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PubMed1986

Effect of 5-fluorouracil, mitoxantrone, methotrexate, and vincristine on the antibacterial activity of ceftriaxone, ceftazidime, cefotiam, piperacillin, and netilmicin.

Using the checkerboard agar dilution technique, antibacterial activity and in vitro interactions of 4 antineoplastic agents and 5 antimicrobial drugs were examined against 56 strains of 7 bacterial species. 5-fluorouracil was found to inhibit all strains of Staphylococcus aureus and of Staphylococcus epidermidis at a concentration of 0.8 micrograms/ml or less. 84% of all gram-negative strains were inhibited synergistically when 5-fluorouracil was combined with beta-lactam antibiotics. Methotrexate and cefotiam were antagonistic in 42% of all combinations, especially when tested against Escherichia coli and Klebsiella pneumoniae.

Anti-Bacterial Agents↗
PubMed1984

Different antimicrobial agents in treatment and prophylaxis of experimentally induced intraabdominal sepsis.

A reproducible experimental model of intraabdominal infection in rats has been worked out in order to simulate intraabdominal sepsis seen in humans and to test different antimicrobial agents in treatment and prophylaxis of intraabdominal infections. This experimental model was used to evaluate the efficacy of benzylpenicillin, benzylpenicillin plus sulbactam, cefoxitin, thienamycin, clindamycin, tinidazole, netilmicin, clindamycin plus netilmicin, and tinidazole plus netilmicin in the treatment of intraabdominal sepsis. Sixty-five per cent of the untreated animals died within two days. Within four days, 43% of the animals receiving clindamycin alone, 22% receiving tinidazole alone and 46% receiving netilmicin alone died. Animals treated with piperacillin, clindamycin plus netilmicin or tinidazole plus netilmicin showed a significantly decreased mortality and increased cure rates during the experimental period. Sixty-five per cent of the untreated animals and the animals given sulbactam alone died within 48 h. Over 90% of the animals given benzylpenicillin died within five days. Animals treated with benzylpenicillin plus sulbactam, cefoxitin or thienamycin had a significantly decreased mortality. Within four days 22% of the animals receiving tinidazole alone, 43% receiving clindamycin alone and 46% receiving netilmicin alone died. Animals treated with tinidazole plus netilmicin or clindamycin plus netilmicin had a significantly decreased mortality and increased cure rates during the experimental period. Only 5% of these animals died. In the prophylaxis experiment the following agents were tested: cefoxitin, doxycycline, tinidazole plus netilmicin, clindamycin plus netilmicin, and trimethoprim-sulfa plus tinidazole. One dosage of the antimicrobial(s) reduced the mortality rate significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1981

Nonparallel nephrotoxicity dose-response curves of aminoglycosides.

Nephrotoxicity comparisons of aminoglycosides in rats, utilizing large multiples of human doses, have indicated an advantage for netilmicin. However, no nephrotoxicity advantage of netilmicin has been demonstrated at the lower doses used in clinics. Some high-dose studies in rats have also suggested that the slope of the nephrotoxicity dose-response curve of netilmicin was less steep than the slopes of other aminoglycosides. Therefore, the slopes of the nephrotoxicity dose-response curves of gentamicin, amikacin, and netilmicin were compared in 200 rats at low multiples (one to five times) of human clinical doses. Histopathological evaluations of both kidneys from each rat revealed that netilmicin produced equivalent or greater nephrotoxicity as compared with gentamicin and amikacin and that the slope of the nephrotoxicity dose-response curve of netilmicin was approximately one-half as steep as the slopes of amikacin and gentamicin, which were parallel. The distribution of casts excreted in the urine after 2 weeks of dosing and the terminal gross observations corroborated the flatter dose-response slope of netilmicin. Nephrotoxicity advantages predicted by high-dose comparisons with netilmicin in rats are apparently a function of its less steep dose-response slope and therefore may have no relevance to lower doses.

