Antimicrobial Classes Research Articles

Unveiling biological activities of biosynthesized starch/silver-selenium nanocomposite using Cladosporium cladosporioides CBS 174.62

Background and objectivesMicrobial cells capability to tolerate the effect of various antimicrobial classes represent a major worldwide health concern. The flexible and multi-components nanocomposites have enhanced physicochemical characters with several improved properties. Thus, different biological activities of biosynthesized starch/silver-selenium nanocomposite (St/Ag-Se NC) were assessed.MethodologyThe St/Ag-Se NC was biosynthesized using Cladosporium cladosporioides CBS 174.62 (C. cladosporioides) strain. The shape and average particle size were investigated using scanning electron microscope (SEM) and high-resolution transmission electron microscope (HR-TEM), respectively. On the other hand, the St/Ag-Se NC effect on two cancer cell lines and red blood cells (RBCs) was evaluated and its hydrogen peroxide (H2O2) scavenging effect was assessed. Moreover, its effects on various microbial species in both planktonic and biofilm growth forms were examined.ResultsThe St/Ag-Se NC was successfully biosynthesized with oval and spherical shape and a mean particle diameter of 67.87 nm as confirmed by the HR-TEM analysis. St/Ag-Se NC showed promising anticancer activity toward human colorectal carcinoma (HCT-116) and human breast cancer (MCF-7) cell lines where IC50 were 21.37 and 19.98 µg/ml, respectively. Similarly, little effect on RBCs was observed with low nanocomposite concentration. As well, the highest nanocomposite H2O2 scavenging activity (42.84%) was recorded at a concentration of 2 mg/ml. Additionally, Staphylococcus epidermidis (S. epidermidis) ATCC 12,228 and Candida albicans (C. albicans) ATCC 10,231 were the highly affected bacterial and fungal strains with minimum inhibitory concentrations (MICs) of 18.75 and 50 µg/ml, respectively. Moreover, the noticeable effect of St/Ag-Se NC on microbial biofilm was concentration dependent. A high biofilm suppression percentage, 87.5% and 68.05%, were recorded with S. epidermidis and Staphylococcus aureus (S. aureus) when exposed to 1 mg/ml and 0.5 mg/ml, respectively.ConclusionThe biosynthesized St/Ag-Se NC showed excellent antioxidant activity, haemocompatibility, and anti-proliferative effect at low concentrations. Also, it exhibited promising antimicrobial and antibiofilm activities.

Antimicrobial properties of triazolato terpyridine Pd(II) and Pt(II) complexes formed by [3+2] cycloaddition coupling reaction

Modern classes of antimicrobials are crucial because most drugs in development today are basically antibiotic derivatives. Even though a large number of metal-based compounds have been studied as antimicrobial agents, relatively few studies have examined the antimicrobial properties of Pd(II) and Pt(II) compounds. The [3+2] cycloaddition reactions of [M(N3)L]PF6 (M = Pd(II) and Pt(II); L = 4′-(2-pyridyl)-2,2′:6′,2″-terpyridine) with 4,4,4-trifluoro-2-butynoic acid ethyl ester gave the corresponding triazolate complexes. The reaction products were fully characterized with a variety of analytical and spectroscopic tools including X-ray crystallographic analysis. The crystal structure of [Pd(triazolatoCF3,COOCH2CH3)L]PF6 provided cut-off evidence that the kinetically formed N1-triazolato isomer favoured the isomerization to the thermodynamically stable N2-analogue. The experimental work was complemented with computational work to get an insight into the nature of the predominant triazolate isomer. The lysozyme binding affinity of the triazolate complexes was examined by mass spectrometry. An analysis of the lysozyme Pd(II) adducts suggests a coordinative covalent mode of binding via the loss of the triazolato ligand. The free ligand and its triazolate complexes displayed selective toxicity against Candida albicans and Cryptococcus neoformans, while no cytotoxicity was observed against the normal human embryonic kidney cell line.

14-Year Epidemiologic study of Pseudomonas aeruginosa bloodstream infection incidence and resistance in the Veterans Health Administration system, 2009-2022.

Multidrug resistant Pseudomonas aeruginosa (PA) represents a serious threat to hospitalized patients. Characterizing the incidence of PA infection and degree of resistance can inform empiric treatment and preventative measures. We sought to describe trends in incidence and resistance characteristics of PA bloodstream infections (BSI) observed within the Veterans Health Administration (VHA) system and identify factors contributing to higher observed mortality within this population. We characterized demographic and clinical features of unique patients among the VHA population presenting with their first episode of PA-BSI between 2009 and 2022 and summarized trends related to mortality and resistance phenotype based on year and geographical location. We additionally used logistic regression analysis to identify predictors of 30-day mortality among this cohort. We identified 8039 PA-BSIs during the study period, 32.7% of which were hospital onset. Annual PA-BSI cases decreased by 35.8%, and resistance among all antimicrobial classes decreased during the study period, while the proportion of patients receiving early active treatment based on susceptibility testing results increased. Average 30-day mortality rate was 23.3%. Higher Charlson Comorbidity Index, higher mAPACHE score, VHA facility complexity 1b and hospital-onset cases were associated with higher mortality, and early active treatment was associated with lower mortality. PA-BSI resistance decreased across the VHA system during the study period. Further investigation of antimicrobial stewardship measures possibly contributing to the observed decreased resistance in this cohort and identification of measures to improve on the high mortality associated with PA-BSI in the VHA population is warranted.

