Long-term Antibiotic Use Research Articles

Association between Antibiotic Use and Subsequent Risk of Breast Cancer: A Nationwide Retrospective Cohort Study in South Korea.

Several studies have revealed a possible association between antibiotic use and breast cancer in the Western population of women. However, its association with the Asian population remains unclear. Data utilized in this nationwide population-based retrospective cohort study was obtained from the Korean National Health Insurance Service (NHIS) database. The study population consisted of 4,097,812 women who were followed up from January 1, 2007, to December 31, 2019. Cox proportional hazards regression was utilized to calculate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for the risk of breast cancer according to cumulative days of antibiotic use and the number of antibiotic classes used. It was discovered that women who used antibiotics for more than 365 days had a higher risk of breast cancer (aHR, 1.15; 95% CI, 1.09-1.21) in comparison to those who did not use antibiotics. In addition, an association was found among women who used five or more classes of antibiotics, showing a higher risk of breast cancer (aHR, 1.11; 95% CI, 1.05-1.17) compared to non-users. Furthermore, compared to antibiotic non-users, only users of cephalosporins (aHR 1.09; 95% CI, 1.02-1.17) and lincosamides (aHR 1.70; 95% CI, 1.20-2.42) had a higher risk of breast cancer. These findings support epidemiological evidence that long-term use of antibiotics may be associated with a higher risk of breast cancer. This underscores the need for further studies to address the potential for residual confounding, confirm causation, and elucidate the underlying mechanisms.

A case of penicillin-resistant group B Streptococcus isolated from a patient in the UK.

In England, group B streptococci (GBS; Streptococcus agalactiae) are considered universally susceptible to penicillin. Reports from Africa, Asia, North America and a few European countries have described GBS isolates with penicillin MICs above the epidemiological cut-off (0.125 mg/L). Our aim was to characterize a penicillin-resistant GBS (PRGBS) isolate recovered in 2016 from a patient treated with long-term antimicrobials in the UK. Antibiotic susceptibility of a referred isolate from a discharging sinus overlying a chronic prosthetic joint infection was determined using gradient strip testing for seven antibiotics. Illumina short read sequencing was carried out using a HiSeq 2500 platform to determine MLST, capsular type, to detect mutations in the pbp genes, and to compare the isolate with contemporaneous GBS isolates circulating in the UK. The GBS isolate belonged to capsular type Ia and MLST 144. We observed resistance to penicillin (MIC = 1 mg/L) and tetracycline (32 mg/L) with susceptibility to linezolid (1 mg/L), erythromycin (0.064 mg/L), clindamycin (0.064 mg/L), teicoplanin (0.064 mg/L) and vancomycin (0.25 mg/L). Deduced amino acid sequences revealed substitutions and non-synonymous changes in PBP2x and PBP2b. Genomic analysis of contemporaneous cases (n = 34) from across the UK identified single nucleotide polymorphism (SNP) variation ranged from 153-6596 SNPs. We confirm the first identification of a PRGBS isolate amongst referrals to the UK's national reference laboratory. Substitutions in pbp1a, pbp2a, pbp2x and pbp2b were identified that likely developed in the face of long-term beta-lactam antibiotic use.

Management of adult bronchiectasis - Consensus-based Guidelines for the German Respiratory Society (DGP) e. V. (AWMF registration number 020-030)

Bronchiectasis is an etiologically heterogeneous, chronic, and often progressive respiratory disease characterized by irreversible bronchial dilation. It is frequently associated with significant symptom burden, multiple complications, and reduced quality of life. For several years, there has been a marked global increase in the prevalence of bronchiectasis, which is linked to a substantial economic burden on healthcare systems. This consensus-based guideline is the first German-language guideline addressing the management of bronchiectasis in adults. The guideline emphasizes the importance of thoracic imaging using CT for diagnosis and differentiation of bronchiectasis and highlights the significance of etiology in determining treatment approaches. Both non-drug and drug treatments are comprehensively covered. Non-pharmacological measures include smoking cessation, physiotherapy, physical training, rehabilitation, non-invasive ventilation, thoracic surgery, and lung transplantation. Pharmacological treatments focus on the long-term use of mucolytics, bronchodilators, anti-inflammatory medications, and antibiotics. Additionally, the guideline covers the challenges and strategies for managing upper airway involvement, comorbidities, and exacerbations, as well as socio-medical aspects and disability rights. The importance of patient education and self-management is also emphasized. Finally, the guideline addresses special life stages such as transition, family planning, pregnancy and parenthood, and palliative care. The aim is to ensure comprehensive, consensus-based, and patient-centered care, taking into account individual risks and needs.