Amikacin↗
PubMed2006

In vitro effects of fluoroquinolone and aminoglycoside antibiotics on human keratocytes.

PURPOSE: The purpose of this study was to assess the cytotoxic effects of the fluoquinolone ofloxacin and the aminoglycoside netilmicin on stromal human keratocytes in vitro. METHODS: Cultured human keratocytes were exposed to various concentrations of ofloxacin or netilmicin (0.16-5.0 mg/mL). Both cell proliferation (MTT assay) and cell morphology (phase-contrast microscopy) were evaluated after 1, 4, 12, and 24 hours of incubation. Measurement of annexin V binding performed in association with the dye exclusion test using propidium iodide (PI) was also performed by FACS analysis after 4 hours of exposure. RESULTS: Both antimicrobials induced dose- and time-dependent morphologic changes in keratocytes, yet the effects of netilmicin were minimal. After 24 hours of exposure, both drugs induced a dose-dependent inhibition of cell proliferation; however, ofloxacin demonstrated significantly more toxic effects than netilmicin (t test for ED50 values, P < 0.0001). Statistical differences between 2 antibiotics start at concentrations above 1.25 mg/mL (ANOVA with post-hoc test, P < 0.01). Expression of the apoptotic marker annexin V was unaffected by antibiotic exposure, whereas the uptake of the necrotic marker PI was increased by ofloxacin (5 mg/mL) but not by netilmicin (ofloxacin versus netilmicin, ANOVA, P < 0.05). CONCLUSIONS: Relative effects of aminoglycosides and fluoroquinolones on stromal keratocytes appear to be different: netilmicin was shown to be significantly less toxic than ofloxacin. This finding is particularly relevant in deciding the optimal antibiotic to be applied in clinical situations in which the epithelium is absent or compromised, as after photorefractive keratectomy, alkali burns, or ulcerative keratitis.

Adult↗
PubMed1982

Comparative pharmacokinetics of aminoglycoside antibiotics in guinea pigs.

The pharmacokinetics of netilmicin, gentamicin, and tobramycin in plasma and in perilymph of guinea pigs were studied after a single intravenous injection of 40 mg/kg. Detailed pharmacokinetic analysis of the plasma drug concentration-time data up to 36 h after the intravenous dose revealed that the pharmacokinetics of the aminoglycoside antibiotics can be best described as a three-compartment open model. The disposition half-lives (t1/2) in plasma of the three antibiotics were comparable and within the following ranges: t1/2 alpha of 0.09 to 0.16 h; t1/2 beta of 0.88 to 1.01 h; and t1/2 gamma of 7.87 to 8.29 h. The volume of distribution in the central compartment and the total body clearance of netilmicin (294 ml/kg, 5.74 ml/min per kg) were greater than those of gentamicin (160 ml/kg, 3.40 ml/min per kg) and tobramycin (204 ml/kg, 4.63 ml/min per kg). Pharmacokinetic analysis of the perilymph drug concentration-time data indicated that all three antibiotics penetrated the perilymph readily, but netilmicin cleared from the perilymph compartment faster than gentamicin and tobramycin. The maximum perilymph drug concentrations were 4.17, 8.05, and 6.78 micrograms/ml and occurred at 1, 2, and 4 h for netilmicin, gentamicin, and tobramycin, respectively. The ratio of area under the curve of perilymph to plasma was lowest for netilmicin (0.27), followed by gentamicin (0.39) and tobramycin (0.57). These results suggest that the differences in pharmacokinetics and concentrations of netilmicin in the perilymph may account for less ototoxic liability of netilmicin compared with gentamicin and tobramycin.

Aminoglycosides↗
PubMed1988

Time-kill studies and synergy testing of broad-spectrum antibiotics against blood culture isolates.

