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1.
Background – The problem of antibacterial drug resistance is increasing worldwide, in part due to the therapeutic concentrations currently used based on the minimal inhibitory concentration (MIC) as a measure of potency are often the very concentrations required to selectively enrich the resistant mutant portion of the population. A mutant prevention concentration (MPC)‐based dosing strategy is suggested to improve the therapeutic outcome based on the MIC. Objective – Our aim was to investigate the MPC and mechanism of resistance to various fluoroquinolones using recent Staphylococcus pseudintermedius isolates from canine pyoderma. Methods – The broth microdilution method for MIC and a series of agar plates containing different concentrations of fluoroquinolones were inoculated with ～1010 colony‐forming units of the bacterial culture for MPC were used. PCR was used to identify mutation in the resistant isolates. Results – The rank order of potency based on MIC and MPC was ciprofloxacin = enrofloxacin ≥ marbofloxacin > difloxacin ≥ orbifloxacin. Integrating our data with reported pharmacokinetic data at the recommended dose ranges revealed that only high doses of ciprofloxacin, enrofloxacin and marbofloxacin could achieve a maximal plasma concentration (Cmax) greater than the MPC of 90% of isolates (Cmax/MPC90). The overall rank of potency against S. pseudintermedius, based on Cmax/MIC, Cmax/MPC, the area under concentration–time curve (AUC)/MIC and AUC/MPC values, was in decreasing order: enrofloxacin > ciprofloxacin ≥ marbofloxacin ≥ orbifloxacin = difloxacin. Sequencing of the quinolone resistant determining region of gyrA, gyrB, grlA and grlB of resistant strains showed a base‐pair substitution in both gyrA and gyrB that resulted in Ser‐84 to Leu and Ser‐80 to Arg amino acid changes, respectively. Conclusions and clinical importance – High doses of ciprofloxacin, enrofloxacin and marbofloxacin could minimize the selection of resistant mutants, whereas the possibility of selecting mutants with the conventional doses of difloxacin and orbifloxacin, and low clinical doses of all fluoroquinolones, seems high.  相似文献   

2.
The pharmacokinetics after oral application of the fluoroquinolones (FQs), enrofloxacin, difloxacin, marbofloxacin and orbifloxacin were compared in independent crossover studies in Beagle dogs. Commercially available tablet formulations were given at common dosage recommended by the manufacturers which were 2.0 mg/kg body weight (bw) for marbofloxacin, 2.5 mg/kg bw for orbifloxacin and 5.0 mg/kg bw for enrofloxacin and difloxacin. Analysis was performed by an agar diffusion assay. Pharmacokinetic parameters were calculated by noncompartmental methods. All FQs were rapidly absorbed and achieved average peak serum concentrations of 1.41, 1.11, 1.47 and 1.37 mug/mL for enrofloxacin, difloxacin, marbofloxacin and orbifloxacin, respectively. Enrofloxacin was eliminated at a terminal half-life (t(1/2)) of 4.1 h, difloxacin at 6.9 h, orbifloxacin at 7.1 h and marbofloxacin at 9.1 h. While the area under the serum concentration-time curve of the 24-h dosing interval (AUC0--24) for marbofloxacin and orbifloxacin were similar (approximately 13 microg x h/mL), enrofloxacin attained an AUC(0-24) of 8.7 and difloxacin of 9.3 microg x h/mL. Because of its favourable pharmacokinetics combined with excellent in vitro activity, enrofloxacin exhibited superior pharmacodynamic predictors of in vivo antimicrobial activity as C(max)/MIC (maximum serum concentration/minimum inhibitory concentration) and AUC(0-24)/MIC (area under the 24-h serum concentration--time curve/minimum inhibitory concentration) compared with other FQs.  相似文献   

