Lower respiratory tract infections, which include community-acquired pneumonia (CAP), are the most common cause of death among all infectious diseases. The presence of a comorbid pathology in a patient with CAP suggests a possibility of mutual influence and changes in the course of both the underlying disease and comorbidities, as well as changes in the effectiveness and safety of ongoing drug therapy. The aim of the study was to analyse literature data on the structure of comorbidity in CAP patients and its impact on the efficacy and safety of therapy with β-lactam antibiotics. It has been established that CAP most often occurs in patients with chronic obstructive pulmonary disease, cardiovascular diseases (ischemic heart disease, arterial hypertension, and chronic heart failure), cerebrovascular disease, chronic kidney disease, diabetes mellitus, bronchial asthma, leukemia, anemia, dementia, neurological disorders, and cancer. The most common causative agent of CAP, regardless of the patient’s age and comorbidity, is pneumococcus (Streptococcus pneumoniae), followed by intracellular pathogens (mycoplasmas, chlamydia) and Haemophilus influenzae, as well as respiratory viruses. With this in mind, the initial empiric therapy for CAP mainly includes β-lactam antibiotics, which are effective against pneumococcus. If patients with CAP have concomitant chronic diseases and conditions, the spectrum of pneumonia pathogens may differ from that in the general population and include rare pathogens and multidrug-resistant strains. The effectiveness of antibiotic therapy in such patients is reduced, which leads to a worsening of the course of both CAP and concomitant diseases. This patient population may require longer treatment with antibiotics, including β-lactams, or the use of antibiotics at doses that provide a higher minimum inhibitory concentration, which is associated with a high risk of adverse reactions and a decrease in the safety of antibiotic therapy.

Aztreonam is the only approved monocyclic β-lactam antibiotic for human use that is active against Gram-negative aerobes, primarily Pseudomonas аeruginosa. Aztreonam has been used for more than 35 years, and aztreonam lysine has been on the market for 15 years. Although the medicinal products show clinical and microbiological efficacy in severe infections and are significant for cystic fibrosis patients, little information is published on their safety. In the meantime, new data have accumulated.

The aim of the study was to analyse the data on adverse reactions in patients of different age groups receiving aztreonam, collected in the safety monitoring databases VigiBase and Pharmacovigilance.

Materials and methods: the data on adverse reactions associated with aztreonam, in any dosage form, from the individual case reports submitted to VigiBase (the database of the Uppsala Monitoring Centre) before 15.09.2021 and to Pharmacovigilance (the database for spontaneous reports in the Automated Information System of the Federal Service for Surveillance in Healthcare of the Russian Federation) before 05.10.2021.

Results: the analysis of adverse reactions during the use of aztreonam for approved indications showed differences in frequency, types and severity of the adverse reactions amongst the age groups. The most common adverse reaction with aztreonam was cystic fibrosis referred to in 1828 reports (12.0%). It was recorded more often in patients aged 18–44 years (39.2%).

Conclusions: the data obtained allowed the authors to identify a new safety signal for aztreonam, namely an increased risk of inefficacy or insufficient efficacy in cystic fibrosis considered an adverse reaction in the individual reports from the databases of spontaneous reports. Confirmation of the signal requires further monitoring.

β-lactam antibiotics, including cephalosporins, are the drugs of choice for empirical antibiotic therapy (ABT) in patients with community-acquired pneumonia. Unreasonable and irrational use of antibiotics leads to an increased risk of adverse reactions, contributes to the growth of antibiotic resistance.

The aim of the study was to analyse data on the efficacy and safety of initial empirical ABT using cephalosporins for community-acquired pneumonia in middle-aged patients of multidisciplinary hospitals in Moscow.

