Defining Trimester-Specific Reference Intervals for Thyroid Hormones: Insights from a Bulgarian Monocenter Study.

Background and Objectives: Pregnancy introduces various interfering factors that, alongside individual variations, impact the assessment of thyroid function tests. This underscores the necessity of defining trimester-specific reference intervals for thyroid-stimulating hormone (TSH) levels. Differences in population characteristics, including ethnicity, socio-economic factors, iodine prophylaxis, and obesity, emphasize the need to establish trimester-specific TSH ranges for women of reproductive age in the respective region or center. The aim of the present study was to establish first- and second-trimester-specific reference intervals for TSH and free thyroxine (FT4) in a relevant pregnant population. Materials and Methods: A retrospective monocenter analysis utilized the electronic database of Ob/Gyn Hospital "Dr. Shterev", Sofia, Bulgaria. The analysis involved data from 497 pregnant and 250 non-pregnant women, all without evidence of thyroid dysfunction or a family history thereof, no indication of taking medication interfering with thyroid function, no evidence of levothyroxine treatment, and no history of sterility treatment. To establish the limits of the TSH reference range, the percentile method was applied using a bootstrapping procedure following the recommendations of the International Federation of Clinical Chemistry (IFCC). Results: Trimester-specific reference intervals for TSH and FT4 in our center were established as follows: first trimester-0.38-2.91 mU/L, FT4-12.18-19.48 pmol/L; second trimester-0.72-4.22 mIU/L and 9.64-17.39 pmol/L, respectively. We also established the normal reference range for the non-pregnant control group, which is similar to that applicable in our laboratory. Conclusions: Our results differ from the fixed limits recommended by the American Thyroid Association, European Thyroid Association, and Endocrine Society Guidelines. Following the relevant established intervals would significantly impact timely diagnosis and therapy requirements for a substantial proportion of pregnant women.

Effect of increasing doses of colchicine on the treatment of 333 COVID-19 inpatients.

BACKGROUND: Previous research done in Bulgaria demonstrated a fivefold reduction in mortality from COVID-19 with increased doses of colchicine from two hospitals in the country. We report here a further 333 cases of COVID-19 inpatients, treated with different doses of colchicine and its effect on mortality. MATERIALS AND METHODS: A case-control comparison from two additional hospitals was conducted between increased doses of colchicine and added bromhexine to standard of care (SOC) versus current SOC. Risk and odds ratio, as well as subgroup analysis, was conducted with newly reported data, alongside aggregate data from all hospital centers to determine the extent of mortality reduction in COVID-19 inpatients. RESULTS: There was a clear reduction in the mortality of inpatients with increasing doses of colchicine-between twofold and sevenfold. Colchicine loading doses of 4 mg are more effective than those with 2 mg. Despite these doses being higher than the so-called "standard doses," colchicine inpatients experienced lower mortality than SOC patients (5.7% vs. 19.53%). This mortality benefit was evident in different age subgroups, with a 4-mg loading dose of colchicine proving slightly superior to a 2-mg loading dose. Colchicine led to an overall relative risk reduction of 70.7%, with SOC patients having 3.91 higher odds of death. The safety of the doses was not different than the reported in the summary of product characteristics. CONCLUSION: Inpatients in Bulgaria with added colchicine and bromhexine to SOC achieved better clinical and mortality outcomes than those on SOC alone. These results question the World Health Organization-recommended strategy to inhibit viral replication. We posit that our treatment strategy to inhibit the Severe acute respiratory syndrome coronavirus 2 entry into the cell with inhaled bromhexine and the hyperactivated NLRP3 inflammasome with higher doses of colchicine, prevents the development of cytokine storm. The timing of the initiation of treatment seems critical.

A Comparison between Bulgarian Tanacetum parthenium Essential Oil from Two Different Locations.

