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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">This article aims to review severe infectious conditions caused by bacteria that&#44; either due to skin involvement as a primary manifestation&#44; or due to a skin manifestation that indicates severe systemic involvement&#44; must be considered as mandatory knowledge for dermatologists&#44; regardless of their main area of expertise&#46; Currently&#44; several authors&#44; particularly in the field of infectious diseases and surgery&#44; prefer to use the term necrotizing soft tissue infections &#40;NSTIs&#41;&#44; which includes the various infections that evolve to skin necrosis&#44; such as necrotizing fasciitis &#40;NF&#41;&#44; Fournier gangrene&#44; Meleney&#39;s synergistic gangrene &#40;post-operative&#41;&#44; gas gangrene&#44; necrotizing cellulitis&#44; and myonecrosis&#46;<a class="elsevierStyleCrossRefs" href="#bib0410"><span class="elsevierStyleSup">1&#8211;3</span></a> However&#44; for greater clarity and considering the prevalence of these conditions&#44; the study adopts the classic terminology of NF and Fournier gangrene&#44; and includes ecthyma gangrenosum &#40;EG&#41; and cutaneous infections caused by methicillin-resistant <span class="elsevierStyleItalic">Staphylococcus aureus</span> &#40;MRSA&#41;&#44; with emphasis on furunculosis and abscesses&#46; The review of the host&#39;s defense mechanisms&#44; bacterial resistance to antibiotics&#44; virulence&#44; and microbiome is beyond the scope of this article&#59; therefore&#44; only the essential mechanisms to understand the etiology and physiopathogenesis of the disease under discussion were included&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Necrotizing fasciitis</span><p id="par0010" class="elsevierStylePara elsevierViewall">NF is an unusual&#44; acute&#44; fast-progressing infectious process that evolves with superficial and even deep muscle fascia necrosis of the subcutaneous tissue&#44; dermis&#44; and epidermis&#44; and can progress to sepsis&#44; shock&#44; and death in up to 40&#37; of cases&#46;<a class="elsevierStyleCrossRefs" href="#bib0425"><span class="elsevierStyleSup">4&#44;5</span></a> Under the name &#8220;hospital gangrene&#44;&#8221; this condition was described in the 19th century&#44; with the publication&#44; in 1871&#44; of 2642 cases observed by surgeon Joseph Jones of the Confederate army during the American civil war&#44; as mentioned by Faraklas et al&#46;<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">3</span></a> In 1952&#44; American surgeon B&#46; Wilson coined the term necrotizing fasciitis&#44; currently in universal use&#44; to designate the infectious processes that progress through the plane of the superficial muscular fascia and that evolve to necrosis of the subcutaneous tissues to the epidermis&#44; and even to the deep fascia and muscular plane&#46;<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">6</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">In the absolute majority of cases&#44; NF starts by inoculation of the pathogen or pathogens through injury to the skin resulting from trauma&#44; perforating injuries&#44; human or animal bites&#44; insect bites&#44; small procedures&#44; catheter insertion&#44; injection of medication or illicit drugs&#44; and post-varicella complications&#44; among others&#44; including contusion without loss of continuity in the skin&#46;<a class="elsevierStyleCrossRefs" href="#bib0440"><span class="elsevierStyleSup">7&#8211;11</span></a> The most common topographic location of NF is the lower limbs&#44; but involvement of the upper limbs &#40;including the hands&#41;&#44; head&#44; face&#44; neck&#44; and trunk are not exceptional&#46;<a class="elsevierStyleCrossRefs" href="#bib0460"><span class="elsevierStyleSup">11&#8211;15</span></a> The condition presents no predilection for sex or age&#44; being observed in children and young people&#44; but it is more frequent in adults and elderlyy&#46; The main predisposing factors are age&#44; diabetes mellitus&#44; obesity&#44; alcoholism&#44; malnutrition&#44; immunosuppression&#44; chronic kidney or liver disease&#44; peripheral vascular disease&#44; and chronic use of illicit drugs&#44; but it may even occur in seemingly healthy individuals&#46;<a class="elsevierStyleCrossRefs" href="#bib0455"><span class="elsevierStyleSup">10&#8211;12</span></a> Recently&#44; NF has been reported in association with the use of targeted therapies&#44; such as tyrosine kinase inhibitors&#59; however&#44; the cause-effect relationship in the reported cases is difficult to define&#44; given the presence of several possible cofactors in these patients&#46;<a class="elsevierStyleCrossRef" href="#bib0485"><span class="elsevierStyleSup">16</span></a> From an etiopathogenic standpoint&#44; the condition progresses rapidly due to the action of endo- and exotoxins produced by the infecting bacterial species&#44; evolving to obliterating endarteritis&#44; local microcirculatory thrombosis&#44; and necrosis&#46;<a class="elsevierStyleCrossRefs" href="#bib0425"><span class="elsevierStyleSup">4&#44;7&#44;12</span></a> If the condition is left untreated&#44; is treated late&#44; or is only treated clinically&#44; it can evolve to toxemia&#44; sepsis&#44; disseminated intravascular coagulation&#44; multiple organ failure&#44; and death&#46;<a class="elsevierStyleCrossRefs" href="#bib0440"><span class="elsevierStyleSup">7&#44;11&#44;12</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">A widely used NF classification designates as type I the disease caused by a synergistic association of aerobic or anaerobic bacteria&#59; therefore&#44; polymicrobial necrotizing fasciitis&#44; which includes Group A <span class="elsevierStyleItalic">Streptococcus</span>&#44; <span class="elsevierStyleItalic">Staphylococcus aureus</span> or other species of <span class="elsevierStyleItalic">Staphylococci</span>&#44; <span class="elsevierStyleItalic">Escherichia coli</span>&#44; <span class="elsevierStyleItalic">Klebsiella</span> spp&#46;&#44; and&#44; less often&#44; other Gram-negative bacteria&#46;<a class="elsevierStyleCrossRefs" href="#bib0425"><span class="elsevierStyleSup">4&#44;7&#44;17</span></a> The estimated frequency of this type I ranges from 70&#37; to 80&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">4</span></a> Type II NF&#44; which is monomicrobial&#44; is also termed &#8220;streptococcal gangrenous cellulitis&#46;&#8221; It is caused by Group A beta-hemolytic streptococci &#40;also termed flesh-eating bacteria&#41;&#44; and its frequency is estimated between 20&#37; and 30&#37; of NF cases&#46;<a class="elsevierStyleCrossRefs" href="#bib0440"><span class="elsevierStyleSup">7&#44;18&#44;19</span></a> The most frequent species of <span class="elsevierStyleItalic">Streptococcus</span> is <span class="elsevierStyleItalic">Streptococcus pyogenes</span> serotypes M1 and M3&#44; which have the ability to modify the host&#39;s phagocytic defense response&#44; produce hemolysins and exotoxins with superantigen properties and&#44; consequently&#44; induce excessive proliferation of T lymphocytes and release of pro-inflammatory cytokines&#46;<a class="elsevierStyleCrossRefs" href="#bib0440"><span class="elsevierStyleSup">7&#44;20</span></a> These act as triggers for the streptococcal toxic shock syndrome&#44; which can occur in up to 14&#37; of severe streptococcal infections and are associated with high mortality&#46;<a class="elsevierStyleCrossRefs" href="#bib0440"><span class="elsevierStyleSup">7&#44;19</span></a> It is important to remember that septic shock is a syndromic condition triggered by a severe infectious condition&#44; either by Gram-positive or Gram-negative bacteria&#44; and that results in the release of pro-inflammatory mediators&#44; including TNF-alpha&#44; produced by monocytes&#44; neutrophils&#44; and macrophages&#44; which induce vasodilation&#44; extravasation of plasma from the vessels&#44; cardiac malfunction&#44; immunosuppression&#44; and multiple organ failure&#46;<a class="elsevierStyleCrossRefs" href="#bib0440"><span class="elsevierStyleSup">7&#44;20</span></a> It is not uncommon for <span class="elsevierStyleItalic">Staphylococcus aureus</span> or other species of staphylococci to be associated with streptococcal infection&#44; potentiating its deleterious effects&#46;<a class="elsevierStyleCrossRef" href="#bib0510"><span class="elsevierStyleSup">21</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">The