Multidrug-resistant Isolates Research Articles

Study of MIC of silver and zinc oxide nanoparticles, strong and cost-effective antibacterial against biofilm-producing Acinetobacter baumannii in Shiraz, Southwest of Iran

BackgroundAcinetobacter baumannii resistant strains lead to increased mortality, treatment costs, and an increase in the length of hospitalization. Nowadays, nanoparticles are considered a substitute for antibiotics. This study aimed to determine the MIC of Silver (Ag) and Zinc Oxide (ZnO) Nanoparticles (NPs) on Biofilm-Producing Acinetobacter baumannii and determine the relationship between MIC and frequency of efflux pump genes in cutaneous specimens in Shiraz, Southwest Iran in 2021–2022.MethodsIn this study, specimens were collected from April 2021 to June 2022 at Namazi and Faqihi Hospitals in Shiraz. Investigation of biofilm production in multidrug resistance (MDR) isolates was done by the microtiter plate method. Synthesized nanoparticles were characterized by UV–vis spectrum, X-ray diffraction (XRD), and electron microscopy. The MIC of AgNPs and ZnONPs for isolates was done using the method described in the CLSI guideline (2018). The antibacterial effect of MIC of NPs on inanimate objects was done by colony counts. The prevalence of efflux pump genes (adeR, adeC, adeA, abeM, adeK, adeI) was also investigated by PCR technique.ResultsThe highest ceftriaxone resistance (68%) and lowest colistin resistance (7%) were identified. 57% of isolates were MDR. In addition, 71.9% could produce biofilm and 28.1% of isolates could not produce biofilm. The average size of AgNPs and ZnONPs in the present study is 48 and < 70 nm, respectively. The nanoparticles were spherical. The MIC and the MBC of the ZnONPs were in the range of 125 to 250 µg/mL respectively. Also, for AgNPs, the MIC and the MBC were in the range of 62.5 to 250 µg/ml, respectively. AbeM gene had the highest frequency and the AdeK gene had the lowest frequency. Statistical analysis showed that there is a relationship between the frequency of adeA, adeC, and adeM genes with the MIC of AgNPs and ZnONPs.ConclusionAccording to the results of the present study, inanimate objects such as scalpels in contact with AgNPs (6000 µg/ml for 240 min) or ZnONPs (5000 µg/ml for 120 min) can be free of biofilm producing Acinetobacter baumannii with efflux pump genes.

The Highly Durable Antibacterial Gel-like Coatings for Textiles.

Hospital-acquired infections are considered a priority for public health systems since they pose a significant burden for society. High-touch surfaces of healthcare centers, including textiles, provide a suitable environment for pathogenic bacteria to grow, necessitating incorporating effective antibacterial agents into textiles. This paper introduces a highly durable antibacterial gel-like solution, Silver Shell™ finish, which contains chitosan-bound silver chloride microparticles. The study investigates the coating's environmental impact, health risks, and durability during repeated washing. The structure of the Silver Shell™ finish was studied using transmission electron microscopy (TEM) and energy-dispersive X-ray spectroscopy (EDX). The TEM images showed a core-shell structure, with chitosan forming a protective shell around groupings of silver microparticles. The field-emission scanning electron microscopy (FESEM) demonstrated the uniform deposition of Silver Shell™ on the surfaces of the fabrics. AATCC Test Method 100 was employed to quantitatively analyze the antibacterial properties of the fabrics coated with silver microparticles. Two types of bacteria, Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli), were used in this study. The antibacterial results showed that after 75 wash cycles, a 100% reduction for both S. aureus and E. coli in the coated samples using crosslinking agents was observed. The coated samples without a crosslinking agent exhibited 99.88% and 99.81% reductions for S. aureus and E. coli after 50 washing cycles. To compare the antibacterial properties toward non-pathogenic and pathogenic strains of the same species, MG1655 model E. coli strain (ATCC 29213) and a multidrug-resistant clinical isolate were used. The results showed the antibacterial efficiency of the Silver ShellTM solution (up to 99.99% reduction) coated on cotton fabric. AATCC-147 was performed to investigate the coated samples' leaching properties and the crosslinking agent's effects against S. aureus and E. coli. All coated samples demonstrated remarkable antibacterial efficacy, even after 75 wash cycles. The crosslinking agent facilitated durable attachment between the silver microparticles and cotton substrate, minimizing the release of particles from the fabrics. Color measurements were conducted to assess the color differences resulting from the coating process. The results indicated fixation values of 44%, 32%, and 28% following 25, 50, and 75 washing cycles, respectively.

