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Tuberculosis remains a formidable global health challenge, with drug-resistant strains posing significant hurdles in its eradication efforts. Addressing the challenge of drug-resistant and multidrug-resistant tuberculosis requires a multifaceted approach encompassing enhanced diagnostics, novel therapeutics, and patient-centered care models. This study aims to find the treatment outcomes of DR-TB patients registered at tertiary care settings along estimation of impact of associated adverse events. This retrospective study was undertaken at a tertiary care setting of Lahore Punjab Pakistan during the year 2023. Using a predefined scheme of variables data was collected Regression analysis was applied by taking death and treatment failure as adverse outcomes excluding the treatment defaulter patients as their final fate was not known. A total of 1438 drug resistant TB patients comprising of 49.4% males and 50.6 females with mean age of patients at the time of registration as 35.08±15.91 years were included in final analysis. A high number of 17.4% patients were died, 56.2% patients were cured and 10.4% successfully completed their treatment. Rate of loss to follow up was noted to be 11.1% and treatment failure were 4.9% in this study. Regression model showed that patients aged =34 years, patients having previous history of treatment and treatment strategy other than LTR are at greater risk of adverse events. Overall success rate of treatment remained to be 66.6% remained far below of the target laid down by the WHO. A high mortality rate was found to be associated with drug resistant tuberculosis patients. Age =34 years, prior history of TB treatment and treatment strategy are risk factors for death of DR TB patients. [ABSTRACT FROM AUTHOR]

Expected and unexpected donor-derived infections are a rare complication of solid organ transplantation, but can result in significant morbidity and mortality. Over the last years, the growing gap existing between patients on the waiting list and available organs has favored the use of organs from donors with suspected or confirmed infections, thanks to the improvement of risk mitigation strategies against transmission of well recognized and emerging infections. Given the recent developments, the particular interest of this review is to summarize data on how to maximize utilization of HIV+ donors in HIV+ recipients, the use of HCV-viremic donors and HBV positive donors. This article also covers the implications for recipient of organs from donors with bacteremia and the challenge of multidrug resistant (MDR) infections. Lastly this review describes emerging risks associated with recent Coronavirus Disease-2019 (COVID-19) pandemics. [ABSTRACT FROM AUTHOR]

Background: The 2016 IDSA guideline recommends a treatment duration of at least 7 days for hospital-acquired (HAP)/ventilator-associated pneumonia (VAP). The limited literature has demonstrated higher rates of recurrence for non-glucose fermenting gram-negative bacilli with short course therapy, raising the concern of optimal treatment duration for these pathogens. Therefore, we aimed to compare the outcomes for patients receiving shorter therapy treatment (≤ 8 days) versus longer regimen (> 8 days) for the treatment of multidrug resistant (MDR) Pseudomonas pneumonia. Methods: A single-center, retrospective cohort study was conducted to evaluate adult patients receiving an antimicrobial regimen with activity against MDR Pseudomonas aeruginosa in respiratory culture between 2017 and 2020 for a minimum of 6 consecutive days. Exclusion criteria were inmates, those with polymicrobial pneumonia, community-acquired pneumonia, and infections requiring prolonged antibiotic therapy. Results: Of 427 patients with MDR P. aeruginosa respiratory isolates, 85 patients were included. Baseline characteristics were similar among groups with a median age of 65.5 years and median APACHE 2 score of 20. Roughly 75% had ventilator-associated pneumonia. Compared to those who received ≤ 8 days of therapy, no difference was seen for clinical success in patients treated for more than 8 days (80% vs. 65.5%, p = 0.16). The number of 30-day and 90-day in-hospital mortality, 30-days relapse, and other secondary outcomes did not significantly differ among the treatment groups. Conclusions: Prolonging treatment duration beyond 8 days did not improve patient outcomes for MDR P. aeruginosa HAP/VAP. [ABSTRACT FROM AUTHOR]

Fungal infections are a significant threat to human health and the environment. The emergence of multidrug-resistant strains of fungi and the growing prevalence of azole resistance in invasive fungal infections exacerbate the problem, with efflux pumps being a major cause of antifungal resistance and a prime target for several counteractive strategies. In Candida albicans, the ATP-binding cassette superfamily transporter CaCdr1p is the predominant efflux pump involved in azole resistance. Marine organisms have unique phenotypic characteristics to survive in challenging environments, resulting in biologically active compounds. The cyclodepsipeptides unnarmicin A and C have shown promising results as inhibitors of rhodamine 6G efflux in cells expressing CaCdr1p. Herein, a series of unnarmicin analogues were designed and docked against a CaCdr1p efflux pump based on the cryogenic electron microscopy structure available to select the most promising compounds. Analogue 33 was predicted to be the best considering its high affinity for the efflux pump and pharmacokinetic profile. These results pave the way for further synthesis and in vitro biological studies of novel unnarmicins seeking a synergistic effect with fluconazole. [ABSTRACT FROM AUTHOR]

Cannabis sativa L. has garnered attention as a potential source for new antimicrobial agents, particularly due to the increased prevalence of microbial resistance to conventional antimicrobials and the emergence of multidrug-resistant pathogens. This review, conducted according to the PRISMA 2020 statement, systematically analyzed the antimicrobial properties of C. sativa extracts and cannabinoids against various bacteria, fungi, viruses, and parasites. Data were collected from the scientific literature (102 papers) and clinical trials (5 studies) from 2014 to June 2024. Findings revealed that cannabinoids, especially CBD, demonstrate significant antimicrobial activity against Gram-positive bacteria like MRSA, Gram-negative bacteria such as Pseudomonas aeruginosa, various Candida species, SARS-CoV-2, and HIV. Additionally, CBD showed efficacy against parasitic infections like Echinococcus granulosus and Leishmania species. These results suggest that cannabinoids may represent a new class of antimicrobial agents with unique and diverse mechanisms of action, potentially effective in broad-spectrum therapies. This study highlights the urgent need for further research and standardized clinical trials to validate these findings and to develop cannabinoid-based treatments. The antimicrobial properties of C. sativa align with WHO priorities and support global health initiatives, offering promising avenues for addressing antimicrobial resistance and improving public health outcomes. [ABSTRACT FROM AUTHOR]

VIM-type-producing Gram-negative bacteria (GNB) infections are difficult to treat. This is a retrospective single-center study of 34 patients who received cefiderocol for the treatment of VIM-type-producing GNB infections, including 25 Pseudomonas spp., 7 Enterobacterales, and 5 Achromobacter sp. Primary outcomes were clinical failure (defined as death, lack of clinical improvement, or a switch to another drug) at day 14 and 30-day all-cause mortality. The median age was 59 years (IQR 53.7–73.4), and the median Charlson comorbidity index was 3.5 (IQR 2–5). The main infections were respiratory tract infections (n = 9, 27%) and skin and soft tissue infections (n = 9, 27%). Eight patients exhibited bacteremia. In 9/17 patients with a drainable focus, drainage was performed. The median cefiderocol treatment duration was 13 days (IQR 8–24). Five patients (15%) experienced clinical failure on day 14, and the thirty-day mortality rate was 9/34 (27%); two cases occurred because of an uncontrolled infection source, and one was due to a new infection caused by the same bacteria. The other six deaths were unrelated to the index infection. Five patients experienced microbiological recurrence within three months. Susceptibility testing revealed the development of cefiderocol resistance in 1/7 cases with persistent or recurrent positive cultures. Cefiderocol, even in monotherapy, could be considered for the treatment of VIM-type-producing GNB infections. [ABSTRACT FROM AUTHOR]

Cannabis sativa L. has garnered attention as a potential source for new antimicrobial agents, particularly due to the increased prevalence of microbial resistance to conventional antimicrobials and the emergence of multidrug-resistant pathogens. This review, conducted according to the PRISMA 2020 statement, systematically analyzed the antimicrobial properties of C. sativa extracts and cannabinoids against various bacteria, fungi, viruses, and parasites. Data were collected from the scientific literature (102 papers) and clinical trials (5 studies) from 2014 to June 2024. Findings revealed that cannabinoids, especially CBD, demonstrate significant antimicrobial activity against Gram-positive bacteria like MRSA, Gram-negative bacteria such as Pseudomonas aeruginosa, various Candida species, SARS-CoV-2, and HIV. Additionally, CBD showed efficacy against parasitic infections like Echinococcus granulosus and Leishmania species. These results suggest that cannabinoids may represent a new class of antimicrobial agents with unique and diverse mechanisms of action, potentially effective in broad-spectrum therapies. This study highlights the urgent need for further research and standardized clinical trials to validate these findings and to develop cannabinoid-based treatments. The antimicrobial properties of C. sativa align with WHO priorities and support global health initiatives, offering promising avenues for addressing antimicrobial resistance and improving public health outcomes.

