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Nasser, Mahfouz, Snehal Palwe, Ram Naresh Bhargava, Marc G. J. Feuilloley, and Arun S. Kharat. "Retrospective Analysis on Antimicrobial Resistance Trends and Prevalence of β-lactamases in Escherichia coli and ESKAPE Pathogens Isolated from Arabian Patients during 2000–2020." Microorganisms 8, no. 10 (October 21, 2020): 1626. http://dx.doi.org/10.3390/microorganisms8101626.
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The production of diverse and extended spectrum β-lactamases among Escherichia coli and ESKAPE pathogens is a growing threat to clinicians and public health. We aim to provide a comprehensive analysis of evolving trends of antimicrobial resistance and β-lactamases among E. coli and ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acine to bacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) in the Arabian region. A systematic review was conducted in Medline PubMed on papers published between January 2000 and February 2020 on countries in the Arab region showing different antibiotic resistance among E. coli and ESKAPE pathogens. A total of n = 119,144 clinical isolates were evaluated for antimicrobial resistance in 19 Arab countries. Among these clinical isolates, 74,039 belonged to E. coli and ESKAPE pathogen. Distribution of antibiotic resistance among E. coli and ESKAPE pathogens indicated that E. coli (n = 32,038) was the predominant pathogen followed by K. pneumoniae (n = 17,128), P. aeruginosa (n = 11,074), methicillin-resistant S. aureus (MRSA, n = 4370), A. baumannii (n = 3485) and Enterobacter spp. (n = 1574). There were no reports demonstrating Enterococcus faecium producing β-lactamase. Analyses revealed 19 out of 22 countries reported occurrence of ESBL (Extended-Spectrum β-Lactamase) producing E. coli and ESKAPE pathogens. The present study showed significantly increased resistance rates to various antimicrobial agents over the last 20 years; for instance, cephalosporin resistance increased from 37 to 89.5%, fluoroquinolones from 46.8 to 70.3%, aminoglycosides from 40.2 to 64.4%, mono-bactams from 30.6 to 73.6% and carbapenems from 30.5 to 64.4%. An average of 36.9% of the total isolates were reported to have ESBL phenotype during 2000 to 2020. Molecular analyses showed that among ESBLs and Class A and Class D β-lactamases, blaCTX-M and blaOXA have higher prevalence rates of 57% and 52.7%, respectively. Among Class B β-lactamases, few incidences of blaVIM 27.7% and blaNDM 26.3% were encountered in the Arab region. Conclusion: This review highlights a significant increase in resistance to various classes of antibiotics, including cephalosporins, β-lactam and β-lactamase inhibitor combinations, carbapenems, aminoglycosides and quinolones among E. coli and ESKAPE pathogens in the Arab region.
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Chapartegui-González, Itziar, María Lázaro-Díez, Santiago Redondo-Salvo, Jesús Navas, and José Ramos-Vivas. "Antimicrobial Resistance Determinants in Genomes and Plasmids from Acinetobacter baumannii Clinical Isolates." Antibiotics 10, no. 7 (June 22, 2021): 753. http://dx.doi.org/10.3390/antibiotics10070753.
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Acinetobacter baumannii is a Gram-negative coccoid rod species, clinically relevant as a human pathogen, included in the ESKAPE group. Carbapenem-resistant A. baumannii (CRAB) are considered by the World Health Organization (WHO) as a critical priority pathogen for the research and development of new antibiotics. Some of the most relevant features of this pathogen are its intrinsic multidrug resistance and its ability to acquire rapid and effective new resistant determinants against last-resort clinical antibiotics, mostly from other ESKAPE species. The presence of plasmids and mobile genetic elements in their genomes contributes to the acquisition of new antimicrobial resistance determinants. However, although A. baumannii has arisen as an important human pathogen, information about these elements is still not well understood. Current genomic analysis availability has increased our ability to understand the microevolution of bacterial pathogens, including point mutations, genetic dissemination, genomic stability, and pan- and core-genome compositions. In this work, we deeply studied the genomes of four clinical strains from our hospital, and the reference strain ATCC®19606TM, which have shown a remarkable ability to survive and maintain their effective capacity when subjected to long-term stress conditions. With that, our aim was presenting a detailed analysis of their genomes, including antibiotic resistance determinants and plasmid composition.
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Meurle, Tobias, Johannes Knaus, Agustin Barbano, Katharina Hoenes, Barbara Spellerberg, and Martin Hessling. "Photoinactivation of Staphylococci with 405 nm Light in a Trachea Model with Saliva Substitute at 37 °C." Healthcare 9, no. 3 (March 11, 2021): 310. http://dx.doi.org/10.3390/healthcare9030310.
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The globally observed rise in bacterial resistance against antibiotics has increased the need for alternatives to antibiotic treatments. The most prominent and important pathogen bacteria are the ESKAPE pathogens, which include among others Staphylococcus aureus, Klebsiella pneumoniae and Acinetobacter baumannii. These species cause ventilator-associated pneumonia (VAP), which accounts for 24% of all nosocomial infections. In this study we tested the efficacy of photoinactivation with 405 nm violet light under conditions comparable to an intubated patient with artificial saliva for bacterial suspension at 37 °C. A technical trachea model was developed to investigate the visible light photoinactivation of Staphylococcus carnosus as a non-pathogen surrogate of the ESKAPE pathogen S. aureus (MRSA). The violet light was coupled into the tube with a fiber optic setup. The performed tests proved, that photoinactivation at 37 °C is more effective with a reduction of almost 3 log levels (99.8%) compared to 25 °C with a reduction of 1.2 log levels. The substitution of phosphate buffered saline (PBS) by artificial saliva solution slightly increased the efficiency during the experimental course. The increased efficiency might be caused by a less favorable environment for bacteria due to for example the ionic composition.
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Vostal, Alexander C., Melissa Grance, Uzo Chukwuma, Carlos Morales, Charlotte Lanteri, Kalyani Telu, Edward Parmelee, John H. Powers, and Katrin Mende. "914. Epidemiology of Patients with ESKAPE Pathogen Bloodstream Infection in the US Military Health System." Open Forum Infectious Diseases 7, Supplement_1 (October 1, 2020): S492. http://dx.doi.org/10.1093/ofid/ofaa439.1102.
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Abstract Background Bloodstream infections (BSI) are associated with both inpatient mortality and substantial morbidity in the United States. We sought to characterize the epidemiology of BSIs with ESKAPE pathogens on patients served by the United States Military Healthcare System (MHS), which actively prospectively captures clinical and microbiological data from US service members and their beneficiaries. Methods We performed a retrospective analysis of MHS patients with blood cultures positive for ESKAPE pathogens (E. faecium, S. aureus, K. pneumoniae, A. baumannii, P. aeruginosa, and Enterobacter spp.), as well as Neisseria gonorrhoeae and Raoultella spp. between January 2010 and December 2015. Microbiological data from the Navy and Marine Core Public Health Center was retrospectively collated with clinical and demographic data from the MHS Data Repository. Results We identified 7,404 patients who experienced 8,791 episodes of ESKAPE (including N. gonorrhoeae and Raoultella spp.) BSI. The patients were predominately active duty (N=688) or retired (N=2,517) Armed Forces service members and their dependents (N=2,361). Further, 59.4% were male and 47.5% were >65 years old. A total of 5,594 (75.5%) of BSI episodes were associated with hospital admission, with an average length of stay of 14.9 days (SD of 27.5 days) and 47.4% (N=2,650) of those admissions were associated with an ICU stay averaging 8.6 days (SD of 18.0 days). The most common pathogens detected were E. coli (34.6%, N= 3,042) followed by S. aureus (28.0%,N=2,464), with 7.6% and 40.7% of isolates resistant to ceftriaxone and methicillin, respectively. We found a larger proportion of E. coli BSI in females (47.4% versus 26.2%) and S. aureus BSI in males (32% versus 21.9%). The frequency of A. baumannii BSI in younger patients, ages 18-30, was an average 4.5 fold higher than in older age groups (30-50, 50-65 and >65). Conclusion We noted epidemiological differences in the burden of ESKAPE pathogen BSIs, in various populations including sex and age specific risk factors in a population served by the MHS. Further work is underway to evaluate risk factors for infection and outcomes with pathogens with in vitro resistance controlling for factors such as age, gender, co-morbid diseases and severity of illness. Disclosures All Authors: No reported disclosures
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Seitz, Tamara, Sebastian Baumgartner, Christoph Wenisch, and Alexander Zoufaly. "115. Evaluation of the Clinical Impact of the T2MR for the Diagnosis of Bloodstream Infections." Open Forum Infectious Diseases 6, Supplement_2 (October 2019): S89. http://dx.doi.org/10.1093/ofid/ofz360.190.
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Abstract Background The EK-189 study evaluates the clinical impact of T2 magnetic resonance (T2MR) for rapid detection of bloodstream infections (BSI) caused by ESKAPE-pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumanii, Pseudomonas aeruginosa, and Escherichia coli) compared with blood culture (BC). Here we present preliminary results from this ongoing study. Methods Patients newly admitted to an infectious diseases department with suspected blood stream infection with ESKAPE pathogens (based on predefined criteria) are included and randomized into BSI diagnosis with (a) T2MR and blood culture or (b) blood culture alone. Routine diagnostic workup including chest X-ray, complete laboratory workup (including blood count, C-reactive protein, interleukin-6) is performed in all patients. Antibiotic regimens are selected empirically based on suspected pathogens and are switched to targeted therapy at the discretion of the treating physician once a pathogen is detected. Outcome parameters include time to targeted (predefined) antibiotic therapy and time to discharge. Test characteristics of the T2MR compared with BC are also assessed. Results So far 44 patients were included (22 in each group). In 9/22 patients (41%) in the T2MR-group a pathogen was detected (4 Escherichia coli, 2 Klebsiella pneumoniae, 1 Staphylococcus aureus, 1 Pseudomonas aeruginosa and 1 Acinetobacter baumanii) and in 3/22 (14%) patients in the BC-group (all E. coli). The comparison of T2MR vs. BC is depicted in Table 1. Sensitivity and specificity of T2MR in comparison to BC were 100% and 64.7%. All positive results in T2MR were considered true positive results. The days until clinical improvement, the need for admission at ICU and the in-hospital mortality were similar in both groups. Conclusion The results from this preliminary analysis show that in patients with suspected BSI with ESKAPE pathogens, T2MR detects more pathogens than BC and potentially provides a quicker detection and shorter time to targeted therapy. Further analyses of this ongoing study with a larger sample size are needed to evaluate the impact of the use of T2MR on patient’s outcome Disclosures All authors: No reported disclosures.
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Skleenova, E. Yu, I. S. Azizov, Е. А. Shek, M. V. Edelstein, R. S. Kozlov, and A. V. Dekhnich. "Pseudomonas aeruginosa: the history of one of the most successful nosocomial pathogens in Russian hospitals." Clinical Microbiology and Antimicrobial Chemotherapy 20, no. 3 (2018): 164–71. http://dx.doi.org/10.36488/cmac.2018.3.164-171.
