Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q86TM3 (cage)
 29,987 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Enrofloxacin (2.5 mg/kg of body weight) and danofloxacin (1.25 mg/kg) were administered subcutaneously to ruminating calves (n = 8) fitted with subcutaneous tissue cages. Concentrations of enrofloxacin, its metabolite ciprofloxacin, and danofloxacin in blood (plasma), tissue cage exudate (following intracaveal injection of 0.3 ml of 1% [vol/wt] carrageenan), and bronchial secretions were measured by high-performance liquid chromatography (HPLC) and microbiological assay (enrofloxacin plus ciprofloxacin and danofloxacin). Mean maximum concentrations (C(max)) +/- standard deviations of enrofloxacin (0.24 +/- 0.08 microg/ml), ciprofloxacin (0.11 +/- 0.03 [total, 0.34 +/- 0.10] microg/ml), and danofloxacin (0.23 +/- 0.05 microg/ml) were detected in the plasma of calves by HPLC. The C(max) were 0.49 +/- 0.17 microg/ml (enrofloxacin equivalents) and 0.24 +/- 0.03 microg/ml (danofloxacin) when they were measured by microbiological assay. Mean C(max) in exudate (HPLC) were 0.18 +/- 0.07 microg/ml (enrofloxacin), 0.10 +/- 0.04 microg/ml (ciprofloxacin), 0.27 +/- 0.09 microg/ml (enrofloxacin plus ciprofloxacin), and 0.19 +/- 0.05 microg/ml (danofloxacin), and concentrations in exudate exceeded those in plasma from 8 h (enrofloxacin and ciprofloxacin) or 6 h (danofloxacin) after drug administration. The C(max) were 0.34 +/- 0.09 microg/ml (enrofloxacin equivalents) and 0.22 +/- 0.04 microg/ml (danofloxacin) in exudate when they were measured by the microbiological assay. The maximum mean concentration achieved in bronchial secretions (HPLC) were 0.07 +/- 0.04 microg/ml (enrofloxacin), 0.04 +/- 0.07 microg/ml (ciprofloxacin), 0.10 +/- 0. 05 microg/ml (enrofloxacin plus ciprofloxacin), and 0.12 +/- 0.09 microg/ml (danofloxacin). The maximum mean concentration in bronchial secretions from a limited number of animals from which samples were available for microbiological assay were 0.27 +/- 0.11 microg/ml (n = 4 [enrofloxacin equivalents]) and 0.14 +/- 0.02 microg/ml (n = 3 [danofloxacin]). With predictive models of efficacy (C(max)/MIC and area under the concentration-time curve/MIC ratios in plasma) for Pasteurella multocida (MIC of enrofloxacin, 0.06 microg/ml [24]; MIC of danofloxacin, 0.06 microg/ml [6]), enrofloxacin produced scores of 8.17 and 52.00, respectively, compared to those of danofloxacin, which were 4.02 and 23.05, respectively. With the dosing rates recommended in some markets by manufacturers, enrofloxacin and danofloxacin achieved concentrations above the MICs for important pathogenic organisms in plasma, tissue cage exudate, and bronchial secretion. Since fluoroquinolones display concentration-dependent activities, C(max)/MIC ratios may be critical to efficacy. In the United States enrofloxacin is currently the only fluoroquinolone licensed for food animals and dosages for acute respiratory disease are 2.5 to 5 mg/kg for 3 days or 7.5 to 12. 5 mg/kg once. The higher dosages on a single occasion are likely to confer C(max)/MIC ratios that are associated with greater clinical efficacy.
 ...
PMID:Pharmacokinetics of enrofloxacin and danofloxacin in plasma, inflammatory exudate, and bronchial secretions of calves following subcutaneous administration. 1042 24

