Modern approaches to antibacterial therapy of hospital infections

Modern approaches to antibacterial therapy of hospital infections

In everyday practice in a hospital, a clinician has to deal with two groups of infectious diseases. The first of these includes community-acquired infections - infectious processes that arose outside the hospital and for which the patient was admitted to the hospital. The second group includes hospital-acquired (nosocomial, nosocomial) infections that developed in a patient in a hospital.

Practically important differences between these two groups of infectious diseases concern their etiological structure and antibiotic resistance of pathogens. Community-acquired infections are characterized by a limited and fairly stable composition of the most likely pathogens, depending on the localization of the infectious process. The spectrum of pathogens causing nosocomial infections is generally somewhat less predictable. Pathogens of community-acquired infections, in comparison with pathogens of hospital-acquired infections, are also characterized by a significantly lower level of antibiotic resistance. These differences are important for choosing rational empirical treatment for infections in a hospital.

In hospitals, in conditions of close contact between individual patients, as well as between patients and staff, it becomes possible to exchange strains of microorganisms. In parallel, against the background of intensive use of antibiotics, selection of antibiotic-resistant strains occurs.

As a result, a microecological situation develops in medical institutions, characterized by the dominance of certain strains of microorganisms and the predominance of antibiotic-resistant strains among them. The dominant strains in a medical institution are called hospital strains. There are no clear criteria for recognizing a particular strain as hospital-acquired. Antibiotic resistance is an important but optional feature.

When entering a hospital, the patient inevitably comes into contact with hospital strains of bacteria. At the same time, as the length of stay in a medical institution lengthens, the likelihood of replacing the patient’s own microflora with hospital microflora increases, and, accordingly, the development of infections caused by hospital microflora. It is quite difficult to accurately determine the period during which colonization of the patient’s non-sterile loci by hospital microflora occurs, since this is determined by many factors (age, stay in intensive care units, severity of concomitant pathology, antibiotic therapy or the use of antibiotics for prophylactic purposes). Accordingly, it is also difficult to establish the time interval when an emerging infection should be considered hospital-acquired. In most cases, an infection is considered as such when clinical symptoms appear 48 hours or more after the patient’s hospitalization.

It is difficult to assess the frequency of hospital infections in our country due to the lack of official registration of these diseases. According to international multicenter studies, the average incidence of nosocomial infections in medical institutions is 5–10% [1–3], and in intensive care units (ICU) reaches 25–49% [4–6]. A significant part of the studies devoted to the etiology of hospital infections reflects the situation in those hospitals in which this work was carried out. Therefore, their results can be extrapolated to other institutions only with a large degree of conditionality. Even multicenter studies cannot be considered exhaustive, although they are the most representative.

The structure and etiology of infections in the ICU have been most fully studied. According to a multicenter study conducted on one day in 1417 ICUs in 17 European countries and covering more than 10 thousand patients undergoing treatment, 44.8% of patients had some kind of infection, and the frequency of ICU-associated infections was 20.6 % [6]. The most frequently reported cases in the ICU were pneumonia (46.9%), lower respiratory tract infections (17.8%) and urinary tract infections (UTI) (17.6%), and angiogenic infections (12%). The etiological structure of infections was dominated by gram-negative bacteria of the family Enterobacteriaceae (34.4%), Staphylococcus aureus (30.1%), Pseudomonas aeruginosa (28.7%), coagulase-negative staphylococci (CNS) (19.1%), fungi (17. 1%). Many etiologically significant microorganisms were characterized by resistance to traditional antibiotics, in particular, the incidence of methicillin-resistant staphylococci was 60%; in 46% of cases, P. aeruginosa was resistant to gentamicin [7].

Similar results regarding the etiological structure of infections were obtained in another study [4], which also found that the majority of patients in the ICU (72.9%) received antibiotics for therapeutic or prophylactic purposes. The most frequently prescribed drugs were aminoglycosides (37.2%), carbapenems (31.4%), glycopeptides (23.3%), and cephalosporins (18.0%). The range of drugs used indirectly confirms the high level of antibiotic resistance in the ICU.

The US Nosocomial Infection Surveillance System (NNIS) continuously monitors nosocomial infections and antibiotic resistance. In 1992–1997 a prevalence of urinary tract infections (31%), pneumonia (27%), primary angiogenic infections (19%) was revealed in the ICU, with 87% of primary angiogenic infections associated with central venous catheters, 86% of pneumonia with artificial ventilation (ALV) ) and 95% of urinary infections occur with urinary catheters [5]. The leading pathogens of pneumonia associated with mechanical ventilation (nosocomial pneumonia during mechanical ventilation - NPV) were Enterobacteriaceae (64%), P. aeruginosa (21%), S. aureus (20%); among the causative agents of angiogenic infections were CNS (36%), enterococci (16%), S. aureus (13%), fungi (12%). Fungi and Enterobacteriaceae predominated in urinary infections.

Thus, in the etiological structure of the most common forms of hospital infections, five groups of microorganisms are of greatest importance, accounting for up to 90% of all cases of disease: Staphylococcus aureus; KNS, among which S. epidermidis and S. saprophyticus are of greatest importance; enterococci, especially E. faecalis and E. faecium; Enterobacteriaceae, among which E. coli, Klebsiella spp., Enterobacter spp., Proteus spp., Serratia spp. dominate; a group of non-fermenting bacteria, primarily P. aeruginosa and to a lesser extent Acinetobacter spp.

