呼吸机相关性肺炎（VAP）的流行病学及预防（英文PPT）Prevention of Ventilator Associated Pneumonia (VAP）.ppt

1、Tracking NI has become difficult,Shorter inpatient stays (average postoperative stay, now approximately 5 days, is usually shorter than the 5- to 7-day incubation period for S. aureus surgical wound infections) Surveillance systems are optional to hospitals with infection-control programs,Prevention

2、 of Ventilator Associated Pneumonia (VAP),AACN VAP Practice Alert,Lecture Content,Epidemiology of VAP Prevention strategies HOB elevation Ventilator equipment changes Continuous removal of subglottic secretions Handwashing,AACN VAP Practice Alert,Epidemiology of Ventilator Associated Pneumonia (VAP)

3、,AACN VAP Practice Alert,Nosocomial Pneumonias,Account for 15% of all hospital associated infections Account for 27% of all MICU acquired infections Primary risk factor is mechanical ventilation (risk 6 to 21 times the rate for nonventilated patients),CDC Guideline for Prevention of Healthcare Assoc

4、iated Pneumonias 2003 Cook et al, Ann Intern Med 1998;129:433,AACN VAP Practice Alert,Critical Care Interventions Increase Susceptibility to Nosocomial Pneumonias,Tracheal Colonization,Altered Host Defenses,Increased Nosocomial Pneumonias,Intubation,AACN VAP Practice Alert,VAP Etiology,Most are bact

5、erial pathogens, with Gram negative bacilli common: Pseudomonas aeruginosa Proteus spp Acinetobacter spp Staphlococcus aureus Early VAP associated with non-multi-antibiotic-resistant organisms Late VAP associated with antibiotic-resistant organism,AACN VAP Practice Alert,Significance of Nosocomial P

6、neumonias,Mortality ranges from 20 to 41%, depending on infecting organism, antecedent antimicrobial therapy, and underlying disease(s) Leading cause of mortality from nosocomial infections in hospitals,CDC Guideline for Prevention of Healthcare Associated Pneumonias 2003 Heyland et al, Am J Respir

7、Crit Care Med 1999;159:1249 Bercault et al, Crit Care Med 2001;29:2303,AACN VAP Practice Alert,Significance of Nosocomial Pneumonias,Increases ventilatory support requirements and ICU stay by 4.3 days Increases hospital LOS by 4 to 9 days Increases cost -,Heyland et al, Am J Respir Crit Care Med 199

8、9;159:1249 Craven D. Chest 2000;117:186-187S Rello et al, Chest 2002;122:2115,AACN VAP Practice Alert,VAP Prevention,AACN VAP Practice Alert,Continuous Removal of Subglottic Secretions,Use an ET tube with continuous suction through a dorsal lumen above the cuff to prevent drainage accumulation,CDC G

9、uideline for Prevention of Healthcare Associated Pneumonias 2003 Kollef et al, Chest 1999;116;1339,AACN VAP Practice Alert,HOB Elevation,HOB at 30-45o,CDC Guideline for Prevention of Healthcare Associated Pneumonias 2003 Drakulovic et al, Lancet 1999;354:1851,Frequency of Equipment Changes,Ventilato

10、r Tubing,Inner Cannulas of Trachs,Ambu Bags,No Routine Changes,Not Enough Data,Between Patients,CDC Guideline for Prevention of Healthcare Associated Pneumonias 2003,AACN VAP Practice Alert,Handwashing,What role does handwashing play in nosocomial pneumonias?,Albert, NEJM 1981; Preston, AJM 1981; Ta

11、blan, 1994,AACN VAP Practice Alert,VAP Prevention,All recommendations are level IA,CDC Guideline for Prevention of Healthcare Associated Pneumonias 2003 AACN Practice Alert for VAP, 2004,Wash hands before and after suctioning, touching ventilator equipment, and/or coming into contact with respirator

12、y secretions.,AACN VAP Practice Alert,Use a continuous subglottic suction ET tube for intubations expected to be 24 hours Keep the HOB elevated to at least 30 degrees unless medically contraindicated,VAP Prevention,All recommendations are level II,CDC Guideline for Prevention of Healthcare Associate

13、d Pneumonias 2003 AACN Practice Alert for VAP, 2004,AACN VAP Practice Alert,No Data to Support These Strategies,Use of small bore versus large bore gastric tubes Continuous versus bolus feeding Gastric versus small intestine tubes Closed versus open suctioning methods Kinetic beds,CDC Guideline for

14、Prevention of Healthcare Associated Pneumonias 2003,AACN VAP Practice Alert,Potential consequences of inappropriate antibiotic therapy,Inappropriate empiric antibiotic therapy can lead to increases in: mortality morbidity length of hospital stay cost burden resistance selection,Inappropriate antibio

