High Levels Of Antibiotic Resistance Research Articles

Epidemiology of Bacteremia in Patients with Hematological Malignancies and Hematopoietic Stem Cell Transplantation and the Impact of Antibiotic Resistance on Mortality: Data from a Multicenter Study in Argentina

The epidemiology of bacteremia and the antibiotic resistance profile (ARP) of Gram-negative bacilli (GNB) in hematological malignancies (HM) and hematopoietic stem cell transplant (HSCT) patients may differ according to geographic region. In addition, multidrug-resistant organisms (MDROs) may impact mortality. This is a prospective, observational, and multicenter study. The first episodes of bacteremia in adult patients with HM or HSCT were included. The risk factors for 30-day mortality were identified. One thousand two hundred and seventy-seven episodes were included (HM: 920; HSCT: 357). GNB were isolated in 60.3% of episodes, with Enterobacterales (46.9%) and P. aeruginosa (8.5%) being the most frequent. Gram-positive cocci were isolated in 41.9% of episodes, with coagulase-negative staphylococci (19.8%) and S. aureus (10.4%) being the most frequent. MDROs were isolated in 40.2% (24.4% GNB). The ARP of GNB in patients with HM vs. HSCT was cefepime: 36.8% vs. 45.7% (p = 0.026); piperacillin–tazobactam: 31.05% vs. 45.2% (p < 0.0001); carbapenems: 18.9% vs. 27.3% (p = 0.012); and aminoglycosides: 9.3% vs. 15.4% (p = 0.017), respectively. Overall mortality between patients with HM and HSCT was 17.5% vs. 17.6% (p = 0.951), respectively. The risk factors for mortality were relapsed and refractory underlying disease, corticosteroids use, respiratory source, septic shock, and GNB resistant to meropenem, while 7-day clinical response was a protective factor for survival. Bacteremia was frequently caused by GNB, with a large proportion of MDROs and a high level of antibiotic resistance, especially in patients with HSCT. Carbapenem-resistant GNB bacteremia was associated with a significant increase in mortality.

An investigative study on Yersinia enterocolitica in animals, humans and dried milk in New Valley Governorate, Egypt

BackgroundYersiniosis is one of the most significant intestinal disorders caused by Yersinia enterocolitica and affects both humans and animals. This study aimed to investigate the prevalence of Y. enterocolitica in New Valley Governorate, Egypt in animals, humans, fresh milk and dried milk. Additionally, this study analyzed the presence of virulence genes, including ail and Yst in tested isolates and conducted a phylogenetic analysis to determine the genetic similarity between human, and animal Y. enterocolitica isolates. Finally, the antimicrobial resistance patterns of the isolates were examined.ResultsAmong the 982 samples examined, the prevalence of Y. enterocolitica based on ISO10273-2017 was 11.7% in animal samples including 12.8% of animal faeces, and 10.4% in milk samples. Moreover, the prevalence of Y. enterocolitica was 13.2% in human stool, and 9.5% in dried milk samples. The molecular characterization of the six randomly selected isolates showed that the 16S rRNA, ail and Yst genes were found in 50, 33.3 and 100% of the examined Y. enterocolitica isolates, respectively. Phylogenetic analysis of animal and human isolates based on the 16S rRNA gene revealed a high degree of similarity between the isolates. All the tested animal and human Y. enterocolitica isolates (100%) were resistant to ampicillin and cefotaxime, but highly sensitive to norfloxacin.ConclusionsThe high prevalence of Y. enterocolitica in animal and human samples with high degrees of genetic similarity poses a threat to public and animal health. Animal faeces, milk and milk powder represent the main sources of Y. enterocolitica infection in humans. Additionally, high levels of antibiotic resistance of Y. enterocolitica can cause public health hazards by leading to the failure of disease prevention and treatment programs in humans and animals.

Surface hydrophilicity promotes bacterial twitching motility.

The bacterial type IV pilus (T4P) is a critical virulence factor for many medically important pathogens, some of which are prioritized by the World Health Organization for their high levels of antibiotic resistance. The T4P is known to propel bacterial twitching motility, the analysis of which provides a convenient assay for T4P functionality. Here, we show that bile salts and other detergents augment the twitching of multiple bacterial pathogens. We identified the underlying mechanism as the alteration of surface hydrophilicity by detergents. Consequently, hydrophilic surfaces like those of glass or plasma-treated polystyrene promote bacterial twitching, bypassing the requirement for detergents. The implication is that surface properties, such as those of tissues and medical implants, significantly impact the functionality of bacterial T4P as a virulence determinant. This offers valuable insights for developing countermeasures against the colonization and infection by bacterial pathogens of critical importance to human health on a global scale.

