SM-Clinic pulmonologist spoke about bacterial pneumonia in adults

According to statistics, bacterial pneumonia affects an average of about 1000 patients per 100 thousand population. This form of the disease occurs especially often in elderly people over 75 years of age or those who suffer from chronic pathologies ALENA PARETSKAYA
Pathophysiologist, immunologist, WHO expert ELENA ZARYANOVA Candidate of Medical Sciences, pulmonologist of the highest category, somnologist "SM-Clinic" »
Bacterial pneumonia is a common complication in patients treated in hospitals and clinics. In recent years, there has been an increase in severe forms that lead to death.

Causes of bacterial pneumonia in adults

Bacterial pneumonia is most often caused by bacteria, which are considered part of the microflora of the respiratory tract.
These microorganisms belong to the category of opportunistic pathogens. If the body is healthy, not weakened, the immune system is working properly, bacteria do not harm in any way. But during stress, operations, exacerbation of chronic diseases, severe acute respiratory viral infections, bacteria can become dangerous. There are two types of bacterial pneumonia - community-acquired and nosocomial. They vary greatly in the type of bacteria that causes inflammation.

In community-acquired pneumonia, the inflammatory process is usually provoked by pneumococcus, Haemophilus influenzae or streptococcus.

Nosocomial pneumonia is caused by particularly aggressive bacteria that are resistant to many antibiotics. These pathogens usually live in clinics - Staphylococcus aureus, Pseudomonas aeruginosa, Enterobacteriaceae and some others. Often such pneumonia occurs in people who undergo mechanical ventilation.

If patients suffer from immunodeficiency, pneumonia can be caused by Legionella, Mycoplasma, Pneumococcus, Haemophilus influenzae and Pneumocystis.

Bacteria penetrate into the lungs from the air, with the blood flow from inflammatory foci in the body or with the lymph flow, directly, with chest wounds. Risk factors that increase the likelihood of pneumonia are:

• frequent ARVI and influenza;
• bad habits (they weaken the immune system);
• constant stress and overwork;
• deficiency of vitamins and minerals;
• age over 65 - 70 years;
• living in areas with air pollution.

Pneumonia is likely in people with COPD, heart problems, diabetics, against the background of sinusitis, after operations and injuries.

Macrolides and their importance in the treatment of community-acquired pneumonia of various etiologies

I.V. LESCHENKO

, Doctor of Medical Sciences, Professor,
Z.D.
BOBYLEVA , Doctor of Medical Sciences,
Ural State Medical University of the Ministry of Health of Russia, Yekaterinburg
The success of antibiotic therapy depends on the correctly chosen antibiotic, the timeliness of its administration, the state of the macroorganism (patient) and microorganism (resistance of the bacterial pathogen to the drug), bioavailability and bioequivalence . The latter applies to generic drugs, which are so widely represented on the domestic pharmacological market.

Macrolide antibiotics occupy one of the leading places in the antibacterial therapy of community-acquired pneumonia (CAP) of various etiologies. According to their pharmacokinetic characteristics, macrolides are classified as tissue antibiotics. Features of the pharmacokinetics of the antibiotics most often prescribed in the treatment of CAP (beta-lactams and macrolides) include the ability of macrolides to be more concentrated at the site of infection than in the blood plasma ( Table 1

) [1].

One of the macrolide antibiotics widely represented on the pharmacological market is azithromycin.
It has been proven that azithromycin can act not only bacteriostatically, like other macrolides, but also, unlike antibiotics of this class, bactericidal. The bactericidal effect is achieved due to the ability of azithromycin to create very large intracellular concentrations against many pathogens located inside cells [2]. Already on the first day of administration, azithromycin creates concentrations at the site of infection, mainly in alveolar macrophages, many times higher than the minimum inhibitory concentration (MIC) ( Fig. 1, 2

) [3].

A feature of azithromycin is the ability to create not only high concentrations at the site of infection, but also to provide a drug concentration several times higher than the MIC after a 3-day dose for 7 days, which practically corresponds to 10 days of antibacterial therapy [4].

Azithromycin exhibits a post-antibiotic effect and post-antibiotic sub-MIC, i.e., an effect on microorganisms after exposure to subinhibitory concentrations of the antibiotic not only against Streptococcus pneumoniae, but also against Streptococcus pyogenes, Haemophilus influenzae, Legionella pneumophila. Azithromycin is the only macrolide with natural activity against Haemophilus Influenzae, and it is superior to clarithromycin in the duration of post-antibiotic effect in Haemophilus Influenzae and Legionella pneumophila [5].

