Microbial Drug Resistance

Drug Resistance Analysis and Prediction Model Construction of Carbapenem-Resistant
Jin C, Xu T and Xie Q
This study analyzed the antimicrobial resistance profiles and risk factors for carbapenem-resistant Acinetobacter baumannii (CRAB) in a tertiary hospital and developed a predictive model for infection control. Among 64 Acinetobacter baumannii isolates collected in 2024 from the First People's Hospital of Chuzhou, CRAB accounted for 40.63% (26/64), with sputum being the most common specimen source (85.94%) and the highest isolation rate observed in respiratory wards. CRAB exhibited significantly higher resistance to most antibiotics compared to carbapenem-sensitive strains (CSAB), except for polymyxin and tigecycline ( < 0.05). Multivariate analysis identified ≥3 underlying diseases, prior use of compound antibiotics, and tracheal intubation/incision as independent risk factors for CRAB infection. A nomogram prediction model constructed with R software demonstrated high predictive accuracy (C-index: 0.985). The findings highlight a concerning prevalence and multidrug resistance of CRAB in this setting, underscoring the need to enhance monitoring, early risk factor identification, and targeted interventions to reduce transmission and optimize antimicrobial stewardship.
Whole Genome Features and Analysis of Antibiotic Resistance Determinants in Strain CYZ
Zhao W, Feng J, Wu Y, Ding W, Xie L, Han L and Wang C
is an opportunistic pathogen that exhibits a strong resistance ability to antibiotics. The complete genome of CYZ was sequenced using a PacBio RS II system. The functions of all the predicted genes and proteins were classified and annotated using the Clusters of Orthologous Groups of proteins, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes databases. Furthermore, the antimicrobial resistance genes were also analyzed via the Comprehensive Antibiotic Resistance Database, and several types of antibiotics were selected to test the antimicrobial susceptibility. Phylogenetic relationships were investigated using the single nucleotide polymorphisms (SNPs) from 228 clinically isolated strains. The genome size of CYZ is 6,382,603 bp and contains 5,807 protein-coding genes, with an average G + C content of 66.44%. Functional genomic analysis via the annotations of the databases identified a total of 499 antimicrobial resistance genes. CYZ showed resistance to 14 types of antibiotics. The phylogenetic analysis revealed that CYZ was closely related to PAO1. The strains exhibited no geographical specificity, and the variation in core genome SNPs was nonrandomly distributed. Our findings give valuable insight into the genetic antimicrobial-resistant features of as well as provide a genetic basis for the further study of the phenotype.
Resistance Patterns and Optimization of Empirical Therapy for Urinary Tract Infections in Patients on Trimethoprim-Sulfamethoxazole Prophylaxis Against
Sugiyama K, Hirai K, Kibe M, Fukumoto N, Suyama Y, Furuya K, Ito K, Sakurai K and Itoh K
Trimethoprim-sulfamethoxazole (SXT) is widely used for pneumonia prophylaxis. However, prolonged use may induce antimicrobial resistance, potentially compromising empirical therapy for urinary tract infections (UTIs). We retrospectively analyzed 3,525 patients with positive urine cultures at Shizuoka General Hospital (2018-2023). Among them, 149 received SXT prophylaxis. Antimicrobial susceptibility and the relationship between prophylaxis duration and resistance were evaluated. and were the most common pathogens. In the SXT prophylaxis group, susceptibility to SXT was significantly reduced (21.2% vs. 87.4%). Susceptibility to other antibiotics also declined, including ampicillin (31.2% vs. 71.6%), piperacillin (32.5% vs. 74.8%), levofloxacin (57.5% vs. 74.7%), and ciprofloxacin (56.2% vs. 74.1%). Susceptibility to expanded-spectrum cephalosporins, including second-, third-, and fourth-generation agents remained preserved. Receiver operating characteristic analysis identified a prophylaxis duration >406 days as predictive of SXT resistance (area under the curve 0.82, sensitivity 94%, and specificity 60%). Short-term prophylaxis (≤30 days) mitigated resistance, although susceptibility to SXT was still limited (47.8%). Prophylactic SXT use markedly reduces susceptibility to multiple antibiotics, especially penicillins and fluoroquinolones. Resistance correlates with prophylaxis duration. For empirical UTI therapy, intravenous expanded-spectrum cephalosporins may be preferable.
