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PubMed1993

The in-vivo activity of co-amoxiclav with netilmicin against experimental methicillin and gentamicin resistant Staphylococcus epidermidis infection in rabbits.

This study compared co-amoxiclav, vancomycin and teicoplanin with and without netilmicin or amikacin for treating experimental subcutaneous fibrin-clot infection in rabbits due to a clinical beta-lactamase-positive methicillin- and gentamicin-resistant Staphylococcus epidermidis strain (MGRSE). MICs (mg/L) for this strain were: oxacillin 125, gentamicin 32, vancomycin 4, teicoplanin 8, netilmicin 1, amikacin 4, amoxycillin 64 with clavulanate at 2 mg/L. In rabbits treated with a single-dose i.v. regimen (netilmicin 8 mg/kg, amikacin 20 mg/kg, vancomycin 30 mg/kg, teicoplanin 15 mg/kg, co-amoxiclav 150-30 mg/kg), the bacterial count 24 h post-dose was reduced whatever the combination used (ANOVA, P < or = 0.001). Regimens were statistically classified in decreasing order of efficacy as follows: co-amoxiclav combined with netilmicin > vancomycin either alone or combined with either netilmicin or amikacin, teicoplanin with netilmicin > netilmicin and co-amoxiclav alone > teicoplanin or co-amoxiclav combined with amikacin, and teicoplanin alone > amikacin > no drug. From these findings, it is concluded that: co-amoxiclav could be useful for the treatment of beta-lactamase-positive and methicillin-resistant S. epidermidis infection; some enzyme-resistant aminoglycoside could be considered for treating gentamicin-resistant but netilmicin/amikacin-sensitive S. epidermidis infection; the combination of co-amoxiclav with netilmicin was synergistic and more rapidly bactericidal than vancomycin in this animal model.

Amoxicillin↗

PubMed1979

Pharmacokinetic properties of netilmicin in newborn infants.

Netilmicin and gentamicin susceptibilities of 258 gram-negative organisms and 25 strains of Staphylococcus aureus were nearly identical. The pharmacokinetic properties of netilmicin 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 mug/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.

Bacteria↗

PubMed2000

In vitro synergistic effects of double and triple combinations of beta-lactams, vancomycin, and netilmicin against methicillin-resistant Staphylococcus aureus strains.

Several studies have previously reported synergistic effects between vancomycin and a given beta-lactam or a given aminoglycoside against methicillin-resistant Staphylococcus aureus (MRSA) strains. The aim of our study was to exhaustively compare the effects of different combinations of a beta-lactam, vancomycin, and/or an aminoglycoside against 32 clinical MRSA strains with different aminoglycoside susceptibility patterns. The effects of 26 different beta-lactam-vancomycin and 8 different aminoglycoside-vancomycin combinations were first studied using a disk diffusion screening method. The best interactions with vancomycin were observed with either imipenem, cefazolin, or netilmicin. By checkerboard studies, imipenem-vancomycin and cefazolin-vancomycin each provided a synergistic bacteriostatic effect against 22 strains; the mean fractional inhibitory concentration (FIC) indexes were 0.35 and 0.46 for imipenem-vancomycin and cefazolin-vancomycin, respectively. The vancomycin-netilmicin combination provided an indifferent effect against all of the 32 strains tested; the mean of FIC index was 1. 096. The mean concentrations of imipenem, cefazolin, netilmicin, and vancomycin at which FIC indexes were calculated were clinically achievable. Killing experiments were then performed using imipenem, cefazolin, netilmicin, and vancomycin at one-half of the MIC, alone and in different combinations, against 10 strains. The vancomycin-netilmicin regimen was rarely bactericidal, even against strains susceptible to netilmicin. The imipenem-vancomycin and cefazolin-vancomycin combinations were strongly bactericidal against six and five strains, respectively. The addition of netilmicin markedly enhanced the killing activity of the combination of cefazolin or imipenem plus vancomycin, but only for the MRSA strains against which the beta-lactam-vancomycin combinations had no bactericidal effect. It is noteworthy that the latter strains were both susceptible to netilmicin and heterogeneously resistant to methicillin.

Anti-Bacterial Agents↗

PubMed1978

Netilmicin: a review of toxicity in laboratory animals.

