Treatment of pneumonia

Complex treatment of pneumonia should be aimed at suppressing infection, restoring pulmonary and general resistance, improving the drainage function of the bronchi, eliminating complications of the disease.

Indications for hospitalization

The first question that the doctor must decide is where the patient with community-acquired pneumonia should be treated: in a hospital or at home? According to modern ideas, most patients with uncomplicated community-acquired pneumonia can be treated at home.

Read also: Pneumonia - Treatment regimen and nutrition Antibacterial drugs for the treatment of pneumonia Pathogenetic treatment of pneumonia Symptomatic treatment of pneumonia Fighting complications of acute pneumonia Physiotherapy, exercise therapy, respiratory gymnastics with pneumonia Sanatorium treatment and rehabilitation for pneumonia

Indications for hospitalization of patients with community-acquired pneumonia (European Respiratory Society, 1997)

• Septic shock
• PaO ₂ <60 mm Hg. Art. Or PaCO ₂ > 50 mm Hg. Art. When breathing room air
• Leukopenia <4 x 70 ⁹ / L or leukocytosis> 20 x 10 ⁹ / L
• Anemia (hemoglobin <90 g / l or hematocrit <30%)
• Renal insufficiency (urea> 7 mmol / L)
• Social indications (impossibility of caring for a patient at home)

The main factors determining the solution of the question of the place of treatment of a patient with pneumonia are the severity of the disease, the presence of complications, as well as the risk factors for the unfavorable course of the disease and the lethal outcome. It should be remembered, however, that social and domestic factors, such as the inability to care for the patient at home, can influence the final decision on hospitalization.

In severe pneumonia, which is associated with high mortality, the patient should be admitted to the intensive care unit or intensive care unit (ICU). Currently, the following are the main indications for the hospitalization of a patient:

• respiratory rate> 30;
• the need for ventilation;
• X-ray signs of rapid progression of pneumonia (an increase in the size of pneumonic infiltration> 50% within 48 hours);
• septic shock (absolute indication);
• the need to introduce vasopressor drugs to maintain systemic blood pressure;
• severe respiratory failure, in particular the ratio of oxygen tension in the arterial blood to the oxygen fraction in the inspired gas mixture (PaO2 / PCO2) <250 (or <200 with COPD) and signs of fatigue of the respiratory muscles;
• acute renal insufficiency;
• diuresis <30 ml / h;
• other complications of pneumonia, including the syndrome of disseminated intravascular coagulation, meningitis, etc.

Etiotropic treatment of pneumonia

The basis for the treatment of pneumonia is antibacterial drugs. The choice of the most effective of them depends on many factors, primarily on the accuracy of identification of the causative agent of pneumonia, its sensitivity to antibiotics and the early onset of adequate treatment of pneumonia with antibiotics. Nevertheless, even in the presence of a well-equipped microbiological laboratory, the etiology of pneumonia can be established only in 50-60% of cases. Moreover, to obtain the results of the microbiological analysis, no less than 24-48 hours are required, whereas the treatment of pneumonia with antibiotics should be administered as soon as the diagnosis of pneumonia is established.

It should also be borne in mind that in 10-20% of cases the cause of pneumonia are bacterial associations (myxinfection), for example, "typical" and "atypical") (intracellular) pathogens (mycoplasma, chlamydia, legionella, etc.). The latter, as is known, can not be detected by classical routine methods of microbiological research, which creates serious difficulties in the selection of adequate etiotropic treatment.

In this regard, the initial choice of an antibiotic, as a rule, is of an empirical nature and is based on an analysis of the specific clinical and epidemiological situation in which the patient developed pneumonia, and taking into account factors that increase the risk of infection by one or another pathogen.

The choice of an antibiotic for the empirical treatment of community-acquired pneumonia

Recall that the most frequent pathogens of community-acquired pneumonia are:

• pneumococci (Streptococcus pneumoniae);
• Haemophilus influenzae;
• Moraxella (Moraxella catarrhalis) \
• mycoplasma (Mycoplasma spp.);
• chlamydia (Chlamydophila or Chlamydia pneumoniae),
• legionella (Legionella spp.).

In this case, the share of pneumococcal infection accounts for more than half of cases of community-acquired pneumonia, and about 25% of pneumonia is caused by a hemophilic rod, moraxel or intracellular microorganisms. Much less frequently (in 5-15% of cases) the causative agents of community-acquired pneumonia are some gram-negative bacteria of the Enterobakteriaceae family, Staphylococcus aureus, anaerobic bacteria, Pseudomonas aeruginosa and others. It should be remembered that in recent years, the number of drug-resistant strains of pneumococci and other pathogens has significantly increased, which significantly complicates the selection of an adequate antibacterial agent for etiotropic treatment of community-acquired pneumonia.

The table shows the most important modifying factors that increase the risk of infection with antibiotic-resistant strains of pneumococci, Gram-negative bacteria and Pseudomonas aeruginosa.

Modifying foktorov, increasing the risk of infection with certain pathogens (according to N. Cossiere et ai, 2000)

Virulent pathogens	Modifying factors
Penicillin-resistant, drug-resistant pneumococci	Age over 65 years Administration of beta-lactam antibiotics during the last | 3 months Alcoholism Immunosuppressive conditions and diseases (including glucocorticoid therapy) The presence of several concomitant diseases Visiting of children by creches / kindergartens
Gram-negative bacteria	Inhabitants of nursing homes Concomitant diseases of the lungs and heart The presence of several concomitant diseases Recently conducted treatment of pneumonia with antibiotics
Pseudomonas aeruginosa	Diseases with changes in the lung structure (eg, bronchiectasis) Corticosteroid therapy (more than 10 mg of prednisolone per day) Reception of broad-spectrum antibiotic for more than 7 days within the last month Poor nutrition

Currently, a large number of schemes for the empirical treatment of community-acquired pneumonia have been proposed, in which preference is given to certain antibacterial drugs.