Tanacetum parthenium L. (Asteraceae) is a perennial herbaceous plant with a long-standing historical use in traditional medicine. Recently Tanacetum parthenium L. essential oil has been associated with a promising potential for future applications in the pharmaceutical industry, in the cosmetics industry, and in agriculture. Investigations on the essential oil (EO) have indicated antimicrobial, antioxidant, and repellent activity. The present study aimed to evaluate the chemical composition of Bulgarian T. parthenium essential oil from two different regions, to compare the results to those reported previously in the literature, and to point out some of its future applications. The essential oils of the air-dried flowering aerial parts were obtained by hydrodistillation using a Clevenger-type apparatus. The chemical composition was evaluated using gas chromatography with mass spectrometry (GC-MS). It was established that the oxygenated monoterpenes were the predominant terpene class, followed by the monoterpene hydrocarbons. Significant qualitative and quantitative differences between both samples were revealed. Camphor (50.90%), camphene (16.12%), and bornyl acetate (6.05%) were the major constituents in the feverfew EO from the western Rhodope Mountains, while in the EO from the central Balkan mountains camphor (45.54%), trans-chrysanthenyl acetate (13.87%), and camphene (13.03%) were the most abundant components.

History of development of undergraduate public health education in Bulgaria.

OBJECTIVE: The study aims to present a historical review and analysis of the establishment and development of undergraduate public health (PH) education in Bulgaria from 1878 until 2019. METHODS: А search and selection of historical documents was performed, including laws, rules, regulations, government plans, programmes, scientific publications from periodical medical press, journals, specialized monographs, and books. A retrospective analysis of the normative documents related to the organization of the sanitation and public health activities, and to the provision of professional undergraduate education of the public health workforce in Bulgaria has been carried out. The required competences and tasks of the specialists exercising public health control services were extracted. RESULTS: The development in the public health educational activities were followed in three consecutive periods: the newly independent state (1878-1944); the socialist state (1945-1990); the democratizing state (1990-2019). The development of organized PH activities began after the liberation of Bulgaria in 1878. The historical analysis reveals a direct link between the major socioeconomic changes in the country and the organization of PH undergraduate education which passed through dynamic transformations. The professional education in the sphere of PH started with the training of feldshers, followed by sanitary feldsher and sanitary health inspectors performed in secondary vocational medical schools during the socialist period, reaching the stage of undergraduate university PH education provided by medical colleges associated with universities in the third period. CONCLUSION: Despite the continuous development in the organization of undergraduate PH education in Bulgaria, its content is still not fully compatible with the basic European PH services and actions. There is a growing need for wider standardization and integration of undergraduate PH education in the EU so that the specialty can reach the status of a regulated health profession similar to medicine, nursing, and others.

Are the elements zinc, copper, magnesium, and rubidium related to nutrition and iodine deficiency in pregnant Bulgarian women from iodine deficient region?

OBJECTIVE: Trace elements are essential for the biochemistry of the cell. Their reference values have been found to differ considerably in pregnant women stratified by age, place of residence, anthropometric status, and length of pregnancy. In optimal amounts, these elements reduce the risk of pregnancy complications. Subclinical hypothyroidism in pregnancy is associated with adverse maternal and neonatal outcomes. The aim of the study was to determine the effects of zinc (Zn), copper (Cu), magnesium (Mg), and rubidium (Rb) on pregnant women in an iodine deficiency region and find the relationship with the thyroid status and nutrition. METHODS: We evaluated the iodine status of 61 healthy pregnant women from an iodine deficient region in Bulgaria. Thyroid stimulating hormone (TSH) and thyroxin free (FT4) levels were measured using ELISA. RESULTS: We found elevated levels of copper that differed the most between the first and second trimesters; Cu and TSH were found to be positively correlated (р < 0.05). Lower Cu levels were found in pregnant women consuming pulses more than 2-3 times a week (р = 0.033). The women consuming fish more than 2-3 times a week had higher levels of Rb. We found a pronounced iodine deficiency in more than half of the examined women in the first to third trimesters, without any effect of pregnancy on the ioduria (р=0.834). All second and third trimester cases were associated with severe ioduria (< 150 µg/L). CONCLUSION: The high Cu levels were associated with subclinical hypothyroidism (SCH) and less pulse consumption during pregnancy in an iodine deficiency endemic area. SCH was found in 24% of the pregnant women in such an area while in 13% of them SCH had progressed to overt hypothyroidism.