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Pseudomonas aeruginosa is recognized as one of the six most important pathogens in terms of antimicrobial resistance («ESKAPE» pathogens), and included by WHO in the group of microorganisms for which the need for development of new antimicrobial agents is crucial. In 2015, P. aeruginosa was the second (after Klebsiella spp.) most common nosocomial bacterial pathogen in Russia with the following resistance rates: amikacin – 45.2%, imipenem – 51.5%, meropenem – 53.3%, colistin – 2.2%, piperacillin/tazobactam – 61.4%, ceftazidime – 56.8%, ciprofloxacin – 61.2%. The majority of carbapenemase-producing isolates in Russia belong to the two epidemic lineages – CC235 and CC654.
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Hewitt, Curt, Katharina Weber, Danielle LeSassier, Anthony Kappell, Kathleen Schulte, Nicole Westfall, Nicolette Albright, et al. "Evaluating Metagenomic Analysis for Pathogen Transmission in Healthcare Settings." Infection Control & Hospital Epidemiology 41, S1 (October 2020): s224. http://dx.doi.org/10.1017/ice.2020.768.
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Background: The prevalence of healthcare-acquired infections (HAIs) and rising levels of antimicrobial resistance place a significant burden on modern healthcare systems. Cultures are typically used to track HAIs; however, culture methods provide limited information and are not applicable to all pathogens. Next-generation sequencing (NGS) can detect and characterize pathogens present within a sample, but few research studies have explored how NGS could be used to detect pathogen transmission events under HAI-relevant scenarios. The objective of this CDC-funded project was to evaluate and correlate sequencing approaches for pathogen transmission with standard culture-based analysis. Methods: We modeled pathogen transfer via hand contact using synthetic skin. These skin coupons were seeded with a community of commensal organisms to mimic the human skin microbiome. Pathogens were added at physiologically relevant high or low levels prior to skin-to-skin contact. The ESKAPE pathogens: E. faecium, S. aureus, K. pneumoniae, A. baumannii, P. aeruginosa, and Enterobacter spp plus C. difficile were employed because they are the most common antibiotic resistant HAIs. Pathogen transfer between skin coupons was measured following direct skin contact and fomite surface transmission. The effects of handwashing or fomite decontamination were also evaluated. Transferred pathogens were enumerated via culture to establish a robust data set against which DNA and RNA sequence analyses of the same samples could be compared. These data also provide a quantitative assessment of individual ESKAPE+C pathogen transfer rates in skin contact scenarios. Results: Metagenomic and metatranscriptomic analysis using custom analysis pipelines and reference databases successfully identified the commensal and pathogenic organisms present in each sample at the species level. This analysis also identified antibiotic resistance genes and plasmids. Metatranscriptomic analysis permitted not only gene identification but also confirmation of gene expression, a critical factor in the evaluation of antibiotic resistance. DNA analysis does not require cell viability, a key differentiator between sequencing and culturing reflected in simulated handwashing data. Sensitivity remains a key limitation of metagenomic analysis, as shown by the poor species identification and gene content characterization of pathogens present at low abundance within the simulated microbial community. Species level identification typically failed as ratios fell below 1:1,000 pathogen CFU:total community CFU. Conclusions: These findings demonstrate the strengths and weaknesses of NGS for molecular epidemiology. The data sets produced for this study are publicly available so they can be employed for future metagenomic benchmarking studies.Funding: NoneDisclosures: None
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Orosz, László, György Lengyel, Noel Ánosi, Lóránt Lakatos, and Katalin Burián. "Changes in resistance pattern of ESKAPE pathogens between 2010 and 2020 in the clinical center of University of Szeged, Hungary." Acta Microbiologica et Immunologica Hungarica 69, no. 1 (March 2, 2022): 27–34. http://dx.doi.org/10.1556/030.2022.01640.
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Abstract The acronym ESKAPE stands for six antibiotic-resistant bacterial pathogens namely, Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp. Monitoring their resistance is an important task for clinical microbiology laboratories. Our aim was to analyze the resistance patterns of these bacteria over ten years in clinical samples of our department. We examined the sample types from which these pathogens were most frequently isolated. The incidence of tests with resistant results for each pathogen in aggregate and the most important subgroups of each was also analyzed. We have also intended to predict the local priorities amongst these pathogens. The results of 1,268,126 antibiotic susceptibility tests performed on a total of 70,099 isolates over this period were examined. Most strains were derived from urine, blood culture, trachea, vagina, wounds, and abscesses. Prevalence of ESKAPE bacteria increased between 2011 and 2020 however, the steepest intensifications were seen in the cases of K. pneumoniae and P. aeruginosa. The number of antibiotic susceptibility tests with resistant results has also increased over the decade but the most notable increase was detected in E. faecium and A. baumannii. Based on the calculation of antimicrobial resistance index for each pathogen, the most serious challenges for us at present are A. baumannii, P. aeruginosa, and E. faecium and their multi-resistant forms. The theoretical prediction of proportion of resistant tests between 2020 and 2030 in our care area draws attention to a worrying trend in the cases of vancomycin-resistant E. faecium and carbapenem-resistant A. baumannii strains.
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Mogokotleng, Ruth, Husna Ismail, Olga Perovic, and Sabelle Jallow. "A Retrospective Analysis of Culture-Confirmed Enterococci Bloodstream Infections in South Africa, 2016–2020: A Cross-Sectional Study." Tropical Medicine and Infectious Disease 8, no. 1 (December 27, 2022): 19. http://dx.doi.org/10.3390/tropicalmed8010019.
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(1) Background: The emergence of multidrug resistance enterococci is a major public health concern. This study aimed to determine the prevalence and antimicrobial resistance of enterococci isolated from blood cultures over a five-year period (2016–2020) at public hospitals in South Africa. (2): Methods: A retrospective analysis of clinical enterococci isolated from bloodstream infection samples at the South African public hospitals was conducted. The ESKAPE dataset from January 2016 to December 2020 was obtained from the central data warehouse (CDW) at the National Health Laboratory Service (NHLS). (3): Results: Following de-duplication, a total of 130,352/306,592 organisms isolated from blood cultures were identified as ESKAPE pathogens. In this study, K. pneumoniae (25%; 33,082/130,352), was the most frequently isolated pathogen from blood cultures, followed by S. aureus (23%; 29,922/130,352) and enterococci (16%; 21,339/130,352). Of the enterococci cases, about 43% (9132/21,339) of cases were from the infants aged (<1-year old) and 32% (6745/21,339) from the adult patients. No changes observed in vancomycin, teicoplanin, and linezolid susceptibility; however, E. faecium and E. faecalis blood culture isolates remained highly susceptible (>97%) to these antibiotics. (4): Conclusions: The current study revealed a significant increase of E. faecalis and E. faecium blood culture isolates as compared to the previous national ESKAPE data. Low vancomycin resistance was observed. Continuous monitoring of antimicrobial resistant Enterococcus species is warranted in South Africa.
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Karthick, Dr Mowna. "Pseudomonas aeruginosa: distribution and antibiotic profile of one of the ESKAPE pathogen." Tropical Journal of Pathology and Microbiology 5, no. 9 (September 30, 2019): 678–83. http://dx.doi.org/10.17511/jopm.2019.i09.10.
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Lin, Qiao, Berthony Deslouches, Ronald C. Montelaro, and Y. Peter Di. "Prevention of ESKAPE pathogen biofilm formation by antimicrobial peptides WLBU2 and LL37." International Journal of Antimicrobial Agents 52, no. 5 (November 2018): 667–72. http://dx.doi.org/10.1016/j.ijantimicag.2018.04.019.
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Dekic, Svjetlana, Jasna Hrenovic, Tomislav Ivankovic, and Erna van Wilpe. "Survival of ESKAPE pathogen Acinetobacter baumannii in water of different temperatures and pH." Water Science and Technology 78, no. 6 (September 25, 2018): 1370–76. http://dx.doi.org/10.2166/wst.2018.409.
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Abstract Bacterium Acinetobacter baumannii is an emergent pathogen associated with nosocomial infections, which can be also found in natural waters. The impact of ecological factors on A. baumannii is insufficiently investigated. The aim was to examine the influence of temperatures (−20 to 80 °C) and pH values (2 to 12) on the survival of environmental and clinical isolates of A. baumannii in nutrient-deprived spring water (SW) and nutrient-rich diluted nutrient broth during 5 months. A. baumannii successfully survived at −20 to 44 °C and neutral pH for 5 months, which is consistent with the persistence of this pathogen in the hospital environment. At temperatures 50 to 80 °C the survival of A. baumannii ranged from 5 days to 5 min. The pH 2 was the most lethal with survival time up to 3 hours, suggesting that acidic conditions are promising for disinfection of water contaminated with A. baumannii. Although the type of media was not statistically significant for long-time survival, the extensively resistant or pandrug-resistant isolates survived better in SW than susceptible or multidrug-resistant isolates. Two distinct colony phenotypes were recorded at extreme temperatures and pH values. The results of this study provide insight into the behaviour of this emerging pathogen in the environment.
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Zhu, Hua, Jasper Swierstra, Changsheng Wu, Geneviève Girard, Young Hae Choi, Willem van Wamel, Stephanie K. Sandiford, and Gilles P. van Wezel. "Eliciting antibiotics active against the ESKAPE pathogens in a collection of actinomycetes isolated from mountain soils." Microbiology 160, no. 8 (August 1, 2014): 1714–25. http://dx.doi.org/10.1099/mic.0.078295-0.
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The rapid emergence of multidrug-resistant (MDR) bacterial pathogens poses a major threat for human health. In recent years, genome sequencing has unveiled many poorly expressed antibiotic clusters in actinomycetes. Here, we report a well-defined ecological collection of >800 actinomycetes obtained from sites in the Himalaya and Qinling mountains, and we used these in a concept study to see how efficiently antibiotics can be elicited against MDR pathogens isolated recently from the clinic. Using 40 different growth conditions, 96 actinomycetes were identified – predominantly Streptomyces – that produced antibiotics with efficacy against the MDR clinical isolates referred to as ESKAPE pathogens: Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and/or Enterobacter cloacae. Antimicrobial activities that fluctuated strongly with growth conditions were correlated with specific compounds, including borrelidin, resistomycin, carbomethoxy-phenazine, and 6,7,8- and 5,6,8-trimethoxy-3-methylisocoumarin, of which the latter was not described previously. Our work provided insights into the potential of actinomycetes as producers of drugs with efficacy against clinical isolates that have emerged recently and also underlined the importance of targeting a specific pathogen.
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Serapide, Francesca, Angela Quirino, Vincenzo Scaglione, Helen Linda Morrone, Federico Longhini, Andrea Bruni, Eugenio Garofalo, et al. "Is the Pendulum of Antimicrobial Drug Resistance Swinging Back after COVID-19?" Microorganisms 10, no. 5 (May 2, 2022): 957. http://dx.doi.org/10.3390/microorganisms10050957.
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The COVID-19 pandemic may have had an effect on antimicrobial resistance. We compared the prevalence of ESKAPE multidrug-resistant (MDR) bacterial infections in COVID-19 affected/unaffected patients admitted to intensive care units (ICU) or infectious disease units at the “Mater Domini” University Hospital of Catanzaro between 1 March 2020 and 31 July 2021. Moreover, an analysis of MDR rates in ICU comparing the pre-pandemic period with the pandemic period was performed, and the possible consequence on in-hospital mortality was explored. One hundred and eighty-four ESKAPE isolates were analyzed from 362 SARS-CoV-2 positive and 199 negative patients. In total, 116 out of 171 Gram-negative isolates were classified as MDR, and a higher frequency was observed in COVID-19 compared with non-COVID-19 patients (74.2% vs. 60.3%; p = 0.052). A higher rate of MDR ESKAPE bacteria was observed in COVID-19 patients admitted to the ICU compared with COVID-19 unaffected patients admitted to the same ward in 2019 (88% vs. 80.4%; p = 0.186). Acinetobacter baumannii was the main pathogen in COVID-19 patients (58.7%), where it was the most frequent cause of bloodstream infection with the highest mortality rate (68.7%). Increase in MDR appeared to be associated with COVID-19 but only in the ICU setting. Acinetobacter baumannii was associated with the risk of death, indicating the importance of implementing infection control measures urgently.
