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

Because persistence of infections associated with prosthetic material despite the use of appropriate antibiotics is a major clinical problem, the antimicrobial susceptibility of bacteria responsible for a chronic subcutaneous tissue cage infection in rat was investigated ex vivo. Three to 6 weeks after the initiation of infection, suspensions of two strains of Staphylococcus aureus recovered from the foreign body surface and surrounding fluid were exposed to either oxacillin, vancomycin, fleroxacin, gentamicin, or rifampin. The MBCs of these bacteria were markedly elevated, in most cases 128 to greater than 256 times higher than the MBC of batch culture S. aureus in either logarithmic or stationary phase. Kinetic studies showed the bacteria did not grow when incubated for 2 h in Mueller-Hinton broth, possibly reflecting dormancy. Their killing was slow and incomplete by all antibiotics at greater than 8 times their MIC. These data provide direct evidence of a decreased susceptibility of S. aureus to the killing effect of antimicrobials during chronic foreign body infections in vivo.
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PMID:Resistance of Staphylococcus aureus recovered from infected foreign body in vivo to killing by antimicrobials. 190 1

The postantibiotic effect (PAE) of cefcanel, a new oral cephalosporin with high in vitro activity against Gram-positive bacteria, was investigated. Ten clinical isolates of Streptococcus pyogenes group A and one reference strain (M12, P1800) were exposed to 5 X MIC of cefcanel for 2 h in vitro. The PAE was found to be 2.3 (range 1.7-3.2) h. To investigate the PAE in vivo, a newly developed animal model with implanted tissue cages in rabbits was used. The rabbits received different doses of cefcanel i.v. and unbound concentrations in the tissue cage fluid (TCF) were measured. The protein binding of cefcanel in TCF was approximately 98%. Above a certain dose level, unexpectedly high TCF concentrations were found, indicating that the albumin binding capacity for the drug was surpassed. A PAE in vivo of 0.9-2.6 h was confirmed for cefcanel when the free drug concentration in TCF exceeded 3 X MIC.
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PMID:The postantibiotic effect of cefcanel on beta-hemolytic streptococci group A in vitro and in vivo. 209 8

A postantibiotic effect (PAE) in vivo was induced in group A streptococci established in a tissue cage model in rabbits. The bacteria were exposed to 10 x MIC of benzylpenicillin in tissue cage fluid (TCF) for 2 h. TCF was then aspirated, penicillin was eliminated by washing and the bacteria were transferred to tissue cages in other rabbits in order to study the in-vivo killing kinetics of streptococci in the postantibiotic phase. In these latter rabbits the concentration of benzylpenicillin in TCF corresponded to 10 or 0.3 x MIC. Bacteria not previously exposed to penicillin were used as controls. Streptococci in postantibiotic phase were killed as effectively after re-exposure to 10 x MIC in vivo as the growing controls. Although the concentration of penicillin fell below the MIC after 12 h, no regrowth was seen during the following 12 h in either culture. When only subinhibitory concentrations in TCF were used in the second phase, a killing of approximately 1 log10 cfu/ml was noted both in the previously exposed cultures and in controls. Both cultures started to multiply first after 6-7 h.
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PMID:Effects of supra- and sub-MIC benzylpenicillin concentrations on group A beta-haemolytic streptococci during the postantibiotic phase in vivo. 221 56

The pharmacodynamics of antibiotics, i.e. the rate of killing and the time before regrowth of surviving bacteria, may be important factors for determination of the dosage interval. In the present study the effect of protein binding, antibiotic concentrations, bacterial growth phase and bacterial inoculum on the rate of bacterial killing was investigated. The postantibiotic effect (PAE) was also studied in vitro and in vivo. The killing rate of S. aureus did not differ when the bacteria were exposed to the same free concentrations of dicloxacillin in medium with and without albumin. Protein binding per se did thus not diminish the bactericidal activity. A paradoxically reduced bactericidal effect was noted when S. aureus was exposed to high concentrations of dicloxacillin, cloxacillin and benzylpenicillin. For determination of PAE of imipenem on Ps. aeruginosa, counts of viable bacteria were compared with assay of bacterial intracellular ATP. Both methods demonstrated a PAE for the strains tested at an inoculum of 10(6) cfu/ml. At an inoculum of 10(8) cfu/ml no PAE was found, which coincided with a lack of bactericidal effect. Both the PAE and the bactericidal effect were restored with aeration of the cultures, indicating insufficient penetration of imipenem to the target sites at low oxygen tension. An in vivo model in rabbits with implanted tissue cages was developed for evaluation of the PAE. Group A beta-hemolytic streptococci showed a PAE of approximately 2 h in vivo, which correlated well with the PAE found in vitro. Despite that streptococci in postantibiotic phase (PA-phase) were non-multiplying, such bacteria were killed as efficiently as previously untreated controls when exposed to 10xMIC of penicillin both in vitro and in vivo. However, streptococci in PA-phase were much more sensitive to the repeated challenge to subinhibitory concentrations of penicillin than previously untreated controls. In vivo, no difference in sensitivity to sub-MIC penicillin concentrations between streptococci in PA-phase and untreated controls was seen, probably due to the presence of host factors in the tissue cage fluid. It seems that for streptococci, subinhibitory antibiotic concentrations are more important for the sucess with intermittent dosing than the PAE, especially when a normal host defence is present.
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PMID:Pharmacodynamics of beta-lactam antibiotics. Studies on the paradoxical and postantibiotic effects in vitro and in an animal model. 249 24