Abstract Background The 2016 IDSA guideline recommends a treatment duration of at least 7 days for hospital-acquired (HAP)/ventilator-associated pneumonia (VAP). The limited literature has demonstrated higher rates of recurrence for non-glucose fermenting gram-negative bacilli with short course therapy, raising the concern of optimal treatment duration for these pathogens. Therefore, we aimed to compare the outcomes for patients receiving shorter therapy treatment (≤ 8 days) versus longer regimen (> 8 days) for the treatment of multidrug resistant (MDR) Pseudomonas pneumonia. Methods A single-center, retrospective cohort study was conducted to evaluate adult patients receiving an antimicrobial regimen with activity against MDR Pseudomonas aeruginosa in respiratory culture between 2017 and 2020 for a minimum of 6 consecutive days. Exclusion criteria were inmates, those with polymicrobial pneumonia, community-acquired pneumonia, and infections requiring prolonged antibiotic therapy. Results Of 427 patients with MDR P. aeruginosa respiratory isolates, 85 patients were included. Baseline characteristics were similar among groups with a median age of 65.5 years and median APACHE 2 score of 20. Roughly 75% had ventilator-associated pneumonia. Compared to those who received ≤ 8 days of therapy, no difference was seen for clinical success in patients treated for more than 8 days (80% vs. 65.5%, p = 0.16). The number of 30-day and 90-day in-hospital mortality, 30-days relapse, and other secondary outcomes did not significantly differ among the treatment groups. Conclusions Prolonging treatment duration beyond 8 days did not improve patient outcomes for MDR P. aeruginosa HAP/VAP.

Tuberculosis (TB) remains a disease of clinical and public health importance globally with over nine million cases occurring yearly. An increasing number of cases has been identified all over the world in the past two decades because of the Human Immunodeficiency Virus pandemic. The emergence of mutated drug resistant and multidrug resistant strains offers new challenges to the clinician as well as the public health physician. The present case report draws attention to the problem of multidrug resistant TB and the implications for TB control if not adequately tackled.

There is scant information on Salmonella in indigenous poultry in Nigeria. We investigated the occurrence and characterized Salmonella serovars in indigenous poultry and their drinking water sources to enhance the monitoring of the infection in poultry and to promote public health. We collected 1208 samples, poultry droppings (n = 1108), and water (n = 100) across 15 markets in North Central Nigeria. Salmonella spp. were isolated following World Organisation for Animal Health guidelines. Salmonella spp., confirmed through invA gene detection by a polymerase chain reaction assay, were 6.8% (75/1108) droppings and 3% (3/100) water. Susceptibility testing against 13 antimicrobials showed 60.3% (47/78) susceptibility to all the antimicrobials tested while 14.1% (11/78) were multidrug resistant. Serotyping and whole-genome sequencing were carried out on 44 of the isolates, and 23 different serovars were identified. Genomes of serovars Luedinghausen, Laredo, Widemarsh, and Lansing are being documented in Africa for the first time. Twenty (20) antimicrobial resistance (AMR) gene markers encoding for resistance to aminoglycosides, tetracyclines, sulphonamides, quinolones, trimethoprim, penicillins and phenicols were found. Phylogenetic cluster analysis showed close relatedness among isolates from different sources. This study shows both low Salmonella prevalence and AMR, but since uncommon serovars are circulating, continuous monitoring is recommended so as to ensure food safety and poultry health. [ABSTRACT FROM AUTHOR]

Background: Enterococci are emerging nosocomial pathogen showing resistance to broad spectrum antibiotics. As reported by the center for disease control and prevention, enterococci (13.9%) are the second leading cause of urinary tract infection, after Escherichia coli. After the first report of vancomycin-resistant enterococci in England (1988), India reported its first vancomycin resistant enterococci isolate from New Delhi (1999). The prevalence of vancomycin resistant enterococci ranges from 1-9%, in India. To evaluate the prevalence of vancomycin resistant enterococci among urinary isolates and to check their antimicrobial resistance pattern. Methods: A retrospective observational study conducted at a tertiary care hospital. Data were analysed from November, 2017 to October, 2018. A total of 12,129 urine samples were received and subjected to culture on HiCrome UTI agar (Hi-Media laboratories, Mumbai) and incubated at 37 °C for a period of 18-24 hours. Antimicrobial susceptibility was performed using Kirby–Bauer disc diffusion method. Identification was done on the basis of colony colour and species identification was done by using biochemical test as per standard laboratory protocol. In one case automated siemens microscan walkaway identification system was used for confirmation. Results: Enterococci were isolated in 4.06% from urine cultures out of which 7.52% were vancomycin resistant. Most of the vancomycin resistant enterococci isolate (86.49%) were multi drug resistant. Conclusion: In vancomycin resistant enterococci related urinary tract infection, nitrofurantoin can be used as an appropriate first choice in uncomplicated cases and linezolid should be reserved for serious and complicated urinary tract infections. [ABSTRACT FROM AUTHOR]

Multidrug-resistant (MDR) and extensively drug-resistant (XDR) Acinetobacter baumannii infections pose challenges for clinical treatment and cause high mortality, particularly in intensive care units (ICUs). To systematically summarize and analyse the risk factors for MDR/XDR A. baumannii -infected patients admitted to ICUs. PubMed, Embase, Web of Science, and the Cochrane Library were searched for eligible original studies published in English before October 2023. Meta-analysis was conducted where appropriate, with mean differences (MDs) and odds ratios (ORs) calculated for continuous and nominal scaled data. The quality of included studies was assessed using the Newcastle–Ottawa Scale (NOS). Ten studies reporting 1199 ICU patients (604 from general ICUs, 435 from neonatal ICUs, and 160 from paediatric ICUs) from eight countries were included in our analysis. Risk factors associated with MDR A. baumannii infection among patients admitted to general ICUs included high Acute Physiology And Clinical Health II (APACHE Ⅱ) score (mean difference (MD): 7.52; 95% confidence interval (CI): 3.24–11.80; P = 0.0006), invasive procedures (odds ratio (OR): 3.47; 95% CI: 1.70–7.10; P = 0.0006), longer ICU stay (MD: 3.40; 95% CI: 2.94–3.86; P < 0.00001), and use of antibiotics (OR: 2.69; 95% CI: 1.22–5.94; P = 0.01). In the sub-group analysis, longer neonatal ICU stay (MD: 16.88; 95% CI: 9.79–23.97; P < 0.00001) was associated with XDR A. baumannii infection. Close attention should be paid to patients with longer ICU stays, undergoing invasive procedures, using antibiotics, and with high APACHE Ⅱ scores to reduce the risk of MDR and XDR A. baumannii infections. [ABSTRACT FROM AUTHOR]

Gram-negative Enterobacteriaceae pathogenic strains of Shigella organisms cause bacillary dysentery and shigellosis. Three serogroups-Shigella dysenteriae, flexneri, boydii, and sonnei and one serotype-Sonnei, are groups A, B, C, and D, respectively. Shigella flexneri is the most common serogroup worldwide. Fecaloral transmission is the main method, but sexual transmission has been recorded. These groups are among the most responsible for diarrheal diseases. In children, this species can lead to stunted growth due to severe and life-threatening illnesses. In the present day situation, managing this infection is still challenging as it can easily resist many antimicrobials, and overcoming this and finding potential inhibitors can help reduce this infection. As a result, this research aims to determine the potential inhibitors against the potential protein target through molecular docking analysis. According to the virulence factor, subcellular localisation, and role in infection, the aminoglycoside'-(9)O-adenyltransferase protein was the most potent target protein. The three-dimensional structure was designed and validated, it became known that designed model has a promising profile according to the Ramachandran plot analysis. Further, the molecular docking analysis targeted available ligands in ZINC databases and found 10 potential novel inhibitors. Among these, only 6 inhibitors were found to have the most potential as per toxicity analysis. These findings suggested that these selected inhibitors can be utilised to combat this infection; however, further experimental validation is required to confirm their efficacy. [ABSTRACT FROM AUTHOR]

