ABSTRACT
The safety and efficacy of cefepime empiric monotherapy compared with standard broad-spectrum combination therapy for hospitalized adult patients with moderate to severe community-acquired bacterial infections were evaluated. In an open-label, multicenter study, 317 patients with an Acute Physiology and Chronic Health Evaluation (APACHE II) score ranging from >5 to =19 were enrolled with documented pneumonia (n=196), urinary tract infection (n=65), intra-abdominal infection (n=38), or sepsis (n=18). Patients were randomly assigned 1:1 to receive cefepime 1 to 2 g IV twice daily or three times a day or IV ampicillin, cephalothin, or ceftriaxone ± aminoglycoside therapy for 3 to 21 days. For both treatment groups, metronidazole, vancomycin, or macrolide therapy was added as deemed necessary. The primary efficacy variable was clinical response at the end of therapy. Two hundred ninety-six (93 percent) patients met evaluation criteria and were included in the efficacy analysis. Diagnoses included the following: 180 pneumonias (90 cefepime, 90 comparator), 62 urinary tract infections (29 cefepime, 33 comparator), 37 intra-abdominal infections (19 cefepime, 18 comparator), and 17 sepses (8 cefepime, 9 comparator). At the end of therapy, overall clinical success rates were 131/146 (90 percent) for patients treated with cefepime vs 125/150 (83 percent) for those treated with comparator (95 percent confidence interval [CI]: - 2.6 percent to 16.3 percent). The clinical success rate for patients with community-acquired pneumonia, the most frequent infection, was 86 percent for both treatment groups. Among the patients clinically evaluated, 162 pathogens were isolated and identified before therapy. The most commonly isolated pathogens were Escherichia coli (n=49), Streptococcus pneumoniae (n=29), Haemophilus influenzae (n=14), and Staphylococcus aureus (n=11). Bacteriologic eradication/presumed eradication was 97 percent for cefepime vs 94 percent for comparator-treated patients. Drug-related adverse events were reported in 16 percent of cefepime patients and 19 percent of comparator patients. In conclusion, cefepime had higher cure rates compared with broad-spectrum combination therapy as an initial empiric treatment for hospitalized patients with moderate to severe community-acquired infections, including urinary tract infections, intra-abdominal infections, and sepsis