Prevalence Of Antibiotic Resistance Research Articles

Unveiling Potential Biomarkers for Urinary Tract Infection: An Integrated Bioinformatics Approach.

Urinary tract infections (UTIs) are a widespread health concern with high recurrence rates and substantial economic impact, and they can increase the prevalence of antibiotic resistance. This study employed an integrated bioinformatics approach to identify key genes associated with UTI development, offering potential targets for interventions. For this study, the microarray dataset GSE124917 from the Gene Expression Omnibus (GEO) database was selected and reanalyzed. The differentially expressed genes (DEGs) between UTIs and healthy samples were identified using the LIMMA package in R software. In this section, Enrichr database was utilized to perform functional enrichment analysis of DEGs. Subsequently, the protein-protein interaction (PPI) network of the DEGs was constructed and visualized through Cytoscape, utilizing the STRING online database. The identification of hub genes was performed using Cytoscape's cytoHubba plug-in employing various methods. Receiver operating characteristic (ROC) analysis was performed to assess the diagnostic accuracy of hub genes. Among the outcomes of the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, the tumor necrosis factor (TNF) signaling pathway was identified as one of the notable pathways. The PPI network of the DEGs was successfully established and visualized in Cytoscape with the aid of the STRING online database. Using cytoHubba with different methods, we identified seven hub genes (STAT1, IL6, IFIT1, IFIT3, IFIH1, MX1, and IRF7). Based on the ROC analysis, all hub genes showed high diagnostic value. These findings provide a valuable baseline for future research aimed at unraveling the intricate molecular mechanisms behind UTI.

Design of a Helicobacter pylori multi-epitope vaccine based on immunoinformatics.

Helicobacter pylori (H. pylori) is an infectious bacterium that colonizes the stomach of approximately half of the global population. It has been classified as a Group I carcinogen by the World Health Organization due to its strong association with an increased incidence of gastric cancer and exacerbation of stomach diseases. The primary treatment for H. pylori infection currently involves triple or quadruple therapy, primarily consisting of antibiotics and proton pump inhibitors. However, the increasing prevalence of antibiotic resistance poses significant challenges to this approach, underscoring the urgent need for an effective vaccine. In this study, a novel multi-epitope H. pylori vaccine was designed using immunoinformatics. The vaccine contains epitopes derived from nine essential proteins. Software tools and online servers were utilized to predict, evaluate, and analyze the physiochemical properties, secondary and tertiary structures, and immunogenicity of the candidate vaccine. These comprehensive assessments ultimately led to the formulation of an optimal design scheme for the vaccine. Through constructing a novel multi-epitope vaccine based on immunoinformatics, this study offers promising prospects and great potential for the prevention of H. pylori infection. This study also provides a reference strategy to develop multi-epitope vaccines for other pathogens.

MODERN VIEW ON THE PROBLEM OF ANTIBIOTIC RESISTANCE IN PULMONOLOGY AND PHTHISIATRY (LITERATURE REVIEW)

Introduction. The problem of antibiotic resistance (AR) is threatening for patients with respiratory tract diseases (RTD). The use of antibiotics in the treatment of pneumonia, which can be prescribed in the schemes for the tuberculosis (TB) treatment, creates the prerequisites for the formation of chemoresistance of mycobacterium tuberculosis (MBT). The purpose of our research is to analyze the scientific literature on the causes and factors of the occurrence of AR of the сommon RTD pathogens (pneumonia, tuberculosis). Materials and methods. The information on AR of pneumonia and tuberculosis causative agents obtained from scientific publications published in the «pubmed» and «scopus» databases has been analyzed. Results. The main factors causing AR in European countries today are: low awareness of the public and medical professionals about AR, over-the-counter purchase of antibiotics, use of antibiotic residues, the desire of doctors to avoid complications of the disease, advertising of pharmaceutical products, frequent lack of diagnostic tests to detect common infections. The vast majority of antibiotic prescriptions in ambulatory practice are for the treatment of respiratory tract infections, but up to 90% of them are unwarranted. Сoncomitant diseases of the patient (chronic kidney disease, bronchopulmonary diseases, liver diseases), previous colonization of the oropharynx with AR pathogens, bedridden state, age up to 2 years can be risk factors for AR of pneumonia pathogens. The physician should be alert for M. tuberculosis infection and perform appropriate diagnosis in patients with suspected pneumonia, especially in children, the elderly, and patients with HIV and comorbidities. It has been established that less than 65 years of age, living in a large family, history of TB treatment, contact with TB patients, history of hospitalization and visits to medical institutions, TB/HIV co‑infection, bad habits (smoking, alcohol consumption), glycosylated hemoglobin level ˃ 7% were risk factors for chemoresistant TB in adults. Risk factors for chemoresistant extrapulmonary TB in children were: up to 1 year of age, living in a village, poor family income, contact with bacterial isolates of resistant MBT strains, lack of BCG vaccination, concomitant pathology. Conclusions. In order to reduce the prevalence of AR of the RTD pathogens, clear algorithms for prescribing antibiotics should be developed, patients should be trained in their correct use, and methods of diagnosing common infections should be improved. In order to overcome CR TB, it is necessary to detect patients in time and block the transmission of infection, develop clear control algorithms for the detection and treatment of CR TB in risk groups, for example, among patients with diabetes, intensify the development of drugs with new mechanisms of action, initiate testing for the detection of TB in risk groups with suspected pneumonia.