Antibiotic resistance and virulence characteristics of Vibrio vulnificus isolated from Ningbo, China.

Vibrio vulnificus (V. vulnificus) is a deadly opportunistic human pathogen with high mortality worldwide. Notably, climate warming is likely to expand its geographical range and increase the infection risk for individuals in coastal regions. However, due to the absence of comprehensive surveillance systems, the emergence and characteristics of clinical V. vulnificus isolates remain poorly understood in China. In this study, we investigate antibiotic resistance, virulence including serum resistance, and hemolytic ability, as well as molecular characteristics of 21 V. vulnificus isolates collected from patients in Ningbo, China. The results indicate that all isolates have been identified as potential virulent vcg C type, with the majority (16 of 21) classified as 16S rRNA B type. Furthermore, these isolates exhibit a high level of antibiotic resistance, with 66.7% resistance to more than three antibiotics and 61.9% possessing a multiple antibiotic resistance (MAR) index exceeding 0.2. In terms of virulence, most isolates were categorized as grade 1 in serum resistance, with one strain, S12, demonstrating intermediate sensitivity in serum resistance, belonging to grade 3. Whole genome analysis disclosed the profiles of antibiotic resistance genes (ARGs) and virulence factors (VFs) in these strains. The strains share substantial VF genes associated with adherence, iron uptake, antiphagocytosis, toxin, and motility. In particular, key VFs such as capsule (CPS), lipopolysaccharide (LPS), and multifunctional autoprocessing repeats-in-toxin (MARTX) are prevalent in all isolates. Specifically, S12 possesses a notably high number of VF genes (672), which potentially explains its higher virulence. Additionally, these strains shared six ARGs, namely, PBP3, adeF, varG, parE, and CRP, which likely determine their antibiotic resistance phenotype. Overall, our study provides valuable baseline information for clinical tracking, prevention, control, and treatment of V. vulnificus infections.

Prevalence and Antibiotic Sensitivity Profile of Pseudomonas aeruginosa Isolated from Patients with Otitis Media in Kirkuk City

Background: Otitis media (OM) is middle ear inflammation, it is a prevalent health care disorder that affects people of all ages and both genders. Pseudomonas aeruginosa (P. aeruginosa) is the most prevalent pathogen bacteria that causes the disease and has a high level of antibiotic resistance. The P. aeruginosa possess virulence characteristics which cause damages to the middle ear mucosa.Antibiotic resistance constitutes the main threat to people's health. Objective: The objective of the current study is to evaluate the frequency of P. aeruginosa isolated from Otitis media patients and investigate their antibiotic susceptibility pattern. Materials and Methods: total of 235 ear swabs were collected from otitis media patients who visited a specialized outpatient center in Kirkuk City and the ENT consultation facility at Kirkuk Hospitals. Antibiotic susceptibility testing by the VITEK 2 AST card and bacterial isolation and identification were both done. Results: The results of this study reveal that out of 235 ear swabs collected from patients with otitis media showed 22/235 (9.4 %) isolation rate for P. aeruginosa. And among the most effective antibiotics against the most of the detected pathogenic bacteria were Amikacin (95.4%), followed by Ceftazidime/ Avibactam, Piperacillin /Tazobactam, and Ceftolozane/ Tazobactam each with (91%), Colistin (86%), Imipenemand and Meropenem (81.8%, 86.4%) respectively, Ceftazidime, Cefeime, Levofloxacin, and Azreonam each with ( 77.3%), Ciprofloxacin and Ofloxacin both (72.7%) with Gentamicin (68.2%). Conclusion: The bacteria P. aeruginosa was most common prevalent isolate in the ear swabs, and this bacteria is multidrugs resistance (MDR). Additionally, the most efficient antibiotic against P. aeruginosa isolates responsible for otitis media was Amikacin.

Distribution of Nosocomial Pathogens and Antimicrobial Resistance among Patients with Burn Injuries in China: A Comprehensive Research Synopsis and Meta-Analysis.

