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Antibiotic contamination from hospitals, animal husbandry, and municipal wastewater is graver than imagined, and it possess serious risks to the health of humans and animals, with the emergence of multidrug resistant bacteria; those affect the growth of higher plants too. Conventional wastewater treatment methods adopted today are inadequate for removing antibiotics from wastewater. Intuitively, the remediation process using mixed algae should be effective enough, for which algae-based remediation technologies have emerged as sustainable remedial methods. This review summarized the detection of antibiotics in field water in most countries; a comprehensive overview of algae-based technologies, algal adsorption, accumulation, biodegradation, photodegradation, hydrolysis, and the use of algae-bacteria consortia for the remediation of antibiotics in wastewaters in done. Green algae namely, Chlamydomonas sp., Chlorella sp., C. vulgaris, Spyrogira sp. Scenedesmus quadricauda, S. obliquus, S. dimorphus, Haematoccus pluvialis, and Nannochlopsis sp., had been reporting have 90–100% antibiotic removal efficiency. The integration of bioelectrochemical systems and genetically engineered prokaryotic algal species offer promising avenues for improving antibiotic removal in the future. Overall, this review highlights the need for tenacious research and development of algae-based technologies to reduce antibiotic contamination in aquatic environments, for holistic good. [ABSTRACT FROM AUTHOR]

Antibiotics, often hailed as 'miracle drugs' in the 20th century, have revolutionised medicine by saving millions of lives in human and veterinary medicine, effectively combatting bacterial infections. However, the escalating global challenge of antimicrobial resistance and the appearance and spread of multidrug-resistant pathogens necessitates research into alternatives. One such alternative could be lactoferrin. Lactoferrin, an iron-binding multifunctional protein, is abundantly present in mammalian secretions and exhibits antimicrobial and immunomodulatory activities. An often overlooked aspect of lactoferrin is its proteolytic activity, which could contribute to its antibacterial activity. The proteolytic activity of lactoferrin has been linked to the degradation of virulence factors from several bacterial pathogens, impeding their colonisation and potentially limiting their pathogenicity. Despite numerous studies, the exact proteolytically active site of lactoferrin, the specific bacterial virulence factors it degrades and the underlying mechanism remain incompletely understood. This review gives an overview of the current knowledge concerning the proteolytic activity of lactoferrins and summarises the bacterial virulence factors degraded by lactoferrins. We further detail how a deeper understanding of the proteolytic activity of lactoferrin might position it as a viable alternative for antibiotics, being crucial to halt the spread of multi-drug resistant bacteria. [ABSTRACT FROM AUTHOR]

Introduction: This study investigated the interaction with membrane mimetic systems (LUVs), bacterial membranes, the CD spectra, and the bactericidal activity of two designed trematocine mutants, named Trem-HK and Trem-HSK. Mutants were constructed from the scaffold of Trematocine (Trem), a natural 22-amino acid AMP from the Antarctic fish Trematomus bernacchii, aiming to increase their positive charge. Methods: The selectivity of the designed AMPs towards bacterial membranes was improved compared to Trematocine, verified by their interaction with different LUVs and their membranolytic activity. Additionally, their α-helical conformation was not influenced by the amino acid substitutions. Our findings revealed a significant enhancement in antibacterial efficacy against ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacteriaceae family) pathogens for both Trem-HK and Trem-HSK. Results: Firstly, we showed that the selectivity of the two new designed AMPs towards bacterial membranes was greatly improved compared to Trematocine, verifying their interaction with different LUVs and their membranolytic activity. We determined that their α-helical conformation was not influenced by the amino acid substitutions. We characterized the tested bacterial collection for resistance traits to different classes of antibiotics. The minimum inhibitory and bactericidal concentration (MIC and MBC) values of the ESKAPE collection were reduced by up to 80% compared to Trematocine. The bactericidal concentrations of Trematocine mutants showed important membranolytic action, evident by scanning electron microscopy, on all tested species. We further evaluated the cytotoxicity and hemolytic activity of the mutants. At 2.5 μM concentration, both mutants demonstrated low cytotoxicity and hemolysis, indicating selectivity towards bacterial cells. However, these effects increased at higher concentrations. Discussion: Assessment of in vivo toxicity using the Galleria mellonella model revealed no adverse effects in larvae treated with both mutants, even at concentrations up to 20 times higher than the lowest MIC observed for Acinetobacter baumannii, suggesting a high potential safety profile for the mutants. This study highlights the significant improvement in antibacterial efficacy achieved by increasing the positive charge of Trem-HK and Trem-HSK. This improvement was reached at the cost of reduced biocompatibility. Further research is necessary to optimize the balance between efficacy and safety for these promising AMPs. [ABSTRACT FROM AUTHOR]

The increasing emergence of multidrug-resistant (MDR) pathogens due to antibiotic misuse translates into obstinate infections with high morbidity and high-cost hospitalizations. To oppose these MDR superbugs, new antimicrobial options are necessary. Although both quaternary ammonium salts (QASs) and phosphonium salts (QPSs) possess antimicrobial effects, QPSs have been studied to a lesser extent. Recently, we successfully reported the bacteriostatic and cytotoxic effects of a triphenyl phosphonium salt against MDR isolates of the Enterococcus and Staphylococcus genera. Here, aiming at finding new antibacterial devices possibly active toward a broader spectrum of clinically relevant bacteria responsible for severe human infections, we synthesized a water-soluble, sterically hindered quaternary phosphonium salt (BPPB). It encompasses two triphenyl phosphonium groups linked by a C12 alkyl chain, thus embodying the characteristics of molecules known as bola-amphiphiles. BPPB was characterized by ATR-FTIR, NMR, and UV spectroscopy, FIA-MS (ESI), elemental analysis, and potentiometric titrations. Optical and DLS analyses evidenced BPPB tendency to self-forming spherical vesicles of 45 nm (DLS) in dilute solution, tending to form larger aggregates in concentrate solution (DLS and optical microscope), having a positive zeta potential (+18 mV). The antibacterial effects of BPPB were, for the first time, assessed against fifty clinical isolates of both Gram-positive and Gram-negative species. Excellent antibacterial effects were observed for all strains tested, involving all the most concerning species included in ESKAPE bacteria. The lowest MICs were 0.250 µg/mL, while the highest ones (32 µg/mL) were observed for MDR Gram-negative metallo-β-lactamase-producing bacteria and/or species resistant also to colistin, carbapenems, cefiderocol, and therefore intractable with currently available antibiotics. Moreover, when administered to HepG2 human hepatic and Cos-7 monkey kidney cell lines, BPPB showed selectivity indices > 10 for all Gram-positive isolates and for clinically relevant Gram-negative superbugs such as those of E. coli species, thus being very promising for clinical development. [ABSTRACT FROM AUTHOR]

Infections by drug-resistant microorganisms are a threat to global health and antimicrobial peptides are considered to be a new hope for their treatment. Temporin-WY2 was identified from the cutaneous secretion of the Ranidae frog, Amolops wuyiensis. It presented with a potent anti-Gram-positive bacterial efficacy, but its activity against Gram-negative bacteria and cancer cell lines was unremarkable. Also, it produced a relatively high lytic effect on horse erythrocytes. For further improvement of its functions, a perfect amphipathic analogue, QUB-1426, and two lysine-clustered analogues, 6K-WY2 and 6K-1426, were synthesised and investigated. The modified peptides were found to be between 8- and 64-fold more potent against Gram-negative bacteria than the original peptide. Additionally, the 6K analogues showed a rapid killing rate. Also, their antiproliferation activities were more than 100-fold more potent than the parent peptide. All of the peptides that were examined demonstrated considerable biofilm inhibition activity. Moreover, QUB-1426, 6K-WY2 and 6K-1426, demonstrated in vivo antimicrobial activity against MRSA and E. coli in an insect larvae model. Despite observing a slight increase in the hemolytic activity and cytotoxicity of the modified peptides, they still demonstrated a improved therapeutic index. Overall, QUB-1426, 6K-WY2 and 6K-1426, with dual antimicrobial and anticancer functions, are proposed as putative drug candidates for the future. [ABSTRACT FROM AUTHOR]

Live biotherapeutics products (LBP) are a novel range of therapeutic options in medicine. In this review, authors discuss basic composition and mechanism of action of LBP, provide a comprehensive focused overview of published in vitro and in vivo studies on efficacy of LBP for prevention and treatment of infectious diseases such as viral (HIV, COVID-19), bacterial (C.difficile infection, bacterial vaginosis, multi-drug resistant organisms) and fungal (Candida) organisms. This review should be of interest to clinicians to understand the broad application of LBP in infectious diseases world beyond recurrent C.difficile infection and to researchers on unexplored prospects of LBP and the need for further investigation in this emerging field to improve its clinical application. [ABSTRACT FROM AUTHOR]