Based on the primary localization of the source of infection, one can judge the presumed etiology of the disease, which, of course, serves as a reliable guide in choosing an empirical regimen of antibacterial therapy (Table 1).

The difficulties of treating hospital-acquired infections depend on the following factors:

• the severity of the patient’s condition due to the underlying disease;
• frequent isolation of two or more microorganisms from a wound or abdominal cavity;
• the increased resistance of microorganisms to traditional antibacterial drugs in recent years, primarily penicillins, cephalosporins, aminoglycosides, and fluoroquinolones.

In addition, the unjustified, often unsystematic use of antibiotics leads to the rapid selection and spread of resistant strains of microorganisms within the hospital.

Carrying out rational antibacterial therapy for hospital infections is impossible without modern knowledge about the etiological structure of infectious diseases and the antibiotic resistance of their pathogens. In practice, this means the need to identify the etiological agent of infection using microbiological methods and assess its antibiotic sensitivity. Only after this can we talk about choosing the optimal antibacterial drug.

However, in practical medicine the situation is not so simple, and even the most modern microbiological techniques are often unable to give the clinician a quick answer or even generally clarify the causative agent of the disease. In this case, knowledge about the most likely etiological agents of specific nosological forms of hospital infections (Table 1), the spectrum of natural activity of antibiotics and the level of acquired resistance to them in a given region and a specific hospital comes to the rescue. The latter seems to be the most important when planning antibacterial therapy for hospital infections in a hospital, where the highest level of acquired resistance is observed, and the insufficient equipment of microbiological laboratories and the low level of standardization of studies to assess antibiotic sensitivity do not allow forming a real idea of ​​the epidemiological situation in a medical institution and developing balanced recommendations for treatment.

Of the most common mechanisms of antibiotic resistance in hospitals in our country, the following ones, which have the greatest practical importance, should be highlighted.

• Staphylococci resistant to methicillin (oxacillin). Methicillin-resistant staphylococci exhibit resistance to all β-lactam antibiotics (penicillins, cephalosporins, carbapenems), including inhibitor-protected ones, as well as associated resistance to many other groups of drugs, including aminoglycosides, macrolides, lincosamides, fluoroquinolones. These microorganisms in all cases remain sensitive only to vancomycin and linezolid; most of them are also sensitive to rifampicin, fusidine, and co-trimoxazole.
• Vancomycin-resistant enterococci (VRE). They occur with high frequency in ICUs in the United States; there are no data for our country, but there are reports of VRE isolation. VRE remain sensitive to linezolid and, in some cases, ampicillin.
• Microorganisms of the Enterobacteriaceae family (primarily Klebsiella spp. and E. coli), producing extended-spectrum β-lactamases and resistant to cephalosporins of the I, II, III generations. The most reliable in this case are carbapenems; in some cases, cefepime and cefoperazone/sulbactam retain activity. Among other mechanisms of resistance of enterobacteria, one should note the overproduction by some representatives (primarily Enterobacter spp., Serratia spp., Citrobacter freundii) of class C chromosomal β-lactamases, which also effectively hydrolyze third-generation cephalosporins and, in addition, are not sensitive to the action of β-lactamase inhibitors. lactamase (clavulanic acid, sulbactam, tazobactam). Cefepime and carbapenems remain active against these microorganisms.
• P. aeruginosa, resistant to many antibiotics up to pan-resistant strains. It is difficult to predict the resistance phenotype of P. aeruginosa in each specific case, so local data on antibiotic resistance are of particular importance. In recent years, the prevalence of P. aeruginosa strains exhibiting resistance to carbapenems and cephalosporins has increased. The most active antipseudomonal antibiotics include ceftazidime, cefepime, meropenem, and amikacin.

Taking into account the indicated difficulties in the treatment of hospital infections (the severity of the patient’s condition, the often polymicrobial nature of the infection, the possibility of isolating pathogens with multiple resistance to antibacterial agents during nosocomial infections), it is necessary to formulate the following principles for the rational use of antibiotics in the hospital.

• Antibacterial therapy should be started immediately when an infection is registered until the results of a bacteriological study are obtained.
• The choice of the starting empirical treatment regimen should be made taking into account the likely spectrum of pathogens (Table 1) and their possible resistance (data from local monitoring of antibiotic resistance).
• An initial assessment of the effectiveness of therapy is carried out within 48–72 hours after the start of treatment to reduce the severity of fever and intoxication. If no positive effect is observed within this period, the treatment regimen should be adjusted.
• The prophylactic use of antibiotics in the postoperative period (in the absence of clinical signs of infection) should be considered irrational and undesirable.
• Antibiotic administration should be carried out in accordance with official instructions. The main routes of administration are intravenous, intramuscular, and oral. Other methods (intraarterial, endolymphatic, intraabdominal, endotracheal, etc.) do not have proven advantages over traditional ones.

