High prevalence of multi-drug resistant organisms in the gut flora of healthy rural individuals in northern India.

Background & objectives Presence of resistant gut flora in the community is associated with increasing multi-drug resistance (MDR) infections. In this study, the prevalence of MDR organisms in the gut flora of a healthy rural population residing in northern India was determined. Methods Healthy individuals aged 18-45 yr from Nuh district, Haryana, India were included in this study. Risk factors associated with dysbiosis, diet, lifestyle and exposure to animals was assessed. Qualitative food frequency questionnaire and inflammatory diet score was calculated. Pathogens in stool sample were detected by MALDI-TOF. Evaluation of antimicrobial susceptibility was done by automated Vitek-2 System. The presence of antimicrobial resistance (AMR) genes was evaluated using PCR. An isolate having resistance to at least one antibiotic out of the three or more classes of antibiotics tested was labelled as MDR. Results Among 153 individuals included in this study (mean age-32.5±8.6 yr, females-58.2%, vegetarian-68.6%), the most frequent organism isolated was E. coli (n=137, 89.5%) followed by K. pneumoniae (n=19, 12.4%) and Enterobacter species (n=23, 15%). Forty seven (30.7%) individuals had sensitive and 42 (27.4%) had MDR organisms. Fifty one (33.3%) were positive for ESBL, 5 (3.3%) were positive for carbapenems, and 18 (11.8%) were positive for both genes. Age, gender, body mass index, diet pattern, or diet score were similar between participants with sensitive and resistant organisms. Resistance against fluoroquinolones was highest [92(48.7%)] among all isolates. Forty nine (25.9%), 25 (13.2%), 24 (12.7%) and 21 (11.1%) isolates, respectively were positive for blaTEM, blaSHV, blaCTXM-1 and OXA-48 genes. Interpretation & conclusions Overall the study findings suggest that 27 per cent individuals from rural northern India carry MDR organisms in their fecal flora, with an ESBL carriage rate of 44 per cent.

Thymus algeriensis essential oil: Phytochemical investigation, bactericidal activity, synergistic effect with colistin, molecular docking, and dynamics analysis against Gram-negative bacteria resistant to colistin.

Due to the increasing resistance prevalence to the last line of antibiotics, such as colistin, and the rising threat of multi-drug resistant bacteria, it is crucial to find alternative therapeutic options. The current study focuses on evaluating antibacterial activities alone and in combination with colistin of Thymus algeriensis essential oil (TA-EO) against colistin-resistant Klebsiella pneumoniae, Pseudomonas aeruginosa, and Escherichia coli co-harboring mcr-1 gene. GC/MS was used to determine the chemical composition of TA-EO. Disc diffusion and microdilution techniques were used to evaluate the antimicrobial activities of TA-EO. Synergism between colistin and TA-EO was evaluated by checkerboard assay. The major compounds of TA-EO were docked with known enzymes involved in resistance to colistin, as well as the biosynthesis of peptidoglycan and amino acids. GC/MS revealed that TA-EO was of carvacrol chemotype (67.94 %). The TA-EO showed remarkable antibacterial activities against all Gram-negative bacterial strains, with the diameter of inhibition zones varied between 30 and 50 mm and a ratio MBC/MIC equal to 1 for the vast majority of bacterial isolates. Interestingly, the checkerboard showed synergism between TA-EO and colistin against colistin-resistant Escherichia coli co-harboring mcr-1 gene (FICI˂1) and reduced the MIC of colistin by 16- to 512-fold and those of TA-EO by 4- to 16-fold. The docking study demonstrated that carvacrol had high binding free energies against MCR-1, a phosphoethanolamine transferase extracellular domain, and its catalytic domain implicated in resistance to colistin, and undecaprenyl pyrophosphate synthase in complex with magnesium which is involved in bacterial peptidoglycan biosynthesis. The molecular dynamics study for 100-ns also revealed the stability of the MCR-1/carvacrol complex with a constant surface area over the simulation. These results support using carvacrol or TA-EO as a bactericidal agent, either alone or in combination with colistin, to treat infections caused by colistin-resistant Gram-negative bacteria.