The alarming rise in antimicrobial resistance (AMR) has created a significant public health challenge, necessitating the discovery of new therapeutic agents to combat infectious diseases and oxidative stress-related disorders. The Lentzea flaviverrucosa strain E25-2, isolated from Moroccan forest soil, represents a potential avenue for such research. This study aimed to identify the isolate E25-2, obtained from soil in a cold Moroccan ecosystem, and further investigate its antimicrobial and antioxidant activities. Phylogenetic analysis based on 16S rRNA gene sequences revealed the strain's classification within the Lentzea genus, with a sequence closely resembling that of Lentzea flaviverrucosa AS4.0578 (96.10% similarity). Antimicrobial activity in solid media showed moderate to strong activity against Staphylococcus aureus ATCC 25923, Bacillus cereus strain ATCC 14579, Escherichia coli strain ATCC 25922, Candida albicans strain ATCC 60193 and 4 phytopathogenic fungi. In addition, ethyl acetate extract of this isolate demonstrated potent antimicrobial activity against 7 clinically multi-drug resistant bacteria. Furthermore, it demonstrated antioxidant activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) free radicals, as well as a significant increase in ferric reducing antioxidant power. A significant positive correlation was observed between antioxidant activities and total content of phenolic compounds (p < 0.0001), along with flavonoids (p < 0.0001). Furthermore, gas chromatography-mass spectrometry (GC-MS) analysis revealed the presence of amines, hydroxyl groups, pyridopyrazinone rings, esters and pyrrolopyrazines. The Lentzea genus could offer promising prospects in the fight against antibiotic resistance and in the prevention against oxidative stress related diseases. [ABSTRACT FROM AUTHOR]

Multidrug resistant bacteria have been a global health threat currently and frontline clinical treatments for these infections are very limited. To develop potent antibacterial agents with new bactericidal mechanisms is thus needed urgently to address this critical antibiotic resistance challenge. Natural products are a treasure of small molecules with high bioactive and low toxicity. In the present study, we demonstrated that a natural compound, honokiol, showed potent antibacterial activity against a number of Gram-positive bacteria including MRSA and VRE. Moreover, honokiol in combination with clinically used ß-lactam antibiotics exhibits strong synergistic antimicrobial effects against drug-resistant S. aureus strains. Biochemical studies further reveal that honokiol may disrupt the GTPase activity, FtsZ polymerization, cell division. These biological impacts induced by honokiol may ultimately cause bacterial cell death. The in vivo antibacterial activity of honokiol against S. aureus infection was also verified with a biological model of G. mellonella larvae. The in vivo results support that honokiol is low toxic against the larvae and effectively increases the survival rate of the larvae infected with S. aureus. These findings demonstrate the potential of honokiol for further structural advancement as a new class of antibacterial agents with high potency against multidrug-resistant bacteria. [ABSTRACT FROM AUTHOR]

Background People with cystic fibrosis (pwCF) are particularly susceptible to respiratory infections, including those caused by multidrug-resistant (MDR) pathogens. Ceftolozane/tazobactam (C/T) is an antibacterial agent combination active against MDR gram-negative bacteria that has shown promising results in isolates from pwCF. This subanalysis is the first extensive observation of real-world C/T use in pwCF. Methods The multicenter observational CONDUCT study included consecutive patients, some with cystic fibrosis, who received ≥1 dose of C/T at 28 centers throughout France. Patients were treated according to hospital standards and followed up until the end of C/T treatment (EOT). Results Among 260 patients who had received ≥1 dose of C/T, 63 were pwCF, including 12 with previous lung transplant. The median age was 34 years and 55.6% of patients were female. Pseudomonas aeruginosa was the most frequently isolated pathogen (n = 40/41 [97.6%]). Most tested P aeruginosa strains (n = 65/73 [91.5%]) and all other isolated strains (Escherichia coli , Citrobacter koseri , Proteus mirabilis , and Serratia marcescens) were susceptible to C/T. Most patients completed the treatment duration, including those with historical β-lactam hypersensitivity. Reasons for stopping treatment were planned EOT and improvement in condition; overall, 88.9% of patients (n = 56/63) experienced improvement in condition. No new safety signals were identified. Mean forced expiratory volume in 1 second improved from 1.33 L to 1.47 L before and after C/T treatment, respectively (n = 52; P =.057). Conclusions C/T treatment was well tolerated and effective in pwCF, including those with previous β-lactam hypersensitivity. [ABSTRACT FROM AUTHOR]

This study interrogates infection related data in the Burns Registry of Australia and New Zealand (BRANZ), to examine associations of multi-drug resistant organisms (MDROs) and blood stream infection (BSI). Data between July 2016 and June 2021 were analysed to determine prevalence, risk factors and outcomes associated with BSIs and MDROs: Methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), carbapenem-resistant Pseudomonas spp. (CRP), and carbapenem-resistant Enterobacter (CRE). Data completeness and value for quality improvement activity were assessed. We found a low incidence (3.4%) of the resistant organisms of interest, and no change over the study period. Fequency varied between services and increased with age and size of burn. MRSA was the commonest organism in all age groups. A positive BSI result occurred in 1.6% of patients (12.1% of cultures taken) at a median time of 10.2 days post injury. Free text identification of organisms was inconsistently documented. The low rate and patterns of acquisition of MDROs of interest and BSIs is comparable with reports from countries with low incidence of massive burns. Wider adoption of a standardized laboratory reporting framework would help realise the potential of clinical quality registries to provide data which supports evidence based infection prevention initiatives. • The registry has excellent data completeness for resistant organism items. • Overall frequency of multi-drug resistant organisms is low, but high in patients with massive burns. • Frequency of acquisition did not increase during the study. • MRSA acquisition is not associated with poorer outcomes in adults with severe burns. [ABSTRACT FROM AUTHOR]

This retrospective study aimed to assess the effectiveness and safety of colistin used in combination therapy for treating nosocomial bloodstream infections caused by multi-drug resistant gram-negative pathogens in pediatric patients. Patients aged between 1 month and 18 years consecutively hospitalized with healthcare-associated bloodstream infections necessitating the administration of intravenous colistin at Dr. Sami Ulus Training and Research Hospital between January 2015 and January 2020 were included in the study. Patient-specific detailed clinical information, prognoses, and laboratory findings on days 1, 3, and 7 of colistin treatment were obtained from medical records. The study included 45 pediatric patients receiving intravenous colistin; 26 (57.8%) were male and 19 (42.2%) were female, with a median age of 18 months. While the clinical response was observed at 82.2% and microbiological response at 91.1% with colistin treatment, two patients (4.4%) discontinued treatment due to side effects without assessing treatment response. The most common adverse effect associated with the use of colistin was nephrotoxicity, which occurred in eight patients (17.8%). Among these patients, only one had pre-existing chronic kidney failure. Conclusion: Colistin used in combination therapy may be effective and safe for treating nosocomial infections caused by multi-drug resistant gram-negative bacteria in pediatric patients, who often have high mortality rates and limited treatment options. What is Known: • Colistin is an antibacterial agent used in the treatment of infections caused by multidrug-resistant Gram-negative bacteria (MDR-GNB) and is associated with significant adverse effects such as nephrotoxicity. • The increasing prevalence of hospital-acquired infections has led to the expanded use of colistin in clinical practice. What is New: • The study demonstrates a high clinical and microbiological response rate to combination therapy with colistin in the treatment of infections caused by MDR-GNB. • The study highlights the importance of monitoring nephrotoxicity in pediatric patients receiving colistin, showing that these effects can be reversible after treatment cessation. [ABSTRACT FROM AUTHOR]

The treatment of sepsis caused by multidrug-resistant (MDR) Gram-negative bacterial infections remains challenging. With these pathogens exhibiting resistance to carbapenems and new generation cephalosporins, the traditional antibiotic polymyxin B (PMB) has reemerged as a critical treatment option. However, its severe neurotoxicity and nephrotoxicity greatly limit the clinical application. Therefore, we designed negatively charged high-density lipoprotein (HDL) mimicking nanodiscs as a PMB delivery system, which can simultaneously reduce toxicity and enhance drug efficacy. The negative charge prevented the PMB release in physiological conditions and binding to cell membranes, significantly reducing toxicity in mammalian cells and mice. Notably, nanodisc-PMB exhibits superior efficacy than free PMB in sepsis induced by carbapenem-resistant Acinetobacter baumannii (CRAB) strains. Nanodisc-PMB shows promise as a treatment for carbapenem-resistant Gram-negative bacterial sepsis, especially caused by Acinetobacter baumannii , and the nanodiscs could be repurposed for other toxic antibiotics as an innovative delivery system. Multidrug-resistant Gram-negative bacteria, notably carbapenem-resistant Acinetobacter baumannii , currently pose a substantial challenge due to the scarcity of effective treatments, rendering Polymyxins a last-resort antibiotic option. However, their therapeutic application is significantly limited by severe neurotoxic and nephrotoxic side effects. Prevailing polymyxin delivery systems focus on either reducing toxicity or enhancing bioavailability yet fail to simultaneously achieve both. In this scenario, we have developed a distinctive HDL-mimicking nanodisc for polymyxin B, which not only significantly reduces toxicity but also improves efficacy against Gram-negative bacteria, especially in sepsis caused by CRAB. This research offers an innovative drug delivery system for polymyxin B. Such advancement could notably improve the therapeutic landscape and make a significant contribution to the arsenal against these notorious pathogens. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Staphylococcus aureus (S. aureus) is a leading cause of skin and soft tissue infections, with antibiotic-resistant strains causing potentially life-threatening diseases. This study explored the antimicrobial potential of Acacia ehrenbergiana (Hayne) and Prosopis juliflora using a Caenorhabditis elegans (C. elegans) in vivo model infected with methicillin-susceptible (MSSA) and methicillin-resistant (MRSA) S. aureus strains. Methods: Wild-type C. elegans were exposed to MSSA strain ATCC 25923 and MRSA strains ATCC BF195 and ATCC BC 3820 using an agar-based killing assay. The impact of ethanol extracts from A. ehrenbergiana and P. juliflora on the survival of infected C. elegans was assessed by analyzing the survival rates of infected and non-infected worms. The effects of the plant extracts on C. elegans feeding rate and colonization of MSSA and MRSA in the worm's gut were also examined. Additionally, in vitro assays were conducted to assess the bactericidal and/or bacteriostatic effects of the plant extracts. Results: Exposure to MSSA and MRSA strains significantly reduced C. elegans lifespan, with a mean time to death (TDmean) of 72 ± 1.3 h. Treatment with 100–500 μg/ml of either plant extract increased C. elegans survival by 65–70%. The extracts did not affect C. elegans pharyngeal pumping. Colony-forming Unit (CFU) assays showed a significant reduction in MSSA and MRSA colonization in the worm intestine with P. juliflora, but not A. ehrenbergiana extracts. In vitro Minimum Inhibitory Concentration (MIC) assays indicated that neither extract had direct bactericidal activity, suggesting the observed reduction in bacterial infection in worms was likely due to enhanced host immune response rather than direct antibacterial effects. Conclusion: These findings suggest that A. ehrenbergiana and P. juliflora extracts enhance C. elegans survival upon infection through indirect mechanisms, possibly involving immune system activation. This study highlights the potential of these extracts as antibacterial agents against MSSA and MRSA strains. [ABSTRACT FROM AUTHOR]