ANTIMICROBIAL EFFECT OF OZONIZED PHYSIOLOGICAL SOLUTION ON BACTERIA CAUSING CYSTITIS IN DOGS

Bacterial cystitis is a common clinical problem among dogs and is one of the reasons for the empirically administration of antimicrobials. This practice facilitates the selection of bacteria that are multidrug-resistant to antibiotics. In this context, it is urgent to understand and validate therapeutic modalities that complement antimicrobial treatment in cystitis cases. Ozone therapy has been proposed by scientists both in human and animal medicine. Thus, the objective of this study was evaluated the in vitro antimicrobial activity of ozonized saline solution over standard strains and resistant or multi-drug resistant isolates commonly associated with cystitis in dogs. The plating method was used to evaluate the antimicrobial activity of the exposure of 1 mL of phosphate buffer solution containing 108 colony forming units (CFU) mL-1 for 60 s to 4 mL of ozonized saline solution at 78 µg mL-1 over the standard strains (Staphylococcus aureus and Escherichia coli) and resistant or multi-resistant isolates (Proteus mirabillis, Klebsiella sp. e Enterococcus sp.), and the broth microdilution test to determine the minimum inhibitory and bactericidal concentration for S. aureus, E. coli and Pseudomonas aeruginosa strains from the same solution. The plating was the only assay in which treatment with ozonized saline resulted in bactericidal activity, promoting a reduction of more than 99% of colony-forming units for most of the tested strains, except for P. mirabillis. These results are promising, as these disease is the most common lower urinary tract disorder in dogs, with limited allopathic therapy due to increased bacterial resistance.

Novel quinazoline sulfonamide-based scaffolds modulate methicillin-resistant Staphylococcus aureus (MRSA) pneumonia in immunodeficient irradiated model: Regulatory role of TGF-β

A library of new quinazoline pharmacophores bearing benzenesulfonamide moiety was designed and synthesized. Compounds 3a–n were screened for their in vitro antimicrobial activity against eight multidrug-resistant clinical isolates. Compounds 3d and 3n exhibited prominent antibacterial activity, specifically against MRSA. After exhibiting relative in vitro and in vivo safety, compound 3n was selected to assess its anti-inflammatory activity displaying promising COX-2 inhibitory activity compared to Ibuprofen. In vivo experimental MRSA pneumonia model was conducted on immunodeficient (irradiated) mice to reveal the antimicrobial and anti-inflammatory responses of compound 3n compared to azithromycin (AZ). Treatment with compound 3n (10 and 20 mg/kg) as well as AZ resulted in a significant decrease in bacterial counts in lung tissues, suppression of serum C-reactive protein (CRP), lung interleukin-6 (IL-6), myeloperoxidase activity (MPO) and transforming growth factor-β (TGF-β). Compound 3n showed a non-significant deviation of lung TGF-β1 from normal values which in turn controlled the lung inflammatory status and impacted the histopathological results. Molecular docking of 3n showed promising interactions inside the active sites of TGF-β and COX-2. Our findings present a new dual-target quinazoline benzenesulfonamide derivative 3n, which possesses significant potential for treating MRSA-induced pneumonia in an immunocompromised state.

