Contemporary Therapeutic Options In Carbapenem-Resistant Non-Fermenters In Bulgaria

Резюме:Въведение: Неферментиращите бактерии с клинично значение Acinetobacter baumannii и Pseudomonas aeruginosa, обичайно считани за опортюнистични патогени, днес заплашват да се превърнат в едни от най-проблемните причинители на инфекции. Терапевтичните рестрикции от една страна се дължат на тяхната вродена резистентност към широк набор от антибиотици, a от друга на все по-нарастващата придобита резистентност.Цел: Да се анализират най-честите механизми на карбапенемна резистентност сред неферментиращите бактерии в страната и да се препоръчат опции за справяне с терапевтичните рестрикции.Методи: Обикновено се използват както фенотипни, така и генетични методи за определяне на резистентност към карбапенеми. Най-чести фенотипни методи за детекция на карбапенемази при неферментиращите бактерии са Модифицираният Ходж тест и Carba NP-тестът. Класически PCR се използва за доказване на гени, кодиращи карбапенемази, a qRT-PCR за оценка на експресията на ключови ефлукс помпи, вродената AmpC и трансмембранния OprD рецептор при Pseudomonas.Резултати и обсъждане: Две независими проучвания в България доказаха, че свръхекспресията на MexXY-OprM ефлукс помпата е главна причина за карбапенемна резистентност при изолатите P. aeruginosa. При A. baumannii продукцията на OXA-23 карбапенемази е основен фактор за този тип резистентност. Най-новите терапевтични стратегии включват използването на сулбактам при лечение на инфекции, причинени от OXA-23 продуциращи A. baumannii, поради липсата на активност на тези карбапенемази към сулбактам, както и поради вроден ефект на този бета-лактамен инхибитор при род Acinetobacter. На базата на анализирания опит в страната и света, както и на собствени проучвания, считаме, че антибиотични комбинации с колистин, рифампицин и фосфомицин могат да бъдат подходяща алтернатива при инфекции, причинени от двата микроорганизма: Pseudomonas and Acinetobacter.Introduction: The non-fermenters of clinical significance Acinetobacter baumannii and Pseudomonas aeruginosa, usually considered as opportunistic pathogens, nowadays emerge to evolve in some of the most problematic causative agents of infections. The therapeutic restrictions are determined on one hand due to their intrinsic resistance to a great variety of antibiotics and on the other, due to the arising acquired resistance.Aim: The aim of this article is to analyze the most often detected mechanisms of carbapenem resistance among non-fermenters in the country and to recommend options to manage the therapeutic restrictions.Methods: Both methods - phenotypic and genetic, are usually combined to evaluate the mechanisms of resistance to carbapenems. As phenotypic tests for detection of common carbapenemases a Modified Hodge test and a Carba NP-test are used. A classical PCR investigation is used to detect the most frequent carbapenemases for both microorganisms and a qRT-PCR to assess the expression of main efflux pumps, the intrinsic AmpC and the transmembrane receptor OprD in Pseudomonas.Results and Discussion: Two independent studies proved that in Bulgarian clinical isolates P. aeruginosa, the increased expression or overexpression of MexXY-OprM efflux pump, is the main mechanism of determining carbapenem resistance. The main reason for carbapenem resistance in A. baumannii isolates is the production of OXA-23 carbapenemases. The newest therapeutic strategies include the use of sulbactam for infections provoked by OXA-23 producing A.baumannii due to the lack of activity of these carbapenemases against it and the intrinsic effect of this beta-lactamase inhibitor against Acinetobacter spp. Antibiotic schemes including colistin, rifampicin and phosphomycin could be an appropriate alternative for infections provoked by both Pseudomonas and Acinetobacter

BIOLOGICAL ACTIVITY OF BULGARIAN FOLIA BETULAE DRY EXTRACT

Objective: The aim of this study was to investigate the biological activity of dry Folia Betulae (FB) extract.Methods: Extracts from birch leaves were obtained by different technological methods–maceration and percolation, extraction with different concentrations of ethanol, changes in temperature regimen. The influence of the technological factors on the content of the biologically active substances (BAS) was examined. A phytochemical characterization of the extracts and their standardization were made, according to important groups of BAS–flavonoids (rutin, quercetin) and terpenes (betulin and betulinic acid), by means of HPLC methods for detection and quantitative determination. A model extract, with optimal content of BAS was chosen for subsequent in vitro investigation of its biological activity. Antimicrobial activity was studied via in vitro tests using bacterial isolates–Staphylococcus aureus, Escherichia coli and Candida albicans. The physiological activity was investigated by using in vitro test with smooth muscle strips. The antiproliferative activity of FB extract on eukaryotic cells was examined on cell cultures in vitro. Two cell cultures were used: the mouse lymphoma cell line L5178Y and the serum-free McCoy-Plovdiv cells.Results: The dry extract from FB has a dose–dependent antibacterial effect. The bactericidal effect on Staphylococcus aureus is stronger than the one on Escherichia coli. Results prove that adding the extract leads to stimulating effect on muscle contractility. It demonstrates biological activity, expressed as changes in cell morphology, proliferation and vitality as well as initiation of apoptosis.Conclusion: The results obtained largely overlap with literature data and explain some of the applications of this plant in traditional medicine.Â