According to domestic and most European recommendations, aminopenicillins (amoxicillin, amoxicillin / clavulonic acid, amoxicles) and modern macrolides (clarithromycin, azithromycin, roxithromycin, spiramycin, etc.) are the drugs of choice for the treatment of community-acquired pneumonia of mild and moderate severity. In patients who have risk factors, it is advisable to prescribe combined treatment of pneumonia with beta-lactams (cephalosporins II-III generation, amoxicles, etc.) in combination with "new" macrolides. It is also possible to use monotherapy with "respiratory" fluoroquinolones of III-IV generations (levofloxacin, moxifloxacin).

Amoxicillin is a modern drug from the group of aminopepicillips. Its effect extends to the Gram-positive and Gram-negative microflora (streptococci, pneumococci, hemophilic rod, moraxella, Escherichia coli, Proteus, Legionella, Helicobacter, etc.). The Pseudomonas aeruginosa, Klebsiella, enterobacter, etc. Are not sensitive to amoxicillin.

Amoxicillin is an ampicillin derivative, but it is far superior in its pharmacokinetic properties and more active against pneumococci. Due to its high bioavailability (about 85-90%), amoxicillin is the world's best oral antibiotic. Usual dose for adults with oral administration is 0.5-1.0 g 3 times a day, and for parenteral (intravenous or intramuscular) administration - 1 g every 8-12 hours.

Amoxicillin / Clavulonate (Amoxicillum, Augmentin) is a combined preparation of amoxicill and pa and clavulonic acid, which is an inhibitor of beta-lactamases produced by many modern strains of staphylococci, gram-negative bacteria and some anaerobes and destroying the beta-lactam ring of pepicillins, cephalosporins and monobactams. Due to the ability of clavulonic acid to inhibit the negative effect of beta-lactamase bacteria, the spectrum of action is significantly expanded and the activity of amoxicillin significantly increases with respect to the majority of staphylococci, gram-negative bacteria, non-spore forming anaerobes and some strains of Klebsiella spp. And E. Coli.

With regard to pneumococci, the activity of amoxiclav does not differ from that of amoxicillin (without clavulonate), since pneumococci do not release beta-lactamase. As well as amoxicillin, amoxiclav is not effective in the treatment of infections caused by Pseudomonas aeruginosa. Inside amoksiklav appoint 375-625 mg (for amoxicillin) 3 times a day in the form of tablets or powder to prepare a suspension. Parenteral drug is administered at 1.2 g every 6-8 hours.

Ampicillin also belongs to the group of aminopepicillins and, in the spectrum of its action, resembles amoxicillin, affecting gram-positive and, to a lesser extent, gram-negative flora, including streptococcus, pneumococcus, Escherichia coli, Proteus, moraxella, etc. The drug is less active than amoxicillin, but well is tolerated, and toxic reactions rarely develop, even with prolonged use of high doses of the drug. Parenteral ampicillin is prescribed in a daily dose of 2-4 g, divided into 3-4 injections. Most strains of staphylococci are not sensitive to ampicillin. However, with the use of "protected" ampicillin (ampicillin / sulbactam), its spectrum expands and the drug becomes active against many strains of golden and epidermal staphylococcus.

In medical practice, a combined ampiox preparation with a fixed ratio of ampicillin and oxacillin (2: 1 for parenteral administration) was widely used. Theoretically, ampiox has the properties inherent in both components. Oxacillin is known to be one of the effective anti-staphylococcal drugs, demonstrating its activity towards penicillin-resistant staphylococcus aureus (PRSA), which is resistant to ampicillin and other "unprotected" aminopenicillins. Meanwhile, the activity of oxacillin against pneumococci, streptococci is comparatively small. The drug is inactive in relation to all Gram-negative aerobes, enterococci, all anaerobes and intracellular pathogens.

Nevertheless, an important property of oxacillin, which is part of ampiox, has so far been its ability to bind peniillinase (ß-lactamase) of gram-negative bacteria and thereby prevent the destruction of these bacteria by the beta-lactam ring of ampicillin. However, at present, this positive property of oxacillin appears to be highly questionable, since most gram-negative microorganisms produce beta-lactamases, which in fact destroy both components that make up ampiox. In other words, the effectiveness of ampioxa against gram-negative pathogens in most cases is not so high. In addition, the content of oxacillin in ampiox (only 1/3 of the combined preparation) is clearly not enough to effectively affect staphylococci.

Thus, the combination of ampicillin and oxacillin in ampiox is now absolutely unjustified and obsolete. It is much more effective to use "protected" ampicillin / sulbactam or amoxiclav, which if necessary can be combined with the administration of adequate doses of "pure" oxacillin, aminoglycosides (gentamicin, amikacin) or with other antistaphylococcal agents.

Macrolides are a group of antibiotics that are highly active against gram-positive cocci (streptococci, pneumococci, golden and epidermal staphylococci), some gram-negative bacteria (hemophilic rod), some anaerobes (B./ragilis, clostridia, etc.), and intracellular pathogens chlamydia, mycoplasmas, legionella, campylobacter, rickettsia, etc.). Macrolides are not effective against gram-negative bacteria of the E. Coli family, Pseudomonas aeruginosa, enterococci and some others.

Currently, the so-called "new" macrolides of III-IV generations are used for the treatment of pneumonia:

• clarithromycin;
• roxitromia;
• azithromycin;
• spiramycin.

It is not recommended oral administration of "old" macrolides (erythromycin, oleandomycin) due to the lack of reliable information on the effectiveness and bioavailability of serially produced erythromycin preparations. If necessary, the parenteral form of erythromycin may be used, which is administered intravenously in a jet or as an infusion at a dosage of 0.2-0.5 g 4 times a day. Table 3.19 shows approximate daily doses of "new" macrolides that are recommended for the treatment of community-acquired pneumonia.