Azithromycin and other macrolides are known to have immunomodulatory and anti-inflammatory effects [6]. The uniqueness of azithromycin not only as an antibiotic with antibacterial but also immunomodulatory properties may be associated with the special structure of the molecule. According to its chemical structure, azithromycin is a 15-membered macrolide and its fundamental difference from the “classical” 14-membered macrolides is that its molecule contains a nitrogen atom. In an experiment on healthy volunteers who took azithromycin at a dose of 500 mg per day for 3 days, a biphasic immunomodulatory effect of the drug was demonstrated [7]. The early immunomodulatory effect of azithromycin manifests itself in enhancing the body's natural immune response to infection, while the late (delayed) anti-inflammatory effect of the antibiotic helps resolve inflammation. Macrolides, and in particular azithromycin, increase the activity of T-killers. They accumulate in neutrophils, monocytes and macrophages, enhance their migration to the site of inflammation, increase phagocytic activity, and stimulate the secretion of interleukins IL-1, IL-2, IL-4. In addition, azithromycin accelerates neutrophil apoptosis after pathogen eradication. The anti-inflammatory effect of macrolides is associated with a decrease in airway hyperreactivity, which usually accompanies bronchopulmonary infections [6, 8]. The mechanisms of the immunomodulatory action of azithromycin are shown in Figure 3

.

An important condition when choosing an antibiotic is the expected frequency and severity of adverse events. Azithromycin, like macrolides in general, is one of the least toxic antibiotics [9]. More often than other adverse events when using it, adverse reactions from the gastrointestinal tract are observed (<12%). They are usually mild and, as a rule, do not require discontinuation of the drug. With parenteral use of azithromycin, pain at the site of venipuncture and post-infusion phlebitis are observed, which are recorded in 6.5 and 3% of cases, respectively [10]. Adverse events requiring discontinuation of the drug are significantly less common (<3%): rash, persistent diarrhea, nausea and vomiting, laboratory signs of cytolysis and cholestasis, abdominal pain and drowsiness. Allergic reactions are also extremely rare [9]. A characteristic feature of allergic manifestations when using azithromycin is the resumption of allergic reactions in the long term after the cessation of symptomatic therapy, which requires 3-4 weeks of observation of the patient. Slightly more common macrolide intolerance

observed when antibiotics are prescribed in high doses. However, even with intravenous administration of 4.0 g of azithromycin solution, the incidence of abdominal pain and nausea does not exceed 0.5%.

One of the important aspects of the safety of antibiotics is the determination of their cardiotoxicity associated with the effect on the conduction system of the heart. The results of the studies convincingly indicate the cardiovascular safety of macrolides. The incidence of life-threatening arrhythmias with their use is extremely low and does not exceed 1 case per 100 thousand prescriptions [11]. In an experiment (Poluzzi E. et al.) and in a study by H. Svanstrom et al. It was found that among macrolides, azithromycin has the least arrhythmogenic potential [12, 13].

As for hepatotoxicity, compared to many antibiotics, azithromycin has the lowest frequency of hepatotoxic reactions, including compared to other macrolides ( Fig. 4

) [14, 15].

In this regard, the widespread myths about the hepato- and cardiotoxicity of macrolides (azithromycin) are unacceptable, since this can lead to excessive consumption of the remaining classes of antibiotics and an increase in the resistance of microorganisms [16].

According to national and international recommendations for CAP, azithromycin is used for the treatment of non-severe CAP both as monotherapy (group 1 of patients with CAP) and as combination antibacterial therapy (ABT) (group 2) [17, 18].

Indications for prescribing macrolides for mild cases of CAP are:

• suspicion of an “atypical” etiology of the disease (Mycoplasma pneumoniae, Chlamydia pneumoniae, Legionella spp.); • allergy to β-lactams; • lack of effect when treated with β-lactams. Based on national recommendations for community-acquired pneumonia in adults, we have developed an algorithm for the management of patients with CAP in an outpatient setting, presented in Tables 2 and 3

[19].

Combined antibacterial therapy for CAP, including macrolides, is used for non-severe CAP in patients with concomitant pathologies or when patients indicate an appointment within the last 3 months. antibacterial drugs? 2 days. Macrolides are most often used in patients with CAP who require hospitalization, including in the intensive care unit [17, 18]. In this aspect, macrolides should be considered not only as a means of “covering” against intracellular pathogens, but also as an antibiotic with potentiation of the effect against pneumococcus [20]. Table 4

Antibacterial treatment regimens for CAP in hospitalized patients of varying severity are presented [17, 18].