initial clinical manifestation may be subtle and discreet&#44; with erythema&#44; edema&#44; and local heat suggesting a picture of erysipela or cellulitis&#44; which delays the diagnostic suspicion related to severity&#46; However&#44; pain disproportionate to the apparent benignity of the condition is noteworthy&#46; As a rule&#44; there is a rapid evolution &#40;in 24&#8211;72<span class="elsevierStyleHsp" style=""></span>h&#41; to an erythematous-violaceous condition&#59; the limits of the lesion are lost&#44; hemorrhagic vesicles are observed&#44; and infiltration is identified by firm tissue induration&#44; edema&#44; and pain beyond the noticeable limits of the erythema &#40;<a class="elsevierStyleCrossRefs" href="#fig0005">Figs&#46; 1 and 2</a>&#41;&#46; Subsequently&#44; areas of pallor are observed&#59; the pain disappears or is markedly reduced as a result of the necrosis of the local nerve branches&#46; In addition to these dermatological signs&#44; general signs of fever&#44; lethargy&#44; mental confusion&#44; toxemia and&#44; potentially&#44; sepsis and shock are observed in various degrees&#46; As a consequence of thromboembolism of the local&#47;regional microcirculation&#44; there is practically no bleeding during the biopsy procedure or local exploratory surgical incision &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#46; Depending on the duration of the clinical history&#44; signs of cutaneous emphysema and a foul-smelling discharge may be observed during the procedure&#44; indicating tissue necrosis&#46; Computed tomography &#40;CT&#41; or magnetic resonance imaging &#40;MRI&#41; are useful to demonstrate the presence of subcutaneous edema&#44; fascia thickening&#44; collection of purulent material&#44; and even the presence of gas&#44; an evidence of severity that distinguishes NF from severe cellulitis&#46;<a class="elsevierStyleCrossRefs" href="#bib0515"><span class="elsevierStyleSup">22&#8211;24</span></a> Deep incisional biopsy&#44; down to the fascia&#44; or frozen cuts for quick analysis&#44; may also be useful&#46; However&#44; requesting and waiting for such procedures require time&#44; which can be crucial for these cases&#46; If the diagnosis is not established or if appropriate interventions are not instituted&#44; signs of sepsis manifest themselves between the fourth and sixth day of infection&#44; and may be anticipated or postponed&#46; Therefore&#44; diagnostic suspicion based on the history and clinical and dermatological examination must be raised as early as possible&#44; prescribing broad antibiotic coverage and indicating surgical debridement&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">The Laboratory Risk Indicator for Necrotizing Fasciitis &#40;LRINEC&#41;&#44; proposed by Wong et al&#46; in 2004&#44; is a scoring system that can be a useful diagnostic aid&#44; despite the lack of consensus on its specificity&#46; The LRINEC uses data from c-reative protein &#40;CRP&#41;&#44; leukogram&#44; hemoglobin&#44; serum sodium&#44; creatinine&#44; and glycemia collected when the patient is first seen or when NF is first suspected&#44; which are graded according to the intensity of the detected laboratory alteration&#46; A final score of 6 would be equivalent to an intermediate risk of NF and scores equal to or greater than 8 are indicative of a high risk of NF &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0530"><span class="elsevierStyleSup">25&#44;26</span></a> In addition to this laboratory data&#44; it is important to gather the information obtained from manipulation of the lesion by a surgeon in order to preliminarily incise and expose the tissue&#44; and to evaluate the presence of gross necrosis of the fascia and whether the fascia can be easily detached from its superior planes&#46; In case of suspicion&#44; biopsy and culture of tissue fragments should be performed and blood culture should be collected more than once&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">The differential diagnosis includes infectious conditions of the skin&#44; subcutaneous tissue and muscle&#44; including erysipelas and severe&#44; bullous cellulitis&#44; abscesses&#44; infected hematoma&#44; pyoderma gangrenosum&#44; pyomyositis&#44; gas gangrene&#44; and postoperative or post-procedure infection&#46; The semiological knowledge&#44; and the peculiarities of dermatological and clinical history aided by laboratory data&#44; shown in <a class="elsevierStyleCrossRef" href="#tbl0005">table 1</a>&#44; raise diagnostic suspicion and allow clinical diagnosis&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Antibiotic coverage should be instituted immediately in the face of suspicion&#59; it is not necessary to wait for a final diagnosis&#46; The antibiotic therapy should be able to cover&#44; albeit empirically&#44; polymicrobial NF&#44; acting against Gram-positive&#44; Gram-negative&#44; and anaerobic bacteria&#46; An attempted analysis through systematic review&#44; using the Cochrane methodology&#44; did not result in definitive information regarding antibiotic therapy in necrotizing infections affecting soft tissues&#46;<a class="elsevierStyleCrossRef" href="#bib0540"><span class="elsevierStyleSup">27</span></a> In summary&#44; those authors concluded that&#58; &#8220;There is no empirical antimicrobial therapy validated by clinical trial&#46; &#8230; topics &#40;items&#41; should be considered&#44; among which the antimicrobial strategy in patients with or without comorbidities and in patients with a risk factor for MRSA infection&#46;&#8221;<a class="elsevierStyleCrossRef" href="#bib0540"><span class="elsevierStyleSup">27</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Based on literature data and the personal experience of the authors&#44; the use of one of the following schemes is suggested&#58; &#40;1&#41; Piperacillin sodium<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>tazobactan sodium &#40;active against Gram-positive&#44; even if producers of &#946;-lactamases&#44; active against Gram-negative&#44; not active against MRSA&#41;&#44; &#43; vancomycin &#40;active against MRSA&#41;<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>clindamycin &#40;active against Gram-positive aerobic and anaerobic bacteria&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0440"><span class="elsevierStyleSup">7&#44;9&#44;11&#44;17&#8211;19&#44;21</span></a> &#40;2&#41; Imipenem&#47;meropenem &#40;of the carbapenem class&#59; active against Gram-positive&#44; even if producers of &#946;-lactamases&#44; active against Gram-negative&#44; not active against MRSA&#41;<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>vancomycin<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>clindamycin&#46; &#40;3&#41; Cefepime &#40;fourth-generation cephalosporin&#59; active against Gram-positive&#44; even if producers of &#946;-lactamases&#44; active against Gram-negative&#44; not active against MRSA&#41;&#44; &#43; vancomycin<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>clindamycin&#46; The results obtained from culture&#47;blood culture and antibiogram may lead to adjustments in the proposals above&#44; particularly in the assessment of the need to associate an antibiotic of the aminoglycoside class to the scheme&#46; If necessary or convenient&#44; clindamycin can be replaced by metronidazole 1<span class="elsevierStyleHsp" style=""></span>g every 12<span class="elsevierStyleHsp" style=""></span>h&#44; intravenously&#46; It is important to note that several of the drugs listed above require correction for creatinine clearance when indicated&#59; in children below 40<span class="elsevierStyleHsp" style=""></span>kg or neonates&#44; the dose must be adjusted&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Associated with antibacterial treatment&#44; surgical debridement is also an essential emergency procedure &#40;<a class="elsevierStyleCrossRefs" href="#fig0005">Figs&#46; 1C and 2B</a>&#41;&#46; It is not uncommon for the dermatologist to have to convince the emergency surgeons of the need for the procedure&#46; The debridement must be wide&#44; excising all necrotic subcutaneous tissue including the fascia&#44; and going beyond the gross necrosis as a safety margin &#40;<a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0410"><span class="elsevierStyleSup">1&#44;2&#44;7&#44;11&#44;17</span></a> It is necessary to assess whether there is associated myonecrosis and whether the involved limb must be amputated&#46; The surgical