Current guidelines and recommendations for the management of skin and soft tissue infections

Transcription

1 REVIEW C URRENT OPINION Current guidelines and recommendations for the management of skin and soft tissue infections Philippe Montravers a,b, Aurelie Snauwaert a, and Camille Welsch a Purpose of review The incidence of severe skin and soft tissue infections (SSTIs) has significantly increased over the last years. In addition, major ecological changes have been reported with the emergence of community-acquired methicillin-resistant Staphylococcus aureus (MRSA), involved in a large proportion of these cases. A large number of expert opinions, guidelines, and recommendations for the management of SSTIs have been published over the last decade. The purpose of this review is to compare these guidelines. Recent findings A total of six official publications have presented recommendations for the management of SSTIs. During the same period, other guidelines for the management of MRSA infections have also been published, including some recommendations for SSTIs. Summary The applicability of the guidelines is questionable in many ways. The distinction between necrotizing/ nonnecrotizing infections is valuable but difficult to apply prior to surgical management. The prescribers should choose a pragmatic approach to empirical antibiotic therapy, taking into account the patient s initial severity, the extent of infection and risk factors for resistant microorganisms essentially related to healthcareassociated circumstances. Keywords cellulitis, guidelines, methicillin-resistant Staphylococcus aureus, necrotizing infections, skin and soft tissue infections INTRODUCTION Severe skin and soft tissue infections (SSTIs) are associated with high morbidity and mortality rates leading to prolonged hospital stay, surgery, and antimicrobial therapy. U.S. emergency department visits for SSTI have increased significantly since the late 1990s [1]. During the same period, major ecological changes have been reported with the emergence of community-acquired methicillin-resistant Staphylococcus aureus (MRSA), involved in a large proportion of these new cases. A large number of expert opinions, guidelines, and recommendations for the management of SSTIs have been published over the last decade. Several changes can explain this abundance of guidelines, such as ageing of the population with growing proportions of underlying disease, increased proportions of obese patients, community-acquired MRSA issues, or the release of new antibiotics active against Gram-positive bacteria. The purpose of this review is to compare the guidelines published during this period. A total of six publications have presented recommendations for the management of SSTIs [2 5,6 &&,7 && ]. The issues addressed in these papers are summarized in Table 1. During the same period, other guidelines for the management of MRSA infections have also been published, including some recommendations for SSTIs [8 11]. DEFINITIONS Skin infections are usually grouped under a single acronym, most frequently SSTI, suggesting that the infectious process involves the skin, subcutaneous a Département d Anesthésie-Réanimation, CHU Bichat Claude- Bernard HUPNVS, Assistance Publique-Hôpitaux de Paris, Université Denis Diderot and b University Denis Diderot, PRESS Sorbonne Cité, Paris, France Correspondence to Philippe Montravers, Département d Anesthésie- Réanimation, CHU Bichat Claude-Bernard HUPNVS, Assistance Publique-Hôpitaux de Paris, Université Denis Diderot, PRESS Sorbonne Cité, 46 Rue Henri-Huchard, Paris, France. Tel: ; philippe.montravers@bch.aphp.fr Curr Opin Infect Dis 2016, 29: DOI: /QCO Copyright ß 2016 Wolters Kluwer Health, Inc. All rights reserved.

