ceftobiprole and Skin-Diseases--Infectious

To investigate the clinical efficacy and safety of ceftobiprole for acute bacterial skin and skin structure infections (ABSSSIs).. PubMed, Web of Science, EBSO, Ovid Medline, ClinicalTrial.gov and Cochrane Library were searched until 25 December 2020. Only randomized controlled trials that compared the treatment efficacy of ceftobiprole with that of other antibiotics for adult patients with ABSSSIs were included in this meta-analysis.. The 3 RCTs involving 2291 adult patients with ABSSSIs were included. No significant difference in clinical success, as measured by the TOC, was observed between ceftobiprole and comparators among the intention-to-treat population (OR, 1.06; 95% CI, 0.85-1.33;. Ceftobiprole can achieve similar clinical and microbiological responses as alternative antibiotics in patients with ABSSSIs. In addition, ceftobiprole shares a similar safety profile to comparators.

Topics: Adult; Anti-Bacterial Agents; Cephalosporins; Humans; Randomized Controlled Trials as Topic; Skin Diseases, Infectious; Treatment Outcome

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

Population pharmacokinetic analysis demonstrated that renal function, as assessed by creatinine clearance (CL(CR)), was the patient characteristic that had a clinically relevant impact on ceftobiprole pharmacodynamics. Dosing adjustments based on CL(CR) for subjects with renal impairment should provide ceftobiprole exposure similar to that in patients with normal renal function.

Topics: Anti-Bacterial Agents; Case-Control Studies; Cephalosporins; Clinical Trials, Phase III as Topic; Computer Simulation; Creatinine; Humans; Infusions, Intravenous; Kidney Function Tests; Male; Metabolic Clearance Rate; Microbial Sensitivity Tests; Models, Biological; Population; Skin Diseases, Infectious; Software

Ceftobiprole, a broad-spectrum cephalosporin with activity against methicillin (meticillin)-resistant staphylococci, was statistically noninferior to a combination of vancomycin plus ceftazidime in patients with complicated skin and skin structure infections (cSSSI). This analysis used data from this clinical trial to determine the relationship between therapeutic outcome and the percentage of time that the unbound ceftobiprole concentration exceeds the MIC (percent T>MIC). From the trial of ceftobiprole (500 mg every 8 h, 2-h infusion) for cSSSI due to gram-positive and/or gram-negative bacteria, data from 309 patients in the microbiological intent-to-treat analysis set with measured ceftobiprole concentrations and baseline MICs were used to assess the relationship between percent T>MIC and therapeutic outcome. Individual pharmacokinetic (PK) profiles were obtained from a three-compartment population PK model. The relationship between percent T>MIC and a clinical cure was determined. For the clinical trial dosing regimen, individual percent T>MICs were used to calculate fractional target attainment rates (TARs) for >or=30 and >or=50% T>MIC targets at various MICs. There was a statistically significant relationship between achieving a >or=30 or >or=50% T>MIC and a clinical cure (P = 0.003 and P = 0.007, respectively; Pearson's chi(2) test). The fractional TAR was greater than 90% at a MIC of MIC and a clinical cure with ceftobiprole was demonstrated. A ceftobiprole regimen of 500 mg every 8 h as a 2-h infusion has a high probability of achieving a target of >or=30 or >or=50% T>MIC for patients with cSSSI due to gram-positive and gram-negative pathogens.

Topics: Anti-Bacterial Agents; Ceftazidime; Cephalosporins; Female; Humans; Male; Microbial Sensitivity Tests; Skin Diseases, Infectious; Treatment Outcome; Vancomycin