Le infezioni dei tessuti molli a rapida evoluzione

Transcript

1 DAL CASO CLINICO ALLA DECISIONE Bologna, novembre 2013 Quello che le linee guida non dicono Le infezioni dei tessuti molli a rapida evoluzione Francesco Cristini Malattie Infettive Bologna

2 INFEZIONI CUTANEE SUPERFICIALI INFEZIONI CUTANEE PROFONDE NON NECROTIZZANTI NECROTIZZANTI INFEZIONI NECROTIZZANTI ESTESE AI TESSUTI MOLLI FASCITI NECROTIZZANTI GANGRENA GASSOSA GANGRENA di FOURNIER

3 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 lesione lesioni cutanee poco circoscritte edema esteso anche oltre la sede di lesione presenza di flittene crepitio cutaneo correlato a presenza di gas in sottocute rapida evoluzione locale e sistemica NECESSITA DI APPROCCIO MEDICO-CHIRUGICO PRECOCE RUOLO DECISIVO DELLA CORRETTA TERAPIA ANTIMICROBICA MORTALITA ANCORA SIGNIFICATIVAMENTE ELEVATA

4 PUBMED: necrotizing fasciitis

5 Group A Streptococcal Necrotizing Fasciitis in the Emergency Department Jiun-Nong Lin et al - J Emerg Med 2013 Aug 9 on line Patients visiting the ED from January 2005 through December 2011 with the diagnosis of GAS necrotizing fasciitis were enrolled. All patients with the diagnosis of noninvasive skin and soft-tissue infections caused by GAS were included as the control group. During the study period, 75 patients with GAS necrotizing fasciitis were identified. The most prevalent 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% of patients. Overall mortality rate for GAS necrotizing fasciitis was 16%. Patients aged >60 years with diabetes mellitus, liver cirrhosis, and gout were considerably more likely to have GAS necrotizing fasciitis than noninvasive infections. Patients presenting with bacteremia, shock, duration of symptoms/signs <5 days, low white blood cell count, low platelet count, and prolonged prothrombin time were associated with increased mortality.

6 Quello che le linee guida non dicono

7 FASCITI NECROTIZZANTI CLINICA Anaya DA, Dellinger EP Clin Infect Dis 2007; 44: LATTACIDEMIA?

8 Use of Admission Serum Lactate and Sodium Levels to Predict Mortality in Necrotizing Soft-Tissue Infections Yaghoubian A et al, Arch Surg. 2007;142: One hundred twenty-four patients were identified with NSTI. The overall mortality rate was 21 of 124 (17%). CLASSIFICATION and REGRESSION TREE ANALYSIS for MORTALITY Serum LACTATE < 6 mmol/l > 6 mmol/l < 135 meq/l Serum SODIUM > 135 meq/l Predicted mortality 32% Predicted mortality 19% Predicted mortality 0%

9

10 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

11 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 of necrotizing infections. In these cases, emergent surgical evaluation is of paramount importance for both diagnostic and therapeutic reasons. dozens of microbes may cause soft-tissue infections, and although specific bacteria may cause a particular type of infection, considerable overlaps in clinical presentations exist.

13 Prognostic factors and monomicrobial necrotizing fasciitis: gram-positive versus gram negative pathogens Lee CY et al, BMC Infectious Diseases 2011, 11:5

14 Prognostic factors and monomicrobial necrotizing fasciitis: gram-positive versus gram negative pathogens Lee CY et al, BMC Infectious Diseases 2011, 11:5

15 FONDAMENTI TERAPEUTICI DELLE FASCITI NECROTIZZANTI Precocità diagnostica Precocità ed aggressività chirurgica Approccio intensivistico Terapia antibiotica precoce - spettro ampio comprendente anche patogeni emergenti CA-MRSA S. pyogens MLS-R P. aeruginosa in soggetti immunodepressi Enterobacteriaceae ESBL + in G. di Fournier e diabetici - attività battericida massimale - azione correlata ad inibizione della sintesi proteica

16 Practice Guidelines for the Diagnosis and Management of Skin and Soft-Tissue Infections Dennis L. Stevens et al - Clinical Infectious Diseases 2005; 41:

18 Review of the guidelines for complicated skin and soft tissue infections and intra-abdominal infections are they applicable today? Caìnzos M Clin Microbiol Infect 2008; 14 (Suppl. 6): 9 18 Current treatment guidelines for the management of csstis and ciais do not reflect the availability of new antibiotics, or the latest trends in bacterial resistance

19 Acute bacterial skin infections: developments since the 2005 Infectious diseases society of america (idsa) guidelines Gregory J. Moran et al - J Emerg Med Jun;44(6):e When the Infectious Diseases Society of America (IDSA) prepared their 2005 guidelines on the management of skin and soft tissue infections, the role of CA-MRSA was not yet recognized, and therefore, empiric treatment of this organism was not recommended.