Isolation of Escherichia coli bacteriophages from Domestic Wastewater in Tangerang Selatan

In recent years, there has been a continuous increase in the prevalence of antibiotic resistance among bacteria responsible for infectious diseases. Several studies have shown that the occurrence of the COVID-19 pandemic is a major factor contributing to this rapid increase. To overcome this challenge, one promising approach is the use of bacteriophages as a treatment option. Therefore, this study aims to isolate E. coli lytic bacteriophages as an alternative antibiotic for treating secondary bacterial infections of COVID-19. Isolation of bacteriophages was carried out using the plaque assay method with double layer agar technique. The isolate obtained was purified and tested for effectiveness in lysing E. coli ATCC 25922 bacterial cells. The results showed that E. coli had resistance to antibiotics, such as Amoxicillin, Clindamycin, Ciprofloxacin, Azithromycin, and Trimethoprim/sulfamethoxazole. BEB1 isolate obtained from domestic waste had activity in inhibiting the growth of the test bacteria with an effectiveness of 72% at the 25th hour. Based on these findings, it had the potential to be developed as an alternative antibiotic agent to overcome infectious diseases caused by E. coli ATCC 25922.

Antibiogram of Pseudomonas aeruginosa Clinical Isolates Tested for Pan, Extensive and Multidrug Resistances

Background: Pseudomonas aeruginosa usually cause nosocomial infections with concurrent morbidity and mortality and is generally resistant to many antibiotics.
 Aim: This study was aimed to determine the proportion of pan-drug-resistant (PDR), extensively drug-resistant (XDR), and multidrug-resistant (MDR) P. aeruginosa strains recovered from human samples.
 Methodology: The retrospective study was conducted in the University of Nigeria Teaching Hospital Enugu in 2023. Clinical samples obtained from patients between October 2022 and April 2023 were analysed. A total of 100 Pseudomonas aeruginosa isolates recovered from 780 clinical samples were used. Standard microbiological techniques were used to identify and categorize the isolates. Antibiotic susceptibility pattern was determined using the Kirby Bauer disc diffusion method.
 Results: Isolates recovered from wound was 38%, voided urine, catheter tip urine, ear swab, and high vaginal swab samples recorded 29%, 11%, 10% and 4%, respectively. Ceftazidime recorded the highest level of resistance (70.0%) and the least was Colistin (20%). Resistance patterns showed that 32(32.0%) bacterial strains were MDR, 68(68.0%) were XDR and no PDR was recorded.
 Conclusions: For the best selection of empirical therapy, P. aeruginosa susceptibility monitoring is essential due to the high prevalence of antibiotic resistance. The resistance pattern raises the possibility of misuse of broad-spectrum antibiotics. Treatment for bacterial infections should be directed by the results of antimicrobial susceptibility tests.

A COVID-19 Silver Lining-Decline in Antibiotic Resistance in Ischemic Leg Ulcers during the Pandemic: A 6-Year Retrospective Study from a Regional Tertiary Hospital (2017-2022).