Epidemiology of bronchiectasis at a single center in Japan: a retrospective cohort study

BackgroundThe characteristics of bronchiectasis (BE) in Asia, including Japan, remain largely unknown. We aimed to provide insights into the clinical characteristics and treatment outcomes of BE, especially regarding nontuberculous mycobacteria (NTM) infection and its poorly understood impact on prognosis. We also aimed to clarify the effect of long-term macrolide antibiotic use in patients with BE, who had no history of exacerbations.MethodsIn this single-center, retrospective study, the medical records of patients who satisfied the BE criteria between January 1, 2012, and August 31, 2023, were reviewed. Severe exacerbations and mortality during the observation period were recorded. Baseline characteristics and overall survival of patients with and without NTM infection, and factors influencing the time to the first exacerbation and death were analyzed. Additionally, the effects of long-term macrolide antibiotic use in patients without a history of severe exacerbations were estimated.ResultsIn a cohort of 1044 patients with BE, the rate of severe exacerbation was 22.3%, with mortality rates of 3.2% over 3 years. Notably, the high prevalence of NTM infection (n = 410, 39.3%) in this cohort was distinctive. NTM infection was not associated with either the time to first severe exacerbation (p = 0.5676, adjusted hazard ratio = 1.11) or mortality (p = 0.4139, adjusted hazard ratio = 0.78). Compared with the NTM group, the non-NTM group had a higher proportion of elevated inflammatory markers, with significant differences in C-reactive protein levels (p = 0.0301) and blood neutrophil counts (p = 0.0273). Pseudomonas aeruginosa colonization was more frequent in the non-NTM group (p = 0.0003). Among patients with non-NTM infection and without a history of exacerbation in the past 2 years, 38.2% received long-term macrolide antibiotics that did not invariably prolong the time to first severe exacerbation (p = 0.4517, IPW p = 0.3555).ConclusionsThis study highlights BE epidemiology in Japan, noting that the presence of NTM infection may not necessarily worsen the prognostic outcomes and advising caution in the casual use of macrolides for milder cases without a history of exacerbations.Clinical trial registrationUMIN Clinical Trials Registry Number: UMIN000054726 (Registered on 21 June 2024).

Surgical Treatment of Purulent Complications and Widespread Paraprosthetic Infection in the Area of the Mesh Prosthesis After Laparoscopic Transabdominal Preperitoneal Hernioplasty on the Right with Involvement of Abdominal Organs Using Laparoscopic Access

Laparoscopic transabdominal, preperitoneal hernioplasty for inguinal hernia using a synthetic mesh prosthesis is the most common operation in modern surgical practice. Given the minimally invasive approach, infectious complications are rare. Despite the rarity of infectious complications, their development requires additional use of medications, long-term use of antibiotics, repeated traumatic surgical interventions, which leads to prolonged pain syndrome, hernia recurrence and is accompanied by a serious deterioration in the mental and physical condition of patients. Ultrasound and computed tomography with contrast are quite informative research methods for diagnosing abscesses associated with the implantation of a synthetic mesh prosthesis. In this article, we consider a clinical observation: a 36-year-old man with an abscess in the area of a synthetic mesh prosthesis after laparoscopic prosthetic preperitoneal hernioplasty on the right for inguinal hernia 4 months after the initial operation. The infectious process spread from the area of the infected prosthesis into the abdominal cavity, was limited by internal organs with the formation of an abscess. The resulting complication was treated by laparoscopic access. The purpose of our article is to draw the attention of surgeons to the possibility of a rare infectious complication in the area of the synthetic mesh prosthesis after right laparoscopic preperitoneal hernioplasty for inguinal hernia 4 months after the initial operation, after which the infectious process may spread from the area of the infected prosthesis into the abdominal cavity. The emphasis is placed on the difficulties of preoperative diagnosis of the complication and its surgical correction by laparoscopic access.

