A multicenter comparative study of cefepime versus broad-spectrum antibacterial therapy in moderate and severe bacterial infections

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%) 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%) for patients treated with cefepime vs 125/150 (83%) for those treated with comparator (95% confidence interval [CI]: -2.6% to 16.3%). The clinical success rate for patients with community-acquired pneumonia, the most frequent infection, was 86% 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% for cefepime vs 94% for comparatortreated patients. Drug-related adverse events were reported in 16% of cefepime patients and 19% 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. Key Words: Cefepime, ampicillin, caphalotin, ceftriaxone, aminoglycoside, urinary tract infections, intra-abdominal infections, sepsis. The initial selection of an empiric antimicrobial regimen for the treatment of hospitalized patients with serious community-acquired infections requires the use of broadspectrum antibiotics. It has been common practice to treat presumed bacterial infections (e.g. pneumonia, urinary tract infection, sepsis) with combination antibiotic therapy, such as a β-lactam plus an aminoglycoside, in order to cover likely Gram-positive and Gram-negative organisms. In addition, combination therapy is prescribed to provide synergy against difficult-to-treat pathogens or ones that are likely to emerge resistant (e.g...

Combination Therapy for Treatment of Infections with Gram-Negative Bacteria

“…The ability of this organism to simultaneously express multiple mechanisms of resistance adds to the challenge of effectively treating it (104,157). Several studies evaluating morbidity and mortality with dual and single antipseudomonal agents for the treatment of P. aeruginosa infections have been conducted, as outlined below (7,15,44,70,112,152,180,211,224,227,228,246).…”

Effect of Cefepime in Patients with Cirrhosis and Spontaneous Acid Infection

“…The application of cephotaxim at least for 5 days 4-8 gr/day is the most often applied treatment method in the last years (14). In the other side, the effective use of cefepime, which is the first member of the fourth generation cephalosporins, on other peritonitis types like secondary peritonitis was declared in the literature (23)(24)(25). However there is not a study concerning the use and efficiency of cefepime in SAI.…”

“…Since ß-lactamases synthesized under the control of plasmid and chromosome show lower affinity to cefepime, cefepime is resistant against these enzymes (22). As a result, cefepime being the first member of the fourth generation cephalosporins has an effective use on other peritonitis types like secondary peritonitis (23)(24)(25). However in the literature there isn't too many data concerning the use and effectiveness of cefepime on SAI.…”

The safety of cefepime in the treatment of infection

“…Cefepime proved at least as efficacious as comparators, usually ceftazidime, in terms of clinical cure and bacteriologic eradication of the involved pathogens on treatment of urinary tract infections where E. coli and Gram-negative bacilli were the most frequently isolated bacteria [1, [78][79][80][81] .…”

“…Overall, from clinical trials, cefepime seems to be generally well tolerated; adverse effects are comparable to those induced by comparators [57][58][59][66][67][68][69][70][71][72][73][75][76][77][78][79][80][81][82] . As recently reviewed [84] , the frequency of adverse events and adverse events requiring discontinuation were similar for cefepime versus comparator drugs.…”