3.
The antibacterial activity, selection of Escherichia coli (E. coli) mutants and mechanisms of fluoroquinolone resistance were investigated by integrating the minimum inhibitory concentration (MIC), mutant prevention concentration (MPC) and in vitro dynamic model approaches. Difloxacin and orbifloxacin, for which the above information has been scarce, were used. A range of area under curve over a 24h interval (AUC(24h))/MIC ratios and selected E. coli strains were investigated using the dynamic models. Continuous incubation for three days in the presence of difloxacin or orbifloxacin resulted in losses in E. coli susceptibility. An AUC(24h)/MIC (AUC(24h)/MPC)-dependent fluoroquinolone activity and selection of E. coli mutants was confirmed. Maximum losses in susceptibility occurred at AUC(24h)/MIC ratios of 54 (orbifloxacin) and 57.3 (difloxacin). AUC(24h)/MIC ratios of 169.8 (orbifloxacin) and 199.5 (difloxacin) were estimated to be protective against the selection of E. coli mutants, and the corresponding ratios based on AUC(24h)/MPC predictions were 34 (orbifloxacin) and 36.3 (difloxacin). When integrating our in vitro data with pharmacokinetic data in dogs, the conventional clinical doses of both drugs were found to be inadequate to attain the above protective values for 90% of the mutant subpopulation (AUC(24h)/MPC(90)). Both target mutations, esp. at codon 83 (Ser to Leu) of gyrA, and overexpression of efflux pumps contributed to resistance development, with mutants also showing decreased susceptibility to enrofloxacin and marbofloxacin. Additional studies would determine the role of mutations found outside the QRDR, at codon 24 of gyrA, and at codon 116 of parC, and establish the significance of these observations in vivo.  相似文献   

4.
The purpose of this study was to compare susceptibilities of ear and skin Pseudomonas spp. isolates to enrofloxacin, marbofloxacin, and ciprofloxacin. Specimens were obtained from dogs examined in a veterinary dermatology referral hospital. Susceptibilities of ear isolates to enrofloxacin, marbofloxacin, and ciprofloxacin were 46.9%, 66.7%, and 75.0%, respectively. Susceptibilities of skin isolates to the same drugs were 76.2%, 81.0%, and 80.0%, respectively. Ear isolates were significantly less susceptible to enrofloxacin than to ciprofloxacin (P=0.021), and ear isolates were significantly less susceptible to enrofloxacin than were skin isolates (P=0.034). When fluoroquinolone resistance was present, ear isolates were significantly less susceptible to enrofloxacin than to ciprofloxacin (P<0.001) and marbofloxacin (P=0.014).  相似文献   

5.
A total of 100 Pseudomonas aeruginosa (P. aeruginosa) isolates were collected over a 1.5-year period from cases of canine otitis. Sensitivities to enrofloxacin, marbofloxacin, and orbifloxacin were determined using minimum inhibitory concentration testing (MICT). Isolates were also tested for sensitivities to enrofloxacin and marbofloxacin using disk-diffusion susceptibility testing (DDST). Isolates were significantly more sensitive to marbofloxacin than to enrofloxacin (z = -4.57; P<0.05) or orbifloxacin (z = -5.02; P<0.05). Agreement was 87% between MICT and DDST for marbofloxacin, with approximately equal numbers of overestimation and underestimation errors. Agreement was 74% between MICT and DDST for enrofloxacin, but DDST tended to overestimate the number of enrofloxacin-susceptible strains. These results suggest that marbofloxacin is more effective against P. aeruginosa than either enrofloxacin or orbifloxacin and that relying on DDST may lead to ineffective enrofloxacin treatment.  相似文献   

6.
考察马波沙星对猪临床分离病原菌的体外抑菌活性,以期为临床应用提供依据。采用琼脂二倍稀释法测定马波沙星对猪临床分离大肠杆菌、金黄色葡萄球菌和链球菌的最小抑菌浓度(MIC),并以土霉素、恩诺沙星、诺氟沙星、环丙沙星、庆大霉素和多西环素作为对照药物。结果表明:马波沙星对猪临床分离病原菌大肠杆菌、金黄色葡萄球菌和链球菌均有较低的最小抑菌浓度,对临床分离大肠杆菌、金黄色葡萄球菌和链球菌的抑菌活性明显高于诺氟沙星、环丙沙星、庆大霉素和强力霉素,对临床分离大肠杆菌的抑菌活性高于恩诺沙星。马波沙星对引起猪乳房炎-子宫炎-无乳综合征(MMA)的主要病原菌的抑菌活性优于常用抗菌药。  相似文献   