Performance of the GeneXpert® MRSA/SA SSTI Test in Periprosthetic Joint Infections: Rate of failure, Outcomes and Risk Factors

BackgroundThe GeneXpert® MRSA/SA SSTI test allows early detection of methicillin-resistant staphylococci in intraoperative samples of prosthetic joint infections (PJI) in order to stop early broad-spectrum antibiotics. Questions/Purpose(1) What is the rate of false-negative GeneXpert® MRSA/SA SSTI test results? (2) Does a false-negative GeneXpert® MRSA/SA SSTI test result increase the risk of treatment failure for the patient with a PJI? (3) What are the risk factors of a false-negative result? MethodA retrospective study was carried out to compare all GeneXpert® assays to conventional cultures in prosthetic joint infections from April 1st, 2012 to October 1st, 2016. False-negative (FN) results (absence of methicillin-resistant staphylococci (MRS) with GeneXpert® test, but presence in the culture) were identified. We compared the rate of treatment failure between FN results and other test results and we established the risk factors of having a FN result. ResultsAmong the 612 GeneXpert® results, the rate of FN results was 3.6 % (22/612). We found a significant increase in treatment failures for prosthetic joint infection with a FN result with 14 treatment failures (14/22) compared to 198 treatment failures (198/590) in the other test results (OR, 2.1; 95 % CI, 1.3-3.4, p = 0.0019). Not considering suppressive antibiotics as a treatment failure, we found no significant difference in the rate of treatment failures between the false-negative tests and the other tests (OR, 1.36; 95 % CI, 0.66-2.81, p = 0.41). Tobacco use (OR, 3.8; 95 % CI, 1.4-10.3, p = 0.004), ASA classification (OR, 2,4; 95 % CI, 0.9-6.9, p = 0.064), history of infection in the joint (OR, 3.2; 95 % CI, 1.2-9.6, p = 0.007), chronic infections (OR, 3.2; 95 % CI, 0.8-17.5, p = 0.01) and polymicrobial infections (OR, 3.2; 95 % CI, 1.1-9.2, p < 0.0001) were risk factors for a FN result. ConclusionGeneXpert® tests in prosthetic joint infections showed a low rate of FN results. An increased risk of treatment failures was observed in FN results only when long-term use of suppressive antibiotics was considered as treatment failure. Level of evidenceIII; Diagnostic retrospective case control study.

Association between antibiotics use and the risk of rheumatoid arthritis: a retrospective cohort study in South Korea.

Certain studies propose that antibiotic use may influence rheumatoid arthritis (RA) incidence, but the clear association between antibiotics and RA remains unclear. Therefore, this study aimed to examine the relationship between antibiotics and RA risk to provide additional epidemiological evidence. This population-based retrospective cohort study was conducted with adults aged 40 years or older using the Korean National Health Insurance Service (NHIS) database. Antibiotic exposure was measured from 2003 to 2007. Study participants were followed up from January 1, 2008, to December 31, 2019. Multivariable Cox hazard regression was utilized to evaluate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for the risk of RA according to accumulative days of antibiotic use and the number of antibiotic classes used, respectively. During 3,395 590 person-years of follow-up, 29 274 cases of RA were identified. Participants who used antibiotics for 91 or more days had a higher risk of RA (aHR, 1.79; 95% CI, 1.67-1.92) than antibiotic non-users. Additionally, individuals who used four or more kinds of antibiotic classes had a higher risk of RA (aHR, 1.61; 95% CI, 1.51-1.71) than those who did not prescribe antibiotics. The risk of RA was positively associated with both higher cumulative days of antibiotic exposure and a larger number of drug classes. These trends were maintained in sensitivity analyses, including variations in antibiotic exposure periods. Our findings suggest a possible association between the long-term use of antibiotics and RA incidence. Further studies are necessary for a clearer understanding of this association.

