Complicated Skin And Soft Tissue Infections Research Articles

Complicated and suppurative skin soft tissue infections: our four-year cases

Skin and soft tissue infections (SSTIs) are common community and hospital-acquired infections and rarely result in severe morbidity and mortality. It is not always possible to obtain cultures and isolate the causative agent in these patients, primarily treated with empirical antibiotics. In this retrospective cross-sectional study, 57 patients with complicated SSTI followed between 2018 and 2022 with purulent and necrotizing characteristics or growth in blood cultures were included. Thirty-eight patients (66.7%) were male, and 39 (68.4) had diabetes. In 43 (75.5%) patients, the infection was in the lower extremity and gluteal region. Gram-positive agents were detected in 35 patients (61.4%), Gram-negative agents were found in 13 patients (22.8%), and Gram-positive and Gram-negative mixed growth was detected in 1 patient (1.8%), and no causative agent could be produced in 8 (14%) patients. Of the 21 Staphylococcus aureus produced, 4 (19%) were methicillin-resistant (MRSA). Growth was detected in blood cultures in three patients (5.3%), and all were streptococcal bacteria. It was observed that 31 patients (54.4%) required hospitalization for treatment, and 29 (50.8%) required surgical intervention such as drainage, aspiration, debridement, or amputation. Three patients (5.3%) died, and four (7%) underwent amputation. There was no significant difference between diabetic and non-diabetic patients regarding factors and mortality–morbidity. In the logistic regression analysis, none of the variables of gender, type of causative agent, presence of diabetes, and site of infection significantly affected severe morbidity and mortality. Since it was detected at a low rate in our cases, it can be said that MRSA and P.aeruginosa do not need to be considered in every patient for the initial empirical treatment, Gram-negative rods can be taken into account, especially in diabetics, and broad-spectrum and combined antibiotics are not needed in the vast majority of patients. Microbiological follow-up and sensitivity studies at regional and global scales will need to continue to guide empirical treatments in SSTIs.

The role of multidrug and extensive-drug resistant Gam-negative bacteria in skin and soft tissue infections.

Whereas Staphylococcus aureus remains the leading cause of skin and soft tissue infections (SSTI), Gram-negative bacilli (GNB) are increasingly reported as a cause of monomicrobial or polymicrobial infections. This review examines the expanding role of GNB in SSTI and discusses the risks for and the frequency of multidrug-resistance (MDR) and extensive drug-resistance (XDR) and the implications with regard to outcome and therapy. Although the global epidemiology and role of GNB in SSTIs have not been studied systematically, complicated SSTIs caused by resistant GNB are increasing particularly in vulnerable patients with long-standing infections, those in long-term care facilities, and those with a history of recent hospitalization or prior antibiotic therapy. Mixed infections also occur in up to 25% of SSTIs, and inappropriate therapy occurs in 40% of cases. Prompt identification of the causative pathogen requires that patients with SSTI be risk stratified according to the likelihood of resistance to enable early recognition and swift initiation of appropriate therapy. For individual treatment decisions in SSTIs, institutional diagnostic and treatment algorithms based on local epidemiology and risk factors are pivotal to reducing the incidence of treatment failure and improving outcomes associated with resistant GNB.

The role of carbapenem-resistant pathogens in cSSTI and how to manage them.