7.
The in vitro activity of difloxacin against canine bacterial isolates from clinical cases was studied in the United States and The Netherlands. Minimal inhibitory concentrations (MIC), the postantibiotic effect, the effect of pH on antimicrobial activity, and the bacterial killing rate tests were determined according to standard techniques. The MICs of American and Dutch isolates agreed in general. The MICs of the American gram-negative isolates ranged from 0.06 to 2.0 microg/ml, and the MICs of the Dutch gram-negative isolates ranged from 0.016 to 8.0 microg/ml. A few European strains of Proteus mirabilis and Klebsiella pneumoniae had relatively high MICs. Bordetella bronchiseptica also was less susceptible to difloxacin. The MICs of the American gram-positive cocci ranged from 0.125 to 4.0 microg/ml, and the MICs of Dutch isolates ranged from 0.125 to 2.0 microg/ ml. Difloxacin induced a concentration-dependent postantibiotic effect that lasted 0.2-3 hours in cultures with Escherichia coli, Staphylococcus intermedius, Streptococcus canis, Proteus spp., and Klebsiella pneumoniae. There was no postantibiotic effect observed against canine Pseudomonas aeruginosa. Decreasing the pH of the medium increased the MIC of Proteus mirabilis for difloxacin. The MICs of Escherichia coli and Klebsiella pneumoniae were lowest at neutral pH and were slightly increased in acid or alkaline media. At a neutral pH, most tested bacterial species were killed at a difloxacin concentration of 4 times the MIC. Similar results were obtained when these same bacteria were tested against enrofloxacin. A Klebsiella pneumoniae strain in an acidic environment was readily killed at difloxacin or enrofloxacin MIC, but at neutral pH the drug concentration had to be raised to 4 times the MIC for a bactericidal effect. After 24 hours of incubation at pH 7.1, difloxacin and enrofloxacin had similar bactericidal activity for all bacteria tested except Staphylococcus intermedius. Against S. intermedius, difloxacin was more bactericidal than enrofloxacin.  相似文献   

8.
Enrofloxacin was administered i.v. to five adult mares at a dose of 5 mg/kg. After administration, blood and endometrial biopsy samples were collected at regular intervals for 24 h. The plasma and tissue samples were analyzed for enrofloxacin and the metabolite ciprofloxacin by high-pressure liquid chromatography. In plasma, enrofloxacin had a terminal half-life (t(1/2)), volume of distribution (area method), and systemic clearance of 6.7 +/- 2.9 h, 1.9 +/- 0.4 L/kg, and 3.7 +/- 1.4 mL/kg/min, respectively. Ciprofloxacin had a maximum plasma concentration (Cmax) of 0.28 +/- 0.09 microg/mL. In endometrial tissue, the enrofloxacin Cmax was 1.7 +/- 0.5 microg/g, and the t(1/2) was 7.8 +/- 3.7 h. Ciprofloxacin Cmax in tissues was 0.15 +/- 0.04 microg/g and the t(1/2) was 5.2 +/- 2.0 h. The tissue:plasma enrofloxacin concentration ratios (w/w:w/v) were 0.175 +/- 0.08 and 0.47 +/- 0.06 for Cmax and AUC, respectively. For ciprofloxacin, these values were 0.55 +/- 0.13 and 0.58 +/- 0.31, respectively. We concluded that plasma concentrations achieved after 5 mg/kg i.v. are high enough to meet surrogate markers for antibacterial activity (Cmax:MIC ratio, and AUC:MIC ratio) considered effective for most susceptible gram-negative bacteria. Endometrial tissue concentrations taken from the mares after dosing showed that enrofloxacin and ciprofloxacin both penetrate this tissue adequately after systemic administration and would attain concentrations high enough in the tissue fluids to treat infections of the endometrium caused by susceptible bacteria.  相似文献   