wound must remain open and be reassessed in 24<span class="elsevierStyleHsp" style=""></span>h&#59; if necessary&#44; the excision must be extended&#44; as the infectious process and thrombosis of the local microcirculation often progress despite antibiotic therapy&#46;</p><elsevierMultimedia ident="fig0020"></elsevierMultimedia><p id="par0055" class="elsevierStylePara elsevierViewall">As an adjunct treatment to broad-spectrum antibiotic therapy and surgical debridement&#44; there are reports of the use of intravenous immunoglobulin &#40;IVIG&#41;&#44; hyperbaric oxygen therapy&#44; and negative pressure therapy &#40;NPT&#41;&#46; IVIG is mentioned as a treatment in cases associated with septic shock&#44; due to the possibility of neutralizing the formation of superantigens&#46;<a class="elsevierStyleCrossRef" href="#bib0545"><span class="elsevierStyleSup">28</span></a> However&#44; a retrospective cohort study of 164 patients concluded that IVIG had no apparent impact on mortality or length of hospitalization beyond that achieved with debridement and antibiotics&#46;<a class="elsevierStyleCrossRef" href="#bib0550"><span class="elsevierStyleSup">29</span></a> Regarding hyperbaric oxygen therapy&#44; a Cochrane systematic review failed to demonstrate relevant clinical evidence to support or refute the effectiveness of this therapy in NF&#46;<a class="elsevierStyleCrossRef" href="#bib0555"><span class="elsevierStyleSup">30</span></a> The literature features many articles &#40;primarily case reports and series&#41; on the use of NPT&#44; a method used to accelerate healing&#59; however&#44; randomized clinical trials to ensure its validity are lacking&#46;<a class="elsevierStyleCrossRefs" href="#bib0560"><span class="elsevierStyleSup">31&#44;32</span></a> It is important to emphasize that supportive and intensive care measures must be available and used as indicated&#46; With the patient&#39;s recovery&#44; the surgical wound can be repaired by local grafting when the bottom is clean and tissue granulation is observed&#44; or by healing by second intention&#46;<a class="elsevierStyleCrossRef" href="#bib0490"><span class="elsevierStyleSup">17</span></a> Esthetic&#44; functional&#44; or social sequelae deserve equal effort to be reduced or solved in the best possible way&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Fournier gangrene</span><p id="par0060" class="elsevierStylePara elsevierViewall">In 1883&#44; the French dermatologist Jean-Alfred Fournier &#40;1832&#8211;1914&#41;&#44; head of the Department of Dermatology and Syphilography at the H&#244;pital Saint Louis de Paris&#44; reported an infection and rapid evolution to necrosis of the perineum and scrotum in five patients&#59; he termed this evolution <span class="elsevierStyleItalic">gangr&#232;ne foudroyante de la verge</span>&#44; <span class="elsevierStyleItalic">i&#46;e&#46;</span>&#44; rapid gangrene of the penis&#46;<a class="elsevierStyleCrossRefs" href="#bib0570"><span class="elsevierStyleSup">33&#44;34</span></a> Currently&#44; this condition is recognized as a variant of necrotizing fasciitis with an initial and specific location in the perineum&#44; genitalia&#44; or perianal region&#44; and is now known as Fournier gangrene&#46;<a class="elsevierStyleCrossRef" href="#bib0575"><span class="elsevierStyleSup">34</span></a> It is an uncommon disease&#44; whose mortality rates range from 7&#46;5&#37; to 22&#46;5&#37; of cases in different series&#46;<a class="elsevierStyleCrossRefs" href="#bib0575"><span class="elsevierStyleSup">34&#8211;36</span></a> It can be confined to the scrotum or extend toward the perineum&#44; penis&#44; pubis&#44; and abdominal wall&#46; Although more frequent in males&#44; who account for 52&#37; to 100&#37; of cases in different series&#44; it can also be observed in females&#46;<a class="elsevierStyleCrossRefs" href="#bib0575"><span class="elsevierStyleSup">34&#8211;36</span></a> The age group most affected is that above 50 years of age&#44; but cases in children and adolescents&#44; although very rare&#44; have been described&#46;<a class="elsevierStyleCrossRefs" href="#bib0575"><span class="elsevierStyleSup">34&#8211;36</span></a> In a review study of 40 cases diagnosed in Brazil&#44; the authors identified diabetes mellitus as the main comorbidity&#44; present in 70&#37; of patients&#44; followed by systemic arterial hypertension &#40;35&#37;&#41;&#44; heart disease &#40;15&#37;&#41;&#44; and dyslipidemia and obesity in 7&#46;5&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0590"><span class="elsevierStyleSup">37</span></a> Alcohol abuse and malnutrition are also mentioned as predisposing factors&#46; The triggering factors are varied&#59; prior infection of the urinary tract&#44; perianal infection&#44; surgical manipulation &#40;including postectomy&#41;&#44; penile prosthesis&#44; genital trauma &#40;including penis-enlargement fillings&#41;&#44; and scrotal trauma are listed as the most important and frequent&#46;<a class="elsevierStyleCrossRefs" href="#bib0575"><span class="elsevierStyleSup">34&#8211;39</span></a> In women&#44; traumas&#44; microtraumas related to hair removal&#44; episiotomy&#44; and infection of the vulvar region and perineum are mentioned&#46;<a class="elsevierStyleCrossRefs" href="#bib0575"><span class="elsevierStyleSup">34&#44;35</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">The etiology is polymicrobial in most cases&#44; ranging from 54&#37; to 80&#37; in different series&#46; The most common infectious agent is <span class="elsevierStyleItalic">Escherichia coli</span>&#44; but bacteria of the genera <span class="elsevierStyleItalic">Streptococcus</span>&#44; <span class="elsevierStyleItalic">Bacteroides</span>&#44; <span class="elsevierStyleItalic">Enterobacter</span>&#44; <span class="elsevierStyleItalic">Staphylococcus</span>&#44; including MRSA&#44; <span class="elsevierStyleItalic">Enterococcus</span>&#44; <span class="elsevierStyleItalic">Pseudomonas</span>&#44; <span class="elsevierStyleItalic">Corynebacterium</span>&#44; <span class="elsevierStyleItalic">Klebsiella</span>&#44; or even <span class="elsevierStyleItalic">Candida albicans</span> are also common&#46; Such agents can act alone or in association&#46;<a class="elsevierStyleCrossRefs" href="#bib0580"><span class="elsevierStyleSup">35&#44;40&#8211;42</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">Fournier gangrene progresses through the superficial and deep planes of the urogenital and anogenital fascia&#46;<a class="elsevierStyleCrossRef" href="#bib0575"><span class="elsevierStyleSup">34</span></a> The sequence of events mirrors that of classic cutaneous NF&#58; infection&#44; vascular occlusion&#44; infarction&#44; and tissue necrosis&#46; The condition progresses very quickly in males&#44; as Colles&#8217; fascia of the perineum&#44; Dartos&#8217; fascia of the penis and scrotum&#44; and Scarpa&#39;s fascia of the anterior abdominal wall form a continuum&#44; allowing the infection to progress through these planes&#46;<a class="elsevierStyleCrossRefs" href="#bib0440"><span class="elsevierStyleSup">7&#44;34</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">The initial condition is erythema and edema with increased volume and&#44; as in classical NF&#44; is accompanied by pain that is disproportional to the clinical appearance&#46;<a class="elsevierStyleCrossRefs" href="#bib0575"><span class="elsevierStyleSup">34&#44;35&#44;37</span></a> The sequence of dermatological signs can be described as edema&#44; swelling&#44; poorly defined erythema&#44; violaceous erythema&#44; and finally pallor and cutaneous necrosis&#44; also identified in cases of vulvar lesions &#40;<a class="elsevierStyleCrossRef" href="#fig0025">Fig&#46; 5</a>&#41;&#46;</p><elsevierMultimedia ident="fig0025"></elsevierMultimedia><p id="par0080" class="elsevierStylePara elsevierViewall">Clinical evaluation and diagnostic suspicion must be raised as early as possible and the intervention must not wait for histological or microbiological confirmation&#46; Although the diagnostic referral can be dermatological&#44; the intervention is urological&#44; gynecological&#44; and surgical&#44; aiming to remove all devitalized tissue&#44; and combined with antibiotic coverage targeted at the aforementioned pathogens&#46;<a class="elsevierStyleCrossRefs" href="#bib0580"><span class="elsevierStyleSup">35&#44;40&#8211;42</span></a> The antibiotic prescription cannot be mild&#58; it must be intravenous and can be summarized&#44; as