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Biomedical subjects

P Karayiannakos

Publications and source records attributed to P Karayiannakos.

8 recordsLinked to original sources

Evidence of less severe aortic valve destruction after treatment of experimental staphylococcal endocarditis with vancomycin and dexamethasone.

The beneficial effects of therapy combining an antibiotic and dexamethasone have been reported in human studies on meningitis and in experimental studies on septic arthritis, nephritis, and endophthalmitis. Since most patients with staphylococcal endocarditis need a combination of medical and surgical treatment, the purpose of this study was to determine whether the addition of dexamethasone to vancomycin has any beneficial effect regarding the degree of valve tissue damage or the course of experimental aortic valve endocarditis caused by a methicillin-resistant strain of Staphylococcus aureus. Rabbits with catheter-induced aortic valve vegetations were randomly assigned to a control group and to groups receiving dexamethasone (0.5 mg/kg of body weight, intravenously [i.v.], twice a day [b.i.d]), vancomycin (30 mg/kg, i.v., b.i.d), or dexamethasone plus vancomycin, for a total of 10 doses (two doses per day for 5 days). The severity of valve tissue damage was significantly less in groups receiving vancomycin plus dexamethasone compared with that of the group receiving vancomycin alone (P < 0.001). The severity of tissue damage was inversely correlated with the mean polymorphonuclear leukocyte number in valve tissue. No statistically significant differences were observed between the vancomycin-treated group and the vancomycin-plus-dexamethasone-treated group in survival, blood culture sterilization rate, or reduction of the microbial burden (in CFU per gram) in valvular tissue. In conclusion, treatment with a combination of vancomycin and dexamethasone for 5 days reduces the severity of valve tissue damage in experimental staphylococcal aortic valve endocarditis. These findings could have significant implications in the treatment of staphylococcal endocarditis and deserve further confirmation in clinical trials.

Animals↗

Single-oral-dose azithromycin prophylaxis against experimental streptococcal or staphylococcal aortic valve endocarditis.

Azithromycin and ampicillin protected 94 and 72% of animals challenged with Streptococcus oralis, respectively (P = 0.177), while azithromycin and vancomycin protected 59 and 94% of the methicillin-resistant Staphylococcus aureus (MRSA)-challenged animals, respectively (P = 0.018). Azithromycin is effective in preventing experimental streptococcal endocarditis, but against MRSA it is less effective than vancomycin.

Administration, Oral↗

Successful trovafloxacin prophylaxis against experimental streptococcal aortic valve endocarditis.

Single-dose trovafloxacin (15 mg/kg given intravenously [i.v.]) and ampicillin (40 mg/kg given i.v.) protected 38 and 33% of animals challenged with an ampicillin-tolerant strain of Streptococcus oralis, respectively. As a double-dose regimen, trovafloxacin afforded total protection (100%; P < 0.001 versus controls). Trovafloxacin is the first fluoroquinolone effective in preventing experimental streptococcal endocarditis.

Ampicillin↗

Successful single-dose teicoplanin prophylaxis against experimental streptococcal, enterococcal, and staphylococcal aortic valve endocarditis.

Teicoplanin is a glycopeptide antibiotic that is administered both intramuscularly and intravenously. It has a prolonged half-life and a less toxic profile in comparison to those of vancomycin. The efficacy of a single dose of teicoplanin (18 mg/kg of body weight given intramuscularly) for the prevention of endocarditis due to Streptococcus oralis, Enterococcus faecium, and methicillin-resistant Staphylococcus aureus (MRSA) was evaluated after applying the rabbit model. Vancomycin at a single dose of 30 mg/kg given intravenously was used as the comparative agent for the prevention of endocarditis due to MRSA and E. faecium, while ampicillin at a single dose of 40 mg/kg given intravenously was used as the comparative agent for the prevention of endocarditis due to S. oralis. Rabbits in the teicoplanin group were infected at 1 h postdosing with approximately 10(7) CFU of each strain. Rabbits in the other groups were infected at 0.5 h postdosing with approximately 10(7) CFU of S. oralis (ampicillin group) or E. faecium and MRSA (vancomycin group). All rabbits were sacrificed 5 days later. Teicoplanin and vancomycin protected the animals challenged with E. faecium by 87.5 and 50%, respectively, and protected the animals challenged with MRSA by 100 and 92%, respectively. Teicoplanin and ampicillin protected the animals challenged with S. oralis by 100 and 77%, respectively. Prevention of endocarditis by teicoplanin was likely to be due to a prolonged inhibition of bacterial growth by the sustained supra-MICs. It is concluded that teicoplanin is very effective in preventing experimental streptococcal, enterococcal, and staphylococcal endocarditis and may be an attractive alternative antibiotic in patients allergic to beta-lactams, especially in the outpatient setting.

