Abstract
Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) are correlated
with high mortality rates worldwide. Thus, the administration of antibiotic therapy
with appropriate dosing regimen is critical. An efficient antibiotic is needed to
maintain an adequate concentration at the infection site, for a sufficient period
of time, to achieve the best therapeutic outcome. It can, however, be challenging
for antibiotics to penetrate the pulmonary system due to the complexity of its structure.
Crossing the blood alveolar barrier is a difficult process determined by multiple
factors that are either drug related or infection related. Thus, the understanding
of pharmacokinetics/pharmacodynamics (PK/PD) of antibiotics identifies the optimum
dosing regimens to achieve drug penetration into the epithelial lining fluid at adequate
therapeutic concentrations. Critically ill patients in the ICU can express augmented
renal clearance (ARC), characterized by enhanced renal function, or may have renal
dysfunction necessitating supportive care such as continuous renal replacement therapy
(CRRT). Both ARC and CRRT can alter drug elimination, thus affecting drug concentrations.
PK of critically ill patients is less clear due to the multiple variabilities associated
with their condition. Therefore, conventional dosing regimens often lead to therapeutic
failure. Another major hurdle faced in optimizing treatment for HAP/VAP is the reduction
of the in vitro potency. Therapeutic drug monitoring (TDM), if available, may allow
health care providers to personalize treatment to maximize efficacy of the drug exposures
while minimizing toxicity. TDM can be of significant importance in populations whom
PK are less defined and for resistant infections to achieve the best therapeutic outcome.
Keywords
nosocomial pneumonia - pharmacokinetics/pharmacodynamics - drug optimization - augmented
renal clearance - continuous renal replacement therapy - antibiotic resistance - therapeutic
drug monitoring