Mapping the Bulgarian Diabetes Register to OMOP CDM: Application Results.

BACKGROUND: The Bulgaria Diabetes Register (BDR) contains more than 380 millions of pseudonymized outpatient records with proprietary data structures and format. OBJECTIVES: This paper presents the application results and experience acquired during the process of mapping such observational health data to OMOP CDM with the objective of publishing it in the European Health Data and Evidence Network (EHDEN) Portal. METHODS: The data mapping follows the activities of the well-structured Extract-Transform-Load process. Unlike other publications, we focus on the need for preprocessing the data structures of raw data, cleaning data and procedures for assuring quality of data. RESULTS: This paper provides quantitative and statistical measures for the records in the CDM database as published in the EHDEN Portal. CONCLUSION: The mapping of data from the BDR to OMOP CDM provides the EHDEN community with opportunities for including these data in large-scale project for evidence generation by applying standard analytical tools.

Molecular Diagnostics and Treatment Patterns in Metastatic Non-small Cell Lung Cancer Patients: Real World Evidence from Greece: LACHESIS Study.

BACKGROUND/AIM: Lung cancer, primarily non-small cell lung cancer (NSCLC), is the leading cause of cancer deaths globally. In Greece in 2020, 8,960 new cases were reported. NSCLC's 5-year survival rates range from 54% (stage I) to less than 2% (stage IV); however, innovative therapies like immune check points inhibitors (ICIs) and targeted treatments have notably enhanced outcomes. The aim of this study was to assess the 1st and 2nd line treatment patterns with the introduction of new treatment modalities. Additionally, we evaluated biomarker testing approaches in NSCLC. PATIENTS AND METHODS: LACHESIS was a retrospective multinational study, collecting and analyzing data from adult patients from Russia, Bulgaria, and Greece with metastatic NSCLC either newly diagnosed or relapsed from earlier stages, who had the option to undergo biomarker testing (genetic alterations/programmed death-ligand 1 protein expression levels, PD-L1), and who received 1st line treatment for squamous (SQ) or non-squamous (N-SQ) NSCLC. Subsequent lines of therapy were also reported. RESULTS: The Greek site registered retrospective data from 250 NSCLC patients, of whom 206 were newly diagnosed (ND) metastatic NSCLC patients and 44 were patients relapsed from earlier stages. Seventy-two had SQ NSCLC and 169 had N-SQ NSCLC. For these patients, treatment patterns including immunotherapy±chemotherapy combinations were recorded. Biomarker testing patterns, including genetic alterations and PD-L1 expression levels were also documented. CONCLUSION: LACHESIS provides treatment patterns and biomarker testing data. Greek patients were treated according to international guidelines, with immunotherapy as a viable option, particularly for PD-L1 levels over 50%. Biomarker testing, crucial for non-squamous (N-SQ) cases, should yield timely results for driver mutations, prioritizing patient benefits.

The acoustics of Contemporary Standard Bulgarian vowels: A corpus study.

A comprehensive examination of the acoustics of Contemporary Standard Bulgarian vowels is lacking to date, and this article aims to fill that gap. Six acoustic variables-the first three formant frequencies, duration, mean f0, and mean intensity-of 11 615 vowel tokens from 140 speakers were analysed using linear mixed models, multivariate analysis of variance, and linear discriminant analysis. The vowel system, which comprises six phonemes in stressed position, [ε a ɔ i ɤ u], was examined from four angles. First, vowels in pretonic syllables were compared to other unstressed vowels, and no spectral or durational differences were found, contrary to an oft-repeated claim that pretonic vowels reduce less. Second, comparisons of stressed and unstressed vowels revealed significant differences in all six variables for the non-high vowels [ε a ɔ]. No spectral or durational differences were found in [i ɤ u], which disproves another received view that high vowels are lowered when unstressed. Third, non-high vowels were compared with their high counterparts; the height contrast was completely neutralized in unstressed [a-ɤ] and [ɔ-u] while [ε-i] remained distinct. Last, the acoustic correlates of vowel contrasts were examined, and it was demonstrated that only F1, F2 frequencies and duration were systematically employed in differentiating vowel phonemes.