Doses of "new" macrolides in the treatment of pneumonia in adults (according to Yu.B. Belousov and SM Shotunov, 2001)

Macrolide drug	Doses
	Ingestion	With intravenous administration
Spiramycin	6-9 million IU (2-3 grams) per day In 2 divided doses, regardless of food intake	4.5-9 million IU per day In 2 injections
Roxitromia	By 0,15-0,3 2 times a day before meals	-
Clarithromycin	On 0,25-0,5 2 times a day, regardless of food intake	500 mg per day for 5 days, then ingestion for 5 more days
Aetromycin	0.5-1.0 g once a day for an hour or 2 hours after a meal
	5-day course: 1st day - 0.5-1 g once a day; the following days: 0.25-0.5 g per day
	3-day course: daily 0.5-1 g once a day

Cephalosporins also belong to ß-lactam antibiotics and have a broad spectrum of antibacterial activity, acting on gram-negative and gram-positive flora and 5-10 times less likely to cause allergic reactions. With community-acquired pneumonia, cephalosporins of the second and third generations are usually used.

For pneumonia of mild severity, in particular for the treatment of patients at home, the use of an oral preparation of the second generation cefuroxime (Ketocepha, Zinacef) is recommended, which has a high activity against pneumococci and certain gram-negative bacteria - Haemophilus influenzae, Moraxella catarrhalis, E. Coli and Drug taken in a dose of 250-500 mg 2 times a day after meals. With a more severe course of the disease, cefuroxime is administered intravenously or intramuscularly at a dose of 750-1500 mg 3 times a day.

If necessary, the parenteral use of cephalosporins in recent years more often use third-generation drugs - cefotaxime and ceftriaxone. They excel other antibiotics of this group by the severity of the action on most gram-negative pathogens and streptococci. Ceftriaxone (Rocefii, Lendacin) has a particularly high activity against hemophilic rods and pneumococci. In recent years, the drug is preferred because, due to the long half-life, it can be administered once a day at a dose of 1-2 g. Cefotaxime is somewhat inferior to ceftriaxone in action on Gram-positive and Gram-negative bacteria. It is administered in a dose of 3-6 g per day for 3 injections.

To cephalosporins of the IV generation are cefepime and cefpir. They show very high activity against gram-negative bacteria, including against strains resistant to other cephalosporins, including the Pseudomonas aeruginosa. They are highly effective for gram-positive flora, including streptococci and staphylococci. Very high activity of cephalosporins of the IV generation is manifested to the hemophilic rod, Neisseria, moraxelle and anaerobes. Cefepime is prescribed intramuscularly or intravenously, 1 g 2 times a day, and cefpir - intravenously 1-2 g every 12 h. Cephalosporins of the fourth generation are advisable to use only in severe course of community-acquired pneumonia and / or the presence of concomitant diseases and other risk factors that increase the likelihood adverse outcomes of the disease.

Fluoroquinolones - a group of antibiotics that have a pronounced bactericidal effect on gram-negative and gram-positive flora. Nevertheless, it should be remembered that ciprofloxacin (fluoroquinolone II generation), widely used in clinical practice, shows relatively low activity against pneumococci, mycoplasmas and chlamydia.

Currently, pneumonia is recommended to use the so-called "respiratory" fluoroquinolones III and IV generations (levofloxacin, moxifloxacin, etc.), which have very high activity against pneumococci, chlamydia, mycoplasmas, and gram-negative pathogens. Moxifloxacin, in addition, exhibits activity against non-spore-forming anaerobes (B. Fragilis, etc.).

Levofloxacin (Tavanic) - a preparation of the third generation - is used in a dose of 250-500 mg. Once a day for ingestion and 0.5-1.0 g per day for intravenous administration. Moxifloxacin - (a preparation of IV generation) is taken orally at a dose of 400 mg once a day.

It should be added that some antibiotics, which are still widely used in medical practice for the treatment of community-acquired pneumonia (gentamia, amikacin, co-trimoxazole, etc.), although highly effective antimicrobials, have a relatively narrow spectrum of action, mainly directed at gram-negative flora, anaerobes, staphylococci, etc. As a rule, they have very low activity against pneumococci, hemophilic rod and intracellular pathogens, i.e. For the most common etiological factors of community-acquired pneumonia. The expediency of using these drugs occurs only in severe pneumonia or in the presence of concomitant diseases and risk factors that worsen the prognosis of the disease, which are associated with gram-negative microflora and anaerobes. In the case of mild to moderate pneumonia, the use of these drugs in most cases is meaningless and even harmful, since it increases the risk of unwanted side effects and complications of such therapy (frequent allergic reactions, pseudomembranous colitis, Stevens-Johnson syndrome, Lyell syndrome, etc.).

As mentioned above, in most cases, the empirical etiotropic treatment of pneumonia involves the use of one of the listed effective antibiotics (monotherapy with amoxicillin, modern macrolides, cephalosporins of II-III generations, "respiratory" fluoroquinolones).

With a mild course of community-acquired pneumonia that does not require hospitalization of the patient (treatment at home), and the absence of risk factors, oral amoxicillin, amoxiclav or modern macrolides may be taken. If necessary, alternative oral medications (amoxiclav, cefuroxime, levofloxacin, moxifloxacin) are prescribed.

Treatment of community-acquired pneumonia of moderate severity and patients with aggravating risk factors is advisable to begin with parenteral (intravenous or intramuscular) administration of "protected" aminopenicillins or modern macrolides, if necessary, combining them with each other friend. With the low effectiveness of such treatment of pneumonia, alternative drugs are prescribed:

• cephalosporins II and III generations (parenterally cefuroxime, ceftriaxone or cefotaxime), preferably in combination with modern macrolides;
• monotherapy with "respiratory" fluoroquinolones of III-IV generations (parenteral levofloxacin).

