Turmeric and curcumin as adjuncts in controlling Helicobacter pylori-associated diseases: a narrative review.

Non-antibiotic adjuncts may improve Helicobacter pylori infection control. Our aim was to emphasize curcumin benefits in controlling H. pylori infection. We discussed publications in English mostly published since 2020 using keyword search. Curcumin is the main bioactive substance in turmeric. Curcumin inhibited H. pylori growth, urease activity, three cag genes, and biofilms through dose- and strain-dependent activities. Curcumin also displayed numerous anticancer activities such as apoptosis induction, anti-inflammatory and anti-angiogenic effects, caspase-3 upregulation, Bax protein enhancement, p53 gene activation, and chemosensitization. Supplementing triple regimens, the agent increased H. pylori eradication success in three Iranian studies. Bioavailability was improved by liposomal preparations, lipid conjugates, electrospray-encapsulation, and nano-complexation with proteins. The agent was safe at doses of 0.5->4 g daily, the most common (in 16% of the users) adverse effect being gastrointestinal upset. Notably, curcumin favorably influences the intestinal microbiota and inhibits Clostridioides difficile. Previous reports showed the inhibitory effect of curcumin on H pylori growth. Curcumin may become an additive in the therapy of H. pylori infection, an adjunct for gastric cancer control, and an agent beneficial to the intestinal microbiota. Further examination is necessary to determine its optimal dosage, synergy with antibiotics, supplementation to various eradication regimens, and prophylactic potential.

Role of compliance in Helicobacter pylori eradication treatment: Results of the European Registry on H. pylori management.

BACKGROUND: Adherence to Helicobacter pylori (H. pylori) eradication treatment is a cornerstone for achieving adequate treatment efficacy. OBJECTIVE: To determine which factors influence compliance with treatment. METHODS: A systematic prospective non-interventional registry (Hp-EuReg) of the clinical practice of European gastroenterologists. Compliance was considered adequate if ≥90% drug intake. Data were collected until September 2021 using the AEG-REDCap e-CRF and were subjected to quality control. Modified intention-to-treat analyses were performed. Multivariate analysis carried out the factors associated with the effectiveness of treatment and compliance. RESULTS: Compliance was inadequate in 646 (1.7%) of 38,698 patients. The non-compliance rate was higher in patients prescribed longer regimens (10-, 14-days) and rescue treatments, patients with uninvestigated dyspepsia/functional dyspepsia, and patients reporting adverse effects. Prevalence of non-adherence was lower for first-line treatment than for rescue treatment (1.5% vs. 2.2%; p < 0.001). Differences in non-adherence in the three most frequent first-line treatments were shown: 1.1% with proton pump inhibitor + clarithromycin + amoxicillin; 2.3% with proton pump inhibitor clarithromycin amoxicillin metronidazole; and 1.8% with bismuth quadruple therapy. These treatments were significantly more effective in compliant than in non-compliant patients: 86% versus 44%, 90% versus 71%, and 93% versus 64%, respectively (p < 0.001). In the multivariate analysis, the variable most significantly associated with higher effectiveness was adequate compliance (odds ratio, 6.3 [95%CI, 5.2-7.7]; p < 0.001). CONCLUSIONS: Compliance with Helicobacter pylori eradication treatment is very good. Factors associated with poor compliance include uninvestigated/functional dyspepsia, rescue-treatment, prolonged treatment regimens, the presence of adverse events, and the use of non-bismuth sequential and concomitant treatment. Adequate treatment compliance was the variable most closely associated with successful eradication.

In Vitro Antimicrobial Activity of Five Newly Approved Antibiotics against Carbapenemase-Producing Enterobacteria-A Pilot Study in Bulgaria.