Traditional Bulgarian Fermented Foods as a Source of Beneficial Lactic Acid Bacteria.

BACKGROUND: Traditional Bulgarian fermented foods are prominent for their uniqueness of local ingredients, production methods, and endemic microbial species. The present research investigated the diversity and beneficial biological potential of lactic acid bacteria (LAB) isolated from various types of unique Bulgarian fermented foods. METHODS: Species identification was performed via 16S rDNA sequencing. Biological activity was evaluated by determining antibacterial activity (via agar well diffusion assay), H2O2 production, spectrophotometrically determined auto- and co-aggregation, microbial adhesion to hydrocarbon, and biofilm formation. The biosafety of the isolated lactic acid bacteria was established based on hemolytic activity and phenotypic and genotypic antibiotic susceptibility. RESULTS: Forty-five strains were isolated from fermented foods (sauerkraut, fermented green tomatoes, fermented cucumbers, kefir, white cheese, and Izvara (curdled milk)). Five species were detected: Lactiplantibacillus plantarum, Levilactobacillus koreensis, Levilactobacillus brevis, Lactobacillus helveticus, and Levilactobacillus yonginensis. The most prominent species was L. plantarum, at 47%. For the first time, L. koreensis and L. yonginensis, isolated from unique Bulgarian fermented foods, are reported in this study. The antibacterial effect of the cell-free supernatants was evaluated. An antagonistic effect was observed against Escherichia coli (57%) and Salmonella enterica subsp. enterica serotype Enteritidis (19%) for several L. plantarum strains. Only one L. brevis (Sauerkraut, S15) strain showed activity against E. coli. The best autoaggregation ability at hour 4 was observed for L. koreensis (fermented cucumbers, FC4) (48%) and L. brevis S2 (44%). The highest percentage of co-aggregation with Candida albicans, at hou 4 in the experiments, was observed for strains L. koreensis (fermented green tomato, FGT1) (70%), L. plantarum strains S2 (54%), S13 (51%), and S6 (50%), while at hour 24 for strains L. koreensis FGT1 (95%), L. brevis (Kefir, K7) (89%), L. plantarum S2 (72%), and L. koreensis FC2 (70%). Seven of the isolated LAB strains showed hydrophobicity above 40%. Our results showed that the ability of biofilm formation is strain-dependent. No hemolytic activity was detected. The antibiotic resistance to 10 antibiotics from different groups was tested phenotypically and genotypically. No amplification products were observed in any strains, confirming that the isolates did not carry antibiotic-resistance genes. CONCLUSIONS: Traditional fermented Bulgarian foods can be considered functional foods and beneficial LAB sources.

Initial experience with Bulgarian Arthroplasty Register.

INTRODUCTION: National arthroplasty registries date back to 1975, when the Swedish Knee Arthroplasty Register was founded. This method of database collecting has since been employed for both patient follow-up and the creation of annual statistical reports. In Bulgaria, there is currently no state-approved software that offers these features.

Complications after limb salvage surgeries for musculoskeletal malignancies: 10-year experience of the main sarcoma center in Bulgaria.

INTRODUCTION: Limb salvage surgery is currently the most frequently used treatment option in Bulgaria for individuals with musculoskeletal malignancies. Clinical data about complications from these procedures is limited in the country, with only a few studies currently available.

Fine-grained differences in gender-cue strength affect predictive processing in children: Cross-linguistic evidence from Russian and Bulgarian.