The role of moxifloxacin and levofloxacin pharmacokinetics (PK) in antimicrobial efficacy and in the selection of fluoroquinolone-resistant Streptococcus pneumoniae strains was investigated using the rabbit tissue cage abscess model. A rabbit tissue cage was created by insertion of sterile Wiffle balls in the dorsal cervical area. Animals orally received a range of moxifloxacin or levofloxacin doses that simulate human PK for 7 days 48 h after the Wiffle balls were inoculated with fluoroquinolone-sensitive S. pneumoniae (10(7) CFU). Abscess fluid was collected on a daily basis over 14 days to measure bacterial density and MICs. Moxifloxacin regimens produced a range of area under the concentration-time curve (AUC)/MIC ratios ranging from 9.2 to 444 and peak/MIC ratios ranging from 1.3 to 102. Levofloxacin doses produced AUC/MIC ratios of 5.1 to 85.5 and peak/MIC ratio of 0.9 to 14.8. Moxifloxacin at 6.5, 26, and 42 mg/kg reduced the bacterial log CFU per milliliter in abscess fluid (percentage of that in a sterile animal) by 4.2 +/- 2.2 (20%), 5.8 +/- 0.4 (100%), and 5.4 +/- 0.4 (100%), respectively, over the dosing period. Levofloxacin at 5.5, 22, and 32 mg/kg reduced the log CFU per milliliter in abscess fluid (percentage of that in a sterile animal) by 2.8 +/- 0.7 (20%), 5.1 +/- 1.3 (80%), and 4.6 +/- 1.3 (60%), respectively. Moxifloxacin has a greater bactericidal rate as determined by regression of log CFU versus time data. The AUC/MIC and peak/MIC ratios correlated with the efficacy of both drugs (P < 0.05). Resistance to either drug did not develop with any of the doses as assessed by a change in the MIC. In conclusion, data derived from this study show that moxifloxacin and levofloxacin exhibit rapid bactericidal activity against S. pneumoniae in vivo, and moxifloxacin exhibits enhanced bactericidal activity compared to levofloxacin, with AUC/MIC and peak/MIC ratios correlated with antimicrobial efficacy for both drugs. The development of fluoroquinolone-resistant S. pneumoniae was not observed with either drug in this model.
 ...
PMID:Streptococcus pneumoniae response to repeated moxifloxacin or levofloxacin exposure in a rabbit tissue cage model. 1118 63

Clinical and animal studies indicate that with optimal dosing, penicillin may still be effective against penicillin-nonsusceptible pneumococci (PNSP). The present study examined whether the same strains of penicillin-susceptible pneumococci (PSP) and PNSP differed in their pharmacodynamic responses to penicillin by using comparable penicillin dosing regimens in four animal models: peritonitis, pneumonia, and thigh infection in mice and tissue cage infection in rabbits. Two multidrug-resistant isolates of Streptococcus pneumoniae type 6B were used, one for which the penicillin MIC was 0.016 microg/ml and the other for which the penicillin MIC was 1.0 microg/ml. Two additional strains of PNSP were studied in the rabbit. The animals were treated with five different penicillin regimens resulting in different maximum concentrations of drugs in serum (C(max)s) and times that the concentrations were greater than the MIC (T(>MIC)s). The endpoints were bacterial viability counts after 6 h of treatment in the mice and 24 h of treatment in the rabbits. Similar pharmacodynamic effects were observed in all models. In the mouse models bactericidal activity depended on the T(>MIC) and to a lesser extent on the Cmax/MIC and the generation time but not on the area under the concentration-time curve (AUC)/MIC. Maximal bactericidal activities were similar for both PSP and PNSP, being the highest in the peritoneum and blood (approximately 6 log10 CFU/ml), followed by the thigh (approximately 3 log10 CFU/thigh), and being the lowest in the lung (approximately 1 log10 CFU/lung). In the rabbit model the maximal effect was approximately 6 log10 CFU/ml after 24 h. In the mouse models bactericidal activity became marked when T(>MIC) was > or =65% of the experimental time and C(max) was > or =15 times the MIC, and in the rabbit model bactericidal activity became marked when T(>MIC) was > or =35%, Cmax was > or =5 times the MIC, and the AUC at 24 h/MIC exceeded 25. By optimization of the Cmax/MIC ratio and T(>MIC), the MIC of penicillin for pneumococci can be used to guide therapy and maximize therapeutic efficacy in nonmeningeal infections caused by PNSP.
 ...
PMID:Penicillin pharmacodynamics in four experimental pneumococcal infection models. 1125 18