Intravenous combined with aerosolised polymyxins versus intravenous polymyxins monotherapy for ventilator-associated pneumonia: a systematic review and meta-analysis.

Polymyxins was applied to treat ventilator associated pneumonia (VAP) caused by carbapenem-resistant Gram-negative bacteria (CR-GNB) via different administration routes. The potential benefits of aerosolised polymyxins as adjunctive treatment for patients still were contradictory. This review assessed the safety and efficacy of intravenous combined with aerosolised polymyxins versus intravenous polymyxins monotherapy in patients with VAP caused by CR-GNB. Two reviewers independently evaluated and extracted date from Pubmed, Embase, Cochrane library and Web of science. The primary outcome was all-cause mortality and secondary outcomes included clinical cure rate, clinical improvement rate, microbiological eradication and nephrotoxicity. Differences for dichotomous outcomes were expressed as odds ratios (OR) with 95% confidence intervals (CI). Eleven eligible studies were included. The results showed that compared with intravenous polymyxins monotherapy, intravenous plus aerosolised polymyxins therapy significantly reduced all-cause mortality rate (OR = 0.75, 95% CI 0.57 - 0.99, P = 0.045) and improved clinical improvement rate (OR = 1.62, 95% CI 1.02 - 2.60, P = 0.043) and microbial eradication rate (OR = 2.07, 95% CI 1.40 - 3.05, P = 0.000). However, there were no significant difference in terms of clinical cure rate (OR = 1.59, 95% CI 0.96 - 2.63, P = 0.072) and nephrotoxicity (OR = 1.14, 95% CI 0.80 - 1.63, P = 0.467) for intravenous plus aerosolised polymyxins therapy. Subgroup analysis revealed that the clinical improvement rate was improved significantly in case-control studies. Aerosolised polymyxins maybe a useful adjunct to intravenous polymyxins for CR-GNB VAP patients.

Native ß-barrel substrates pass through two shared intermediates during folding on the BAM complex.

The assembly of ß-barrel proteins into membranes is mediated by the evolutionarily conserved ß-barrel assembly machine (BAM) complex. In Escherichia coli, BAM folds numerous substrates which vary considerably in size and shape. How BAM is able to efficiently fold such a diverse array of ß-barrel substrates is not clear. Here, we develop a disulfide crosslinking method to trap native substrates in vivo as they fold on BAM. By placing a cysteine within the luminal wall of the BamA barrel as well as in the substrate ß-strands, we can compare the residence time of each substrate strand within the BamA lumen. We validated this method using two defective, slow-folding substrates. We used this method to characterize stable intermediates which occur during folding of two structurally different native substrates. Strikingly, these intermediates occur during identical stages of folding for both substrates: soon after folding has begun and just before folding is completed. We suggest that these intermediates arise due to barriers to folding that are common between ß-barrel substrates, and that the BAM catalyst is able to fold so many different substrates because it addresses these common challenges.

A unique cell division protein critical for the assembly of the bacterial divisome.

Identification of unique essential bacterial genes is important for not only the understanding of their cell biology but also the development of new antimicrobials. Here, we report a previously unrecognized core component of the Acinetobacter baumannii divisome. Our results reveal that the protein, termed Aeg1 interacts with multiple cell division proteins, including FtsN, which is required for components of the divisome to localize to the midcell. We demonstrate that the FtsAE202K and FtsBE65A mutants effectively bypassed the need of Aeg1 by A. baumannii, as did the activation variants FtsWM254I and FtsWS274G. Our results suggest that Aeg1 is a cell division protein that arrives at the division site to initiate cell division by recruiting FtsN, which activates FtsQLB and FtsA to induce the septal peptidoglycan synthase FtsWI. The discovery of the new essential cell division protein has provided a new target for the development of antibacterial agents.

A Nomogram Based on a Non-Invasive Method to Distinguish Between Gram-Positive and Gram-Negative Bacterial Infections of Liver Abscess.