The choice of antibacterial drug can be made based on the established etiology of the disease and the specified sensitivity of the pathogen to antibiotics - such therapy is defined as etiotropic. In other situations, when the pathogen is not identified, the drug is prescribed empirically. In the latter case, the choice of antibiotic is based on the likely spectrum of microorganisms causing an infection at a certain location, and knowledge of the main trends in antibiotic resistance of the most likely pathogens. It is clear that in clinical practice, until the etiology of the disease is clarified, the empirical approach is most often used.

For severe infections, it is fundamentally important to prescribe an adequate antibacterial therapy regimen at the first stage of treatment, which implies the use of empirical therapy with the most complete coverage of all potential causative agents of infection in a given localization. This principle of initial empirical therapy, carried out in full, is especially relevant in the treatment of infections such as NSAIDs, peritonitis, sepsis, since it has been established that in the case of inadequate initial therapy, the risk of death significantly increases [8–10]. According to our data [11], in case of inadequate choice of initial empirical therapy with NSAIDs, the risk of death increases 3 times.

Adequate empirical antibiotic therapy must meet the following requirements.

• The chosen treatment regimen covers all potential infectious agents.
• When choosing an antibacterial drug, the risk of selection of multidrug-resistant strains of pathogens is taken into account.
• The antibacterial therapy regimen should not contribute to the selection of resistant strains of bacteria in the department.

Recommendations for the empirical prescription of antibacterial drugs for the treatment of nosocomial infections in all cases will be very conditional, since they do not take into account local data on the level of antibiotic resistance in each specific medical institution. Therefore, the recommendations below only outline the list of antibiotics that are potentially most effective for specific infections, taking into account global trends and the state of antibiotic resistance in the country, and therefore the drugs are listed in alphabetical order. In treatment programs, the given antibacterial therapy regimens are divided into two groups - optimal means and alternative means.

Optimal means mean antibacterial therapy regimens, the use of which, in the opinion of the author and from the standpoint of evidence-based medicine, is most likely to achieve a clinical effect. At the same time, the principle of reasonable sufficiency was also taken into account, i.e., whenever possible, antibiotics with the narrowest spectrum of antimicrobial activity were recommended as the means of choice.

When compiling the recommendations presented, the authors also took into account a number of documents published in recent years [12–15].

Antibacterial therapy is carried out until stable positive dynamics of the patient’s condition are achieved and the main symptoms of infection disappear. Due to the lack of pathognomonic signs of bacterial infection, absolute criteria for stopping antibiotic therapy are difficult to establish. Usually, the issue of stopping antibiotic therapy is decided individually, based on a comprehensive assessment of the dynamics of the patient’s condition. In general, the criteria for the sufficiency of antibacterial therapy can be presented as follows:

• normalization of body temperature (maximum daytime temperature < 37°C);
• positive dynamics of the main symptoms of infection;
• no signs of a systemic inflammatory response;
• negative blood culture.

The persistence of only one sign of bacterial infection (fever or leukocytosis) is not an absolute indication for continued antibiotic therapy. There are studies showing that while patients are in the ICU on mechanical ventilation, achieving normal temperature, disappearance of leukocytosis and sterilization of the trachea are unlikely even with adequate antibacterial therapy [16]. Isolated low-grade fever (maximum daytime temperature within 37.9°C) without chills and changes in peripheral blood may be a manifestation of post-infectious asthenia or non-bacterial inflammation after surgery and does not require continued antibacterial therapy, as well as persistence of moderate leukocytosis (9– 12 x 109/l) in the absence of a shift to the left and other signs of bacterial infection.

The usual duration of antibacterial therapy for hospital infections of various locations ranges from 5 to 10 days. Longer antibiotic therapy is not advisable due to the development of possible complications of treatment, the risk of selection of resistant strains and the development of superinfection. In the absence of a stable clinical and laboratory response to adequate antibacterial therapy within 5–7 days, additional examination (ultrasound, CT, etc.) is necessary to identify complications or a source of infection in another location.

Certain clinical situations require longer antibiotic regimens. Typically, this approach is recommended for infections localized in organs and tissues in which therapeutic concentrations of antibiotics are difficult to achieve and, therefore, there is a higher risk of persistence of pathogens and relapse of infection. This applies primarily to osteomyelitis, infective endocarditis, and secondary purulent meningitis. In addition, for infections caused by S. aureus, longer courses of antibiotic therapy—2–3 weeks—are also usually recommended.

The presented antibacterial therapy regimens are effective against the most typical and frequently encountered hospital infections in medical practice. However, some complex clinical situations are not considered within the scope of this article, as they are difficult to standardize. In such cases, the question of treatment tactics should be decided together with a specialist in antimicrobial chemotherapy or a clinical pharmacologist.