Selection of antibacterial aptamers against Pseudomonas plecoglossicida and analysis on their potential binding proteins

Pseudomonas plecoglossicida is one of the main pathogens causing visceral white spot disease of the large yellow croaker (Pseudosciaena crocea). Although antibiotics are used to control P. plecoglossicida infections, the long-term and large-scale use of antibiotics can lead to the development of drug-resistant bacteria as well as environmental pollution. Therefore, it is necessary to develop novel antibacterial agents to treat P. plecoglossicida infections. In this study, we first developed a two-step-centrifugation method to isolate live and dead P. plecoglossicida cells. Subsequently, we used the Systematic Evolution of Ligands by Exponential Enrichment (SELEX) screening based on inhibition rate to directly isolate antibacterial aptamers from the random library without post-processing. We isolated five antibacterial aptamers, namely B1, B2, B4, B8, and B109, which showed good inhibitory effects against P. plecoglossicida. Among these, B4 showed the highest inhibitory effect (62.40 ± 4.17 %). Further analysis revealed no positive correlation between the inhibitory effect of aptamers and their affinities with the target bacterium. The B4- and B109-binding proteins were isolated from P. plecoglossicida by magnetic separation and sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS-PAGE). Mass spectrometry analysis revealed that the 26 kDa ribosomal protein L2 was the probable B4-binding protein, while the 26 kDa ribosomal protein S3 and 75 kDa ribosomal protein S1 or succinate dehydrogenase flavoprotein subunit were the probable B109-binding proteins. Structural and subcellular localization analyses of these potential B4- and B109-binding proteins were also conducted. Our findings suggest that the inhibitory activity of the antibacterial aptamers against P. plecoglossicida may be mediated via their interaction with the ribosomal proteins, which can interfere with the protein synthesis process in the bacterium, affecting its growth. These findings provide the scientific basis for the development of functional antibacterial aptamers and the elucidation of their mechanisms of action.

Commensal consortia decolonize Enterobacteriaceae via ecological control

Persistent colonization and outgrowth of potentially pathogenic organisms in the intestine can result from long-term antibiotic use or inflammatory conditions, and may perpetuate dysregulated immunity and tissue damage1,2. Gram-negative Enterobacteriaceae gut pathobionts are particularly recalcitrant to conventional antibiotic treatment3,4, although an emerging body of evidence suggests that manipulation of the commensal microbiota may be a practical alternative therapeutic strategy5–7. Here we isolated and down-selected commensal bacterial consortia from stool samples from healthy humans that could strongly and specifically suppress intestinal Enterobacteriaceae. One of the elaborated consortia, comprising 18 commensal strains, effectively controlled ecological niches by regulating gluconate availability, thereby re-establishing colonization resistance and alleviating Klebsiella- and Escherichia-driven intestinal inflammation in mice. Harnessing these activities in the form of live bacterial therapies may represent a promising solution to combat the growing threat of proinflammatory, antimicrobial-resistant Enterobacteriaceae infection.

Clinical and cost-effectiveness of spironolactone in treating persistent facial acne in women: SAFA double-blinded RCT.