Materials and methods: the authors analysed 177 archived medical records of the patients admitted to three multidisciplinary hospitals (I.V. Davydovsky City Clinical Hospital, City Clinical Hospital 52 and City Clinical Hospital 4) in Moscow from 2017 to 2019 and prescribed mono- and/or combination therapy including a cephalosporin antibiotic as a starting therapy for community-acquired pneumonia. The initial ABT was considered effective if a patient’s body temperature normalised within 48–72 h following initiation of treatment and safe if no adverse reactions developed during the period of inpatient treatment.

Results: the combination of ceftriaxone and azithromycin was the most frequently prescribed ABT regimen; its effectiveness was 71.9%. Ceftriaxone monotherapy was the second in frequency of prescription; its effectiveness amounted to 77.2%. The third regimen included cefotaxime and azithromycin and was effective in 70% of cases. The patients who needed a change in initial ABT had a significantly higher incidence of developing severe community-acquired pneumonia and complications. The study results indicate that the structure of comorbidity did not affect the effectiveness of initial empirical ABT. Streptococcus pneumoniae was found to be the most common causative agent of community-acquired pneumonia in the studied population (44.8% of cases). Only 13% of the patients faced adverse reactions associated with the use of antibiotics as part of the initial empirical ABT; the most common were leukopenia and diarrhoea.

Сonclusions: the results of the study indicate the feasibility of mono- and/or combination ABT including a cephalosporin antibiotic as a starting empirical therapy for community-acquired pneumonia due to its effectiveness and favourable safety profile.

Vancomycin is a drug of choice for the infections caused by methicillin-resistant strains of staphylococci. Its use requires individualised dosing and renal function monitoring.

The aim of the study was to evaluate, using therapeutic drug monitoring (TDM), the frequency of reaching target trough serum concentrations (TSCs) and the frequency of renal function impairment in orthopaedic infection patients receiving vancomycin therapy.

Materials and methods: the authors carried out a retrospective analysis of vancomycin TSC test results of 457 patients admitted to a purulent osteology department in 2019–2021. The results were grouped according to the number of TSC determination performed as part of TDM (tests 1, 2, and 3). Each of the 3 groups was further divided into 4 subgroups according to the TSCs of vancomycin: ≤9.9 µg/ml (extremely low), 10–14.9 µg/ml (recommended for mild infections), 15–19.9 µg/ml (recommended for bone and joint infections), ≥20 µg/ml (potentially toxic). The results obtained in each group were analysed separately.

Results: according to the 1st TDM test, only 9.6% of patients achieved the TSCs of vancomycin recommended for bone and joint infections. Extremely low TSCs, insufficient for treatment of the infections, were found in 64.8% of patients. According to the 2nd and 3rd TSC determinations, dose corrections decreased the percentage of patients with extremely low TSCs to 49.9% and 41.2%, respectively. Potentially toxic TSCs of vancomycin were detected in 48 (10.5%) patients, but renal dysfunction was observed only in 8 (1.75%) of them. The authors exemplify the use of TDM to control the efficacy and safety of vancomycin in patients with pronounced signs of renal function impairment by two clinical cases.

Conclusion: with a standard dose of vancomycin, the concentrations recommended for bone and joint infections were reached only in every tenth patient. There was a large percentage of patients with extremely low serum concentrations of the medicinal product (64.8%), but it decreased after dose adjustments. Monitoring of vancomycin concentrations allows for individualised dosing, efficacy control and significant reduction of the risk of adverse kidney reactions.

Vancomycin is prescribed to patients in serious condition with infections caused by Gram-positive microorganisms; however, if the therapeutic plasma concentration of the medicinal product is exceeded, it can have a nephrotoxic effect.

The aim of the study was to demonstrate the possibility of using therapeutic drug monitoring (TDM) to reduce the risk of developing nephropathy in intensive care unit patients with sepsis.

Materials and methods: the study comprised a retrospective analysis of four clinical cases of patients with sepsis admitted to intensive care units of I.V. Davydovsky City Clinical Hospital in 2021 and treated with vancomycin. TDM of vancomycin plasma levels was performed by reverse-phase high-performance liquid chromatography with mass spectrometric detection.

