A Survey From Major Guidelines..in the treatment of CAP & bronchitis Prepared by: Magdy El-Shafei...

A Survey From Major Guidelines..in the treatment of CAP & bronchitis

Prepared by:Magdy El-Shafei

Pharm BGroup Product Manager

Medical Union PharmaceuticalsM.U.P.

For the memory of a great Egyptian person in industry, Medical

practice and Manhood..

Prof./ Zakareya Gad

Honorarium

To discuss the recommendationsoutlined by major guidelines

For Bronchitis and CAP

Infectious Diseases Society of America American Thoracic SocietyThe Canadian guidelines for the management of AECB,

With a particular focus on what M.U.P.Offers for the best of our patients, Doctors and medical practice.

Objective

Controversial role of antibiotics•FEV1 > 50%•Exacerbations =OR> 4 /Yr.•Heart diseases•Use of Oxygen

•Antibiotics in the last 3 mo.

In AECB(ABECB)

How the antibiotics Are chosen for AECB

Evidence-based practiceEvidence-based practiceBest outcome for patientsBest outcome for patientsBest use of resourceBest use of resourceLeast resistanceLeast resistanceLeast costLeast costRestricts idiosyncratic Restricts idiosyncratic behaviourbehaviour

Strept. Pneumonia

Haemophylus influenzae

Contribute -With M. Ctarrahlalis- to 30-50% of bronchitis

Klebsiella Pneumonia

Staph. aureus

10-15%

Legionella PneumophilaChlamydia PneumoniaMycoplasma Pneumonia

>5 to15%

Strept. Pneumonia



Staph. aureus


In Pneumonia

Probably the most common cause of community-acquired pneumonia

35.735.7 % % MortalityMortality

70% of the cases 1% Co-morbidities, Elderly31.8 %31.8 %

14.7 %14.7 %

P. aeruginosaP. aeruginosa

61.061.0% %

Strept. Pneumonia



Staph. aureus



G+

G-

Atypical

Antibiotics differences

Ampicillin Amoxicillin

Clinical treatment failure

Strept. Pneumonia



Staph. aureus



G+

G-

Atypical


Macrolides

azithromycinClarithromycin

(spiramycin)

Strept. Pneumonia



Staph. aureus



G+

G-

Atypical


3rd generation cephalosporins

As penicillin resistance rates increase the rates and degrees of cephalosporin

resistance increase

Recent Studies done In Kasr El Aini Hospitals: 2009 – 2010

E.coli and Klebsiella producing cephalosporinase (ESBL) reached 75% in

one study and 90% in another study*

*Prof Dr. Maha Gaafar IC Dept. ElQuasr el Einy univ. hosp 2010

Strept. Pneumonia



Staph. aureus



G+

G-

Atypical


FQ

Ciproxacin

Strept. Pneumonia



Staph. aureus



G+

G-

Atypical


FQ

Moxifloxacinlevofloxacin

2010- 11 Surfing across major guidelines

• In cases of acute exacerbations of chronic bronchitis (AECB) and community-acquired pneumonia (CAP), recent guidelines suggest:

using fluoroquinolone (moxifloxacin – levofloxacin) antibiotics as first-line therapy.

• This suggestion is based on level I evidence from several trials (clinical and microbial superiority of these agents).

• Fluoroquinolones (moxifloxacin – levofloxacin) shorten hospital stay, reduce recurrences, and lower costs.

• Resistance is still very low.

M. Balter – CFP 2002 & 2010

Canadian guidelines recommendations for the treatment of AECB

Baseline Clinical Status

PathogensCriteria Factors

TreatmentAlternative For ttt.Failure

0 - Acute tracheobronchitis

Usually viral Cough and sputum

None,

consider macrolide (SPIRAMYCIN)or tetracycline

I- Simple chronic bronchitis

H influence, M catarrhalis, S pneumonia (Possible B-lectern resistance)

FEV1 > 50% increased sputum volume and purulence

Quinolone, penicillin + B- lactamase inhibitor(Amox. – Clav)Or (AMPICILLIN/SULBACTAM)

IIChronic bronchitis(with risk factors)

H influence, M catarrhalis, S pneumonia (resistance to B-lactams common)

As for class 2+any one of: FEV1

<50%. Advanced age, > 4 exacerbations, significant co morbidity

, May require parentral therapy or hosp.