Background: The use of plants in the treatment of microbial diseases is increasing worldwide; especially with the increase of bacterial resistance to antibiotics and the development of new diseases that have no cure in modern medicines. Aim: This research was designed to determine the antimicrobial activities of bioactive compounds isolated from Acacia nilotica (A. nilotica) against multi-drug resistant bacteria. Methods: Acacia nilotica samples (i.e., leaves, pods, and back) were collected within Aliero local government area, in Nigeria. Metabolite extraction was performed through maceration. The obtained extract was tested in vitro against multi-drug resistant bacteria that cause diarrhea: Salmonella typhimurium, S. paratyphi, Salmonella sp, Shigella dysenteriae, Shigella sp, and Shigella flexneri, using the agar well diffusion assay. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined using the micro-plate serial dilution method. The synergistic (Pod + Leave Steam back) ethanolic crude extract was subjected to column and thin-layer chromatography (TLC) analyses. The obtained fractions were tested against multi-drugs resistance bacteria, and MIC and MBC of the fractions were also determined. Results: The results showed that the synergistic A. nilotica crude extract had the highest mean antibacterial activity recording inhibition zones that ranged from 15.0± 0.58 to 22.7± 0.33 mm. The MIC of ethanolic crude extracts ranged from 100 to 200 mg/ml, while the MBC ranged from 100 to > 400 mg/ ml. Conclusion: The antibacterial potential of the synergistic ethanolic fractions recorded higher activity that ranged from 16.7± 1.20 to 31.0±1.00 mm against all the tested bacteria, compared to the crude extracts. [ABSTRACT FROM AUTHOR]

Antibiotic misuse has led to the development and spread of multidrug-resistant (MDR) microorganisms. This study evaluated the antibacterial activity of n-hexane, ethyl acetate, and aqueous extracts of the marine sponge Amphimidon chloros. The antibacterial activity of n-hexane, ethyl acetate, and aqueous extracts was evaluated using broth microdilution and disc diffusion. The chemical composition of the extracts was analysed using Liquid Chromatography-Mass spectrometry (LC-MS). The antibacterial potency of the extracts was in the following order: aqueous > n-hexane > ethyl acetate extracts. The most significant inhibitory activity of the aqueous extract was against Shigella flexneri, with an inhibition zone of 20.6 mm. Klebsiella pneumonia, Pseudomonas aeruginosa, and Listeria monocytogenes were utterly resistant to ampicillin and chloramphenicol; however, the aqueous extract efficiently inhibited these bacteria. The extract MIC ranged from 0.0195-2.5 mg/mL. With maximal inhibition against Staphylococcus aureus (0.0195 mg/mL), Bacillus cereus (0.0390 mg/mL), Shigella flexneri (0.0390 mg/mL), and Salmonella enterica (0.0781 mg/mL). While L. monocytogenes (0.3125 mg/mL) and S. aureus (0.625 mg/mL) were the only Gram-positive bacteria inhibited, the ethyl acetate extract was equally effective (MIC of 0.3125 mg/mL) against Gram-negative bacteria, including K. pneumonia, S. typhi, S. enterica, Enterobacter aerogenes, and E. coli. The n-hexane extract inhibited S. aureus, S. flexneri, and S. enterica with a MIC value of 0.1562/mL. The most prevalent phytochemicals in the aqueous and n-hexane extracts from the LC-MS study were nakinadine and kermaphidine. The study revealed that the aqueous extract of A. chloros possesses both Gram-positive and Gram-negative antibacterial activity. [ABSTRACT FROM AUTHOR]

Background: Antimicrobial resistance affects the treatment of several bacterial infections, including pneumonia. This subsequently increased the morbidity and mortality rates of patients with bacterial pneumonia, especially in resource-limited settings. In this study, we aimed to determine the patterns of multidrug-resistant (MDR) bacteria isolated from the sputum samples of patients with bacterial pneumonia attending a tertiary hospital in Tanzania. Methodology: A retrospective cross-sectional study was conducted. It involved reviewing the laboratory sputum data in the laboratory information system at Muhimbili National Hospital in Tanzania. The sputum samples were previously processed using standard methods (culture, Gram staining, and biochemical tests) to isolate and identify the bacteria. At the same time, antibiogram profiles were determined using antimicrobial susceptibility tests. Bacterial isolates that expressed MDR patterns were identified. Demographic information was collected from patients' medical records. We used the chi-square test to determine factors associated with MDR. A p-value < 0.05 was considered significant. Results: We retrieved and analysed 169 laboratory records of patients with a provisional clinical diagnosis of bacterial pneumonia confirmed in the microbiology laboratory. Nearly 98% of the records were from adult patients. The patients' mean age was 48.3 years and 17.3 standard deviations. About 84% of the isolated bacteria were Gram-negative; the most predominant was Klebsiella pneumoniae (59/142; 41.5%). The predominant Gram-positive bacteria was Staphylococcus aureus (25/27; 92.6%). Furthermore, 80 out of 169 (47.3%) bacteria were MDR; Klebsiella pneumoniae (32.5%) was predominant. In addition, 50% of Staphylococcus aureus was methicillin resistance. MDR bacterial pneumonia was highly observed in patients admitted to the Intensive Care Unit (p < 0.05). Conclusions: Although our study was limited by variations in the number of bacterial isolates subjected to the same antibiotic drugs and a lack of information on risk factors such as occupation, smoking history, and marital status, we observed that a high proportion of bacterial pneumonia is caused by MDR Gram-negative bacteria in our local setting. These results inform the need to improve infection prevention control measures in hospitals to reduce the burden of MDR bacteria in our settings and other similar resource-limited settings. [ABSTRACT FROM AUTHOR]

The development of antibiotic resistance compromises the effectiveness of our most effective defenses against bacterial infections, presenting a threat to global health. To date, a large number of research articles exist in the literature describing the case reports associated with extensively drug-resistant (XDR) and multidrug-resistant (MDR) bacterial strains. However, these findings are scattered, making it time-consuming for researchers to locate promising results and there remains a need for a comparative study to compile these case reports from various geographical regions including the Kingdom of Saudi Arabia. Additionally, no study has yet been published that compares the genetic variations and case reports of MDR and XDR strains identified from Saudi Arabia, the Middle East, Central Europe, and Asian countries. This study attempts to provide a comparative analysis of several MDR and XDR case reports from Saudi Arabia alongside other countries. Furthermore, the purpose of this work is to demonstrate the genetic variations in the genes underlying the resistance mechanisms seen in MDR and XDR bacterial strains that have been reported in Saudi Arabia and other countries. To cover the gap, this comprehensive review explores the complex trends in antibiotic resistance and the growing risk posed by superbugs. We provide context on the concerning spread of drug-resistant bacteria by analyzing the fundamental mechanisms of antibiotic resistance and looking into individual case reports. In this article, we compiled various cases and stories associated with XDR and MDR strains from Saudi Arabia and various other countries including China, Egypt, India, Poland, Pakistan, and Taiwan. This review will serve as basis for highlighting the growing threat of MDR, XDR bacterial strains in Saudi Arabia, and poses the urgent need for national action plans, stewardship programs, preventive measures, and novel antibiotics research in the Kingdom. [ABSTRACT FROM AUTHOR]

