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Le infezioni dei tessuti molli a rapida evoluzione

Francesco Cristini – Malattie Infettive Bologna

DAL CASO CLINICO ALLADECISIONE

Bologna, 15‐16 novembre 2013

INFEZIONI CUTANEE SUPERFICIALI

INFEZIONI CUTANEE PROFONDE NON NECROTIZZANTI

NECROTIZZANTI

INFEZIONI NECROTIZZANTI ESTESE AI TESSUTI MOLLI

FASCITI NECROTIZZANTI

GANGRENA GASSOSA

GANGRENA di FOURNIER

INFEZIONI NECROTIZZANTI DI CUTE +/- TESSUTI MOLLI

Caratteristiche comuni

• SEGNI e SINTOMI SISTEMICI

da FEBBRE a SEPSI, SEPSI SEVERA, SHOCK SETTICO • SEGNI e SINTOMI LOCALI

dolore importante, spesso non proporzionato all’entità della lesionelesioni cutanee poco circoscritteedema esteso anche oltre la sede di lesionepresenza di flittenecrepitio cutaneo correlato a presenza di gas in sottocuterapida evoluzione locale e sistemica

• NECESSITA’ DI APPROCCIO MEDICO-CHIRUGICO PRECOCE

• RUOLO DECISIVO DELLA CORRETTA TERAPIA ANTIMICROBICA

• MORTALITA’ ANCORA SIGNIFICATIVAMENTE ELEVATA

2009 20122000 20062003

PUBMED: “necrotizing fasciitis”

1990

Group A Streptococcal Necrotizing Fasciitis in the Emergency DepartmentJiun-Nong Lin et al - J Emerg Med 2013 Aug 9 on line

Patients visiting the ED from January 2005 throughDecember 2011 with the diagnosis of GAS necrotizingfasciitis were enrolled. All patients with the diagnosisof noninvasive skin and soft-tissue infections causedby GAS were included as the control group.

During the study period, 75 patients with GASnecrotizing fasciitis were identified. The mostprevalent underlying disease was diabetes mellitus(45.3%). Bullae were recognized in 37.3% of patients.One third of cases were complicated by bacteremia.Polymicrobial infections were found in 30.7% ofpatients. Overall mortality rate for GAS necrotizingfasciitis was 16%. Patients aged >60 years withdiabetes mellitus, liver cirrhosis, and gout wereconsiderably more likely to have GAS necrotizingfasciitis than noninvasive infections. Patientspresenting with bacteremia, shock, duration ofsymptoms/signs <5 days, low white blood cell count, lowplatelet count, and prolonged prothrombin time wereassociated with increased mortality.

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Anaya DA, Dellinger EP Clin Infect Dis 2007; 44:705–10

FASCITI NECROTIZZANTICLINICA

LATTACIDEMIA ? LATTACIDEMIA ?

Use of Admission Serum Lactate and Sodium Levels to Predict Mortality inNecrotizing Soft-Tissue Infections Yaghoubian A et al, Arch Surg. 2007;142:840-846

CLASSIFICATION and REGRESSION TREE ANALYSIS for MORTALITY

Serum LACTATE

> 6 mmol/L

Predicted mortality

32%

< 6 mmol/L

Serum SODIUM

> 135 mEq/L< 135 mEq/L

Predicted mortality

0%

Predicted mortality

19%

One hundred twenty-four patients were identified with NSTI. The overall mortality rate was 21 of 124 (17%).

Clinical assessment of the severity of infection is crucial…

Patients with soft-tissue infection and SEPSIS (e.g., fever or

hypothermia, tachycardia, tachypnea), or with SEVERE SEPSIS

(e.g, hypotension) HOSPITALIZATION

Search for definitive etiologic diagnosis

Prompt surgical evaluation for suspected necrotizing infections

Prompt antimicrobial therapy

Other clues to potentially severe deep soft-tissue infection include the following:

- pain disproportionate to the physical findings,- violaceous bullae,- cutaneous hemorrhage,- skin sloughing,- skin anesthesia,- gas in the tissue,- rapid progression

Unfortunately, these signs and symptoms often appear later in the course ofnecrotizing infections. In these cases, emergent surgical evaluation is of paramountimportance for both diagnostic and therapeutic reasons.… dozens of microbes may cause soft-tissue infections, and although specificbacteria may cause a particular type of infection, considerable overlaps in clinicalpresentations exist.