To solve the problem with pan-drug resistant and extensively drug-resistant Gram-negative microbes, newly approved drugs such as ceftazidime/avibactam, cefiderocol, plazomicin, meropenem/vaborbactam, and eravacycline have been introduced in practice. The aim of the present study was to collect carbapenemase-producing clinical Enterobacterales isolates, to characterize their carbapenemase genes and clonal relatedness, and to detect their susceptibility to commonly used antimicrobials and the above-mentioned newly approved antibiotics. Sixty-four carbapenemase producers were collected in a period of one year from four Bulgarian hospitals, mainly including Klebsiella pneumoniae (89% of the isolates) and also single Proteus mirabilis, Providencia stuartii and Citrobacter freundii isolates. The main genotype was blaNDM-1 (in 61%), followed by blaKPC-2 (23%), blaVIM-1 (7.8%) and blaOXA-48 (7.8%). Many isolates showed the presence of ESBL (blaCTX-M-15/-3 in 76.6%) and AmpC (blaCMY-4 in 37.5% or blaCMY-99 in 7.8% of isolates). The most common MLST type was K. pneumoniae ST11 (57.8%), followed by ST340 (12.5%), ST258 (6.3%) and ST101 (6.3%). The isolates were highly resistant to standard-group antibiotics, except they were susceptible to tigecycline (83.1%), colistin (79.7%), fosfomycin (32.8%), and aminoglycosides (20.3-35.9%). Among the newly approved compounds, plazomicin (90.6%) and eravacycline (76.3%) showed the best activity. Susceptibility to ceftazidime/avibactam and meropenem/vaborbactam was 34.4% and 27.6%, respectively. For cefiderocol, a large discrepancy was observed between the percentages of susceptible isolates according to EUCAST susceptibility breakpoints (37.5%) and those of CLSI (71.8%), detected by the disk diffusion method. This study is the first report to show patterns of susceptibility to five newly approved antibiotics among molecularly characterized isolates in Bulgaria. The data may contribute to both the improvement of treatment of individual patients and the choice of infection control strategy and antibiotic policy.

Effectiveness of Helicobacter pylori Treatments According to Antibiotic Resistance.

INTRODUCTION: Antibiotic resistance is one of the main factors that determine the efficacy of treatments to eradicate Helicobacter pylori infection. Our aim was to evaluate the effectiveness of first-line and rescue treatments against H. pylori in Europe according to antibiotics resistance. METHODS: Prospective, multicenter, international registry on the management of H. pylori (European Registry on H. pylori Management). All infected and culture-diagnosed adult patients registered in the Spanish Association of Gastroenterology-Research Electronic Data Capture from 2013 to 2021 were included. RESULTS: A total of 2,852 naive patients with culture results were analyzed. Resistance to clarithromycin, metronidazole, and quinolones was 22%, 27%, and 18%, respectively. The most effective treatment, regardless of resistance, were the 3-in-1 single capsule with bismuth, metronidazole, and tetracycline (91%) and the quadruple with bismuth, offering optimal cure rates even in the presence of bacterial resistance to clarithromycin or metronidazole. The concomitant regimen with tinidazole achieved an eradication rate of 99% (90/91) vs 84% (90/107) with metronidazole. Triple schedules, sequential, or concomitant regimen with metronidazole did not achieve optimal results. A total of 1,118 non-naive patients were analyzed. Resistance to clarithromycin, metronidazole, and quinolones was 49%, 41%, and 24%, respectively. The 3-in-1 single capsule (87%) and the triple therapy with levofloxacin (85%) were the only ones that provided encouraging results. DISCUSSION: In regions where the antibiotic resistance rate of H. pylori is high, eradication treatment with the 3-in-1 single capsule, the quadruple with bismuth, and concomitant with tinidazole are the best options in naive patients. In non-naive patients, the 3-in-1 single capsule and the triple therapy with levofloxacin provided encouraging results.

Comparison of the management of Helicobacter pylori infection between the older and younger European populations.

The prevalence of Helicobacter pylori remains high in the older population. Specific age-related peculiarities may impact the outcomes of H. pylori treatment. The aim of the study was to evaluate the diagnostics and effectiveness of H. pylori eradication between the younger and older European populations. "European Registry on H. pylori Management (Hp-EuReg)" data from 2013 to 2022 were analyzed. Patients were divided into older (≥ 60 years) and younger (18-59 years) groups. Modified intention-to-treat (mITT) and per-protocol (PP) analysis was performed. 49,461 patients included of which 14,467 (29%) were older-aged. Concomitant medications and penicillin allergy were more frequent among the older patients. Differences between younger and older populations were observed in treatment duration in first-line treatment and in proton pump inhibitors (PPIs) doses in second-line treatment. The overall incidence of adverse events was lower in the older adults group. The overall first-line treatment mITT effectiveness was 88% in younger and 90% in the older patients (p < 0.05). The overall second-line mITT treatment effectiveness was 84% in both groups. The effectiveness of the most frequent first- and second-line triple therapies was suboptimal (< 90%) in both groups. Optimal efficacy (≥ 90%) was achieved by using bismuth and non-bismuth-based quadruple therapies. In conclusion, the approach to the diagnostics and treatment of H. pylori infection did not generally differ between younger and older patients. Main differences were reported in the concurrent medications, allergy to penicillin and adverse events both in first- and second-line treatment. Optimal effectiveness rates were mostly achieved by using bismuth and non-bismuth-based quadruple therapies. No clinically relevant differences in the effectiveness between the age groups were observed.