The objective of this cross-sectional study was to determine associations between calf management practices, the number of antimicrobial treatments, and antimicrobial resistance in preweaning heifers on Canadian dairy farms. A composite of 5 fecal samples from preweaning calves was collected from 142 dairy farms in 5 provinces and analyzed for phenotypic antimicrobial susceptibility with the microbroth dilution method. Questionnaires were used to capture herd characteristics and calf management practices used on the farm. Calf treatment records were collected during the farm visits. Escherichia coli was isolated from all 142 fecal samples with the highest resistance to tetracycline (41%), followed by sulfisoxazole (36%), streptomycin (32%), chloramphenicol (28%), ampicillin (16%), trimethoprim-sulfamethoxazole (15%), ceftriaxone (4.2%), cefoxitin (2.8%), amoxicillin-clavulanic acid (2.1%), ciprofloxacin (2.1%), nalidixic acid (2.1%), azithromycin (1.4%), and gentamicin (1.4%). Multidrug resistance was observed in 37% of E. coli isolates. Three-quarters of farms used fresh colostrum as the most common type of colostrum fed to calves. Colostrum quality was checked on 49% of farms, but the transfer of passive immunity was only checked on 32% of farms in the last 12 mo. Almost 70% of farms used straw or hay or a combination as the bedding material for calves. Among the 142 farms, a complete set of calf records were collected from 71 farms. In a multivariable logistic regression model, farms with ≥1.99 to 32.57 antimicrobial treatments/calf-year were 3.2 times more likely to have multidrug resistant E. coli in calf feces compared farms with <1.99 antimicrobial treatments/calf-year. Farms using hay or straw beddings were 5.1 times less likely to have multidrug resistant E. coli compared with those with other bedding materials including shavings or sawdust. Bedding management practices on farms may need to be investigated to reduce the potential effect on disseminating multidrug resistant bacteria. [ABSTRACT FROM AUTHOR]

The global surge in multi-drug resistant bacteria, including extended-spectrum β-lactamase (ESBL)-producing Escherichia coli has led to a growing need for new antibacterial compounds. Despite being promising, the potential of fish-derived antimicrobial peptides (AMPs) in combating ESBL-producing E. coli is largely unexplored. In this study, native African catfish antimicrobial peptides (NACAPs) were extracted from the skin mucus of farmed African catfish, Clarias gariepinus, using a combination of 10% acetic acid solvent hydrolysis, 5 kDa ultrafiltration, and C18 hydrophobic interaction chromatography. Peptides were then sequenced using Orbitrap Fusion Lumos Tribrid Mass Spectrometry. The identified peptides were screened for potential antibacterial activity using Random Forest and AdaBoost machine learning algorithms. The most promising peptide was chemically synthesized and evaluated in vitro for safety on rabbit red blood cells and activity against ESBL-producing E. coli (ATCC 35218) utilizing spot-on-lawn and broth dilution methods. Eight peptides ranging from 13 to 22 amino acids with molecular weights between 968.42 and 2434.11 Da were identified. Peptide NACAP-II was non-hemolytic to rabbit erythrocytes (p > 0.05) with a zone of inhibition (ZOI) of 22.7 ± 0.9 mm and a minimum inhibitory concentration (MIC) of 91.3 ± 1.2 μg/mL. The peptide is thus a candidate antibacterial compound with enormous potential applications in the pharmaceutical industry. However, further studies are still required to establish an upscale production strategy and optimize its activity and safety in vivo. [ABSTRACT FROM AUTHOR]

The antimicrobial properties of copper ions can reduce the overgrowth of microorganisms to a certain extent. That reduces the amount of antibiotics used, to avoid superbugs and potential harm. The authors reviewed the antimicrobial mechanisms of copper and copper‐containing nanoparticles (NPs), focusing on the factors influencing their antimicrobial properties. They concluded that the antimicrobial properties were better in environments conducive to the precipitation of copper ions and exposure to microorganisms. Comparing copper with other metal ions leads to the question of why copper is such an important antimicrobial metal ion. In recent years, with the development of science and technology and the understanding of the microscopic world, scientists have skillfully applied the antimicrobial properties of copper in various settings, from direct contact with food to breeding and hygienic environments, and have confirmed the safety of the application. However, because of the toxic effect of NPs, the future goal is to synthesize a copper‐containing NP with good biocompatibility and antibacterial efficiency to benefit human society. [ABSTRACT FROM AUTHOR]

Solid organ transplant (SOT) recipients are particularly susceptible to infections caused by multidrug-resistant organisms (MDRO) and are often the first to be affected by an emerging resistant pathogen. Unfortunately, their prevalence and impact on morbidity and mortality according to the type of graft is not systematically reported from high-as well as from low and middle-income countries (HIC and LMIC). Thus, epidemiology on MDRO in SOT recipients could be subjected to reporting bias. In addition, screening practices and diagnostic resources may vary between countries, as well as the availability of new drugs. In this review, we aimed to depict the burden of main Gram-negative MDRO in SOT patients across HIC and LMIC and to provide an overview of current diagnostic and therapeutic resources. [ABSTRACT FROM AUTHOR]

Background: Urinary tract infections (UTI) constitute a major public health problem, especially in developing countries such as Burkina Faso. They are commonly encountered in hospitals, particularly in patients suffering from chronic kidney disease whose management requires special measures to avoid treatment failures which are frequent. The objective of this study is to determine the microbial profiles of urinary tract infections (UTIs) in these patients. Methodology: This was a cross-sectional study of hospitalized patients with UTIs in the nephrology-haemodialysis department of the CHUB from August 1 to November 31, 2020. Socio-demographic and clinical data of selected patients were collected by a well-designed data collection form. Cytobacteriological analysis of urine (CBAU) was carried out on voided or catheter-urine sample of each patient using standard microbiological technique. The disc diffusion method in agar medium modified according to the recommendations of the 2020 CA-SFM-EUCAST was used to determine the antibiotic susceptibility of each isolate. Data were processed and analyzed using Excel 2013, IBM SPSS Statistics 25.0 and CSpro 7.5 software. Results: Urine samples were collected from a total of 77 eligible participants, 49 (63.6%) of which were CBAU positive, with 56 microbial pathogens isolated. Enterobacterales represented 58.9% (n=33), including 39.4% Escherichia coli (n=13) and 36.4% Klebsiella spp (n=12). Non-fermentative Gram-negative bacilli represented 7.1% (n=4) including Acinetobacter baumannii (n=3) and Pseudomonas aeruginosa (n=1). Staphylococcus aureus was isolated in 5.4% (n=3) and Candida spp in 28.6% (n=16). The most active antimicrobials in vitro against the bacterial pathogens were amikacin and imipenem, and clotrimazole and nystatin against the Candida spp. A total 35.7% (n=20) were multi-drug resistant bacteria with 32.1% by ESBL in Gram-negative bacteria and 66.7% (2/3) by MRSA in Grampositive bacteria. Conclusion: The high resistance of pathogens to antimicrobials, resulting in therapeutic failures, constitutes a significant challenge in the management of urinary tract infection, especially in people with chronic kidney disease. It is therefore necessary to put in place urgent measures aimed at the rational use of antimicrobials and strict compliance with good hospital hygiene practices. [ABSTRACT FROM AUTHOR]

Background: Bloodstream infections are serious health problem because of the significant morbidity and mortality they cause. The number of deaths increases in the presence of multidrug resistant bacteria. The aim of this study was to determine the bacteriological and resistance profiles of bacteria isolated from blood cultures. Methodology: This is a retrospective descriptive study over 3 years (1st January 2019 to 31st December 2021) of all blood cultures received in the Bacteriology-Virology Laboratory at CHU-YO. Bacteria were isolated from blood cultures after routine processing in automated BD BACTEC FX40 machine. Bacteria identification and antibiotic susceptibility test (AST) was by conventional biochemical tests and API 20E, and Kirby-Bauer disc diffusion method respectively from Jan to Sept 2019, and by BD Phoenix M50 from Sept 2019 to Dec 2021. All proven cases of bacteraemia documented by culture, identification and AST were included in the study. Data analysis was done using EPI-INFO 7.2.4.0 software. Results: A total of 335 pathogenic bacteria were isolated from non-duplicate blood cultures collected from a total of 2345 patients, with 1209 males and 1136 females, giving a male to female ratio of 1.06. Gram-negative bacilli accounted for 63.6% (n=213) with a predominance of Enterobacteriaceae (40.6%, n=136). The leading species were Klebsiella spp (18.5%, n=62) followed by E. coli (14.0%, n=47). Gram-positive cocci accounted for 36.4% (n=122), mostly Staphylococcus aureus (22.1%, n=74). Klebsiella spp and E. coli strains showed high levels of resistance to beta-lactams (60 to 71.0% for piperacillin-tazobactam, 87 to 89.0% for amoxicillin-clavulanic acid and 79 to 90.0% for ceftriaxone), fluoroquinolones (75 to 78.0% for ciprofloxacin) and sulphonamides (82 to 96.0% for cotrimoxazole). The lowest levels of resistance were observed with cefoxitin (5-20.0%) and imipenem (5-7.0%). Strain sensitivity to aminoglycosides was highly variable, ranging from 0-5.0% for amikacin to 54- 67.0% for gentamicin. The main mechanism of resistance of Klebsiella spp and E. coli strains to beta-lactam antibiotics was ESBL production; 64.5% (40/62) and 60.0% (28/47), respectively. Staphylococcus aureus strains were resistant to methicillin (MRSA) in 13.0% of cases. All were sensitive to fusidic acid and vancomycin. Conclusion: Klebsiella pneumoniae, E. coli and S. aureus are the main bacteria responsible for bacteremia in Burkina Faso. Their resistance to antibiotics is very high and remains of concern. The introduction of rapid tests to detect resistant bacteria directly from blood culture broths is essential for the early adaptation of empirical antibiotic therapy. [ABSTRACT FROM AUTHOR]

