[The role and place of pathogenetic therapy with glucocorticosteroid hormones in the treatment of patients with novel coronavirus infection (COVID-19)].

In December 2019, in Wuhan (PRC), there was an outbreak of a new coronavirus infection (COVID-19) caused by coronavirus type 2 (SARS-CoV-2), which has a zoonotic origin. The World Health Organization announced the COVID-19 pandemic on March 11, 2020. In most cases, the disease is asymptomatic or mild. However, up to 15% of patients require hospitalization, and 5% develop a critical condition. To date, no effective antiviral drug COVID-19 has been found that can reduce mortality. Pathological changes in the lungs are manifested by diffuse alveolar damage, which is clinically manifested by increasing respiratory failure, accompanied by a decrease in saturation and oxygen concentration in arterial blood. It is assumed that autoimmune reactions play an important role in the development of multiple organ failure. Generalized inflammation is characterized by an increase in the concentration of C-reactive protein, ferritin, interleukin-1 and interleukin-6, and other markers. At the stage of development of infection in the form of a cytokine storm, proinflammatory cytokines can themselves become pathogenetic factors in the development of critical conditions, multiple organ failure and deaths. Therefore, a key challenge in treating hospitalized patients with COVID-19 is to control generalized inflammation. Glucocorticosteroid hormones (GCS) are widely used as anti-inflammatory drugs in the clinic of infectious diseases. However, until recently, there was no convincing data on the effectiveness of GCS in patients with COVID-19. Recently published results of a large randomized clinical trial (RECOVERY) showing the efficacy of GCS (dexamethasone) in the treatment of critically ill patients with COVID-19. At the same time, the feasibility and effectiveness of GCS in patients with COVID-19 outside critical conditions, the pathogenetic mechanisms that determine the effectiveness/ineffectiveness of these drugs and the validity of their use remain insufficiently studied.

Multicentre Study of the Prevalence and Clinical Value of Hospital-Acquired Infections in Emergency Hospitals of Russia: ERGINI Study Team.

BACKGROUND: Hospital-acquired infection (HAI) is a common problem in intensive care units (ICU) and other hospital units. The methodical system of surveillance of hospital-acquired infections (HAI) is not available in Russia and there is no reliable data about the prevalence or epidemiology of HAI. We aimed in this pioneer study to determine the prevalence, epidemiological and microbiological characteristics, risk factors, clinical value and outcomes of HAI in different units of emergency multifields hospitals of Russia. METHODS: This prospective multicentre 1-day prevalence study with 28-days follow-up was realized between January and May 2013. Thirty two emergency hospitals with more than 500-beds from 18 cities participated in this study. The study was conducted separately on 5 different days in ICU, therapeutic, surgical, urology and neurology units. All patients treated in the unit on the day of the study were examined for the presence of HAI according to CDC criterias. Risk factors of HAI, nosological and etiological structure, susceptibility of pathogens were also evaluated. RESULTS: Totally 3809 patients were included in the study during 5 days of investigation in ICU and therapeutic, surgical, urology and neurology units (respectively 449, 1281, 1431, 342 and 306 patients). The total number of registered HAI was 290 and the prevalence of HAI was 7.61% (95% CI 6.81%, 8.50%). The greatest rate of HAI was registered in ICU (26.28%) and neurological unit (13.73%); the rate was lower in therapeutic, surgical and urology units (4.76, 4.12 and 2.92%). The prevalence of HAI.was similar in adult and pediatric hospitals .(7.62 and 7.54%). The prevalence of community-acquired infections was 28.53%. The lower respiratory tract was the most common site of infection, accounting for 42.4%.of HAIs followed by the urinary tract (19.0%), skin and soft tissue (13.4%), abdomen (11.4%) and intravascular (4.8%). 311 pathogens were isolated: 58.8% of isolates were gram-negative, 32.8% gram-positive, and 8.4% Candida spp. The most common bacterial isolates were Klebsiella spp. (19.6%), E.coli (12.2%), S.aureus (11.3%), Acinetobacter spp. (10.9%), E.faecalis (7.4%) and P.aeruginosa (7.1%). The resistance rate of E.coli and Klebsiella spp. to 3rd generation of cephalosporins was 60.5 and 95.1%. Only 26.5% of Acinetobacter isolates and 59,1% of P.aeruginosa isolates were susceptible to imipenem. The MRSA rate was 48.6%; 17,4% of E.faecalis were resistant to ampicillin. The mortality rate was higher in patients with HAI (16.5%) than in patients without HAI (3.0%); the mean length of hospital stay was also higher in patients with HAI (24.6±11,4 vs. 16.2±15,3 days). CONCLUSION: The prevalence of HAI in Russian hospitals is high. According to the prevalence data the estimating annual number of HAI in Russia is approximately 2,300,000 cases. The multi-drug resistant microorganisms were dominated among causative agents of HAI.