The data on the toxicity of netilmicin in laboratory animals as well as preliminary data in man are reviewed. Netilmicin is less toxic to the VIIIth nerve than is gentamicin in all species tested. The data suggest that it probably is less ototoxic than tobramycin, although confirmatory studies should be performed. Netilmicin is also nephrotoxic than gentamicin in all species tested. It is less nephrotoxic than tobramycin in the rat and dog. Comparisons in the rat suggest that netilmicin has a flat dose--response curve that resembles the curve produced by streptomycin. In animals, netilmicin produces more neuromuscular blockade than gentamicin; however, neuromuscular blockade with aminoglycosides in man is rare and thus far no episodes have been associated with netilmicin during clinical investigation. Initial clinical studies in man indicate that netilmicin is efficacious and well tolerated. Presently available data suggest that netilmicin offers distinct advantages over older aminoglycosides. Final conclusions must await prospective randomized double-blind trials in man.

Abnormalities, Drug-Induced↗

PubMedDate not supplied

Aspects on the ototoxic potential of netilmicin.

The organ culture system using the 16th gestational day inner ear explant from fetal mice was used for ototoxicity screening of netilmicin. Organ cultures were incubated in 1, 10, 100 and 1000 micrograms/ml, respectively, of netilmicin base in the nutrient solution. After constant exposure to the drug during 5 days, the inner ears (N = 56) were analyzed morphologically at the light and electron microscopic levels. All specimens were serially sectioned. Exposure to 1 and 10 micrograms/ml of netilmicin base, doses that are reached during in vivo conditions in man, did not cause morphological damage to hair cells as observed in the light microscope at the end of the 5-day period. At the ultrastructural level, minor changes characteristic for aminoglycosides occurred in hair cell mitochondria. Incubation with 100 and 1000 micrograms/ml of netilmicin base caused morphological changes in many types of epithelia and not only in vestibular hair cells. This indicates a general sign of toxicity of netilmicin in these doses. The dose response relationship with regard to inner ear pathology was obvious in the vestibular part of the labyrinth. In the cochlea, however, few cytological changes occurred independent of dose. As compared with gentamicin, exposure in the same concentrations as in the present study and under similar experimental conditions, the less ototoxic effect of netilmicin was obvious. The results of the present study indicate that the less ototoxic potential of netilmicin as compared with other aminoglycosides is probably due to the drug itself and not primarily due to a poor penetration of netilmicin into the inner ear.

Animals↗

PubMed1980

The nephrotoxic potential of netilmicin as determined in a rat model.

The nephrotoxicity of netilmicin, an ethyl derivative of a dehydrogenated Cla gentamicin, was studied in Sprague-Dawley rats. Netilmicin toxicity was initially compared to gentamicin toxicity at equal doses across a broad range. These studies indicated that netilmicin was significantly less toxic than gentamicin. Netilmicin, gentamicin, tobramycin, amikacin, kanamycin, streptomycin, and sisomicin were then given to groups of rats at three dosage levels corresponding to 10, 15 or 25 times the recommended human dose on a weight basis daily for 15 days. Decreased urine osmolality, increased excretion of protein and Beta-n-acetyl hexosaminidase were dose related features of nephrotoxicity. All aminoglycosides accumulated in renal tissue. Streptomycin and netilmicin exhibited a flat dose response curve with respect to histologic damage, as compared to the other drugs. The examination of creatinine clearance and renal tissue suggested the following order of increasing toxicity: (1) controls, (2) streptomycin, (3) netilmicin, (4) tobramycin, (5) sisomicin, amikacin, and kanamycin, and (6) gentamicin. To assess the effect of non-aminoglycoside antibiotics on netilmicin nephrotoxicity, ampicillin, methicillin, carbenicillin, cefamandole, and clindamycin were given to groups of rats receiving netilmicin at either of two doses. These studies suggested that the nephrotoxicity was not affected by the administration of non-aminoglycoside antibiotics.

Aminoglycosides↗

PubMed1977

In vitro activity of netilmicin, gentamicin, and amikacin.

