ICU获得性感染

nullnullDept of Critical Care Medicine Peking Union Medical College HospitalICU-acquired Infection and Strategy of Antibiotic TherapyCost of Hospital Stay Associated with ResistanceCost of Hospital Stay Associated with ResistanceNosocomial Infection in ICUNosocomial Infection in ICUan overall risk of 18% of acquiring an infection during ICU stay one of the most common causes of death in ICUsNosocomial Infection in ICUNosocomial Infection in ICUEuropean Prevalence of Infection in Intensive Care Study (EPIC) Held on April 29, 1992 an overall of 9567 patients from 1417 ICUsEPIC DataEPIC Dataa total of 45% of patients had an infection ICU-acquired infection 21% community-acquired infection 14% hospital-acquired infection other than ICU 10%Nosocomial Infection Vincent et al. JAMA 1995; 374: 639-644 (EPIC)Nosocomial Infection Vincent et al. JAMA 1995; 374: 639-644 (EPIC)Nosocomial Infection in ICUNosocomial Infection in ICUPredisposing risk factorsprolong length of ICU stay antibiotic usage mechanical ventilation urinary catheterizationpulmonary artery catheterization central venous access stress ulcer prophylaxis use of steroid nutritional statusNosocomial Infection in ICUNosocomial Infection in ICUNosocomial Infection in ICUNosocomial Infection in ICUUse of Antibiotics -- EPIC data of 10,038 patients, 62% received antibiotics for either prophylaxis or treatmentNosocomial Infection in ICUNosocomial Infection in ICUPrevious exposure to antibiotics modify intestinal flora, leading to colonization with resistant bacteria 3rd generation cephalosporins fluoroquinolones vancomycin favor the selection of inducible beta-lactamase producing GNB, such as Pseudomonoas aeruginosa, Enterobacter clocae, Serratia spp., and Citrobacter freundiiNosocomial Infection in ICUNosocomial Infection in ICUCommon pathogens community-acquired infection and early (< 4d) hospital-acquired infections Streptococcus pneumoniae Haemophilus influenzae Enterobacteriaceae (Escherichia coli, Proteus spp., Klebsiella pneumoniae) MSSA Streptococci anaerobesNosocomial Infection in ICUNosocomial Infection in ICUCommon pathogens late (> 4d) hospital-acquired infections Enterobacter spp. Serratia spp. ESBL-producing microorganisms Pseudomonas aeruginosa Acinetobacter spp. MRSA enterococci fungiEPIC DataEPIC Datamost common pathogens S. aureus 30% P. aeruginosa 29% Coagulase-negative staphylococci 19% E. coli 13% Enterococcus spp. 12%nullnullEmerging PathogensEmerging PathogensData from ICU, PUMCH 1999Emerging PathogensEmerging PathogensMechanism of Resistance to Beta-lactam AntibioticsMechanism of Resistance to Beta-lactam AntibioticsDepartment of Critical Care Medicine Peking Union Medical College HospitalPrinciple of beta-lactam actionPrinciple of beta-lactam actiona rigid bacterial cell wall protects bacteria from mechanical and osmotic insult beta-lactam inhibits PBPs preventing formation of the peptide bridges producing weakened wall activating cell wall degrading enzymes -- autolysin beta-lactam interferes with normal cell wall biosynthesis, causing impaired cellular function, altered cell morphology or lysisMechanism of Antibiotic ResistanceMechanism of Antibiotic ResistanceDoes beta-lactamase confer resistance?Does beta-lactamase confer resistance?The amount of enzyme products its ability to hydrolyse the antibiotic in question its interplay with the cellular permeability barriersInducible Beta-lactamaseInducible Beta-lactamasealso called class I beta-lactamase or constitutive beta-lactamase or AmpC beta-lactamase most are chromosome-mediated major producers Pseudomonas aeruginosa Enterobacter sp. Citrobacter sp. Serratia sp. Morganella morganniiInducible Beta-lactamaseInducible Beta-lactamasetransient elevation in beta-lactamase synthesis when a beta-lactam is present enzyme production returns to a low level when the inducer is removed low level