Treatment Of Skin And Soft Tissue Infections Research Articles

Efficacy and safety of intravenous daptomycin in Japanese patients with skin and soft tissue infections

Daptomycin is a lipopeptide antibiotic active against gram-positive organisms and recently approved for marketing in Japan. This study investigates the efficacy and safety of daptomycin in Japanese patients with skin and soft tissue infections (SSTIs) caused by methicillin-resistant Staphylococcus aureus (MRSA) for regulatory filing in Japan. Overall, 111 Japanese patients with SSTI were randomized in this open-label, randomized, active-comparator controlled, parallel-group, multicenter, phase III study. Patients received intravenous daptomycin 4 mg/kg once daily or vancomycin 1 g twice daily for 7–14 days. Efficacy was determined by a blinded Efficacy Adjudication Committee. Among patients with SSTIs caused by MRSA, 81.8 % (95 % CI, 69.1–90.9) of daptomycin recipients and 84.2 % (95 % CI, 60.4–96.6) of vancomycin recipients achieved a successful clinical response at the test-of-cure (TOC) visit. The microbiological success rate against MRSA at the TOC visit was 56.4 % (95 % CI, 42.3–69.7) with daptomycin and 47.4 % (95 % CI, 24.4–71.1) with vancomycin. Daptomycin was generally well tolerated; most adverse events were of mild to moderate severity. The measurement of daptomycin concentration in plasma revealed that patients with mild or moderate impaired renal function showed similar pharmacokinetics profiles to patients with normal renal function. Clinical and microbiological responses, stratified by baseline MRSA susceptibility, suggested that patients infected with MRSA of higher daptomycin MIC showed a trend of lower clinical success with a P value of 0.052 by Cochran–Armitage test. Daptomycin was clinically and microbiologically effective for the treatment of MRSA-associated SSTIs in Japanese patients.

Tratamiento con daptomicina en las infecciones complicadas de piel y partes blandas

In recent years, Staphylococcus aureus, the most commonly identified infectious agent causing skin and soft tissue infections (SSTIs), has shown an increase in methicillin resistance and decreased susceptibility to vancomycin. Because of its spectrum, microbiological activity, pharmacokinetics, and safety, as well as clinical experience in its use, daptomycin seems to be a highly appropriate antibiotic in the treatment of SSTIs, especially those produced by methicillin-resistant S. aureus.

Primary Care Management of Pediatric Community-Acquired Methicillin-Resistant Staphylococcus aureus Skin and Soft Tissue Infections

Background The prevalence of pediatric community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) skin and soft tissue infections (SSTIs) have been well documented, yet evidence supporting treatment standards for short- and long-term resolutions is equivocal. Objective To review the healthcare challenge of pediatric CA-MRSA SSTIs and describe current evidence concerning treatment of uncomplicated infections. Implications and recommendations for primary care practice are presented. Review of Literature Databases were searched using the keywords CA-MRSA, skin, soft tissue infections, antibiotics, incision and drainage, clindamycin, and trimethoprim-sulfamethoxazole to locate the highest level of evidence available. Further searches were conducted to investigate the epidemiology, history of antibiotic resistance, and past treatment of SSTIs including CA-MRSA. Results When treating a pediatric patient for an uncomplicated CA-MRSA SSTI, the primary care practitioner needs to consider patient history and comorbid conditions, location of the infection, size of lesion, community prevalence of CA-MRSA and its susceptibility, history of antibiotic use, family or close contact history of CA-MRSA, immunocompetence, and physical signs of the patient. Conclusion Treatment changes are paramount in the fight against CA-MRSA, and practitioners must follow the clinical practice guidelines and begin to utilize incision and drainage more frequently and antibiotics less frequently.