Desmoglein autoantibodies and disease severity in pemphigus patients – correlations and discrepancies

Aim: To assess the correlation between the levels of anti-desmoglein-1 and anti-desmoglein-3 autoantibodies and disease severity in pemphigus patients. Materials and methods: Thirty-eight pemphigus patients aged 30 to 87 years were included in the study. All patients underwent clinical examination, pemphigus disease zone index assessment, histopathological and direct immunofluorescence tests, and assessment of desmoglein-1 and desmoglein-3 autoantibodies by enzyme-linked immunosorbent assay. Results: Twenty-eight out of 38 serum samples exceeded the cut-off value of anti-desmoglein-1, and 26 of 38 sera had positive anti-desmoglein-3 antibodies. One serum from 38 controls had positive anti-desmoglein-1 antibodies. Seven (18.4%) patients experienced a mild course of the disease, 16 (42.1%) patients experienced moderate, and 15 (39.5%) patients suffered from severe pemphigus. A significant correlation between disease severity and both autoantibody levels was observed, but there were exceptions. Conclusions: There is a significant correlation between anti-desmoglein antibodies and disease severity in the entire group, but there are also discrepancies in some cases

Primary immunodeficiency screening in an infant with cytomegalovirus disease reveals HIV infection

Cytomegalovirus is widely spread worldwide, and it is not uncommon for it to complicate the congenital human immunodeficiency virus (HIV) disease as an acquired or congenital coinfection. However, the association of the two infections is not common amongst infants with primary immune deficiencies. We describe a case of a 6-month-old infant with acquired cytomegalovirus and HIV infections, diagnosed in the course of the patient’s clinical and laboratory workup for a presumed primary immunodeficiency. To date, this is the first reported case of such a combination in a child from Bulgaria

Fatal Chemotherapy-induced Combined Infection in a Hodgkin’s Disease Patient: a Case Report

Multimodal therapy, used for the treatment of patients with Hodgkin’s disease (HD), makes them prone to life-threatening infections, attributed mainly to febrile neutropenia. Herein, we present a case report of fatal combined bacterial and viral infection in a 49-year-old female patient, subject to polychemotherapy for HD. Rapid microbiological diagnosis performed by multiplex polymerase chain reaction elucidated the causes of the infection within hours. Listeria monocytogenes was detected in both the cerebrospinal fluid and blood samples. Nasopharyngeal swabs returned positive for two swine-derived strains of influenza A virus. We aimed to emphasize the importance of these pathogens and draw attention to their association in the aetiology of infections among patients receiving chemotherapy. In conclusion, better surveillance is needed to improve the early diagnosis of infectious complications in these patients

A study of flavonoid composition and antimicrobial activity of Scutellaria altissima L. from different floristic regions of Bulgaria

Introduction: Scutellaria extracts and its constituents, especially the characteristic flavonoids such as baicalein and its glycoside baicalin, exhibit significant antimicrobial activity. Aim: To perform a comparative analysis of flavonoid composition and antimicrobial activity of extracts obtained from aerial parts and roots of Scutellaria altissima from the regions of Mezek and Bachkovo, Bulgaria. Materials and methods: 70% ethanol and aqueous extracts of aerial parts and roots of S. altissima were used. HPLC analysis of S. altissima extracts was performed. Microbiological tests were done on clinical isolates of Streptococcus mitis, Staphylococcus aureus, Escherichia coli, and Candida albicans. Minimal bactericidal and minimal bacteriostatic concentrations of S. altissima extracts were determined by the agar method. Results: The ethanol extracts contain flavonoids approximately twice as much in comparison with the aqueous extracts. The baicalin content in the aerial parts of S. altissima from the region of Mezek is 5 times higher than that in the roots. S. altissima extracts have effective antimicrobial activity against S. mitis only. The minimal bactericidal concentration of ethanol extracts of S. altissima aerial parts and S. altissima roots is 2000 µg/ml and 8000 µg/ml at 24 hours, respectively. The bactericidal effect of aqueous extracts occurs at 48 hours at minimal bactericidal concentration of S. altissima aerial parts – 2000 µg/ml and of S. altissima roots – 6000 µg/ml. Conclusions: The finding that extracts of Bulgarian S. altissima possess effective antimicrobial properties against S. mitis suggests that it can be used as a potential source for the development of natural antimicrobial agents to suppress oral pathogens and prevent some oral infections

