Assessment of three antibiotic combination regimens against Gram-negative bacteria causing neonatal sepsis in low- and middle-income countries. - Related Documents




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226401.0000Assessment of three antibiotic combination regimens against Gram-negative bacteria causing neonatal sepsis in low- and middle-income countries. Gram-negative bacteria (GNB) are a major cause of neonatal sepsis in low- and middle-income countries (LMICs). Although the World Health Organization (WHO) reports that over 80% of these sepsis deaths could be prevented through improved treatment, the efficacy of the currently recommended first- and second-line treatment regimens for this condition is increasingly affected by high rates of drug resistance. Here we assess three well known antibiotics, fosfomycin, flomoxef and amikacin, in combination as potential antibiotic treatment regimens by investigating the drug resistance and genetic profiles of commonly isolated GNB causing neonatal sepsis in LMICs. The five most prevalent bacterial isolates in the NeoOBS study (NCT03721302) are Klebsiella pneumoniae, Acinetobacter baumannii, E. coli, Serratia marcescens and Enterobacter cloacae complex. Among these isolates, high levels of ESBL and carbapenemase encoding genes are detected along with resistance to ampicillin, gentamicin and cefotaxime, the current WHO recommended empiric regimens. The three new combinations show excellent in vitro activity against ESBL-producing K. pneumoniae and E. coli isolates. Our data should further inform and support the clinical evaluation of these three antibiotic combinations for the treatment of neonatal sepsis in areas with high rates of multidrug-resistant Gram-negative bacteria.202438729951
155110.9998Mechanisms of Resistance in Gram-Negative Urinary Pathogens: From Country-Specific Molecular Insights to Global Clinical Relevance. Urinary tract infections (UTIs) are the most frequent hospital infections and among the most commonly observed community acquired infections. Alongside their clinical importance, they are notorious because the pathogens that cause them are prone to acquiring various resistance determinants, including extended-spectrum beta-lactamases (ESBL); plasmid-encoded AmpC β-lactamases (p-AmpC); carbapenemases belonging to class A, B, and D; qnr genes encoding reduced susceptibility to fluoroquinolones; as well as genes encoding enzymes that hydrolyse aminoglycosides. In Escherichia coli and Klebsiella pneumoniae, the dominant resistance mechanisms are ESBLs belonging to the CTX-M, TEM, and SHV families; p-AmpC; and (more recently) carbapenemases belonging to classes A, B, and D. Urinary Pseudomonas aeruginosa isolates harbour metallo-beta-lactamases (MBLs) and ESBLs belonging to PER and GES families, while carbapenemases of class D are found in urinary Acinetobacter baumannii isolates. The identification of resistance mechanisms in routine diagnostic practice is primarily based on phenotypic tests for the detection of beta-lactamases, such as the double-disk synergy test or Hodge test, while polymerase chain reaction (PCR) for the detection of resistance genes is mostly pursued in reference laboratories for research purposes. As the emergence of drug-resistant bacterial strains poses serious challenges in the management of UTIs, this review aimed to appraise mechanisms of resistance in relevant Gram-negative urinary pathogens, to provide a detailed map of resistance determinants in Croatia and the world, and to discuss the implications of these resistance traits on diagnostic approaches. We summarized a sundry of different resistance mechanisms among urinary isolates and showed how their prevalence highly depends on the local epidemiological context, highlighting the need for tailored interventions in the field of antimicrobial stewardship.202133925181
570020.9998Gram-negative bacterial colonization in the gut: Isolation, characterization, and identification of resistance mechanisms. BACKGROUND: The gut microbiome is made up of a diverse range of bacteria, especially gram-negative bacteria, and is crucial for human health and illness. There is a great deal of interest in the dynamic interactions between gram-negative bacteria and their host environment, especially considering antibiotic resistance. This work aims to isolate gram-negative bacteria that exist in the gut, identify their species, and use resistance-associated gene analysis to define their resistance mechanisms. METHODS: Samples were collected from all patients who had a stool culture at a tertiary care center in Lebanon. Each type of bacteria that was identified from the stool samples was subjected to critical