Introduction Infective endocarditis (IE) is a disease that may frequently lead to significant morbidity and is associated with high mortality rates. Even though IE is classically caused by Gram-positive bacteria, Gram-negative bacteria may seldom cause IE. Antimicrobial resistance (AMR) may pose significant problems in treating IE, especially for carbapenem-resistant pathogens. This study aimed to review all cases of IE by carbapenem-resistant Gram-negative bacteria in a systematic way and present information on epidemiology, clinical findings, treatment, and outcomes. Methods A systematic review of PubMed, Cochrane Library, and Scopus (all published studies up to 6 August 2023) for published studies providing information on epidemiology, clinical findings, treatment, and outcomes of IE by carbapenem-resistant Gram-negative bacteria was performed. Results A total of 24 studies containing data from 26 patients were included. Among all patients, 53.9% were male, and the median age was 66 years. Among all patients, 38.5% had a history of a prosthetic valve. The most commonly affected valve was the aortic, followed by the mitral valve. Fever, sepsis, emboli, and shock were the most frequent clinical findings. The most commonly isolated pathogens were Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter baumannii. Aminoglycosides, colistin, cephalosporins, and carbapenems were the most commonly used antimicrobials. Surgery was performed in 53.8% of patients. Mortality was 38.5%. Conclusions The development of infection control measures and antimicrobial stewardship interventions is needed to reduce the spread of AMR and the likelihood of this fatal infection. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance (AMR) is now a major challenge to clinicians in treating patients. The purpose of our study was to determine the incidence of multidrug resistant (MDR) strains and antibiotic resistance profile in department of dermatology-venereology from a Romanian infectious disease's hospital. We analyzed 1,152 bacterial strains, we obtained 34.5% MDR strains, identifying the following species: staphylococcus aureus 43.6%, enterococcus spp 16.7%, escherichia coli 31.0%, proteus spp 27.1%, klebsiella spp. 22.4%, pseudomonas spp. 34.8%. Overall, the rate of methicillin-resistant staphylococcus aureus was 76.1%; extended spectrum beta-lactamase production was 46.1% for escherichia coli and 66.0% for klebsiella pneumoniae; carbapenems-resistance was 51.0% for pseudomonas aeruginosa. All strains of E. coli and klebsiella were sensitive to meropenem. Our results confirm the high level of AMR, and continuous monitoring is essential for updating the local diagnostic and treatment protocols for dermatological infections. [ABSTRACT FROM AUTHOR]

This study depicts the drug-resistance and phylogenomic characteristics of 365 Escherichia coli (EC) and 76 Klebsiella pneumoniae (KP) isolated from stray dogs (293) in and around Kolkata, India. Initial screening found 59 isolates, including 48 E. coli and 11 KP multidrug resistant, which included 33 extended-spectrum β-lactamase, 41 AmpC β-lactamase and 18 metallo-β-lactamase producers carrying blaNDM-1 (11) and blaNDM-5 (7) genes. Majority of them had the resistant genes such as blaCTX-M (33), blaTEM (18), blaSHV (4), blaOXA (17), blaFOX (2), blaDHA (2), blaCITM (15), blaCMY-2 (13), blaGES (2) and blaVEB (2), qnrS (15), qnrB (3), aac-6′-Ib-cr (14), tetA (26), tetB (14), sul-1 (25), armA (2) and rmtB (6), in addition to adherence genes such as csgA (33), fimA (27), fliC (13), sdiA (33), rcsA (38), and rpoS (39). They also carried plasmid of diverse replicon types of which IncFIA and FIB were the most frequent. Phylogrouping categorized most of the MDR E. coli in phylogroup A (20), B1 (14), and B2 (6). Enterobacteriaceae repetitive intergenic consensus-polymerase chain reaction (ERIC-PCR) showed genetic diversity of multidrug resistant isolates irrespective of their origin, resistance, and virulence types, differentiating the EC in five clades (A–E) and KP in four clades (A–D). As these stray dogs, which had no history or scope of previous antimicrobial therapy, were found to have contracted potential antimicrobial resistance pathogens, the role of environment in spread of such pathogens and further possibility of human infections cannot be ruled out. [ABSTRACT FROM AUTHOR]

Abstract Objectives In the recent years, multidrug resistant (MDR) neonatal septicemia-causing Enterobacterales has been dramatically increased due to the extended-spectrum beta-lactamases (ESBLs) and AmpC enzymes. This study aimed to assess the antibiotic resistance pattern, prevalence of ESBLs/AmpC beta-lactamase genes, and Enterobacterial Repetitive Intergenic Consensus Polymerase Chain Reaction (ERIC-PCR) fingerprints in Enterobacterales isolated from neonatal sepsis. Results In total, 59 Enterobacterales isolates including 41 (69.5%) Enterobacter species, 15 (25.4%) Klebsiella pneumoniae and 3 (5.1%) Escherichia coli were isolated respectively. Resistance to ceftazidime and cefotaxime was seen in all of isolates. Furthermore, all of them were multidrug-resistant (resistant to three different antibiotic categories). The phenotypic tests showed that 100% of isolates were ESBL-positive. Moreover, AmpC production was observed in 84.7% (n = 50/59) of isolates. Among 59 ESBL-positive isolates, the highest percentage belonged to bla CTX−M−15 gene (66.1%) followed by bla CTX−M (45.8%), bla CTX−M−14 (30.5%), bla SHV (28.8%), and bla TEM (13.6%). The frequency of bla DHA, bla EBC, bla MOX and bla CIT genes were 24%, 24%, 4%, and 2% respectively. ERIC-PCR analysis revealed that Enterobacterales isolates were genetically diverse. The remarkable prevalence of MDR Enterobacterales isolates carrying ESBL and AmpC beta-lactamase genes emphasizes that efficient surveillance measures are essential to avoid the more expansion of drug resistance amongst isolates.

This review explores the evolution of the concept of Healthcare-Associated Pneumonia (HCAP) in light of the 2016 guidelines from the Infectious Diseases Society of America (IDSA). These updated guidelines prioritize patient-specific risk factors over healthcare system interactions in pneumonia classification. Recent research has revealed that the risk of contracting Multidrug-Resistant (MDR) pathogens is more closely linked to individual patient risk factors than to healthcare system interactions. Consequently, administering empiric antibiotic therapy targeting MDR bacteria for patients meeting HCAP criteria is discouraged unless specific risk factors for MDR infections are identifiable. Hospital-Acquired Pneumonia (HAP) is a significant challenge, particularly in intensive care units, leading to elevated hospitalization costs and extended inpatient care. The review also delves into the emergence and global prevalence of Carbapenem-Resistant Acinetobacter baumannii (CRAB) infections, known for their high mortality rates. In response to the rising threat of CRAB infections, the review introduces Sulbactam-Durlobactam (SUL-DUR) as a promising therapeutic solution. It examines the unique characteristics of Sulbactam and Durlobactam, both individually and in combination, and their potential in treating CRAB infections. Clinical trial data is presented to demonstrate the effectiveness and safety of SUL-DUR in addressing Hospital-Acquired Bacterial Pneumonia (HABP), Ventilator-Associated Bacterial Pneumonia (VABP), and bacteremia caused by the Acinetobacter baumannii-Calcoaceticus complex. The review also covers FDA-approved prescribing guidelines, dosage recommendations, adverse reactions, drug interactions, and usage in specific populations, including pregnant and lactating individuals. The management of renal and hepatic impairment and underscores the importance of monitoring for potential overdosage. While initial clinical evidence is promising, further research is essential to establish the full efficacy and safety profile of SUL-DUR. [ABSTRACT FROM AUTHOR]

Background and Objectives: Multi-drug-resistant pathogens pose a significant threat as they can rapidly spread, leading to severe healthcare-associated invasive infections. In developing countries, diarrheagenic Escherichia coli (DEC) is a major bacterial pathogen responsible for causing diarrhea. However, the outbreak of resistant strains has made the treatment of DEC infections much more challenging. This study aimed to investigate the relationship between antibiotic resistance genes and other virulence categories in E. coli strains that cause diarrhea, particularly DEC. Materials and Methods: The phylogenetic grouping was defined using PCR and multi-locus sequence type (MLST) methods. Results: Among the isolates analyzed, 14 were identified as resistant and were classified into eight distinct sequence types: ST3, ST53, ST77, ST483, ST512, ST636, ST833, and ST774, indicating genetic diversity among the resistant strains. Certain sequence types, notably ST512 and ST636, were found to be associated with multiple antibiotic resistance in DEC. Regarding antibiotic susceptibility, strains showed the highest resistance to amoxicillin, suggesting that this antibiotic may not be effective in treating DEC infections. On the other hand, the isolates demonstrated susceptibility to amikacin and chloramphenicol, implying that these antibiotics could be more suitable treatment options for DEC infections. Conclusion: The findings underscore the importance of promptly identifying antibiotic resistance patterns and their correlation with specific pathogenic virulence categories, as this knowledge can aid in selecting the most appropriate antibiotics for treating DEC infections. Considering the antibiotic resistance profiles and associated resistance genes is crucial in managing and containing diarrheal outbreaks and in selecting effective antibiotic therapies for DEC infections. [ABSTRACT FROM AUTHOR]