Detection of Heteroresistant Vancomycin-Intermediate Among Blood Isolates
Manoharan M, Sistla S and Amberpet R
is frequently associated with infections in hospitalized patients and acts as a reservoir for antibiotic resistance genes. The widespread use of vancomycin in treating serious infections has led to the emergence of heteroresistance to vancomycin in certain isolates. This study aimed to determine the rate of heteroresistant vancomycin-intermediate (hVISH) among 166 blood isolates collected from patients admitted to Jawaharlal Institute of Postgraduate Medical Education and Research between January 2017 and June 2018. E-test was done to determine vancomycin minimum inhibitory concentration (MIC). Heteroresistance screening was performed using brain heart infusion agar containing 4 µg/mL vancomycin (BHIV). Confirmation of heteroresistance was performed by population analysis-profile area under curve (PAP-AUC) analysis. Whole-genome sequencing was performed on eight isolates. All isolates were vancomycin-susceptible by E-test, while 18.7% exhibited heteroresistance by PAP-AUC. The sensitivity, specificity, positive predictive value, negative predictive value, and kappa agreement of BHIV with PAP-AUC were 64.5%, 97.8%, 87%, 92.3%, and 0.692, respectively. Mutational analysis of the eight isolates revealed variations in , , , yyc, , , , , PBP, , , and operons, along with novel mutations in cell wall synthesis operons. The rate of hVISH isolation in our study is in agreement with other studies worldwide. As the sensitivity of BHIV is only moderate, it may be prudent to consider alternate antibiotics if MIC of vancomycin approaches the breakpoint. Furthermore, our analysis revealed multiple mutations within glycopeptide resistance operons, providing a better understanding of the molecular mechanisms underlying heteroresistance in and its implications for antimicrobial therapy and surveillance strategies.
Phylogenetic Diversity, Biofilm Production, and Antibiotic Resistance Profiling of Uropathogenic Isolated from Children with Vesicoureteral Reflux: Complicating Factors for Treatment and Recurrent Urinary Tract Infections
Nasrollahian S, Halaji M, Mostaghimi T, Rajabnia M, Sourkhi H, Teimourian M, Mohammadi M and Pournajaf A
Uropathogenic (UPEC) are the most common cause of urinary tract infections (UTI). This study investigated the genetic relatedness, biofilm-forming capacity, and antimicrobial resistance profiles in the extended-spectrum beta-lactamase (ESBL)-producing UPEC collected from children with vesicoureteral reflux (VUR) suffering from UTI. In this cross-sectional investigation, a total of 80 nonduplicated UPEC isolates were collected from children afflicted with VUR. Antimicrobial susceptibility testing and phenotypic production of ESBL were conducted according to the Clinical and Laboratory Standards Institute (2023) recommendations. Furthermore, PCR tests were used to detect the presence of ESBL genes. Biofilm formation in 96-well microtiter plates was assessed. Finally, the clonal diversity of the isolates was examined using the Enterobacterial Repetitive Intergenic Consensus (ERIC)-PCR. Out of all collected isolates, 71.2% ( = 57/80) were ESBL producers and 31.2% ( = 25/80) were multidrug resistant (MDR). The frequency of the gene was 65.0% and 77.5% of the isolates were biofilm producers. ESBL-producing UPEC isolates were clustered by the ERIC-PCR method into the nine groups labeled A-I. Our findings indicate a high and rising prevalence of MDR and ESBL-producing UPEC among children with VUR. This underscores the urgent need for appropriate empirical antibiotic selection, routine monitoring of resistance patterns, and long-term prophylactic strategies to reduce recurrence and improve clinical management in this vulnerable population.
