Treatment of pneumonia

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

Indications for hospitalization

The first question a doctor must decide is where a patient with community-acquired pneumonia should be treated: in a hospital or at home? According to modern concepts, 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 Combating complications of acute pneumonia Physiotherapy, exercise therapy, breathing exercises for pneumonia Sanatorium and resort treatment and rehabilitation for pneumonia

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

• Septic shock
• PaO2 < 60 mmHg or PaCO2 _> 50 mmHg 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 failure (urea > 7 mmol/l)
• Social indications (inability to care for the patient at home)

The main factors determining the decision on the place of treatment of a patient with pneumonia are the severity of the disease, the presence of complications, as well as risk factors for an unfavorable course of the disease and a fatal outcome. However, it should be remembered that the final decision on hospitalization may be influenced by social and everyday factors, such as the impossibility of caring for the patient at home.

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

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

Etiotropic treatment of pneumonia

Antibacterial drugs are the basis of pneumonia treatment. The choice of the most effective one depends on many factors, primarily on the accuracy of identification of the pneumonia pathogen, determination of its sensitivity to antibiotics and early initiation of adequate treatment of pneumonia with antibiotics. However, even with a well-equipped microbiological laboratory, the etiology of pneumonia can be established only in 50-60% of cases. Moreover, it takes at least 24-48 hours to obtain the results of microbiological analysis, while antibiotic treatment of pneumonia should be prescribed immediately after the diagnosis of pneumonia is established.

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

In this regard, the initial choice of antibiotic is usually empirical in nature and is based on an analysis of the specific clinical and epidemiological situation in which a given patient developed pneumonia, and taking into account factors that increase the risk of infection with a particular pathogen.

Choice of antibiotic for empirical treatment of community-acquired pneumonia

Let us recall that the most common pathogens of community-acquired pneumonia are:

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

Moreover, pneumococcal infection accounts for more than half of community-acquired pneumonia cases, and another 25% of pneumonia cases are caused by Haemophilus influenzae, Moraxella 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 increased significantly, which significantly complicates the choice of an adequate antibacterial agent for the etiotropic treatment of community-acquired pneumonia.

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

Modifying factors that increase the risk of infection with certain pathogens (according to H. Cossiere et al., 2000)

Virulent pathogens	Modifying factors
Penicillin-resistant, drug-resistant pneumococci	Age over 65 years Prescription of beta-lactam antibiotics within the last | 3 months Alcoholism Immunosuppressive conditions and diseases (including glucocorticoid therapy) The presence of several concomitant diseases Children attending nurseries/kindergartens
Gram-negative enterobacteria	Residents of nursing homes Concomitant diseases of the lungs and heart The presence of several concomitant diseases Recent antibiotic treatment for pneumonia
Pseudomonas aeruginosa	Diseases with changes in the structure of the lungs (eg, bronchiectasis) Corticosteroid therapy (more than 10 mg prednisolone per day) Taking a broad-spectrum antibiotic for more than 7 days in the last month Poor nutrition

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

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

Amoxicillin is a modern drug from the aminopeptic cillip group. Its action extends to gram-positive and gram-negative microflora (streptococci, pneumococci, Haemophilus influenzae, Moraxella, Escherichia coli, Proteus, Legionella, Helicobacter, etc.). Pseudomonas aeruginosa, Klebsiella, Enterobacter, etc. are not sensitive to amoxicillin.

Amoxicillin is a derivative of ampicillin, but significantly surpasses it in its pharmacokinetic properties and is more active against pneumococci. Due to its high bioavailability (about 85-90%), amoxicillin is considered the best oral antibiotic worldwide. The usual dose for adults when taken orally is 0.5-1.0 g 3 times a day, and when administered parenterally (intravenously or intramuscularly) - 1 g every 8-12 hours.

Amoxicillin/clavulanate (Amoxiclov, Augmentin) is a combination drug of amoxicillin and PA and clavulanic 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 pepicilins, cephalosporins and monobactams. Due to the ability of clavulanic acid to inhibit the negative effect of bacterial beta-lactamases, the spectrum of action is significantly expanded and the activity of amoxicillin against most staphylococci, gram-negative bacteria, non-spore-forming anaerobes and some strains of Klebsiella spp. and E. coli is significantly increased.

Amoxiclav's activity against pneumococci is no different from that of amoxicillin (without clavulanate), since pneumococci do not secrete beta-lactamases. Like amoxicillin, amoxiclav is not effective in treating infections caused by Pseudomonas aeruginosa. Amoxiclav is prescribed orally at 375-625 mg (for amoxicillin) 3 times a day in the form of tablets or powder for suspension. Parenterally, the drug is administered at 1.2 g every 6-8 hours.