It should be remembered that the effectiveness of the treatment of pneumonia with antibiotics is evaluated, first of all, by the clinical state of the patient and the results of some laboratory tests that, when choosing an adequate treatment for pneumonia, should improve in the next 48-72 hours. During this time, the treatment of pneumonia with antibiotics, including the appointment of alternative drugs, in most cases, community-acquired pneumonia is unreasonable, since it is proved that even with adequate treatment, fever can persist for 2-4 days, and leukocytosis 4-5 days. The exception is cases where the patient's condition clearly and rapidly deteriorates: fever, intoxication, progresses respiratory failure, auscultatory and radiologic signs of pneumonia increase, leukocytosis and a nuclear shift to the left increase. In these cases, a thorough follow-up examination (repeated chest X-ray, bronchoscopy with obtaining material from the lower sections of the respiratory tract, computed tomography, etc.), which help the visual ize portions formed destruction of lung tissue, pleural effusion, and other pathological changes were absent in the primary study. Microbiological examination of sputum and the material obtained during bronchoscopy can reveal antibiotic-resistant or unusual pathogens, for example, mycobacterium tuberculosis, fungi, and the like.

Severe course of community-acquired pneumonia and the presence of risk factors worsening the prognosis of the disease usually requires the appointment of a combined treatment for pneumonia, primarily directed at the often detected polymicrobial associations of pathogens in these cases. The most commonly used treatment regimens are:

• parenteral amoxiclav in combination with parenteral macrolides (spiramycin, clarithromycin, erythromycin);
• cephalosporins of the third generation (cefotaxime or ceftriaxone) in combination with parenteral macrolides;
• cephalosporins of the IV generation (cefepime) in combination with macrolides;
• monotherapy with respiratory fluoroquinolones (iv levofloxacin).

The combination of cephalosporins with macrolides increases their antipneumococcal effect. This combination "overlaps" almost the entire spectrum of possible causative agents of community-acquired pneumonia of severe course. No less effective is the monotherapy of "respiratory" parenteral fluoroquinolones with increased antipnevmokokkova activity. It should be borne in mind that the use of "old" fluoroquinolones (ciprofloxacin) does not have great advantages over beta-lactam antibiotics.

As alternative drugs for the treatment of community-acquired pneumonia of severe course, intravenous infusions of carbapenems (imipemem, meropenem), including in combination with modern macrolides, can be used.

Carbapenems are ß-lactam antibiotics of the ultra-wide spectrum of action. They show a high activity against gram-positive and gram-negative aerobic and anaerobic microflora, including Pseudomonas aeruginosa, acipetobacter, enterobacteria, Escherichia coli, Klebsiella, Proteus, Salmonella, Hemophilus rod, Enterococcus, Staphylococcus, Listeria, Mycobacteria, etc. Imipeptem (tienam) more effective against Gram-positive pathogens. Meropepem shows a higher activity in relation to gram-negative pathogens, especially enterobacteria, hemophilic rod, Pseudomonas aeruginosa, acipetobacter, etc.

Carbapenems are inactive for methicillin-resistant staphylococci (S. Aureus, S. Epidermalis), certain strains of Enterococcus faecium and intracellular pathogens. The latter circumstance underscores the need for a combination of carbapenems with parenteral modern macrolides.

Particular attention should be paid to the treatment of abscessed pneumonia, the pathogens of which are usually a mixed flora - a combination of anaerobes (often Prevotella melaninogenlca) with aerobes (more often Staphylococcus aureus, less often Gram-negative bacteria, including Pseudomonas aeruginosa).

If suspicion of the role of Gram-negative microflora in the genesis of abscessed pneumonia, including Pseudomonas aeruginosa, it is advisable to use so-called antipseudomonasal ß-lactam antibiotics (cefazidime, cefepime, imipepema, meropenem) in combination with parenteral macrolides and ciprofloxacin. In the treatment of abscessed pneumonia, antianaerobic antibiotics (metronidazole) combinations with antistaphylococcal agents (1st generation cephalosporins) are often used. Monotherapy with parenteral fluoroquinolones of III and IV generations is also effective. The use of antibiotics for abscessed pneumonia should only be parenteral and in most cases continue for at least 6-8 weeks.

The table shows the average duration of antibiotic treatment of patients with pneumonia, depending on the pathogen. In most cases, with an adequate choice of antibiotics, 7-10 days of its use is sufficient. With pneumonia caused by atypical pathogens, the optimal treatment time increases to 14 days, and with legionella or staphylococcal infection - up to 21 days. Treatment of pneumonia caused by gram-negative enterobacteria or Pseudomonas aeruginosa should be at least 21-42 days.

The average duration of antibiotic treatment, depending on the pathogen of pneumonia (according to Yu.K. Novikov)

Causative agent	Duration of therapy
Pneumococcus	3 days after the normalization of temperature (not less than 5-7 days)
Enterobacteria and Pseudomonas aeruginosa	21-42 days
Staphylococcus aureus	21 days
Pneumocystis	14-21 days
Legionella	21 days
Pneumonia complicated by abscess formation	42-56 days

The most reliable guidelines for the abolition of antibiotics, in addition to the positive dynamics of the clinical picture of the disease, are the normalization of the radiographic pattern, hemograms and sputum. It should be remembered that in the majority of patients with pneumococcal pneumonia a full "X-ray recovery" occurs within 4-5 weeks, although in some patients it is delayed for 2-3 months. In cases of pneumococcal pneumonia complicated by bacteremia, the complete reverse development of pneumonic infiltration during 8 pedules is observed only in 70% of patients, and in the remaining patients - only to 14-18 pedules. The timing of radiologic recovery of community-acquired pneumonia is most influenced by the prevalence of pneumonic infiltration, the nature of the pathogen and the age of the patients.

Slowly resolving (prolonged) pneumonia is characterized by a slow reverse development of radiologic changes (reduction in the size of pneumonic infiltration by less than 50% within 4 weeks). Prolonged pneumonia should not be confused with cases of the disease, resistant to the treatment of pneumonia. The main risk factors for prolonged pneumonia are:

• age over 55;
• chronic alcoholism;
• concomitant diseases (COPD, congestive heart failure, renal failure, malignant neoplasms, diabetes mellitus);
• severe course of pneumonia;
• multiple-lobe pneumonic infiltration;
• pneumonia caused by highly virulent pathogens (legionella, staphylococcus, gram-negative enterobacteria, etc.);
• tobacco smoking;
• bacteremia.

The choice of an antibiotic for the empirical therapy of hospital pneumonia.