mentioned above for the NF&#44; as the following options&#58; &#40;1&#41; Piperacillin sodium<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>tazobactan sodium&#44; &#43; vancomycin<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>clindamycin&#46; &#40;2&#41; Imipenem&#47;meropenem<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>vancomycin<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>clindamycin&#46; &#40;3&#41; Cefepime<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>vancomycin<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>clindamycin&#46; As with NF&#44; clindamycin can also be replaced by metronidazole&#46; Such measures&#44; evidently&#44; must be associated with analgesia and care in an intensive care unit &#40;ICU&#41; setting&#46; The prognosis is variable&#46; In a series of 40 cases in Brazil&#44; mortality was 22&#46;5&#37; and was strongly correlated with the presence of sepsis at hospital admission and the length of ICU stay&#59; these results were very similar to those observed in a recent study from Korea with 41 patients&#44; where the mortality rate was 22&#46;0&#37;&#46;<a class="elsevierStyleCrossRefs" href="#bib0590"><span class="elsevierStyleSup">37&#44;41</span></a> In a wide literature review that compiled 1726 cases&#44; the observed mortality rates ranged from 3&#37; to 45&#37;&#44; with a median of 16&#37;&#44; and was mostly associated with sepsis and diabetes&#46;<a class="elsevierStyleCrossRef" href="#bib0580"><span class="elsevierStyleSup">35</span></a> Such data show the extreme importance of early diagnosis&#44; specialized intervention&#44; and support in an intensive care unit&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Ecthyma gangrenosum</span><p id="par0085" class="elsevierStylePara elsevierViewall">The first mention of ecthyma gangrenosum &#40;EG&#41; appeared in 1897 in an article by LF Barker on clinical manifestations related to an infection caused by <span class="elsevierStyleItalic">Baccilus pyocyaneus</span>&#44; which at the time was the denomination for the current <span class="elsevierStyleItalic">Pseudomonas aeruginosa</span>&#46;<a class="elsevierStyleCrossRef" href="#bib0620"><span class="elsevierStyleSup">43</span></a> The name &#8220;ecthyma gangrenosum&#44;&#8221; which appeared in 1951 in a publication by RH Broughton&#44; has since been of universal use and implies&#44; conceptually&#44; the state of sepsis by <span class="elsevierStyleItalic">P&#46; aeruginosa</span>&#46;<a class="elsevierStyleCrossRef" href="#bib0625"><span class="elsevierStyleSup">44</span></a> As knowledge evolved&#44; EG became associated with other Gram-negative&#44; Gram-positive bacteria&#44; and even fungi&#44; especially of the genera <span class="elsevierStyleItalic">Candida</span> and <span class="elsevierStyleItalic">Fusarium</span>&#46;<a class="elsevierStyleCrossRefs" href="#bib0440"><span class="elsevierStyleSup">7&#44;45</span></a> Some authors refer to non-<span class="elsevierStyleItalic">P&#46; aeruginosa</span> cases as ecthyma gangrenosum-like&#44; but the main message is that the dermatological manifestation is practically identical and&#44; for diagnostic suspicion&#44; the first intervention should be directed to <span class="elsevierStyleItalic">P&#46; aeruginosa</span> while the etiology of the disease is investigated&#46;<a class="elsevierStyleCrossRefs" href="#bib0630"><span class="elsevierStyleSup">45&#44;46</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">Clinically&#44; it is characterized by the rapid evolution of a localized lesion&#44; initially vesiculobullous or papulonodular&#44; in an erythematous&#44; edematous background&#44; evolving in 12&#8211;24<span class="elsevierStyleHsp" style=""></span>h to local signs of skin necrosis and an ulceronecrotic lesion&#46;<a class="elsevierStyleCrossRefs" href="#bib0630"><span class="elsevierStyleSup">45&#8211;49</span></a> These dermatological clinical manifestations correspond to the invasion of the venules by the infectious agent&#44; with consequent damage of the vascular wall&#44; induction of thrombosis in the arterioles&#44; inflammation process&#44; edema and vascular obstruction&#44; and localized skin necrosis&#46; The lesions are generally small in number&#44; but they can be multiple and at different stages of evolution &#40;<a class="elsevierStyleCrossRefs" href="#fig0030">Figs&#46; 6&#8211;8</a>&#41;&#46; The preferred locations are the perineum&#44; buttocks&#44; inguinocrural fold &#40;<a class="elsevierStyleCrossRef" href="#fig0045">Fig&#46; 9</a>&#41;&#44; intergluteal cleft&#44; and distal extremities&#44; but lesions can affect any area&#44; including the head&#44; face&#44; and neck&#46;<a class="elsevierStyleCrossRefs" href="#bib0630"><span class="elsevierStyleSup">45&#44;48&#8211;51</span></a> The general clinical picture associated with skin lesions may already indicate fever&#44; toxemia&#44; or sepsis&#59; it may even be observed in previously asymptomatic or oligosymptomatic patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0665"><span class="elsevierStyleSup">52&#44;53</span></a> The differential diagnosis of skin lesions should include lesions of severe small vessel leukocytoclastic vasculitis&#44; sepsis skin lesions&#44; disseminated vascular coagulation&#44; and septic emboli associated with endocarditis&#46; Although meningococcemia is mentioned in the literature as a differential of EG&#44; purpura fulminans lesions are distinct&#58; they are purpuric&#44; net-like rashes without blisters&#46;<a class="elsevierStyleCrossRefs" href="#bib0675"><span class="elsevierStyleSup">54&#44;55</span></a></p><elsevierMultimedia ident="fig0030"></elsevierMultimedia><elsevierMultimedia ident="fig0035"></elsevierMultimedia><elsevierMultimedia ident="fig0040"></elsevierMultimedia><elsevierMultimedia ident="fig0045"></elsevierMultimedia><p id="par0095" class="elsevierStylePara elsevierViewall">In a review study of 167 cases of EG reported in the literature retrieved in PubMed&#44; MEDLINE&#44; and ScienceDirect between 1975 and 2014&#44; the authors identified that in 73&#46;6&#37; of the total cases the agent was <span class="elsevierStyleItalic">P&#46; aeruginosa</span>&#44; in 17&#46;3&#37; another bacterium&#44; and in 9&#37; the etiology was fungal&#46; It is noteworthy that EG was a manifestation of sepsis in only 58&#46;5&#37; of the cases where the agent was <span class="elsevierStyleItalic">P&#46; aeruginosa</span>&#46;<a class="elsevierStyleCrossRef" href="#bib0630"><span class="elsevierStyleSup">45</span></a> These data are relevant&#44; as they demonstrate that starting the empirical treatment aiming at <span class="elsevierStyleItalic">Pseudomonas</span> is the correct conduct while the real etiology is not identified&#44; and that EG can be a manifestation of bacteremia associated with a still stable clinical picture&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">EG affects any age group&#44; but childhood as a whole deserves particular attention&#44; as the younger the patient&#44; the greater the severity of the prognosis&#46;<a class="elsevierStyleCrossRefs" href="#bib0630"><span class="elsevierStyleSup">45&#44;47&#44;49</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">The predisposing factor is often immunosuppression and&#47;or neutropenia&#44; primary or secondary to chemotherapy&#46; In patients with lymphoproliferative diseases undergoing chemotherapy&#44; fungal etiology must be considered with a certain priority&#46;<a class="elsevierStyleCrossRefs" href="#bib0630"><span class="elsevierStyleSup">45&#44;49&#8211;51</span></a> In general&#44; the most prevalent underlying diseases or clinical situations are&#58; leukemia&#47;lymphoma&#44; other malignancies&#44; severe burns&#44; transplant patients&#44; and patients on immunosuppressive therapy&#46;<a class="elsevierStyleCrossRefs" href="#bib0630"><span class="elsevierStyleSup">45&#44;49&#8211;51</span></a> In more than one case&#44; EG was a telltale sign of severe infection by <span class="elsevierStyleItalic">P&#46; aeruginosa</span> in the context of primary neutropenia hitherto hidden&#46;<a class="elsevierStyleCrossRefs" href="#bib0640"><span class="elsevierStyleSup">47&#44;49</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">In the face of clinical suspicion&#44; the etiological diagnosis relies on blood culture and culture for bacteria and fungi in a biopsy fragment of the lesion&#44; which is collected at the edge of the ulcer or in a non-necrotic