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Thompson, Mitchell G., Chad C. Black, Rebecca L. Pavlicek, Cary L. Honnold, Matthew C. Wise, Yonas A. Alamneh, Jay K. Moon, et al. "Validation of a Novel Murine Wound Model of Acinetobacter baumannii Infection." Antimicrobial Agents and Chemotherapy 58, no. 3 (December 16, 2013): 1332–42. http://dx.doi.org/10.1128/aac.01944-13.
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ABSTRACTPatients recovering from traumatic injuries or surgery often require weeks to months of hospitalization, increasing the risk for wound and surgical site infections caused by ESKAPE pathogens, which includeA. baumannii(the ESKAPE pathogens areEnterococcus faecium,Staphylococcus aureus,Klebsiella pneumoniae,Acinetobacter baumannii,Pseudomonas aeruginosa, andEnterobacterspecies). As new therapies are being developed to counterA. baumanniiinfections, animal models are also needed to evaluate potential treatments. Here, we present an excisional, murine wound model in which a diminutive inoculum of a clinically relevant, multidrug-resistantA. baumanniiisolate can proliferate, form biofilms, and be effectively treated with antibiotics. The model requires a temporary, cyclophosphamide-induced neutropenia to establish an infection that can persist. A 6-mm-diameter, full-thickness wound was created in the skin overlying the thoracic spine, and after the wound bed was inoculated, it was covered with a dressing for 7 days. Uninoculated control wounds healed within 13 days, whereas infected, placebo-treated wounds remained unclosed beyond 21 days. Treated and untreated wounds were assessed with multiple quantitative and qualitative techniques that included gross pathology, weight loss and recovery, wound closure, bacterial burden, 16S rRNA community profiling, histopathology, peptide nucleic acid-fluorescencein situhybridization, and scanning electron microscopy assessment of biofilms. The range of differences that we are able to identify with these measures in antibiotic- versus placebo-treated animals provides a clear window within which novel antimicrobial therapies can be assessed. The model can be used to evaluate antimicrobials for their ability to reduce specific pathogen loads in wounded tissues and clear biofilms. Ultimately, the mouse model approach allows for highly powered studies and serves as an initial multifacetedin vivoassessment prior to testing in larger animals.
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Sapegin, Alexander, Elizaveta Rogacheva, Lyudmila Kraeva, Maxim Gureev, Marine Dogonadze, Tatiana Vinogradova, Petr Yablonsky, Saeed Balalaie, Sergey V. Baykov, and Mikhail Krasavin. "Novel 5-Nitrofuran-Tagged Imidazo-Fused Azines and Azoles Amenable by the Groebke–Blackburn–Bienaymé Multicomponent Reaction: Activity Profile against ESKAPE Pathogens and Mycobacteria." Biomedicines 10, no. 9 (September 6, 2022): 2203. http://dx.doi.org/10.3390/biomedicines10092203.
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A chemically diverse set of 13 5-nitrofuran-tagged heterocyclic compounds has been prepared via the Groebke–Blackburn–Bienaymé multicomponent reaction. The testing of these compounds against the so-called ESKAPE panel of pathogens identified an apparent lead compound—N-cyclohexyl-2-(5-nitrofuran-2-yl)imidazo[1,2-a]pyridine-3-amine (4a)—which showed an excellent profile against Enterobacter cloacae, Staphylococcus aureus, Klebsiella pneumoniae, and Enterococcus faecalis (MIC 0.25, 0.06, 0.25 and 0.25 µg/mL, respectively). Its antibacterial profile and practically convenient synthesis warrant further pre-clinical development. Certain structure-activity relationships were established in the course of this study which were rationalized by the flexible docking experiments in silico. The assessment of antitubercular potential of the compounds synthesized against drug sensitive H37v strain of Mycobacterium tuberculosis revealed little potential of the imidazo-fused products of the Groebke–Blackburn–Bienaymé multicomponent reaction as chemotherapeutic agents against this pathogen.
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Chen, Donald, Liyi Xu, Mary Fortunato-Habib, Andrew Hoss, Melissa Chanza, Changhong Yin, Raivo Kolde, et al. "1248. Genomic Sequencing and Clinical Data Integration for Next-Generation Infection Prevention." Open Forum Infectious Diseases 5, suppl_1 (November 2018): S379—S380. http://dx.doi.org/10.1093/ofid/ofy210.1081.
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Abstract Background Typical Infection Prevention to detect pathogen transmission in hospitals has relied on observation of (1) uncommon pathogen phenotypes or (2) greater than expected number of pathogen phenotypes in a given timeframe and/or location. Genome sequencing of targeted organisms in conjunction with routine patient geo-temporal information and antibiotic susceptibility data holds promise in identifying transmissions with greater sensitivity and specificity, saving time and effort in reviewing for transmission events. Methods In an on-going genomic sequencing surveillance effort in a tertiary care hospital, drug-resistant clinical isolates from the “ESKAPE” pathogens were routinely sequenced in 2017. In parallel, potential clusters were identified for 2017 through conventional Infection Prevention approaches. Groups identified by their genetic distances along with visualizations on antimicrobial susceptibilities, and patient location histories and dates were displayed in an interactive interface, Philips IntelliSpace Epidemiology (PIE), and reviewed by Infection Prevention. Results Among 656 patients, 1,239 drug-resistant ESKAPE samples were sequenced. Thirty-eight genetically related groups involving 196 patients were identified. Groups ranged in size from two to 44 patients, primarily consisting of VRE and MRSA. Notably, a review of the 38 groups identified 20 groups where the information at hand suggested a concern for transmission. 16 of the 20 were not previously identified by Infection Prevention. Using PIE to review all 38 groups identified from 1 year’s worth of data required 3 hours of time by an Infection Prevention professional, averaging less than 5 minutes per cluster, less than 1 minute per patient, and 11 minutes of review time per actionable opportunity. By conventional means, approximately 23 hours would have been required to review the genomic groups without the aid of the PIE tool. Conclusion The use of PIE’s genomic-defined groups, along with the integrated clinical data platform, allows for a greater ability, certainty, and speed to detect clusters of organisms representing transmission in the hospital setting. Applied prospectively, PIE can detect transmissions sooner than by conventional means for potential patient safety gains and cost savings. Disclosures D. Chen, Philips: Scientific Advisor, Consulting fee. M. Fortunato-Habib, Philips Healthcare: Collaborator and Employee, Salary. A. Hoss, Philips: Employee, Salary. R. Kolde, Philips: Employee, Salary. A. Dhand, Merck: Speaker’s Bureau, Speaker honorarium. Astellas: Scientific Advisor, Consulting fee. R. Sussner, Philips: Scientific Advisor, Consulting fee. J. Carmona, Philips Healthcare: Employee, Salary. B. Gross, Philips Healthcare: Employee, Investigator, Research Contractor, Scientific Advisor and Shareholder, Salary. J. Fallon, Philips Healthcare: Investigator, Research support.
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Shelenkov, Andrey, Lyudmila Petrova, Valeria Fomina, Mikhail Zamyatin, Yulia Mikhaylova, and Vasiliy Akimkin. "Multidrug-Resistant Proteus mirabilis Strain with Cointegrate Plasmid." Microorganisms 8, no. 11 (November 12, 2020): 1775. http://dx.doi.org/10.3390/microorganisms8111775.
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Proteus mirabilis is a component of the normal intestinal microflora of humans and animals, but can cause urinary tract infections and even sepsis in hospital settings. In recent years, the number of multidrug-resistant P. mirabilis isolates, including the ones producing extended-spectrum β-lactamases (ESBLs), is increasing worldwide. However, the number of investigations dedicated to this species, especially, whole-genome sequencing, is much lower in comparison to the members of the ESKAPE pathogens group. This study presents a detailed analysis of clinical multidrug-resistant ESBL-producing P. mirabilis isolate using short- and long-read whole-genome sequencing, which allowed us to reveal possible horizontal gene transfer between Klebsiella pneumoniae and P. mirabilis plasmids and to locate the CRISPR-Cas system in the genome together with its probable phage targets, as well as multiple virulence genes. We believe that the data presented will contribute to the understanding of antibiotic resistance acquisition and virulence mechanisms for this important pathogen.
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Tomar, Jyoti Singh, Rama Krishna Peddinti, and Ramakrishna V. Hosur. "Aminoglycoside antibiotic resistance conferred by Hpa2 of MDR Acinetobacter baumannii: an unusual adaptation of a common histone acetyltransferase." Biochemical Journal 476, no. 5 (March 6, 2019): 795–808. http://dx.doi.org/10.1042/bcj20180791.
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AbstractAntibiotic-resistant bacteria pose the greatest threat to human health. Among the list of such bacteria released by WHO, carbapenem-resistant Acinetobacter baumannii, for which almost no treatment exists, tops the list. A. baumannii is one of the most troublesome ESKAPE pathogens and mechanisms that have facilitated its rise as a successful pathogen are not well studied. Efforts in this direction have resulted in the identification of Hpa2-Ab, an uncharacterized histone acetyltransferase enzyme of GNAT superfamily. Here, we show that Hpa2-Ab confers resistance against aminoglycoside antibiotics using Escherichia coli DH5α strains in which Hpa2 gene is expressed. Resistivity for aminoglycoside antibiotics is demonstrated with the help of CLSI-2010 and KB tests. Isothermal titration calorimetry, MALDI and acetylation assays indicate that conferred resistance is an outcome of evolved antibiotic acetylation capacity in this. Hpa2 is known to acetylate nuclear molecules; however, here it is found to cross its boundary and participate in other functions. An array of biochemical and biophysical techniques were also used to study this protein, which demonstrates that Hpa2-Ab is intrinsically oligomeric in nature, exists primarily as a dimer and its interface is mainly stabilized by hydrophobic interactions. Our work demonstrates an evolved survival strategy by A. baumannii and provides insights into the mechanism that facilitates it to rise as a successful pathogen.
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Vu, Thi Huyen, Erika Adhel, Katarina Vielfort, Ngûyet-Thanh Ha Duong, Guillaume Anquetin, Katy Jeannot, Philippe Verbeke, Sofia Hjalmar, Åsa Gylfe, and Nawal Serradji. "Modified Fluoroquinolones as Antimicrobial Compounds Targeting Chlamydia trachomatis." International Journal of Molecular Sciences 23, no. 12 (June 16, 2022): 6741. http://dx.doi.org/10.3390/ijms23126741.