Results: using the four cases of septic patients, the study demonstrated that vancomycin at adequate case-specific doses may result in plasma concentrations beyond the therapeutic range. TDM of vancomycin concentrations helped to prevent further deterioration of renal dysfunction in one septic patient having developed acute kidney injury and to control the achievement of therapeutic vancomycin concentrations or timely adjust the dose to that effect in the other three cases.

Conclusions: a timely correction of vancomycin dosing with plasma TDM allows for achieving high antimicrobial efficacy in patients with sepsis and minimising the nephrotoxic effect of the medicinal product. Studies of the feasibility of using TDM as a treatment personalisation tool for patients in serious condition will continue in the future.

Cirrhosis is one of the major health problems worldwide; and ascites is often its first and foremost manifestation. Despite the advances in modern hepatology, the presence of ascites is associated with a poor prognosis and high mortality. The aim of the study was to analyse data on the efficacy and safety of ascites treatment options, taking into account the pathophysiology of the condition. The analysis of literature and international guidelines on ascites management showed that cirrhotic ascites is treated with medication or surgery that interfere with pathogenetic mechanisms underlying the condition. Treatment of uncomplicated ascites depends on the severity of clinical manifestations. Patients with grade 1 ascites do not require treatment. Therapy for grade 2–3 ascites is aimed at reducing sodium intake and promoting its excretion with diuretics. The effect of diuretics should be assessed by daily monitoring of body weight. Close monitoring of serum creatinine and electrolyte levels is necessary to avoid severe electrolyte imbalance and mitigate the risk of diuretic-associated acute kidney injury. Another medical option to increase diuresis is the use of vasoconstrictors. Large volume paracentesis is the treatment of choice for patients with grade 3 ascites and refractory ascites. The most dangerous complication of paracentesis is circulatory dysfunction, which is prevented by limiting the volume of fluid removed to 5–6 liters per procedure and using plasma substitutes. If paracentesis is ineffective, new minimally invasive methods of treatment should be considered: transjugular intrahepatic portosystemic shunting and automated low-flow ascitic fluid removal system. However, given the poor prognosis, all patients with refractory ascites should be considered candidates for liver transplantation, which is currently the only effective treatment. The efficacy and safety of therapy may be enhanced by a personalised approach to choosing the treatment for ascites in cirrhosis, as well as further investigation of means to mitigate adverse reactions to medication and minimally invasive surgery.

Epilepsy is a fairly common disease which challenges social life, therefore the use of information systems and software to support patients with epilepsy is a promising trend in electronic and mobile medicine. The aim of the study was to analyse data on the existing information systems, devices, and mobile applications used to support patients with epilepsy and control risks associated with pharmacotherapy, and to assess the prospects for the development of information systems to support patients with epilepsy. The results of an advanced search and systematisation of literature and Internet data suggest a high demand for mobile and e-health. Mobile applications for patients with epilepsy have a large share of e-health tools. The applications help to monitor seizures, record the frequency of taking medications, receive advice on emergency treatment of seizures, adjust the dosage regimen, and, in general, help to reduce the risks of anticonvulsant therapy, increase patient compliance and the competence of the participants in the treatment process. The analysis of the convenience and functionality of the foreign-produced mobile applications: Epilepsy Journal, Seizure Tracker, Helpilepsy, Seizure First Aide, did not reveal any significant differences between them. The following shortcomings of the mobile applications were identified: lack of Russian language support (except Epilepsy Journal), lack of advertisement blocking options in free applications, incomplete use of video recording capabilities and location-based systems. Global trends in the development of mobile medicine suggest the need for Russian-produced software that would address the identified shortcomings of the existing foreign applications and help support patients with epilepsy.

Bowel-cleansing PEG-based agents, including Moviprep^®, are commonly used to prepare the large intestine for diagnostic examinations. PLNV-next is a newly developed fixed combination medicinal product with a composition similar to that of Moviprep^®.

The aim of the study was to estimate the pharmacological efficacy and toxicity of PLNV-next.