2 Skin and soft tissue infections KEY POINTS A large number of recommendations have been published for the management of skin and soft tissue infections. Optimal therapy is based on a timely and aggressive source control. The prescriber should differentiate necrotizing and nonnecrotizing infections. The empirical antibiotic therapy should take into account the patient s initial severity, the extent of infection, and the risk factors for resistant microorganisms. tissue, fascia or muscle. The term skin and skin structure infections (SSSIs), mainly used by the U.S. Food and Drug Administration (FDA) definitions for therapeutic trials, specifically excludes deep space (fascia and muscles) infections and necrotizing infections. The ABSSI acronym is used by the FDA in a guidance for industry and corresponds to acute bacterial SSSI with a lesion area of at least 75 cm 2 (measured by the area of redness, oedema or induration) [12]. Complicated SSSIs are distinguished from simple infections by the need for inpatient management, surgical procedures, or significant underlying disease that complicates the therapeutic response [12]. Most infections requiring surgical management are complicated infections, with the exception of minor cellulitis at incision sites. Diabetic foot ulcers and infected burns are usually excluded from these analyses. For clarity of presentation, we will use the term SSTI, comprising both superficial and deep infections. A wide range of clinical infections are described in guidelines (erysipelas, cellulitis, fasciitis, necrotizing infections...) with many different definitions Table 1. Topics addressed in recent guidelines for the management of skin and soft tissues infections SEQ/SEMI 2006 [2] SIS 2009 [3] ISID/ISC 2011 [4] JSC/JAID 2011 [5] WSES 2014 [6 && ] IDSA 2014 [7 && ] Clinical diagnosis Nonnecrotizing superficial infections Abscesses þ þ þ þ Impetigo þ þ þ þ þ Erysipelas þ þ þ þ þ Cellulitis þ þ þ þ þ Pyomyositis þ þ Necrotizing infections þ þ þ þ þ þ Clostridial gas gangrene þ þ þ þ Nonclostridial gas gangrene þ þ Myonecrosis þ þ þ Necrotizing fasciitis þ þ þ þ Synergistic gangrene þ þ Fournier s gangrene þ þ þ Bites þ þ þ Immunosuppressed patients þ þ Surgical infection þ þ þ þ þ Diagnosis and management Imaging procedures þ þ þ þ þ Antibiotic therapy þ þ þ þ þ þ Nutrition þ Surgical techniques þ þ þ Dressing and postoperative care þ þ Hyperbaric oxygen þ þ þ þ þ þ Immunoglobulins þ þ þ þ IDSA, Infectious Diseases Society of America; ISID/ISC, Italian Society of Infectious Diseases/International Society of Chemotherapy; JSC/JAID, Japanese Society of Chemotherapy/Japanese Association for Infectious Diseases; SEQ/SEMI, Sociedad Espanola de Quimioterapia:Sociedad Espanola de Medicina Interna; SIS, Surgical Infection Society; WSES, World Society of Emergency Surgery Volume 29 Number 2 April 2016

3 Guidelines for the treatment of skin and soft tissue infections Montravers et al. largely contributing to confusion in the prescriber s mind. The Infectious Diseases Society of America (IDSA) guidelines identify 10 different types of infection including superficial and deep infections [7 && ]. Many terms and definitions have been proposed for necrotizing infections, related to microbiological characteristics (anaerobic streptococcal myositis, synergistic necrotizing cellulitis, clostridial myonecrosis...) or the anatomical site (myositis suggestive of muscular infection, Fournier gangrene for perineal infections...)[7 && ]. The terms used are sometimes restricted to a single pathogen, such as clostridial gas gangrene [2,7 && ] or necrotizing fasciitis due to group A beta-haemolytic streptococci [4]. Subgroups can be so closely related that the need for distinction may be questionable such as necrotizing fasciitis by mixed pathogens and synergic necrotizing fasciitis [4]. Some definitions can also be synonyms such as clostridial myonecrosis and clostridial gas gangrene [3,5]. In practice, these more specific terms are rarely used. The most frequent terms, cellulitis and erysipelas, are used inconsistently, some clinicians using a single term to describe both