cefepime and Skin-Diseases--Infectious

Since infection develops in significant numbers of hospitalized patients, the problem of resistance to third-generation cephalosporins is of increasing concern. We evaluated the efficacy of cefepime 1 g bd as treatment for acute, moderately severe bacterial infection in 239 hospitalized patients (mean age 60 years). Of these patients, 204 were evaluated clinically for urinary tract infection (UTI) (n = 90), lower respiratory tract infection (LRTI) (n = 70), skin and soft tissue infection (S/STI) (n = 12) and bacteraemia which was associated with either UTI or LRTI (n = 32) but not included in the previously mentioned UTI and LRTI groups. Amongst the pathogens isolated (36 Gram-positive, 150 Gram-negative), the most predominant species were Escherichia coli in UTI and bacteraemia (n = 81), Streptococcus pneumoniae in LRTI and bacteraemia (n = 23), Haemophilus influenzae in LRTI (n = 16), Pseudomonas aeruginosa (n = 4) and Enterobacter cloacae (n = 2) in S/STI. The mean duration of treatment was 8.5 days and was the same for the 204 clinically evaluable patients. Overall, the clinical cure rate for cefepime was 94% (191/204). Pathogen eradication was achieved in 93% (185/199) of infections. Of the patients with associated bacteraemia, the clinical cure rate was 97% (31/32) and 94% (16/17) of the pathogens were eradicated. Cefepime therapy was well-tolerated. Treatment was discontinued in eight patients (3%) because of local intolerance and in five patients (2%) because of drug-related adverse events (rash, headache and pruritus). Cefepime 1 g bd is as safe and effective as other parenteral cephalosporins for the treatment of acute bacterial UTI, LRTI and S/STI, including those cases with associated bacteraemia. The bd dosing schedule and reported lack of cross-resistance with other cephalosporins against some species of aerobic Gram-negative bacilli make cefepime an attractive treatment option in hospitalized patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bacteremia; Bacteria; Bacterial Infections; Cefepime; Cephalosporins; Female; Freeze Drying; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Powders; Respiratory Tract Infections; Skin Diseases, Infectious; Therapeutic Equivalency; Urinary Tract Infections

Multi-resistant strains of Gram-negative bacteria are rapidly emerging as a frequent cause of serious bacterial infection in the hospital environment. Effective treatment must include an antibiotic with activity against these organisms. In an open multicentre study, cefepime was evaluated as empirical therapy in 156 hospitalized patients (mean age 57 years) with serious infection of the urinary tract (n = 43), lower respiratory tract (n = 101) and skin and soft tissue (n = 12). In 18 patients, septicaemia/bacteraemia was also diagnosed. Cefepime, 2 g bd, was administered for a maximum of 16 days (mean 8). Of 98 pathogens isolated, 75 were Gram-negative and 23 were Gram-positive species. Ninety-four of the pathogens were susceptible to cefepime, including multi-resistant isolates such as Pseudomonas aeruginosa and Enterobacter cloacae. The overall clinical cure rate, excluding septicaemia/bacteraemia, was 92% (94/102); the corresponding bacterial eradication rate was 95% (52/55). In patients with septicaemia/bacteraemia, the clinical cure rate was 87% (13/15) despite eradication of 100% (11/11) of the assessable pathogens. Cefepime was well-tolerated, although 14 (9%) patients experienced local intolerance at the infusion site. Other drug-related adverse events were reported in six (4%) patients and included diarrhoea, pruritus, rash and urticaria. Cefepime is safe and effective as empirical treatment for serious infections commonly found in the hospital setting. Clinical cure and bacterial eradication can be achieved with a convenient bd dosing schedule.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bacteria; Bacterial Infections; Cefepime; Cephalosporins; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Respiratory Tract Infections; Risk Factors; Sepsis; Skin Diseases, Infectious; Urinary Tract Infections

We undertook a prospective, randomized open comparison of the broad-spectrum cephalosporins cefepime and ceftazidime in treatment of hospitalized subjects with skin or wound infections and complicated nosocomial urinary tract infections. Cefepime treatment (dosage, 2.0 g intravenously twice daily for 4 to 28 days) was successful in 36 (90%) of 40 infections of the skin and skin structure or wounds and in 16 (84%) of 19 nosocomial urinary tract infections. Ceftazidime treatment, 2.0 g every 8 h, was successful in 34 (96%) of 36 infections of the skin and skin structure and in 15 (88%) of 17 urinary tract infections. Microbiological eradication rates of each agent overall and for Pseudomonas aeruginosa were greater than 90%. In the cefepime group, one death occurred, contributed to by an enterococcal superinfection acquired during study drug therapy, and there were two mild and transient adverse experiences observed. Cefepime was comparable to ceftazidime in treatment of infections of the skin and skin structure requiring hospitalization and of complicated nosocomial urinary tract infections.