area&#46; The antibiogram is mandatory and should not be dismissed&#46; Simultaneously&#44; an eventual focus for the emission of bacteremia must be identified&#44; paying special attention to the lungs&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Treatment should immediately target the most likely etiology&#44; <span class="elsevierStyleItalic">i&#46;e&#46;</span>&#44; intravenous antibiotic coverage against <span class="elsevierStyleItalic">P&#46; aeruginosa</span>&#44; with the use of aminoglycosides&#44; preferably amikacin at a dose of 7&#46;5&#8211;15<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;day IV or IM&#44; divided in two or three infusions&#47;applications&#46;<a class="elsevierStyleCrossRefs" href="#bib0630"><span class="elsevierStyleSup">45&#44;48</span></a> In children&#44; the recommended dose is 15&#8211;20<span class="elsevierStyleHsp" style=""></span>mg&#47;kg per day&#44; with a maximum dose of 1&#46;5<span class="elsevierStyleHsp" style=""></span>g&#44; divided into IV infusions every eight hours or IM every 12&#47;12<span class="elsevierStyleHsp" style=""></span>h&#46; There is a need for dose adjustment in situations of altered creatinine clearance&#46; The use of carbapenems is also possible&#46; If imipenem is chosen&#44; the recommended dose is 1&#8211;2<span class="elsevierStyleHsp" style=""></span>g&#47;day IV infused every six hours&#46; In children weighing less than 40<span class="elsevierStyleHsp" style=""></span>kg&#44; the recommended dose is 15&#8211;25<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;day IV&#44; divided into infusions every 6<span class="elsevierStyleHsp" style=""></span>h&#44; with a maximum total dose of 2<span class="elsevierStyleHsp" style=""></span>g&#47;day&#46; Imipenem dose correction is required for patients with renal failure with creatinine clearance below 50<span class="elsevierStyleHsp" style=""></span>mL&#47;min&#46; Meropenem is the most widely used and recommended carbapenem at a dose of up to 6<span class="elsevierStyleHsp" style=""></span>g&#47;day&#44; IV&#44; divided into infusions every 6<span class="elsevierStyleHsp" style=""></span>h&#46; For children under 40<span class="elsevierStyleHsp" style=""></span>kg&#44; the dose is limited to 20&#8211;40<span class="elsevierStyleHsp" style=""></span>mg&#47;kg per infusion&#44; every eight hours&#46; In patients with renal impairment&#44; the dose should also be corrected in light of the patient&#39;s creatinine clearance&#46; As for possible adverse effects&#44; the potential for nephrotoxicity and ototoxicity associated with aminoglycosides in general is noteworthy&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">Surgical debridement of the lesion is a useful adjuvant method in EG&#44; but it is not as essential as in NF and Fournier gangrene&#46;<a class="elsevierStyleCrossRef" href="#bib0630"><span class="elsevierStyleSup">45</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">EG prognosis depends on the patient&#39;s general condition&#44; immunological status&#44; underlying disease and&#44; in cases of concomitant sepsis&#44; on the possible delay in diagnosis before the start of treatment&#46; In non-septic patients&#44; EG has a lower mortality rate &#40;16&#37;&#41; when compared with septic patients &#40;38&#37; <span class="elsevierStyleItalic">vs&#46;</span> 96&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0685"><span class="elsevierStyleSup">56</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Skin infections caused by methicillin-resistant <span class="elsevierStyleItalic">Staphylococcus aureus</span> &#40;MRSA&#41;</span><p id="par0130" class="elsevierStylePara elsevierViewall">In the 1880s&#44; Alexander Ogston first detected <span class="elsevierStyleItalic">Staphylococcus aureus</span> from a purulent abscess exudate located on the leg of a patient and&#44; in 1884&#44; Friedrich Julius Rosenbach formally isolated this bacterium&#46;<a class="elsevierStyleCrossRef" href="#bib0690"><span class="elsevierStyleSup">57</span></a><span class="elsevierStyleItalic">S&#46; aureus</span> is a Gram-positive bacterium coccus that is well adapted to the human host and the health care environment&#46; It is part of the normal human microbiota&#44; often found on the skin&#44; especially the armpit&#44; inguinal region&#44; and in the nasal cavity&#44; with a prevalence of around 25&#8211;30&#37;&#46; It is one of the main agents that cause endocarditis&#44; bacteremia&#44; pneumonia&#44; osteomyelitis&#44; and skin and soft tissue infections &#40;SSTI&#41;&#44; triggering mild to fatal conditions&#46;<a class="elsevierStyleCrossRef" href="#bib0695"><span class="elsevierStyleSup">58</span></a></p><p id="par0135" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">S&#46; aureus</span> has quickly become one of the main causes of hospital-related infections&#46; Initially a bacterium sensitive to penicillin&#44; resistance was observed in the 1940s&#44; mediated by the &#946;-lactamase blaZ gene&#46; In 1960&#44; the first semi-synthetic anti-staphylococcal penicillins were developed and strains of MRSA were observed within one year of their first clinical use&#46;<a class="elsevierStyleCrossRefs" href="#bib0700"><span class="elsevierStyleSup">59&#44;60</span></a></p><p id="par0140" class="elsevierStylePara elsevierViewall">Until the 1980s&#44; MRSA infections occurred in patients with known predisposing factors such as hospitalization&#44; presence of an invasive device&#44; history of surgery&#44; hemodialysis&#44; immunosuppression&#44; or residence in a nursing home&#46; Subsequently&#44; MRSA infections were reported in healthy populations without risk factors&#44; <span class="elsevierStyleItalic">i&#46;e&#46;</span>&#44; with no recent history of contact with hospitals or health services&#44; with an increase in the number of reports in the 2000s&#46;<a class="elsevierStyleCrossRef" href="#bib0710"><span class="elsevierStyleSup">61</span></a> The MRSA strains that caused infections in patients without the previously described risk factors were shown to be different from those in hospitals&#44; giving rise to the term community-acquired MRSA &#40;CA-MRSA&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0715"><span class="elsevierStyleSup">62</span></a> To differentiate hospital strains&#44; the term hospital-acquired MRSA &#40;HA-MRSA&#41; was added for those related to health care services&#46;<a class="elsevierStyleCrossRef" href="#bib0720"><span class="elsevierStyleSup">63</span></a></p><p id="par0145" class="elsevierStylePara elsevierViewall">Resistance to methicillin occurs due to chromosomal segments present in some strains of <span class="elsevierStyleItalic">S&#46; aureus</span> that carry the methicillin resistance gene &#40;mecA&#41;&#44; called SCCmec &#40;staphylococcal chromosome cassette mec&#41;&#44; being distinct in HA-MRSA &#40;SCCmec types I&#44; II&#44; and III&#41; and CA-MRSA &#40;SCCmec types IV&#8211;XI&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0725"><span class="elsevierStyleSup">64</span></a> MecA expression conferred resistance to the available &#946;-lactam antibiotics&#44; while resistance to non-&#946;-lactam antibiotics commonly associated with HA-MRSA is due to a variety of mechanisms&#46;<a class="elsevierStyleCrossRef" href="#bib0720"><span class="elsevierStyleSup">63</span></a> The first reports of CA-MRSA in Latin America were described in 2002 and 2003 in southern Brazil&#46;<a class="elsevierStyleCrossRef" href="#bib0730"><span class="elsevierStyleSup">65</span></a></p><p id="par0150" class="elsevierStylePara elsevierViewall">Essentially&#44; CA-MRSA infections differ from HA-MRSA infections by three main characteristics&#58; first&#44; the affected populations are younger and generally healthier&#44; with no previously defined risk factors&#59; second&#44; presence of epidemic clones&#44; classified as USA300 or USA400&#59; third&#44; CA-MRSA clones contain a resistance mechanism produced <span class="elsevierStyleItalic">via</span> SCCmec IVa &#40;present in 84&#37; of CA-MARS strains&#41; with production of Panton-Valentine leukocidin &#40;PVL&#41;&#44; which determines great tissue destruction&#44; leading to severe SSTI and necrotic pneumonia&#46;<a class="elsevierStyleCrossRefs" href="#bib0735"><span class="elsevierStyleSup">66&#8211;69</span></a> It is important to highlight that the SCCmec IV pathway promotes resistance to &#946;-lactam antibiotics in general&#44; but not to other