Literature

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2. Intensive Care Antimicrobial Resistance Epidemiology (ICARE) Surveillance Report, data summary from January 1996 through December 1997: a report from the National Nosocomial Infections Surveillance (NNIS) System. Am J Infect Control 1999; 27: 279–284.
3. Centers for Disease Control and Prevention. Detailed ICU surveillance component: national nosocomial infection surveillance scheme 1-80. Atlanta, GA: Centers for Disease Control and Prevention, 1997.
4. Esen S., Leblebicioglu H. Prevalence of nosocomial infections at intensive care units in Turkey: a multicentre 1-day point prevalence study. Scand J Infect Dis 2004; 36(2): 144–148.
5. Richards MJ, Edwards JR, Culver DH, Gaynes RP Nosocomial infections in medical intensive care units in the United States. National Nosocomial Infections Surveillance System. Crit Care Med 1999; 27(5): 887–892.
6. Vincent JL, Bihari DJ, Suter PM et al. The prevalence of nosocomial infection in intensive care units in Europe: results of the European Prevalence of Infection in Intensive Care (EPIC) Study. EPIC International Advisory Committee. JAMA 1995; 274:639–644.
7. Vincent JL Microbial resistance: lessons from EPIC study. European prevalence of infection. Intensive Care Med 2000; 26:1:3–8.
8. Kollef MH, Sherman G., Ward S., Fraser VJ Inadequate antimicrobial treatment of infections: a risk factor for hospital mortality among critically ill patients. Chest 1999; 115(2): 462–474.
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S. V. Yakovlev, Doctor of Medical Sciences, Professor of MMA named after. I. M. Sechenova, Moscow

Antibacterial therapy of acute respiratory diseases

A.S. POLYAKOVA

, Ph.D.,
D.D.
GADLIYA ,
T.A.
KHOKHLOVA ,
O.A.
ROGOVA ,
M.D.
BAKRADZE , MD,
V.K.
TATOCHENKO , Doctor of Medical Sciences, Professor,
Scientific Center for Children's Health, Moscow
The etiological structure of respiratory diseases (ARD) is represented by both viral and bacterial pathogens [1]. It is obvious that viral infections in children cause the majority of respiratory tract diseases, while treatment with antibiotics is at least useless, and most often seems irrational due to the development of many adverse events. Antibiotic therapy can cause allergic reactions, disruption of the biocenosis of the respiratory tract and the colonization of their mucous membrane with unusual, often intestinal, flora, and the most important danger is the development of global antibiotic resistance of the microbial flora, which is currently one of the most serious health problems [2]. However, a bacterial infection, if not detected in a timely manner and inadequately treated, poses a great threat of developing serious complications, and therefore requires meaningful prescription of systemic antibacterial therapy.

The choice of antibacterial drugs is based on the etiological spectrum of pathogens of a particular nosology and its expected sensitivity. The choice of route of antibiotic administration is also important [3].

Structure of acute respiratory diseases

In most cases, children with acute respiratory infections are diagnosed with acute nasopharyngitis, acute bronchitis, bronchiolitis and croup, which practically do not require antibiotics; at the same time, such forms of acute respiratory infections as community-acquired pneumonia, acute rhinosinusitis and acute otitis media, acute tonsillitis, without the use of antibiotics, have serious complications and a poor prognosis.

In this article, we present the recommendations of international consensus documents on differential diagnosis and antibacterial therapy of these forms of acute respiratory infections, as well as the results of our own research conducted at the Department of Diagnostics and Rehabilitation Treatment of the Federal State Budgetary Institution Scientific Center for Health. The study included children admitted to the department in the period 2013-2014. with acute respiratory tract infections - a total of 218 patients.

We studied the frequency of antibiotic use by local doctors and the compliance of treatment with modern recommendations for rational antibiotic therapy.

In the department, the diagnosis was made on the basis of clinical data and the results of laboratory and instrumental studies. The choice of antibiotic was made empirically according to the expected microbial spectrum.

Community-acquired pneumonia

According to the Russian classification, pneumonia was diagnosed in children with respiratory distress syndrome, physical findings (local weakening of breathing and/or the presence of bronchial breathing, moist fine rales, dullness of percussion sound), as well as infiltrative changes on the radiograph. Under such criteria, the bacterial etiology of the disease is almost always confirmed, and the leading causative agent of typical pneumonia (with dense alveolar infiltrate, often with destruction and pleurisy) is S. pneumoniae (up to 90% in children under 6 years of age and up to 40-60% in older children) [2]. Atypical pneumonias are most often caused by M. pneumoniae - they are rare at an early age, becoming more frequent from the age of 5-6 years. Pneumonia occasionally occurs in school-age children, in the etiology of which the role of C. pneumoniae can be proven [4]. This division of pneumonia determines a fundamentally different approach to antibacterial therapy. Recommendations for the treatment of pneumonia are very uniform throughout the world. The choice of the primary antibacterial agent and its replacement if ineffective is almost always carried out empirically. The antibiotic is changed in the absence of clinical effect within 36 hours for non-severe pneumonia and 48-72 hours for severe pneumonia, as well as in the event of the development of adverse drug reactions.

All international and Russian recommendations indicate amoxicillin or amoxicillin/clavulanate as the drug of choice; with signs of atypical etiology - on macrolides. Uncomplicated, mild pneumonia can be treated with oral antibiotics. In the case of parenteral initiation of treatment, you should switch to the oral form after achieving the effect of stopping the fever.

Since pneumococci until recently remained sensitive to macrolides, their use was allowed as starting antibiotics along with β-lactam antibiotics. Convenience of use has become the reason for their prescription for almost any disease of outpatients. Such uncontrolled administration of macrolides resulted in a colossal increase in the resistance of microbial flora [5]. So, if in 2006-2009. According to the results of the Russian multicenter study PeGAS III, the resistance of S. pneumoniae in Russia to erythromycin and azithromycin was less than 10% [6], then consideration of this issue in recent years, including on the basis of the National Center for Disease Control, showed that the resistance of pneumococcus to these antibiotics close to 30% [7]. The lowest level of pneumococcal resistance of all macrolides has been recorded to josamycin, both previously and now [6, 7, 8].

