of Haemophilus influenzae to chloramphenicol and eight beta-lactam antibiotics

Thirumoorthi¹,

Kobos²,

Dajani³

1981

We examined the minimal inhibitory concentrations and minimal bactericidal concentrations of chloramphenicol, ampicillin, ticarcillin, cefamandole, cefazolin, cefoxitin, cefotaxime, ceforanide, and moxalactam for 100 isolates ofHaemophilus influenzae, 25 of which produced fl-lactamase. Susceptibility was not influenced by the capsular characteristic of the organism. The mean minimal inhibitory concentrations of cefamandole, ticarcillin, and ampicillin for f-lactamase-producing strains were 3-, 120-, and 400-fold higher than their respective mean minimal inhibitory concentrations for ,8-lactamase-negative strains. No such difference was noted for the other antibiotics. We performed time-kill curve studies, using chloramphenicoL ampicillin, cefamandole, cefotaxime, and moxalactam with two concentrations of the antimicrobial agents (4 or 20 times the minimal inhibitory concentrations) and two inoculum sizes (10' or 106 colony-forming units per ml).The inoculum size had no appreciable effect on the rate of killing of fi-lactamasenegative strains. The rates at which ,B-lactamase-producing strains were killed by chloramphenicoL cefotaxime, and moxalactam were not influenced by the inoculum size. Whereas cefamandole in high concentrations was able to kill at 106 colony-forming units/ml of inoculum, it had only a temporary inhibiting effect at low drug concentrations. Methicillin and the ,-lactamase inhibitor CP-45,899 were able to neutralize the inactivation of cefamandole by a large inoculum of ,-lactamase-producing H. influenzae.