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Chlamydia trachomatis causes the most common sexually transmitted bacterial infection and trachoma, an eye infection. Untreated infections can lead to sequelae, such as infertility and ectopic pregnancy in women and blindness. We previously enhanced the antichlamydial activity of the fluoroquinolone ciprofloxacin by grafting a metal chelating moiety onto it. In the present study, we pursued this pharmacomodulation and obtained nanomolar active molecules (EC50) against this pathogen. This gain in activity prompted us to evaluate the antibacterial activity of this family of molecules against other pathogenic bacteria, such as Neisseria gonorrhoeae and bacteria from the ESKAPE group. The results show that the novel molecules have selectively improved activity against C. trachomatis and demonstrate how the antichlamydial effect of fluoroquinolones can be enhanced.
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Chatterjee, Rahul, Panchanan Sahoo, Soumya Ranjan Mahapatra, Jyotirmayee Dey, Mrinmoy Ghosh, Gajraj Singh Kushwaha, Namrata Misra, Mrutyunjay Suar, Vishakha Raina, and Young-Ok Son. "Development of a Conserved Chimeric Vaccine for Induction of Strong Immune Response against Staphylococcus aureus Using Immunoinformatics Approaches." Vaccines 9, no. 9 (September 18, 2021): 1038. http://dx.doi.org/10.3390/vaccines9091038.
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Staphylococcus aureus is one of the most notorious Gram-positive bacteria with a very high mortality rate. The WHO has listed S. aureus as one of the ESKAPE pathogens requiring urgent research and development efforts to fight against it. Yet there is a major layback in the advancement of effective vaccines against this multidrug-resistant pathogen. SdrD and SdrE proteins are attractive immunogen candidates as they are conserved among all the strains and contribute specifically to bacterial adherence to the host cells. Furthermore, these proteins are predicted to be highly antigenic and essential for pathogen survival. Therefore, in this study, using the immunoinformatics approach, a novel vaccine candidate was constructed using highly immunogenic conserved T-cell and B-cell epitopes along with specific linkers, adjuvants, and consequently modeled for docking with human Toll-like receptor 2. Additionally, physicochemical properties, secondary structure, disulphide engineering, and population coverage analysis were also analyzed for the vaccine. The constructed vaccine showed good results of worldwide population coverage and a promising immune response. For evaluation of the stability of the vaccine-TLR-2 docked complex, a molecular dynamics simulation was performed. The constructed vaccine was subjected to in silico immune simulations by C-ImmSim and Immune simulation significantly provided high levels of immunoglobulins, T-helper cells, T-cytotoxic cells, and INF-γ. Lastly, upon cloning, the vaccine protein was reverse transcribed into a DNA sequence and cloned into a pET28a (+) vector to ensure translational potency and microbial expression. The overall results of the study showed that the designed novel chimeric vaccine can simultaneously elicit humoral and cell-mediated immune responses and is a reliable construct for subsequent in vivo and in vitro studies against the pathogen.
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Sutton, Kristin A., Jennifer Breen, Thomas A. Russo, L. Wayne Schultz, and Timothy C. Umland. "Crystal structure of 5-enolpyruvylshikimate-3-phosphate (EPSP) synthase from the ESKAPE pathogenAcinetobacter baumannii." Acta Crystallographica Section F Structural Biology Communications 72, no. 3 (February 16, 2016): 179–87. http://dx.doi.org/10.1107/s2053230x16001114.
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The enzyme 5-enolpyruvylshikimate-3-phosphate (EPSP) synthase catalyzes the sixth step of the seven-step shikimate pathway. Chorismate, the product of the pathway, is a precursor for the biosynthesis of aromatic amino acids, siderophores and metabolites such as folate, ubiquinone and vitamin K. The shikimate pathway is present in bacteria, fungi, algae, plants and apicomplexan parasites, but is absent in humans. The EPSP synthase enzyme produces 5-enolpyruvylshikimate 3-phosphate and phosphate from phosphoenolpyruvate and shikimate 3-phosphateviaa transferase reaction, and is the target of the herbicide glyphosate. TheAcinetobacter baumanniigene encoding EPSP synthase,aroA, has previously been demonstrated to be essential during host infection for the growth and survival of this clinically important drug-resistant ESKAPE pathogen. Prephenate dehydrogenase is also encoded by the bifunctionalA. baumannii aroAgene, but its activity is dependent upon EPSP synthase since it operates downstream of the shikimate pathway. As part of an effort to evaluate new antimicrobial targets, recombinantA. baumanniiEPSP (AbEPSP) synthase, comprising residues Ala301–Gln756 of thearoAgene product, was overexpressed inEscherichia coli, purified and crystallized. The crystal structure, determined to 2.37 Å resolution, is described in the context of a potential antimicrobial target and in comparison to EPSP synthases that are resistant or sensitive to the herbicide glyphosate.
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Ihssane, Benzaarate, Elotmani Fatima, Khazaz Aboubakr, Mohammed Timinouni, and Nayme Kaotar. "New alternative therapeutic strategies against Pseudomonas aeruginosa, an opportunistic multi-resistant pathogen with a myriad of virulence factors." Journal of Infection in Developing Countries 17, no. 07 (July 27, 2023): 891–904. http://dx.doi.org/10.3855/jidc.17739.
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Pseudomonas aeruginosa (PA) has emerged as a significant cause of Gram-negative infections, particularly in patients with impaired host defenses. It is one of the six ESKAPE pathogens that majorly cause severe nosocomial infections. In addition to biofilm formation, PA possesses various virulence factors. It can be life-threatening due to his remarkable capacity to resist antibiotics, either intrinsically, developing adaptative resistance, or following the acquisition of resistance genes. The situation worsens when these mechanisms co-exist, conferring worrying multi-resistant phenotypes. Therapeutic options are becoming limited, which has led to the development of new antibiotics and novel alternative therapeutic strategies that require the exploration of other therapeutic avenues. Although mostly at the preclinical stages, many recent studies have reported several innovative therapeutic technologies that have demonstrated pronounced effectiveness in fighting against drug-resistant Pa strains. This literature review aims to discuss the mechanism of pyocyanic bacillus resistance to antibiotics, highlight the current state of some novel antibiotics and combination therapies, and the new alternative therapeutic approaches for treating PA infections.
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Iruegas, Ruben, Katharina Pfefferle, Stephan Göttig, Beate Averhoff, and Ingo Ebersberger. "Feature architecture aware phylogenetic profiling indicates a functional diversification of type IVa pili in the nosocomial pathogen Acinetobacter baumannii." PLOS Genetics 19, no. 7 (July 27, 2023): e1010646. http://dx.doi.org/10.1371/journal.pgen.1010646.
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The Gram-negative bacterial pathogen Acinetobacter baumannii is a major cause of hospital-acquired opportunistic infections. The increasing spread of pan-drug resistant strains makes A. baumannii top-ranking among the ESKAPE pathogens for which novel routes of treatment are urgently needed. Comparative genomics approaches have successfully identified genetic changes coinciding with the emergence of pathogenicity in Acinetobacter. Genes that are prevalent both in pathogenic and a-pathogenic Acinetobacter species were not considered ignoring that virulence factors may emerge by the modification of evolutionarily old and widespread proteins. Here, we increased the resolution of comparative genomics analyses to also include lineage-specific changes in protein feature architectures. Using type IVa pili (T4aP) as an example, we show that three pilus components, among them the pilus tip adhesin ComC, vary in their Pfam domain annotation within the genus Acinetobacter. In most pathogenic Acinetobacter isolates, ComC displays a von Willebrand Factor type A domain harboring a finger-like protrusion, and we provide experimental evidence that this finger conveys virulence-related functions in A. baumannii. All three genes are part of an evolutionary cassette, which has been replaced at least twice during A. baumannii diversification. The resulting strain-specific differences in T4aP layout suggests differences in the way how individual strains interact with their host. Our study underpins the hypothesis that A. baumannii uses T4aP for host infection as it was shown previously for other pathogens. It also indicates that many more functional complexes may exist whose precise functions have been adjusted by modifying individual components on the domain level.
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Li, Tingting, Zhaoyinqian Li, Li Huang, Jingyang Tang, Zixuan Ding, Zhangrui Zeng, Yao Liu, and Jinbo Liu. "Cigarette Smoking and Peripheral Vascular Disease are Associated with Increasing Risk of ESKAPE Pathogen Infection in Diabetic Foot Ulcers." Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy Volume 15 (October 2022): 3271–83. http://dx.doi.org/10.2147/dmso.s383701.
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Na, Seok-Hyeon, Hyejin Jeon, Man-Hwan Oh, Yoo-Jeong Kim, Mingi Chu, Ill-Young Lee, and Je-Chul Lee. "Therapeutic Effects of Inhibitor of ompA Expression against Carbapenem-Resistant Acinetobacter baumannii Strains." International Journal of Molecular Sciences 22, no. 22 (November 12, 2021): 12257. http://dx.doi.org/10.3390/ijms222212257.
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The widespread of carbapenem-resistant Acinetobacter baumannii (CRAB) is of great concern in clinical settings worldwide. It is urgent to develop new therapeutic agents against this pathogen. This study aimed to evaluate the therapeutic potentials of compound 62520, which has been previously identified as an inhibitor of the ompA promoter activity of A. baumannii, against CRAB isolates, both in vitro and in vivo. Compound 62520 was found to inhibit the ompA expression and biofilm formation in A. baumannii ATCC 17978 at sub-inhibitory concentrations in a dose-dependent manner. These inhibitory properties were also observed in clinical CRAB isolates belonging to sequence type (ST) 191. Additionally, compound 62520 exhibited a bacteriostatic activity against clinical clonal complex (CC) 208 CRAB isolates, including ST191, and ESKAPE pathogens. This bacteriostatic activity was not different between STs of CRAB isolates. Bacterial clearance was observed in mice infected with bioimaging A. baumannii strain 24 h after treatment with compound 62520. Compound 62520 was shown to significantly increase the survival rates of both immunocompetent and neutropenic mice infected with A. baumannii ATCC 17978. This compound also increased the survival rates of mice infected with clinical CRAB isolate. These results suggest that compound 62520 is a promising scaffold to develop a novel therapeutic agent against CRAB infections.
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Shi, Yu, Qin Cao, Jingdu Sun, Xiaofang Hu, Zhi Su, Yongchang Xu, Huimin Zhang, Lefu Lan, and Youjun Feng. "The opportunistic pathogen Pseudomonas aeruginosa exploits bacterial biotin synthesis pathway to benefit its infectivity." PLOS Pathogens 19, no. 1 (January 23, 2023): e1011110. http://dx.doi.org/10.1371/journal.ppat.1011110.
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Pseudomonas aeruginosa is an opportunistic pathogen that predominantly causes nosocomial and community-acquired lung infections. As a member of ESKAPE pathogens, carbapenem-resistant P. aeruginosa (CRPA) compromises the limited therapeutic options, raising an urgent demand for the development of lead compounds against previously-unrecognized drug targets. Biotin is an important cofactor, of which the de novo synthesis is an attractive antimicrobial target in certain recalcitrant infections. Here we report genetic and biochemical definition of P. aeruginosa BioH (PA0502) that functions as a gatekeeper enzyme allowing the product pimeloyl-ACP to exit from fatty acid synthesis cycle and to enter the late stage of biotin synthesis pathway. In relative to Escherichia coli, P. aeruginosa physiologically requires 3-fold higher level of cytosolic biotin, which can be attributed to the occurrence of multiple biotinylated enzymes. The BioH protein enables the in vitro reconstitution of biotin synthesis. The repertoire of biotin abundance is assigned to different mouse tissues and/or organ contents, and the plasma biotin level of mouse is around 6-fold higher than that of human. Removal of bioH renders P. aeruginosa biotin auxotrophic and impairs its intra-phagosome persistence. Based on a model of CD-1 mice mimicking the human environment, lung challenge combined with systemic infection suggested that BioH is necessary for the full virulence of P. aeruginosa. As expected, the biotin synthesis inhibitor MAC13772 is capable of dampening the viability of CRPA. Notably, MAC13772 interferes the production of pyocyanin, an important virulence factor of P. aeruginosa. Our data expands our understanding of P. aeruginosa biotin synthesis relevant to bacterial infectivity. In particular, this study represents the first example of an extracellular pathogen P. aeruginosa that exploits biotin cofactor as a fitness determinant, raising the possibility of biotin synthesis as an anti-CRPA target.