Therefore, at present, the only recommended treatment for typical pneumococcal pneumonia is the administration of amoxicillin at a dose of 45–90 mg/kg/day [9, 10]. If there is an allergic reaction to penicillins, it is possible to prescribe 2-3rd generation cephalosporins (cefuroxime/ceftriaxone), since cross-allergy to penicillins and cephalosporins is extremely rare; if you are allergic to all lactams, you can use josamycin as the most active macrolide against pneumococci. Oral cephalosporins of the third generation - cefixime (Ceforal Solutab) and ceftibuten (Cedex) are inconsistently active against pneumococcus, so pneumonia is not included in the instructions for their use.

In severe cases, intravenous inhibitor-protected penicillins (amoxicillin/clavulanate, ampicillin/sulbactam) are used; II-III generation cephalosporins (cefuroxime, ceftriaxone, cefotaxime, cefoperazone).

Atypical pneumonia in children, in the presence of clear clinical and radiological signs, can be empirically treated with macrolides. In doubtful cases, you can prescribe amoxicillin and, if it is ineffective, switch to macrolides after 24-48 hours. Unfortunately, this opportunity is rarely used in outpatient practice, when a child is hospitalized if β-lactam therapy is ineffective, without trying to replace it with a macrolide.

Recommendations of the Russian Federation allow the prescription of both groups of drugs, for example, if it is impossible to monitor the patient. For 2013-2014 Of the children hospitalized at the clinic, 53 were diagnosed with typical pneumonia. 36 children received systemic antibacterial therapy at the prehospital stage. Of these, only one child was treated with amoxicillin and was hospitalized with a controlled fever. 14-15-membered macrolides were received by 22% of patients, and in 88% of cases they were ineffective ( Table 1

). About one third of patients were treated with third-generation oral cephalosporins, which was unsuccessful in 81% of cases. One child taking levofloxacin also became afebrile by the time of hospitalization. 14 children with typical pneumonia received amoxicillin/clavulanate before hospitalization, of which 11 (79%) received it at a dose below 45 mg/kg, which demonstrated the ineffectiveness of this dosage. In the hospital department, increasing the dose of the same drug showed a positive result. Ceftriaxone and amoxicillin/clavulanate in adequate doses were effective in all cases of the disease.

It can be concluded that children who received amoxicillin on an outpatient basis for non-severe community-acquired pneumonia were not hospitalized due to the onset of the effect.
During hospitalization, 23 patients were diagnosed with atypical pneumonia; in another four, the diagnosis raised doubts regarding its etiology. All these children were combined into one group (27 people), 17 of them (63%) received therapy with β-lactam antibiotics before hospitalization, often for 4-6 days, which explains the hospitalization of most of them due to the lack of effect. Only three (11%) were successfully treated with macrolides. When changing an ineffective antibiotic, in most cases amoxicillin was successfully used for typical pneumonia (including in combination with clavulanic acid), less often - cephalosporins. Josamycin was used in children with atypical pneumonia and in four children suspected of having it, which confirmed its effectiveness in 100% of cases. In general, assessing prehospital treatment, it was noted that an effective (but often suboptimal) drug in a sufficient dose was prescribed only in 20-25% of cases.

The duration of therapy should be sufficient to suppress the vital activity of the pathogen, the elimination of which is completed by immunological mechanisms. With an adequate choice of antibiotic and a rapid onset of effect, the duration of therapy for non-severe community-acquired pneumonia is 5 days; for severe and complicated forms, treatment continues for a longer time [2].

Acute rhinosinusitis and acute otitis media

According to the classification proposed by the European Guidelines for Rhinosinusitis and Nasal Polyposis (EPOS 2012), rhinosinusitis (ARS) lasting less than 12 weeks is defined as acute. with complete resolution of symptoms. According to this classification, acute rhinosinusitis is divided into: viral rhinosinusitis, postviral and bacterial. Viral rhinosinusitis is an acute respiratory viral infection with symptoms lasting less than 10 days; their intensification after the 5th day or persistence after the 10th day, but less than 12 weeks. considered as post-viral rhinosinusitis, only a small number of patients (0.5-2%, in children - 5-10%) develop acute bacterial rhinosinusitis, which is facilitated by a decrease in mucociliary clearance [11, 14]. Differential diagnosis of post-viral and bacterial ARS is often difficult. EPOS 2012 highlights the following signs of a potentially bacterial disease:

1. Discharge from the nose (with a predominance of one half) and purulent contents in the nasal cavity. 2. Severe local pain (predominant on one side). 3. Fever (>38 °C). 4. Increase in ESR and/or CRP. 5. “Deterioration after improvement” or “second wave of the disease.”

The Infectious Diseases Society of America (IDSA) identifies another form of bacterial rhinosinusitis: with initially severe symptoms (fever ≥ 39 ° C, purulent nasal discharge, facial pain) lasting 3-4 days in a row.