15、tic therapy,Inappropriate antibiotic therapy can be defined as one or more of the following: ineffective empiric treatment of bacterial infectionat the time of its identification the wrong choice, dose or duration of therapy use of an antibiotic to which the pathogen is resistant,Evidence of improve

16、d clinical outcomes with appropriate empiric antibiotic therapy,A number of studies have demonstrated the benefits of early use of appropriate empiric antibiotic therapy for patients with nosocomial infections Several key clinical studies are reviewed in the following slides,Inappropriate antibiotic

17、 therapy is a risk factor for mortality among patients in the intensive care unit (ICU),Infection-related mortality rates were assessed in a prospective cohort, single-centre study of 2000 patients admitted to medical/surgical ICUs 655 patients had a clinically recognised infection: 442 (67.5%) had

18、a community-acquired infection 286 (43.7%) developed a nosocomial infection 73 (11.1%) had both community-acquired and nosocomial infections 169 (25.8%) patients received inappropriate initial antimicrobial treatment,Kollef et al. Chest 1999;115:462474,Inappropriate antibiotic therapy is a risk fact

19、or for mortality among patients in the ICU,Kollef et al. Chest 1999;115:462474,Hospital mortality (%),0,20,50,60,Appropriate therapy,Inappropriate therapy,40,30,10,All causes,Infectious disease-related,p0.001,p0.001,Mortality type,Appropriate antibiotic therapy reduces mortality and complications in

20、 patients with nosocomial pneumonia,The frequency of and reasons for changing empiric antibiotics during the treatment of hospital-acquired pneumonia were assessed in a prospective multicentre study across30 Spanish hospitals Of the 16 872 patients initially enrolled, 530 developed565 episodes of pn

21、eumonia after ICU admission Empiric antibiotics (administered in 490 86.7% of episodes) were modified in 214 (43.7%) cases because of: isolation of micro-organism not covered by treatment (62.1%) lack of clinical response (36.0%) development of resistance (6.6%),Alvarez-Lerma et al. Intensive Care M

22、ed 1996;22:387394,Alvarez-Lerma et al. Intensive Care Med 1996;22:387394,Appropriate antibiotic therapy reduces mortality and complications in patients with nosocomial pneumonia,Appropriatetherapy (n=284),Attributable mortality No. complications/patient Shock Gastrointestinal bleeding Respiratory fa

23、ilure Multiple organ failure Extrapulmonary infection,Inappropriatetherapy (n=146),p-value,16.2% 1.73 1.82 17.1% 10.7% 24.9% 12.5% 13.2%,24.7% 2.25 1.98 28.8% 21.2% 32.2% 21.2% 17.1%,0.04 0.001 0.005 0.003 NS NS NS,Appropriate early antibiotic therapy reduces mortality rates in patients with suspect

24、ed ventilator-associated pneumonia (VAP) (Study 1),A prospective observation and bronchoscopy study of patients with VAP assessed the impact of bronchoalveolar lavage (BAL) data on the selection of antibiotics and clinical outcomes in a medical/surgical ICU 132 mechanically ventilated patients (hosp

25、italised72 hours) with clinically confirmed VAP underwentBAL within 24 hours of diagnosis 107 patients received antibiotics prior to bronchoscopy 25 patients received antibiotics immediately after bronchoscopy Mortality rates were assessed in relation to the adequacy and time of initiation of antibi

26、otic therapy,Luna et al. Chest 1997;111:676685,Luna et al. Chest 1997;111:676685,Appropriate early antibiotic therapy reduces mortality rates in patients with suspected VAP(Study 1),Mortality (%),Pre-BAL,Post-BAL,Post-cultureresult,0,60,100,20,40,80,p0.001,Appropriate antibiotic,No antibiotic,Inappr

27、opriate antibiotic,Appropriate early antibiotic therapy reduces mortality rates and length of hospital stay in patients with bloodstream infection (Study 1),An observational prospective cohort study of patients with bloodstream infection examined whether appropriate antibiotic therapy improved survi

28、val rate Of the 3413 evaluable patients, 2158 (63%) received early appropriate antibiotics defined as starting within 2 days of the first positive blood culture, and if the causative pathogen was susceptiblein vitro to the administered drug Mortality rates and median duration of hospital stay for su

29、rviving patients were determined,Leibovici et al. J Intern Med 1998;244:379386,Appropriate early antibiotic therapy reduces mortality rates and length of hospital stay in patients with bloodstream infection (Study 1),Leibovici et al. J Intern Med 1998;244:379386,Appropriatetherapy (n=2158),Mortality