Time-kill studies and synergy testing were performed with blood culture isolates from 80 patients with septicemia. Ten isolates each of Escherichia coli, Proteus mirabilis, indole-positive Proteus, Klebsiella pneumoniae, Enterobacter cloacae, Pseudomonas aeruginosa, Staphylococcus aureus, and coagulase-negative staphylococci were included. The isolates were tested against netilmicin, piperacillin, cefoxitin, cefuroxime, and cefotaxime, alone and in different combinations. Cefotaxime was the most active agent against Enterobacteriaceae, whereas netilmicin was the most active agent against P. aeruginosa and staphylococci. The most active antibiotic combinations were netilmicin-cefotaxime and netilmicin-piperacillin, where a synergistic activity was observed in 68 and 61%, respectively. The highest synergistic activity was against Enterobacteriaceae, but the netilmicin-cefotaxime combination also acted synergistically against more than half of the S. aureus isolates. A relatively low synergistic activity was noted against P. aeruginosa. No case of antagonism was observed. Subinhibitory concentrations of netilmicin, in combination with a greater than or equal to MIC concentration of one of the tested beta-lactam antibiotics, significantly improved the killing of the isolates. Netilmicin exerted a more rapid and pronounced bacterial reduction than the beta-lactam antibiotics tested.

Anti-Bacterial Agents↗
PubMed1994

Teicoplanin: a well-tolerated and easily administered alternative to vancomycin for gram-positive infections in intensive care patients.

A prospective, randomized multicentre study was conducted in order to evaluate the potentially superior tolerability profile of teicoplanin plus netilmicin compared with vancomycin plus netilmicin in patients in ICUs. We considered that these glycopeptides have been shown to have comparable efficacy and that comparative tolerability is of paramount importance, particularly in severely ill patients. A total of 56 patients were enrolled into the study (36 males and 20 females). Twenty-four patients were included in the teicoplanin plus netilmicin group (15 males, 9 females: mean age 56.8 years). The mean simplified acute physiological score (SAPS) was 9.4 (range 4-20). Thirty-two patients were randomized to receive vancomycin plus netilmicin (21 males, 11 females; mean age 56.4 years). The mean SAPS was 9.3 (range 2-16). Septicaemia was the most common infection (14 cases in each group). Most infections were caused by Staphylococcus aureus or coagulase-negative staphylococci. The mean daily doses were: for teicoplanin, 457 mg (6.7 mg/kg); for vancomycin, 1678 mg (24.4 mg/kg); and for netilmicin 263.3 mg (3.9 mg/kg) in the teicoplanin group and 248 mg (3.8 mg/kg) in the vancomycin group. The trough levels of teicoplanin in the serum remained mostly between 7 and 10 mg/l, while more fluctuation was seen in patients receiving vancomycin. The mean trough levels of netilmicin in the serum were 1.2 (SD 0.9) mg/l in the teicoplanin group, compared with 1.7 (SD 1.4) mg/l in the vancomycin group (NS: p > 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Incorporation, release and in-vitro antibacterial activity of liposomal aminoglycosides against Pseudomonas aeruginosa.

Amikacin, netilmicin and tobramycin were incorporated into either anionic or cationic liposomes prepared by sonication. The influence of lipid constituents (charges) on encapsulation efficiency was determined after lysis of vesicles by 0.2% (v/v) Triton X-100. The in-vitro activities of the liposomal aminoglycosides were evaluated against Pseudomonas aeruginosa by agar dilution and compared with free antibiotics. Normal human pooled sera, incubated at 37 degrees C, were supplemented with anionic or cationic liposomes containing known fixed concentrations of amikacin, netilmicin or tobramycin. At various time intervals (0-48 h), samples were taken and antibiotic concentrations determined by the enzyme multiplied immunoassay technique (EMIT). The encapsulation efficiency of cationic liposomes (amikacin 17.1 +/- 1.55%, netilmicin: 5.63 +/- 1.13%, tobramycin 6.7 +/- 0.5%) was approximately 30% higher than that of anionic liposomes (amikacin 12.3 +/- 0.95%, netilmicin 4.0 +/- 0.06%, tobramycin 5.13 +/- 0.18%). Anionic and cationic liposomes in human serum still retained 79.13 +/- 4.04% and 82.71 +/- 2.6% of amikacin, 50.67 +/- 1.8% and 38.6 +/- 0.8% of netilmicin, and 89.09 +/- 1.0% and 88.93 +/- 0.4% of tobramycin, respectively, after 48 h of incubation at 37 degrees C under 5% CO2. The MICs of amikacin (2, 16 and 2 mg/L), netilmicin (2, 1 and 4 mg/L) and tobramycin (1, 2 and 4 mg/L) in free, anionic or cationic liposomal formulations, respectively, were relatively comparable except for anionic liposomal amikacin for which the MIC was increased eight-fold. Empty cationic or anionic liposomes had no effect on bacterial growth. Cationic liposomes containing aminoglycosides should be evaluated further for the treatment of pseudomonal infection.