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Dubashynskaya, Natallia V., and Yury A. Skorik. "Polymyxin Delivery Systems: Recent Advances and Challenges." Pharmaceuticals 13, no. 5 (April 29, 2020): 83. http://dx.doi.org/10.3390/ph13050083.
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Polymyxins are vital antibiotics for the treatment of multiresistant Gram-negative ESKAPE pathogen infections. However, their clinical value is limited by their high nephrotoxicity and neurotoxicity, as well as their poor permeability and absorption in the gastrointestinal tract. This review focuses on various polymyxin delivery systems that improve polymyxin bioavailability and reduce drug toxicity through targeted and controlled release. Currently, the most suitable systems for improving oral, inhalation, and parenteral polymyxin delivery are polymer particles, liposomes, and conjugates, while gels, polymer fibers, and membranes are attractive materials for topical administration of polymyxin for the treatment of infected wounds and burns. In general, the application of these systems protects polymyxin molecules from the negative effects of both physiological and pathological factors while achieving higher concentrations at the target site and reducing dosage and toxicity. Improving the properties of polymyxin will be of great interest to researchers who are focused on developing antimicrobial drugs that show increased efficacy and safety.
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Ghotbi, Marjan, Ole Kelting, Martina Blümel, and Deniz Tasdemir. "Gut and Gill-Associated Microbiota of the Flatfish European Plaice (Pleuronectes platessa): Diversity, Metabolome and Bioactivity against Human and Aquaculture Pathogens." Marine Drugs 20, no. 9 (September 9, 2022): 573. http://dx.doi.org/10.3390/md20090573.
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Similar to other marine holobionts, fish are colonized by complex microbial communities that promote their health and growth. Fish-associated microbiota is emerging as a promising source of bioactive metabolites. Pleuronectes platessa (European plaice, plaice), a flatfish with commercial importance, is common in the Baltic Sea. Here we used a culture-dependent survey followed by molecular identification to identify microbiota associated with the gills and the gastrointestinal tract (GIT) of P. platessa, then profiled their antimicrobial activity and metabolome. Altogether, 66 strains (59 bacteria and 7 fungi) were isolated, with Proteobacteria being the most abundant phylum. Gill-associated microbiota accounted for higher number of isolates and was dominated by the Proteobacteria (family Moraxellaceae) and Actinobacteria (family Nocardiaceae), whereas Gram-negative bacterial families Vibrionaceae and Shewanellaceae represented the largest group associated with the GIT. The EtOAc extracts of the solid and liquid media cultures of 21 bacteria and 2 fungi representing the diversity of cultivable plaice-associated microbiota was profiled for their antimicrobial activity against three fish pathogens, human bacterial pathogen panel (ESKAPE) and two human fungal pathogens. More than half of all tested microorganisms, particularly those originating from the GIT epithelium, exhibited antagonistic effect against fish pathogens (Lactococcus garvieae, Vibrio ichthyoenteri) and/or human pathogens (Enterococcus faecium, methicillin-resistant Staphylococcus aureus). Proteobacteria represented the most active isolates. Notably, the solid media extracts displayed higher activity against fish pathogens, while liquid culture extracts were more active against human pathogens. Untargeted metabolomics approach using feature-based molecular networking showed the high chemical diversity of the liquid extracts that contained undescribed clusters. This study highlights plaice-associated microbiota as a potential source of antimicrobials for the control of human and the aquaculture-associated infections. This is the first study reporting diversity, bioactivity and chemical profile of culture-dependent microbiota of plaice.
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Chathuranga, Gayashan, Thushari Dissanayake, Neluka Fernando, and Chandanie Wanigatunge. "Appropriateness of the Empirical Antibiotics Prescribed and Their Concordance with National Guidelines for Three Selected Infections among Cancer Patients in a Tertiary Care Centre in Sri Lanka." International Journal of Microbiology 2021 (September 28, 2021): 1–7. http://dx.doi.org/10.1155/2021/7572215.
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Background. Prophylactic and empirical antibiotic use is essential in cancer patients due to the underlying immune deficiencies. We examined the spectrum of causative bacteria and the appropriateness of empirical antibiotic prescription for three selected infections in cancer patients. Methodology. A descriptive cross-sectional study was conducted at the National Institute of Cancer (NIC), Sri Lanka, from June 2018 to February 2019. Bacterial isolates obtained from adult cancer patients with a diagnosis of lower respiratory tract infections (LRTI), skin and soft tissue infections (SSTI), or urinary tract infections (UTI) were included. Causative bacteria were identified and the antibiotic susceptibility was determined by standard microbiological methods. Empirical therapy was defined as appropriate if the isolated pathogen was susceptible in vitro to the given antibiotic. Results. A total of 155 bacterial isolates were included in the analysis. LRTI were the most prevalent infections (37.2%, 55/148) encountered during the study period. Majority (90.9%) of the isolated bacteria were ESKAPE pathogens. Klebsiella pneumoniae was the most frequent pathogen causing LRTI (42.4%, 25/59), whereas Escherichia coli (32%, 16/50) and Staphylococcus aureus (26.1%, 12/46) predominated in UTI and SSTI, respectively. Meropenem was the most prescribed empirical antibiotic for LRTI (29.1%, 16/55) and SSTI (26.6%, 11/43) while it was ceftazidime for UTI (36%, 18/50). Only 20.6% (32/155) of the isolated bacteria were susceptible to the empirical antibiotic prescribed while 48.4% (75/155) were resistant to them. The prescribed empirical antibiotic did not have the spectrum of activity for the isolated bacteria in 29% (45/155) of cases. Conclusion. High resistance rates were observed against the prescribed empirical antibiotics. National empirical antibiotic guidelines should be revised with updated data on causative organisms and their susceptibility patterns to ensure appropriate empirical antibiotic prescription.
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Elmassry, Moamen M., Jane A. Colmer-Hamood, Jonathan Kopel, Michael J. San Francisco, and Abdul N. Hamood. "Anti-Pseudomonas aeruginosa Vaccines and Therapies: An Assessment of Clinical Trials." Microorganisms 11, no. 4 (March 31, 2023): 916. http://dx.doi.org/10.3390/microorganisms11040916.
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Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen that causes high morbidity and mortality in cystic fibrosis (CF) and immunocompromised patients, including patients with ventilator-associated pneumonia (VAP), severely burned patients, and patients with surgical wounds. Due to the intrinsic and extrinsic antibiotic resistance mechanisms, the ability to produce several cell-associated and extracellular virulence factors, and the capacity to adapt to several environmental conditions, eradicating P. aeruginosa within infected patients is difficult. Pseudomonas aeruginosa is one of the six multi-drug-resistant pathogens (ESKAPE) considered by the World Health Organization (WHO) as an entire group for which the development of novel antibiotics is urgently needed. In the United States (US) and within the last several years, P. aeruginosa caused 27% of deaths and approximately USD 767 million annually in health-care costs. Several P. aeruginosa therapies, including new antimicrobial agents, derivatives of existing antibiotics, novel antimicrobial agents such as bacteriophages and their chelators, potential vaccines targeting specific virulence factors, and immunotherapies have been developed. Within the last 2–3 decades, the efficacy of these different treatments was tested in clinical and preclinical trials. Despite these trials, no P. aeruginosa treatment is currently approved or available. In this review, we examined several of these clinicals, specifically those designed to combat P. aeruginosa infections in CF patients, patients with P. aeruginosa VAP, and P. aeruginosa–infected burn patients.
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Yarets, Yu I. "PATHOGENIC POTENTIAL OF ESKAPE GROUP BACTERIA ISOLATED FROM WOUNDS: CHARACTERIZATION OF PHENOTYPIC AND GENOTYPIC MARKERS AND POSSIBILITY OF THEIR PRACTICAL APPLICATION." Journal of the Grodno State Medical University 20, no. 4 (September 9, 2022): 400–413. http://dx.doi.org/10.25298/2221-8785-2022-20-4-400-413.
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Backgroud. Evaluation of the biological properties of isolates obtained from the clinical samples of patients will increase the informative value of the microbiological study and optimize the interpretation of the culture results in order to substantiate further wound treatment tactics. Aim. To analyze the phenotypic and genotypic properties of ESKAPE bacteria and to determine the possibility of practical use of the parameters characterizing the bioprofile of the isolate when interpreting the results of microbiological culture of the wound swabs. Material and methods. Pheno- and genotypic markers of the pathogenic potential of ESKAPE isolates were analyzed: Enterococcus faecalis (n=93), Staphylococcus aureus (n=177), Klebsiella pneumoniae (n=7), Acinetobacter baumannii (n=32), Pseudomonas aeruginosa (n=45), Enterobacterales (Proteus mirabilis, n=26). Microorganisms were isolated from the wound swabs of patients with acute and chronic wounds, who were admitted to the burn department of the Gomel City Clinical Hospital No. 1 for specialized medical care during the period 2012-2020. Integumentary tissue defects were represented by post-traumatic wounds (mechanical trauma, thermal burns), postnecrotic wounds (after purulent-inflammatory diseases of the skin and underlying tissues), trophic ulcers (on the stumps of the lower extremities after prolonged wearing of the prosthesis; neurotrophic ulcers after mechanical trauma to peripheral nerves); pressure ulcers stage III after prolonged tissue compression. When describing the isolates, the duration of the wounds and the presence of clinical signs of infectious inflammation were taken into account. Results. The relationship between the clinical state of the wound (no signs of inflammation, critical colonization, infection) and the bioprofile of the isolate obtained from the wound swabs was determined. Potentially pathogenic S. aureus, possessing colonization, invasive and cytotoxic properties, was found in wounds with a minimum duration of up to 4 days, but the absence of clinical manifestations of infection suggested contamination. Biofilm formation, persistent properties, genetic markers of pathogenicity in S. aureus and E. faecalis in combination with pathological changes in fine-grained granulations in the wound indicated colonization. The inflammatory status of the wounds (critical colonization and infection according to NERDS&STONEES criteria) from which P. aeruginosa and A. baumannii were isolated, the presence of genetic virulence markers, and antibiotic resistance indicated the clinical significance of these isolates as etiological agents of the infectious process. P. mirabilis isolated from critically colonized and infected wounds did not have the full range of virulence markers in all cases, especially in associations. K. pneumoniae was isolated only from the wounds showing signs of inflammation and demonstrated various combinations of genetic determinants of virulence, variability in capsular polysaccharide overproduction and biofilm formation. Conclusion. An algorithm has been developed for interpreting the results of microbiological culture of wound swabs with the use of pheno- and genotypic markers, which are recommended for determining the leading pathogen that colonizes the wound and disrupts the healing process. The algorithm allows assessing the etiological significance of mixed cultures isolated from critically colonized and infected wounds, which will determine the further tactics of treating patients.
