Search

Escherichia coli is a Gram-negative bacterium and part of the intestinal microbiota. However, it can cause various diarrhoeal illnesses, i.e., traveller's diarrhoea, dysentery, and extraintestinal infections when the bacteria are translocated from the intestine to other organs, such as urinary tract infections, abdominal and pelvic infections, pneumonia, bacteraemia, and meningitis. It is also an important pathogen in intensive care units where cross-infection may cause intrahospital spread with serious consequences. Within this study, four E. coli isolates from the tracheal aspirates of a tracheotomised paediatric patient on chronic respiratory support were analysed and compared for antibiotic resistance and virulence potential. Genomes of all four isolates (5381a, 5381b, 5681, 5848) were sequenced using Oxford Nanopore Technology. According to PFGE analysis, the clones of isolates 5681 and 5848 were highly similar, and differ from 5381a and 5381b which were isolated first chronologically. All four E. coli isolates belonged to an unknown sequence type, related to the E. coli ST131, a pandemic clone that is evolving rapidly with increasing levels of antimicrobial resistance. All four E. coli isolates in this study exhibited a multidrug-resistant phenotype as, according to MIC data, they were resistant to ceftriaxone, ciprofloxacin, doxycycline, minocycline, and tetracycline. In addition, principal component analyses revealed that isolates 5681 and 5848, which were recovered later than 5381a and 5381b (two weeks and three weeks, respectively) possessed more complex antibiotic resistance genes and virulence profiles, which is concerning considering the short time period during which the strains were isolated. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To determine the antimicrobial resistance pattern in Linezolid-resistant coagulase negative staphylococcus (CoNS) isolates in Pakistan. METHODS: This cross-sectional study was conducted from February and July 2022, at a private laboratory in Lahore, with samples collected from various regions across Pakistan. The study included microbiological samples such as blood and wound specimens, from which 4,153 isolates of CoNS were identified. Of these, only 64 isolates that were both coagulase-negative and Linezolid-resistant were selected for further investigation. The antimicrobial susceptibility patterns of these Linezolid-resistant isolates were analyzed. The antibiotics tested included amikacin, ciprofloxacin, clindamycin, doxycycline, erythromycin, fusidic acid, gentamicin, oxacillin, teicoplanin, trimethoprim-sulfamethoxazole, and vancomycin. Data analysis was performed using SPSS version-22. RESULTS: Among 4153 samples, 64 (1.54%) were Linezolid-resistant CoNS isolates, predominantly from adults (aging 18-59 years) and senior adults (aging >59 years), with a higher prevalence in males (56.3%). Resistance was observed in 51.6% of blood and 48.4% of pus samples. Most isolates were also resistant to teicoplanin (100%), ciprofloxacin (92.2%), oxacillin (89.1%), and fusidic acid (84.4%), while sensitivity was highest for vancomycin (85.9%) and doxycycline (79.7%). Statistically significant differences were noted for all antibiotics except erythromycin. CONCLUSION: Our findings highlight the importance of monitoring the evolution of Linezolid resistance in CoNS as Linezolid resistant isolates also showed high resistance to some other major antimicrobial drugs (e.g. teicoplanin, ciprofloxacin, oxacillin etc.). Linezolid resistance must be closely monitored, especially when frequent and prolonged Linezolid therapy is indicated to implement control measures and reduce the risk of CoNS spreading in the community.

Abstract Antimicrobial resistance (AMR) leads to a decrease in the adequacy of antimicrobial agents and an increase in the rate of adverse effects and mortality. The main objective of this project is to investigate the synergistic effect of BiAu@NCLin-T1 and its substructures as an antimicrobial photodynamic therapy (aPDT) agent to combat microbial resistance. In addition, the effect of photothermal therapy (PTT) on some of the designed nanostructures at a temperature of 40 °C was also tested. The antimicrobial test was carried out using the growth curve method against Escherichia coli and Staphylococcus aureus. Computational methods were used to investigate the stability and entropy of oligonucleotide sequence structures. Various analyses were performed to identify the nanostructures, including Ultraviolet–visible (UV–vis) spectroscopy, Fourier-transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), transmission electron microscopy (TEM), X-ray diffraction (XRD), scanning electron microscopy (SEM), energy-dispersive X-ray analysis (EDS) and fluorescence analysis. The BiAu@NCLin-T1 appeared the significant aPDT impact against the gram-negative E.coli strain at two distinctive oligonucleotide concentrations (1, and 1.5 micromolar (µM)). Based on the results, the outlined nanostructures can act as a photosensitizer (PS), a photothermal treatment (PTT) agent, and an antimicrobial agent to combat resistant bacteria.

Abstract Background In the present study, we aimed to determine the frequency of the csgA, fimH, mrkD, foc, papaGI, papGII and papGIII genes, to provide and to design fimbrial adhesin gene (FAG) patterns and profiles for the isolated uropathogenic Escherichia coli (UPEC) strains. Methods The enrollment of 108 positive urine samples was performed during seven months, between January 2022 and July 2022. The UPEC strains were confirmed through the standard microbiological and biochemical tests. The antimicrobial susceptibility test was performed through the Kirby–Bauer disc diffusion method. Molecular screening of FAGs was done through the polymerase chain reaction technology. The statistical analyses including chi square and Fisher’s exact tests were performed to interpret the obtained results in the present study. Results As the main results, the antimicrobial resistance (AMR) patterns, multi- (MDR) and extensively drug-resistance (XDR) patterns and FAG patterns were designed and provided. fimH (93.3%), csgA (90.4%) and papG (37.5%) (papGII (30.8%)) genes were recognized as the top three FAGs, respectively. Moreover, the frequency of csgA-fimH gene profile was identified as the top FAG pattern (46.2%) among the others. The isolates bearing csgA-fimH gene profile were armed with a versatile of phenotypic AMR patterns. In the current study, 27.8%, 69.4% and 1.9% of the UPEC isolates were detected as extended-spectrum ß-lactamases (ESBLs) producers, MDR and XDR strains, respectively. Conclusions In conclusion, detection, providing and designing of patterns and profiles in association with FAGs, AMR feature in UPEC strains give us an effective option to have a successful and influential prevention for both of UTIs initiation and AMR feature.

Abstract The use of antimicrobial drugs in food-producing animals contributes to the selection pressure on pathogenic and commensal bacteria to become resistant. This study aims to evaluate the existence of trade-offs between treatment effectiveness, cost, and the dynamics of resistance in gut commensal bacteria. We developed a within-host ordinary differential equation model to track the dynamics of antimicrobial drug concentrations and bacterial populations in the site of infection (lung) and the gut. The model was parameterized to represent enrofloxacin treatment for bovine respiratory disease (BRD) caused by Pastereulla multocida in cattle. Three approved enrofloxacin dosing regimens were compared for their effects on resistance on P. multocida and commensal E. coli: 12.5 mg/kg and 7.5 mg/kg as a single dose, and 5 mg/kg as three doses. Additionally, we explored non-FDA-approved regimes. Our results indicated that both 12.5 mg/kg and 7.5 mg/kg as a single dose scenario increased the most the treatment costs and prevalence of P. multocida resistance in the lungs, while 5 mg/kg as three doses increased resistance in commensal E. coli bacteria in the gut the most out of the approved scenarios. A proposed non-FDA-approved scenario (7.5 mg/kg, two doses 24 h apart) showed low economic costs, minimal P. multocida, and moderate effects on resistant E. coli. Overall, the scenarios that decrease P. multocida, including resistant P. multocida did not coincide with those that decrease resistant E. coli the most, suggesting a trade-off between both outcomes. The sensitivity analysis suggests that bacterial populations were the most sensitive to drug conversion factors into plasma ( $${\beta}$$ β ), elimination of the drug from the colon ( $$\vartheta$$ ϑ ), fifty percent sensitive bacteria (P. multocida) killing effect ( $${\text{L}}_{\text{s50}}$$ L s50 ), fifty percent of bacteria (E. coli) above ECOFF killing effect ( $${\text{C}}_{\text{r50}}$$ C r50 ), and net drug transfer rate in the lung ( $$\gamma$$ γ ) parameters.

