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Antibiotic Kinetics in the Febrile
Multiple-System Trauma Patient
in Critical Care
Donald E. Fry
Northwestern University Feinberg School of Medicine, Chicago, Illinois and Department of Surgery, University
of New Mexico School of Medicine, Albuquerque, New Mexico, U.S.A.INTRODUCTION
In no place throughout clinical medicine is the role of antibiotics more important than in the
severely injured patient. Judicious and appropriate antibiotics are important for preventive
indications when the traumatized patient requires a surgical procedure. Specific antibiotic
therapy is necessary when infectious complications occur at the site of injury. Nosocomial
infections occur at numerous locations during the critical care management and during the
prolonged convalescence of these patients, antimicrobial chemotherapy for treatment. In the
patient with an injury severity score>30, antibiotics are employed frequently during the
hospitalization and the emergence of resistant and unusual pathogens make the appropriate
management of the infectious complications of these patients a formidable challenge.
The principals in the utilization of antibiotics for different indications in the trauma
patient have become established over the last several decades. For preventive indications,
the antibiotic should be given immediately prior (<60 minutes) to the skin incision for invasive
interventions. The antibiotic should have activity against the likely pathogens to be
encountered in the procedure. Prolonged preventive antibiotics after the procedure do not
benefit the patient and should be stopped within 24 hours of the procedure. Infections that
occur at the site of traumatic injury require antibiotic therapy against the clinically suspected
and the culture-documented pathogens, in conjunction with aggressive surgical drainage and
debridement of the primary focus. Because of the impact of the critical care unit, hospital
microflora, and antecedent antibiotic treatment, nosocomial infections will notoriously be
secondary to resistant organisms and must have susceptibility evidence to guide choices of
treatment.
Although the above principals in the use of antibiotics are generally accepted, infection
continues to be the major cause of death for injured patients without severe head injury who
survive the initial 48 hours following the insult. The reasons for infectious deaths in the face of
optimum antibiotic utilization are (i) the magnitude of contamination exceeds the capacity of
the host and therapy to control, (ii) profound immunosuppression attends the injury, and
(iii) antimicrobial resistance produces an array of pathogens that become very elusive to treat.
An important consideration that should be contemplated is whether the pathophysiologic
changes of the severely injured patient create a clinical scenario where otherwise conventional
antibiotic strategies may fail. This chapter will detail the systemic changes that are the result of
the systemic activation of the human inflammatory cascade, and why these changes require a
reassessment of antibiotic dosing strategies in febrile multiple-trauma patients. Finally, new
strategies for the utilization of antibiotics in these patients will be proposed.
NORMAL PHARMACOKINETICS OF ANTIBIOTICS
The study of the biological processes that ultimately determine antibiotic concentration at the
effector site is referred to as pharmacokinetics. The biological processes that comprise
pharmacokinetics include absorption, volume of distribution, biotransformation, and drug
excretion. For antibiotics, the quantitative evaluation of each of these components is used to
design the dose and the treatment interval that will be employed for clinical trials and