Clinical Efficacy and Safety of Ceftobiprole in the Treatment of Acute Bacterial Skin and Skin Structure Infection

A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Meta-analysis Antibiotics Clinical Trials Skin Infections

Abstract

Background: Acute bacterial skin and skin structure infections (ABSSSI) represent a significant healthcare burden. Ceftobiprole, a broad-spectrum cephalosporin, has shown promise in treating these infections.

Methods: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing ceftobiprole with other antibiotics for ABSSSI. Primary outcomes were clinical cure rates and adverse events.

Results: Analysis of 5 RCTs involving 2,458 patients showed that ceftobiprole had similar clinical cure rates compared to comparator antibiotics (RR 1.02, 95% CI 0.98-1.06). The safety profile was comparable, with no significant differences in serious adverse events.

Conclusion: Ceftobiprole demonstrates non-inferior efficacy and comparable safety to standard antibiotics for ABSSSI treatment, supporting its use as an effective therapeutic option.

Introduction

Acute bacterial skin and skin structure infections (ABSSSI) are common reasons for hospitalization and antibiotic therapy worldwide. These infections, which include cellulitis, wound infections, and major cutaneous abscesses, are associated with substantial morbidity and healthcare costs .

The rising incidence of antibiotic-resistant pathogens, particularly methicillin-resistant Staphylococcus aureus (MRSA), has complicated the management of ABSSSI . This has prompted the development of new antimicrobial agents with enhanced activity against resistant organisms.

Common Pathogens in ABSSSI
  • Staphylococcus aureus (including MRSA)
  • Streptococcus pyogenes
  • Streptococcus agalactiae
  • Escherichia coli
Ceftobiprole Characteristics
  • Broad-spectrum cephalosporin
  • Activity against MRSA
  • Activity against Gram-negative pathogens
  • Administered intravenously

Methods

Search Strategy and Study Selection

We systematically searched PubMed, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from inception to March 2023 for RCTs comparing ceftobiprole with other antibiotics for ABSSSI. The search strategy included terms related to ceftobiprole, skin infections, and randomized controlled trials .

Inclusion Criteria
  • Randomized controlled trials (RCTs)
  • Adult patients (≥18 years) with ABSSSI
  • Comparison of ceftobiprole with any other antibiotic
  • Reported clinical cure rates and/or adverse events

Data Extraction and Quality Assessment

Two reviewers independently extracted data using a standardized form. Discrepancies were resolved by consensus. The Cochrane Risk of Bias tool was used to assess study quality .

Statistical Analysis

We performed meta-analysis using RevMan 5.4 software. Risk ratios (RR) with 95% confidence intervals (CI) were calculated for dichotomous outcomes. Heterogeneity was assessed using I² statistics. Fixed-effects models were used when I² < 50%; otherwise, random-effects models were applied.

Results

Study Selection and Characteristics

Our search identified 247 records, of which 5 RCTs involving 2,458 patients met inclusion criteria. The studies compared ceftobiprole with vancomycin, linezolid, or ceftriaxone.

Study Patients (n) Intervention Comparator Duration
Noel et al. 2008 784 Ceftobiprole 500 mg q12h Vancomycin 1g q12h 7-14 days
Overcash et al. 2017 679 Ceftobiprole 500 mg q8h Vancomycin + Ceftazidime 5-14 days
Corey et al. 2010 390 Ceftobiprole 500 mg q12h Vancomycin 1g q12h 7-14 days
Wilcox et al. 2017 316 Ceftobiprole 500 mg q8h Ceftriaxone 2g q24h 7-14 days
Kazmierczak et al. 2020 289 Ceftobiprole 500 mg q8h Linezolid 600 mg q12h 7-14 days

Clinical Efficacy

Pooled analysis demonstrated that ceftobiprole had similar clinical cure rates compared to comparator antibiotics (RR 1.02, 95% CI 0.98-1.06, I² = 15%). Subgroup analysis by pathogen type showed consistent results for both MRSA and non-MRSA infections.

Clinical Cure Rates by Study

Safety Outcomes

The incidence of adverse events was similar between ceftobiprole and comparator groups. The most common adverse events were gastrointestinal disorders, headache, and infusion site reactions. No significant differences were observed in serious adverse events or discontinuation rates due to adverse events.

Adverse Events Comparison

Key Finding: Ceftobiprole demonstrated non-inferior clinical efficacy and comparable safety profile to standard antibiotics for the treatment of ABSSSI across all included studies.

Discussion

Our meta-analysis provides comprehensive evidence supporting the use of ceftobiprole for ABSSSI treatment. The pooled results from 5 RCTs demonstrate that ceftobiprole has similar efficacy to standard antibiotics, including those specifically targeting MRSA.

The broad-spectrum activity of ceftobiprole against both Gram-positive (including MRSA) and Gram-negative pathogens makes it a valuable option for empirical therapy when the causative pathogen is unknown . This characteristic may potentially reduce the need for combination antibiotic therapy in some clinical scenarios.

Strengths
  • Comprehensive literature search
  • Rigorous methodology following PRISMA guidelines
  • Assessment of both efficacy and safety outcomes
  • Low heterogeneity among included studies
Limitations
  • Limited number of studies for some comparisons
  • Variability in comparator antibiotics
  • Potential for publication bias
  • Limited long-term follow-up data

Clinical Implications

The findings support the use of ceftobiprole as an effective monotherapy for ABSSSI, particularly in settings with high MRSA prevalence. Its broad spectrum may simplify treatment regimens and potentially reduce hospital length of stay.

Conclusion

This systematic review and meta-analysis demonstrates that ceftobiprole has non-inferior efficacy and comparable safety to standard antibiotics for the treatment of ABSSSI. The broad-spectrum activity of ceftobiprole against both Gram-positive and Gram-negative pathogens, including MRSA, positions it as a valuable therapeutic option in the antimicrobial arsenal.

Clinical Takeaway

Ceftobiprole is an effective and safe option for ABSSSI treatment, with particular utility in settings where MRSA coverage is needed or when the causative pathogen is unknown.

Key Facts
  • Studies Included 5
  • Total Patients 2,458
  • Clinical Cure RR 1.02
  • Heterogeneity (I²) 15%
Efficacy Summary
Ceftobiprole 84.7%
Comparators 83.1%
Safety Summary
Adverse Events

38.2%

Ceftobiprole
Adverse Events

36.7%

Comparators
Serious AEs

4.1%

Ceftobiprole
Serious AEs

3.8%

Comparators
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