Acne is common, can cause significant impact on quality of life and is a frequent reason for long-term antibiotic use. Spironolactone has been prescribed for acne in women for many years, but robust evidence is lacking. To evaluate whether spironolactone is clinically effective and cost-effective in treating acne in women. Pragmatic, parallel, double-blind, randomised superiority trial. Primary and secondary healthcare and community settings (community and social media advertising). Women aged 18 years and older with facial acne persisting for at least 6 months, judged to potentially warrant oral antibiotic treatment. Participants were randomised 1:1, using an independent web-based procedure, to either 50 mg/day spironolactone or matched placebo until week 6, increasing to 100 mg/day spironolactone or matched placebo until week 24. Participants continued usual topical treatment. Primary outcome was the adjusted mean difference in Acne-Specific Quality of Life symptom subscale score at 12 weeks. Secondary outcomes included Acne-Specific Quality of Life total and subscales; participant self-assessed improvement; Investigator's Global Assessment; Participant's Global Assessment; satisfaction; adverse effects and cost-effectiveness. Of 1267 women assessed for eligibility, 410 were randomised (201 intervention, 209 control), 342 in the primary analysis (176 intervention, 166 control). Mean age was 29.2 years (standard deviation 7.2) and 7.9% (28/356) were from non-white backgrounds. At baseline, Investigator's Global Assessment classified acne as mild in 46%, moderate in 40% and severe in 13%. At baseline, 82.9% were using topical treatments. Over 95% of participants in both groups tolerated the treatment and increased their dose. Mean baseline Acne-Specific Quality of Life symptom subscale was 13.0 (standard deviation 4.7) across both groups. Mean scores at week 12 were 19.2 (standard deviation 6.1) for spironolactone and 17.8 (standard deviation 5.6) for placebo [difference favouring spironolactone 1.27 (95% confidence interval 0.07 to 2.46) adjusting for baseline variables]. Mean scores at week 24 were 21.2 (standard deviation 5.9) in spironolactone group and 17.4 (standard deviation 5.8) in placebo group [adjusted difference 3.77 (95% confidence interval 2.50 to 5.03) adjusted]. Secondary outcomes also favoured spironolactone at 12 weeks with greater differences at 24 weeks. Participants taking spironolactone were more likely than those taking placebo to report overall acne improvement at 12 weeks {72.2% vs. 67.9% [adjusted odds ratio 1.16 (95% confidence interval 0.70 to 1.91)]} and at 24 weeks {81.9% vs. 63.3% [adjusted odds ratio 2.72 (95% confidence interval1.50 to 4.93)]}. Investigator'sGlobalAssessment was judged successful at week 12 for 31/201 (18.5%) taking spironolactone and 9/209 (5.6%) taking placebo [adjusted odds ratio 5.18 (95% confidence interval 2.18 to 12.28)]. Satisfaction with treatment improved in 70.6% of participants taking spironolactone compared with 43.1% taking placebo [adjusted odds ratio 3.12 (95% confidence interval 1.80 to 5.41)]. Adverse reactions were similar between groups, but headaches were reported more commonly on spironolactone (20.4% vs. 12.0%). No serious adverse reactions were reported. Taking account for missing data through multiple imputation gave an incremental cost per quality-adjusted life-year of £27,879 (adjusted) compared to placebo or £2683 per quality-adjusted life-year compared to oral antibiotics. Spironolactone resulted in better participant-reported and investigator-reported outcomes than placebo, with greater differences at week 24 than week 12. This trial is registered as ISRCTN12892056 and EudraCT (2018-003630-33). This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 16/13/02) and is published in full in Health Technology Assessment; Vol. 28, No. 56. See the NIHR Funding and Awards website for further award information.

Association between antibiotics use and osteoporotic fracture risk: a nationally representative retrospective cohort study

SummaryThis population-based retrospective cohort study aimed to estimate the association between antibiotic exposure and osteoporotic fracture risk. Long-term antibiotic use was associated with the risk of osteoporotic fracture. An increase in the number of antibiotic classes prescribed may also be associated with an increased osteoporotic fracture risk.PurposeThis study aims to examine the association between antibiotic usage and osteoporotic fractures in a large cohort of Korean adults, with a specific focus on the duration of antibiotic exposure and the number of antibiotic classes used.MethodsThis retrospective cohort study from the National Health Insurance Service-National Health Screening Cohort (NHIS-HEALS) database from January 1, 2002, to December 31, 2019, included 167,370 Korean adults aged 50 years or older (mean [SD] age, 59.3 [7.82] years; 65,425 [39.09%] women). The cumulative antibiotic prescription days and the classes of antibiotics prescribed between 2004 and 2008 were exposure variables, respectively. The main outcome was a newly diagnosed osteoporotic fracture during follow-up. Cox proportional hazard regression was used to determine the adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for the incident osteoporotic fractures associated with antibiotic exposure.ResultsThe antibiotic user group with 91 days had a higher risk of osteoporotic fracture in comparison to the antibiotic non-user group (aHR, 1.12; 95% CI, 1.03–1.21). Additionally, those who used more than four different antibiotic classes had an elevated risk of osteoporotic fracture compared to the non-user group (aHR, 1.10; 95% CI, 1.02–1.18).ConclusionThis extensive population-based cohort study conducted on a large population has identified an association between the utilization of antibiotics and an elevated risk of osteoporotic fractures. The cumulative days exposed to antibiotics and osteoporotic fractures may be positively associated.