evaluations, and all discovered strains underwent antimicrobial susceptibility testing. Polymerase chain reaction was used to profile the genes for Carbapenem-resistant Enterobacteriaceae (CRE), Extended-spectrum beta-lactamase (ESBL), and that of Pseudomonas aeruginosa strains. RESULTS: Escherichia coli, Klebsiella species, and Pseudomonas aeruginosa turned out to be the predominant microbiota members. Escherichia coli strains had a high frequency of extended-spectrum beta-lactamase genes, with the most discovered gene being bla CTX-M. Additionally, a considerable percentage of isolates had carbapenemase-resistant Enterobacteriaceae genes, suggesting the rise of multidrug-resistant strains. Multidrug resistance genes, such as bla mexR, bla mexB, and bla mexA, were found in strains of Pseudomonas aeruginosa, highlighting the possible difficulties in treating infections brought on by these bacteria. CONCLUSION: The findings highlight the critical importance of effective surveillance and response measures to maintain the effectiveness of antibiotics considering the introduction of multidrug resistance genes in Pseudomonas aeruginosa and ESBL and CRE genes in Escherichia coli.202439216133
226530.9998Genotypic Patterns of Multidrug-Resistant Acinetobacter baumannii: A Systematic Review. Acinetobacter baumannii (A. baumannii) is one of the most common bacteria in nosocomial infections. Inappropriate usage of antibiotics has led to expanding emergence resistance to A. baumannii as a multidrug-resistant (MDR) strain. Empirical antibiotic therapy is necessary to evaluate the resistant gene pattern of MDR A. baumannii. For this purpose, the present study evaluated the resistance genes pattern of MDR A. baumannii collected from hospitalized patients using a genotypic diagnostic technique. To find evidence related to the study objectives, databases were searched such as Google Scholar, Web of Science, Science Direct, PubMed, and Scopus from 2000 to 2022, with specified keywords in the title and text of the articles. Articles were included based on inclusion and exclusion criteria. The mentioned database displayed 284 articles. After screening, 65 eligible articles were included. The results showed that various b-lactamases genes, aminoglycoside-modifying enzymes (AMEs) genes, and pump-expressing genes are resistance gene patterns in MDR A. baumannii isolates. MDR A. baumannii has significantly become resistant to b-lactams, carbapenems, and aminoglycosides.202337200758
231540.9998The Profile of Bacterial Infections in a Burn Unit during and after the COVID-19 Pandemic Period. Infections represent a major complication for burn-injured patients. The aim of this study was to highlight the changes in the incidence and antimicrobial resistance of bacterial strains isolated from burn patients, at the end of the COVID-19 pandemic, in relation to the antibiotics used during the pandemic. A comparative analysis of the demographic data and the microorganisms identified in the clinical samples of two groups of burn patients admitted to a university hospital in Romania was carried out. The first group consisted of 48 patients and the second of 69 patients, hospitalized in January-August 2020 and 2023, respectively. The bacterial species with the highest incidence were S. aureus, A. baumannii, Pseudomonas spp. The significant changes between 2023 and 2020 are reflected in the increase in the frequency of non-fermentative Gram-negative bacteria, especially S. maltophilia, and the increase in antimicrobial resistance of Pseudomonas and Klebsiella spp. Klebsiella spp. did not change in frequency (7%), but there was a significant increase in the incidence of K. pneumoniae strains with pan-drug resistant behaviour to antibiotics (40%), including colistin. The phenomenon can be explained by the selection of specimens carrying multiple resistance genes, as a result of antibiotic treatment during the COVID-19 period. The post-pandemic antimicrobial resistance detected in burn patients indicates the need for permanent surveillance of the resistance trends, primarily due to the limited therapeutic options available for these patients.202439334997
567950.9997Surveillance of antibiotic resistance. Resistance among bacteria is on the rise, both in the hospital and in the community. Surveillance is needed for guided empiric treatment and to detect new resistance mechanisms at an early stage. Surveillance shows a wide variation in resistance among hospitals and countries. Especially methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci are uncommon in north western European countries but frequently observed otherwise elsewhere. Among Gram-negative bacteria regional differences are less obvious. Many hospitals all over the world suffer from recurrent outbreaks by Enterobacteriaceae that produce extended spectrum beta-lactamases, Acinetobacter, etc. Because of the evolving pattern of resistance, surveillance should be done at regular intervals in all hospitals and in the community.199917035793