Resistance Profile and Molecular Insights of Carbapenem-Resistant Clinical Isolates: A Preliminary Experience from a Tertiary Care Hospital
Goel V, Devi K, Singh N, Chauhan V, Sharma R and Srivastava S
Carbapenems are the last-line antibiotic defense against gram-negative extended spectrum β-lactamase producers. Carbapenem-resistant Enterobacteriaceae, especially carbapenem-resistant (CRKP), is recognized as one of the well-known public health problems, which is increasingly being reported around the world. The present study focused on analyzing the carbapenemase-producing isolates obtained from patients admitted to the intensive care unit of a tertiary care hospital in Western Uttar Pradesh, India, and the results confirmed the presence of resistant genes using real-time polymerase chain reaction (PCR). A total of 103 isolates were screened for carbapenem resistance using the VITEK 2 compact system (bioMérieux, France). Carbapenemase was detected using genotypic characterization by real-time PCR; 49.5% of isolates were confirmed as , including 64.7% CRKP. The most common carbapenemase genes identified were New Delhi metallo-β-lactamase (; 93.9%), followed by (90.9%) and (69.7%). In conclusion, our study results depict a high prevalence of carbapenemase-producing . In conclusion, our findings demonstrate a high prevalence of carbapenemase-producing in critically ill patients. As there are no new drugs available and prevalence incidence varies regionally, real-time PCR probe-based detection of these genes is beneficial for early detection, developing infection control protocols, and promoting appropriate antibiotic use.
Clinical Epidemiology and Antimicrobial Susceptibility of Carbapenemase-Producing Enterobacterales from a German University Hospital During a 5-Year Period
Sommer J, Esse J, Held J, Voigtländer S, Bogdan C and Valenza G
The primary purpose of this study was to assess the prevalence and the antimicrobial susceptibility rates of carbapenemase-producing Enterobacterales (CPE) in a German University Hospital during a 5-year period. From January 2020 to December 2024, all Enterobacterales detected were molecularly investigated for carbapenemases in every case of elevated minimum inhibitory concentration of ertapenem, meropenem, or imipenem. Subsequently, CPE were tested for susceptibility to reserve antibiotics. Overall, 101 CPE were identified. Most of the CPE strains harbored only one carbapenemase gene, such as ( = 32, 31.6%), ( = 27, 26.7%), and ( = 14, 13.8%). The annual number of CPE detected increased during the observation period (2020, = 5; 2021, = 5; 2022, = 24; 2023, = 29; 2024, = 38). We also observed a progressive rise of the proportion of CPE harboring a metallo-β-lactamase gene such as or (2020, 0.0%; 2021, 0.0%; 2022, 50.0%; 2023, 55.2%; 2024, 65.8%). Regarding the antimicrobial susceptibility, only 3.3% of all CPE isolates tested showed resistance to aztreonam/avibactam. In contrast, the resistance rates for cefiderocol and ceftazidime/avibactam amounted respectively to 12.8% and 53.9%. The increasing annual number of CPE at our hospital is associated with a rise of the proportion of metallo-β-lactamase-producing strains. The newly available antibiotic aztreonam/avibactam showed promising activity against CPE.
Evaluation of the Antimicrobial Resistance Pattern and Distribution of Strains Isolated from Adult Patients with Lower Respiratory Tract Infection at a Tertiary Care Hospital in Western Turkey
Altan G, Ece G and Yıldırım M
Hospital-acquired respiratory infections caused by antimicrobial-resistant bacteria have become a major public health problem worldwide. This study aimed to evaluate the distribution and antimicrobial resistance profiles of bacterial strains isolated from adult patients treated with a diagnosis of lower respiratory tract infection in our hospital. Respiratory tract samples of adult patients hospitalized in our hospital were included. The identification of the isolated strains and their antibiotic susceptibilities were studied by the PHOENIX 100 (Becton Dickinson, USA) automated system, and results were evaluated according to the European Committee on Antimicrobial Susceptibility Testing criteria. In this study, we observed that Gram-negative bacteria were more common than Gram-positive bacteria in lower respiratory tract samples. The multidrug resistance rate in , , and isolates is detected as 59%, 12.9%, and 96.4%, respectively. Carbapenem resistance rates for ( = 261), ( = 250), and ( = 132) were 88.9%, 97.2%, and 43.2%, respectively. The multidrug resistance and carbapenem resistance rates detected in lower respiratory tract samples in our study are alarming. It is noteworthy that the resistance rates we found are higher than the rates reported in other studies conducted in our country.
