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The effectiveness of ß-lactam antibiotics is increasingly threatened by resistant bacteria that harbor hydrolytic ß-lactamase enzymes. Depending on the class of ß-lactamase present, ß-lactam hydrolysis can occur through one of two general molecular mechanisms. Metallo-ß-lactamases (MBLs) require active site Zn2+ ions, whereas serine-ß-lactamases (SBLs) deploy a catalytic serine residue. The result in both cases is drug inactivation via the opening of the ß-lactam warhead of the antibiotic. MBLs confer resistance to most ß-lactams and are non-susceptible to SBL inhibitors, including recently approved diazabicyclooctanes, such as avibactam; consequently, these enzymes represent a growing threat to public health. Aspergillomarasmine A (AMA), a fungal natural product, can rescue the activity of the ß-lactam antibiotic meropenem against MBL-expressing bacterial strains. However, the effectiveness of this ß-lactam/ß-lactamase inhibitor combination against bacteria producing multiple ß-lactamases remains unknown. We systematically investigated the efficacy of AMA/meropenem combination therapy with and without avibactam against 10 Escherichia coli and 10 Klebsiella pneumoniae laboratory strains tandemly expressing single MBL and SBL enzymes. Cell-based assays demonstrated that laboratory strains producing NDM-1 and KPC-2 carbapenemases were resistant to the AMA/meropenem combination but became drug-susceptible upon adding avibactam. We also probed these combinations against 30 clinical isolates expressing multiple ß-lactamases. E. coli, Enterobacter cloacae, and K. pneumoniae clinical isolates were more susceptible to AMA, avibactam, and meropenem than Pseudomonas aeruginosa and Acinetobacter baumannii isolates. Overall, the results demonstrate that a triple combination of AMA/avibactam/meropenem has potential for empirical treatment of infections caused by multiple ß-lactamase-producing bacteria, especially Enterobacterales.

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One of the biggest threats to human well-being and public health is antibiotic resistance. If allowed to spread unchecked, it might become a major health risk and trigger another pandemic. This proves the need to develop antibiotic resistance-related global health solutions that take into consideration microdata from various global locations. Establishing positive social norms, guiding individual and group behavioral habits that support global human health, and ultimately raising public awareness of the need for such action could all have a positive impact. Antibiotic resistance is not just a growing clinical concern but also complicates therapy, making adherence to current guidelines for managing antibiotic resistance extremely difficult. Numerous genetic components have been connected to the development of resistance; some of these components have intricate paths of transfer between microorganisms. Beyond this, the subject of antibiotic resistance is becoming increasingly significant in medical microbiology as new mechanisms underpinning its development are identified. In addition to genetic factors, behaviors such as misdiagnosis, exposure to broad-spectrum antibiotics, and delayed diagnosis contribute to the development of resistance. However, advancements in bioinformatics and DNA sequencing technology have completely transformed the diagnostic sector, enabling real-time identification of the components and causes of antibiotic resistance. This information is crucial for developing effective control and prevention strategies to counter the threat.

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Antimicrobial resistance is a growing global health problem, and it is especially relevant among liver transplant recipients where infections, particularly when caused by microorganisms with a difficult-to-treat profile, are a significant cause of morbidity and mortality. We provide here a complete dissection of the antibiotics active against multidrug-resistant Gram-negative bacteria approved over the last years, focusing on their activity spectrum, toxicity profile and PK/PD properties, including therapeutic drug monitoring, in the setting of liver transplantation. Specifically, the following drugs are presented: ceftolozane/tazobactam, ceftazidime/avibactam, meropenem/vaborbactam, imipenem/relebactam, cefiderocol, and eravacycline. Overall, studies on the safety and optimal employment of these drugs in liver transplant recipients are limited and especially needed. Nevertheless, these pharmaceuticals have undeniably enhanced therapeutic options for infected liver transplant recipients.