Purpose: The diagnosis of liver abscess (LA) caused by Gram-positive bacteria (GPB) and Gram-negative bacteria (GNB) depends on ultrasonography, but it is difficult to distinguish the overlapping features. Valuable ultrasonic (US) features were extracted to distinguish GPB-LA and GNB-LA and establish the relevant prediction model. Materials and Methods: We retrospectively analyzed seven clinical features, three laboratory indicators and 11 US features of consecutive patients with LA from April 2013 to December 2023. Patients with LA were randomly divided into training group (n=262) and validation group (n=174) according to a ratio of 6:4. Univariate logistic regression and LASSO regression were used to establish prediction models. The performance of the model was evaluated using area under the curve(AUC), calibration curves, and decision curve analysis (DCA), and subsequently validated in the validation group. Results: A total of 436 participants (median age: 55 years; range: 42-68 years; 144 women) were evaluated, including 369 participants with GNB-LA and 67 with GPB-LA, respectively. A total of 11 predictors by LASSO regression analysis, which included gender, age, the liver background, internal gas bubble, echogenic debris, wall thickening, whether the inner wall is worm-eaten, temperature, diabetes mellitus, hepatobiliary surgery and neutrophil(NEUT). The performance of the Nomogram prediction model distinguished between GNB-LA and GPB-LA was 0.80, 95% confidence interval [CI] (0.73-0.87). In the validation group, the AUC of GNB was 0.79, 95% CI (0.69-0.89). Conclusion: A model for predicting the risk of GPB-LA was established to help diagnose pathogenic organism of LA earlier, which could help select sensitive antibiotics before the results of drug-sensitive culture available, thereby shorten the treatment time of patients.

Design, synthesis, and bioactivity investigation of novel cyclic lipopeptide antibiotics targeting top-priority multidrug-resistant gram-negative bacteria.

OBJECTIVES: Polymyxins are the last-line therapy for top-priority multidrug-resistant (MDR) gram-negative bacteria. However, polymyxin nephrotoxicity impedes its clinical application. This study aimed to design, synthesize, and identify a novel and promising polymyxin derivative with high efficacy and low toxicity. METHODS: To design polymyxin derivatives, we reduced the hydrophobicity of the two hydrophobic domains (fatty acyl chain and D-Phe6-L-Leu7) and modified the positive charged L-2,4-diaminobutyric acid (Dab) residues. Twenty-five derivatives were synthesized, and their antibacterial activities in vitro and renal cytotoxicities were determined. The nephrotoxicity and pharmacokinetic parameters of compound 12 were examined in rats. Antibacterial efficacy in vivo was evaluated using a mouse systemic infection model. Surface plasmon resonance analysis, compound 12-rifampicin combination therapy, and scanning electron microscopy were used to study the mechanism of action of compound 12. RESULTS: This research found a new compound, identified as compound 12, which showed similar or increased antibacterial activity against all tested sensitive and carbapenem-resistant gram-negative bacteria. It exhibited reduced renal cytotoxicity and nephrotoxicity, a favorable pharmacokinetic profile, and maintained or improved antibacterial efficacy in vivo. Importantly, its anti-Pseudomonas aeruginosa activity significantly improved. Compound 12, when combined with rifampicin, enhanced the activity of rifampin against gram-negative bacteria. Compound 12 also showed a high affinity for lipopolysaccharide and disrupted cell membrane integrity. CONCLUSION: Reducing the hydrophobicity of the two domains reduced renal cytotoxicity and nephrotoxicity. Shortening the side chain of Dab3 by one carbon maintained or increased its antibacterial activity both in vitro and in vivo. Furthermore, only the length of the side chain of Dab9 could be shortened by one carbon among the Dab1,5 and Dab8,9 residues. The bactericidal effects of compound 12 were related to the disruption of cell membrane integrity. Compound 12 may be a promising candidate for combating sensitive and carbapenem-resistant gram-negative bacterial infections, especially Pseudomonas aeruginosa.

Investigation of the Antibacterial Properties of Janus Micromotors Catalytic Propelled by Manganese Dioxide and Hydrogen Peroxide to Reduce Bacterial Density.

