Cap- Staff Conference

§ § § § § § § § § §

Diseases of the heart Diseases of the vascular system Pneumonia Cancer Accidents Tuberculosis Chronic Obstructive Lung Disease Diabetes Mellitus Diseases of the respiratory system *All Preventable with Education and Public Health Kidney diseases infrastructure (DOH 2006)

Morbidity

Mortality

No. 1 Lower RTIs and Pneumonia

No. 5 Pneumonia

No. 2 Bronchitis/Bronchiolitis No. 6 Tuberculosis

No. 6 Tuberculosis No. 8 Chronic Respiratory Diseases (COPD,AECB)

¾ of all antibiotic consumption is for RTIs (last updated February 11, 2008)

Source : National Epidemiology Center, DOH

Evi dence -B ased Cl in ica l Pra ctice Gui delines in C ommu nit y Ac qui red Pneumoni a 

Ame ri can Coll eg e of Ch est Phy si cians St at eme nt: Mx of CA P in the Home (AC CP 2 005)



The Ph ili pp ine Cl in ical P ract ice Guid el in es on CA P in Adul ts (PC PG 2004 )



Brit ish Th ora cic Societ y ( BTS 2004 )



Ame ri can Thoracic So cie ty (AT S 2001 )



In fectious Dis ease Societ y of Ame rica (I DSA 2000 )



Can adi an Inf ect io us D iseas e So ci et yCa na dia n Thoraci c Soci et y (CI DS- CT S 2000)

Clinical Practice Guidelines Diagnosis, Empiric Management & Prevention of Community Acquired Pneumonia in Immunocompetent Adults: 2004 Update

A Joint Statement of: • Philippine Society for Microbiology and Infectious Diseases • Philippine College of Chest Physicians • Philippine Academy of Family Physicians

Presumptive Definition of CAP as per Phil CPG 04 

LRT I acquir ed f rom the communi ty wit hi n 24 h to < 2 weeks



Acut e cough



RR > 20, H R > 1 00, fev er



Ab norma l chest p hysi cal f ind ings



No pa rt icul ar sympt om or a bn orma l P.E. find in g is s uff ici ent ly sens it ive or spec ifi c to co nfir m or ex clu de t he D x

Value of Chest X-Ray in CAP Diagnosis • Accuracy of predicting CAP by physicians’ clinical judgment is at best 60 – 76% • All the guidelines are unanimous in requiring a chest radiograph to establish the diagnosis and the presence of complications (e.g., pleural effusion, multilobar disease)

2007 JOINT IDSA-ATS CAP 2009 JOINT PSMIDPCCP-PAFP

SITE-OF-CARE Outpatient

•

•

Medical Ward

ICU

Guided by: disease-specific prognostic indicators to assess the initial severity of pneumonia physician’s clinical judgement, supplemented by objective findings

Current Approaches to CAP Therapy

CURB 65 Score 1 point for each:

•Confusion •Urea >7 mmol/L •RR ≥30/min •BP (SBP <90 mmHg or DBP ≤60 mmHg •Age ≥65 years

0 or 1 Home treatment

2

>3

Hospital supervisio n

Hospital / ICU

CURB 65 Sc ore

Risk of mortality/ ICU admission

0

0.7%

No hospitalization

1

3.2%

Hospital referral & assessment: can be outpatient

2

13%

3

17%

4

41.5%

5

57%

1 poin t each :

Dis posi tio n

Hospital referral & assessment: short inpatient or supervised outpatient

C U R B

-

onfusion rea >7 mmol/l espiratory rate > 30/min

lood pressure low, systolic <90 or diast < 60

Age > 65

Sev ere CAP Urgen t hos pit al ad mi ssion Lim et al. Thorax 2003;58:377–382.

• CRB-65 omits blood urea measurement • Applicable to office-based settings

CRB- 65 Scor e

30-Day Mor tal ity ( %)

0

0

1

4.1

2 18.7 • Scores: 0=home 3 43.5 treatment 1=hospital4 54.6 supervised treatment Capelastegui A et al. Eur Respir J. 2006;27:151-157. ≥2=hospitalizati

Which patient will need hospital admission?

Which patient will need hospital admission? 