Mixed (multiple-genotype) Helicobacter pylori infections in Bulgarian patients.

The aim of the study was to evaluate the frequency and characteristics of mixed (multiple-genotype) Helicobacter pylori infections (MGIs) in 155 Bulgarian symptomatic patients (21 children and 134 adults). MGIs were common (36.1%), including double-strain (34.8%) and triple-strain infections (1.3%). None of the 8 ulcer patients harbored multiple subtypes. We detected 18 multiple allelic combinations, of which the most frequent subtypes (17.4%) were vacA s1as2 and vacA s1cs2. The 2 patients with triple-strain infections had vacA s1bs1cs2i1i2/iceA1A2 and vacA s1as1cs2 subtypes. They were both adult men with chronic gastritis and both were examined in 2022. The prevalence of MGIs (51.7%) was 2-fold higher in 2020 to 2022 than in 2015 to 2019 (26.3%). Putative factors for the increase may be the patient's characteristics and COVID-19 pandemic-associated factors. MGI rates corresponded to the high infection seroprevalence (72.4% in 2011) in Bulgaria. The evolution and clinical importance of mixed H. pylori infections merit extensive evaluation.

Analysis of Clinical Phenotypes through Machine Learning of First-Line H. pylori Treatment in Europe during the Period 2013-2022: Data from the European Registry on H. pylori Management (Hp-EuReg).

The segmentation of patients into homogeneous groups could help to improve eradication therapy effectiveness. Our aim was to determine the most important treatment strategies used in Europe, to evaluate first-line treatment effectiveness according to year and country. Data collection: All first-line empirical treatments registered at AEGREDCap in the European Registry on Helicobacter pylori management (Hp-EuReg) from June 2013 to November 2022. A Boruta method determined the "most important" variables related to treatment effectiveness. Data clustering was performed through multi-correspondence analysis of the resulting six most important variables for every year in the 2013-2022 period. Based on 35,852 patients, the average overall treatment effectiveness increased from 87% in 2013 to 93% in 2022. The lowest effectiveness (80%) was obtained in 2016 in cluster #3 encompassing Slovenia, Lithuania, Latvia, and Russia, treated with 7-day triple therapy with amoxicillin-clarithromycin (92% of cases). The highest effectiveness (95%) was achieved in 2022, mostly in Spain (81%), with the bismuth-quadruple therapy, including the single-capsule (64%) and the concomitant treatment with clarithromycin-amoxicillin-metronidazole/tinidazole (34%) with 10 (69%) and 14 (32%) days. Cluster analysis allowed for the identification of patients in homogeneous treatment groups assessing the effectiveness of different first-line treatments depending on therapy scheme, adherence, country, and prescription year.

Clostridioides difficile resistance to antibiotics, including post-COVID-19 data.

INTRODUCTION: Updating data on Clostridioides difficile antibiotic resistance is important for treatment improvement of C. difficile infections (CDIs). AREAS COVERED: Results from 20 countries were included. The mean resistance to 2 mg/l vancomycin, 2 mg/l metronidazole, 4 mg/l moxifloxacin, and 4 mg/l clindamycin was 4.7% (0 to ≥ 26% in two studies), 2.6% (0 to ≥ 40% in 3 studies), 34.9% (6.6->80%), and 61.0% (30->90%), respectively. Resistance to erythromycin (>60-88%), rifampin (>23-55.0%), imipenem (0.6 to > 78% in a clone), tigecycline (0-<5.0%), and fidaxomicin (0-2%) was also found. Resistance to ≥ 5 antibiotics of different classes was reported in some countries. High resistance and multidrug resistance were observed in hypervirulent and epidemic strains. Although only 1% of COVID-19 patients had CDIs, the proportion might be underestimated. EXPERT OPINION: C. difficile antimicrobial susceptibility varied by country/region, study period, and circulating ribotypes. For CDI treatment, fidaxomicin (preferably) or vancomycin is recommended, while metronidazole is suitable for mild infections. New approaches, including biotherapeutics (Rebyota), strains, antibiotics (ridinilazole and ibezapolstat), and monoclonal antibodies/cocktails merit further evaluation. Because of the resistance rate variations, C. difficile antibiotic susceptibility should be regularly monitored. Post-COVID-19 resistance should be separately presented. Some discrepancies between vancomycin and metronidazole results need to be clarified.