Antibiotic resistance (AR) associated with chronic limb-threatening ischemia (CLTI) poses additional challenges for the management of ischemic leg ulcers, increasing the likelihood of severe outcomes. This study assessed AR prevalence in bacteria isolated from CLTI-associated leg ulcers before (1 January 2017-10 March 2020; n = 69) and during (11 March 2020-31 December 2022; n = 59) the COVID-19 pandemic from patients admitted with positive wound cultures to a regional hospital in Chiang Mai (Thailand). There was a marked reduction in AR rates from 78% pre-pandemic to 42% during the pandemic (p < 0.0001), with rates of polymicrobial infections 22 percentage points lower (from 61% to 39%, respectively; p = 0.014). There were reduced AR rates to amoxicillin/clavulanate (from 42% to 4%; p < 0.0001) and ampicillin (from 16% to 2%; p = 0.017), as well as multidrug resistance (19% to 8%; p = 0.026). Factors associated with increased AR odds were polymicrobial infections (adjusted odds ratio (aOR) 5.6 (95% CI 2.1, 15.0); p = 0.001), gram-negative bacteria (aOR 7.0 (95% CI 2.4, 20.5); p < 0.001), and prior use of antibiotics (aOR 11.9 (95% CI 1.1, 128.2); p = 0.041). Improvements in infection control measures and hygiene practices in the community during the pandemic were likely key factors contributing to lower AR rates. Thus, strategic public health interventions, including community education on hygiene and the informed use of antibiotics, may be crucial in mitigating the challenges posed by AR in CLTI. Further, advocating for more judicious use of empirical antibiotics in clinical settings can balance effective treatment against AR development, thereby improving patient outcomes.

Clonal Diversity, Antibiotic Resistance, and Virulence Factor Prevalence of Community Associated Staphylococcus aureus in Southeastern Virginia.

Staphylococcus aureus is a significant human pathogen with a formidable propensity for antibiotic resistance. Worldwide, it is the leading cause of skin and soft tissue infections (SSTI), septic arthritis, osteomyelitis, and infective endocarditis originating from both community- and healthcare-associated settings. Although often grouped by methicillin resistance, both methicillin-resistant (MRSA) and methicillin-sensitive (MSSA) strains are known to cause significant pathologies and injuries. Virulence factors and growing resistance to antibiotics play major roles in the pathogenicity of community-associated strains. In our study, we examined the genetic variability and acquired antibiograms of 122 S. aureus clinical isolates from SSTI, blood, and urinary tract infections originating from pediatric patients within the southeast region of Virginia, USA. We identified a suite of clinically relevant virulence factors and evaluated their prevalence within these isolates. Five genes (clfA, spA, sbi, scpA, and vwb) with immune-evasive functions were identified in all isolates. MRSA isolates had a greater propensity to be resistant to more antibiotics as well as significantly more likely to carry several virulence factors compared to MSSA strains. Further, the carriage of various genes was found to vary significantly based on the infection type (SSTI, blood, urine).

Structure of the Portal Complex from Staphylococcus aureus Pathogenicity Island 1 Transducing Particles In Situ and In Isolation

Staphylococcus aureus is an important human pathogen, and the prevalence of antibiotic resistance is a major public health concern. The evolution of pathogenicity and resistance in S. aureus often involves acquisition of mobile genetic elements (MGEs). Bacteriophages play an especially important role, since transduction represents the main mechanism for horizontal gene transfer. S. aureus pathogenicity islands (SaPIs), including SaPI1, are MGEs that carry genes encoding virulence factors, and are mobilized at high frequency through interactions with specific “helper” bacteriophages, such as 80α, leading to packaging of the SaPI genomes into virions made from structural proteins supplied by the helper. Among these structural proteins is the portal protein, which forms a ring-like portal at a fivefold vertex of the capsid, through which the DNA is packaged during virion assembly and ejected upon infection of the host. We have used high-resolution cryo-electron microscopy to determine structures of the S. aureus bacteriophage 80α portal itself, produced by overexpression, and in situ in the empty and full SaPI1 virions, and show how the portal interacts with the capsid. These structures provide a basis for understanding portal and capsid assembly and the conformational changes that occur upon DNA packaging and ejection.

Prevalence of antibiotic resistance in Clostridium difficile: A meta-analysis

In recent years, the resistance of Clostridium difficile to various common mainstream antibiotics cannot be ignored, the incidence of CDI in many areas is also increasing year by year, posing a great threat to public safety. Literature collection was carried out on 6 open databases, and high-quality literature data conforming to classification criteria were screened and extracted. The WPR and WPF of each antibacterial drug were calculated using the random effects model. Subgroup analysis was used to investigate the influence of regional and experimental methods. Results: A total of 40 studies were included. The WPR of vancomycin was 0.0372, 95%CI: [0.0148; 0.0671], I: 93.7%, WPF was 0.2195, I: 94.0%. The WPR of fidaxomicin was 0.0051, 95%CI: [0.0000; 0.0205], I: 82.7%, WPF was 0.1757, I: 93.6%. The WPR of metronidazole was 0.0318, 95%CI: [0.0056; 0.0727], I: 91.6%. Among the three antibiotics, the highest resistance of C. difficile to metronidazole were mainly distributed in the Middle East and Africa. The conclusion seems to indicate that C. difficile is most sensitive to Fidaxomicin, and the clinical cure rate is better than vancomycin. However, the clinical cure failure rate increased significantly from 2007 to 2019, while the drug resistance rate did not change significantly, suggesting that other factors besides drug resistance may affect the therapeutic effect of fidaxomicin on CDI. There was no significant difference in the results of AGAR dilution and e test, the main methods for drug susceptibility testing.

