Activity of Three Aminoglycosides and Two Penicillins Against Four Species of Gram-Negative Bacilli

Weinstein, Ralph J.; Young, Lowell S.; Hewitt, William L.

doi:10.1128/aac.7.2.172

Cited by 19 publications

(5 citation statements)

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“…VOL. 11, 1977 ucts Inc., Plainview, N.Y.) (18,20), whereas isolates of P. aeruginosa and other gram-negative bacilli were identified by the use of standard criteria (8,10 (12). None of these gentamicin-resistant isolates is included in data summarized for the agar dilution tests.…”

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confidence: 99%

“…Data made available from Schering Corp. and our initial clinical experience indicate that peak serum levels achieved after administration of 1.5 mg of netilmicin per kg and 2.5 mg intramuscularly usually exceed 4 and 8 ,ug/ml, respectively. To relate results of susceptibility tests to achievable blood levels in humans, we have assessed these results by calculating inhibitory indexes, using a technique previously described (20,21). The inhibitory index refers to the ratio between the mean peak serum levels given above and the MIC for at least twothirds of each species tested.…”

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confidence: 99%

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In Vitro Studies with Netilmicin Compared with Amikacin, Gentamicin, and Tobramycin

Dhawan

Marso²,

Martin³

et al. 1977

Antimicrob Agents Chemother

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Netilmicin, a new semisynthetic aminoglycoside derived by ethylation of the 1-N position of the deoxystreptamine ring of'sisomicin, was tested in vitro with 4,070 strains of gram-negative bacilli isolated at the UCLA Medical Center during 1975 to 1976, using the agar dilution technique and an inoculum of approximately 104 organisms. Results were compared with those simultaneously obtained for amikacin, gentamicin, and tobramycin. Using Mueller-Hinton medium, inhibitory concentrations in broth correlated with those obtained by the agar dilution method except for Pseudomonas aeruginosa, where a 2-to 16-fold difference in susceptibility was noted. For most clinically significantEnterobacteriaceae and P. aeruginosa, the activity of netilmicin in vitro was comparable or superior to that of gentamicin, tobramycin, and amikacin with respect to potency by weight and achievable blood levels. Against gentamicin-resistant strains (MIC > 16 ,ug/ml), the activity of netilmicin paralleled that of amikacin with the exception ofProvidencia stuartii, which was inhibited by amikacin but not by netilmicin.Gram-negative bacilli are responsible for an increasing number of the serious infections occurring in hospitalized patients (3). Gentamicin and other aminoglycoside antibiotics have been used successfully to treat many such infections. Nonetheless, the emergence of resistant gramnegative bacilli in certain clinical settings (5, 7, 9, 13, 16) and toxic side effects of these agents present a serious problem. There are increasing reports of bacterial resistance to gentamicin on the basis of either selection of naturally occurring resistant organisms or spread of highly resistant strains that possess resistance transfer factors (2). This changing pattern of antimicrobial susceptibility serves as a constant stimulus for the development of new antimicrobial agents and for structural modification of existing compounds. For these reasons, the evaluation of a new aminoglycoside antibiotic with a broadened anti-gram-negative bacillary spectrum but with increased potency and relatively less toxicity is an important goal of laboratory and clinical research.Netilmicin (Sch 20569) is a new semisynthetic aminoglycoside antibiotic derived by ethylation of the 1-N position of the deoxystreptamine ring of sisomicin. This synthetic modification has resulted in a compound that is resistant to inactivation by gentamicin adenyltransferase 1 and relatively resistant to gentamicin acetyltransferase 1. Netilmicin possesses no active site for kanamycin phosphotransferase inactivation, but the compound is inactivated by kanamycin acetyltransferase and gentamicin acetyltransferase 2. Preliminary reports (12, 15) have indicted that netilmicin has a broad spectrum of activity against most Enterobacteriaceae and Pseudomonas aeruginosa. In this respect, it resembles the parent compound, sisomicin. Because the biosynthetic reaction that has yielded netilmicin is similar to the process by which amikacin was derived from kanamycin A, we were particularly interes...