Between 2015 and 2017, 90% of Chinese adults were reported to have periodontitis of varying degrees, highlighting the importance of novel, inexpensive, and affordable treatments for the public. The fact that more and more pathogens are becoming resistant to antibiotics further highlights this prevalence. This article addresses a novel micromotor capable of generating reactive oxygen species, as proven by a Fenton-like reaction. Such reactions allow the targeting of Gram-negative bacteria such as Escherichia coli, which are eliminated order of magnitude more effectively than by pure hydrogen peroxide, thereby addressing pathogens relevant in oral infections. The basis of the micromotors, which generate reactive oxygen species on site, reduces the likelihood of resistance developing in these types of bacteria. Catalytically reducing hydrogen peroxide in this process, these micromotors propel themselves forward. This proof of principle study paves the way for the utilization of micromotors in the field of skin disinfection utilizing hydrogen peroxide concentrations which were in previous works proven noncytotoxic.

Impact of Bacterial Etiology on Procalcitonin, C-reactive Protein and Hematological Parameters: Evaluating Mean Platelet Volume for Differentiating Gram-Negative and Gram-Positive Bacteria in Odontogenic Versus Non-odontogenic Head and Neck Abscesses.

Introduction Head and neck abscesses, which can originate from odontogenic or non-odontogenic sources, pose significant diagnostic challenges due to their diverse bacterial etiologies. This study aims to investigate the impact of bacterial etiology on procalcitonin (PCT), C-reactive protein (CRP), and various hematological parameters, and to assess the diagnostic performance of mean platelet volume (MPV) in differentiating between Gram-negative bacteria (GNB) and Gram-positive bacteria (GPB) in adults with odontogenic and non-odontogenic head and neck abscesses. Materials and methods Our retrospective analysis of a prospective study comprised 80 patients: 50 individuals (56% men, average age 41.6±18.18 years) with odontogenic and 30 patients (66.7% men, average age 44.53±15.49 years) with non-odontogenic head and neck abscesses during the period from July 2021 to June 2022. White blood cell count (WBC); neutrophil (Neu) and lymphocyte (Ly) count; MPV, and platelet count (PLT) were derived from the results of complete blood count. MPV/PLT (MPI) was calculated by dividing MPV by PLT. CRP levels (mg/l) were quantified via immunoturbidimetric analysis utilizing latex-enhanced particles and PCT levels (ng/ml) by latex-enhanced immunoturbidimetric assay. Results In 25 (31.3%) of all 80 patients, no microorganisms were isolated (sterile cultures); in 28 (35%) resident microflora were isolated; in seven (8.8%) GNB were isolated; and in 17 (21.3%) GPB were isolated. CRP and Neu were significantly higher in patients with odontogenic abscesses compared to non-odontogenic ones. PLT and PCT were lower in patients with odontogenic abscesses vs those with non-odontogenic abscesses. Additionally, according to bacterial type, MPV, MPI and PCT were significantly higher in GPB compared to GNB. WBC, Neu and PLT were higher in patients with GNB vs GPB. Significant correlations were found between MPV and Ly, and between MPV and Neu, regardless of the abscess origin or etiological factor. MPI exhibited an area under the curve of the receiver operating characteristic (AUC-ROC)=0.776, MPV of 0.541, and PCT of 0.568 in distinguishing patients with GPB from GNB. A cut-off value of 0.029 was derived for MPI (70.6% sensitivity and 80% specificity). Conclusions This study highlights the impact of bacterial etiology on inflammatory and hematological markers in head and neck abscesses. Odontogenic abscesses showed higher CRP and Neu, indicating a stronger inflammatory response, while non-odontogenic abscesses had higher PLT, Ly, and PCT. MPI proved to be a more effective diagnostic marker (cut-off value of 0.029) than MPV or PCT for distinguishing between GPB and GNB, suggesting its valuable role in clinical practice for accurate and timely diagnosis.

Refined egoist: the toxin-antitoxin immune system of T6SS.

The Type VI secretory system (T6SS) is a key regulatory network in the bacterial system, which plays an important role in host-pathogen interactions and maintains cell homeostasis by regulating the release of effector proteins in specific competition. T6SS causes cell lysis or competitive inhibition by delivering effector molecules, such as toxic proteins and nucleic acids, directly from donor bacterial cells to eukaryotic or prokaryotic targets. Additionally, it orchestrates synthesis of immune effectors that counteract toxins thus preventing self-intoxication or antagonistic actions by competing microbes. Even so, the mechanism of toxin-antitoxin regulation in bacteria remains unclear. In response, this review discusses the bacterial T6SS's structure and function and the mechanism behind toxin-antitoxin secretion and the T6SS's expression in order to guide the further exploration of the pathogenic mechanism of the T6SS and the development of novel preparations for reducing and replacing toxins and antitoxins.