Over the past decade, numerous studies have described the types of pathogens and their antibiotic resistance patterns in patients with burn injuries in China; however, the findings have generally been inconsistent. We conducted a literature search and meta-analysis to summarize the infection spectra and antimicrobial resistance patterns in patients with burn injuries. We searched the PubMed, Embase, Web of Science, China National Knowledge Infrastructure, China Biomedical Literature, Wanfang, and Weipu databases for relevant articles published between January 2010 and December 2023. The DerSimonian-Laird random-effects model was used to estimate the proportions and 95% confidence intervals (CIs) of pathogens among Chinese patients with burn injuries. Meta-regression analyses were performed to explore differences in the proportions of pathogens among different subgroups and their resistance patterns. This study was registered with PROSPERO (CRD42024514386). The database searches yielded 2017 records; after removing duplicates and conducting initial screening, 219 articles underwent full-text screening. Ultimately, 60 studies comprising a total of 62,819 isolated strains reported the proportions of pathogens in patients with burn injuries and were included in this meta-analysis. Meta-analyses were conducted on 18 types of pathogens. The most common pathogens causing infections in Chinese patients with burn injuries were Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, and Staphylococcus epidermidis. Similar results were observed in the subgroup analysis focusing on wound infections. Since 2015, there has been a significant decrease in the proportion of Pseudomonas aeruginosa (R2 = 4.89%) and a significant increase in the proportion of Klebsiella pneumoniae (R2 = 9.60%). In terms of antibiotic resistance, there has been a significant decrease in the resistance of Staphylococcus aureus to multiple antibiotics and an increasing trend in the resistance of Klebsiella pneumoniae. We systematically summarized the epidemiological characteristics and antibiotic resistance patterns of pathogens among individuals suffering from burns in China, thus providing guidance for controlling wound infections and promoting optimal empirical antimicrobial therapy. The observed high levels of antibiotic resistance underscore the need for ongoing monitoring of antibiotic usage trends.

Regulatory interactions between daptomycin- and bacitracin-responsive pathways coordinate the cell envelope antibiotic resistance response of Enterococcus faecalis.

Enterococcal infections frequently show high levels of antibiotic resistance, including to cell envelope-acting antibiotics like daptomycin (DAP). While we have a good understanding of the resistance mechanisms, less is known about the control of such resistance genes in enterococci. Previous work unveiled a bacitracin resistance network, comprised of the sensory ABC transporter SapAB, the two-component system (TCS) SapRS and the resistance ABC transporter RapAB. Interestingly, components of this system have recently been implicated in DAP resistance, a role usually regulated by the TCS LiaFSR. To better understand the regulation of DAP resistance and how this relates to mutations observed in DAP-resistant clinical isolates of enterococci, we here explored the interplay between these two regulatory pathways. Our results show that SapR regulates an additional resistance operon, dltXABCD, a known DAP resistance determinant, and show that LiaFSR regulates the expression of sapRS. This regulatory structure places SapRS-target genes under dual control, where expression is directly controlled by SapRS, which itself is up-regulated through LiaFSR. The network structure described here shows how Enterococcus faecalis coordinates its response to cell envelope attack and can explain why clinical DAP resistance often emerges via mutations in regulatory components.

Unveiling Antibiotic Resistance, Clonal Diversity, and Biofilm Formation in E. coli Isolated from Healthy Swine in Portugal.

Escherichia coli, a commensal microorganism found in the gastrointestinal tract of human and animal hosts, plays a central role in agriculture and public health. Global demand for animal products has promoted increased pig farming, leading to growing concerns about the prevalence of antibiotic-resistant E. coli strains in swine populations. It should be noted that a significant portion of antibiotics deployed in swine management belong to the critically important antibiotics (CIA) class, which should be reserved for human therapeutic applications. This study aimed to characterize the prevalence of antibiotic resistance, genetic diversity, virulence characteristics, and biofilm formation of E. coli strains in healthy pigs from various farms across central Portugal. Our study revealed high levels of antibiotic resistance, with resistance to tetracycline, ampicillin, tobramycin, and trimethoprim-sulfamethoxazole. Multidrug resistance is widespread, with some strains resistant to seven different antibiotics. The ampC gene, responsible for broad-spectrum resistance to cephalosporins and ampicillin, was widespread, as were genes associated with resistance to sulfonamide and beta-lactam antibiotics. The presence of high-risk clones, such as ST10, ST101, and ST48, are a concern due to their increased virulence and multidrug resistance profiles. Regarding biofilm formation, it was observed that biofilm-forming capacity varied significantly across different compartments within pig farming environments. In conclusion, our study highlights the urgent need for surveillance and implementation of antibiotic management measures in the swine sector. These measures are essential to protect public health, ensure animal welfare, and support the swine industry in the face of the growing global demand for animal products.