Clostridioides difficile can cause mild to dangerous diarrhea in people following antibiotic use. Many antibacterial agents can cause diseases. However, treatment is limited to three antibiotics. The study of resistance to them is important for improving the treatment of infections. The study of resistance to other antibiotics helps to understand the spread and risks of infections. We discussed data about C. difficile antibiotic resistance from 20 countries according to recent publications. For the treatment of C. difficileinfections, fidaxomicin is the drug of choice with 0­2% resistance to it. Resistance to the two other antibiotics used to treat infections is less than 5% of isolates. Much higher resistance was found to antibiotics that can cause C. difficile infections such as ciprofloxacin, clindamycin, ceftriaxone, erythromycin, and others. The resistance varies according to the country, patients' groups, years of study, and circulating strains. The resistance was high in hypervirulent and epidemic strains. In some studies, there was resistance to 5 and 6 antibiotics of different classes. Antibiotic use and incidence of infections during the COVID-19 pandemic varied. However, the evolution of C. difficile infection during the pandemic has yet to be determined.

Anaerobes in specific infectious and noninfectious diseases: new developments.

With the buildup of new research data, newer associations between anaerobic bacteria and diseases/conditions were evaluated. The aim of the mini-review was to draw attention and to encourage further multidisciplinary studies of the associations. We considered microbiome-disease correlations such as a decrease of fecal Faecalibacterium prausnitzii abundance in inflammatory bowel disease (IBD) and IBD recurrence, suggesting that F. prausnitzii could be a good biomarker for IBD. A link of subgingival Porphyromonas gingivalis with cardiovascular diseases was reported. Decreased Roseburia abundance was observed in the gut of Alzheimer's and Parkinson's disease patients. Akkermansia muciniphila was found to improve adipose/glucose metabolism, however, its intestinal abundance was observed in neurodegenerative diseases as well. Severe Clostridioides difficile infections have been reported in neonates and young children. Carcinogenic potential of anaerobes has been suggested. Fusobacterium nucleatum was implicated in the development of oral and colorectal cancer, Porphyromonas gingivalis and Tannerella forsythia were linked to esophageal cancer and Cutibacterium acnes subsp. defendens was associated with prostate cancer. However, there are some controversies about the results. In a Swedish longitudinal study, neither P. gingivalis nor T. forsythia exhibited oncogenic potential. The present data can enrich knowledge of anaerobic bacteria and their multifaceted significance for health and disease and can draw future research directions. However, more studies on large numbers of patients over prolonged periods are needed, taking into account the possible changes in the microbiota over time.

Clostridioides difficile, a New "Superbug".

Clostridioides difficile is a Gram-positive, spore-forming, anaerobic bacterium. The clinical features of C. difficile infections (CDIs) can vary, ranging from the asymptomatic carriage and mild self-limiting diarrhoea to severe and sometimes fatal pseudomembranous colitis. C. difficile infections (CDIs) are associated with disruption of the gut microbiota caused by antimicrobial agents. The infections are predominantly hospital-acquired, but in the last decades, the CDI patterns have changed. Their prevalence increased, and the proportion of community-acquired CDIs has also increased. This can be associated with the appearance of hypervirulent epidemic isolates of ribotype 027. The COVID-19 pandemic and the associated antibiotic overuse could additionally change the patterns of infections. Treatment of CDIs is a challenge, with only three appropriate antibiotics for use. The wide distribution of C. difficile spores in hospital environments, chronic persistence in some individuals, especially children, and the recent detection of C. difficile in domestic pets can furthermore worsen the situation. "Superbugs" are microorganisms that are both highly virulent and resistant to antibiotics. The aim of this review article is to characterise C. difficile as a new member of the "superbug" family. Due to its worldwide spread, the lack of many treatment options and the high rates of both recurrence and mortality, C. difficile has emerged as a major concern for the healthcare system.