High prevalence and genetic diversity of multidrug-resistant and extended-spectrum ß-lactamase-producing Escherichia coli and Klebsiella pneumoniae in mothers and neonates in a Cameroonian labor ward

Escherichia coli and Klebsiella pneumoniae rank among the primary bacterial culprits in neonatal infections and fatalities in sub-Saharan Africa. This study characterized the phenotypic and genotypic features of E coli and K pneumoniae in a labor ward in Yaoundé, Cameroon. A prospective and cross-sectional study spanning 5months, from February 21, 2022 to June 30, 2022. Rectovaginal swabs were obtained from expectant mothers, and nasopharyngeal swabs were collected from their babies. Hand swabs of health care workers and environmental samples were also collected. The samples were cultured on eosin methylene blue agar. Extended-spectrum ß-lactamase (ESBL) production was assessed using CHROMAgar ESBL and the double-disk synergy test. A polymerase chain reaction was employed to detect ß-lactamase genes. A total of 93 mothers and 90 neonates were collected. Almost all pregnant women (90%) were colonized by one or more multidrug-resistant (MDR) isolates with 58% being concomitantly ESBL producers. Altogether, 14 of 22 (64%) neonates were colonized by MDR isolates, while out of the 5 workers positive to Enterobacterales, all were colonized by MDR isolates. E coli predominated in pregnant women (55%) and neonates (73%), while K pneumoniae (83%) predominated in health care workers. The blaCTX-M (75%) was the leading ß-lactamase gene detected. Our study suggests that drug-resistant E coli and K pneumoniae are circulating at high prevalence in thelabor ward in Yaoundé and emphasizes the necessity for effective infection prevention and control along with antimicrobial stewardship measures.

Dalbavancin, a Second Generation Lipoglycopeptide is a New Addition to Therapy Armamentarium

Gram-positive infections with widespread developing resistance have posed considerable challenges to the long stay of antimicrobials in the market. Also, there has been a dearth in the provision of a suitable antimicrobial to treat the evolving resistance. Dalbavancin a 2nd generation lipoglycopeptide has shown its activity against gram-positive and multidrug resistant isolates. Owing to a favorable pharmacokinetic profile and supporting evidence this drug moiety has been used as long-term therapy for various indications. These indications include infective endocarditis (IE), osteomyelitis, bloodstream infections, and prosthetic joint infections. However, it is approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) only for acute bacterial skin and skin structure infections (ABSSSIs). Dalbavancin can be a valuable alternative to daily in-hospital intravenous or outpatient antimicrobial regimens in the treatment of long-term Gram-positive infections and ‘niche’ but important indications. This systematic review demonstrates comparative microbiology, chemistry, in vitro susceptibility, pharmacokinetics, clinical efficacy, safety, tolerability, dosage, and administration of dalbavancin. Additionally, it highlights past, present, and upcoming evidence of real-world use of dalbavancin alone or in combination with different indications. Keywords: Dalbavancin, Acute bacterial skin and skin structure infections, Gram-positive, Long-term, and pharmacokinetics.

Broad synergistic antiviral efficacy between a novel elite controller-derived dipeptide and antiretrovirals against drug-resistant HIV-1.

The naturally occurring dipeptide Tryptophylglycine (WG) is enhanced in human immunodeficiency virus (HIV-1) infected Elite Controllers (EC). We have shown that this dipeptide has an anti-HIV-1 effect and evaluated now its synergistic antiretroviral activity, in combination with current antiretrovirals against multi-drug resistant HIV-1 isolates. Drug selectivity assay with WG-am and ARVs agains HIV-1 resistant isolates were carried out. Subsequently, two methods, Chou-Talalay's Combination Index (CI) and ZIP synergy score (SS), were used to quantify the synergism. WG-am had a moderate/strong synergism with the four tested antiretrovirals: raltegravir, tenofovir, efavirenz, darunavir. WG-am:TDF had strong synergism at ED50, ED75, ED90 (CI: <0.2) in isolates resistant to protease inhibitors or integrase strand inhibitors (INSTI), and a slightly less synergism in isolates resistant to non-nucleoside or nucleotide reverse transcriptase inhibitors. WG-am combined with each of the four drugs inhibited all drug-resistant isolates with over 95% reduction at maximum concentration tested. The highest selectivity indexes (CC50/ED50) were in INSTI-resistant isolates. Our data suggest that WG, identified as occurring and enhanced in Elite Controllers has a potential to become a future treatment option in patients with HIV-1 strains resistant to any of the four major categories of anti-HIV-1 compounds.

