The use of 4-Hexylresorcinol as antibiotic adjuvant.

Ever decreasing efficiency of antibiotic treatment due to growing antibiotic resistance of pathogenic bacteria is a critical issue in clinical practice. The two generally accepted major approaches to this problem are the search for new antibiotics and the development of antibiotic adjuvants to enhance the antimicrobial activity of known compounds. It was therefore the aim of the present study to test whether alkylresorcinols, a class of phenolic lipids, can be used as adjuvants to potentiate the effect of various classes of antibiotics. Alkylresorcinols were combined with 12 clinically used antibiotics. Growth-inhibiting activity against a broad range of pro- and eukaryotic microorganisms was determined. Test organisms did comprise 10 bacterial and 2 fungal collection strains, including E. coli and S. aureus, and clinical isolates of K. pneumoniae. The highest adjuvant activity was observed in the case of 4-hexylresorcinol (4-HR), a natural compound found in plants with antimicrobial activity. 50% of the minimal inhibitory concentration (MIC) of 4-HR caused an up to 50-fold decrease in the MIC of antibiotics of various classes. Application of 4-HR as an adjuvant revealed its efficiency against germination of bacterial dormant forms (spores) and prevented formation of antibiotic-tolerant persister cells. Using an in vivo mouse model of K. pneumoniae-induced sepsis, we could demonstrate that the combination of 4-HR and polymyxin was highly effective. 75% of animals were free of infection after treatment as compared to none of the animals receiving the antibiotic alone. We conclude that alkylresorcinols such as 4-HR can be used as an adjuvant to increase the efficiency of several known antibiotics. We suggest that by this approach the risk for development of genetically determined antibiotic resistance can be minimized due to the multimodal mode of action of 4-HR.

Prevalence and Antibiotic Resistance of Carbapenemase-Producing Gram-Negative Bacteria in Saint Petersburg and Some Other Regions of the Russian Federation.

Carbapenemase-producing gramnegative bacteria, which hydrolyze most offi-lactams, including carbapenems, is of global health care system threat. The number of the known carbapenemases is constantly increasing, however only four types are widely distributed: NDM-type, KPC-type, OXA-48-type and VIM-type. The frequency of carbapenemase-producing Klebsiellapneumoniae in hospitals of Saint Petersburg reached 9.2% (5.9% for NDM-type, 1.4% for OXA-48-type, 1.9% for NDM-type + OXA-48-type). Carbapenemase producers were also detected in hospitals of Moscow, Yekaterinburg, Vologda, Murmansk, Kurgan, Krasnoyarsk, Izhevsk, Krasnodar and Perm. In total 281 carbapenemase producers were recorded within 2011-2016, which were isolated from infected or colonized patients (K.pneumoniae - 247 isolates, Acinetobacter spp - 29 isolates, Enterobacter cloacae - 2 isolates, Serratia marcescens - 1 isolate, Escherichia coli - 1 isolate and Proteus mirabifis - 1 isolate). The carbapenemase-producing K.pneumoniae isolates were distinguished by considerable genetic diversity, the NDM-type carbapenemase-producers belonged to eight, KPC-type - to three and OXA-48-type - to four different sequence-types (STs) respectively. The representatives of the globally dominant genetic line, Clonal Group 258 (CG258), and also a number of the less common lines (ST147, ST273, ST307 and ST377) were detected. The K.pneumoniae strains were distinguished by a high frequency of cross-resistance and the associated resistance to antibiotics of different groups. The frequency of resistance to cephalosporins and fluoroquinolones reached 100%. Among the NDM-type carbapenemase producers the frequency of resistance to aminoglycosides exceeded 90%, among the KPC-type carbapenemase producers the frequency of resistance corresponded to 66% for amikacin and 93% for gentamicin, among the OXA-48 type carbapenemase producers the frequency of resistance was even lower (50% and 73% respectively). Approximately 80% of the NDM-type, 90% of the KPC-type and only 60% of the OXA-48-type carbapenemase producers showed a high level of resistance to imipenem and meropenem. The frequency of resistance to tigecycline varied within 6.7% to 14.8% and the frequency of resistance to polymyxin was within 4.2% to 20%. The OXA-40- and OXA-23-types carbapenemase-producing Acinetobacter spp. remained susceptible only to polymyxin. It is obvious that the possibility of antibacterial therapy of infections caused by carbapenemases producers is limited.