Antimicrobial resistance (AMR) leads to a decrease in the adequacy of antimicrobial agents and an increase in the rate of adverse effects and mortality. The main objective of this project is to investigate the synergistic effect of BiAu@NCLin-T1 and its substructures as an antimicrobial photodynamic therapy (aPDT) agent to combat microbial resistance. In addition, the effect of photothermal therapy (PTT) on some of the designed nanostructures at a temperature of 40 °C was also tested. The antimicrobial test was carried out using the growth curve method against Escherichia coli and Staphylococcus aureus. Computational methods were used to investigate the stability and entropy of oligonucleotide sequence structures. Various analyses were performed to identify the nanostructures, including Ultraviolet–visible (UV–vis) spectroscopy, Fourier-transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), transmission electron microscopy (TEM), X-ray diffraction (XRD), scanning electron microscopy (SEM), energy-dispersive X-ray analysis (EDS) and fluorescence analysis. The BiAu@NCLin-T1 appeared the significant aPDT impact against the gram-negative E.coli strain at two distinctive oligonucleotide concentrations (1, and 1.5 micromolar (µM)). Based on the results, the outlined nanostructures can act as a photosensitizer (PS), a photothermal treatment (PTT) agent, and an antimicrobial agent to combat resistant bacteria. [ABSTRACT FROM AUTHOR]

Background: In the present study, we aimed to determine the frequency of the csgA, fimH, mrkD, foc, papaGI, papGII and papGIII genes, to provide and to design fimbrial adhesin gene (FAG) patterns and profiles for the isolated uropathogenic Escherichia coli (UPEC) strains. Methods: The enrollment of 108 positive urine samples was performed during seven months, between January 2022 and July 2022. The UPEC strains were confirmed through the standard microbiological and biochemical tests. The antimicrobial susceptibility test was performed through the Kirby–Bauer disc diffusion method. Molecular screening of FAGs was done through the polymerase chain reaction technology. The statistical analyses including chi square and Fisher's exact tests were performed to interpret the obtained results in the present study. Results: As the main results, the antimicrobial resistance (AMR) patterns, multi- (MDR) and extensively drug-resistance (XDR) patterns and FAG patterns were designed and provided. fimH (93.3%), csgA (90.4%) and papG (37.5%) (papGII (30.8%)) genes were recognized as the top three FAGs, respectively. Moreover, the frequency of csgA-fimH gene profile was identified as the top FAG pattern (46.2%) among the others. The isolates bearing csgA-fimH gene profile were armed with a versatile of phenotypic AMR patterns. In the current study, 27.8%, 69.4% and 1.9% of the UPEC isolates were detected as extended-spectrum ß-lactamases (ESBLs) producers, MDR and XDR strains, respectively. Conclusions: In conclusion, detection, providing and designing of patterns and profiles in association with FAGs, AMR feature in UPEC strains give us an effective option to have a successful and influential prevention for both of UTIs initiation and AMR feature. [ABSTRACT FROM AUTHOR]

Tigecycline is a last-resort drug used to treat serious infections caused by multidrug-resistant bacteria. tet(X4) is a recently discovered plasmid-mediated tigecycline resistance gene that confers high-level resistance to tigecycline and other tetracyclines. Since the first discovery of tet(X4) in 2019, it has spread rapidly worldwide, and as a consequence, tigecycline has become increasingly ineffective in the clinical treatment of multidrug-resistant infections. In this study, we identified and analyzed tet(X4)-positive Escherichia coli isolates from duck farms in Hunan Province, China. In total, 976 samples were collected from nine duck farms. Antimicrobial susceptibility testing and whole-genome sequencing (WGS) were performed to establish the phenotypes and genotypes of tet(X4)- positive isolates. In addition, the genomic characteristics and transferability of tet (X4) were determined based on bioinformatics analysis and conjugation. We accordingly detected an E. coli strain harboring tet(X4) and seven other resistance genes in duck feces. Multi-locus sequence typing analysis revealed that this isolate belonged to a new clone, and subsequent genetic analysis indicated that tet(X4) was carried in a 4608-bp circular intermediate, flanked by ISVsa3-ORF2-abh elements. Moreover, it exhibited transferability to E. coli C600 with a frequency of 10-5. The detection of tet(X4)-harboring E, coli strains on duck farms enhances our understanding of tigecycline resistance dynamics. The transferable nature of the circular intermediate of tet(X4) contributing to the spread of tigecycline resistance genes poses a substantial threat to healthcare. Consequently, vigilant monitoring and proactive measures are necessary to prevent their spread. [ABSTRACT FROM AUTHOR]

The use of antimicrobial drugs in food-producing animals contributes to the selection pressure on pathogenic and commensal bacteria to become resistant. This study aims to evaluate the existence of trade-offs between treatment effectiveness, cost, and the dynamics of resistance in gut commensal bacteria. We developed a within-host ordinary differential equation model to track the dynamics of antimicrobial drug concentrations and bacterial populations in the site of infection (lung) and the gut. The model was parameterized to represent enrofloxacin treatment for bovine respiratory disease (BRD) caused by Pastereulla multocida in cattle. Three approved enrofloxacin dosing regimens were compared for their effects on resistance on P. multocida and commensal E. coli: 12.5 mg/kg and 7.5 mg/kg as a single dose, and 5 mg/kg as three doses. Additionally, we explored non-FDA-approved regimes. Our results indicated that both 12.5 mg/kg and 7.5 mg/kg as a single dose scenario increased the most the treatment costs and prevalence of P. multocida resistance in the lungs, while 5 mg/kg as three doses increased resistance in commensal E. coli bacteria in the gut the most out of the approved scenarios. A proposed non-FDA-approved scenario (7.5 mg/kg, two doses 24 h apart) showed low economic costs, minimal P. multocida, and moderate effects on resistant E. coli. Overall, the scenarios that decrease P. multocida, including resistant P. multocida did not coincide with those that decrease resistant E. coli the most, suggesting a trade-off between both outcomes. The sensitivity analysis suggests that bacterial populations were the most sensitive to drug conversion factors into plasma (β ), elimination of the drug from the colon (ϑ ), fifty percent sensitive bacteria (P. multocida) killing effect ( L s50 ), fifty percent of bacteria (E. coli) above ECOFF killing effect ( C r50 ), and net drug transfer rate in the lung (γ ) parameters. [ABSTRACT FROM AUTHOR]

Understanding the epidemiology of carbapenem-resistant A. baumannii complex (CRAB) and the patients impacted is an important step toward informing better infection prevention and control practices and improving public health response. Active, population-based surveillance was conducted for CRAB in 9 U.S. sites from January 1 to December 31, 2019. Medical records were reviewed, isolates were collected and characterized including antimicrobial susceptibility testing and whole genome sequencing. Among 136 incident cases in 2019, 66 isolates were collected and characterized; 56.5% were from cases who were male, 54.5% were from persons of Black or African American race with non-Hispanic ethnicity, and the median age was 63.5 years. Most isolates, 77.2%, were isolated from urine, and 50.0% were collected in the outpatient setting; 72.7% of isolates harbored an acquired carbapenemase gene (aCP), predominantly bla OXA-23 or bla OXA-24/40 ; however, an isolate with bla NDM was identified. The antimicrobial agent with the most in vitro activity was cefiderocol (96.9% of isolates were susceptible). Our surveillance found that CRAB isolates in the U.S. commonly harbor an aCP, have an antimicrobial susceptibility profile that is defined as difficult-to-treat resistance, and epidemiologically are similar regardless of the presence of an aCP. [ABSTRACT FROM AUTHOR]