Ampicillin also belongs to the aminopepicilin group and resembles amoxicillin in its spectrum of action, 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 is well tolerated, and its use rarely causes toxic reactions, 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 administrations. Most strains of staphylococci are not sensitive to ampicillin. However, when using "protected" ampicillin (ampicillin / sulbactam), its spectrum of action expands and the drug becomes active against many strains of Staphylococcus aureus and Staphylococcus epidermidis.

In medical practice, the combined drug ampiox with a fixed ratio of ampicillin and oxacillin (2:1 for parenteral administration) has become widespread. Theoretically, ampiox has properties inherent in both components. Oxacillin is known to be one of the effective anti-staphylococcal drugs, showing its activity against penicillin-resistant staphylococcus (PRSA), which is resistant to ampicillin and other "unprotected" aminopenicillins. Meanwhile, the activity of oxacillin against pneumococci and streptococci is relatively low. The drug is inactive against all gram-negative aerobes, enterococci, all anaerobes and intracellular pathogens.

Nevertheless, an important property of oxacillin, which is part of ampiox, has until now been considered its ability to bind penicillinase (ß-lactamase) of gram-negative bacteria and thereby prevent these bacteria from destroying the beta-lactam ring of ampicillin. However, at present, this positive property of oxacillin seems highly questionable, since most gram-negative microorganisms produce beta-lactamases, which in fact destroy both components of ampiox. In other words, the effectiveness of ampiox 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 drug) is clearly insufficient for effective action on staphylococci.

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

Macrolides are a group of antibiotics that are highly active against gram-positive cocci (streptococci, pneumococci, Staphylococcus aureus and Staphylococcus epidermidis), some gram-negative bacteria (Haemophilus influenzae), some anaerobes (B./ragilis, clostridia, etc.), and intracellular pathogens (chlamydia, mycoplasma, 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 the III-IV generation are mainly used for the treatment of pneumonia:

• clarithromycin;
• roxithromycin;
• azithromycin;
• spiramycin.

Oral administration of "old" macrolides (erythromycin, oleandomycin) is not recommended due to the lack of reliable information on the efficacy and bioavailability of commercially available erythromycin preparations. If necessary, parenteral erythromycin can be used, which is administered intravenously by jet stream or infusion at a dose of 0.2-0.5 g 4 times a day. Table 3.19 presents 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 S.M. Shotunov, 2001)

Macrolide drug	Doses
	When taken orally	When administered intravenously
Spiramycin	6-9 million IU (2-3 g) per day in 2 divided doses, regardless of meals	4.5-9 million IU per day in 2 doses
Roxithromycin	0.15-0.3 2 times a day before meals	-
Clarithromycin	0.25-0.5 2 times a day, regardless of food intake	500 mg per day for 5 days, then orally for another 5 days
Aethromycin	0.5-1.0 g once a day one hour or 2 hours after meals
	5-day course: 1st day - 0.5-1 g once a day; subsequent days: 0.25-0.5 g per day
	3-day course: daily 0.5-1 g 1 time per 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 causing allergic reactions 5-10 times less often. In community-acquired pneumonia, cephalosporins of the second and third generations are usually used.

In mild cases of pneumonia, in particular when treating patients at home, it is recommended to use the oral second-generation drug cefuroxime (Ketocef, Zinacef), which has high activity against pneumococci and some gram-negative bacteria - Haemophilus influenzae, Moraxella catarrhalis, E. Coli, etc. The drug is taken at a dose of 250-500 mg 2 times a day after meals. In more severe cases of the disease, cefuroxime is administered intravenously or intramuscularly at a dose of 750-1500 mg 3 times a day.

In recent years, when parenteral administration of cephalosporins is necessary, third-generation drugs have been used more often - cefotaxime and ceftriaxone. They surpass other antibiotics of this group in the severity of their action on most gram-negative pathogens and streptococci. Ceftriaxone (Rocefii, Lendacin) has a particularly high activity against Haemophilus influenzae and pneumococci. The drug has been preferred in recent years because, due to its long half-life, it can be administered once a day in a dose of 1-2 g. Cefotaxime is somewhat inferior to ceftriaxone in its action on gram-positive and gram-negative bacteria. It is administered in a dose of 3-6 g per day in 3 administrations.

The fourth-generation cephalosporins include cefepime and cefpirome. They exhibit very high activity against gram-negative bacteria, including strains resistant to other cephalosporins, and act on Pseudomonas aeruginosa. They are also highly effective against gram-positive flora, including streptococci and staphylococci. Fourth-generation cephalosporins exhibit very high activity against Haemophilus influenzae, Neisseria, Moraxella and anaerobes. Cefepime is administered intramuscularly or intravenously at 1 g 2 times a day, and cefpirome is administered intravenously at 1-2 g every 12 hours. It is advisable to use fourth-generation cephalosporins only in severe cases of community-acquired pneumonia and/or the presence of concomitant diseases and other risk factors that increase the likelihood of unfavorable outcomes of the disease.