Soft Tissue Infections Caused by Marine Bacterial Pathogens: Epidemiology, Diagnosis, and Management

Skin and soft tissue infections (SSTIs) are one of the most common infection syndromes and may be caused by a large number of microorganisms. Some principles of aquatic injuries are different than those of land-based trauma. Wounds sustained in marine environment are exposed to a milieu of bacteria rarely encountered in different settings. These include Vibrio spp., Aeromonas spp., Shewanella spp., Erysipelothrix rhusiopathiae, Mycobacterium marinum, Streptococcus iniae, and other microbes. Failure to recognize and treat these uncommon pathogens in a timely manner may result in significant morbidity or death. These infections are frequently contracted as a result of recreational swimming, fishing injuries, or seafood handling. The spectrum of manifestations is wide, varying from cases of mild cellulitis, to severe life-threatening necrotizing fasciitis requiring radical surgery, to sepsis and death. This review will focus on the epidemiology, clinical manifestations, and treatment of SSTIs caused by the most important marine pathogens.

Treatment of skin and soft tissue infections in the Elderly: A review

Background: Skin and soft tissue infections (SSTIs) have become the second most common type of infection among persons residing in long-term care facilities. Objective: The purpose of this article was to review the latest information on SSTIs among the elderly, including age-related changes, challenges, and treatment strategies in the era of emerging bacterial resistance. Methods: Relevant information was identified through a search of MEDLINE (1970—April 2010), International Pharmaceutical Abstracts (1970—April 2010), and Google Scholar using the terms skin and soft tissue infection, skin and skin structure infection, cellulitis, treatment guidelines, and elderly. Additional publications were found by searching the reference lists of the identified articles. Trials published since 1970 were selected for this review if they prospectively evaluated mostly adults (≥18 years of age), included >50 patients, and reported diagnostic criteria as well as clinical outcomes in patients treated for simple or complicated SSTIs. Results: Fifty-eight of 664 identified studies were selected and included in this review. A search of the literature did not identify any prospective clinical trials that were conducted exclusively in the elderly. Information on the treatment of SSTIs in the elderly was based solely on clinical studies that were conducted in adults in general. As recommended by the Infectious Diseases Society of America (IDSA) 2008 update, SSTIs should be suspected in elderly patients who have skin lesions and present with a decline in functional status, with or without fever. Patients who present with symptoms of systemic toxicity should be hospitalized for further evaluation. Current challenges in the management of SSTIs include the rapid emergence of community-acquired, methicillin-resistant Staphylococcus aureus (CA—MRSA), the emergence of macrolide-resistant streptococci within the past decade, and the lack of a reliable algorithm to differentiate potentially life-threatening SSTIs that require aggressive interventions and prompt hospitalization from those that can be managed in an outpatient setting. S aureus was the most common cause of SSTIs, being isolated in 42.8% (5015/11,723) of wounds, followed by streptococci. Common SSTIs in the elderly such as shingles, diabetic foot infections, infected pressure ulcers, and scabies, and their treatment were also discussed. Based on reviews of published trials, treatment of simple SSTIs generally consisted of administration of agents with activity against S aureus and Streptococcus species such as a penicillinase-resistant β-lactam, a first-generation cephalosporin, or clindamycin. Broadening of the antimicrobial spectrum to include gram-negative and anaerobic organisms should be implemented for complicated SSTIs such as diabetic foot infections and infected pressure ulcers. Local rates of MRSA, CA—MRSA, and macrolide-resistant streptococci should be considered when selecting empiric therapy. Conclusions: A search of the literature did not identify any prospective clinical trials on the treatment of SSTIs in the elderly; therefore, it is recommended to follow treatment based on the current IDSA guidelines. More research and publications are needed to establish proper selection of antimicrobial agents, treatment strategies, and duration of therapy of SSTIs in the elderly population.

Daptomycin Versus Other Antimicrobial Agents for the Treatment of Skin and Soft Tissue Infections: A Meta-Analysis