Amikacin↗
PubMed1985

Chemotherapy of systemic murine infection due to beta-lactam antibiotic 'tolerant' and non-'tolerant' Staphylococcus aureus.

Two in vitro beta-lactam antibiotic (oxacillin, cefotaxime) 'tolerant' (MBC:MIC ratios = greater than 32) strains of Staphylococcus aureus served to intraperitoneally infect cyclophosphamide-pretreated (leukopenic) NMRI mice. With larger bacterial inocula (approximately 5 X 10(8) CFU) neither oxacillin nor gentamicin or netilmicin yielded optimal chemotherapeutic results. Only combination chemotherapy, in particular oxacillin combined with netilmicin, consistently reduced mouse mortality significantly (p less than 0.001). In contrast, moderate 'tolerant' staphylococcal inocula (approximately 2 X 10(8) CFU) were amenable to chemotherapy with either oxacillin or netilmicin, but not with cefotaxime or gentamicin. Oxacillin combined with either gentamicin or netilmicin resulted in significantly lowered murine mortality rates (p less than 0.001). Cefotaxime combined with either aminoglycoside antibiotic gave less satisfactory results. Systemic murine infections due to three non-'tolerant' strains of S. aureus were amenable to chemotherapy with oxacillin, cefotaxime or netilmicin alone and to combination chemotherapy. It is recommended that cases of life-threatening S. aureus infection, not complicated by acute endocarditis, initially be treated with oxacillin plus netilmicin until availability of laboratory results (antibiogram, documentation of 'tolerance').

Animals↗
PubMed1980

Natural history of aminoglycoside nephrotoxicity in the dog.

The natural history of aminoglycoside nephrotoxicity is not well described. This study investigated in the dog renal functional and electrolyte abnormalities during and for 20 days following a 10-day course of low-dose gentamicin (7 mg/kg/day), high-dose gentamicin (30 mg/kg/day), and netilmicin (30 mg/kg/day). Renal histology was examined at the end of the study. Renal functional abnormalities occurred only in animals receiving high-dose gentamicin. A fall in maximal urinary osmolality (1579 +/- 347 mOsm/kg/H2O to 450 +/- 118, p less than 0.05) was followed by renal glycosuria and a fall in GFR (66.9 +/- 11.9 ml/min to 21.3 +/- 8.6, p less than 0.05). These three functional indices had recovered by day 30 in the survivors. Plasma potassium fell in animals receiving high-dose gentamicin (3.8 +/- 0.02 mEq/L to 3.3 +/- 0.4, p less than 0.05) and reached the lowest values (2.7 and 2.9 mEq/L) just prior to death in two animals dying in uremia. Netilmicin also caused a significant fall in plasma potassium (4.3 +/- 0.1 mEq/L to 3.9 +/- 0.1, p less than 0.05). Hypocalcemia (10.0 +/- 1.3 mg/dl to 7.8 +/- 1.4, p less than 0.05) but not hypomagnesemia developed following high-dose gentamicin. Peak serum aminoglycoside levels after high-dose gentamicin and netilmicin were comparable, but trough levels rose only in high-dose gentamicin animals and paralleled the fall in GFR. Light microscopy of the kidney 3 weeks after high-dose gentamicin demonstrated no proximal tubular necrosis but extensive focal tubulointerstitial nephritis, especially in the juxtamedullary cortex. Similar but less extensive derangements were noted in animals receiving low-dose gentamicin, despite the absence of functional abnormalities. Minor histological abnormalities were noted in animals receiving netilmicin. To summarize: 1) major renal functional and electrolyte abnormalities developed only following high-dose gentamicin and included impaired urinary concentration, glycosuria, reduced GFR, hypokalemia, and hypocalcemia (except for a fall in plasma potassium, similar doses of netilmicin were not nephrotoxic); (2) tubulointerstitial nephritis, particularly in the juxtamedullary cortex, occurred with low-dose gentamicin as well as high-dose gentamicin and may be a factor in delayed or incomplete recovery from gentamicin nephrotoxicity; (3) in this model, netilmicin at comparable doses was substantially less nephrotoxic than gentamicin; (4) renal postassium wasting may be a heretofore unrecognized consequence of aminoglycoside administration.

