Gastrolearning VIII lezione
Le infezioni nel cirrotico: aspetti fisiopatologici - Prof. M. Venditti (Università Roma La Sapienza)
www.gastrolearning.it
Le infezioni nel cirrotico: aspetti fisiopatologici - Gastrolearning®
1. Infezioni e cirrosi
Alcuni aspetti clinici, epidemiologici e microbiologici
Mario Venditti
Dipartimento di Malattie Infettive
Università “La Sapienza”
Roma
3. Cirrhotic Patients Are at Risk for Health Care–
Associated Bacterial Infections
Merli M et al Clin Gastoenterol Hepatol 2010;8:979–985
Clinical Complications in 150 Cirrhotic Patients With and Without Infections
4. Cirrhotic Patients Are at Risk for Health Care–
Associated Bacterial Infections
Merli M et al Clin Gastoenterol Hepatol 2010;8:979–985
Clinical Complications in 150 Cirrhotic Patients With and Without sepsis
6. Cirrhotic Patients Are at Risk for Health Care–
Associated Bacterial Infections
Merli M et al Clin Gastoenterol Hepatol 2010;8:979–985
Variables Associated With Infection at Univariate Analysis in the Patients Included in the Study
7. Variables Independently Associated With Infection
and Sepsis at Multivariate Analysis
Merli M et al Clin Gastoenterol Hepatol 2010;8:979–985
8. Cirrhotic Patients Are at Risk for Health Care–
Associated Bacterial Infections
Merli M et al Clin Gastoenterol Hepatol 2010;8:979–985
Prevalence of Factors That May Be Involved in the Development of HA Infections
9. Characteristics of the 54 Episodes of Infection According to the
Epidemiology Classification
Merli M et al Clin Gastoenterol Hepatol 2010;8:979–985
10. High Prevalence of Antibiotic-Resistant Bacterial Infections Among
Patients With Cirrhosis at a US Liver Center
Puneeta T et al Clin Gastroenterol Hepatol 10: 1291, 2012
• 115 patients in a liver unit from July 2009 to November 2010
• Data were analyzed on 169 infectious episodes: 30%
nosocomial infections. 32% UTI, 24% SBP…..
• 70 infections were culrure positive
• 33(47%) were caused by an AR organism (12 VRE, 9 ESBL
enterobacteriaceae, 7 cipro R garmnegative bacilli, and 5
MRSA)
• Exposure to rifamixin was not associated to AR organisms.
• Exposure tosystemic antibiotics within 30 days (OR 5.2)
before infection and nosocomial infection (OR 4.2) was
associated to AR organism
11.
12.
13. Criteri per inclusione in gruppo HCAP
Venditti M et al Ann Intern Med 150: 19-26, 2009
28%
15. Tassi di mortalità (%) per CAP e
HCAP in differenti studi
Falcone M, Shindo Y, Venditti M & Kollef M Int J Infect Dis in press
p<0.052
p<0.001
p<0.001
p<0.001
p<0.001
p<0.02
p<0.007
16. Rischio di morte
Rischio di etiologie multiresitenti
HCAP HAP/VAP
CAP
Venditti
Kollef Shindo &BouzaI Lee
USA Japan taly & Corea
Spaina
17. HEALTHCARE-ASSOCIATED PNEUMONIA: DIAGNOSTIC CRITERIA AND
DISTINCTION FROM COMMUNITY-ACQUIRED PNEUMONIA
Falcone M, Shindo Y, Venditti M, Kollef M, Int J Antimicrob Agents, 2012
Odd ratios for mortality in patients with HCAP treated with inappropriate antimicrobial therapy
or with antibiotics not recommended in the ATS/IDSA guidelines
STUDY ODDS LOWER UPPER Z- P-VALUE
NAME RATIO LIMIT LIMIT VALUE
MICEK
2.549 1.673 3.884 0.000
4.356
ZILBERDERG
1.900 1.141 3.165 0.014
2.467
VENDITTI
3.436 1.037 11.383 0.043
2.020
SHINDO
2.350 0.659 8.386 1.316 0.188
2.330 1.718 3.158 5.448 0.000
18.