Impact of the COVID-19 pandemic on Haemophilus influenzae infections in pediatric patients hospitalized with community acquired pneumonia

The COVID-19 pandemic has altered the infection landscape for many pathogens. This retrospective study aimed to compare Haemophilus influenzae (H. influenzae) infections in pediatric CAP patients hospitalized before (2018–2019) and during (2020–2022) the COVID-19 pandemic. We analyzed the clinical epidemiology and antimicrobial resistance (AMR) patterns of H. influenzae from a tertiary hospital in southwest China. A total of 986 pediatric CAP patients with H. influenzae-associated infections were included. Compared to 2018, the positivity rate increased in 2019 but dropped significantly in 2020. Although it rose in the following 2 years, the rate in 2022 remained significantly lower than in 2019. Patients’ age during the pandemic was significantly higher than in 2018 and 2019, while gender composition remained similar across both periods. Notably, there were significant changes in co-infections with several respiratory pathogens during the pandemic. Resistance rates of H. influenzae isolates to antibiotics varied, with the highest resistance observed for ampicillin (85.9%) and the lowest for cefotaxime (0.0%). Resistance profiles to various antibiotics underwent dramatic changes during the COVID-19 pandemic. Resistance to amoxicillin-clavulanate, cefaclor, cefuroxime, trimethoprim-sulfamethoxazole, and the proportion of multi-drug resistant (MDR) isolates significantly decreased. Additionally, MDR isolates, alongside isolates resistant to specific drugs, were notably prevalent in ampicillin-resistant and β-lactamase-positive isolates. The number of pediatric CAP patients, H. influenzae infections, and isolates resistant to certain antibiotics exhibited seasonal patterns, peaking in the winter of 2018 and 2019. During the COVID-19 pandemic, sharp decreases were observed in February 2020, and there was no resurgence in December 2022. These findings indicate that the COVID-19 pandemic has significantly altered the infection spectrum of H. influenzae in pediatric CAP patients, as evidenced by shifts in positivity rate, demographic characteristics, respiratory co-infections, AMR patterns, and seasonal trends.

Prevalence and Antimicrobial Resistance Pattern of Uropathogenic Escherichia coli at a Tertiary Care Hospital: A Retrospective Study

Background: Uropathogenic Escherichia coli (UPEC) is the most common cause of urinary tract infection in humans including cystitis and pyelonephritis. Antimicrobial resistance (AMR) in UPEC is one of the global public challenges that is due to prevalent use of antibiotics in healthcare setting. Therefore, the purpose of this study is to investigate the frequency and antibiotic resistance pattern of UPEC isolated from patients admitted to Modares Hospital in Saveh, Iran. Methods: In this study, in total 633 isolates were evaluated. UPEC isolates were obtained from patients with urinary tract infection and identified using conventional microbiological protocols. Antibiotic resistance pattern of UPEC against different antibiotic were determined using disk diffusion method. SPSSTM software was used for statistical analysis Results: In this study, the most sample was related to outpatients and the lowest sample was related to the CCU wards. The highest antibiotic resistance showed against cephalothin (63.8%) and nalidixic acid (62.2%) antibiotics. The highest effective antibiotics for the tested UPEC was nitrofurantoin (90.7%) and gentamicin (77.3%). Cephalothin and nalidixic acid in hospitalized patients in ICU and emergency wards, respectively, showed the highest antibiotic resistance. Out of 633 UPEC, the rate of Multi Drug Resistant (MDR) isolates were 343 (54.2%). Conclusion: The result of this study highlighted the role of UPEC as one of the important cause of UTI in individuals. Also, nitrofurantoin then gentamicin are the most effective antibiotics against UPEC infections. Logical prescription of antibiotics and infection control strategies are needed for prevention and control of nosocomial infections especially urinary tract infection.

In Silico Detection of Integrons and Their Relationship with Resistance Phenotype of Salmonella Isolates from a Brazilian Pork Production Chain.