infections. RECOGNITION OF SKIN AND SOFT TISSUE INFECTIONS Even when severe SSTI is highly suspected in a patient with high WBC counts, pain out of proportion to examination, or abnormal appearance of the skin such as bullae or blisters, the extent or depth of the infectious process can be difficult to assess. In contrast, occult SSTIs are rare. However, few grading systems have been proposed to assess disease severity and to help clinicians speed-up the diagnosis process. The standardized early warning system (SEWS) [13] and the laboratory risk indicator for necrotizing fasciitis (LRINEC) score [14] have been proposed with this purpose in mind. However, the published guidelines have provided only limited recommendations in this field. The stage of severe sepsis or septic shock remains a common pathway for ICU admission which, in some cases, may already correspond to a delayed diagnosis. Computed tomography, magnetic resonance imaging, and ultrasound studies are recommended in the diagnostic process of necrotizing SSTI, but with a low level of proof [6 &&,7 && ]. These imaging techniques could be helpful to evaluate the extent of the injury, but experts emphasize the fact that these procedures must not delay surgical management. Additional diagnostic tools are deceptive. Biomarkers are not proposed by the experts. In nonnecrotizing infections, blood cultures are rarely positive (<5% of cases), whereas the rate of positive results from either needle aspiration or punch biopsy ranges from 5 to 40% of cases [3]. The use of full-thickness biopsy and frozen section examination has been proposed for necrotizing infections. In immunocompromised patients and febrile neutropenic patients, biopsy or aspiration of the lesion for cytological/histological evaluation is recommended as an early diagnostic procedure [7 && ]. In doubtful situations, the experts generally recommend surgical exploration or large biopsies to allow direct examination of the suspected lesion [3]. Cultures of vesicles, infected fluids, and tissues should be obtained during the initial surgical debridement and the results should be used to tailor specific antibiotic management. The algorithm proposed by the IDSA guidelines for diagnostic procedures is the only one taking into account the severity and site of the SSTI [7 && ]. PRINCIPLES OF TREATMENT Source control Although antiinfective agents are important adjuncts to management, the cornerstone of treatment for SSTIs remains early and aggressive surgical debridement, especially in necrotizing infections. Without adequate surgical source control, mortality rates can be as high as 100%. However, the balance between effective debridement and unnecessary overexcision can be difficult to achieve. Debridement is rarely complete after a single operation and many publications report additional procedures to remove persistent clusters of infection. Few recommendations to guide surgical management have been published in this field. Only three of the recent guidelines for SSTIs have provided some general comments [3,6 &&,7 && ]. The IDSA guidelines emphasized the absence of discussion of the treatment of surgical site infections in textbooks [7 && ]. This remark could be applied to the global management of infected wounds. Nursing management and postoperative wound care are not addressed by the guidelines. Nonadherent compressive dressings should be applied, followed by repeated wound inspection and cleaning, at least on a daily basis or even more frequently for the first few days of management. This point is particularly important during the first days of treatment when wounds can discharge copious amounts of fluid [7 && ]. When infection is controlled and debridement is no longer required, wound healing can be facilitated by topical negative pressure therapy and vacuum-associated closure (TNP/VAC), especially in complex cases [15]. A recent consensus document published by the GISIG (Groupo Italiano di Studio Copyright ß 2016 Wolters Kluwer Health, Inc. All rights reserved

