infecciuon piel y tejidos blandos

7/31/2019 Infecciuon piel y tejidos blandos

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localised area of tender erythema and swelling andspreads rapidly with advancing margins (figure 2). Thedistinctive features of erysipelas are the following: thelesion is fiery red and markedly oedematous (peaudorange), the margins are raised, and there is cleardistinction from surrounding tissue.3234 Because of theinvolvement of the lymphatics, there is usually associatedlymphangitis and lymphadenopathy.17,21 Systemic mani-festations of fever and chills are usually present, and thepatient may be markedly toxic. Erysipelas typically

involves the face. However, distribution patterns havechanged, and the lower extremities are currently thepredominant location, although any area of skin may beinvolved (figure 3).32,34 Although a serious disease,erysipelas is not typically life threatening, with afavourable clinical evolution occurring in over 80% ofpatients with appropriate antimicrobial therapy.35,36

Progression to deeper soft tissue layers occurs inapproximately 10% of cases, while systemic complications(eg, bacteraemia) was reported in 25% of cases.35

Cellulitis is an infection of the lower dermis andsubcutaneous soft tissue. Most are produced by group Astreptococcus, S aureus, or both.3,33,37 Clinically, cellulitis ischaracterised by ill-defined blanching erythema, oedemaand warmth, accompanied by pain and tenderness. There

may be blister formation if the infection causes sufficient

separation of soft tissues such that the overlyingepidermis and dermis are raised. There may belymphangitis or regional lymphadenopathy, particularlyin cases associated with group A streptococcus. Systemicfeatureseg, fever and leucocytosisare usually present.

Erysipelas and cellulitis can usually be distinguishedclinically, although it is not always possible. However,clinical distinction between cellulitis caused by S pyogenesversus that caused by S aureus is not reliable. The majorobjectives when a patient presents with such an infectionare to recognise that group A streptococcus may bepresent and to ensure that there is no deeper tissueinvolvement.

The deep SSTIs caused by group A streptococcus consist

of necrotising fasciitis and myonecrosis.16,32,38 Necrotisingfasciitis is a deep-seated infection of the subcutaneoustissue that results in the rapidly progressive destruction offat and fascia. Necrotising fasciitis can be monomicrobial(type II), in which group A streptococcus alone or withS aureus is the most frequent cause, or may bepolymicrobial (type I), in which a mixture of Gram-positive and Gram-negative aerobes and anaerobes areidentified.15,17,39 Monomicrobial necrotising fasciitis ismore common among idiopathic or community-acquired cases, whereas postoperative necrotising fasciitis

502 http://infection.thelancet.com Vol 5 August 2005

Figure 1: Erysipelas(A) Erysipelas of lower extremity arising from an area of tinea pedis involving the web space of the fourth and fifth

toes. (B) Area of tinea pedis involving web space of fourth and fifth toes serving as portal of entry.

JohnEmbil

JohnEmbil

Figure 2: Erysipelas of the face demonstrating the distinctive features of

fiery red discoloration and raised margins in contrast to normal surroundingskin


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and necrotising fasciitis involving the head and neck area

or the genitourinary tract (eg, Fourniers gangrene) aretypically polymicrobial,1113,18,39,40 although reports exist ofgroup A streptococcus necrotising fasciitis of theperineum related to human bites.41 Streptococcalmyonecrosis usually occurs in association withnecrotising fasciitis as an expansion of the destructiveprocess, but can be isolated, resulting from hematogenousseeding of the organism to muscle.42 Risk factors forinvasive group A streptococcus SSTIs are multiple andinclude minor injuries, recent primary varicella-zostervirus infection (in which a lesion becomes superinfected),diabetes mellitus, and use of non-steroidal anti-inflammatory drugs, although it can also occur inpreviously healthy individuals.40,43,44

In necrotising fasciitis and myonecrosis, the diseaseprogresses rapidly. In the later stages of the diseases, theaffected area develops oedema and erythema, followed byanaesthesia of the area due to infarction of superficialnerves. Subsequently, bullae appear, initially filled withclear fluid, but rapidly becoming haemorrhagic orviolaceous, signifying dermal necrosis.15,17,32 Invisible to thebedside observer, the infection spreads rapidly alongfascial planes and can lead to tenderness beyond themargins of erythema. There are marked systemicsymptoms, with early onset of shock and organ failure.The diagnosis of necrotising fasciitis or myonecrosis atthis stage is clear but too late. Early recognition is

fundamental in management of this complication.Although there are no features in the early stages thatreliably distinguish erysipelas or cellulitis fromnecrotising fasciitis or myonecrosis, the presence oftenderness on physical examination out of proportion tothe appearance of the area, the presence of systemicinflammatory response features (temperature 36C or38C, systolic blood pressure


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a first-generation cephalosporin (eg, cefazolin) may beused.33,37