9.
OBJECTIVES AND DESIGN: 1) A prospective study to determine in vitro concentrations for a range of fluoroquinolones, gentamicin and amoxycillin-clavulanate required to inhibit growth of recently collected, feline and canine Escherichia coli and canine Staphylococcus intermedius isolates. 2) A comparative retrospective study to compare the minimum inhibitory concentrations (MICs) of ciprofloxacin, enrofloxacin and amoxycillin-clavulanate for archived canine E coli and S intermedius isolates collected ten to twenty years earlier, with those for recently collected isolates. PROCEDURE: Susceptibility was assessed using disk diffusion, agar dilution susceptibility testing and Epsilometer tests (E-tests) for both recently collected and archived isolates. RESULTS: All feline E coli isolates and recently collected canine S intermedius isolates were susceptible to all fluoroquinolones. There was a statistically significant increase in the MIC range of ciprofloxacin and enrofloxacin for recently collected E coli, and in the MIC range of amoxycillin-clavulanate for recently collected S intermedius isolates compared to archived isolates. Twelve of 59 recently collected canine E coli isolates were resistant to both ciprofloxacin and enrofloxacin. Resistant canine E coli isolates were associated with complicating host or infection site factors. CONCLUSION: This is the first report comparing the MICs for all veterinary fluoroquinolones currently available in Australia for a representative sample of canine and feline E coli and canine S intermedius isolates. Importantly, this study identified 12 of 59 canine E coli isolates resistant to fluoroquinolones and identified the development of low level resistance in canine E coli to ciprofloxacin and enrofloxacin and canine S intermedius to amoxycillin-clavulanate.  相似文献   

10.

  1. The pharmacokinetics of enrofloxacin and marbofloxacin was studied in Japanese quails and common pheasants. Healthy mature birds from both species and both genders were treated intravenously and orally with enrofloxacin (10 mg/kg) and marbofloxacin (5 mg/kg).

  2. After intravenous administration enrofloxacin was extensively metabolised to ciprofloxacin. Metabolites of marbofloxacin were not detected. Values of volume of distribution were respectively 4.63 l/kg and 3.67 l/kg for enrofloxacin and 1.56 l/kg and 1.43 l/kg for marbofloxacin. In quails, total body clearance values were higher than those in pheasants and other avian species.

  3. After oral application enrofloxacin was rapidly absorbed in quails, more rapidly than marbofloxacin. Pheasants absorbed both antimicrobials at a lower rate. Higher bioavailability was observed for marbofloxacin (118%). Relatively low bioavailability was established in quails for enrofloxacin (26.4%), accompanied by extensive conversion to ciprofloxacin.

  4. Generally, quails absorbed and eliminated both fluoroquinolones more rapidly than pheasants; the latter showed pharmacokinetics similar to poultry. Because of favourable pharmacokinetic properties, marbofloxacin should be preferred for oral administration in Japanese quails and pheasants for treatment of infections caused by equally susceptible pathogens.

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11.
Rapidly growing mycobacteria (RGM) and Nocardiae can cause severe or refractory infections in cats and dogs. Prolonged antibacterial therapy is required to cure these infections. As fluoroquinolones have been used in combination therapy for treating RGM infections, isolates from the Mycobacterium smegmatis cluster (n=64), Mycobacterium fortuitum cluster (n=17), and M. mageritense cluster (n=2), collected from feline and canine patients, underwent susceptibility testing to pradofloxacin. The MIC(50), MIC(90) and tentative epidemiological cut-off (ECOFF) values as determined by microbroth dilution susceptibility testing that inhibited growth of the M. smegmatis and M. fortuitum clusters were 0.063, 0.125 and ≤ 0.25; and 0.125, 0.250 and ≤ 1.0 μg/mL, respectively. E-Test results showed similar trends but MICs were lower than those for microbroth dilution. In summary, pradofloxacin demonstrated effective in vitro activity against RGM isolates. Additionally, veterinary isolates of Nocardia nova (n=18), Nocardia farcinica (n=3) and Nocardia cyriacigeorgica (n=1) underwent microbroth dilution testing to ciprofloxacin, enrofloxacin and pradofloxacin. The MIC(50) and MIC(90) of pradofloxacin, ciprofloxacin and enrofloxacin that inhibited growth of Nocardia nova isolates were 2 (4), 8 (16), 16 (32) μg/mL, respectively. The tentative ECOFF values for pradofloxacin and ciprofloxacin were 32 μg/mL and for enrofloxacin 64 μg/mL. The MIC or MIC range for the three N. farcinica isolates of pradofloxacin, ciprofloxacin and enrofloxacin were 0.25-0.5, 2 and 2 μg/mL and for the single N. cyriacigeorgica isolate were 1, 4 and 4 μg/mL, respectively. On the basis on these results, fluoroquinolones appear to have limited therapeutic potential for most Nocardia infections.  相似文献   

