Presentation on theme: "Prompting Appropriate Empirical Antimicrobial Therapy for Patients with Community-acquired Infections Shey-Ying Chen, MD Department of Emergency Medicine."— Presentation transcript:
Prompting Appropriate Empirical Antimicrobial Therapy for Patients with Community-acquired Infections Shey-Ying Chen, MD Department of Emergency Medicine National Taiwan University Hospital August 14, 2007
Leading Causes of Death USA, 2001 Flu and pneumonia (7th: 2.57%) Sepsis (10th: 1.33%) Taiwan, 2002 Pneumonia (7th: 20.17/100,000, 3.17%) Sepsis (13th: 4.28/100,000, 0.76%) (3.9 %) (3.93 %)
Epidemiology of Severe Sepsis Acute hospitalized patients in 847 USA hospitals, 1995 Estimate case number and incidence 751,000 cases (1.5% increasing yearly) Incidence 3 cases/1,000 population 2.26 cases/100 hospital discharge 51.1% required ICU care Mortality ： 28.6% Estimate nation-wide cases: 215,000 desths 9.3% of all mortality of the year ， equal to AMI deaths Crit Care Med. 2001;29:1303-1310
Incidence/Mortality in Severe Sepsis – Age Crit Care Med. 2001;29:1303-1310 10% (children) ~ 38.4% (> 85 yrs) 0.2/1000 pop (children) ~ 26.2/1000 pop (> 85 yrs)
Mortality in Severe Sepsis - Comorbidity Crit Care Med. 2001;29:1303-1310
Inappropriate Antibiotics Use in Severe Community-acquired Bacteremia Independent predictor for ICU mortality (OR, 4.11) Attributable mortality increases as disease severity 10.7%: APACHE II score < 15 41.8%: APACHE II score ≧ 25 Chest. 2003;123:1615-1624
Critical Patients Receiving Inappropriate Antibiotics Studies in ICU setting Inappropriate empirical antibiotics: 8.5%~17% Significant impact on Survival Length of hospital stay Total hospital cost Chest. 2003;123:1615-1624 Crit Care Med. 2003;31:2742-2751 Chest. 1999;115:462-474
Empirical Antibiotics Selection Infection site Potential pathogen Hemodynamic stability - EGDT Risk of short-term mortality Possible presence of antimicrobial resistance
Resistance Due to Selection Spontaneous mutation occurs in the absence of drug selection in a sensitive population Drug treatment J Infect Dis 1986;154:792-800 Mutant is selected for by drug treatment as sensitive strains die off Resistance becomes clinically manifested during therapy Resistant clone grows within what used to be a sensitive population
Evolution of Antimicrobial Resistance S. aureus Penicillin  Penicillin-resistant S. aureus,  Methicillin  Methicillin-resistant S. aureus (MRSA),  Vancomycin-resistant enterococcus (VRE),  Vancomycin  Vancomycin intermediate resistant S. aureus,  Vancomycin- Resistant S. aureus [ ? ]
Risk of Nosocomial Colonization with MDR Pathogens Age Different underlying diseases Severity of illness Inter-hospital transferred or nursing home patients Extended length of stay Invasive procedures Anti-infective therapies Ann Intern Med. 2002;136:834-844
Risk Factors of Nosocomial MRSA Colonization/infection Advanced age Severity of illness Inter-hosp transfer /nursing home patients Extended length of stay GI surgery Central catheter Intubation/ventilator Cephalosporin treated Receiving multiple antibiotics Ann Intern Med. 2002;136:834-844
Risks Factors of Nosocomial VRE Colonization/infection Advance age ESRD Hematologic cancer Severity of illness Inter-hosp transfer /nursing home patients Extended length of stay GI surgery Transplantation Central catheter NG tube Cephalosporin treated Clindamycin treated Vancomycin treated Fluoroquinolones treated Receiving multiple antibiotics Ann Intern Med. 2002;136:834-844
Risks Factors of Nosocomial ESBL-GNB Colonization/infection Severity of illness Inter-hosp transfer /nursing home patients Extended length of stay GI surgery Central catheter Urinary catheter Intubation/ventilator NG tube Fluoroquinolones treated Receiving multiple antibiotics Ann Intern Med. 2002;136:834-844
Risks Factors of Nosocomial C. difficile Colonization/infection Advance age ESRD Severity of illness Inter-hosp transfer /nursing home patients Extended length of stay GI surgery Transplantation NG tube Cephalosporin treated Penicillins treated Clindamycin treated Vancomycin treated Receiving multiple antibiotics Ann Intern Med. 2002;136:834-844
Risks Factors of Nosocomial Candida Colonization/infection Advance age ESRD Hematologic cancer Hepatic failure Inter-hosp transfer /nursing home patients Extended length of stay GI surgery Transplantation Central catheter Urinary catheter Vancomycin treated Receiving multiple antibiotics Ann Intern Med. 2002;136:834-844