19.
20. Epidemiology of Multidrug-Resistant Bacteria
in Patients With Long Hospital Stays
Buke C et al Infect Control Hosp Epidemiol 2007; 28:1255-1260
Distribution of Multidrug-Resistant Pathogens in 439 Patients as Shown by Screening
Within 3 Days After the Thirtieth Day of the Hospital Stay (D30 Screening)
21. Carriage of Methicillin-Resistant Staphylococcus aureus in
Home Care Settings
Lucet JC Arch Intern Med. 2009;169(15):1372-1378
Variables Associated With MRSA Carriage at Hospital Discharge to Home Health
Care
14.5%
eRisk categories for MRSA carriage were as follows: low risk: hematologic, orthopedic, or AIDS diagnosis; moderate
risk: cancer diagnosis; substantial risk: cardiovascular or other diagnosis; and high risk: neurologic diagnosis.
22. Carriage of Methicillin-Resistant Staphylococcus
aureus in Home Care Settings
Lucet JC Arch Intern Med. 2009;169(15):1372-1378
Time to methicillin-resistant Staphylococcus aureus (MRSA) clearance in 148
MRSA carriers admitted to home health care then monitored for 1 year.
23. Multidrug-resistant gram-negative bacteria at a long-term
care facility: assessment of residents, healthcare workers,
and inanimate surfaces
O’Fallon E, ICHE 2009;30:1172-9
• Point-prevalence study in 4 separate wards at a 600-bed urban LTCF
that was conducted from October 31, 2006 through February 5, 2007.
• 161 LTCF residents and 13 HCWs
• Nasal and rectal samples were obtained for culture from each resident,
selected environmental surfaces in private and common rooms, and the
hands and clothing of HCWs in each ward.
• A total of 37 (22.8%), 1 (0.6%), and 18 (11.1%) residents were colonized
with MDR gram-negative bacteria, VRE, and MRSA, respectively.
• MDR gram-negative bacteria were also found in the environment and in
HCWs
• Molecular typing identified clonally related MDR gram-negative strains
in LTCF residents
• Common areas in LTCFs may provide a unique opportunity for person-
to-person transmission of MDR gram-negative bacteria
24. Clinical impact of broad-spectrum empirical antibiotic therapy in patients with
healthcare-associated pneumonia: a multicenter interventional study
Falcone M, Corrao S, Licata G, Serra P, Venditti M Intern Emerg Med 2012
Distribuzione geografica dei centri partecipanti del secondo studio SIMI
25. Clinical impact of broad-spectrum empirical antibiotic therapy in patients with
healthcare-associated pneumonia: a multicenter interventional study
Falcone M, Corrao S, Licata G, Serra P, Venditti M
Intern Emerg Med 2012
Criteri di diagnosi di HCAP pre e post intervento
26. Clinical impact of broad-spectrum empirical antibiotic therapy in patients with
healthcare-associated pneumonia: a multicenter interventional study
Falcone M, Corrao S, Licata G, Serra P, Venditti M Intern Emerg Med 2012
Caratteristiche dei pazienti arruolati
u
Variabile Pre Post p
intervento intervento
Scompenso cardiaco 37% 21% 0.009
Insufficienza renale 25% 40% 0.044
Impegno bilaterale a rx torace 34% 19% 0.014
Variabili non singnificative
Età, sesso, BPCO, demenza, diabete mellito, malnutrizione, neoplasia e malattia cronica
epatica, presenza di 2 o più comorbidità, diagnosi etiologica, depressione del sensorio,
anti H2, aerosol-terapia, febbre, dispnea, tosse,espettorazione purulenta, dolore toracico
tipo pleurico, leucopenia, leucocitosi, infiltrati multilobari, versamento pleurico,
precedente intubazione (30 giorni), tracheostomia, possibile polmonite da aspirazione
27. Clinical impact of broad-spectrum empirical antibiotic therapy in patients with