30、 rate Median duration of hospital stay,Inappropriatetherapy (n=1255),p-value,20.2% 9 days(range 0117),34.4% 11 days(range 0209),0.0001 0.0001,Summary,Clinical evidence suggests that early use of appropriate empiric antibiotic therapy improves patient outcomes in terms of: reduced mortality reduced m

31、orbidity reduced duration of hospital stay,Resistance to antibacterial agents,Antibiotic resistance either arises as a result of innate consequences or is acquired from other sources Bacteria acquire resistance by: mutation: spontaneous single or multiple changes in bacterial DNA addition of new DNA

32、: usually via plasmids, which can transfer genes from one bacterium to another transposons: short, specialised sequences of DNA that can insert into plasmids or bacterial chromosomes,Mechanisms of antibacterial resistance (1),Structurally modified antibiotic target site, resulting in: reduced antibi

33、otic binding formation of a new metabolic pathway preventing metabolism of the antibiotic,Structurally modified antibiotic target site,Interior of organism,Cell wall,Target site,Binding,Antibiotic,Antibiotics normally bind to specific binding proteins on the bacterial cell surface,Structurally modif

34、ied antibiotic target site,Interior of organism,Cell wall,Modified target site,Antibiotic,Changed site: blocked binding,Antibiotics are no longer able to bind to modified binding proteins on the bacterial cell surface,Mechanisms of antibacterial resistance (2),Altered uptake of antibiotics, resultin

35、g in: decreased permeability increased efflux,Altered uptake of antibiotics: decreased permeability,Interior of organism,Cell wall,Porin channel into organism,Antibiotic,Antibiotics normally enter bacterial cells via porin channels in the cell wall,Altered uptake of antibiotics: decreased permeabili

36、ty,Interior of organism,Cell wall,New porin channel into organism,Antibiotic,New porin channels in the bacterial cell wall do not allow antibiotics to enter the cells,Altered uptake of antibiotics: increased efflux,Interior of organism,Cell wall,Porin channel through cell wall,Antibiotic,Entering,En

37、tering,Antibiotics enter bacterial cells via porin channels in the cell wall,Altered uptake of antibiotics: increased efflux,Interior of organism,Cell wall,Porin channel through cell wall,Antibiotic,Entering,Exiting,Active pump,Once antibiotics enter bacterial cells, they are immediately excluded fr

38、om the cellsvia active pumps,Mechanisms of antibacterial resistance (3),Antibiotic inactivation bacteria acquire genes encoding enzymes that inactivate antibiotics Examples include: -lactamases aminoglycoside-modifying enzymes chloramphenicol acetyl transferase,Antibiotic inactivation,Interior of or

39、ganism,Cell wall,Antibiotic,Target site,Binding,Enzyme,Inactivating enzymes target antibiotics,Antibiotic inactivation,Interior of organism,Cell wall,Antibiotic,Target site,Binding,Enzyme,Enzymebinding,Enzymes bind to antibiotic molecules,Antibiotic inactivation,Interior of organism,Cell wall,Antibi

40、otic,Target site,Enzyme,Antibioticdestroyed,Antibiotic altered, binding prevented,Enzymes destroy antibiotics or prevent binding to target sites,Many pathogens possess multiple mechanisms of antibacterial resistance,+,Quinolones,+,Trimethoprim,+,Sulphonamide,+,Macrolide,+,Chloramphenicol,+,Tetracycl

41、ine,+,+,Aminoglycoside,+,Glycopeptide,+,+,+,-lactam,Modified target,Altered uptake,Drug inactivation,Focus on -lactam antibiotic resistance mechanisms,Three mechanisms of -lactam antibiotic resistance are recognised: reduced permeability inactivation with -lactamase enzymes altered penicillin-bindin

42、g proteins (PBPs),Multiple antibiotic resistance mechanisms: the -lactams,-lactam antibiotic resistance,AmpC and extended-spectrum -lactamase (ESBL) production are the most important mechanisms of -lactam resistance in nosocomial infections The antimicrobial and clinical features of these resistance

43、 mechanisms are highlighted in the following slides,-lactam resistance:AmpC -lactamase production,Worldwide problem: incidence increased from 1723% between 1991 and 2001 in UK Very common in Gram-negative bacilli AmpC gene is usually sited on chromosomes, but can be present on plasmids Enzyme produc

44、tion is either constitutive (occurring all the time) or inducible (only occurring in the presence of the antibiotic),Pfaller et al. Int J Antimicrob Agents 2002;19:383388 Sader et al. Braz J Infect Dis 1999;3:97110; Livermore et al. Int J Antimicrob Agents 2003;22:1427,-lactam resistance: ESBL produ

45、ction,An increasing global problem Found in a small, expanding group ofGram-negative bacilli, most commonly the Enterobacteriaceae spp. Usually associated with large plasmids Enzymes are commonly mutants of TEM- andSHV-type -lactamases,Jones et al. Int J Antimicrob Agents 2002;20:426431 Sader et al.