insufficient to protect bacteria even against drugs rapidly hydrolysed by the enzymes enzyme hyperproducer = mutants that produce Class I enzymes continuously at a high levelInducible Beta-lactamaseInducible Beta-lactamaseInduction is lost within 4 to 6 hrs once the strong inducer is removed. Little need for concern if therapy with a strong inducer is discontinued and the drug replaced by a weak inducer.Activity of Drugs Against Organisms with Elevated Beta-Lactamase LevelsActivity of Drugs Against Organisms with Elevated Beta-Lactamase LevelsDecreased Activity Monobactams Second-, Third-generation cephalosporins Broad-spectrum penicillins Maintain Activity Imipenem, Meropenem Fourth-generation cephalosporins Ciprofloxacin, ofloxacin, etc SMZ/TMPco (except P. Aeruginosa) AminoglycosidesAntibiogram of EnterobacterAntibiogram of EnterobacterEnterobacter Bacteremia: Clinical Features and Emergence of Antibiotic Resistance during TherapyEnterobacter Bacteremia: Clinical Features and Emergence of Antibiotic Resistance during TherapyChow JW, et al Ann Int Med 1991; 115: 585-90Multiresistant EnterobacterMultiresistant Enterobacter*Antibiotics received in the 2 weeks before the initial positive blood cultureAssociation of Previously Administered Antibiotics with Multiresistant Enterobacter in the Initial Blood CultureMultiresistant EnterobacterMultiresistant EnterobacterEmergence of Resistance to Cephalosporin, Aminoglycoside, and Other Beta-Lactam Therapy* Cefotaxime, ceftazidime, ceftriaxone, ceftizoxime ** Gentamicin, tobramicin, amikacin, netilmicin *** Imipenem, piperacillin, ticarcillin, aztreonam, mezlocillin, ticarcillin-clavulanateMultiresistant EnterobacterMultiresistant EnterobacterFactors Associated with Mortality in Patients with Enterobacter BacteremiaExtended spectrum beta-lactamaseExtended spectrum beta-lactamaseMost are plasmid mediated 1 to 4 amino acid changes from broad-spectrum beta-lactamases, therefore greatly extending substrate range Major producers E. Coli (TEM) Klebsiella sp. (SHV) inhibited by beta-lactamase inhibitorsReliable (relatively) agents for ESBL-producing pathogensReliable (relatively) agents for ESBL-producing pathogensCarbapenems Amikacin Cephamycins (except MIR-1 type; 30% of strains) Beta-lactamase inhibitors pip/tazo 30% R in Chicago 1996 26% R in ICU, PUMCH 1999Antibiogram of E. coliAntibiogram of E. coliAntibiogram of KlebsiellaAntibiogram of KlebsiellaPrevalence of CAZ-R KlebsiellaPrevalence of CAZ-R KlebsiellaFrom Itokazu G, et al. Nationwide Study of Multiresistance Among Gram-Negative Bacilli from ICU patients Clinical Infectious Diseases 1996; 23: 779-85Cross-Resistance in CAZ-R KlebsiellaCross-Resistance in CAZ-R KlebsiellaFrom Itokazu G, et al. Nationwide Study of Multiresistance Among Gram-Negative Bacilli from ICU patients Clinical Infectious Diseases 1996; 23: 779-85Prevalence of ESBLPrevalence of ESBLData from Intensive Care Unit, Peking Union Medical College Hospital, 1999Cross-Resistance in CAZ-R KlebsiellaCross-Resistance in CAZ-R KlebsiellaData from Intensive Care Unit, Peking Union Medical College Hospital, 1995-1999Effect of ESBL on MortalityEffect of ESBL on MortalityAnalysis of mortality in 216 bacteremic patients caused by Klebsiella pneumoniaePatterson et al. 37th ICAAC, 1997, Abstr J-210Effect of ESBL on MortalityEffect of ESBL on MortalityPatterson et al. 37th ICAAC, 1997, Abstr J-210Empiric antibiotic therapy in 32 bacteremic patients caused by ESBL-positive Klebsiella pneumoniaeMolecular Epidemiology of CAZ-R E. Coli and K. Pneumoniae Blood IsolatesMolecular Epidemiology of CAZ-R E. Coli and K. Pneumoniae Blood IsolatesSchiappa D, et al Rush University and University of Illinois, Chicago IL Journal of infectious Diseases 1996; 174: 529-37Risk Factors for CAZ-R Klebsiella BacteremiaRisk Factors for CAZ-R Klebsiella BacteremiaCAZ-R Klebsiella BacteremiaCAZ-R Klebsiella