Introduction: Non-typhoidal Salmonella (NTS) bacteremia is common in sub-Saharan Africa. We examined the prevalence of antibiotic resistance to fluoroquinolones, third-generation cephalosporins, and multi-drug resistance (MDR) in NTS human isolates from sub-Saharan Africa. Methods: A systematic review was conducted using a search in Ovid Medline, Embase, and African Index Medicus of publications between 2000 and 2021. A random-effects model meta-analysis was performed using data from 66 studies that included 29,039 NTS blood and 1,065 stool isolates. Results: The pooled prevalence proportions of MDR were 0.685 (95% CI 0.574–0.778) and 0.214 (0.020–0.785) in blood vs. stool isolates. The corresponding estimates of fluoroquinolones resistance were 0.014 (0.008–0.025) vs. 0.021 (0.012–0.036) and third-generation cephalosporins resistance 0.019 (0.012–0.031) vs. 0.035 (0.006–0.185). Similar results were found for children and adults. Resistance prevalence to these antibiotics in blood isolates increased between 2000–2010 and 2011–2021. The guidelines employed to determine antimicrobial resistance and epidemiological characteristics (e.g. sample size, study duration) correlated with the resistance prevalence. Conclusions: The prevalence of MDR and resistance to fluoroquinolones and third-generation cephalosporins in NTS in sub-Saharan Africa is alarming. Expert opinion: Standardized surveillance of antimicrobial drug resistance in NTS in sub-Saharan Africa is warranted to guide healthcare policymaking and antibiotic stewardship programs. Plain Language Summary: Non-typhoidal Salmonella (NTS) usually causes diarrheal disease, but some patients might develop bloodstream infection. The occurrence and case fatality of bloodstream infections caused by NTS are high in sub-Saharan Africa. However, the information on antibiotic resistance of these bacteria in this region is scarce. We performed a systematic review and meta-analysis to examine the prevalence of multi-drug resistance (MDR) and resistance to antibiotics used to treat NTS bloodstream infection: fluoroquinolones and third-generation cephalosporins in NTS isolates from patients from sub-Saharan Africa. We used data from 66 studies. In NTS blood isolates, the combined prevalence was 1.4% for fluoroquinolones resistance, 1.9% for resistance to third-generation cephalosporins, and 68.5% for MDR. These estimates were 2.1%, 3.5%, and 21.4% in stool isolates. The prevalence of resistance to fluoroquinolones and third-generation cephalosporins in blood isolates has increased in the past 2 decades. The guidelines employed to determine antimicrobial resistance and the study epidemiological characteristics were related to the resistance prevalence. The high prevalence of MDR in NTS raises concerns, and the emergence of resistance to fluoroquinolones and third-generation cephalosporins is worrisome. Strengthening the monitoring of antimicrobial drug resistance in NTS is essential to guide patients' care and policymaking in sub-Saharan Africa. [ABSTRACT FROM AUTHOR]

Background and Objectives: Urinary tract infections (UTIs), one of the most prevalent bacterial infections, are facing limited treatment options due to escalating concern of antibiotic resistance. Urine cultures significantly help in identification of etiological agents responsible for these infections. Assessment of antibiotic susceptibility patterns of these bacteria aids in tackling the emerging concern of antibiotic resistance and establishment of empirical therapy guidelines. Our aim was to determine various agents responsible for urinary tract infections and to assess their antibiotic susceptibility patterns. Materials and Methods: This cross-sectional study was performed over a period of six months from January 2023 to July 2023 in Department of Microbiology of Pakistan Institute of Medical Sciences (PIMS). Results: Out of 2957 positive samples, Gram negative bacteria were the most prevalent in 1939 (65.6%) samples followed by Gram positive bacteria in 418 (14.1%) and Candida spp. in 269 (9.1%) samples. In gram negative bacteria, Escherichia coli (E. coli) was the most prevalent bacteria isolated from 1070 samples (55.2%) followed by Klebsiella pneumoniae in 397 samples (20.5%). In Gram positive bacteria, Enterococcus spp. was the most common bacteria in 213 samples (51%) followed by Staphylococcus aureus in 120 samples (28.7%). Amikacin was the most sensitive drug (91%) for Gram negative bacteria. Gram positive bacteria were most susceptible to linezolid (97%-100%). Conclusion: The generation of a hospital tailored antibiogram is essential for the effective management of infections and countering antibiotic resistance. By adopting antimicrobial stewardship strategies by deeper understanding of sensitivity patterns, we can effectively combat antibiotic resistance. [ABSTRACT FROM AUTHOR]

Background: There is a concerning rise in antifungal‐resistant dermatophytosis globally, with resistance to terbinafine conferred by point mutations in the squalene epoxidase (SQLE) gene. Objectives: Report changes in the prevalence and profile of SQLE mutations in onychomycosis patients in the United States. Methods: A longitudinal cohort study of toenail samples was collected from suspected onychomycosis patients over an 18‐month period from 2022 to 2023. Samples were submitted from across the United States and subjected to multiplex real‐time polymerase chain reactions for dermatophyte detection, with further screening of SQLE mutations at four known hotspots (393Leu, 397Phe, 415Phe and 440His). Results: A total of 62,056 samples were submitted (mean age: 57.5 years; female: 60.4%). Dermatophytes were detected in 38.5% of samples, primarily Trichophyton rubrum complex (83.6%) and T. mentagrophytes complex (10.7%). A survey of SQLE mutations was carried out in 22,610 dermatophyte samples; there was a significant increase in the prevalence of SQLE mutations between the first quarter of 2022 and the second quarter of 2023 (29.0 to 61.9 per 1000 persons). The Phe397Leu substitution was the predominant mutation; Phe415Ser and His440Tyr have also emerged which were previously reported as minor mutations in skin samples. The temporal change in mutation rates can be primarily attributed to the Phe415Ser substitution. Samples from elderly patients (>70 years) are more likely to be infected with the T. mentagrophytes complex including strains harbouring the Phe415Ser substitution. Conclusion: The prevalence of SQLE mutations among onychomycosis patients with Trichophyton infections may be underestimated. Older individuals may have a higher risk. [ABSTRACT FROM AUTHOR]

Yokenella regensburgei is a Gram-negative rod part of the Enterobacteriaceae family (order Enterobacterales) and a rare cause of human infections. Although improved diagnostic methods have led to an increase in reports of this elusive pathogen, information remains limited. In order to provide a better understanding of this bacterium, we developed the first comprehensive review of its biology, biochemical profile, antimicrobial resistance pattern, virulence factors, natural reservoir and involvement in various veterinary and human infections. Human infections with this bacterium are scarcely reported, most probably due to constraints regarding its identification and biochemical similarities to Hafnia alvei. Multiple systematic searches revealed 23 cases of human infection, with a seemingly worldwide distribution, mostly in middle-aged or elderly male patients, often associated with immunosuppression. To date, Y. regensburgei has been reported in skin and soft tissue infections, bacteremia and sepsis, osteoarticular infections and in others such as urinary tract and digestive infections. The unique ability of Y. regensburgei to degrade polystyrene presents a novel and promising avenue for addressing plastic pollution in the near future. However, large-scale applications of this bacterium will undoubtedly increase human exposure, highlighting the necessity for comprehensive research into its role in human and veterinary infections, pathogenicity and antibiotic resistance. [ABSTRACT FROM AUTHOR]

The rise of drug-resistant pathogens, driven by the misuse and overuse of antibiotics, has created a formidable challenge for global public health. Antimicrobial peptides and proteins have garnered considerable attention as promising candidates for novel antimicrobial agents. These bioactive molecules, whether derived from natural sources, designed synthetically, or predicted using artificial intelligence, can induce lethal effects on pathogens by targeting key microbial structures or functional components, such as cell membranes, cell walls, biofilms, and intracellular components. Additionally, they may enhance overall immune defenses by modulating innate or adaptive immune responses in the host. Of course, development of antimicrobial peptides and proteins also face some limitations, including high toxicity, lack of selectivity, insufficient stability, and potential immunogenicity. Despite these challenges, they remain a valuable resource in the fight against drug-resistant pathogens. Future research should focus on overcoming these limitations to fully realize the therapeutic potential of antimicrobial peptides in the infection control.

Abstract The emergence of drug-resistant Mycobacterium tuberculosis strains is a threat to global health necessitating the discovery of novel chemotherapeutic agents. Natural products drug discovery, which previously led to the discovery of rifamycins, is a valuable approach in this endeavor. Against this backdrop, we set out to investigate the in vitro antimycobacterial properties of medicinal plants from Ghana and South Africa, evaluating 36 extracts and their 252 corresponding solid phase extraction (SPE) generated fractions primarily against the non-pathogenic Mycobacterium smegmatis and Mycobacterium aurum species. The most potent fraction was further evaluated in vitro against infectious M. tuberculosis strain. Crinum asiaticum (bulb) (Amaryllidaceae) emerged as the most potent plant species with specific fractions showing exceptional, near equipotent activity against the non-pathogenic Mycobacterium species (0.39 µg/ml ≤ MIC ≤ 25 µg/ml) with one fraction being moderately active (MIC = 32.6 µg/ml) against M. tuberculosis. Metabolomic analysis led to the identification of eight compounds predicted to be active against M. smegmatis and M. aurum. In conclusion, from our comprehensive study, we generated data which provided an insight into the antimycobacterial properties of Ghanaian and South African plants. Future work will be focused on the isolation and evaluation of the compounds predicted to be active.