IIIChronicsuppurative bronchitis

Above + Enterobacteria, P aeruginosa

class 3 + continuous sputum throughout year

2002

second- or third-generation cephalosporin

second-generation macrolide

If symtoms persist >10 D

Aminopenicllin

2011

second- or third-gen. cephalosporin 2nd gen. macrolide Ciprofloxacin

Moxifloxacin- levofloxacinpenicillin + B- lactamase inhibitor(Amox. – Clav)Or (AMPICILLIN/SULBACTAM)

Initial empiric therapy for suspected bacterial community-acquired pneumonia (CAP) in immunocompetent adults.

LAST UPDATES: I D S A G U I D E L I N E S

Out patients

Inpatients

UNICTAM

3 Gram

Richard R. Yates Chest 1999

COULD CEPHALOSPRINS resistanceBE REVERSED??

Rahal; JAMA, October, 1999

COULD CEPHALOSPRINS resistanceBE REVERSED??

Managing AECB & CAP

In today`s guidelines

Combination penicillins

B- lactamase irreversible

Inhibitors

Like

Ampicillin/sulbactam

Amoxicillin/ clavlanic

(in CAP:Plus a macrolide)

Respiratory quinolones

3rd generation

(levofloxacin)

4th generation(Moxifloxacin)

Alone or plus Amp./sulbactam

CDCIDSA

Mayo Clinic

Moxifloxacin structure activity relationship

• Minimizes development of resistance

• Enhances anaerobic activity

• Higher gram-positive activity

• Minimizes efflux (S. pneumoniae, S. aureus)

Petersen et al 1996 Domagala, JM 1994

F

O OH

H

H

NH

NN

O6

5

7

H3CO

8

4

1

2

3

A greater binding Affinity to the topoisomerase enzyme

Mode of action that minimizes micro resistance

WIEDEMANN, Poster P0773, ECCMID Berlin 1999

11 000000 000000 CFUCFU

TOTO

11 000000 CFUCFU

Eradication in Eradication in 33 hrshrs..

Bactericidal inBactericidal inRECORD TIMERECORD TIME

Moxifloxacin

Modern 4Modern 4thth Generation F.Quinolone Generation F.QuinoloneWithWith Greater antimicrobial power on G +ve bacteriaG +ve bacteria

MoxifloxacinMoxifloxacin inhibits about

90%90% of strept. strains, while

International Journal of Antimicrobial Agents 20 )2002( 196/200

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

killedstreptococci

killedstreptococci

resiatant

ciprofloxacin only inhibits 42%.

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

killedstreptococci

ciprofloxacin

moxifloxacin

MOMORDERN: RDERN: 4th Generation F.Quinolone4th Generation F.Quinolone

55 times higher concentrations

over ciprofloxacinciprofloxacin

In

Alveolar Macrophages

Data on File*Mean ± SD measured 3H after dosing with 400 mg Andrews, et al. JAC 40:573-577, 1997**Measured 2 and 4H after dosing with 500 mg ciprofloxacin

Tissue Penetration

MoxifloxacinMoxifloxacin High Respiratory Tissue High Respiratory Tissue PenetrationPenetration

0.01

0.1

1

10

100

100

0.12 S.pneumoniae , M.Catarrhalis

0.06 H.influenzae

MIC90

(mg/

l)

Andrews J et al.38th ICAAC, 1998;San Diego, A29

Respiratory tissue concentration after one single p.o dose

Bronchial

Mucosa

Epithelial LiningFluid(ELF)

Alveolar Macrophage

moxifloxacin

Clinical Success

CMAJ. 2008 March

comparisons of effectiveness and safety between

fluoroquinolones and β-lactam antibiotics. indicates a statistically significant

difference favours fluoroquinolone

therapy;.