Detection of Extended Spectrum ß-Lactamase-Producing Escherichia coli with Biofilm Formation from Chicken Meat in Istanbul.

Antimicrobial resistance is one of the major public health problems worldwide. This study aimed to detect the presence of extended-spectrum β-lactamase-(ESBL-)producing Escherichia (E.) coli in chicken meat in Istanbul, Türkiye. Raw chicken meat samples (n = 208) were collected from different sale points and analyzed for ESBL-producing E. coli. In total, 101 (48.5%) isolates were confirmed as E. coli by PCR, of which 80/101 (79.2%) demonstrated multiple antibiotic resistance. Resistance against amoxicillin-clavulanic acid was most frequent (87.1%). Eighteen isolates (17.8%) demonstrated phenotypical ESBL resistance, as assessed by the double disc synergy test (DDST). Isolates were tested for the presence of β-lactamase genes and mobilized colistin-resistant genes. The blaTEM group was most frequently detected (97.02%), followed by blaCTX m (45.5%), blaSHV (9.9%), and blaOXA-2 (0.9%). However, mcr genes and blaNDM,blaKPC, blaVIM, and blaOXA-48 genes were not found in any isolate. E. coli strains were tested for biofilm formation in six different media [Nutrient broth, LB broth, Tryptone Soya broth (TSB), TSB containing 1% sucrose, TSB containing 0.6% yeast extract, and BHI]. Biofilm formation by E. coli isolates (44/101, 43.5%) was highest in TSB with 1% sucrose. It is worth noting that all biofilm-producing isolates were found to harbor the blaTEM-1 gene, which can indicate a high level of antibiotic resistance. This is the first report about ESBL-producing E. coli in poultry meat, the exposure of consumers in Istanbul metropolitan areas, and the ability of E. coli from this region to produce biofilms.

Pseudomonas aeruginosa strains isolated from animal with high virulence genes content and highly sensitive to antimicrobials

P. aeruginosa is one of the most metabolically versatile bacteria having the ability to survive in multiple environments through its accessory genome. An important hallmark of P. aeruginosa is the high level of antibiotic resistance, which often makes eradication difficult and sometimes impossible. Evolutionary forces have led to this bacterium to develop high antimicrobial resistance with a variety of elements contributing to both intrinsic and acquired resistance. The objectives were to genetically and phenotypically characterizer P. aeruginosa strains isolated from companion animals of different species. We characterized a collection of 39 P. aeruginosa strains isolated from infected animals. The genetic characterization was in relation to chromosomal profile by PFGE; content of virulence gene; presence of genomic islands (GIs); genes of the cytotoxins exported by T3SS: exoU, exoS, exoT and exoY; and type IV pili allele. The phenotypic characterization was based on patterns of susceptibility to different antimicrobials. Each strain had a PFGE profile, a high virulence genes content, and a large accessory genome. However, most of the strains presented high sensitivity to almost all antimicrobials tested, showing no acquired resistance (no β-lactamases). The exception to this lack of resistance was seen with penicillin. P. aeruginosa could be a naturally sensitive bacterium to standard antimicrobials but could rapidly develop intrinsic and acquired resistance when the bacterium is exposed to pressure exerted by antibiotics, as observed in hospital settings.

Antimicrobial resistance patterns, virulence genes, and biofilm formation in enterococci strains collected from different sources