Cutibacterium acnes (formerly Propionibacterium acnes): friend or foe?

Cutibacterium acnes protects skin homeostasis. The species has three subspecies, and associations between C. acnes subsp. acnes and acne, C. acnes subsp. defendens and prostate cancer, and C. acnes subsp. elongatum and progressive macular hypomelanosis have recently been suggested. Different phylotypes/clonal complexes may cause prosthetic joint and other infections, and virulence factors such as fimbriae, biofilms, multidrug-resistance plasmids, porphyrin, Christie-Atkins-Munch-Petersen factors and cytotoxicity contribute to infections. Isolates are subtyped by multiplex PCR or multi- or single-locus sequence typing; however, these methods could be better synchronized. Resistance of acneic strains to macrolides (25.0-73.0%), clindamycin (10.0-59.0%) and tetracyclines (up to 37.0%) is worrisome, but susceptibility testing is now facilitated by European Committee on Antimicrobial Susceptibility Testing disk diffusion breakpoints. New therapeutic approaches include sarecycline, antimicrobial peptides and bacteriophages.

What is this summary about? Cutibacterium acnes is necessary for skin health. However, different subspecies and types may be associated with different diseases. At present, the species has three known subspecies and six known major phylotypes. What were the results? Acne results from a disturbance of the skin bacteria. It has often been linked to C. acnes, whereas associations of other subspecies with prostate cancer, skin disease and various infections have been observed. Strain typing can be performed with different techniques; however, methods should be better synchronized. Resistance of isolates from acne to antibiotics is high. Antibiotic susceptibility testing is necessary and is being facilitated. New treatments with newer antibiotics, antimicrobial peptides and phages are promising. What do the results mean? C. acnes has three subspecies and numerous types that can support skin health or be linked to different diseases. New associations between different subspecies and prostate cancer, skin disease and infections have been studied. C. acnes resistance to antibiotics is frequent; however, susceptibility testing has already been simplified.

Evolution of Helicobacter pylori Resistance to Antibiotics: A Topic of Increasing Concern.

Antibiotic resistance among Helicobacter pylori strains is the major cause of eradication failure. Resistance prevalence is dynamic and can greatly vary among countries over the years. We revealed H. pylori resistance trends for five antibiotics in 14 countries through articles predominantly published in 2018-2022, since the latest data can best show the most recent trends in resistance evolution. Amoxicillin resistance generally exhibited no evolution, yet it increased in Bulgaria, Iran, China, and Vietnam. Metronidazole resistance exhibited different trends, including an increase, a decrease and no evolution in six, three, and five studies, respectively. Clarithromycin resistance increased in Australia, Belgium, Bulgaria, Italy, Iran, and Taiwan, but remained stable in France, Spain, Russia, China, Chile, and Colombia. Tetracycline resistance was low and stable except in Iran. Levofloxacin resistance increased in four European and six other countries/regions, without significant increases in France, Spain, and Chile. In Chile, triple resistance also increased. In countries such as France and Spain, resistance to most antibiotics was stabilized, while in Bulgaria, Belgium, Iran and Taiwan, resistance to three or more agents was reported. Use of non-recommended regimens, national antibiotic consumption, patient's compliance, host factors, strain virulence, migrations, and azithromycin overuse during the COVID-19 pandemic can influence resistance evolution. New drugs, eradication regimens and diagnostic methods, such as next-generation sequencing can improve H. pylori infection control.

Geographic distribution of antibiotic resistance of Helicobacter pylori: A study in Bulgaria.