Molecular Epidemiology of Non-Tuberculous Mycobacteria Among Tuberculosis-Suspected Patients in Iran: Species Distribution and Drug Resistance
Rahimi M, Akhavan Sepahi A, Sakhaee F, Siadat SD and Fateh A
In high-burden tuberculosis (TB) settings such as Iran, non-tuberculous mycobacteria (NTM) are increasingly identified among presumptive TB cases. However, their epidemiology and drug resistance patterns remain inadequately described. This study investigated the prevalence, species distribution, and antimicrobial susceptibility of NTM isolates from 3,000 clinical specimens collected from patients with presumptive TB at the Pasteur Institute of Iran between March 2022 and March 2023. Identification was performed through culture and sequencing of the , , and genes. Drug susceptibility testing (DST) was conducted using the broth microdilution method in accordance with Clinical and Laboratory Standards Institute guidelines. Among 145 acid-fast bacilli-positive cultures, 45 (31%) were identified as NTM. The predominant species were (51.1%) and (40.0%), followed by less common isolates of , , and . The majority of NTM isolates (86.7%) originated from respiratory specimens. Phenotypic analyses revealed high resistance rates to first-line anti-TB drugs such as isoniazid and rifampicin, while susceptibility varied across fluoroquinolones, aminoglycosides, and sulfonamides. These findings underscore the importance of species-level identification and DST-guided therapy to improve the clinical management of NTM infections in TB-endemic regions.
Biofilm Formation and Antibiotic Resistance in Uropathogenic : A Molecular Characterization and Antibiogram Study
Saman , Siddique AB, Aslam B and Nawaz Z
Biofilm formation is a key virulence factor in urinary tract infections, and serves as a prominent causative agent, more resistant to antimicrobial agents. This study focused on isolation and phenotypic and genotypic characterization of from urine samples on the basis of their biofilm-forming capacity. In the present study, a total of 804 human urine samples were collected from different clinical facilities of Faisalabad. After phenotypic and genotypic affirmation, biofilm forming potential of uropathogenic (UPEC) was determined by using microtiter plate assay (MPA) and the Congo red agar method. Antimicrobial susceptibility testing was conducted, and a comparison was executed between biofilm formers and non-formers. Biofilm production by the MPA and Congo red agar methods was 88% and 68%, respectively. UPEC isolates showed maximum resistance to amoxicillin-clavulanate (97%), cefoparazone (93%), cefotaxime (91%), and ampicillin (90%). Significant association between resistance to antibiotic and biofilm formation with value <0.05 was observed in case of piperacillin-tazobactam, imipenem, meropenem, amikacin, norfloxacin, nitrofurantoin, polymyxin B, and nalidixic acid. Biofilm producer strains were progressed for molecular characterization using polymerase chain reaction for biofilm-forming genes including H, A, A, 43, C, and G, which showed prevalence of 89% (118/132), 87% (116/132), 86% (114/132), 81% (107/132), 47% (61/132), and 33% (43/132), respectively.
Simultaneous Detection of Fluoroquinolone- and Macrolide-Resistant in Retail Chicken Meat Using Multiplex-PCR
Fukuda A, Matsui A, Furuya Y, Suzuki Y, Tamura Y, Nakajima C and Usui M
contamination in chicken meat, particularly with fluoroquinolone- and macrolide-resistant strains, is a significant public health concern. Therefore, developing an easy and rapid detection method for fluoroquinolone- and macrolide-resistant will improve food safety. In this study, we designed and evaluated a multiplex-Polymerase Chain Reaction (PCR) method for the simultaneous detection of fluoroquinolone- and macrolide-resistant and in chicken meat. Our multiplex-PCR-targeted mutations in the and genes of species confer resistance to fluoroquinolones and macrolides, respectively. Overall, this method could detect contamination and identify and as well as their susceptibility to fluoroquinolone and macrolide. Spiking of chicken meat samples revealed that multiplex-PCR can detect at least 0.72 Colony-Forming Unit (CFU)/g /. Among 277 retail chicken meat samples, / were detected in 54 samples using multiplex-PCR, with isolation from 52 samples using microbial culture. The susceptibility of the isolates to fluoroquinolones and macrolides was determined using both the PCR and culture methods, and a comparison of these methods showed that the accuracy, specificity, and sensitivity were all above 95%. The culture method required approximately 8 days for isolation and antimicrobial susceptibility testing. Multiplex-PCR could determine the contamination with / and susceptibility to fluoroquinolones and macrolides within 2-3 days from the enrichment culture to final determination. These results indicate that the proposed multiplex-PCR enables rapid and simultaneous detection of fluoroquinolone- and macrolide-resistant / in chicken meat and its utility for monitoring their contamination in food.