Hospital (nosocomial) pneumonia is known to have the most severe course and high lethality, reaching on average 10-20%, and with infection with Pseudomonas aeruginosa - 70-80%. Recall that the main pathogens of nosocomial pneumonia are:

• pneumococcusa {Streptococcus pneumoniae);
• Staphylococcus aureus (Staphylococcus aureus);
• klebsiella (Klebsiella pneumoniae);
• E. Coli (Escherichiae coli);
• Proteus (Proteus vulgaris);
• Pseudomonas aeruginosa;
• Legionella (Legionella pneumophila)]
• anaerobic bacteria (Fusohacterium spp., Bacteroides spp., Peptostreptococcus spp.)

Thus, among the pathogens of nosocomial pneumonia, the specific gravity of gram-negative microflora, staphylococcus and anaerobic bacteria is very high. Hospital pneumonia, not associated with the use of intubation or ICL. The most frequent pathogens of hospital pneumonia, the genesis of which is not associated with the use of endotracheal tube or ventilation, are hemophilic rod, klebsiella, gram-negative enterococci, pneumococci and Staphylococcus aureus. In these cases, the empirical treatment of moderate pneumonia begins with parenteral administration of the following antibacterial agents:

• "Protected" aminopenicillins (amoxiclav, ampicillin / sulbactam);
• cephalosporin II-IV generations (cefuroxime, cefotaxime, ceftriaxone, cefpir, cefepime);
• "Respiratory" fluoroquinolones (levofloxacin).

If there is no effect or severe course of pneumonia, it is recommended to use one of the following combination therapy regimens:

• combination of "protected" aminopenicillins (amoksiklav, ampicillin / sulbactam) with aminoglycosides II-III generations (amikacin, gentamycin);
• combination of cephalosporins II-IV generations (cefuroxime, cefotaxime, ceftriaxone, cefpyr, cefepime) with amikacin or gentamycin;
• a combination of "protected" ureidopenicillins (antinsinonex penicillins) with aminoglycosides II and III generations;
• a combination of "respiratory" fluoroquinolones (levofloxacia) with aminoglycosides II and III generations.

In all the above schemes, aminoglycosides II and III generations are included in the combined antimicrobial treatment of pneumonia. This is due to the fact that modern aminoglycosides (gentamicin, amikacin, etc.) are effective agents for the treatment of severe infections. Aminoglycosides have a high activity against certain gram-positive (staphylococcus and / faecalis) and most gram-negative pathogens, including the enterococcus family (Escherichia coli, Klebsiella, Proteus, Enterobacter, etc.). Gentamicin and amikacin are highly active against hemophilic rod, mycoplasma, and also Pseudomonas aeruginosa. Therefore, the main indication for their use are hospital pneumonias, whereas in the case of community-acquired pneumonia of mild and moderately severe course, their use is impractical.

It should be emphasized that amikacin has a slightly wider spectrum of action than classical gentamicin. Gentamycin is prescribed in a dose of 1.0-2.5 mg / cc every 8-12 hours, and amikacin - 500 mg every 8-12 hours.

In the absence of effect, carbapepam monotherapy is indicated. Perhaps their combination with aminoglycosides II and III generations.

If patients with hospital pneumonia are more likely to have an anaerobic infection, a combination of cephalosporin II-III generations with modern macrolides or a combination of aminoglycosides with ciprofloxacin or "respiratory" fluoroquinolones is advisable. It is also possible to combine a broad-spectrum antibiotic with metronidazole.

For example, in patients with OHMK, patients after thoracoabdominal operations or with the presence of a nasogastric tube, when the aspiration of the oropharyngeal microflora is the main pathogenetic factor in the development of the oropharyngeal pneumonia, the pathogens of hospital pneumonia are anaerobic microorganisms (Bacteroides spp., Peptostreptoxoccus spp., Fusohacterium nucleatum, Prevotella spp.), Staphylococcus aureus (often antibiotic resistant strains), Gram-negative enterobacteria (Klebsiella pneumoniae, Escherichiae coli), as well as Pseudomonas aeruginosa and Proteus vulgaris. In these cases, "protected" aminopenicillins, cephalosporins of II-III generations, carbapenems, a combination of metronidazole and fluoroquinolones are used.

In patients with diabetes mellitus, chronic alcoholism, in which pneumonia is most often caused by gram-negative flora (klebsiella, hemophilic rod, legionella, etc.), the drugs of choice are:

• "Respiratory" fluoroquinolones;
• combination of cephalosporins II-III generation with modern macrolides. Hospital-associated ventilator-associated pneumonia (BAII).

Hospital pneumonia, developed in patients with ventilation, - ventilator-associated pneumonia (VAP), are characterized by particularly severe course and high mortality. The causative agent of early VAP is most often pneumococci, hemophilic rod, Staphylococcus aureus and anaerobic bacteria. The causative agent of late VAP are drug resistant strains of enterobacteria, Pseudomonas aeruginosa, Klebsiella, Proteus, Acinetobacter spp. and methicillin-resistant strains of Staphylococcus aureus (MRSA).

In these latter cases, it is advisable to prescribe antibiotics with high antisignogenic activity:

• combinations of anti-synergistic cephalosporin (ceftazidime) with aminoglycosides of the third generation (amikacin);
• combinations of ceftazidime with respiratory fluoroquinolones;
• a combination of "protected" anti-synergic ureidopenicillins (ticarcillin / clavulonic acid, piperacillin / tazobactam) with amikacin;
• monotherapy with cephalosporinium IV generation (cefepime);
• monotherapy with carbanenem (imipepem, meropepem);
• combinations: ceftazidime, cefepime, meropepem or imipepem
• + Fluoroquinolope II generation (ciprofloxacin)
• + modern macrolides.