BackgroundCurrently, antibiotic-resistant strains of Enterococcus are considered to be one of the critical health challenges globally. This study aimed to investigate the antibiotic susceptibility pattern, biofilm formation capacity, and virulence genes of enterococci isolated from different sources.MethodsIn this cross-sectional study, environmental and fecal samples were collected from the hospital environment, volunteers, and hospital staff from October 2018 to August 2019. The isolates were identified by morphological and biochemical tests (gram staining, catalase, bile resistance, esculin hydrolysis, carbohydrate fermentation, growth in 6.5% NaCl, Pyrrolidonyl arylamidase, arginine dehydrolase), and PCR for ddl gene. An antimicrobial susceptibility test was performed by the standard disk agar diffusion method according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. Quantitative microplate assays were used to assess biofilm production. The bacterial DNAs were extracted by alkaline lysis method and polymerase chain reaction technique was used detect the esp, ace, and efaA virulence genes.ResultsOut of 145 isolates, 84 (57.9%) were identified as E. faecalis and 61 (42.1%) as E. faecium. Resistance to kanamycin and quinupristin-dalfopristin was 82.1% (69/84) and 85.7% (72/84), respectively, in E. faecalis isolates. Out of 61 E. faecalis isolates, 38 (62.4%) were resistant to kanamycin. Among the E. faecalis isolates, esp was the most dominant virulence gene (73.80%), followed by efaA, and ace, which were detected in 60.71%, and 30.95% isolates, respectively. In total, 68.27% of the strains were biofilm producers. Further, esp and efaA genes were more frequently found among E. faecalis strains with moderate and strong biofilm biomass.ConclusionsAccording to the findings of our study, enterococci strains isolated from different samples possess distinctive patterns of virulence genes. The esp, ace, and efaA genes were more prevalent among E. faecalis than E. faecium. Besides, the high level antibiotic resistance of normal flora and environmental enterococci strains is alarming the researchers.

Analysis of the infectious agent’s structure and antibiotic resistance parameters in patients in intensive care units of a multidisciplinary hospital

Introduction. Nosocomial infections are a common complication in patients treated in the intensive care unit (ICU). Microorganisms with multidrug resistance are one of the significant risk factors for death in this category of patients. Aim. To study structure of infectious agents in ICU patients and parameters of their antibiotic resistance. Materials and methods. Retrospective pharmacoepidemiological study of medical records of adult patients with infections diagnosed in ICU who were treated in City Clinical Hospital No. 24 of the Department of Health (Moscow, Russian Federation) in the period 08/20/2022 — 07/31/2023 (n=199). The analysis (gender, age of patients, localization of the infectious process, data on the structure of pathogens and sensitivity to antibacterial drugs) included records with data on bacterial culture ( n=141). Results. In the structure of pathogens detected in ICU patients, gram-negative microflora predominated (54 %). Among the pathogens with a clinically significant growth, leaders were K. pneumoniae (22 %), Candida spp. (20 %) and Staphylococcus spp. (19 %). K. pneumoniae was characterized by resistance to beta-lactams, aminoglycosides, and levofloxacin, the highest susceptibility was reported to colistin, 88.9 %. Candida spp. was overwhelmingly susceptible to all drugs used. Among Staphylococ caceae, S. aureus was the most common (70 % resistance to ampicillin and cefoxitin). Conclusion. In the structure of infectious agents detected in ICU patients, a predominance of ESKAPE pathogens (the most prognostically important microorganisms: Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp.) was observed, including K. pneumoniae, S. aureus, A. baumannii, P. aeruginosa. For all these microorganisms, except for Staphylococcaceae, a high level of antibiotic resistance was demonstrated.

Emergence of High-Level Antibiotic Resistance in Klebsiella pneumoniae: A Narrative Review

In an era marked by remarkable advancements in medicine, the persistent emergence of high-level antibiotic resistance in Klebsiella pneumoniae poses a critical threat to public health globally. As the worldwide spread of extensively drug-resistant (XDR) and pan-drug-resistant (PDR) K. pneumoniae strains continues to grow, a significant shift in how we approach treatment is on the horizon. The complex interaction of genetic factors, which encompasses a wide range of beta-lactamases, aminoglycoside-modifying enzymes, and chromosomal mutations, creates a dynamic resistance mechanism that counters the effects of antibiotics. These intricate adaptations, arising from both gene transfers facilitated by plasmids and changes in the genome itself, present a challenging obstacle to our efforts in managing antimicrobial effectiveness. Klebsiella infections come back stronger armed with molecular tactics that challenge healthcare systems, prolong hospital stays, and increase mortality. Beyond healthcare settings, the economic and social dimensions grow as resources are redirected, intensifying the impact on vulnerable groups. This review delves into the intricate mechanisms behind the high-level antibiotic resistance in K. pneumoniae, examining its epidemiological, molecular, and clinical facets. Highlighting the necessity for coordinated research, medical protocols, and policies, the review underscores the importance of judicious antibiotic utilization, drug innovation, and rigorous infection management.