20 Antimicrobial resistance surveillance in Europe 2010

21 Antimicrobial resistance surveillance in Europe 2010

22 (Bologna) Empirical Management of SUSPECTED NECROTIZING SSTI PAIN UNRELATED TO CLINICAL FINDINGS NOT DEMARCATE, RAPIDLY EVOLVING LESION ALWAYS CONSIDER POTENTIAL NECROTIZING SSTI MICROBIOLOGY SERIOUS SEPSIS BL/BLI + CLINDAMYCIN LIFE THREATENING > SEVERE SEPSIS DAPTOMYCIN + CARBAPENEM + CLINDAMYCIN

23 SINDROME DELLO SHOCK TOSSICO DIAGNOSI di CERTEZZA IA + II (A + B) DIAGNOSI di PROBABILITA IB + II (A + B) DEFINIZIONE di CASO Working 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 < / 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 gangrena

24 TERAPIA TSS IMMUNOGLOBULINE ad alto dosaggio strumento di prevenzione e trattamento della TSS azione correlata ad antagonismo verso i super-antigeni di GAS riduzione della mortalità in studi retrospettivi riduzione mortalità a 28 giorni (10% vs 36%) in piccolo studio prospettico Darenberg J et al, Clin Infect Dis 2003; 37: dati clinici non decisivi assenza di consenso sulla posologia (0.5 g/kg per 2 giorni) Darenberg J et al, Clin Infect Dis 2003; 37:

25 Toxic Shock Syndrome: Major Advances in Pathogenesis, But Not Treatment Donald E. Low - Crit Care Clin 2013 Jul;29(3): Toxic shock syndrome (TSS) is primarily the result of a superantigen-mediated cytokine storm and M proteinmediated neutrophil activation, resulting in the release of mediators leading to respiratory failure, vascular leakage, and shock. Mortality for streptococcal TSS still hovers at 50%. There is evidence to support a role for intravenous immunoglobulin (IVIG) in the treatment of streptococcal TSS. An observational study suggests that an initial conservative surgical approach combined with the use of immune modulators, such as IVIG, may reduce the morbidity associated with extensive surgical exploration in hemodynamically unstable patients without increasing mortality. (GAS) Staphylococcal TSS is secondary to a localized infection, whereas STSS is the result of an invasive infection.

26 trappole e forme subdole

27 Ten days after an uncomplicated vaginal delivery at home, a 35-year-old woman presented to the ED with a 16 h history of severe, burning right breast pain, and 2 h of diarrhoea and vomiting. On examination, her temperature was 37.9 C, she was tachycardic (120/min), and her blood pressure was 100/70 mm Hg. Her chest was clear, with oxygen saturation 96% on air. Blood tests showed leucocytosis of ⁹/L and a high C-reactive protein (CRP) of 61 mg/l. The initial diagnosis was mastitis. Despite two intravenous doses of amoxi/clav acid, her pain worsened and the erythema continued to extend. Over the next 8 h, pain prevented her from breastfeeding; she was hypotensive and had rigors and persisting pyrexia (38.0 C). Blood tests showed leucocytosis ( ⁹/L) and high CRP (183 mg/l) and creatine kinase (150 IU/L).

28 FASCITE NECROTIZZANTE Group A streptococcal necrotising fasciitis masquerading as mastitis Tillett R L et al, Lancet 2006; 368: 174 Intravenous clindamycin (600 mg four times daily) and imipenem (1.0 g four times daily) was started according to the hospital s protocol; intravenous polyspecific immunoglobulin (20 g) was also given. 11 h after presentation, our patient was transferred for emergency surgical debridement. Microbiological examination of specimens showed chains of gram-positive cocci, later yielding GAS. On day 13, her breast wound was resurfaced with a split skin graft. In December, 2003, her breast was reconstructed with a subpectoral tissue expander. When last seen in April, 2005, the patient was happy with her breast reconstruction.

29 Immunocompromised Status in Patients With Necrotizing Soft-Tissue Infection Emily Z. Keung et al - JAMA Surg. 2013;148(5): Corticosteroid use, active malignancy, receipt of chemotherapy or radiation therapy, diagnosis of HIV or AIDS, or prior solid organ or bone marrow transplantation with receipt of chronic immunosuppression.

30 Immunocompromised Status in Patients With Necrotizing Soft-Tissue Infection Emily Z. Keung et al - JAMA Surg. 2013;148(5):

31 ECTIMA GANGRENOSO Caso clinico Infezione cutanea su base ematogena, conseguente ad invasione batterica dei vasi del derma con vasculite necrotizzante. Si manifesta con la formazione di aree nodulari indolenti, necrotiche con componente emorragica che si espandono progressivamente ma restano sempre ben delimitata dalla cute sana. Ad esso si associano segni e sintomi di SIRS Occorre in paziente immunocompromessi (specie in soggetti con emopatie maligne, HIV, terapie immunodeprimenti, 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.

32 ECTIMA GANGRENOSO Caso clinico Le localizzazioni preminenti sono a carico di regione glutea o perineale (>50%), estremità (30%), tronco (10%) volto (10%). La diagnosi etiologica si basa su emocolture e colture di biopsie cutanee La terapia antipseudomonas, se iniziata precocemente si associa ad elevate percentuali 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

33 ECTIMA GANGRENOSO Caso clinico Ectima gangrenoso in soggetto maschio affetto da NHL Emocolture positive per P. aeruginosa

34 ECTIMA GANGRENOSO Caso clinico Associata VAC-therapy

35 ECTIMA GANGRENOSO Caso clinico Evoluzione locale dopo 2 settimane di VAC therapy Successiva guarigione con lembo

36 Caso clinico Mucormicosi da Rhizopus spp Paziente cirrotico, diabetico scompensato, IRC, ipopituitarismo in terapia steroidea cronica.

37 INFEZIONI cute e tessuti molli DEL PAZIENTE IMMUNODEPRESSO