Molecular typing and integron detection of multidrug-resistant Klebsiella pneumoniae clinical isolates recovered from Baquba Teaching Hospital in Iraq

Klebsiella pneumoniae is a gram-negative bacterium that causes severe illnesses and is antibiotic-resistant. This study aimed to determine the antibiotic resistance profile and prevalence of classII and III Iintegrons and ERIC -PCR among clinical isolates of K. pneumoniae. The study was conducted between September 2022 and January 2023. Fifty isolates were obtained from 230 specimens (wounds, burns, blood, fluid, ears,urine and sputum). Macroscopic, microscopic, and biochemical assays were used to identify all K.pneumoniae isolates, which were confirmed with the genetically by 16S rRNA. All isolates were examined for various types of clinically significant antibiotic drugs. The results of resistance to antibiotics indicated resistance to Amoxilline-clavulanc acid(98%), Meropenem (38%), Ceftazidime (96%), Amikacin (48%), Trimethopri-sulfamethoxazole (58.62%) and Levofloxacin (46%).The testing for antibiotic susceptibility of the K.pneumoniaeisolate showed that 24 (48%) of the isolates were multi-drug resistant (MDR). K.pneumoniae β-lactamase producers (ESBL) appeared33(66%). Enterobacterial repetitive intergenic consensus (ERIC) amplification of 16 clinical K. pneumoniae isolates showed 14 (87.5 %) of Each of them revealed at least one amplification band. ERIC-PCR typing found two groups, A and B, with identical antimicrobial resistance patterns within the same group. While IntegronII showed that 1(6.25 %) of K. pneumoniae isolates was integrase gene positive. Class III integrons were seen in all isolates at a rate of 16 (100%).Continuous monitoring and characterization of integrons and their associated gene cassettes could be helpful in controlling the rate of antibiotic resistance by planning to take preventive measures to hinder the spread of resistant strains

Self-assembly of H2S-responsive nanoprodrugs based on natural rhein and geraniol for targeted therapy against Salmonella Typhimurium

Salmonellosis is a globally extensive food-borne disease, which threatens public health and results in huge economic losses in the world annually. The rising prevalence of antibiotic resistance in Salmonella poses a significant global concern, emphasizing an imperative to identify novel therapeutic agents or methodologies to effectively combat this predicament. In this study, self-assembly hydrogen sulfide (H2S)-responsive nanoprodrugs were fabricated with poly(α-lipoic acid)-polyethylene glycol grafted rhein and geraniol (PPRG), self-assembled into core–shell nanoparticles via electrostatic, hydrophilic and hydrophobic interactions, with hydrophilic exterior and hydrophobic interior. The rhein and geraniol are released from self-assembly nanoprodrugs PPRG in response to Salmonella infection, which is known to produce hydrogen sulfide (H2S). PPRG demonstrated stronger antibacterial activity against Salmonella compared with rhein or geraniol alone in vitro and in vivo. Additionally, PPRG was also able to suppress the inflammation and modulate gut microbiota homeostasis. In conclusion, the as-prepared self-assembly nanoprodrug sheds new light on the design of natural product active ingredients and provides new ideas for exploring targeted therapies for specific Enteropathogens.Graphical Graphical illustration for construction of self-assembly nanoprodrugs PPRG and its antibacterial and anti-inflammatory activities on experimental Salmonella infection in mice

Staphylococcus epidermidis joint isolates: Whole-genome sequencing demonstrates evidence of hospital transmission and common antimicrobial resistance.