Differences between Hospital- and Community-acquired Infections Isolates distribution Antimicrobial susceptibility Eur J Clin Microbiol Infect Dis. 2002;21:849-855
What Has Been Changed in Today’s Community Spread of drug-resistant bacteria in the community Changing pattern of health care OPD invasive procedure Hemodialysis clinics Nursing home care Recently discharged patients
Diversity in Antimicrobial Susceptibility in Community-acquired Bacteremia Isolates Clin Infect Dis. 2002;34:1431-9 A ： True community-acquired B ： Recently discharge (30 days) C ： OPD procedure D ： Nursing home
New Classification -Definition of Healthcare-associated Infection Hospital-acquired Healthcare-associated (HcA) Parenteral treatment in 30 days OPD chemotherapy or hemodialysis in 30 days Hospitalization for 2 days in recent 90 days Nursing home residence Community-acquired (CA) Ann Intern Med. 2002;137:791-797
Healthcare-associated (HcA) Bloodstream Infections HcA infection similar to HA infection in Comorbidities and predisposing factor Primary site of infection Pathogen pattern and drug-susceptibility Mortality Clinical importance Empirical antibiotics use Infection control strategy Ann Intern Med. 2002;137:791-797
Bacteremia in previously Hospitalized community patients Prospective observational study, NTUH 2001-2002 Antimicrobial-resistant bacteria MRSA Multi-drug resistant Enterobacteriaceae Multi-drug resistant NFGNB 304 community bacteremia patients with previous hospitalization in 360 days 38 (12.5%) with ARB infection Ann Emerg Med. (In revise)
Dilemma in selecting empirical antibiotics Inappropriate antibiotics Increase mortality in severe sepsis Prolonged hospitalization Overuse of broad-spectrum antibiotics Emergence of drug-resistant micro- organism Medical cost
Low antimicrobial resistance in micro-organisms isolated from community patients without healthcare-associated exposure Diag Microb Infect Dis. 2006;55:135-141
MDR-GNB in the Community Clin Infect Dis. 2005;40:1792-1780 1998-2003, Boston, USA Increasing prevalence of MDR-GNB isolates recovered from patients at their initial 48 hours hospitalization
MDR-GNB in the Community Independent factors for carrying MDR-GNB among community patients OR95% CI. Age ≧ 65 years2.81.1-7.4 Prior Abx ≧ 14 days ＃ 8.72.5-30 Long-term care facility P ’ t3.51.3-9.4 ＃ In 90 days prior to this admission Clin Infect Dis. 2005;40:1792-1780
MRSA in the Community 1997-2002, Boston, USA Increasing carriage percentage in community p ’ t All with HA exposure No CA-MRSA in this study Independent risk factors Previous MRSA infection/colonization ＃ (OR, 17) Cellulitis (OR, 4) Presence of CVC (OR, 3) ＃ Skin ulcer (OR, 3) ＃ In 90 days prior to this admission J Antimicrob Chemother. 2004;53:474-9.
Susceptibility of S. aureus Bloodstream Isolates in North Taiwan (2001) Percentage of MRSA bacteremia Without healthcare- associated exposure: 2.7 % (1/37) With healthcare- associated exposure : 57.1 % (32/56) Diag Microb Infect Dis. 2005;53:85-92
Methicillin Resistance among Community- onset S. aureus Bacteremia 2001-2006, NTUH ED, North Taiwan Different HA exposure Nursing home = 26/29 (90.0 %) OPD invasive procedure = 63/119 (52.9 %) Previously hospitalized = 78/217 (35.9 %)
Antimicrobial-resistant Bacteremia in previously hospitalized patients - Decreased as Duration after Discharge Ann Emerg Med. (In revise)
Antimicrobial-resistant Bacteremia in Previously Hospitalized Patients ED, NTUH 304 bacteremia patients who were previously hospitalized in 360 days ARB MRSA MDR-GNB (Enterobacteriaceae, NFGNB) Risk factors Prior ICU stay in 180 days Prior MRSA carriage in 360 days Ann Emerg Med. (In revise)
Empirical Antibiotics for Community Patients with Infection - discrimination for healthcare-associated risk Baseline antimicrobial susceptibility in true community patients Patients with healthcare-associated risk Nursing home residence Regular OPD invasive procedure in 30 days Recent hospitalization in 90 days Prior ICU admission Bed-ridden patients Prior prolonged hospitalization > 30 days Prior carriage of MRSA or multi-drug resistant bacteria in 360 days
Patient with Impaired Immunity Advanced age ( ≧ 65 years) Liver cirrhosis Cancer patients Receiving chemotherapy Alcoholism Diabetes (?)