Drug repurposing (repositioning) is a dynamically-developing area in the search for effective therapy of infectious diseases. Repositioning existing drugs with a well-known pharmacological and toxicological profile is an attractive method for quickly discovering new therapeutic indications. The off-label use of drugs for infectious diseases requires much less capital and time, and can hasten progress in the development of new antimicrobial drugs, including antibiotics. The use of drug repositioning in searching for new therapeutic options has brought promising results for many viral infectious diseases, such as Ebola, ZIKA, Dengue, and HCV. This review describes the most favorable results for repositioned drugs for the treatment of bacterial infections. It comprises publications from various databases including PubMed and Web of Science published from 2015 to 2023. The following search keywords/strings were used: drug repositioning and/or repurposing and/or antibacterial activity and/ or infectious diseases. Treatment options for infections caused by multidrugresistant bacteria were taken into account, including methicillin-resistant staphylococci, multidrug-resistant Mycobacterium tuberculosis, or carbapenem-resistant bacteria from the Enterobacteriaceae family. It analyses the safety profiles of the included drugs and their synergistic combinations with antibiotics and discusses the potential of antibacterial drugs with antiparasitic, anticancer, antipsychotic effects, and those used in metabolic diseases. Drug repositioning may be an effective response to public health threats related to the spread of multidrug-resistant bacterial strains and the growing antibiotic resistance of microorganisms. [ABSTRACT FROM AUTHOR]

Systemic antibiotics are an effective adjunct in the treatment of periodontitis, but their judicious use is necessary as antimicrobial resistance is a growing global concern. This review aims to explore the current understanding and insight related to antibiotic resistance in the subgingival microbiota of periodontitis patients. A search of MEDLINE (PubMed) was carried out from 1 January 2012 to 25 November 2021 for studies related to antibiotic resistance in periodontitis patients. Of the 90 articles identified, 12 studies were selected for inclusion. A significant incidence of antibiotic resistant isolates was reported for Porphyromonas gingivalis, Prevotella intermedia, Prevotella denticola, Prevotella melaninogenica, Fusobacterium nucleatum, Tanerella forsythia, Aggretibacter actinomycetemcomitans, Streptococcus constellatus, Streptococcus intermedius, and Parvimonas micra, but resistance to specific antibiotics did not reach above 10% of isolates in most studies except for amoxicillin resistance in Aggretibacter actinomycetemcomitans. The highest frequency of resistance across all bacterial species was for amoxicillin, clindamycin, and metronidazole. However, resistance patterns were widely variable across geographical locations, and the high heterogeneity between antibiotic-resistant isolates across studies precludes any clinical recommendations from this study. Although antibiotic resistance has yet to reach critical levels in periodontitis patients, an emphasis on antibiotic stewardship interventions such as point-of-care diagnostics and education for key stakeholders is needed to curb a growing problem. [ABSTRACT FROM AUTHOR]

Background: Improvements in liver transplant (LT) outcomes are attributed to advances in surgical techniques, use of potent immunosuppressants, and rigorous pre-LT testing. Despite these improvements, post-LT infections remain the most common complication in this population. Bacteria constitute the most common infectious agents, while fungal and viral infections are also frequently encountered. Multi-drug–resistant bacterial infections develop because of polymicrobial overuse and prolonged hospital stays. Immediate post-LT infections are commonly caused by viruses. Conclusions: Appropriate vaccination, screening of both donor and recipients before LT and antiviral prophylaxis in high-risk individuals are recommended. Antimicrobial drug resistance is common in high-risk LT and associated with poor outcomes; epidemiology and management of these cases is discussed. Additionally, we also discuss the effect of coronavirus disease 2019 (COVID-19) infection and monkeypox in the LT population. [ABSTRACT FROM AUTHOR]

Epidemiological data on extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales are most often based on microbiological laboratory isolates and do not consider important clinical data such as infection or colonisation, treatment, and outcome. This study aimed to assess prevalence of ESBL-producing Enterobacterales as the cause of infection in patients with suspected sepsis in the emergency department based on clinical data. It also examined the number of patients with suspected sepsis who had ESBL-producing pathogens, comparing estimates that were based on laboratory data versus a combination of laboratory and clinical data. Patients with suspected sepsis in the emergency department at Skåne University Hospital, Lund, Sweden were included consecutively. Data were collected retrospectively from medical records. Of the 764 included patients, 223 patients had growth of Enterobacterales in any specimen (i.e. colonisation or infection according to laboratory data), while 191 patients had Enterobacterales detected in the blood or in the suspected focus of infection (i.e. an infection according to clinical and laboratory data). Eighteen patients had ESBL-producing Enterobacterales in any clinical specimen, 11 of whom had an infection with ESBL-producing Enterobacterales, resulting in a prevalence of infections with ESBL-producing Enterobacterales in infected patients with suspected sepsis of 1.8%. The number of patients with ESBL-producing Enterobacterales was not significantly different when infection was defined using laboratory data alone versus a combination of laboratory and clinical data [18/223 (8.1%) vs 11/191 (5.8%), p = 0.36]. The prevalence of ESBL-producing Enterobacterales infections among patients with suspected sepsis is low in an acute care setting in Sweden. [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]

Background and Objectives: Urinary tract infections (UTIs), one of the most prevalent bacterial infections, are facing limited treatment options due to escalating concern of antibiotic resistance. Urine cultures significantly help in identification of etiological agents responsible for these infections. Assessment of antibiotic susceptibility patterns of these bacteria aids in tackling the emerging concern of antibiotic resistance and establishment of empirical therapy guidelines. Our aim was to determine various agents responsible for urinary tract infections and to assess their antibiotic susceptibility patterns. Materials and Methods: This cross-sectional study was performed over a period of six months from January 2023 to July 2023 in Department of Microbiology of Pakistan Institute of Medical Sciences (PIMS). Results: Out of 2957 positive samples, Gram negative bacteria were the most prevalent in 1939 (65.6%) samples followed by Gram positive bacteria in 418 (14.1%) and Candida spp. in 269 (9.1%) samples. In gram negative bacteria, Escherichia coli (E. coli) was the most prevalent bacteria isolated from 1070 samples (55.2%) followed by Klebsiella pneumoniae in 397 samples (20.5%). In Gram positive bacteria, Enterococcus spp. was the most common bacteria in 213 samples (51%) followed by Staphylococcus aureus in 120 samples (28.7%). Amikacin was the most sensitive drug (91%) for Gram negative bacteria. Gram positive bacteria were most susceptible to linezolid (97%-100%). Conclusion: The generation of a hospital tailored antibiogram is essential for the effective management of infections and countering antibiotic resistance. By adopting antimicrobial stewardship strategies by deeper understanding of sensitivity patterns, we can effectively combat antibiotic resistance.

Introduction. Urinary Tract Infection (UTI) is one of the most common bacterial infections encountered by clinicians worldwide. The emergence of multidrug-resistant uropathogens necessitates a review of their susceptibility profiles. This study aims to assess the susceptibility trends of uropathogens to a panel of drugs, with special emphasis on Nitrofurantoin (NFT). Methods. A retrospective analysis was conducted on 2,099 mid-stream clean catch urine samples processed by standard microbiological methods. Clinical and Laboratory Standards Institute (CLSI) guidelines (2019) were followed. Statistical analysis was performed. Results. Out of all samples, 212 were culture positive. Escherichia coli (34.9%) and Enterococcus spp. (15.1%) were the most common Gram-negative and Gram-positive organisms, respectively. Gram-negative isolates were most susceptible to Colistin (97.38%), followed by NFT (69.35%). Gram-positive uropathogens were most sensitive to Linezolid (100%), followed by Vancomycin and NFT, each with 92.45% susceptibility. Conclusion. The increase in antibiotic resistance among various uropathogens underscores the need for surveillance data to inform the appropriate selection of antibiotics. Our study highlights that, among the panel of antibiotics tested, NFT appears to be a viable alternative for treating multidrug-resistant uropathogens.