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In Vitro Studies with Netilmicin Compared with Amikacin, Gentamicin, and Tobramycin

Dhawan

Marso²,

Martin³

et al. 1977

Antimicrob Agents Chemother

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“…Early clinical investigation with netilmicin indicates that the blood levels achieved are equal to or greater than those achieved with gentamicin, which it closely resembles pharmacologically (L. S. Young, personal communication, 1976). This study was designed to compare the in vitro effectiveness ofnetilmicin with other aminoglycosides currently licensed or under clinical investigation, i.e., amikacin (8,9,11,12,15,19,20), sisomicin (8,9,20), and tobramycin (8,9,13,20 (6,10). Freezethaw extraction of the agar media was performed.…”

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confidence: 99%

In Vitro Susceptibility of Gentamicin-Resistant Enterobacteriaceae and Pseudomonas aeruginosa to Netilmicin and Selected Aminoglycoside Antibiotics

Meyer

Kraus²,

Pasiecznik³

1976

Antimicrob Agents Chemother

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Netilmicin (Sch 20569), a semisynthetic aminoglycoside related to gentamicin C 1a , was evaluated in vitro in agar dilution testing against 224 different clinical isolates of gentamicin-resistant Enterobacteriaceae and Pseudomonas aeruginosa in parallel with amikacin, gentamicin, sisomicin, and tobramycin. Netilmicin showed a very high degree of activity against gentamicin-resistant organisms, but amikacin was more active in vitro, particularly against Providencia stuartii and P. aeruginosa . Sisomicin and tobramycin were consistently less active than either netilmicin or amikacin. Netilmicin was bactericidal in broth testing against P. aeruginosa . Netilmicin showed a greater difference between results with agar and broth dilution testing than did amikacin.

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“…On the right side of the maximum with ticarcillin still 25(,/o of the strains are found with lower MICs; with ticarcillin and gentamicin 45°/o are found on the right side, and combined with tobramycin even 71%. Regarding the gentamicin resistant strains (table I) it can be stated that out of 15,6 are resistant also to tobramycin, but only 2 to ticarcillin. In combination with gentamicin and even more with tobramycin the MICs are lowered by about a third to a tenth.…”

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“…These data are comparable with the MIC values to be found in the literature. However, the data using Isotonic Sensitest Broth may be more relevant clinically and more realistic than using the other media [8,15].…”

Section: Discussionmentioning

confidence: 99%

Antibacterial Activity of Ticarcillin, Tobramycin and Gentamicin alone and in Combination against <i>Pseudomonas aeruginosa in vitr</i><i>o</i>

Ullmann¹

1977

Chemotherapy

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Using the biophotometer with ticarcillin no persistent bactericidal effect was found against Pseudomonas aeruginosa NCTC 10490. After addition of 1.2 µg/ml gentamicin an increase of multiplication of bacteria was observed, but not after 1.2µg/ml tobramycin. With 6.2µg/ml ticarcillin and 1.2µg/ml tobramycin bactericidal effects lasted more than 24 h. In tube dilution test with Isotonic Sensi-test Broth out of 109 examined strains 51% were resistant to gentamicin, 16% to tobramycin and 4.5% to ticarcillin. If MIC values of gentamicin and tobramycin were calculated for magnesium-free media the resistance rate would be 10% for gentamicin and 3% for tobramycin. Combining subinhibitory doses of gentamicin or tobramycin with ticarcillin, most of the strains resistant to gentamicin and tobramycin became susceptible. The rate of inactivation of tobramycin by ticarcillin depends on the fluid into which they are placed. In combination therapy both antibiotics should be applied separately and immediately one after the other.

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Activity of Three Aminoglycosides and Two Penicillins Against Four Species of Gram-Negative Bacilli

Cited by 19 publications

References 19 publications

In Vitro Studies with Netilmicin Compared with Amikacin, Gentamicin, and Tobramycin

In Vitro Studies with Netilmicin Compared with Amikacin, Gentamicin, and Tobramycin

In Vitro Susceptibility of Gentamicin-Resistant Enterobacteriaceae and Pseudomonas aeruginosa to Netilmicin and Selected Aminoglycoside Antibiotics

Antibacterial Activity of Ticarcillin, Tobramycin and Gentamicin alone and in Combination against <i>Pseudomonas aeruginosa in vitr</i><i>o</i>

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