Impact of DM on Mortality in Patients with Community-acquired Bacteremia J Infect. 2007;55:27-33. ν ν ν ν ν ν ν
Impact of Diabetes on Community-acquired Infections Higher risk in acquiring infections No survival differences between DM and non-DM patients Community-acquired pneumococcal bacteremia Community-acquired bacteremia Early diagnosis > Role of Abx Diabetes Care. 2004;27:1143-7. Diabetes Care. 2004;27:70-6. J Infect. 2007;55:27-33.
Impact of Cirrhosis on Mortality in Patients with Community-acquired Bacteremia Clin Infect Dis. In submit.
Common Primary Site of Infection in Sepsis Patients Low respiratory tract infection Lung abscess Genito-urinary tract Intra-abdominal Hepatobiliary SBP Liver abscess Soft tissue Necrotizing fasciitis Orthopedics Endovascular Infective endocarditis Catheter-related Central venous system Febrile neutropenia Primary bacteremia
Specific Consideration in Taiwan Patient Liver cirrhosis/HCC Pathogen K. pneumoniae Vibrio spp. Aeromonas spp Diseases SBP Biliary tract infection/liver abscess Necrotizing fasciitis
Lung Abscess - High Prevalence of K. pneumoniae in Taiwan Traditionally focused on anaerobes 1996-2003, NTUH Total 336 cases 120 case with documented bacteriology 90 case were community-acquired 73 (81%) were male 51 (57%) were smoker 33 (37%) with chronic lung disease 28 (31%) with DM Clin Infect Dis. 2005;40;915-22.
Lung Abscess High Prevalence of K. pneumoniae in Taiwan 21 % due to K. pneumoniae Anaerobes and Streptococcus milleri increasing resistance to PCN and Clindamyin Recommendation for empirical antibiotics 2 ° or 3 ° generation cephalosporin + clindamycin/metronidazole β-lactam/β-lactam inhibitor Clin Infect Dis. 2005;40;915-22.
Liver Abscess Highly association with DM DM history may not present Increasing liver abscess in non-DM patients Biliary tract enzyme: not usually elevated Easily missed Fever without apparent focus in ER K. pneumoniae as a predominant pathogen
Optimal Treatment for KP Liver Abscess - Comparison between Extended- Spectrum Cephalosporin and Cefazolin Metastatic lesions Endophthalmitis Septic pul. embolism Prostatic abscess Renal abscess Epidural abscess Necrotizing fasciitis Severe complication rate (P<0.001) Cefazolin: 37.3% ESCeph: 6.3% Antimocrob Agent Chemother. 2003;47:2088-92. P = 0.02 P < 0.01 P = 0.42
Optimal Treatment for KP Liver Abscess - Comparison between Extended- Spectrum Cephalosporin and Cefazolin No difference among the two study groups in Demographic Comorbidity Severity of acute illness Clinical presentation Early drainage Combine aminoglycoside (P<0.001) Cefazolin (50/59, 84.7%) ESCeph (21/48, 43.8%) Antimocrob Agent Chemother. 2003;47:2088-92.
Optimal Treatment for KP Liver Abscess - Comparison between Extended- Spectrum Cephalosporin and Cefazolin Factors favoring lower risk of severe complications OR (95% CI.) Platelet > 100 x 109/liter0.03 (0.004-0.28) ALP < 300 U/liter0.19 (0.04-0.78) No gas formation in abscess0.2 (0.05-0.92) APACHE III score < 400.07 (0.01-0.39) Extended-spectrum cephalosporin use ＃ 0.01 (0.001-0.12) Early drainage ＊ 0.11 (0.02-0.53) ＃ For at least 3 days within the first 5 days of hospitalization ＊ Within 3 days of diagnosis Antimocrob Agent Chemother. 2003;47:2088-92.
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