Mutation-driven resistance development in wastewater E. coli upon low-level cephalosporins: Pharmacophore contribution and novel mechanism

Cephalosporins have been widely applied in clinical and veterinary settings and detected at increasing concentrations in water environments. They potentially induce high-level antibiotic resistance at environmental concentrations. This study characterized how typical wastewater bacteria developed heritable antibiotic resistance under exposure to different cephalosporins, including pharmacophore-resistance correlation, resistance mechanism, and occurrence of resistance-relevant mutations in different water environments. Wastewater-isolated E. coli JX1 was exposed to eight cephalosporins individually at 25 µg/L for 60 days. Multidrug resistance developed and diverse mutations arose in selected mutants, where a single mutation in ATP phosphoribosyltransferase encoding gene (hisG) resulted in up to 128-fold increase in resistance to meropenem. Molprint2D pharma RQSAR analysis revealed that hydrogen-bond acceptors and hydrophobic groups in the R1 and R2 substituents of cephalosporins contributed positively to antibiotic resistance. Some of these pharmacophores may persist during bio- or photo-degradation in the environment. hisG mutation confers a novel resistance mechanism by inhibiting fatty acid degradation, and its variants were more abundant in water-related E. coli (especially in the effluent of wastewater treatment plants) compared with those in non-water environments. These results suggest that specific degradation of particular pharmacophores in cephalosporins could be useful for controlling resistance development, and mutations in previously unreported resistance genes (e.g., hisG) can lead to overlooked antibiotic resistance risks in water environments.

Detection of the effect of synthetic siRNA on efflux pump MexA gene expression and antibiotic resistance in clinical isolates of Pseudomonas aeruginosa

Introduction and Aim: Pseudomonas aeruginosa is a nosocomial infection with an ability to develop high levels of antibiotic resistance. The efflux pump system is one of the mechanisms that is linked to multidrug resistance in P. aeruginosa. In this study, we employed siRNA loaded on gold nanoparticles against the MexA efflux pump gene to decrease the MexA gene expression in P. aeruginosa and estimated antibiotic resistance after gene silencing. Materials and Methods: This study examined four strains of P. aeruginosa isolated from patients in various hospitals in Baghdad. Bacteria isolated were identified by biochemical tests and Vitek compact 2 system. Single-stranded siRNA (33bp) designed in this study was loaded onto gold nanoparticles (AuNPls). Detection of the MexA gene was carried out by conventional PCR technique. The expression of MexA gene was examined by qRT-PCR in order to determine if the siRNA have impacted on MexA gene expression and on the antibiotic resistance in aeruginosa Results: This study showed that the mRNA expression level of the MexA gene exhibited a decrease in fold change CT -2 in P. aeruginosa (isolates numbers 67, 66,49, and PDR(5p)) when examined in vitro. The specific fold change values observed were (0.202, 0.040, 0.063, and 0.163) respectively. The resistance percentages of antibiotics tested was observed to increase after MexA gene silencing. Conclusion: Targeting the MexA gene with synthetic siRNA may be a unique approach to diminish P. aeruginosa resistance to antibiotics. However, many unexpected consequences may occur when utilizing any genetic manipulation in bacteria.

Time-dependent pharmacodynamics of amikacin on Mycobacterium abscessus growth and resistance emergence.

Mycobacterium abscessus pulmonary disease is increasing in prevalence globally, particularly for individuals with cystic fibrosis. These infections are challenging to treat due to a high rate of resistance. Amikacin is critical to treatment, but the development of toxicity, amikacin resistance, and treatment failure are significant challenges. Amikacin has been characterized previously as peak-dependent and extended-interval dosing is commonly used. In our hollow fiber infection model of M. abscessus, amikacin exhibited time-dependent rather than the expected peak-dependent pharmacodynamics. Humanized amikacin exposures with more frequent, short-interval dosing (continuous infusion or every 12 hours) yielded improved microbiological response compared to extended-interval dosing (every 24 hours or 1-3 times per week). Short-interval dosing inhibited growth with a mean (SD) maximum Δlog10 colony forming units of -4.06 (0.52), significantly more than extended-interval dosing (P = 0.0013) every 24 hours, -2.40 (0.58), or 1-3 times per week, -2.39 (0.38). Growth recovery, an indicator of resistance emergence, occurred at 6.56 (0.70) days with short-interval dosing but was significantly earlier with extended-interval dosing (P = 0.0032) every 24 hours, 3.88 (0.85) days, and 1-3 times per week, 3.27 (1.72) days. Microbiological response correlated best with the pharmacodynamic index of %T > minimum inhibitory concentration (MIC), with an EC80 for growth inhibition of ~40%T > MIC. We used a previously published population model of amikacin to determine the probability of achieving 40%T > MIC and show that current dosing strategies are far below this target, which may partially explain why treatment failure remains so high for these infections. These data support a cautious approach to infrequent amikacin dosing for the treatment of M. abscessus.IMPORTANCEPulmonary disease caused by Mycobacterium abscessus complex (MABSC) is increasing worldwide, particularly in patients with cystic fibrosis. MABSC is challenging to treat due to high levels of antibiotic resistance. Treatment requires 2-4 antibiotics over more than 12 months and has a significant risk of toxicity but still fails to eradicate infection in over 50% of patients with cystic fibrosis. Antibiotic dosing strategies have been largely informed by common bacteria such as Pseudomonas aeruginosa. The "pharmacodynamic" effects of amikacin, a backbone of MABSC treatment, were thought to be related to maximum "peak" drug concentration, leading to daily or three times weekly dosing. However, we found that amikacin MABSC kill and growth recovery, an indicator of antibiotic resistance, are dependent on how long amikacin concentrations are above the minimum inhibitory concentration, not how high the peak concentration is. Therefore, we recommend a re-evaluation of amikacin dosing to determine if increased frequency can improve efficacy.