[Discovery of Genetic Markers of Resistance to ß-Lactams in Gramnegative Microorganisms by PCR Diagnosis].

Fifteen specimens of the hemoculture and 89 specimens of the broncho-alveolar lavage were used in the study. Monocultures of gramnegative bacteria resistant to cefotaxime, cefepime, imipenem and meropenem were isolated from the specimens. The PCR method with detection of the results in the real time regimen (PCR test-system Litekh) provided detection of the beta-lactamase genes: bla(CTX-M-like) (72/104, 69.2%), bla(NDM) (6/104, 5.8%), bla(VIM) (49/104, 47.1%) and bla(OXA48-like) (59/104, 56.7%). There was identified correlation between the phenotype of resistance of Acinetobacter spp., Pseudomonas aeruginosa, Klebsiella pneumoniae and Escherichia coli to cefotaxime and carbopenems and detection of the bla(CTX-M-like) and bla(NDM) genes. At the same time, up to 70% of the K. pneumoniae isolates from the biological specimes positive with respect to the presence of the carbapenase bla(VIM) and bla(OXA48-like) genes demonstrated their phenotypic susceptibility to carbopenems. The results of the study confirmed the prognostic value of the genetic diagnosis for improvement of the routine bacteriological investigations.

[The first experience of endovideosurgical treatment of organic hyperinsulinism].

In connection with the development of endovideosurgical technologies, they are actively used for the treatment of organic hyperinsulinism. The robotized interventions have been applied in the last years. The experience of the laparoscopic and robotized operations performed on 7 patients with established diagnosis of organic hyperinsulinism was shown by the authors. The treatment was effective in all cases. The postoperative period was without complications in majority of patients. An acute postoperative pancreatitis with formation of acute liquid accumulation occurred in one case. This case required the performing of percutaneous puncture interventions using ultrasonics control. Thus, the application of endovideosurgical technologies was accompanied by low percent (14%) of postoperative complications.

[Pharmacological protection of the myocardium with reamberin in coronary artery bypass grafting in patients with postinfarction angina].

AIM: To assess efficacy of reamberin in preoperative preparation and after coronary bypass (CB) in patients with macrofocal myocardial infarction (MI) complicated with postinfarction angina. MATERIAL AND METHODS: A total of 45 patients with Q-positive MI complicated with postinfarction angina pectoris entered the trial. The study group consisted of 20 (44.4%) patients given 200-400 ml injections of 1.5% reamberin solution for 3 days before coronary artery bypass grafting (CABG) and 3-5 days after it. The control group consisted of 25 (55.6%) patients given basic therapy without cardioprotection. ECTG-60, echocardiography, CM-ECG, laboratory tests were made before CABG. CABG was made in conditions of artificial blood circulation in all the patients. RESULTS: Clinical stabilization was observed after direct myocardial revascularization in hospitalized 25 (100%) patients of the study group and 22 (88%) patients of the control group. Early postoperative acute cardiac failure (ACF) developed in 3 (12%) patients from the study group and 9 (36%) from the control group (p = 0.04), arrhythmia occurred in 2(8%) and 8(32%) patients, respectively (p = 0.03). Two (8%) control patients died in early postoperative period from acute cardiac failure. Perioperative MI occurred in 2(8%) control patients. After 12 months of the follow-up, patients of the study group had no recurrent angina pectoris, while among the controls 4(16%) patients had recurrent angina of FC III. After surgical intervention at discharge and 12 months after treatment patients of both groups improved systolic and diastolic functions of the left ventricle. Normalization of the diastolic function was registered in 80% patients of the study group (p < 0.001) and in 44% from the control group (p < 0.001) after 1 year follow-up. CONCLUSION: Reamberin reduces the number of postoperative complications, ischemic damage to the myocardium, significantly improves systolic and diastolic functions of the left ventricle.

