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A 53-year-old man suffered a severe traumatic brain injury after being struck in an automobile-pedestrian accident. He was intubated in the field and stabilized in the emergency department (ED). He has a previous history of a hernia repair (15 years) and no pertinent social history. His admission height and weight are 71 inches and 80 kg, respectively. He remains stable until hospital day 7 when a leukocytosis develops (WBCs 10.6 to 15.7 cells/mm3), and he was febrile overnight (Tmax, rectal 101.2°F) and develops macroscopically cloudy urine. The serum creatinine level rose from baseline 0.8 mg/dL to 2.1 mg/dL. A Foley catheter is in place. Serum lactate concentration is at 4.4 mmol/L His morning chest radiograph is unremarkable, showing an endotracheal tube in good position. Urinalysis is reported as cloudy with WBC clumps, 30 WBCs, and positive leukocyte esterase. Arterial blood gas levels on an inspiratory oxygen concentration of 40% are as follows: pH 7.31, Paco2, 36 mm Hg; Pao2, 76 mm Hg; and HCO3, 20 mEq/L; blood pressure (BP), 91/50 mm Hg (mean arterial pressure [MAP], 64 mm Hg); heart rate (HR), 109 bpm; respiratory rate (RR), 29 bpm. The team diagnoses this patient with severe sepsis and activates the institution’s severe sepsis pathway. They draw blood and urine cultures, initiate fluid resuscitation with a normal saline bolus of 30 mL/kg, and empiric antibiotics are started.

What factors should be considered when selecting appropriate empiric antimicrobial therapy for this patient?

Selecting appropriate empiric antibiotics for a suspected infection is the focus of this chapter. As you prepare to initiate antimicrobial therapy for this patient, applying a systematic approach will lead to choosing antimicrobials more wisely. The clinical and laboratory findings suggest a catheter-associated urinary tract infection (CA-UTI) that has developed into severe sepsis. The patient’s end-organ dysfunction is evidenced by a serum creatinine level of 2.1 mg/dL and serum lactate concentration of 4.4 mmol/L. The overall plan of therapy includes volume resuscitation, elimination of the causative pathogen, clinical stabilization, and symptom resolution. Samples for culture should be taken from all suspected sources including two sets of blood cultures. Doing so prior to antibiotic initiation prevents false negatives, enabling much needed antimicrobial stewardship efforts to take place. Also, having blood cultures to guide therapy once empiric antibiotics are started enables clinicians to mindfully adjust or de-escalate therapy over time. If samples yield growth of an organism, then modifications to the regimen can be made in order to minimize unnecessary drug exposure and reduce the risk for developing resistance.

Early initiation of antibiotics is critical to the survival of patients with severe sepsis and septic shock. Kumar et al showed that mortality increases by 7% every hour antibiotics are delayed from the time of hypotension onset.1 Moreover, this relationship between antibiotic delays and mortality risk has been demonstrated in several ...

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