Pts w/ stable VS:   

   

RR < 30 breaths/min, PR < 125 beats/min, SBP > 90 mmHg or DBP > 60 mmHg & Temp >36oC and <40oC

No altered mental status of acute onset (NEW) No or stable comorbid condition * No evidence of aspiration CXR: localized infiltrates; no evidence of pleural effusion nor abscess

LOW Ris k C A P -- -> Ou tpa ti ent Ca re

* Comorbid conditions include:         

Diabetes mellitus (DM) Neoplastic disease Neurologic disease Congestive heart failure (CHF) Coronary artery disease (CAD) Renal failure COPD Chronic liver disease Chronic alcohol abuse

Which patient will need hospital admission? ANY OF THE FOLLOWING 

Patients with unstable sign    

   

RR > 30/min PR > 125/min Temp > 40oC or <36oC SBP<90mmHg or DBP <60mmHg

Altered mental status of acute onset Suspected aspiration Unstable comorbid conditions* CXR: multilobar, pleural effusion, abscess

Mode rate Ris k C A P ---> In -pat ient

*Unstable comorbid conditions include:        

uncontrolled diabetes mellitus (DM) active malignancies neurologic disease in evolution congestive heart failure (CHF) Class II-IV unstable coronary artery disease (CAD) renal failure on dialysis uncompensated COPD decompensated liver disease

Which patient will need hospital admission?

 

Any criteria under moderate risk category plus Septic shock with need for vasopressor Need for mechanical ventilation (invasive or non-invasive)

Hig h Ri sk C A P - --> Inten si ve ca re

What microbiologic studies are necessary in CAP? Low Risk CAP • Sputum GS CS (optional for CAP pts with co-morbid conditions)

High Risk CAP  

Moderate Risk CAP   

Blood CS 2 sites Sputum GS CS



Blood CS 2 sites Respiratory secretion GS CS Urine Ag Test for L. pneumophila DFA Test for L. pneumophila

Treatment

Initial Inadequate Antibiotic Therapy Increases Mortality Alvarez-Lerma,1996

Initial adequate therapy

Rello, 1997

Initial inadequate therapy

Kollef, 1999 Kollef, 1998

Anti biot ics sh oul d be ini tia ted w it hi n 4 Ibrahim, 2000 hours of D x of CAP Luna, 1997 0

20

40

60

80

% Mortality Alvarez-Lerma F, et al. Intensive Care Med. 1996;22:387-394. Kollef MH, et al. Chest. 1998;113:412-420. Ibrahim EH, et al. Chest. 2000;118L146-155. Luna CM, et al. Chest. 1997;111:676-685. Kollef MH, et al. Chest. 1999; 115:462-474. Rello J, et al. Am J Respir Crit Care Med. 1997;1 56:196-200.

100

Antibiotic Treatment Major goal of therapy:

Major goal of therapy: eradication of the infecting organism, with resultant resolution of clinical disease

Thus, ANTIMICROBIALS are a mainstay of treatment



Until more accurate and rapid diagnostic methods are available, the initial treatment for most patients is EMPIRIC



Selection of antibiotics for empirical therapy is based on prediction of the most likely pathogens and knowledge of local susceptibility patterns

Principles of Empirical Therapy in Management of CAP 

give antibiotics / therapy as soon as possible after the diagnosis is considered likely (IDSA/ATS 2007)



cannot reliably differentiate etiology on basis of clinical findings



Treat most likely pathogens    

S. pneumoniae; H. Influenzae Atypicals Others (local epidemiology) *co-morbid conditions, recent antibiotic use, recent hospitalization, hypersensitivity

Most common etiologies of CAP

Outpatient Streptococcus pneumoniae Mycoplasma pneumoniae Haemophilus influenzae Chlamydophila pneumoniae Respiratory viruses

Inpatient (non-ICU) S. pneumoniae  M. pneumoniae  C. pneumoniae  H. influenzae  Legionella species  Aspiration  Respiratory viruses 

Inpatient (ICU) •S. pneumoniae •Staphylococcus aureus

•Legionella species •Gram-negative bacilli •H. influenzae

Evidences – Aetiologic distribution of Community-acquired pneumonia in Asian Countries Aetiology (n=390) Streptococcus pneumoniae Klebsiella pneumoniae Haemophilus influenzae Pseudomonas aeruginosa Staphylococcus aureus Mycobacterium tuberculosis Moraxella catarrhalis Other pathogens Mycoplasma pneumoniae Chlamydia pneumoniae Legionella