The fluoroquinolone antimicrobial drug danofloxacin was administered to sheep intravenously (i.v.) and intramuscularly (i.m.) at a dose of 1.25 mg/kg of body weight in a two-period crossover study. The pharmacokinetic properties of danofloxacin in serum, inflamed tissue cage fluid (exudate), and noninflamed tissue cage fluid (transudate) were established by using a tissue cage model. The in vitro and ex vivo activities of danofloxacin in serum, exudate, and transudate against a pathogenic strain of Mannheimia haemolytica were established. Integration of in vivo pharmacokinetic data with the in vitro MIC provided mean values for the area under the curve (AUC)/MIC for serum, exudate, and transudate of 60.5, 85.6, and 45.7 h, respectively, after i.v. dosing and 55.9, 77.9, and 49.1 h, respectively, after i.m. dosing. After i.m. dosing, the maximum concentration/MIC ratios for serum, exudate, and transudate were 10.8, 3.0, and 1.6, respectively. The ex vivo growth inhibition data after i.m. dosing were fitted to the inhibitory sigmoid E(max) equation to provide the values of AUC/MIC required to produce bacteriostasis, bactericidal activity, and elimination of bacteria. The respective values for serum were 17.8, 20.2, and 28.7 h, and slightly higher values were obtained for transudate and exudate. It is proposed that use of these data might provide a novel approach to the rational design of dosage schedules.
 ...
PMID:Pharmacokinetics (PK), pharmacodynamics (PD), and PK-PD integration of danofloxacin in sheep biological fluids. 1254 70

The pharmacokinetics and pharmacodynamics of danofloxacin were studied in calves after intravenous (IV) and intramuscular (IM) administration, at a dose of 1.25 mg/kg in a two period cross-over study, using tissue cages to monitor aspects of extravascular distribution. Danofloxacin had a high volume of distribution (3.90 L/kg) and relatively rapid clearance (1.02 L/kgh) after IV dosing. Terminal half-life was 2.65 and 4.03 h, respectively, after IV and IM administration. Danofloxacin penetrated slowly into and was cleared slowly from tissue cage fluid (transudate), elimination half-life (10.2 h after IV and 8.9 h after IM dosing) being greater than for serum. The antibacterial actions of danofloxacin against the pathogen Mannheimia haemolytica 3575 were established in vitro in Mueller Hinton Broth, serum and transudate. These data were used together with in vivo pharmacokinetic parameters, C(max) and AUC to determine the surrogate markers of antimicrobial activity, C(max)/MIC, AUC/MIC and T>MIC. The antibacterial actions of danofloxacin were also determined ex vivo in serum and transudate samples harvested at pre-determined times after IM danofloxacin dosing. Ex vivo AUC/MIC data were integrated with ex vivo bacterial count to establish values producing a bacteriostatic action, inhibition of bacterial count by 50%, reduction in bacterial count by 99.9% (bactericidal action) and elimination of bacteria. Mean values were, respectively, 15.9, 16.7, 18.15 and 33.5h for serum and 15.0, 16.34, 17.8 and 30.7 h for transudate. The AUC/MIC-effect relationships for serum may be regarded as representative of a shallow compartment of blood and well perfused tissues, whilst AUC/MIC-effect relationships for transudate may be considered to represent a deep peripheral compartment of poorly perfused tissues. A novel approach to selecting antimicrobial drug dosage for evaluation in clinical trials, using AUC/MIC values producing either bactericidal activity or elimination of bacteria together with MIC(90) values for calf pathogens, is proposed. This approach can be expected to optimise efficacy and minimise the development of resistance.
 ...
PMID:Pharmacokinetic-pharmacodynamic integration of danofloxacin in the calf. 1272 44

The therapeutic activity of daptomycin was compared with that of vancomycin in a rat model of subcutaneously implanted tissue cages chronically infected with strain Rev1, a spontaneous methicillin-susceptible revertant of the methicillin-resistant Staphylococcus aureus strain MRGR3, showing equivalent virulence to its parent. The MIC and MBC of daptomycin (in Mueller-Hinton broth supplemented with 50 mg/L Ca2+) or vancomycin for strain Rev1 were 1-2 and 2-4 or 1 and 2 mg/L, respectively. In vitro elimination of strain Rev1 in the presence of 50% tissue cage fluid was more rapid with daptomycin 4 mg/L compared with vancomycin. After 2 weeks of infection, viable counts of strain Rev1 averaged 6.49 log10 cfu/mL of tissue cage fluid (n = 87). Intraperitoneal administration of daptomycin 30 mg/kg once daily, or vancomycin 50 mg/kg twice daily, produced antibiotic levels continuously above MBC. After 7 days of therapy with daptomycin or vancomycin, mean +/- S.E.M. counts of Rev1 decreased (P < 0.05) by 1.11 +/- 0.25 (n = 28) or 0.80 +/- 0.31 (n = 35) log10 cfu/mL, respectively, compared with cages of untreated animals, but were not significantly different from each other. In daptomycin-treated rats, three cages yielded subpopulations with reduced susceptibility to daptomycin. In conclusion, a low dose regimen of daptomycin was at least equivalent to vancomycin against chronic foreign body infections due to S. aureus. Drug dosage should be adapted to obtain inflammatory fluid levels of daptomycin minimizing emergence of resistant subpopulations.
 ...
PMID:Comparative efficacy of daptomycin and vancomycin in the therapy of experimental foreign body infection due to Staphylococcus aureus. 1277 78