healthcare-associated pneumonia: a multicenter interventional study
Falcone M, Corrao S, Licata G, Serra P, Venditti M Intern Emerg Med 2012
Gravità della HCAP e della condizione clinica pre e post intervento
28. Clinical impact of broad-spectrum empirical antibiotic therapy in patients with
healthcare-associated pneumonia: a multicenter interventional study
Falcone M, Corrao S, Licata G, Serra P, Venditti M Intern Emerg Med 2012
Etiologie di HCAP pre e post intervento
29. Antibiotic Therapy of Health-Care-Associated Pneumonia: a multicenter
outcomes research interventional study
Falcone M, Corrao S, Licata G, Serra P, Venditti M & SIMI study group
Esito clinico pre e post intervento
30. Antibiotic Therapy of Health-Care-Associated Pneumonia: a multicenter
outcomes research interventional study
Falcone M, Corrao S, Licata G, Serra P, Venditti M & SIMI study group
Fattori associati a morte intraospedaliera alla analisi di regressione logistica
31. Optimizing antibiotic therapy for
HCAP
Clinical failure
Overtreatment
Increased mortality
Antibiotic resistance
Increase of costs
Broad-spectrum
antibiotics Restricted
spectrum
32. Caso Clinico
•Uomo 45 aa
•Nazionalità Rumena.
•Ex muratore.
Ricovero in Ospedale in data 26/10/2011
Motivo del ricovero:
Grave insufficienza epatica acuta ( Maddrey score >32)
iperbilirubinemica ( bilirubina totale 33 mg/dl) secondaria ad
abuso etilico recente.
33. Anamnesi Patologica Remota:
•Etilista dall’ età di 16 anni. Assumeva nell’ ultimo periodo 20-25 Unità
alcoliche /die
•Per lo stesso quadro clinico ( iperbilirubinemia associata ad insufficienza
epatica) il paziente aveva già eseguito nel mese precedente ricovero presso
altro Ospedale dove era stato trattato con Metilprednisolone 40 mg/die e
MARS terapia con scarso beneficio clinico. Alla luce di ciò veniva inserito in
lista per eventuale trapianto di fegato.
Terapia domiciliare
Omeprazolo 40 mg, Metilprednisone 40 mg , Canrenone 200 mg,
lattulosio.
34. Caso Clinico
Esame obiettivo
Nulla di rilevante all’ esame
Condizioni generali scadute
obiettivo dei vari organi ed
Vigile, Itterico. Presenza di apparati ad eccezione di una
edemi declivi bilateralmente minima quota di versamento
improntabili fino al ginocchio. ascitico.
Parametri vitali
PA 110/60 mmHg
FC 100 bpm R
FR 35 atti/min
TC 36 °C
36. Caso Clinico
27/10/2011
FR > 20 atti/ min
GB > 12000 / mm3 = SIRS
FC > 90 bpm Infezione?
Richiesta quindi consulenza infettivologica la quale consigliava “previa
esecuzione di Rx torace, prelievo paracentesi , Emocolture ed
urinocoltura …. di iniziare, alla luce del recente ricovero ospedaliero,
terapia con Imipenem 500 mg 1f ogni 6 h e Teicoplanina 400 mg 1fl
ogni 24 h , dopo carico (N.d.r il paziente aveva presentato nel ricovero
precedente infezione urinaria da E. faecium !!)”.
PS. Poiché paziente ad alto rischio per IPA considerare es.
dell’ espettorato/siero per Aspergillus spp e ricerca
galattomannano, soprattutto se esame RX torace alterato.
39. Caso Clinico
“Assenza di franchi addensamenti flogisitici o noduli
solidi patologici nel parenchima polmonare”
40. Caso Clinico
•Rx torace e TC torace negativa
•Emocolture ed urinocoltura negative.
•Paracentesi negativa per PBS.
•Veniva comunque inviato ricerca Aspergillus spp
(t. nasale; espettorato non possibile).
• Galattomannano su siero (no espettorato!).
Galattomannano eseguito il 29/10/2011
su siero 1.6 UI/dl ( valori normali Fino a 0.5) .
Positivo!!
Rx torace : Negativo!