Correlation between CGRP Levels and the Neuropathic and Inflammatory Component of Postoperative Pain

Introduction: In surgical procedures, tissue damage results in the release of a number of bioactive substances. Calcitonin gene-related peptide (CGRP) is a peptide released from sensory nerves, which determines its role in pain sensation. Its distribution in tissues deter­mines its role as a primary afferent neurotransmitter.Aim: To determine the effect of CGRP on postoperative pain and reactive inflammatory process after surgical removal of impacted mandibular third molars, as well as the factors that have influence upon the perception of pain.Materials and methods: Forty patients with bilaterally impacted mandibular third molars were included in the study. Venous blood samples were collected before and 24 hours after the surgical procedure in order to test their serum levels of CGRP and procalcitonin. Two weeks later the procedure was repeated. The difficulty of the surgical procedure, its duration and complications were assessed in all patients.Results: The influence of some of the studied factors upon postoperative pain was established. Differences in the sensation of pain between the two sexes were found when comparing pain intensity reported by the patients. Significant difference between pain inten­sity after the 1st and 2nd surgical procedures (6 hours) was found in females (Z=2.63, p=0.009;), whereas in males the difference was observed at 24 hours (Z=1.99; p=0.047).Regarding the existence of sex-related association, а significant, strong positive correlation between CGRP levels after the 1st and 2nd surgical procedures (24 hours) was found in males (rxy=0.78; p=0.004), whereas in females this correlation was also significant, although moderately significant (rxy=0.44; p=0.020). CGRP levels at the first and second extractions were generally similar in males, and not as much in females. We proved significantly moderate positive association between CGRP and pulse levels measured before the second surgery (rxy=0.37, p=0.021).Conclusion: The results of our study suggest a significant role of CGRP in reactive (neurogenic) inflammation

CHANGES IN SERUM LEVELS OF IL-6 IN THE EARLY POSTOPERATIVE PERIOD AFTER PREEMPTIVE ANALGESIA WITH NIMESULIDE, METAMIZOLE SODIUM AND PLACEBO IN REMOVAL OF IMPACTED MANDIBULAR THIRD MOLARS

Abstract Objective: The objective of this study is to determine the change in IL-6 serum levels in patients undergoing preemptive analgesia and surgical removal of an impacted mandibular third molar. Study Design: This is a prospective, double-blind, placebo-controlled study in 80 patients who had an atypical extraction of an impacted mandibular third molar. Results: After surgical removal of impacted mandibular third molars, elevated levels of IL-6 in the early postoperative period were found, and the highest level was 14 pg/ml. Conclusion: Postoperative IL-6 levels rise regardless of the medication used for preemptive analgesia. In the group treated with nimesulide, a trend to reducing IL-6 levels was observed, but further study in a larger number of patients is needed

Platelet-rich plasma efficacy in alopecia areata patients with normal and elevated levels of antibodies against thyroglobulin and thyroid peroxidase

Aim: To evaluate and compare the efficacy of platelet-rich plasma (PRP) therapy in alopecia areata (AA) patients with normal and with elevated levels of anti-thyroglobulin antibodies and/or anti-thyroid peroxidase antibodies. Materials and methods: The study included 30 AA patients divided into two groups: AA patients with normal (Group 1) and with elevated antithyroid antibodies (Group 2). PRP was applied in three consecutive monthly sessions. Treatment results were evaluated by clinical photography, assessment of scalp hair, trichoscopy, and assessment of patients’ quality of life. Results: The mean age of patients was 42.10 years, 23 (76.6%) patients were with normal and seven (23.3%) were with elevated antithyroid antibodies. Eleven (50%) patients from Group 1 had significant hair growth, of which ten with AA partialis (45.5%), one with AA reticularis (4.6%). Two patients with alopecia reticularis and two with alopecia totalis had insignificant hair growth. Worsening was found in four patients with alopecia reticularis and alopecia totalis. In Group 2 one patient with alopecia partialis (14.3%) had a significant hair growth, five patients with alopecia reticularis and one with alopecia totalis had insignificant hair growth, and none of the patients worsened. Conclusions: PRP therapy was effective in patients with mild to moderate form of AA and most had normal antithyroid antibodies. Patients with severe AA, AA ophiasis and alopecia totalis, with normal and elevated antibodies, did not benefit from PRP therapy