For suspected necrotising fasciitis or myonecrosis,emergency surgical exploration is required. At surgery,material should be obtained for immediate Gram stainand histopathological examination to confirm thediagnosis. The presence of only Gram-positive cocci inpairs and chains is consistent with Streptococcus spp. Finalmicrobiological identification of the isolate can beconfirmed by subsequent bacterial culture. Debridement,

usually extensive, with subsequent re-explorations arenecessary.12,51 When initiating antibiotic treatment forsuspected necrotising fasciitis presumed to be caused bygroup A streptococci, it is important to ensure thatpenicillin, a highly effective agent against S pyogenes, isincluded in the treatment regimen. A frequently usedantibiotic regimen is the combination of high-dosepenicillin (4 million units intravenously every 4 hours)with clindamycin (600900 mg intravenously every8 hours).17,32,42 The rationale is that penicillin, a beta-lactam,


Pathogen and clinical condition Predisposing factors Antimicrobial choices*

Gram-positive pathogensGroup A streptococcus (Streptococcus pyogenes)

Erysipelas Trauma to skin or minor skin breaks (eg, toe web intertrigo), First line: penicillin

lymphoedema, chronic venous insufficiency Alternate therapy: first-generation cephalosporin, or clindamycin, or macrolides, or

glycopeptides, or expanded spectrum fluoroquinolones

Cellulitis Trauma to skin or minor skin breaks First line: first-generation cephalosporin or semi-synthetic pencillinase-resistant

penicillin

Alternate therapy: clindamycin, or macrolides, or glycopeptides, or expanded spectrum

fluoroquinolones

Necrotising fasciitis with or without myonecrosis Trauma to skin or minor skin breaks, superinfection First line: high-dose penicillin G intravenously with clindamycin

o f v ar ice ll a l esi on , d iabe te s me ll it us, po ssi bl e A lt er nate th er apy: cl in damy ci n

association with use of non-steroidal anti-inflammatory

drugs

Group B streptococcus (S agalactiae)

Necrotising fasciitis Diabetes mellitus, premature neonates First line: high-dose penicillin G intravenously with clindamycin

Alternate therapy: clindamycin

Community-acquired meticillin-resistant There do not appear to be specific risk factors nor First line: glycopeptide||

Staphylococcus aureus (community-acquired MRSA) associations for acquisition of community-acquired Alternate therapy: clindamycin, or co-trimoxazole (trimethoprim/MRSA unlike nosocomial MRSA, where contact with sulfamethoxazole), or linezolid||

health-care facilities is the major risk factor

Clostridium spp Grossly contaminated wounds (C perfringens) , Fi rs t l in e: h ig h-do se pen ic il lin G i nt rave no us ly w it h c li ndam yci n

associated with colonic neoplasms (C septicum), Al ter na te therap y: clindamycin, or metr onida zol e

intravenous drug use (C sordellii, C noyvi)

Gram-negative pathogens

Pasteurella spp Dog bites (P canis),** cat bites (P multocida)** First line: Mild infectionsbeta-lactam/beta-lactamase inhibitor (eg, amoxici ll in/

clavulanate); moderate to severe infectionspiperacillin/tazobactam intravenously or,

second or third-generation cephalosporin intravenously combined with metronidazole

if polymicrobial infection suspected

Alternate therapy: mild and moderate to severe infectionsclindamycin with

fluoroquinolone, or clindamycin with co-trimoxazole

Aeromonas spp (eg,A hydrophila) Freshwater exposure, medicinal leeches First line: fluoroquinolones

Alternate therapy: co-trimoxazole, or third-generation cephalosporins,

or aminoglycosides, or aztreonam

Vibrio spp (eg, V vulnificus) Chronic liver d isease; salt wat er exposure, including First l ine: minocycline wit h thir d-g ener ation cepha losp orin

improperly cooked crustaceans Alternate therapy: ciprofloxacinKlebsiella pneumoniae Chronic liver disease, diabetes melli tus Cephalosporins of any generation based upon antimicrobial susceptibi li ty profiles,

or beta-lactam/beta-lactamase inhibitors, or carbapenems,or fluoroquinolones, or

aminoglycosides

Eschericheria coli Cirrhosis Cephalosporins of any generation based upon antimicrobial susceptibility profiles,

or beta-lactam/beta-lactamase inhibitors, or carbapenems,or fluoroquinolones, or

aminoglycosides

Serratia marcescens Chronic renal fai lure, diabetes melli tus Third or forth-generation cephalosporins, or beta-lactam/beta-lactamase inhibitors, or

carbapenems, or fluoroquinolones, or aminoglycosides

Pseudomonas aeruginosa Neutropenia, haematological malignancy, First l ine: antipseudomonal beta-lactam, combined with aminoglycoside

b ur ns , H IV inf ec ti on , in je ct io n dru g u se A lt er nate th er apy: an tipseu do mo nal b et a- lact am wi th flu or oq uin ol on e

