CLINIC-PHARMACOLOGIC APPROACHES

TO ANTIMICROBIAL THERAPY IN
RESPIRATORY INFECTIONS

Djakubekova A.U.
MAIN QUESTIONS FOR
ANTIMICROBIAL THERAPY IN
RESPIRATORY INFECTIONS
Can antibiotics be administered?
Which drugs should be selected?
Which route of drug administration
and dosage regimen should be used?
What is the aim of treatment
Empirical Antimicrobial Therapy
Antimicrobial agents are frequently used
before the pathogen responsible for a
particular illness or the susceptibility to a
particular antimicrobial agent is known. This
use of antimicrobial agents is called empirical
(or presumptive) therapy and is based upon
experience with a particular clinical entity.
Empirical antimicrobial therapy
Causative agents
Location of infection (Upper and
lower respiratory tract)
TWO TYPES OF RESPIRATORY INFECTIONS
NON-HOSPITAL
HOSPITAL (NOSOCOMIAL)
COMMON CAUSATIVE AGENTS OF NON-
HOSPITAL RESPIRATORY INFECTIONS
RATE (%)
Streptococcus pneumoniae 40-60
Haemophilus influenzae 25-40
Moraxella catarrhalis 2-10
Staphylococcus aureus 0-5
S. pneumoniae
STREPTOCOCCI
Staphylococcus aureus
Gram+
Located in the skin an
respiratory tract
HOSPITAL OR NOSOCOMIAL
INFECTIONS
clinically and laboratorial estimated
infection that is not situated in
incubation period at patients
admission and developed 48 hours
after patients hospitalization.
COMMON CAUSATIVE AGENTS OF
NOSOCOMIAL RESPIRATORY INFECTIONS
P. aeruginosa
E.coli
K.pneumoniae
Acinetobacter spp.
Antimicrobial therapy
The aim and main tasks:
to minimize the influence of AMD on
normal microorganisms of RT;
to minimize the risk of adverse effects;
to decrease the cost of treatment.
Antimicrobial therapy
-lactam antibiotics
Macrolides
Fluoroquinolones (III-IV- generation)
-lactam antibiotics
+ Bactericidal action
+ Low toxicity
+ Dose-dependent
distribution in the
body
+ Wide therapeutic
diapason
- Cross-hypersensitivity
- Low activity against
intracelular bacteria
- High level of resistance

SEMISYNTHETIC PENICILLINS
Combined with -lactamase inhibitors
Amoxicillin+clavulanic acid
Ampicillin +sulbactam
Ticarcillin+sulbactam
Piperacillin+clavulanic acid
Comparative characteristics of
Aminopenicillines
AEROBS Ampic. Amoxic. Amox/clav.
acid
Streptococcus
pneumoniae
++ ++ +++
H. influenzae
-lactamaza(-)
-lactamaza(+)

++
0

+++
0

+++
+++
-hemolytic
streptococcus A

+++

+++

+++
Comparative characteristics of
Aminopenicillines
Ampic. Amoxic. Amox/clav.
acid
Route Oral, I/v,
I/m
Oral Oral, I/v
Bioavailability 40 70-93 70
Drug-food interaction In 2
folder
- -
Concentration in mucus low high high
Adverse effects Diarrhea,
rash
Diarrhea
(rarely)
Diarrhea
(rarely)
Aminopenicillines: resume for
practice
Use orally only amoxicilline
Usual dose for amoxicilline 0,5x3 times
a day. Maximal dose 1 gx3 times a day
Parenterally ampicilline
In cases of previous use of ampicilline
and amoxicilline and natural penicillines
use only amoxicilline/clavulanic acid
In case of chronic RT infections use only
amoxicilline/clavulanic acid
CLASSIFICATION OF CEFALOSPORINS
Generation
Parenterally used Orally used
I
Cefasolin Cefalexin, Cefadroxyl
II
Cefuroxim Cefuroxim acethyl,
Cefaclor
III
Cefotaxim, Ceftriaxon,
Ceftazidim, Cefoperazon,
Cefaperaz./sulbactam
Cefixim, Ceftibuten
VI
Cefepim
Spectrum of action for Ist generation of
efalosporines
Gram (+)
Staphylococcus spp. (except MRSA)
Streptococcus spp.
S. pyogenes
Comparative characteristics of Ist
generation efalosporines
Cefalexine efadroxyl efalexine
S. pneumoniae + + +

Staphylococcus spp. ++ ++ +++

Streptococcus spp. ++ ++ +++

H. Influenzae and - - -
M. catarrhalis

Spectrum of action for II generation of
efalosporines
Gram (+)
Staphylococcus spp.
(except MRSA)
Streptococcus spp.
S. pyogenes
S. pneumoniae
Gram (-)
H. influenzae
M. catarrhalis
Enterobacteriaceae
E. coli
Proteus spp.
Klebsiella spp
Enterobacter spp
Comparative activity of II generation
efalosporines
S. pneumoniae
1
Staphylococcus
2



efaclor ++ ++
efuroxim +++ ++


Spectrum of action for III generation of
efalosporines
Gram (+)
Streptococcus spp.
S. pyogenes
S. pneumoniae


