Tobramycin, amikacin, sissomicin, and gentamicin resistant Gram-negative rods.
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Sensitivities to gentamicin, sissomicin, tobramycin, and amikacin were compared in 196 gentamicin-resistant Gram-negative rods and in 212 similar organisms sensitive to gentamicin, mainly isolated from clinical specimens. Amikacin was the aminoglycoside most active against gentamicin-resistant organisms, Pseudomonas aeruginosa, klebsiella spp, Escherichia coli, Proteus spp, Providencia spp, and Citrobacter spp being particularly susceptible. Most of the gentamicin-resistant organisms were isolated from the urine of patients undergoing surgery. Gentamicin was the most active antibiotic against gentamicin-sensitive E coli, Proteus mirabilis, and Serratia spp. Pseudomonas aeruginosa and other Pseudomonas spp were most susceptible to tobramycin. (+info)
Clindamycin plus gentamicin as expectant therapy for presumed mixed infections.
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The prevalence of obligate anaerobes was studied prospectively in 60 patients with severe sepsis of intra-abdominal, soft tissue, female genital or oropulmonary origin. In addition, the efficacy of clindamycin (for anaerobes) plus gentamicin (for aerobic bacteria, especially coliforms) as initial empiric therapy in these patients was evaluated. Among 54 patients with cultural proof of infection, anaerobic pathogens were recovered from 52%. Nineteen patients had bacteremia; Bacteroides fragilis and Klebsiella pneumoniae were the most prevalent pathogens, being isolated in five patients each. Infection was eradicated in 56 of the 60 patients (93%). Mortality related to sepsis was 7% in the entire group, 16% in patients with bacteremia and 2% in patients without bacteremia. Eighty-five percent of aerobic isolates tested were susceptible in vitro to either gentamicin or clindamycin; 97% of anaerobic isolates were inhibited by 5 mug/ml of clindamycin. (+info)
UK-18892, a new aminoglycoside: an in vitro study.
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UK-18892 is a new aminoglycoside antibiotic, a derivative of kanamycin A structurally related to amikacin. It was found to be active against a wide range of pathogenic bacteria, including many gentamicin-resistant strains. The spectrum and degree of activity of UK-18892 were similar to those of amikacin, and differences were relatively minor. UK-18892 was about twice as active as amikacin against gentamicin-susceptible strains of Pseudomonas aeruginosa. Both amikacin and UK-18892 were equally active against gentamicin-resistant strains of P. aeruginosa. There were no appreciable differences in the activity of UK-18892 and amikacin against Enterobacteriaceae and Staphylococcus aureus. Cross-resistance between these two antimicrobials was also apparent. (+info)
Methoxyflurane nephropathy.
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Investigations of methoxyflurane-induced nephrotoxicity in man have been extensively aided by the use of an animal model. To be of value the animal model must share similar metabolic pathways with man and have the same clinical manifestations of the diseases process. The Fischer 344 rat appears to meet these criteria. The predominant factors in the production of methoxyflurane nephrotoxicity appear to be high methoxyflurane dosage and serum inorganic fluoride concentration. It is likely that secondary factors include: (1) a high rate of methoxyflurane metabolism and sepsitivity of the kidney to inorganic fluoride toxicity: (2) concurrent treatment with other nephrotoxic drugs; (3) preexisting renal disease; (4) surgery of the urogenital tract, aorta, or renal vasculative; (5) repeat administration of methoxyflurane due to accumulation of inorganic fluoride and, perhaps, methoxyflurane induction of its own metabolism: and (6) concurrent treatment with enzyme-inducing drugs such as phenobarbital. (+info)
Two-step acquisition of resistance to the teicoplanin-gentamicin combination by VanB-type Enterococcus faecalis in vitro and in experimental endocarditis.
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The activity of vancomycin and teicoplanin combined with gentamicin was investigated in vitro against strains of Enterococcus faecalis resistant to vancomycin and susceptible to teicoplanin (VanB type) and against mutants that had acquired resistance to teicoplanin by three different mechanisms. In vitro, gentamicin selected mutants with two- to sixfold increases in the level of resistance to this antibiotic at frequencies of 10(-6) to 10(-7). Teicoplanin selected teicoplanin-resistant mutants at similar frequencies. Both mutations were required to abolish the activity of the gentamicin-teicoplanin combination. As expected, simultaneous acquisition of the two types of mutations was not observed. In therapy with gentamicin or teicoplanin alone, each selected mutants in three of seven rabbits with aortic endocarditis due to VanB-type E. faecalis BM4275. The vancomycin-gentamicin combination selected mutants that were resistant to gentamicin and to the combination. In contrast, the teicoplanin-gentamicin regimen prevented the emergence of mutants resistant to one or both components of the combination. These results suggest that two mutations are also required to suppress the in vivo activity of the teicoplanin-gentamicin combination. (+info)
Synergy of an investigational glycopeptide, LY333328, with once-daily gentamicin against vancomycin-resistant Enterococcus faecium in a multiple-dose, in vitro pharmacodynamic model.
