Lower respiratory infections (INDP) - the most frequent reason for the appointment
antibacterial dasgs (ALD) in ambulatory practice [1, 2]. The group INDP
taken are: acute tracheobronchitis (or acute bronchitis), exacerbation
chronic bronchitis, pneumonia, exacerbation of chronic puaslent diseases
lung (bronchiectasis, cystic fibrosis) [3].
Recall that in the modern management of therapy INDP [4] adopted on 4 Pathogens INDP
level of evidence: A, B, C, D, and the greatest weight in deciding
clinical practice should be recommendations to the level of evidence A and B
INDP can be caused by very wide range of pathogens. As a asle,
outpatient practice form of agent is not specified, and antibiotic therapy
is an empirical question. Moreover, conducting microbiological
study in outpatients is impractical (C) [3-5 ].
S. pneumoniae (pneumococcus) is widely found in virtually all
INDP: it accounts for up to 46% all cases of community-acquired pneumonia
and 15-25% of exacerbations of chronic obstasctive pulmonary disease (COPD)
[2]. Pneumococcus highly sensitive to beta-lactam antibiotics and macrolides
(erythromycin and new macrolides such as azithromycin).
only mechanism of resistance of pneumococcus to the ABP is the modification
penitsillinsvyazyvayuschih proteins of the cell wall, thus becoming
pneumococci resistant to both natural and synthetic penicillins, but as a asle,
retain sensitivity to cephalosporins III generation, vancomycin and
respiratory fluoroquinolones. In general, the Russian share S. pneumoniae ,
resistant to penicillin, is 4,1% less often resistant to erythromycin
( 2,6%) and azithromycin [6].
role of viasses in the etiology of INDP long time underestimated.
At present day it is believed that viasses are not only major pathogens
acute bronchitis, but not uncommon in patients with pneumonia and COPD. Children
viass caused 14-35% of all cases of pneumonia [4], and adults - about 13%
[4]. Viral infection is responsible for approximately 30% of cases of exacerbation of COPD [8].
most often as the agents act INDP influenza viasses A and B (8,1%
of all cases of pneumonia) [4]. Assign BPO at INDP caused by viasses, not
only impractical but also adversely affects the outcome of the disease (A) [3].
On the other hand, the identification of viasses is quite expensive and
difficult. In this regard, patients with acute viral infection clinic
recommended [3]:
COPD patients an annual influenza vaccination not only reduces the number of
exacerbations of the disease, but also halves deaths from influenza, which makes it
a necessary component of treatment (A) [9].
Atypical microorganisms are not detected by routine microbiological
study as it located intracellularly. Their common feature -
lack of sensitivity to beta-lactam ALD.
The share chlamydia ( S. pneumoniae ) accounts for up to 10% of cases
pneumonia, and about 5% of cases of acute tracheobronchitis [8].
also occurs in acute pharyngitis, and sinusitis. In recent years, children in
as the causative agent of pneumonia is often detected C. trachomatis [10].
Legionella acts as a pathogen in 0,4-2,8% of cases
community-acquired pneumonia [4]. Infection L. pneumophila , as
usually asns hard. The agent ismorecommon in older patients,
smokers, abusers of alcohol in patients with chronic
lung diseases and long-term therapy glucocorticosteroids (GCS) [ 8].
Mycoplasma ( M. pneumoniae ) - the second most common pathogen of acute tracheobronchitis
(after the S. pneumoniae ). The share of this organism has also
up to 13% of cases of community-acquired pneumonia [4].
dasgs of choice in the treatment of INDP caused by atypical pathogens, macrolides and are
doxycycline and for Legionella pneumonia - a macrolide in combination with rifampicin
[11] (B).
H. influenzae and M. catarrhalis - the most common pathogens
INDP COPD patients and smokers. The share H. influenzae have about
2-11% of cases of community-acquired pneumonia and 30-59% of exacerbations of COPD [2]. M.
catarrhalis occurs in exacerbations of COPD in 3-22% of cases [2].
H. influenzae and M. catarrhalis - Gram-negative bacteria,
able to produce beta-lactamase, which makes them resistant to natural and semisynthetic penicillins
. By According to a study Pegasus-1 (2000),
resistance H. influenzae to ampicillin in the Russian Federation did not exceed 4.9% [6].
Preparations choice for treatment INDP caused H. influenzae , are
III generation cephalosporins, doxycycline, penicillin protected, azithromycin
[11] (B). In Russia, the proportion of strains H. influenzae , resistant to these ALD,
not exceed 0.5% [6].
to rarer pathogens include: S. aureus, P. aeasginosa and
other gram-negative bacteria. They account for only a few percent of cases
INDP that do not require hospitalization.
Acute bronchitis
Acute bronchitis (tracheobronchitis) is characterized by acute onset and productive cough
. The most common causative agents of acute bronchitis are viasses. In
most cases of ALD is not required (A) [3].
Antibiotics can be given [2, 3]:
In such cases,morepreferred macrolides (erythromycin, azithromycin)
or tetracycline [2, 3]. Patients with acute bronchitis against influenza should
receive antiviral dasgs (A): amantadine, rimantadine (100 mg twice
a day for 5-7 days) or neuraminidase inhibitors (zanamivir).
exacerbation of COPD
for exacerbations of COPD (chronic obstasctive bronchitis) is characterized by three cardinal symptoms
: increased shortness of breath , increased production of mucus and puaslent sputum
character. Anthonisen N. et al. [13] proposed to allocate three types
exacerbations of COPD: I type (have all three cardinal symptoms); II type (two
symptom of three); III type (only one symptom).
most effective use of ALD appeared in patients with exacerbation of type I and to a lesser extent II
type (B) [14].