Pharmacokinetic (PK) and pharmacodynamic (PD) properties for the selection of resistant pneumococci were studied by using three strains of the same serotype (6B) for mixed-culture infection in time-kill experiments in vitro and in three different animal models, the mouse peritonitis, the mouse thigh, and the rabbit tissue cage models. Treatment regimens with penicillin were designed to give a wide range of T(>MIC)s, the amounts of time for which the drug concentrations in serum were above the MIC. The mixed culture of the three pneumococcal strains, 10(7) CFU of strain A (MIC of penicillin, 0.016 micro g/ml; erythromycin resistant)/ml, 10(6) CFU of strain B (MIC of penicillin, 0.25 micro g/ml)/ml, and 10(5) CFU of strain C (MIC of penicillin, 4 micro g/ml)/ml, was used in the two mouse models, and a mixture of 10(5) CFU of strain A/ml, 10(4) CFU of strain B/ml, and 10(3) CFU of strain C/ml was used in the rabbit tissue cage model. During the different treatment regimens, the differences in numbers of CFU between treated and control animals were calculated to measure the efficacies of the regimens. Selective media with erythromycin or different penicillin concentrations were used to quantify the strains separately. The efficacies of penicillin in vitro were similar when individual strains or mixed cultures were studied. The eradication of the bacteria, independent of the susceptibility of the strain or strains or the presence of the strains in a mixture or on their own, followed the well-known PK and PD rules for treatment with beta-lactams: a maximum efficacy was seen when the T(>MIC) was >40 to 50% of the observation time and the ratio of the maximum concentration of the drug in serum to the MIC was >10. It was possible in all three models to select for the less-susceptible strains by using insufficient treatments. In the rabbit tissue cage model, a regrowth of pneumococci was observed; in the mouse thigh model, the ratio between the different strains changed in favor of the less-susceptible strains; and in the mouse peritonitis model, the susceptible strain disappeared and was overgrown by the less-susceptible strains. These findings with the experimental infection models confirm the importance of eradicating all the bacteria taking part in the infectious process in order to avoid selection of resistant clones.
 ...
PMID:Selection of resistant Streptococcus pneumoniae during penicillin treatment in vitro and in three animal models. 1287 11

Antimicrobial efficacy in orthopedic device infections is diminished because of bacterial biofilms which express tolerance to antibiotics. Recently, the use of high doses of levofloxacin with rifampin has been recommended for staphylococcal infections. In the present study, we evaluated the efficacy of levofloxacin at doses of 50 mg/kg/day and 100 mg/kg/day (mimicking the usual and high human doses of 500 mg/day and 750 to 1,000 mg/day, respectively) and compared it to that of to linezolid, cloxacillin, vancomycin, and rifampin in a rat tissue cage model of experimental foreign-body infection by Staphylococcus aureus. The antimicrobial efficacy in vitro (by MIC, minimum bactericidal concentration, and kill curves) for logarithmic- and stationary-phase bacteria was compared with the in vivo efficacy. In vitro bactericidal activity at clinically relevant concentrations was reached by all drugs except rifampin and linezolid in the log-phase studies but only by levofloxacin in the stationary-phase studies. The bacterial count decreases from in vivo tissue cage fluids (means) for levofloxacin at 50 and 100 mg/kg/day, rifampin, cloxacillin, vancomycin, linezolid, and controls, respectively, were: -1.24, -2.26, -2.1, -1.56, -1.47, -1.15, and 0.33 (all groups versus controls, P < 0.05). Levofloxacin at 100 mg/kg/day (area under the concentration-time curve/MIC ratio, 234) was the most active therapy (P = 0.03 versus linezolid). Overall, in vivo efficacy was better predicted by stationary-phase studies, in which it reached a high correlation coefficient even if the rifampin group was excluded (r = 0.96; P < 0.05). Our results, including in vitro studies with nongrowing bacteria, pharmacodynamic parameters, and antimicrobial efficacy in experimental infection, provide good evidence to support the use of levofloxacin at high doses (750 to 1,000 mg/day), as recently recommended for treating patients with orthopedic prosthesis infections.
 ...
PMID:Efficacy of high doses of levofloxacin in experimental foreign-body infection by methicillin-susceptible Staphylococcus aureus. 1701 30