[Hepatitis E virus antibodies in the macaques and in the personnel serving the macaques of the Adler apery].

There is evidence for the rather high detection rate of antibodies against hepatic E virus (HEV) was rather high in the macaques from the Adler apery in 1999-2005. Anti-HEV was detected in 232 (57.3%) out of 405 examined rhesus macaques (Macaca mulata) and in 16 (16%) out of 100 Java ones (M. fascicularis). The detection rate of anti-HEV ranged from 12.5 to 89.5%% among the rhesus macaques and from 5.9 to 37.5% among the Java ones. Class M anti-HEV was found only in 3 (4.3%) out of 69 Java macaques and in none of the rhesus ones. Of importance are the data of detection of anti-HEV in 3 (7.5%) out of 40 examined employees of the Research Institute of Medical Primatology, all 3 (18.8%) out of 10 employees looking after the monkeys that belonged to the highest-risk group. The epidemiological and epizootological aspects of this infection require further studies.

[Standardization of the cytological conclusions in adenomas and cancer of the rectum]. / K voprosu o standartizatsii tsitologicheskikh zakliuchenii pri adenomakh i rake priamoi kishki.

The histological patterns of 120 adenomas and 365 carcinomas of the rectum were established cytologically in accordance with the WHO Histological Classification of Tumours on the basis of morphological, cellular and functional characteristics of neoplasm differentiation. It was found that cytological methods cannot be fully relied upon in the identification of the histological pattern of adenoma. Three degrees of adenoma cell atypia are distinguished: mild, moderate and severe. The latter is more characteristic of villous tumor. The following cytological classification of rectal cancer is suggested: 1. Adenocarcinoma: (a) well-differentiated, (b) moderately-differentiated. 2. Mucinous adenocarcinoma. 3. Signet-ring cell carcinoma. 4. Squamous cell carcinoma: (a) keratinizing, (b) non-keratinizing. 5. Undifferentiated cell carcinoma. 6. Carcinoma (histologically unidentifiable).

[Clinico-electromyographic studies in compression and reflex syndromes of spinal osteochondrosis]. / Kliniko-élektromiograficheskie issledovaniia pri kompressionnykh i reflektornykh sindromakh osteokhondroza pozvonochnika.

The authors carried out electromyographic (EMG) examinations of 115 patients with the compression and reflectory syndromes of vertebral osteochondritis using superficial and needle electrodes. The use of muscular innervation schemes developed by Soviet authors has made it possible to reveal a monoradicular pathology in 32 out of 54 patients examined. It was also found that the electromyographic phenomena characteristic for the pathology of the 1st sacral radicle were more marked than those characterizing the pathology of the Vth lumbar radicle. In patients with cervical osteochondrosis, prevalent were reflectory syndromes to which diffuse EMG changes corresponded. The EMG examinations with the use of needle electrodes revealed a low-amplitude spontaneous activity, a slight deceleration of the rhythm, and a lowered amplitude of the oscillations in the affected muscle. However especially demonstrative was a prolongation of the potential of the motor units on the side of the affection. The clinical, electromyographic, and roentgenological findings taken together contribute to a more precise diagnosing of the compression and reflectory syndromes of vertebral osteochondritis.

[Retrospective evaluation of the pre-infarct period]. / Retrospektivnaia otsenka predinfarktnogo perioda.

It is shown on the basis of retrospective appraisal of the course of ischemic heart disease in 235 patients hospitalized for acute macrofocal myocardial infarction that 78% of them had a prodromal period. The prodromal symptoms corresponded to those registered by WHO as preinfarction state. It was also shown that stable ischemic changes in the ECG during dynamic examination are of vital importance in the diagnosis of a preinfarction state. Problems of the medical tactics employed in the prodromal period of acute myocardial infarction are discussed.