Topics: Adult; Aged; Aged, 80 and over; Cefepime; Ceftazidime; Cephalosporins; Female; Hospitalization; Humans; Male; Middle Aged; Random Allocation; Skin Diseases, Infectious; Surgical Wound Infection; Urinary Tract Infections

The safety and efficacy of cefepime, a new broad-spectrum, semisynthetic parenteral cephem antibiotic, were evaluated in an open trial at a single hospital. Seventy patients were treated with cefepime: 44 had lower respiratory tract infections, 4 had urinary tract infections, and 22 had skin or soft tissue infections. Of 65 clinically evaluable patients, 64 (98%) had satisfactory responses. No mortality or superinfections occurred. Of 57 respiratory and urinary tract pathogens, 54 (95%) were eradicated and 3 (5%) persisted after therapy. Five bacteremias (two with Streptococcus pneumoniae and one each with Staphylococcus aureus, Proteus mirabilis, and a coagulase-negative staphylococcus) were eradicated. MICs ranged from 1 to 8 micrograms/ml for 13 S. aureus and 9 Pseudomonas aeruginosa isolates and were less than or equal to 0.125 micrograms/ml for 10 streptococcal isolates. Adverse effects occurred in two patients: transient diarrhea and Clostridium difficile toxin in the stool in one patient and loose bowel movements and increased transaminases in the other patient. Cefepime appeared to be well tolerated in humans and was effective against a wide range of isolates, including S. aureus and P. aeruginosa.

Topics: Cefepime; Cephalosporins; Clinical Trials as Topic; Follow-Up Studies; Hospitalization; Humans; Infections; Lung; Microbial Sensitivity Tests; Respiratory Tract Infections; Skin; Skin Diseases, Infectious; Urinary Tract Infections; Urine

Ceftobiprole, a broad-spectrum cephalosporin with activity against methicillin-resistant Staphylococcus aureus (MRSA) (P. Hebeisen et al., Antimicrob. Agents Chemother. 45:825-836, 2001), was evaluated in a subcutaneous skin infection model with Staphylococcus aureus Smith OC 4172 (methicillin-susceptible S. aureus [MSSA]), S. aureus OC 8525 (MRSA), Pseudomonas aeruginosa OC 4351 (having an inducible AmpC beta-lactamase), and P. aeruginosa OC 4354 (overproducing AmpC beta-lactamase). In the MSSA and MRSA infection models, ceftobiprole, administered as the prodrug ceftobiprole medocaril, was more effective in reducing CFU/g skin (P < 0.001) than were cefazolin, vancomycin, or linezolid based on the dose-response profiles. Skin lesion volumes in MSSA-infected animals treated with ceftobiprole were 19 to 29% lower than those for cefazolin-, vancomycin-, or linezolid-treated animals (P < 0.001). In MRSA infections, lesion size in ceftobiprole-treated mice was 34% less than that with cefazolin or linezolid treatment (P < 0.001). Against P. aeruginosa, ceftobiprole at similar doses was as effective as meropenem-cilastatin in reductions of CFU/g skin, despite 8- and 32-fold-lower MICs for meropenem; both treatments were more effective than was cefepime (P < 0.001) against the inducible and overproducing AmpC beta-lactamase strains of P. aeruginosa. Ceftobiprole was similar to meropenem-cilastatin and 47 to 54% more effective than cefepime (P < 0.01) in reducing the size of the lesion caused by either strain of P. aeruginosa in this study. These studies indicate that ceftobiprole is effective in reducing both bacterial load and lesion volume associated with infections due to MSSA, MRSA, and P. aeruginosa in this murine model of skin and soft tissue infection.

Topics: Animals; Anti-Bacterial Agents; Area Under Curve; Bacterial Proteins; beta-Lactamases; Cephalosporins; Colony Count, Microbial; Dose-Response Relationship, Drug; Female; Gram-Negative Bacteria; Gram-Positive Bacteria; Half-Life; Immunocompromised Host; Methicillin-Resistant Staphylococcus aureus; Mice; Mice, Hairless; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections; Skin Diseases, Infectious; Staphylococcal Infections; Staphylococcus aureus