Days of Antibiotic Spectrum Coverage (DASC) as a Metric for Evaluating the Impact of Prospective Audit and Feedback (PAF) against Long-Term Broad-Spectrum Antibiotic Use.

The present study aimed to evaluate the impact of prospective audit and feedback (PAF) on the use of inpatient broad-spectrum antibiotics for more than 10 days using days of therapy (DOT) and a novel metric called days of antibiotic spectrum coverage (DASC) to assess whether the antimicrobial spectrum was narrowed. Conducted at Aichi Medical University Hospital in Japan, the study compared a six-month baseline period (April to September 2022) with a six-month intervention period (April to September 2023). The primary outcome measures were changes in DOT/patient and DASC/patient for broad-spectrum antibiotics. Propensity score matching was performed between two periods and a total of 172 patients were included in the study (pre-intervention, n = 86; intervention, n = 86). The DASC/patient of broad-spectrum antibiotics was statistically decreased in the intervention period compared to that in the baseline period (153.3 vs. 122.7, p < 0.05). Additionally, our PAF intervention led to a switch to narrow-spectrum antimicrobial therapy without increasing all-cause 30-day mortality (5.8% vs. 5.8%, p = 1.0). However, the DOT/patient, DASC/patient, and DASC/DOT of all antimicrobials were not significantly changed. Our study concluded that we should reconsider the timing of PAF intervention by evaluating the effort of PAF by using DOT and DASC.

Antibacterial activity of a polysaccharide isolated from litchi (Litchi chinensis Sonn.) pericarp against Staphylococcus aureus and the mechanism investigation

The long-term use of antibiotics can cause drug resistance. Natural polysaccharides are a novel means of treating bacterial infections, and the development and utilization of litchi pericarp polysaccharide (LPPs) as a bacteriostatic active substance offer a new research direction for the high-value utilization of litchi by-products. This study revealed that LPPs inhibited Staphylococcus aureus more than Escherichia coli, Listeria monocytogenes, and Salmonella typhimurium, with the minimum inhibitory concentrations of 145, 205, 325, and 445 μg/mL, respectively. The inhibitory activity of LPPs was insignificant for Bacillus subtilis at 505 μg/mL. The assessment of antibacterial mechanisms revealed that LPPs influenced the growth, conductivity, protein, and nucleic acid, reducing sugar, respiratory chain dehydrogenase activity, bacterial lipid peroxidation, intracellular adenosine triphosphate, and extracellular alkaline phosphatase levels of S. aureus. Of note, LPPs could modify the cell wall integrity and cell membrane permeability of S. aureus, resulting in the leakage of intracellular large and small molecules, inhibition of cellular respiratory metabolism, and oxidative losses. These processes exhibited an inhibitory effect and made the bacterium nonfunctional, thereby affecting its growth and metabolism or causing cell death. These findings provide support and insights into the potential application of LPPs as a natural antimicrobial agent.

Comparison of surgical site infection in patients undergoing laparoscopic cholecystectomy with or without prior ERCP.

Objective: To compare the risk of surgical site infections in patients undergoing laparoscopic cholecystectomy with or without prior ERCP. Study Design: Prospective Comparative study. Setting: Surgical Unit-I of Holy Family Hospital, Rawalpindi. Period: December 2021 to May 2022. Methods: Total 140 patients were included. Group A had ERCP before their laparoscopic cholecystectomy. Those, who had laparoscopic cholecystectomy without first undergoing ERCP included in Group B. For this study, we used SPSS to analyze the data we gathered (version 23.0). Two groups were compared for surgical site infection using the Chi-square test. The level of significance was set at P 0.05. Results: Total 140 patients with biliary tract disease (choledocholithiasis, cholangitis and cholelithiasis) were enrolled in this study. In group-A, there were 16(22.9%) males and 54(77.1%) females, while in Group-B, there were 14(20.0%) males and 56(80.0%) females. In patients with prior ERCP group, 28(40.0%) developed surgical site infections, while in patients without ERCP group, 13(18.6%) developed surgical site infections with a p-value of 0.005, which is statistically significant. Conclusion: An increase in the incidence of SSI following laparoscopic cholecystectomy by two- fold is connected with pre-operative (ERCP) so we plan to assess if this technique is linked to a higher risk of wound infection after surgery. we suggest that long term use of antibiotics can reduce the rate of SSI and longer stay of patients in hospital.