Background and Objectives: Over the last decade, hospital-acquired infections, particularly in the critical care setting, have become more common, with Gram-negative bacterial infections having the highest prevalence. This study aims to determine the prevalence and antibiotic susceptibility pattern of Pseudomonas species to WHO's, aware class of antibiotics, which are commonly prescribed across various ICU's, medical and surgical wards of our tertiary care teaching hospital. Materials and Methods: This prospective study conducted from January 2021 to June 2022 at a tertiary care centre of central India identified Pseudomonas species from clinical samples using standard procedures and antimicrobial susceptibility testing performed as per Clinical Laboratory Standards Institute (CLSI) guidelines (M100; 32th Edition). Results: A total of 1490 non duplicate Pseudomonas species isolates were grown from 21,019 culture positive clinical samples, of which 1247 were Pseudomonas aeruginosa. Out of these 1247 Pseudomonas aeruginosa 384 were MDR (30.7%). Pseudomonas aeruginosa were most commonly isolated from the pus samples (85%). ICU isolates were significantly more resistant to antibiotics than those from other units. P. aeruginosa strains from ICUs showed the highest rates of resistance to ceftazidime (93.9%). Reserve drug colistin showed good susceptibility (98.2%). All the 18 colistin resistant strains were found to be negative for plasmid mediated mcr-1,2,3 genes. Conclusion: The study shall help to generate and disseminate the data so that proper antibiotic policy can be made for judicious use of Access, Watch and Reserve antibiotics and antibiotic de-escalation plan can be put forth. [ABSTRACT FROM AUTHOR]

Bacteriophages, which are viruses with restricted tropism for bacteria, have been employed for over a century as antimicrobial agents; they have been largely abandoned in Western countries but are constantly used in Eastern European countries with the advent of antibiotics. In recent decades, the growing spread of multidrug-resistant bacteria, which pose a serious threat to worldwide public health, imposed an urgent demand for alternative therapeutic approaches to antibiotics in animal and human fields. Based on this requirement, numerous studies have been published on developing and testing bacteriophage-based therapy. Overall, the literature largely supports the potential of this perspective but also highlights the need for additional research as the current standards are inadequate to receive approval from regulatory authorities. This review aims to update and critically revise the current knowledge on the application of bacteriophages to treat bacterial-derived infectious diseases in animals in order to provide topical perspectives and innovative advances. [ABSTRACT FROM AUTHOR]

Antibiotics in animal farms play a significant role in the proliferation and spread of antibiotic-resistant genes (ARGs) and antibiotic-resistant bacteria (ARB). The dissemination of antibiotic resistance from animal facilities to the nearby environment has become an emerging concern. The present study was focused on the isolation and molecular identification of Escherichia coli (E. coli) isolates from broiler chicken meat and further access their antibiotic-resistant profile against different antibiotics. Broiler chicken meat samples were collected from 44 retail poultry slaughter shops in Prayagraj district, Uttar Pradesh, India. Standard bacteriological protocols were followed to first isolate the E. coli, and molecular characterization was performed with genus-specific PCR. Phenotypic and genotypic antibiotic-resistant profiles of all confirmed 154 E. coli isolates were screened against 09 antibiotics using the disc diffusion and PCR-based method for selected resistance genes. In antibiotic sensitivity testing, the isolates have shown maximum resistance potential against tetracycline (78%), ciprofloxacin (57.8%), trimethoprim (54.00%) and erythromycin (49.35%). E. coli bacterial isolates have shown relative resistant to amoxicillin-clavulanic acid (43.00%) and against ampicillin (44.15%). Notably, 64.28% E. coli bacteria were found to be multidrug resistant. The results of PCR assays exposed that tetA and blaTEM genes were the most abundant genes harboured by 83 (84.0%) and 82 (82.0%) out of all 99 targeted E. coli isolates, followed by 48.0% for AmpC (CITM) gene and cmlA (23.00%) for chloramphenicol resistance. It is notable that most of the isolates collected from chicken meat samples were multidrug resistant (> 3 antibiotics), with more than 80% of them carrying tetracycline (tetA) and beta-lactam gene (blaTEM). This study highlights the high risk associated with poultry products due to MDR-E. coli and promote the limited use of antibiotics in poultry farms. [ABSTRACT FROM AUTHOR]

The current trend in microbiological research aimed at limiting the development of biofilms of multidrug-resistant microorganisms is increasingly towards the search for possible synergistic effects between various compounds. This work presents a combination of a naturally occurring compound, β-aescin, newly synthesized alkylamidobetaines (AABs) with a general structure—CnTMDAB, and antifungal drugs. The research we conducted consists of several stages. The first stage concerns determining biological activity (antifungal) against selected multidrug-resistant strains of Candida glabrata (C. glabrata) with the highest ability to form biofilms. The second stage of this study determined the activity of β-aescin combinations with antifungal compounds and alkylamidobetaines. In the next stage of this study, the ability to eradicate a biofilm on the polystyrene surface of the combination of β-aescin with alkylamidobetaines was examined. It has been shown that the combination of β-aescin and alkylamidobetaine can firmly remove biofilms and reduce their viability. The last stage of this research was to determine the safety regarding the cytotoxicity of both β-aescin and alkylamidobetaines. Previous studies on the fibroblast cell line have shown that C9 alkylamidobetaine can be safely used as a component of anti-biofilm compounds. This research increases the level of knowledge about the practical possibilities of using anti-biofilm compounds in combined therapies against C. glabrata. [ABSTRACT FROM AUTHOR]

This study presents an innovative and environmentally friendly approach for synthesizing silver nanoparticles by using the aqueous extract of Lasiodiplodia theobromae, an endophytic fungus isolated from medicinal plant. The primary aim was to investigate the silver nanoparticles potential in combating bacterial infections, specifically those caused by multidrug-resistant Klebsiella pneumoniae strains carrying the CTX-M-15 and AmpC genes. The synthesis of silver nanoparticles was confirmed through UV spectrophotometric analysis; their characteristics were studied using SEM, zeta sizer, and zeta potential analysis. A series of antibacterial assays, including agar well diffusion, minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and antibiofilm assays, were conducted. The findings demonstrated that the synthesized silver nanoparticles displayed significant antibacterial and antibiofilm activities, surpassing the effectiveness of standard antibiotics. These results highlight the substantial promise of the synthesized silver nanoparticles as an alternative for treating infections caused by multidrug-resistant Klebsiella pneumoniae strains expressing CTX-M-15 and AmpC genes. This research introduces an innovative and sustainable approach to addressing the critical global health concern of antibiotic-resistant bacterial infections. [ABSTRACT FROM AUTHOR]

Background: Enterococci are emerging nosocomial pathogen showing resistance to broad spectrum antibiotics. As reported by the center for disease control and prevention, enterococci (13.9%) are the second leading cause of urinary tract infection, after Escherichia coli. After the first report of vancomycin-resistant enterococci in England (1988), India reported its first vancomycin resistant enterococci isolate from New Delhi (1999). The prevalence of vancomycin resistant enterococci ranges from 1-9%, in India. To evaluate the prevalence of vancomycin resistant enterococci among urinary isolates and to check their antimicrobial resistance pattern. Methods: A retrospective observational study conducted at a tertiary care hospital. Data were analysed from November, 2017 to October, 2018. A total of 12,129 urine samples were received and subjected to culture on HiCrome UTI agar (Hi-Media laboratories, Mumbai) and incubated at 37 °C for a period of 18-24 hours. Antimicrobial susceptibility was performed using Kirby–Bauer disc diffusion method. Identification was done on the basis of colony colour and species identification was done by using biochemical test as per standard laboratory protocol. In one case automated siemens microscan walkaway identification system was used for confirmation. Results: Enterococci were isolated in 4.06% from urine cultures out of which 7.52% were vancomycin resistant. Most of the vancomycin resistant enterococci isolate (86.49%) were multi drug resistant. Conclusion: In vancomycin resistant enterococci related urinary tract infection, nitrofurantoin can be used as an appropriate first choice in uncomplicated cases and linezolid should be reserved for serious and complicated urinary tract infections.