No. of Isolates (%) 114 (29.2) 60 (15.4) 59 (15.1) 26 (6.7) 19 (4.9) 13 (3.3) 12 (3.1) 77 (19.7) 61/556 (11) 55/411 (13.4) 7 /648 (1.1)

Epidemiology and Clinical outcomes of Community-acquired pneumonia in Adult patients in Asian countries: A prospective study by the Asian network for Surveillance of Resistance pathogens. Jae-Hoon song et.a. International Journal of Antimicrobial Agents 31 (2008): 107-114

Resistance pattern of

Streptococcus pneumoniae 2004 2005 2006 2007 Penicillin Cotrimoxazole Chloramphe nicol

5

11

6

1

15

16

14

18

5

4

5

5

Celia C. Carlos, ARSP, DOH

Resistance pattern of

Haemophilus influenza 2004 2005 2006 2007 Ampicillin

10

10

9

11

Cotrimoxazole Chloramphe nicol

36

15

16

13

10

20

14

8

Celia C. Carlos, ARSP, DOH

Resistance pattern of

Moraxella catarrhalis 2004 2005 2006 2007 Ampicillin

9

16

15

19.6

Coamoxiclav Cotrimoxazole Erythromyci n

1

7

5

11.4

38

50

59

49.6

27

32

24

32.7

Celia C. Carlos, ARSP, DOH

What is the empiric treatment for CAP?

IDSA/ATS Consensus Guidelines on CAP 2007 (Clinical Infectious Diseases 2007;44:S27OU TPAT IENT IN PAT IENT: INPA TIENT: 72) GENERAL W ARD

Previou sly heal th y, no antib io ti cs th e pas t 3 mont hs: A ma cro lid e (I) Doxy cy cli ne (III )

750)

+

Co -mor bid it y or rece nt anti bio tic use: Re spirat or y FQ (L evo (I ) Hig h-dose beta -la ct am* macrolid e (I) * Amox 1g tid Co-am ox 2g bid Ce ftria xo ne,

Re spirat or y Flu oroq uin olon e (le vo, mox i or gemi) (I ) OR Be ta-lac ta m* + Ma crolide (I) or Dox ycyclin e (II I) *ce fot ax im e, ce tria xo ne , ampic illi n-sulbact am ertapenem For ca refully selec te d patie nts wit ho ut ris k fact or s for DRS P or GNR,

mo no the ra py w it h azit hr omy cin ca n be co nsid ered

ICU ( SE VERE C AP)

No Pseudomonal risk: Beta-lactam (cefotaxime, ceftriaxone, ampicillinsulbactam) PLUS

IV Macrolide (II)

or

IV Fquinolone (I)

Pseudomonal risk factors present:  Anti-Pseudo, Anti-pneumo Blactam (cefepime, piptazo, imipenem, meropenem) PLUS Cipro or Levofloxacin (750 mg)  Above beta-lactam PLUS IV aminoglycoside or IV antipneumococcal FQ *Add Vanco or Linezolid for CAMRSA

LOW RISK CAP

What is the empiric treatment for Low Risk CAP? Low Risk CAP with no co morbid conditions



2004 Recommendation  





Amoxicillin OR Extended macrolides 



Alternative 

Co-trimoxazole

2009 Recommendation Amoxicillin

Alternative 

Extended Macrolides: azithromycin dihydrate, clarithromycin

What is the empiric treatment for Low Risk CAP? Low Risk CAP with stable co morbid conditions Recommendation (2004/2009): co-amoxiclav or sultamicillin or 2nd gen cephalosporin (cefuroxime axeteil, cefaclor) or extended macrolide (azithromycin dihydrate, clarithromycin)

Moderate Risk CAP

Moderate Risk CAP Recommendation (2004/2009): IV nonpseudomonal b-lactam +/b-lactamase inhibitor + macrolide Alternative: antipneumococcal FQ

Nonpseudomonal β-lactam 

IV β-lactams  





2nd gen cephalosporin (cefuroxime sodium) 3rd gen cephalosporins (ceftriaxone, cefotaxime) those w/ anaerobic activity (cefoxitin, ceftizoxime, ertapenem)