A new experimental model to evaluate the postantibiotic effect (PAE) in vivo was developed using subcutaneously implanted tissue cages in rabbits with normal host defence mechanisms. The rabbits received benzylpenicillin i.v. in a dose giving a free penicillin concentration of 10 X MIC in the tissue cage fluid (TCF). A log-phase suspension of group A streptococci was injected into the tissue cages exposing them to penicillin in vivo. After 2 h bacterial samples were withdrawn, treated with penicillinase and transferred to 2 tissue cages in untreated rabbits. Simultaneously, unexposed streptococci were implanted in 2 other cages in the same animals. By repeated sampling of TCF, growth curves of the streptococci exposed to penicillin and the controls could be compared and a PAE of 1.6-2.4 h demonstrated. The PAE was of the same magnitude as that found in vitro. The model has several advantages for the demonstration of PAE in vivo: repeated samplings are easy to perform percutaneously, the effect of subinhibitory antibiotic concentrations are avoided, interindividual variations are eliminated since each animal is its own control, and the experiments can be performed in animals with undisturbed host defence mechanisms.
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PMID:An in vivo model for evaluation of the postantibiotic effect. 328 24

The refractory period and the killing rate of beta-haemolytic streptococci after exposure to phenoxymethylpenicillin were tested in an in-vivo model. beta-Haemolytic streptococci were injected into steel net chambers implanted subcutaneously on the backs of rabbits. The rabbits were treated with infusions of phenoxymethylpenicillin, either as a single dose to measure the refractory period or as repeated doses in order to measure the killing rate of streptococci. The peak concentration of phenoxymethylpenicillin in tissue chamber fluid occurred about 16-120 min post infusion, and reached 0.4 mg/l in infected and 0.6 mg/l in uninfected tissue cage fluid. In the tissue cage fluid the phenoxymethylpenicillin concentration exceeded 0.03 mg/l, the MIC-value for the streptococcal strain used, for at least 6 h. After a single infusion there was a decline in viable count. The bacteria did not reach their original numbers until 60-70 h later. After the sixth infusion streptococci were no longer detectable in tissue cage fluid. There was a close correlation between viable counts before treatment and the time required for eradication of bacteria. L-phase variants of beta-haemolytic streptococci were not found when tissue cage fluid was plated on special media.
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PMID:Studies in vivo on the killing rate and refractory period of penicillin V in an experimental streptococcal infection. 392 81

The penetration of various aminoglycosides into uninfected and infected fluids of steel net cages, implanted subcutaneously into rabbits, was studied. The pharmacokinetics of the antibiotics tested in these fluids were characterized by a peak concentration which was delayed in relation to that in serum after both intramuscular and intravenous administration, and by a slower elimination from cage fluids than from serum. Comparing amikacin, gentamicin, netilmicin and tobramycin, the latter seemed to have a somewhat lower penetrability into uninfected cage fluids. Infection of the cage fluids with gram-negative aerobic bacteria resulted in a reduction of the measurable concentrations of amikacin, gentamicin or netilmicin in the cage fluids when compared to those obtained in uninfected fluids in the same rabbits. Elimination of the aminoglycosides from the infected cage fluids was slower than from the uninfected ones. The lower concentrations of the aminoglycosides in infected cage fluids were considered to be primarily due to a penetration barrier created by the infection. The viable counts in infected cage fluids were only marginally affected in cages where the aminoglycoside concentrations were above the minimum inhibitory concentrations (MIC's) of the aminoglycosides against the bacterial strains used for infection when tested in vitro according to standard techniques. In infected cage fluids the pO2 and pH were low, while the pCO2 was high. The number of viable bacteria was high. These factors, which in vitro increased the MIC's of the agents, and the low concentrations achieved in infected cage fluids could explain the inefficacy of aminoglycoside treatment in this experimental model.
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PMID:Studies on some variables influencing aminoglycoside efficacy in vivo and in vitro. 679 55