12.
The aim of this study was to compare the in vitro antimicrobial activity of the veterinary fluoroquinolones against a panel of recently isolated porcine and bovine bacterial pathogens. The study used enrofloxacin as a benchmark against which other agents were compared, being the most common fluoroquinolone used in treatment of bovine and porcine infections. The activity of ciprofloxacin was also assessed as it is the main metabolite of enrofloxacin in cattle. Enrofloxacin and ciprofloxacin generally showed higher antibacterial activity, in terms of MIC(50) values, for most pathogen species when compared with marbofloxacin, difloxacin, danofloxacin and norfloxacin. Ciprofloxacin showed significantly greater in vitro antibacterial activity than enrofloxacin against M. haemolytica, P. multocida and E. coli, whereas enrofloxacin showed greater activity than ciprofloxacin against S. aureus. Marbofloxacin was significantly more active than enrofloxacin against M. haemolytica, E. coli and B. bronchiseptica but less active against P. multocida, S. aureus, coagulase negative Staphylococci, S. dysgalactiae, S. uberis, A. pleuropneumoniae and S. suis. Danofloxacin was significantly less active than enrofloxacin against P. multocida, E. coli, S. uberis, A. pleuropneumoniae and S. suis. Enrofloxacin and its metabolite ciprofloxacin showed the highest in vitro activities against most bovine pathogens tested and the porcine pathogens also showed a high degree of sensitivity to enrofloxacin. These data facilitate further pharmacokinetic/pharmacodynamic comparison of fluoroquinolones currently used in veterinary medicine.  相似文献   

13.
Therapeutic options for multi-drug resistant (MDR) Escherichia coli in dogs or cats are limited. The objective of this study was to establish in vitro susceptibility of canine and feline E. coli to fosfomycin. Two sources of isolates were categorized based on susceptibility as to no resistance (NDR), single drug resistance (SDR), multidrug resistance (MDR) or extreme drug resistance (XDR). Clinical isolates were collected from throughout the US from dogs (n=157) or cats (n=43) with naturally occurring infection between March 2008 and January 2010. Experimental isolates were collected from fecal samples of dogs treated with no drug (NDR), amoxicillin (expressing SDR) or enrofloxacin (expressing MDR or XDR). Fosfomycin minimum inhibitory concentrations (MIC) were determined using E-Test(?). For clinical isolates, most (165/200) originated from the urinary tract, with the number of isolates per resistant category being: NDR (N=44, 22%), SDR (N=65, 32.5%), MDR (N=74, 37%), and XDR (N=17, 8.5%). Of these isolates, 99% (197/200) were susceptible to fosfomycin with the MIC(90) and MIC(50) being 2 and 1 μg/ml, respectively (range: 0.25-196 μg/ml). The number of experimental isolates in each category was NDR (3), SDR (23), MDR (38), and XDR (11) (29.3, 44, and 14.7%, respectively). Of these, 100% were susceptible to fosfomycin with MIC(90) and MIC(50) being 1.5 and 1 μg/ml (range: 0.38-4 μg/ml), respectively. The susceptibility of canine and feline MDR and XDR E. coli to fosfomycin at concentrations well below the susceptible breakpoint supports further investigation for its use when treating E. coli resistant to alternative antimicrobials.  相似文献   