Antibacterial effectors in Dictyostelium discoideum: specific activity against different bacterial species.

Dictyostelium discoideum is a phagocytic amoeba continuously eating, killing, and digesting bacteria. Previous studies have detected in D. discoideum cell extracts a bacteriolytic activity effective against Klebsiella pneumoniae bacteria. In this study, we characterized bacteriolytic activities found in D. discoideum cell extracts against five different bacteria (K. pneumoniae, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Bacillus subtilis). We first analyzed the bacteriolytic activity against these five bacteria in parallel over a range of pH values. We then measured the remaining bacteriolytic activity in D. discoideum kil1 and modA knockout mutants. We also performed partial fractionation of D. discoideum extracts and assessed activity against different bacteria. Together our results indicate that optimal bacteriolytic activity against different bacteria results from the action of different effectors. Proteomic analysis allowed us to propose a list of potential bacteriolytic effectors.IMPORTANCEMany antibacterial effectors have been characterized over the past decades, and their biological importance, mode of action, and specificity are often still under study. Here we characterized in vitro bacteriolytic activity in D. discoideum extracts against five species of Gram-negative and Gram-positive bacteria. Our results reveal that optimal lysis of different bacteria mobilizes different effectors. Proteomic analysis generated a list of potential bacteriolytic effectors. This work opens the way for future analysis of the role of individual effectors in living D. discoideum cells.

Paeonol potentiates colistin efficacy against K. pneumoniae by promoting membrane disruption and oxidative damage.

BACKGROUND: Although colistin is widely recognized as the last line of antibiotics against gram-negative bacteria, the emergence and spread of colistin resistance severely diminish its clinical efficacy and application. An alternative strategy to alleviate this crisis is to identify promising colistin adjuvants with enhanced antibacterial activity. PURPOSE: In this study, the adjuvant effects of paeonol on colistin and the underlying mechanisms were investigated. METHOD: Minimum Inhibitory Concentration (MIC) and checkerboard assays were used to investigate the adjuvant activity and structure-activity relationship of paeonol on the antibacterial effect of colistin in vitro. Time-dependent killing and resistance development assays were used to investigate the bactericidal effects and emergence of colistin resistance. Different fluorescent probes and competitive inhibition tests were used to investigate bacterial membrane functions and potential targets. Skin infection and peritonitis-sepsis models were used to evaluate the combined in vivo effects of colistin and paeonol in vivo. RESULT: Paeonol enhanced the antibacterial effects of colistin against gram-negative bacteria, particularly Klebsiella pneumoniae. Structure-activity relationship analysis showed that the hydroxyl, 4-methoxy and ketone carbonyl side chains of the benzene ring contributed to the adjuvant effect of paeonol. Paeonol enhances the bactericidal effects of colistin and minimizes the emergence of colistin resistance. Notably, mechanistic studies demonstrated that the combination of colistin and paeonol enhances membrane disruption and oxidative damage, possibly via interactions with phosphatidylethanolamine (PE), phosphatidylglycerol (PG), and cardiolipin (CAL). Importantly, paeonol enhanced the efficacy of colistin in both the skin and peritonitis infection models. CONCLUSION: This is the first report on the adjuvant potential of paeonol in colistin to combat K. pneumoniae by promoting membrane disruption and oxidative damage via targeting membrane phospholipids. Notably, the verified target, PE, provides an additional avenue for screening new colistin adjuvants.The combination therapy of paeonol and colistin is a promising strategy for treating infections caused by gram-negative pathogens to address antibiotic resistance issues.

Gadolinium doped carbon dots for anti-gram-negative bacteria and visible light photodynamic enhancement of antibacterial effect.

