Correlation of Netilmicin Agar Dilution and Disk Diffusion Susceptibilities

Abstract

A study of 283 isolates of gram-negative bacilli revealed a good correlation (r = -0.74) between disk diffusion zones of inhibition and agar dilution minimal inhibitory concentrations. Regression analysis suggested that strains with zone sizes 11 mm should be considered resistant, but 34 of 45 strains resistant by minimal inhibitory concentration (including 27 strains ofPseudomonas aeruginosa) would have been called susceptible using this break point.Netilmicin (Sch 20569), the 1-N-ethyl derivative of sisomycin, is a new aminoglycoside with a pharmacokinetic profile similar to that of gentamicin (8). Netilmicin has been reported to have considerable activity against gram-negative clinical isolates (2,3,5,6,(8)(9)(10) and to be effective against some gentamicin-resistant strains (3,(7)(8)(9). This in vitro study evaluates the correlation between netilmicin agar dilution minimal inhibitory concentrations (MICs) and disk diffusion zone diameters.Two hundred eighty-three clinical isolates of gram-negative bacilli were studied: 69 strains of Pseudomonas aeruginosa, 6 strains ofPseudomonas sp., 20 strains of indole-positive Proteus, 28 strains of Enterobacter, 64 strains of Klebsiella, 10 strains of Serratia, 10 strains of Citrobacter, and 76 strains of Escherichia coli. MICs were performed by the agar dilution method as recommended by the International Collaborative Study of the World Health Organization (4). Bacteria were grown overnight in Mueller-Hinton broth (BBL). Serial twofold dilutions of the antibiotics to be tested were prepared in Mueller-Hinton agar (BBL). The Mueller-Hinton agar plates were inoculated with approximately 104 organisms using a Steers replicator. Plates were read after 24 h of incubation at 37C. Gentamicin resistance was defined as an MIC 58 ,ug/ml. Disk diffusion susceptibility testing was performed according to the method of Bauer et al.(1) using a 10-,.g netilmicin disk. Correlation between netilmicin zone diameters and MICs was examined by linear regression analysis. Netilmicin sulfate and netilmicin sulfate disks were supplied by the Schering Corp. There was good correlation between log2 MICs for netilmicin obtained by the agar dilution technique and zone diameters obtained by the Bauer-Kirby method. The linear regression curve for all 283 strains is shown in Fig. 1

Antibiotic Pharmacokinetics in Cystic Fibrosis

“…McNeill et al (1984) reported that 87% of P. aeruginosa collected from 5 centres were amikacin resistant. Goldmann et al (1977) found P. aeruginosa isolated primarily from cystic fibrosis patients had a unimodal distribution of susceptibility to netilmicin in the range of 0.5 to 128 mg/L with the median being 8 mg/L. These data suggest that half the strains would be netilmicin resistant.…”

Quality control parameters for susceptibility tests with 30-micrograms netilmicin disks

“…Disk diffusion tests for determining susceptibility to netilmicin have been evaluated (1,(3)(4)(5) and 30-tLg disks have been recommended (5). A controlled three-laboratory study has been performed to define quality control parameters for tests with 30-,ug netilmicin disks (Schering Corp., data on file).…”