We investigated genetic, epidemiologic, and environmental factors contributing to positive Staphylococcus epidermidis joint cultures. Retrospective cohort study with whole-genome sequencing (WGS). We identified S. epidermidis isolates from hip or knee cultures in patients with 1 or more prior corresponding intra-articular procedure at our hospital. WGS and single-nucleotide polymorphism-based clonality analyses were performed, including species identification, in silico multilocus sequence typing (MLST), phylogenomic analysis, and genotypic assessment of the prevalence of specific antibiotic resistance and virulence genes. Epidemiologic review was performed to compare cluster and noncluster cases. In total, 60 phenotypically distinct S. epidermidis isolates were identified. After removal of duplicates and impure samples, 48 isolates were used for the phylogenomic analysis, and 45 (93.7%) isolates were included in the clonality analysis. Notably, 5 S. epidermidis strains (10.4%) showed phenotypic susceptibility to oxacillin yet harbored mecA, and 3 (6.2%) strains showed phenotypic resistance despite not having mecA. Smr was found in all isolates, and mupA positivity was not observed. We also identified 6 clonal clusters from the clonality analysis, which accounted for 14 (31.1%) of the 45 S. epidermidis isolates. Our epidemiologic investigation revealed ties to common aspirations or operative procedures, although no specific common source was identified. Most S. epidermidis isolates from clinical joint samples are diverse in origin, but we identified an important subset of 31.1% that belonged to subclinical healthcare-associated clusters. Clusters appeared to resolve spontaneously over time, suggesting the benefit of routine hospital infection control and disinfection practices.

Flagellar interference with plasmid uptake in biofilms: a joint experimental and modeling study.

Plasmid conjugation is a key facilitator of horizontal gene transfer (HGT), and plasmids encoding antibiotic resistance drive the increasing prevalence of antibiotic resistance. In natural, engineered, and clinical environments, bacteria often grow in protective biofilms. Therefore, a better understanding of plasmid transfer in biofilms is needed. Our aim was to investigate plasmid transfer in a biofilm-adapted wrinkly colony mutant of Xanthomonas retroflexus (XRw) with enhanced matrix production and reduced motility. We found that XRw biofilms had an increased uptake of the broad host-range IncP-1ϵ plasmid pKJK5 compared to the wild type (WT). Proteomics revealed fewer flagellar-associated proteins in XRw, suggesting that flagella were responsible for reducing plasmid uptake. This was confirmed by the higher plasmid uptake of non-flagellated fliM mutants of the X. retroflexus wrinkly mutant as well as the wild type. Moreover, testing several flagellar mutants of Pseudomonas putida suggested that the flagellar effect was more general. We identified seven mechanisms with the potential to explain the flagellar effect and simulated them in an individual-based model. Two mechanisms could thus be eliminated (increased distances between cells and increased lag times due to flagella). Another mechanism identified as viable in the modeling was eliminated by further experiments. The possibility of steric hindrance of pilus movement and binding by flagella, reducing the frequency of contact and thus plasmid uptake, proved viable, and the three other viable mechanisms had a reduced probability of plasmid transfer in common. Our findings highlight the important yet complex effects of flagella during bacterial conjugation in biofilms.IMPORTANCEBiofilms are the dominant form of microbial life and bacteria living in biofilms are markedly different from their planktonic counterparts, yet the impact of the biofilm lifestyle on horizontal gene transfer (HGT) is still poorly understood. Horizontal gene transfer by conjugative plasmids is a major driver in bacterial evolution and adaptation, as exemplified by the troubling spread of antibiotic resistance. To either limit or promote plasmid prevalence and dissemination, we need a better understanding of plasmid transfer between bacterial cells, especially in biofilms. Here, we identified a new factor impacting the transfer of plasmids, flagella, which are required for many types of bacterial motility. We show that their absence or altered activity can lead to enhanced plasmid uptake in two bacterial species, Xanthomonas retroflexus and Pseudomonas putida. Moreover, we demonstrate the utility of mathematical modeling to eliminate hypothetical mechanisms.

Phenotypic shifts induced by environmental pre-stressors modify antibiotic resistance in Staphylococcus aureus.

Escalating prevalence of antibiotic resistance in Staphylococcus aureus has necessitated urgent exploration into the fundamental mechanisms underlying antibiotic resistance emergence, particularly in relation to its interaction with environmental stressors. This study aimed to investigate the effects of environmental stressors prior to antibiotic exposure on the antibiotic resistance of S. aureus. We used Raman spectroscopy and flow cytometry to measure prior stress-induced phenotypic alterations of S. aureus, and identified the association between phenotypic shifts and the antibiotic resistance. The results revealed a multifaceted relationship between stressors and the development of antibiotic resistance. The stressors effectuate distinct phenotypic diversifications and subsequently amplify these phenotypic alterations following antibiotic treatments, contingent upon the specific mode of action; these phenotypic shifts in turn promote the development of antibiotic resistance in S. aureus. This study's findings demonstrated that the presence of pre-stress conditions triggered an augmentation of resistance to vancomycin (VAN), while concurrently attenuating resistance to norfloxacin. Marked shifts in Raman peaks associated with lipids and nucleic acids demonstrated correlations with elevated survival rates following VAN treatment. Consequently, these observations indicate that pre-stress conditions "prime" bacterial cells for differential responses to antibiotics and bear significant implications for formulating clinical therapeutic strategies.