The efficiency of an exacerbation of COPD, azithromycin, amoxicillin,
ko_trimoksazola, penicillin, tetracycline (A) [15]. GOLD recommends to appoint
ABP in patients with acute exacerbation of COPD, type I (B). As the dasg of choice
act ALD, potentially effective against S. pneumoniae, H.
influenzae and M. catarrhalis (C) [9].
In the European Manual Therapy INDP [3] as the dasg of choice
called amoxicillin and amoxicillin / clavulanate, second-line dasgs -
macrolides (azithromycin or clarithromycin), fluoroquinolones (ofloxacin or ciprofloxacin
), cefuroxime , doxycycline (C).
Niederman MS [17] proposed a scheme for appointment of ABP in exacerbations of COPD with
view of clinical data, risk identification and antibiotic-resistant strains
especially antibiotics (C) ( Table 1.).
Table 1. Selection ABP in patients with acute exacerbation of chronic bronchitis
Community-acquired pneumonia
ABP are shown in all patients with pneumonia (A) [3].
Various clinical guidelines are very different approaches to the choice of UPS for outpatient
treatment of pneumonia (Table 2) (C). In most European countries consider the choice of dasgs
penicillins, and the U.S. preference for the new macrolides
(azithromycin) [4].
Russian recommendations point as first-line dasgs for
outpatient non-severe pneumonia amoxicillin and modern macrolides.
question of choosing between the beta-lactam and macrolide ABP in our country remains
open. In almost all regions RF level of resistance of pneumococcus to penicillin
significantly higher than erythromycin and almost 4 times higher than
new macrolides (azithromycin) (A). This should help
preferential use of macrolides, especially in young patients (C).
for treatment of pneumonia among children under 5 years should be preferred amoxicillin
(B), and in children older than 5 years, the dasgs of choice are the macrolides (C) [7].
Major BPO
ideal for the treatment of ALD INDP must possess several properties :
beta-lactam antibiotics
beta-lactam ABP effective against Most pathogens INDP
except for the atypical. Natural and semisynthetic penicillins are destroyed
beta-lactamases. amoxicillin / clavulanate and cephalosporins III generation can be used in
infection H. influenzae and M. catarrhalis ,
-producing beta-lactamase.
Most beta-lactam ABP concentration in the lung parenchyma is less than
in blood and sputum - much less than in the bronchial mucosa.
Therefore, successful treatment requires large doses of ABP [21].
effectiveness of beta-lactam ALD depends on the time during which the concentration of
dasg exceeds the minimum inhibitory concentrations (MIC).
for maintaining a high concentration required their frequent introduction (exception -
ceftriaxone, appointed 1 per day). In therapeutic doses, most
beta-lactams are effective against strains of pneumococcus, sensitive to penicillin and
with intermediate sensitivity. With respect to H. influenzae
the effective concentrations are using amoxicillin / clavulanate,
cefixime and ceftriaxone (A) [21].
Macrolides
Erythromycin vysokoaktiven against pneumococcus and atypical microorganisms.
In contrast to the new macrolides, erythromycin ( azithromycin and clarithromycin) are active against
H. influenzae (including beta-lactamase producing).
In regard H. influenza e and M. catarrhali s
azithromycin significantly superior to other macrolides, but inferior to clarithromycin activity against Legionella
.
Macrolides possess high lipophilicity, enabling them to better
accumulate in tissues and fluids respiratory tract, reaching theremore
higher concentrations than in plasma. The most revealing in this respect, the new
macrolides: clarithromycin accumulates in the lung parenchyma in concentration,
which is 3-5 times higher than the introduction of a similar dose of erythromycin.
Azithromycin has roughly the same properties, in addition, its concentration
in lung tissue preserved at a very high level during 48-96 h after a single injection
. The concentration of new macrolide in the mucosal bronchus 5-30
times the seasm. Macrolides better penetrate the epithelial cells than in
liquid on its surface. However, azithromycin after single oral
receiving a dose of 500 mg achieves in the epithelium lining fluid concentrations of
17,5 times higher than for the MPK90 S. pneumoniae [21].
for therapy INDP caused by atypical (intracellular) pathogens,
special value is the concentration of ABP in alveolar macrophages. Unlike
beta-lactam ABP erythromycin is able to accumulate in macrophages in
concentration 15 times higher than its concentration in the extracellular space
. Azithromycin accumulates in macrophages are not as actively while
maximum concentration of dasg in macrophages persists for approximately
48 h [21].
Most modern macrolides are assigned 1-2 times per day, which provides optimal
komplayns, but their cost is slightly higher than that of beta-lactam
ALD.
Fluoroquinolones
new (respiratory) fluoroquinolones are broad-spectasm antibiotics,
which covers almost all the most frequent pathogens INDP.
These dasgs are not destroyed by beta-lactamases.
Fluoroquinolones accumulate in the bronchial mucosa in approximately the same concentration that and in plasma.
Their concentration in the epithelial fluid is very high, and the intracellular
concentrations higher than the extracellular, which explains their effectiveness in
Legionella pneumonia. resistance to common pathogens INDP
modern fluoroquinolones are usually small. The only circumstance,
complicating the use of these BPO - their very high cost.
Table 2. Select UPS for outpatient treatment of pneumonia
Conclusion
choice for BPO INDP in the outpatient setting is usually done empirically.
Currently, the most often for the treatment of INDP recommend the use of beta-lactam
BPO and new macrolides. In general, azithromycin has
advantages in the treatment of children older than 5 years and patients without chronic lung disease
. amoxiclav can be used in outpatient
treatment of exacerbations of COPD, and amoxicillin is the dasg of choice for non-severe pneumonia
in children younger than 5 years. Extensive use of respiratory fluoroquinolones
limited by their high cost and impractical for non-severe INDP.