46、 Diagn Microbiol Infect Dis 2002;44:273280,Antimicrobial features of ESBLs,Inhibited by -lactamase inhibitors Usually confer resistance to: first-, second- and third-generation cephalosporins(eg ceftazidime) monobactams (eg aztreonam) carboxypenicillins (eg carbenicillin) Varied susceptibility to pi

47、peracillin/tazobactam Typically susceptible to carbapenems and cephamycins Often clinically and/or microbiologically non-susceptible to fourth-generation cephalosporins,Clinical features of ESBLs,Even if sensitive to fourth-generation cephalosporinsin vitro, treatment failures occur in clinical prac

48、tice Create clinical difficulties due to cross-resistance with other antibiotic classes (eg aminoglycosides) Associated with nosocomial outbreaks of high morbidity and mortality Result in overuse of other broad-spectrum agents,Clinical failure in the presence of ESBLs,Recent data show high clinical

49、failure rates among patients treated with cephalosporins for serious infections caused by ESBL-producing pathogens susceptible to cephalosporins in vitro 4/32 patients received cephalosporins to which pathogens showed intermediate susceptibility and all failed treatment 15/28 remaining patients with

50、 cephalosporin-susceptible pathogens failed treatment and 4 died 11 patients required a change in antibiotic therapy,Paterson et al. J Clin Microbiol 2001;39:22062212,Patients who failed cephalosporin therapy for serious infections due to ESBL-producing organisms,Paterson et al. J Clin Microbiol 200

51、1;39:22062212,Clinical failure rate (%),0,60,100,20,1,40,80,2,4,8,Cephalosporin MIC (g/mL),Features of methicillin-resistant Staphylococcus aureus (MRSA),Introduction of methicillin in 1959 was followed rapidly by reports of MRSA isolates Recognised hospital pathogen since the 1960s Major cause of n

52、osocomial infections worldwide contributes to 50% of infectious morbidity in ICUs in Europe surveillance studies suggest prevalence has increased worldwide, reaching 2550% in 1997,Jones. Chest 2001;119:397S404S,Serious infections testing positive for MRSA isolates among hospitalised patients (1997 S

53、ENTRY data),Patients (%),0,30,50,10,Pneumonia,20,40,UTI,Wound,Bloodstream,Infection type,Jones. Chest 2001;119:397S404S,UTI,UTI = urinary tract infection,Features of MRSA: epidemic strains,Problem escalated in the early 1980s with emergence of epidemic strains (EMRSA) first recognised in the UK 17 E

54、MRSAs identified to date Impact on hospitals is variable presence of EMRSA can account for 50% of S. aureus isolates,Aucken et al. J Antimicrob Chemother 2002;50:171175,Risk factors for colonisation or infection with MRSA in hospitals,Chambers. Emerg Infect Dis 2001;7:178182,Admission to an ICU,Surg

55、ery,Prior antibiotic exposure,Exposure to an MRSA-colonised patient,Emergence of MRSA in the community,MRSA in hospitals leads to an associated rise in incidence in the community Community-acquired MRSA strains may be distinct from those in hospitals In a hospital-based study, 40% of MRSA infections

56、 were acquired prior to admission Risk factors for community acquisition included: recent hospitalisation previous antibiotic therapy residence in a long-term care facility intravenous drug use Colonisation and transmission are also seen in individuals (including children) lacking these risk factors

57、,Hiramatsu et al. Curr Opin Infect Dis 2002;15:407413 Layton et al. Infect Control Hosp Epidemiol 1995;16:1217; Naimi et al. 2003;290:29762984,Antimicrobial features of MRSA (1),Mechanism involves altered target site new penicillin-binding protein PBP 2 (PBP 2a) encoded by chromosomally located mecA

58、 gene Confers resistance to all -lactams Gene carried on a mobile genetic element staphylococcal cassette chromosome mec (SCCmec) Laboratory detection requires care Not all mecA-positive clones are resistant to methicillin,Hiramatsu et al. Trends Microbiol 2001;9:486493 Berger-Bachi 178:165171,Antim

59、icrobial features of MRSA (2),Cross-resistance common with many other antibiotics Ciprofloxacin resistance is a worldwide problem in MRSA: involves 2 resistance mutations usually involves parC and gyrA genes renders organism highly resistant to ciprofloxacin, with cross-resistance to other quinolones Intermediate resistance to gly