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Oladunjoye, Iyiola Olatunji, Yusuf Amuda Tajudeen, Habeebullah Jayeola Oladipo, and Mona Said El-Sherbini. "Planetary Health and Traditional Medicine: A Potential Synergistic Approach to Tackle Antimicrobial Resistance." Challenges 13, no. 1 (June 1, 2022): 24. http://dx.doi.org/10.3390/challe13010024.
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Antimicrobials are compounds that impede the activities of bacteria, viruses, parasites, or fungi. Continuous antimicrobial overuse, misuse, and improper use for human, animal, and agricultural purposes are raising concerns about antibiotic residue pollution in the environment, and antibiotic resistance genes (ARGs). Because antimicrobial-resistant diseases are linked to human–-microbial ecosystems, environmental pollution from antibiotic residue and ARGs alters the makeup and diversity of human gut microbiota, putting resistance under selection pressure. This perspective proposes that antibiotic-induced microbiome depletion is linked to environmental quality and has repercussions for human health via the gut microbiome’s sensitive ecosystem. This has stimulated new global efforts and multidisciplinary, integrative approaches to addressing Antimicrobial Resistance (AMR) awareness in communities. Several academic papers published in recent years have shown that medicinal plant extracts are effective against diseases on WHO’s pathogen priority lists (PPL), such as the ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species). Traditional medicine, with its knowledge of medicinal plants, promises to be a valuable source of next-generation powerful antimicrobials. Examples include the recent discovery of Artemisinin, a highly active antimalarial drug derived from Artemisia annua, and the discovery of Taxol, an active chemotherapeutic drug derived from the bark of the Pacific yew, Taxus brevifolia. The connections between small and large ecosystems’ vitality, biodiversity protection, and human health have been acknowledged by Planetary Health principles. To address these intertwined concerns, a Planetary Health and Traditional Medicine approach can be adopted, and antimicrobial resistance can be addressed by expanding the screening of medicinal plants for bioactive compounds.
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Tyumentseva, Marina, Yulia Mikhaylova, Anna Prelovskaya, Konstantin Karbyshev, Aleksandr Tyumentsev, Lyudmila Petrova, Anna Mironova, Mikhail Zamyatin, Andrey Shelenkov, and Vasiliy Akimkin. "CRISPR Element Patterns vs. Pathoadaptability of Clinical Pseudomonas aeruginosa Isolates from a Medical Center in Moscow, Russia." Antibiotics 10, no. 11 (October 26, 2021): 1301. http://dx.doi.org/10.3390/antibiotics10111301.
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Pseudomonas aeruginosa is a member of the ESKAPE opportunistic pathogen group, which includes six species of the most dangerous microbes. This pathogen is characterized by the rapid acquisition of antimicrobial resistance, thus causing major healthcare concerns. This study presents a comprehensive analysis of clinical P. aeruginosa isolates based on whole-genome sequencing data. The isolate collection studied was characterized by a variety of clonal lineages with a domination of high-risk epidemic clones and different CRISPR/Cas element patterns. This is the first report on the coexistence of two and even three different types of CRISPR/Cas systems simultaneously in Russian clinical strains of P. aeruginosa. The data include molecular typing and genotypic antibiotic resistance determination, as well as the phylogenetic analysis of the full-length cas gene and anti-CRISPR genes sequences, predicted prophage sequences, and conducted a detailed CRISPR array analysis. The differences between the isolates carrying different types and quantities of CRISPR/Cas systems were investigated. The pattern of virulence factors in P. aeruginosa isolates lacking putative CRISPR/Cas systems significantly differed from that of samples with single or multiple putative CRISPR/Cas systems. We found significant correlations between the numbers of prophage sequences, antibiotic resistance genes, and virulence genes in P. aeruginosa isolates with different patterns of CRISPR/Cas-elements. We believe that the data presented will contribute to further investigations in the field of bacterial pathoadaptability, including antimicrobial resistance and the role of CRISPR/Cas systems in the plasticity of the P. aeruginosa genome.
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Miernikiewicz, Paulina, Jakub Barylski, Aleksandra Wilczak, Anna Dragoš, Izabela Rybicka, Sophia Bałdysz, Aleksander Szymczak, et al. "New Phage-Derived Antibacterial Enzyme PolaR Targeting Rothia spp." Cells 12, no. 15 (August 4, 2023): 1997. http://dx.doi.org/10.3390/cells12151997.
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Rothia is an opportunistic pathogen, particularly life-threatening for the immunocompromised. It is associated with pneumonia, endocarditis, peritonitis and many other serious infections, including septicemia. Of note, Rothia mucilaginousa produces metabolites that support and increase overgrowth of Pseudomonas aeruginosa, one of the ESKAPE bacteria. Endolysins are considered as antibacterial enzymes derived from bacteriophages that selectively and efficiently kill susceptible bacteria without harming human cells or the normal microbiome. Here, we applied a computational analysis of metagenomic sequencing data of the gastric mucosa phageome extracted from human patients’ stomach biopsies. A selected candidate anti-Rothia sequence was produced in an expression system, purified and confirmed as a Rothia mucilaginosa- and Rothia dentocariosa-specific endolysin PolaR, able to destroy bacterial cells even when aggregated, as in a biofilm. PolaR had no cytotoxic or antiproliferative effects on mammalian cells. PolaR is the first described endolysin selectively targeting Rothia species, with a high potential to combat infections caused by Rothia mucilaginosa and Rothia dentocariosa, and possibly other bacterial groups. PolaR is the first antibacterial enzyme selected from the gastric mucosa phageome, which underlines the biological complexity and probably underestimated biological role of the phageome in the human gastric mucosa.
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Haudiquet, Matthieu, Amandine Buffet, Olaya Rendueles, and Eduardo P. C. Rocha. "Interplay between the cell envelope and mobile genetic elements shapes gene flow in populations of the nosocomial pathogen Klebsiella pneumoniae." PLOS Biology 19, no. 7 (July 6, 2021): e3001276. http://dx.doi.org/10.1371/journal.pbio.3001276.
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Mobile genetic elements (MGEs) drive genetic transfers between bacteria using mechanisms that require a physical interaction with the cellular envelope. In the high-priority multidrug-resistant nosocomial pathogens (ESKAPE), the first point of contact between the cell and virions or conjugative pili is the capsule. While the capsule can be a barrier to MGEs, it also evolves rapidly by horizontal gene transfer (HGT). Here, we aim at understanding this apparent contradiction by studying the covariation between the repertoire of capsule genes and MGEs in approximately 4,000 genomes of Klebsiella pneumoniae (Kpn). We show that capsules drive phage-mediated gene flow between closely related serotypes. Such serotype-specific phage predation also explains the frequent inactivation of capsule genes, observed in more than 3% of the genomes. Inactivation is strongly epistatic, recapitulating the capsule biosynthetic pathway. We show that conjugative plasmids are acquired at higher rates in natural isolates lacking a functional capsular locus and confirmed experimentally this result in capsule mutants. This suggests that capsule inactivation by phage pressure facilitates its subsequent reacquisition by conjugation. Accordingly, capsule reacquisition leaves long recombination tracts around the capsular locus. The loss and regain process rewires gene flow toward other lineages whenever it leads to serotype swaps. Such changes happen preferentially between chemically related serotypes, hinting that the fitness of serotype-swapped strains depends on the host genetic background. These results enlighten the bases of trade-offs between the evolution of virulence and multidrug resistance and caution that some alternatives to antibiotics by selecting for capsule inactivation may facilitate the acquisition of antibiotic resistance genes (ARGs).
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Polishchuk, N. M., D. L. Kyryk, and I. Ye Yurchuk. "Microbiological monitoring as a component of efficient prevention and treatment of purulent-septic infections in an orthopedics and traumatology department." Zaporozhye Medical Journal 23, no. 3 (June 7, 2021): 381–87. http://dx.doi.org/10.14739/2310-1210.2021.3.229667.
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Efficient monitoring of circulating purulent-septic infectious agents in a clinical setting and a study on antibiotic susceptibility of isolated strains of microorganisms allows identifying changes in the pathogen structure and trends in antibiotic resistance development, which helps to determine the tactics of antibacterial therapy and elaborate appropriate measures. The aim of the study. Retrospective analysis of the results of microbiological monitoring of purulent-septic infectious (PSI) agents in the Orthopedics and Traumatology Department (OTD) of the Zaporizhzhia Central Ambulance and Emergency Care Hospital over the period 2017–2020 to determine the main antibacterial drugs for empirical therapy. Materials and methods. We analyzed the bacteriological test results of 664 clinical material samples obtained from OTD patients using bacteriological examination statistical reporting and analytical data of the WHONET 5.6 software. Results. The main PSI pathogens in the OTD were from the ESKAPE group: E. coli, S. aureus, K. pneumoniae, A. baumannii, E. faecalis, P. aeruginosa and S. epidermidis, P. mirabilis, C. amycolatum. Isolates of E. faecalis were sensitive to vancomycin, linezolid, S. aureus – to linezolid, tigecycline, netilmicin, A. baumannii – to tigecycline. All P. aeruginosa strains were resistant to ticarcillin/clavulanate, cefepime, chloramphenicol, imipenem, meropenem, aztreonam, ciprofloxacin. E. coli and K. pneumoniae were resistant to ampicillin, ticarcillin/clavulanate, aztreonam, ceftriaxone, cefepime. The number of isolates sensitive to piperacillin/tazobactam, carbapenems, levofloxacin, gentamicin, amikacin, chloramphenicol ranged from 37 % to 65 %. Conclusions. E. coli, S. aureus, K. pneumoniae, A. baumannii, E. faecalis, P. aeruginosa, S. epidermidis, P. mirabilis, C. amycolatum play an important role in the structure of PSI pathogens in the Orthopedics and Traumatology Department of Zaporizhzhia Central Ambulance and Emergency Care Hospital. The antibiotics of choice as the antibacterial empirical therapy for enterococcal infections are vancomycin, linezolid, for staphylococcal infections – vancomycin, linezolid, tigecycline, netilmicin. PSI pathogens continually evolve developing antibiotic resistance, and it is of particular importance to monitor antibiotic susceptibility of microorganisms within the OTD.
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Mielko, Karolina Anna, Sławomir Jan Jabłoński, Łukasz Pruss, Justyna Milczewska, Dorota Sands, Marcin Łukaszewicz, and Piotr Młynarz. "Metabolomics Comparison of Drug-Resistant and Drug-Susceptible Pseudomonas aeruginosa Strain (Intra- and Extracellular Analysis)." International Journal of Molecular Sciences 22, no. 19 (October 6, 2021): 10820. http://dx.doi.org/10.3390/ijms221910820.
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Pseudomonas aeruginosa is a common human pathogen belonging to the ESKAPE group. The multidrug resistance of bacteria is a considerable problem in treating patients and may lead to increased morbidity and mortality rate. The natural resistance in these organisms is caused by the production of specific enzymes and biofilm formation, while acquired resistance is multifactorial. Precise recognition of potential antibiotic resistance on different molecular levels is essential. Metabolomics tools may aid in the observation of the flux of low molecular weight compounds in biochemical pathways yielding additional information about drug-resistant bacteria. In this study, the metabolisms of two P. aeruginosa strains were compared—antibiotic susceptible vs. resistant. Analysis was performed on both intra- and extracellular metabolites. The 1H NMR method was used together with multivariate and univariate data analysis, additionally analysis of the metabolic pathways with the FELLA package was performed. The results revealed the differences in P. aeruginosa metabolism of drug-resistant and drug-susceptible strains and provided direct molecular information about P. aeruginosa response for different types of antibiotics. The most significant differences were found in the turnover of amino acids. This study can be a valuable source of information to complement research on drug resistance in P. aeruginosa.