The emergence of the global problem of multi-drug resistant bacteria (MDR) is closely related to the improper use of antibiotics, which gives birth to an urgent need for antimicrobial innovation in the medical and health field. Silver nanoparticles (AgNPs) show significant antibacterial potential because of their unique physical and chemical properties. By accurately regulating the morphology, size and surface properties of AgNPs, the antibacterial properties of AgNPs can be effectively enhanced and become a next generation antibacterial material with great development potential.The detection of the inhibitory effect of AgNPs on MDR provides more possibilities for the research and development of new antimicrobial agents.Promote the formation of AgNPs by redox reaction; determine the minimum inhibitory concentration (MIC) of AgNPs to bacteria by broth microdilution method; evaluate the killing efficacy of AgNPs against multi-drug-resistant bacteria by plate counting; evaluate the inhibitory effect of AgNPs on biofilm construction by crystal violet staining; study the drug resistance of bacteria by gradually increasing the concentration of AgNPs; and detect the toxicity of AgNPs to cells by CCK-8 method.AgNPs has a significant bactericidal effect on a variety of drug-resistant bacteria. After exposure to AgNPs solution for 12 hours, the number of E. coli decreased sharply, and S. aureus was basically eliminated after 16 hours. In particular, AgNPs showed stronger inhibition against Gram-negative bacteria. In addition, AgNPs can effectively hinder the formation of bacterial biofilm, and its inhibitory effect increases with the increase of AgNPs solution concentration. When AgNPs is used for a long time, the development of bacterial resistance to it is slow. From the point of view of safety, AgNPs has no harmful effects on organisms and has biosafety.AgNPs can inhibit MDR, and the bacteriostatic ability of Gram-negative bacteria is higher than that of Gram-positive bacteria. It can also inhibit the formation of bacterial biofilm, avoid drug resistance and reduce cytotoxicity. [ABSTRACT FROM AUTHOR]

Some multidrug-resistant bacteria particularly Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacterspp (ESKAPE pathogens) are associated with nosocomial infections. This study investigated the antibacterial activities of Newbouldia laevis and Dracaena arborea against some ESKAPE pathogens isolated from hospital environments. One hundred and twenty-five (125) samples were collected from wounds, urine, and hospital beds from Bishop Shanahan Hospital Nsukka. Ethical clearance was obtained before the collection of samples. Bacteria were isolated and characterized using appropriate microbiological and biochemical techniques. Plants methanol extracts were prepared using standard method. Antibiotic sensitivity testing was done using the Kirby Bauer disc diffusion method following Clinical Laboratory Standards Institute (CLSI) guidelines 2024. Multi-drug resistant isolates were randomly selected for plant extract sensitivity testing. Staphylococcus aureus, Pseudomonas aeruginosa, and Klebsiella pneumonia isolates had a prevalence of 75%, 83.3%, and 78.6% respectively. Multiple antibiotic resistance indices (MARI) of the isolates showed mostly high values (0.5-1.0). Newbouldia laevis methanol extract showed varying degrees of antibacterial activity on most of the isolates at different concentrations (50, 100, 200, and 400 mg/mL). However, following the CLSI standard, only 100 mg/mL of the extract produced significant inhibition (≥ 11.0 mm) on 3/8 and 3/7 of S. aureus and P. aeruginosa susceptible isolates respectively; no inhibition was observed for K. pneumoniae. Dracaenaarborea had no activity against any of the isolates. These results buttress the need for the use of Newbouldia laevis extract as a promising alternative against antibioticresistant ESKAPE pathogens. [ABSTRACT FROM AUTHOR]

Objective: Preparation and characterization of nano-emulsion formulations for Asparagus densiflorus aerial and root parts extracts. Significance: Genus Asparagus is known for its antimicrobial and anticancer activities, however, freeze dried powder of aqueous – alcoholic extract prepared in this study, exhibited a limited water solubility, limiting its therapeutic application. Thus, encapsulation of its phytochemicals into nano-emulsion is proposed as a solution to improve water solubility, and facilitate its clinical translation. Methods: the composition of extracts for both aerial and root parts of Asparagus densiflorus was identified by HPLC and LC-MS analysis. Nano-emulsion was prepared via homogenization where a mixture of Castor oil: phosphate buffered saline (10 mM, pH 7.4): Tween 80: PEG 600 in a ratio of 10: 5: 2.5: 2.5, respectively. Nano-emulsion formulations were characterized for particle size, polydispersity index (PDI), zeta potential, TEM, viscosity and pH. Then, the antibacterial and anticancer activities of nano-emulsion formulations versus their pure plant counterparts was assessed. Results: The analysis of extracts identified several flavonoids, phenolics, and saponins which were reported to have antimicrobial and anticancer activities. Nano-emulsion formulations were monodispersed with droplet sizes ranging from 80.27 ± 2.05 to 111.16 ± 1.97 nm, and polydispersity index ≤0.3. Nano-emulsion formulations enhanced significantly the antibacterial (multidrug resistant bacteria causing skin and dental soft tissues infections) and anticancer (HuH7, HEPG2, H460 and HCT116) activities compared to their pure plant extract counterparts. Conclusion: Employing a nano-delivery system as a carrier for phytochemicals might be an effective strategy to enhance their pharmacological activity, overcome their limitations, and ultimately increase their potential for clinical applications. [ABSTRACT FROM AUTHOR]

Background: The incidence of microorganisms with extended-spectrum beta-lactamase (ESBL) is on the rise, posing a significant public health concern. The current application of machine learning (ML) focuses on predicting bacterial resistance to optimize antibiotic therapy. This study employs ML to forecast the occurrence of bacteria that generate ESBL and demonstrate resistance to multiple antibiotics (MDR). Methods: Six popular ML algorithms were initially trained on antibiotic resistance test patient reports (n = 489) collected from Al-Hussein/Salt Hospital in Jordan. Trained outcome models predict ESBL and multidrug resistance profiles based on microbiological and patients' clinical data. The results were utilized to select the optimal ML method to predict ESBL's most associated features. Results: Escherichia coli (E. coli, 82%) was the most commonly identified microbe generating ESBL, displaying multidrug resistance. Urinary tract infections (UTIs) constituted the most frequently observed clinical diagnosis (68.7%). Classification and Regression Trees (CART) and Random Forest (RF) classifiers emerged as the most effective algorithms. The relevant features associated with the emergence of ESBL include age and different classes of antibiotics, including cefuroxime, ceftazidime, cefepime, trimethoprim/ sulfamethoxazole, ciprofloxacin, and gentamicin. Fosfomycin nitrofurantoin, piperacillin/tazobactam, along with amikacin, meropenem, and imipenem, had a pronounced inverse relationship with the ESBL class. Conclusion: CART and RF-based ML algorithms can be employed to predict the most important features of ESBL. The significance of monitoring trends in ESBL infections is emphasized to facilitate the administration of appropriate antibiotic therapy. [ABSTRACT FROM AUTHOR]

The Global increase in colonization by multidrug-resistant (MDR) bacteria poses a significant concern. The precise impact of MDR colonization in solid organ transplant recipients (SOTR) remains not well established. To assess the impact of MDR colonization on SOTR's mortality, infection, or graft loss. Data from PROSPERO, OVID Medline, OVID EMBASE, Wiley Cochrane Library, ProQuest Dissertations, Theses Global, and SCOPUS were systematically reviewed, spanning from inception until 20 March 2023. The study protocol was registered with PROSPERO (CRD42022290011) and followed the PRISMA guidelines. Cohorts and case–control studies that reported on adult SOTR colonized by Methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), extended-spectrum β-lactamase (ESBL) or carbapenem-resistant Enterobacteriaceae. (CRE), or MDR-pseudomonas, and compared to noncolonized, were included. Two reviewers assessed eligibility, conducted a risk of bias evaluation using the Newcastle-Ottawa Scale, and rated certainty of evidence using the GRADE approach. We employed RevMan for a meta-analysis, using random-effects models to compute pooled odds ratios (OR) and 95% confidence intervals (CI). Statistical heterogeneity was determined using the I2 statistic. 15,202 SOTR (33 cohort, six case–control studies) were included, where liver transplant and VRE colonization (25 and 14 studies) were predominant. MDR colonization significantly increased posttransplant 1-year mortality (OR, 2.35; 95% CI, 1.63–3.38) and mixed infections (OR, 10.74; 95% CI, 7.56–12.26) across transplant types (p < 0.001 and I2 = 58%), but no detected impact on graft loss (p 0.41, I2 = 0). Subgroup analysis indicated a higher association between CRE or ESBL colonization with outcomes (CRE: death OR, 3.94; mixed infections OR, 24.8; ESBL: mixed infections OR, 10.3; no mortality data) compared to MRSA (Death: OR, 2.25; mixed infection: OR, 7.75) or VRE colonization (Death: p 0.20, mixed infections: OR, 5.71). MDR colonization in SOTR, particularly CRE, is associated with increased mortality. Despite the low certainty of the evidence, actions to prevent MDR colonization in transplant candidates are warranted. [ABSTRACT FROM AUTHOR]

Herein, silver ions modified α-Fe2O3 (Ag: α-Fe2O3) nanoparticles were synthesized using a sol-gel auto-combustion method comprising of dual phase i.e. trigonal structure of α-Fe2O3 and FCC structure of Ag. The refinement results verified the existence of both the phase with R-3c: R s and Fm-3 m space group. Transmission Electron Microscopy (TEM) showed the crystallite size around 34.24 ± 2.00 nm. The percentage of Ag0 and Ag+ verified through X-ray Photoelectron Spectroscopy (XPS) clearly indicate that around 74% of the Ag present is in the metallic form. The cyclic voltammetry showed that the Csp of the Ag: α-Fe2O3 NPs modified electrode is 132 Fg − 1 and 100 Fg − 1 when recorded at a scan rate of 50 mVs− 1 and 75 mVs− 1, respectively. The Zones of Inhibition (ZOI) against bacterial strains generated by utilizing Ag: α-Fe2O3 NPs are clearly showed the ZOI of 19 ± 1 mm against Bacillus subtilis. The synthesized nanoparticles exhibited higher inhibition against the bacterial strains in comparison to the standard antibiotic ampicillin. Further, cell viability analysis suggested to use a concentration of 9 to 12 µg/ml for Ag: α-Fe2O3in invitro experiments. [ABSTRACT FROM AUTHOR]