We tested predictive gender agreement processing in adjective-noun phrases by 45 4- to 6-year-old Russian- and Bulgarian-speaking children using the visual world eye-tracking paradigm. Russian and Bulgarian are closely related languages that have three genders but differ in the nature and number of gender cues on adjectives. Analysis of the proportion and time course of looks to the target noun showed that only Bulgarian children used gender cues to predict the upcoming noun. We argue that the cross-linguistic difference in the gender cue strength is revealed through the operation of economy, transparency, and interdependence in a gender complexity matrix. The documented advantage for Bulgarian children in gender agreement processing and acquisition underscores the need for a comparative language acquisition approach to typologically close languages.

Evaluation of disease-specific quality of life and its influencing factors in Bulgarian patients with Graves' orbitopathy.

PURPOSE: Graves' orbitopathy (GO) profoundly affects patients' quality of life (QoL). Our aim was to assess QoL in patients with different forms of GO and to search for predictors of QoL. METHODS: This was a cross-sectional study involving 221 consecutive unselected GO patients (77.4% females, mean age 52 ± 11.6) referred to our clinic in the period 2017-2021. Detailed medical history was obtained from all patients, followed by hormonal and immunological testing and comprehensive ocular status. QoL was assessed by a disease-specific questionnaire (GO-QoL), consisting of two scales-one related to visual functioning (QoL-VF) and the other-to physical appearance (QoL-AP). The results were calculated by formula and expressed as percentages. RESULTS: Mild GO patients had significantly higher scores on both scales of GO-QoL compared to moderate-to-severe and sight-threatening GO patients (82.0 vs. 54.6% and 27.3% for QoL-VF; 70.1 vs. 54.4% and 36.9% for QoL-AP). Patients with active GO had significantly poorer QoL-VF (56.6 vs. 76.6%) and QoL-AP (53.1 vs. 67.5%) in comparison to patients with inactive GO. The stepwise linear regression analysis showed that the variables with major predictive value for QoL-VF were: CAS, diplopia score, visual acuity and severity of the symptoms (R2 = 0.44), whereas gender, CAS, diplopia score and proptosis best predicted QoL-AP (R2 = 0.39). CONCLUSIONS: The impact of GO on patients' QoL depends on the severity and activity of the disease. The clinical predictors of the impairment of QoL should be taken into account when considering the optimal adjunctive treatment approaches aiming to improve patients' QoL.

Clinical and virological profile of locally acquired acute hepatitis E in South Bulgaria.

INTRODUCTION: Acute hepatitis E virus (HEV) infection is recognized as a zoonosis in several European countries. We describe the characteristics and outcomes of locally acquired acute HEV hepatitis. METHODOLOGY: A prospective study was conducted among adult patients with acute HEV hepatitis at the University Hospital in Plovdiv, South Bulgaria between January 2020 and May 2022. An acute HEV infection case was a patient with acute hepatitis and laboratory-confirmed anti-HEV IgM antibodies and/or HEV RNA in serum. Demographic data, clinical manifestations, laboratory test results, and outcomes were recorded. RESULTS: A total of 46 patients were selected. Median age of 65 years (interquartile range [IQR] 50.8-74.3). 28 (60.87%) were male. 22 (47.83%) had comorbidities such as diabetes (15), liver cirrhosis (3), hepatitis B virus infection (2), and malignancies (2). Of the 46, 18 (39.13%) patients were viremic and, HEV genotype 3 was detected. The median (IQR) serum alanine aminotransferase, aspartate aminotransferase, bilirubin, platelet, and international normalized ratio levels were 992 (495.8-1714.3) U/L, 715 (262.5-1259.3) U/L, 204 (132.3-235.5) µmol/L, 204 (132.3-235.5) ×109 L, and 1.0 (0.89-1.19), respectively. Six patients with underlying liver diseases had severe hepatitis. A young patient with osteoarthritis progressed to acute liver failure and died. The persistent HEV infection was ruled out in 2 malignant patients who tested HEV RNA negative three months after discharge. CONCLUSIONS: Acute HEV hepatitis is a diagnosis to consider after excluding other causes of acute viral hepatitis. A diagnostic workup should include timely testing for HEV to identify the most vulnerable to severe consequences.