*Because of the lack of randomised, placebo-controlled trials, treatment recommendations are based on in-vitro data, experimental animal models, observational studies, and/or reports of cases. Susceptibility testing of clinical

isolates should be done and modification of antimicrobial therapy based on susceptibility profiles may be necessary. Specific doses have not been provided and should be verified with the product monographs and adjusted for

renal and hepatic impairment where necessary. If no evidence of immediate (type 1, IgE-mediated) hypersensitivity. In addition to the first-generation cephalosporins, the second-generation agents will be effective, as will

certain third-generation agentseg, ceftriaxone. Glycopeptideseg, vancomycin or tiecoplaninmay be an alternate choice in those with documented hypersensitivity to beta-lactams. Extended spectrum fluoroquinolones

refers to the quinolones with documented efficacy against the aerobic Gram-positive coccieg, levofloxacin, gatifloxacin, and moxifloxacin. They should be considered only in patients unable to tolerate the other regimens.

Note: fluoroquinolone-resistant S aureus may preclude the use ofthese agents. ||The therapeutic choices for MRSA depend upon the local epidemiology and local susceptibility profiles. Empirical therapy must always beconfirmed with culture reports. With community-acquired MRSA, inducible clindamycin resistance during therapy is a concern. **Animal bites may be polymicrobial. Antipseudomonal beta-lactam refers to ceftazidime,

cefepime, carbapenems, and extended spectrum penicillinseg, piperacillin.

Table: Suggested potential therapeutic regimens


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inhibits bacterial cell wall formation and therefore

prevents the proliferation ofS pyogenes. However, even inthe absence of active division, toxin-mediated tissuenecrosis continues.48 Clindamycin inhibits toxinproduction by acting at the level of bacterial ribosomes.However, the evidence for the concurrent use ofclindamycin is primarily from animal models. Humantrials to validate the benefit of antimicrobial agents withefficacy in arresting protein synthesis currently do notexist.52,53 In addition to arresting toxin production byinterfering with protein synthesis, the antibacterialspectrum of clindamycin targets S aureus and anaerobes.There is also clinical data that support the use ofintravenous immune globulin as adjunctive therapy insevere invasive group A streptococcus infections, although

the evidence for benefit is in the presence of streptococcaltoxic shock syndrome.38,54,55 The effect of intravenousimmune globulin for necrotising fasciitis or myonecrosis,in the absence of streptococcal toxic shock syndrome,requires further studies.

Clostridium perfringensClostridium perfringens is a ubiquitous Gram-positive,anaerobic, spore-forming rod. It is the most commonaetiological agent of clostridial myonecrosis, or gasgangrene, which is a rapidly progressive, destructiveinfection of skeletal muscle.2,13,17 Historically, clostridialmyonecrosis was a deadly complication of contaminated

war wounds.

13

Nowadays, it usually occurs after deeptrauma with gross contamination, surgery, or minortrauma (including parenteral injections).2,15,16 Clostridialmyonecrosis may also occur in the absence of trauma viahaematogenous seeding of skeletal muscle byClostridium septicum; this complication usually occurs inassociation with colonic neoplasms.2 Recent reports haveidentified other Clostridium spp (eg, Clostridium sordellii,Clostridium noyvi) as causes of necrotising soft tissueinfections among intravenous drug users.5658

The incubation period between injury and onset ofsymptoms is approximately 13 days, but can be asshort as hours.2,17 Typically, the onset is sudden. There issevere pain out of proportion to the external evidence of

infection. The pain can extend beyond the originalmargins of the wound and clinically the patient appearstoxic. Cutaneous manifestations consist of tense,oedematous, pale skin that progresses to tense bullaefilled with serosanguineous fluid, followed byviolaceous dermal necrosis (figure 4).16,40 There is anassociated brownish, foul-smelling discharge, typicallycalled dishwater exudate,15 which characteristicallycontains numerous organisms and few leucocytes.2,40

Gas is vigorously produced by C perfringens, andtherefore, gas bubbles may exude from the wound.Crepitus may also be present, although it is a latefinding.13 It has been suggested that the triad of pain,which may be severe, tachycardia out of proportion tothe fever, and crepitus is strongly suggestive of

clostridial myonecrosis.17 A Gram stain of woundexudate may reveal Gram-positive box-car shapedrods. In cases of clostridial myonecrosis, radiographsmay reveal gas in the tissues. As the infectionprogresses, there is usually associated hypotension,acute renal failure, or other organ dysfunction.However, despite the severity of the infection, patientsmay remain alert and lucid.13 Eventually, in the laterstages of the disease, they may develop a toxic