Prevalence and antimicrobial susceptibility characterization of Escherichia coli isolated from the intestines of freshwater fish from the Mindu dam in Morogoro, Tanzania

Background: The Mindu dam, an open system, serves as a microbial reservoir, housing uropathogenic microorganisms like Escherichia coli. Morogoro municipality relies on the dam for water and fish. This study aimed to assess the antimicrobial susceptibility of Escherichia coli isolated from fish and water in Mindu dam. Methods: In May 2019, a cross-sectional study was conducted in Morogoro municipality. Selected antimicrobials, including ampicillin, tetracycline, cefoxitin, erythromycin, trimethoprim, gentamicin, enrofloxacin, and nalidixic acid, were tested using the disc diffusion method. E. coli ATCC 25922 served as a positive control for quality assurance during bacterial isolation. The potential source of antimicrobial contamination was identified through the multiple antibiotic resistance index. Results: Out of 148 samples, E. coli was found in 24, none in water. E. coli showed high resistance (≥50.0%) to erythromycin (62.5%), nalidixic acid (79.2%), and ampicillin (75%). Additionally, 58.0% of isolates displayed multi-drug resistance across antimicrobial classes, with a multiple antibiotic resistance index ranging from 0.00 to 0.75. Conclusion: Antimicrobial-resistant E. coli in the food chain may heighten the spread of complex urinary tract infections in the municipality. It underscores the necessity for robust municipal surveillance of antimicrobial resistance and effective antimicrobial stewardship for enhanced infection prevention and control.

Molecular Analysis of Carbapenem and Aminoglycoside Resistance Genes in Carbapenem-Resistant Pseudomonas aeruginosa Clinical Strains: A Challenge for Tertiary Care Hospitals.

Carbapenem-resistant Pseudomonas aeruginosa (P. aeruginosa) strains have become a global threat due to their remarkable capability to survive and disseminate successfully by the acquisition of resistance genes. As a result, the treatment strategies have been severely compromised. Due to the insufficient available data regarding P. aeruginosa resistance from Pakistan, we aimed to investigate the resistance mechanisms of 249 P. aeruginosa strains by antimicrobial susceptibility testing, polymerase chain reaction for the detection of carbapenemases, aminoglycoside resistance genes, extended-spectrum beta-lactamases (ESBLs), sequence typing and plasmid typing. Furthermore, we tested silver nanoparticles (AgNPs) to evaluate their in vitro sensitivity against antimicrobial-resistant P. aeruginosa strains. We observed higher resistance against antimicrobials in the general surgery ward, general medicine ward and wound samples. Phenotypic carbapenemase-producer strains comprised 80.7% (201/249) with 89.0% (179/201) demonstrating genes encoding carbapenemases: blaNDM-1 (32.96%), blaOXA48 (37.43%), blaIMP (7.26%), blaVIM (5.03%), blaKPC-2 (1.12%), blaNDM-1/blaOXA48 (13.97%), blaOXA-48/blaVIM (1.68%) and blaVIM/blaIMP (0.56%). Aminoglycoside-modifying enzyme genes and 16S rRNA methylase variants were detected in 43.8% (109/249) strains: aac(6')-lb (12.8%), aac(3)-lla (12.0%), rmtB (21.1%), rmtC (11.0%), armA (12.8%), rmtD (4.6%), rmtF (6.4%), rmtB/aac(3)-lla (8.2%), rmtB/aac(6')-lla (7.3%) and rmtB/armA (3.6%). In total, 43.0% (77/179) of the strains coharbored carbapenemases and aminoglycoside resistance genes with 83.1% resistant to at least 1 agent in 3 or more classes and 16.9% resistant to every class of antimicrobials tested. Thirteen sequence types (STs) were identified: ST235, ST277, ST234, ST170, ST381, ST175, ST1455, ST1963, ST313, ST207, ST664, ST357 and ST348. Plasmid replicon types IncFI, IncFII, IncA/C, IncL/M, IncN, IncX, IncR and IncFIIK and MOB types F11, F12, H121, P131 and P3 were detected. Meropenem/AgNPs and Amikacin/AgNPs showed enhanced antibacterial activity. We reported the coexistence of carbapenemases and aminoglycoside resistance genes among carbapenem-resistant P. aeruginosa with diverse clonal lineages from Pakistan. Furthermore, we highlighted AgNP's potential role in handling future antimicrobial resistance concerns.