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Prognostic factors and monomicrobial necrotizing fasciitis: gram-positive versus gramnegative pathogens

Lee CY et al, BMC Infectious Diseases 2011, 11:5

Prognostic factors and monomicrobial necrotizing fasciitis: gram-positive versus gramnegative pathogens

Lee CY et al, BMC Infectious Diseases 2011, 11:5

FONDAMENTI TERAPEUTICI DELLE FASCITI NECROTIZZANTI

Precocità diagnostica

Precocità ed aggressività chirurgica

Approccio intensivistico

Terapia antibiotica precoce- spettro ampio comprendente anche patogeni emergenti

CA-MRSAS. pyogens MLS-RP. aeruginosa in soggetti immunodepressiEnterobacteriaceae ESBL + in G. di Fournier e diabetici

- attività battericida massimale- azione correlata ad inibizione della sintesi proteica

Practice Guidelines for the Diagnosis and Management of Skin and Soft-TissueInfections

Dennis L. Stevens et al - Clinical Infectious Diseases 2005; 41:1373–406

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“… Current treatment guidelines for the management of cSSTIsand cIAIs do not reflect the availability of new antibiotics, or thelatest trends in bacterial resistance…”

Review of the guidelines for complicated skin and soft tissue infections andintra-abdominal infections—are they applicable today?

Caìnzos M Clin Microbiol Infect 2008; 14 (Suppl. 6): 9–18

Acute bacterial skin infections: developments since the 2005 Infectious diseasessociety of america (idsa) guidelines

Gregory J. Moran et al - J Emerg Med. 2013 Jun;44(6):e397-412

When the Infectious Diseases Society of America (IDSA) prepared their 2005guidelines on the management of skin and soft tissue infections, the role of CA-MRSAwas not yet recognized, and therefore, empiric treatment of this organism was notrecommended.

Antimicrobial resistance surveillance in Europe 2010

Antimicrobial resistance surveillance in Europe 2010

(Bologna) Empirical Management of SUSPECTED NECROTIZING SSTI

PAIN UNRELATED TO CLINICAL FINDINGS

NOT DEMARCATE, RAPIDLY EVOLVING LESION

MICROBIOLOGY

SERIOUS LIFE THREATENING

SEPSIS > SEVERE SEPSIS

BL/BLI

+

CLINDAMYCIN

DAPTOMYCIN

+

CARBAPENEM

+

CLINDAMYCIN

ALWAYS CONSIDER POTENTIAL NECROTIZING SSTI

SINDROME DELLO SHOCK TOSSICO

DEFINIZIONE di CASOWorking Group on Severe Streptococcal Infection, JAMA 1993

I. Isolamento di S. pyogenes

A. da sito normalmente sterile (sangue / ferita chirurgica)

B. da sito non sterile (cavo orale/ vagina / lesione cutanea)

II. Segni Clinici

A. Ipotensione (sistolica < 90 mmHg)

B. Due o più dei seguenti segni

1. Creatinina > 2 mg/dl

2. Piastrine < 100.000 / mmc o quadro di CID

3. AST o ALT o Bilirubina > 2 volte limite superiore di norma

4. ARDS

5. Esantema micro-papulare disseminato

6. Fascite necrotizzante e/o mionecrosi o gangrenaDIAGNOSI di CERTEZZA

IA + II (A + B)DIAGNOSI di PROBABILITA’

IB + II (A + B)

TERAPIA TSS

IMMUNOGLOBULINE ad alto dosaggiostrumento di prevenzione e trattamento della TSS azione correlata ad antagonismo verso i super-antigeni di GASriduzione della mortalità in studi retrospettiviriduzione mortalità a 28 giorni (10% vs 36%) in piccolo studio prospettico

Darenberg J et al, Clin Infect Dis 2003; 37:333-340

dati clinici non decisiviassenza di consenso sulla posologia (0.5 g/kg per 2 giorni)

Darenberg J et al, Clin Infect Dis 2003; 37:333-340

Toxic Shock Syndrome: Major Advances in Pathogenesis, But Not TreatmentDonald E. Low - Crit Care Clin 2013 Jul;29(3):651-75

Toxic shock syndrome (TSS) is primarily the result of a superantigen-mediated cytokine storm and M protein-mediated neutrophil activation, resulting in the release of mediators leading to respiratory failure, vascularleakage, and shock. Mortality for streptococcal TSS still hovers at 50%. There is evidence to support a role forintravenous immunoglobulin (IVIG) in the treatment of streptococcal TSS. An observational study suggests that aninitial conservative surgical approach combined with the use of immune modulators, such as IVIG, may reduce themorbidity associated with extensive surgical exploration in hemodynamically unstable patients without increasingmortality.