Abstract Background Antimicrobial resistance poses a huge risk to human health worldwide, while Bangladesh is confronting the most severe challenge between the food supply and the huge consumption of antibiotics annually. More importantly, probiotics containing Bacillus spp. are claimed to be an alternative to antimicrobial stewardship programs. However, their antibiotic resistance remains elusive. Thus, we employed the antimicrobial susceptibility test and PCR to assess the prevalence of resistance, including multidrug resistance (MDR) and resito-genotyping of isolated Bacillus spp. Results The phenotypic profile showed that Bacillus spp. were 100% sensitive to gentamicin (2 µg/mL), whereas lowered sensitivity to levofloxacin (67.8%, 0.5–1 µg/mL), ciprofloxacin (62.3%, 0.5–1 µg/mL), clindamycin (52.2%, 0.25–0.5 µg/mL), amoxicillin-clavulanic acid (37.6%, 0.06 µg/mL), azithromycin (33.4%, 1–2 µg/mL), tetracycline (25.6%, 2–4 µg/mL), nitrofurantoin (21.1%, 16–32 µg/mL), co-trimoxazole (19.2%, 2 µg/mL), and erythromycin (18.8%, 0.25–0.5 µg/mL). The strains were completely resistant to penicillin, amoxicillin-clavulanic acid, cefixime, ceftriaxone, vancomycin, and co-trimoxazole, and a species-specific trend was seen in both phenotypic and genotypic resistance patterns. Genotypic resistance indicated prevalence of the bla1 (71.5%), tetA (33%), erm1 (27%), bla TEM (13.1%), bla CTX-M-1/bla CTX-M-2 /sul1 (10.1%), bla SHV (9.6%), and qnrS (4.1%) genes. The β-lactamase resistance gene bla1 was found in all penicillin-resistant (MIC ≥ 32 µg/mL) Bacillus spp. One hundred ninety-one isolates (89.6%) were MDR, with 100% from diarrhea, 90.3% from food, and 88.7% from animal feed. Conclusion Based on the MIC value and profile analysis of antibiotic resistance genes, this is the first study that Bacillus spp. antimicrobial susceptibilities have been identified in Bangladesh, and our study will shed light on the adverse effects of feed-borne Bacillus spp. emerging from animal feed to the food chain. A comprehensive investigation is urgently needed by policymakers on tolerance limits and harmful effects in the animal industry.

Abstract Background The occurrence of multidrug-resistant and hypervirulent Klebsiella pneumoniae (MDR-hvKp) worldwide poses a great challenge for public health. Few studies have focused on ST218 MDR-hvKp. Methods Retrospective genomic surveillance was conducted at the Peking University Third Hospital from 2017 and clinical information was obtained. To understand genomic and microbiological characteristics, antimicrobial susceptibility testing, plasmid conjugation and stability, biofilm formation, serum killing, growth curves and whole-genome sequencing were performed. We also assessed the clinical and microbiological characteristics of ST218 compared with ST23. Results A total of eleven ST218 Kp isolates were included. The most common infection type was lower respiratory tract infection (72.7%, 8/11) in our hospital, whereas ST23 hvKp (72.7%, 8/11) was closely associated with bloodstream infection. Notably, nosocomial infections caused by ST218 (54.5%, 6/11) was slightly higher than ST23 (36.4%, 4/11). All of the ST218 and ST23 strains presented with the virulence genes combination of iucA + iroB + peg344 + rmpA + rmpA2. Interestingly, the virulence score of ST218 was lower than ST23, whereas one ST218 strain (pPEKP3107) exhibited resistance to carbapenems, cephalosporins, β-lactamase/inhibitors and quinolones and harbored an ~ 59-kb IncN type MDR plasmid carrying resistance genes including bla NDM-1, dfrA14 and qnrS1. Importantly, bla NDM-1 and qnrS1 were flanked with IS26 located within the plasmid that could successfully transfer into E. coli J53. Additionally, PEKP2044 harbored an ~ 41-kb resistance plasmid located within tetA indicating resistance to doxycycline. Conclusion The emergence of bla NDM-1 revealed that there is great potential for ST218 Kp to become a high-risk clone for MDR-hvKp, indicating the urgent need for enhanced genomic surveillance.

Abstract The number of infections and deaths caused by multidrug resistant (MDR) tuberculosis is increasing globally. One of the efflux pumps, that makes Mycobacterium tuberculosis resistant to a number of antibiotics and results in unfavourable treatment results is Tap or Rv1258c. In our study, we tried to utilize a rational drug design technique using in silico approach to look for an efficient and secure efflux pump inhibitor (EPI) against Rv1258c. The structure of Rv1258c was built using the homology modeling tool MODELLER 9.24. 210 phytocompounds were used for blind and site-specific ligand docking against the modelled structure of Rv1258c using AutoDock Vina software. The best docked plant compounds were further analysed for druglikeness and toxicity. In addition to having excellent docking scores, two plant compounds—ellagic acid and baicalein—also exhibited highly desirable drug-like qualities. These substances outperform more well-known EPIs like piperine and verapamil in terms of effectiveness. This data shows that these two compounds might be further investigated for their potential as Rv1258c inhibitors.

Pseudomonas aeruginosa (P. aeruginosa) presents a complex challenge in terms of pathogenicity and antibiotic resistance. This versatile pathogen adeptly colonises various host tissues and evades the immune system through its intricate virulence factors. The review delves into the antimicrobial resistance mechanisms at play, which encompass inherent resistance characteristics and those acquired through genetic mutations and horizontal gene transfer. Notably, efflux pump systems and limited membrane permeability underpin its inherent resistance, rendering many conventional antibiotics ineffective. Multidrug Resistant (MDR) strains are on the rise, posing a substantial threat to patient care and infection control. In response, innovative strategies are being explored, including combination therapies to enhance the effectiveness of existing antibiotics and drug repurposing, redirecting existing medications to target P. aeruginosa. Phage therapy, which leverages bacteriophages to combat P. aeruginosa infections, is gaining attention as a promising solution. Infection prevention and control are pivotal, particularly in healthcare settings, to curtail the spread of P. aeruginosa. Surveillance programs are crucial for monitoring the prevalence and dissemination of antibiotic-resistant strains and guiding response strategies during outbreaks. Comprehending P. aeruginosa’s complex virulence and resistance mechanisms is paramount for developing efficient treatments and effective infection control measures. Ongoing research and collaborative efforts are instrumental in mitigating the substantial impact of P. aeruginosa infections on public health, underscoring the need for sustained vigilance and innovation in infectious disease management.

Introduction: Over the recent decades, the importance of Urinary Tract Infections (UTI) has been increasingly recognised in children. The occurrence of UTI during childhood may lead to acute and/or chronic consequences, such as impaired renal function, renal scarring, and hypertension. Due to the irrational use of antimicrobials, multidrug resistant bacterial strains are frequent. Hence, there is an urgent need for continuous surveillance of the microbiological profile of UTI. Aim: To investigate the microbial profile and antibiotic sensitivity pattern from the urine of paediatric patients suspected to have UTI in Idukki district, Kerala and to explore its association with seasonal variations. Materials and Methods: This clinical cross-sectional study was conducted in Al Azhar Medical College and Super Specialty Hospital, Thodupuzha, Idukki, Kerala, India, from January 2019 to December 2021. The study involved 882 paediatric patients in the age group 0-15 years with symptoms and signs suggestive of UTI. Data regarding age, gender, season, laboratory and culture results, and antibiotic sensitivity pattern were considered as variables of interest. Analysis was performed using mean and standard deviation for quantitative variables, and frequency and proportion for categorical variables. The statistical analyses were conducted using Statistical Package for Social Sciences (SPSS) version 20.0 and Microsoft Excel 2010. Results: The study involved 882 patients, of which 399 were males (45.2%) and 483 were females (54.8%) with a male-to-female ratio of 0.8:1. The mean age of patients was four years, and a peak incidence was observed in children in the age group of 1-3 years, with 333 (37.8%) children. Microbial growth was observed in the urine of 325 (36.8%) patients. After excluding normal commensal perineal flora and insignificant bacteriuria, 233 samples had significant growth, with males accounting for 106 (45.5%) and females 127 (54.5%). The male-to-female ratio was 0.8 to 1. These samples mostly exhibited growth of aerobic bacteria (232, 99.6%) and Candida albicans (1, 0.4%). E. coli (106, 45.5%) was identified as the most predominant aetiological agent for paediatric UTI. Conclusion: The results of this study suggest that it would be advisable for paediatricians in Idukki district to refrain from using Ampicillin to treat cases suspected to have UTI. Preventive measures should be advised to all patients, with emphasis on urinary hygiene during the monsoon and winter seasons.