In AECB

A single-arm analysis, comparing the efficacy of moxifloxacin with ciprofloxacin in patients with acute exacerbation of chronic bronchitis (AECB) Adapted from ref. 1

1.Mittmann N, Jivarj F, Wong A, Yoon A. Oral fluoroquinolones in the treatment of pneumonia, bronchitis and sinusitis. Can J Infect Dis. 2002; 13 (5): 293-300.

AECB ( Cont’d)

A randomized, non-blinded, multinational, multicentre study comparing the efficacy of moxifloxacin with amoxicillin/clavulanate in 512 evaluable patients with clear signs of AECB.

Adapted from ref. 2

2.Schaberg T, Ballin I, Huchon G, et al. A multinational, multicentre, non-blinded, randomized study of moxifloxacin oral tablets compared with co-amoxiclav oral tablets in the treatment of acute exacerbation of chronic bronchitis. J Int Med Res 2001;

29( 4 :)314-28.

Fast Eradication of Respiratory pathogens.

Quick relief of symptoms.

Rapid and Complete clinical cure.

Rare bacterial resistance.

Minimal Risk of Drug/food Interaction.

No Dose adjustment in elderly , renal or hepatic patients.

Empirical Antimicrobial Therapy for Community-Acquired Pneumonia In Immunocompetent Adults

Patient, SettingCommon PathogensEmpirical Therapy

Severely ill

S. Pneumoniae §Legionella spp.Gram-negative bacilliM. pneumoniaeVirusesS. aureus

Azithromycin, or fluoroquinolone‡ and cefotaxime, ceftriaxone, or beta-lactam or beta-lactamase inhibitor¶

If P. aeruginosa possible—IV macrolide or fluoroquinolone and aminoglycoside IV, or antipseudomonal quinolone and antipseudomonal beta-lactamIf MRSA possible, add vancomycin or linezolid

‡Levofloxacin, gatifloxacin, moxifloxacin.§Critically ill patients in areas with significant rates of high-level pneumococcal resistance and a suggestive sputum Gram stain should receive vancomycin or a newer quinolone pending microbiologic diagnosis.

¶ ampicillin-sulbactam or Piperacillin-tazobactam. ¶Cefpodoxime, cefuroxime, high-dose amoxicillin, amoxicillin-clavulanate, or parenteral ceftriaxone followed by oral cefpodoxime. **Cefotaxime, ceftriaxone, ampicillin-sulbactam, or high-dose ampicillin

Be sure to cure in the time of

BIG CHALLENGE RTIs

What MUP offers

• Quality

• Scientific credibility

• Price

Best outcome for patientsBest outcome for patientsBest use of resourceBest use of resourceLeast resistanceLeast resistanceLeast costLeast costRestricts idiosyncratic Restricts idiosyncratic

Prof/ Maha Gaafar IC Dept. ElQuasr el Einy univ. hosp 2010

UNICTAM

Saving Cephalosporins abuse

Ampicillin/sulbactam

What MUP offers

• Quality

• Scientific credibility

• Price

Best outcome for patientsBest outcome for patientsBest use of resourcesBest use of resources

Least resistanceLeast resistanceLeast costLeast cost

Restricts idiosyncraticRestricts idiosyncratic

From Cleveland to Baltimore to Cairo

Few years ago with Prof. Dr Awad Tag ElDin

For what the martyrs died forbetter, free & dignity Egypt

The Egyptian Society of Chest &

Tuberculosis

•FEV1 > 50%•Exacerbations =OR> 4 /Yr.•Heart diseases•Use of Oxygen

•Antibiotics in the last 3 mo.