Most often, viral ORS is caused by adenovirus, RS virus, and coronavirus [12, 13]. Bacterial sinusitis is most often caused by H. influenzae, S. Pneumoniae, less often by M. catarrhalis, S. pyogenes or staphylococci [11, 15]. Since most ARS is not bacterial, giving an antibiotic does not speed recovery; in 80% of patients who did not receive systemic treatment, the symptoms of the disease were relieved within 2 weeks. [16, 17]. The choice of antibacterial drugs is covered below.

Acute otitis media (AOM) is experienced by 60 to 85% of children in the first year of life; after 5 years, the incidence sharply decreases [18, 19]. The risk of developing NDE increases when attending preschool institutions. The etiological structure of AOM has not changed significantly; being a complication of ARVI with dysfunction of the auditory tube, in a third of cases AOM has a viral etiology. The spectrum of bacterial pathogens practically coincides with the etiology of ARS, which determines uniform approaches to the selection of a systemic antibiotic: S. pneumoniae, non-typeable H. influenzae and, less commonly, M. catarrhalis [20]. Since most AOM resolves with symptomatic therapy and adequate care of the nasopharynx, indications for prescribing an antibiotic are associated with the age of the child and the severity of the disease ( Table 2

) [21].

For the treatment of both ARS and AOM, the drug of choice is amoxicillin - 45 mg/kg/day. The ineffectiveness of the starting dose of amoxicillin is often associated with resistance of S. pneumoniae strains. If they are likely, it is necessary to increase the dose of amoxicillin to 80-100 mg/kg/day, especially since otitis media creates a lower concentration of the antibiotic in the middle ear cavity. Thus, the concentration of amoxicillin in the middle ear fluid when administered a single dose of 13 mg/kg was 0.68 +/- 0.86 μg/ml, not reaching the minimum inhibitory concentration (MIC) of resistant pneumococcus (2 μg/ml), while with the introduction of 30 mg/kg, it reached 4.34 ± 2.06 μg/ml [22]. The absence of a clinical effect from amoxicillin within 72 hours may indicate the role of β-lactamase-producing strains of hemophilus (36 and 38% of cases in ARS and AOM, respectively, which is a reason to prescribe amoxicillin/clavulanate or third-generation CS (cefixime) [23].

As with pneumonia, in case of a proven allergic reaction to penicillins, preference is given to cephalosporins (cefuroxime/cefuroxime axetil at a dose of 30 mg/kg/day or ceftriaxone at a dose of 50 mg/kg/day).

If there are contraindications to the use of lactams, treatment is carried out with macrolides, again with priority for the 16-membered ones - josamycin. The duration of antibiotic treatment for ORS should be at least 7-14 days,

for children aged 2 to 5 years with AOM, a 7-day course of antibacterial therapy is recommended, up to 2 years, and also for severe cases - 10 days. Shorter treatment is acceptable in children over 6 years of age (5-7 days) [11, 24].

In 2013-2014 In our department there were 52 children with AOM (33 boys, 19 girls) aged 4 months. up to 10 years. Before hospitalization, 26 received systemic antibacterial therapy ( Table 3

). 12 children were treated with macrolides, which was 46%; in all cases, the therapy was ineffective. 50% of children received oral cephalosporins of the third generation, of which 85% were unsuccessful. The choice of starting antibiotic for AOM was rational only in 5 children (19%), although 2 of them received a low dose of antibiotic without effect.

In the department, the reason for changing the antibacterial drug upon admission to the clinic was, in addition to the irrational choice of antibiotic, the persistence of fever for 48 hours or more; there were 19 such patients (79%). In department 5 children, therapy was successfully continued with the same drug with an increase in the dose of amoxicillin/clavulanate.

Acute tonsillitis
Acute tonsillitis is an episode of inflammation predominantly of the palatine tonsils, as well as the surrounding mucous membrane, occurring with hyperemia, often with exudate on the tonsils and reaction of the regional lymph nodes. Up to 10% of children suffer from tonsillitis every year [25].

Acute tonsillitis is most often caused by respiratory viruses (especially adenovirus) and the Epstein-Barr virus; most cases of acute tonsillitis (AT) end with spontaneous resolution. According to various sources, from 10 to 30% of RT are caused by group A β-hemolytic streptococcus (GABHS). Such tonsillitis without systemic antibacterial treatment can be complicated by severe diseases, such as pharyngeal abscesses of various locations, as well as acute rheumatic fever, rheumatic heart disease, post-streptococcal glomerulonephritis, etc. It is streptococcal tonsillitis that is the reason for prescribing systemic antibacterial therapy [26]. The role of other pathogens of OT (bacterial, fungal) is extremely small and they usually do not require systemic treatment.

Differential diagnosis of tonsillitis based on the clinical picture is difficult: both viral and bacterial forms are accompanied by fever, plaque on the tonsils and enlarged cervical lymph nodes. However, viral variants are usually accompanied by catarrhal symptoms and are more common in children under 12 years of age. Streptococcal tonsillitis is rare in preschool and especially young children, but in children over 12 years of age, almost half of cases of OT are caused by streptococcus [27].

