Effects of the Immune System

The majority of in vitro models commonly used are devoid of immune system factors that is, antimicrobial effects are studied in an environment that does not contain the host defense factors. The antimicrobial effect may thus be underestimated, because organisms are free from the inhibitory action of such immune system factors as leukocytosis, phagocytosis, and immunoglobulins. Shah 22 employed a model that incorporated fresh human blood from healthy volunteers in an effort to replicate in vivo...

Human Infections

Bacteriological cure in patients with acute otitis media and acute maxillary sinusitis provides a sensitive model for determining the relationship between outcome and time above MIC for multiple P-lactam antibiotics. A variety of clinical trials have included pretherapy and repeat sinus puncture or tympanocentesis of middle ear fluid after 2-7 days of therapy to determine whether the initial organism isolated had been eradicted 25,32,33,48,54,77,79 . Figure 6 demonstrates the relationship...

Twocompartment Model

The two-compartment model simulates biexponential pharmacokinetics following intravenous administration. Murakawa et al. 11 designed a model representing the central and peripheral compartments connected by tubing. This model consists of a central compartment that contains the antibiotic and organism. Medium constantly flows into this central compartment. Medium is then pumped from the central compartment to a peripheral compartment (free of antibiotic) and is subsequently pumped back into the...

Tissue Penetration

Because of the difficulties associated with measuring tissue concentrations of drugs, we generally use serum concentration as a surrogate marker in pharmacodynamic models. Although most common bacterial pathogens are extracellular, infections occur in the tissues, and it is the pharmacodynamic profile of an antibiotic at the site of infection that ultimately determines its clinical efficacy. Antibiotic concentrations can vary significantly depending on the type of tissue. Drug penetration into...

Correlation To In Vitro Resistance

Clinical studies evaluating resistance rates and patient outcomes have been primarily conducted in respiratory tract infections. In comparison to other infection sites, respiratory tract infections are more prevalent and recovery of bacteria is primarily noninvasive, allowing more data to be compiled. A limitation to interpreting these data is that only a handful of the most commonly isolated bacteria are studied, often excluding serious pathogens such as vancomycin-resistant En-terococcus...