Animals↗
PubMed1986

Susceptibility of enterococci. II. Inhibitory and bactericidal activity of drugs in combination against Streptococcus faecalis and Streptococcus faecium.

The microbiological utility of antibiotic combinations against Streptococcus faecalis and Streptococcus faecium strains was studied. The drugs used were netilmicin + amoxicillin (20 strains); netilmicin + piperacillin (20 strains); netilmicin- + vancomycin (20 strains); netilmicin + rifampicin (20 strains). Netilmicin used in combination with the penicillins was advantageous against Streptococcus faecalis, but not uniformly against Streptococcus faecium. The combinations of netilmicin with vancomycin or rifampicin were no more effective than the single drugs in most cases, although the response varied for the different strains of the two species.

Anti-Bacterial Agents↗
PubMed1985

[Resistance of blood culture isolates in vitro to 4 aminoglycoside antibiotics in Austria--1982/83].

Over the period September 1982 to February 1983 268 blood culture isolates were consecutively collected in 4 microbiological laboratories in Austria (Linz, Vienna, Graz, Feldkirch) and 251 of these strains (streptococci excluded) were tested for resistance to Gentamicin (G), Tobramycin (T), Netilmicin (N) and Amikacin (A) using a microtitre broth dilution method. This investigation was part of an international study. Of the bacterial strains examined 57% were staphylococci (34% Staphylococcus aureus) and 43% gram-negative rods (18% E. coli, 17% other enterobacteriaceae and 5% Pseudomonas aeruginosa etc.). 25% of all strains tested were resistant to Gentamicin (MIC greater than 4 mg/l), 27% to Tobramycin (MIC greater than 4 mg/l), 6% to Netilmicin (MIC greater than 4 mg/ml) and 5% to Amikacin (MIC greater than 8 mg/l). The resistance rate of staphylococci was markedly greater towards Gentamicin (35%) and Tobramycin (39%) than Netilmicin (4%) and Amikacin (6%). The respective percentages of resistant gram-negative rods were considerably smaller, except in the case of Netilmicin (G 13%, T 11%, N 8%, A 4%). Regional differences were observed between Linz and Vienna in the resistance of staphylococci to Gentamicin (24% versus 49%) and Tobramycin (33% versus 53%). On a weight basis Netilmicin was the most active substance in combating nearly all groups of bacteria. Also in strains sensitive to the other aminoglycosides the MIC values of Netilmicin were considerably lower than for the other substances. A noteworthy feature in comparison with the results of other countries participating in this international study was the distinctly higher incidence of staphylococci among the blood culture isolates and the considerably higher percentage of aminoglycoside-resistant strains in Austria. Analysis of the data suggests that the high resistance rates among staphylococci are a consequence of selection by frequently used antibiotics. Hence, it appears essential to observe the development of aminoglycoside resistance in Austria closely and to recommend that these substances, of extreme value in the treatment of severe infections, should be used solely for the most stringent indications.