Bacteremia* p = 0.02Outcome of Patients with CAZ-R Bacteremia Who Received Appropriate vs. Inappropriate Therapy Within 72 Hours of Bacteremic EventCeftazidime -- emergence of resistanceCeftazidime -- emergence of resistanceEmergence of Antibiotic-Resistant Pseudomonas aeruginosa: Comparison of Risks Associated with Different Antipseudomonal Agents by Carmeli Y, et al. Antimicrobial Agents and Chemotherapy 1999; 43 (6): 1379-82Ceftazidime -- emergence of resistanceCeftazidime -- emergence of resistancea 320-bed urban tertiary-care teaching hospital in Boston, Mass. 11,000 admissions per year 4 study agents with antipseudomonal activity ceftazidime, ciprofloxacin, imipenem, piperacillin a total of 271 patients (followed for 3,810 days) with infections due to P. Aeruginosa were treated with the study agents resistance emergence in 28 patients (10.2%), with an incidence of 7.4 per 1,000 patient-daysCeftazidime -- emergence of resistanceCeftazidime -- emergence of resistanceTable. Multivariable Cox hazard models for the emergence of resistance to any of the four study drugsClassification of Antibiotic TherapyClassification of Antibiotic TherapyProphylactic Use Therapeutic Use Empiric therapy Definitive therapyEmpiric Antibiotic TherapyEmpiric Antibiotic TherapyDepartment of Critical Care Medicine Peking Union Medical College HospitalEmpiric Antibiotic TherapyEmpiric Antibiotic TherapyWhen treating seriously ill patients who are at risk of developing septic shock when pathogens are unknown or not confirmed antibiotic selection according to epidemiology of NI in the ward resistance profile of most common pathogensEmpiric Antibiotic TherapyEmpiric Antibiotic TherapySearching for infection focus collecting samples for culture starting empiric antibiotic therapy as soon as possible referring to definitive antibiotic therapy as soon as possibleAntibiotic Therapy and PrognosisAntibiotic Therapy and PrognosisObjective: To evaluate the relationship between the adequacy of antibiotic treatment for BSI and clinical outcomes among ICU pts Design: Prospective cohort study Setting: A medical ICU (19 beds) and a surgical ICU (18 beds) from a university-affiliated urban teaching hospital Patients: 492 pts from July 1997 to July 1999 Intervention: NoneAntibiotic Therapy and PrognosisAntibiotic Therapy and Prognosis147 (29.9%) pts received inadequate antimicrobial treatment for their BSI The most commonly identified bloodstream pathogens and their associated rates of inadequate antimicrobial treatment included vancomycin-resistant enterococci (n = 17; 100%) Candida species (n = 41; 95.1%) MRSA (n = 46; 32.6%) SCoN (n = 96; 21.9%) Pseudomonas aeruginosa (n = 22; 10.0%) Antibiotic Therapy and PrognosisAntibiotic Therapy and PrognosisHospital mortality rate pts with a BSI receiving inadequate antimicrobial tx (61.9%) pts with a BSI receiving adequate antimicrobial tx (28.4%) (RR, 2.18; 95% CI, 1.77 to 2.69; p < 0.001) Independent determinant of hospital mortality by multiple logistic regression analysis administration of inadequate antimicrobial tx (OR, 6.86; 95% CI, 5.09 to 9.24; p < 0.001)Antibiotic Therapy and PrognosisAntibiotic Therapy and PrognosisIndependent predictor of the administration of inadequate antimicrobial tx by multiple logistic regression analysis BSI attributed to Candida species (OR, 51.86; 95% CI, 24.57 to 109.49; p < 0.001) prior administration of antibiotics during the same hospitalization (OR, 2.08; 95% CI, 1.58 to 2.74; p = 0.008) decreasing serum albumin concentrations (1-g/dL decrements) (OR, 1.37; 95% CI, 1.21 to 1.56; p = 0.014) increasing central catheter duration (1-day increments) (OR, 1.03; 95% CI, 1.02 to 1.04; p = 0.008)Inappropriate empiric antibiotic therapyInappropriate empiric antibiotic therapyObjective: to assess the incidence, risk, and prognosis factors of NP acquired during mechanical ventilation (MV) Settings a 1,000-bed teaching hospital April 1987 through May 1988 Patients 78 (24%) episodes of NP in 322 consecutive mechanically ventilated patientsInappropriate empiric antibiotic therapyInappropriate empiric antibiotic therapyFrom: Torres et al. Incidence, risk, and prognosis factors of nosocomial pneumonia in mechanically ventilated patients. Am Rev Respir Dis 1990 Sep;142(3):523-8Difficulty in empiric antibiotic therapyDifficulty in empiric antibiotic therapyObjective: To assess the frequency of and the reasons for changing empiric antibiotics during the treatment of pneumonia acquired in ICU Design: A prospective multicenter study of 1 year's duration Setting: Medical and surgical ICUs in 30 hospitals all over Spain. Patients: Of a total of 16,872 patients initially enrolled into the study, 530 patients developed 565 episodes of pneumonia after admission to the ICU.Difficulty in empiric antibiotic therapyDifficulty in empiric antibiotic therapyEmpiric antibiotics in 490 (86.7%) of the 565 episodes of pneumonia The most frequently used antibiotics amikacin 120 cases tobramycin 110 ceftazidime 96 cefotaxime 96 Monotherapy in 135 (27.6%) of the 490 episodes Combination of 2 antibiotics in 306 episodes (62.4%) Combination of 3 antibiotics in 49 episodes (10%)Difficulty in empiric antibiotic therapyDifficulty in empiric antibiotic therapyThe empiric tx modified in 214 (43.7%) cases isolation of a microorganism not covered by treatment 133 (62.1%) cases lack of clinical response 77 (36%) development of resistance 14 (6.6%) Individual factors associated with modification of empiric treatment identified in the multivariate analysis microorganism not covered (RR 22.02; 95%CI 11.54 to 42.60; p < 0.0001) administration of more than one antibiotic (RR 1.29; 95% CI 1.02 to 1.65; p = 0.021) previous use of antibiotics (RR 1.22; 95% CI 1.08 to 1.39; p = 0.0018)Difficulty in empiric antibiotic therapyDifficulty in empiric antibiotic therapyCompared with appropriate empiric therapy, inappropriate therapy was associated with higher mortality (p=0.0385) more complications (p<0.001) higher incidence of shock (p<0.005) more GIB (p=0.003)From: Alvarez-Lerma F. Modification of empiric antibiotic treatment in patients with pneumonia acquired in the intensive care unit. ICU-Acquired Pneumonia Study Group. Intensive Care Med 1996 May;22(5):387-94Difficulty in empiric antibiotic therapyDifficulty in empiric antibiotic therapyObjective To define the impact of BAL data on the selection of antibiotics and the outcomes of patients with VAP Design: Prospective observation and bronchoscopy with BAL, performed within 24 h of dx of a new episode of hospital-acquired VAP or progression of a prior episode of NP Setting: A 15-bed medical and surgical ICUDifficulty in empiric antibiotic therapyDifficulty in empiric antibiotic therapyPatients: 132 pts hospitalized for more than 72 h mechanically ventilated a new or progressive lung infiltrate plus at least two of the following three clinical criteria for VAP abnormal temperature (> 38 C or < 35 C) abnormal WCC (> 10,000 or < 3,000) purulent bronchial secretions Interventions: Bronchoscopy with BAL within 24 h of clinical dx of VAP or progression of an infiltrate due to prior VAP or NP All patients received antibiotics, 107 prior to bronchoscopy and 25 immediately after bronchoscopy. Difficulty in empiric antibiotic therapyDifficulty in empiric antibiotic therapyFrom: Luna CM, Vujacich P, Niederman MS, Vay C, Gherardi C, Matera J, Jolly EC. Impact of BAL data on the therapy and outcome of ventilator-associated pneumonia. Chest 1997 Mar;111(3):676-85 Difficulty in empiric antibiotic therapyDifficulty in empiric antibiotic therapyFrom: Kollef MH, Ward S The influence of mini-BAL cultures on patient outcomes: implications for the antibiotic management of ventilator-associated pneumonia. Chest 1998 