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

Currently, for pneumonia, it is recommended to use the so-called "respiratory" fluoroquinolones of the third and fourth generations (levofloxacin, moxifloxacin, etc.), which have very high activity against pneumococci, chlamydia, mycoplasma, and gram-negative pathogens. Moxifloxacin, in addition, exhibits activity against non-spore-forming anaerobes (B. fragilis, etc.).

Levofloxacin (Tavanic) - a third-generation drug - is used in a dose of 250-500 mg. Once a day when taken orally and 0.5-1.0 g per day when administered intravenously. Moxifloxacin - (a fourth-generation drug) is taken orally in 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 (gentamicin, amikacin, co-trimoxazole, etc.), although they are highly effective antimicrobial drugs, have a relatively narrow spectrum of action, directed mainly at gram-negative flora, anaerobes, staphylococci, etc. As a rule, they have very low activity against pneumococci, Haemophilus influenzae and intracellular pathogens, i.e. against the most frequent etiologic factors of community-acquired pneumonia. The use of these drugs is advisable only in severe cases of 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 mild and moderate cases of community-acquired pneumonia, the use of these drugs in most cases is pointless and even harmful, since it increases the risk of developing unwanted side effects and complications of such therapy (frequent allergic reactions, pseudomembranous colitis, Stevens-Johnson syndrome, Lyell's syndrome, etc.).

As stated above, in most cases, empirical etiotropic treatment of pneumonia includes the use of one of the listed effective antibiotics (monotherapy with amoxicillin, modern macrolides, second- and third-generation cephalosporins, “respiratory” fluoroquinolones).

In mild cases of community-acquired pneumonia that do not require hospitalization of the patient (treatment at home) and the absence of risk factors, oral administration of amoxicillin, amoxiclav or modern macrolides is allowed. If necessary, alternative oral drugs are prescribed (amoxiclav, cefuroxime, levofloxacin, moxifloxacin).

Treatment of community-acquired pneumonia of moderate severity and patients with aggravating risk factors should be started in hospital conditions (or, where possible, at home) with parenteral (intravenous or intramuscular) administration of "protected" aminopenicillins or modern macrolides, combining them with each other if necessary. If such treatment of pneumonia is ineffective, alternative drugs are prescribed:

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

It should be remembered that the effectiveness of antibiotic treatment of pneumonia is assessed primarily by the clinical condition of the patient and the results of some laboratory tests, which, when choosing adequate treatment for pneumonia, should improve in the next 48-72 hours. During this time, changing the treatment of pneumonia with antibiotics, including the appointment of alternative drugs, in most cases of community-acquired pneumonia is inappropriate, since it has been proven that even with adequate treatment, fever can persist for 2-4 days, and leukocytosis for 4-5 days. Exceptions are cases when the patient's condition clearly and rapidly worsens: fever and intoxication increase, respiratory failure progresses, auscultatory and radiographic signs of pneumonia increase, leukocytosis and nuclear shift to the left increase. In these cases, it is necessary to conduct a thorough additional examination (repeat chest radiography, bronchoscopy with obtaining material from the lower respiratory tract, computed tomography, etc.), which help to visualize areas of developing lung tissue destruction, pleural effusion and other pathological changes that were absent during the initial examination. Microbiological examination of sputum and material obtained during bronchoscopy can reveal antibiotic-resistant or unusual pathogens, such as Mycobacterium tuberculosis, fungi, etc.

Severe course of community-acquired pneumonia and the presence of risk factors that worsen the prognosis of the disease, as a rule, require the appointment of combined treatment of pneumonia, aimed primarily at polymicrobial associations of pathogens that are often detected in these cases. The following treatment regimens are most often used:

• parenteral amoxiclav in combination with parenteral macrolides (spiramycin, clarithromycin, erythromycin);
• third generation cephalosporins (cefotaxime or ceftriaxone) in combination with parenteral macrolides;
• fourth generation cephalosporins (cefepime) in combination with macrolides;
• monotherapy with "respiratory" fluoroquinolones (intravenous levofloxacin).

The combination of cephalosporins with macrolides enhances their antipneumococcal action. Such a combination "covers" almost the entire spectrum of possible pathogens of severe community-acquired pneumonia. No less effective is monotherapy with "respiratory" parenteral fluoroquinolones with increased antipneumococcal activity. It should be borne in mind that the use of "old" fluoroquinolones (ciprofloxacin) does not have much advantage over beta-lactam antibiotics.