Infection with gram-negative bacteria is the main source of the most serious infectious pathogens. Developing new antibacterial materials that break through their external membranes and stay in the bacterial body to result in an antibacterial effect is the key to achieving high efficiency against Gram-negative bacteria. A Gd-doped carbon dot (GRCD) was prepared using the approved therapeutic diagnostic agents Rose Bengal (RB) and gadolinium ions (Gd3+), which was used to resist Gram-negative bacteria (e.g. E. coli, Escherichia coli). GRCD not only showed strong antibacterial activity by destroying the external membranes of E. coli (inhibition rate against E. coli was 92.0 % at 20 µg/mL) but also bound to E. coli DNA and generated single oxygen (1O2) (quantum yield was 0.50) through visible light-driven catalysis, thus decomposing the DNA of E. coli and further enhancing the antibacterial performance of GRCD. Under visible light conditions, the inhibition rate against E. coli reached 95.8 % at a low concentration of 2.5 µg/mL, without obvious cytotoxicity to NIH3T3 cells. The use of GRCD in treating wound infections in mice caused by E. coli was quite good, without side reactions on the mice's essential organs. In this study, a new approach has been provided to the design and synthesis of carbon dot nanocomposites for use against Gram-negative bacteria.

Structural characterization of the POTRA domains from A. baumannii reveals new conformations in BamA.

Recent studies have demonstrated BamA, the central component of the ß-barrel assembly machinery (BAM), as an important therapeutic target to combat infections caused by Acinetobacter baumannii and other Gram-negative pathogens. Homology modeling indicates BamA in A. baumannii consists of five polypeptide transport-associated (POTRA) domains and a ß-barrel membrane domain. We characterized the POTRA domains of BamA from A. baumannii in solution using size-exclusion chromatography small angle X-ray scattering (SEC-SAXS) analysis and determined crystal structures in two conformational states that are drastically different than those previously observed in BamA from other bacteria, indicating that the POTRA domains are even more conformationally dynamic than has been observed previously. Molecular dynamics simulations of the POTRA domains from A. baumannii and Escherichia coli allowed us to identify key structural features that contribute to the observed novel states. Together, these studies expand on our current understanding of the conformational plasticity within BamA across differing bacterial species.

Pharmacokinetic and Preclinical Safety Studies of Endolysin-Based Therapeutic for Intravenous Administration.

Pharmacokinetics and safety studies of innovative drugs is an essential part of drug development process. Previously we have developed a novel drug for intravenous administration (lyophilizate) containing modified endolysin LysECD7-SMAP that showed notable antibacterial effect in different animal models of systemic infections. Here we present data on pharmacokinetics of endolysin in mice after single and multiple injections. Time-concentration curves were obtained, and pharmacokinetic parameters for preparation (C0, kel t1/2, AUC0-∞, MRT, ClT, Vss) were calculated. It was shown that although endolysin is rather short-lived in blood serum (t1/2 = 12.5 min), the therapeutic concentrations of LysECD7-SMAP (in degraded and non-degraded form) were detected for 60 minutes after injection that is sufficient for antibacterial effect. Based on the obtained data, it was proposed that endolysin distributes presumably in murine blood, degrades in blood and liver, and is eliminated via glomerular filtration. Safety profile of the preparation relating to general toxicity, immunotoxicity and allergenicity was assessed in rodents. It was demonstrated that LysECD7-SMAP in potential therapeutic (12.5 mg/kg), 10-fold (125 mg/kg) and 40-fold (500 mg/kg) doses showed no signs of intoxication and significant abnormalities after single and repeated i.v. administrations, preparation was non-immunogenic and induced minor and reversible allergic reaction in animals.

The 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.

Nanostructures for Delivery of Flavonoids with Antibacterial Potential against Klebsiella pneumoniae.

Flavonoids are secondary metabolites that exhibit remarkable biological activities, including antimicrobial properties against Klebsiella pneumoniae, a pathogen responsible for several serious nosocomial infections. However, oral administration of these compounds faces considerable challenges, such as low bioavailability and chemical instability. Thus, the encapsulation of flavonoids in nanosystems emerges as a promising strategy to mitigate these limitations, offering protection against degradation; greater solubility; and, in some cases, controlled and targeted release. Different types of nanocarriers, such as polymeric nanoparticles, liposomes, and polymeric micelles, among others, have shown potential to increase the antimicrobial efficacy of flavonoids by reducing the therapeutic dose required and minimizing side effects. In addition, advances in nanotechnology enable co-encapsulation with other therapeutic agents and the development of systems responsive to more specific stimuli, optimizing treatment. In this context, the present article provides an updated review of the literature on flavonoids and the main nanocarriers used for delivering flavonoids with antibacterial properties against Klebsiella pneumoniae.