Current status and prognosis of Raphidiopsis raciborskii distribution in Bulgaria as part of the southeastern region of Europe.

The cyanobacterial species Raphidiopsis raciborskii (Woloszynska) Aguilera et al. has a high invasiveness potential, which in less than a century leads to its cosmopolitan spread. In the temperate climate of Europe, R. raciborskii has been reported in many countries, but there is still a lack of detailed information about the current status of its distribution in lakes of Bulgaria, as a part of the southeastern range of its spread in Europe. We investigated the distribution of the species using data on the phytoplankton of 122 lakes surveyed during 13-years period (2009-2022). The species was found in 33 lakes (up to 324 m asl), and 14 new localities were registered during the studied period. The results reveal that the number of lakes with the presence of R. raciborskii (27 % of all research lakes) and its contribution to the total phytoplankton biomass, has increased significantly over the last decade. The species has successfully adapted and dominated the phytoplankton in 9 lakes, forming a bloom in 8 of them. The dominant position of R. raciborskii causes loss of species and functional diversity of phytoplankton and displaces the native bloom-forming cyanobacteria. Lakes with and without the species were compared based on the available data on bioclimatic and local environmental variables. Statistically significant differences were established with respect to water transparency, conductivity, maximum depth and maximum air temperature in the warmest month. Species distribution models (SDMs) were used to identify lakes in high risk of future invasion by R. raciborskii. The results of the SDMs implementation confirmed the high maximum air temperature and low water transparency to be important predictors of the occurrence of R. raciborskii in freshwater lakes in Bulgaria. In the areas with high summer temperatures the most suitable for R. raciborskii development were found to be shallow polymictic or medium deep lakes with small surface area and low water transparency. In areas with a suitable climate, the large, deep reservoirs with high transparency as well as macrophyte dominated lakes have a low probability of occurrence of R. raciborskii. Future colonization of lakes above 500 m asl (but most likely below 700 m asl) is also possible, especially in the conditions of global warming. SDMs account for climatic and biogeographic differences of lakes and could help in elucidating the underlying factors that control the occurrence and adaptation of R. raciborskii in a given area.

Occurrence and distribution of lost molars and furcation defects in a Bulgarian population: A retrospective three-dimensional study.

OBJECTIVES: To identify the ocuurrence, distribution, and factors associated with lost molars and furcation defects in a sample of the Bulgarian population. MATERIAL AND METHODS: The full mouth cone-beam computed tomography of 56 male and 57 female patients, aged between 19 and 84 years, were examined. A comprehensive evaluation was performed on a total of 675 molars-339 in maxilla and 336 in mandible. Associations with variables such as age, gender, and periodontal disease were analyzed. RESULTS: With aging the number of missing teeth and interradicular lesions increased. No significant links between gender and molar loss (p = .64) or gender and furcation involvement (p = .25) was found. Periodontitis was strongly associated with both studied dental problems (p < .001). The occurrence of furcation defects was more frequently observed in the maxilla than in the mandible. CONCLUSION: The occurrence and distribution of lost molars and furcation defects is substantial within the studied sample. Further investigation with a larger patient cohort is needed. Pertinent healthcare strategies to address the observed dental health issues also have to be developed.

High-resolution characterization of KIR genes polymorphism in healthy subjects from the Bulgarian population-A pilot study.

