Tawanda Gumbo

..The result is a rational starting point in drug regimen design. Such regimens can then be compared with standard therapies in randomized clinical trials...

..With the proposed breakpoints, the rates of multidrug-resistant tuberculosis could become 4-fold higher than currently assumed...

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..In addition, PK/PD driven doses have been proposed for new anti-tuberculosis agents such as moxifloxacin and PA-824...

..3 kg above which serum clearance increased by approximately 50%. Patients with weight >66.3 kg may need larger doses to achieve similar exposures to those <66.3 kg. However, the clinical implications are still unknown...

..This review examines recent advances in echinocandin pharmacokinetics and pharmacodynamics, and discusses how these studies could lead to newer dosing strategies for the treatment of invasive candidiasis...

..tuberculosis, (ii) the achievement of a free C(max)/MIC of >175 that can be tolerated by patients, and (iii) a long postantibiotic effect duration...

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..Once-weekly micafungin therapy is as efficacious as daily therapy in a murine model of disseminated candidiasis...

..We examined the veracity of this cornerstone belief...

..This pharmacokinetic-pharmacodynamic picture of anidulafungin persistence in tissues and the resultant persistent fungal decline should be exploited to improve the efficacy of anidulafungin therapy for candidemia...

..CONCLUSION: A moxifloxacin dose of 800 mg/day is likely to achieve excellent M. tuberculosis microbial kill and to suppress drug resistance. However, tolerability of this higher dose is still unknown...

..On the other hand, such reduced AUCs could lead to therapy failure. Thus, new and individualized ethambutol dosing regimens need to be designed for obese and extremely obese patients...

..For patients infected with susceptible isolates, however, 800 mg a day should be examined for safety and efficacy for disseminated M. avium disease...

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..avium in Middlebrook broth. Given that the modal MIC of clinical isolates is around 2 mg/liter, most isolates should be considered ethambutol resistant...

..Over the past 15 years, considerable PK-PD data have been derived from infected patients for many classes of antimicrobial agents. These data provide the opportunity to confirm knowledge gained from animal PK-PD infection models...

..One of the explanations for why early bactericidal activity fails to predict sterilization may be the emergence of a resistant subpopulation, which only becomes >/=1% at the end of the early bactericidal activity studies...

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..In each instance, quinolone antimicrobials were examined. More investigations with other pathogens and drug classes are required...

..Ethambutol is used for the treatment of tuberculosis in cases where there is isoniazid resistance. We examined the emergence of drug resistance to ethambutol monotherapy in pharmacokinetic-pharmacodynamic studies of a hollow-fiber system...

..Use of pharmacodynamic/pharmacokinetic models has resulted in design of new doses and dosing schedules for disseminated MAC, as well as new susceptibility breakpoints for ethambutol and moxifloxacin...

..tuberculosis killing. We conclude that current efforts aimed at better pharmacokinetic matching to decrease M. tuberculosis resistance emergence are likely futile and counterproductive...

..We conclude that current recommended doses for children are likely suboptimal and that isoniazid doses in children are best individualized based on disease process, age, and acetylation status...

..098 (CI, 0.047 to 0.193) at 60 mg/kg of pyrazinamide. Thus, high-dose pyrazinamide did not significantly increase hepatotoxicity. This suggests that a considerable portion of hepatotoxicity rates may be idiosyncratic...

..These steps outline a more rational approach than that of current methods for designing regimens and predicting outcome so that both new and older antituberculosis agents can shorten therapy duration...

..Furthermore, micafungin SCL continues to increase as weight increases, with no obvious plateau. This leads to a requirement for strategies to determine individualized dosing levels for obese and extremely obese patients...

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..These patient factors, the covariates for pharmacokinetic variability, and PK-PD factors suggest the need to individualize therapy for patients with tuberculosis in order to optimize outcomes and reduce the duration of therapy...

..In summary, a pSUM-protein expression vector and a mammalian IL-6 reporter cell line provide new tools for understanding the pathogenic mechanisms deployed by various mycobacterial species...

..07% of controls. The long-term outlook in patients with proven tuberculous meningitis adequately treated with current standard tuberculous therapy is bleak. A re-examination of treatment strategies is urgently needed...

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..2-130] and chronic renal failure (OR 14.7; 95% CI 1.2-184). These data suggest that careful long-term follow-up of patients with C. glabrata fungemia is important and present an opportunity to explore secondary prophylaxis...

..A particularly big problem is the emergence of multidrug resistant tuberculosis. The current application will apply pharmacokinetic-pharmacodynamic solutions to this public health problem. ..