568360.9997Association between antimicrobial resistance among Enterobacteriaceae and burden of environmental bacteria in hospital acquired infections: analysis of clinical studies and national reports. BACKGROUND: WHO has named three groups of gram-negative bacteria "our critical antimicrobial resistance-related problems globally". It is thus a priority to unveil any important covariation of variables behind this three-headed epidemic, which has gained alarming proportions in Low Income Countries, and spreads rapidly. Environmental bacteria including Acinetobacter spp. are common nosocomial pathogens in institutions that have high rates of antimicrobial resistance among other groups of gram-negative bacteria. METHODS: Based on two different data sources, we calculated the correlation coefficient (Pearson's r) between pathogenic burden of Acinetobacter spp. and antimicrobial resistance among Enterobacteriaceae in European and African nosocomial cohorts. CLINICAL REPORTS: Database search for studies on nosocomial sepsis in Europe and Africa was followed by a PRISMA-guided selection process. NATIONAL REPORTS: Data from Point prevalence survey of healthcare-associated infections published by European Centre for Disease Prevention and Control were used to study the correlation between prevalence of Acinetobacter spp. and antimicrobial resistance among K. pneumoniae in blood culture isolates. FINDINGS: The two approaches both revealed a strong association between prevalence of Acinetobacter spp. and rates of resistance against 3. generation cephalosporins among Enterobacteriaceae. In the study of clinical reports (13 selected studies included), r was 0.96 (0.80-0.99) when calculated by proportions on log scale. Based on national reports, r was 0.80 (0.56-0.92) for the correlation between resistance rates of K. pneumoniae and proportion of Acinetobacter spp. INTERPRETATION: The critical antimicrobial resistance-related epidemics that concern enteric and environmental gram-negative bacteria are not independent epidemics; they have a common promoting factor, or they are mutually supportive. Further, accumulation of antimicrobial resistance in nosocomial settings depends on the therapeutic environment. Burden of Acinetobacter spp. as defined here is a candidate measure for this dependence.201931372534
251570.9997High-risk Pseudomonas aeruginosa clones harboring β-lactamases: 2024 update. Carbapenem-resistant Pseudomonas aeruginosa is defined by the World Health Organization as a "high priority" in developing new antimicrobials. Indeed, the emergence and spread of multidrug-resistant (MDR) or extensively drug-resistant (XDR) bacteria increase the morbidity and mortality risk of infected patients. Genomic variants of P. aeruginosa that display phenotypes of MDR/XDR have been defined as high-risk global clones. In this mini-review, we describe some international high-risk clones that carry β-lactamase genes that can produce chronic colonization and increase infected patients' morbidity and mortality rates.202539850428
226680.9997Bloodstream infections in intensive care unit patients: distribution and antibiotic resistance of bacteria. Bloodstream infections (BSIs) are among the leading infections in critically ill patients. The case-fatality rate associated with BSIs in patients admitted to intensive care units (ICUs) reaches 35%-50%. The emergence and diffusion of bacteria with resistance to antibiotics is a global health problem. Multidrug-resistant bacteria were detected in 50.7% of patients with BSIs in a recently published international observational study, with methicillin resistance detected in 48% of Staphylococcus aureus strains, carbapenem resistance detected in 69% of Acinetobacter spp., in 38% of Klebsiella pneumoniae, and in 37% of Pseudomonas spp. Prior hospitalization and antibiotic exposure have been identified as risk factors for infections caused by resistant bacteria in different studies. Patients with BSIs caused by resistant strains showed an increased risk of mortality, which may be explained by a higher incidence of inappropriate empirical therapy in different studies. The molecular genetic characterization of resistant bacteria allows the understanding of the most common mechanisms underlying their resistance and the adoption of surveillance measures. Knowledge of epidemiology, risk factors, mechanisms of resistance, and outcomes of BSIs caused by resistant bacteria may have a major influence on global management of ICU patients. The aim of this review is to provide the clinician an update on BSIs caused by resistant bacteria in ICU patients.201526300651