antibiotics&#44; unlike HA-MRSA infections&#44; which generally show resistance to various classes of antibiotics&#46;<a class="elsevierStyleCrossRef" href="#bib0755"><span class="elsevierStyleSup">70</span></a></p><p id="par0155" class="elsevierStylePara elsevierViewall">Although CA-MRSA infection is not associated with the risk factors for HA-MRSA&#44; some groups are at higher risk for developing infection by this bacterial agent&#44; such as young adults&#44; those incarcerated&#44; African-Americans&#44; illicit drug users&#44; athletes&#44; indigenous people&#44; people with HIV&#47;AIDS&#44; and men who have sex with men&#46;<a class="elsevierStyleCrossRef" href="#bib0760"><span class="elsevierStyleSup">71</span></a></p><p id="par0160" class="elsevierStylePara elsevierViewall">CA-MRSA is predominantly related to SSTI of varying degrees of severity&#59; it sometimes also causes pneumonia and severe and fatal bone and joint infections&#46;<a class="elsevierStyleCrossRefs" href="#bib0695"><span class="elsevierStyleSup">58&#44;72</span></a></p><p id="par0165" class="elsevierStylePara elsevierViewall">The term SSTI is generic and can be applied to a wide variety of infections including impetigo&#44; folliculitis&#44; furunculosis&#44; cellulitis&#44; and abscesses&#46; The focus of this review will be on cases of furunculosis and abscesses&#44; due to the characteristic formation of purulent collections and exudation&#44; which are often caused by MRSA&#46;<a class="elsevierStyleCrossRef" href="#bib0770"><span class="elsevierStyleSup">73</span></a></p><p id="par0170" class="elsevierStylePara elsevierViewall">Furuncles mainly affect areas rich in hair follicles&#44; such as the armpits and the gluteal region&#44; with the formation of abscesses in the hypodermis&#46; Hair follicles are the gateway to <span class="elsevierStyleItalic">S&#46; aureus</span>&#44; favoring its development&#46; It usually presents as an erythematous&#44; painful&#44; and floating nodule&#44; with pustules on the surface and a drainage point&#46; A single or multiple concomitant lesions can be observed &#40;<a class="elsevierStyleCrossRef" href="#fig0050">Fig&#46; 10</a>&#41;&#46;</p><elsevierMultimedia ident="fig0050"></elsevierMultimedia><p id="par0175" class="elsevierStylePara elsevierViewall">Carbuncle is the coalescence of two or more furuncles in the same locus&#44; with multiple drainage sinus tracts&#44; which tends to extend more deeply into the hypodermis &#40;<a class="elsevierStyleCrossRef" href="#fig0055">Fig&#46; 11</a>&#41;&#46; Systemic symptoms are usually present and regional lymphadenopathy can be observed&#46; Carbuncle can appear anywhere with hair&#59; however&#44; it is more common in the posterior cervical region&#44; back&#44; and thighs&#46;<a class="elsevierStyleCrossRef" href="#bib0775"><span class="elsevierStyleSup">74</span></a> Predisposing factors for the development of furuncles&#44; including recurrent furuncle&#44; are eczema&#44; diabetes mellitus&#44; alcohol use&#44; malnutrition&#44; immunodeficiency&#44; obesity&#44; poor hygiene&#44; chronic MRSA colonization&#44; hyperhidrosis&#44; and anemia&#46;<a class="elsevierStyleCrossRef" href="#bib0780"><span class="elsevierStyleSup">75</span></a></p><elsevierMultimedia ident="fig0055"></elsevierMultimedia><p id="par0180" class="elsevierStylePara elsevierViewall">Cutaneous abscesses are focal collections of pus located in the dermis and hypodermis&#44; which usually present as painful&#44; erythematous nodules&#44; often surmounted by a pustule and with an erythematous-edematous border&#46; They often present with floating points or signs of spontaneous drainage&#46; In the early stages and in deeper presentations&#44; they may not show the classic fluctuation sign&#46; In association&#44; cellulitis that extends radially from the purulent focus may be observed&#46;<a class="elsevierStyleCrossRef" href="#bib0770"><span class="elsevierStyleSup">73</span></a><span class="elsevierStyleItalic">S&#46; aureus</span> is isolated in approximately 60&#8211;75&#37; of cases of uncomplicated skin abscesses&#44; of which 50&#8211;70&#37; are MRSA&#46; Coagulase-negative staphylococcus is the next most isolated species&#44; followed by a variety of &#946;-hemolytic streptococcal species&#46;<a class="elsevierStyleCrossRef" href="#bib0785"><span class="elsevierStyleSup">76</span></a> Risk factors for recurrent abscesses include intramuscular injections&#59; hair removal from legs&#44; armpits&#44; pubis and scalp&#59; and previous colonization or infection with CA-MRSA&#46;</p><p id="par0185" class="elsevierStylePara elsevierViewall">The diagnosis of furunculosis and abscess is essentially clinical&#44; but ultrasound can be a useful complement in cases of abscesses where fluctuation is absent or difficult to locate&#46;<a class="elsevierStyleCrossRef" href="#bib0790"><span class="elsevierStyleSup">77</span></a> When possible&#44; sampling of purulent exudate for culture and antibiogram should be performed in order to better guide the conduct&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">The treatment of isolated and small furuncles can be performed with topical antibiotics&#44; fusidic acid&#44; or mupirocin&#44; three times a day&#44; for seven to ten days&#46; Early squeezing of the lesion should be avoided&#59; however&#44; surgical drainage must be performed in the fluctuation phase&#46; As for larger furuncles&#44; carbuncle&#44; and abscesses&#44; incision and drainage are strongly recommended when they are in the fluctuation phase&#46;<a class="elsevierStyleCrossRef" href="#bib0795"><span class="elsevierStyleSup">78</span></a> Incision and drainage involve a single linear incision&#44; followed by blunt dissection&#46; Needle aspiration has been shown to be generally inferior to incision and drainage of abscesses&#46; However&#44; needle aspiration may be preferred on the face&#44; as it provides the best cosmetic results&#46; Systemic antibiotic therapy is indicated as adjuvant&#44; and is mandatory when there is an erythematous halo of &#8805;2<span class="elsevierStyleHsp" style=""></span>cm around the furuncle and in cases of carbuncle&#46; As previously mentioned&#44; CA-MRSA is resistant to &#946;-lactam antibiotics&#44; such as penicillins&#44; first- to fourth-generation cephalosporins&#44; carbapenems&#44; and monobactams&#46; Cephalosporins resistance is relevant to clinical practice&#44; as they are among the most used antimicrobials for the treatment of SSTI and community-acquired pneumonia&#46; Therefore&#44; CA-MRSA infections may not be treatable by most treatment regimens empirically used for such infections&#46;<a class="elsevierStyleCrossRef" href="#bib0800"><span class="elsevierStyleSup">79</span></a> The antibiotics indicated are those with action against MRSA&#44; such as sulfamethoxazole plus trimethoprim or clindamycin for at least seven days in uncomplicated cases&#44; and vancomycin or daptomycin in complicated cases &#40;<span class="elsevierStyleItalic">i&#46;e&#46;</span>&#44; those with extensive involvement and toxicity or in immunocompromised patients&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0795"><span class="elsevierStyleSup">78&#44;80&#44;81</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Final remarks</span><p id="par0195" class="elsevierStylePara elsevierViewall">Considering these data&#44; it should be noted that the semiological training and practical and theoretical knowledge of the diseases described here and others that can be considered in the differential diagnosis make the dermatologist a key element in the suspicion&#44; early diagnosis&#44; and treatment&#47;referral of potentially severe&#47;fatal SSTI&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Financial support</span><p id="par0210" class="elsevierStylePara elsevierViewall">None declared&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Authors&#8217; contributions</span><p id="par0200" class="elsevierStylePara elsevierViewall">Silvio Alencar Marques&#58; Conception and planning of the study&#59; elaboration and drafting of the manuscript&#44; critical review of the literature&#59; critical review of the manuscript&#59; approval of the final version of the manuscript&#46;</p><p id="par0205" class="elsevierStylePara elsevierViewall">Luciana PF Abbade&#58; Elaboration and drafting of the manuscript&#59; critical review of the literature&#59; critical review of the manuscript&#59; approval of the final version of the manuscript&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Conflicts of interest</span><p id="par0215" class="elsevierStylePara elsevierViewall">None declared&#46;</p></span><span id="sec1045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Acknowledgements</span><p id="par0225" class="elsevierStylePara elsevierViewall">To Eliete Correia Soares&#44; photographer of the Dermatology Department at FMB-Unesp&#44; for documenting several of the cases shown in this article&#46; To Dr&#46; Hamilton Ometto Stolf for the shared medical attention to the cases mentioned in this article and for his enthusiasm in the study of clinical and surgical emergencies in dermatology&#46;</p></span><p id="par9020" class="elsevierStylePara elsevierViewall"><elsevierMultimedia ident="tbl0140"></elsevierMultimedia></p><p id="par9021" class="elsevierStylePara elsevierViewall"><elsevierMultimedia ident="tbl0141"></elsevierMultimedia></p></span>"