[Characteristics of ertapenem use in critical state patients].

Characteristics of the use of ertapenem, a beta-lactam antibiotic of the carbapenem group, are discussed.

[Actual aspects of sepsis].

Cases of sepsis with bacteriemia detected in the S. P. Botkin State Clinical Hospital within 2000-2007 were analysed. The sources of the bacteriemia, the etiological pattern of the pathogens and their susceptibility to antibacterials were estimated. The study enrolled 256 patients with sepsis. The antibiotic susceptibility of 227 isolates from the blood samples was tested. More than a half of the infection sources was detected in the organs of the respiratory tract and abdominal cavity. All the grampositive pathogens were susceptible to vancomycin and linesolid. The overwhelming majority of the enterococcal isolates proved to be susceptible to carbapenem and cefepim.

[Multicentre study of comparative efficacy of meropenem and combined regimens for empirical antibacterial therapy of severe nosocomial infections: results of clinical and pharmacoeconomic analysis].

Adequacy and effectiveness of empirical antibacterial therapy of severe nosocomial infections with meropenem vs. combined regimens of antibacterial therapy were investigated and the ratio of the cost and effectiveness of the compared regimens was evaluated. A prospective, randomized, open, comparative study of two initiative regimens of empirical antibacterial therapy of severe nosocomial infections was performed: meropenem in a daily dose of 1.5-3 g and the standard regimen with the use of betalactams and fluoroquinolones in combination with aminoglycosides and/or metronidazole. Patients with recorded diagnosis of nosocomial pneumonia (including the ventilator-associated one) or abdominal infection with the signs of severe sepsis and severity of APACHE II > 14 were enrolled. The patients were stratified into 2 groups subject to the disease severity, i.e. APACHE II 15-20 and APACHE II 21-25. One hundred thirty five out of 166 patients with recorded nosocomial infection were included into the final estimate of the therapy adequacy and effectiveness (Protocol Analysis): 62 patients were treated with meropenem and in the treatment of 73 patients the standard antibacterial therapy was used. In the group of the patients treated with meropenem there were stated significantly higher clinical effectiveness (recovery in 80.6% of the patients vs. the control of 46.6%, p < 0.01) and pathogen eradication (89.6 and 48.1% respectively, p < 0.01). The difference in the clinical and bacteriological effectiveness of meropenem and the standard therapy was more evident in the subgroups of more severe patients (APACHE > 20). With the use of meropenem the probability of recovery from nosocomial infection was significantly higher (RR 1.73-1.94, p < 0.001) vs. the control. Meropenem provided significantly higher eradication of the pathogens: P. aeruginosa (88 and 40% respectively, p = 0.007), E. coli (100 and 46.7%, p = 0.003), Acinetobacter spp. (90.9 and 40%, p = 0.02). The antibacterial therapy with the use of meropenem was assessed as adequate in 51 out of 56 patients (91.1%), that was 3 times as frequent as with the use of the standard antibacterial therapy (33.9%). The cost-effectiveness coefficient with the use of meropenem was 2.2 times lower vs. the control. Therefore, the empirical therapy of severe nosocomial infections with meropenem proved to be more adequate and from the economic viewpoint more advantageous vs. the standard combined regimens of antibacterial therapy, that was evident from significantly higher clinical and bacteriological efficacy of the treatment and decrease of the terms of the patients hospitalization in intensive care units (on the average by 5 days).

[Etiology of severe hospital infections in intensive care units and antibiotic resistance of pathogens].