encephalopathy.Suspected cases of clostridial myonecrosis requireemergency surgical exploration and debridement of allinvolved muscle. Antibiotic therapy consists of high-doseintravenous penicillin in combination with clindamycin(table), based on data from murine models of gasgangrene.2 For patients allergic to penicillin, clindamycinor metronidazole may be used, again based onexperimental evidence.59 Hyperbaric oxygen therapy(100% at 3 atmospheres13) has been recommended forperioperative use in clostridial myonecrosis, based on in-vitro evidence that it inhibits bacterial growth and toxinproduction, as well as on animal studies that show asurvival benefit when used in addition to surgery and

antibiotics.17,60 Hyperbaric oxygen may also have abeneficial effect on both mortality and tissue preservationin other forms of necrotising fasciitis.61,62 However, suchevidence is limited to small retrospective case studies;furthermore, a beneficial effect has not been consistentlydemonstrated. Unfortunately, there are no prospective,randomised controlled studies on hyperbaric oxygen use,nor are there strong studies to identify which patientswould most benefit from it. A major obstacle to conclusivebenefit of this modality is the fact that few hospitalspossess hyperbaric facilities, and the critical status ofpatients often precludes lengthy transport to areas withthese specialised units.14,62 Therefore, the role ofhyperbaric oxygen therapy, if any, remains adjunctive tocombined surgical and medical intervention.

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Figure 4: Clostridial myleonecrosis extending into the distal aspect of belowknee amputation in a patient who presented with a rapidly progressive

crepitant cellulitis following trauma while farming

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Pasteurella speciesPasteurella spp are Gram-negative coccobacilli that arecommensals found in the oral cavity of many animals.Although traditionally associated with cats only,Pasteurella spp can also be frequently isolated from dogbites,20,63 although the isolated species vary. In one study,Pasteurella canis was the most common isolate from dogbites, accounting for up to 50% of pathogens recoveredfrom such wounds, whereas Pasteurella multocidasubspecies multocida and septica were the most commonisolates from cat bites, representing 75% of the bacteriarecovered.20 Common co-pathogens include oralanaerobes (eg, bacteroides, fusobacterium) and oral

aerobes (eg, streptococci).

20,64

Bites, scratches, or licking ofany open wounds by such animals may result in a rapidlyprogressive cellulitis within hours, manifested by acuteonset of intense oedema, erythema, tenderness, withserosanguinous wound discharge. Lymphangitis, regionaladenopathy, fever, and chills may also be present.65 Aninadequately treated infection can become complicated,most commonly with tenosynovitis, osteomyelitis, andseptic arthritis.66

Uncomplicated Pasteurella spp cellulitis may be treatedin an out-patient setting. However, rapidly progressivecellulitis or evidence of deeper soft tissue involvementrequires hospitalisation for intravenous antibiotictherapy and possible surgical intervention. The

diagnosis of tenosynovitis is based on the presence ofKanavels cardinal signs:67 finger held in slight flexion,fusiform swelling, tenderness along the flexor tendonsheath, and pain with passive extension of the digit(figure 5). Osteomyelitis may be diagnosed clinically (eg,visible bone, positive probe-to-bone test) or withdiagnostic imaging (eg, nuclear imaging, MRI). Septicarthritis may be diagnosed with clinical examination andarthrocentesis.

The antimicrobial agents of choice for Pasteurella sppinfections are penicillin, ampicillin,or amoxicillin (table),66

which may be suitable when administered orally for mildinfections. However, parenteral therapy is frequentlynecessary for more substantial infections, particularlythose spreading quickly. A consideration that must be

made is that beta-lactamase production by Pasteurella spp

has been described,

68

although this resistance can beovercome with a beta-lactamase inhibitoreg, clavulanicacid. Because of this possibility for resistance, and becausemost infections related to dog or cat bites arepolymicrobial, including oral streptococci, anaerobes, andpossibly S aureus from the patients skin, a beta-lactamcombined with a beta-lactamase (eg, amoxicillin/clavulanate) is often recommended for treatment ofanimal bites and scratches.69,70 Tetracyclines, fluoro-quinolones, co-trimoxazole (trimethoprim/sulfameth-oxazole), and chloramphenicol are also active againstP multocida and are considered acceptable alternatives totherapy in patients allergic to penicillin.71 For thoserequiring parenteral therapy, a second-generation or

third-generation cephalosporin may be selected inconjunction with anti-anaerobe therapy; first-generationcephalosporins must be avoided because of their sub-optimal activity against Pasturella spp.72,73 The presence oftenosynovitis is a surgical emergency, since this infectioncan lead to loss of function. Thus, surgical evaluationshould be done promptly. Duration of therapy isindividualised.

Aeromonas hydrophilaAeromonas spp are facultatively anaerobic, Gram-negativebacilli commonly found in natural bodies of freshwaterand saltwater. These microorganisms commonly cause

infectious diseases in cold-blooded animals.