The in vitro activity of netilmicin (Sch 20569), a new semisynthetic derivative of gentamicin, was compared with that of gentamicin and amikacin. One hundred and ninety-two clinical isolates of Enterobacteriaceae, Pseudomonas aeruginosa, and Staphylococcus aureus were tested using both agar and broth dilution techniques. Netilmicin was comparable to gentamicin, with the following exceptions: (i) for Serratia marcescens and P. aeruginosa, gentamicin was more active than netilmicin; (ii) all strains of Escherichia coli, Klebsiella, Enterobacter, Proteus mirabilis, and Citrobacter freundii, which were resistant to gentamicin, were susceptible to netilmicin; (iii) some strains of S. marcescens, indole-positive Proteus, and Providencia, which were resistant to gentamicin, were susceptible to netilmicin. Netilmicin was more active than amikacin for all Enterobacteriaceae and S. aureus and equal to amikacin in activity against gentamicin-susceptible strains of P. aeruginosa. All strains of P. aeruginosa, resistant to gentamicin, were also resistant to netilmicin but were susceptible to amikacin. Minimal inhibitory concentrations (MICs) obtained with broth and agar showed no significant differences except for P. mirabilis, where broth MICs were twofold greater than agar MICs, and for P. aeruginosa, where agar MICs were twofold higher than broth MICs. The minimal bactericidal concentration (MBC) was either identical to or within one twofold dilution of the MIC for the strains tested. A 100-fold increase in inoculum size produced less increase in MIC and MBC with netilmicin than with gentamicin or amikacin.

Amikacin↗

PubMed2006

Adsorptive stripping voltammetric determination of netilmicin in the presence of formaldehyde.

A linear sweep adsorptive stripping voltammetric method for the determination of netilmicin in the presence of formaldehyde has been proposed for the first time. In the presence of 3.0 x 10(-3) g ml(-1) formaldehyde, netilmicin exhibits a sensitive cathodic peak at -1.30 V (vs. the saturated calomel electrode, SCE) in a medium of Britton-Robinson buffer (pH 8.7) with a scan rate of 100 mV s(-1) after a preconcentration period of 120 s at -1.10 V (vs. SCE). The peak current showed a linear dependence on the netilmicin concentration over the range 4.2 x 10(-9)-1.0 x 10(-7) g ml(-1). The achieved limits of detection and quantitation were 1.0 x 10(-10) and 3.3 x 10(-10) g ml(-1) netilmicin, respectively. It was deduced from the experiments that the amine-aldehyde condensation product formed between netilmicin and formaldehyde is mainly responsible for the appearance of the peak. The electrochemical behavior of netilmicin in the presence of formaldehyde has been studied. The method was applied to the direct determination of netilmicin in injectable formulations and spiked human urine and serum samples.

Adsorption↗

PubMed2006

Pharmacokinetics of a netilmicin loading dose on the first postnatal day in preterm neonates with very low gestational age.

OBJECTIVE: Pharmacokinetic parameters are important for dose adjustment of aminoglycosides, but they are highly variable in neonates. In this study the pharmacokinetics of a netilmicin loading dose was investigated on the first postnatal day in preterm neonates with very low gestational age (GA). METHODS: In an open prospective study, 20 neonates with GA between 22.9 and 32.0 weeks and suspected postnatal bacterial infection received an intravenous loading dose of 5 mg/kg netilmicin over 1 h during the first postnatal day. Netilmicin serum concentrations were determined by an enzyme multiplied immunoassay. RESULTS: The systemic clearance of netilmicin normalized to body weight (BW) was not significantly different in three GA subgroups (0.59+/- 0.02 ml/min/kg for GA <24 weeks, 0.72+/-0.14 ml/min/kg for GA 24-27 weeks, and 0.62+/-0.19 ml/min/kg for GA 27-32 weeks, P=0.123). Similar results were also obtained for serum elimination half-time and for the distribution volume normalized to BW. Multiple regression analysis showed that systemic clearance and volume of distribution (both not normalized to BW) significantly correlated with BW (P<0.0001) but not with GA. In the entire group, 20% of peak concentrations were below the target of 6 mg/l, and 63% of trough concentrations were above the target of 2 mg/l. CONCLUSION: In neonates with very low GA, the pharmacokinetic parameters of netilmicin determined after an intravenous loading dose were not dependent on GA when normalized to BW. A number of neonates did not reach targeted peak and trough netilmicin serum concentrations, suggesting that a higher loading dose and a prolonged dosing interval might enhance the effectiveness and safety of netilmicin in preterm neonates immediately after birth.