Che fare?
41. Caso Clinico
2/11/2011
Nuova consulenza infettivologica
“Quadro clinico stabile. Al momento non segni
di infezioni in atto. Reperto di galattomannano
serico positivo. Sospendere antibiotici e
ripetere eventuale Rx torace, galattomannano e
beta-d-glucano…….”.
42. Caso Clinico 3/11/2011
“Disomogeneo addensamento parenchimale in sede basale
sinistra con obliterazione del seno costo-frenico omolaterale .”
43. Caso Clinico 3/11/2011
Galattomannano positivo su siero
Fattori di rischio
+ per Aspergillosi invasiva
+
Manifestazioni cliniche ( sintomi, segni, caratteristiche
radiologiche)
Aspergillosi Polmonare Invasiva Probabile (???!!)
Iniziava terapia con Ambisome 3 mg/ Kg ev ogni 24h.
Richieste sottopopolazioni linfocitarie. In itinere galattomannano e beta-D-
glucano su siero + ricerca Aspergillus spp nell’ espettorato……
44. Caso Clinico
In data 4/11/2011
3/11/2011 rendeva manifesta la
Paziente iniziava terapia con MARS e progressione deficit
continuava cortisone… di forza dagli arti
inferiori vs arti
superiori.
Sulla base del quadro clinico ed ENG veniva posta
diagnosi di Neuropatia periferica compatibile con
S. di Guillan- Barrè ( NB quadro NON preceduto da
episodi infettivi respiratori o gastroenterici)
45. Caso Clinico
7/11/2011
…e nonostante MARS e terapia farmacologica
Peggioramento della funzionalità epatica con INR pari a 3.3
Comparsa all’ esame obiettivo del torace di un’ottusità plessica in
sede basale sinistra con rumori di tipo discontinuo nella stessa sede. Si
ottiene dell’espettorato per esame colturale……
( pH 7.41 , pO2 55 mmHg, pCO2 32 mmHgHCO3- 20.3 mEq/L
Ulteriore peggioramento della neuropatia periferica
46. Caso Clinico
XI giornata di ricovero ( IV di terapia con Ambisome)
Paziente andava incontro a MOF …….
Il paziente decide d i fare ritorno a domicilio
Post- mortem
Exitus del Esame colturale espettorato
paziente in XII positivo per Aspergillus spp.
β- D glucano >523
giornata dal
Galattamano su siero 3.2
ricovero linfociti T CD4+ 234/mmc
47. Aspergillus
Catalogato nel 1729 dal sacerdote e biologo italiano
Pier Antonio Micheli
La vista dei funghi al microscopio gli
fece venire in mente la forma di un
ASPERSORIO (latino aspergillum)
48. “Multiple formazioni nodulari solide a margini regolari e
densità disomogenea con livelli idro-aerei
Multiple formazioni nodulari satelliti
Diffusi addensamenti parenchimali a vetro smerigliato”
49. Invasive aspergillosis in patients with liver disease
Falcone M, Massetti AP, Russo A, Vullo V, Venditti M
Medical Mycology december issue, 2010 Early Online
Pazienti con aspergillosi invasiva in due diversi periodi: 1973-99 vs 2000-
09
caratteristica 1972-99 2000-09
(n=31) (n=41)
maschi, età media 71%; 42 aa 71%, 48
aa
Cirrosi avanzata 19% 71%
Danno epatico acuto 64% 29%
Steroidi 71% 49%
Infezione disseminata 48% 17%
Infezione polmonare (sola) 51% 78%
Infezione SNC 42% 19%
Infezione cardiaca 19% 7%
Terapia antifungina 23% 68%
Morti 67% 58%
Diagnosi post mortem 84% 41%
50. Invasive aspergillosis in patients with liver disease
Falcone M, Massetti AP, Russo A, Vullo V, Venditti M
Medical Mycology december issue, 2010 Early Online
Deficit immunologici pro-Aspergillus nei pazienti con danno epatico
Depressione della immunità umorale
Depressione della immunità cellulomediata
• CD 4 in CP-A: 515/uL
• CD4 in CP-B: 514/uL
• CD4 in CP-C: 307/uL
• Soggetti sani: 1313/uL
Depressione della fagocitosi in CP-B e C
• Quantitativa
• Qualitativa
• Ridotta migrazione PMN
51. Corticosteroidi e aspergillosi
Gli steroidi sono un fattore di crescita per Aspergillus
Lionakis et al. Lancet 2003; 362:1828– Ng et al. Microb 1994; 140:2475–79
52.