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

Carbapenems are ß-lactam antibiotics with an ultra-broad spectrum of action. They exhibit high activity against gram-positive and gram-negative aerobic and anaerobic microflora, including Pseudomonas aeruginosa, Acipetobacter, Enterobacter, Escherichia coli, Klebsiella, Proteus, Salmonella, Haemophilus influenzae, Enterococci, Staphylococci, Listeria, Mycobacteria, etc. Imipepem (tienam) is more effective against gram-positive pathogens. Meropepem exhibits higher activity against gram-negative pathogens, especially Enterobacter, Haemophilus influenzae, Pseudomonas aeruginosa, Acipetobacter, etc.

Carbapenems are inactive against methicillin-resistant staphylococci (S. aureus, S. epidermalis), some strains of Enterococcus faecium and intracellular pathogens. The latter circumstance emphasizes the need for a combination of carbapenems with parenteral modern macrolides.

Special attention should be paid to the treatment of abscessing pneumonia, the causative agents of which are usually mixed flora - a combination of anaerobes (usually Prevotella melaninogenlca) with aerobes (usually Staphylococcus aureus, less often - gram-negative bacteria, including Pseudomonas aeruginosa).

If a role of gram-negative microflora, including Pseudomonas aeruginosa, in the genesis of abscessing pneumonia is suspected, it is advisable to use the so-called antipseudomonas ß-lactam antibiotics (cefazidime, cefepime, imipepem, meropenem) in combination with parenteral macrolides and ciprofloxacin. In the treatment of abscessing pneumonia, combinations of an antianaerobic antibiotic (metronidazole) with drugs that have an antistaphylococcal effect (first-generation cephalosporins) are often used. Monotherapy with parenteral fluoroquinolones of the third and fourth generations is also effective. The use of antibiotics in abscessing pneumonia should be only parenteral and in most cases continue for at least 6-8 weeks.

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

Average duration of antibiotic treatment depending on the causative agent of pneumonia (according to Yu.K. Novikov)

Exciter	Duration of therapy
Pneumococcus	3 days after temperature normalization (at least 5-7 days)
Enterobacteria and Pseudomonas aeruginosa	21-42 days
Staphylococcus	21 days
Pneumocystis	14-21 days
Legionella	21 days
Pneumonia complicated by abscess formation	42-56 days

The most reliable guidelines for discontinuing antibiotics, in addition to the positive dynamics of the clinical picture of the disease, are the normalization of the X-ray picture, hemogram and sputum. It should be remembered that in most patients with pneumococcal pneumonia, complete "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, complete reverse development of pneumonic infiltration within 8 weeks is observed only in 70% of patients, and in the remaining patients - only by 14-18 weeks. The timing of X-ray recovery from community-acquired pneumonia is most affected by the prevalence of pneumonic infiltration, the nature of the pathogen and the age of the patients.

Slowly resolving (protracted) pneumonia is characterized by slow reverse development of radiographic changes (reduction in the size of pneumonic infiltration by less than 50% over 4 weeks). Protracted pneumonia should not be confused with cases of the disease that are resistant to the treatment of pneumonia. The main risk factors for protracted pneumonia are:

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

Choice of antibiotic for empirical therapy of hospital-acquired pneumonia.

Hospital (nosocomial) pneumonia is known to have the most severe course and high mortality, reaching an average of 10-20%, and in case of infection with Pseudomonas aeruginosa - 70-80%. Let us recall that the main causative agents of nosocomial pneumonia are:

• pneumococcus {Streptococcus pneumoniae);
• Staphylococcus aureus;
• Klebsiella pneumoniae;
• Escherichia coli;
• proteus (Proteus vulgaris);
• Pseudomonas aeruginosa;
• Legionella (Legionella pneumophila)]
• anaerobic bacteria (Fusohacterium spp., Bacteroides spp., Peptostreptococcus spp.)

Thus, among the pathogens of hospital-acquired pneumonia, the proportion of gram-negative microflora, staphylococcus and anaerobic bacteria is very high. Hospital pneumonia not associated with the use of intubation or ICL. The most common pathogens of hospital pneumonia, the genesis of which is not associated with the use of an endotracheal tube or artificial ventilation, are Haemophilus influenzae, Klebsiella, gram-negative enterococci, pneumococci and Staphylococcus aureus. In these cases, empirical treatment of moderate pneumonia begins with parenteral administration of the following antibacterial agents:

• "protected" aminopenicillins (amoxiclav, ampicillin/sulbactam);
• cephalosporins of II-IV generations (cefuroxime, cefotaxime, ceftriaxone, cefpirome, cefepime);
• "respiratory" fluoroquinolones (levofloxacin).