Although killer-cell immunoglobulin-like receptor (KIR) gene content has been widely studied in health and disease, with the advancement of next-generation sequencing (NGS) technology the high-resolution characterization of this complex gene region has become achievable. KIR allele-level diversity has lately been described across human populations. The present study aimed to analyze for the first time the allele-level polymorphism of nine KIR genes in 155 healthy, unrelated individuals from the Bulgarian population by applying NGS. The highest degree of polymorphism was detected for the KIR3DL3 gene with 40 observed alleles at five-digit resolution in total, 22 of which were common. On the other hand, the KIR3DS1 gene was found to have the lowest degree of polymorphism among the studied KIR genes with one common allele: KIR3DS1*01301 (31.6%). To better understand KIR allelic associations and patterns in Bulgarians, we have estimated the pairwise linkage disequilibrium (LD) for the 10 KIR loci, where KIR2DL3*00501 allele was found in strong LD with KIR2DL1*00101 (D' = 1.00, R2 = 0.742). This is the first study investigating KIR polymorphism at the allele level in a population from the South-East European region. Considering the effect of the populationally shaped KIR allelic polymorphism on NK cell function, this data could lead to a better understanding of the genetic heterogeneity of this region and can be carried into clinical practice by improvement of the strategies taken for NK-mediated diseases.

A Retrospective Study on the Seroprevalence of West Nile Virus Among Donkeys and Mules in Bulgaria.

Background: West Nile virus (WNV) infection, caused by a flavivirus, emerged in Europe and America in the past two decades. The etiological agent causes asymptomatic to life-threatening infection in humans and in some animal species. The objective of this study was to evaluate the seroprevalence of WNV among donkeys and mules in Bulgaria. Methods: A total of 200 archived serum samples were tested by competitive enzyme-linked immunosorbent assay (ELISA). Positive samples were additionally analyzed by virus neutralization assay. Results: Seroprevalence of 7% (14/200) was established among tested animals by ELISA. Two samples were subsequently verified for the presence of virus neutralizing antibodies; thus, the seroprevalence against WNV was determined to be 1% (2/200 [confidence interval = 0.12-3.61]). Positive results among mules included in the study were not found. Conclusion: The findings in the present research demonstrate that donkeys are exposed to WNV infection and seroconvert, which adds to the understanding of virus circulation among donkeys in settlements in north and south Bulgaria.

First detection of a cefiderocol-resistant and extensively drug-resistant Acinetobacter baumannii clinical isolate in Bulgaria.

Cefiderocol (CFDC) is a first-in-class siderophore cephalosporin with potent activity against multidrug-resistant Gram-negative bacteria including carbapenem-resistant Acinetobacter baumannii. The present study aimed to explore the CFDC resistance mechanisms of an extensively drug-resistant A. baumannii isolate from Bulgaria. The A. baumannii Aba52 strain (designated Aba52) was obtained in 2018 from a blood sample of a critically ill patient. The methodology included antimicrobial susceptibility testing, whole-genome sequencing (WGS), reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR), multilocus sequence typing, and phylogenomic analysis. The isolate demonstrated high-level resistance to CFDC (MIC = 64 mg L-1), resistance to carbapenems, aminoglycosides, fluoroquinolones, sulfamethoxazole-trimethoprim, and tigecycline, as well as susceptibility only to colistin. WGS-based resistome analysis revealed the existence of blaOXA-23, blaOXA-66 and blaADC-73. Seven non-conservative missense mutations affecting iron transport-related genes were detected: exbD4 (p.Ser61Pro), tonB2 (p.Ala268Val), bauA (p.Thr61Ala), ftsI (p.Ala515Val), piuA (p.Gly216Val), and feoB (p.Ser429Pro and p.Thr595Ala). A variety of virulence factors associated with adherence, biofilm formation, enzyme production, immune invasion, iron uptake, quorum sensing, and two-component regulatory systems were identified, suggesting a significant pathogenic potential of Aba52. The performed RT-qPCR analysis showed diminished (0.17) and absent expression of the pirA and piuA genes, respectively, encoding TonB-dependent siderophore receptors. Aba52 belonged to the widespread high-risk sequence type ST2 (Pasteur scheme). To the best of our knowledge, this is the first documented case of CFDC-resistant A. baumannii in Bulgaria even though, CFDC has never been applied in our country. The emerging resistance highlights the crucial need for nationwide surveillance targeting the implementation of novel antibiotics.