RESUMO
In Tanzania, limited laboratory services often preclude routine identification of microorganisms that cause infections in persons with diabetes. Thus, we carried out this study to determine the utility of a Gram stain alone versus culture in guiding appropriate antimicrobial therapy. During February 2006 to December 2007 (study period), deep tissue biopsies were obtained from persons with diabetes presenting to the Muhimbili National Hospital (MNH) with infected limb ulcers. Specimens were Gram-stained then cultured for bacteria and fungi. Biopsies were obtained from 128 patients. Of 128 cultures, 118 (92%) yielded bacterial or fungal growth; 59 (50%) of these 118 cultures yielded mixed growth (80% included Gram-negative organisms); 38 (32%) and 20 (17%) yielded Gram-negative and Gram-positive organisms alone, respectively. The predictive value positive of a Gram stain for bacterial growth was 93% (110/118); a Gram-positive stain was 75% (15/20) predictive of growth of Gram-positive organisms whereas a Gram-negative stain was 82% (31/38) predictive of growth of Gram-negative organisms. In regions with limited resources, a Gram stain of an ulcer biopsy that is carefully procured is largely predictive of the type of microorganism causing infection. Gram staining of deep tissue biopsies might have a potential role to play in the management of infected diabetic limb ulcers.
Assuntos
Complicações do Diabetes/microbiologia , Violeta Genciana , Úlcera da Perna/microbiologia , Fenazinas , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Pé Diabético/microbiologia , Feminino , Bactérias Gram-Negativas/isolamento & purificação , Bactérias Gram-Positivas/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: NN703 (tabimorelin) is an orally active growth hormone (GH) secretagogue intended for use as an alternative to daily injections of GH. In vitro studies in human liver microsomes have indicated that NN703 is a mechanism-based inhibitor of CYP3A4. The aim of the present study was to investigate in man the effects of NN703 on the pharmacokinetics of midazolam, a substrate of CYP3A4. METHODS: Seventeen adult male subjects were enrolled in the study, and each received an oral dose of midazolam (7.5 mg) on four occasions: at baseline (day 1), after one dose of NN703 (day 3), after 7 days once daily NN703 treatment (day 9) and after a 7-day washout period (day 16). The pharmacokinetics of midazolam and its main metabolite, alpha-hydroxymidazolam, were investigated. RESULTS: Following a single dose of NN703 (day 3), the AUC of both midazolam and alpha-hydroxymidazolam increased by 64% and 34%, respectively (P=0.0001 for both). After repeated NN703 dosing (day 9), NN703 levels reached steady state, and midazolam AUC further increased to 93% relative to baseline (P=0.0001), whereas alpha-hydroxymidazolam AUC decreased slightly and was 11% higher than baseline (n.s.). Following the washout period (day 16), midazolam AUC decreased to values lower than those on day 3 and day 9, but still significantly (45%) higher than baseline levels (P=0.0001). The C(max) values of midazolam and alpha-hydroxymidazolam demonstrated a pattern similar to the AUC, but the effect following repeated NN703 dosing was more pronounced. The t(1/2) of midazolam increased from day 1 to day 3 (P=0.0483) but was essentially unchanged at steady state on day 9. CONCLUSION: This study shows that administration of NN703 and midazolam, a CYP3A4 substrate, leads to a significant increase in exposure of midazolam. This is consistent with NN703 inhibition of CYP3A4 activity.