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Antimicrobial resistance is regarded as a global threat to public health, animals, and the environment, emerging in response to extensive utilization of antimicrobials. The determinants of antimicrobial resistance are transported to susceptible bacterial populations through genetic recombination or through gene transfer, mediated by bacteriophages, plasmids, transposons, and insertion sequences. To determine the penetration of antimicrobial resistance into the bacterial population of the Thiruvandarkoil Lake, a water body located in the rural settings of Puducherry, India, culture-based microbiological and genomic approaches were used. Resistant bacterial isolates obtained from microbiological screening were subjected to whole genome sequencing and the genetic determinants of antimicrobial resistance were identified using in silico genomic tools. Cephalosporin-resistant isolates were found to produce extended spectrum beta lactamases, encoded by blaVEB-6 (in Proteus mirabilis PS01), blaSHV-12 and ompK36 mutation (in Klebsiella quasipneumoniae PS02) and blaSHV-12, blaACT-16, blaCTX-M and blaNDM-1 in (Enterobacter hormaechei PS03). Genes encoding heavy metal resistance, virulence and resistance to detergents were also detected in these resistant isolates. Among ESBL-producing organisms, one mcr-9-positive Enterobacter hormaechei was also identified in this study. To our knowledge, this is the first report of mcr-9 carrying bacterium in the environment in India. This study seeks the immediate attention of policy makers, researchers, government officials and environmental activists in India, to develop surveillance programs to monitor the dissemination of antimicrobial resistance in the environment.

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The design of inhibitors against metallo-ß-lactamases (MBLs), the largest family of carbapenemases, has been a strategic goal in designing novel antimicrobial therapies. In this regard, the development of bicyclic boronates, such as taniborbactam (TAN) and xeruborbactam, is a major achievement that may help in overcoming the threat of MBL-producing and carbapenem-resistant Gram-negative pathogens. Of concern, a recent report has shown that New Delhi MBL-9 (NDM-9) escapes the inhibitory action of TAN by a single amino acid substitution with respect to New Delhi MBL-1 (NDM-1), the most widely disseminated MBL. Here, we report a docking and computational analysis that identifies that "escape variants" against TAN can arise by disruption of the electrostatic interaction of negative charges in the active site loops of MBLs with the N-(2-aminoethyl)cyclohexylamine side chain of TAN. These changes result in non-productive binding modes of TAN that preclude reaction with the MBLs, a phenomenon that is not restricted to NDM-9. This analysis demonstrates that single amino acid substitutions in non-essential residues in MBL loops can unexpectedly elicit resistance to TAN.

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INTRODUCTION: The spread of multidrug-resistant bacteria, particularly carbapenem-resistant Gram-negative bacilli (CR-GNB), has become a serious challenge for clinicians due to limited therapeutic options. The aim of the study was to investigate the prevalence of carbapenemase production among clinical isolates recovered from 352 samples collected in Tebessa hospital, Algeria. METHODOLOGY: Bacterial isolates were identified by 16S RNA gene sequencing and susceptibility to antibiotics was determined by disk diffusion method. Carbapenem-resistant isolates were screened for carbapenemase production using modified carba Nordmann-Poirel test, modified Hodge test and imipenem-EDTA combined disc test. Extended-spectrum ß-lactamases (ESBL) were detected using double-disk synergy test. Molecular characterization of carbapenemases and ESBL genes was performed by polymerase chain reaction (PCR) and sequencing. RESULTS: A total of 85 Gram-negative bacilli isolates were recovered mainly from urine samples and were identified as: Klebsiella pneumoniae (17.65%), Serratia odorifera (15.29%), Escherichia coli (12.94%), Raoultella ornithinolytica, Enterobacter cloacae (11.76%), Serratia marcescens (10.59%), Morganella morganii (7.06%), Proteus mirabilis (5.88%), Acinetobacter baumannii (4.70%) and Pseudomonas aeruginosa (2.35%). All strains were resistant or intermediate to imipenem and/or ertapenem. ESBL, carbapenemase and metallo-beta-lactamases (MBL) phenotypes were detected in 19 (22.35%), 9 (10.59%) and 2 (2.35%) GNB isolates, respectively. PCR results in nine carbapenemase-producing GNB strains chosen showed the presence of one to four carbapenemase genes (blaGES, blaSME, blaNDM-1, blaVIM, blaGIM, blaSPM, blaOXA-48) in four strains; however, seven strains had at least one ESBL gene (blaTEM-1, blaCTXM-15, blaSHV). CONCLUSIONS: In this study, we report the first incidence of blaNDM-1 gene in Enterobacter cloacae isolated from urine sample in Algeria.