53. Principali patogeni nelle IAI
Primarie: Enterobacteriaceae
Streptococcus pneumoniae
Secondarie: Generalmente polimicrobiche Enterobacteriacae
Anaerobi
Streptococchi
S. aureus
Terziarie: Enterobacteriaceae
Anaerobi
Stafilococchi
Enterococchi
P. aeruginosa
Candida spp.
55. Approach to the management of suspected spontaneous bacterial
peritonitis
IMMEDIATE
THERAPY
56. SPONTANEOUS BACTERIAL PERITONITIS
A unique term for different clinical conditions …
Diagnosis Features Comments
PMN > 250
SPB cell/mcl To be treated
Culture positive
Culture-negative neutrocytic PMN > 250 Behaves similar to SPB
ascites cell/mcl
To be treated
Culture negative
PMN < 250 30-40% will progress to
Bacterascites cell/mcl SPB
Culture positive To be strictly observed
PMN > 5000 Due to abdominal
Secondary Peritonitis cell/mcl perforation
Culture positive To be operated
Runyon B Hepatology 2004; 39: 1-16
Strauss E & Caly WR Expert Rev Anti Infect Ther 2006; 4: 249-250
57. Main results of controlled, randomized trials in the treatment of SBP
58. Microbiology of SBP
Increasing frequency of Gram-positive bacteria in spontaneous bacterial
peritonitis Cholongitas E et al, Liver International 2005: 25: 57–61
1998–1999
anaerobes 1998-2002
gram pos 5% Enterobacteriaceae 45,2%
20% Enterococcus spp 16,6
2000–2002
CoNS 14,3
75% NFGN rods 9,5
gram neg gram pos
Streptococcus spp 7,2 41%
59%
S. aureus 4,8
gram neg
anaerobes 2,4
59. Nosocomial Spontaneous Bacterial Peritonitis and Bacteremia in Cirrhotic
Patients: Impact of Isolate Type on Prognosis and Characteristics of Infection
Campillo B et al. Clin Infect Dis, 2002;35:1-10
Types of bacteria isolated from cultures of ascitic fluid
N and blood samples
S. aureus (85% MRSA) 83
Enterobacteriaceae 71 ASCITIC FLUID
BLOOD
Streptcoccus spp 63
Enterococcus spp 52
NFGN rods 16
CoNS 12
Anaerobes 4
60. Nosocomial Spontaneous Bacterial Peritonitis and Bacteremia in Cirrhotic
Patients: Impact of Isolate Type on Prognosis and Characteristics of Infection
Campillo B et al. Clin Infect Dis, 2002;35:1-10
63 episodes of SBP occurred in pts treated with prophylaxis
with quinolones …
pathogens
61. Nosocomial Spontaneous Bacterial Peritonitis and Bacteremia
in Cirrhotic Patients: Impact of Isolate Type on Prognosis and
Characteristics of Infection
Campillo B et al. Clin Infect Dis, 2002;35:1-10
Variables associated with mortality in
multivariate analysis
Variable OR 95% CI p
Older age 1.045 1.013–1.078 .0048
higher Child-Pugh score 1.372 1.134–1.659 .0011
infection due to staphylococci 2.845 1.421–5.695 .0031
62. MICROBIOLOGY of PERITONITIS
Primary Secondary Tertiary
Peritonitis Peritonitis peritonitis
Enterobacteriacea Enterobacteriacea Enterobacteriacea
e e e
S. aureus Anaerobic bacteria Anaerobic bacteria
Enterococci Viridans Enterococci
streptococci
Candida spp Candida spp
Non-fermentative
gram negative
ESBL risk ? rods
Candida risk?