Staphylococcal destructive pneumonia. If suspected of the occurrence of staphylococcal pneumonia, the following schemes of parenteral etiotropic treatment may be effective:

• Oxacillin in the maximum permissible doses (do not use "ampiox"!);
• "Protected" aminopenicillins (amoksiklav, ampicillin / sulbactam);
• cephalosporins I, II and IV generations (cefazolin, cefuroxime, cefepime); cephalosporins of the third generation (cefotaxime, ceftriaxone, ceftazidime, etc.) are not effective in staphylococcal infection;
• carbapepem;
• lincosamides (clindamycin);
• fusidic acid;
• Respiratory fluoroquinolones.

Combined treatment of pneumonia is also recommended:

• combination of beta-lactams with aminoglycosides of the third generation (amikacin);
• combination of clindamycin or lincomycin with amikacin;
• combination of beta-lactams with rifampicin;
• combination of beta-lactams with fusidic acid;
• combination of fusidic acid with rifampicin.

If the treatment is ineffective, the use of a glycopeptide - vancomycin, which is active against all, including against methicillin-resistant and oxacillin-resistant staphylococci, is expedient. Effective combinations of vancomycation with beta-lactams, II and III aminoglycosides, rifampicin or levofloxacin are possible.

When microbiological confirmation of the etiology of pneumonia, etiopropletic therapy is adjusted taking into account the definition of individual sensitivity to antibiotics. The table shows an approximate list of antibacterial drugs that have activity against certain pathogens of pneumonia. Separately isolated ineffective and ineffective antimicrobial drugs.

Activity of antibacterial drugs against the most likely pathogens of pneumonia

Antibacterial drugs with high activity	Low-effective and ineffective drugs
Pneumococci
Aminopenicillins (amoxicillin, amoxiclav, ampicillin / sulbactam, etc.)	"Old" fluoroquinolones (ofloxacin, ciprofloxacin)
Modern macrolides (clarithromycin, roxithromycin, azithromycin, spiramycin)	Aminoglycosides (gentamicin, amikacin)
Cephalosporins of I-IV generations (cefazolinum, cefuroxime, cefotaxime, ceftriaxone, cefazidime, cefemol, etc.)
"Respiratory" fluoroquinolones (levofloxacin, moxifloxacin)
Carbapenems (imipenem, meropenem)
Vancomycin
"Protected" ureidopenicillins (picarcillin / clavulanate, piperacillin / tazobactam)
Lincosamides (clindamycin, lincomycin)
Hemophilus influenzae
Aminopenicillins (amoxicillin, amoxiclav, ampicillin / sulbactam)	Cephalosporins of the first generation (cefazolin)
Cephalosporins of II-IV generations (cefuroxime, cefotaxime, ceftriaxone, cefazidime, cefepime, etc.)	Lincosamides (lincomycin, clarithromycin)
"Respiratory" fluoroquinolones (levofloxacin, moxifloxacin)
Modern macrolides (azithromycin, clarithromycin, spiramycin, roxithromycin)
Moraçella
Aminopenicillins (amoxicillin, amoxiclav, ampicillin / sulbactam)	Lincosamides
Cephalosporins of the second generation (cefuroxime, etc.)
Fluoroquinolones
Macrolides
Staphylococci (golden, epidermal, etc.)
Oxacillin	Oral cephalosporins of the third generation (cefotaxime, ceftriaxone, etc.)
"Protected" aminopenicillins (amoksiklav, ampicillin / sulbactam, etc.)	Amoxicillin ("unprotected" aminopenicillin)
Aminoglycosides II and III generations (gentamicin, amikacin)
Cephalosporins I, II and IV generations
Fluoroquinolones
Macrolides
Gipocopypeptides (vancomycin)
Co-trimoxazole
Lincosamides (lincomycin, clarithromycin)
Doxycycline
Carbapenems
Fusidic acid
Methicillin-resistant Staphylococcus strains
Glycoleptides (vancomycin)	All ß-lactams
Fluoroquinones of III-IV generations	Lincosamides
Fusidia cispota
Co-trimoxazole
Intracellular pathogens (mycoplasma, chlamydia, legionella)
Macrolides (clarithromycin, roxithromycin, azithromycin, spiramycin)	Aminopenicillins
Doxycycline	Cephalosporins of 1-IV generations
"New" fluoroquinolones	Ciprofloxacin
Rifampicin	Aminoglycosides
	Ureido disciplines
Gram-negative enterococci (intestinal group)
Cephalosporins III and IV generations (ceftriaxone, cefotaxime, cefepime)	"Unprotected" aminopenicillins
Carbapenems	Macrolides
Fluoroquinolones	Cephalosporins 1 and II
"Protected" aminopenicillins (amoksiklav, ampitsipin / supbaktam, etc.)	Lincosamides
Co-trimoxazole
Aminoglycosides II and III of bunches (amikacin, gentamicin)
Anaerobes
Cephalosporins of III-IV generations (cefotaxime, cefepime)	Aminoglycosides 11-111 generations
Macrolides
Ureido disciplines
Lincosamides
Pseudomonas aeruginosa
Ceftazidime
Aminoglycosides (amikacin)
Cephalosporins of the fourth generation (cefepime)
Carbapenems (imipenem, meropenem)
Fluoroquinolones
"Protected" (anti-synergic) ureidopeniplines (ticarcillin / clavulanate, piperacillin / tazobactam)

It must be added that when choosing etiotropic treatment for pneumonia, whenever possible, one should strive to prescribe monotherapy with one of the effective antibiotics. In these cases, antibacterial effects, potential toxicity and cost of treatment are minimized.

[1], [2], [3], [4], [5], [6], [7]

Improvement of drainage function of the bronchi

Improving the drainage function of the bronchi is one of the most important conditions for the effective treatment of pneumonia. The violation of bronchial patency in this disease is due to several mechanisms:

• a significant amount of viscous purulent exudate coming from the alveoli into the bronchi;
• inflammatory edema of the bronchial mucosa, the draining focus of inflammation of the lung tissue;
• damage to the ciliated epithelium of the bronchial mucosa and violation of the mechanism of mucociliary transport;
• increased production of bronchial secretion, due to the involvement of bronchial mucosa in the inflammatory process (hypercrinia);
• significant increase in sputum viscosity (discrinia);
• increased tonus of smooth muscles of small bronchi and a tendency to bronchospasm, which makes it even more difficult to separate sputum.