154790.9997The KPC type beta-lactamases: new enzymes that confer resistance to carbapenems in Gram-negative bacilli. Antimicrobial resistance due to the continuous selective pressure from widespread use of antimicrobials in humans, animals and agriculture has been a growing problem for last decades. KPC beta-lactamases hydrolyzed beta-lactams of all classes. Especially, carbapenem antibiotics are hydrolyzed more efficiency than other beta-lactam antibiotics. The KPC enzymes are found most often in Enterobacteriaceae. Recently, these enzymes have been found in isolates of Pseudomonas aeruginosa and Acinetobacter spp. The observations of blaKPC genes isolated from different species in other countries indicate that these genes from common but unknown ancestor may have been mobilized in these areas or that blaKPC-carrying bacteria may have been passively by many vectors. The emergence of carbapenem resistance in Gram-negative bacteria is worrisome because the carbapenem resistance often may be associated with resistance to many beta-lactam and non-beta-lactam antibiotics. Treatment of infections caused by KPC-producing bacteria is extremely difficult because of their multidrug resistance, which results in high mortality rates. Therapeutic options to treat infections caused by multiresistant Gram-negative bacteria producing KPC-carbapenemases could be used polymyxin B or tigecycline.200920430717
1908100.9997Hospital sewage in Brazil: a reservoir of multidrug-resistant carbapenemase-producing Enterobacteriaceae. The One Health concept recognizes that human health is clearly linked to the health of animals and the environment. Infections caused by bacteria resistant to carbapenem antibiotics have become a major challenge in hospitals due to limited therapeutic options and consequent increase in mortality. In this study, we investigated the presence of carbapenem-resistant Enterobacteriaceae in 84 effluent samples (42 from hospital and 42 from non-hospital) from Campo Grande, midwest Brazil. First, sewage samples were inoculated in a selective culture medium. Bacteria with reduced susceptibility to meropenem and ertapenem were then identified and their antimicrobial susceptibility was determined using the Vitek-2 system. The blaKPC genes were detected using PCR and further confirmed by sequencing. Carbapenem-resistant Enterobacteriaceae (CRE) were identified in both hospital (n=32) and non-hospital effluent (n=16), with the most common being Klebsiella pneumoniae and of the Enterobacter cloacae complex species. This is the first study to indicate the presence of the blaKPC-2 gene in carbapenem-resistant Enterobacteriaceae, classified as a critical priority by the WHO, in hospital sewage in this region. The dissemination of carbapenem antibiotic-resistant genes may be associated with clinical pathogens. Under favorable conditions and microbial loads, resistant bacteria and antimicrobial-resistance genes found in hospital sewage can disseminate into the environment, causing health problems. Therefore, sewage treatment regulations should be implemented to minimize the transfer of antimicrobial resistance from hospitals.202438985067
5698110.9997Evolutionary Trajectories toward High-Level β-Lactam/β-Lactamase Inhibitor Resistance in the Presence of Multiple β-Lactamases. β-Lactam antibiotics are the first choice for the treatment of most bacterial infections. However, the increased prevalence of β-lactamases, in particular extended-spectrum β-lactamases, in pathogenic bacteria has severely limited the possibility of using β-lactam treatments. Combining β-lactam antibiotics with β-lactamase inhibitors can restore treatment efficacy by negating the effect of the β-lactamase and has become increasingly important against infections caused by β-lactamase-producing strains. Not surprisingly, bacteria with resistance to even these combinations have been found in patients. Studies on the development of bacterial resistance to β-lactam/β-lactamase inhibitor combinations have focused mainly on the effects of single, chromosomal or plasmid-borne, β-lactamases. However, clinical isolates often carry more than one β-lactamase in addition to multiple other resistance genes. Here, we investigate how the evolutionary trajectories of the development of resistance to three commonly used β-lactam/β-lactamase inhibitor combinations, ampicillin-sulbactam, piperacillin-tazobactam, and ceftazidime-avibactam, were affected by the presence