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

Effect of betamethasone and diclofenac sodium on serum and tissue concentration of amoxicillin: in vivo study in rats Efeito da betametasona e do diclofenaco sódico na concentração sérica e tecidual da amoxicilina: estudo in vivo em ratos

OBJECTIVE: Antimicrobial agents in combination with anti-inflammatory drugs have been usually prescribed in both Medicine and Dentistry. However, few scientific reports support this clinical practice. The aim of this study was to evaluate the effect of betamethasone and diclofenac sodium on serum and tissue concentration of amoxicillin in rats. METHODS: Four polyurethane sponges were implanted in the back skin of 48 rats. After seven days the animals were divided into 6 groups (n=8). Group 1: amoxicillin (25 mg/kg); G2: diclofenac sodium (2.5 mg/kg); G3: betamethasone (0.1 mg/kg); G4: diclofenac sodium and amoxicillin; G5: betamethasone and amoxicillin; and G6: 0.9% sodium chloride solution (1.0 mL - control group). All drugs were administered in a single dose. After 90 minutes, the granulomatous tissues of each animal were surgically removed and weighed. Blood was collected from cervical plexus, centrifuged and 10µL of serum was placed on paper discs. In order to estimate amoxicillin concentration, serum and granulomatous tissues were separately submitted to microbiological assay, which used 10(8)cfu/mL of Staphylococcus aureus ATCC 25923 (penicillin-susceptible strain). After incubation (18 hours, 37ºC) the inhibition zones were measured and compared to a regression curve. RESULTS: No inhibition zones were observed for groups 2, 3 and 6. Tissue and serum concentrations of both G1 (4.14µg/g and 2.06µg/mL, respectively) and G5 (3.87µg/g and 1.70µg/mL, respectively) showed statistically significant differences (Kruskal-Wallis, p<0.05) in comparison to G4 (1.45µg/g and 0.41µg/mL, respectively). G1 and G5 did not differ significantly (p>0.05). CONCLUSION: Considering single doses, betamethasone did not interfere with amoxicillin levels but diclofenac sodium reduced both tissue and serum levels of amoxicillin in rats.<br>OBJETIVO: A prescrição de antimicrobianos associados a antiinflamatórios é uma prática comum em odontologia, embora na maioria das vezes não haja justificativa para tal conduta. O objetivo deste trabalho foi avaliar, em um estudo in vivo em ratos, os efeitos da betametasona e do diclofenaco sódico nas concentrações sérica e tecidual da amoxicilina. MÉTODOS: Foram utilizados 48 ratos Wistar machos (6 grupos, n=8), com idade de 60 dias. Esponjas de PVC (policlorovinil) foram implantadas em quatro pontos no dorso de cada animal. Após sete dias, foram administrados por via intragástrica ou intramuscular: Grupo 1: amoxicilina (25 mg/kg); G2: diclofenaco sódico (2,5 mg/kg/i.m.); G3: betametasona (0,1 mg/kg/i.m.); G4: diclofenaco sódico e amoxicilina; G5: betametasona e amoxicilina; e G6: solução de cloreto de sódio a 0,9% (1,0 mL - grupo controle). Após 90 minutos, foram colhidos 2 tecidos granulomatosos e amostras séricas de cada animal e colocados em meios de cultura inoculados com 10(8) ufc/mL de Staphylococcus aureus ATCC 25923. Os halos de inibição foram medidos após 18 horas de incubação (37ºC), e através do teste microbiológico foram obtidas as concentrações séricas e teciduais da amoxicilina. RESULTADOS: Não foram observados halos de inibição para os grupos 2, 3 e 6. As concentrações séricas e teciduais de G1 (4,14µg/g e 2,06µg/mL, respectivamente) e G5 (3,87µg/g e 1,70µg/mL, respectivamente) demonstraram diferenças estatisticamente significantes (Kruskal-Wallis, p<0,05) em comparação a G4 (1,45µg/g e 0,41µg/mL, respectivamente). G1 e G5 não apresentaram diferença estatística (p>0,05). CONCLUSÃO: Considerando uma dose única, a betametasona não interferiu nas concentrações sérica e tecidual de amoxicilina, enquanto o diclofenaco sódico reduziu as concentrações sérica e tecidual de amoxicilina em ratos