The Comparative Characterization of a Hypervirulent Acinetobacter baumannii Bacteremia Clinical Isolate Reveals a Novel Mechanism of Pathogenesis.

Acinetobacter baumannii is an opportunistic Gram-negative pathogen with exquisite survival capabilities under various environmental conditions and displays widespread resistance to common antibiotics. A. baumannii is a leading cause of nosocomial infections that result in high morbidity and mortality rates. Accordingly, when multidrug resistance rates surpass threshold levels, the percentage of A. baumannii clinical isolates surges. Research into A. baumannii has increased in the past decade, and multiple mechanisms of pathogenesis have been identified, including mechanisms underlying biofilm development, quorum sensing, exotoxin production, secretion system utilization, and more. To date, the two gold-standard strains used to investigate different aspects of A. baumannii pathogenesis include ATCC 17978 and ATCC 19606. Here, we report a comparative characterization study of three additional A. baumannii clinical isolates obtained from different infection types and derived from different anatomical regions of infected patients. The comparison of three clinical isolates in addition to the ATCC strains revealed that the hypervirulent bacteremia clinical isolate, known as HUMC1, employs a completely different mechanism of pathogenesis when compared to all its counterparts. In stark contrast to the other genetic variants, the hypervirulent HUMC1 isolate does not form biofilms, is antibiotic-susceptible, and has the capacity to reach higher levels of quorum compared to the other clinically relevant strains. Our data also reveal that HUMC1 does not shed endotoxin into the extracellular milieu, rather secretes the evolutionarily conserved, host-mimicking, Zonula occludens toxin (Zot). Taken together, our hypothesis that HUMC1 cells have the ability to reach higher levels of quorum and lack biofilm production and endotoxin shedding, accompanied by the substantial elaboration of Zot, suggests a novel mechanism of pathogenesis that appears to afford the hypervirulent pathogen with stealth-like capabilities when disseminating through the circulatory system in a state of bacteremia.

Genome sequences of 70 multidrug-resistant Gram-negative isolates in high-risk neonates in the Northeast of Mexico.

Infections by multidrug-resistant pathogens are steadily increasing worldwide. A considerable proportion of neonatal intensive care admissions have a bacterial infection with multidrug-resistant bacteria during their hospital stay. In this work, we report draft genome sequences of 70 selected isolates from high-risk neonates in the Northeast of Mexico.

Aztreonam-avibactam for the treatment of intra-abdominal infections.

INTRODUCTION: Intra-abdominal infections are becoming increasingly common and can lead to significant morbidity and mortality. The incidence of these infections due to resistant gram-negative organisms is also increasing. Given this resistance, new antibiotic combinations are being developed, often utilizing older antibiotics and newer ß-lactamase inhibitors. Aztreonam/avibactam (ATM-AVI) is one of the combination antibiotics, which combines aztreonam, a monobactam, with avibactam, a broad-spectrum ß-lactamase inhibitor for the treatment of complicated intra-abdominal infections in combination with metronidazole. AREAS COVERED: In this drug evaluation manuscript, we provide an overview of intra-abdominal infections and an overview of currently available antimicrobial agents used to treat these infections. ATM-AVI is introduced, including chemistry, pharmacodynamics, pharmacokinetics and clinical studies of this compound. EXPERT OPINION: There are limited treatment options for complicated intra-abdominal infections due to resistant gram-negative organisms, especially those with metallo-ß-lactamases. One treatment option for these infections is ATM-AVI, which was recently approved in Europe, in addition to metronidazole. These bacteria are difficult to treat, and this new compound is a safe and effective option for empiric treatment in places with a high incidence of infections due to these bacteria, and also treatment for infections when these resistant bacteria are isolated in culture.