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          "titulo" => "Keywords"
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          "titulo" => "Introduction"
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          "titulo" => "Necrotizing fasciitis"
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          "titulo" => "Fournier gangrene"
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        5 => array:2 [
          "identificador" => "sec0020"
          "titulo" => "Ecthyma gangrenosum"
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          "identificador" => "sec0025"
          "titulo" => "Skin infections caused by methicillin-resistant Staphylococcus aureus &#40;MRSA&#41;"
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          "titulo" => "Final remarks"
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          "titulo" => "Acknowledgements"
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          "titulo" => "References"
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    "fechaRecibido" => "2020-04-14"
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            0 => "Bacterial infections"
            1 => "Ecthyma"
            2 => "Fasciitis&#44; necrotizing"
            3 => "Fournier gangrene"
            4 => "Furunculosis"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">The severe bacterial diseases discussed herein are those that present dermatological lesions as their initial manifestations&#44; for which the dermatologist is often called upon to give an opinion or is even the first to examine the patient&#46; This review focuses on those that evolve with skin necrosis during their natural history&#44; that is&#44; necrotizing fasciitis&#44; Fournier gangrene&#44; and ecthyma gangrenosum&#46; Notice that the more descriptive terminology was adopted&#59; each disease was individualized&#44; rather than being referred by the generic term &#8220;necrotizing soft tissue infections&#8221;&#46; Due to their relevance and increasing frequency&#44; infections by methicillin-resistant <span class="elsevierStyleItalic">Staphylococcus aureus</span> &#40;MRSA&#41; were also included&#44; more specifically abscesses&#44; furuncle&#44; and carbuncle&#44; and their potential etiologies by MRSA&#46; This article focuses on the epidemiology&#44; clinical dermatological manifestations&#44; methods of diagnosis&#44; and treatment of each of the diseases mentioned&#46;</p></span>"
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          "leyenda" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">The sum of scores &#60; 5&#44; &#8804;50&#37; risk &#40;low risk&#41;&#46;</p><p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Between 6 and 7<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>intermediate risk&#59; &#62;8<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>75&#37; risk &#40;high risk&#41;&#46;</p>"
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Parameters&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Leukocytes &#40;10<span class="elsevierStyleSup">9</span>&#47;L&#41;</td><td class="td" title="\n
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                  \t\t\t\t">Sodium &#40;mmoL&#47;L&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Creatinine &#40;moL&#47;mL&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">C-reactive protein&nbsp;\t\t\t\t\t\t\n
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          "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Laboratory data indicative of risk for the diagnosis of necrotizing fasciitis &#40;Laboratory Risk Indicator for Necrotizing Fasciitis &#91;LRINEC&#93;&#41;&#46;</p>"
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t" style="border-bottom: 2px solid black"><span class="elsevierStyleBold">CME Questions</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">1&#46; Regarding necrotizing fasciitis &#40;NF&#41;&#44; check the correct alternative&#58;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">a&#41; It is an infection that affects the superficial and even deep muscular fascia of the subcutaneous tissue&#44; of the dermis&#44; and of the epidermis&#44; with evolution to local necrosis&#44; toxemia&#44; and possible sepsis&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">b&#41; NF that is associated with infection by multiple bacterial species &#40;polymicrobial&#41;&#44; called type I&#44; is considered more frequent&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">c&#41; NF type II is the one in which Streptococcus pyogenes is the only or predominant agent and&#44; therefore&#44; is called monomicrobial&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">d&#41; All alternatives are correct&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="1" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">2&#46; Which of the following are correct regarding NF&#63;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">a&#41; NF can occur even in the absence of loss of continuity of the skin&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">b&#41; The most common infectious agent is Escherichia coli&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">c&#41; Human or animal bites do not trigger NF&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">d&#41; Pain is not an important phenomenon in the natural history of NF&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="1" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">3&#46; Which of the conditions listed below constitutes a predisposing factor to NF&#63;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">a&#41; Alcoholism and malnutrition&#46;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">b&#41; Illicit drugs use&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">c&#41; Obesity and diabetes mellitus&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">d&#41; All of the above&#46;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="1" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">4&#46; In the Laboratory Risk Indicator for Necrotizing Fasciitis &#40;LRINEC&#41; NF scoring system&#44; the factor that most contributes to the diagnosis is&#58;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">a&#41; Polymerase chain reaction &#40;PCR&#41; value&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">b&#41; Blood glucose value at admission&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">c&#41; Serum creatinine value&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">d&#41; Leukogram data on admission&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="1" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">5&#46; Considering that Fournier&#39;s gangrene is a local presentation of necrotizing fasciitis&#44; which of the conducts listed below are correct for both diseases&#58;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">a&#41; Broad-spectrum intravenous antibiotic therapy as soon as the diagnostic is suspected&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">b&#41; Consider the debridement of the necrotic tissue that may be present as a surgical emergency&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">c&#41; Proceed to the etiological investigation from the suspected diagnosis through blood cultures and culture of tissue fragments from the skin lesion&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">d&#41; All of the above are correct&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="1" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">6&#46; Ecthyma gangrenosum