Introduction: Many viral and bacterial respiratory tract infections can present with respiratory signs and progress to complicated pneumonia. In the recent Coronavirus Disease2019 (COVID-19) pandemic, it is crucial to test all Severe Acute Respiratory Infection (SARI) patients for other microbial infections in addition to COVID-19, enabling timely diagnosis and treatment to reduce morbidity and mortality. The automated system, BioFire FilmArray, utilises multiplex Polymerase Chain Reaction (PCR) to rapidly detect and identify multiple respiratory pathogens, including selected Antimicrobial Resistance (AMR) genes, within an hour. Aim: To detect bacterial and/or viral pathogens associated with hospitalised COVID-19-negative SARI patients using the BioFire FilmArray Pneumonia Panel (BFPP). Materials and Methods: This laboratory-based cross-sectional study was conducted at All India Institute of Medical Sciences (AIIMS), Nagpur, Maharashtra, India, from June 2020 to February 2021. Respiratory samples, such as sputum, tracheal aspirate, Endotracheal (ET) secretions, and Bronchoalveolar Lavage (BAL), were collected from COVID-19-negative hospitalised SARI cases. A total of 81 patients were included in the study. The samples were tested using the BFPP (multiplex PCR) system and processed using conventional culture techniques. Patient characteristics, clinical and laboratory investigation data, and findings of respiratory viral and bacterial agents, as well as antibiotic resistance genes detected by BioFire FilmArray, were recorded using paper case reports. The data were collected and analysed using Statistical Package for Social Sciences (SPSS) software. Results: Out of the 81 clinical samples processed, the BFPP detected 168 bacterial and 18 viral pathogens. Bacterial-viral codetection was observed in 13 (16%) samples. Atypical bacteria were detected in 3% of cases. Among the bacterial pathogens, the AMR gene for New Delhi Metallo-beta-lactamases (NDM) was detected in 42 (25.9%) cases, followed by CTX-M betalactamases, VIM, and the oxacillinase group of β-lactamases. Conclusion: The BFPP test is a valuable tool for the rapid detection of a wide range of pathogens, including associated AMR genes, with high sensitivity and specificity. This can greatly aid in treatment decisions.

We describe detection of the previously rarely reported gram-positive bacterium Auritidibacter ignavus in 3 cases of chronic ear infections in Germany. In all 3 cases, the patients had refractory otorrhea. Although their additional symptoms varied, all patients had an ear canal stenosis and A. ignavus detected in microbiologic swab specimens. A correct identification of A. ignavus in the clinical microbiology laboratory is hampered by the inability to identify it by using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Also, the bacterium might easily be overlooked because of its morphologic similarity to bacterial species of the resident skin flora. We conclude that a high index of suspicion is warranted to identify A. ignavus and that it should be particularly considered in patients with chronic external otitis who do not respond clinically to quinolone ear drop therapy.

Nosocomial infections in the neonatal intensive care unit (NICU) tend to cluster and multidrug-resistant (MDR) pathogens are rising in developing countries. We did a retrospective cohort study of neonates admitted to a NICU in Brazil with late-onset neonatal sepsis (LOS) confirmed by blood culture from October 2012 to December 2016 and from July 2018 to December 2021. We defined a cluster of infection when at least two cases of LOS occurred within two different time intervals: 15 and 30 days with the same pathogen in different patients. A random amplified polymorphic DNA (RAPD) was performed from samples from one of these clusters. A logistic regression model was applied having death as the outcome and the infection with an MDR pathogen as the exposure of interest. There were 987 blood cultures from 754 neonates, 621 (63%) were gram-positive cocci, 264 (30%) were gram-negative rods and 72 (7%) fungi. A third of Enterobacterales were resistant to cefepime and a third of non-fermenting glucose rods were resistant to carbapenems. There were 100 or 104 clusters of infection in the 15- or 30-day interval, respectively. A RAPD analysis from an outbreak of MDR Acinetobacter baumannii showed that all five samples belonged to a single clone. An infection with an MDR pathogen was associated with death (OR 1.82, 95% CI 1.03–3.21). In conclusion, clusters of infections in a Brazilian NICU are a frequent phenomenon as seen elsewhere. They suggest cross-transmission of pathogens with increasing antimicrobial resistance and should prompt intensified surveillance and infection control measures. [ABSTRACT FROM AUTHOR]

Background and Objectives: Antimicrobial resistance has emerged as a significant global health threat. Infections caused by Multi Drug-Resistant (MDR) bacteria pose formidable challenges in terms of treatment options and patient outcomes. Pus cultures serve as crucial diagnostic tools in identifying the agents responsible for various infections, and their antimicrobial susceptibility patterns which help in establishment of empirical therapy guidelines. This study was conducted to determine the pathogen and its susceptibility pattern from pus cultures and to generate antibiogram in our tertiary care setting. Materials and Methods: It was a cross-sectional study, conducted for a period of six months, from July 2022 to December 2022, in the Pathology Department of Pakistan Institute of Medical Sciences (PIMS). Results: Out of total 2507 samples received, 1242 (49.5%) showed positive culture. Among the 1242 positive samples, 364 were Gram positive cocci (GPCs) and 878 were Gram negative rods (GNRs). Methicillin resistant Staphylococcus aureus (MRSA) was the most common isolate (23%) followed by Klebsiella pneumoniae (22.6%), Pseudomonas aeruginosa (16.9%), Enterobacter spp. (15.5%) and Escherichia coli (14.2%). Vancomycin was found to be highly effective (100%) against MRSA. GPCs were highly susceptible to linezolid (98%) while GNRs showed high level of sensitivity to colistin (96%) and tigecycline (92%). Conclusion: The generation of a local antibiogram specific to the hospital setting is essential to effectively manage infections empirically and preserve the efficacy of existing antibiotics. By implementing antimicrobial stewardship practices based on a better understanding of antibiotic susceptibility patterns, we can contribute to the mitigation of antibiotic resistance and improve patient outcomes. [ABSTRACT FROM AUTHOR]

Background: Antimicrobial resistance is a global health problem, due to morbidity, mortality, and healthcare costs. The misuse of antimicrobials is the main cause of antimicrobial resistance. The aim of this study was to report antimicrobial resistance and antibiotic consumption in a secondary care hospital in Mexico. Methods: Within a cross-sectional study, antimicrobial resistance data on ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) and antibiotic consumption from 2020 to 2022 were collected. Antimicrobial resistance was reported based on percentages of resistance and consumption was analyzed using the defined daily dose (DDD)/100 bed days and the AWaRe (Access, Surveillance, Reservation) antibiotic group. Results: Antibiotic consumption in 2020, 2021 and 2022 was 330, 175 and 175 DDD/100 beds day, respectively. The rate of ceftriaxone resistance in E. coli (n = 526) and K. pneumoniae (n = 80) was 76% and 69%, respectively, the rate of carbapenem resistance in A. baumannii (n = 168) and P. aeruginosa (n = 108) was 92% and 52%, respectively; the rate of oxacillin resistance in S. aureus (n = 208) was 27%; and the rate of vancomycin resistance in E. faecium (n = 68) was 47%. Conclusion: The reported results are congruent with global estimates of antibiotic resistance and consumption, providing an overview that could generate actions for antimicrobial optimization at the local and regional levels. [ABSTRACT FROM AUTHOR]

Purpose: Antibiotic-resistant bacterial pneumonia poses a significant therapeutic challenge. In China, Chinese herbal compound (CHC) is commonly used to treat bacterial pneumonia. We aimed to evaluate the efficacy and safety of CHC and identify core herb combinations for the treatment of multidrug-resistant or extensively drug-resistant bacterial pneumonia. Methods: Stata 16 and TSA 0.9.5.10 beta software were used for meta-analysis and trial sequential analysis (TSA), respectively. Exploring the sources of heterogeneity through meta-regression and subgroup analysis. Results: Thirty-eight studies involving 2890 patients were included in the analyses. Meta-analysis indicated that CHC combined with antibiotics improved the response rate (RR = 1.24; 95% CI: 1.19-1.28; p < 0.0001) and microbiological eradication (RR = 1.41; 95% CI: 1.27-1.57; p < 0.0001), lowered the white blood cell count (MD = -2.09; 95% CI: -2.65 to -1.53; p < 0.0001), procalcitonin levels (MD = -0.49; 95% CI: -0.59 to -0.40; p < 0.0001), C-reactive protein levels (MD = -11.80; 95% CI: -15.22 to -8.39; p < 0.0001), Clinical Pulmonary Infection Scores (CPIS) (MD = -1.97; 95% CI: -2.68 to -1.26; p < 0.0001), and Acute Physiology and Chronic Health Evaluation (APACHE)-II score (MD = -4.08; 95% CI: -5.16 to -3.00; p < 0.0001), shortened the length of hospitalization (MD = -4.79; 95% CI: -6.18 to -3.40; p < 0.0001), and reduced the number of adverse events. TSA indicated that the response rate and microbiological eradication results were robust. Moreover, Scutellaria baicalensis Georgi, Fritillaria thunbergii Miq, Lonicera japonica Thunb, and Glycyrrhiza uralensis Fisch were identified as core CHC prescription herbs. Conclusion: Compared with antibiotic treatment, CHC + antibiotic treatment was superior in improving response rate, microbiological eradication, inflammatory response, CPIS, and APACHE-II score and shortening the length of hospitalization. Association rule analysis identified four core herbs as promising candidates for treating antibiotic-resistant bacterial pneumonia. However, large-scale clinical studies are still required. [ABSTRACT FROM AUTHOR]