Feb;113(2):412-20Hospital Infection ControlHospital Infection ControlDepartment of Critical Care Medicine Peking Union Medical College HospitalScheduled Changes of Empiric Antibiotic TherapyScheduled Changes of Empiric Antibiotic TherapyObjective: To determine the impact of a scheduled change of abx classes, used for the empiric tx of suspected gram-negative bacterial infections, on the incidence of VAP and nosocomial bacteremia Patients: 680 patients undergoing cardiac surgery were evaluated Intervention: During a 6-mo period (i.e., the before-period), our traditional practice of prescribing a 3rd generation cephalosporin (ceftazidime) for the empiric tx of suspected gram-negative bacterial infections was continued This was followed by a 6-mo period (i.e., the after-period) during which a quinolone (ciprofloxacin) was used in place of the third-generation cephalosporin.Scheduled Changes of Empiric Antibiotic TherapyScheduled Changes of Empiric Antibiotic TherapyFrom: Kollef MH, Vlasnik J, Sharpless L, Pasque C, Murphy D, Fraser V Scheduled change of antibiotic classes: a strategy to decrease the incidence of ventilator-associated pneumonia. Am J Respir Crit Care Med 1997 Oct;156(4 Pt 1):1040-8 Nosocomial Infection ControlNosocomial Infection ControlScheduled changes of antibiotic classes for empiric treatment of suspected or documented GNB infections Time period 1 (n=1323) ceftazidime Time period 2 (n=1243) ciprofloxacin Time period 3 (n=1102) cefepimeNosocomial Infection ControlNosocomial Infection ControlScheduled changes of antibiotic classes targeted at the empiric treatment of gram-negative bacterial infections can reduce the occurrence of inadequate antimicrobial treatment of nosocomial infections reducing the administration of inadequate antimicrobial treatment for patients with an APACHE II  15 can improve hospital survivalFrom Kollef MH. The clinical impact of scheduled antibiotic class changes for the empiric treatment of nosocomial gram-negative bacterial infections in the intensive care unit (ICU) setting. Abstracts of 39th ICAAC 1999: 594Evaluation of Clinical Practice Guidelines on Outcome of Infection in Patients in the Surgical Intensive Care UnitEvaluation of Clinical Practice Guidelines on Outcome of Infection in Patients in the Surgical Intensive Care UnitPrice J, et al Critical Care Medicine 1999; 27: 2118-24BackgroundBackgroundWilliam Beaumont Hospital Royal Oak, Michigan 929-bed, community-based teaching hospital newly constructed SICU with 20 private rooms pathogens highly resistant to 3rd-generation cephalosporinsClinical Practice Guideline -- empiric antibioticsClinical Practice Guideline -- empiric antibioticsClinical Practice Guideline -- empiric antibioticsClinical Practice Guideline -- empiric antibioticsClinical Practice Guideline -- empiric antibioticsClinical Practice Guideline -- empiric antibioticsClinical Practice GuidelineClinical Practice GuidelineStudy Design prospective analysis of all ICU patients phase I 51 days before guideline implementation intervening period 8 mths guideline implementation phase II 34 days after guideline implementationClinical Practice Guideline --Clinical OutcomeClinical Practice Guideline --Clinical OutcomeClinical Practice Guideline --Clinical OutcomeClinical Practice Guideline --Clinical OutcomeHandwashing and DisinfectionHandwashing and DisinfectionOutbreaks are often related to failure in infection control techniques or disregard for infection control guidelines The most common mode of transmission is the hands of a health-care worker Handwashing = effectively prevent horizontal transmission of infections Compliance with handwashing policies seldom exceeds 40%Handwashing and DisinfectionHandwashing and Disinfectiona: ICU beds 12; Nurses/shift 3; Working hours/shift 8; Patient contacts/hr 5; 12X3X8X5X2 min (0.5 min) b: Nursing time lost/8 hr shift = 48/8