Background & Aims: Non-Fermenting Gram-Negative Bacilli [NFGNB] which are considered as environmental contaminants have emerged as multidrug-resistant bacteria and are of serious concern to the treating physician. The aim of this study was to determine the proportion of metallo-beta-lactamase producing Pseudomonas aeruginosa and Acinetobacter species in clinical samples received in the Microbiology Laboratory and to study the antibiotic sensitivity pattern of metallo-beta-lactamase (MBL) producing strains. Materials & Methods: Various samples (pus, sputum, urine, blood and body fluids, etc.) were processed according to standard protocols. P.aeruginosa and Acinetobacter spp were isolated and identified with the help of various culture media, staining methods and biochemical reactions. Antibiotic susceptibility test was done by using Kirby-bauer disc diffusion method. MBL producers were identified using CLSI guidelines. Results: Out of 600 positive culture isolates from various samples, 65 (10.8%) were non-fermenting gram-negative bacilli, 40 (61.53%) were Pseudomonas aeruginosa, and 25 (38.47%) were Acinetobacter species. The overall incidence of MBL positive isolates in our study was 12.3% (8 of 65). All the isolates of Pseudomonas aeruginosa and Acinetobacterspecies were 100% sensitive to Colistin and Tigecycline. Conclusion: The study helps in understanding the antibiotic resistance pattern of isolates causing nosocomial infections, helping clinicians in making appropriate antibiotic choices as an empirical therapy and the policy-makers to bring out the measures in controlling the superbugs.

Introduction: Infection of the skin and soft tissue due to injury, surgery, or burns may result in the formation of allexudates. Dead leucocytes, cellular debris and necrotic tissue are responsible for formation of exudates. Relentless exposure to devitalized tissue associated with a slow-healing chronic wound is likely to promote the colonisation and establishment of a wide range of bacteria. Mixed populations of both aerobic and anaerobic microorganisms are accountable for most acute and chronic wound infections. Therefore this study was carried out to investigate the aerobic bacterial isolates responsible for pyogenic wound infections and their antimicrobial susceptibility pattern for clinical management. Material and Methods: Pus samples were collected with sterile disposable cotton swabs and pus aspirates in syringes from suspected patients of pyogenic wound infections. They were processed using standard microbiological techniques and identification of isolate from positive cultures was done using conventional biochemical test. The antibiotic sensitivity testing of all isolates was performed by Kirby Bauer disc diffusion method on Muller Hinton agar and interpreted as per CLSI guidelines. Results: In our study out of 288 samples, 192(66.66%) were culture positive isolates and 96 (33.33%) were culture negative isolates. Out of 192 culture positive isolates, 76(39.58%) were Gram positive isolates and 116(60.41%) were Gram negative isolates. Staphylococcus aureus was most commonly isolated among all culture positive isolates. Conclusion: This study gives an outline of antibiotic susceptibility pattern of clinical isolates causing pyogenic wound infections which will help in empirical treatment of patients.

In recent decades, antimicrobial resistance has become a major global public health problem. A distinct category of pathogens, known by the acronym ESKAPE, has become of particular concern because of their ability to escape the effects of available antimicrobial treatments. This acronym represents a select group of pathogenic bacteria, some of which are highly resistant to antibiotics and can cause severe and potentially fatal infections. The term "ESKAPE" is an acronym derived from the initials of these bacteria and includes Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp. Antimicrobial resistance in these pathogens is fuelled by several factors, including overuse and misuse of antibiotics, natural selection and transfer of resistance genes between bact. To meet this challenge, the global community is engaged in multiple efforts, including research and development of new antibiotics, improving practices in the use of these drugs and promoting antimicrobial research and education. In the fight against pathogens and their antimicrobial resistance, we face a constant challenge in contemporary medicine, with significant implications for healthcare delivery and public health.

VIM-type-producing Gram-negative bacteria (GNB) infections are difficult to treat. This is a retrospective single-center study of 34 patients who received cefiderocol for the treatment of VIM-type-producing GNB infections, including 25 Pseudomonas spp., 7 Enterobacterales, and 5 Achromobacter sp. Primary outcomes were clinical failure (defined as death, lack of clinical improvement, or a switch to another drug) at day 14 and 30-day all-cause mortality. The median age was 59 years (IQR 53.7–73.4), and the median Charlson comorbidity index was 3.5 (IQR 2–5). The main infections were respiratory tract infections (n = 9, 27%) and skin and soft tissue infections (n = 9, 27%). Eight patients exhibited bacteremia. In 9/17 patients with a drainable focus, drainage was performed. The median cefiderocol treatment duration was 13 days (IQR 8–24). Five patients (15%) experienced clinical failure on day 14, and the thirty-day mortality rate was 9/34 (27%); two cases occurred because of an uncontrolled infection source, and one was due to a new infection caused by the same bacteria. The other six deaths were unrelated to the index infection. Five patients experienced microbiological recurrence within three months. Susceptibility testing revealed the development of cefiderocol resistance in 1/7 cases with persistent or recurrent positive cultures. Cefiderocol, even in monotherapy, could be considered for the treatment of VIM-type-producing GNB infections.

Background: Antimicrobial resistance poses a huge risk to human health worldwide, while Bangladesh is confronting the most severe challenge between the food supply and the huge consumption of antibiotics annually. More importantly, probiotics containing Bacillus spp. are claimed to be an alternative to antimicrobial stewardship programs. However, their antibiotic resistance remains elusive. Thus, we employed the antimicrobial susceptibility test and PCR to assess the prevalence of resistance, including multidrug resistance (MDR) and resito-genotyping of isolated Bacillus spp. Results: The phenotypic profile showed that Bacillus spp. were 100% sensitive to gentamicin (2 µg/mL), whereas lowered sensitivity to levofloxacin (67.8%, 0.5–1 µg/mL), ciprofloxacin (62.3%, 0.5–1 µg/mL), clindamycin (52.2%, 0.25–0.5 µg/mL), amoxicillin-clavulanic acid (37.6%, 0.06 µg/mL), azithromycin (33.4%, 1–2 µg/mL), tetracycline (25.6%, 2–4 µg/mL), nitrofurantoin (21.1%, 16–32 µg/mL), co-trimoxazole (19.2%, 2 µg/mL), and erythromycin (18.8%, 0.25–0.5 µg/mL). The strains were completely resistant to penicillin, amoxicillin-clavulanic acid, cefixime, ceftriaxone, vancomycin, and co-trimoxazole, and a species-specific trend was seen in both phenotypic and genotypic resistance patterns. Genotypic resistance indicated prevalence of the bla1 (71.5%), tetA (33%), erm1 (27%), blaTEM (13.1%), blaCTX-M-1/blaCTX-M-2 /sul1 (10.1%), blaSHV (9.6%), and qnrS (4.1%) genes. The β-lactamase resistance gene bla1 was found in all penicillin-resistant (MIC ≥ 32 µg/mL) Bacillus spp. One hundred ninety-one isolates (89.6%) were MDR, with 100% from diarrhea, 90.3% from food, and 88.7% from animal feed. Conclusion: Based on the MIC value and profile analysis of antibiotic resistance genes, this is the first study that Bacillus spp. antimicrobial susceptibilities have been identified in Bangladesh, and our study will shed light on the adverse effects of feed-borne Bacillus spp. emerging from animal feed to the food chain. A comprehensive investigation is urgently needed by policymakers on tolerance limits and harmful effects in the animal industry. [ABSTRACT FROM AUTHOR]

The number of infections and deaths caused by multidrug resistant (MDR) tuberculosis is increasing globally. One of the efflux pumps, that makes Mycobacterium tuberculosis resistant to a number of antibiotics and results in unfavourable treatment results is Tap or Rv1258c. In our study, we tried to utilize a rational drug design technique using in silico approach to look for an efficient and secure efflux pump inhibitor (EPI) against Rv1258c. The structure of Rv1258c was built using the homology modeling tool MODELLER 9.24. 210 phytocompounds were used for blind and site-specific ligand docking against the modelled structure of Rv1258c using AutoDock Vina software. The best docked plant compounds were further analysed for druglikeness and toxicity. In addition to having excellent docking scores, two plant compounds—ellagic acid and baicalein—also exhibited highly desirable drug-like qualities. These substances outperform more well-known EPIs like piperine and verapamil in terms of effectiveness. This data shows that these two compounds might be further investigated for their potential as Rv1258c inhibitors.Key points: Rv1258c is an important efflux pump which provides multidrug resistance in mycobacteria. The structure of the pump was prepared using homology modeling and docking studies were conducted against a number of phytocompounds looking for possible efflux pump inhibitors (EPIs). Based on in silico studies, two phytocompounds ellagic acid and baicalein show desirable properties of being an efficient EPI. [ABSTRACT FROM AUTHOR]