Aminoglycosides↗
PubMed1984

Comparative nephrotoxicity of hydroxygentamicin and other aminoglycosides in rats.

The nephrotoxicity of hydroxygentamicin and amikacin was examined in young adult Fischer 344 rats. Serum creatinine (SCr) and urea nitrogen (BUN) levels were not significantly affected following sc injection of 80 or 160 mg/kg/day of hydroxygentamicin for 15 days. However, 250 mg/kg of amikacin produced significant increases in both parameters and in kidney/body weight ratios. The ratios were also significantly increased after 80 or 160 mg/kg of hydroxygentamicin, but kidneys of rats receiving amikacin were considerably heavier than those of rats treated with hydroxygentamicin. The antibacterial potency of 250 mg/kg of amikacin is comparable to that of 100 mg/kg of hydroxygentamicin. Additional studies, directly comparing hydroxygentamicin, a mutational biosynthetic, with gentamicin or netilmicin, all at 40, 80, and 160 mg base/kg, and incorporating renal function parameters as well as SCr, BUN, organ weight, tissue concentration, and kidney histopathology, revealed a characteristic pattern typical of aminoglycoside nephrotoxicity in mature adult male rats. In most parameters, values in rats given hydroxygentamicin or netilmicin were normal and comparable to those in controls, but kidney/body weight ratios were significantly increased at high doses. However, kidneys of rats medicated with gentamicin at comparable doses were considerably heavier than those of hydroxygentamicin-treated rats. Significant nephrotoxicity also was seen in rats given low doses of gentamicin or netilmicin. Eosinophilic granulation and vacuolization of renal proximal tubular epithelium, interstitial inflammation, and tubular dilation were observed microscopically with all three drugs in the following descending order of severity: gentamicin greater than netilmicin greater than hydroxygentamicin. The effects on proximal tubular epithelial cells following treatment with amikacin, netilmicin, or hydroxygentamicin correlated reasonably well with renal drug concentrations, but drug concentrations of gentamicin, which produced the most extensive kidney injury, were lower than those of the other three aminoglycosides. Elevated SCr or BUN were indicative of the presence of nephrosis, but early stages of tubular epithelial degeneration were not predicted by increases in BUN or SCr. Although minimal or mild nephrosis was seldom predicted by polyuria, proteinuria, or changes in osmolality, effects observed in renal function parameters usually correlated well with renal histopathology. However, a decrease in osmolality correlated best with enlarged kidneys and changes in renal morphology.

Amikacin↗
PubMedDate not supplied

Antimicrobial therapy of febrile children with malignancies and possible sepsis.

A prospective study of 100 pediatric patients (2 months to 17 years of age) who had malignancies and fever was conducted. Gentamicin or netilmicin and a beta-lactam antibiotic were administered as initial empiric treatment. Before therapy profound granulocytopenia (fewer than 500 polymorphonuclear leukocytes/microliter) was present in 66% of children and persisted to the end of therapy in 42% of children. Of the 40 children with microbiologically documented infections, 38 (95%) responded to therapy. The aminoglycoside dosing regimen of 2 mg/kg/dose intravenously over 60 minutes every 6 hours produced antibiotic concentrations in serum of 5.8 +/- 0.3 microgram/ml at the end of the infusion in the netilmicin group and 1.5 +/- 0.1 microgram/ml 6 hours after the infusion and of 6.2 +/- 0.2 and 0.9 +/- 0.1 microgram/ml for the two time periods in the gentamicin group. The serum half-lives, volumes of distribution and the total body clearance rates were comparable for netilmicin and gentamicin. No accumulation of netilmicin or gentamicin was noted. Seven patients had renal compromise, five before institution of antibiotic therapy and two while on therapy. Four episodes of ototoxicity were not related to antibiotic therapy. Superinfection occurred in five children. The combination of either gentamicin or netilmicin with a beta-lactam antibiotic produced excellent results for episodes of fever in neutropenic children with cancer. In children with severe underlying disease and/or granulocytopenia, antibiotic combinations have achieved an optimal efficacy. Future emphasis should be placed on prevention, immunoregulation and nonbacterial pathogens.

