a survey from major guidelines..in the treatment of cap & bronchitis prepared by: magdy...
TRANSCRIPT
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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.
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For the memory of a great Egyptian person in industry, Medical
practice and Manhood..
Prof./ Zakareya Gad
Honorarium
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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
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Controversial role of antibiotics•FEV1 > 50%•Exacerbations =OR> 4 /Yr.•Heart diseases•Use of Oxygen
•Antibiotics in the last 3 mo.
In AECB(ABECB)
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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%
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Strept. Pneumonia
Haemophylus influenzae
Klebsiella Pneumonia
Staph. aureus
Legionella PneumophilaChlamydia PneumoniaMycoplasma Pneumonia
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% %
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Strept. Pneumonia
Haemophylus influenzae
Klebsiella Pneumonia
Staph. aureus
Legionella PneumophilaChlamydia PneumoniaMycoplasma Pneumonia
P. aeruginosaP. aeruginosa
G+
G-
Atypical
Antibiotics differences
Ampicillin Amoxicillin
Clinical treatment failure
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Strept. Pneumonia
Haemophylus influenzae
Klebsiella Pneumonia
Staph. aureus
Legionella PneumophilaChlamydia PneumoniaMycoplasma Pneumonia
P. aeruginosaP. aeruginosa
G+
G-
Atypical
Antibiotics differences
Macrolides
azithromycinClarithromycin
(spiramycin)
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Strept. Pneumonia
Haemophylus influenzae
Klebsiella Pneumonia
Staph. aureus
Legionella PneumophilaChlamydia PneumoniaMycoplasma Pneumonia
P. aeruginosaP. aeruginosa
G+
G-
Atypical
Antibiotics differences
3rd generation cephalosporins
As penicillin resistance rates increase the rates and degrees of cephalosporin
resistance increase
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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
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Strept. Pneumonia
Haemophylus influenzae
Klebsiella Pneumonia
Staph. aureus
Legionella PneumophilaChlamydia PneumoniaMycoplasma Pneumonia
P. aeruginosaP. aeruginosa
G+
G-
Atypical
Antibiotics differences
FQ
Ciproxacin
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Strept. Pneumonia
Haemophylus influenzae
Klebsiella Pneumonia
Staph. aureus
Legionella PneumophilaChlamydia PneumoniaMycoplasma Pneumonia
P. aeruginosaP. aeruginosa
G+
G-
Atypical
Antibiotics differences
FQ
Moxifloxacinlevofloxacin
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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
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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)
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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
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UNICTAM
3 Gram
Richard R. Yates Chest 1999
COULD CEPHALOSPRINS resistanceBE REVERSED??
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Rahal; JAMA, October, 1999
COULD CEPHALOSPRINS resistanceBE REVERSED??
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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
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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
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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
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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
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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
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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
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moxifloxacin
Clinical Success
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CMAJ. 2008 March
comparisons of effectiveness and safety between
fluoroquinolones and β-lactam antibiotics. indicates a statistically significant
difference favours fluoroquinolone
therapy;.
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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.
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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.
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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.
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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
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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
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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
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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
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•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
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• 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
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• 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
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• 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
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• 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
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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.
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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