A Survey of the Prevalence Rate and Antibiotic Resistance Pattern of Microbial Agents in Preterm Neonatal Sepsis

Background: Sepsis is one of the most dangerous neonatal infections. Bacterial causes of neonatal septicemia are different. Objectives: This study aimed to investigate the prevalence and antibiotic resistance pattern of microbial agents causing preterm neonatal sepsis. Methods: This descriptive study was performed on 1000 infants admitted to neonatal intensive care units 1 and 2 and the neonatal ward of Al-Zahra Medical Center in Tabriz, Iran, from March 2019 to June 2020. Sampling was completed through the convenience sampling method. Data were collected using a researcher-made questionnaire after evaluating its validity and reliability. The questionnaire included personal information of neonates, causes of infection, antibiotic use, hospitalization time, and medication resistance pattern. Antibiotic susceptibility testing was performed by disk diffusion technique according to the Clinical and Laboratory Standards Institute guidelines. SPSS software version 22 was used for data analysis. Results: Among all studied neonates, 78 cases (7.8%) had positive blood cultures. The most common cause of neonatal infection was preterm birth (80.8%), and the most common bacterial causes of sepsis were coagulase-negative Staphylococcus (46.15) and Klebsiella pneumonia (28.2%). The highest antibiotic susceptibility of Gram-positive (coagulase-negative Staphylococcus) and Gram-negative bacteria was to ceftriaxone (47.3%) and piperacillin/tazobactam (100%), respectively, and the highest antibiotic resistance was to ampicillin and gentamicin (nearly 100%). Conclusions: Resistance to antibiotics used to treat sepsis has increased, which will cause irreparable problems in the treatment of preterm neonates if not addressed. Due to different microbial agents and drug resistance patterns in distinct regions, annual surveys should be conducted to determine drug resistance patterns, emphasizing preventive measures.

Antibiotic resistance of Helicobacter pylori in Nanjing, China: a cross-section study from 2018 to 2023.

The increasing prevalence of antibiotic resistance in cases of Helicobacter pylori (H. pylori) infection has emerged as a significant global issue. This study offers a comprehensive examination of the alterations in drug resistance exhibited by H. pylori in the Nanjing region of China during the preceding five years. Another important objective is to investigate the influence of levofloxacin medication history on genotypic and phenotypic resistance. This research screened 4277 individuals diagnosed with H. pylori infection between April 2018 and May 2023. The phenotype and genotypic resistance were evaluated using the Kirby-Bauer disk diffusion and PCR method. The most recent primary resistance rates for metronidazole, clarithromycin, levofloxacin, amoxicillin, furazolidone, and tetracycline were recorded at 77.23% (2385/3088), 37.24% (1150/3088), 27.72% (856/3088), 0.52% (16/3088), 0.19% (6/3088), and 0.06% (2/3088), respectively. For the recent five years, we observed a notable upsurge in the rate of metronidazole resistance and a slight elevation of clarithromycin and levofloxacin resistance. The documented resistance rates to single-drug, dual-drug, triple-drug, and quadruple-drug regimens were 35.39%, 28.32%, 25.72%, and 0.21%, respectively. The prevalence of multidrug-resistant strains escalated, rising from 37.96% in 2018 to 66.22% in 2023. The rate of phenotypic and genotypic resistance rate (57.10% and 65.57%) observed in strains obtained from patients without a levofloxacin treatment history was significantly lower than the rate in strains obtained from those with a history of levofloxacin treatment (88.73% and 94.74%). The prevailing gyrA mutations were primarily N87K (52.35%, 345/659), accompanied by D91N (13.96%, 92/659), and closely followed by D87G (10.77%, 71/659). For gyrA mutations, the 91-amino acid mutants exhibit a higher likelihood of discrepancies between phenotypic and genotypic resistance than the 87-amino acid mutants. The extent of antibiotic resistance within H. pylori remains substantial within the Nanjing region. If levofloxacin proves ineffective in eradicating H. pylori during the initial treatment, its use in subsequent treatments is discouraged. The employment of levofloxacin resistance genotype testing can partially substitute conventional antibiotic sensitivity testing. Notably, predicting phenotypic resistance of levofloxacin through PCR requires more attention to the mutation type of gyrA to improve prediction accuracy.