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Background: Data on risk factors for carbapenem-resistant Enterobacterales (CRE) with wider applicability are needed to inform preventive measures and efficient design of randomised trials. Methods: An international matched case-control-control study was performed in 50 hospitals with high CRE incidence from March 2016 to November 2018 to investigate different aspects of infections caused by CRE (NCT02709408). Cases were patients with complicated urinary tract infection (cUTI), complicated intraabdominal (cIAI), pneumonia or bacteraemia from other sources (BSI-OS) due to CRE; control groups were patients with infection caused by carbapenem-susceptible Enterobacterales (CSE), and by non-infected patients, respectively. Matching criteria included type of infection for CSE group, ward and duration of hospital admission. Conditional logistic regression was used to identify risk factors. Findings: Overall, 235 CRE case patients, 235 CSE controls and 705 non-infected controls were included. The CRE infections were cUTI (133, 56.7%), pneumonia (44, 18.7%), cIAI and BSI-OS (29, 12.3% each). Carbapenemase genes were found in 228 isolates: OXA-48/like, 112 (47.6%), KPC, 84 (35.7%), and metallo-ß-lactamases, 44 (18.7%); 13 produced two. The risk factors for CRE infection in both type of controls were (adjusted OR for CSE controls; 95% CI; p value) previous colonisation/infection by CRE (6.94; 2.74-15.53; <0.001), urinary catheter (1.78; 1.03-3.07; 0.038) and exposure to broad spectrum antibiotics, as categorical (2.20; 1.25-3.88; 0.006) and time-dependent (1.04 per day; 1.00-1.07; 0.014); chronic renal failure (2.81; 1.40-5.64; 0.004) and admission from home (0.44; 0.23-0.85; 0.014) were significant only for CSE controls. Subgroup analyses provided similar results. Interpretation: The main risk factors for CRE infections in hospitals with high incidence included previous colonization, urinary catheter and exposure to broad spectrum antibiotics. Funding: The study was funded by the Innovative Medicines Initiative Joint Undertaking (https://www.imi.europa.eu/) under Grant Agreement No. 115620 (COMBACTE-CARE).

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Chryseobacterium indologenes is gram-negative bacteria that cause infection in humans. It is less frequently isolated in the laboratory. The development of drug-resistant and its intrinsic ability to resist a wide range of antimicrobials enables them to cause mortality in an immunocompromised patient with a longer hospital stay. Our study objectives are to investigate antimicrobial-resistant patterns, drug-resistant enzymes, and the risk factor analysis associated with multidrug-resistant (MDR), extensively drug-resistant (XDR), and Pan-drug resistant (PDR) within 2 years. Altogether 53 strains of Chryseobacterium indologens were obtained from 5000 specimens that were processed for routine bacterial culture. The bacterial identification was done using conventional techniques (colony morphology, gram staining, flexirubin test, and biochemical tests) as well as the VITEK-2 System to further confirm. The bacterial isolate were processed to observe antimicrobial susceptibility test (AST) using disk diffusion method. MDR XDR and PDR were classified following European Centre for Disease Prevention and Control guidelines. C. indologens strains with beta-lactamases such as extended-spectrum beta-lactamases (ESBL), metallo beta-lactamases (MBL), and Amp-C beta-lactamases (Amp-C) were detected phenotypically. The highest isolation of C. indologens was observed in a sputum sample. In vitro antimicrobial susceptibility test revealed susceptibility to tigecycline followed by levofloxacin, cotrimoxazole, and piperacillin-tazobactam. From 53 isolates of C. indologens, MDR accounts for 56.60% and 22.64% for XDR. Combined antimicrobial therapy and longer hospital stay were found to be the leading risk factor. All 53 C. indologenes strains were detected as MBL. Total ESBL was detected in 16.98% of MBL producer strains and Amp-C was observed in 13.20% of MBL-producing strains. All 3 enzyme co-oproducers were seen in only 5.66% of C. indologens. Although it is rarely encountered in the laboratory, it showed a remarkable effect in patients with underlying predisposing factors and prolonged hospital stays. The presence of betalactamases determined the drug-resistant activity on a wide spectrum of tested antibiotics.