Copyright of Baghdad Science Journal is the property of Republic of Iraq Ministry of Higher Education & Scientific Research (MOHESR) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

A growing increase in the number of serious infections caused by multidrug resistant bacteria (MDR) is challenging our society. Despite efforts to discover novel therapeutic options, few antibiotics targeting MDR have been approved by the Food and Drug Administration (FDA). Lactic acid bacteria have emerged as a promising therapeutic alternative due to their demonstrated ability to combat MDR pathogens in vitro. Our previous co-culture studies showed Lacticaseibacillus rhamnosus CRL 2244 as having a potent killing effect against carbapenem-resistant Acinetobacter baumannii (CRAB) strains. Here we report that cell-free conditioned media (CFCM) samples obtained from Lcb. rhamnosus CRL 2244 cultures incubated at different times display antimicrobial activity against 43 different pathogens, including CRAB, methicillin-resistant Staphylococcus aureus (MRSA) and carbapenemase Klebsiella pneumoniae (KPC)-positive strains. Furthermore, transwell and ultrafiltration analyses together with physical and chemical/biochemical tests showed that Lcb. rhamnosus CRL 2244 secretes a <3 kDa metabolite(s) whose antimicrobial activity is not significantly impaired by mild changes in pH, temperature and various enzymatic treatments. Furthermore, sensitivity and time-kill assays showed that the bactericidal activity of the Lcb. rhamnosus CRL 2244 metabolite(s) enhances the activity of some current FDA approved antibiotics. We hypothesize that this observation could be due to the effects of Lcb. rhamnosus CRL 2244 metabolite(s) on cell morphology and the enhanced transcriptional expression of genes coding for the phenylacetate (PAA) and histidine catabolic Hut pathways, metal acquisition and biofilm formation, all of which are associated with bacterial virulence. Interestingly, the extracellular presence of Lcb. rhamnosus CRL 2244 induced the transcription of the gene coding for the CidA/LgrA protein, which is involved in programmed cell death in some bacteria. Overall, the findings presented in this report underscore the promising potential of the compound(s) released by Lcb. rhamnosus CRL2244 as an alternative and/or complementary option to treat infections caused by A. baumannii as well as other MDR bacterial pathogens. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the epidemiological characteristics and trends over time of carbapenemase-producing (e.g., KPC, NDM, VIM, IMP, and OXA-48) Gram-negative bacteria (CPGNB). Non-duplicated multi-drug resistant Gram-negative bacteria (MDRGNB) were collected from the First Affiliated Hospital of Zhengzhou University from April 2019 to February 2023. Species identification of each isolate was performed using the Vitek2 system and confirmed by matrix-assisted laser desorption ionization-time of flight mass spectrometry according to the manufacturer's instructions. PCR detected carbapenem resistance genes in the strains, strains carrying carbapenem resistance genes were categorized as CPGNB strains after validation by carbapenem inactivation assay. A total of 5705 non-repetitive MDRGNB isolates belonging to 78 different species were collected during the study period, of which 1918 CPGNB were validated, with the respiratory tract being the primary source of specimens. Epidemiologic statistics showed a significant predominance of ICU-sourced strains compared to other departments. Klebsiella pneumoniae, Escherichia coli, Acinetobacter baumannii, and Pseudomonas aeruginosa were the significant CPGNB in Henan, and KPC and NDM were the predominant carbapenemases. Carbapenem-resistant infections in Henan Province showed an overall increasing trend, and the carriage of carbapenemase genes by CPGNB has become increasingly prevalent and complicated. The growing prevalence of CPGNB in the post-pandemic era poses a significant challenge to public safety. [ABSTRACT FROM AUTHOR]

Since 2018, the 'Superbugs' initiative at Cardiff University (United Kingdom) has been delivering projects that take a research-driven approach to public engagement, involving rigorous evaluation of the methodologies of delivery and the mechanics of communication. The overall aim of Superbugs is to raise awareness and improve public knowledge of microbiology, infection and antimicrobial resistance (AMR). In the present project, four postgraduate students were recruited to undertake research projects as part of their Master of Science (MSc) studies. After a period of literature appraisals, the students chose to focus on the topic of personal and food hygiene and were tasked with collecting information on effective strategies for educating young children. Taking advantage of a focus group of primary school teachers, the students then designed evidence-informed educational activities and the evaluation strategies by which the impact of these would be assessed. A pilot delivery of these activities was carried out in a community setting at a local public library, before final delivery as part of a school outreach workshop. The MSc students produced three new elements of educational material; a story book, a treasure hunt and an interactive card game, primarily built around the concepts of challenge and gamification. Feedback collected from primary school pupils aged 6-7 years old and teachers indicated that the activities developed were successful in both being engaging to young people and resulting in an improved knowledge on the chosen topics. Taken together, we present evidence that postgraduate research training, underpinned by active and service learning, represents a valid and effective way of delivering impactful public engagement. In turn, the experience holds benefit for the students not only in terms of their academic study and core scientific skills, but also their wider appreciation and confidence in being effective engagers and science communicators. [ABSTRACT FROM AUTHOR]

The ESKAPE pathogens, including Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp., are multidrug-resistant (MDR) nosocomial pathogens that can "escape" current antimicrobials through various mechanisms. These pathogens are listed as urgent or serious threats to public health by organizations such as the World Health Organization (WHO) and the Center for Disease Control and Prevention (CDC). The article discusses the intrinsic and acquired antimicrobial resistance mechanisms employed by these pathogens and explores future therapeutic avenues, such as bacteriophage therapy, antisense oligonucleotide (ASO) therapeutics, and antimicrobial peptides (AMPs). However, more research is needed before these novel therapeutics can become standard interventions. The review emphasizes the importance of addressing antimicrobial resistance through global research efforts, antimicrobial stewardship, infection prevention and control measures, strict antibiotic prescription, and public education. [Extracted from the article]

Nanoparticle-based therapies are emerging as a pivotal frontier in biomedical research, showing their potential in combating infections and facilitating wound recovery. Herein, selenium-tellurium dopped copper oxide nanoparticles (SeTe-CuO NPs) with dual photodynamic and photothermal properties were synthesized, presenting an efficient strategy for combating bacterial infections. In vitro evaluations revealed robust antibacterial activity of SeTe-CuO NPs, achieving up to 99% eradication of bacteria and significant biofilm inhibition upon near-infrared (NIR) irradiation. Moreover, in vivo studies demonstrated accelerated wound closure upon treatment with NIR-activated SeTe-CuO NPs, demonstrating their efficacy in promoting wound healing. Furthermore, SeTe-CuO NPs exhibited rapid bacterial clearance within wounds, offering a promising solution for wound care. Overall, this versatile platform holds great promise for combating multidrug-resistant bacteria and advancing therapeutic interventions in wound management. Metal-based nanoparticles are promising agents used for photothermal and photodynamic therapy, and as an efficient strategy against multi-drug resistant bacteria. Here, the authors report a one-pot synthesis of SeTe-CuO nanoparticles for such dual-mode therapy, achieving near-infrared activated eradication of bacteria and inhibition of biofilm formation in vitro, as well as promoting wound healing in vivo. [ABSTRACT FROM AUTHOR]

Background and Objectives: Bloodstream infection (BSI) is defined by the presence of viable microorganisms in the bloodstream. BSI is one of the major causes of sepsis and subsequent adverse clinical outcomes all across the globe. The present study was undertaken to identify clinico-epidemio-microbiological variables associated with 30-day mortality in patients having BSI with WHO priority pathogens. Materials and Methods: The study was conducted at a public sector tertiary care institute in central India from April 2019 to March 2021. Blood samples collected from patients with clinical suspicion of sepsis, were processed by automated bacterial culture system and interpreted as per CLSI guidelines. Calculated sample size was 150. Data was analyzed by R software. Results: Respiratory tract infection was the most common source (43.3%) of BSI, followed by the gastrointestinal (20%) and urinary tract (18.7%). Among the patients, 33% required invasive mechanical ventilation, and 31% required inotropes. Diabetes mellitus (DM) was the most common co-morbidity (34%). The incidence of multi-drug resistant organisms (MDRO) was 59.3%. Escherichia coli was the most commonly (24%) isolated organism, followed by Klebsiella pneumoniae (17.3%) and Acinetobacter baumannii (16%). Conclusion: Higher age, higher qSOFA score / SIRS score / mean SOFA score at presentation had higher mortality. Use of mechanical ventilation and inotropes during treatment and isolation of critical category organisms of WPP and multi drug resistant organisms were independent 30-day mortality predictors. [ABSTRACT FROM AUTHOR]