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

• a combination of “protected” aminopenicillins (amoxiclav, ampicillin/sulbactam) with aminoglycosides of the second and third generations (amikacin, gentamicin);
• a combination of cephalosporins of the II-IV generations (cefuroxime, cefotaxime, ceftriaxone, cefpirome, cefepime) with amikacin or gentamicin;
• a combination of “protected” ureidopenicillins (anti-pseudomonas penicillins) with aminoglycosides of the second and third generations;
• a combination of "respiratory" fluoroquinolones (levofloxacin) with aminoglycosides of the second and third generations.

In all the above schemes, the combination antimicrobial treatment of pneumonia includes aminoglycosides of the second and third generations. This is due to the fact that modern aminoglycosides (gentamicin, amikacin, etc.) are effective in treating severe infections. Aminoglycosides are highly active against some gram-positive (staphylococci and / faecalis) and most gram-negative pathogens, including the enterococci family (E. coli, Klebsiella, Proteus, Enterobacter, etc.). Gentamicin and amikacin are highly active against Haemophilus influenzae, mycoplasma, and Pseudomonas aeruginosa. Therefore, the main indication for their use is hospital pneumonia, while in the case of community-acquired pneumonia of mild to moderate severity, their use is inappropriate.

It should be emphasized that amikacin has a somewhat broader spectrum of action than classic gentamicin. Gentamicin is prescribed at a dose of 1.0-2.5 mg/h every 8-12 hours, and amikacin - 500 mg every 8-12 hours.

If there is no effect, monotherapy with carbapepems is indicated. Their combination with aminoglycosides of the second and third generations is possible.

If the probability of anaerobic infection is increased in patients with hospital pneumonia, a combination of second- and third-generation cephalosporins with modern macrolides or a combination of aminoglycosides with ciprofloxacin or "respiratory" fluoroquinolones is advisable. A combination of a broad-spectrum antibiotic with metronidazole is also possible.

For example, in patients with OHMC, patients after thoracoabdominal operations or with a nasogastric tube, when the main pathogenetic factor in the development of iosocomial pneumonia is aspiration of oropharyngeal microflora, the causative agents 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, second- and third-generation cephalosporins, carbapenems, and a combination of metronidazole with fluoroquinolones are used.

In patients with diabetes mellitus, chronic alcoholism, in whom pneumonia is most often caused by gram-negative flora (Klebsiella, Haemophilus influenzae, Legionella, etc.), the drugs of choice are:

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

Hospital-acquired pneumonias that develop in patients on mechanical ventilation, ventilator-associated pneumonias (VAP), are characterized by a particularly severe course and high mortality. The causative agents of early VAP are most often pneumococci, Haemophilus influenzae, Staphylococcus aureus and anaerobic bacteria. The causative agents 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 antipseudomonal activity:

• combinations of antipseudomonal cephalosporin (ceftazidime) with third-generation aminoglycosides (amikacin);
• combinations of ceftazidime with “respiratory” fluoroquinolones;
• a combination of "protected" antipseudomonal ureidopenicillins (ticarcillin/clavulanic acid, piperacillin/tazobactam) with amikacin;
• monotherapy for IV generation cephalosporniomas (cefepime);
• monotherapy with carbanenems (imipepem, meropepem);
• combinations: ceftazidime, cefepime, meropepem or imipepem
• + second generation fluoroquinolones (ciprofloxacin)
• + modern macrolides.

Staphylococcal destructive pneumonia. If staphylococcal pneumonia is suspected, the following parenteral etiotropic treatment regimens may be effective:

• oxacillin in maximum permissible doses (do not use "ampiox"!);
• "protected" aminopenicillins (amoxiclav, ampicillin/sulbactam);
• cephalosporins of the first, second and fourth generations (cefazolin, cefuroxime, cefepime); cephalosporins of the third generation (cefotaxime, ceftriaxone, ceftazidime, etc.) are not effective against staphylococcal infection;
• carbapepems;
• lincosamides (clindamycin);
• fusidic acid;
• "respiratory" fluoroquinolones.

Combination treatment of pneumonia is also recommended:

• combination of beta-lactams with third-generation aminoglycosides (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 treatment is ineffective, it is advisable to use the glycopeptide vancomycin, which is active against all, including methicillin-resistant and oxacillin-resistant staphylococci. Effective combinations of vancomycin with beta-lactams, aminoglycosides of the second and third generations, rifampicin or levofloxacin are possible.

When the etiology of pneumonia is confirmed microbiologically, etioprophylactic therapy is adjusted taking into account the determination of individual sensitivity to antibiotics. The table provides an approximate list of antibacterial drugs that are active against individual pathogens of pneumonia. Low-effective and ineffective antimicrobial drugs are highlighted separately.

