Bai-Yi Chen MD. FCCP

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1 Treatment strategies for hospitalized versus nonhospitalized CAP patients: Asian perspective Bai-Yi Chen MD. FCCP Professor of Medicine Division of Infectious Disease, Infection Control Team The First Hospital of China Medical University Shen-Yang, China

2 CAP: Incidence and Outcomes 6th leading cause of death in United States 2-3 million cases/year 500,000 admissions/year 45,000 deaths/year Mortality Outpatient < 1% Admit (ward) 10%-14% ICU 30%-40% Bartlett JG et al. Clin Infect Dis. 2000;31:

3 Percent Mortality Impact of Pneumonia in the Elderly: Long-Term Prognosis Examined hospital and 1-year mortality of community-acquired pneumonia (CAP) in patients age 65 years 158,960 patients with CAP and 794,333 controls (5 per case) matched for age, sex, and race 1-year mortality higher for patients with CAP than for controls NOT explained by underlying illness and did not correct after controlling for comorbidity CAP Control Hospital Mortality 1-Year Mortality Kaplan V, et al. Arch Intern Med. 2003;163: All differences P<0.001

4 Best practice in managing CAP Risk assessment -to decide site of care (outpatient VS hospital VS ICU ) Early optimal antibiotic therapy -good clinical outcome/less resistance As short a duration as possible -less cost and resistance

5 Mortality and Time to ICU Admission for CAP 172 ICUs in UK- >17,869 cases 59% admitted from 0-2d 21.5% 2-7d 19.5% > 7d 54.5% admitted on MV Risk assessment? Mortality and Admission to ICU for CAP Day 0-2 Day 2-7 >day 7 Woodhead et al Critical Care 2006:10:s1 Time from admission to ward to admission to ICU

6 Accuracy of Assessments Tools in Predicting Need for IRVS % PSI IV + V CURB-65 Grp 3 SMARTCOP>3pts x100 Sensitivity Specificity PPV NPV AUC Charles PGP, et al. CID 2008; 47:375-84

7 Keypad Question. What is the value of assessment tools (PSI/CURB-65 )? 1.To identify patients at high risk for mortality 2.To identify patients at low risk for outpatient care 3.Both 4.Neither

8 Value of the Rules The true strength of PSI is their negative predictive value the identification of patients who are not at risk of death New rules such as SMART-COP are required to guide need for ICU admission

9 CAP Treatment Consensus Risk assessment -to decide site of care Early optimal antibiotic therapy -good clinical outcome/less resistance As short a duration as possible -less cost and resistance

10 Considerations in Optimal Antibiotic therapy Which antibiotic? possible pathogens on site of infection antibiotics requirement -coverage/ resistance pattern/tissue penetration /safety/cost Optimizing PK/PD Physiology and pathophysiology advanced age/children/pregnant women/breast feeding renal/heptic dysfunction/combined dysfunction Other considerations cidal or static/monotherapy or combination/iv or Oral/duration

11 Community-acquired pneumonia in Europe* Organism Community Hospital ICU Studies, n Streptococcus pneumoniae 19,3 25,9 21,7 Haemophilus influenzae 3,3 4,0 5,1 Legionella spp 1,9 4,9 7,9 Staphylococcus aureus 0,2 1,4 7,6 GNB 0,4 2,7 7,5 Mycoplasma pneumoniae 11,1 7,5 2 Chlamydia psittaci 1,5 1,9 1,3 Viruses 11,7 10,9 5,1 No Pathogen identified 49,8 43,8 41,5 *Woodhead M. Eur Resp J 2002; 20: Suppl. 36, 20-27

12 CAP: Atypical Pathogens Worldwide Incidence of Atypical Pathogens University of Louisville Infectious Diseases Atypical Pathogens Reference Laboratory Database Region I: 22% North America Region II: 28% Europe Region III: 21% Latin America Region IV: 20% Asia and Africa The study included a total of 4337 patients The rage of atypical pathogens was 20% to 28% The range between groups for atypical pathogens ranged from 10% to 91% (P<0.01). Arnold FW, Summersgill JT, LaJoie AS, et al; CAP Organization (CAPO) Investigators. A worldwide perspective of atypical pathogens in CAP. AJRCCM. 2007;175:

