New Antibiotics for Healthcare-Associated Pneumonia

Abstract and Introduction

Abstract

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.

Introduction

The American Thoracic Society and Infectious Diseases Society of America recommend empirical treatment with broad-spectrum antibiotic therapy targeted against multidrug-resistant pathogens, including methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, and other resistant gram-negative bacilli in patients with proven or suspected healthcare-associated pneumonia (HCAP). Choice of empirical therapy may include vancomycin or linezolid plus an antipseudomonal cephalosporin, carbapenem, ß-lactam/ß-lactamase inhibitor, and/or a fluoroquinolone or aminoglycoside.^[1] Despite the breadth of available antibiotics for the treatment of HCAP, clinical failures due to the development of resistance, intolerance due to adverse effects, or reduced penetration at the site of infection still occur. Several alternatives for the treatment of HCAP are under investigation or are newly approved by the U.S. Food and Drug Administration (FDA). The mechanism of action, spectrum of activity relating to HCAP pathogens, pharmacokinetics and dosing, adverse effects, and clinical efficacy of these compounds are reviewed.

Cite this: New Antibiotics for Healthcare-Associated Pneumonia - Medscape - Feb 01, 2009.

Table 1. Spectrum of Activity of New Antibiotics for HCAP
	Doripenem	Ceftobiprole	Ceftaroline	Iclaprim	Dalbavancin	Telavancin	Oritavancin
HCAP Pathogens
MSSA	+	+	+	+	+	+	+
MRSA	-	+	+	+	+	+	+
VISA/hVISA/VRSA	-	+	+	+	+	+	+
Enterobacteriaceae	+	+	+	±	-	-	-
Pseudomonas aeruginosa	+	+	-	-	-	-	-
AmpC producers	+	+	-	U	-	-	-
ESBL producers	+	-	-	U	-	-	-
Acinetobacter spp.	±	-	-	±	-	-	-
Stenotrophomonas maltophilia	-	-	-	±	-	-	-
Other pathogens of interest
Enterococcus faecalis	±	±	-	±	+	+	+
Enterococcus faecium	-	-	-	±	±	+	+
Streptococcus pneumoniae	+	+	+	+	+	+	+
Gram + Anaerobes	+	+	+	-	+	+	+
Gram - Anaerobes	+	-	-	-	-	-	-

U, = unknown.
± = in vitro results conflicting, clinical utility unclear.
Gram-positive anaerobes including Peptostreptococcus spp., Proprionibacterium spp.
Gram-negative anaerobes including Bacteroides fragilis, Prevotella spp.
ESBL = extended-spectrum ß-lactamases (ESBLs); HCAP = healthcare-associated pneumonia; hVISA = heterointermediate resistance to vancomycin S. aureus; MRSA = methicillin-resistant Staphylococcus aureus; MSSA = methicillin-sensitive Staphylococcus aureus; VISA = vancomycin-intermediate Staphylococcus aureus; VRSA = vancomycin-resistant Staphylococcus aureus.