Also, an increase in the level of markers of bacterial inflammation does not allow us to reliably judge the form of OT, since during a viral infection, an increase in the level of leukocytes, C-reactive protein and even procalcitonin is often recorded [26-28].

The similarity of clinical and hematological signs of OT has led to the fact that at the outpatient stage, almost all tonsillitis accompanied by plaque are unjustifiably treated with a systemic antibiotic, and milder forms or tonsillitis without plaque are also unjustifiably left without treatment. To date, the only reliable method for isolating streptococcal tonsillitis is a cultural examination of material from the tonsils and posterior pharyngeal wall or a rapid test for determining GABHS, based on latex agglutination. The growth of streptococcus or its high probability is an indication for mandatory systemic antibacterial treatment; for all other forms of OT, it is sufficient to prescribe only symptomatic therapy [26, 29].

Considering the 100% sensitivity of Streptococcus pyogenes to penicillins, the drug of choice for streptococcal tonsillitis is amoxicillin at a dose of 45 mg/kg/day. The clinical ineffectiveness of unprotected aminopenicillins, most often due to the production of β-lactamases by oral flora or the presence of biofilms on the tonsils, dictates the need to protect amoxicillin with clavulanic acid [30]. An allergic reaction to penicillins or the inability to exclude an Epstein-Barr viral infection should be a reason to prescribe third-generation oral cephalosporins (cefixime).

In the last decade, a rapid increase in resistance of Streptococcus pyogenes to macrolides has been recorded. Already at the beginning of the century, its overall resistance to this group of drugs was 13.3%, for example, to erythromycin - 19.1% in adults and 11.8% in children. However, for josamycin this figure did not exceed 1.5% [31]. The resistance of streptococcus pyogenes to 14- and 15-membered macrolides (erythromycin, clarithromycin, azithromycin) in Irkutsk exceeds 28%, while to 16-membered josamycin, according to the results of the same study, it did not exceed 0.7% [8].

It is for this reason that macrolides have lost their place as drugs of choice for OT, and if their prescription is necessary (intolerance to all lactams), preference should be given to 16-membered ones, in particular josamycin. The duration of antibacterial treatment of streptococcal throat infections with penicillins should not be less than 10 days; the use of 2nd-3rd generation oral cephalosporins (cefixime) can reduce this period by 2 times without increasing the frequency of clinical and bacteriological relapses [32, 40]. In case of lactam intolerance, josamycin can be prescribed for a period of 7 days [33, 34].

Over a two-year period, 86 children with acute tonsillitis were hospitalized in our department. Of these, 18 were bacterial forms, 12 were caused by respiratory viruses, and 56 patients were diagnosed with infectious mononucleosis. Of the 86 children, 54 (63%) received systemic treatment at the prehospital stage.

Of the 18 children with bacterial tonsillitis, i.e. those who should have received a systemic antibiotic, only 6 (33%) were treated before admission to the clinic. Two received aminopenicillins in a sufficient dose with good effect, and two were prescribed cephalosporins. Two more children were treated with 14-15 member macrolides without effect. The clinic continued treatment of 6 children with bacterial tonsillitis, the remaining 12 were prescribed amoxicillin or 2-3rd generation cephalosporins with a rapid effect.

48 out of 68 (89%) children with viral forms of OT received antibacterial therapy at the prehospital stage, that is, they were treated unreasonably. Among them, 46 out of 56 children had infectious mononucleosis (82%), while in 9 cases a second antibiotic was prescribed on an outpatient basis due to the ineffectiveness of the first. Aminopenicillins were prescribed to 34% of patients with infectious mononucleosis, which caused the appearance of “ampicillin rash” in five children. Cephalosporins were used in 34% of cases, macrolides in 29%, and 1 child received lincomycin.

We were able to stop antibiotic administration in 37 of 48 children (in 11 children this was prevented by parents) who received them before admission; in 20 children who were not treated before admission, antibiotics were not prescribed.

Conclusion

The vast majority of acute respiratory infections are of viral origin, and the protection of this category of patients from unjustified, sometimes harmful, antibacterial treatment depends on the doctor’s knowledge. On the other hand, timely detection and adequate treatment of bacterial infection is the most important factor in preventing serious purulent and systemic complications, as well as reducing mortality.

The analysis shows that in modern pediatric practice there are significant shortcomings in determining the indications for antibacterial therapy for children with acute respiratory infections and choosing the drug. In addition, the efforts of researchers to identify the resistance spectra of microbes remain unclaimed for a long time.

The result is an excessive prescription of antibacterial agents and an increase in the resistance of the most common pathogens, which led at the beginning of the century to the ineffectiveness of co-trimoxazole, and in our time - 14- and 15-membered macrolides. And this, in turn, makes “habitual” antibiotic prescriptions less and less effective.

Due to its high activity against most pathogens, amoxicillin is the drug of choice for acute bacterial diseases of the respiratory tract. It has very high bioavailability, is more easily absorbed in the intestine than ampicillin (about 70% compared to 50% for ampicillin), providing adequate plasma concentrations.

Amoxicillin/clavulanate is an indispensable antibiotic for infections caused by β-lactamase-producing strains, even in cases of complicated diseases, both on an outpatient basis and in a hospital. Against the backdrop of increasing resistance to macrolides, josamycin is one of the few macrolides that still retains its effectiveness against coccal flora, but it is used much less frequently than less effective macrolides.