Thus, violations of bronchial patency in patients with pneumonia are associated not only with the natural drainage of the inflammation focus and the entry of viscous alveolar exudate into the bronchi, but also with the frequent involvement of the bronchus themselves in the inflammatory process. This mechanism acquires special significance in a patient with bronchopneumonia of various genesis, as well as in patients with concomitant chronic bronchial diseases (chronic obstructive bronchitis, bronchiectasis, cystic fibrosis, etc.).

Deterioration of bronchial patency, observed at least in some patients with pneumonia, contributes to an even greater disruption of the processes of local, including immunological, protection, re-seeding of the airways and prevents the healing of the inflammatory focus in the lung tissue and the restoration of pulmonary ventilation. Reduction of bronchial patency contributes to aggravation of ventilation-perfusion ratios in the lungs and to progress of respiratory failure. Therefore, the comprehensive treatment of patients with pneumonia involves the mandatory appointment of funds that have expectorant, mucolytic and bronchodilator effect.

It is known that sputum present in the lumen of the bronchi in patients with pneumonia consists of two layers: the upper, the more viscous and dense (gel), lying over the cilia, and the lower liquid layer (sol), in which the cilia swim and contract. The gel consists of macromolecules of glycoproteins linked together by disulfide and hydrogen bonds, which gives it viscous and elastic properties. When the water content in the gel decreases, the sputum viscosity increases and the movement of the bronchial secretion toward the oropharynx slows or even stops. The speed of this movement becomes even less if it thines out the layer of the liquid layer (sol), which to a certain extent prevents the sputum from adhering to the walls of the bronchi. As a result, in the lumen of the small bronchi, mucous and muco-purulent plugs are formed, which with great difficulty are removed only by a strong expiratory flow of air during bouts of excruciating coughing.

Thus, the ability of unimpeded removal of sputum from the respiratory tract is primarily determined by its rheological properties, the water content in both phases of the bronchial secretion (gel and sol), and by the intensity and coordination of the activity of the cilia of the ciliated epithelium. The use of mucolytic and mucoregulatory drugs is aimed at restoring the ratio of sol and gel, diluting sputum, rehydration, and stimulation of the cilia of the ciliated epithelium.

Pneumonia: treatment with non-pharmacological methods

Non-medicamentous ways to improve the drainage function of the bronchi are a mandatory component of complex treatment of patients with pneumonia.

A plentiful warm drink (alkaline mineral water, milk with the addition of a small amount of sodium bicarbonate, honey, etc.) contributes to an increase in the water content in the gel layer and, accordingly, to reduce the viscosity of sputum. In addition, the natural rehydration of the bronchial contents leads to a certain increase in the thickness of the liquid layer of the sol, which facilitates the movement of cilia and the movement of sputum in the lumen of the bronchi.

Chest massage (percussion, vibrating, vacuum) is also used to improve the drainage function of the bronchi. Percussion massage is performed with the edge of the palm, pokolachivaya chest wall of the patient with a frequency of 40-60 per minute. In me and with the bridge from the patient's condition, massage lasts 10-20 minutes in cycles of 1-2 mn, after which they pause, during which the patient is asked to clear his throat.

Vibration massage is carried out with the help of special vibromassers with adjustable frequency and amplitude of vibrations.

The vacuum (canary) chest massage, which combines elements of mechanical and reflex stimulation, improves pulmonary blood flow and a kind of autohemotherapy due to the formation of intraluminal hemorrhages, has also not lost its value. This facilitates the drainage of the lungs and decreases the severity of inflammatory changes in the lung tissue.

It should be remembered that any kind of chest massage is contraindicated in case of a threat of pulmonary hemorrhage, with abscessing, with a chest injury or a suspected tumor in the lungs.

Respiratory gymnastics is an effective means of restoring the drainage function of the bronchi. Deep respiratory movements stimulate a cough reflex, and breathing with the creation of artificial resistance during exhalation (through closed lips, special flutters or other devices) prevents the expiratory collapse of small bronchi and the formation of micro-teleclactases.

With caution, respiratory gymnastics should be conducted with the threat of spontaneous pneumothorax.

Expectorants

Expectorants in the narrow sense of the word is a group of drugs that affect the rheological properties of phlegm and facilitate its departure. All expectorants are conditionally divided into two groups:

1. Means stimulating expectoration:
   • preparations of reflex action;
   • preparations of resorptive action.
2. Mucolytic and mucoregulatory means.

Means stimulating expectoration increase the activity of the ciliated epithelium and the endothelial movement of bronchioles, facilitating the movement of sputum to the upper respiratory tract. In addition, under the influence of these drugs, the secretion of bronchial glands intensifies and a certain decrease in the viscosity of sputum occurs.

Expectorants of the emetic-reflex action (the herb of thermopsis, the root of the ipecacuan, terpin hydrate, the root of the wasteland, etc.) with oral administration have a mild irritant effect on the receptors of the gastric mucosa, which leads to an increase in the activity of the centers of the vagus nerve. As a result, endothelial contractions of the smooth muscles of the bronchi are intensified, the secretion of the bronchial glands is increased, and the amount of liquid bronchial secretion is increased. Reducing the viscosity of the sputum is accompanied by the relief of its departure.

One of the effects of the reflex action of these drugs on the tone of the vagus nerve is nausea and vomiting. Therefore, it is necessary to take these medicines and cute, individually selected, doses, at least 5-6 times a day.

Expectorants of resorptive action (potassium iodide, etc.) also increase the secretion of the bronchial glands, but not the reflector, but due to their secretion by the mucosa of the airways after ingestion. Stimulation of the secretion of the bronchial glands is accompanied by some dilution of sputum and an improvement in its retreatment.

Mucolytics and mukoregulatory drugs are prescribed primarily to improve the rheological properties of sputum, facilitating its separation. At present, the most effective mucolytics are acetylcysteine, mesentium, bromhexine and ambroxol.