Antibiotic Resistance of and Isolated from Wild Raccoon Dogs in Shanghai, China
Xiong X, Chen C, Tao J, Wei M, Wang X, Wang C, Ye W, Zhou W, Liu G and Zhang K
Wild animals may act as reservoirs for resistant bacteria, and resident bacteria carried by wild animals in cities may also be subject to anthropogenic pressures that affect their resistance. This study aimed to evaluate the antibiotic susceptibility and biofilm formation ability of and isolated from wild raccoon dogs from Shanghai, China, and to identify the genes responsible for resistance to different classes of antibiotics. The horizontal transfer of resistant plasmids was assessed by plasmid conjugation assays and characterized by third-generation nanopore sequencing. and isolated from wild raccoon dogs in Shanghai had strong biofilm formation ability. They had high resistance rates to amoxicillin, co-trimoxazole, tetracycline, and other antibiotics, but they were still sensitive to advanced antibiotics. The isolates contained prevalent resistance genes and virulence genes, and plasmids could be transferred horizontally. The resistant plasmids are rich in gene transfer elements such as insertion sequences. This is the first description of the antimicrobial resistance status and genes of wild raccoon dogs in Shanghai. These results highlight the urgent need to understand the origin and spread of resistance genes in wild animals such as urban raccoon dogs in Shanghai.
Comparative Analysis of ESBL Phenotypes and Antimicrobial Resistance in Associated with Urinary Tract Infections and in Commensal Strains
Guilcazo D, López L, Calderón D, Vasquez K, Chávez C, Price LB, Graham JP, Eisenberg J and Trueba G
is a genetically versatile organism capable of thriving in diverse environments, acting as a commensal in the intestine or as a pathogen in the urinary tract. causing urinary tract infections has acquired genes that enable it to colonize the urinary tract, survive immune response, and resist antimicrobials. In this study, we investigated the association between the ESBL (Extended Spectrum Beta Lactamase) phenotype and other antimicrobial resistances in associated with urinary tract infections (UTI-; = 1,139) and compared them with commensal strains ( = 405) isolated from human fecal samples in the same communities and during the same period. Among UTI- strains, 16.9% were ESBL producers compared to 7.6% in commensal strains, and resistance to other antimicrobials was also significantly higher in UTI-. These results suggest that many UTI- and commensal lineages have been subjected to distinct antimicrobial pressures over time.
Overcoming Multi-Drug-Resistant Infections
Javan N, Ghotaslou R, Samadi Kafil H, Memar MY, Sadeghi J and Ghotaslou P
Antimicrobial resistance (AMR) is one of the most important concerns in the world, occurring for both Gram-positive and Gram-negative bacteria. () is a Gram-negative bacterium belonging to the family of Enterobacteriaceae and also plays an important role in development of nosocomial infections. Three forms have emerged as a result of AMR including multi-drug resistant (MDR), extensively drug-resistant, and pan-drug-resistant. Nowadays, physicians cannot save most of the patients that suffer from MDR infections by typical antibiotics, so they should try other useful alternative treatments. Our aim in this review study was to search about the latest useful alternative methods against MDR infections. We collected some articles from PubMed, MEDLINE, and Google Scholar by the keywords of multi-drug-resistant , AMR, and alternative treatments, where finally 183 articles were selected. Also, inclusion criteria and exclusion criteria were identified separately. It was understood that there are novel therapeutic options against MDR infections, which include odilorhabdins, drug delivery systems, antibody drug conjugation treatments, nano-antibiotics, bacteriocins, probiotics, fecal transplant therapy, predatory bacteria, combined antibiotics, double-carbapenem therapy, synthetic lipopeptides, and phage therapy.
