Resistant Pathogen-associated Skin and Skin-structure Infections: Antibiotic Options

Daniel Curcio

Disclosures

Expert Rev Anti Infect Ther. 2010;8(9):1019-1036. 

In This Article

Abstract and Introduction

Abstract

Complicated skin and skin-structure infections (cSSSIs) are among the most common infections treated in the hospital setting. They are a significant clinical problem, partially owing to increasing resistance of infecting bacteria to current antibiotic therapies (nosocomial and community-acquired methicillin-resistant Staphylococcus aureus, extended spectrum β-lactamase-producing-Enterobacteriaceae, and multidrug-resistant [MDR] Pseudomonas aeruginosa, among others). The optimal choice of antibacterial therapy among the few available options for infections caused by MDR pathogens is fundamental to maximize clinical effectiveness and minimize the likelihood of further resistance development. Few antimicrobial agents are currently available to treat MDR bacteria in cSSSIs. In this context, the use of new antibiotic agents (i.e., linezolid, daptomycin and tigecycline) and the optimization of the pharmacodynamic targets of classic antibiotics (i.e., carbapenems) is one potential solution to these problems, and some of these agents are highlighted in this article. The purpose of this article is to provide clinicians with an evidence-based review of MDR pathogens causing cSSSIs, the implications of resistance to currently used drug therapy, and to identify new therapeutic options for resistant pathogens causing cSSSIs.

Introduction

Skin and skin-structure infections (SSSIs) are defined as infections of the epidermis, dermis or subcutaneous tissue. They represent one of the most common indications for antibiotic therapy and account for approximately 10% of hospital admissions in the USA.[1] Direct infection of the skin occurs by invasion of the epidermis, usually after damage to the skin, and infection may affect any anatomical layer.[2]

Simple, uncomplicated SSSIs include erysipelas, cellulitis, furuncles, superficial abscesses and wound infections, whereas deeper complicated SSSIs (cSSSIs) include necrotizing fasciitis, myositis and gas gangrene. A SSSI is considered complicated if it involves deeper skin structures such as fascia or muscle layers, requires significant surgical intervention or occurs in the presence of significant comorbidities (e.g., HIV and diabetes mellitus).[3]

These criteria generally include patients with surgical site infection, necrotizing soft tissue infection and signs of systemic toxicity. Identifying the cause of infection or the type of injury that has led to a cSSSI can help in discerning the likely causative organisms and guiding treatment decisions.

While staphylococci and streptococci are the most common causes of community-acquired SSSIs, the etiology is much more varied in hospitals where multidrug-resistant (MDR) pathogens are frequently implicated: Gram-positive (methicillin-resistant Staphylococcus aureus [MRSA] and vancomycin-resistant enterococci [VRE]) and, in some cases, Gram-negative pathogens (Pseudomonas aeruginosa, extended-spectrum β-lactamase [ESBL]-producing Escherichia coli and Klebsiella spp. and AmpC-producing Enterobacter spp.).[4] Major shifts in the community epidemiology are occurring, particularly with respect to community-acquired MRSA (CA-MRSA).[5,6] Many of these infections are mild or moderate, although serious life-threatening infections have been described with these strains.

Early empirical antimicrobial therapy should be initiated after obtaining samples for culture and appropriate changes should be made according to the culture results. Selection of empirical antimicrobial therapy depends on whether the infection is uncomplicated or complicated, whether the infection is community- or hospital-acquired and on local resistance patterns.

Few antimicrobial agents are currently available to treat resistant bacteria in cSSSI; vancomycin is currently the drug of choice against resistant Gram-positive cocci; however, increases in the MIC values and resistance to this agent have appeared in enterococci and S. aureus. Several new antibiotics such as linezolid, tigecycline and daptomycin, among others, are now available for the management of cSSSI. Other agents are under investigation and should be available soon to increase treatment options for cSSSI caused by MDR Gram-negative bacteria.

Based on these data, clinicians need to be clear in which situations they should consider using specific antimicrobial management, which includes newer agents rather than current standards of care.

The purpose of this article is to provide clinicians with an evidence-based review of the MDR pathogens causing cSSSIs, the implications of resistance to currently used drug therapy, and to identify new therapeutic options for resistant pathogens causing cSSSIs.

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