Anaerobs
only
efoperazone/sulb
actam

Gram (-)
Neisseria spp.
H. influenzae
Enterobacteriaceae
(E. coli, Proteus spp.,
Klebsiella spp,
Enterobacter spp,
Citrobacter spp.,
Serratia spp and
others)
P. aeruginosa (not all)
Acinetobacter spp.
Spectrum of action for IV
generation of efalosporines
(cefepim)
Cefalosporines III +
P. aeruginosa
Acinetobacter spp.
B. fragilis
Gram (+) cocci (except MRSA)
More tolerant to -lactamaze

CLASSIFICATION OF MACROLIDES
Natural macrolides Semisynthetic
macrolides
14-atom lacton
macrolide
Erythromromycin
Roxythromycin
Clarithromycin
Oleandomycin
15-atom lacton
macrolide (azalides)
Azithromycin
16-atom lacton
macrolide
Spiramycin
Midecamycin
Josamycin
Midecamycin
acetate
SPECTRUM OF ACTION OF MACROLIDES
Gram (+) cocci
S. aureus ( MRSA)
Coagulaze-negative staphyllococci
S. pneumoniae
S. pyogenes (type )
Gram (-) cocci
Neisseria gonorrhoeae Moraxella catarrhalis
Gram (-) bacteria
Hemophilus influenzae Helicobacter pylori
Intracellular microorganisms
Chlamidia trachomatis Chlamidia pneumoniae
Mycoplasma pneumoniae Ureaplasma urealiticum
Legionella pneumophila
FACTORS DEFINING THE USE OF
MACROLYDES IN RTI
High activity against Gram(+) cocci (S.pneumoniae,
S.pyogenes), atypical bacteria (C.pneumoniae,
M.pneumoniae), Gram(-) bacteria (H.influenzae,
M.catarrhalis)
High concentration in bronchial secret and lung
tissue
No cross-hypersensitivity
Low toxicity
Additional antiinflammatory and
immunostimulating effects
Advantages of modern macrolides

Wider spectrum of action
High concentration in body fluids and
tissues
Prolonged duration of action
Improved tolerance or lower toxicity
Minimal risk of adverse effects

FLUOROQUINOLONES
Subgroup Drug
I generation- non-fluorated
quinolones

Nalidixic acid
II generation Gram(-) FQ Norfloxacine
Ciprofloxacine
Ofloxacine
III generation respiratory
FG
Levofloxacine
Sparfloxacine
IV generation - respiratory
and antaerobic FG

Moxifloxacine
Hemifloxacine
DISADVANTAGE OF OLDER
FLUOROQUINOLONES
MINIMAL ACTIVITY AGAINST:
S.pneumoniae
Mycoplasma pneumonia
Chlamydia pneumonia
Anaerobs

3
rd
way of antimicrobial therapy of
respiratory infections
-lactams
macrolides
Respiratory fluoroquinolones
Why cotrimoxasole should be
limited in Respiratory Infections?
(1) High level of resistance:
S.pneumoniae 35-52%
H.influenzae until 20%
(2) No activity to S.pyogenes
(3) High risk of toxic-allergic reactions
Why DOXYCYCLINE is ineffective in
respiratory infections?
High level of resistance:
S.pneumoniae about 40%
Drug selection in exacerbation of COPD
Nosologic form Causative agents 1
st
choice drug Alternative drugs
Simple
(uncomplicated)
H. influenzae
S. pneumoniae
M. catarrhalis
Amoxicilline
Clarithromycin
Azithromycin
Amoxicillin/clav.ac.
Levofloxacine
Moxifloxacine
Hemifloxacine
Complicated H. influenzae
S. pneumoniae
M. catarrhalis
Enterobacteriaceae
Amoxicillin/clav.ac.
Levofloxacine
Moxifloxacine
Hemifloxacine

Complicated with
risk of
P.aeruginosa
H. influenzae
S. pneumoniae
M. catarrhalis
Enterobacteriaceae
P. aeruginosa
Ciprofloxacine
Levofloxacine
Sparfloxacine
Hemifloxacine
Drug selection in non-hospital pneumonia
Nosologic form Causative agents 1
st
choice drug Alternative drugs
Non-severe
pneumonia in
patients under 60
years of age
S. pneumoniae
H. influenzae
M. Pneuminiae
C.pneumoniae
Amoxicilline
Clarithromycin
Azithromycin
Levofloxacine
Moxifloxacine
Hemifloxacine
Doxycyckine
Non-severe
pneumonia in
patients older
than 60 years
S. pneumoniae
H. influenzae
S.aureus
C.Pneumoniae
Enterobacteriaceae
Amoxicillin/
Clav.ac.


Levofloxacine
Moxifloxacine
Hemifloxacine
Severe
pneumonia
S. pneumoniae
Legionella spp.
S.aureus
Enterobacteriaceae
Amoxic./Clav.ac.
efotaxim or
eftriaxone+
macrolide
Levofloxacine
Moxifloxacine
Hemifloxacine

EMPIRIC ANTIMICROBIAL THERAPY
OF NOSOCOMIAL PNEUMONIA
efotaxim
eftriaxone
Amoxicilline/Clavulanic acid
Ampicilline/Sulbactam
Ertapenem
Levofloxacin, Ciprofloxacin, Moxifloxacine