Adolescent↗
PubMed1996

Influence of pH on adaptive resistance of Pseudomonas aeruginosa to aminoglycosides and their postantibiotic effects.

Adaptive resistance to aminoglycosides in Pseudomonas aeruginosa and other gram-negative bacilli is usually induced by the initial exposure to the drug. We investigated the influence of pH on the adaptive resistance of a clinical P. aeruginosa strain to aminoglycosides in vitro and on their postantibiotic effects. For adaptive resistance, the first-exposure concentrations of both amikacin and netilmicin were one, two, four, and eight times the MIC of each drug and the second-exposure concentrations were two times the MIC of each drug. Adaptive resistance was greater and more prolonged with higher initial aminoglycoside concentrations, and the bactericidal effects of the aminoglycosides were concentration dependent at pH 7.4. At pH 6.5, the killing rates of amikacin and netilmicin were far lower than those observed at pH 7.4. At pH 5.5, amikacin and netilmicin exerted practically no bactericidal effect on the P. aeruginosa strain used. However, with media at pH 5.5 and 6.5, adaptive resistance of P. aeruginosa preexposed to amikacin and netilmicin was also clearly exhibited, with the degree of adaptive resistance depending on the bactericidal effects of both drugs on nonpreexposed controls. Maximal adaptive resistance occurred between 0 and 4 h after preexposure. The postantibiotic effects of amikacin and netilmicin against the P. aeruginosa strain were shown to be concentration dependent and were reduced at acidic pHs. No changes in outer and inner membrane proteins occurred during the adaptive-resistance interval.

Adaptation, Physiological↗
PubMed1987

Evaluation of the AutoMicrobic system for susceptibility testing of aminoglycosides and gram-negative bacilli.

The AutoMicrobic system (AMS; Vitek Systems, Inc., Hazelwood, Mo.) was compared with a reference broth microdilution MIC method to determine the accuracy and reproducibility of aminoglycoside susceptibility testing of gram-negative bacilli. Stock clinical isolates (n = 176) which demonstrated resistance to at least one aminoglycoside, extended-spectrum penicillin, or broad-spectrum cephalosporin (or a combination) were selected for this study. Isolates with moderate susceptibility to the aminoglycosides were also included. Of these isolates, 116 were either resistant or moderately susceptible to one or more of amikacin, gentamicin, netilmicin, and tobramycin. When AMS MIC results for 704 antimicrobial agent-organism combinations were compared with parallel microdilution MIC results, exact agreement (AMS MIC = reference MIC) rates were: amikacin, 71.6%; gentamicin, 71.6%; netilmicin, 83.0%; and tobramycin, 69.3%. Agreement rates within +/- 1 log2 dilution were: amikacin, 96.0%; gentamicin, 93.8%; netilmicin, 97.2%; and tobramycin, 96.0%. When National Committee for Clinical Laboratory Standards criteria were used to qualitatively evaluate performance, the overall agreement rates were: amikacin, 100.0%; gentamicin, 99.4%; netilmicin, 98.9%; and tobramycin, 99.4%. There were only four very major discrepancies, which represented 0.6% of the tests performed, and there were no major discrepancies. The percentages of minor discrepancies were: amikacin, 9.6%; gentamicin, 14.2%; netilmicin, 11.9%; and tobramycin, 10.8%. Of the overall average of 11.6% minor discrepancies, 9.7% occurred even though the AMS MIC was within +/- 1 log2 dilution of the reference MIC. The intralaboratory reproducibility ranged from 93.3 to 100% for the four drugs examined. With this challenge group of gram-negative bacilli, the AMS generated aminoglycoside MIC results that were comparable to those obtained by a reference broth microdilution method.

Acinetobacter↗