Anti-Bacterial Agents↗

PubMed1989

Prospective study of amikacin versus netilmicin in the treatment of severe infection in hospitalized patients.

PURPOSE: Four previous studies comparing netilmicin and amikacin have yielded inconclusive results concerning efficacy and rates of nephrotoxicity and ototoxicity. For this reason, we conducted a prospective, randomized, controlled trial of the two drugs in the treatment of hospitalized patients with severe infection. PATIENTS AND METHODS: A total of 202 patients were enrolled in the study; 100 received netilmicin and 102 received amikacin. Concomitant antimicrobials were restricted to metronidazole and benzylpenicillin. Peak and trough aminoglycoside levels were assayed within the first 36 hours and at least every 72 hours thereafter. A full blood cell count, serum electrolytes, creatinine, bilirubin, and liver enzymes were measured before therapy, weekly thereafter, and within 48 hours after the discontinuation of therapy. Nephrotoxicity and ototoxicity were assessed in patients. A standard agar dilution procedure was used to determine minimal inhibitory concentrations. RESULTS: No significant pretreatment differences were found between the two groups. Patients in the amikacin group responded significantly better to treatment than did patients in the netilmicin group (90% versus 79%; p less than 0.05). A notable finding was the markedly inferior response rate of Pseudomonas aeruginosa infections to netilmicin as compared with amikacin (13 of 24 with a favorable response compared with 25 of 26). No significant difference in ototoxicity was found, whereas nephrotoxicity appeared to be significantly less with amikacin (4% versus 12%, p less than 0.05). Although amikacin seemed less nephrotoxic than netilmicin, this may have been related to the significantly greater number of patients with initial renal dysfunction who received netilmicin. CONCLUSIONS: Amikacin appears to be significantly more efficacious than netilmicin for the treatment of P. aeruginosa infections, especially those in non-urinary tract sites. There is no apparent difference between the two drugs in terms of ototoxicity.

Acute Disease↗

PubMed2003

Effects on adhesiveness and hydrophobicity of sub-inhibitory concentrations of netilmicin.

The effect of sub-inhibitory concentrations (SICs) of netilmicin on bacterial hydrophobicity and adhesiveness to conjunctival cells was investigated. One strain each of Pseudomonas aeruginosa, Pseudomonas spp., Staphylococcus aureus and S. epidermidis was investigated for its susceptibility to netilmicin, its adherence to conjunctival cells and to the effect of hydrocarbon hexadecane before and after treatment with SIC of netilmicin. All of the bacteria tested were susceptible to netilmicin except for Pseudomonas spp. which showed intermediate resistance. Netilmicin-treated Pseudomonas strains exhibited a lower level of hydrophobicity towards n-hexadecane compared with non-treated strains, while netilmicin-treated S. epidermidis and S. aureus showed a slight increase of hydrophobicity. Adherence of the two Pseudomonas strains to conjunctival cells was significantly reduced after growth in the presence of netilmicin, while the adherence of the two staphylococci was only slightly reduced.

Alkanes↗

PubMed1986

Comparative bactericidal activity of penicillin-netilmicin and penicillin-gentamicin against enterococci.

The synergistic bactericidal activity of netilmicin in combination with penicillins was compared with that of gentamicin and streptomycin against 16 clinical isolates of enterococci. In a macrodilution chessboard assay against multiple combinations of penicillin, gentamicin and netilmicin, bactericidal activity uniformly occurred at two- to four-fold lower concentrations of penicillin + netilmicin than with penicillin + gentamicin. With four strains, penicillin + netilmicin produced up to ten-fold greater killing than penicillin + gentamicin after 6 h of incubation. With one strain, 3 X log10 greater killing occurred with netilmicin after 24 h. Netilmicin was two- to four-fold more active than gentamicin when combined with penicillinase-resistant penicillins. The bactericidal activity of netilmicin against enterococci is equal to or greater than that of gentamicin, either alone or when combined with penicillins.

Drug Synergism↗

PubMed1991

Ionic binding, adaptive resistance and post-antibiotic effect of netilmicin and ciprofloxacin.