The leading pathogens of severe infections in intensive care units were the following: respiratory tract infections--bacteria of the famility of Enterobacteriaceae (33.8%), Pseudomonas spp. (24.9%), Acinetobacter spp. (18.1%), Staphylococcus aureus (16.0%), blood flow infections--coagulase negative staphylococci (33.6%), S. aureus (26.1%), Enterobacteriaceae (17.6%), wound infections--Enterobacteriaceae (35.7%), coagulase negative staphyloccocci (17.8%), Pseudomonas spp. (14.3%). As for various species of Enterobacteriaceae, susceptibility was preserved in 91-100% of the isolates to meropenem, in 72-100% to cefoperazone/sulbactam, in 51-65% to cefepime, in 72-86% to amikacin, and in less than 50% to cephalosporins and fluoroquinolones. As for P.aeruginosa, 28% of the isolates was resistant to all the antibacterials, except polymyxin. The highest susceptibility to cefoperazone/sulbactam and meropenem was revealed in the isolates of Acinetobacter baumannii. Oxacillin resistance was detected in 64.9% of the S.aureus isolates. The oxacillin resistance as a rule was associated with resistance to macrolides, aminoglycosides and fluoroquinolones. As for coagulase negative staphylococci, oxacillin resistance was stated in 75.6% of the isolates. All the isolates of the Staphylococcus spp. preserved their susceptibility to vancomycin and linezolid.

Meningococcal disease in patients with late complement component deficiency: studies in the U.S.S.R.

The purpose of this study was to examine the occurrence of late complement component deficiency (LCCD) states in the USSR. Thirty deficient individuals were detected: 27 with C8 beta and 3 with C7 deficiency. Among individuals with a first episode of meningococcal infection, about 1% had LCCD, whereas among patients with recurrent bacterial meningitis the prevalence of LCCD rose to approximately 50%. This corresponds to a prevalence for LCCD of approximately 12 per 100,000 in the general population. The individuals with LCCD identified in this study experienced about 77 episodes of meningococcal disease and acute bacterial meningitis. Mathematical analysis of the morbidity from meningococcal disease in individuals with LCCD demonstrated that the probability of disease did not change with the age of the patient and was not affected by prior episodes of infection. This finding suggest that in contrast to the situation in the general population, prior infection fails to protect the deficient individual from recurrent disease. In comparison to complement-sufficient persons, the course of disease in individuals with LCCD is less severe, as shown by a reduction in the number of episodes of endotoxic shock and mortality as well as their more rapid recovery. These findings suggest that exuberant complement activation and concomitant formation of membrane attack complexes during meningococcal infection in complement-sufficient patients plays an important role in the activation and injury of peripheral blood cells and endothelial cells during endotoxic shock.

[A clinical and pathothysiological study of protein C in patients with generalized meningococcosis]. / Kliniko-patofiziologicheskoe issledovanie proteina C u bol'nykh s generalizovannoi formoi meningokokkovoi infektsii.

The clinical-and-pathogenetic significance of protein C was dynamically investigated within the infection processes in 23 patients (mean age 44 years) with meningococcemia. A reliably lower concentration of protein C in blood plasma (mean 37.8%) was registered versus the normal parameters (N = 70-130%) at exacerbation irrespective of a disease outcome. Leyden mutation was detected in 30.5% of patients. The presence of the above genetic defect denoted a predisposition to a severe disseminated intravascular coagulation (DIC) syndrome in patients of the studied group. A lower concentration of protein C was detected in blood plasma of patients with meningococcemia; it correlated with severity of the infection process and with the development of organic malfunction. The study of the concentration of protein C enabled an evaluation of the functional condition of anticoagulation mechanisms in the DIC development and can be regarded as an important extra criterion for the evaluation of thrombohemorrhagic syndrome in patients with meningococcemia.

[Clinical features of meningococcal infection in subjects with deficient terminal components of complement]. / Klinicheskie osobennosti meningokokkovoi infektsii u lits s defitsitom terminal'nykh komponentov komplementa.

