Diagnostic Microbiology and Infectious Disease
Oral β-lactams applied to uncomplicated infections of skin and skin structures
Introduction
Skin infections vary in importance from relatively mild, shallow and localized-to-severe, and life threatening, leading to widely varying treatments. Many simple skin infections can be treated with locally applied topical antibacterial ointments; necrotizing or gangrenous infections, on the other hand, must be treated aggressively, often with intravenous antimicrobials and surgical intervention. This review will focus on uncomplicated skin and skin structure infections (uSSSIs) that can be treated with oral or topical antimicrobial agents.
Section snippets
Uncomplicated skin and skin structure infections
Among the most common uSSSIs are impetigo, erysipelas, folliculitis, simple abscesses, and cellulitis. The common causative bacterial pathogens of superficial infections include the staphylococci, particularly Staphylococcus aureus and coagulase-negative species (CoNS), and streptococci, such as Streptococcus pyogenes (group A β-hemolytic streptococci).
Impetigo most often affects children and can be highly contagious. It usually occurs around the nose and mouth, or on the hands and forearms,
Pathogens
As reviewed above, the primary causative agents of uSSSI are S. pyogenes and S. aureus, and empiric treatment should be directed toward these pathogens, unless demonstrated otherwise. Although both are Gram-positive cocci, differences in drug resistance patterns complicate empirical therapeutic choices. S. aureus is usually not treatable with penicillin because >90% are β-lactamase producers, and, with increasing methicillin resistance, it is decreasingly susceptible to the full β-lactam drug
Pharmacokinetics/pharmacodynamics
Determining drug efficacy has historically been assessed using in vitro activity, animal infection models, and clinical studies. Human clinical trial studies, however, have significant limitations, particularly for diseases with high rates of spontaneous resolution, or where the effect of treatment is in improving time to disease resolution (Craig, 1998). The background rate of spontaneous resolution provides misleading data on actual cure rates with any antimicrobial agent (Marchant et al.,
Amoxicillin and amoxicillin–clavulanate
Amoxicillin is a useful agent for treating streptococcal infections, whereas amoxicillin–clavulanate is a useful agent for treating methicillin-susceptible staphylococcal infections because the addition of the β-lactamase inhibitor, clavulanate, inhibits staphylococcal β-lactamase. These agents diffuse readily into most body tissues and fluids. Amoxicillin–clavulanate is indicated for treatment of β-lactamase–producing S. aureus, Escherichia coli, and Klebsiella spp. skin and soft tissue
Published treatment guidelines
Treatment guidelines often provide categories and grades, indicating both the strength of each recommendation and the quality of the evidence upon which the recommendation is based (Stevens et al., 2005). The strength of evidence in support of a particular treatment is given a letter grade of A through E, from good evidence for A to good evidence against E, with moderate for/against B and D, and poor evidence C as the intermediate categories. The quality of evidence is determined by source of
Clinical trials of uSSSI
Because treatment recommendations are supposed to be based on scientifically valid evidence-based conclusions, it is worthwhile to examine the underpinnings of the clinical trial study designs that contribute the various data points used in decision making in uSSSI. The randomized, double-blind, controlled clinical trial, with sample sizes providing adequate statistical power, is often considered the “gold standard” of objective evidence wherein the study agent is demonstrated to be superior to
Conclusions
Most of the β-lactam agents tested against uSSSI perform as well as comparators and many are recommended and/or approved for treatment of such infections. However, as is the case in many other infections, none of the clinical trials tested agents against a placebo control, making it impossible to determine the background rate of spontaneous resolution. Consequently, the agents and comparators may be performing as well as no treatment at all. An uncomplicated infection, almost by definition, is
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