(GAS)

Staphylococcal TSS is secondary to a localized infection, whereas STSS is the result of an invasive infection.

trappole e forme subdole

Despite two intravenous doses ofamoxi/clav acid, her pain worsened andthe erythema continued to extend. Overthe next 8 h, pain prevented her frombreastfeeding; she was hypotensive andhad rigors and persisting pyrexia (38.0 C).Blood tests showed leucocytosis (125 10⁹/L) and high CRP (183 mg/L) andcreatine kinase (150 IU/L).

Ten days after an uncomplicated vaginaldelivery at home, a 35-year-old womanpresented to the ED with a 16 h historyof severe, burning right breast pain, and2 h of diarrhoea and vomiting. Onexamination, her temperature was37.9 C, she was tachycardic (120/min),and her blood pressure was 100/70 mmHg. Her chest was clear, with oxygensaturation 96% on air. Blood testsshowed leucocytosis of 11 3 10⁹/L anda high C-reactive protein (CRP) of 61mg/L. The initial diagnosis was mastitis.

Intravenous clindamycin (600 mg four timesdaily) and imipenem (1.0 g four times daily)was started according to the hospital’sprotocol; intravenous polyspecificimmunoglobulin (20 g) was also given. 11 hafter presentation, our patient wastransferred for emergency surgicaldebridement.Microbiological examination of specimensshowed chains of gram-positive cocci, lateryielding GAS.On day 13, her breast wound was resurfacedwith a split skin graft. In December, 2003,her breast was reconstructed with asubpectoral tissue expander. When last seenin April, 2005, the patient was happy withher breast reconstruction.

Group A streptococcal necrotising fasciitis masquerading as mastitis

Tillett R L et al, Lancet 2006; 368: 174

FASCITE NECROTIZZANTE

Immunocompromised Status in Patients With Necrotizing Soft-Tissue InfectionEmily Z. Keung et al - JAMA Surg. 2013;148(5):419-426

Corticosteroid use, active malignancy, receipt of chemotherapy or radiation therapy, diagnosis of HIV or AIDS, orprior solid organ or bone marrow transplantation with receipt of chronic immunosuppression.

Immunocompromised Status in Patients With Necrotizing Soft-Tissue InfectionEmily Z. Keung et al - JAMA Surg. 2013;148(5):419-426

ECTIMA GANGRENOSO

Infezione cutanea su base ematogena,conseguente ad invasione batterica dei vasi delderma con vasculite necrotizzante.

Si manifesta con la formazione di aree nodulariindolenti, necrotiche con componenteemorragica che si espandono progressivamentema restano sempre ben delimitata dalla cutesana.

Ad esso si associano segni e sintomi di SIRS

Occorre in paziente immunocompromessi (speciein soggetti con emopatie maligne, HIV, terapieimmunodeprimenti, diabete) o critici (ustionati)

L’agente etiologico preminente è P. aeruginosa

Pz, di anni 72 affetta da LLC afferita con quadro di sepsi grave, evoluta in shock settico nel volgere di poche ore.

Caso clinicoCaso clinico

ECTIMA GANGRENOSO

Le localizzazioni preminenti sono a carico diregione glutea o perineale (>50%),estremità (30%), tronco (10%) volto (10%).

La diagnosi etiologica si basa su emocolturee colture di biopsie cutanee

La terapia antipseudomonas, se iniziataprecocemente si associa ad elevatepercentuali di successo.

Trattata con terapia empirica “presuntiva” anti-Pseudomonas, con risoluzione del quadro sistemico e progressivo miglioramento delle lesioni.

Emocolture e coltura biopsia cutanea positive per P. aeruginosa

Caso clinicoCaso clinico

Ectima gangrenoso in soggetto maschio affetto da NHL

Emocolture positive per P. aeruginosa

ECTIMA GANGRENOSO Caso clinicoCaso clinico

Associata VAC-therapy

ECTIMA GANGRENOSO Caso clinicoCaso clinico

Evoluzione locale dopo 2 settimane di VAC therapy

Successiva guarigione con lembo

ECTIMA GANGRENOSO Caso clinicoCaso clinico

Paziente cirrotico, diabetico scompensato, IRC, ipopituitarismo in terapia steroidea cronica.

Mucormicosi da Rhizopus spp

Caso clinicoCaso clinico

INFEZIONI cute e tessuti molli DEL PAZIENTE IMMUNODEPRESSO