Skin and soft tissue infections (SSTIs) are common in everyday clinical practice. Daptomycin has been shown to achieve very good concentrations in skin and soft tissues. To compare the effectiveness and toxicity of daptomycin with that of other antimicrobials for the treatment of SSTIs. PubMed, Scopus, and the Cochrane Central Register of Controlled Trials were searched for articles published up to March 2009. Comparative studies in which daptomycin was used in the intervention group were included in this meta-analysis. The primary outcome of interest was clinical success; secondary outcomes were microbiologic success, clinical success in subsets with complicated SSTIs (cSSTIs) or infections due to methicillin-resistant Staphylococcus aureus (MRSA), clinical success of daptomycin-versus vancomycin-treated patients, time to clinical cure, treatment-related adverse events, withdrawal from treatment due to toxicity, all-cause mortality, and development of resistance. Four studies were included in the analysis (3 were randomized controlled trials [RCTs]). Vancomycin and semisynthetic penicillins were used in the comparator arm. Three studies reported on patients with cSSTIs. The intention-to-treat (ITT) population was 1557 patients. No statistically significant difference between daptomycin and comparators was found regarding clinical success in clinically evaluable (OR 0.89; 95% CI 0.63 to 1.25 in the 3 RCTs and OR 1.34; 95% CI 0.38 to 4.66 with all 4 studies included), ITT, MRSA-infected patients, and those with cSSTIs. Two studies reported that significantly fewer patients with cSSTIs required prolonged treatment in the daptomycin arm and that clinical cure was faster than with comparators. No difference between the compared regimens was found in other outcomes. Daptomycin is effective and safe for the treatment of SSTIs. Studies evaluating the optimal duration of daptomycin therapy for cSSTIs, comparing daptomycin with new agents, and focusing on proven MRSA SSTIs will be helpful for the further evaluation of the drug.

Linezolid versus vancomycin for MRSA skin and soft tissue infections (systematic review and meta‐analysis)

This review aims to compare the effectiveness of linezolid to vancomycin for the treatment of Methicillin Resistant Staphylococcus Aureus (MRSA) skin and soft tissue infections (SSTIs) in inpatients. MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials and reference lists were searched in March 2007. We included randomized controlled trials that looked at inpatients treated with linezolid versus vancomycin for the treatment of hospital-acquired MRSA SSTIs. Outcome measures were clinical cure (resolution of symptoms and signs) and microbiological cure (eradication of MRSA on wound culture). The validity of the included trials was assessed. The results were combined in meta-analyses, the robustness of which was tested in sensitivity analyses. Four trials were included in this review: three for clinical outcomes (174 participants) and three for microbiological outcomes (439 participants). For clinical outcomes there were non-significant trends in favour of linezolid (RR 0.34; 95% CI 0.04, 2.89; P = 0.32). For microbiological outcomes there was weak evidence of linezolid outperforming vancomycin (RR 0.55; 95% CI 0.30, 1.01; P = 0.05). Sensitivity analyses did not change the conclusions taken from the main analysis. With the current available data no difference could be detected between the two treatments, but a trend towards higher effectiveness of linezolid was observed. More data will be required to determine if linezolid is superior to vancomycin for the treatment of MRSA SSTIs. Further systematic reviews are needed to look at other outcomes (length of hospital stay, safety and tolerability, cost-effectiveness) and at MRSA infections at other sites.

Treatment Options for Uncomplicated Community-Acquired Skin and Soft Tissue Infections Caused by Methicillin-Resistant Staphylococcus aureus: Oral Antimicrobial Agents

In the United States, methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of skin and soft tissue infections (SSTIs), and toxin-producing community-acquired MRSA (CA-MRSA) strains are becoming the leading cause of SSTIs presenting to emergency departments and outpatient settings. Many of these infections can be treated with oral antibiotics. This review is intended to delineate the types of SSTIs that require antibiotic treatment and to explain which CA-MRSA SSTIs can be treated with oral antibacterial agents. Review of the literature related to the treatment of CA-MRSA SSTIs with oral antibacterial agents. Oral antimicrobial agents are available for the treatment of MRSA infection, and most SSTIs caused by CA-MRSA can be treated with these oral agents in an outpatient setting. Variable susceptibilities have been observed for CA-MRSA vs. hospital-acquired MRSA, pointing up the need for clinicians to be vigilant in determining susceptibility patterns. The growing prevalence of CA-MRSA in SSTIs and the increasing number of these infections observed in both the community and the hospital setting indicates that early, appropriate recognition and treatment are necessary. Many oral antimicrobial agents are available for the treatment of these infections.