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Wintachai, Phitchayapak, Komwit Surachat, Ganyalak Chaimaha, Abdi Wira Septama, and Duncan R. Smith. "Isolation and Characterization of a Phapecoctavirus Infecting Multidrug-Resistant Acinetobacter baumannii in A549 Alveolar Epithelial Cells." Viruses 14, no. 11 (November 19, 2022): 2561. http://dx.doi.org/10.3390/v14112561.
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Multidrug-resistant Acinetobacter baumannii (MDR A. baumannii) is an emerging pathogen in the ESKAPE group. The global burden of antimicrobial resistance has led to renewed interest in alternative antimicrobial treatment strategies, including phage therapy. This study isolated and characterized a phage vB_AbaM_ ABPW7 (vABPW7) specific to MDR A. baumannii. Morphological analysis showed that phage vABPW7 belongs to the Myoviridae family. Genome analysis showed that the phage DNA genome consists of 148,647 bp and that the phage is a member of the Phapecoctavirus genus of the order Caudovirales. A short latent period and a large burst size indicated that phage vABPW7 was a lytic phage that could potentially be used in phage therapy. Phage vABPW7 is a high-stability phage that has high lytic activity. Phage vABPW7 could effectively reduce biofilm formation and remove preformed biofilm. The utility of phage vABPW7 was investigated in a human A549 alveolar epithelial cell culture model. Phage vABPW7 was not cytotoxic to A549 cells, and the phage could significantly reduce planktonic MDR A. baumannii and MDR A. baumannii adhesion on A549 cells without cytotoxicity. This study suggests that phage vABPW7 has the potential to be developed further as a new antimicrobial agent against MDR A. baumannii.
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Купцов, Н. С., М. А. Корниенко, Р. Б. Городничев, Д. И. Данилов, М. В. Малахова, Т. В. Парфенова, Г. И. Макаренко, Е. А. Шитиков, and Е. Н. Ильина. "Эффективность препаратов бактериофагов против патогенов группы ESKAPE." CIRCULATING RNA, no. (3)2020 (May 25, 2020): 19–26. http://dx.doi.org/10.24075/vrgmu.2020.029.
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Ежегодный рост числа случаев выявления бактерий с множественной лекарственной устойчивостью делает актуальной задачу поиска альтернативы применяемым антибиотикам. Такой альтернативой могут быть препараты на основе вирулентных бактериофагов. Целью работы было оценить эффективность коммерческих фаговых препаратов и моноизолятов бактериофагов, выделенных из природных источников, против клинических штаммов Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae и Pseudomonas aeruginosa. Была собрана коллекция из 147 штаммов, типированных методом МЛСТ. Оценку эффективности бактериофагов проводили методом спот-тестирования. Наиболее эффективными оказались препараты против S. aureus («Бактериофаг стафилококковый», 86%), K. pneumoniae («Пиобактериофаг поливалентный очищенный», 87,8%) и P. aeruginosa («Бактериофаг псевдомонас аеругиноза», 87,5%; «Пиобактериофаг комплексный», 79,5–90%; «Пиобактериофаг поливалентный очищенный», 90–92,5%). Для E. faecium эффективность препарата «Интести-бактериофаг» составила лишь 4,2%. При этом эффективность терапевтических препаратов, активных против S. aureus и K. pneumoniae, была выше эффективности отдельных моноизолятов бактериофагов (фаг S. aureus vB_SauP-436-3w — 60%, фаг K. pneumoniae vB_Kp_M_Seu621 — 5,9%). Таким образом, исследуемые препараты обладают высокой активностью против штаммов P. aeruginosa, K. pneumoniae и S. aureus. В свою очередь препаратов, действующих против остальных членов группы ESKAPE-патогенов (Acinetobacter baumannii и Enterobacter cloacae), а также эффективных против E. faecium, не представлено на рынке, что подчеркивает необходимость поиска новых бактериофагов.
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Grabski, Hovakim, Lernik Hunanyan, Susanna Tiratsuyan, and Hrachik Vardapetyan. "Interaction of N-3-oxododecanoyl homoserine lactone with transcriptional regulator LasR of Pseudomonas aeruginosa: Insights from molecular docking and dynamics simulations." F1000Research 8 (March 22, 2019): 324. http://dx.doi.org/10.12688/f1000research.18435.1.
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Background: In 2017, the World Health Organization announced a list of the most dangerous superbugs. Among them is Pseudomonas aeruginosa, an opportunistic human pathogen with high levels of resistance to antibiotics that is listed as one of the ‘ESKAPE’ pathogens, which are the leading cause of nosocomial infections. A major issue is that it mostly affects vulnerable patients such as those suffering from AIDS, cystic fibrosis, cancer and severe burns. P. aeruginosa creates and inhabits surface-associated biofilms which increase resistance to antibiotics and host immune responses and contribute to the ineffectiveness of current antibacterial treatments. It is therefore imperative to find new antibacterial treatment strategies against P. aeruginosa. The LasR protein is a major transcriptional activator of P. aeruginosa and plays a pivotal role in biofilm formation and the activation of many virulence genes, although detailed characteristics of the LasR protein are not currently known. In the present study, we aimed to analyse the molecular properties of the LasR protein as well as its interactions with the signalling molecule N-3-oxododecanoyl homoserine lactone (3OC12-HSL). Methods: We used a combination of molecular docking, molecular dynamics (MD) simulations and machine learning techniques to study the interaction of the LasR protein with the 3OC12-HSL ligand. We assessed conformational changes occurring upon their interaction and analysed the molecular details of their binding. Results: A new possible interaction site for 3OC12-HSL and LasR was found, involving conserved residues from the ligand binding domain (LBD), beta turns in the short linker region (SLR) and the DNA-binding domain (DBD). This interaction is referred to as the LBD-SLR-DBD bridge or ‘the bridge’ interaction. Conclusions: This study may enable future experimental studies to detect the interaction of signalling molecules with “the bridge” of the LasR protein and suggests a potential new interaction site to assist antibacterial drug design.
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Pennone, Vincenzo, Miguel Prieto, Avelino Álvarez-Ordóñez, and José F. Cobo-Diaz. "Antimicrobial Resistance Genes Analysis of Publicly Available Staphylococcus aureus Genomes." Antibiotics 11, no. 11 (November 16, 2022): 1632. http://dx.doi.org/10.3390/antibiotics11111632.
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Staphylococcus aureus is a pathogen that can cause severe illness and express resistance to multiple antimicrobial agents. It is part of the ESKAPE organisms and it has been included by the Centers for Disease Control and Prevention (CDC) of USA in the list of serious threats to humans. Many antimicrobial mechanisms have been identified, and, in particular, antimicrobial resistance genes (ARGs) can be determined by whole genome sequencing. Mobile genetic elements (MGEs) can determine the spread of these ARGs between strains and species and can be identified with bioinformatic analyses. The scope of this work was to analyse publicly available genomes of S. aureus to characterise the occurrence of ARGs present in chromosomes and plasmids in relation to their geographical distribution, isolation sources, clonal complexes, and changes over time. The results showed that from a total of 29,679 S. aureus genomes, 24,765 chromosomes containing 73 different ARGs, and 21,006 plasmidic contigs containing 47 different ARGs were identified. The most abundant ARG in chromosomes was mecA (84%), while blaZ was the most abundant in plasmidic contigs (30%), although it was also abundant in chromosomes (42%). A total of 13 clonal complexes were assigned and differences in ARGs and CC distribution were highlighted among continents. Temporal changes during the past 20 years (from 2001 to 2020) showed that, in plasmids, MRSA and macrolide resistance occurrence decreased, while the occurrence of ARGs associated with aminoglycosides resistance increased. Despite the lack of metadata information in around half of the genomes analysed, the results obtained enable an in-depth analysis of the distribution of ARGs and MGEs throughout different categories to be undertaken through the design and implementation of a relatively simple pipeline, which can be also applied in future works with other pathogens, for surveillance and screening purposes.
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Kyriakidis, Ioannis, Eleni Vasileiou, Zoi Dorothea Pana, and Athanasios Tragiannidis. "Acinetobacter baumannii Antibiotic Resistance Mechanisms." Pathogens 10, no. 3 (March 19, 2021): 373. http://dx.doi.org/10.3390/pathogens10030373.
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Acinetobacter baumannii is a Gram-negative ESKAPE microorganism that poses a threat to public health by causing severe and invasive (mostly nosocomial) infections linked with high mortality rates. During the last years, this pathogen displayed multidrug resistance (MDR), mainly due to extensive antibiotic abuse and poor stewardship. MDR isolates are associated with medical history of long hospitalization stays, presence of catheters, and mechanical ventilation, while immunocompromised and severely ill hosts predispose to invasive infections. Next-generation sequencing techniques have revolutionized diagnosis of severe A. baumannii infections, contributing to timely diagnosis and personalized therapeutic regimens according to the identification of the respective resistance genes. The aim of this review is to describe in detail all current knowledge on the genetic background of A. baumannii resistance mechanisms in humans as regards beta-lactams (penicillins, cephalosporins, carbapenems, monobactams, and beta-lactamase inhibitors), aminoglycosides, tetracyclines, fluoroquinolones, macrolides, lincosamides, streptogramin antibiotics, polymyxins, and others (amphenicols, oxazolidinones, rifamycins, fosfomycin, diaminopyrimidines, sulfonamides, glycopeptide, and lipopeptide antibiotics). Mechanisms of antimicrobial resistance refer mainly to regulation of antibiotic transportation through bacterial membranes, alteration of the antibiotic target site, and enzymatic modifications resulting in antibiotic neutralization. Virulence factors that may affect antibiotic susceptibility profiles and confer drug resistance are also being discussed. Reports from cases of A. baumannii coinfection with SARS-CoV-2 during the COVID-19 pandemic in terms of resistance profiles and MDR genes have been investigated.
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Hennessen, Fabienne, Marcus Miethke, Nestor Zaburannyi, Maria Loose, Tadeja Lukežič, Steffen Bernecker, Stephan Hüttel, et al. "Amidochelocardin Overcomes Resistance Mechanisms Exerted on Tetracyclines and Natural Chelocardin." Antibiotics 9, no. 9 (September 18, 2020): 619. http://dx.doi.org/10.3390/antibiotics9090619.
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The reassessment of known but neglected natural compounds is a vital strategy for providing novel lead structures urgently needed to overcome antimicrobial resistance. Scaffolds with resistance-breaking properties represent the most promising candidates for a successful translation into future therapeutics. Our study focuses on chelocardin, a member of the atypical tetracyclines, and its bioengineered derivative amidochelocardin, both showing broad-spectrum antibacterial activity within the ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) panel. Further lead development of chelocardins requires extensive biological and chemical profiling to achieve favorable pharmaceutical properties and efficacy. This study shows that both molecules possess resistance-breaking properties enabling the escape from most common tetracycline resistance mechanisms. Further, we show that these compounds are potent candidates for treatment of urinary tract infections due to their in vitro activity against a large panel of multidrug-resistant uropathogenic clinical isolates. In addition, the mechanism of resistance to natural chelocardin was identified as relying on efflux processes, both in the chelocardin producer Amycolatopsis sulphurea and in the pathogen Klebsiella pneumoniae. Resistance development in Klebsiella led primarily to mutations in ramR, causing increased expression of the acrAB-tolC efflux pump. Most importantly, amidochelocardin overcomes this resistance mechanism, revealing not only the improved activity profile but also superior resistance-breaking properties of this novel antibacterial compound.