Meat and meat products as potential sources of emerging MDR Bacillus cereus: groEL gene sequencing, toxigenic and antimicrobial resistance

BackgroundBacillus cereus is implicated in severe foodborne infection in humans. This study intended to assess the occurrence, groEL gene sequencing, biofilm production, and resistance profiles of emerged multidrug resistant (MDR) B. cereus in meat and meat product samples. Moreover, this work highlights the virulence and toxigenic genes (hblABCD complex, nheABC complex, cytK, ces, and pc-plc) and antimicrobial resistance genes (bla1, tetA, bla2, tetB, and ermA).MethodsConsequently, 200 samples (sausage, minced meat, luncheon, beef meat, and liver; n = 40 for each) were indiscriminately collected from commercial supermarkets in Port Said Province, Egypt, from March to May 2021. Subsequently, food samples were bacteriologically examined. The obtained isolates were tested for groEL gene sequence analysis, antibiotic susceptibility, biofilm production, and PCR screening of toxigenic and resistance genes.ResultsThe overall prevalence of B. cereus among the inspected food samples was 21%, where the highest predominance was detected in minced meat (42.5%), followed by beef meat (30%). The phylogenetic analysis of the groEL gene exposed that the examined B. cereus strain disclosed a notable genetic identity with other strains from the USA and China. Moreover, the obtained B. cereus strains revealed β-hemolytic activity, and 88.1% of the recovered strains tested positive for biofilm production. PCR evidenced that the obtained B. cereus strains usually inherited the nhe complex genes (nheA and nheC: 100%, and nheB: 83.3%), followed by cytK (76.2%), hbl complex (hblC and hblD: 59.5%, hblB: 16.6%, and hblA: 11.9%), ces (54.7%), and pc-plc (30.9%) virulence genes. Likewise, 42.9% of the examined B. cereus strains were MDR to six antimicrobial classes and encoded bla1, bla2, ermA, and tetA genes.ConclusionIn summary, this study highlights the presence of MDR B. cereus in meat and meat products, posing a significant public health risk. The contamination by B. cereus is common in minced meat and beef meat. The molecular assay is a reliable fundamental tool for screening emerging MDR B. cereus strains in meat and meat products.

Prevalence and Genetic Characterization of Methicillin-Resistant Staphylococcus aureus Isolated from Pigs in Japan.

We investigated the prevalence of livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) in pig slaughterhouses from 2018 to 2022 in Japan and the isolates were examined for antimicrobial susceptibility and genetic characteristics by whole-genome analysis. Although the positive LA-MRSA rates on farms (29.6%) and samples (9.9%) in 2022 in Japan remained lower than those observed in European countries exhibiting extremely high rates of confirmed human LA-MRSA infections, these rates showed a gradually increasing trend over five years. The ST398/t034 strain was predominant, followed by ST5/t002, and differences were identified between ST398 and ST5 in terms of antimicrobial susceptibility and the resistance genes carried. Notably, LA-MRSA possessed resistance genes toward many antimicrobial classes, with 91.4% of the ST398 strains harboring zinc resistance genes. These findings indicate that the co-selection pressure associated with multidrug and zinc resistance may have contributed markedly to LA-MRSA persistence. SNP analysis revealed that ST398 and ST5 of swine origin were classified into a different cluster of MRSA from humans, showing the same ST in Japan and lacking the immune evasion genes (scn, sak, or chp). Although swine-origin LA-MRSA is currently unlikely to spread to humans and become a problem in current clinical practice, preventing its dissemination requires using antimicrobials prudently, limiting zinc utilization to the minimum required nutrient, and practicing fundamental hygiene measures.

Antimicrobial consumption and resistance in bacteria from humans and food-producing animals: Fourth joint inter-agency report on integrated analysis of antimicrobial agent consumption and occurrence of antimicrobial resistance in bacteria from humans and food-producing animals in the EU/EEA JIACRA IV - 2019-2021.

The fourth joint inter-agency report on integrated analysis of antimicrobial consumption (AMC) and the occurrence of antimicrobial resistance (AMR) in bacteria from humans and food-producing animals (JIACRA) addressed data obtained by the Agencies' EU-wide surveillance networks for 2019-2021. The analysis also sought to identify whether significant trends in AMR and AMC were concomitant over 2014-2021. AMC in both human and animal sectors, expressed in mg/kg of estimated biomass, was compared at country and European level. In 2021, the total AMC was assessed at 125.0 mg/kg of biomass for humans (28 EU/EEA countries, range 44.3-160.1) and 92.6 mg/kg of biomass for food-producing animals (29 EU/EEA countries, range 2.5-296.5). Between 2014 and 2021, total AMC in food-producing animals decreased by 44%, while in humans, it remained relatively stable. Univariate and multivariate analyses were performed to study associations between AMC and AMR for selected combinations of bacteria and antimicrobials. Positive associations between consumption of certain antimicrobials and resistance to those substances in bacteria from both humans and food-producing animals were observed. For certain combinations of bacteria and antimicrobials, AMR in bacteria from humans was associated with AMR in bacteria from food-producing animals which, in turn, was related to AMC in animals. The relative strength of these associations differed markedly between antimicrobial class, microorganism and sector. For certain antimicrobials, statistically significant decreasing trends in AMC and AMR were concomitant for food-producing animals and humans in several countries over 2014-2021. Similarly, a proportion of countries that significantly reduced total AMC also registered increasing susceptibility to antimicrobials in indicator E. coli from food-producing animals and E. coli originating from human invasive infections (i.e., exhibited 'complete susceptibility' or 'zero resistance' to a harmonised set of antimicrobials). Overall, the findings suggest that measures implemented to reduce AMC in food-producing animals and in humans have been effective in many countries. Nevertheless, these measures need to be reinforced so that reductions in AMC are retained and further continued, where necessary. This also highlights the importance of measures that promote human and animal health, such as vaccination and better hygiene, thereby reducing the need for use of antimicrobials.