63. Letalità a 21 giorni in 97 batteriemie da
enterobacteriaceae in rapporto
alla terapia antibiotica iniziale con agenti attivi in vitro
Antibiotico n. casi % sopravvissuti p
Aminoglicoside 20 75 0.40
BL/BL inibitore 33 87 0.24
Carbapenem OK! 28 96 .01
Ciprofloxacina KO! 16 50 <.001
Tumbarello M et al Antimicrob Agents Chemother 51:1987, 2007
64. Uso di antibiotici e antibiotico
resistenza in un ospedale di New York
1995 1996 % cambio
Cefalo III (grammi) 5558 1106 - 80*
Imipenem (grammi) 197 474 + 141
Ceftazidime-resistenti
K. pneumoniae 150 84 - 44*
Per 1,000 gg osped 0.75 0.48 - 36
MDR
K. pneumoniae 8 0
Imipenem-resistenti
P. aeruginosa 67 113 + 69†
*P < 0.001
†
P < 0.01 Rahal JJ et al. JAMA. 1998;280:1233-1237.
65. Relazione tra consumo antibiotico e
antibioticoresistenza in P. aeruginosa
Imipenem consumption (DDDs)
Imipenem resistance (%)
Lepper PM et al. Antimicrob Agents Chemother. 2002;46:2920-2925.
66. Possibile selezione di BGN antibiotico-resistenti
nei reparti ad alto rischio infettivo
abuso cefalo III gen
Cef -R P.aeruginosa Klebsiella ESBL+
E.coli ESBL+
Enterobacter
Citrobacter
Maggior impiego Carbapenem
Enterobacter, Klebsiella spp, E. coli, Proteus spp
VIM1 o KPC positive
Carba-R P.aeruginosa S.maltophilia Carba-R Acinetobater
67.
68. HOW TO DEPLOY TIGECYCLINE ?
One of the most attractive applications
seems to be in the ABDOMINAL
SURGICAL SETTING where the likely
pathogens include Enterobacteriaceae,
streptococci and anaerobes, as well as
Enterococci and MRSA. No other single
agent covers this spectrum.
69. Le infezioni gravi in Italia: dati su 5115
ceppi isolamenti
Resistenza di P. aeruginosa a: Comunitarie Nosocomiali
604
649
Carbapenem >=35-40%
355
465 276 267
Piperacillina<=20%
200 44
297 176 169
262
159 141 111
97 78 90 72
69 70 44 24
16
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S. aer
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Se
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P. che roc . ep Kle t ero toc A. S.
Es te S En ep
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Progetto Infezioni Gravi 2004 – Fadda, Nicoletti, Schito, ISS
70. INDUZIONE DELLA RESISTENZA
ANTIBIOTICA
Cefalo III >= Carba
> Pip & amox/clav
>pip/tazo & ampi/sulba
SPETTRO DELLA RESISTENZA
INDOTTA
Carba > Cefalo III
> Pip & amox/clav
>pip/tazo & ampi/sulba
71. < selezione di P/T,A/S e A/a.Cl
POSSIBILE SELEZIONE DI PATOGENI ANTIBIOTICO RESISTENTI IN REPARTI AD
POSSIBILE SELEZIONE DI PATOGENI ANTIBIOTICO RESISTENTI IN REPARTI AD
ELEVATO RISCHIO INFETTIVO. I.
ELEVATO RISCHIO INFETTIVO. I.
Cefalosporina 3^ gen
Cefalosporina 3^ gen
abuso
abuso
CR P.aeruginosa
CR P.aeruginosa Klebsiella-ESBL+
Klebsiella-ESBL+ MSSA
MSSA Enterococcus
Enterococcus
E.coli-ESBL+
E.coli-ESBL+ MRSA
Enterobacter
Enterobacter
>> FQ
MRSA
vancomicina
vancomicina
Citrobacter
Citrobacter
selezione
selezione
GISA
GISA VRE
VRE
imipenem
imipenem
IR P.aeruginosa S.maltophilia
S.maltophilia IR Acinetobacter
IR Acinetobacter
72. < selezione con pip/tazo
POSSIBILE SELEZIONE DI PATOGENI ANTIBIOTICO RESISTENTI IN REPARTI AD
POSSIBILE SELEZIONE DI PATOGENI ANTIBIOTICO RESISTENTI IN REPARTI AD
ELEVATO RISCHIO INFETTIVO. I.