Skin and soft tissue infections (SSTIs) with a wide spectrum of disease severity ranging from uncomplicated to potentially lethal are still a leading cause of morbidity and mortality. The burden of carbapenem-resistant gram-negative bacteria (CR-GNB) in SSTIs is increasing. Luckily, the armamentarium of drugs available is recently expanding as well. The present review looks at data on the role CR-GNB in SSTIs and on the old and new drugs available for the treatment of carbapenem-resistant Enterobacteriaceae (CRE), Pseudomonas, and Acinetobacter. The most recent information concern the availability of new antibiotics that, even if no specific clinical trials on complicated SSTIs (cSSTIs) have been performed, may play a role in clinical practice also for the treatment of cSSTIs caused by CR-GNB. Ceftolozane-tazobactam has been found to be a good option for CR Pseudomonas infections including SSTIs. Ceftazidime-avibactam is approved for several indications, including aerobic GNB infections with limited treatment options. Meropenem-vaborbactam therapy has been associated with decreased mortality in infections caused by CRE. Eravacycline has the potential to become useful for the treatment of CR Acinetobacter for which the treatment options are limited. In the carbapenem resistance era, the physicians goal should be to stratify patients according to risk factors for CR-GNB causing SSTIs in order to minimize inappropriate initial therapies. Some recently approved drugs seem destined to become the backbone of target therapy in patients with severe infections caused by susceptible CR-GNB strains. Prompt diagnosis of cSSTIs is crucial and, when feasible, surgical debridement as source control is essential as well.

The role of dalbavancin in skin and soft tissue infections

The increase of skin and soft tissue infections (SSTIs) represents a major concern both in community and in the hospital setting. Staphylococcus aureus is the most frequently isolated pathogen, and the rise in infections due to methicillin-resistant Staphylococcus aureus (MRSA) has been associated with inadequate antibiotic treatment and increased morbidity. A number of new antimicrobials with activity against drug-resistant Gram-positive pathogens, including MRSA, have been recently approved for the treatment of SSTIs. New lipoglycopeptides, in particular dalbavancin, are long-acting antibiotics with potential for infrequent administration, offering the possibility for outpatient treatment and early hospital discharge. Dalbavancin is a new lipoglycopeptide showing high activity against Gram-positive bacteria, including drug-resistant strains. Dalbavancin presents a distinctive pharmacokinetic profile with a terminal prolonged half-life of approximately 14 days. This characteristic allows once-weekly dosing interval, avoiding the need for daily dosing and offering an advantage over other compounds for potential use in the outpatient setting or to promote early hospital discharge. Dalbavancin has a favorable adverse effect profile and appears to be a promising new alternative for treatment of SSTIs. We have reviewed the pharmacokinetic properties of dalbavancin and the clinical evidence for its use in complicated SSTIs and other potential applications.

Tigecycline Susceptibility Trends Among Pathogens Isolated from Complicated Skin and Soft-Tissue Infections in North and Latin America: 2012–2016

Background The Tigecycline Evaluation Surveillance Trial (TEST) monitors the activity of tigecycline and other antimicrobials against clinically-relevant pathogens collected globally. This study reports the activity of tigecycline (TGC) against Gram-positive and Gram-negative isolates collected in North and Latin America from patients with complicated skin and soft-tissue infections (CSSTI).Methods Hospital sites from North America (NA) and Latin America (LA) collected non-duplicate clinical Gram-positive and -negative isolates from various complicated skin and skin structure infection sources during 2012–2016. Organism identification and antibiotic susceptibility (S) testing was performed by the local laboratories. Susceptibility testing was determined using the broth microdilution method according to CLSI guidelines and categorical interpretation of results was done using CLSI or FDA (tigecycline) breakpoint criteria where appropriate. Cefoxitin disk testing was performed for all S. aureus to determine methicillin susceptibility (i.e., MRSA and MSSA).ResultsThe table provides %S and MIC90 data for TGC against CSSTI isolates Region, n, %S, MIC 90 (µg/ml) North America Latin America Organism n %S MIC 90 n %S MIC 90 S. aureus 22701000.123101000.25 Enterobacter spp. 92596.4115992.52 P. aeruginosa 758na*> 8165na> 8 E. coli 71699.90.252411000.25 Enterococcus spp. 69199.30.121351000.12 S. agalactiae 5031000.12581000.06 K. pneumoniae 47194.9215291.52 S. marcescens 34796.826797.02 A. baumannii 310na*297na1 K. oxytoca 20499.00.5151001*na = not applicable or no breakpoints available for this species.ConclusionBased on %S and MIC90 data TGC exhibited potent activity against isolates of all organism groups from complicated skin and soft-tissue infections, regardless of the geographic region. However, given the potential many of these organisms have for developing resistance, continued and careful surveillance monitoring is warranted.Disclosures M. Renteria, IHMA, Inc.: Employee, Salary. H. Leister-Tebbe, Pfizer: Employee, Salary