The Benefit of Empiric Treatment for Methicillin-Resistant Staphylococcus Aureus

Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) has emerged as a major pathogen causing skin and soft tissue infections (SSTI). It is unclear whether treatment with antibiotics active in vitro against CA-MRSA improves patient outcomes. At our institution, where there is a high rate of CA-MRSA SSTI, we have adopted an empiric treatment algorithm that promotes both the use of antibiotics likely active against CA-MRSA and early incision and drainage of abscesses. The objective of this research was to study the effectiveness of an empiric treatment algorithm for SSTI directed against CA-MRSA. The study was a retrospective chart review. Treatment was categorized as either conforming or not conforming to the algorithm. Outcomes were categorized as worsening of infection or improvement, according to predefined criteria. There were 50 consecutive Emergency Department patients treated as outpatients for MRSA SSTI. Treatment conformed to the algorithm in 29 of 50 cases. Clinical failure occurred in 3% of cases treated according to the algorithm, compared with 62% of those not treated according to the algorithm (p < 0.001). Among 37 cases that underwent immediate incision and drainage, initial treatment with antibiotics active in vitro against the MRSA isolate was associated with a decreased clinical failure rate when compared to those treated with inactive antibiotics (0% vs. 67%, p < 0.001). Empiric treatment of CA-MRSA SSTI according to an algorithm that promotes use of antibiotics active in vitro against CA-MRSA is associated with improved clinical outcomes.

Treatment and prevention of community-associated methicillin-resistantStaphylococcus aureusskin and soft tissue infections

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has emerged as a pathogen in the community with a range of clinical manifestations. Although skin and soft tissue infections (SSTIs) are the most common presentation, invasive and more virulent disease has been observed. Colonization and infection with CA-MRSA can occur in individuals with no prior healthcare exposures but also in distinct groups whose common characteristic appears to be close person-to-person contact. Outbreaks with CA-MRSA have occurred in day care centers, athletic teams, and prisons, and transmission has been documented among family members and within the hospital. Treatment of SSTIs involves incision and drainage, oral or parenteral antibiotic therapy, or topical therapy. Healthcare practitioners in outpatient and inpatient settings need to be familiar with prevention and treatment strategies for CA-MRSA.

Once-daily cefazolin and probenecid for skin and soft tissue infections.

To review the pharmacokinetic and clinical evidence for the use of once-daily cefazolin and probenecid in the treatment of skin and soft tissue infections (SSTI). MEDLINE (1966-July 2003), EMBASE (1980-July 2003), and PubMed (1966-July 2003) databases for English language, human reports were searched. Search terms included cefazolin, probenecid, cellulitis, and soft tissue infections. Studies that described pharmacokinetic and clinical outcomes that evaluated the use of cefazolin in conjunction with probenecid for SSTI were included. All studies were evaluated independently by both authors. For pharmacokinetic studies, the effect of probenecid on the pharmacokinetics of cefazolin was evaluated. For clinical trials, efficacy and safety endpoints were evaluated. For efficacy endpoints, definition of cure was used as defined by each trial. In all 3 pharmacokinetic studies identified, the addition of probenecid to cefazolin therapy prolonged the half-life and increased serum concentrations of cefazolin. This process allowed serum concentrations to be above the minimal inhibitory concentrations (MIC) for the most likely skin pathogens (Staphylococcus aureus, beta-hemolytic streptococci) at the end of the dosing interval. In the first of 2 clinical trials, 7 (7%) of 96 patients receiving intravenous ceftriaxone 2 g and oral probenecid 1 g daily were reported to fail therapy compared with 8 (8%) of 98 patients receiving intravenous cefazolin 2 g and oral probenecid 1 g daily. In the second clinical trial, clinical success was reported in 51 (86%) of 59 patients receiving the same doses of cefazolin and probenecid as above compared with 55 (96%) of 57 patients receiving intravenous ceftriaxone 1 g and oral placebo daily. Limited pharmacokinetic and clinical data suggest that intravenous cefazolin 2 g and oral probenecid 1 g daily is an effective regimen in the treatment of SSTI.

Newer treatment options for skin and soft tissue infections.