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Metallo beta lactamases (MBLs) are among the most problematic resistance mechanisms of multidrug-resistant Gram-negative pathogens due to their broad substrate spectrum and lack of approved inhibitors. In this study, we propose the integration of catechol substructures into the design of thiol-based MBL inhibitors, aiming at mimicking bacterial siderophores for the active uptake by the iron acquisition system of bacteria. We synthesised two catechol-containing MBL inhibitors, as well as their dimethoxy counterparts, and tested them for in vitro inhibitory activity against NDM-1, VIM-1, and IMP-7. We demonstrated that the most potent catechol-containing MBL inhibitor is able to bind Fe3+ ions. Finally, we could show that this compound restores the antibiotic activity of imipenem in NDM-1-expressing K. pneumoniae, while leaving HUVEC cells completely unaffected. Thus, siderophore-containing MBL inhibitors might be a valuable strategy to overcome bacterial MBL-mediated resistance to beta lactam antibiotics.

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El rápido incremento en las resistencias a los antibióticos entre los bacilos gram negativos (BGN), especialmente en cepas de enterobacterias, P. aeruginosa y A. baumannii, con elevados patrones de resistencia, plantea una enorme amenaza para los sistemas de salud en todo el mundo. En la última década diferentes antibióticos han sido desarrollados contra patrones de resistencia, algunos de los cuales combinan un β-lactámico junto con un inhibidor de β-lactamasa, mientras que otros utilizan inhibidores no β-lactámicos. La mayoría de ellos presenta una adecuada actividad in vitro sobre varias β-lactamasas de clase A, C y D de Ambler. Sin embargo, combinaciones como ceftazidime/avibactam, ceftolozano/tazobactam y meropenem/vaborbactam no presentan actividad contra metalo-β-lactamasas. Nuevas combinaciones como aztreonan/AVI, cefepime/zidebactam, o modernas cefalosporinas como cefiderocol, presentan eficacia contra casi la totalidad de las metalo-β-lactamasas. Aunque algunas de estas combinaciones ya están aprobadas y en fase de comercialización, muchas de ellas aún deben definir su lugar dentro del tratamiento de microorganismos con resistencia elevada a través de estudios clínicos (AU)

The rapid increase in antibiotic (ATB) resistance among Gram-negative bacilli(BGN), especially in strains of Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter baumannii, with high resistance patterns (XDR), poses a huge threat to health systems worldwide. In the last decade, different ATBs have been developed against XDR, some of which combine a lactam β along with a β-lactamase inhibitor, while others use non-β-lactam inhibitors. Most of them have adequate “in vitro” activity on several β-lactamases of class A, C and D of Ambler. However, combinations such as Ceftazidime/avibactam, Ceftolozane/Tazobactam and Meropenem/vaborbactam have no activity against metallo-β-lactamases(MβL). New combinations such as Aztreonan/AVI, Cefepime/Zidebactam, or new cephalosporins such as Cefiderocol, have efficacy against MβL enzymes. Although some of these combinations are already approved and in the commercialization phase, many of them have yet to define their place within the treatment of microorganisms with high resistance through clinical studies (AU)

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The rapid increase in antibiotic(ATB) resistance among Gram-negative bacilli(BGN), especially in strains of Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter baumannii, with high resistance patterns (XDR), poses a huge threat to health systems worldwide. In the last decade, different ATBs have been developed against XDR, some of which combine a lactam ß along with a ß-lactamase inhibitor, while others use non-ß-lactam inhibitors. Most of them have adequate "in vitro" activity on several ß-lactamases of class A, C and D of Ambler. However, combinations such as Ceftazidime/avibactam, Ceftolozane/Tazobactam and Meropenem/vaborbactam have no activity against metallo-ß-lactamases(MßL). New combinations such as Aztreonan/AVI, Cefepime/Zidebactam, or new cephalosporins such as Cefiderocol, have efficacy against MßL enzymes. Although some of these combinations are already approved and in the commercialization phase, many of them have yet to define their place within the treatment of microorganisms with high resistance through clinical studies.