High burden of complicated skin and soft tissue infections in the Indigenous population of Central Australia due to dominant Panton Valentine leucocidin clones ST93-MRSA and CC121-MSSA

BackgroundSuperficial skin and soft tissue infections (SSTIs) are common among the Indigenous population of the desert regions of Central Australia. However, the overall burden of disease and molecular epidemiology of Staphylococcus aureus complicated SSTIs has yet to be described in this unique population.MethodsAlice Springs Hospital (ASH) admission data was interrogated to establish the population incidence of SSTIs. A prospective observational study was conducted on a subset of S. aureus complicated SSTIs (carbuncles and furuncles requiring surgical intervention) presenting during a one month period to further characterize the clinical and molecular epidemiology. High resolution melting analysis was used for clonal complex discrimination. Real-time polymerase chain reaction identifying the lukF component of the Panton Valentine leucocidin (pvl) gene determined pvl status. Clinical and outcome data was obtained from the ASH medical and Northern Territory shared electronic health records.ResultsSSTIs represented 2.1% of ASH admissions during 2014. 82.6% occurred in Indigenous patients (n = 382) with an estimated incidence of 18.9 per 1, 000 people years compared to the non-Indigenous population of 2.9 per 1000, with an incident rate ratio of 6.6 (95% confidence interval 5.1–8.5). Clinical and molecular analysis was performed on 50 isolates from 47 patients. Community-associated methicillin-resistant S. aureus (CA-MRSA) predominated (57% of isolates). The high burden of SSTIs is partly explained by the prevalence of pvl positive strains of S. aureus (90% isolates) for both CA-MRSA and methicillin-susceptible S. aureus (MSSA). ST93-MRSA and CC121-MSSA were the most prevalent clones. SSTIs due to ST93-MRSA were more likely to require further debridement (p = 0.039), however they also more frequently received inactive antimicrobial therapy (p < 0.001).ConclusionsST93-MRSA and CC121-MSSA are the dominant causes of carbuncles and furuncles in Central Australia. Both of these virulent clones harbor pvl but the impact on clinical outcomes remains uncertain. The high prevalence of CA-MRSA supports empiric vancomycin use in this population when antimicrobial therapy is indicated. Prompt surgical intervention remains the cornerstone of treatment.

Susceptibilities of multidrug-resistant pathogens responsible for complicated skin and soft tissue infections to standard bacteriophage cocktails

Skin and soft tissue infections (SSTIs) may represent a wide clinical spectrum from cellulitis to high-mortality associated necrotizing fasciitis. Limitations in therapy due to the multiple drug resistance, leads to increase in the morbidity and mortality rates, especially in complicated SSTIs such as diabetic foot, decubitus, and surgical wound infections. Therefore, alternative treatment strategies other than antibiotics are needed in appropriate clinical conditions. "Bacteriophage therapy", which is an old method and has been used as part of standard treatment in some countries such as Georgia and Russia, has again become popular worldwide. The aim of this study was to investigate the in vitro susceptibilities of multidrug-resistant (MDR) pathogens isolated from patients with complicated SSTIs, against standard bacteriophage (phage) cocktails. Six different ready-made phage preparations [Pyophage, Intestiphage, ENKO, SES, Fersisi and Staphylococcal Bacteriophage (Sb)] used in this study have been provided by G. Eliava Institute, Georgia. Because of the absence of ready-made phage preparations for Acinetobacter baumannii and Klebsiella pneumoniae, Φ1-Φ7 and ΦKL1- ΦKL3 phages were used provided from the same institute's phage library, respectively. Isolation and identification of the pathogens from abscess and wound samples of patients with SSTIs were performed by conventional methods and automatized VITEK(®)-2 (bioMerieux, ABD) system. Antimicrobial susceptibility testing was conducted complying CLSI standards' and the bacteria that were resistant to at least two different antibiotic groups were considered as MDR. Accordingly, a total of 33 isolates, nine of them were E.coli (8 ESBL and 1 ESBL + carbapenemase positive); nine were MDR P.aeruginosa; nine were MDR A.baumannii; three were methicillin-resistant Staphylococcus aureus (MRSA) and three were K.pneumoniae (1 ESBL, 1 carbapenemase and 1 ESBL + carbapenemase positive) were included in the study. The phage susceptibilities of the pathogens were performed by using spot test. In the study, 29 (87.9%) out of 33 MDR pathogens were found to be susceptible to at least one of the tested phage/phage preparations. All MRSA (3/3) strains were susceptible to ENKO, SES, Fersisi and Sb phage cocktails, while all A.baumannii isolates (9/9) were susceptible to Φ5 and Φ7 phages. However, two E.coli, one K. pneumoniae and one P.aeruginosa strains were resistant to the all phage preparations tested. Although the clinical use of phages has not been approved yet, except a few Eastern European countries, this study exhibits the potential use of the topical bacteriophage therapy in the treatment of complicated SSTIs caused by MDR pathogens with limited treatment options, such as diabetic foot, decubitus, and surgical wound infections.