ELEVATO RISCHIO INFETTIVO. I.
Cefalosporina 3^ gen
Cefalosporina 3^ gen
abuso
abuso
CR P.aeruginosa
CR P.aeruginosa Klebsiella-ESBL+
Klebsiella-ESBL+ MSSA
MSSA Enterococcus
Enterococcus
E.coli-ESBL+
E.coli-ESBL+ MRSA
MRSA
Enterobacter
Enterobacter vancomicina
vancomicina
Citrobacter
Citrobacter
selezione
selezione
GISA
GISA VRE
VRE
imipenem
imipenem
Tranne P. aeruginosa:
Tigeciclina OK
IR P.aeruginosa S.maltophilia
S.maltophilia IR Acinetobacter
IR Acinetobacter
73. Emergence of Carbapenem Resistance
in K. pneumoniae: Mediterranean Area
2006 2007
33% 42%
Strains often co-producing ESBL 11% 22%
and showing an XDR phenotype (S
to tigecyline and colistin only)
Psichogiou et al. – JAC 2008 EARSS database.
74. Uso di antibiotici & resistenza
antibiotica
30 800
Ceftazidime resistenza Ceftazidime uso
Pip/Tazo resistenza Pip/Tazo uso 700
25
Grammi di ceftazidime
Grammi di ceftazidime
600
20
500
15 400
300
10
az ne s ser %
200
5
100
t i
0 0
Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4
94 95 96 97
Piperacillin/tazobactam non è appropriato per le
infezioni riconosciute da germi ESBL + Rice LB. Pharmacotherapy. 1999;19:120S-128S.
75. Relation Between Imipenem Consumption
and New Patients Colonized or Infected
with A. baumannii
DDD carbapenem use/100 ICU hospitalization-days
No. of cases/100 ICU admissions
DDD = Defined daily doses of.
Corbella X et al. J Clin Microbiol. 2000;38:4086-4095.
77. I 10 punti di C. difficile
1. Agente della colite da antibiotici (tutti gli antibiotici
possono esserne causa)
2. Principale causa di colite nosocomiale
Ma c’è dell’altro!
3. Le spore sono estremamente diffusibili
Aumentano i casi dopo
4. Possibili microepidemie ospedaliere
5. Principale causa di leucocitosi neutrofila di ndd
trattamento con i
insorgente in ospedale
6. Talvolta autolimitantesi, altre volte evolve vs
chinoloni e………
megacolon tossico
7. Diagnosi ricerca della tossina A, oppure A & B……
8. Terapia: metronidazolo o vancomicina per os per 10
gg
9. Occhio alle recidive. Le spore sono antibiotico
resistenti
10. Occhio cheospedali fino al di colite A-B+!!!!!
in alcuni aumentano i casi 50% di A-B+
78. Pépin J. CMAJ. 2004
1991 1721 casi 2003
866/100,000
Inc>65 aa.
102/100,000
156/100,000
Inc. Gen.
35/100,000
79. Pépin J. CMAJ. 2004
1991 1721 casi 2003
14%
morti 30d
5%
18%
Complicazioni
7%
80.