74

TheAeromonas spp of clinical importance to human diseaseare A hydrophila, Aeromonas caviae, and Aeromonas veroniibiotype sobria.75 A hydrophila is the major pathogenassociated with wound infections.75

A hydrophila wound infections can manifest as threemajor syndromes: cellulitis, myonecrosis, and ecthymagangrenosum. Cellulitis, the most frequently encounteredform, typically occurs in healthy individuals after exposureof a superficial wound or a penetrating injury tofreshwater. Commonly reported activities precedinginfection include swimming, diving, boating, andfishing.75 Although the organism can be found in brackishwater, exposure to saltwater is not a source for skin

infections.75,76 Aeromonas spp-associated cellulitis ischaracterised by intense redness and induration at the siteof an injury.77 The infection often suppurates and mayprogress to bulla formation and skin necrosis.76,78 Systemicsigns and symptoms are common. Surgical debridementof this form of infection is often necessary.76

Aeromonas spp cellulitis has also been reported inassociation with medicinal leeches (Hirudo medicinalis),used to accelerate wound healing after reconstructivesurgeries because of their ability to relieve venouscongestion and improve microrevascularisation(figure 6).79,80 The aeromonads are symbionts of theleeches, residing in their gut and assisting in the digestionof ingested red blood cells.81 Such nosocomial infectionshave been reported in 720% of patients treated with


JohnEmbil

Figure 5: Tenosynovitis and septic arthritis of the metacarpal-phalyngeal joint of left third finger caused by

Pasturella multocida after a cat bite


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leeches.76 To prevent this phenomena, it has been

suggested that leeches be used only on tissues with goodarterial perfusion, to minimise the presence of necrotictissue that would serve as a nidus for Aeromonas sppgrowth.82 Strict leech medium hygiene (entailing storageof leeches in a central site, maintenance in a regularlydisinfected container, and avoidance of municipal tapwater) before their application may be beneficial.80 Also,prophylactic antibiotics should be given when leeches areapplied.79,82

Myonecrosis and ecthyma, the two less commonly seentypes ofAeromonas spp infections, are typically found inpatients who are immunocompromised (eg, chronic liverdisease, underlying malignancy).83,84 Myonecrosis withbullous lesions is characterised by the liquefaction and

gangrene of muscles, with gas formation and crepitus.This form of disease resembles gas gangrene. Thesepatients require urgent aggressive debridement andantimicrobial therapy. Those individuals that fail torespond to these measures may require amputation.85

Ecthyma gangrenosum is a cutaneous necrotic organgrenous pustule that occurs secondary to sepsis.The lesions have an erythematous border surrounding avesicle, which can progress to necrosis of the soft tissuewithin 24 hours. This type of infection can be fatal.77

A hydrophila infections should be suspected in apatient presenting with rapidly spreading cellulitisand a history of freshwater exposure. The infection

requires prompt attention. Most infections are treatedwith fluoroquinolones (table).75,84 Alternate agentsinclude aztreonam, co-trimoxazole, third-generationcephalosporins, and aminoglycosides.75 The organism,however, is resistant to ampicillin.86

Vibrio speciesVibrio spp are halophilic Gram-negative bacilli that havea worldwide distribution. The major species that havebeen associated with necrotising soft tissue infectionsare Vibrio vulnificus, Vibrio parahemolyticus, Vibriodamsela, and Vibrio alginolyticus.15,46 V vulnificus isbelieved to be the most virulent,15,87 and ischaracteristically found in marine animals that inhabit

warm bodies of water with intermediate salinities, suchas the coastal waters along the Gulf of Mexico.88,89

Typical organisms that can harbour V vulnificus areuncooked crabs and molluscan shellfisheg, oystersand clams;8890 however, they have also been described inplankton and certain types of fin-fish.91 Thepredominant season for microbial proliferation are thewarm summer months, where virtually 100% of oysterscarry V vulnificus, V parahaemolyticus,or both.88

Vibrio spp cause three major forms of infectiongastroenteritis, wound infection, and, in particular withV vulnificus, primary septicaemia, defined as bacteraemiawithout an obvious focus of infection. Wound infectionswith V vulnificus have been reported in individualshandling certain types of saltwater-based fish and

seafood. Primary septicaemia typically occurs in people

with chronic liver diseaseeg, from alcoholism,cirrhosis, or haemochromatosis;88,91,92 chronic hepatitis Binfection is a well-known risk factor in Asiancountries.92,93 Other underlying illnesses that are also riskfactors for V vulnificus sepsis include chronic renaldisease/haemodialysis, intravenous iron therapy,diabetes mellitus, long-term administration ofcorticosteroids, and HIV infection.88,89,94,95 The increasedrisk of disease from some of these conditions may relateto the organisms ability to grow rapidly in the presenceof iron. The survival ofV vulnificus in human whole bloodor tissue is higher with raised serum transferrin ironsaturation levels and with greater serum ferritinconcentrations.96 Various defects in host defences are

also contributory.22V vulnificus primary septicaemia typically presents with

fever, hypotension, and cutaneous manifestations, mostcommonly haemorrhagic bullae on the extremities.22,97