Antimicrobial drug resistance within ESKAPE pathogens is a formidable global challenge necessitating innovative solutions. This review explores a multifaceted strategy incorporating nanotechnology, CRISPR/Cas9, and other cutting-edge approaches to effectively combat multidrug resistance in ESKAPE bacteria. Nanotechnology presents a promising avenue through targeted drug delivery systems like antibiotic nanoparticles and antibiotic–antibody conjugates (AACs). While these nanostructures aim to enhance therapeutic efficacy and mitigate resistance spread, challenges such as anti-PEG antibodies and optimal drug release must be considered. Inspired by successful anticancer nanomedicines, nanotechnology seeks to optimize drug penetration and retention within infected tissues. The revolutionary CRISPR/Cas9 gene-editing technology offers a precise and tailored approach by selectively targeting and modifying bacterial resistance genes. This holds the potential to reverse or eliminate drug resistance in ESKAPE pathogens, though challenges like off-target effects and efficient delivery mechanisms require attention for clinical translation. Additionally, alternative approaches such as fecal microbial transplantation, bacteriophage therapy, and probiotic bacterial replacement are actively explored in clinical trials. These strategies diversify the arsenal against antibiotic resistance by targeting unique vulnerabilities in ESKAPE pathogens. A comprehensive and multidisciplinary strategy is imperative to effectively address antimicrobial drug resistance in ESKAPE pathogens. Integration of nanotechnology, CRISPR/Cas9, and emerging approaches offers a synergistic solution, holding promise in overcoming the challenges posed by these resilient multidrug-resistant bacteria. This review provides insights into current research, challenges, and potential breakthroughs, emphasizing the urgency for collaborative efforts to safeguard global health. [ABSTRACT FROM AUTHOR]

Healthcare-associated infections (HAIs) can pose significant risks to patients with cardiovascular disease due to the compromised nature of their health and potential vulnerabilities. In order to reduce the incidence of HAIs and prevent the spread of antibiotic-resistant organisms, it is mandatory to develop surveillance systems. We undertook a retrospective case–control study of all patients presenting HAIs who were admitted to the intensive care unit (ICU) to assess risk factors associated with death among patients with cardiovascular disease. Patients admitted to the ICU who died were more likely to present an infection with a multidrug-resistant bacterium, an infection with Acinetobacter baumannii, and to suffer from acute myocardial infarction. Among the patients enrolled in the study, a higher probability of death was also observed in association with certain Gram-negative pathogens such as Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa. The longer the patient remains admitted in the ICU, the higher the risk of acquiring an infection that can often become fatal. A nosocomial infection, particularly in patients with cardiovascular disease, also increases the length of hospitalization, which will lead to increased expenditure. For this reason, new prophylactic methods and therapeutic approaches are needed, and researchers' efforts should be directed in this direction. [ABSTRACT FROM AUTHOR]

Past anti-bacterial use of bacteriophages (phage therapy) is already well reviewed as a potential therapeutic response to the emergence of multidrug-resistant, pathogenic bacteria. Phage therapy has been limited by the following. (1) The success rate is too low for routine use and Food and Drug Administration (FDA) approval. (2) Current strategies of routine phage characterization do not sufficiently improve the success rate of phage therapy. (3) The stability of many phages at ambient temperature is not high enough to routinely store and transport phages at ambient temperature. In the present communication, we present new and previous data that we interpret as introductory to biophysically and efficiently transforming phage therapy to the needed level of effectiveness. Included are (1) procedure and preliminary data for the use of native gel electrophoresis (a low-cost procedure) for projecting the therapy effectiveness of a newly isolated phage, (2) data that suggest a way to achieve stabilizing of dried, ambient-temperature phages via polymer embedding, and (3) data that suggest means to increase the blood persistence, and therefore the therapy effectiveness, of what would otherwise be a relatively low-persistence phage. [ABSTRACT FROM AUTHOR]

Copyright of Journal of University of Anbar for Pure Science is the property of Republic of Iraq Ministry of Higher Education & Scientific Research (MOHESR) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Aims: Multidrug-resistant bacteria urinary tract infections (MDR-UTI) are a global concern, leading to increased morbidity, mortality and financial costs. The aim of this study was to determine the prevalence of MDR-UTI and establish the epidemiological profile of UTI due to different phenotypes of MDR-UTI. Methodology and results: This is a retrospective study of MDR-UTI assessed at the microbiology laboratory of Mohammed VI University Hospital Center of Oujda over 37 months from March 2016 to April 2019. The study included all requests for cytobacteriological examination of urine (CBEU) according to the instructions of the medical microbiology guidelines. An agar medium was utilized for bacterial culture experimentation. Antibiotic susceptibility testing was performed according to the European Committee on Antimicrobial Susceptibility Testing guidelines. CBEU in UTIs allowed the isolation of 1078 isolates. They were dominated by Gram-negative bacteria (87.65%; n=945), followed by Gram-positive bacteria for 12.34% (n=133). This included 181 (16.80%) multidrug-resistant strains, which were dominated by extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) (n=144; 79.55%). Young male adults exhibited a higher occurrence of isolated ESBL-E and carbapenem-resistant Acinetobacter baumannii (CRAB). As for the distribution by department, there was a near equality between the MDR isolates isolated from outpatients (n= 88; 49%) versus the inpatients (n= 93; 51%). Exactly 152 (84%) isolated MDR cases were observed in patients who did not have a urinary catheter, 157 (87%) and 141 (78%) cases of MDR of UTI were not associated with care and occurred in non-immunocompromised patients, respectively. Prior antibiotic exposure was observed in only 58 (32%) cases. Conclusion, significance and impact of study: This study confirmed the increasing prevalence of multidrug-resistant urinary tract infections in the community and hospitals. The fight against this problem will require all stakeholders' involvement to achieve the goals from one health perspective in line with international agenda. [ABSTRACT FROM AUTHOR]

Antibiotic resistance (AR) is a growing health crisis that has remained underrepresented in coverage across major news publications in the U.S. despite increasing rates of related disease outbreaks and mortality worldwide. This study used content analysis to examine the coverage of AR in two major U.S. news publications before the COVID-19 pandemic (2018-2019) and during it (2020-2021). Coverage of AR in The New York Times (NYT) and The Washington Post (WP) was analyzed according to the use of frames, the quantity of articles published, and a number of other variables including stakeholders, diseases, and terms referring to AR. These factors were used to assess how coverage of AR differed before and during the COVID-19 pandemic, and how it differed between the two newspapers. Pre-COVID-19 coverage focused on AR as an isolated pandemic, while coverage during the early years of the COVID-19 pandemic often used AR as a supplementary component of the coverage to the main topic of COVID-19. This study found that both before and during the outbreak of COVID-19, the majority of the observed articles did not fully explain the scope, severity, or solution for the AR crisis. Instead, they provided readers with baseline information, framing AR as a contemporary issue and generally encouraging action but included very few tangible suggestions for every day, individual action for readers. [ABSTRACT FROM AUTHOR]

Infections due to multidrug-resistant organisms (MDRO) are a serious concern for public health with high morbidity and mortality. Though many antibiotics have been introduced to manage these infections, there are remaining concerns regarding the optimal management of Gram-positive MDROs. A literature search on the PubMed/Medline database was conducted. We applied no language and time limits for the search strategy. In this narrative review, we discuss the current options for managing Gram-positive MDROs as well as non-traditional antibacterial agents in development. Despite their introduction more than 70 years ago, glycopeptides are still the cornerstone in treating Gram-positive infections: all registrative studies of new antibiotics have glycopeptides as control; these studies are designed as not inferior studies, therefore it is almost impossible to give recommendations other than the use of glycopeptides in the treatment of Gram-positive infections. The best evidence on treatments different from glycopeptides comes from post-hoc analysis and meta-analysis. Non-traditional antibacterial agents are being studied to aid in short and effective antibiotic therapies. The use of non-traditional antibacterial agents is not restricted to replacing traditional antibacterial agents with alternative therapies; instead, they should be used in combination with antibiotic therapies. [ABSTRACT FROM AUTHOR]

The clinical role of Acinetobacter baumannii has been highlighted in numerous infectious syndromes with a high mortality rate, due to the high prevalence of multidrug-resistant (MDR) isolates. The treatment and eradication of this pathogen is hindered by biofilm-formation, providing protection from noxious environmental factors and antimicrobials. The aim of this study was to assess the antibiotic susceptibility, antiseptic susceptibility and biofilm-forming capacity using phenotypic methods in environmental A. baumannii isolates. One hundred and fourteen (n = 114) isolates were collected, originating from various environmental sources and geographical regions. Antimicrobial susceptibility testing was carried out using the disk diffusion method, while antiseptic susceptibility was performed using the agar dilution method. Determination of biofilm-forming capacity was carried out using a microtiter-plate based method. Resistance in environmental A. baumannii isolates were highest for ciprofloxacin (64.03%, n = 73), levofloxacin (62.18%, n = 71) and trimethoprim-sulfamethoxazole (61.40%, n = 70), while lowest for colistin (1.75%, n = 2). Efflux pump overexpression was seen in 48.25% of isolates (n = 55), 49.12% (n = 56) were classified as MDR. 6.14% (n = 7), 9.65% (n = 11), 24.65% (n = 28) and 59.65% (n = 68) of isolates were non-biofilm producers, weak, medium, and strong biofilm producers, respectively. No significant differences were observed between non-MDR vs. MDR isolates regarding their distribution of biofilm-producers (P = 0.655). The MIC ranges for the tested antiseptics were as follows: benzalkonium chloride 16–128 μg mL−1, chlorhexidine digluconate 4–128 μg mL−1, formaldehyde 64–256 μg mL−1 and triclosan 2–16 μg mL−1, respectively. The conscientious use of antiseptics, together with periodic surveillance, is essential to curb the spread of these bacteria, and to maintain current infection prevention capabilities. [ABSTRACT FROM AUTHOR]