Among the oral forms of antibiotics, dispersible tablets Flemoxin Solutab, Flemoklav Solutab, Vilprafen Solutab and Suprax Solutab have gained well-deserved popularity. “Solutab” literally means “a tablet that can be dissolved in water,” but it should be noted that as a result of dispersing the tablet, it does not completely dissolve in the physicochemical sense. When a Solutab tablet gets into water, it disintegrates into microgranules with the active substance inside, resulting in the formation of a colloidal solution (suspension). The acid-resistant shell of microgranules protects the active substance from the contents of the stomach, while the full and massive release of microgranules occurs in the duodenum under the influence of an alkaline environment. Thus, the maximum amount of the active substance in unchanged form enters the “absorption window” (zone of maximum absorption), which contributes to its full absorption and increased bioavailability, as with parenteral administration. This bioavailability increases clinical efficacy and safety by reducing the residual concentration of the antibiotic in the intestine. Differences in bioavailability, efficacy and safety compared to other oral formulations have been demonstrated in a number of clinical studies [35–38]. It should be noted that the United Nations Children's Fund (UNICEF) recommends the use of antibacterial drugs in the form of dispersible tablets in resource-limited settings, since these drugs can be used in water shortages and can easily form a liquid form. They also have the advantage of compactness, light weight, convenient storage and a low risk of incorrect dosing, compared to suspensions, since tablets have different dosages and a score dividing the tablet in half [39].

It seems to us necessary to take urgent measures to increase the knowledge and experience of pediatricians in the treatment of the most common types of pathology. It is also important to draw the attention of healthcare administrators to the need to introduce modern methods of auditing and quality control in this vital area.

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Source:

Medical Council, No. 6, 2015

On the use of antibacterial therapy in patients with new coronavirus infection COVID-19

Dear Colleagues!

In 2022, humanity is faced with a pandemic of a new coronavirus infection (COVID-19), which has so far claimed the lives of more than 1 million people. All countries, including the Russian Federation, have undergone significant changes in their healthcare systems aimed at combating the pandemic. At the same time, we must not forget about the global threats to human health, which in the current situation have temporarily faded into the background, in particular, the widespread increase in antimicrobial resistance. It is of great concern that against the backdrop of the new coronavirus infection pandemic in Russia, there has been a significant increase in the sale of antibacterial drugs in pharmacies and their purchases by medical institutions. According to several studies, more than 90% of patients with COVID-19 are currently receiving antibiotics, including combination therapy and parenteral drugs in the outpatient setting. Without a doubt, the current situation will contribute to a significant increase in antimicrobial resistance and have serious adverse consequences in the future. Unjustified antibacterial therapy leads to a number of undesirable effects that can significantly worsen the patient’s condition, and sometimes lead to life-threatening consequences.

In this regard, a number of medical professional organizations consider it their duty to provide additional clarification on the use of antibacterial drugs in patients with COVID-19:

1. Antibacterial drugs are not active against viruses, including the new coronavirus (SARS-Cov-2). Therefore, COVID-19, like any other viral infection, is not an indication for the use of antibiotics.
2. Lung damage in COVID-19 may be associated with immune mechanisms - macrophage activation syndrome with the development of a “cytokine storm”, which is not affected by antibacterial drugs. Experts suggest using instead of the term “pneumonia” for lung damage caused by SARS-Cov-2, the terms “viral interstitial lung injury”, “viral pneumonia” or “viral pneumonitis”, which not only reflect the pathogenesis of the process in COVID-19, but also give every reason to a practicing doctor not to prescribe antibiotics.
3. An increase in the level of C-reactive protein and other laboratory markers of inflammation in patients with COVID-19 is often due to the development of a “hyperimmune response” and cannot be considered as an unambiguous sign of a bacterial complication and, accordingly, as a reason for prescribing antibacterial therapy. The only laboratory marker that allows differentiation between bacterial and immune processes in a patient with COVID-19 is the level of procalcitonin in the blood.
4. Prescribing antibacterial therapy in patients with COVID-19 is justified only if there are convincing signs of a bacterial infection - the appearance of purulent sputum, an increase in blood procalcitonin of more than 0.25–0.5 ng/ml, an increase in the level of blood leukocytes of more than 10 thousand/μl with an increase in the number band neutrophils more than 10% (it must be taken into account that leukocytosis may be due to glucocorticosteroid therapy and not a bacterial infection). The use of antibiotics in patients with nosocomial pneumonia during the course of COVID-19 is carried out according to general rules - taking into account the severity of the patient’s condition, premorbid background, risk factors for infection caused by resistant bacteria, and the results of etiological diagnosis.

Considering the above, we urge practitioners and heads of medical organizations providing care to patients with the new coronavirus infection COVID-19 to refrain from unjustified prescription of antibiotics, especially in hospital settings where there is laboratory confirmation of a bacterial infection, and to comply with the provisions set out in the current version of the Temporary methodological recommendations “Prevention, diagnosis and treatment of new coronavirus infection (COVID-19)” of the Russian Ministry of Health (version 8.1 dated October 1, 2020), regarding the use of antibacterial therapy.

October 17, 2022