726. Risk factor analysis for cefepime and piperacillin/tazobactam resistant organisms

Abstract Background Carbapenems (CAR) are first line therapy for patients with infections caused by multidrug resistant organisms. As the prevalence of antibiotic resistance is increasing, CAR use has become a common choice for empiric therapy. This increase in use is concerning as prior CAR exposure is a risk factor for CAR resistance. Identification of risk factors associated with resistance for other beta-lactam antibiotics could aid in the appropriate use of CAR therapy while minimizing overuse. The objective of this study was to identify risk factors for cefepime (FEP) and piperacillin/tazobactam (PTZ) resistance and which population required CAR as an empiric therapy. Methods This is a retrospective cohort conducted at HonorHealth John C Lincoln Medical Center, Phoenix AZ between January 2020 to July 2021. The case patients will be those who had an infection which is resistant to FEP or PTZ, while control patients have infection which is susceptible to FEP or PTZ. Recurrence of infection after receiving appropriate antimicrobial therapy considered as a separate case. Patients who do not have antimicrobial susceptibilities were excluded. Variables were compared between groups. Multivariate analysis using logistic regression was used to control for confounding variables. Results Overall, 230 patients met inclusion criteria and were evenly distributed between cohorts. The mean age of the population at baseline was 64 ± 17.4, 111 (48.3%) patients were in an ICU and 103 (44.8%) patients required mechanical ventilation. Clinical variables which were significant in univariate analysis were included in multivariate analyses. Multivariate analyses revealed prior resistance to FEP or PTZ in the past 12 months (OR 8.35, 95% CI [2.28-30.50], p=0.001), transferred from outside facility (OR 3.40, 95% CI [1.80-6.42], p&amp;lt; 0.001), prior ICU admission in the past 90 days (OR 4.40, 95% CI [1.72-11.27], p=0.002), and prior antibiotic use in the past 30 days (OR 2.60, 95% CI [1.33-5.09], p=0.005) were associated with increased risk of FEP- or PTZ-resistant infections. Conclusion Patients with prior resistance to FEP and PTZ within the last 12 months can benefit by initiating empiric therapy with CAR due to the increased risk for subsequent FEP- or PTZ-resistant organisms. Further investigation is warranted. Disclosures All Authors: No reported disclosures

Prevalence of Extended Spectrum β-Lactamase Producers (ESBLs) with antibiotic resistance pattern of Gram negative pathogenic bacteria isolated from door handles in hospitals of Pokhara, Western Nepal

BackgroundThe presence of drug-resistant Gram-negative pathogenic bacteria and Extended Spectrum β-Lactamase Producers (ESBLs) in hospital associated fomites like door handles can serve as vehicles in transmission and may be the key factor in epidemiology of ESBL producing bacterial infection not only in a hospital setting but also in the community. The aim of this study was to determine the prevalence of ESBLs and antibiotic resistance of Gram-Negative pathogenic Bacteria isolated from door-handles in two selected hospitals in Pokhara Metropolitan City, Nepal. The study was conducted in selected hospitals in Pokhara Metropolitan City, Western Nepal. A cross-sectional study design was used. The hospitals were selected randomly. A total of 100 swab samples were taken from door-handles. Isolation and identification of bacteria were done using standard microbiological procedures. An antibiotic susceptibility test, screening and confirmation of ESBLs were performed using the Clinical Laboratory Standard Institute’s guidelines. ResultsOut of the 100 swab samples cultured, 96 (96%) showed bacterial growth. A total of one hundred and forty isolates were isolated in this study which were further identified based on cultural, morphological and biochemical characteristics. The study also found that door handles/knobs had higher level of contamination in Outpatient Departments (OPDs), Emergency, Laboratory, General wards and Toilets, in that order as compared to Radiology Room, Staff rooms, Intensive Care Unit and Operation Theatre which were lower. The level of contamination varies depending on the traffic exposure and the environment. The most prevalent Gram-negative bacteria identified was Escherichia coli 28.85%, followed by Klebsiella spp 21.15%, Pseudomonas aeruginosa 15.38%, Proteus spp 11.54%, Enterobacter spp 9.62%, Acenetobacter spp 7.69%, Citrobacter spp 5.77%. The most effective drug of choice was Amikacin, Nitrofurantoin, Norfloxacin, Ciprofloxacin, Tetracycline and Imipenem for many Gram-negative isolates. The overall prevalence of ESBLs in this study was 27.14%. Out of total 15 Escherichia coli isolated, 11(73.3%), Klebsiella spp 9/11 (81.8%); Pseudomonas spp 7/8 (87.5%), Proteus spp 4/6 (66.6%); Enterobacter spp 3/5 (60%), Acenetobacter spp 3/4 (75%) and Citrobacter spp 1/3 (33.3%) were found to be Extended β-Lactamase Producers (ESBLs). ConclusionThe isolation of of pathogenic Gram-negative bacteria and ESBLs in hospital environments and subsequent detection of high drug resistance patterns indicates a potentially serious public health challenge that strengthens the need for the effective and routine cleaning of door-handles in hospitals.