Prevalence of antibiotic resistant Helicobacter pylori was compared between 50 patients living outside the capital city and 50 matched pairs of capital city residents (CCRs). H. pylori isolates from 2018 to 2022 were included. Resistance rates in CCRs and those living elsewhere were 4.0 and 6.0% to amoxicillin, 48.0 and 42.0% to metronidazole, 30 and 30% to clarithromycin, and 4.0 and 4.0% to tetracycline, respectively. Levofloxacin resistance was higher (38.0%) in the capital city vs 20.0% (P = 0.047) in the country. Odd ratio for levofloxacin resistance between pair-matched groups was 2.45 (95% CI, OR 1.0-6.02, P value = 0.05) and relative risk for fluoroquinolone resistance was 1.90 (95% CI for RR 0.98-3.67) for CCRs vs residents in other regions. Resistance rates to levofloxacin and clarithromycin were worryingly high in our study, most probably due to the high quinolone consumption (2.86 DDD/day in 2017) in Bulgaria and the increase in macrolide, lincosamide and streptogramin consumption, especially of azithromycin, by >42% with the start of COVID-19 pandemic. Briefly, antibiotic resistance of H. pylori has a dynamic change, and it can display different patterns in certain geographic regions. The results imply that antibiotic consumption should be carefully controlled and unjustified use of levofloxacin should be restricted, especially in some large cities. Antibiotic policy should be further strengthened and regular monitoring of resistance in various geographic regions is needed for treatment optimization.

Dissemination of High-Risk Clones Enterobacterales among Bulgarian Fecal Carriage Isolates.

The gastrointestinal tract is an important reservoir of high-risk Enterobacteria clones and a driver of antimicrobial resistance in hospitals. In this study, patients from six hospitals in four major Bulgarian towns were included in this study. Overall, 205 cefotaxime-resistant isolates (35.3%) of Enterobacterales order were detected in fecal samples among 580 patients during the period of 2017-2019. ESBL/carbapenemase/plasmidic AmpC producer rates were 28.8%, 2.4%, and 1.2%, respectively. A wide variety of ESBLs: CTX-M-15 (41%), CTX-M-3 (24%), CTX-M-27 (11%), and CTX-M-14 (4%) was found. The carbapenemases identified in this study were New Delhi metalo-ß-lactamase (NDM)-1 (5.4%) and Klebsiella carbapenemase (KPC)-2 (1.5%). Most NDM-1 isolates also produced CTX-M-15/-3 and CMY-4 ß-lactamases. They belonged to ST11 Klebsiella pneumoniae clone. The epidemiology typing revealed three main high-risk K. pneumoniae clones (26%)-ST11, ST258, and ST15 and five main Escherichia coli clones-ST131 (41.7%), ST38, ST95, ST405, and ST69. Sixty-one percent of ST131 isolates were from the highly virulent epidemic clone O25b:H4-ST131. Phylotyping revealed that 69% of E. coli isolates belonged to the virulent B2 and D groups. Almost all (15/16) Enterobacter isolates were identified as E. hormaechei and the most common ST type was ST90. Among all of the isolates, a high ESBL/carbapenemases/plasmid AmpC (32.4%) prevalence was observed. A significant proportion of the isolates (37%) were members of high-risk clones including two pan-drug-resistant K. pneumoniae ST11 NDM-1 producing isolates. Due to extensive antibiotic usage during COVID-19, the situation may worsen, so routine screenings and strict infection control measures should be widely implemented.

Detection of different colistin resistance mechanisms among multidrug resistant Klebsiella pneumoniae isolates in Bulgaria.

The more frequent usage of colistin resulted in an increase of colistin resistance due to lipopolysaccharide modifications. The aim of this study was to reveal the prevalence and mechanisms of colistin resistance among multidrug-resistant Klebsiella pneumoniae isolates collected in Bulgaria. One hundred multidrug resistant K. pneumoniae isolates were collected in a period between 2017 and 2018. Among them, 29 colistin resistant and 8 heteroresistant isolates were observed and further investigated. Clonal relatedness was detected by RAPD and MLST. Сarbapenemases, two component system phoQ/phoP, pmrA/B, and mgrB were investigated by PCR amplification and Sanger sequencing. Among 37 colistin nonsusceptible isolates, we detected 25 NDM-1 producers. The isolates belonged mainly to ST11 (80%), and also to ST147, ST35, ST340, ST219 (1-2 members per clone). Nine colistin resistant isolates showed changes in mgrB. IS903B-like elements truncated mgrB in five isolates. In two isolates, premature stopcodon (Q30stopcodon) was observed and another two isolates did not amplify mgrB, possibly due to bigger deletion or insertion. No isolates showed phoQ/phoP and pmrA/B mutations except for pmrB (four isolates had R256G). All isolates with IS903B insertions belonged to ST11 clone. The mgrB alterations play major role in colistin resistance in K. pneumoniae isolates studied in the current work. We report truncation of mgrB by IS903 like element in colistin resistant NDM-1 producing K. pneumoniae ST11 clone in Bulgaria.