Ionic binding, post-antibiotic effect (PAE) and adaptive resistance to netilmicin and ciprofloxacin were investigated in 11 distinct clinical isolates. Both netilmicin and ciprofloxacin showed concentration dependent kill and PAE when bacteria were exposed to these antibiotics at 37 degrees C. The effects of netilmicin were maintained at 4 degrees C, when there is no energy dependent cell uptake of antibiotic, but were partially inhibited by exposure to NaCl and EDTA although not by Ca++. This supports the concept that ionic binding to the bacterial cell wall is important in the initial uptake of netilmicin. Ciprofloxacin showed no such effects at 4 degrees C. Adaptive resistance (reduced bacterial kill on second exposure) occurred with both netilmicin and ciprofloxacin but was seen more frequently with netilmicin. It persisted longer than classical PAE but, even after continuous exposure, was not enough to suggest a loss of kill with a twice daily dosing regimen of netilmicin or ciprofloxacin.

Ciprofloxacin↗

PubMed1991

Pharmacokinetic and toxicological evaluation of a once-daily regimen versus conventional schedules of netilmicin and amikacin.

The safety and pharmacokinetics of netilmicin (6.6 mg/kg) and amikacin (14.5 mg/kg) once daily (od) have been compared to their corresponding conventional schedules thrice daily (tid), and twice daily (bd), in patients (20 per group) suffering from pelvic inflammatory disease. Sensitive criteria of early renal and auditory alterations, namely urinary excretion of phospholipids and audiometry over a wide frequency range (0.25-18 kHz), respectively, were used. The first criterion (phospholipiduria) was validated by an animal study which demonstrated that rats receiving poly-L-aspartic acid, which protects against gentamicin-induced nephrotoxicity, are also protected against renal phospholipidosis and phospholipiduria caused by this antibiotic. On that basis, netilmicin od was better tolerated than netilmicin tid. Amikacin caused less phospholipiduria than netilmicin, and, given od, resulted in little increase over baseline (95% CI, 95-147% increase). Reduction in threshold by greater than or equal to 15 dB for frequencies between 10-18 kHz occurred in nine of 19 patients receiving netilmicin tid compared with three or four of 19 or 20 patients treated with netilmicin od or amikacin (od or bd). However, changes at lower frequencies (0.25-8 kHz) were infrequent with all regimens (from 0/19 to 2/20). In conclusion, these very sensitive tests of nephro- and oto-toxicity suggest that od dosing of amikacin or netilmicin is, if anything, safer than bd or tid dosing.

Adult↗

PubMed1995

Ototoxicity and nephrotoxicity of gentamicin vs netilmicin in patients with serious infections. A randomized clinical trial.

In the treatment of serious infection by aminoglycoside antibiotics multiple daily treatment with netilmicin is considered to be the least toxic. Studies comparing netilmicin with gentamicin using the less toxic once-daily schedule are lacking. A randomized prospective study was designed to evaluate the efficacy and toxicity of once-daily netilmicin with gentamicin treatment in patients with serious infections. Consecutive patients with serious infections were randomized between gentamicin 4 mg/kg q24h iv or netilmicin 5.5 mg/kg q24h iv. Exclusion criteria were neutropenia or severe renal failure. A good clinical response was observed in 50 of the 54 evaluable patients (92.6%) treated with gentamicin and in 48/52 (92.3%) netilmicin treated patients. Nephrotoxicity developed in 5/72 (6.9%) gentamicin patients and in 10/69 (14.5%) treated with netilmicin. Audiometry was performed with high-frequency audiometry when possible; no significant differences were found between the two aminoglycosides. We conclude that with once-daily treatment no benefit of netilmicin over gentamicin regarding nephro- or ototoxicity could be demonstrated.

Adolescent↗

PubMed1999

Antibiotic susceptibility of blood culture isolates after nearly two decades with netilmicin and ampicillin in neonatal septicaemia.