of three common β-lactamases, TEM-1, CTX-M-15, and OXA-1. First-step resistance was due mainly to extensive gene amplifications of one or several of the β-lactamase genes where the amplification pattern directly depended on the respective drug combination. Amplifications also served as a stepping-stone for high-level resistance in combination with additional mutations that reduced drug influx or mutations in the β-lactamase gene bla(CTX-M-15). This illustrates that the evolutionary trajectories of resistance to β-lactam/β-lactamase inhibitor combinations are strongly influenced by the frequent and transient nature of gene amplifications and how the presence of multiple β-lactamases shapes the evolution to higher-level resistance.202235652643
1556120.9997Resistance to Colistin in Klebsiella Pneumoniae: A 4.0 Strain? The global rise of multidrug-resistant gram-negative bacteria represents an increasing threat to patient safety. From the first observation of a carbapenem-resistant gram-negative bacteria a global spread of extended-spectrum beta-lactamases and carbapenemases producing Klebsiella pneumoniae has been observed. Treatment options for multidrug-resistant K. pneumoniae are actually limited to combination therapy with some aminoglycosides, tigecycline and to older antimicrobial agents. Unfortunately, the prevalence of colistin-resistant and tigecycline-resistant K. pneumoniae is increasing globally. Infection due to colistin-resistant K. pneumoniae represents an independent risk factor for mortality. Resistance to colistin in K. pneumoniae may be multifactorial, as it is mediated by chromosomal genes or plasmids. The emergence of transmissible, plasmid-mediated colistin resistance is an alarming finding. The absence of new agents effective against resistant Gram-negative pathogens means that enhanced surveillance, compliance with infection prevention procedures, and antimicrobial stewardship programs will be required to limit the spread of colistin-resistant K. pneumoniae.201728626539
2304130.9997Antimicrobial consumption and resistance in five Gram-negative bacterial species in a hospital from 2003 to 2011. BACKGROUND: The misuse of antimicrobial agents increases drug resistance in bacteria. METHODS: The correlation between antimicrobial agent consumption and related resistance in the Gram-negative bacteria Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Proteus mirabilis was analyzed during the period 2003-2011. RESULTS: Among these five bacteria, overall E. coli and K. pneumoniae were more commonly isolated from bloodstream than the other species. Regarding Enterobacteriaceae, E. coli and K. pneumoniae showed annual increases of resistance to the tested antimicrobial agents; conversely, P. mirabilis exhibited reduced resistance to cefuroxime, ceftriaxone and cefepime. In contrast to the relatively low antimicrobial resistance in P. aeruginosa, A. baumannii revealed high resistance, which was over 85% resistant rate to the tested antimicrobial agents and over 80% carbapenem resistance in 2011. E. coli, K. pneumoniae, and P. mirabilis differed in development of antimicrobial resistance after consumption of the antimicrobial agents. K. pneumoniae developed resistance to all antimicrobial groups, whereas resistance in P. mirabilis was not related to any antimicrobial consumption. P. aeruginosa developed resistance to β-lactam antimicrobials and aminoglycosides, whereas A. baumanii developed resistance to carbapenems after their use. CONCLUSION: The development of antimicrobial resistance was related to antimicrobial agents and bacterial species.201524863496
1572140.9997Phenotypic and Genomic Characterization of AmpC-Producing Klebsiella pneumoniae From Korea. The prevalence of multidrug-resistant gram-negative bacteria has continuously increased over the past few years; bacterial strains producing AmpC β-lactamases and/or extended-spectrum β-lactamases (ESBLs) are of particular concern. We combined high-resolution whole genome sequencing and phenotypic data to elucidate the mechanisms of resistance to cephamycin and β-lactamase in Korean Klebsiella pneumoniae strains, in which no AmpC-encoding genes were detected by PCR. We identified several genes that alone or in combination can potentially explain the resistance phenotype. We showed that different mechanisms could explain the resistance phenotype, emphasizing the limitations of the PCR and the importance of distinguishing closely-related gene variants.201829611388
