In Vitro Activity of Gentamicin, Amikacin, and Netilmicin Alone and in Combination with Carbenicillin Against Serratia marcescens

Abstract

The inhibitory and bactericidal effects of gentamicin, amikacin, netilmicin (Sch 20569) (MBC 212.5 ,ug/ml). (ii) Most of the 11 isolates with moderate resistance to gentamicin (MBC of 12.5 to 25 ,g/ml) were also susceptible to carbenicillin and resistant to netilmicin. (iii) The 17 isolates with high-level resistance to gentamicin (MBC -50 ,ug/ml) were all highly resistant to carbenicillin (MBC .8,000 ,ug/ml) but susceptible to netilmicin (MBC s6.25 ,ug/ml). The susceptibility to amikacin was unpredictable among these groups of isolates but, overall, 80% of the isolates were killed by 25 ,ug of amikacin/ml, which is within the range of peak serum concentrations used therapeutically. Clinically attainable subinhibitory concentrations of carbenicillin enhanced the activity of the three aminoglycosides against all isolates with MBCs of carbenicillin -2,000 ,ug/ml. The 17 isolates with high-level resistance to carbenicillin and gentamicin, as well as the four isolates with high-level resistance to carbenicillin but not to gentamicin, were not susceptible to such enhancement of aminoglycoside activity by carbenicillin.

Prospective comparative study of efficacy and toxicity of netilmicin and amikacin

“…DISCUSSION An aminoglycoside is usually required for initial therapy of nosocomial suspected or known gram-negative bacillary infection. Two factors to consider are the risk of adverse reactions and the high prevalence of resistance to gentamicin noted in some institutions (18)(19)(20)23). Gentamicin and amikacin have been equally effective with susceptible pathogens and with no differences in toxicity in a double-blind study (27), but amikacin is considered for initial therapy where there is a significant risk of gentamicin resistance (18)(19)(20).…”

“…Mean 1-h peak netilmicin level was 7.4 ,ug/ml ± 4.0, and mean valley level was 3.0 ,ug/ml ± 3.6. Predictable levels were attained initially in most patients by use of calculated creatinine clearances and the nomograms (21)(22)(23) Fig. 1.…”

“…Netilmicin is a new aminoglycoside active in vitro against a wide variety of Enterobacteriaceae and Pseudomonas aeruginosa (4,12,17,21,23,24). It is resistant to two of the enzymes that inactivate gentamicin (17,21) and has significantly less ototoxicity (19) and nephrotoxicity than gentamicin in experimental animals (7,13,15).…”

Effect of Clavulanic Acid on the In Vitro Synergism Between Carbenicillin and Gentamicin Against Serratia marcescens

“…This situation and the low toxic-therapeutic ratio of aminoglycoside antibiotics prompted the evaluation in our laboratory of the synergistic activity between carbenicillin and various aminoglycoside antibiotics against this organism (3). Of the 55 clinical isolates evaluated, 21 were highly resistant to carbenicillin, with minimum bactericidal concentrations (MBCs) 2 8,000 ,ug/ml.…”

“…The final titer of Serratia was approximately 106 bacteria per ml, and the final concentration of clavulanic acid, when present, was 5,ug/ml. The MIC and MBC were as defined previously (3).…”