Blood Cultures in the Evaluation of Uncomplicated Skin and Soft Tissue Infections

Blood cultures are often obtained in children hospitalized with skin and soft tissue infections (SSTIs). Because little evidence exists to validate this practice, we examined the yield of blood cultures in the evaluation of immunocompetent children with SSTIs. Medical records were reviewed for all children admitted between January 1, 2007 and December 31, 2009 after emergency department evaluation and diagnosis of cellulitis or abscess. We compared patients with SSTIs (n = 482) with those with complicated SSTIs (cSSTIs; n = 98). A cSSTI was defined as surgical or traumatic wound infection, need for surgical intervention, or infected ulcers or burns. The SSTI group included patients without complicating factors. None of the patients in the SSTI group had a positive blood culture. In the cSSTI group, 12.5% of blood cultures were positive. The mean length of hospital stay (LOHS) of children with SSTIs was shorter than that of those with cSSTIs (P < .001). In the SSTI group, obtaining a blood culture was associated with a higher mean LOHS (P = .044). Blood cultures are not useful in evaluating immunocompetent children who are admitted to the hospital with uncomplicated SSTIs, and they are associated with a nearly 1-day increase in mean LOHS.

Treatment Failure and Costs in Patients With Methicillin-Resistant Staphylococcus aureus (MRSA) Skin and Soft Tissue Infections: A South Texas Ambulatory Research Network (STARNet) Study

To measure the incidence of treatment failure and associated costs in patients with methicillin-resistant Staphylococcus aureus skin and soft tissue infections (SSTIs). This was a prospective, observational study in 13 primary care clinics. Primary care providers collected clinical data, wound swabs, and 90-day follow-up information. Patients were considered to have "moderate or complicated" SSTIs if they had a lesion ≥5 cm in diameter or diabetes mellitus. Treatment failure was evaluated within 90 days of the initial visit. Cost estimates were obtained from federal sources. Overall, treatment failure occurred in 21% of patients (21 of 98) at a mean additional cost of $1,933.71 per patient. In a subgroup analysis of patients who received incision and drainage, those with moderate or complicated SSTIs had higher rates of treatment failure than those with mild or uncomplicated SSTIs (36% vs. 10%; P=.04). One in 5 patients presenting to a primary care clinic for a methicillin-resistant S. aureus SSTI will likely require additional interventions at an associated cost of almost $2,000 per patient. Baseline risk stratification and new treatment approaches are needed to reduce treatment failures and costs in the primary care setting.