Clinical criteria have been formulated to allow apresumptive diagnosis of V vulnificus sepsis (panel 2).98

The median time between exposure and onset ofsymptoms is 18 hours.91 Patients with shock on initialpresentation or who develop shock within 12 hours ofhospitalisation have the highest mortality rate (>90%).88

The case-fatality rate is high in immunocompromisedindividuals, exceeding 50%.88,90 Therefore, earlyantimicrobial therapy directed against V vulnificus is

essential for successful management (table). Based onclinical case series from Florida, first-line therapy shouldinclude a tetracycline (eg, doxycycline 100 mgintravenously every 12 hours).88,90 In vitro, a regimen ofminocycline (100 mg intravenously every 12 hours) andcefotaxime (2 g intravenously every 8 hours) has been


Figure 6: Soft tissue infection caused byAeromonas hydrophilia(A) Application of medicinal leeches to reduce vascular congestion after auricular reconstruction following trauma

to ear. (B) Cellulitis and resulting tissue necrosis following cellulitis caused by Aeromonas hydrophilia from leechesused to reduce vascular congestion.

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shown to have a synergistic effect on V vulnificus.99 Inexperimental murine models, this combination therapymay be associated with better survival compared with

monotherapy.100 Ciprofloxacin (400 mg intravenouslyevery 12 hours) has been used successfully for thetreatment of wound infections, and the newerfluoroquinolones appear to be as effective as theminocycline-cefotaxime combination both in vitro and invivo.93

Surgical intervention (incision and drainage,debridement, fasciotomy, and amputation) may beconsidered as an adjunct to medical management,although studies demonstrating a beneficial effect onsurvival are lacking.101

Emerging pathogensCommunity-acquired MRSAS aureus is one of the most common causes of cellulitis.Cellulitis caused by S aureus can be difficult, if notimpossible, to distinguish clinically from that caused bygroup A streptococcus, but it is usually associated withskin trauma, and is more likely to be bullous.2 Ifinadequately treated, local abscesses, necrotising fasciitis,or septicaemia may occur. As less than 5% of clinicalisolates ofS aureus are currently susceptible to penicillinbecause of the production of a plasmid-mediatedpenicillinase,102 traditional empirical therapy for simplecellulitis has been either a first-generation cephalosporinor a semi-synthetic penicillinase-resistant penicillin.4 Forpatients allergic to penicillin, clindamycin is the

preferred drug because of its time-tested efficacy;5,103alternately, a fluoroquinolone may be used, althoughresistance to these compounds has occurred because oftheir widespread use.104

S aureus has also been isolated from patients withnecrotising fasciitis, usually in association with otherpathogens. Occasional cases of monomicrobialnecrotising fasciitis caused by S aureus have been reportedamong adults and infants,105108 but remains substantiallyless common that those caused by group A streptococcus.Most cases were rapidly progressive. Two cases wereaccompanied by toxin-mediated manifestations: one withstaphylococcal toxic shock syndrome and one with asunburn-like rash and strawberry tongue followed by skindesquamation.105 Management consisted of surgical

debridement and empirical broad-spectrum antibiotics

that were then adjusted based on culture and susceptibilityresults.The management of this pathogen has become

increasingly complex because of the development ofmeticillin resistance. This resistance is mediated by theproduction of an alternate penicillin-binding protein,encoded by the mecA gene, that has low affinity for beta-lactams.109,110 This gene is encoded on a mobile geneticelement, the staphylococcal chromosomal cassette mec(SCCmec). MRSA was typically considered a nosocomialpathogen, but typing of SCCmec has identifiedcommunity-associated MRSA strains that are distinctfrom the hospital strains.

Community-acquired MRSA has become increasingly

endemic in many parts of the world. It has a predilectionto affect healthy hostseg, children and young, activeadults.111113 Infection commonly presents as furuncles,characterised by necrotic infection of the hair folliclesand involvement of subcutaneous tissue.114,115 Theselesions can progress to cellulitis, or more frequently,abscesses.7,116 The Panton-Valetine leukocidin genes thatencode a leucocyte toxin and other virulence factorsappear to be associated with these lesions.7 Necrotisingfasciitis caused by community-acquired MRSA has alsobeen reported.117 The onset of disease was typicallysubacute, with presence of symptoms for approximately6 days before seeking medical attention. However, in

some patients the infection did rapidly progress overseveral hours. All patients received antimicrobial therapyand surgical debridement; all patients survived.