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OBJECTIVES: Carbapenemase-producing Enterobacterales (CPE) represent a serious threat for human health being frequently resistant to most of available antibiotics classes. Recently, ceftazidime/avibactam (CAZ/AVI) has been approved for treatment of infections by Gram-negative bacteria, including class A CPE (including KPC-producing K. pneumoniae). Following CAZ/AVI commercialization, resistance to this combination has been reported. The aim of this study was to evaluate the prevalence of CAZ/AVI resistance among carbapenem-resistant K. pneumoniae(CR-Kp) isolates recovered from bloodstream infections (BSI) and hospital-acquired pneumonia (HAP), representative of the contemporary southern Italy epidemiology, during the first pandemic wave of SARS-CoV-2. METHODS: From Jan...20-Jun...20, 4 Laboratories, collected all consecutive, non-replicated CR-Kp from BSIs and HAPs. All isolates were subjected to i) MALDI-ToF identification; ii) antimicrobial susceptibility testing by microdilution method. CAZ/AVI resistant (CAZ/AVI-R) isolates were screened for presence of most common carbapenemase genes and subjected to whole genome sequencing for characterization. RESULTS: A total of 89 isolates were collected. The majority of strains retained susceptibility to colistin, gentamicin and amikacin. Three strains (3/89, 3,4%) were CAZ/AVI-R (MIC range 16/4-64/4 mg/L). Among CAZ/AVI-R, one was KPC-type producer (an ST101) while the remaining where NDM-type and VIM-type producers and belonged to ST147, and ST45, respectively. CONCLUSION: During the pandemic period, in southern Italy, CAZ/AVI resistance remained infrequent but high-risk Klebsiella pneumoniae epidemic clones, producing the KPC-31 variant and class B carbapenamases were reported from some of the included centers.

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Introduction: Infections caused by antimicrobial-resistant bacteria are a significant cause of death worldwide, and carbapenemase-producing bacteria are the principal agents. New Delhi metallo-beta-lactamase-1 producing Klebsiella pneumoniae (KP-NDM-1) is an extensively drug-resistant bacterium that has been previously reported in Mexico. Our aim was to conduct a case-control study to describe the risk factors associated with nosocomial infections caused by K. pneumoniae producing NDM-1 in a tertiary-care hospital in Mexico. Methods: A retrospective case-control study with patients hospitalized from January 2012 to February 2018 at the Hospital Civil de Guadalajara "Fray Antonio Alcalde" was designed. During this period, 139 patients with a culture that was positive for K. pneumoniae NDM-1 (cases) and 486 patients hospitalized in the same department and on the same date as the cases (controls) were included. Data were analyzed using SPSS v. 24, and logistic regression analysis was conducted to calculate the risk factors for KP-NDM-1 infection. Results: One hundred and thirty-nine case patients with a KP-NDM-1 isolate and 486 control patients were analyzed. In the case group, acute renal failure was a significant comorbidity, hospitalization days were extended, and significantly more deaths occurred. In a multivariate analysis of risk factors, the independent variables included the previous use of antibiotics (odds ratio, OR = 12.252), the use of a urinary catheter (OR = 5.985), the use of a central venous catheter (OR = 5.518), the use of mechanical ventilation (OR = 3.459), and the length of intensive care unit (ICU) stay (OR = 2.334) as predictors of infection with NDM-1 K. pneumoniae. Conclusion: In this study, the previous use of antibiotics, the use of a urinary catheter, the use of a central venous catheter, the use of mechanical ventilation, and ICU stay were shown to be predictors of infection with NDM-1 K. pneumoniae and were independent risk factors for infection with NDM-1 K. pneumoniae.

