Transcript ..in the treatment of CAP & bronchitis Magdy El-Shafei M.U.P.

A Survey From Major Guidelines
..in the treatment of CAP & bronchitis
Prepared by:
Magdy El-Shafei
Pharm B
Group Product Manager
Medical Union Pharmaceuticals
M.U.P.
Honorarium
For the memory of a
great Egyptian person
in industry, Medical
practice and Manhood..
Prof./ Zakareya Gad
Objective
To discuss the recommendations
outlined by major guidelines
For Bronchitis and CAP
Infectious Diseases Society of America
American Thoracic Society
The 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.
In AECB(ABECB)
Controversial•FEV1
role> of
50%antibiotics
•Exacerbations =OR> 4 /Yr.
•Heart diseases
•Use of Oxygen
•Antibiotics in the last 3 mo.
How the antibiotics Are chosen for AECB
Contribute -With M. Ctarrahlalis- to
Strept. Pneumonia
30-50% of bronchitis 10-15%
Evidence-based practice
Best outcome for patients
Best use of resource
Least resistance
Staph. aureus
Least cost
Restricts idiosyncratic
behaviour
Haemophylus
influenzae
Klebsiella
Pneumonia
>5 to
15%
Mycoplasma Pneumonia
Chlamydia Pneumonia
Legionella Pneumophila
In Pneumonia
70% of the cases
Strept. Pneumonia
1% Co-morbidities,
31.8
%
Elderly
Staph. aureus
61.0 %
35.7 %
Mortality
Haemophylus
influenzae
Probably the most common cause of
community-acquired pneumonia
Mycoplasma Pneumonia
Klebsiella
Pneumonia
P. aeruginosa
14.7 %
Chlamydia Pneumonia
Legionella Pneumophila
Antibiotics differences
Ampicillin
Amoxicillin
G+
Strept. Pneumonia
Staph. aureus
GHaemophylus
influenzae
Klebsiella
Pneumonia
P. aeruginosa
Atypical
Mycoplasma Pneumonia
Chlamydia Pneumonia
Clinical treatment failure
Legionella Pneumophila
Antibiotics differences
Macrolides
G+
azithromycin
Clarithromycin
(spiramycin)
Strept. Pneumonia
Staph. aureus
GHaemophylus
influenzae
Klebsiella
Pneumonia
P. aeruginosa
Atypical
Mycoplasma Pneumonia
Chlamydia Pneumonia
Legionella Pneumophila
Antibiotics differences
3rd generation
cephalosporins
G+
Strept. Pneumonia
Staph. aureus
GAs penicillin resistance rates increase
the rates and degrees of cephalosporin
resistance increase
Haemophylus
influenzae
Klebsiella
Pneumonia
P. aeruginosa
Atypical
Mycoplasma Pneumonia
Chlamydia Pneumonia
Legionella Pneumophila
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
Antibiotics differences
G+
FQ
Strept. Pneumonia
Ciproxacin
Staph. aureus
GHaemophylus
influenzae
Klebsiella
Pneumonia
P. aeruginosa
Atypical
Mycoplasma Pneumonia
Chlamydia Pneumonia
Legionella Pneumophila
Antibiotics differences
G+
FQ
Strept. Pneumonia
Moxifloxacin
levofloxacin
Staph. aureus
GHaemophylus
influenzae
Klebsiella
Pneumonia
P. aeruginosa
Atypical
Mycoplasma Pneumonia
Chlamydia Pneumonia
Legionella Pneumophila
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 2002
2011
Baseline
Clinical
Status
Criteria
Factors
Treatment
Alternative
For ttt.
Failure
0 - Acute
Usually viral
tracheobronc
hitis
Cough and
sputum
None,
consider macrolide
(SPIRAMYCIN)
or tetracycline
I -Simple
chronic
bronchitis
FEV > 1
%50
increased
sputum
volume and
purulence
II
Chronic
bronchitis
(with risk
factors)
Pathogens
H influence ,M
catarrhalis, S
pneumonia
(Possible B-lectern
resistance)
H influence ,M
catarrhalis,
S pneumonia
(resistance to Blactams common)
If symtoms persist
>10 D 
second- or thirdAminopenicllin
generation
cephalosporin
second-generation
macrolide
Quinolone,
penicillin + B -la
ctamase inhibitor
(Amox. – Clav)
Or
(AMPICILLIN/SULBACT
second- or third-gen.
As for class , Moxifloxacin- levofloxacin May require paren
penicillin + B -la
cephalosporin
2+any one
therapy or hosp.
ctamase
inhibitor
nd
2 gen. macrolide
of :FEV1
(Amox. – Clav)
Ciprofloxacin
Or (AMPICILLIN/SULBACTAM)
.%50<
Advanced
age 4 > ,
exacerbation
LAST UPDATES: I D S A G U I D E L I N E S
Initial empiric therapy for suspected bacterial communityacquired pneumonia (CAP) in immunocompetent adults.
Out patients
Inpatients
A study was designed to test whether
COULD CEPHALOSPRINS
resistance
cephalosporin
resistance could be reversed
by
withdrawing BE
theseREVERSED??
agents.
The hospital-wide cephalosporin
class restriction resulted in a
44% reduction in ceftazadineresistant Klebsiella infection and
colonization.
UNICTAM
3 Gram
Richard R. Yates Chest 1999
COULD CEPHALOSPRINS resistance
BE REVERSED??