Introduction: Aeromonas hydrophila and methicillin-resistant Staphylococcus aureus (MRSA) are potent bacterial pathogens posing major hazards to human health via consuming fish harboring these pathogens or by cross-contamination beyond the contaminated environment. The aim of this study was to determine risk variables associated with the presence of certain pathogenic bacteria from Mugil cephalus fish in retail markets in Egypt. The virulence genes of A. hydrophila and S. aureus were also studied. Furthermore, the antibiotic sensitivity and multidrug resistance of the microorganisms were evaluated. Methods: In a cross-sectional investigation, 370 samples were collected from mullet skin and muscle samples, washing water, fish handlers, knives, and chopping boards. Furthermore, fish handlers' public health implications were assessed via their response to a descriptive questionnaire. Results: S. aureus and Aeromonas species dominated the investigated samples with percentages of 26.76% and 30.81%, respectively. Furthermore, A. hydrophila and MRSA were the predominant recovered bacterial pathogens among washing water and knives (53.85% and 46.66%, respectively). The virulence markers aerA and hlyA were found in 90.7% and 46.5% of A. hydrophila isolates, respectively. Moreover, the virulence genes nuc and mec were prevalent in 80% and 60% of S. aureus isolates, respectively. Antimicrobial susceptibility results revealed that all A. hydrophila isolates were resistant to amoxicillin and all MRSA isolates were resistant to amoxicillin and ampicillin. Remarkably, multiple drug resistance (MDR) patterns were detected in high proportions in A. hydrophila (88.37%) and MRSA (100%) isolates. The prevalence of Aeromonas spp. and S. aureus had a positive significant correlation with the frequency of handwashing and use of sanitizer in cleaning of instruments. MRSA showed the highest significant prevalence rate in the oldest age category. Conclusion: The pathogenic bacteria recovered in this study were virulent and had a significant correlation with risk factors associated with improper fish handling. Furthermore, a high frequency of MDR was detected in these pathogenic bacteria, posing a significant risk to food safety and public health. [ABSTRACT FROM AUTHOR]

Background: The occurrence of multidrug-resistant and hypervirulent Klebsiella pneumoniae (MDR-hvKp) worldwide poses a great challenge for public health. Few studies have focused on ST218 MDR-hvKp. Methods: Retrospective genomic surveillance was conducted at the Peking University Third Hospital from 2017 and clinical information was obtained. To understand genomic and microbiological characteristics, antimicrobial susceptibility testing, plasmid conjugation and stability, biofilm formation, serum killing, growth curves and whole-genome sequencing were performed. We also assessed the clinical and microbiological characteristics of ST218 compared with ST23. Results: A total of eleven ST218 Kp isolates were included. The most common infection type was lower respiratory tract infection (72.7%, 8/11) in our hospital, whereas ST23 hvKp (72.7%, 8/11) was closely associated with bloodstream infection. Notably, nosocomial infections caused by ST218 (54.5%, 6/11) was slightly higher than ST23 (36.4%, 4/11). All of the ST218 and ST23 strains presented with the virulence genes combination of iucA + iroB + peg344 + rmpA + rmpA2. Interestingly, the virulence score of ST218 was lower than ST23, whereas one ST218 strain (pPEKP3107) exhibited resistance to carbapenems, cephalosporins, β-lactamase/inhibitors and quinolones and harbored an ~ 59-kb IncN type MDR plasmid carrying resistance genes including blaNDM-1, dfrA14 and qnrS1. Importantly, blaNDM-1 and qnrS1 were flanked with IS26 located within the plasmid that could successfully transfer into E. coli J53. Additionally, PEKP2044 harbored an ~ 41-kb resistance plasmid located within tetA indicating resistance to doxycycline. Conclusion: The emergence of blaNDM-1 revealed that there is great potential for ST218 Kp to become a high-risk clone for MDR-hvKp, indicating the urgent need for enhanced genomic surveillance. [ABSTRACT FROM AUTHOR]

Left ventricular assist devices (LVADs) have been increasingly used as a valid option to improve the prognosis and reduce the symptoms of end-stage heart failure. However, long-term complications, mostly infections and coagulation disorders, are frequent. We described the epidemiology and risk factors for nosocomial infections (NIs) in a cohort of adult patients who underwent continuous-flow LVAD implant between January 2010 and December 2017 in Turin, Italy. Secondary outcomes were the prevalence of multidrug-resistant (MDR) bacteria and mortality. Results: Overall, 64 LVADs were implanted. A total of 32 (50%) patients experienced at least one episode of NI, with a total of 46 infectious events. VAD-related infections occurred in 22 patients (68.8%). Non VAD-related NIs occurred in 12 patients (37.5%), mainly low respiratory tract infections. Length of intensive care unit admission was a risk factor for NI (OR 1.224, 95%CI; 1.049, 1.429). Gram-negative bacilli were responsible for 58.8% of VAD-related infections and 79.5% of non-VAD related infections. In sixteen patients (50%), at least one episode of infection was related to an MDR strain. INTERMACS class and length of MV were independent risk factors for NIs by MDR strains (respectively, OR 2.12, 95%CI: 1.08, 6.80; p = 0.02 and OR 1.46, 95%CI: 1.07, 5.52, p = 0.047). In-hospital mortality was 6.3%. No differences in mortality were observed between infected and non-infected patients (p = 0.61) even when caused by MDR strains (p = 0.143). Conclusion: the rate of nosocomial infections in LVAD patients is associated with the length of ICU admission, and the etiology of nosocomial infection after LVAD implant is mainly due to GNB, including a high rate of MDR strains, especially KPC-KP and MDR PA. [ABSTRACT FROM AUTHOR]

Pseudomonas aeruginosa (P. aeruginosa) presents a complex challenge in terms of pathogenicity and antibiotic resistance. This versatile pathogen adeptly colonises various host tissues and evades the immune system through its intricate virulence factors. The review delves into the antimicrobial resistance mechanisms at play, which encompass inherent resistance characteristics and those acquired through genetic mutations and horizontal gene transfer. Notably, efflux pump systems and limited membrane permeability underpin its inherent resistance, rendering many conventional antibiotics ineffective. Multidrug Resistant (MDR) strains are on the rise, posing a substantial threat to patient care and infection control. In response, innovative strategies are being explored, including combination therapies to enhance the effectiveness of existing antibiotics and drug repurposing, redirecting existing medications to target P. aeruginosa. Phage therapy, which leverages bacteriophages to combat P. aeruginosa infections, is gaining attention as a promising solution. Infection prevention and control are pivotal, particularly in healthcare settings, to curtail the spread of P. aeruginosa. Surveillance programs are crucial for monitoring the prevalence and dissemination of antibiotic-resistant strains and guiding response strategies during outbreaks. Comprehending P. aeruginosa's complex virulence and resistance mechanisms is paramount for developing efficient treatments and effective infection control measures. Ongoing research and collaborative efforts are instrumental in mitigating the substantial impact of P. aeruginosa infections on public health, underscoring the need for sustained vigilance and innovation in infectious disease management. [ABSTRACT FROM AUTHOR]

Introduction: Over the recent decades, the importance of Urinary Tract Infections (UTI) has been increasingly recognised in children. The occurrence of UTI during childhood may lead to acute and/or chronic consequences, such as impaired renal function, renal scarring, and hypertension. Due to the irrational use of antimicrobials, multidrug resistant bacterial strains are frequent. Hence, there is an urgent need for continuous surveillance of the microbiological profile of UTI. Aim: To investigate the microbial profile and antibiotic sensitivity pattern from the urine of paediatric patients suspected to have UTI in Idukki district, Kerala and to explore its association with seasonal variations. Materials and Methods: This clinical cross-sectional study was conducted in Al Azhar Medical College and Super Specialty Hospital, Thodupuzha, Idukki, Kerala, India, from January 2019 to December 2021. The study involved 882 paediatric patients in the age group 0-15 years with symptoms and signs suggestive of UTI. Data regarding age, gender, season, laboratory and culture results, and antibiotic sensitivity pattern were considered as variables of interest. Analysis was performed using mean and standard deviation for quantitative variables, and frequency and proportion for categorical variables. The statistical analyses were conducted using Statistical Package for Social Sciences (SPSS) version 20.0 and Microsoft Excel 2010. Results: The study involved 882 patients, of which 399 were males (45.2%) and 483 were females (54.8%) with a male-tofemale ratio of 0.8:1. The mean age of patients was four years, and a peak incidence was observed in children in the age group of 1-3 years, with 333 (37.8%) children. Microbial growth was observed in the urine of 325 (36.8%) patients. After excluding normal commensal perineal flora and insignificant bacteriuria, 233 samples had significant growth, with males accounting for 106 (45.5%) and females 127 (54.5%). The male-to-female ratio was 0.8 to 1. These samples mostly exhibited growth of aerobic bacteria (232, 99.6%) and Candida albicans (1, 0.4%). E. coli (106, 45.5%) was identified as the most predominant aetiological agent for paediatric UTI. Conclusion: The results of this study suggest that it would be advisable for paediatricians in Idukki district to refrain from using Ampicillin to treat cases suspected to have UTI. Preventive measures should be advised to all patients, with emphasis on urinary hygiene during the monsoon and winter seasons. [ABSTRACT FROM AUTHOR]