Background: Antimicrobial resistance (AMR) is one of the leading causes of worldwide mortality, directly responsible for 1.27 million deaths in 2019. Irrational antibiotic usage is widely reported in the literature and is the most important cause of AMR. Objectives: The objective of this study was to assess awareness and knowledge of antibiotics and AMR among patients attending the general outpatient department (GOPD) of a tertiary-level hospital. Material and Methods: This was a single-center, hospital-based, and descriptive study of cross-sectional design conducted in 2022. All patients aged 18 years or more attending GOPD on the data collection days were eligible to participate. One hundred and seventeen patients were interviewed using a structured schedule, following a systematic sampling design and maintaining standard ethical practice. Besides descriptive statistics, Chi-square tests were used to check for association between variables. All analyses were conducted by the Statistical Package for the Social Sciences version 23. Results: Mean age of the participants was 39.1 years (standard deviation ± 12.3), with 50.4% male. Awareness of antibiotics was 69.2%, while awareness of AMR was a mere 14.5%. Knowledge on antibiotics was higher for antibiotic use rather for antibiotic action. Higher awareness of antibiotics was for the male gender, higher education, and those who were single and currently working. Healthcare providers were the source of knowledge for this population. Conclusion: Awareness and prescription use of antibiotics was high with two out of three aware respondents having correct knowledge on the use of antibiotics. Low awareness of AMR may not sustain the good practice of prescription use of antibiotics. [ABSTRACT FROM AUTHOR]

Introduction: Many viral and bacterial respiratory tract infections can present with respiratory signs and progress to complicated pneumonia. In the recent Coronavirus Disease-2019 (COVID-19) pandemic, it is crucial to test all Severe Acute Respiratory Infection (SARI) patients for other microbial infections in addition to COVID-19, enabling timely diagnosis and treatment to reduce morbidity and mortality. The automated system, BioFire FilmArray, utilises multiplex Polymerase Chain Reaction (PCR) to rapidly detect and identify multiple respiratory pathogens, including selected Antimicrobial Resistance (AMR) genes, within an hour. Aim: To detect bacterial and/or viral pathogens associated with hospitalised COVID-19-negative SARI patients using the BioFire FilmArray Pneumonia Panel (BFPP). Materials and Methods: This laboratory-based cross-sectional study was conducted at All India Institute of Medical Sciences (AIIMS), Nagpur, Maharashtra, India, from June 2020 to February 2021. Respiratory samples, such as sputum, tracheal aspirate, Endotracheal (ET) secretions, and Bronchoalveolar Lavage (BAL), were collected from COVID-19-negative hospitalised SARI cases. A total of 81 patients were included in the study. The samples were tested using the BFPP (multiplex PCR) system and processed using conventional culture techniques. Patient characteristics, clinical and laboratory investigation data, and findings of respiratory viral and bacterial agents, as well as antibiotic resistance genes detected by BioFire FilmArray, were recorded using paper case reports. The data were collected and analysed using Statistical Package for Social Sciences (SPSS) software. Results: Out of the 81 clinical samples processed, the BFPP detected 168 bacterial and 18 viral pathogens. Bacterial-viral codetection was observed in 13 (16%) samples. Atypical bacteria were detected in 3% of cases. Among the bacterial pathogens, the AMR gene for New Delhi Metallo-beta-lactamases (NDM) was detected in 42 (25.9%) cases, followed by CTX-M betalactamases, VIM, and the oxacillinase group of β-lactamases. Conclusion: The BFPP test is a valuable tool for the rapid detection of a wide range of pathogens, including associated AMR genes, with high sensitivity and specificity. This can greatly aid in treatment decisions. [ABSTRACT FROM AUTHOR]

Copyright of Fenerbahce University Journal of Health Sciences (FBU-JOSH) / Fenerbahçe Üniversitesi Sağlık Bilimleri Dergisi is the property of Fenerbahce University Journal of Health Sciences (FBU-JOSH) 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.)

Objective: Comprehensive antimicrobial stewardship programs (ASPs) are needed in Indian healthcare settings due to high rates of communicable diseases and excessive antibiotic use. However, the implementation of both ASPs and clinical pharmacists (CPs) into the system is still in its nascent stages in India. Therefore, our study aims to evaluate the type and acceptance rates of CP interventions in the implementation of ASPs and its impact on antimicrobial utilization. Methods: A single‐center quasi‐experimental study was conducted at Jehangir Hospital, India, wherein prescribed antimicrobials were subjected to evaluation by CPs using the prospective audit and feedback approach. The antimicrobials were reviewed for loading dose, dosages as per creatinine clearance (CrCl), weight, suitability with site of infection, drug interactions, de‐escalations, and therapeutic duplications. Impact on antimicrobial utilization in pre‐intervention (April 2021 to March 2022) and intervention (April 2022 to March 2023) periods were compared using daily defined dose (DDD) per 1000 in‐patient days, following World Health Organization (WHO) guidelines. Results: During the intervention period, 485 out of 609 proposed interventions (79.6%) were implemented. Of these, 417 (85.9%) pertained to intravenous (IV) antimicrobials, while the remaining 68 (14.1%) involved oral formulations. Notably, interventions proposing antibiotic de‐escalations showed higher acceptance rates on Days 3, 5, 7, and 10 compared with other days (p = 0.027). Dosing based on CrCl yielded the highest acceptance rate (50/56, 89.2%). Significant reductions were observed in the DDDs of polymyxins by 58% (3.48–1.29), carbapenems by 7% (57.09–52.85), and glycopeptides by 10% (47.44–42.73). The reduction in these three classes combined was statistically significant (p = 0.04, 95% confidence interval [CI] = 0.3–7.0). Conclusion: This study highlights the vital role of CP interventions within the healthcare team in optimizing antimicrobial pharmacotherapy. The noteworthy reduction in DDDs of restricted antimicrobials provides compelling evidence of the impact CPs can have on antimicrobial consumption and the fight against antimicrobial resistance. [ABSTRACT FROM AUTHOR]

Drug repurposing (repositioning) is a dynamically-developing area in the search for effective therapy of infectious diseases. Repositioning existing drugs with a well-known pharmacological and toxicological profile is an attractive method for quickly discovering new therapeutic indications. The off-label use of drugs for infectious diseases requires much less capital and time, and can hasten progress in the development of new antimicrobial drugs, including antibiotics. The use of drug repositioning in searching for new therapeutic options has brought promising results for many viral infectious diseases, such as Ebola, ZIKA, Dengue, and HCV. This review describes the most favorable results for repositioned drugs for the treatment of bacterial infections. It comprises publications from various databases including PubMed and Web of Science published from 2015 to 2023. The following search keywords/strings were used: drug repositioning and/or repurposing and/or antibacterial activity and/or infectious diseases. Treatment options for infections caused by multidrug-resistant bacteria were taken into account, including methicillin-resistant staphylococci, multidrug-resistant Mycobacterium tuberculosis, or carbapenem-resistant bacteria from the Enterobacteriaceae family. It analyses the safety profiles of the included drugs and their synergistic combinations with antibiotics and discusses the potential of antibacterial drugs with antiparasitic, anticancer, antipsychotic effects, and those used in metabolic diseases. Drug repositioning may be an effective response to public health threats related to the spread of multidrug-resistant bacterial strains and the growing antibiotic resistance of microorganisms.

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.

Background: Early detection of antimicrobial-resistant microorganisms is crucial to prevent subsequent invasive infections and contain their spread in the Neonatal Intensive Care Unit (NICU). This study aims to investigate the association between intestinal colonization (IC) by Gram-negative bacteria and the risk of bloodstream infection (BSI) in critically ill neonates. Methods: Data from the electronic medical records of 678 newborns admitted to a NICU Brazilian between 2018 and 2022 were retrospectively analyzed. Participants were monitored by the National Health Security Network. Results: Among neonates, 6.9 % had IC (56.9 % attributed to Acinetobacter baumannii); of these, 19.1 % developed BSI (66.7 % by Staphylococcus spp.). Within the A. baumannii colonization, 34.5 % occurred during an outbreak in September 2021. Colonized individuals had a longer mean length of stay (49.3 ± 26.4 days) and higher mortality rate (12.8 %) compared to non-colonized individuals (22.2 ± 16.9 days; 6.7 %, respectively). Previous use of antimicrobials and invasive devices significantly increased the risk of colonization. Colonization by drug-resistant microorganisms, along with the occurrence of BSI, was associated with increased mortality and reduced survival time. Conclusions: IC contributed to the incidence of BSI, leading to more extended hospital stays and higher mortality rates. Its early detection proved to be essential to identify an outbreak and control the spread of resistant microorganisms within the NICU.