Rahal; JAMA, October, 1999
Managing
AECB & CAP
In today`s guidelines
Combination
penicillins
Respiratory
quinolones
B- lactamase irreversible
3rd generation
Inhibitors
Like
Ampicillin/sulbactam
Amoxicillin/ clavlanic
(in CAP:Plus a macrolide)
(levofloxacin)
4th generation
(Moxifloxacin)
Alone or plus
Amp./sulbactam
CDC
IDSA
Mayo Clinic
Moxifloxacin structure activity relationship
• Higher gram-positive activity
• Minimizes efflux (S. pneumoniae, S. aureus)
OH
O
Mode of action that minimizes micro
F
resistance
O
5
H
N
4
6
3
7
2
8
1
N
N
H
O
H3C
H
A greater binding
Affinity to the topoisomerase enzyme
• Minimizes development of resistance
• Enhances anaerobic activity
Petersen et al 1996
Domagala, JM 1994
Moxifloxacin
Bactericidal in
RECORD TIME
1000 000
CFU
TO
1000 CFU
Eradication in
3 hrs.
WIEDEMANN, Poster P0773, ECCMID Berlin 1999
Modern 4th Generation F.Quinolone
With Greater antimicrobial power on G
90%
80%
70%
60%
killed
streptococci
50%
resiatant
40%
30%
20%
10%
+ve bacteria
90%
80%
70%
60%
50%
40%
30%
20%
10%
0%
ciprofloxacin
moxifloxacin
killed
streptococci
0%
killed
streptococci
Moxifloxacin inhibits about
90% of strept. strains, while
ciprofloxacin
only inhibits 42%.
International Journal of Antimicrobial Agents 20 (2002) 196/200
MORDERN: 4th Generation F.Quinolone
5 times higher concentrations
over ciprofloxacin
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
Moxifloxacin High Respiratory Tissue
Penetration
10
120
100
0
100
80
10
60
1
40
20
0.1
0
0.01
61.8
24.4
MIC90
5.5
(mg/
l)
0.12 S.pneumoniae,
M.Catarrhalis
0.06 H.influenzae
Bronch
ial
Mucosa
Epithelial Lining
Fluid(ELF)
Respiratory tissue concentration after one single p.o dose
Andrews J et al.38th ICAAC, 1998;San Diego, A29
Alveolar
Macrophag
e
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): 293300.
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 coamoxiclav 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, Setting
Severely ill
Common Pathogens
S. Pneumoniae §
Legionella spp.
Gram-negative bacilli
M. pneumoniae
Viruses
S. aureus
Empirical Therapy
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 betalactam
If 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
What MUP offers
• Quality
• Scientific credibility
• Price
Be sure to cure
Best outcome for patients
Best use of resource
Least resistance
Least cost
Restricts idiosyncratic
in the time of
BIG CHALLENGE
RTIs
UNICTAM
What MUP offers
• Quality
• Scientific credibility
• Price
Ampicillin/sulbactam
Saving Cephalosporins abuse
Best outcome for patients
Best use of resources
Least resistance
Least cost
Restricts idiosyncratic
Prof/ Maha Gaafar IC Dept. ElQuasr el Einy univ. hosp 2010
From Cleveland to Baltimore to
Cairo
The Egyptian
Society of Chest &
Tuberculosis
Few years ago with Prof.
Dr Awad Tag ElDin
For what the martyrs died for
better, free & dignity Egypt
•FEV1 > 50%
•Exacerbations =OR> 4 /Yr.
•Heart diseases
•Use of Oxygen
•Antibiotics in the last 3 mo.
One
Or
More
None
•Group 1
•2nd G Macrolide
•2nd or 3rd G cephalosporins
•TMO-SMX
•Doxycyclene
Improved
•Did not
•improve
•Group II
•FQ
•B-lactam/Blactamase
•Ampicillin/sulbactam
worsen
•FQ
•Moxacin - Levanic
•Group III
•Anbulatory patient
•Hospitalized patient:
Consider Ps. Aeroginosae
Ciprofloxacin infusion
Improved
•Did not
•improve
Can Resp J 2003
CAP:
IDSA-ATS Treatment Guidelines
• 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:
IDSA-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:
IDSA-ATS Treatment Guidelines
• Empiric Treatment –
Hospitalized, non-ICU:
– Beta-lactam (ceftriaxone, cefotaxime,
ampicillin/sulbactam, or ertapenem) + macrolide
or doxycycline
or
– 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
Fluoroquinolones for Respiratory Infections
Comparison of Recent Guidelines for Empiric Initial Therapy of CAP*
Variables
Williams J. Jr.
Drugs Recommended
Modifying Factors
Outpatient
Doxycycline, 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
IDSA (Bartlett et al)
ICU
)Cefalosporin or β-lactam/βlactamase inhibitor)
+
(macrolide or fluoroquinolone)
Prior lung disease: )pseudomonal βlactam [±β-lactamase inhibitor] or
carbapenem)
+ fluoroquinolone (high-dose
ciprofloxacin) β-lactam allergy:
fluoroquinolone
± clindamycin Suspect aspiration:
fluoroquinolone ± (clindamycin,
metronidazole, or β-lactam/βlactamase inhibitor)
Variables
Drugs Recommended
Modifying Factors
Outpatient
1st 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)
CIDS/CTS
(Mandell
et al
1st choice respiratory
fluoroquinolone + (cefotaxime,
ceftriaxone, or β-lactam/βlactamase inhibitor)
or 2nd choice IV macrolide +
)cefotaxime, ceftriaxone, or β-
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+