In practice, the most common combination antibacterial therapy for severe pneumonia is a combination of third-generation cephalosporins and macrolides, and the prescription of a combination of these 2 classes of antibiotics should be used as initial therapy, only in this case the duration of hospitalization is significantly reduced [21]. Answering the question: “Which macrolide should be preferred when combined with third-generation cephalosporins?”, we present the results of a prospective comparative study that shows the advantage of combined therapy with ceftriaxone and azithromycin compared with treatment with ceftriaxone and clarithromycin (Fig. 5) [22].

The importance of macrolides in the treatment of patients with severe pneumonia is evidenced by the results of a systematic review of 28 observational studies of about 10 thousand patients with severe CAP, which showed that the use of macrolides in combination therapy with beta-lactam antibiotics compared with monotherapy led to a decrease in mortality (p = 0.02) [23]. A comparative assessment of mortality rates in patients with severe CAP who received beta-lactams in combination with macrolides and beta-lactams in combination with respiratory fluoroquinolones (RFQs) is noteworthy. It turned out that there was no significant difference between these antibacterial drug regimens (20% beta-lactam + macrolide and 23% beta-lactam + RPC; odds ratio (OR) 0.83, 95% confidence interval (CI) 0.67-1.03, p = 0.09).

Emphasizing the importance of macrolides, and in particular azithromycin, in the treatment of patients with pneumonia, it is necessary to note the importance of this antibiotic in legionella pneumonia (Legionnaires' disease). An epidemic outbreak of legionellosis was registered in the city of Verkhnyaya Pyshma, Sverdlovsk region in July–August 2007 [24]. The etiological diagnosis of legionella pneumonia was established in 61 people, of which in 15 patients (9.1%) the course of the disease was defined as mild (without systemic inflammatory response syndrome) and in 46 (90.9%) - severe, in accordance with the recommendations of the American Society Infectious Diseases Society of America / American Thoracic Society - IDSA / ATS [25]. The mortality rate was 6.6%.

Azithromycin is one of the drugs of choice for Legionnaires' disease. The antibiotic was prescribed as monotherapy for 10 days, 500 mg once, for mild manifestations of Legionella infection orally in 10 cases out of 15 (66.7%) and in 17 patients out of 46 (37.0%) with severe Legionella pneumonia according to the principle of step-down therapy .

As a result of treatment with azithromycin, positive clinical, laboratory and radiological dynamics were achieved in patients with severe Legionella pneumonia. There were no deaths among those treated with azithromycin.

A significant increase in the level of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the peripheral blood after antibiotic therapy with an unusually long course of azithromycin in patients with severe Legionella CAP without concomitant liver diseases was noted [26]. The results obtained correspond with literature data indicating a transient increase in transaminases as a side effect of antibiotics [27-29]. Hepatocyte cytolysis syndrome was transient in nature without signs of liver failure, which was confirmed by normalization of transaminase levels after 12 months. after patients are discharged from the hospital. A comparative assessment of AST and ALT indicators over time in patients with severe Legionella pneumonia treated with azithromycin is presented in Table 5

.

Another confirmation of the need for azithromycin is the results we obtained in the treatment of patients with severe pneumonia during an epidemic outbreak of influenza A (H1N1) pdm09. Of the 250 patients under observation, 104 (41.6%) were treated with a simultaneously prescribed combination of third-generation cephalosporins and azithromycin [30]. Most of them (64 patients) were diagnosed with severe pneumonia due to influenza A (H1N1) pdm09. Parenteral use of third generation cephalosporins and azithromycin at a dose of 500 mg for 3-5 days followed by the administration of inhibitor-protected penicillins provided regression of clinical symptoms and radiological changes in the respiratory system after 16.3 days 95% CI [15.2-17.3] .