AIM: To evaluate clinical characteristics of meningococcal disease (MD) in individuals with terminal complement component deficiency (TCCD) who are thousands times more susceptible to MD than complement-sufficient persons. MATERIALS AND METHODS: 61 cases of MD in TCCD patients and 200 randomly selected cases of MD in complement-sufficient patients were analyzed. RESULTS: Meningitis without meningococcemia accounted for 17% of the MD episodes in the control group of complement-sufficient patients but none in individuals with TCCD who had meningococcemia (10%) or meningococcemia with meningitis (90%). Moderate disease predominated in patients with TCCD (70%) and no episodes of fatal disease were noted, whereas severe disease was more common in the control group which had an 8% case fatality rate and frequent complications such as endotoxic shock (15% of episodes) and brain edema (26%). The severity of the disease in TCCD patients did not differ between the first and subsequent episodes, between males and females, between episodes caused by serogroup A and B meningococci, etc. CONCLUSION: In comparison to complement-sufficient persons, the course of the disease in patients with TCCD is statistically less severe.

[Hemosorption in infectious pathology]. / Gemosorbtsiia pri infektsionnoi patologii.

Hemosorption was used for the treatment of 152 patients with purulent meningitis, sepsis complicated by shock, virus hepatitis and leptospirosis. A favorable effect of hemosorption in infections was based on highly effective correction of microcirculatory disorders as a result of the removal of high molecular substances of microbic and endogenous origin.

[Role of hemosorption in the therapy of infectious toxic shock and the multiple-organ failure syndrome in a fulminating form of meningococcemia]. / Rol' gemosorbtsii v terapii infektsionno-toksicheskogo shoka i sindroma poliorgannoi nedostatochnosti pri molnienosnoi forme meningokokktsemii.

Hemoperfusion was applied to the treatment of 20 patients with fulminant meningococcemia complicated by the infectious-toxic shock, stage III, and the polyorgan insufficiency syndrome. Ten patients recovered while the remaining 10 died mainly because of irreversible lesions of the vitally important organs: kidneys, adrenals, heart and brain. In the deceased patients, the prehospital stage had lasted two times longer than in the convalescents. All the patients had received antishock therapy: correction of acidosis, artificial ventilation of the lungs, dopamine, pharmacological doses of steroids and protease inhibitors as well as moderate infusion therapy. Hemoperfusion was instituted immediately after elimination of arterial hypotension. The use of hemoperfusion promoted the abatement of systemic toxicosis and neurotoxicosis, the recovery and stabilization of the hemodynamics, improvement of rheological properties of the blood, the recovery of effective tissue perfusion, the lowering of specific antigenemia and blood toxicity, and elimination of the pathological protein complexes from the circulating blood.

[The results of a multicenter study of the comparative activity of cefepime and other antibiotics against the causative agents of severe hospital infections (the Micromax program)]. / Rezul'taty mnogotsentrovogo issledovaniia sravnitel'noi aktivnosti tsefepima i drugikh antibiotikov v otnoshenii vozbuditelei tiazhelykh gospital'nykh infektsii (programma "Micromax").

A multicentre trial was performed on the activity of cefepime in comparison with ceftazidime, ceftriaxone, piperacillin/tazobactam, imipenem and ciprofloxacin against severe hospital infection pathogens in intensive care units. The isolates of Escherichia coli and Proteus spp. from the majority of the centres were highly susceptible to the antibiotics (90 to 100 per cent of the isolates). In some centres up to 40 per cent of the isolates produced ESBL. The isolates of Klebsiella spp. were characterized by lower susceptibility, in some centres the frequency of the strains producing ESBL exceeded 90 per cent, by the MIC geometric mean cefepime was superior to the third generation cephalosporins, the frequency of resistance to ciprofloxacin ranged from 0 to 31 per cent, no resistance to imipenem was recorded. The frequency of resistance to the third generation cephalosporins and piperacillin/tazobactam in Enterobacter spp., Serratia spp., Citrobacter spp., Morganella spp., and Providencia spp. ranged from 10 to 52 per cent, the resistance to cefepime equaled 0-11 per cent, 0 to 17 per cent of the isolates were resistant to ciprofloxacin, some isolates were resistant to imipenem. As for the nonfermenting microorganisms their resistance to all the antibiotics tested was comparatively high and markedly differed in various centres. As a whole, 7 per cent of all the isolates of the nonfermenting organisms was resistant to cefepime, 10 per cent was resistant to imipenem, 17 per cent was resistant to ceftazidime, 21 per cent was resistant to piperacillin/tazobactam and 36 per cent was resistant to ciprofloxacin.

