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Prompting Appropriate Empirical Antimicrobial Therapy for Patients with Community-acquired Infections
Shey-Ying Chen, MDDepartment of Emergency
MedicineNational Taiwan University
HospitalAugust 14, 2007
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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 %)
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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
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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)
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Mortality in Severe Sepsis - Comorbidity
Crit Care Med. 2001;29:1303-1310
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Effective Therapies for Mortality Reduction
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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 ≧ 25Chest. 2003;123:1615-1624
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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
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Empirical Antibiotics Selection
Infection site Potential pathogen Hemodynamic stability - EGDT Risk of short-term mortality Possible presence of antimicrobial
resistance
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Antimicrobial Resistance
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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
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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-ResistantS. aureus
[ ? ]
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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
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Risk Factors of Nosocomial MRSA Colonization/infection
Advanced age Severity of illness Inter-hosp transfer /nu
rsing home patients Extended length of sta
y GI surgery Central catheter Intubation/ventilator Cephalosporin treated Receiving multiple anti
biotics
Ann Intern Med. 2002;136:834-844
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Risks Factors of Nosocomial VRE Colonization/infection Advance age ESRD Hematologic cancer Severity of illness Inter-hosp transfer /nursing ho
me 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
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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 antibioti
cs
Ann Intern Med. 2002;136:834-844
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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 antibioti
csAnn Intern Med. 2002;136:834-844
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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 antibioti
cs
Ann Intern Med. 2002;136:834-844
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Differences between Hospital- and Community-acquired Infections
Isolates distribution Antimicrobial susceptibility
Eur J Clin Microbiol Infect Dis. 2002;21:849-855
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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
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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
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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 da
ys Nursing home residence
Community-acquired (CA)Ann Intern Med. 2002;137:791-797
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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
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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)
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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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Low antimicrobial resistance in micro-organisms isolated from community patients without healthcare-associated exposure
Diag Microb Infect Dis. 2006;55:135-141
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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
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MDR-GNB in the Community
Independent factors for carrying MDR-GNB among community patients
OR 95% CI.
Age ≧ 65 years 2.8 1.1-7.4 Prior Abx ≧ 14 days # 8.7 2.5-30 Long-term care facility P’t 3.5 1.3-9.4
# In 90 days prior to this admission
Clin Infect Dis. 2005;40:1792-1780
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MRSA in the Community 1997-2002, Boston, USA Increasing carriage percen
tage 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.
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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
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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 %)
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Antimicrobial-resistant Bacteremia in previously hospitalized patients- Decreased as Duration after Discharge
Ann Emerg Med. (In revise)
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Antimicrobial-resistant Bacteremiain 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)
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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
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Host Factors Consideration
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Patient with Impaired Immunity
Advanced age (≧ 65 years) Liver cirrhosis Cancer patients Receiving chemotherapy Alcoholism
Diabetes (?)
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Impact of DM on Mortality in Patients with Community-acquired Bacteremia
J Infect. 2007;55:27-33.
ν
νν
νν
ν
ν
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Impact of Diabetes on Community-acquired Infections
Higher risk in acquiring infections No survival differences between DM a
nd non-DM patients Community-acquired pneumococcal bac
teremia Community-acquired bacteremia
Early diagnosis > Role of AbxDiabetes Care. 2004;27:1143-7.
Diabetes Care. 2004;27:70-6.
J Infect. 2007;55:27-33.
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Impact of Cirrhosis on Mortality in Patients with Community-acquired Bacteremia
0.00
0.20
0.40
0.60
0.80
1.00
Sur
viva
l (pe
rcen
tage
)
0 10 20 30Days since presentation to the ED
No liver cirrhosis Liver cirrhosis
P=<0.001
Clin Infect Dis. In submit.
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Primary Site of Infection
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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
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Specific Consideration in Taiwan Patient
Liver cirrhosis/HCC Pathogen
K. pneumoniae Vibrio spp. Aeromonas spp
Diseases SBP Biliary tract infection/liver abscess Necrotizing fasciitis
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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.
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Lung AbscessHigh Prevalence of K. pneumoniae in Taiwan
21 % due to K. pneumoniae Anaerobes and Streptococcus milleri incr
easing 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.
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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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K. pneumoniae-A Community Pathogen with Low Antimicrobial Resistance
Diag Microb Infect Dis. 2006;55:135-141
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What’s the Drug of Choice for Liver Abscess
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Retrospective study, 1995-2000, 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;47:2088-92.
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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
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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.
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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/liter 0.03 (0.004-0.28)ALP < 300 U/liter 0.19 (0.04-0.78)No gas formation in abscess 0.2 (0.05-0.92)APACHE III score < 40 0.07 (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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Rationales for Antimicrobial Agents Selection
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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.______________
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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 )
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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 :________)
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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
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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
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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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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. 1.6-11.8)
Clin Infect Dis. 1994;19:1123-8.
Clin Infect Dis. 2001;32:1393-8.