Background: Urinary tract infections are common bacterial and fungal infections in humans, occurring both in the community and in immunocompromised patients in healthcare settings. Urinary tract infections have a significant health impact on HIV-infected patients. Nowadays, drug-resistant pathogens are widespread poses a serious clinical risk, and causes urinary tract infection. The common agents of bacteria and fungi that cause urinary tract infection are Escherichia coli followed by Klebsiella pneumonia, Staphylococcus saprophyticus, Enterococcus faecalis, group B streptococcus, Proteus mirabilis, Pseudomonas aeruginosa, Staphylococcus aureus and Candida. albicans. This study aimed to investigate uro-pathogen, multidrug resistance pattern of bacteria, and associated factors of community-acquired urinary tract infection among HIV-positive patients attending antiretroviral therapy in Dessie comprehensive specialized hospital, Northeast Ethiopia from February 1, 2021, to March 30, 2021. Methods: An institutional-based cross-sectional study was conducted at Dessie Comprehensive Specialized Hospital. Socio-demographic and clinical data were collected by using structured questionnaires from HIV patients suspected of community-acquired urinary tract infections. About 10 ml of clean-catch midstream urine was collected and inoculated into Blood agar, MacConkey, and Cysteine lactose electrolyte deficient media. Yeasts were identified by using Gram stain, germ tube test, carbohydrate fermentation, assimilation tests, and chromogenic medium. Gram stain and biochemical tests were performed to identify isolates and an antimicrobial susceptibility pattern was performed on disc diffusion techniques. Data were entered and analyzed using SPSS version 25. Both bivariate and multivariable logistic regression analysis was performed and a P value of < 0.05 with an adjusted odds ratio with their 95% confidence interval (CI) was used as statistically significant associations. Results: From the total 346 study participants, 92 (26.6%) were culture positive 75 (81.52%) were bacterial and 17 (18.48%) were fungal pathogens. From a total of 75 bacteria isolates 51(68%) were Gram-negative bacteria and the most commonly isolated bacteria were E. coli 16 (21.33%) followed by K. pneumoniae 11(14.67%) and enterococcus species 10(10.87. Of the 17 fungal isolates of fungi, 8(47.1%) were represented by C. tropicalis. Of the isolated bacteria, 61(81.3%) were resistant to three and above classes of antibiotics (drug classes). About 13 (81.3%) of E. coli, 9(81.8%) of K. pneumoniae, 8(80%) of Enterococcus species, 7 (77.8%) of P. aeruginosa, and CoNs 7(87.5%) were the most frequently exhibited three and above classes of antibiotics (multi-drug resistance). Amikacin and gentamicin were effective against Gram-negative Uro-pathogens. Participants aged>44year, female, being daily labor, being farmer, unable to read and write, patients with CD4 count of ≤ 200 cells/mm3 and CD4 count of 201–350 cells/mm3, who had chronic diabetics, patients having a history of hospitalization and who had urgency of urinations were statistically significant association with significant urinary tract infections. Conclusion: The burden of community-acquired urinary tract infections among HIV patients is alarmingly increased. Therefore, behavior change communications might be considered for promoting the health status of HIV patients. Moreover, CD4 level monitoring and therapeutics selection based on microbiological culture are quite advisable for the management of urinary tract infections of HIV patients. [ABSTRACT FROM AUTHOR]

Urinary tract infections (UTIs) are common urological diseases that easily relapse and have led to an increasing economic and health burdens. The China Antimicrobial Surveillance Network (CHINET) system is one of the most influential antimicrobial resistance surveillance networks in China. This study analyzed antimicrobial resistance and distribution trends of uropathogens from 2015 to 2021 using the CHINET system. A total of 261,893 non-duplicate strains were collected; Gram-positive bacteria accounted for 23.8% while Gram-negative bacteria accounted for 76.2%. Escherichia coli, Enterococcus faecium, Klebsiella pneumoniae, and Enterococcus faecalis were the most common species. The resistance to vancomycin, linezolid, and teicoplanin in E. faecalis and E. faecium was less than 3%. The prevalence of carbapenem-resistant strains of E. coli, K. pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii was 1.7%, 18.5%, 16.4%, and 40.3%, respectively. The prevalence of carbapenem-resistant A. baumannii increased from 27.6% in 2015 to 43.4% in 2021. The prevalence of methicillin-resistant Staphylococcus aureus decreased from 40.6% in 2015 to 22.9% in 2021. The resistance rates to most β-lactam antimicrobials, aminoglycosides and fluoroquinolones in E. coli, K. pneumoniae, P. aeruginosa and A. baumannii isolated from ICU inpatients were significantly higher than in those isolated from outpatients and non-ICU inpatients. This study indicates that E. coli, Enterococcus, and K. pneumoniae were the most commonly isolated uropathogens in China. The bacterial species isolated and their antimicrobial resistance patterns differed in different patient populations. More attention must be paid uropathogen resistance surveillance to provide data for the rational use of antimicrobial agents. [ABSTRACT FROM AUTHOR]

Background: Infection prevention and control (IPC) research has long neglected the home healthcare sector with its unique challenges. This study aimed to gain an understanding of the barriers to the implementation of infection prevention practices relevant to this setting, the related attitudes, perceived relevance and priorities from the home healthcare worker perspective in Switzerland. Methods: The mixed-method study involved semi-structured interviews (n = 18) and an anonymous web-based survey (n = 144) among nursing assistants and nurses from two home healthcare organizations in northwest Switzerland. Questions in both sub-studies focused on perceived challenges to infection prevention practices, perceived relevance, and related attitudes and mitigation strategies. Using an exploratory-sequential design, survey questions were designed to quantify and complement the findings from the interview study. Results: Healthcare workers in these two organisations felt adequately protected, trained and supported by their organisations regarding IPC (survey agreement rates > 90%). General challenges to IPC in the home environment most agreed on were lack of cleanliness, lack of space, and the priorities of the patient to be respected (survey agreement rates 85.4%, 77.1%, and 70.8%, respectively). Practices and perceived challenges in the case of colonisation with multi-drug resistant organisms (MDRO) and potentially infectious diarrheal or respiratory illnesses varied highly regarding information transfer, use of protective equipment, and use and disinfection practices of multi-use equipment. Challenges to hand hygiene, sharps safety, waste management and decontamination of equipment did not feature as a prominent concern. Conclusions: This study is the first to characterise the implementation of infection prevention practices and the related challenges in home healthcare in Switzerland. Home healthcare workers describe various challenges related to infection prevention practices as largely manageable in their work routine, and generally show satisfaction with the support provided by their organisations regarding IPC precautions. Key findings regarding challenges amenable to interventions include uncertainty and inconsistency regarding the management of MDRO colonisation and acute illnesses, and gaps in information transfer. Those challenges may benefit from both organisational interventions and further research into the level of precautions that are appropriate to the home healthcare setting. [ABSTRACT FROM AUTHOR]

Drug combinations and repurposing have recently provided promising alternatives to cope with the increasingly severe issue of antibiotic resistance and depletion of natural drug molecular repertoires that undermine traditional antibacterial strategies. Closantel, an effective adjuvant, reverses antibiotic resistance in gram-negative bacteria. Herein, the combined antibacterial enantioselectivity of closantel is presented through separate enantiomer studies. Despite yielding unexpected differences, two closantel enantiomers (R, S) increased colistin activity against gram-negative bacteria both in vitro and in vivo. The fractional inhibitory concentration indices of R-closantel and Sclosantel combined with colistin against Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli ranged from 0.0087 to 0.5004 and from 0.0117 to 0.5312, respectively. This difference was further demonstrated using growth inhibition assays and time-killing curves. Mechanistically, a higher intracellular concentration of R-CLO is more effective in enhancing the antimicrobial activity of combination. A mouse cutaneous infection model confirmed the synergistic stereoselectivity of closantel. This discovery provides novel insights for developing precision medication and containment of increasing antibiotic resistance. [ABSTRACT FROM AUTHOR]

Background: Infections caused by multidrug-resistant gram-negative bacteria present a severe threat to global public health. The WHO defines drug-resistant Klebsiella pneumoniae as a priority pathogen for which alternative treatments are needed given the limited treatment options and the rapid acquisition of novel resistance mechanisms by this species. Longitudinal descriptions of genomic epidemiology of Klebsiella pneumoniae can inform management strategies but data from sub-Saharan Africa are lacking. Methods: We present a longitudinal analysis of all invasive K. pneumoniae isolates from a single hospital in Blantyre, Malawi, southern Africa, from 1998 to 2020, combining clinical data with genome sequence analysis of the isolates. Results: We show that after a dramatic increase in the number of infections from 2016 K. pneumoniae becomes hyperendemic, driven by an increase in neonatal infections. Genomic data show repeated waves of clonal expansion of different, often ward-restricted, lineages, suggestive of hospital-associated transmission. We describe temporal trends in resistance and surface antigens, of relevance for vaccine development. Conclusions: Our data highlight a clear need for new interventions to prevent rather than treat K. pneumoniae infections in our setting. Whilst one option may be a vaccine, the majority of cases could be avoided by an increased focus on and investment in infection prevention and control measures, which would reduce all healthcare-associated infections and not just one. [ABSTRACT FROM AUTHOR]