In recent years, serious skin and soft tissue infections (SSTIs) caused by multidrug resistant pathogens have become more common. While the majority of SSTIs are caused by Staphylococcus aureus or beta-haemolytic streptococci that are methicillin/oxacillin susceptible, the emergence of methicillin-resistant and vancomycin-resistant community-acquired and nosocomial Gram-positive pathogens has created a need for different therapeutic agents, such as linezolid, quinupristin/dalfopristin, daptomycin, and newer generation carbapenems and fluoroquinolones. This review focuses on agents presently in clinical development for the treatment of SSTIs caused by Gram-positive pathogens such as staphylococci, streptococci and enterococci including methicillin-resistant S. aureus (MRSA) and vancomycin-resistant enterococci (VRE). Newer-generation carbapenems, such as meropenem and ertapenem, are characterised by a broad-spectrum of activity against Gram-positive and -negative aerobes and anaerobes, and are resistant to hydrolysis by many beta-lactamases. Current-generation fluoroquinolones, such as levofloxacin, moxifloxacin and gatifloxacin, have demonstrated better eradication rates for S. aureus than conventional penicillin and cephalosporins. These antimicrobial agents can be used to treat methicillin-susceptible staphylococcal and streptococcal strains. Oxazolidinones, streptogramin combinations and cyclic lipopeptides have novel mechanisms of action and have been studied in several multinational phase III clinical trials in the treatment of complicated and uncomplicated SSTIs. They possess a broad spectrum of activity against multidrug-resistant pathogens, including MRSA and VRE. Linezolid has been shown to be active against a wide variety of community-acquired and nosocomial antimicrobial-resistant pathogens with comparability to vancomycin, as well as resulting in reduced lengths of hospital stay. Cyclic lipopeptides such as daptomycin have a unique mechanism of action by disruption of bacterial membrane electric potentials with less likelihood for development of cross-resistance. Daptomycin has recently been US FDA approved for the treatment of complicated SSTI. However, rapid development of resistance to some of these newer agents has already been reported and this trend magnifies the importance of further need for effective antimicrobial agents. Several investigational agents, such as dalbavancin, oritavancin and tigecycline, are in advanced stages of development and are likely to proceed to licensing in the next few years. With their long half-lives, these agents have an advantage of less frequent dose administration with more rapid bactericidal activity and less likelihood for development of resistance. However, because of their proven activity against highly resistant organisms, these antibacterial agents should be reserved only for life-threatening situations and/or when resistant pathogens are suspected. Rational antimicrobial use coupled with awareness of infection control measures is paramount to avert the emergence of multidrug-resistant organisms.

A Practical Guide to the Treatment of Complicated Skin and Soft Tissue Infections

Complicated skin and soft tissue infections (SSTIs) remain a common reason for hospitalisation. Optimal management of complicated SSTIs begins with a physical examination, and obtaining the complete social and medical history of the patient. Empirical intravenous antibacterial therapy is guided by expected pathogens, patient factors and diagnostic procedure reports, such as the Gram-stained smear of discharge or exudates. The majority of community-acquired SSTIs are caused by Staphylococcus aureus and beta-haemolytic streptococci. On the basis of recent surveillance data, 80-90% of these pathogens remain susceptible to cefazolin or oxacillin. Consequently, a first generation cephalosporin or an antistaphylococcal penicillin remains the first line empirical therapy for community-acquired skin and soft tissue infections. Vancomycin may be an appropriate alternative when vancomycin-resistant S. aureus is highly suspected on the basis of patient history and co-morbid conditions. With the global emergence and spread of macrolide-resistant S. aureus and beta-haemolytic streptococci, clindamycin rather than a macrolide is the recommended agent for empirical antibacterial therapy of community-acquired SSTIs in penicillin-allergic patients. Nosocomial complicated SSTIs are predominantly caused by S. aureus, Pseudomonas aeruginosa, Enterococcus spp., Escherichia coli and other Enterobacteriaceae. Piperacillin/tazobactam with or without vancomycin is the preferred agent for empirical treatment depending on local resistance statistics. The newer fluoroquinolones may have a role in the treatment of complicated SSTIs, especially in penicillin-allergic patients. More clinical studies are needed before a formal recommendation can be made. Many of the newer antimicrobial agents such as the carbapenems, oxazolidinones and streptogramins have been shown to be effective for the treatment of complicated SSTIs. However, because of their proven activity against highly resistant organisms including methicillin-resistant S. aureus and vancomycin-resistant enterococci (oxazolidinones and streptogramins), and Gram-negative bacilli producing extended spectrum beta-lactamases (carbapenems), these antibacterials should be reserved for life-threatening situations and/or when resistant pathogens are suspected. Complicated skin and soft tissue infections are often associated with exudates, ulcerations, fluid collections or abscesses. Adequate debridement of devitalized tissues and drainage of abscesses and fluid collections in addition to systemic antibacterial therapy is an integral part of appropriate management.

