DAL CASO CLINICO ALLA
DECISIONE
Bologna, 15‐16 novembre 2013
Quello che le linee guida non dicono
Le infezioni dei tessuti molli a rapida
evoluzione
Francesco Cristini – Malattie Infettive Bologna
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 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
PUBMED: “necrotizing fasciitis”
1990
2000
2003 2006 2009
2012
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.
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FASCITI NECROTIZZANTI
CLINICA
Anaya DA, Dellinger EP Clin Infect Dis 2007; 44:705–10
LATTACIDEMIA ?
Use of Admission Serum Lactate and Sodium Levels to Predict Mortality in
Necrotizing Soft-Tissue Infections
Yaghoubian A et al, Arch Surg. 2007;142:840-846
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
Predicted mortality
Serum SODIUM
< 135 mEq/L
> 135 mEq/L
Predicted mortality
Predicted mortality
19%
0%
32%
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 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.
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Prognostic factors and monomicrobial necrotizing fasciitis: gram-positive versus gram
negative pathogens
Lee CY et al, BMC Infectious Diseases 2011, 11:5
Prognostic factors and monomicrobial necrotizing fasciitis: gram-positive versus gram
negative 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-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
Practice Guidelines for the Diagnosis and Management of Skin and Soft-Tissue
Infections
Dennis L. Stevens et al - Clinical Infectious Diseases 2005; 41:1373–406
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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…”
Acute bacterial skin infections: developments since the 2005 Infectious diseases
society 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 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.
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
ALWAYS CONSIDER POTENTIAL NECROTIZING SSTI
MICROBIOLOGY
SERIOUS
LIFE THREATENING
SEPSIS
> SEVERE SEPSIS
BL/BLI
DAPTOMYCIN
+
+
CLINDAMYCIN
CARBAPENEM
+
CLINDAMYCIN
SINDROME DELLO SHOCK TOSSICO
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 < 100.000 / mmc o quadro di CID
3. AST o ALT o Bilirubina > 2 volte limite superiore di norma
4. ARDS
DIAGNOSI di CERTEZZA
IA + II (A + B)
DIAGNOSI di PROBABILITA’
IB + II (A + B)
5. Esantema micro-papulare disseminato
6. Fascite necrotizzante e/o mionecrosi o gangrena
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; 37:333-340
 dati clinici non decisivi
assenza di consenso sulla posologia (0.5 g/kg per 2 giorni)
Darenberg J et al, Clin Infect Dis 2003; 37:333-340
Toxic Shock Syndrome: Major Advances in Pathogenesis, But Not Treatment
Donald 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 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.
trappole e forme subdole
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 11 3 10⁹/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 (12
5 10⁹/L) and high CRP (183 mg/L) and
creatine kinase (150 IU/L).
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.
Immunocompromised Status in Patients With Necrotizing Soft-Tissue Infection
Emily 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, or
prior solid organ or bone marrow transplantation with receipt of chronic immunosuppression.
Immunocompromised Status in Patients With Necrotizing Soft-Tissue Infection
Emily Z. Keung et al - JAMA Surg. 2013;148(5):419-426
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.
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
precocemente
si
associa
ad
percentuali di successo.
iniziata
elevate
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
ECTIMA GANGRENOSO
Ectima gangrenoso in soggetto maschio affetto da NHL
Emocolture positive per P. aeruginosa
Caso clinico
ECTIMA GANGRENOSO
Caso clinico
Associata VAC-therapy
ECTIMA GANGRENOSO
Evoluzione locale dopo 2 settimane di VAC therapy
Successiva guarigione con lembo
Caso clinico
Caso clinico
Mucormicosi da
Rhizopus spp
Paziente cirrotico, diabetico
scompensato, IRC,
ipopituitarismo in terapia
steroidea cronica.
INFEZIONI cute e tessuti molli DEL PAZIENTE IMMUNODEPRESSO