MICROBIAL LOAD AND ANTIBIOTICS RESISTANCE PATTERNS OF BACTERIAL ISOLATES FROM NIGERIA NAIRA NOTES

In our society today, exchange of goods and services usually involves exchange of currency notes by hand. This can serve as a means of transferring microorganisms and antibiotics resistant bacterial isolates. This study was aimed at assessing the contamination of Naira notes in Ungwan Rimi area of Kaduna State and to determine the antibiotics resistance patterns of the isolated bacteria. A total of 160 samples of naira notes, were collected randomly from staff and students, marketers, hospital and pharmacies, food vendors and transporters at strategic spots in Ungwan Rimi. Bacteria isolation and identification of samples were carried out using spread plate technique on medium and standard biochemical characterization, respectively. Antibiotics susceptibility testing were carried out using agar disc diffusion method. Isolates that were non-susceptible to at least one antimicrobial agent in three or more antimicrobial classes were classified as multidrug resistant (MDR), those that remain susceptible to agent(s) in only one or two classes as extended drug resistant (XDR) while pandrug resistant (PDR) isolates were classified as those isolates that were resistant to all antibiotics used. Highest bacterial load was observed with N100 notes with marketers (5.33 x 105) while the least bacterial load was 1.2 x 104 in N50 notes from hospitals and pharmacies. The following bacteria were isolated Staphylococcus aureus 70 (26.8%), Bacillus spp 60 (23.0%), Clostridium spp 31 (11.9%), Escherichia coli 30 (11.5%), Streptococcus species 25 (9.6%), Klebsiella spp 24 (9.2%), Salmonella 15 (5.8%), Shigella species 4 (1.5%) and Pseudomonas species 2 (0.8%)...

Tularemia Clinical Manifestations, Antimicrobial Treatment, and Outcomes: An Analysis of US Surveillance Data, 2006-2021.

Tularemia, a potentially fatal zoonosis caused by Francisella tularensis, has been reported from nearly all US states. Information on relative effectiveness of various antimicrobials for treatment of tularemia is limited, particularly for newer classes such as fluoroquinolones. Data on clinical manifestations, antimicrobial treatment, and illness outcome of patients with tularemia are provided voluntarily through case report forms to the US Centers for Disease Control and Prevention by state and local health departments. We summarized available demographic and clinical information submitted during 2006-2021 and evaluated survival according to antimicrobial treatment. We grouped administered antimicrobials into those considered effective for treatment of tularemia (aminoglycosides, fluoroquinolones, and tetracyclines) and those with limited efficacy. Logistic regression models with a bias-reduced estimation method were used to evaluate associations between antimicrobial treatment and survival. Case report forms were available for 1163 US patients with tularemia. Francisella tularensis was cultured from a clinical specimen (eg, blood, pleural fluid) in approximately half of patients (592; 50.9%). Nearly three-quarters (853; 73.3%) of patients were treated with a high-efficacy antimicrobial. A total of 27 patients (2.3%) died. After controlling for positive culture as a proxy for illness severity, use of aminoglycosides, fluoroquinolones, and tetracyclines was independently associated with increased odds of survival. Most US patients with tularemia received high-efficacy antimicrobials; their use was associated with improved odds of survival regardless of antimicrobial class. Our findings provide supportive evidence that fluoroquinolones are an effective option for treatment of tularemia.

Global surveillance of antimicrobial resistance in food animals using priority drugs maps

Antimicrobial resistance (AMR) in food animals is a growing threat to animal health and potentially to human health. In resource-limited settings, allocating resources to address AMR can be guided with maps. Here, we mapped AMR prevalence in 7 antimicrobials in Escherichia coli and nontyphoidal Salmonella species across low- and middle-income countries (LIMCs), using 1088 point-prevalence surveys in combination with a geospatial model. Hotspots of AMR were predicted in China, India, Brazil, Chile, and part of central Asia and southeastern Africa. The highest resistance prevalence was for tetracycline (59% for E. coli and 54% for nontyphoidal Salmonella, average across LMICs) and lowest for cefotaxime (33% and 19%). We also identified the antimicrobial with the highest probability of resistance exceeding critical levels (50%) in the future (1.7–12.4 years) for each 10 × 10 km pixel on the map. In Africa and South America, 78% locations were associated with penicillins or tetracyclines crossing 50% resistance in the future. In contrast, in Asia, 77% locations were associated with penicillins or sulphonamides. Our maps highlight diverging geographic trends of AMR prevalence across antimicrobial classes, and can be used to target AMR surveillance in AMR hotspots for priority antimicrobial classes.