A history of repeated antibiotic usage leads to microbiota-dependent mucus defects

ABSTRACT Recent evidence indicates that repeated antibiotic usage lowers microbial diversity and ultimately changes the gut microbiota community. However, the physiological effects of repeated – but not recent – antibiotic usage on microbiota-mediated mucosal barrier function are largely unknown. By selecting human individuals from the deeply phenotyped Estonian Microbiome Cohort (EstMB), we here utilized human-to-mouse fecal microbiota transplantation to explore long-term impacts of repeated antibiotic use on intestinal mucus function. While a healthy mucus layer protects the intestinal epithelium against infection and inflammation, using ex vivo mucus function analyses of viable colonic tissue explants, we show that microbiota from humans with a history of repeated antibiotic use causes reduced mucus growth rate and increased mucus penetrability compared to healthy controls in the transplanted mice. Moreover, shotgun metagenomic sequencing identified a significantly altered microbiota composition in the antibiotic-shaped microbial community, with known mucus-utilizing bacteria, including Akkermansia muciniphila and Bacteroides fragilis, dominating in the gut. The altered microbiota composition was further characterized by a distinct metabolite profile, which may be caused by differential mucus degradation capacity. Consequently, our proof-of-concept study suggests that long-term antibiotic use in humans can result in an altered microbial community that has reduced capacity to maintain proper mucus function in the gut.

Modern understanding of the problem of infections caused by Staphylococcus aureus

The article analyzes current literature data from 28 domestic and foreign sources on changes in the microbiological structure of nosocomial staphylococcus against the background of longterm use of antibiotics in clinical practice. New toxigenic characteristics of nosocomial strains of staphylococcus associated with its genome are described. New information has been obtained on the immunogenesis of staphylococcal infections, taking into account the action of their toxins. In the above epidemiological studies in various regions, a significant spread of methicillin-resistant staphylococci was revealed in medical institutions. It has been established that the assessment of the etiological features of nosocomial staphylococcal infections is key to the formation of effective prevention strategies aimed at reducing the likelihood of nosocomial infections.

1-Minute Pearls/Pitfalls for the Clinician

This article describes a few pearls/pitfalls pertinent to the use of colchicine in patients with coronary artery disease and the use of long-term prophylactic antibiotics in patients with cirrhosis.

Характеристика перебігу епідемічного процесу скарлатини у сучасних умовах

S carlet fever is one of the most common nosological forms of group A streptococcal infection (SGA). In recent years, there has been an increase in the incidence of this infection in the countries of Europe and Asia, the USA and Canada. The analysis of professional publications of different countries of the world regarding the manifestations of the epidemic process of scarlet fever was carried out, as well as information on epidemiological studies conducted by the authors was provided. It has been established that children remain the leading risk group for scarlet fever, men are more often affected among adults, but the role of young women who care for children as a source of infection is increasing. The aerosol-aspiration mechanism of transmission of the causative agent of scarlet fever is realized by airborne and contact-household ways of its transmission. There is an intensification of the contact-household way of transmission of the pathogen. An atypical course of scarlet fever is observed with manifestations of co-infection, in particular, gastroenterocolitis, chicken pox and respiratory infections. A significant number of publications are devoted to the influence of environmental factors on the course of the epidemic process of scarlet fever. The authors note a direct correlation between the incidence of scarlet fever and atmospheric air pollutants, meteorological factors, as well as the influence of social and economic factors on the epidemic situation of this infection. Long-term use of antibiotics has contributed to the development of antibiotic resistance to the most common drugs, which prompts scientists to develop vaccines against iSGA. So, scarlet fever is characterized by widespread distribution, impression of mainly children, co-infection, atypical clinical course, especially in immunocompromised persons, and implementation of the contact-household way of transmission of the pathogen. The influence of social, natural and environmental factors on the course of the epidemic process of scarlet fever has been established, which is important to consider when conducting epidemiological surveillance of this infection. The introduction of vaccination against iSGA will contribute to the reduction of antibiotic resistance, which is currently a global problem for humanity. We consider it necessary to include scarlet fever and other iSGA in the list of infectious diseases subject to registration in Ukraine. Key words: scarlet fever, incidence, risk groups, ways of pathogen transmission, atypical course, co-infection, environmental factors, antibiotic resistance.