4 Skin and soft tissue infections sulle Infezioni Gravi) analysed TNP/VAC in complicated skin and skin-structure infections, but limited their analysis to deep surgical site infections [9]. The experts concluded that TNP/VAC was a possible alternative to standard therapy. However, they emphasized the need for a standardized protocol for the use of TNP/VAC and for the standard care of infected wounds [9]. guidelines indicate dose recommendations corresponding to the usually prescribed dose without any discussion of monitoring or dose changes related to clinical conditions [4,5,6 && ]. The best guidelines for adult and paediatric dosages are the IDSA recommendations, but dose monitoring and adjustments related to clinical conditions are not clearly addressed [7 && ]. Antimicrobial therapy Many treatment options have been proposed for SSTIs, using monotherapy or combinations. Guidelines address both superficial and necrotizing infections (Tables 2 and 3). Guidelines are also confusing in that the experts rarely address the same types of infections (Tables 2 and 3). Overall, it is difficult to establish an overview of the various diseases, related to different modes of spread of infection, types of microorganisms involved and different clinical conditions. Because of the high proportion of Grampositive bacteria involved in SSTIs, most regimens take these organisms into account. The development of community-acquired MRSA infections has led to specific guidelines for SSTIs (Table 4). It is noteworthy that these guidelines do not define target populations in terms of geographical regions, which can be a source of concern, as the epidemiology of resistance varies from one country to another, especially for community-acquired MRSA. Consequently, readers must be very cautious when extrapolating guidelines when they are not familiar with their local epidemiology. Few guidelines address the issue of resistance, except for MRSA. Cultured pathogens are susceptible to conventional treatments in the majority of the cases. In a recent analysis of five European registries from Germany, Italy, Spain, and France comprising 254 cases of severe SSTI, 30% of patients had at least one resistant pathogen at baseline [16]. MRSA was reported as the resistant organism in 86% of these cases, suggesting that resistance is not a major issue for other microorganisms in routine clinical practice [16]. Pharmacokinetic issues Although pharmacokinetic issues are an increasingly important element in the management of severe infections, this topic is not discussed in guidelines. Some guidelines do not even provide any dose recommendations [2]. The Surgical Infection Society (SIS) guidelines indicate the need to prescribe high dose of antibiotics, using several examples such as penicillin or clindamycin, but do not provide any detailed suggestions [3]. Several Antitoxin therapy Linezolid and clindamycin may be able to significantly reduce the early release of exotoxins from Gram-positive pathogens. These agents that inhibit toxin production have been proposed in severe infections, in patients with evidence of toxic shock syndrome, and in streptococcal and staphylococcal infections [3,6 &&,7 && ]. For the IDSA experts, the combination of penicillin and clindamycin constitutes a strong recommendation but with a low level of proof, whereas the World Society of Emergency Surgery (WSES) experts strongly recommend the use of clindamycin with low-quality evidence [6 &&,7 && ]. The SIS guidelines and other guidelines recommend the use of clindamycin and linezolid without specifying whether these proposals are purely based on their antibiotic capacities or their antitoxin properties (Tables 2 and 3). Infections in neutropenic and immunocompromised patients Neutropenic and immunocompromised patients are at increased risk of harboring resistant and/or difficult-to-treat pathogens. Few guidelines have been published in this field [6 &&,7 && ]. The experts recommend performing skin biopsy to speed-up the diagnostic process. Because of their high initial mortality rates, the IDSA guidelines emphasize the need to take Gram-negative organisms and polymicrobial infections into account in these patients, although Gram-positive pathogens are the most common isolates [7 && ]. Broad-spectrum empirical therapy is recommended using a combination of glycopeptides, daptomycin, ceftaroline or linezolid and antipseudomonal agents. Drainage of soft tissue abscesses should be planned after bone marrow recovery, whereas debridement for necrotizing infections should be performed immediately. The recommended duration of therapy ranges between 7 and 14 days [7 && ]. De-escalation Although de-escalation is largely recommended in clinical practice, few guidelines address this issue Volume 29 Number 2 April 2016