MEndoB, a chimeric lysin featuring a novel domain architecture and superior activity for the treatment of staphylococcal infections.

Bacterial infections are a growing global healthcare concern, as an estimated annual 4.95 million deaths are associated with antimicrobial resistance (AMR). Methicillin-resistant Staphylococcus aureus is one of the deadliest pathogens and a high-priority pathogen according to the World Health Organization. Peptidoglycan hydrolases (PGHs) of phage origin have been postulated as a new class of antimicrobials for the treatment of bacterial infections, with a novel mechanism of action and no known resistances. The modular architecture of PGHs permits the creation of chimeric PGH libraries. In this study, the chimeric enzyme MEndoB was selected from a library of staphylococcal PGHs based on its rapid and sustained activity against staphylococci in human serum. The benefit of the presented screening approach was illustrated by the superiority of MEndoB in a head-to-head comparison with other PGHs intended for use against staphylococcal bacteremia. MEndoB displayed synergy with antibiotics and rapid killing in human whole blood with complete inhibition of re-growth over 24 h at low doses. Successful treatment of S. aureus-infected zebrafish larvae with MEndoB provided evidence for its in vivo effectiveness. This was further confirmed in a lethal systemic mouse infection model in which MEndoB significantly reduced S. aureus loads and tumor necrosis factor alpha levels in blood in a dose-dependent manner, which led to increased survival of the animals. Thus, the thorough lead candidate selection of MEndoB resulted in an outstanding second-generation PGH with in vitro, ex vivo, and in vivo results supporting further development.IMPORTANCEOne of the most pressing challenges of our era is the rising occurrence of bacteria that are resistant to antibiotics. Staphylococci are prominent pathogens in humans, which have developed multiple strategies to evade the effects of antibiotics. Infections caused by these bacteria have resulted in a high burden on the health care system and a significant loss of lives. In this study, we have successfully engineered lytic enzymes that exhibit an extraordinary ability to eradicate staphylococci. Our findings substantiate the importance of meticulous lead candidate selection to identify therapeutically promising peptidoglycan hydrolases with unprecedented activity. Hence, they offer a promising new avenue for treating staphylococcal infections.

Insights into Kinases of ESKAPE Pathogens for Therapeutic Interventions.

Multidrug-resistant ESKAPE pathogens are the leading cause of hospital-acquired infections across the globe, posing challenges for clinicians. Random genetic mutations and constant exposure to antibiotics in healthcare settings result in strains resistant to commonly used antibiotics, creating life-threatening conditions. If the magic of "antibiotics" is to be sustained, a new class of antimicrobials against novel targets is urgently needed. This necessitates understanding and identifying novel biochemical pathways and bacterial virulence factors that can be targeted for therapeutic interventions. Keeping in view the unambiguous role of the kinome in bacterial survival and virulence, this review provides a survey of effector bacterial kinases involved in evading host immune responses and drug resistance. The formation of biofilms is a critical feature associated with the pathogenesis and survival of ESKAPE organisms in the hostile host milieu. Hence, kinases involved in the biofilm pathway are also elucidated for clinical relevance. In addition, endeavors in the development of therapeutics against ESKAPE kinases are also summarized to provide direction to researchers pursuing the field.

Rare serovars of non-typhoidal Salmonella enterica isolated from humans, beef cattle and abattoir environments in Nigeria.

Salmonella is considered one of the most significant pathogens in public health since it is a bacterium that is frequently linked to food-borne illnesses in humans. Some Salmonella serovars are responsible for outbreaks that are connected to the consumption of animal products. Cattle are connected to humans through a shared environment and the food chain as a significant source of animal protein. In Nigeria, antimicrobial medications are easily accessible for use in food-producing animals. Abattoir environments are reservoirs of foodborne bacteria like non-typhoidal Salmonella enterica (NTS), that have become resistant to antibiotics used for prophylaxis or treatment in animals. This study investigated the prevalence and resistance patterns of Salmonella enterica serovars in abattoir employees, beef cattle and abattoir environments in Abuja and Lagos, Nigeria. A total of 448 samples were collected from healthy personnel, slaughtered cattle, and abattoir environments between May and December 2020. Using Kirby-Bauer disk diffusion method, the resistance profile of NTS isolates were determined. Multidrug resistance (MDR) was considered when NTS was resistant to ≥3 antimicrobial drug classes. We performed phenotypic and genotypic characterizations of all Salmonella isolates including serotyping. Descriptive statistics were used to analyze the data. Twenty-seven (6%) NTS isolates were obtained. Prevalence of NTS was highest in abattoir environments (15.5%; 9/58), followed by cattle (4.8%;13/272) and abattoir employees (4.2%; 5/118). A high prevalence of resistance was observed for gentamicin (85.2%; 23/27) and tetracycline (77.8%; 21/27). Whole-genome sequencing of 22 NTS showed dissemination of aac(6')-laa (22/22), qnrB19 (1/22), fosA7 (1/22), and tetA (1/22) genes. Serovar diversity of NTS varied with source. S. Anatum, a rare serovar predominated with a prevalence of 18.2% (4/22). Chromosomal point mutations showed ParC T57S substitution in 22 NTS analyzed. Among 22 NTS, 131 mobile genetic elements (MGEs) were detected including insertion sequences (56.5%) and miniature inverted repeats (43.5%). Two integrating MGEs IS6 and IS21 were observed to carry the tetA gene + Incl-1 on the same contig in NTS originating from cattle. Rare serovars namely S. Abony and S. Stormont with MDR phenotypes recovered from cattle and abattoir environments were closely related with a pairwise distance of ≤5 SNPs. First report of rare serovars in Nigeria with MDR phenotypes in humans, cattle, and abattoir environments. This study demonstrates the spread of resistance in the abattoir environment possibly by MGEs and emphasizes the importance of genomic surveillance. Beef cattle may be a risk to public health because they spread a variety of rare Salmonella serovars. Therefore, encouraging hand hygiene among abattoir employees while processing beef cattle will further reduce NTS colonization in this population. This requires a One Health collaborative effort among various stakeholders in human health, animal health, and environmental health.