The aim of the study was to investigate the in vitro antibiotic susceptibility of blood culture isolates after almost 20 years with ampicillin and methicillin as empirical treatment for neonatal septicaemia. All blood culture isolates and their antibiograms obtained in a single tertiary neonatal intensive care unit from 1 January 1989 to 31 December 1994 were reviewed. Two hundred and six blood cultures from 181 infants containing 223 bacterial and 11 fungal isolates were identified during 4416 admissions. Fifteen (6.7%) of the bacterial isolates were resistant to ampicillin and netilmicin. Fourteen per cent of the staphylococcal spp. were susceptible to penicillin while more than 90% were susceptible to netilmicin. The coagulase-negative staphylococci (CONS) were resistant to netilmicin, methicillin and gentamicin in 12%, 49% and 65%, respectively. Eighty-nine per cent of the methicillin-resistant CONS were susceptible to netilmicin as opposed to 17% to gentamicin (p<0.001). Except for one strain of Acinetobacter sp., all Gram-negative bacteria were susceptible to netilmicin. Our data show that the ampicillin-netilmicin combination still provides a high in vitro coverage (93%) against bacteria identified in blood cultures from newborns in our unit. Netilmicin has a significantly better in vitro effectiveness against CONS than gentamicin.

Ampicillin↗

PubMed1990

Effect of concomitant administration of piperacillin on the dispositions of netilmicin and tobramycin in patients with end-stage renal disease.

The effect of piperacillin administration on the dispositions of netilmicin and tobramycin was assessed in 12 chronic hemodialysis patients. Six subjects each received netilmicin (2 mg/kg) or tobramycin (2 mg/kg) alone and in combination with piperacillin (4 g every 12 h for four doses). Subjects also received a single dose of piperacillin (4 g) on a separate occasion. The serum concentration-versus-time profiles of netilmicin and tobramycin were biexponential. The terminal elimination half-life (t1/2 beta) of tobramycin was markedly reduced (59.62 +/- 25.18 [mean +/- standard deviation] versus 24.71 +/- 5.41 h) and total body clearance (CLP) was significantly increased in the presence of piperacillin (3.45 +/- 1.61 versus 7.16 +/- 1.64 ml/min). In contrast, the t1/2 beta (41.80 +/- 13.24 versus 40.07 +/- 10.37 h) and CLP (5.11 +/- 2.15 versus 5.55 +/- 2.32 ml/min) of netilmicin were not significantly altered when netilmicin was administered in combination with piperacillin. No change in the central or steady-state volume of distribution of netilmicin or tobramycin was observed. The disposition of piperacillin in hemodialysis patients was not altered in the presence of either aminoglycoside antibiotic. Although no adjustment in netilmicin dosing is required, tobramycin should be administered more frequently when given concomitantly with piperacillin to hemodialysis patients to avoid prolonged periods of subtherapeutic concentrations.

Adult↗

PubMed1995

Vancomycin or vancomycin plus netilmicin for methicillin- and gentamicin-resistant Staphylococcus aureus aortic valve experimental endocarditis.

Using a rabbit model of aortic valve endocarditis, we studied the efficacy of vancomycin alone or in combination with netilmicin and/or rifampin against a methicillin- and gentamicin-resistant strain of Staphylococcus aureus (MGRSA). Antibiotics were given for 6 to 12 days, as follows: vancomycin (15 mg/kg of body weight every 12 h [BID] intravenously), vancomycin plus netilmicin (2.5 mg/kg BID intramuscularly), vancomycin plus rifampin (10 mg/kg BID intramuscularly), and vancomycin plus netilmicin plus rifampin at the same routes, dosages, and schedules mentioned above. Netilmicin was given to two additional groups at a higher dosage (6 mg/kg every 24 h intramuscularly) alone or in combination with vancomycin (15 mg/kg BID intravenously) for 12 days. All regimens resulted in undetectable bacterial counts in a significant proportion of vegetations (except netilmicin alone) or reduced the bacterial counts in the vegetations compared with the counts in the untreated controls (P<0.01 to P<0.001). No resistance to rifampin or netilmicin developed during therapy. It is concluded that in the treatment of experimental aortic valve endocarditis caused by MGRSA (i) vancomycin as monotherapy is as efficacious as the triple combination, (ii) the addition of netilmicin (once daily or BID) to vancomycin does not improve the efficacy of the latter antibiotic, even in the presence of rifampin, and (iii) a 12-day course in more effective than a 6-day one, but not at a statistically significant level.

Animals↗