Cephalosporins currently in early clinical trials for the treatment of bacterial infections

Expert Opin Investig Drugs. 2014 Oct;23(10):1375-87. doi: 10.1517/13543784.2014.930127. Epub 2014 Jun 23.

Abstract

Introduction: Healthcare-associated infections caused by multi-drug resistant bacteria remain a major cause of worldwide mortality. With the recent approval of agents such as hetero-resistant cocci (i.e., ceftaroline, ceftobiprole, telavancin) for the treatment of Gram-positive infections by and drugs like fidaxomicin for treating Clostridium difficile, present-day research on antibacterials has largely shifted to developing interventions for diseases caused by Gram-negative bacilli. Cephalosporins have gained significant interest as antipseudomonals to be used in hospitals for treating device- and procedure-associated infections. With extended-spectrum activity against many enterobacterial pathogens, the introduction of new antipseudomonal cephalosporin-based treatments will mark a significant advancement in the management of hospital-borne diseases.

Areas covered: The following review examines the present-day status of investigational cephalosporins currently in preclinical, Phase I and Phase II stage development. The article focuses specifically on treatments used for healthcare-associated infections due to Gram-negative bacteria.

Expert opinion: There is an urgent need for new antimicrobials to treat nosocomial infections due to multi-drug resistant Gram-negative bacteria. The impending approvals of antipseudomonal cephalosporins co-formulated with a β-lactamase inhibitor will allow clinicians to treat more hetero-resistant infections with cephalosporins, while avoiding the use of more toxic agents such as colistin. The growing interest in developing new β-lactamase inhibitor combinatorial treatments with approved β-lactam antibiotics is anticipated to decrease the number of novel cephalosporins entering clinical trials this decade.

Keywords: Enterobacteriaceae; MRSA; Pseudomonas; antibacterial; ceftolozane; cephalosporin; β-lactam.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use*
  • Cephalosporins / pharmacology
  • Cephalosporins / therapeutic use*
  • Clinical Trials as Topic
  • Cross Infection / drug therapy
  • Cross Infection / microbiology
  • Drug Approval
  • Drug Design
  • Drug Resistance, Multiple, Bacterial
  • Gram-Negative Bacteria / drug effects
  • Gram-Negative Bacteria / isolation & purification
  • Gram-Negative Bacterial Infections / drug therapy*
  • Gram-Negative Bacterial Infections / microbiology
  • Humans

Substances

  • Anti-Bacterial Agents
  • Cephalosporins