Thus, at present, macrolides have one of the leading places in the antibacterial therapy of community-acquired pneumonia, regardless of their etiology and severity of the disease, and azithromycin is one of the main representatives of this class of antibiotics.
References 1. Gordon EM, Blumer JL. Pharmacokinetics and pharmacodynamics: azithromycin concentrates in tissues. Pediatr. Infect. Dis. J., 2004. 23(suppl 2): ​​S102-S107. 2. Odenholt-Tornqvist I, Lowdin E, Cars 0. Postantibiotic effects and postantibiotic sub-MIC effects of roxithromycin, clarithromycin, and azithromycin on respiratory tract pathogens. Antimicrob. Agents. Chemother., 1995. 39: 221-226. 3. Baldwin DR, Wise R, Andrews JM et al. Azithoromycin concentrations at the sites of pulmonary infection. Eur. Respira. J., 1990. 3: 886-890. 4. Lode H. Azithromycin in the Treatment of Community-Acquired Pneumonia in Adults. Cambrige Medical Publications, 2002. 24. 5. Fang GD, Stout JE, Yu VL. Comparison of intracellular postantibiotic effect of azithromycin and clarithromycin vs. erythromycin against Legionella pneumophila serogroup 1. In: The 36th International Conference on Antimicrobial Agents and Chemotherapy, New Orleans, 1996. abstr. A91. 6. Lukyanov S.V. Clinical pharmacology of macrolides. Consilium medicum, 2004. 10: 769–773. 7. Culi O, Erakovi V, Cepelak I et al. Azithromycin modulates neutrophil function and circulatig inflammatory mediators in healthy human subjects. Eur. J. Pharmacol., 2002. 450 (3): 277-89. 8. Strachunsky L.S., Kozlov S.N. Macrolides in modern clinical practice. 9. Stetsyuk O.U., Andreeva I.V., Kolosov A.V., Kozlov R.S. Safety and acceptability of antibiotics in outpatient practice. KMAH, 2011. 13. 1: 67-84. 10. Plouffe J, Schwartz D, Kolokathis A et al. Clinical efficacy of intravenous followed by oral azithromycin monotherapy in hospitalized patients with community-acquired pneumonia. The Azithromycin Intravenous Clinical Trials Group. Antimicrob. Agents Chemother., 2000. 44 (7): 1796-802. 11. Mosholder AD, Alexander JJ, Smith H et al Cardiovascular risks with azithromycin and other antibacterial drugs. N.Engl. J. Med., 2013. 368: 1665-1668. 12. Poluzzi E, Raschi E, Motola D et al. Antimicrobials and the risk of torsades de pointes: the contribution from data mining of the US FDA Adverse Event Reporting System. Drug. Saf., 2010. 33(4): 303-314. 13. Svanstrom H, Pasternak B, Hviid A. Use of Azithromycin and Death from Cardiovascular Causes. N.Engl. J. Med., 2013. 368: 1704-1712. 14. Sinopalnikov A.I., Andreeva I.V., Stetsyuk O.U. Safety of macrolide antibiotics: a critical review. Clinical Medicine, 2012. 3: 23-30. 15. Andrade RJ, Tulkens PM. Hepatic safety of antibiotics used in primary care. J. Antimicrob. Chemother., 2011. 66(7): 1431-1446. 16. Kozlov R.S. et al. Antimicrobial Therapeutics Summit Resolution. Consilium Medicum, 2014. 16 (11): 33-36. 17. Chuchalin A.G., Sinopalnikov A.I., Kozlov R.S., Tyurin I.E. Rachina S.A. Community-acquired pneumonia in adults: practical recommendations for diagnosis, treatment and prevention. A manual for doctors. M., 2010: 82 p. 18. Guidelines for the management of adult lower respiratory tract infections/Guest Editor: Didier Raoult. The official publication of the European Respiratory Society and European Society for Clinical Microbiology and Infectious Diseases. Clin Microbiol Infect, 2011. 17(Suppl. 6): 1-24. 19. Leshchenko I.V., Bobyleva Z.D., Trifanova N.M. and others. Clinical and organizational algorithm for the management of patients with community-acquired pneumonia. Guidelines. Under the general editorship. A.G. Chuchalina. 2nd ed., revised. and additional, Moscow, LLC "Elikon-Design" 2012. 70 p. 20. Girard D, Finegan SM, Dunne MW et al. Enhanced efficacy of single-dose versus multi-dose azithromycin regimens in preclinical infection models. J. Antimicrob. Chemoter, 2005. 56 (2): 65-71. 21. Stahl JE, Barza M, DesJardin J et al. Effects of macrolides as part of initial emperic therapy on length of stay in patients hospitalized with CAP. Arch. Intern. Med., 1999. 159: 2576-2580. 22. Sanchez F, Mensa J, Martinez JA et al. Is azithromycin the first-choice macrolide for treatment of community-acquired pneumonia? Clin. Infect. Dis., 2003. 36: 1239–1245. 23. Sligl WI, Asadi L, Eurich DT et al. Macrolides and Mortality in Critically Ill Patients With Community-Acquired Pneumonia: A Systematic Review and Meta-Analysis. Critical Care Medicine, 2014. 42 (2): 420–432. 24. Mikhailova D.O., Leshchenko I.V., Bobyleva Z.D. et al. The first outbreak of legionella infection in the Sverdlovsk region. Algorithm for diagnosis and treatment. Ural Medical Journal, 2007. 8: 4-10. 25. Bobyleva Z.D., Leshchenko I.V., Vinokurova A.N. Comparative analysis of clinical, laboratory and radiological data in patients with legionellosis and non-legionella pneumonia during the epidemic outbreak of legionellosis in the Sverdlovsk region. Pulmonology, 2009. 6: 45-52. 26. Bobyleva Z.D., Leshchenko I.V. Features of the clinical course and long-term results of legionella pneumonia during the epidemic outbreak of legionellosis in the Sverdlovsk region. Clinical Medicine, 2010. 4: 72-77. 27. Sherlock S. Diseases of the liver and biliary tract (translated from English). M., 1999: 386–423. 28. DeLeve LD. Mechanisms of drug-induced liver disease. N. Clin. N. Amer., 1995. 24: 787–810. 29. Schiano TD Drug-induced and toxic liver disease. Schiano TD, Black M. In: Friedman LS, Keefe EB, Maddrey WC (ed.). Handbook of Liver Disease. Churcill. Livingstone, 1998: 103-123. 30. Leshchenko I.V., Krivonogov A.V. Features of the course of pneumonia during pandemic influenza A/H1N1/09. Pulmonology, 2011. 6: 62-68.

