New antibiotic agents: problems and prospects.

Background: Surgical site infections are the third most common healthcare-associated infection, often leading to prolonged hospital stay and excessive expenditures. Management of these infections has become more challenging due to rising rates of multi-drug-resistant organisms and few new antibiotic options.

Methods: This paper reviews the literature, summarizes the epidemiology of surgical site infections and the threat of antibiotic-resistant bacteria, and provides an insight into new treatment options for this condition.

Results: Patients with surgical site infections are at greater risk of acquiring healthcare-associated antibiotic-resistant pathogens, including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE) sp., and extended-spectrum beta-lactamase-(ESBL)-producing Escherichia coli and Klebsiella pneumoniae. Multi-drug-resistant Pseudomonas aeruginosa and Bacteroides fragilis are also a growing problem. Several useful drugs have recently become available for the management of serious, gram-positive infections (e.g., daptomycin, linezolid, telithromycin). Tigecycline, the first-in-class glycylcycline, has broad-spectrum in vitro activity, including against MRSA, VRE, resistant enteric gram-negative bacilli (e.g., Acinetobacter sp.), "atypical" pathogens, and anaerobes. Phase 3 clinical trials suggest that tigecycline will be an excellent option for antibiotic monotherapy for complicated skin and soft tissue infections (cSSSI) and intra-abdominal infections. Oritavancin and dalbavacin, two novel glycopeptide antibiotics that are also in late-stage clinical development, appear that they, too, will be useful for cSSSI due to resistant, gram-positive bacteria.

Conclusions: Multi-drug-resistant pathogens are threatening the success of available antibiotic therapy. Many new options are useful for infections due to multi-drug-resistant, gram-positive bacteria. Tigecycline is a promising new agent that provides coverage against a broad spectrum of gram-positive and gram-negative, aerobic, facultative, and anaerobic strains, including resistant isolates, and may make broad-spectrum, single-agent therapy possible.