was initially described as a manifestation of bacteremia caused by&#58;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">a&#41; Streptococcus pyogenes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">b&#41; Staphylococcus aureus&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">c&#41; Escherichia coli&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">d&#41; Pseudomonas aeruginosa&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="1" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">7&#46; Regarding ecthyma gangrenosum&#44; it is correct to state&#58;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">a&#41; If carbapenems are chosen&#44; even if there is renal failure&#44; it is not necessary to correct the dose by creatinine clearance&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">b&#41; Treatment must be initiated upon suspicion&#44; aimed towards infection by S&#46; pyogenes or other Gram-positive bacteria&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">c&#41; Skin biopsy is not an adequate method to reach the etiological diagnosis&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">d&#41; Primary immunodeficiency or neutropenia are frequent predisposing factors&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="1" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">8&#46; Check the correct alternative for skin infections caused by methicillin-resistant Staphylococcus aureus &#40;MRSA&#41;&#58;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">a&#41; Infections caused by this agent should only be suspected in patients with a history of current or recent hospitalization&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">b&#41; Cellulitis and erysipelas without formation of purulent collections are the main skin manifestations&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">c&#41; There are two different types of MRSA strains&#44; CA-MRSA and HA-MRSA&#44; which occur in populations with different epidemiological profiles&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">d&#41; MRSA infections occur predominantly in immunosuppressed patients&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="1" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">9&#46; Characteristics of CA-MRSA infections are&#58;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">a&#41; Young and healthy patients&#44; such as athletes&#44; and bacterial clones with production of Panton-Valentine leukocidin&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">b&#41; Patients with a history of hospitalization and resistance to &#946;-lactam antibiotics&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">c&#41; User of illicit drugs with a history of hospitalization&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">d&#41; Immunosuppressed patients who constantly refer to health services&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="1" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">10&#46; Check the correct statement&#58;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">a&#41; The first approach to an abscess is antibiotic therapy&#44; while surgical drainage should be reserved for cases where there is no improvement&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">b&#41; The first choice of antibiotics for furuncles and anthrax are first-generation cephalosporins&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">c&#41; Surgical furuncle drainage is contraindicated&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">d&#41; The antibiotics of choice for treating furuncles are sulfamethoxazole plus trimethoprim or clindamycin&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="1" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr></tbody></table>
                  """
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                0 => """
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                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">ANSWERS<span class="elsevierStyleBold">Post-finasteride syndrome&#46; An Bras Dermatol&#46; 2020&#59;95&#40;3&#41;&#58;271-277&#46;</span></td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">1&#46; d&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">3&#46; b&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">5&#46; d&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">7&#46; a&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">9&#46; c&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">2&#46; d&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">4&#46; d&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">6&#46; c&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">8&#46; d&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">10&#46;a&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0015"
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            0 => array:3 [
              "identificador" => "bib0410"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Acute cutaneous necrosis&#58; a guide to early diagnosis and treatment"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "K&#46; Karime"
                            1 => "A&#46; Odhav"
                            2 => "R&#46; Kollipara"
                            3 => "J&#46; Fike"
                            4 => "C&#46; Stanford"
                            5 => "J&#46;C&#46; Hall"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1177/1203475417708164"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Cutan Med Surg"
                        "fecha" => "2017"
                        "volumen" => "21"
                        "paginaInicial" => "425"
                        "paginaFinal" => "437"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28470091"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0415"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Evaluation and management of necrotizing soft tissue infections"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "S&#46; Bonne"
                            1 => "S&#46;S&#46; Kadri"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.idc.2017.05.011"
                      "Revista" => array:6 [
                        "tituloSerie" => "Infect Dis Clin North Am"
                        "fecha" => "2017"
                        "volumen" => "31"
                        "paginaInicial" => "497"
                        "paginaFinal" => "511"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28779832"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0420"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A multi-center review of care patterns and outcomes in necrotizing soft tissue infections"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "I&#46; Faraklas"
                            1 => "D&#46; Yang"
                            2 => "M&#46; Eggerstedt"
                            3 => "Y&#46; Zhai"
                            4 => "P&#46; Liebel"
                            5 => "G&#46; Graves"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Surg Infect &#40;Larchmt&#41;"
                        "fecha" => "2016"
                        "volumen" => "17"
                        "paginaInicial" => "773"
                        "paginaFinal" => "778"
                        "itemHostRev" => array:3 [
                          "pii" => "S1054139X19305245"
                          "estado" => "S300"
                          "issn" => "1054139X"
                        ]
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                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0425"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Necrotizing fasciitis&#58; current concepts and review of the literature"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "B&#46; Sarani"
                            1 => "M&#46; Strong"
                            2 => "J&#46; Pascual"
                            3 => "C&#46;W&#46; Schwab"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jamcollsurg.2008.10.032"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Am Coll Surg"
                        "fecha" => "2009"
                        "volumen" => "208"
                        "paginaInicial" => "279"
                        "paginaFinal" => "288"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19228540"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0430"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
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