Primary antibiotic resistance of Helicobacter pylori in the Asia-Pacific region between 1990 and 2022: an updated systematic review and meta-analysis

We previously showed rising primary antibiotic resistance of Helicobacter pylori during 1990-2015 in the Asia-Pacific region. However, whether primary antibiotic resistance continues to rise is unknown. Therefore, we aimed to assess the latest prevalence of H pylori antibiotic resistance in this region. We did an updated systematic review and meta-analysis of observational studies and randomised controlled trials published in PubMed, Embase, and Cochrane Library between Jan 1, 1990, and July 12, 2023. Studies investigating primary H pylori resistance to clarithromycin, metronidazole, levofloxacin, amoxicillin, or tetracycline in individuals naive to eradication therapy in the Asia-Pacific region (as defined by the UN geoscheme) were eligible for inclusion. There were no language restrictions. Studies that focused on specific subpopulations (eg, children) were excluded. Using a standardised extraction form, two authors independently reviewed and extracted summary data from all eligible articles. The updated prevalence of antibiotic resistance was generated by meta-analysis under a random-effects model and subgroup analyses were done by countries and periods of study. Between-study variability was assessed by use of I2. The study is registered in PROSPERO, CRD42022339956. A total of 351 studies, including 175 new studies and 176 studies from our previous analysis, were included in this meta-analysis. The overall prevalence of primary antibiotic resistance of H pylori between 1990 and 2022 was 22% (95% CI 20-23; I2=96%) for clarithromycin, 52% (49-55; I2=99%) for metronidazole, 26% (24-29; I2=96%) for levofloxacin, 4% (3-5; I2=95%) for tetracycline, and 4% (3-5; I2=95%) for amoxicillin. Prevalence varied considerably between countries and across study periods. From 1990 to 2022, the prevalence of primary resistance increased for clarithromycin, metronidazole, and levofloxacin but remained stable for amoxicillin and tetracycline. The latest primary resistance prevalences were 30% (95% CI 28-33; I2=93%) for clarithromycin, 61% (55-66; I2=99%) for metronidazole, 35% (31-39; I2=95%) for levofloxacin, 4% (2-6; I2=96%) for tetracycline, and 6% (4-8; I2=96%) for amoxicillin in the Asia-Pacific region. Treatment guidelines should be adapted in response to the rising primary resistance of key antibiotics for H pylori eradication. A global policy to control and monitor the antibiotic resistance of H pylori is urgently needed. Ministry of Health and Welfare of Taiwan, National Science and Technology Council of Taiwan, and National Taiwan University. For the Chinese translation of the abstract see Supplementary Materials section.

Effect of booster disinfection on the prevalence of microbial antibiotic resistance and bacterial community in a simulated drinking water distribution system

Booster disinfection was often applied to control the microorganism's growth in long-distance water supply systems. The effect of booster disinfection on the changing patterns of antibiotic resistance and bacterial community was investigated by a simulated water distribution system (SWDS). The results showed that the antibiotic resistance bacteria (ARB) and antibiotic resistance genes (ARGs) were initially removed after dosing disinfectants (chlorine and chloramine), but then increased with the increasing water age. However, the relative abundance of ARGs significantly increased after booster disinfection both in buck water and biofilm, then decreased along the pipeline. The pipe materials and disinfectant type also affected the antibiotic resistance. Chlorine was more efficient in controlling microbes and ARGs than chloramine. Compared with UPVC and PE pipes, SS pipes had the lowest total bacteria, ARB concentration, and ARB percentage, mainly due to higher disinfectant residuals and a smoother surface. The significant correlation (rs = 0.77, p < 0.001) of the 16S rRNA genes was observed between buck water and biofilm, while the correlations of targeted ARGs were found to be weak. Bray-Curtis similarity index indicated that booster disinfection significantly changed the biofilm bacterial community and the disinfectant type also had a marked impact on the bacterial community. At the genus level, the relative abundance of Pseudomonas, Sphingomonas, and Methylobacterium significantly increased after booster disinfection. Mycobacterium increased after chloramination while decreased after chlorination, indicating Mycobacterium might resist chloramine. Pseudomonas, Methylobacterium, and Phreatobacter were found to correlate well with the relative abundance of ARGs. These results highlighted antibiotic resistance shift and bacterial community alteration after booster disinfection, which may be helpful in controlling potential microbial risk in drinking water.