Profile of antibiotic resistance of Staphylococcus aureus isolated from patients and bacterial carriers of the Astrakhan region as the basis for the selection of bacteriophage producing strains for further combined phage therapy

Staphylococcus aureus has a high level of antibiotic resistance and is a common cause of nosocomial infections, which primarily requires development of new therapeutic strategies.Aim of the study was to investigate the level and spectrum of antibiotic resistance of S. aureus isolates for further isolation of virulent bacteriophages.Material and methods. The study used samples of clinical material obtained on the basis of the City Clinical Hospital No. 3 named after S.M. Kirov (Astrakhan). Bacterial strains isolated from patients were identified on the basis of morphological, cultural, biochemical and molecular genetic characteristics. The determination of the resistance of the isolated cultures was carried out by the disco-diffusion method using standardized commercial discs with antibiotics, in accordance with the guidelines.Results. Evaluation of antibiotic resistance of Staphylococcus aureus isolated during the study of clinical material from patients and analysis of sensitivity level of isolated strains of S. aureus allow us to conclude that all S. aureus isolated from patients are resistant to at least one antibiotic, and most strains are characterized by multidrug resistance to antibiotics.Conclusions. The presence of multi-resistant strains indicates the need to search for new approaches in the treatment of staphylococcal infection and to develop effective means for combination therapy based on virulent staphylococcal bacteriophages.

Antimicrobial resistance profiles of Pseudomonas aeruginosa, Escherichia coli and Klebsiella pneumoniae strains isolated from broiler chickens

Globally, the spread of multidrug-resistant Pseudomonas aeruginosa, Escherichia coli, and Klebsiella pneumoniae from food to humans poses a severe threat to public health. The aim of this study was to assess the co-occurrence of colistin and β-lactamase resistance genes in E. coli, K. pneumoniae, and P. aeruginosa strains isolated from faeces of abattoir broiler chickens. The E. coli, P. aeruginosa and K. pneumoniae isolates were successfully detected from faecal samples by polymerase chain reaction (PCR) at infection rates of 60.7%, 22.5% and 16.7% respectively. The isolates displayed the highest levels of antibiotic resistance (AR) against ampicillin (82.3%) and amoxicillin-clavulanic acid (74.2%) for E. coli, followed by cefoxitin (70.6%) for K. pneumoniae, whilst P. aeruginosa displayed 26.1% antibiotic resistance (AR) against both ampicillin and colistin sulphate. The colistin mcr-1 gene was harboured by 46.8%, 47.1% and 21.7%, E. coli, K. pneumonia and P. aeruginosa isolates respectively. Ten out of 62 (16.1%), 6/17 (35.3%), 4/23 (17.4%) isolates were phenotypically classified as ESBL E. coli, K. pneumoniae, and P. aeruginosa respectively. The ESBL-E. coli isolates respectively possessed blaCTX-M (60%), blaTEM (20%) and blaCTX-M-9 (10%) genes. The ESBL-K. pneumoniae harboured, blaCTX-M (50%), blaOXA (33%), blaCARB (17%), and blaCTX-M-9 (17%) genes respectively, whilst, P. aeruginosa isolates respectively carried blaTEM (75%), blaCTX-M (50%), blaOXA (25%) and blaCARB (25%) genes. Molecular analysis identified the blaCTX-Mβ-lactamase-encoding genes collectively from E. coli, P. aeruginosa, K. pneumoniae isolates. Colistin and β-lactamase genes were present in only 16.7%, 6.9%, and 2.9% of E. coli, K. pneumoniae, and P. aeruginosa isolates, respectively. A total of 17, 7 and 3 isolates for E. coli, K. pneumoniae and P. aeruginosa respectively carried both colistin and β-lactamase antibiotics resistant genes. This is a public health threat that points to a challenge in the treatment of infections caused by these zoonotic bacteria. Data generated from this study will contribute to formulation of new strategies for combating spread of E. coli, K. pneumoniae, and P. aeruginosa isolates as well as prevention of their AR development.

