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Prompting Appropriate Empirical Antimicrobial Therapy for Patients with Community-acquired Infections Shey-Ying Chen, MD Department of Emergency Medicine.

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Presentation on theme: "Prompting Appropriate Empirical Antimicrobial Therapy for Patients with Community-acquired Infections Shey-Ying Chen, MD Department of Emergency Medicine."— Presentation transcript:

1 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

2 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 %)

3 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:

4 Incidence/Mortality in Severe Sepsis – Age Crit Care Med. 2001;29: % (children) ~ 38.4% (> 85 yrs) 0.2/1000 pop (children) ~ 26.2/1000 pop (> 85 yrs)

5 Mortality in Severe Sepsis - Comorbidity Crit Care Med. 2001;29:

6 Effective Therapies for Mortality Reduction

7 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 < %: APACHE II score ≧ 25 Chest. 2003;123:

8 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: Crit Care Med. 2003;31: Chest. 1999;115:

9 Empirical Antibiotics Selection Infection site Potential pathogen Hemodynamic stability - EGDT Risk of short-term mortality Possible presence of antimicrobial resistance

10 Antimicrobial Resistance

11 Resistance Due to Selection Spontaneous mutation occurs in the absence of drug selection in a sensitive population Drug treatment J Infect Dis 1986;154: 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

12 Evolution of Antimicrobial Resistance S. aureus Penicillin  [1943] Penicillin-resistant S. aureus, [1944] Methicillin  [1959] Methicillin-resistant S. aureus (MRSA), [1960] Vancomycin-resistant enterococcus (VRE), [1989] Vancomycin [1997] Vancomycin intermediate resistant S. aureus, [1997] Vancomycin- Resistant S. aureus [ ? ]

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14 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:

15 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:

16 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:

17 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:

18 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:

19 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:

20 Differences between Hospital- and Community-acquired Infections Isolates distribution Antimicrobial susceptibility Eur J Clin Microbiol Infect Dis. 2002;21:

21 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

22 Diversity in Antimicrobial Susceptibility in Community-acquired Bacteremia Isolates Clin Infect Dis. 2002;34: A : True community-acquired B : Recently discharge (30 days) C : OPD procedure D : Nursing home

23 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:

24 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:

25 Bacteremia in previously Hospitalized community patients Prospective observational study, NTUH 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)

26 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

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28 Low antimicrobial resistance in micro-organisms isolated from community patients without healthcare-associated exposure Diag Microb Infect Dis. 2006;55:

29 MDR-GNB in the Community Clin Infect Dis. 2005;40: , Boston, USA Increasing prevalence of MDR-GNB isolates recovered from patients at their initial 48 hours hospitalization

30 MDR-GNB in the Community Independent factors for carrying MDR-GNB among community patients OR95% CI. Age ≧ 65 years Prior Abx ≧ 14 days # Long-term care facility P ’ t # In 90 days prior to this admission Clin Infect Dis. 2005;40:

31 MRSA in the Community , 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.

32 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

33 Methicillin Resistance among Community- onset S. aureus Bacteremia , 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 %)

34 Antimicrobial-resistant Bacteremia in previously hospitalized patients - Decreased as Duration after Discharge Ann Emerg Med. (In revise)

35 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)

36 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

37 Host Factors Consideration

38 Patient with Impaired Immunity Advanced age ( ≧ 65 years) Liver cirrhosis Cancer patients Receiving chemotherapy Alcoholism Diabetes (?)

39 Impact of DM on Mortality in Patients with Community-acquired Bacteremia J Infect. 2007;55: ν ν ν ν ν ν ν

40 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: Diabetes Care. 2004;27:70-6. J Infect. 2007;55:27-33.

41 Impact of Cirrhosis on Mortality in Patients with Community-acquired Bacteremia Clin Infect Dis. In submit.

42 Primary Site of Infection

43 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

44 Specific Consideration in Taiwan Patient Liver cirrhosis/HCC Pathogen K. pneumoniae Vibrio spp. Aeromonas spp Diseases SBP Biliary tract infection/liver abscess Necrotizing fasciitis

45 Lung Abscess - High Prevalence of K. pneumoniae in Taiwan Traditionally focused on anaerobes , 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;

46 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;

47 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

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50 K. pneumoniae -A Community Pathogen with Low Antimicrobial Resistance Diag Microb Infect Dis. 2006;55:

51 What ’ s the Drug of Choice for Liver Abscess

52 Retrospective study, , TSGH, Taiwan 107 KP liver abscess Cefazolin: 59 (55.1%) ESCeph: 48 (44.9%) Optimal Treatment for KP Liver Abscess - Comparison between Extended- Spectrum Cephalosporin (ESCeph) and Cefazolin Antimocrob Agent Chemother. 2003;47:

53 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: P = 0.02 P < 0.01 P = 0.42

54 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:

55 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 ( ) ALP < 300 U/liter0.19 ( ) No gas formation in abscess0.2 ( ) APACHE III score < ( ) Extended-spectrum cephalosporin use # 0.01 ( ) Early drainage * 0.11 ( ) # For at least 3 days within the first 5 days of hospitalization * Within 3 days of diagnosis Antimocrob Agent Chemother. 2003;47:

56 Rationales for Antimicrobial Agents Selection

57 1. 可參考的微生物學報告 ____ 年 ____ 月 ____ 日 ○血液○痰液○尿液○膿液○其它 ________ 菌株 1.______________ 2. ______________ 3.______________

58 2. 敗血症高死亡率病患 敗血性休克 ( 收縮壓 :_________mmHg) 嚴重敗血症 ( ◎ lactate ≧ 4 mM ,或◎器官衰竭 ____ 腦 ____ 肺 ____ 腎 ____ 肝 ) 中樞神經感染 低中性球發燒 肝膿瘍 壞死性筋膜炎 惡性外耳炎 嚴重肺炎 ( ◎呼吸窘迫 / 衰竭 ◎嚴重度評分大於 90 分 ( 需附 評分表 ) ) 免疫功能低下 ( ◎年齡大於 70 歲 ◎肝硬化併衰竭◎腫瘤病 患 )

59 3. 具抗藥性細菌感染風險病患 三個月內曾住院 (________________ 醫院 : ____/____/____~____/____/____) 安養中心病患 門診侵入性治療 ( ◎化療 ◎ H/D ◎ TPN ◎其 它 :________)

60 4. 混合型感染 吸入性肺炎 牙源性感染 頸部深部感染 中隔腔炎 腹腔內感染 糖尿病足部病變合併感染

61 5. 前一線抗生素治療失敗 使用至少超過 48 小時沒有改善 自 ____ 月 ____ 日 ~____ 月 ____ 日使用 _______________________ 抗生素

62 6. 其他特殊臨床考量 請說明選用此抗生素之理由 並照會感染科醫師

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65 Colonization Duration and Risk Factors for Prolonged MRSA Colonization Estimated half-life of MRSA colonization: 40 months Detection of MRSA colonization Nares (Sen, 93%; NPV, 95%) Cutaneous sites (Sen, ≦ 39%; NPV ≦ 69%). Risk factor for prolonged colonization Break in skin (OR. 4.34; 95% CI ) Clin Infect Dis. 1994;19: Clin Infect Dis. 2001;32:


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