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Acinetobacter baumannii is a notorious bacterial pathogen that can cause an array of nosocomial infections in clinical settings. However, the data from the veterinary settings is limited and especially in Pakistan, no such study is conducted so far. To investigate the prevalence, antimicrobial resistance, and distribution of specific sequence types of A. baumannii in cattle, a total of 1,960 samples were collected from cattle over 18 months from Punjab, Pakistan. The isolates obtained were identified using the API20NE system and confirmed through PCR. The isolated A. baumannii isolates were further screened for antimicrobial susceptibility and the presence of resistance genes. Multilocus sequence typing was carried out to characterize the carbapenem-resistant A. baumannii (CRAB) isolates. Results revealed an overall prevalence of A. baumannii at 3.31% (65/1,960) with a higher prevalence of 7.38% (54/731) in dairy cattle compared to beef cattle at 4.41% (11/249). Among 65 A. baumannii isolates, 27.7% (18/65) were CRAB. All CRAB isolates harbor class D ß-lactamases genes blaOXA-23 and blaOXA-51, whereas 94.4% (17/18) CRAB isolates carried class B ß-lactamases gene blaIMP, and only one isolate had blaNDM-1 gene. The commonly found sequence types for CRAB isolates were ST2 and ST642 corresponding to 10 and 05 isolates, respectively. The presence of CRAB in cattle indicates an alarming situation that necessitates an urgent and efficient surveillance system to limit the transmission of CRAB among the cattle population and its possible transmission to humans and the environment.

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OBJECTIVES: To assess the current prevalence, distribution, and main clonal types of carbapenem-resistant Enterobacterales (CRE) in the United Arab Emirates. METHODS: A total of 504 CRE collected over a 9-month period in 15 hospitals were studied. Antibiotic susceptibility and the presence of common carbapenemase, 16S methylase, and mobile colistin resistance genes were assessed. Selected strains forming larger clusters by pulsed field gel electrophoresis were subjected to whole genome sequencing to identify their sequence types and core genome MLST. RESULTS: Strains expressing OXA and NDM type carbapenemases and 16S methylases were present in all major hospitals. Considerable interhospital differences were noticed, suggesting the role of specific clones. A total of three major Klebsiella pneumoniae clones (CC14, ST231, and CC147) were identified, accounting for 48.6% of all CRE. All clones were significantly more resistant than sporadic isolates. CC14 strains exhibited a significant association with Emirati patients. CONCLUSIONS: Nearly half of CRE infections in the country are due to a limited number of clones. The data indicate the possibility of interhospital transmission, combined in some hospitals with inadequate stewardship practices. The study also revealed an association of the largest, most resistant clone (CC14) with Emirati patients. The specific reasons for it should be clarified by further investigations.

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Metallo-beta-lactamases-producing (MBL) Enterobacterales is a growing problem worldwide. The optimization of antibiotic therapy is challenging. The pivotal available therapeutic options are either the combination of ceftazidime/avibactam and aztreonam or cefiderocol. Colistin, fosfomycin, tetracyclines and aminoglycosides are also frequently effective in vitro, but are associated with less bactericidal activity or more toxicity. Prior to the availability of antibiotic susceptibility testing, severe infections should be treated with a combination therapy. A careful optimization of the pharmacokinetic/pharmacodynamic properties of antimicrobials is instrumental in severe infections. The rules of antibiotic therapy are also reported and discussed. To conclude, treatment of severe MBL infections in critically ill patients is difficult. It should be individualized with a close collaboration of intensivists with microbiologists, pharmacists and infection control practitioners.

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QPX7728 is a cyclic boronate ultrabroad-spectrum beta-lactamase inhibitor, with potent activity against both serine beta-lactamases and metallo-beta-lactamases. QPX7728 can be delivered systemically by the intravenous (i.v.) or oral route of administration. Oral beta-lactam antibiotics alone or in combination with QPX7728 were evaluated for (i) sensitivity to hydrolysis by various common beta-lactamases and inhibition of hydrolysis by QPX7728, (ii) the impact of non-beta-lactamase-mediated resistance mechanisms on potency of beta-lactams, and (iii) in vitro activity against a panel of clinical strains producing diverse beta-lactamases. The carbapenem tebipenem had stability for many serine beta-lactamases from all molecular classes, followed by the cephalosporin ceftibuten. Addition of QPX7728 to tebipenem, ceftibuten, and amdinocillin completely reversed beta-lactamase-mediated resistance in cloned beta-lactamases from serine enzyme and metalloenzyme classes; the degree of potentiation of other beta-lactams varied according to the beta-lactamase produced. Tebipenem, ceftibuten, and cefixime had the lowest MICs against laboratory strains with various combinations of beta-lactamases and the intrinsic drug resistance mechanisms of porin and efflux mutations. There was a high degree of correlation between potency of various combinations against cloned beta-lactamases and efflux/porin mutants and the activity against clinical isolates, showing the importance of inhibition of beta-lactamase along with minimal impact of general intrinsic resistance mechanisms affecting the beta-lactam. Tebipenem and ceftibuten appeared to be the best beta-lactam antibiotics when combined with QPX7728 for activity against Enterobacterales that produce serine beta-lactamases or metallo-beta-lactamases.

