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.

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.

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.

Rifamycin use for treatment of Helicobacter pylori infection: a review of recent data.

Helicobacter pylori eradication has become increasingly challenging. We focused on recent data about rifamycin resistance and rifamycin-containing regimens. Rifampin (rifampicin) resistance rates were <1-18.8% (often ≤7%), while those to rifabutin were 0-<4%. To detect rifabutin resistance by rifampin, 4 mg/l breakpoint was suggested. Eradication success by rifaximin-based regimens was disappointing (<62%), while that of rifabutin-containing regimens was 54.5->96%, reaching >81% in four studies. Some newer rifamycin analogs like TNP-2092 need further investigation. Briefly, although rifabutin-based regimens carry a risk of adverse effects or increasing mycobacterial resistance, they may be a rational choice for some multidrug-resistant H. pylori strains and as a third-line eradication therapy. Bismuth addition to rifabutin-based therapy and combined rifabutin-containing capsules (Talicia) are promising treatment options.

Multidrug resistance in Helicobacter pylori: current state and future directions.

Introduction: Helicobacter pylori antibiotic resistance has increased worldwide and multidrug resistance (MDR), which seriously hampers eradication success of the frequent chronic infection, has often been reported. Areas covered: H. pylori MDR rates are discussed, mostly from recent articles published since 2015. Present approaches and future directions to counteract the MDR are outlined. Expert opinion: Alarming presence of triple, quadruple and, in some studies, quintuple and sextuple resistance was detected. Primary MDR rates ranged from <10% in most European countries to >40% in Peru. Post-treatment or overall MDR rates were >23-36% in about half of the studies. MDR prevalence has varied both among and within the countries. Factors linked to the MDR are national antibiotic consumption, antibiotic misuse, treatment failures and bacterial factors such as mutations, efflux pumps, and biofilms. Important directions to counteract the MDR increase can be optimization of present and new eradication regimens, wider use of bismuth-containing regimens, assessment of benefit of vonoprazan, new antibiotics such as newer fluoroquinolones and oxazolidinone analogues, adjuvants involving N-acetylcysteine and probiotics, anti-biofilm approaches using anti-biofilm peptides and rhamnolipid and development of vaccines and non-invasive tests for resistance detection. However, more efforts and studies are required. Strain susceptibility testing is increasingly important.

Primary Helicobacter pylori resistance in elderly patients over 20 years: A Bulgarian study.

We evaluated the antibiotic susceptibility of 233 Helicobacter pylori strains isolated in the period 2011-2016, involving 62 strains from elderly patients aged 66-93years and 171 strains from younger adults. To assess resistance evolution, primary resistance rates in 92 strains from as many patients aged ≥60years in 1996-2003 were compared with those in 85 strains from infected patients in the same age group in 2011-2016. In the patients aged >65years evaluated during the last 6 years, amoxicillin resistance according to EUCAST and prior breakpoints was 1.6 and 0%, respectively. Resistance rates were the same by both breakpoint systems to metronidazole (35.5%), clarithromycin (22.6%), tetracycline (1.6%) and levofloxacin (32.3%). In 2011-2016, there were no significant differences between resistance rates in the subjects aged >65years and the younger adults. Notably, during the last 6 years, double/triple resistance was found in 21.0% of the subjects aged >65years. Moreover, the prevalence of quinolone primary resistance (30.0%) was significantly (3.4-fold) higher than that (8.9%) observed in 1996-2003. Briefly, the presence of both combined resistance and a strikingly high primary levofloxacin resistance in the elderly implies a cautious antibiotic choice for H. pylori eradication. In vitro susceptibility testing of the strains is highly important in this age group. The results can be linked to more frequent comorbidities and co-infection treatment in older compared with younger patients and, additionally, to the national antibiotic consumption. The high prevalence of quinolone resistance in the elderly patients is an alarming finding.