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

Netilmicin and gentamicin susceptibilities of 258 gram-negative organisms and 25 strains of Staphylococcus aureus were nearly identical. The pharmacokinetic properties of netilrnicin were evaluated in 101 newborn infants and related to birth weight, gestational age, chronological age, and route of administration. Mean peak serum concentrations of 5.6 to 6.9 and 7.8 to 8.4 ,ug/ml were observed 30 min after 3-and 4-mg/kg doses, respectively, were given intramuscularly. The peak concentrations were directly related to gestational age. The average serum half-life values varied from 3.4 to 4.7 h and in general were inversely related to birth weight, gestational age, and postnatal age. The pharmacokinetics of netilmicin in 10 infants were similar after intramuscular and intravenous administration. A comparative study of netilmicin and gentamicin in seven neonates revealed greater variability in serum concentrations of gentamicin and a shorter half-life for netilmicin. There was evidence of accumulation of netilmicin in 12 low-birth weight, premature infants who received 4-mg/kg doses for an average of 6.4 days. Serum and urine levels of netilmicin were measured up to 11 days after discontinuation of the drug. These data are well characterized by a two-compartment model. Additional studies of efficacy and long-term toxicity of netilmicin in neonates are necessary.Netilmicin is a new semisynthetic aminoglycoside that is a 1-N-ethyl sisomicin derivative produced by Micromonospora inyoensis. Its antimicrobial spectrum is similar to that of gentamicin with an added advantage that an increasing number of Enterobacteriaceae possess adenylating enzymes mediating resistance to gentamicin, but not to netilmicin (4,10,16,21,28). Animal studies indicate that substantially less ototoxicity and nephrotoxicity result from repeated doses of netilmicin than of gentamicin (9,12,16). In an experimental rabbit model ofEscherichia coli meningitis, netilmicin has also been shown to have greater bactericidal activity in cerebrospinal fluid' than does gentamicin (24). These observations suggest that netilmicin may be potentially useful for therapy of neonatal bacterial infections.In this study we have evaluated the pharmacokinetics of netilnicin in 101 neonates and related these properties to birth weight, gestational age, chronological age, and route of administration. We have also measured netilmicin in serum and/or urine for as long as 12 days after discontinuation of therapy and have fit these data to a two-compartment model as has been described for aminoglycosides in older children and adults (3,17,20,25,30). MATERIALS AND METHODSSusceptibility studies. The susceptibilities to gentamicin and netilmicin of 258 gram-negative organisms and 25 Staphylococcus aureus strains isolated from blood, cerebrospinal fluid, or urine of sick neonates and from rectal culture of normal newborns were determined by a modified agar plate dilution method (1) with a multiple inoculating apparatus (27). Serial twofold dilutions of laboratory standards of net...

Section: Resultsmentioning

confidence: 99%

Pharmacokinetic Properties of Netilmicin in Newborn Infants

Siegel

McCracken

Thomas

et al. 1979

“…However, cephalothin plus netilmicin resulted in a 4 to 8-fold and 4 to 32-fold enhancement of the antibacterial activity of cephalothin and netilmicin, respectively. Not noted in Table 3 (5,7,14). However, organisms resistant to gentamicin have been frequently less susceptible to netilmicin than to amikacin (7,13), as demonstrated in this study.…”

mentioning

confidence: 49%

“…Synergistic activity could be demonstrated in vitro with combinations of cephalothin plus netilmicin, at concentrations achievable in serum (5,15), and with TMP plus SMZ. With the latter two agents, synergism occurred at concentrations barely attainable in blood (8).…”

mentioning

confidence: 99%

Outbreak of Multiply Drug-Resistant Proteus mirabilis Originating in a Surgical Intensive Care Unit: In Vitro Susceptibility Pattern

Yoshikawa

Shibata

Chow

et al. 1978

A multiply drug-resistant strain of Proteus mirabilis was isolated from 14 patients on a surgical service. Antimicrobial susceptibility studies demonstrated that the organism was highly resistant to numerous antibiotics, including gentamicin, tobramycin, and sisomicin. The organism was susceptible in vitro to amikacin but had low-level resistance to netilmicin. In vitro susceptibility studies with combinations of cephalothin with netilmicin and trimethoprim with sulfamethoxazole showed these drugs to be synergistic. Other drug combinations failed to act synergistically.

“…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). Although active in vitro against many gentamicin-resistant bacilli, netilmicin is less active than amikacin against gentamicin-resistant P. aeruginosa and P. stuartii (4,17). 17,1980 Our in vitro data for pretherapy organisms (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…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).…”

mentioning

confidence: 99%

Prospective comparative study of efficacy and toxicity of netilmicin and amikacin

Bock¹,

Edelstein²,

Meyer³

1980

Eighty patients were treated with either amikacin or netilmicin in a prospective randomized study of serious gram-negative bacillary infections, including 11 due to gentamicin-resistant pathogens. Thirty-six treated with netilmicin and 35 treated with amikacin were evaluable for efficacy or toxicity, or both. The overall groups differed significantly only in age. There were no significant differences in efficacy of the two drugs. There were no statistically significant differences at the 95% level between the netilmicin group and the amikacin group with respect to nephrotoxic reactions (38 versus 28%, respectively) or ototoxic reactions (9 versus 25%, respectively). Further comparative trials of netilmicin and other aminoglycosides appear warranted before it is widely used.