Activity of antibacterial drugs against the most likely causative agents of pneumonia

Haemophilus influenzae

Pseudomonas aeruginosa

Antibacterial drugs with high activity	Ineffective and low-efficiency drugs
Pneumococci
Aminopenicillins (amoxicillin, amoxiclav, ampicillin/sulbactam, etc.)	"Old" fluoroquinolones (ofloxacin, ciprofloxacin)
Modern macrolides (clarithromycin, roxithromycin, azithromycin, spiramycin)	Aminoglycosides (gentamicin, amikacin)
Cephalosporins of the 1st-4th generations (cefazolin, cefuroxime, cefotaxime, ceftriaxone, cefazidime, cefelim, etc.)
"Respiratory" fluoroquinolones (levofloxacin, moxifloxacin)
Carbapenems (imipenem, meropenem)
Vancomycin
"Protected" ureidopenicillins (picarcillin/clavulanate, piperacillin/tazobactam)
Lincosamides (clindamycin, lincomycin)
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)
Moraxella
Aminopenicillins (amoxicillin, amoxiclav, ampicillin/sulbactam)	Lincosamides
Second generation cephalosporins (cefuroxime, etc.)
Fluoroquinolones
Macrolides
Staphylococci (golden, epidermal, etc.)
Oxacillin	Oral cephalosporins of the third generation (cefotaxime, ceftriaxone, etc.)
"Protected" aminopenicillins (amoxiclav, ampicillin/sulbactam, etc.)	Amoxicillin ('unprotected' aminopenicillin)
Aminoglycosides of the II and III generations (gentamicin, amikacin)
Cephalosporins of the first, second and fourth generations
Fluoroquinolones
Macrolides
Gpicopeptides (vancomycin)
Co-trimoxazole
Lincosamides (lincomycin, clarithromycin)
Doxycycline
Carbapenems
Fusidic acid
Methicillin-resistant staphylococci
Glycoleptides (vancomycin)	All ß-lactams
Fluoroquinones III-IV generations	Lincosamides
Fusidic acid
Co-trimoxazole
Intracellular pathogens (mycoplasma, chlamydia, legionella)
Macrolides (clarithromycin, roxithromycin, azithromycin, spiramycin)	Aminopenicillins
Doxycycline	Cephalosporins 1-4 generations
"New" fluoroquinolones	Ciprofloxacin
Rifampicin	Aminoglycosides
	Ureidopenicillins
Gram-negative enterococci (intestinal group)
Cephalosporins of the III and IV generation (ceftriaxone, cefotaxime, cefepime)	"Unprotected" aminopenicillins
Carbapenems	Macrolides
Fluoroquinolones	Cephalosporins 1 and II pens
"Protected" aminopenicillins (amoxiclav, ampicipin/supbactam, etc.)	Lincosamides
Co-trimoxazole
Aminoglycosides of the II and III generations (amikacin, gentamicin)
Anaerobes
Cephalosporins III-IV generations (cefotaxime, cefepime)	Aminoglycosides 11-111 generations
Macrolides
Ureidopenicillins
Lincosamides
Ceftazidime
Aminoglycosides (amikacin)
Cephalosporins IV penny (cefepime)
Carbapenems (imipenem, meropenem)
Fluoroquinolones
"Protected" (antipseudomonas) ureidopenicillins (ticarcillin/clavulanate, piperacillin/tazobactam)

It should 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, the antibacterial effect, potential toxicity and cost of treatment are minimized.

[ 1 ], [ 2 ]

Improving the drainage function of the bronchi

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

• a significant volume of viscous purulent exudate coming from the alveoli into the bronchi;
• inflammatory edema of the bronchial mucosa draining the site of inflammation of the lung tissue;
• damage to the ciliated epithelium of the bronchial mucosa and disruption of the mucociliary transport mechanism;
• an increase in the production of bronchial secretions caused by the involvement of the bronchial mucosa in the inflammatory process (hypercrinia);
• a significant increase in the viscosity of sputum (dyscrinia);
• increased tone of the smooth muscles of the small bronchi and a tendency to bronchospasm, which makes it even more difficult to separate sputum.

Thus, bronchial obstruction in patients with pneumonia is associated not only with the natural drainage of the inflammation site and the entry of viscous alveolar exudate into the bronchi, but also with the frequent involvement of the bronchi themselves in the inflammatory process. This mechanism is of particular importance in patients with bronchopneumonia of various origins, 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 local, including immunological, defense processes, re-seedling of the airways and prevents healing of the inflammatory focus in the lung tissue and restoration of pulmonary ventilation. Decreased bronchial patency contributes to the aggravation of ventilation-perfusion relations in the lungs and the progression of respiratory failure. Therefore, complex treatment of patients with pneumonia includes the mandatory administration of drugs with expectorant, mucolytic and bronchodilator effects.