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Yin, Supeng, Guangtao Huang, Yulong Zhang, Bei Jiang, Zichen Yang, Zhiwei Dong, Bo You, et al. "Phage Abp1 Rescues Human Cells and Mice from Infection by Pan-Drug Resistant Acinetobacter Baumannii." Cellular Physiology and Biochemistry 44, no. 6 (2017): 2337–45. http://dx.doi.org/10.1159/000486117.
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Background/Aims: As an “ESKAPE” pathogen, Acinetobacter baumannii is one of the leading causes of drug-resistant infections in humans. Phage therapy may be a useful strategy in treating infections caused by drug-resistant A. baumannii. Among 21 phage strains that were isolated and described earlier, we investigated the therapeutic efficacy of Abp1 because of its relatively wide host range. Methods: Phage stability assays were used to evaluate thermal and pH stability of Abp1. Abp1 was co-cultured with A. baumannii (AB1) over a range of multiplicities of infection to determine its bactericidal efficacy. HeLa or THP-1 cells were used in the cytotoxicity and protection assays. Finally, the therapeutic effects of Abp1 on local and systemic A. baumannii infection in mice were determined. Results: We found that Abp1 exhibits high thermal and pH stability and has a low frequency of lysogeny. Bacteriophage resistance also occurs at a very low frequency (3.51±0.46×10-8), and Abp1 can lyse almost all host cells at a MOI as low as 0.1. Abp1 has no detectable cytotoxicity to HeLa or THP-1 cells as determined by LDH release assay. Abp1 can rescue HeLa cells from A. baumannii infection, even if introduced 2 hours post infection. In both local and systemic A. baumannii infection mouse models, Abp1 treatment exhibits good therapeutic effects. Conclusion: Abp1 is an excellent candidate for phage therapy against drug-resistant A. baumannii infections.
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Tawre, Madhumita S., Ekta E. Kamble, Shital N. Kumkar, Mansura S. Mulani, and Karishma R. Pardesi. "Antibiofilm and antipersister activity of acetic acid against extensively drug resistant Pseudomonas aeruginosa PAW1." PLOS ONE 16, no. 2 (February 2, 2021): e0246020. http://dx.doi.org/10.1371/journal.pone.0246020.
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Pseudomonas aeruginosa is an ESKAPE pathogen associated with difficult-to-treat burn wound and surgical-site infections. This study aimed to characterise an extensively drug resistant (XDR) P. aeruginosa isolate (designated PAW1) and to investigate the antibiofilm and antipersister effect of acetic acid on PAW1. PAW1 was identified using biotypic (VITEK) and genotypic (16S rDNA) analysis. Minimum inhibitory concentration (MIC) and disc susceptibility testing showed high level resistance against all antibiotics from classes including beta lactams, cephems, carbapenems and fluoroquinolones. It was therefore identified as extensively drug resistant (XDR), showing resistance to all antibiotics except for, aminoglycoside (gentamicin and netilmicin) and lipopeptides (polymyxin B). Time kill assays showed antibiotic tolerant, persister cell formation in presence of 100X MICs of gentamicin and polymyxin B. Other virulence traits such as ability to produce lipase, protease, haemolysin, and siderophores and to form biofilms were additional factors which may contribute to its pathogenicity. PAW1 showed promising susceptibility against acetic acid with MIC and minimum biofilm inhibitory concentration of 0.156% (v/v). Percent viability of PAW1 was dependent on dose and treatment time of acetic acid. 0.625% acetic acid treatment of 5 minutes was effective in killing >90% planktonic cells showing lesser toxicity to L929 cells (IC50 = 0.625%). Biofilm disruption caused due to acetic acid was also dose dependent, showing 40.57% disruption after treatment with 0.625% acetic acid for 5 minutes. FESEM imaging and live dead staining of planktonic and biofilm forms of PAW1 confirmed that acetic acid treatment caused 19.04% of cell shrinkage and disruption of extracellular matrix resulting in killing of cells. Antipersister activity of acetic acid was demonstrated by showing complete killing of PAW1 at 4X MIC. Overall, this study characterised an XDR isolate P. aeruginosa showing resistance and tolerance to various antibiotics. Antipersister and antibiofilm effect of acetic acid demonstrates the importance of forgotten topical agents as an effective strategy to treat XDR pathogens.
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Markulin, Georgiy-Julian, Denys Yurkin, Ivanna Shchigel, Liudmyla Levchenko, and Andriy Gorlach. "TAXONOMIC STRUCTURE OF PANCREATIC INFECTIOUS AGENTS IN PATIENTS WITH ACUTE NECROTIC PANCREATITIS." Ukrainian Scientific Medical Youth Journal 111, no. 3 (September 9, 2019): 29–39. http://dx.doi.org/10.32345/usmyj.3(111).2019.29-39.
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The article describes the change in the level of antimicrobial resistance of infectious agents of acute infected necrotizing pancreatitis in patients in the dynamics of the disease and the treatment, classified the data according to the sensitivity of microorganisms. The main purpose of the prospective cohort study is to determine the taxonomic structure of pathogens of pancreatic infection in patients with acute necrotizing pancreatitis in the dynamics The relevance of the study of this pathology is the importance of the phenomenon of increasing the level of antibiotic resistance during long-term antibiotic therapy, which is shown to patients with pancreatic infection. The methodology of the study consisted of three-stage bacteriological monitoring and subsequent qualitative and quantitative evaluation of microbial agents and antibiotic resistance characteristics according to the stratified classification of the European Center for Disease Control ( Magiorakos et al., 2012): the taxonomic structure of pancreatic pathogens in 123 microbial isolates identified during the study was evaluated using antibioticogram results. The duration of the study was the entire duration of the diagnosed infectious process and averaged 33.4 days. The object of the study was selected microbial isolates, which were isolated in the above terms from the biological material of patients: aspirate parapancreatic fluid clusters in the initial stage, removed pancreatic sequesters in the second stage, and isolation from the drainage of the bursa omentalis and retroperitoneum in the third stage. The study empirically confirms and theoretically proves that the qualitative component of microbial pathogens of acute infected necrotic pancreatitis is characterized by time dependence: the level of classified resistance is higher in the third stage of the study compared with the obtained characteristics of the microorganisms in the first stage and, accordingly, in the second stage of the study; a consistent bacteriological characteristic indicates a transition from mono- to mixed infection (р< 0,001) with the inclusion of all members of the 'ESKAPE'-group in the second stage and the predominance of the gram-negative flora at each stage. The fungal component of the microorganisms is represented by the sole pathogen since the second stage of the study in the group with bacteria only. The results of the study may be useful in predicting the success of antibiotic therapy at different stages of the disease and the expected bacteriological characteristics in successive bacteriological crops of biological material of patients during the acute infected necrotizing pancreatitis.
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Saha, Mousumi, and Agniswar Sarkar. "Review on Multiple Facets of Drug Resistance: A Rising Challenge in the 21st Century." Journal of Xenobiotics 11, no. 4 (December 13, 2021): 197–214. http://dx.doi.org/10.3390/jox11040013.
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With the advancements of science, antibiotics have emerged as an amazing gift to the human and animal healthcare sectors for the treatment of bacterial infections and other diseases. However, the evolution of new bacterial strains, along with excessive use and reckless consumption of antibiotics have led to the unfolding of antibiotic resistances to an excessive level. Multidrug resistance is a potential threat worldwide, and is escalating at an extremely high rate. Information related to drug resistance, and its regulation and control are still very little. To interpret the onset of antibiotic resistances, investigation on molecular analysis of resistance genes, their distribution and mechanisms are urgently required. Fine-tuned research and resistance profile regarding ESKAPE pathogen is also necessary along with other multidrug resistant bacteria. In the present scenario, the interaction of bacterial infections with SARS-CoV-2 is also crucial. Tracking and in-silico analysis of various resistance mechanisms or gene/s are crucial for overcoming the problem, and thus, the maintenance of relevant databases and wise use of antibiotics should be promoted. Creating awareness of this critical situation among individuals at every level is important to strengthen the fight against this fast-growing calamity. The review aimed to provide detailed information on antibiotic resistance, its regulatory molecular mechanisms responsible for the resistance, and other relevant information. In this article, we tried to focus on the correlation between antimicrobial resistance and the COVID-19 pandemic. This study will help in developing new interventions, potential approaches, and strategies to handle the complexity of antibiotic resistance and prevent the incidences of life-threatening infections.
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Masoud, Salim S., Anna Kovacevich, Raidah Gangji, Helmut Nyawale, Mary Nyange, and Albert Ntukula. "Extent and Resistance Patterns of ESKAPE Pathogens Isolated in Pus Swabs from Hospitalized Patients." Canadian Journal of Infectious Diseases and Medical Microbiology 2022 (October 31, 2022): 1–7. http://dx.doi.org/10.1155/2022/3511306.
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Antimicrobial resistance has persisted as a global threat with increasing associated numbers of morbidity and mortality. ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.) were termed by the Infectious Diseases Society of America as a group of bacteria with rapid antibiotic resistance development. The aim of the study was to describe the extent and resistance patterns of ESKAPE pathogens isolated in pus swabs from patients admitted at Muhimbili National Hospital, Tanzania. A retrospective cross-sectional study was performed in August 2019. A total of 75 admitted patients with open wounds and surgical site infections were recruited. Files were analyzed to collect microbiology laboratory data and relevant patient data. A total of 76 clinically significant bacteria were isolated of which 52 bacteria were categorized as ESKAPE pathogens. The most common bacteria isolated were 25% (n = 19/76) P. aeruginosa and 17.1% S. aureus. A high level of antibiotic resistance was shown in all ESKAPE and non-ESKAPE pathogens. The Gram-negative bacteria of ESKAPE pathogens were further analyzed comparing 3rd generation cephalosporin and carbapenems resistance patterns. A. baumannii showed the highest resistance towards 3rd generation cephalosporin and carbapenems. In addition, P. aeruginosa showed high resistance to 3rd generation cephalosporins with 89.5% resistance, with E. coli showing high resistance to carbapenems with 50.0% resistance. The burden of ESKAPE pathogens is high in pus swabs obtained from admitted patients at Muhimbili National Hospital. The results showed high antibiotic resistance within ESKAPE and non-ESKAPE pathogens including the “last resort” antibiotics: 3rd generation cephalosporin and carbapenems.
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Li, Zhaoyinqian, Jingling Xie, Jiaxin Yang, Siyi Liu, Zixuan Ding, Jingchen Hao, Yinhuan Ding, Zhangrui Zeng, and Jinbo Liu. "Pathogenic Characteristics and Risk Factors for ESKAPE Pathogens Infection in Burn Patients." Infection and Drug Resistance Volume 14 (November 2021): 4727–38. http://dx.doi.org/10.2147/idr.s338627.
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