Treatment Of Skin And Skin-structure Infections Research Articles

Ceftaroline for complicated skin and skin-structure infections

Importance of the field: A dramatic increase in infections caused by methicillin-resistant Staphylococcus aureus (MRSA) has been observed, in part as a result of the epidemic of community-associated MRSA skin and skin-structure infections (SSSIs). Simultaneously, decreasing sensitivities of S. aureus to vancomycin have been reported and invasive infections caused by these strains have been associated with worse clinical outcomes. Clearly, new agents active against MRSA are needed. Ceftaroline is a new cephalosporin active against MRSA and many Gram-negative bacteria, though it is not active against Pseudomonas spp. and extended spectrum β-lactamase producers (ESBL).Areas covered in this review: In this review we focus on the properties of ceftaroline such as in vitro activity, the pharmacokinetic and pharmacodynamic characteristics, and its efficacy and safety observed in the clinical trials of patients with SSSI. Finally, we provide an overview of the possible future role of ceftaroline and other compounds in development for the treatment of SSSIs. The literature search was based on PubMed articles plus review of the abstracts presented in the most important international conferences in the field.What the reader will gain: The reader will gain clear concepts to understand the value that ceftaroline might have in the treatment of SSSIs, including those caused by MRSA.Take home message: Ceftaroline has shown bactericidal activity against common pathogens associated with SSSIs including MRSA, noninferiority in clinical trials of patients with complicated SSSI (cSSSI), and a favorable safety profile.

Penetration of ertapenem into skeletal muscle and subcutaneous adipose tissue in healthy volunteers measured by in vivo microdialysis

Ertapenem is FDA approved for the treatment of skin and skin-structure infections (SSSI), but its in vivo penetration into the interstitial space of soft tissues is unknown. The present microdialysis study was conducted to measure free, protein-unbound ertapenem concentrations in muscle and subcutaneous tissue. In a single-centre, prospective, open-label study six healthy volunteers (three females, 22-37 years) were treated with 1 g ertapenem given as a single intravenous dose. Microdialysis and plasma samples were collected before and at different time points up to 12 h after medication. Drug concentrations were determined by a validated LC-MS-MS method. No serious or microdialysis-associated adverse events were observed. Ertapenem concentrations in plasma reached a maximum (C(max)) of 103.3 +/- 26.3 mg/L, a terminal elimination half-life (t(1/2)) of 3.8 +/- 0.6 h and an AUC(0-infinity) of 359.7 +/- 66.5 mg.h/L. Mean peak concentrations of free, protein-unbound ertapenem in interstitial space fluid of skeletal muscle and subcutaneous adipose tissue were much lower (C(max) = 6.7 +/- 4.1 and 4.0 +/- 1.6 mg/L, respectively). This degree of tissue distribution is consistent with high concentration-dependent plasma protein binding of ertapenem (84-96%). AUC(0-infinity) values for both muscle and adipose tissue were lower as well (39.7 +/- 24.8 and 18.6 +/- 4.6 mg.h/L). However, unbound interstitial fluid concentrations exceeded MIC(90) values for the important SSSI pathogens for 7 (subcutis) and 10 h (muscle) after dosing. These results support the previously observed clinical efficacy of ertapenem in the treatment of SSSI.

Emerging Issues in the Diagnosis and Management of Infections Caused by Multi-Drug-Resistant, Gram-Positive Cocci

Rising rates of multi-drug-resistant, gram-positive cocci (e.g., methicillin-resistant Staphylococcus aureus [MRSA], vancomycin-resistant Enterococcus spp. [VRE]) have created treatment challenges for clinicians in both the hospital and community settings. These organisms have become especially problematic for hospitalized patients with pneumonia, complicated intra-abdominal infections, and skin and skin-structure infections (SSSIs). A review of the recent literature (1990 onwards) was undertaken in order to review the epidemiology, diagnostic issues, and clinical trial data of available and forthcoming therapies for the treatment of multi-drug resistant, gram-positive isolates, with an emphasis on selected MRSA infections (i.e., pneumonia, SSSI, diabetic foot infections, blood stream) and infections caused by VRE. The rate of healthcare-associated MRSA in 2004 rose to an incidence of 59.5% in the United States compared with data from 1998-2002, making MRSA the predominant gram-positive etiology of S. aureus infections in hospitalized patients. Methicillin-resistant S. aureus has also emerged as an important pathogen in both the non-ICU and community settings. Similarly, 28.5% of all enterococcal isolates were identified as vancomycin-resistant in 2003 (a 12% increase). However, these rates may be underestimated, as detection methods for determining susceptibility have proved to be inadequate. Recognition that prior inadequate antibiotic therapy is common in patients with antibiotic-resistant bacteria, and is associated with higher mortality rates, emphasizes the importance of selecting appropriate empiric therapy. Currently available therapies for resistant gram-positive infections include quinupristin-dalfopristin, linezolid, and daptomycin, although each of these agents has limitations (e.g., daptomycin is not indicated for MRSA pneumonia due to inadequate lung tissue penetration and inactivation by surfactant). Three agents with broad-spectrum activity against gram-positive organisms that are at an advanced stage of testing include two new glycopeptides (oritavancin and dalbavancin), and a first-in-class glycylcycline (tigecycline). These agents have demonstrated efficacy in the treatment of SSSIs, including those caused by MRSA. New antimicrobial agents are needed to combat the increasing prevalence of multi-drug-resistant, gram-positive pathogens such as MRSA. The emergence of resistance to available therapies such as vancomycin underscores this urgency.