•Group 1•2nd G Macrolide•2nd or 3rd G cephalosporins•TMO-SMX•Doxycyclene

NoneOneOrMore

Improved worsen•FQ•Moxacin - Levanic

•Group II•FQ

•B-lactam/Blactamase•Ampicillin/sulbactam

Improved•Did not•improve

•Did not•improve

•Group III•Anbulatory patient•Hospitalized patient:

Consider Ps. AeroginosaeCiprofloxacin infusion

Can Resp J 2003

• Empiric Treatment – Outpatient:

– No confounding factors: macrolide (azithromycin 500mg x 1 day then 250mg Qday or clarithromycin 500mg po Q12hrs or clarithro-ER 1000mg Qday) or doxycycline 100mg Q12hrs

CAP:IDSIDSA-ATS Treatment Guidelines

• Empiric Treatment – Outpatient:

– Confounding factors present:

respiratory quinolone (levofloxacin 750mg Qday, moxifloxacin 400mg Qday)

or

beta-lactam (amoxicillin 1g Q8hrs, amox-clav-ER 2gm Q12hrs,

cefpodoxime 200mg Q12hrs, cefdinir 300mg Q12hrs, etc) + macrolide

or

beta-lactam + doxycycline

CAP:IDSIDSA-ATS Treatment Guidelines

• Empiric Treatment – Hospitalized, non-ICU:

– Beta-lactam (ceftriaxone, cefotaxime, ampicillin/sulbactam, or ertapenem) + macrolide or doxycyclineor

– Respiratory quinolone alone (levofloxacin, moxifloxacin, gemifloxacin)

CAP:IDSA-ATS Treatment Guidelines

• Empiric Treatment – Hospitalized, ICU:

– Beta-lactam (ceftriaxone, cefotaxime, or ampicillin/sulbactam) + macrolide or respiratory quinolone

– PCN-allergic = resp quinolone + aztreonam

CAP:IDSA-ATS Treatment Guidelines

Fluoroquinolones for Respiratory Infections

Comparison of Recent Guidelines for Empiric Initial Therapy of CAP*

VariablesDrugs RecommendedModifying Factors

IDSA (Bartlett et al)

OutpatientDoxycycline, macrolide, or fluoroquinolone (no distinction)

Older patients: many prefer fluoroquinolone Underlying disease: many prefer fluoroquinolone Prevalence high PCN resistance: consider fluoroquinolone

Hospitalized ward

Cefalosporin + (macrolide or fluoroquinolone) or; β-lactam/β-lactamase inhibitor + macrolide;or; fluoroquinolone alone

ICU

)Cefalosporin or β-lactam/β-lactamase inhibitor)+ (macrolide or fluoroquinolone(

Prior lung disease: (pseudomonal β-lactam [±β-lactamase inhibitor] or carbapenem)+ fluoroquinolone (high-dose ciprofloxacin) β-lactam allergy: fluoroquinolone ± clindamycin Suspect aspiration: fluoroquinolone ± (clindamycin, metronidazole, or β-lactam/β-lactamase inhibitor)

Williams J. Jr.

VariablesDrugs RecommendedModifying Factors

CIDS/CTS (Mandell et al

Outpatient1st choice macrolide, or 2nd choice doxycycline

COPD: 1st choice newer macrolide, or 2nd choice doxycycline COPD + recent antibiotic or steroid: 1st choice respiratory fluoroquinolone (eg, levofloxacin or newer generation), or 2nd choices (amoxicillin/clavulonate+ macrolide), or 2nd-generation cephalosporin+ macrolide Suspect aspiration: 1st choice amoxicillin/clavulonate ± macrolide or 2nd choice respiratory fluoroquinolone + (clindamycin or metronidazole) Nursing home: respiratory fluoroquinolone

Hospitalized ward

1st choice IV respiratory fluoroquinolone or 2nd choice (2nd-, 3rd-, or 4th-generation cephalosporin+ macrolide(

ICU

1st choice respiratory fluoroquinolone + (cefotaxime, ceftriaxone, or β-lactam/β-lactamase inhibitor) or 2nd choice IV macrolide + (cefotaxime, ceftriaxone, or β-lactam/β-lactamase inhibitor)

Pseudomonas suspected: 1st choice antipseudomonal fluoroquinolone (eg, ciprofloxacin)+ (antipseudomonal β-lactam or aminoglycoside) or 2nd choice triple therapy with antipseudomonal β-lactam (eg, ceftazidime, piperacillin-tazobactam, imipenem, or meropenem) + aminoglycoside+ macrolide

A Survey From Major Guidelines..in the treatment of CAP & bronchitis Prepared by: Magdy El-Shafei...

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