5021150.9997Beta-lactamases in Enterobacteriaceae infections in children. Multi-drug resistance in Gram negative bacteria, particularly in Enterobacteriaceae, is a major clinical and public health challenge. The main mechanism of resistance in Enterobacteriaceae is linked to the production of beta-lactamase hydrolysing enzymes such as extended spectrum beta-lactamases (ESBL), AmpC beta-lactamases and carbapenemases (Carbapenemase Producing Enterobacteriaceae (CPE)). ESBL and CPE resistance genes are located on plasmids, which can be transmitted between Enterobacteriaceae, facilitating their spread in hospitals and communities. These plasmids usually harbour multiple additional co-resistance genes, including to trimethoprim-sulfamethoxazole, aminoglycosides, and fluoroquinolones, making these infections challenging to treat. Asymptomatic carriage in healthy children as well as community acquired infections are increasingly reported, particularly with ESBL. Therapeutic options are limited and previously little used antimicrobials such as fosfomycin and colistin have been re-introduced in clinical practice. Paediatric experience with these agents is limited hence there is a need to further examine their clinical efficacy, dosage and toxicity in children. Antimicrobial stewardship along with strict infection prevention and control practices need to be adopted widely in order to preserve currently available antimicrobials. The future development of novel agents effective against beta-lactamases producers and their applicability in children is urgently needed to address the challenge of multi-resistant Gram negative infections.201627180312
2303160.9997Patterns of Drug-Resistant Bacteria in a General Hospital, China, 2011-2016. Drug-resistant bacteria has been a threat to public life and property. We described the trends and changes in antibiotic resistance of important pathogens in a general hospital in Zhengzhou, China from 2011 to 2016, to control antimicrobial-resistant bacteria in hospital and provide support to clinicians and decision-making departments. Five dominant bacteria were enrolled based on the data from the general hospital during 6 years. The results of antimicrobial susceptibility testing were interpreted according to Clinical and Laboratory Standards Institute (CLSI). From 2011 to 2016, a total of 19,260 strains of bacteria were isolated, of which Klebsiella pneumoniae, Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Acinetobacter baumannii accounted for 51.98%. The resistance rate of K. pneumoniae and E. coli to carbapenem was less than 15%, but resistance of K. pneumoniae to carbapenems increased with time and resistance of E. coli to meropenem increased. The rate of extended-spectrum beta-lactamase (ESBL) production among K. pneumoniae and E. coli was decreasing. For most antibiotics, the resistance rate of ESBL-positive isolates was higher than that of ESBL-negative isolates, excluding carbapenems and cefoxitin. For S. aureus, the rate of methicillin-resistant S. aureus (MRSA) was stable. Resistance of S. aureus to mostly antibiotics decreased with time. Besides polymyxin B, P. aeruginosa and A. baumannii showed high resistance to other antibiotics. For A. baumannii, the resistance rate to mostly antibiotics was increasing. The bacteria showed high levels of resistance and multiple drug resistance. Continuous surveillance and optimizing the use of antibiotics are essential. Drug-resistant bacteria has been a threat to public life and property. We described the trends and changes in antibiotic resistance of important pathogens in a general hospital in Zhengzhou, China from 2011 to 2016, to control antimicrobial-resistant bacteria in hospital and provide support to clinicians and decision-making departments. Five dominant bacteria were enrolled based on the data from the general hospital during 6 years. The results of antimicrobial susceptibility testing were interpreted according to Clinical and Laboratory Standards Institute (CLSI). From 2011 to 2016, a total of 19,260 strains of bacteria were isolated, of which Klebsiella pneumoniae, Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Acinetobacter baumannii accounted for 51.98%. The resistance rate of K. pneumoniae and E. coli to carbapenem was less than 15%, but resistance of K. pneumoniae to carbapenems increased with time and resistance of E. coli to meropenem increased. The rate of extended-spectrum beta-lactamase (ESBL) production among K. pneumoniae and E. coli was decreasing. For most antibiotics, the resistance rate of ESBL-positive isolates was higher than that of ESBL-negative isolates, excluding carbapenems and cefoxitin. For S. aureus, the rate of methicillin-resistant S. aureus (MRSA) was stable. Resistance of S. aureus to mostly antibiotics decreased with time. Besides polymyxin B, P. aeruginosa and A. baumannii showed high resistance to other antibiotics. For A. baumannii, the resistance rate to mostly antibiotics was increasing. The bacteria showed high levels of resistance and multiple drug resistance. Continuous surveillance and optimizing the use of antibiotics are essential.201931250593