Whole-Genome Sequencing Analysis of the Multidrug-Resistant Strain AC1520 Isolated from a Patient with Urinary Tract Infection
Xie T, Chen J, Wang S, Zhang Q, Xia W, Su S, Lin X, Yang F, Deng J, Li X, Su W and Ni W
The Gram-negative bacterium is an important opportunistic facultative anaerobic pathogen. In the present study, we aimed to elucidate the whole-genome sequence of the multidrug-resistant (MDR) strain AC1520, detailing its acquired antibiotic resistance genes (ARGs) and their genetic elements. The strain AC1520 was isolated from a urine sample taken from a patient with urinary tract infection. Whole-genome sequencing was performed following strain identification and antimicrobial susceptibility testing. Overall, we identified ARGs, integrons, insertion sequences (IS), and transposons acquired by strain AC1520, systematically analyzing the genetic elements associated with these ARGs. The strain AC1520 contained a circular chromosome and a plasmid. Multilocus sequence typing revealed that this strain belonged to ST-1056. All ARGs within this strain were distributed on the circular chromosome. We identified two MDR regions: (1) IS common region 1 (IS) and class 1 integron (Int) elements associated with , , , (two copies), (two copies), and ; one gene cluster structure (IS----IS); (2) Two Int elements, linked to , , , , , and . Notably, these two MDR regions were not only present in but also in other bacteria, such as , , and . The strain AC1520 with two separate MDR regions and 20 ARGs, conferring resistance to aminoglycoside, fluoroquinolone, phenicol, sulfonamide, beta-lactam, macrolide, rifampicin, and trimethoprim, was identified in a hospital in China. Mobile genetic elements including Tn, IS, IS, IS, IS, Tn, IS, and Tn, were found within the MDR region, which could play important roles in the global dissemination of these resistance genes.
Investigating the Relationship Between Mutations in and Genes and Resistance to Fluoroquinolones in Uropathogenic Isolates
Ghaffari Lashkenari E, Mir MS, Mohammadi M, Javadi K and Halaji M
Fluoroquinolone resistance in , particularly uropathogenic (UPEC), is a growing concern worldwide. This study investigates the association between mutations in the and genes and fluoroquinolone resistance in UPEC isolates from Urine samples in Iran. In total, 150 UPEC isolates were collected, and then, 12 ciprofloxacin-resistant isolates were selected for molecular analysis. Antimicrobial susceptibility testing was performed using the disk diffusion method, and minimum inhibitory concentrations (MICs) of ciprofloxacin were determined by microbroth dilution. Polymerase chain reaction and sequencing were used to detect mutations in the quinolone resistance-determining regions (QRDRs) of and . All isolates had MIC >4 and were resistant to all four fluoroquinolones and quinolones tested, including ciprofloxacin, norfloxacin, ofloxacin, and nalidixic acid. All isolates harbored mutations in both genes. The most frequent mutations in were Ser-83→Leu and Asp-87→Asn, found in 100% of isolates. Similarly, mutations in , including Ser-80→Ile (83.3%) and Glu-84→Val (58.3%), were prevalent. Additional nucleotide substitutions in both genes were observed. These mutations likely contribute to the high-level fluoroquinolone resistance observed in the isolates. The results of this study confirm that mutations in the and genes primarily drive fluoroquinolone resistance in UPEC isolates. The presence of specific alterations within the QRDRs significantly reduces bacterial susceptibility to fluoroquinolones, contributing to the persistence and spread of resistant strains. Identifying these mutations provides critical insights into resistance mechanisms, which can aid in developing more effective antimicrobial therapy strategies.