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The pharmacodynamics of an investigational glycopeptide, LY333328 (LY), alone and in combination with gentamicin, against one vancomycin-susceptible and two vancomycin-resistant Enterococcus faecium strains were studied with a multiple-dose, in vitro pharmacodynamic model (PDM). Dose-range data for the PDM studies were obtained from static time-kill curve studies. In PDM experiments conducted over 48 h, peak LY concentrations of 0.1x and 1x the MIC every 24 h and peak gentamicin concentrations of 18 micrograms/ml every 24 h (Gq24 h) and 6 micrograms/ml every 8 h (Gq8 h) were studied alone and in the four possible LY-gentamicin combinations. Compared to either antibiotic alone, LY-gentamicin combination regimens produced significantly higher apparent killing rates (KRs) calculated during the initial 2 h postdosing. The mean KRs for LY or gentamicin alone versus those for the LY-gentamicin combination regimens were 0.35 +/- 0.55 log10 CFU/ml/h (95% confidence interval [CI95%], 0 to 0.70) and 1.46 +/- 0.71 log10 CFU/ml/h (CI95%, 1.01 to 1.91), respectively (P < 0.0001). Bacterial killing at 48 h (BK48), which was calculated by subtracting the bacterial counts at 48 h from the initial inoculum, with a negative value indicating net growth, was also significantly greater. The mean BK48S were -0.69 +/- 0.44 log10 CFU/ml (CI95%, -0.41 to -0.97) and 3.72 +/- 2.28 log10 CFU/ml (CI95%, 2.28 to 5.17) for LY or gentamicin alone versus LY-gentamicin combination regimens, respectively (P < 0.0001). None of the 12 regimens with LY or gentamicin alone but 75% (9 of 12) of the LY-gentamicin combination regimens were bactericidal. Eighty-three percent (10 of 12) of the LY-gentamicin combination regimens also demonstrated synergy. No significant differences between the pharmacodynamics of LY-gentamicin combination regimens containing Gq24 h versus those containing Gq8h were detected. (+info)
Evaluation of bactericidal activities of LY333328, vancomycin, teicoplanin, ampicillin-sulbactam, trovafloxacin, and RP59500 alone or in combination with rifampin or gentamicin against different strains of vancomycin-intermediate Staphylococcus aureus by time-kill curve methods.
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This in vitro study evaluated the activities of vancomycin, LY333328, and teicoplanin alone and in combination with gentamicin, rifampin, and RP59500 against Staphylococcus aureus isolates with intermediate susceptibilities to vancomycin. Ampicillin-sulbactam and trovafloxacin were also evaluated. LY333328 and ampicillin-sulbactam resulted in bactericidal activity against all isolates. The combination of gentamicin with glycopeptides showed synergistic activity, while rifampin had no added benefit. (+info)
Automated homogeneous immunoassay for gentamicin on the dimension clinical chemistry system.
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BACKGROUND: Monitoring of the concentration of gentamicin in serum and plasma during therapy is widely recommended and practiced in hospitals. Our aim was to develop a homogeneous immunoassay based on particle-enhanced turbidimetric inhibition immunoassay technology to quantify gentamicin on the Dimension clinical chemistry system. METHODS: Assay performance was assessed on each of the Dimension models in a 15-instrument interlaboratory comparison study. A split-sample comparison (n = 1171) was also performed between the gentamicin methods on the Dimension system and the Abbott TDx analyzer, using multiple reagent and calibrator lots on multiple instruments. RESULTS: The Dimension method was linear to 25.1 micromol/L (12.0 microg/mL) with a detection limit of 0.63 micromol/L (0.3 microg/mL). Calibration was stable for 30 days. The within-run imprecision (CV) was <1.3%, and total imprecision ranged from 1.8% to 3.2% between 4.2 micromol/L (2.0 microg/mL) and 16.7 micromol/L (8.0 microg/mL) gentamicin. Linear regression analysis of the results on the Dimension method (DM) vs the Abbott TDx yielded the following equation: DM = 0.98TDx - 0.42; r = 0.987. Minimal interference was observed from structurally related compounds such as sagamicin, netilmicin, and sisomicin. CONCLUSION: The monoclonal antibody used in this method has similar reactivities toward the individual gentamicin subspecies C1, C1a, and C2, thus providing analytical recovery not significantly dependent on relative subspecies concentrations. (+info)