ceftobiprole and iclaprim

There is a constant need for new antibacterial agents because of the unavoidable development of bacterial resistance that follows the introduction of antibiotics in clinical practice. As observed in many fields, innovation generally comes by series. For instance, a wide variety of broad-spectrum antibacterial agents became available between the 1970s and the 1990s, such as cephalosporins, penicillin/beta-lactamase inhibitor combinations, carbapenems, and fluoroquinolones. Over the last 2 decades, the arrival of new antibacterial drugs on the market has dramatically slowed, leaving a frequent gap between isolation of resistant pathogens and effective treatment options. In fact, many pharmaceutical companies focused on the development of narrow-spectrum antibiotics targeted at multidrug-resistant Gram-positive bacteria (e.g. methicillin-resistant Staphylococcus aureus, penicillin resistant Streptococcus pneumoniae, and vancomycin-resistant Enterococcus faecium). Therefore, multidrug-resistant Gram-negative bacteria (e.g. extended-spectrum beta-lactamase-producing Enterobacteriaceae, carbapenem-resistant Pseudomonas aeruginosa and Acinetobacter baumannii) recently emerged and rapidly spread worldwide. Even if some molecules were developed, new molecules for infections caused by these multidrug-resistant Gram-negative bacteria remain remarkably scarce compared to those for Gram-positive infections. This review summarises the major microbiological, pharmacological, and clinical properties of systemic antibiotics recently marketed in France (i.e. linezolid, daptomycin, tigecycline, ertapenem, and doripenem) as well as those of antibacterial drugs currently in development (i.e. ceftobiprole, ceftaroline, dalbavancin, telavancin, oritavancin, iclaprim, and ramoplanin) or available in other countries (i.e. garenoxacin, sitafloxacin, and temocillin).

Topics: Acetamides; Aminoglycosides; Anti-Infective Agents; beta-Lactams; Carbapenems; Cephalosporins; Daptomycin; Doripenem; Drug Resistance, Bacterial; Ertapenem; Fluoroquinolones; France; Humans; Linezolid; Lipoglycopeptides; Minocycline; Oxazolidinones; Penicillins; Pyrimidines; Teicoplanin; Tigecycline

Current antibiotics available for the treatment of healthcare-associated pneumonia (HCAP) may result in clinical failure due to resistance development, side effect intolerance, or poor pharmacokinetic-pharmacodynamic profiles. New agents active against common HCAP pathogens are needed. The mechanism of action, spectrum of activity, pharmacokinetics, adverse effects, and clinical efficacy of seven new agents in clinical development or recently approved with either methicillin-resistant Staphylococcus aureus (MRSA) or pseudomonal activity are reviewed. They include doripenem, a new antipseudomonal carbapenem; ceftobiprole and ceftaroline, two anti-MRSA cephalosporins; iclaprim, a selective dihydrofolate reductase antagonist; and three glycopeptides, dalbavancin, telavancin, and oritavancin.

Topics: Aminoglycosides; Anti-Bacterial Agents; Carbapenems; Ceftaroline; Cephalosporins; Cross Infection; Doripenem; Glycopeptides; Lipoglycopeptides; Methicillin-Resistant Staphylococcus aureus; Pneumonia, Bacterial; Pseudomonas Infections; Pyrimidines; Staphylococcal Infections; Teicoplanin

In bacterial and fungal infections, optimal outcomes are obtained through the timely provision of adequate antimicrobial coverage in an initial anti-infective treatment regimen. However, selecting appropriate antimicrobial regimens to treat infections in the intensive care unit is challenging because of the expansion of antibiotic resistance. Multidrug anti-infective regimens are typically needed to adequately cover common important pathogens in ICUs. Here, we describe novel antibacterial agents in the late stages of clinical development that show potential for treating methicillin-resistant Staphylococcus aureus (MRSA) infections. These include the fifth-generation cephalosporins, ceftaroline and ceftobiprole; the glycopeptides, dalbavancin, oritavancin, and telavancin; and iclaprim.

Topics: Aminoglycosides; Anti-Bacterial Agents; Ceftaroline; Cephalosporins; Glycopeptides; Humans; Lipoglycopeptides; Methicillin-Resistant Staphylococcus aureus; Pyrimidines; Staphylococcal Infections; Teicoplanin

Despite increasing antimicrobial resistance and multiple drug resistance in clinical isolates of both Gram-positive and Gram-negative bacteria, there are few novel antimicrobial agents in development. The few new agents that have been recently licensed have tended to have narrow spectra of activity, focused on Gram-positive pathogens, especially methicillin-resistant Staphylococcus aureus (MRSA). This situation is rightly causing concern among clinicians and public health authorities worldwide. This article reviews available data on three new antibacterials currently in development. The cephalosporin ceftobiprole is active against MRSA, Enterococcus faecalis and penicillin-resistant Streptococcus pneumoniae, but otherwise has a spectrum of activity similar to that of other recent cephalosporins. In a clinical trial, ceftobiprole was non-inferior to vancomycin for the treatment of MRSA-associated complicated skin and skin structure infections (cSSSIs). Doripenem, a new carbapenem, has some activity against MRSA, but otherwise has an anti-Gram-positive spectrum of activity similar to that of imipenem and an anti-Gram-negative spectrum similar to that of meropenem. In a clinical trial, it was non-inferior to meropenem for the treatment of complicated intra-abdominal infections. Iclaprim is a dihydrofolate reductase inhibitor with greatly enhanced activity, as compared with trimethoprim, against a range of Gram-positive and Gram-negative pathogens. The limited literature concerning this agent has concentrated on its potential role in the treatment of infections with Gram-positive bacteria. A clinical trial has demonstrated the non-inferiority of iclaprim, as compared with linezolid, in the treatment of cSSSIs, including those associated with MRSA.

Topics: Anti-Bacterial Agents; Bacteria; Bacterial Infections; Carbapenems; Cephalosporins; Doripenem; Drug Resistance, Multiple, Bacterial; Humans; Pyrimidines; Research

Antibiotics currently under study by the Food and Drugs Administration include: faropenem (for treatment of sinusitis, bronchitis, and community-acquired pneumonia), dalbavancin (for catheter infections), telavancin (for treatment of nosocomial pneumonia), oritavancin (for bacteremia), ceftobiprole and iclaprim (for pneumonias). Moreover, all of them would be useful for skin and soft tissue infections.

Topics: Aminoglycosides; Animals; Anti-Bacterial Agents; Bacteria; beta-Lactams; Cephalosporins; Drug Approval; Drug Resistance, Bacterial; Glycopeptides; Humans; Lipoglycopeptides; Pyrimidines; Skin Diseases, Bacterial; Skin Diseases, Viral; Teicoplanin; United States; United States Food and Drug Administration