13 A prevalence analysis of Mycoplasma pneumoniae and Chlamydophila pneumoniae in Asian adults with community acquired pneumonia Chin J Infect Chemother,2008;8(2):89~93 Conclusions: -In light of significant morbidity and diagnostic difficulties, empiric coverage of both M pneumoniae and C pneumoniae needed in Asian adults CAP

14 CAP pathogens in China Single bacteria infection % Unknown % % Mixed pathogens infection % Single atypical pathogen infection Liu Youning, Chen Minjun, et al Chin J Tub Respir.Dis

15 Considerations in Optimal Antibiotic therapy Which antibiotic? possible pathogens on site of infection antibiotics requirement -coverage/ resistance pattern/tissue penetration /safety/cost Optimizing PK/PD Physiology and pathophysiology advanced age/children/pregnant women/breast feeding renal/heptic dysfunction/combined dysfunction Other considerations An abx covering probable pathogen(s) + An era of antibiotics An era of resistance cidal or static/monotherapy or combination/iv or Oral/duration

16 Seldom touched questions Role of co-morbidity in Abx decision? -more drugs in patient with co-morbidities? Role of Infection Severity in Abx Decision? -more or wide spectrum abx in serious infection? Cunha,BA. Empiric Therapy of CAP CHEST 2004; 125: )

17 Role of co-morbidity in Abx decision Systemic disorders-prognostic significance and can predict complications/icu admission, but should have no effect on antibiotic selection -Pts with asplenia with overwhelming S pneumoniae bacteremia are treated with penicillin or ß-lactam. -Pts with intact B-cell immunity and non life-threatening S pneumoniae bacteremia are treated the same way (same drug, dose, route of administration, and duration of therapy). Adding another drug makes little sense since the target of therapy is pathogen, unaffected by morbidities

18 Role of Infection Severity in Abx Decision Severity primarily dependent on underlying functional capacity of lung, heart, and immune system. Severity of infection not a reason to increase spectrum or to add another antibiotic -In COPD pts with compromised pulmonary function,a avirulent pathogen (eg, M catarrhalis) CAP can lead to severe CAP requiring ICU admission. -if enough coverage for PRSP/common bacteria/legionella, There is no reason for adding P aeruginosa coverage in non-cystic fibrosis/chronic bronchiectasis pts. If severe CAP treated initially with appropriate empiric monotherapy, no reason for expanded coverage!

19 Role of Infection Severity in Abx Decision Therapeutic choice is determined -by the probable pathogen -NOT the severity of illness. Severity determines -ICU admission/initial mode of abx use -not choice of abx

20 What s in the guidelines IDSA,CIDS-CTS, ATS and BTS CAP Outpatient Inpatient Ward ICU

21 CAP: ATS-IDSA Guidelines for Outpatient Treatment CAP Outpatient Therapy Previously Healthy No recent antibiotic Recent antibiotic Macrolide or Doxycycline Respiratory FQs alone, or advanced Macrolide + -lactam Mandell LA, et al. Clin Infect Dis 2007;.

22 CAP: ATS-IDSA Guidelines for Outpatient Treatment CAP Outpatient Therapy Asia Previously Healthy >25% high-level (MIC 16 g/ml) mac-resistant S. pneumoniae respiratory FQs Regimen selected will depend on nature of recent antibiotic therapy -lactam + macrolide or respiratory FQs Mandell LA, et al. Clin Infect Dis 2007;.

23 CAP: ATS-IDSA Guidelines for Outpatient Treatment CAP Outpatient Therapy No recent antibiotic Comorbidities Recent antibiotic chronic heart/lung/liver/renal DM Alcoholism Malignancies Asplenia Immunosuppressive or use of immunosuppressing drugs -lactam + macrolide or respiratory FQs Respiratory FQs or advanced macrolide + -lactam Regimen selected will depend on nature of recent antibiotic therapy Mandell LA, et al. Clin Infect Dis 2007;.