5047170.9997Phenotypic and Genotypic Characterization of Pan-Drug-Resistant Klebsiella pneumoniae Isolated in Qatar. In secondary healthcare, carbapenem-resistant Enterobacterales (CREs), such as those observed in Klebsiella pneumoniae, are a global public health priority with significant clinical outcomes. In this study, we described the clinical, phenotypic, and genotypic characteristics of three pan-drug-resistant (PDR) isolates that demonstrated extended resistance to conventional and novel antimicrobials. All patients had risk factors for the acquisition of multidrug-resistant organisms, while microbiological susceptibility testing showed resistance to all conventional antimicrobials. Advanced susceptibility testing demonstrated resistance to broad agents, such as ceftazidime-avibactam, ceftolozane-tazobactam, and meropenem-vaborbactam. Nevertheless, all isolates were susceptible to cefiderocol, suggested as one of the novel antimicrobials that demonstrated potent in vitro activity against resistant Gram-negative bacteria, including CREs, pointing toward its potential therapeutic role for PDR pathogens. Expanded genomic studies revealed multiple antimicrobial-resistant genes (ARGs), including bla(NMD-5) and bla(OXA) derivative types, as well as a mutated outer membrane porin protein (OmpK37).202438534710
1574180.9997Plethora of Resistance Genes in Carbapenem-Resistant Gram-Negative Bacteria in Greece: No End to a Continuous Genetic Evolution. Carbapenem-resistant Gram-negative bacteria are a public health threat that requires urgent action. The fact that these pathogens commonly also harbor resistance mechanisms for several other antimicrobial classes further reduces patient treatment options. The present study aimed to provide information regarding the multidrug resistance genetic background of carbapenem-resistant Gram-negative bacteria in Central Greece. Strains from a tertiary care hospital, collected during routine practice, were characterized using a DNA microarray-based assay. Various different resistance determinants for carbapenems, other beta-lactams, aminoglycosides, quinolones, trimethoprim, sulfonamides and macrolides were detected among isolates of the same sequence type. Eighteen different multidrug resistance genomic profiles were identified among the twenty-four K. pneumoniae ST258, seven different profiles among the eight K. pneumoniae ST11, four profiles among the six A. baumannii ST409 and two among the three K. oxytoca. This report describes the multidrug resistance genomic background of carbapenem-resistant Gram-negative bacteria from a tertiary care hospital in Central Greece, providing evidence of their continuous genetic evolution.202235056608
5680190.9997Multidrug-Resistant Acinetobacter baumannii Genetic Characterization and Spread in Lithuania in 2014, 2016, and 2018. Bacterial resistance to antimicrobial agents plays an important role in the treatment of bacterial infections in healthcare institutions. The spread of multidrug-resistant bacteria can occur during inter- and intra-hospital transmissions among patients and hospital personnel. For this reason, more studies must be conducted to understand how resistance occurs in bacteria and how it moves between hospitals by comparing data from different years and looking out for any patterns that might emerge. Multidrug-resistant (MDR) Acinetobacter spp. was studied at 14 healthcare institutions in Lithuania during 2014, 2016, and 2018 using samples from human bloodstream infections. In total, 194 isolates were collected and identified using MALDI-TOF and VITEK2 analyzers as Acinetobacter baumannii group bacteria. After that, the isolates were analyzed for the presence of different resistance genes (20 genes were analyzed) and characterized by using the Rep-PCR and MLVA (multiple-locus variable-number tandem repeat analysis) genotyping methods. The results of the study showed the relatedness of the different Acinetobacter spp. isolates and a possible circulation of resistance genes or profiles during the different years of the study. This study provides essential information, such as variability and diversity of resistance genes, genetic profiling, and clustering of isolates, to better understand the antimicrobial resistance patterns of Acinetobacter spp. These results can be used to strengthen the control of multidrug-resistant infections in healthcare institutions and to prevent potential outbreaks of this pathogen in the future.202133669401