5 Guidelines for the treatment of skin and soft tissue infections Montravers et al. Table 2. Antimicrobial therapy recommended for nonnecrotizing skin and soft tissue infections in recent guidelines Erysipelas Cellulitis Subcutaneous abscesses Bites SEQ/SEMI [2] Penicillin G or amoxicillin or amoxicillin/clavulanate or clindamycin Cloxacillin or cephalexin or cefazolin or clindamycin or levofloxacin or moxifloxacin Linezolid or vancomycin or teicoplanin or TMP/SMX or clindamycin for severe infection or risk of MRSA infection SIS [3] Penicillin G (1C) Penicillin G (1C) Clindamycin or macrolide alone or in combination with cell-wall active agents in severe cases (1B/1C) Antistaphylococcal penicillins or cefazolin or ceftriaxone (2B/C) Clindamycin or macrolide alone or in combination with cell-wall active agents in severe cases (1B/1C) Antistaphylococcal penicillins or cefazolin or ceftriaxone (2B/C) ISID/ISC [4] Amoxicillin/clavulanate or oxacillin or cephalexin or ampicillin/ sulbactam or first-generation cephalosporin or clindamycin or fluoroquinolones with Grampositive activity IDSA [7 && ] Penicillin G or ceftriaxone or cefazolin or clindamycin for empiric therapy of moderate cases Vancomycin plus piperacillin/ tazobactam for empiric therapy of severe cases Penicillin G or ceftriaxone or cefazolin or clindamycin for empiric therapy of moderate cases Vancomycin plus piperacillin/ tazobactam for empiric therapy of severe cases No antibiotic in patients with normal defences and lesions <5 cm diameter (A3) Clindamycin, TMP/SMX, tetracyclines, linezolid, rifampin, fusidic acid in zones of high prevalence of community-acquired MRSA Vancomycin, teicoplanin, daptomycin, linezolid, tigecycline or telavancin in more serious infections TMP/SMX or doxycycline for empiric therapy of moderate cases Vancomycin or daptomycin or linezolid or telavancin or ceftaroline for empiric therapy of severe cases Amoxicillin/clavulanate or ertapenem or thirdgeneration cephalosporin þ metronidazole or levofloxacin þ metronidazole or ciprofloxacin þ clindamycin Amoxicillin/clavulanate Amoxicillin/clavulanate a or ampicillin/ sulbactam a or piperacillin/tazobactam or carbapenems a or doxycycline a or penicillin þ dicloxacillin or TMP/SMX or metronidazole or clindamycin or secondgeneration cephalosporins or third-generation cephalosporins or fluoroquinolones Strength of recommendation: 1, strong recommendation; 2, weak recommendation. Quality of evidence: A, good-quality/high-quality evidence; B, moderate-quality evidence; C, low/very low quality evidence. IDSA, Infectious Diseases Society of America; ISID/ISC, Italian Society of Infectious Diseases/International Society of Chemotherapy; MRSA, methicillin-resistant Staphylococcus aureus; SEQ, Sociedad Espanola de Quimioterapia; SEQ/SEMI, Sociedad Espanola de Quimioterapia:Sociedad Espanola de Medicina Interna; SIS, Surgical Infection Society; TMP/SMX, trimethoprim sulfamethoxazole. a Proposed for animal and human bites Copyright ß 2016 Wolters Kluwer Health, Inc. All rights reserved