The antimicrobial susceptibility of community-acquiredMRSA also distinguishes it from its nosocomialcounterpart. Although community-acquired MRSAmaintains resistance to all current beta-lactams, it isusually susceptible to clindamycin, co-trimoxazole, andtetracyclines (table).7 However, there are concerns thatclindamycin resistance may emerge during therapy.118 Thedistinction between community-acquired MRSA andnosocomial MRSA becomes apparent only after theresults of susceptibility testing are available. Therefore, inareas with high prevalence of community-acquired

MRSA, empirical therapy with vancomycin should beconsidered for SSTIs.7,119

Other streptococciGroup B beta-haemolytic streptococcus, or S agalactiae, isincreasingly being reported as a causative agent ofnecrotising soft tissue infections. Traditionally, group Bstreptococcus was predominantly a pathogen of pregnantwomen and neonates. With respect to SSTIs, it is often acausative agent in diabetic foot infections.4 Recent reportshave documented that the bacteria can also cause invasivediseaseie, necrotising fasciitis and streptococcal toxicshock-like syndrome.2325 15 cases of monomicrobialnecrotising fasciitis due to group B streptococcus in adultshave been described in the English literature. Among


Panel 2: Criteria for the presumptive clinical diagnosis ofVibrio vulnificus sepsis

G Hypotension, shock, or other signs suggestive of sepsis (eg, for wound infections,

evidence of rapidly progressive cellulitis or myositis).

G History of chronic liver disease (eg, alcoholism, cirrhosis, haemochromatosis), or

immunosuppression (although not proposed in the original criteria, chronic renal

disease/haemodialysis should be considered a risk factor).

G History of recent consumption of uncooked shellfish (and likely foods that have been

exposed to them), or exposure of wounds to estuarine water.

G Presence of characteristic bullous skin lesions.

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these cases, diabetes mellitus was a frequent comorbidity

of the affected patients. The clinical presentation wassimilar to that of group A streptococcus. In all cases,surgical debridement was necessary. The antimicrobialtherapy recommended is the same as for group Astreptococcus (ie, high-dose penicillin and clindamycin),although such recommendations are based on casereports.

Group G streptococci have also been described as acause of necrotising SSTIs, although the onset of illness isless rapid than the previously discussed pathogens,typically in the order of 23 days.26

EnterobacteriaceaeKlebsiella pneumoniae, a facultatively anaerobic Gram-

negative bacillus, has been reported as a cause ofmonomicrobial necrotising fasciitis in 11 patients in theEnglish literature.27 Most of the affected patients had anunderlying illness that rendered them immuno-compromised (eight had diabetes mellitus, two hadchronic liver disease). In conjunction with necrotisingfasciitis, most of patients also had visceral organinvolvement (ie, liver, kidneys, pancreas, eye) andassociated bacteraemia. The mortality rate was high.Given the multifocal septic phenomenon that appearsunique to Klebsiella-related necrotising fasciitis,haematogenous spread from an originating non-cutaneous source to the skin appears to be responsible for

necrotising fasciitis. Furthermore, the multifocal nature ofthe infection potentially provides a clue to the presence ofthis organism. In patients with liver abscesses caused byK pneumoniae who subsequently develop signs of SSTIs(eg, erythema, swelling, tenderness), there should be ahigh index of clinical suspicion for necrotising fasciitis.39 Ifmonomicrobial Klebsiella-associated necrotising fasciitis ispresent, the clinician should be aware of potential septicinvolvement of other organs (eg, endophthalmitis).39

Among the other Enterobacteriaceae, E coli andS marcescens have been reported as monomicrobialcauses of necrotising SSTIs.10,28,120127 The predominantrisk factor for the former pathogen appears to becirrhosis,10,120,122,123,127 whereas for the latter, major

predisposition is associated with chronic renal failureand diabetes mellitus.28,124126,128 The clinical presentation isthat of a blistering cellulitisthere is rapid progressionof erythema, formation of haemorrhagic bullae, anddevelopment of necrosis and gangrene, accompanied bysystemic toxicity. In most cases reported, cultures ofbullous fluid demonstrated the pathogen. Because of thesporadic nature of disease caused by these pathogens,there are no guidelines regarding optimal management.E coli necrotising SSTIs seem to be particularly difficultto treat because of the associated chronic liver disease; itis estimated that the mortality rate for patients withcirrhosis who develop Gram-negative cellulitis and septicshock approaches 100%.10 Nonetheless, experiencereported in the literature recommends standard

management with early, extensive, and multiple surgical

debridements, as well as adequate Gram-negativeantimicrobial coverage (table). It is important toremember that patients with cirrhosis may be onprophylactic therapy for spontaneous bacterial peritonitis(eg, a fluoroquinolone, co-trimoxazole), which mayfavour the emergence ofE coli strains resistant to theseagents. In addition S marcescens potentially has manymechanisms of antimicrobial resistance, includingenzymes that mediate resistance to beta-lactams andcarbapenems, and efflux pumps and mutations in DNAgyrase that allow for fluoroquinolone resistance.129,130

Therefore, if necrotising SSTI caused by Entero-bacteriaceae is highly probable, these factors should beconsidered in choosing empiric antibiotic therapy while

awaiting susceptibility results.