PIN7 Efficacy of Ceftaroline Fosamil and Other Intravenous Antibiotics in the Treatment of Complicated Skin and Soft Tissue Infections (CSSTI): A Network Meta-Analysis (NMA)

PIN7 Efficacy of Ceftaroline Fosamil and Other Intravenous Antibiotics in the Treatment of Complicated Skin and Soft Tissue Infections (CSSTI): A Network Meta-Analysis (NMA)

Import and Spread of Panton-Valentine Leukocidin–Positive Staphylococcus aureus Through Nasal Carriage and Skin Infections in Travelers Returning From the Tropics and Subtropics

Antibiotic-resistant Staphylococcus aureus is a globally emerging pathogen. Exchangeable virulence factors, such as Panton-Valentine leukocidin (PVL), have been proposed to drive this epidemic. We investigated whether skin infections and nasal colonization in travelers contribute to the global spread of such strains. We conducted a case-control study of 38 returnees from the tropics and subtropics with S. aureus-positive skin and soft tissue infections (SSTIs) and 124 control patients with other travel-associated disorders. We collected information on travel characteristics, clinical outcomes of SSTIs, antibiotic sensitivity patterns, and genotypes of S. aureus strains isolated from skin lesions and the nares. S. aureus-positive SSTIs were associated with travel duration and purpose and were most common in returnees from Africa (odds ratio, 4.2; P = .005). PVL-positive (PVL(+)) S. aureus was frequent in the lesional and nasal isolates from travelers with SSTIs but could not be found in the nares of the control patients. The presence of PVL in S. aureus in travelers was associated with complicated disease, reduced antibiotic susceptibility, and secondary spread. The genotypes of PVL(+) S. aureus in returnees were reported to be endemic to the visited destination but rarely observed in Europe. Geographic variation in the risk of SSTIs in travelers supports a globally heterogeneous distribution of virulent S. aureus. Complicated SSTIs in returnees from nontemperate climates are associated with PVL(+) S. aureus and promote the emergence and spread of virulent and antibiotic-resistant strains. We propose a network for the surveillance of imported S. aureus (www.staphtrav.eu).

Complicated skin and soft tissue infection

Skin and soft tissue infections (SSTIs) are common, and complicated SSTIs (cSSTIs) are the more extreme end of this clinical spectrum, encompassing a range of clinical presentations such as deep-seated infection, a requirement for surgical intervention, the presence of systemic signs of sepsis, the presence of complicating co-morbidities, accompanying neutropenia, accompanying ischaemia, tissue necrosis, burns and bites. Staphylococcus aureus is the commonest cause of SSTI across all continents, although its epidemiology in terms of causative strains and antibiotic susceptibility can no longer be predicted with accuracy. The epidemiology of community-acquired and healthcare-acquired strains is constantly shifting and this presents challenges in the choice of empirical antibiotic therapy. Toxin production, particularly with Panton-Valentine leucocidin, may complicate the presentation still further. Polymicrobial infection with Gram-positive and Gram-negative organisms and anaerobes may occur in infections approximating the rectum or genital tract and in diabetic foot infections and burns. Successful management of cSSTI involves prompt recognition, timely surgical debridement or drainage, resuscitation if required and appropriate antibiotic therapy. The mainstays of treatment are the penicillins, cephalosporins, clindamycin and co-trimoxazole. β-Lactam/β-lactamase inhibitor combinations are indicated for polymicrobial infection. A range of new agents for the treatment of methicillin-resistant S. aureus infections have compared favourably with the glycopeptides and some have distinct pharmacokinetic advantages. These include linezolid, daptomycin and tigecycline. The latter and fluoroquinolones with enhanced anti-Gram-positive activity such as moxifloxacin are better suited for polymicrobial infection.

Community-Associated Methicillin-ResistantStaphylococcus AureusSkin and Soft Tissue Infections

The prevalence of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections is increasing globally and in Singapore. Skin and soft tissue infections (SSTIs) are the most common manifestations, ranging from common furuncles to the rare but life-threatening necrotizing fasciitis. Surgical drainage and debridement where feasible are the mainstay of therapy, whereas MRSA-active antibiotics are essential when surgery is not possible or as adjunctive therapy for severe and/or complicated SSTIs. In itself, the continued inexorable rise in CA-MRSA rates poses difficult challenges for primary healthcare and hospital infection control. Innovative approaches are required to mitigate its impact in both the community and hospital settings.