Abstract Background Multidrug-resistant organism (MDRO) screening may identify high-risk patients for MDRO infection and curb the spread of these resistant pathogens. However, the heterogeneous practices in MDRO screening and the diversity of MDRO risk factors necessitate a tailored approach for successful implementation. This study aimed to evaluate the performance of tailored MDRO screening in predicting MDRO carriage compared to universal screening. Methods Critically ill patients who underwent MDRO screening tests upon intensive care unit admission between September 2015 and December 2019 were included in the study. A risk-predicting model was developed using risk factors identified through multivariable logistic regression analysis. If an individual had one or more identified risk factors, the individual was deemed to be at risk of MDRO carriage and undergo tailored screening. The sensitivity of tailored screening was compared with universal screening for methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant Gram-negative bacilli (carbapenem-resistant Acinetobacter baumannii and carbapenem-resistant Enterobacterales). Results The use of tracheostomy or endotracheal tubes, previous antibiotic exposure, previous multidrug-resistant Gram-negative bacilli carriage history, admission to the medical department, peripheral vascular disease, and liver disease were associated with positive screening for multidrug-resistant Gram-negative bacilli. These six risk factors accounted for all positive screening for multidrug-resistant Gram-negative bacilli, requiring 38.6% of all tests. Notably, MRSA had different risk factor profiles, and the risk factor-based screening approach detected only 43.1% (31 out of 72) of MRSA-positive cases. Conclusions Tailored screening based on identified risk factors showed variable sensitivities to individual MDROs compared to universal screening. A tailored screening approach for individual MDROs may enhance the overall effectiveness of MDRO screening programs.

Escherichia coli is a Gram-negative bacterium and part of the intestinal microbiota. However, it can cause various diarrhoeal illnesses, i.e., traveller’s diarrhoea, dysentery, and extraintestinal infections when the bacteria are translocated from the intestine to other organs, such as urinary tract infections, abdominal and pelvic infections, pneumonia, bacteraemia, and meningitis. It is also an important pathogen in intensive care units where cross-infection may cause intrahospital spread with serious consequences. Within this study, four E. coli isolates from the tracheal aspirates of a tracheotomised paediatric patient on chronic respiratory support were analysed and compared for antibiotic resistance and virulence potential. Genomes of all four isolates (5381a, 5381b, 5681, 5848) were sequenced using Oxford Nanopore Technology. According to PFGE analysis, the clones of isolates 5681 and 5848 were highly similar, and differ from 5381a and 5381b which were isolated first chronologically. All four E. coli isolates belonged to an unknown sequence type, related to the E. coli ST131, a pandemic clone that is evolving rapidly with increasing levels of antimicrobial resistance. All four E. coli isolates in this study exhibited a multidrug-resistant phenotype as, according to MIC data, they were resistant to ceftriaxone, ciprofloxacin, doxycycline, minocycline, and tetracycline. In addition, principal component analyses revealed that isolates 5681 and 5848, which were recovered later than 5381a and 5381b (two weeks and three weeks, respectively) possessed more complex antibiotic resistance genes and virulence profiles, which is concerning considering the short time period during which the strains were isolated.

Abstract Background Contact investigation is an important tool to identify unrecognized patients who are colonized with antibiotic-resistant bacteria. Many Dutch hospitals include already discharged contact patients by sending them a self-sampling request at home, incl. an information letter and sampling materials. Each hospital composes these information letters on their own initiative, however, whether discharged patients comprehend and comply with these requests remains unclear. Therefore, the aim was to provide insight into patients’ comprehension of and self-reported compliance with self-sampling requests post-discharge. Methods This mixed-methods study was performed in eight Dutch hospitals. First, the Common European Framework of Reference (CEFR) language level of self-sampling request letters was established. Second, a questionnaire about patients’ comprehension of the letter, self-reported compliance, and reasons for compliance or non-compliance were sent to patients that received such a request in 2018/2019. Finally, a random selection of questionnaire respondents was interviewed between January and March 2020 to gain additional insights. Results CEFR levels of 15 letters were established. Four letters were assigned level B1, four letters B1–B2, and seven letters B2. The majority of patients reported good comprehension of the letter they had received. Conversely, some respondents indicated that information about the bacterium (18.4%), the way in which results would be communicated (18.1%), and the self-sampling instructions (9.7%) were (partially) unclear. Furthermore, self-reported compliance was high (88.8%). Reasons to comply were personal health (84.3%), the health of others (71.9%), and general patient safety (96.1%). Compliant patients appeared to have a need for confirmation, wanted to protect family and/or friends, and felt they were providing the hospital the ability to control the transmission of antibiotic-resistant bacteria. Although a limited number of non-compliant patients responded to the questionnaire, it seemed that more patients did not comply with self-sampling requests when they received a letter in a higher CEFR-level (B2) compared to a lower CEFR-level (

Abstract Background The present review envisages the role of nanovaccines to combat the global challenges of antimicrobial resistance. Nanovaccines are a novel formulation comprised of nanomaterials coupled with an immunogenic component to elicit the immune response and provide protection against the desired infectious disease. The nanovaccines with unique physicochemical properties can be more efficient against targeting the desired tissues in the body, aids in prolong circulation to promote antigen-presenting cells to act upon the target antigens. Main content The present review envisages the development of nanovaccines against antimicrobial-resistant pathogens. The use of nanovaccines can exhibit potent antigenicity with prolonged retention and controlled release to induce both cell- and antibody-mediated responses. Nanovaccines usage is still in the early stages and can be next-generation immunisation for prophylactic and therapeutic efficiency. The future development of nanovaccines against multi-drug-resistant pathogens can explore new avenues. Based on these facts, the present review is designed from the previously reported scientific studies and compiled with the fact that nanovaccines can revolutionise vaccine strategies. The articles were extracted from reputed databases like PubMed, Scopus, and ESCI. The size and conjugating chemistry of nanomaterials can be beneficial in developing novel multi-nanovaccine formulations that can target pools of antimicrobial resistance mechanisms. Conclusion Overall, the nanovaccines can form one of the best effective modes of targeting multi-drug-resistant pathogens. The nanovaccines can stimulate the innate immune response and generate effective immune-therapeutic novel formulation against infectious pathogens. Based on these facts and considerations, the present article makes an alarming call to develop nanovaccines to counter multi-drug resistance.

Background and Objectives: Antimicrobial resistance has emerged as a significant global health threat. Infections caused by Multi Drug-Resistant (MDR) bacteria pose formidable challenges in terms of treatment options and patient outcomes. Pus cultures serve as crucial diagnostic tools in identifying the agents responsible for various infections, and their antimicrobial susceptibility patterns which help in establishment of empirical therapy guidelines. This study was conducted to determine the pathogen and its susceptibility pattern from pus cultures and to generate antibiogram in our tertiary care setting. Materials and Methods: It was a cross-sectional study, conducted for a period of six months, from July 2022 to December 2022, in the Pathology Department of Pakistan Institute of Medical Sciences (PIMS). Results: Out of total 2507 samples received, 1242 (49.5%) showed positive culture. Among the 1242 positive samples, 364 were Gram positive cocci (GPCs) and 878 were Gram negative rods (GNRs). Methicillin resistant Staphylococcus aureus (MRSA) was the most common isolate (23%) followed by Klebsiella pneumoniae (22.6%), Pseudomonas aeruginosa (16.9%), Enterobacter spp. (15.5%) and Escherichia coli (14.2%). Vancomycin was found to be highly effective (100%) against MRSA. GPCs were highly susceptible to linezolid (98%) while GNRs showed high level of sensitivity to colistin (96%) and tigecycline (92%). Conclusion: The generation of a local antibiogram specific to the hospital setting is essential to effectively manage infections empirically and preserve the efficacy of existing antibiotics. By implementing antimicrobial stewardship practices based on a better understanding of antibiotic susceptibility patterns, we can contribute to the mitigation of antibiotic resistance and improve patient outcomes.