14.
Infections with antimicrobial-resistant bacteria are a great challenge in both human and veterinary medicine. The purpose of this study was to determine antimicrobial susceptibility of 106 strains of Pseudomonas aeruginosa isolated from dogs with otitis and pyoderma from 2003 to 2006 in the United States. Three antimicrobial panels, including 6 classes and 32 antimicrobial agents, were used. A wide range of susceptibility patterns were noted with some isolates being resistant to between 8 and 28 (mean 16) of the antimicrobials tested. Among the beta-lactams, all isolates were resistant to ampicillin, cefoxitin, cefpodoxime, cephalothin and cefazolin followed by amoxicillin/clavulanic acid (99%), ceftiofur (97%), ceftriaxone (39%), cefotaxime (26%), and cefotaxime/clavulanic acid (20%), whereas less than 7% of isolates were resistant to ceftazidime/clavulanic acid, ceftazidime, piperacillin/tazobactam or cefepime. Two isolates were resistant to the carbapenems. Among the quinolones and fluoroquinolones, the most isolates were resistant to naladixic acid (96%), followed by orbifloxacin (52%), difloxacin (43%), enrofloxacin (31%), marbofloxacin (27%), gatifloxacin (23%), levofloxacin (21%), and ciprofloxacin (16%). Among the aminoglycosides, the most resistance was seen to kanamycin (90%), followed by streptomycin (69%), gentamicin (7%), and amikacin (3%). Of the remaining antimicrobials 100% of the isolates were resistant to chloramphenicol followed by tetracycline (98%), trimethoprim/sulfamethoxazole (57%), and sulfisoxazole (51%). Point mutations were present in gyrA, gyrB, parC, and/or parE genes among 34 of the 102 naladixic acid-resistant isolates. Two isolates contained class 1 integrons carrying aadA gene conferring streptomycin and spectinomycin resistance. The findings suggest that many antimicrobial agents commonly used in companion animals may not constitute appropriate therapy for canine pseudomonas infections.  相似文献   

15.
Monitoring of susceptibility to antibiotics in field isolates of pathogenic avian mycoplasmas is important for appropriate choice of treatment. Our study compared in vitro susceptibility to enrofloxacin and difloxacin in recent (2005-2006) isolates of Mycoplasma gallisepticum and Mycoplasma synoviae from meat-type turkey flocks with archived (1997-2003) isolates and reference strains. Comparison of minimal inhibitory concentration (MIC) values determined by microtest, agar dilution and commercial Etest showed good agreement, but underscored the need for standardized methods for testing. Notably, while the commercial Etest was convenient and accurate for determining MICs for enrofloxacin in the range 0.002-0.094mug/ml, the endpoint of inhibition for M. gallisepticum and M. synoviae strains with MIC values >/=1.0mug/ml could not be determined. A decrease in susceptibility to both fluoroquinolones was detected in archived strains but to a greater degree in recent isolates, most of which had MICs above the NCCLS susceptibility breakpoint for these antibiotics (相似文献   

16.
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17.
The purpose of this study was to establish the pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin in the plasma and interstitial fluid (ISF) following subcutaneous (s.c.) administration of enrofloxacin. Ultrafiltration probes were placed in the s.c. tissue, gluteal musculature, and pleural space of five calves. Each calf received 12.5 mg/kg of enrofloxacin. Plasma and ISF samples were collected for 48 h after drug administration and analyzed by high pressure liquid chromatography. Plasma protein binding of enrofloxacin and ciprofloxacin was measured using a microcentrifugation system. Tissue probes were well tolerated and reliably produced fluid from each site. The mean +/- SD plasma half-life was 6.8 +/- 1.2 and 7.3 +/- 1 h for enrofloxacin and ciprofloxacin, respectively. The combined (ciprofloxacin + enrofloxacin) peak plasma concentration (Cmax) was 1.52 microg/mL, and the combined area under the curve (AUC) was 25.33 microg/mL. The plasma free drug concentrations were 54% and 81% for enrofloxacin and ciprofloxacin, respectively, and free drug concentration in the tissue fluid was higher than in plasma. We concluded that Cmax/MIC and AUC/MIC ratios for free drug concentrations in plasma and ISF would meet suggested ratios for a targeted MIC of 0.06 microg/mL.  相似文献   

18.
Plasma, urine, and skin drug concentrations were determined for dogs (n=12) given five daily oral doses of marbofloxacin (MAR) (2.75 mg/kg), enrofloxacin (ENR) (5.0 mg/kg) or difloxacin (DIF) (5.0 mg/kg). Concentrations of the active metabolite of ENR, ciprofloxacin (CIP), were also determined. The three-period, three-treatment crossover experimental design included a 21-day washout period between treatments. Area under the plasma drug concentration vs. time curve (AUC0-last, microg/mLxh of MAR was greater than for ENR, CIP, ENR/CIP combined, and DIF. Maximum concentration (Cmax) of MAR was greater than ENR, CIP, and DIF. Time of maximum plasma concentration (Tmax) was similar for MAR and DIF; Tmax occurred earlier for ENR and later for CIP. Plasma half-life (t1/2) of MAR was longer than for ENR, CIP, and DIF. Urine concentrations of DIF were less than MAR or ENR/CIP combined, but urine concentrations of MAR and ENR/CIP combined did not differ. DIF skin concentrations were less than the concentrations of MAR or ENR/CIP combined 2 h after dosing, but skin concentrations of MAR and ENR/CIP combined did not differ.  相似文献   