Pseudomonas speciesPseudomonas aeruginosa can cause a variety of skininfections, including green nail syndrome, web spaceinfections, otitis externa, and cutaneous folliculitis; theseinfections tend to be mild to moderate in severity andsubacute to indolent in onset.131,132 Ecthymagangrenosum is a sudden-onset, rapidly progressiveSSTI that occurs in immunocompromised patients (eg,haematological malignancy, neutropenia, HIV).29,133,134 Itis usually a manifestation of life-threateningpseudomonas septicaemia, although it may also be

caused by other microorganisms.

135

Two pathogenicmechanisms of ecthyma gangrenosum have beenpostulated:135140 in the bacteraemic (or classic) form, thecutaneous lesion is the result of haematogenousdissemination of septic emboli to the skin; consequently,associated blood cultures tend to be positive. In the non-bacteraemic form, the lesion occurs at the site ofinoculation of the bacteria into the skin; however, ifinadequately treated the lesion may lead to a secondarybacteraemia. The classic form is associated with a worseprognosis: patients with Pseudomonas spp bacteraemiahave mortality rates ranging from 20% to 70%,141,142

whereas the much smaller number of patients with non-bacteraemic pseudomonal ecthyma gangrenosum had

mortality rates ranging from 7% to 15%.136,139Clinically, the cutaneous lesion starts as an

inflammatory macule, papule, or plaque that iserythematous, oedematous, and tender (figure 7).Within hours, it can progress into haemorrhagic blisterswith an erythematous base. After the blister ruptures, acentral necrotic ulcer develops, covered by an eschar,and surrounded by an raised purple-red ring. Thelesions may be multiple, particularly if the portal of entryto the skin is bloodborne. The preferred sites are theaxillary and perianal regions.

Treatment of ecthyma gangrenosum must beaggressive, given the immunocompromised status of thehost. Immediate antipseudomonal combination therapyis recommended until the antibiogram results are



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available; such empiric combination regimens increases

the likelihood of susceptibility to at least one of theantimicrobial agents and has been associated withimproved survival.143146 No specific combination regimenhas proven superior to others (table). Once the results ofsusceptibility testing are available, monotherapy with anappropriate antipseudomonal beta-lactam or intensive-dosing fluoroquinolone appears to be adequate.142,144,145

Monotherapy with aminoglycosides is not encouraged;however, if necessary, high doses (eg, 7 mg/kg per day)should be used.142,145 It should be noted that the optimalantimicrobial management ofP aeruginosa bacteraemiaremains controversial and is based on observationalstudies. Surgical intervention, in the form of incisionand drainage of subcutaneous abscesses, should be done

if skin lesions persist in association with a toxicstate.147,148

ConclusionsWhen a patient presents with a rapidly progressive SSTI,the potential consequences of the disease can befrightening. Clinicians must remember that only alimited number of common organisms can produce thisentity. Clinically, it may be impossible to differentiatethe aetiological agents responsible for the episode ofrapidly progressive SSTI. Clues from the history,combined with characteristic clinical findingseg,lesions with distinct raised borders or rapidly spreading

crepitant processesmay guide the clinician to thepotential diagnosis and the initiation of an appropriateempirical therapy. The severity or depth of infection canbe determined by clinical presentation and physicalexamination. Deep infections should promptconsideration of a surgical evaluation. Early empiricalantibiotic therapy directed at the most likely pathogen(s)elicited by history is important.

Conflicts of interest

We declare that we have no conflicts of interest.

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Figure 7: Ecthyma gangrenosum

(A) Ecthyma gangrenosum in a patient with chronic myelogenous leukaemia

who was bacteraemic with Pseudomonas aeruginosa. Note the well-circumscribed

lesion. (B) Close up of (A), note the well-circumscribed lesion that began as apapule but progressed to have a necrotic base.

RobMathison

Search strategy and selection criteria

Data for this review were identified by searches of papers

published in English on Medline, spanning the years 1975

through February 1, 2005 with the key words: cellulitis,

skin, soft tissue infection, rapidly progressive, rapidly

spreading, rapid, necrotizing, fasciitis, myonecrosis,

management, and treatment in association with group

A streptococcus, Streptococcus pyogenes, Pasteurella,

Clostridium, Aeromonas, and Vibrio. Relevant

references were also obtained from articles acquired through

the search strategy. Clinical practice guidelines were reviewed

where available.


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