Objective: To investigate the isolation rates, antimicrobial resistance rates, minimum inhibitory concentration values of antimicrobial agents, and clonal relationships of Enterococcus faecalis and Enterococcus faecium due to the relocation of a hospital to a newly constructed building. Method: The comparative, prospective study was conducted at adult general intensive care units of the Mus State Hospital, Mus, Turkey, in two phases; before the relocation from January 25 to December 1, 2014, and after the relocation from February 10 to May 24, 2015. Rectal swab samples were collected 72 hours post-hospitalisation. Identification of Enterococcus faecalis and Enterococcus faecium isolates was determined by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and antimicrobial resistance with minimum inhibitory concentration values was detected with Vitek 2 system. The clonal relatedness among the strains was investigated by pulsed-field gel electrophoresis. Data was analysed using SPSS 23. Results: Of the 69 patients, 37(53.62%) related to pre-relocation phase; 20(54.1%) females and 17(45.9%) males with mean age 62.81±21.71 years. There were 32(46.37%) patients in the post-relocation phase; 13(40.6%) females and 19(59.4%) males with mean age 62.69±21.35 years (p>0.05). Of the 84 enterococci strains isolated, 51(60.7%) were Enterococcus faecium; 28(55%) before relocation and 23(45%) after relocation (p=0.77). The remaining 33(39.3%) isolates were Enterococcus faecalis; 16(48.5%) before relocation and 17(51.5%) after relocation (p=0.73). Multiple strains were located in 7(18.9%) patients before relocation and in 7(21.9%) after relocation. In 1(3.1%) patient after relocation, 2(8.7%) Enterococcus faecium isolates with different resistance and pulsed-field gel electrophoresis patterns were detected. There were no significant differences between the isolation and antibiotic resistance rates before and after relocation (p>0.05), and a clonal relation between the isolates was not detected (p>0.05). Decreased minimum inhibitory concentration values were noted for some antibiotics (p

We evaluated the impact of the FilmArray blood culture identification (BCID) panel on the time taken to administer effective antibiotics and the clinical outcomes of bloodstream infections. We retrospectively screened patients with bloodstream infections who underwent BCID testing and compared them to a historical control group that received conventional culture testing. A total of 144 and 214 patients who underwent BCID and conventional cultures, respectively, were compared. The 30-day mortality (BCID: 9.7% vs. conventional method: 10.7%, p = 0.755), time to effective antibiotic administration (3 h for both BCID and conventional method, p = 0.789), and time to appropriate antibiotic administration did not differ significantly between the groups. BCID was not significantly associated with 30-day mortality after adjusting for the Pitt bacteremia score and the Charlson comorbidity index (adjusted OR = 0.833, CI; 0.398–1.743). Compared with conventional methods, BCID reduced the time to administration of effective antibiotics in cases of carbapenem-resistant Enterobacterales (CRE) (39 h vs. 93 h, p = 0.012) and vancomycin-resistant enterococci (VRE) (50 h vs. 92 h, p < 0.001) bacteremia. BCID did not affect the clinical outcomes of overall bloodstream infections; however, it contributed to the early administration of effective antibiotics in cases of CRE and VRE bacteremia. [ABSTRACT FROM AUTHOR]

Early detection of antimicrobial-resistant microorganisms is crucial to prevent subsequent invasive infections and contain their spread in the Neonatal Intensive Care Unit (NICU). This study aims to investigate the association between intestinal colonization (IC) by Gram-negative bacteria and the risk of bloodstream infection (BSI) in critically ill neonates. Data from the electronic medical records of 678 newborns admitted to a NICU Brazilian between 2018 and 2022 were retrospectively analyzed. Participants were monitored by the National Health Security Network. Among neonates, 6.9 % had IC (56.9 % attributed to Acinetobacter baumannii); of these, 19.1 % developed BSI (66.7 % by Staphylococcus spp.). Within the A. baumannii colonization, 34.5 % occurred during an outbreak in September 2021. Colonized individuals had a longer mean length of stay (49.3 ± 26.4 days) and higher mortality rate (12.8 %) compared to non-colonized individuals (22.2 ± 16.9 days; 6.7 %, respectively). Previous use of antimicrobials and invasive devices significantly increased the risk of colonization. Colonization by drug-resistant microorganisms, along with the occurrence of BSI, was associated with increased mortality and reduced survival time. IC contributed to the incidence of BSI, leading to more extended hospital stays and higher mortality rates. Its early detection proved to be essential to identify an outbreak and control the spread of resistant microorganisms within the NICU. [ABSTRACT FROM AUTHOR]

Background: Pseudomonas aeruginosa (PA) is one of the most predominant pathogens of lung infections, often causing exacerbations in adult patients with cystic fibrosis (CF). Materials and Methods: Microbiological characterization of 74 PA isolates and to evaluate the correlations between the bacterial features and 44 adult Polish CF cohort clinical parameters. Results: The most common variant in the CF transmembrane conductance regulator (CFTR) gene was F508del (76.3%), followed by 3849+10kbC>T (26.3%). A total of 39.4% of the PA isolates showed multiple resistances. In patients with parameters pointing to a decline in lung function, there was a statistically significant moderate correlation with β-lactam resistance and a weak correlation between hospital frequency and colistin resistance. The mucoidity did not correlate with the biofilm formation ability, which showed 41.9% of the isolates. Proteolytic activity, observed in 60.8% of the clinical isolates, was weakly associated with motility detected in 78.4% of the strains. The genetic profiles of the PA were highly heterogeneous, and a weak positive correlation was established between cluster group and biofilm formation. Conclusion: The findings suggest that there is a high variety in P. aeruginosa populations in adult CF patients. There is a need to monitor PA strains in groups of patients with cystic fibrosis, in particular, in terms of the occurrence of antibiotic resistance related to a decline in lung function. [ABSTRACT FROM AUTHOR]

Background: Multidrug-resistant organism (MDRO) screening may identify high-risk patients for MDRO infection and curb the spread of these resistant pathogens. However, the heterogeneous practices in MDRO screening and the diversity of MDRO risk factors necessitate a tailored approach for successful implementation. This study aimed to evaluate the performance of tailored MDRO screening in predicting MDRO carriage compared to universal screening. Methods: Critically ill patients who underwent MDRO screening tests upon intensive care unit admission between September 2015 and December 2019 were included in the study. A risk-predicting model was developed using risk factors identified through multivariable logistic regression analysis. If an individual had one or more identified risk factors, the individual was deemed to be at risk of MDRO carriage and undergo tailored screening. The sensitivity of tailored screening was compared with universal screening for methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant Gram-negative bacilli (carbapenem-resistant Acinetobacter baumannii and carbapenem-resistant Enterobacterales). Results: The use of tracheostomy or endotracheal tubes, previous antibiotic exposure, previous multidrug-resistant Gram-negative bacilli carriage history, admission to the medical department, peripheral vascular disease, and liver disease were associated with positive screening for multidrug-resistant Gram-negative bacilli. These six risk factors accounted for all positive screening for multidrug-resistant Gram-negative bacilli, requiring 38.6% of all tests. Notably, MRSA had different risk factor profiles, and the risk factor-based screening approach detected only 43.1% (31 out of 72) of MRSA-positive cases. Conclusions: Tailored screening based on identified risk factors showed variable sensitivities to individual MDROs compared to universal screening. A tailored screening approach for individual MDROs may enhance the overall effectiveness of MDRO screening programs. [ABSTRACT FROM AUTHOR]

Purpose: The objective of this study was to determine the association between the presence of a microorganism resistant to the antibiotic used in empirical therapy and the development of intra-abdominal abscesses in children with perforated appendicitis. Methods: A prospective cohort study was conducted in patients under 18 years of age who underwent laparoscopic appendectomy between November 1, 2019, and September 30, 2020, in whom perforated appendicitis was documented intraoperatively. Peritoneal fluid samples were taken for bacteria culture purposes, and clinical and microbiological data were collected from all patients. Results: A total of 232 patients were included in the study. The most isolated microorganisms were Escherichia coli (80.14%) and Pseudomonas aeruginosa (7.45%). In addition, 5.31% of E. coli isolates were classified as ESBL-producing organisms. No association was found between a germ resistant to empiric antimicrobial therapy and the development of a postoperative intra-abdominal abscess. Multivariate analysis showed that being a high-risk patient on admission (OR 2.89 (p = 0.01)) was associated with the development of intra-abdominal abscesses postoperatively. Conclusion: E. coli was the most commonly isolated microorganism, with a low rate of ESBL-producing isolates. No association between resistance and risk of postoperative intra-abdominal abscess was found. However, it was identified that being a high-risk patient on admission was associated with this complication. Type of study: Prognosis study. Level of evidence: Level I. [ABSTRACT FROM AUTHOR]