Associations between Isolation Source, Clonal Composition, and Antibiotic Resistance Genes in Escherichia coli Collected in Washington State, USA.

Antimicrobial resistance (AMR) is a global health problem stemming from the use of antibiotics in humans, animals, and the environment. This study used whole-genome sequencing (WGS) of E. coli to explore patterns of AMR across sectors in Washington State, USA (WA). The WGS data from 1449 E. coli isolates were evaluated for isolation source (humans, animals, food, or the environment) and the presence of antibiotic resistance genes (ARGs). We performed sequence typing using PubMLST and used ResFinder to identify ARGs. We categorized isolates as being pan-susceptible, resistant, or multidrug-resistant (MDR), defined as carrying resistance genes for at least three or more antimicrobial drug classes. In total, 60% of isolates were pan-susceptible, while 18% were resistant, and 22% exhibited MDR. The proportion of resistant isolates varied significantly according to the source of the isolates (p < 0.001). The greatest resistance was detected in isolates from humans and then animals, while environmental isolates showed the least resistance. This study demonstrates the feasibility of comparing AMR across various sectors in Washington using WGS and a One Health approach. Such analysis can complement other efforts for AMR surveillance and potentially lead to targeted interventions and monitoring activities to reduce the overall burden of AMR.

Genomic and phenotypic characterization of multidrug-resistant Salmonella enterica serovar Reading isolates involved in a turkey-associated foodborne outbreak.

Salmonella is a global bacterial foodborne pathogen associated with a variety of contaminated food products. Poultry products are a common source of Salmonella-associated foodborne illness, and an estimated 7% of human illnesses in the United States are attributed to turkey products. From November 2017 to March 2019, the Centers for Disease Control and Prevention reported a turkey-associated outbreak of multidrug-resistant (MDR; resistant to ≥3 antimicrobial classes) Salmonella enterica serovar Reading (S. Reading) linked to 358 human infections in 42 US states and Canada. Since S. Reading was seldom linked to human illness prior to this outbreak, the current study compared genomic sequences of S. Reading isolates prior to the outbreak (pre-outbreak) to isolates identified during the outbreak period, focusing on genes that were different between the two groups but common within a group. Following whole-genome sequence analysis of five pre-outbreak and five outbreak-associated turkey/turkey product isolates of S. Reading, 37 genes located within two distinct chromosomal regions were identified only in the pre-outbreak isolates: (1) an ~5 kb region containing four protein-coding genes including uidA which encodes beta-glucuronidase, pgdA encoding peptidoglycan deacetylase, and two hypothetical proteins and (2) an ~28 kb region comprised of 32 phage-like genes and the xerC gene, which encodes tyrosine recombinase (frequently associated with phage genes). The five outbreak isolates also had a deletional event within the cirA gene, introducing a translational frame shift and premature stop codon. The cirA gene encodes a protein with dual receptor functions: a siderophore receptor for transport of dihydroxybenzoylserine as well as a colicin Ia/b receptor. Significant differences for the identified genetic variations were also detected in 75 S. Reading human isolates. Of the 41 S. Reading isolates collected before or in 2017, 81 and 90% of the isolates contained the uidA and pgdA genes, respectively, but only 24% of the isolates collected after 2017 harbored the uidA and pgdA genes. The truncation event within the cirA gene was also significantly higher in isolates collected after 2017 (74%) compared to before or in 2017 (5%). Phenotypic analysis of the S. Reading isolates for colicin and cefiderocol sensitivities (CirA) and β-methyl-D-glucuronic acid utilization (UidA and accessory proteins) supported the genomic data. Overall, a similar genome reduction pattern was generally observed in both the turkey and human isolates of S. Reading during the outbreak period, and the genetic differences were present in genes that could potentially promote pathogen dissemination due to variation in Salmonella colonization, fitness, and/or virulence.