19.
OBJECTIVE: To investigate the development of enrofloxacin resistance among Escherichia coli isolates obtained from chickens by determining mutant-prevention concentrations (MPCs) and sequence the quinolone resistance-determining regions (QRDRs) of gyrA and parC genes in selected isolates. SAMPLE POPULATION: 15 chicken-derived E coli isolates. PROCEDURES: For all isolates, MPC and minimal inhibition concentration (MIC) of enrofloxacin were determined. The MPCs and maximum serum drug concentrations attained with enrofloxacin doses recommended for treatment of E coli infections in chickens were compared. Mutation frequencies and QRDR sequence changes in gyrA and parC were also determined. RESULTS: In 2 of 15 E coli strains, MPCs were low (0.016 and 0.062 microg/mL), MPC:MIC ratios were 2 and 4, and the GyrA and ParC proteins had no mutations. In 9 susceptible isolates with a GyrA point mutation, MPCs ranged from 2 to 16 microg/mL. For isolates with double mutations in GyrA and a single mutation in ParC, MPCs were > 32 microg/mL (several fold greater than the maximal plasma concentration of enrofloxacin in chickens); mutation frequencies were also much lower, compared with frequencies for single-mutation isolates. CONCLUSIONS AND CLINICAL RELEVANCE: For E coli infections of chickens, MPC appears to be useful for determining enrofloxacin-dosing strategies. The high MPC:MIC ratio may result in enrofloxacin-treatment failure in chickens infected with some wild-type gyrA E coli isolates despite the isolates' enrofloxacin susceptibility (MICs 0.125 to 1 microg/mL). For infections involving isolates with high MPCs, especially those containing mutations in gyrA and parC genes, treatment with combinations of antimicrobials should be adopted.  相似文献   

20.
OBJECTIVE: To compare pharmacokinetics of enrofloxacin administered IV and in various oral preparations to ewes. ANIMALS: 5 mature Katahdin ewes weighing 42 to 50 kg. PROCEDURE: Ewes received 4 single-dose treatments of enrofloxacin in a nonrandomized crossover design followed by a multiple-dose oral regimen. Single-dose treatments consisted of an IV bolus of enrofloxacin (5 mg/kg), an oral drench (10 mg/kg) made from crushed enrofloxacin tablets, oral administration in feed (10 mg/kg; mixture of crushed enrofloxacin tablets and grain), and another type of oral administration in feed (10 mg/kg; mixture of enrofloxacin solution and grain). The multiple-dose regimen consisted of feeding a mixture of enrofloxacin solution and grain (10 mg/kg, q 24 h, for 7 days). Plasma concentrations of enrofloxacin and ciprofloxacin were measured by use of high-performance liquid chromatography. RESULTS: Harmonic mean half-life for oral administration was 14.80, 10.80, and 13.07 hours, respectively, for the oral drench, crushed tablets in grain, and enrofloxacin solution in grain. Oral bioavailability for the oral drench, crushed tablets in grain, and enrofloxacin in grain was 4789, 98.07, and 94.60%, respectively, and median maximum concentration (Cmax) was 1.61, 2.69, and 2.26 microg/ml, respectively. Median Cmax of the multiple-dose regimen was 2.99 microg/ml. CONCLUSIONS AND CLINICAL RELEVANCE: Enrofloxacin administered orally to sheep has a prolonged half-life and high oral bioavailability. Oral administration at 10 mg/kg, q 24 h, was sufficient to achieve a plasma concentration of 8 to 10 times the minimum inhibitory concentration (MIC) of any microorganism with an MIC < or = 0.29 microg/ml.  相似文献   

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