It is known that the sputum present in the lumen of the bronchi in patients with pneumonia consists of two layers: the upper, more viscous and dense (gel), lying above the cilia, and the lower liquid layer (sol), in which the cilia seem to float and contract. The gel consists of glycoprotein macromolecules linked together by disulfide and hydrogen bonds, which gives it viscous and elastic properties. With a decrease in the water content in the gel, the viscosity of the sputum increases and the movement of bronchial secretions towards the oropharynx slows down or even stops. The speed of such movement becomes even slower if the layer of the liquid layer (sol), which to a certain extent prevents the adhesion of sputum to the walls of the bronchi, becomes thinner. As a result, mucous and mucopurulent plugs form in the lumen of the small bronchi, which are removed with great difficulty only by a strong expiratory flow of air during attacks of excruciating, hacking cough.

Thus, the ability to remove sputum from the respiratory tract without hindrance is primarily determined by its rheological properties, the water content in both phases of bronchial secretion (gel and sol), as well as the intensity and coordination of the activity of the cilia of the ciliated epithelium. The use of mucolytic and mucoregulatory agents is aimed at restoring the ratio of sol and gel, liquefying sputum, rehydrating it, and stimulating the activity of the cilia of the ciliated epithelium.

Pneumonia: Treatment with Non-Drug Methods

Non-drug methods of improving the drainage function of the bronchi are a mandatory component of the complex treatment of patients with pneumonia.

Drinking plenty of warm fluids (alkaline mineral waters, milk with a small amount of sodium bicarbonate, honey, etc.) helps to increase the water content in the gel layer and, accordingly, reduce the viscosity of the sputum. In addition, natural rehydration of the bronchial contents leads to some increase in the thickness of the liquid layer of the sol, which facilitates the movement of the cilia and the movement of sputum in the lumen of the bronchi.

Chest massage (percussion, vibration, vacuum) is also used to improve the drainage function of the bronchi. Percussion massage is performed with the edge of the palm, tapping the patient's chest wall at a frequency of 40-60 per minute. Depending on the patient's condition, the massage lasts 10-20 minutes in cycles of 1-2 minutes, after which a pause is made, during which the patient is asked to cough.

Vibration massage is performed using special vibration massagers with adjustable frequency and vibration amplitude.

Vacuum (cupping) massage of the chest has not lost its significance, which combines elements of mechanical and reflex irritation, improvement of pulmonary blood flow and a kind of autohemotherapy due to the formation of interstitial hemorrhages. At the same time, drainage of the lungs is facilitated and the severity of inflammatory changes in the lung tissue is reduced.

It should be remembered that any type of chest massage is contraindicated in the event of a risk of pulmonary hemorrhage, abscess formation, chest trauma or suspicion of a tumor process in the lungs.

Breathing exercises are an effective means of restoring the drainage function of the bronchi. Deep breathing movements stimulate the cough reflex, and breathing with the creation of artificial resistance during exhalation (through closed lips, special flutters or other devices) prevents expiratory collapse of small bronchi and the formation of microatelectasis.

Breathing exercises should be performed with caution if there is a risk of spontaneous pneumothorax.

Expectorants

Expectorants in the narrow sense of the word are a group of medicinal substances that affect the rheological properties of sputum and facilitate its discharge. All expectorants are conventionally divided into two groups:

1. Expectorant agents:
   • reflex action drugs;
   • resorptive drugs.
2. Mucolytic and mucoregulatory agents.

Expectorant agents increase the activity of the ciliated epithelium and the peristaltic movements of the bronchioles, facilitating the movement of sputum to the upper respiratory tract. In addition, under the influence of these drugs, there is an increase in the secretion of the bronchial glands and some decrease in the viscosity of sputum.

Expectorants with an emetic-reflex action (thermopsis herb, ipecac root, terpin hydrate, lycopersicum root, etc.) when taken orally have a mild irritating effect on the receptors of the gastric mucosa, which leads to an increase in the activity of the vagus nerve centers. As a result, peristaltic contractions of the smooth muscles of the bronchi, secretion of the bronchial glands are enhanced, and the amount of liquid bronchial secretion formed increases. A decrease in the viscosity of sputum is accompanied by an easier discharge.

One of the effects of the reflex action of these drugs on the vagus nerve tone is nausea and vomiting. Therefore, the listed drugs should be taken in small, individually selected doses, at least 5-6 times a day.

Expectorants with resorptive action (potassium iodide, etc.) also increase the secretion of the bronchial glands, but not by the reflex, but by their secretion by the mucous membrane of the respiratory tract after oral administration. Stimulation of the secretion of the bronchial glands is accompanied by some liquefaction of sputum and improvement of its discharge.