Acetylcysteine (ACC, flumucil) is an N-derivative of the natural amino acid of L-cysteine. In the structure of its molecule, it contains a free sulfhydryl group SH, which cleaves the disulfide bonds of macromolecules of the sputum glycoprotein, and thereby significantly reduces its viscosity and increases the volume. In addition, ATSTS has distinct antioxidant properties.

Acetylcysteine is used in patients with various diseases of the respiratory system, accompanied by the separation of purulent sputum of increased viscosity (acute and chronic bronchitis, pneumonia, bronchiectasis, cystic fibrosis, etc.). Apply acetylcysteine in the form of inhalation of 2-5 ml of a 20% solution, usually with an equivalent amount of 2% sodium bicarbonate solution, sometimes in a mixture with a standard dose of bronchodilator. The duration of inhalation is 15-20 minutes. In inhalation mode of administration, one should beware of bophorrhoea, which can have undesirable consequences if the patient has a cough reflex (IP Zamotayev).

In severe patients with respiratory failure in the ICU, acetylcysteine can be used in the form of intra-tracheal instillations according to I ml of a 10% solution, as well as for flushing the bronchi during medical bronchoscopy.

If necessary, the drug is administered parenterally: intravenously, 5-10 ml of 10% solution or intramuscularly 1-2 ml of 10% solution 2-3 times a day. The drug begins in 30-90 minutes and lasts about 2-4 hours.

Inside acetylcysteine take in the form of capsules or tablets of 200 mg 3 times a day.

The drug is well tolerated, but its use requires caution in patients prone to bronchospasm or pulmonary hemorrhage.

Mesna (Mistabrone) has a mucolytic effect similar to acetylcysteine, diluting sputum and promoting its separation.

The drug is used in the form of inhalations of 3-6 ml of 20% solution 2-3 times a day. The effect occurs in 30-60 minutes and lasts 2-4 hours.

Bromhexine hydrochloride (bisolvone) has a mucolytic and expectorant effect associated with the depolymerization and destruction of mucoproteins and mucopolysaccharides that make up the gel of bronchial mucus. In addition, bromhexine is able to stimulate the formation of surfactant type II alveolocytes.

When administered orally, the expectorant effect in adults occurs 24-48 hours after the start of treatment and is achieved by applying 8-16 mg of bromhexine 3 times a day. In mild cases, you can reduce the daily dose to 8 mg 3 times a day, and in children younger than 6 years - up to 4 mg 3 times a day.

The drug is usually well tolerated. Occasionally, a slight discomfort on the stomach side is possible.

Ambroxol hydrochloride (lazolvan) is an active metabolite of bromhexine. Due to its pharmacological properties and mechanism of action, it differs little from bromhexine. Ambroxol stimulates the formation of a tracheo-bronchial secretion of reduced viscosity due to destruction of mucopolysaccharides of sputum. The drug improves mucociliary transport, stimulating the activity of the ciliary system. Important is the property of lazolvan to stimulate the synthesis of surfactant.

Adults drug prescribed in a dose of 30 mg (1 tablet) 3 times a day for the first 3 days, and then 30 mg 2 times a day.

Thus, ambroxol and bromhexine have not only mucolytic, but also important mucoregulatory properties.

[8], [9], [10]

Bronchodilators

In some patients pneumonia, especially in patients with severe disease or in persons prone to the occurrence of bronchospastic syndrome, it is advisable to use bronchodilators. Preferred is the use of inhalation forms of beta2-adrenostimulyatorov (beroteka, beroduala, etc.), M-holinolitikov (atroventa) and intravenous infusion of 2.4% solution of euphyllin.

[11], [12], [13], [14], [15], [16], [17], [18], [19]

Detoxification therapy

In severe pneumonia, detoxification therapy is carried out. Intravenous dropwise injection of saline solutions (for example, isotonic sodium solution breed to 1-2 liters per day), 5% glucose solution 400-800 ml per day, polyvinylpyrrolidone 400 ml per day, albumin 100-200 ml per day.

All solutions are administered under strict control of systemic arterial pressure, central venous pressure (CVP) and diuresis. In patients with concomitant pathology of the cardiovascular system and heart failure, the fluid should be administered with great caution, preferably under the control of DZLA and CVP.

[20], [21], [22], [23], [24], [25]

Heparinotherapy

One of the effective treatments for pneumonia is heparin. It is a mucopolysaccharide with a high sulfur content, it has a significant negative charge and is able to interact with various basic and amphoteric substances. The ability of heparin to complex formation determines the variety of its pharmacological properties.

By positively affecting the blood coagulation system, heparin improves blood flow and microvessel lung canal, reducing edema of bronchial mucosa and improving their drainage function. Heparin influences the rheological properties of sputum, thus rendering mucolytic action. At the same time, it affects the reversible component of bronchial obstruction due to anticomplementary binding of calcium ions, stabilization of lysosomal membranes, blockade of inositol triphosphate receptors.

When complicating pneumonia respiratory failure heparin has antihypoxic, antiserotonin, antialdosterone and diuretic effect.

Finally, recent studies have shown the effect of heparin on an active inflammatory process. This effect is explained by inhibition of neutrophil chemotaxis, increased activity of macrophages, inactivation of histamine and serotonin, increased antibacterial activity of chemotherapeutic agents, and a decrease in their toxic effect.

In severe pneumonia, heparin is prescribed for 5,000-10,000 units 4 times a day subcutaneously. It is even better to use modern low molecular weight heparins.

Immunocorrective and immunocompromised treatment of pneumonia

Pneumonia treatment involves the administration of hyperimmune plasma intravenously (4-6 ml / kg) and immunoglobulin of 3 biodosomes intramuscularly daily for the first 7-10 days of the disease. For the entire period of the disease, immunomodulators (methyluracil, sodium nucleate, T-activin, thymalin, decaris, etc.) are prescribed. There are intravenous drip infusions of native and / or freshly frozen plasma (1000-2000 ml for 3 days) or intravenously immunoglobulin 6-10 g per day once.