Preparation of antimicrobial peptides and their combination with hydrogels for wound healing applications

The problem of drug resistance caused by long-term use of antibiotics has been a concern for many years. As this problem worsens, there are various bacterial-induced infections that have a serious impact on human health. Currently, antimicrobial peptides are good alternatives to antibiotics, which have powerful antimicrobial activity and unique antimicrobial mechanisms. Developing bacterial resistance is not easy. In addition, how to reduce the production cost of antimicrobial peptides and improve the screening efficiency are the problems that must be solved for antimicrobial peptide application. In this study, we employed cell membrane chromatography linked with the one-bead-one-substance approach to screen and prepare the antimicrobial peptide (SALSP), which offers the benefits of fast synthetic screening and easy operation. Meanwhile, the antimicrobial peptide showed great antimicrobial activity and biocompatibility. We prepared a conjugated sodium alginate/gelatin hydrogel wound dressing incorporating antimicrobial peptides to promote wound healing. In conclusion, this research provides solutions for the development and application of antimicrobial peptides.

Antibiotic-induced gut microbe dysbiosis alters neurobehavior in mice through modulation of BDNF and gut integrity

Gut microbiota is essential for intestinal integrity and brain functions. Herein we aimed to investigate the effects of alteration of gut microbiome using broad-spectrum antibiotics on CD 1 male mice (germ-modified group (GM). Moreover, we co-administrated probiotics with or without antibiotics for four weeks and evaluated if probiotics could reverse these behavioral and intestinal effects. GM, co-administered antibiotics and probiotics, and probiotics-only groups were compared to control mice of the same sex, age, and weight that did not receive either drug (n=12 in all groups). Cultivation of aerobic and anaerobic bacteria was evaluated by fecal culture of all groups. We tested exploratory behavior, anxiety, memory, depression-like behavior, and hippocampal and frontal lobe BDNF protein level alterations in response to antibiotics and its downstream effect on the PI3K/Akt1/Bcl2 pathway. Intestinal integrity was evaluated using gene expression analysis of ZO-1, claudin, and occludin genes. Additionally, the inflammatory TLR4 and p-p38 MAPK pathways in the intestines were investigated. Twice-daily administration of oral antibiotics for four weeks significantly reduced total bacterial count and upregulated TLR4 and p-p38.GM mice showed a significant reduction in BDNF(P =0.04), impaired spatial memory, and long-term memory as evidenced by decreased T maze correct alternation trails and shortened retention time in the passive avoidance test in GM(P =0.01). Passive avoidance showed significantly increased latency after probiotics intake. Depressive-like behavior was more pronounced in GM mice as assessed by the tail suspension test (P =0.01). GM showed significant upregulation(p<0.001) of the TLR4 and p-p38 MAPK pathway. Co-administration of probiotics with antibiotics showed an increase in BDNF levels, and upregulation of the cell survival PI3K/Akt1/Bcl2 pathway, significantly higher relative abundance in the firmucutes members, a significant decrease in the Firmicutes/Bacteroidetes ratio and downregulation of TLR4 and p-p38 MAPK. The tight junction proteins ZO-1, claudin and occludin were downregulated by antibiotic administration for four weeks and restored by probiotics. Collectively, the data suggest that long-term use of antibiotics appears to disrupt the intestinal epithelial barrier and alter neurobehavioral qualities specifically, long-term memory and exploratory drive, possibly through the reduction of BDNF, and probiotics partially reverse these effects.Our study emphasizes the effect of prolonged intake of antibiotics on production of dysbiosis as well as the impact of the antibiotic induced intestinal inflammation on neurobehavioral aspects in mice as the memory and anxiety-like behavior. We also reveal that co-administration of probiotics can reverse these changes