Device-related infections are difficult to treat with antibiotics alone. Standard susceptibility tests do not correlate with treatment success. Therefore, the utility of a pharmacokinetic in vitro model has been evaluated in comparison with the tissue-cage infection model in guinea pigs. The bactericidal activity of 28 treatment regimens has been studied by using three different test strains. In vitro efficacy was defined as reduction in the number of suspended or adherent bacteria, and in vivo efficacy was defined as reduction in the number of bacteria in tissue-cage fluid. Test results between the two models (in vivo and in vitro) correlated well, with correlation coefficients of 0.85 for in vivo efficacy versus in vitro efficacy against suspended bacteria and 0.72 for in vivo efficacy versus in vitro efficacy against adherent bacteria (P < 0.05) for Staphylococcus aureus, 0.96 and 0.82 (P < 0.05) for Staphylococcus epidermidis, and 0.89 and 0.97 for Escherichia coli, respectively. In contrast, standard susceptibility tests, ratios of MICs to trough or peak levels, ratios of the area under the curve to the MIC, or time above the MIC were not predictive for therapeutic outcome in either the in vitro or in vivo model. In both models, the bactericidal activity levels with combination regimens were significantly higher than those with single-drug regimens (P < 0.001). Furthermore, rifampin combinations with either vancomycin, teicoplanin, fleroxacin, or ciprofloxacin were significantly more bactericidal against adherent bacteria than netilmicin combinations with vancomycin or daptomycin (P < 0.01). Thus, in vivo verification of the pharmacokinetic in vitro model correlated well with the animal model. The in vitro model offers an alternative to ther animal model in experiments that screen and assess antibiotic regimens against device-related infections.
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PMID:In vivo verification of in vitro model of antibiotic treatment of device-related infection. 762 1

The efficacies of imipenem when directed against methicillin-susceptible (MSSA) and methicillin-resistant (MRSA) strains of Staphylococcus aureus were compared with those of oxacillin and vancomycin in a subcutaneous rat model, using chronically infected tissue cages. At three weeks after inoculation, stable chronic infections were established with average bacterial counts exceeding 10(6) cfu/mL tissue cage fluid for both strains. Intraperitoneal administration (twice a day for 7 days) of imipenem (80 mg/kg) or oxacillin (200 mg/kg) produced peak levels of 23 or 45 mg/L and through levels of < 0.1 and 5.7 mg/L, respectively. The therapeutic regimens of either imipenem (P < 0.001) or oxacillin (P < 0.02) administered for 7 days led to significant reductions in bacterial counts in the tissue cage fluids of animals chronically infected with MSSA. In contrast, imipenem was not effective against chronic MRSA tissue cage infections, despite the relatively low MIC of the infecting strain and the use of high dose (120 mg/kg) therapy. In-vitro susceptibility testings of MRSA performed before and after imipenem therapy demonstrated the emergence of a highly resistant subpopulation.
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PMID:Comparative efficacies of imipenem, oxacillin and vancomycin for therapy of chronic foreign body infection due to methicillin-susceptible and -resistant Staphylococcus aureus. 792 12

The postantibiotic effect (PAE) of dirithromycin and erythromycin against strains Streptococcus pyogenes group A M12, NCTC P1800, Streptococcus pneumoniae 23, Staphylococcus aureus Oxford strain 209, Moraxella catarrhalis 15616 and Haemophilus influenzae 5590 was investigated in vitro and in vivo by use of the tissue cage model in rabbits. By exposing strains to 2.5-5 x MIC levels for 6 h or 12 h, both compounds induced in vitro PAEs of 1-9 h, and in two cases >20 h. Cultures in the PAE-phase were then re-exposed to subinhibitory concentrations (0.25 x MIC and 0.5 x MIC) of antibiotic and prolonged suppression of regrowth was obtained for 2->20 h. Following i.v. antibiotic treatment of rabbits (10 mg/kg or 20 mg/kg dirithromycin and 20 mg/kg or 40 mg/kg erythromycin) and bacterial infection of the implanted tissue cages in the same rabbit, the tissue cage fluid (TCF) was sampled 6 h after infection and regrowth was monitored by sampling from new tissue cages in untreated rabbits. These i.v. single doses of both antibiotics induced in vivo PAEs of >6 h, but <20 h against S. pyogenes. Suppression of regrowth in TCF was also obtained for > or = 20 h on infection with exposed S. pyogenes in the PAE-phase in newly implanted tissue cages in rabbits that had been treated with low doses of antibiotic to produce subinhibitory concentrations in the TCE Dirithromycin was in general as active as erythromycin in inducing PAE and in prolonging suppression of bacterial regrowth in the PAE phase.
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PMID:Postantibiotic effect and postantibiotic sub-mic effect of dirithromycin and erythromycin against respiratory tract pathogenic bacteria. 1033 55


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