Tissue cages (TC), implanted subcutaneously in the neck in eight ponies, were inoculated with Staphylococcus aureus (S. aureus) to determine the clinical efficacy of marbofloxacin in the treatment of this infection. From 21 h after inoculation, marbofloxacin (6 mg/kg) was administered intravenously (i.v.) once daily for 7 days. Samples of the tissue cage fluid (TCF) were taken to determine marbofloxacin concentrations (days 1, 3 and 7), using high-pressure liquid chromatography, and numbers of viable bacteria [colony forming units (CFU)] (days 1, 3, 7, 14 and 21). Statistical analysis was used to compare CFU before and after treatment. Clinical signs and CFU were used to evaluate the efficacy of treatment. Although, there was a slight decrease in CFU in all TC initially, the infection was not eliminated by marbofloxacin treatment in any of the ponies and abscesses formed. As the MIC (0.25 microg/mL) did not change during treatment and the concentration of marbofloxacin during treatment (mean concentration in TCF was 0.89 microg/mL on day 1, 0.80 microg/mL on day 3 and 2.77 microg/mL on day 7) was above MIC, we consider that the treatment failure might be attributable to the formation of a biofilm by S. aureus. Based on the present results, i.v. administration of marbofloxacin alone is not suitable for the elimination of S. aureus infections from secluded sites.
 ...
PMID:Clinical efficacy of intravenous administration of marbofloxacin in a Staphylococcus aureus infection in tissue cages in ponies. 1708 60

We compared the efficacy of a novel rifamycin derivative, ABI-0043, with that of rifampin, alone and in combination with levofloxacin, against methicillin-susceptible Staphylococcus aureus ATCC 29213 in a guinea pig tissue-cage infection model. The MIC, logarithmic-growth-phase minimal bactericidal concentration, and stationary-growth-phase minimal bactericidal concentration of ABI-0043 were 0.001, 0.008, and 0.25 microg/ml, respectively; the corresponding concentrations of rifampin were 0.016, 0.8, and 3.6 microg/ml, respectively. After a single intraperitoneal dose of 12.5 mg/kg of body weight, the peak concentration in cage fluid was 1.13 micarog/ml of ABI-0043 and 0.98 microg/ml of rifampin. Five days after completion of treatment, levofloxacin administered alone (5 mg/kg/12 h) resulted in bacterial counts in cage fluid that were similar to those for untreated controls (>8.0 log(10) CFU/ml), whereas rifampin and ABI-0043 administered alone (12.5 mg/kg/12 h) decreased the mean titers of bacteria +/- standard deviations to 1.43 +/- 0.28 log(10) and 1.57 +/- 0.53 log(10) CFU/ml, respectively, in cage fluid. In combination with levofloxacin, both rifamycins cleared bacteria from the cage fluid. The cure rates of cage-associated infections with rifampin and ABI-0043 administered alone were 46% and 58%, respectively, and increased to 88% and 92% in combination with levofloxacin. Emergence of rifamycin resistance was observed in 42% of cages after ABI-0043 therapy and in 38% of cages after rifampin therapy; no emergence of resistance occurred with combination treatment with levofloxacin. In conclusion, ABI-0043 had cure rates comparable to that of rifampin. ABI-0043 in combination with a quinolone has the potential for treatment of implant-associated infections caused by susceptible strains of S. aureus, potentially without drug-drug interactions.
 ...
PMID:Efficacy of a novel rifamycin derivative, ABI-0043, against Staphylococcus aureus in an experimental model of foreign-body infection. 1750 4


<< Previous 1 2 3 4 5 Next >>