Pharmacokinetics and Penetration of a Novel Pharmacodynamically Optimized, Carbapenem-Sparing Antibiotic, WCK 4282 (Cefepime/Tazobactam), into Epithelial Lining Fluid of Healthy, Lung-, and Thigh-Infected Neutropenic Mice
Chavan R, Zope V, Patil K, Takalkar S, Tayde P, Umarkar K, Yeole R and Bhagwat S
Cefepime (FEP), a fourth-generation cephalosporin combined with tazobactam (TAZ), a β-lactamase inhibitor, is being developed by Wockhardt as a pharmacodynamically optimized fixed dose combination (FEP-2 g + TAZ-2 g) for the treatment of multidrug-resistant Gram-negative infections. To undertake an exposure-response analysis for establishing pharmacokinetic (PK)/pharmacodynamic (PD) targets, it is crucial to characterize the PK profile of compounds in surrogate compartments, such as plasma and lung, in clinically relevant animal infection models used to evaluate efficacy. In the current study, PKs of FEP and TAZ were assessed in plasma and in epithelial lining fluid (ELF) of neutropenic noninfected, lung-infected, and thigh-infected mice. Neutropenic mice were infected by intranasal or intramuscular administration of 10-10 colony-forming units per milliliter of to develop infection in lung or thigh. Post 2 hours of infection, single doses of WCK 4282 at 25 + 25, 50 + 50, and 100 + 100 mg/kg were subcutaneously administered. Plasma and bronchoalveolar lavage fluid were collected up to 8 hours post-administration of doses. The PK of FEP and TAZ in plasma/ELF in healthy and infected mice did not differ significantly. The plasma PK profiles of FEP and TAZ were linear and dose proportional with modest ELF penetrations in the neutropenic infected mice. The ELF exposures of FEP and TAZ were slightly lower in thigh-infected mice and higher in lung-infected mice when compared with healthy mice. Irrespective of health condition, the mean ELF/plasma area under the curve penetration ratio for FEP and TAZ was similar and comparable (0.42-0.43). The estimates of FEP and TAZ PK parameters estimated in the current study would help in PK-PD studies for the selection of doses for upcoming efficacy studies.
Carbapenem-Resistant Enterobacterales in Indian ICU Patients: Molecular Insights, Risk Factors, and Clinical Impact
Patwa MK, Verma S, Venkatesh V, Kashyap S, Mohit and Arshad Z
Carbapenem-resistant Enterobacterales (CRE) pose a critical threat in intensive care units (ICUs) due to rapid transmission potential and limited treatment options. The study aimed to determine the incidence of intestinal CRE colonization among ICU patients, characterize the isolates phenotypically and genotypically and identify associated risk factors. This cross-sectional study was conducted in a tertiary care hospital in North India and included 236 ICU patients. Clinical, demographic, lifestyle, and dietary data were collected through standardizedv questionnaires and medical records. CRE isolates were identified using standard microbiological techniques and characterized for resistance genes. CRE colonization was detected in 69.07% of patients. (74.15%) and (21.61%) were the predominant species, with a significant rise in colonization during ICU stays ( = 0.049), suggesting nosocomial transmission. Asthma emerged as a novel independent risk factor ( = 0.023, 100% colonization). Other significant associations included non-vegetarian diet ( = 0.02), prolonged ICU stay ( = 0.010), and prior broad-spectrum antibiotic use ( = 0.028). Molecular analysis showed 84% of CRE isolates harbored the bla gene, while bla was absent. CRE colonization was significantly associated with higher mortality (38.0% vs. 23.3%, = 0.026). The study reveals a high prevalence of intestinal CRE colonization among ICU patients and highlights key modifiable risk factors and regional resistance patterns. Routine rectal screening, stringent infection control, and robust antimicrobial stewardship are urgently needed to limit CRE spread. A deeper understanding of colonization dynamics is essential to improving outcomes in critically ill patients.
Emergence of Pediatric Sepsis Caused by a Strain Coharboring , , and in China
Liu Z, Ma C, Teng X, Yu K and Li J
This study reports the discovery of a (KPN) strain carrying the , , and genes in China for the first time. This strain was isolated from the blood of a 2-year-old pediatric patient with acute lymphoblastic leukemia and sepsis. The strain exhibited high resistance to various antibiotics, including β-lactams, carbapenems, and ceftazidime-avibactam. Through whole-genome sequencing and comparative genomic analysis, we found that these resistance genes coexisted on the transferable IncHI2/IncHI2A-type plasmid pK708696_1, which showed high similarity to plasmid pK710429_2 from strain KPN710429 previously identified in our hospital, indicating their potential for rapid spread through horizontal gene transfer. We also performed conjugation experiments to verify the transferability of the plasmid. The results show that the resistance of this strain to traditional antibiotics significantly limited clinical treatment options, thereby posing a serious threat, especially for pediatric leukemia patients with compromised immune systems. This study provides important scientific evidence and new therapeutic approaches for combating carbapenem-resistant infections and highlights the urgency of developing new antibiotics and alternative therapies.