Materials and methods: The study evaluated pharmacological efficacy of four formulations of PLNV-next in comparison with Moviprep^® after a single administration in a therapeutic dose to outbred rats. The evaluation was carried out based on the laxative effect of the medicinal products. The authors recorded diarrhoea onset latency and the number of defecation boluses and diarrhoea spots produced during the 6-hour observation period. Toxicity of PLNV-next was studied in the formulation containing maximum amounts of the ingredients according to the patent. In the single-dose toxicity study, PLNV-next was administered intragastrically to rats at doses of 4.2 g/kg (maximum human therapeutic dose, MHTD), 21 g/kg (5 MHTD), and 42 g/kg (10 MHTD) and to ferrets at doses of 4.2 g/kg (MHTD) and 21 g/kg (5 MHTD). In the repeated-dose toxicity study, PLNV-next was administered for 14 days at 4.2 g/kg (rats and ferrets), 21 g/kg (5 MHTD, rats), and 12.6 g/kg (3 MHTD, ferrets). Additionally, the repeated-dose toxicity study evaluated safety pharmacology parameters for the cardio-vascular, respiratory and central nervous systems.

Results: All PLNV-next formulations tested exerted a laxative effect equivalent to that of Moviprep^®. No clinical signs of toxicity were observed in rats, with the exception of the laxative effect. Ferrets demonstrated decreased behavioral activity and diarrhoea. Nausea or emesis were noted in 75–90% of the ferrets receiving the doses exceeding the MHTD. A single administration of PLNV-next affected blood sodium concentrations: a slight increase was noted in the 5 MHTD and 10 MHTD groups of rats and in the 5 MHTD group of ferrets. The repeated-dose toxicity study in rats revealed a slight increase in sodium levels with both test doses. After a single administration of 5 MHTD to ferrets, the authors observed a decrease in potassium levels. All the changes were mild and within physiological ranges. PLNV-next toxic effects observed in the rat and ferret studies were similar to those reported in rat and dog toxicity studies of Moviprep^®. 

Conclusion: PLNV-next exerts a marked laxative effect and has a favourable safety profile.

The experts of the Scientific Centre for Expert Evaluation of Medicinal Products analysed administrative decisions of foreign regulatory authorities on the recalls of antibacterial and antiprotozoal medicinal products and/or the need for labelling updates due to changes in the safety profile. The analysis revealed 16 decisions containing information on the following medicines registered in Russia: ertapenem, сeftriaxone, cefazolin, аmoxicillin, сefoperazone+sulbactam, piperacillin+tazobactam, сlindamycin, teicoplanin, rifampin, co-trimoxazole, hydroxychloroquine.

This article is the Russian translation of the Plain Language Summary (PLS) of the Cochrane Review previously published in the Cochrane Database of Systematic Reviews. Original publication: Popp M, Stegemann M, Riemer M, Metzendorf MI, Romero CS, Mikolajewska A, et al. Antibiotics for the treatment of COVID-19. Cochrane Database of Systematic Reviews. Version published: 22 October 2021. https://doi.org/10.1002/14651858.CD015025

Retracted article: Muraviev Yu., Gridneva G. Herpes Zoster in RA Patient treated with Methotrexate. Safety and Risk of Pharmacotherapy. 2014;(4):18–22. (In Russ.)

This article by Muraviev Yu., Gridneva G. has been retracted (i.e. withdrawn from the press) by the editorial staff of Safety and Risk of Pharmacotherapy as a duplicate of the following publication: Muraviev Yu., Gridneva G. Herpes Zoster in RA Patient treated with Methotrexate. Safety and Risk of Pharmacotherapy. 2014;(1):27–30 (In Russ.)

The Editorial board would like to extend their sincere apologies for any inconvenience this retraction may have caused.

Minutes of the meeting of the Editorial Board of the journal Safety and Risk of Pharmacotherapy No. 2 of April 21, 2022.