6 Skin and soft tissue infections Table 3. Antimicrobial therapy recommended for necrotizing skin and soft tissue infections in recent guidelines Necrotizing fasciitis due to mixed pathogens Necrotizing fasciitis by Group A b-haemolytic streptococci Clostridial gas gangrene Fournier s gangrene Myonecrosis SEQ/SEMI [2] Third-generation or fourthgeneration cephalosporin þ metronidazole linezolid /glycopeptides SIS [3] Imipenem-cilastatin or meropenem or ertapenem or piperacillin/tazobactam or ticarcillin/clavulanate or tigecycline (2C) ISID/ISC [4] Ampicillin/sulbactam þ clindamycin þ ciprofloxacin (1C) or piperacillin/tazobactam or carbapenems or fluoroquinolones or thirdgeneration cephalosporin or aminoglycosides þ metronidazole or clindamycin JSC/JAID [5] Penicillin G or piperacillin or piperacillin/tazobactam WSES [6 && ] Linezolid þ piperacillin/ tazobactam or daptomycin þ piperacillin/tazobactam þ clindamycin Penicillin G for moderateto-severe infections (1C); clindamycin or linezolid or erythromycin (1C) Penicillin G þ clindamycin or glycopeptides or linezolid or tigecycline or daptomycin Penicillin G þ clindamycin or clindamycin alone Penicillin G or carbapenems (1C) clindamycin (1C) Penicillin G þ clindamycin Same as necrotizing fasciitis Penicillin þ clindamycin Piperacillin or piperacillin/ tazobactam; ampicillin or sulbactam/ampicillin for C. perfringens infections Piperacillin/tazobactam þ clindamycin or meropenem þ linezolid a Amoxicillin/clavulanate þ clindamycin or linezolid þ piperacillin/tazobactam a or daptomycin þ piperacillin/ tazobactam þ clindamycin a IDSA [7 && ] Vancomycin or linezolid þ piperacillin/tazobactam or carbapenem or þ ceftriaxone and metronidazole or clindamycin (1C) Penicillin þ clindamycin (for documented infection) (1C) Vancomycin þ piperacillin / tazobactam or ampicillin/ sulbactam or carbapenem (1C); penicillin þ clindamycin (for documented infection) (1C) Vancomycin or linezolid þ piperacillin/tazobactam or carbapenem or þ ceftriaxone and metronidazole (1C) Vancomycin þ piperacillin/ tazobactam or ampicillin/ sulbactam or carbapenem (1C) Strength of recommendation: 1, strong recommendation; 2, weak recommendation. Quality of evidence: A, good-quality/high-quality evidence; B, moderate-quality evidence; C, low/very low-quality evidence. IDSA, Infectious Diseases Society of America; ISID/ISC, Italian Society of Infectious Diseases/International Society of Chemotherapy; JSC/JAID, Japanese Society of Chemotherapy/Japanese Association for Infectious Diseases; SEQ, Sociedad Espanola de Quimioterapia; SEQ/SEMI, Sociedad Espanola de Quimioterapia: Sociedad Espanola de Medicina Interna; SIS, Surgical Infection Society; WSES, World Society of Emergency Surgery. a In the presence of signs of severe sepsis Volume 29 Number 2 April 2016

7 Guidelines for the treatment of skin and soft tissue infections Montravers et al. Table 4. Antimicrobial therapy recommended for methicillin-resistant Staphylococcus aureus skin and soft tissues infections BSAC 2009 [8] SIS 2009 [3] GISIG 2010 [9] ISID/ISC 2011 [4] IDSA 2011 [10] SEQ 2013 [11] Vancomycin A A-1 A-1 þ Teicoplanin A A-1 þ Glycopeptides A-1 Daptomycin A-1 C A-1 A-1 þ Telavancin A-1 Linezolid A-1 C-1 D A-1 A-1 þ Clindamycin C-1 A-2/A-3 Erythromycin C-1 Tigecycline B-1 B A-1 Strength of recommendation: A, good evidence; B, moderate evidence; C, poor evidence. Quality of evidence: 1, at least one randomized controlled trial; 2, at least one nonrandomized trial; 3, expert s opinion. No strength of recommendation was given for the SEQ 2013 guidelines. The drugs proposed in this article are indicated by þ. BSAC, British Society of Antimicrobial Chemotherapy; GISIG, Gruppo Italiano di Studio Infezioni Gravi; IDSA, Infectious Diseases Society of America; ISID/ISC, Italian Society of Infectious Diseases/International Society of Chemotherapy; SEQ, Sociedad Espanola de Quimioterapia; SIS, Surgical Infection Society. [3,6 &&,7 && ]. The IDSA guidelines address empirical and definitive treatments for each diagnosis, but the term de-escalation is not mentioned [7 && ]. The WSES experts recommend de-escalation in necrotizing infections (strong recommendation, low level of proof) [6 && ], whereas the SIS guidelines refer to the term de-escalation without describing circumstances, indications, or grading [3]. Duration of antibiotic therapy Duration of therapy is another source of growing concern in many infections related to unduly prolonged treatments. No monitoring techniques or biomarkers have yet been proposed to accurately guide discontinuation of treatment of SSTIs. The FDA licensing trial recorded the use of 7 14 days of treatment without any