Animals↗

Vancomycin or vancomycin plus netilmicin for methicillin- and gentamicin-resistant Staphylococcus aureus aortic valve experimental endocarditis.

Using a rabbit model of aortic valve endocarditis, we studied the efficacy of vancomycin alone or in combination with netilmicin and/or rifampin against a methicillin- and gentamicin-resistant strain of Staphylococcus aureus (MGRSA). Antibiotics were given for 6 to 12 days, as follows: vancomycin (15 mg/kg of body weight every 12 h [BID] intravenously), vancomycin plus netilmicin (2.5 mg/kg BID intramuscularly), vancomycin plus rifampin (10 mg/kg BID intramuscularly), and vancomycin plus netilmicin plus rifampin at the same routes, dosages, and schedules mentioned above. Netilmicin was given to two additional groups at a higher dosage (6 mg/kg every 24 h intramuscularly) alone or in combination with vancomycin (15 mg/kg BID intravenously) for 12 days. All regimens resulted in undetectable bacterial counts in a significant proportion of vegetations (except netilmicin alone) or reduced the bacterial counts in the vegetations compared with the counts in the untreated controls (P<0.01 to P<0.001). No resistance to rifampin or netilmicin developed during therapy. It is concluded that in the treatment of experimental aortic valve endocarditis caused by MGRSA (i) vancomycin as monotherapy is as efficacious as the triple combination, (ii) the addition of netilmicin (once daily or BID) to vancomycin does not improve the efficacy of the latter antibiotic, even in the presence of rifampin, and (iii) a 12-day course in more effective than a 6-day one, but not at a statistically significant level.

Animals↗

Efficacy of ceftazidime and aztreonam alone or in combination with amikacin in experimental left-sided Pseudomonas aeruginosa endocarditis.

The in vivo efficacies of ceftazidime, aztreonam, and the combinations of ceftazidime with amikacin and aztreonam with amikacin were studied in the rabbit left-sided endocarditis model by using two strains of Pseudomonas aeruginosa, one multisusceptible and one multiresistant, in a total of 156 animals. Antibiotics were given intramuscularly for 10 days, as follows: amikacin, 7 mg/kg of body weight every 8 h, and ceftazidime and aztreonam, 50 mg/kg every 8 h. All regimens except amikacin alone significantly reduced the number of CFU per gram of vegetation (P < or = 0.008), but only for the multisusceptible strain for which sterile vegetations were obtained in 20, 25, 21, 75, and 53% of the groups treated with amikacin, ceftazidime, aztreonam, and the combination groups ceftazidime-amikacin and aztreonam-amikacin, respectively (ceftazidime plus amikacin versus controls, P = 0.001). Regarding the decrease in the numbers of colonies in vegetations, (i) all regimens significantly reduced the number of CFU per gram of vegetation (P < 0.001), (ii) results with ceftazidime-amikacin compared with those with monotherapy were significantly different (P < or = 0.007), and (iii) results with aztreonam-amikacin, although better than those with monotherapy, were marginally not statistically significant. At 1 h postdose, mean amikacin, aztreonam, and ceftazidime levels in serum were 35 +/- 19.4, 89.6 +/- 8.16, and 92.61 +/- 11.52 micrograms/ml, respectively. It was concluded that the combination of ceftazidime, and possibly aztreonam, with amikacin given at high doses and short intervals could have a place in the therapy of patients with left-sided endocarditis caused by P. aeruginosa.

Amikacin↗

Evidence for the existence of non-esterified cholesterol carried by albumin in rat serum.

Isolation of non-esterified [14C]cholesterol bound to albumin from rat serum, 8 days after i.p. injection of [14C]cholesterol, was achieved by affinity chromatography, using Cibacron blue F3GA bound to Sepharose 4B and by Sephadex G-150 column chromatography. Both methods permit isolation of large quantities of cholesterol-loaded albumin, free of globulins and lipoproteins. The isolated albumin-cholesterol fraction was estimated to be 4.6 mg/100 ml serum, which represents approx. the 24% of the non-esterified cholesterol present in the rat serum. Albumin-cholesterol, cholesterol glucoside, cholesterol hemisuccinate and hydroxylated derivatives of cholesterol produced a biphasic curve of changes in synaptosomal plasma membranes (SPM)-bound (Na+ + K+)-stimulated ATPase activity. Low concentrations of the ligand progressively increased the enzyme activity, while increasing the ligand concentration above that which maximally stimulated the enzyme activity, produced a progressive inhibition. Lipoproteins did not have any effect on the enzyme activity. The fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene-labeled SPM, increased in albumin-cholesterol derivatives-treated SPM, which is consistent with a general decrease in membrane bilayer fluidity. The results provide evidence that the 'albumin-cholesterol' fraction of the serum may directly affect the cell membrane-bound enzyme activity.

Animals↗