Risk Factors for Developing Infection Among Patients with Previous Carbapenem-Resistant in Respiratory Colonization in the General Wards
Chen G, Liao J, Mo J, Guo B, Niu H and Chen M
Carbapenem-resistant (CRAB) is an opportunistic infectious agent that can cause bacterial colonization and nosocomial infection. This study aims to explore independent risk factors associated with progression from respiratory colonization to infection among CRAB-colonized patients in the general wards. We performed a retrospective study among 202 CRAB-colonized patients in the general wards of our hospital between January 2021 and December 2023. We employed both univariate and multivariable logistic regression models to explore factors associated with the progression from colonization to infection. Among 202 CRAB-colonized patients, 66 experienced progression to subsequent infection and 36 died within 28 days. CRAB-colonized patients with subsequent infection had a significantly higher mortality rate (27.27% vs. 13.24%) than patients without infection ( = 0.014). After performing multivariate logistic regression analysis, CRAB-colonized patients with lower albumin (ALB) levels (OR = 0.94, = 0.029), as well as those receiving antibiotics (OR = 2.49, = 0.020) or glucocorticoids (OR = 2.49, = 0.005), were at higher risk of subsequent infection. Furthermore, among patients with CRAB infection developed after colonization, the use of antifungal drugs (OR = 18.06, = 0.002) and central venous catheter (OR = 10.73, = 0.002) was the factors that associated with 28-day mortality. Our study analyzed CRAB colonization and infection in general medicine wards. Lower ALB levels and antibiotic/glucocorticoid use were risk factors for infection in colonized patients. Among those developing CR-CRAB infection, antifungal use and central venous catheters were associated with 28-day mortality. These findings can inform preventive and therapeutic guidelines for CRAB infections.
Prevalence and Resistance Patterns of Uropathogens in Critically Ill Patients at a Tertiary Care Hospital in Tehran: Implications for Antimicrobial Stewardship in Developing Countries
Kianpour P, Ranjbarian S, Azimi Movahed F, Hamedi S, Mourtami R, Qahari M, Pourfakhr P, Sharifnia H, Mojtahedzadeh M and Najmeddin F
Antimicrobial resistance is a critical global threat in resource-limited settings with underdeveloped laboratory capacity and stewardship programs. Intensive care unit (ICU) patients are at high risk for complicated urinary tract infections (cUTIs) caused by multidrug-resistant (MDR) uropathogens. Local resistance data are essential to guide empirical therapy and design effective stewardship interventions. We conducted a retrospective, cross-sectional study (March 2020-December 2022) of 127 adult ICU patients with cUTIs at a tertiary hospital in Tehran, Iran. Urine isolates were identified by standard phenotypic methods, and antimicrobial susceptibility testing (AST) was performed via disk diffusion following Clinical and Laboratory Standards Institute guidelines. Resistance phenotypes-extended-spectrum beta-lactamase (ESBL) production, carbapenem-resistant Enterobacteriaceae, vancomycin-resistant enterococci (VRE), difficult-to-treat , and pan-drug-resistant (PDR) -were defined using current breakpoints. (52.2%) and (26.9%) predominated. Among Enterobacterales, 60.4% produced ESBL and 30.2% were carbapenem resistant. VRE comprised all enterococcal isolates; PDR occurred in one case. No significant associations were found between resistance profiles and sepsis, septic shock, or mortality. Multivariable analysis identified heart failure (odds ratio [OR] 2.45; 95% confidence interval [CI] 1.15-5.21; = 0.017) and longer ICU stay (OR 1.03 per day; 95% CI 1.01-1.05; = 0.012) as independent predictors of MDR infection. We report an alarming burden of MDR uropathogens in Tehran ICUs, underscoring the need for tailored empirical-therapy guidelines, enhanced antimicrobial stewardship programs, and multicenter surveillance to curb resistance and improve patient outcomes.