IV β-lactams w/ β-lactamase inhibitor  

ampicillin-sulbactam amoxicillin-clavulanic acid

Antipneumococcal Fluoroquinolone 

Moxifloxacin



Levofloxacin

High Risk CAP with No risk for Pseudomonas aeruginosa Recommendation (2009): IV nonpseudomonal antipneumococcal βlactam +/- β-lactamase inhibitor + IV macrolide Alternative: IV antipneumococcal FQ

High Risk CAP with Risk for Pseudomonas aeruginosa Recommendation (2009):

IV antipseudomonal antipneumococcal β-lactam +/- β-lactamase inhibitor + IV macrolide or IV antipneumococcal FQ +/Aminoglycosides or IV Ciprofloxacin

Antipseudomonal Antipneumococcal β-lactam 

IV β-lactams 

Those without anaerobic activity 



Those with anti-anaerobic activity 



4th gen cephalosporin (cefepime)

Carbapenem (Imipenem-cilastatin, Meropenem)

IV β-lactams w/ β-lactamase inhibitor   

Cefoperazone-sulbactam Ticarcillin-Clavulanic acid Piperacillin-tazobactam

Risk Factor for Pseudomonas aeruginosa CAP History of chronic or prolonged (>7 days within the past month) use of broad spectrum antibiotic therapy  Malnutrition  Chronic Use of steroid therapy: > 7.5 mg/day  Severe underlying bronchopulmonary Source: IDSA-ATS 2007 disease (COPD, bronchiectasis) 

As ses smen t of Cli nica l Res pon se a nd D e-Es ca lat ion Th er apy

IV to 





Or al Swi tch Th er apy for CAP

Single most important advance in the treatment of CAP Early IV to oral switch results in similar outcomes with shorter length of hospital stay and cheaper treatment Antibiotic streamlining to a narrow spectrum antibiotic is possible as early as 72 hours of treatment

Cunha BA, Chest 125: 1913-1919, 2004 Phil CPG 2004

Switch Therapy Criteria 1. Cough and dyspnea are improving 2. Patient is afebrile for at least 8 hours 3. White blood cell count is normalizing 4. PO intake and GI absorption are adequate ATS Guidelines

Dur ati on of Ant ibi oti c Use Base d o n Et iolog y Et io lo gic Age nt Mo st b acter ial pn eumo nia ex cept 

GNB, S. aur eus, P. aer ugi nosa 

En te ric Gram (-) pat hoge ns,

S. au reus, P. ae rugi no sa  

My co pl asma & Chl am ydo ph ili a

Legio nel la sp .

Du rat ion of ther ap y (da ys) 5- 7 3 - 5 (a zal ides ) 10- 14 10- 14 14- 21

Oral Agents with Good Bioavailability and Convenient Dosing Schedule for Switch Therapy 

Se cond/ Thir d Genera ti on Cepha lo spo ri ns



Ext ende d Mac rol ide s



Fluo ro quinol ones

Phil CPG 2004

Impact of CPGs on Clinical Practice • Bef ore an d af ter obse rv at io nal cohort st udy : the imple me nt ati on of the ATS guid eli nes re su lt ed in red uct ion in 30- day mo rtal it y amo ng eld er ly pa tie nt s w it h CA P Dean NC, et. al.Am J Med Ap r 15;110(6) :451-7, 2001

• Co hort group man age d acc ording to CP G vs . ret roact iv el y ide nti fied co ntr ol gro up : rat es of hosp it al admis si on de cre ased wi tho ut a de tecta ble di ffer ence in base li ne seve rit y of ill ne ss, resu lte d i n si gn ifican t co st sa vi ng Su chyta MR, et. al. Am J Me d 110: 306-9, 2001

Impact of CPGs on Clinical Practice • Guid el ine s for se ver e CAP as so cia te d wit h no redu ct ion in mo rtal it y Hi ran i. Thorax 19 97 Ja n; 52( 1) :1721

Impact of CPGs on Clinical Practice “Guide li nes are hel pf ul to tho se wh o hav e kn owl ed ge bu t ar e dan ger ous in th e han ds of tho se wh o do not, a gr oup to wh om gu ide li nes may gi ve confiden ce to ex ceed their knowle dg e. A phy sici an wi tho ut kno wle dg e but wi th gu ide li nes is lik e a m onk ey in a t ree wi th a mach in e gun.” Ma rc Baltzan , CM AJ 166: 1 68, 2002.