[Prognosis in meningococcal disease: methodology and practice]. / Prognozirovanie iskhoda meningokokkovoi infektsii: metodologiia i praktika.

78 patients with systemic meningococcal disease admitted to the Intensive Care Unit of the 2nd Moscow Hospital for Infectious Diseases were studied and the composite prognostic score was developed to estimate the risk of lethal outcome. The stepwise variable selection procedure for the multiple logistic regression was applied to 30 potential clinical and laboratory risk factors and markers. Five factors were selected for the score, namely the platelet count (< 150 x 10(6)/ml), the presence of hemorrhages into the eye or mucosal tissue, the interval from the last urination before admission (> 4 h), the respiration rate (> 170% of age-adjusted normal value) and age (< 2 or > 65 years) with regression coefficients 0.3, 0.2, 0.2 and 0.1, respectively. Both for the source clinical group and for the additional test group (64 patients), the scale was able to classify correctly 95% of cases using the data collected at admission. Ten prognostic scores proposed previously by foreign investigators were tested in the same patients and the best four scores were selected (GMSPS, Gedde-Dahl, Niklasson, Kahn); the scores classified correctly 85-90% of cases. This study is an example of methodological approaches to prognostic score construction in medicine.

[The interconnection between the severity of meningococcal infection and the endotoxicity levels and patient's blood complement]. / Sviaz' tiazhesti techeniia meningokokkovoi infektsii s urovniami éndotoksina i komplementa v krovi bol'nykh.

Seventy-eight patients with severe systemic meningococcal disease admitted to the Intensive Care Unit of the Second Moscow Hospital for Infectious Diseases were divided into four groups by complications of their disease: patients with refractory septic shock (RSS)--group 1; patients with early septic shock (ESS)--group 2; patients without shock but with severe mental disorders--group 3; patients without any of these complications--group 4. The LPS concentration in plasma was assessed by chromogenic method. Initial LPS levels in plasma of group 3 or group 4 patients (170 ng/l, median value and 360 ng/l, respectively) were greater than those of healthy donors (LPS < 15 ng/l). LPS concentration was significantly greater in group 2 (920 ng/l) or group 1 (12,400 ng/l). LPS levels declined exponentially in all the patients. The half-life was calculated to be 1.4 (+) -0.3 h. In group 2 and 1, respectively, the classical pathway complement activity in patients' serum was 50 and 10% of normal control values. To estimate significant prognostic factors for fatality in our patients, specificity and factor fatality difference of various clinical and laboratory factors were calculated. The cut-off LPS value for development of ESS was 600 ng/l and that for development of RSS and death was 8000 ng/l. For the prediction of fatality using the former cut-off value of LPS, sensitivity was 84% and specificity 100%. Using plasma complement activity (cut-off--15% of normal value) for prediction, sensitivity was 75% and specificity was 100%. Other factors (platelet and WBC count, blood pH, BP, etc.) had lower predictive power. Thus to date plasma endotoxin level and complement activity are the best prognostic factors in meningococcal disease.

[Hemodynamics and rheologic properties of the blood in meningococcemia associated with meningitis and complicated by septic shock and intracranial hypertension]. / Gemodinamika i reologiia krovi pri meningokoktsemii v sochetanii s meningitom, oslozhnennykh razvitiem septicheskogo shoka i vnutricherephoi gipertenzii.

Central hemodynamic parameters characterizing cardiac contractility and peripheral resistive vascular tone, as well as blood aggregation ability, its structural and dynamic viscosity have been assessed by dynamic (disease duration up to 15 days) and complex studies in 28 patients with septic shock of meningococcal etiology accompanied by signs of meningitis. All the patients revealed signs of intracranial hypertension caused by the onset of acute hydrocephaly or brain edema. It has been demonstrated that on entry all the patients were characterized by the combination of low cardiac output syndrome and second degree high or low blood viscosity. In addition to endotoxemia, acute intracranial hypertension that enhances the afterload and blood viscosity abnormalities are involved in the development of hemodynamic disturbances. Over the whole observation period elevated intracranial pressure had a certain effect on central hemodynamics, changing according to the mechanism similar to that observed in Cushing's syndrome. In addition, central hemodynamics and blood viscosity are directly or indirectly (via affected CNS) influenced by Herpes infection developing on days 2 to 5 of the disease.