The pork production chain is an important reservoir of antimicrobial resistant bacteria. This study identified and characterized integrons in Salmonella isolates from a Brazilian pork production chain and associate them with their antibiotic resistance pattern. A total of 41 whole-genome sequencing data of nontyphoidal Salmonella were analyzed using PlasmidSPAdes and IntegronFinder software. Nine isolates (21.9%) had some integrons identified (complete and/or incomplete). Six complete class 1 integrons were found, with streptomycin resistance genes (aadA1, aadA2) alone or downstream of a trimethoprim resistance gene (dfrA1, dfrA12), and some also containing resistance genes for sulfonamides (sul1, sul3) and chloramphenicol (cmlA1). Class 2 integron was detected in only one isolate, containing dfrA1-sat2-aadA1 gene cassettes. Five isolates harbored CALINs-clusters attC but lacking integrases-with antimicrobial resistance genes typically found in integron structures. In all, integrons were observed among four serotypes: Derby, Bredeney, Panama, and monophasic var. Typhimurium I 4,[5],12:i:-. The association of integrons with antibiotic resistance phenotype showed that these elements were predominantly identified in multidrug resistance isolates, and six of the seven gentamicin-resistant isolates had integrons. So, surveillance of integrons in Salmonella should be performed to identify the potential for the spread of antimicrobial resistance genes among bacteria.

Geogenic high arsenic elevates the groundwater antibiotic resistomes: A blind spot of resistance in Anthropocene

Metals/metalloids, being ubiquitous in the environment, can function as a co-selective pressure on antibiotic resistance genes (ARGs) threatening human health. However, the effect of geogenic arsenic (As) on groundwater antibiotic resistomes and their health risks remain largely unknown. Here, we systematically analyzed bacterial communities, pathogenic bacteria, antibiotic resistomes, and in-situ multidrug-resistant isolates with the assessment of the health risk of ARGs and the pathogenicity of their hosts in high As groundwater from the Hetao basin, Northwestern China. We found that long-term geogenic As exposure shifted the assembly of resistomes and resulted in a high abundance and diversity of ARGs in groundwater. Significantly positive associations among As, As cycling genes, ARGs, and mobile genetic elements (MGEs) revealed by network and pathway analyses, together with genetic evidence of As-tolerant multidrug-resistant isolates by whole genomic sequencing, robustly indicate the geogenic As-induced co-selection for antibiotic resistance in groundwater. Variance partitioning analysis further confirmed the determinative role of geogenic As in groundwater resistomes, with As species and As cycling genes as the core abiotic and biotic drivers, respectively. More seriously, geogenic As accelerated the prevalence of high-risk ARGs and multidrug-resistant bacteria. Our findings highlight the significance of geogenic As-induced co-selection for antibiotic resistance in groundwater and the hidden role of geogenic metals/metalloids in increasing antibiotic resistance. This study provides a basis for groundwater management of both high As and ARGs for human health.

Efficacy of Cefiderocol, a Novel Siderophore Cephalosporin, against Multidrug Resistant Acinetobacter baumannii Clinical Isolates in Japan.

Multidrug-resistant Acinetobacter baumannii (MDRAB) is an important pathogen that causes nosocomial infections and is resistant to almost all antibiotics, including carbapenems. Cefiderocol is a novel siderophore cephalosporin active against a broad spectrum of gram-negative bacteria. However, the susceptibility of MDRAB to cefiderocol has not yet been reported in Japan. In this study, we measured the minimum inhibitory concentrations (MICs) of antibiotics including cefiderocol against MDRAB clinical isolates collected during a nosocomial outbreak between 2009 and 2010 at the Teikyo University Hospital in Japan. We found that all 10 MDRAB clinical isolates tested were susceptible to cefiderocol, with an MIC range of 0.12 to 1 μg/mL. All the isolates also exhibited resistance to ampicillin-sulbactam and an intermediate resistance to colistin, whereas nine of them were susceptible to tigecycline. DNA sequencing revealed that all strains harbored an OXA-51-like carbapenemase, a major cause of carbapenem resistance in A. baumannii in Japan. In conclusion, this study showed that the cefiderocol susceptibility of MDRAB clinical isolates in Japan was equivalent to that to colistin or tigecycline, and thus cefiderocol is a potential treatment option for MDRAB infections.