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.

Review of question and answer session

Prior to the oral presentations at the Skin and Soft Tissue Infections Workshop the audience was polled to assess the participants' knowledge of the epidemiology and aetiology of skin and soft tissue infections (SSTI) as well as to determine their approach to the treatment of complicated SSTIs (cSSTI). Twenty questions were asked before the presentations and audience members were allowed to answer anonymously using an electronic audience response system. The questions fell into four general categories: aetiology of cSSTI, terminology, epidemiology and treatment. This paper discusses the answers to the questions.

Detection and Initial Management of Complicated Skin and Soft Tissue Infections Caused by Methicillin-Resistant Staphylococcus aureus

Accurate diagnosis and initial management of skin and soft tissue infections (SSTIs) are essential to providing adequate care to patients. Methicillin-resistant Staphylococcus aureus (MRSA) is one of the leading causes of SSTIs, and surgeons and other healthcare providers should assess these infections carefully to improve patient outcomes. Review of the pertinent literature and recommendations related to diagnosis and initial treatment with a focus on complicated SSTIs (cSSTIs). Patients with SSTIs presenting to the hospital or outpatient setting need to be evaluated carefully. Clinical assessment of infection severity and underlying patient conditions is important. Purulence is a major feature of infections necessitating further assessment and intervention. Culturing and determination of antimicrobial susceptibility are essential. Incision and drainage, debridement, and administration of antimicrobial agents may be required. Immediate hospitalization and treatment with intravenous antibiotics are needed for more serious cases. The growing prevalence of MRSA, particularly community-acquired MRSA in cSSTIs, and the increasing number of these infections observed in both the community and the hospital setting requires the immediate careful assessment of possible cSSTIs. Rapid, appropriate treatment is necessary to facilitate good patient care and outcomes. Antimicrobial therapy, surgical drainage/debridement, and close monitoring will be required, particularly in the management of cSSTIs resulting from infections with MRSA.

Are Glycopeptides Still Appropriate and Convenient for Empiric Use?

The glycopeptides vancomycin and teicoplanin are widely used, and indeed recommended for, the treatment of severe or resistant Gram-positive infections. Therapeutic drug monitoring is widely used for vancomycin but less commonly for teicoplanin, and remains controversial. We report the cost savings of a formulary decision to re-place teicoplanin with daptomycin for the empiric treatment of complicated skin and soft tissue infections (CSSTIs), staphylococcal bacteraemia and hospital-acquired Gram-positive sepsis. In the Intensive Therapy Unit (ITU) we optimised treatment of serious Gram-positive infections by substituting teicoplanin with vancomycin administered by continuous infusion. Costs were calculated using British National Formulary (BNF) prices and costs for therapeutic drug monitoring. Daptomycin (350 mg/d) use was associated with a cost saving per 7 days of treatment of £86 and vancomycin with £51 (4 g/d) to £276 (2 g/d) compared to the 600 mg teicoplanin dose. Our own formulary re-positioning of glyco/lipopeptides, i.e. the preferential use of vancomycin in the ITU and substitution of teicoplanin with daptomycin, is cost-effective and provides better therapeutic alternatives. Continuous vancomycin infusion in the ITU setting guarantees optimal dosing for severely ill patients. Daptomycin use on surgical and medical wards, apart from being marginally cheaper than teicoplanin, guarantees optimal dosing without the need for drug monitoring.

Is Linezolid Superior to Vancomycin for Complicated Skin and Soft Tissue Infections Due to Methicillin-Resistant Staphylococcus aureus ?