Molecular epidemiology, virulence and antimicrobial resistance of Bulgarian methicillin resistant Staphylococcus aureus isolates.

Background: Severe infections of virulent methicillin-resistant Staphylococcus aureus (MRSA) are a serious health problem. The present study aimed to investigate clonal spread, virulence and antimicrobial resistance rates of Bulgarian MRSA isolates in 2016-2020. Methods: Molecular identification and mecA gene detection were performed with PCR. Clonal relatedness was evaluated by RAPD PCR and MLST. MRSA epidemiology, virulence and resistance patterns were investigated by PCR. Results: All 27 isolates were identified as S. aureus and were mecA positive, and all were susceptible to linezolid, tigecycline and vancomycin. The toxin genes hlg (in 92.6% of isolates), seb (77.8%), sei (77.8%), seh (59.3%), sej (55.6%), and seg (48.1%), were frequently found among the isolates. Epidemiological typing by RAPD identified 4 clones (16 isolates) and 11 were with a unique profile. MLST analysis of the same MRSA isolates showed five MLST clonal complexes and 11 ST types, including CC5 (33.3%) (ST5, ST221, ST4776), CC8 (22.2%) (ST8, ST239, ST72), CC15 (ST582), CC22 (14.8%) (ST217, ST5417), CC30 (ST30) CC398 (ST398), and CC59 (ST59). The isolates from CC5 showed higher virulence potential and almost all were macrolide resistant (ermB or ermC positive). CC8 isolates showed higher level of resistance. Conclusion: To the best of our knowledge, this study is the first describing the clonal spreading of Bulgarian MRSA and the association with their virulence and resistance determinants. Monitoring of MRSA epidemiology, resistance and virulence profile can lead to better prevention and faster therapeutic choice in cases of severe infections.

Increase in amoxicillin resistance in Helicobacter pylori from Bulgarian patients over 15 years.

Helicobacter pylori resistance to amoxicillin has usually been rare. We traced resistance evolution in 474 strains over 15 years. Although minimum inhibitory concentrations MIC50 and MIC90 were similar among subgroups, the overall resistance rate (MICs, >0.125-3 mg/L) significantly increased from 4.2% in 2007-2014 to 8.9% in 2015-2021.

Investigation of multidrug-resistant Helicobacter pylori in pediatric patients: A Bulgarian study and literature data.

Antibiotic resistance of Helicobacter pylori strains from 106 symptomatic children was evaluated according to EUCAST breakpoints and rate of multidrug resistance (MDR) was analyzed. Overall resistance rates were amoxicillin 7.5%, metronidazole 25.5%, clarithromycin 34.0% and ciprofloxacin 14.1%. There were no significant differences in resistance rates according to patients' age (2-6 and 7-18 years) and sex. Combined resistance rate was 19.8%, including double, triple, and quadruple resistance in 13.2% (14 strains), 5.7% (6) and 0.9% (1) of the strains, respectively. MDR was found in 5.9% (5/84) of the children with gastritis and in two of the four children with celiac disease. The MDR was present in three children aged 4-6 years and in four children aged 10-17 years. The total MDR rate (6.6%) in Bulgarian children in 2012-2021 was higher than those in other studies based on EUCAST breakpoints such as those in pediatric patients in Slovenia in 2011-2014 (3.8%), Lithuania in 2013-2015 (0%) and Spain in 2014-2019 (0%), although being lower than those (20.7% in the untreated and 47.0% in the treated children) in China in 2019. In brief, it is of concern that MDR can strongly limit the choice of H. pylori therapy of one out of fifteen Bulgarian children and that overall resistance to both metronidazole and clarithromycin can hinder the treatment of 15.1% of the pediatric patients. Susceptibility-guided tailored eradication therapy of H. pylori infection should be more frequently implemented in the symptomatic children to avoid risks of both the infection itself and multiple antibiotic treatments.