Pneumonia is the third most common cause of death worldwide1 and remains responsible for

approximately 50% of all episodes of sepsis and septic shock. Both community-acquired bacterial
pneumonia (CABP) and hospitalacquired bacterial pneumonia (HABP) are associated with increased
morbidity, mortality, hospital length of stay, and health care costs. Furthermore, patients with ventilator-
acquired bacterial pneumonia (VABP) have longer mean hospital and intensive care unit (ICU) stays,
more mechanical ventilation days, and higher mortality than ICU non-VABP patients. In 2013,
pneumonia was among the 10 most economically charged diseases to the US health care systems, with an
aggregate cost of approximately $9.5 billion.

Despite advances in antimicrobial therapy and improvement in the clinical management of pneumonia,
treatment failure rates for HABP and CABP remain high at 30.0% to 62.0% and 2.4% to 31.0%,
respectively. Although many factors contribute to treatment failures, several of these factors concern the
provision of antibacterial therapy. Foremost, an antibiotic must be selected to which the suspected
causative organism is susceptible. However, the emergence of multidrug resistant (MDR) or extensive-
drug resistant (XDR) pathogens makes this a challenge, both in ensuring adequate likelihood of efficacy
and in preventing the inappropriate use of broadspectrum antibacterials. Indeed, drug resistance is
particularly important, given that the ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus,
Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species)
represent more than 80% of HABP. In addition to selecting the right drug, the right dose must be used.
Many antibacterials lack labeled indications for the treatment of pneumonia. Labeled doses for other
indications may yield insufficient concentrations in lung tissues or fail to account for variation among
patients, such as those with critical illness, obesity, augmented renal clearance, or those receiving organ
replacement therapies, such as hemodialysis or extracorporeal membrane oxygenation.

Optimal antibacterial treatment, which includes the correct selection of 1 or more antibiotics, dosing,
route of administration, and appropriate duration of therapy, significantly improves outcomes of patients
with pneumonia. Certainly, the ideal approach should maximize the likelihood of a satisfactory
microbiological response as well as minimize the exposure-related toxicity and the emergence and spread
of bacterial resistance. In this context, intelligent dosing decisions should be driven by the principles of
pharmacokinetics (PK) and pharmacodynamics (PD).

Although a significant portion of PK/PD studies are performed to identify optimal doses for use in
clinical trials, these methods can also be used in a patient-specific fashion to guide dosing. The latest
Infectious Diseases Society of America/American Thoracic Society (IDSA/ATS) guidelines for the
treatment of HABP/VABP weakly recommend PK/PD-driven dosing strategies. Although the downsides
of this approach are scant, involving cost and personnel burden, limited clinical evidence exists
supporting the practice, garnering the weak recommendation. Under these circumstances, the extent to
which patient-specific adjustment of antibacterial regimens based on PK/PD data should be used and its
potential impact on major outcomes are still under debate.

In the era of multidrug resistance, the optimization of antibiotic efficacy is a priority. Although several
promising new antibiotics are in development, some may lack the clear guidance of a labeled indication,
and others will be routinely used in poorly studied subpopulations. For patient-specific treatment
decisions, an understanding of PK/PD is indispensable. This article reviews the principle considerations
of PK and PD for the treatment of pneumonia, and highlights potential approaches to optimization and
future areas of investigation.