Prevalence of antibiotic resistance in Salmonella Typhimurium isolates originating from Iran: a systematic review and meta-analysis.

Antibiotic resistance in Salmonella represents a significant global public health concern. Among various serovars, Salmonella enterica serovar Typhimurium is prevalent in multiple countries. This study aims to conduct a systematic review and meta-analysis to evaluate the pattern of antibiotic resistance in S. Typhimurium isolates from diverse sources in Iran. We conducted a comprehensive and systematic search for relevant articles until December 2023 in the following databases: PubMed, Scopus, Web of Science, and SID. The collected data were analyzed using Stata software version 17. Eighteen studies examined the pattern of antibiotic resistance in S. Typhimurium for various antibiotics in Iran. Piperacillin and tetracycline exhibited the highest resistance rates, at 79 and 60% respectively, while cefixime and ceftriaxone had the lowest resistance rates at 0%. Our findings indicate a high level of antibiotic resistance among the studied antibiotics. This high level of antibiotic resistance raises concerns and underscores the necessity for monitoring the use of antibiotics. Moreover, resistance to these antibiotics was more prevalent in samples isolated from animals compared to other sources. This highlights the importance of animal screening to detect the presence of drug-resistant isolates, with the ultimate goal of reducing antibiotic resistance and preventing the transmission of resistant strains to humans.

Etiological structure of infections in patients of the surgical intensive care unit in the post-covid era

Objective. To determine etiological structure of infections in the surgical intensive care unit (ICU), identify the most common mechanisms of antibiotic resistance of leading pathogens, and develop recommendations for optimizing antimicrobial therapy in the ICU at the present stage. Materials and Methods. A prospective observational study was conducted in the surgical ICU of the Moscow City Clinical Center «Kommunarka» from September 2022 to February 2024. The subjects of observation were 2120 patients treated in the unit. Microbiological examination of patients’ biological fluids was carried out in accordance with approved methodological guidelines. The results of determining the susceptibility of isolated pathogens were interpreted based on the EUCAST v14.0 criteria. Automatic bacteriological analyzers, MALDI-TOF mass spectrometry for pathogen identification, PCR and immunochromatographic methods for determining resistance mechanisms were used. To determine the etiological structure of infections in hospitalized patients, only original isolates were considered, following the principle of «one patient – one microbe.» Results. A total of 1213 bacterial and 53 fungal pathogens were isolated from 394 patients. The leading pathogens were Klebsiella pneumoniae (18.5%), Acinetobacter baumannii (13.4%), and Pseudomonas aeruginosa (9.5%). Resistance to meropenem was 83.0% for K. pneumoniae, 97.4% for A. baumannii, and 81.5% for P. aeruginosa. The highest in vitro activity against Enterobacterales was exhibited by ceftazidime-avibactam (79.2% of susceptible isolates), while against A. baumannii and P. aeruginosa, it was colistin (98.6% and 90.6% of susceptible isolates, respectively). The genetic mechanisms of carbapenem resistance in Enterobacterales were identified: production of NDM (26.3%), OXA-48 (29.6%), and KPC (44.1%) carbapenemases. Conclusions. The predominant pathogens of infections in surgical ICU patients are gram-negative bacteria with a high level of antibiotic resistance, including carbapenem-resistant Enterobacterales, whose resistance is due to the production of carbapenemases of various molecular classes. An increase in the prevalence of the serine carbapenemase KPC, previously atypical for the Russian Federation, has been noted. Currently, for infections caused by Enterobacterales producing serine carbapenemases, ceftazidime-avibactam can be recommended, and in the case of metallo-beta-lactamase production by Enterobacterales, a combination of ceftazidime-avibactam with aztreonam. For infections caused by A. baumannii and P. aeruginosa, regimens including polymyxins are indicated.