It is with interest that we read the article by J. Weigelt et al. (2). While this study aims to demonstrate that linezolid may be used for complicated skin and soft tissue infections (CSSTIs), we are concerned with the study's conclusions. The study was designed to prove superiority of linezolid over vancomycin with respect to the primary end point of clinical cure, with a power of 0.90 and a significance level of 0.05 for a two-sided test. The primary outcome result was not statistically significant based on the trial design (intent-to-treat [ITT] population clinical cure for linezolid, 92.2%, and for vancomycin, 88.5%; 95% confidence interval, −0.11%, 7.47%). A subgroup analysis based on the microbiological outcomes was performed, and the authors reached the conclusion that linezolid is “… superior to vancomycin in the treatment of CSSTIs due to MRSA” (2). This was based on the methicillin-resistant Staphylococcus aureus (MRSA) subgroup analysis, in which the direct comparison yielded a significantly higher proportion of microbiological outcomes in the linezolid arm than in the vancomycin arm. Baseline characteristics within each MRSA subgroup that could have biased the results in either arm were not provided. In addition, an interaction test to understand if there was a difference in the magnitude of the effect based on the type of microorganism was also not provided. This is not in accordance with the CONSORT guidelines (1) for clinical trial reporting. We performed this analysis with the published data and found no significant treatment by microorganism (MRSA versus non-MRSA organism) interaction for either the MRSA modified intent-to-treat (MITT) (P = 0.24) or MRSA microbiologically evaluable (ME) (P = 0.07) subgroups, indicating that there was not a differential treatment effect based on microorganism type. Also, it was surprising that we could not find the “clinical response” analysis (the primary end point of the study) with respect to this same MRSA subgroup in the published paper. This is of paramount importance. For a microbiological cure to be meaningful, it has to be accompanied by a clinical cure. Due to its obvious importance, the clinical response outcome (cured, improved, failed, or indeterminate) should have been reported within the MRSA subgroup, and results (similar to those of Table 4 [2]) should be presented along with baseline characteristics and interaction tests, as suggested above for the “microbiological outcomes” analysis. In addition, we are concerned with the safety conclusion: “Drug-related adverse events were reported in similar numbers in both the linezolid and the vancomycin arms of the trial” (2). However, this is not appropriate, since thrombocytopenia (P < 0.001), diarrhea (P = 0.0006), and nausea (P = 0.006) were highly statistically significantly more frequent in the linezolid than in the vancomycin arm. In conclusion, this study failed to prove linezolid's superiority over vancomycin in the CSSTI population. The rate of “microbiological cure” (secondary outcome) in the MRSA subgroup was higher with linezolid, but the rate of “clinical cure” (primary outcome) was not presented. Moreover, the absence of significant interaction suggests that the treatment effect was not influenced by the type of microorganism. Another trial needs to be done to confirm the results from the MRSA subgroup analysis. Finally, the paper's conclusion should also state that the rates of thrombocytopenia, diarrhea, and nausea were statistically significantly higher with linezolid than with vancomycin.

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.

Associations of HLA-DRB and -DQB genes with two and five year outcome in rheumatoid arthritis.

To evaluate the clinical usefulness of genomic HLA typing during the first five years of established rheumatoid arthritis (RA). The HLA-DRB and -DQB alleles were determined by restriction length polymorphisms and polymerase chain reaction amplification with sequence specific primers in 99 Swedish patients with RA. Clinical features after two and five years disease duration were related to the genetic pattern. Seventy four patients were seropositive, 25 had nodules, 90 developed erosions, and 15 required joint replacements. Twelve patients were in remission after five years. Disability was assessed by health assessment questionnaire, and radiographic damage in hands and feet by the Larsen method. Eighty seven per cent of the patients carried the conserved third hypervariable region sequence (HVR3), 32% had DRB1*04 on one allele, and 26% had DRB1*04 on both alleles (all frequencies significantly greater than in controls). Frequencies of DRB1*04 associated DQB*0301 and *0302 were normal. Patients carrying DRB1*04 on both alleles tended to have more radiographic changes after two years, but this difference had diminished after five years. Disability did not vary with regard to the genotype. Homozygous HVR3 patients had about three times greater risk of undergoing joint replacement. Homozygosity for HVR3 and presence of DQB*0302 both tended to be associated with erosive disease. We confirmed a strong association of disease with the presence of the shared epitope on one or two alleles. However, genotype was not strongly associated with disease severity after two and five years disease duration, and thus the value of genomic typing to select patients for early aggressive therapy is questionable.