Multidrug-Resistant Acinetobacter and Enterobacterales Causing Neonatal Sepsis at a Tertiary Healthcare Facility in Indonesia

Introduction: Increasing resistance to multiple classes of antimicrobials, leading to multidrug resistance (MDR), provides a major challenge for the management of bloodstream infections in the neonatal intensive care unit (NICU). The dissemination of Acinetobacter and Enterobacterales species were of great importance owing to their high prevalence and resistance against a broad spectrum of available antimicrobials, thereby exacerbating the prognosis for afflicted patients. This study aimed to highlight neonatal sepsis cases caused by MDR Acinetobacter and Enterobacterales in the NICU of a tertiary healthcare center in Surabaya, Indonesia. Methods: This retrospective cohort study was conducted in Dr. Soetomo General Hospital, Surabaya, from January 2020 to August 2022. Documented cases of neonatal sepsis were identified from electronic medical records under the ICD-10 P36 code. Continuous monitoring of blood culture was performed following the initial suspicion of sepsis, complemented with semiautomated antimicrobial susceptibility testing. Results: A total of 75 out of 125 culture-proven neonatal sepsis cases were reported caused by Acinetobacter baumannii ( n = 19; 15.2%) and Enterobacterales ( n = 56; 44.8%) species. These organisms exhibited the MDR rates of 78.9% and 91.1%, respectively. Klebsiella pneumoniae ( K. pneumoniae) emerged as the predominant Enterobacterales, demonstrating an MDR rate of 92.1%. Possible extensively- and possible pan-drug-resistant organisms were also identified at a concerning rate in Acinetobacter (73.7% and 21.1%, respectively) and Enterobacterales (28.6% and 1.8%, respectively). The susceptibility of Acinetobacter to carbapenems was notably low (26.3%), whereas Enterobacterales exhibited a relatively higher susceptibility rate (75%). Notably, 9 and 37 documented deaths were associated with neonatal sepsis because of MDR Acinetobacter and Enterobacterales, respectively. Lower birth weight and shorter length of NICU stay were significantly related to mortality in neonatal sepsis. Conclusion: The alarming rate of MDR underscores further investigations on the extent of inappropriate antibiotic usage in the unit, particularly concerning neonates requiring invasive medical interventions and those with foundational clinical risk factors.

Characteristics of antimicrobial resistance in Escherichia coli isolated from retail meat products in North Carolina.

Escherichia coli is commonly used as an indicator for antimicrobial resistance (AMR) in food, animal, environment, and human surveillance systems. Our study aimed to characterize AMR in E. coli isolated from retail meat purchased from grocery stores in North Carolina, USA as part of the National Antimicrobial Resistance Monitoring System (NARMS). Retail chicken (breast, n = 96; giblets, n = 24), turkey (n = 96), and pork (n = 96) products were purchased monthly from different counties in North Carolina during 2022. Label claims on packages regarding antibiotic use were recorded at collection. E. coli was isolated from meat samples using culture-based methods and isolates were characterized for antimicrobial resistance using whole genome sequencing. Multi-locus sequence typing, phylogroups, and a single nucleotide polymorphism (SNP)-based maximum-likelihood phylogenic tree was generated. Data were analyzed statistically to determine differences between antibiotic use claims and meat type. Of 312 retail meat samples, 138 (44.2%) were positive for E. coli, with turkey (78/138; 56.5%) demonstrating the highest prevalence. Prevalence was lower in chicken (41/138; 29.7%) and pork (19/138;13.8%). Quality sequence data was available from 84.8% (117/138) of the E. coli isolates, which included 72 (61.5%) from turkey, 27 (23.1%) from chicken breast, and 18 (15.4%) from pork. Genes associated with AMR were detected in 77.8% (91/117) of the isolates and 35.9% (42/117) were defined as multidrug resistant (MDR: being resistant to ≥3 distinct classes of antimicrobials). Commonly observed AMR genes included tetB (35%), tetA (24.8%), aph(3'')-lb (24.8%), and blaTEM-1 (20.5%), the majority of which originated from turkey isolates. Antibiotics use claims had no statistical effect on MDR E. coli isolates from the different meat types (X2 = 2.21, p = 0.33). MDR was observed in isolates from meat products with labels indicating "no claims" (n = 29; 69%), "no antibiotics ever" (n = 9; 21.4%), and "organic" (n = 4; 9.5%). Thirty-four different replicon types were observed. AMR genes were carried on plasmids in 17 E. coli isolates, of which 15 (88.2%) were from turkey and two (11.8%) from chicken. Known sequence types (STs) were described for 81 E. coli isolates, with ST117 (8.5%), ST297 (5.1%), and ST58 (3.4%) being the most prevalent across retail meat types. The most prevalent phylogroups were B1 (29.1%) and A (28.2%). Five clonal patterns were detected among isolates. E. coli prevalence and the presence of AMR and MDR were highest in turkey retail meat. The lack of an association between MDR E. coli in retail meat and antibiotic use claim, including those with no indication of antimicrobial use, suggests that additional research is required to understand the origin of resistance. The presence of ST117, an emerging human pathogen, warrants further surveillance. The isolates were distinctly diverse suggesting an instability in population dynamics.