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Citrobacter freundii has acquired resistance to several antimicrobial drugs, including last-resort antibiotics affecting, therefore, clinical efficacy and causing high rates of mortality. In this study, we investigate the whole genome sequence of a carbapenem-resistant C. freundii strain isolated from the hospital environment in Tunisia. A total of 210 samples were taken using sterile swabs, from inanimate surfaces, medical devices, and care staff, during the period extended between March and April 2019. After the microbiological analysis of samples and antimicrobial susceptibility testing, only one strain identified as C. freundii showing resistance to carbapenems was selected for the whole genome sequencing. The genome analysis revealed a high-level resistance to most antibiotics. Interestingly, we have noted the coexistence of blaNDM-1 and blaVIM-48 metallo-ß-lactamase (MBL) encoding genes conferring resistance to carbapenems. Other ß-lactamases encoding genes have also been detected, including blaTEM-1, blaCMY-48, and blaOXA-1. Moreover, genes conferring resistance to aminoglycoside [aac(3)-IId, ant(3″)-Ia, aadA, aac(6')-Ib], macrolide [mph(A)], sulfonamide (sul1), trimethoprim (dfrA1), tetracycline [tet(D)], chloramphenicol [cat(B3)], rifamycin (arr-3), and quinolone (qnrB) have been revealed. The multi-locus sequence typing analysis showed that this isolate could not be assigned to an existing sequence type (ST), but it is almost identical to ST22. The plasmid investigation revealed the presence of five plasmids belonging to diverse incompatibility groups (IncFII, IncHI1A, IncHI1B, IncN, and IncX3). To the best of our knowledge, our findings report the first detection of NDM-1 and VIM-48 coproducing C. freundii in Tunisia and the second detection in the world of the blaVIM-48.

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BACKGROUND: One of the newest antibiotics against multidrug-resistant (MDR) bacteria is Cefiderocol, a siderophore cephalosporin able to overcome most resistance mechanisms, including metallo-beta-lactamases. Several studies are being carried to prove its clinical benefit. CASE PRESENTATION: A 55-year-old male patient was admitted in the ICU undergoing septic shock due to surgical wound infection. Multidrug-resistant Pseudomonasputida grew in blood cultures and Pseudomonas aeruginosa grew in soft tissue cultures. He was treated with colistin and tobramycin, developing nephro and ototoxicity. Compassionate use of cefiderocol was ordered, and the infection was cured within 14 days. CONCLUSIONS: This is the first evidence of cefiderocol treatment in a soft tissue infection within a surgical wound infection. Our experience with cefiderocol in surgical wound infection suggests that it may be helpful in treating infections at that level, but more clinical trials are still needed.

ANTECEDENTES: Uno de los antibióticos más nuevos contra las bacterias multirresistentes (MDR) es el cefiderocol, una cefalos- porina siderófora capaz de superar la mayoría de los mecanismos de resistencia, incluidas las metalobetalactamasas. Se están realizando varios estudios para demostrar su beneficio clínico. PRESENTACIÓN DEL CASO: Paciente masculino de 55 años que ingresó en la UCI con shock séptico por infección de herida quirúrgica. Pseudomonas putida multirresistente creció en hemocultivos y Pseudomonas aeruginosa crecieron en cultivos de tejidos blandos. Fue tratado con colistina y tobramicina, desarrollando nefro y ototoxicidad. Se indicó cefiderocol y la infección se curó en 14 días. CONCLUSIONES: Esta es la primera evidencia de cefiderocol en el tratamiento de una infección de partes blandas dentro de una infección de herida quirúrgica. Nuestra experiencia con cefiderocol en infección de herida quirúrgica sugiere que puede ser útil en el tratamiento de infecciones a ese nivel, pero aún se necesitan más ensayos clínicos.

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