24 2007 ATS/IDSA Guidelines: Inpatients CAP Inpatient Therapy Medical Ward No Recent Antibiotic Recent Antibiotic Respiratory FQs or Advanced macrolide + ß-lactam Advanced macrolide + ß-lactam or Respiratory FQs * Regimen selected will depend on nature of recent antibiotic therapy (Moxi, Levo 750) Mandell LA, et al. Clin Infect Dis 2007

25 2007 ATS/IDSA Guidelines: Inpatients CAP Inpatient Therapy Intensive Care Unit No Pseudomonas Risk Pseudomonas Risk No ß-lactam Allergy ß-lactam Allergy No ß-lactam Allergy ß-lactam Allergy ß-lactam + advanced macrolide OR FQS Respiratory FQs + aztreonam Anti-pseudomonal, antipneumococcal ß-lactam /penem + Cipro/Levo 750 OR + aminoglycoside + Azithromycin Aztreonam + respiratory FQs + aminoglycoside * Regimen selected will depend on nature of recent antibiotic therapy (Moxi, Levo 750) Mandell LA, et al. Clin Infect Dis 2007

26 Why is outpatient management of CAP important? Major cost increment comes with admission to hospital Niederman, et al. Clin Ther. 1998;20: Strategies for Cost Reduction Shift care to outpatient setting Not easily done with current prognostic scoring approaches May be easier with new abx: FQs (high bioavailablity/good penetration) More rapid switch to oral therapy for admitted patients No need for 24-hour observation on oral therapy Comfort level for early discharge may increase with FQs because of high bioavailability

27 Keypad Question. What do you think is the current and future role of oral antibiotics in managing CAP? 1. Outpatient CAP 2. IV to oral switch 3. Moderately severe CAP 4. All of the above

28 Oral Antibiotic Therapy for CAP If IV-to-oral switch therapy good -oral therapy for hospitalized pts with moderate to moderately severe CAP should be sufficient IV abx be largely relegated to pts with severe CAP in ICU setting Cunha,BA. Empiric Therapy of Community-Acquired Pneumonia CHEST 2004; 125: )

29 Oral Antibiotic Therapy for Non-ICU Hospitalized Patients With CAP Question: why hospitalized if solely oral therapy Answer be hospitalized -for monitoring of cardio-pulmonary function -other systemic diseases (eg, liver or renal disease) requiring inhospital observation, diagnostic procedures or oxygen therapy Cunha,BA. Empiric Therapy of Community-Acquired Pneumonia CHEST 2004; 125: )

30 Oral Antibiotic Therapy for Non-ICU Hospitalized Patients With CAP As with IV-to-oral switch programs, physicians need to develop confidence that oral therapy provides the same results as IV therapy for hospitalized, non-icu patients with CAP Guidelines should encourage the transition to oral therapy for all but ICU CAP patients, which would help to change prescribing habits. Cunha,BA. Empiric Therapy of Community-Acquired Pneumonia CHEST 2004; 125: )

31 Oral Antibiotic Therapy for Non-ICU Hospitalized Patients With CAP-CONCLUSION The future is empiric, oral monotherapy with a carefully chosen agent -right spectrum -good PK properties -low resistance potential -orally/iv available -moderately priced Cunha,BA. Empiric Therapy of Community-Acquired Pneumonia CHEST 2004; 125: )

32 Summary Pneumonia continues to be an important cause of morbidity and mortality Rapid administration of appropriate antibiotics leads to the best outcomes Stratify on risks for mortality and ICU admission to decide the site of care very important -delay to ICU admission lead to poor outcome -outpatient care is cost-effective

33 Summary Strategies for Cost Reduction includes -Shift care to the outpatient setting -More rapid switch to oral therapy for admitted patients In the future, oral monotherapy with a carefully chosen agent such as respiratory FQs (eg. Moxifloxacin) ) might be very useful in hospitalized patients with moderately severe CAP

34 THANK YOU

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