81. "Bacteria are
cleaverer than men"
H.C. Neu
Professor and Chief of Internal Medicine
Professor and Chief of Internal Medicine
Columbia University
Columbia University
Science, 1992
Science, 1992
82. Cirrhotic Patients Are at Risk for Health Care–
Associated Bacterial Infections
Merli M et al Clin Gastoenterol Hepatol 2010;8:979–985
Clinical Complications in 150 Cirrhotic Patients With and Without Infections
83. Cirrhotic Patients Are at Risk for Health Care–
Associated Bacterial Infections
Merli M et al Clin Gastoenterol Hepatol 2010;8:979–985
Clinical Complications in 150 Cirrhotic Patients With and Without Infections
Notes de l'éditeur
Rahal et al reported on restriction of third-generation cephalosporin use, which was followed by a reduction in the frequency of isolation of ESBL-producing K. pneumoniae by 44% overall (a 70.9% reduction in all ICUs combined and especially an 87.5% reduction in the surgical ICU). Restriction of ceftazidime, cefotaxime, and ceftriaxone was accomplished by requiring approval by an infectious disease physician. To reduce the use of third-generation cephalosporins as measured in grams, a carbapenem was selected as a replacement therapeutic agent. The result was an increase in the use of imipenem as measured in grams (+141%). The absolute number of patient-related ceftazidime-resistant Klebsiella isolates decreased from 150 in 1995 to 84 in 1996. However, there was also an unintended consequence, as shown by a 68.7% increase in the incidence of imipenem-resistant P. aeruginosa . Use of this slide is mandatory.
Lepper et al studied the impact of antibiotic use on resistance rates in P. aeruginosa . From 1997 to 2000, the authors monitored the consumption of -lactam and other antibiotics in a 600-bed community hospital in Germany. As can be seen in this slide, the rates of resistance of P. aeruginosa to imipenem showed a time course similar to figures for imipenem consumption. Consumption of either ceftazidime or piperacillin/tazobactam had no apparent association with resistance. Periods of imipenem use were also significantly associated with resistance to ceftazidime and piperacillin/tazobactam. The authors concluded that a written antibiotic policy that balances the use of various antibiotic classes may help avoid disturbances of a hospital’s microbial sensitivity patterns. Use of this slide is mandatory.
Ref 4/EARSS/p.60A
The increased use of piperacillin/tazobactam and the decreased use of ceftazidime resulted in a slow decrease in the incidence of ceftazidime-resistant K. pneumoniae . The percent of patients colonized or infected with the ceftazidime-resistant K. pneumoniae declined from 28% to 10.2% ( P < 0.05). Since piperacillin/tazobactam has been used, there has not been an increase in the prevalence of K. pneumoniae resistant to piperacillin/tazobactam. This reflects updated data from the Cleveland VA, beginning with the original outbreak and following the resistance profile through September 1997, a period of 4 years. The reduction in use of ceftazidime and increasing use of piperacillin/tazobactam (represented by the black [ceftazidime] and magenta [piperacillin/tazobactam] lines, respectively) resulted in a reduction of ESBL-producing isolates of K. pneumoniae and an overall reduction in resistance to both ceftazidime (orange bars) and piperacillin/tazobactam (blue bars). Further use of piperacillin/tazobactam and continued minimization of ceftazidime use did not result in increasing resistance to piperacillin/tazobactam. On the contrary, as the results indicate, resistance rates to ceftazidime and piperacillin/tazobactam decreased significantly for both antimicrobial agents. Use of this slide is mandatory.
Beginning in 1992, a sustained outbreak of multiresistant, imipenem-sensitive A. baumannii infections was noted in a 1,000-bed hospital in Barcelona, Spain. High use of imipenem followed and by 1997 carbapenem-resistant strains emerged. As a result, the authors conducted a prospective 18-month intervention trial aimed at the identification of the clinical and microbiological epidemiology of the outbreak and its response to a multicomponent infection-control strategy. The interventions included the restriction of carbapenem antibiotics and strict compliance with infection control. Results showed that patients who had previously received imipenem or those patients who were admitted to a ward with a high density of patients infected with A. baumannii were at significantly greater risk for developing either colonization or infection with carbapenem-resistant A. baumannii . These interventions resulted in a sharp drop in the incidence of both colonization and infection with multidrug-resistant A. baumannii. Use of this slide is mandatory.
1. This slide illustrates the media frenzy in Montreal in June of this year and what I would like to present today is the story behind these headlines.
1. This slide illustrates the media frenzy in Montreal in June of this year and what I would like to present today is the story behind these headlines.