clear justifications. Several guidelines have failed to provide any recommendations for duration of therapy [3,4,5,6 && ]. The Spanish guidelines recommend 5 10 days of therapy for noncomplicated cellulitis and days in severe or extensive cases [2]. The IDSA experts suggest a 7-day regimen for ecthyma or impetigo, 5 10 days for recurrent skin abscesses, 5-day therapy for erysipelas and cellulitis with an extended duration in the absence of improvement, 7 days for superficial streptococcal and staphylococcal infections depending on clinical response, 7 14 days in neutropenic patients and 2 3 weeks in pyomyositis. In MRSA infections, the experts suggest 5 10 days of therapy for outpatients with cellulitis (purulent or nonpurulent) and 7 14 days in hospitalized patients with complicated SSTI which should be adapted according to clinical response [17]. Additional treatment for critically ill patients The management of these life-threatening infections in ICU patients is based on supportive ICU care, adequate nutritional support, and management of associated complications. Only limited data are available concerning the management of patients with SSTIs. Most strategies applied as part of supportive ICU care, such as mechanical ventilation, prevention of thromboembolic complications, or pharmacokinetic issues, are based on extrapolations from management in surgical cases. However, some key issues remain totally unexplored, such as nutritional support. Intravenous immunoglobulins The use of intravenous immunoglobulins for treating necrotizing SSTIs is based on the hypothesis of a potential benefit related to binding of endotoxins produced by streptococci and staphylococci. No standardized antitoxin is available, leading the experts to propose polyclonal immunoglobulins for streptococcal and staphylococcal necrotizing SSTIs. This strategy has been discussed by several guidelines, but the topic remains controversial [3,6 &&,7 && ]. A weak recommendation was proposed by the WSES experts for the early use of immunoglobulins in patients with necrotizing SSTIs associated with severe sepsis and septic shock (level 2C, weak recommendation, very low quality evidence) [6 && ]. The IDSA guidelines discuss this option, but do not provide any recommendations [7 && ]. The SIS experts reached the conclusion that this option may be considered in toxic shock syndrome associated with staphylococcal or streptococcal SSTIs (level 2C) [3] Copyright ß 2016 Wolters Kluwer Health, Inc. All rights reserved

8 Skin and soft tissue infections Hyperbaric oxygen therapy The benefit of hyperbaric oxygen (HBO) therapy remains controversial. No prospective randomized clinical trials have been published on this topic. In addition, therapy should never delay or replace resuscitation and surgical debridement. Patients who may benefit from HBO therapy, optimal timing of therapy, its duration and the incidence of adverse effects remain to be clarified. The IDSA guidelines do not recommend the use of this technique and consider that the level of proof is low [7 && ]. Similarly, the SIS guidelines conclude that the available literature is insufficient to propose any recommendations [3]. On the contrary, the WSES experts suggest that HBO therapy may be considered when it is available (weak recommendations, low level of proof) [6 && ]. Esposito et al. [4] reported the use of HBO therapy for clostridial myonecrosis, but without any clear recommendations. The Japanese guidelines focusing on anaerobic SSTIs suggest the use of HBO in patients with clostridial infections [5]. CONCLUSION Comparison of the recent guidelines results in a general impression of confusion. Their applicability is questionable in many ways. The distinction between necrotizing/nonnecrotizing infections is valuable but difficult to apply prior to surgical management. Our analysis argues in favor of a pragmatic approach to empirical antibiotic therapy, taking into account the patient s initial severity (whether or not the patient requires ICU admission), the extent of infection (superficial or deep infection) and risk factors for resistant microorganisms