Mucolytics and mucoregulatory drugs are prescribed primarily to improve the rheological properties of sputum, facilitating its separation. Currently, the most effective mucolytics are considered to be acetylcysteine, mesiu, bromhexine and ambroxol.

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

Acetylcysteine is used in patients with various respiratory diseases accompanied by the separation of purulent sputum of increased viscosity (acute and chronic bronchitis, pneumonia, bronchiectasis, cystic fibrosis, etc.). Acetylcysteine is used in the form of inhalations of 2-5 ml of a 20% solution, usually with an equivalent amount of 2% sodium bicarbonate solution, sometimes mixed with a standard dose of a bronchodilator. The duration of inhalations is 15-20 minutes. With the inhalation method of administration, one should be wary of bropchorea, which can have undesirable consequences if the patient has a reduced cough reflex (I.P. Zamotayev).

In severely ill patients with respiratory failure in intensive care, acetylcysteine can be used in the form of intratracheal instillations of 1 ml of a 10% solution, as well as for bronchial lavage during therapeutic bronchoscopy.

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

Acetylcysteine is taken orally in the form of capsules or tablets, 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 (mistabron) has a mucolytic effect similar to acetylcysteine, thinning mucus and facilitating its separation.

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

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

When taken orally, the expectorant effect in adults occurs 24-48 hours after the start of treatment and is achieved with the use of 8-16 mg of bromhexine 3 times a day. In mild cases, the daily dose can be reduced to 8 mg 3 times a day, and in children under 6 years of age - to 4 mg 3 times a day.

The drug is generally well tolerated. Minor stomach discomfort is occasionally possible.

Ambroxol hydrochloride (Lazolvan) is an active metabolite of bromhexine. In its pharmacological properties and mechanism of action, it differs little from bromhexine. Ambroxol stimulates the formation of tracheobronchial secretion of low viscosity due to the destruction of mucopolysaccharides in sputum. The drug improves mucociliary transport by stimulating the activity of the ciliary system. An important property of Lazolvan is to stimulate the synthesis of surfactant.

Adults are prescribed the drug at 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.

[ 3 ]

Bronchodilators

In some patients with pneumonia, especially in patients with severe disease or in individuals prone to bronchospastic syndrome, it is advisable to use bronchodilators. Inhalation forms of beta2-adrenergic stimulants (berotek, berodual, etc.), M-anticholinergics (atrovent) and intravenous infusions of 2.4% euphyllin solution are preferable.

[ 4 ], [ 5 ], [ 6 ], [ 7 ], [ 8 ], [ 9 ]

Detoxification therapy

In severe cases of pneumonia, detoxification therapy is carried out. Saline solutions are administered intravenously by drip (for example, isotonic sodium solution up 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 cardiovascular pathology and heart failure, fluids should be administered with great caution, preferably under control of PAWP and CVP.

[ 10 ], [ 11 ], [ 12 ]

Heparin therapy

One of the effective means of treating pneumonia is heparin. It is a mucopolysaccharide with a high sulfur content, has a significant negative charge and is capable of interacting with various basic and amphoteric substances. Heparin's ability to complex is responsible for the diversity of its pharmacological properties.

Positively influencing the blood coagulation system, heparin improves blood flow in the microvascular bed of the lungs, reducing swelling of the bronchial mucosa and improving their drainage function. Heparin affects the rheological properties of sputum, thus providing a mucolytic effect. At the same time, it affects the reversible component of bronchial obstruction due to anticomplementary binding of calcium ions, stabilization of lysosomal membranes, and blockade of inositol triphosphate receptors.

In case of pneumonia complications with respiratory failure, heparin has antihypoxic, antiserotonin, antialdosterone and diuretic effects.

Finally, recent studies have shown the effect of heparin on the active inflammatory process. This effect is explained by the inhibition of neutrophil chemotaxis, increased macrophage activity, inactivation of histamine and serotonin, increased antibacterial activity of chemotherapeutic agents and decreased toxic effects.

In severe cases of pneumonia, heparin is prescribed at 5,000-10,000 U 4 times a day subcutaneously. It is even better to use modern low-molecular heparins.

Immunocorrective and immunoreplacement treatment of pneumonia

Pneumonia treatment involves the administration of hyperimmune plasma intravenously (4-6 ml/kg) and immunoglobulin 3 biodoses intramuscularly daily during the first 7-10 days of the disease. Immunomodulators (methyluracil, sodium nucleinate, T-activin, thymalin, decaris, etc.) are prescribed for the entire period of the disease. Intravenous drip infusions of native and/or fresh frozen plasma (1000-2000 ml over 3 days) or intravenous immunoglobulin 6-10 g per day once are possible.