Symptoms of bacterial pneumonia in adults

In many ways, the symptoms of pneumonia depend on what bacteria is causing them. The more aggressive the microbe, the more severe the manifestations. The most typical manifestations of bacterial pneumonia:

• a sharp increase in temperature, which is poorly controlled by antipyretic drugs;
• severe sweating, chills;
• a cough that is wet from the first days, with copious sputum (has a greenish or rusty color);
• chest pain, especially when breathing deeply;
• severe weakness with malaise;
• headache, aches in muscles and joints;
• pale, sallow skin color;
• low blood pressure, rapid pulse;
• frequent breathing, shortness of breath, wheezing when breathing.

If pneumonia is not treated, respiratory and heart failure, toxicosis and even death can develop. It is extremely rare to have atypical bacterial pneumonia, which has very few symptoms, they are mild, but the lungs are affected to a significant extent.

Diagnostics

The doctor focuses on the patient’s complaints and the data that he sees and hears. If the doctor listens to the chest with a phonendoscope, he will hear typical wheezing, changes in breathing and so-called crepitus (the noise of a lung affected by inflammation). Bacterial pneumonia can be confirmed by:

• blood tests indicating severe inflammation (leukocytosis, changes in protein levels, clotting);
• X-ray of the chest with areas of darkness where the lung is affected;
• CT scan of the lungs, if the diagnosis is not clear on a regular x-ray;
• culture of sputum for flora with identification of a specific bacteria (or several) and determination of sensitivity to antibiotics;
• saturation (oxygen saturation in the blood) less than 95%.

Additionally, if the case is complex, the doctor may order other tests.

Kinds

Depending on the degree of damage, the following types of pneumonia are distinguished:

• focal (damage to a small area of ​​lung tissue);
• segmental (damage to the entire segment of the lung);
• confluent (damage to several segments of lung tissue);
• lobar (damage to the entire lobe of the lung).

Doctors divide bilateral pneumonia into acute and chronic. The causes of the development of bilateral pneumonia have been studied in detail, which allows the successful use of suitable medications and other effective methods of treating the disease.

Modern methods of treatment

Bacterial pneumonia in mild and moderate cases can be treated at home, under the supervision of a doctor.
In severe forms - in the clinic, intensive care ward and resuscitation room. Bed rest, a light diet, and plenty of fluid intake (or intravenous administration) are indicated. The main treatment is antibiotics: the doctor selects them based on test data. Most often, penicillins, cephalosporins or macrolides are used. If these are separate forms of pneumonia, more narrowly targeted drugs are selected. Medicines are taken orally or by intramuscular injection for up to 14 days; in severe cases they are administered intravenously.

Treatment is complemented by:

• antipyretic drugs, anti-inflammatory drugs (Nurofen, Nise, Ibuklin, Rinza, Panadol);
• short course hormonal drugs;
• droppers with protein, saline solutions, vitamins and glucose;
• oxygen therapy;
• drugs for coughing up sputum (Bromhexine, ACC, Ambroxol, Fluimucil).

As the condition improves, the doctor adds breathing exercises, massages, physiotherapy, exercise therapy and subsequent rehabilitation in a sanatorium to the treatment.