essentially related to healthcare-associated circumstances. Acknowledgements None. Financial support and sponsorship None. Conflicts of interest P.M. has received honoraria from Astra Zeneca, Astellas, Basilea, MSD, Pfizer, and the Medicines Company. The remaining authors have no conflicts of interest. REFERENCES AND RECOMMENDED READING Papers of particular interest, published within the annual period of review, have been highlighted as: & of special interest && of outstanding interest 1. May AK. Skin and soft tissue infections: the new surgical infection society guidelines. Surg Infect 2011; 12: Treatment guide for skin and soft tissue infections. Spanish Chemotherapy Society, Spanish Internal Medicine Society, Spanish Association of Surgeons. Rev Esp Quimioter 2006; 19: May AK, Stafford RE, Bulger EM, et al. Treatment of complicated skin and soft tissue infections. Surg infect 2009; 10: Esposito S, Bassetti M, Borre S, et al. Diagnosis and management of skin and soft-tissue infections (SSTI): a literature review and consensus statement on behalf of the Italian Society of Infectious Diseases and International Society of Chemotherapy. J Chemother 2011; 23: Chapter 2-5-3a. Anaerobic infections (individual fields): skin and soft tissue infections. J Infect Chemother 2011; 17 (Suppl 1): && Sartelli M, Malangoni MA, May AK, et al. World Society of Emergency Surgery (WSES) guidelines for management of skin and soft tissue infections. World J Emerg Surg 2014; 9:57. The World Society of Emergency Surgery guidelines are a good summary of the major issues that surgeons, emergency physicians, and intensivists have to address on a daily practice for patients suspected of having slin and soft tissue infections. 7. && Stevens DL, Bisno AL, Chambers HF, et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America. Clin Infect Dis 2014; 59:e10 e52. Infectious Diseases Society of America guidelines give the largest and most recent approach for the treatment of skin and soft tissue infections. 8. Gould FK, Brindle R, Chadwick PR, et al. Guidelines (2008) for the prophylaxis and treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections in the United Kingdom. J Antimicrob Chemother 2009; 63: Pan A, Cauda R, Concia E, et al. Consensus document on controversial issues in the treatment of complicated skin and skin-structure infections. Int J Infect Dis 2010; 14 (Suppl 4):S39 S Liu C, Bayer A, Cosgrove SE, et al. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of methicillinresistant Staphylococcus aureus infections in adults and children: executive summary. Clin Infect Dis 2011; 52: Mensa J, Soriano A, Llinares P, et al. Guidelines for antimicrobial treatment of the infection by Staphylococcus aureus. Rev Esp Quimioter 2013; 26 (Suppl 1): US Department of Health and Human Services. Food and Drug Administration. Guidance for industry-acute bacterial skin and skin structure infections: developing drugs for treatment. In: Edited by Center for Drug Evaluation and Research ComplianceRegulatoryInformation/Guidances/default.htm. [Accessed 17 December 2015] 13. Marwick C, Broomhall J, McCowan C, et al. Severity assessment of skin and soft tissue infections: cohort study of management and outcomes for hospitalized patients. J Antimicrob Chemother 2011; 66: Wong CH, Khin LW, Heng KS, et al. The LRINEC (Laboratory Risk Indicator for Necrotizing Fasciitis) score: a tool for distinguishing necrotizing fasciitis from other soft tissue infections. Crit Care Med 2004; 32: Bronchard R, de Vaumas C, Lasocki S, et al. Vacuum-assisted closure in the treatment of perineal necrotizing skin and soft tissue infections. Intens Care Med 2008; 34: Montravers P, Bassetti M, Dupont H, et al. Efficacy of tigecycline for the treatment of complicated skin and soft-tissue infections in real-life clinical practice from five European observational studies. J Antimicrob Chemother 2013; 68 (Suppl 2):ii15 ii Liu C, Bayer A, Cosgrove SE, et al. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of methicillinresistant Staphylococcus aureus infections in adults and children. Clin Infect Dis 2011; 52:e18 e Volume 29 Number 2 April 2016