Identification of antimicrobial resistance profiles and antimicrobial resistance genes of Campylobacter isolates from broiler farms in Sri Lanka

Antimicrobial resistant (AMR) bacteria including Campylobacter has become an emerging global concern in human and animal health. There are very few researches on AMR Campylobacter conducted in Sri Lanka and none of them studied about AMR genes to the best of our knowledge. The present study focused on the detection of AMR Campylobacter from broiler in Sri Lanka, resistant against frequently used antimicrobials. Further, presence of AMR genes or mutations in responsible genes were compared to the resistant phenotypes. Cloacal swabs were collected from 118 broilers in nine farms covering three provinces in Sri Lanka. One Campylobacter colony per sample was isolated and the antimicrobial susceptibility test of the isolates was performed by inoculating the isolates onto agar plates with threshold concentrations of eight antimicrobial agents which belong to six antimicrobial classes. Three genetic markers for antimicrobial resistance, point mutations in 23S rRNA gene and gyrA gene, and the presence of resistant gene, tet(O) were also investigated. Altogether, 73 samples were Campylobacter positive of which 59 were Campylobacter jejuni, 13 were Campylobacter coli and one was unidentified Campylobacter. All isolates were resistant to three or more antimicrobials tested. The isolates were frequently resistant to ciprofloxacin, nalidixic acid, trimethoprim-sulfamethoxazole, amoxicillin and tetracycline, and susceptible to gentamicin and streptomycin, while the resistance to erythromycin was different between the species. Genetic screening revealed that most of the isolates possessed one or more of these genetic markers. This study urges the need of continuous surveillance for AMR Campylobacter in Sri Lanka.

P06 The effect of ciprofloxacin prophylaxis during haematopoietic cell transplantation on infection episodes, exposure to treatment antimicrobials and antimicrobial resistance: a single-centre retrospective cohort study

Abstract Background Fluroquinolone prophylaxis during haematopoietic cell transplantation (HCT) remains contentious. Objectives To determine the effectiveness of ciprofloxacin prophylaxis across different HCT indications and its association with exposure to treatment antimicrobials and antimicrobial resistance. Methods All admission episodes for HCT (N=400) in a tertiary centre between January 2020 and December 2022 were studied. Allogeneic haematopoietic cell transplantation (allo-HCT) recipients received prophylaxis with ciprofloxacin during chemotherapy-induced neutropenia, while autologous haematopoietic cell transplantation (auto-HCT) recipients did not. Results Allo-HCT was performed for 43.3% (173/400) of patients, auto-HCT for 56.7% (227/400). Allo-HCT was associated with an average of 1.01 fewer infection episodes per 100 admission days (95% CI 0.62–1.40, P&amp;lt;0.001) compared with auto-HCT. In allo-HCT, the total exposure to all antimicrobials was higher (+24.8 days of therapy [DOT]/100 admission days, P&amp;lt;0.001), as was exposure to ciprofloxacin (+40.5 DOT/100 admission days, P&amp;lt;0.001). In contrast, exposure to meropenem (−4.5 DOT/100 admission days, P=0.02), piperacillin/tazobactam (−5.2 DOT/100 admission days, P&amp;lt;0.001), aminoglycosides (−4.5 DOT/100 admission days, P&amp;lt;0.001), glycopeptides (−6.4 DOT/100 admission days, P&amp;lt;0.001), was reduced. Enterobacteriaceae isolated during allo-HCT were more resistant to ciprofloxacin (65.5%, 19/29 versus 6.1%, 2/33, P&amp;lt;0.001), ceftriaxone (65.5%, 19/29 versus 9.1%, 3/33, P&amp;lt;0.001), and other antimicrobial classes. Vancomycin-resistant enterococci were more common in allo-HCT recipients (11%, 19/173 versus 0.9%, 2/227, P&amp;lt;0.001). Inpatient mortality during allo- and auto-HCT was 9.8% (17/173) and 0.4% (1/227) respectively (P&amp;lt;0.001). An invasive bacterial infection was documented in 31.3% (125/400) of cases. Allo-HCT patients were more likely to have an invasive Gram-positive bacterial infection (23.1% versus 12.8%, P=0.01), while a difference was not observed for invasive Gram-negative bacterial infections (19.7% versus 18.5%, P=0.77). Among auto-HSCT recipients, patients with germ cell tumours had the highest probability (P for trend 0.03) of recording an invasive bacterial infection (12/23, 52.2%, 95% CI 31.3–74) compared with other indication for auto-HCT. Conclusions Ciprofloxacin prophylaxis in allo-HCT was associated with fewer infection episodes and reduced exposure to treatment antimicrobials. Mortality in auto-HCT remained low. A significant burden of antimicrobial resistance was detected in allo-HCT recipients. HCT recipients due to germ cell tumours, not receiving ciprofloxacin prophylaxis, recorded the highest incidence of invasive bacterial infections and represent a possible target group for this intervention.