A Retrospective Analysis of Practice Patterns in the Treatment of Methicillin‐Resistant Staphylococcus aureus Skin and Soft Tissue Infections at Three Canadian Tertiary Care Centres

Methicillin-resistant Staphylococcus aureus (MRSA) infections are increasingly being encountered and pose an increasing burden to the health care system in Canada. To elucidate and characterize the factors influencing the current MRSA treatment patterns in patients with skin and soft tissue infections (SSTIs) before linezolid became available on the Canadian market. A retrospective study collected demographic, treatment and resource use data on patients hospitalized at one of three geographically distinct tertiary care facilities, where MRSA SSTI treatment was initiated with intravenous (IV) vancomycin. Analysis of opportunities for IV-to-oral switch therapy was based on eligibility criteria. Of 89 patients identified over a 43-month period, the mean (+/-SD) durations of anti-infective treatment and hospitalization were 22.4+/-21 days and 28.9+/-20.8 days, respectively. An infected surgical wound was most common, representing 62.9% of infections. The mean duration of vancomycin treatment was 19.5 days and the mean number of 1 g doses received was 29.0+/-32.9. The majority of patients (55.1%) initiated vancomycin therapy a mean of 5.4+/-8.9 days after confirmation of MRSA. Of the 70% of patients meeting criteria for IV-to-oral switch therapy, only 10% received oral treatment. The most common reason cited for not switching was lack of an effective oral alternative. Analysis of switch therapy criteria found that IV treatment continued for a mean of 13 days despite the appropriateness of the oral route. Considerable variation exists in treatment patterns for MRSA infections. Improvements in the initiation of therapy and the use of IV-to-oral switch therapy may improve care and reduce the duration of hospitalization for MRSA SSTIs.

Efficacy and safety of linezolid in the treatment of skin and soft tissue infections.

The vast majority of community-acquired skin and soft tissue infections (SSTIs) are caused by gram-positive cocci or are polymicrobial in nature. Hospital-acquired SSTIs are caused by gram-positive cocci in more than 50% of patients. Multidrug-resistant gram-positive cocci are rarely associated with community-acquired SSTIs but are frequently found in hospital-acquired SSTIs. Linezolid is the first member of a new class of antibiotics, the oxazolidinones. These antimicrobial agents have a unique mechanism of action and exhibit excellent activity against a variety of gram-positive organisms, including methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci. Linezolid is 100% orally absorbed, allowing for easy intravenous-to-oral continuation therapy. There is considerable clinical experience with the use of linezolid in SSTIs in phase II and III clinical trials. In comparative trials, linezolid was as effective as oxacillin-dicloxacillin or flucloxacillin in patients with complicated SSTIs caused by gram-positive organisms. Linezolid was also associated with significantly earlier hospital discharge than comparator agents among patients with SSTIs. It was equally effective as vancomycin in patients with SSTIs caused by methicillin-resistant Staphylococcus aureus and has also demonstrated efficacy in patients with SSTIs caused by vancomycin-resistant enterococci. Linezolid is well tolerated: the most common adverse events (gastrointestinal effects, headache) are reported in frequencies similar to those reported for comparator agents. Myelosuppression has been reported after prolonged administration but is reversible after discontinuation of the drug. Overall, linezolid has favorable efficacy and safety profiles and will be an increasingly useful option for the treatment of SSTIs, particularly those due to multidrug-resistant, gram-positive organisms.