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We describe a case of congenital tuberculosis in an extremely premature baby, with rapid molecular detection of a pre-extensively drug-resistant (XDR) pattern of drug resistance. The baby was treated successfully with a regimen including bedaquline and delamanid, drugs not previously described in the treatment of congenital tuberculosis (TB). [ABSTRACT FROM AUTHOR]

Pseudomonas aeruginosa (PA) is an important opportunistic pathogen that causes different infections on immunocompromised patients. Within PA accessory genome, differences in virulence, antibiotic resistance and biofilm formation have been described between strains, leading to the emergence of multidrug-resistant strains. The genome sequences of 17 strains isolated from patients with healthcare-associated infections in a Mexican hospital were genomically and phylogenetically analyzed and antibiotic resistance genes, virulence genes, and biofilm formation genes were detected. Fifteen of the 17 strains were resistant to at least two of the carbapenems meropenem, imipenem, and the monobactam aztreonam. The antibiotic resistance (mexA, mexB, and oprM) and the biofilm formation (pslA and pslD) genes were detected in all strains. Differences were found between strains in accessory genome size. The strains had different sequence types, and seven strains had sequence types associated with global high risk epidemic PA clones. All strains were represented in two groups among PA global strains. In the 17 strains, horizontally acquired resistance genes to aminoglycosides and beta-lactams were found, mainly, and between 230 and 240 genes that encode virulence factors. The strains under study were variable in terms of their accessory genome, antibiotic resistance, and virulence genes. With these characteristics, we provide information about the genomic diversity of clinically relevant PA strains. [ABSTRACT FROM AUTHOR]

We investigated the occurrence and distribution of genes encoding for extended-spectrum betalactamase (ESBL) production and quinolone resistance among multi-drug resistant (MDR) Escherichia coli and Klebsiella pneumoniae isolated from poultry, domestic pigs, and environment samples in the Msimbazi basin in Tanzania. A total of 130 non-duplicated isolates obtained from the poultry (n = 40), domestic pigs (n = 52) and environment (n = 38) were screened for ESBL genes (blaCTX-M, blaTEM, and blaSHV)and plasmid-mediated quinolone resistance (PMQR) genes (qnrA, qnrB, qnrS, qnrC, qnrD, qepA, and aac (6)-Ib-cr) using polymerase chain reaction (PCR). The most commonly detected ESBL genes were blaCTX-M (31.5%, n=41) and blaTEM (10%, n=13), while quinolone resistance genes were qnrS (27.7%, n=36), qnrB (6.9%, n=9) and aac (6)-lb-cr (5.4%, n=7). ESBL gene blaSHV and quinolone resistance genes qnrA, qnrC, and qepA were not detected in any of the isolates. Resistance genes were highest in isolates from the environmental samples (86%, n=33), followed by poultry 72.5% (n=29), and domestic pigs 21.4%, (n=9). Overall, the most frequent resistance gene was qnrS, followed by blaCTX-M and blaTEM. About 17.7% (n=23) of the E. coli and K. pneumoniae isolates depicted co-existence of ESBL and quinolone resistance genes. One Health interventional measures, involving different disciplines across human, animal, and environmental sectors, are needed to control the spread of antimicrobial resistance in the Msimbazi River Basin in Tanzania. [ABSTRACT FROM AUTHOR]

Infectious diseases account for nine percent of annual human deaths, and the widespread emergence of antimicrobial resistances threatens to significantly increase this number in the coming decades. The prospect of antimicrobial peptides (AMPs) derived from venomous animals presents an interesting alternative for developing novel active pharmaceutical ingredients (APIs). Small, cationic and amphiphilic peptides were predicted from the venom gland transcriptome of Pamphobeteus verdolaga using a custom database of the arthropod's AMPs. Ninety-four candidates were chemically synthesized and screened against ATCC® strains of Escherichia coli and Staphylococcus aureus. Among them, one AMP, named PvAMP66, showed broad-spectrum antimicrobial properties with selectivity towards Gram-negative bacteria. It also exhibited activity against Pseudomonas aeruginosa, as well as both an ATCC® and a clinically isolated multidrug-resistant (MDR) strain of K. pneumoniae. The scanning electron microscopy analysis revealed that PvAMP66 induced morphological changes of the MDR K. pneumoniae strain suggesting a potential "carpet model" mechanism of action. The isobologram analysis showed an additive interaction between PvAMP66 and gentamicin in inhibiting the growth of MDR K. pneumoniae, leading to a ten-fold reduction in gentamicin's effective concentration. A cytotoxicity against erythrocytes or peripheral blood mononuclear cells was observed at concentrations three to thirteen-fold higher than those exhibited against the evaluated bacterial strains. This evidence suggests that PvAMP66 can serve as a template for the development of AMPs with enhanced activity and deserves further pre-clinical studies as an API in combination therapy. [ABSTRACT FROM AUTHOR]

Defending against antibiotic‐resistant infections is similar to fighting a war with limited ammunition. As the new century unfolded, antibiotic resistance became a significant concern. In spite of the fact that phage treatment has been used as an effective means of fighting infections for more than a century, researchers have had to overcome many challenges of superbug bacteria by manipulating phages and producing engineered enzymes. New enzymes and phages with enhanced properties have a significant impact on the ability to fight antibiotic‐resistant infections, which is considered a window of hope for the future. This review, therefore, illustrates not only the challenges caused by antibiotic resistance and superbug bacteria but also the engineered enzymes and phages that are being developed to solve these issues. Our study found that engineered phages, phage proteins, and enzymes can be effective in treating superbug bacteria and destroying the biofilm caused by them. Combining these engineered compounds with other antimicrobial substances can increase their effectiveness against antibiotic‐resistant bacteria. Therefore, engineered phages, proteins, and enzymes can be used as a substitute for antibiotics or in combination with antibiotics to treat patients with superbug infections in the future. [ABSTRACT FROM AUTHOR]

In recent decades, antimicrobial resistance has become a major global public health problem. A distinct category of pathogens, known by the acronym ESKAPE, has become of particular concern because of their ability to escape the effects of available antimicrobial treatments. This acronym represents a select group of pathogenic bacteria, some of which are highly resistant to antibiotics and can cause severe and potentially fatal infections. The term "ESKAPE" is an acronym derived from the initials of these bacteria and includes Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp. Antimicrobial resistance in these pathogens is fuelled by several factors, including overuse and misuse of antibiotics, natural selection and transfer of resistance genes between bact. To meet this challenge, the global community is engaged in multiple efforts, including research and development of new antibiotics, improving practices in the use of these drugs and promoting antimicrobial research and education. In the fight against pathogens and their antimicrobial resistance, we face a constant challenge in contemporary medicine, with significant implications for healthcare delivery and public health. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance (AMR) among milk pathogens is increasing, which is a serious threat to consumers’ health. Therefore, this study aims to assess the current antibiotic profile of coliforms and Staphylococcus spp. in milk samples. For this, thirty milk samples were collected from various locations in Kathmandu district. Isolation and enumeration were done on selective media using streak-plate and pour-plate techniques, respectively. Antibiotic susceptibility testing (AST) was done by the Kirby-Bauer disk diffusion method. A total of 48 bacteria were isolated, of which 31 were coliform and 17 Staphylococcus spp. Among the coliforms, Klebsiella spp. (n=17, 54.84%) was the most predominant in both raw (n=12, 70.6%) and pasteurized milk (n=5, 29.4%), followed by E. coli and Citrobacter spp. While for Staphylococcus spp., 15 (88.24%) were S. aureus and 2 (11.76%) were coagulase negative Staphylococcus (CONS). S. aureus was dominant in raw milk (n=13) rather than pasteurized milk (n=2). The AST of coliforms showed higher resistance towards ampicillin (96.75%), followed by cefoxitin, ciprofloxacin, nalidixic acid, nitrofurantoin, piperacillin, co-trimoxazole, ceftriaxone, chloramphenicol, and amikacin in descending order. In the case of S. aureus, higher resistance was observed for penicillin G (100.00%), followed by cefoxitin, ampicillin, ceftriaxone, tetracycline, ciprofloxacin, and amikacin. Further, 12 (70.53%) S. aureus were confirmed as methicillin-resistant S. aureus (MRSA). And a total of 10 (32.25%) coliforms and 9 (52.95%) S. aureus were identified as multiple drug resistant (MDR) strains. Thus, it can be concluded that antibiotic resistance among milk isolates of the coliform and Staphylococcus spp. is highly prevalent, and these can be a potential source of incurable milk-borne infections. Thus, routine assessment of microbial quality as well as AMR surveillance should be done on milk isolates to ensure the safety of consumer’s health. [ABSTRACT FROM AUTHOR]