Antimicrobial resistance and self-reported hand hygiene awareness before and after an infection prevention and control programme: A 7-year analysis in a small animal veterinary teaching hospital

Infection prevention and control (IPC) in veterinary medicine is crucial to protect patients, owners, staff, and the public. An IPC programme is recommended for every animal hospital. The objective of this retrospective longitudinal study was to describe the changes in bacterial and multidrug-resistant (MDR) bacterial isolates and self-reported hand hygiene awareness and practices after an IPC programme to assess the long-term effect of this programme in small animal veterinary medicine. The IPC programme was implemented at our veterinary teaching hospital in April 2018, which included the establishment of an infection control task force, regular IPC lectures and poster campaigns, infrastructure improvement, and manual refinement. Laboratory-based surveillance was retrospectively conducted before and after the programme (January 2016–December 2022). Level and slope changes in bacterial isolates were evaluated using interrupted time-series analysis. Self-reported hand hygiene awareness and practices were assessed using an annual questionnaire. Additionally, hygiene product purchases during the study period were investigated.The monthly number of total and MDR bacterial isolates decreased significantly after the programme (MDR level change: −0.426; 95% confidence interval: −0.744, −0.109; P = 0.009; and MDR slope change: −0.035; 95% confidence interval: −0.058, −0.011; P = 0.003). Additionally, awareness of hand hygiene before touching animals improved after the programme. Overall self-reported hand hygiene practices improved, and hygiene product purchases significantly increased. These results suggested that the IPC programme may have long-term effects regarding reducing total and MDR bacterial isolates and improving hand hygiene awareness in veterinary medicine.

Drug resistance and epidemiological success of modern Mycobacterium tuberculosis lineages in western India.

Transmission is contributing to the slow decline of tuberculosis (TB) incidence globally. Drivers of TB transmission in India, the country estimated to carry a quarter of the World's burden, are not well studied. We conducted a genomic epidemiology study to compare epidemiological success, host factors and drug resistance (DR) among the four major Mycobacterium tuberculosis (Mtb) lineages (L1-4) circulating in Pune, India. We performed whole-genome sequencing (WGS) of Mtb sputum culture-positive isolates from participants in two prospective cohort studies and predicted genotypic susceptibility using a validated random forest model. We used maximum likelihood estimation to build phylogenies. We compared lineage specific phylogenetic and time-scaled metrics to assess epidemiological success. Of the 642 isolates that underwent WGS, 612 met sequence quality criteria. Most isolates belonged to L3 (44.6%). The majority (61.1%) of multidrug-resistant isolates belonged to L2 (P < 0.001). In molecular dating, L2 demonstrated a higher rate and more recent resistance acquisition. We measured higher clustering, and time-scaled haplotypic density (THD) for L4 and L2 compared to L3 and/or L1 suggesting higher epidemiological success. L4 demonstrated higher THD and clustering (OR 5.1 (95% CI 2.3-12.3) in multivariate models controlling for host factors and DR. L2 shows a higher frequency of DR and both L2 and L4 demonstrate evidence of higher epidemiological success than L3 or L1 in the study setting. Our findings highlight the need for contact tracing around TB cases, and heightened surveillance of TB DR in India.

Molecular Detection of Virulence Genes Associated With Multi- Drug Resistant Pseudomonas Aeruginosa Isolated from Clinical and Environmental Samples within Maiduguri

Pseudomonas aeruginosa is an ubiquitous opportunistic pathogen having numerous virulence factors and the ability to acquire multidrug resistant traits. This study aimed to determine the presence of the virulence genes algD and lasB in multidrug resistant Pseudomonas aeruginosa isolated from clinical and environmental samples within Maiduguri. A total of 200 samples were collected from four sources namely; Farm soil at root region of groundnut, abattoir waste water, commercial boreholes and urine of urinary tract infected patients. All positive growths on cetrimide agar were further identified biochemically. Antibiotic profile of confirmed Pseudomonas aeruginosa was determined using Kirby-Baeur disc diffusion method. The genes algD and lasB were detected in the multidrug resistant isolates. The result also showed that 90.90%, 81.81% and 81.81% of the urine isolates were resistant to nalidixic acid, chloramphenicol and tetracycline respectively while highest sensitivity was observed against amikacin at 81.81%. Highest resistance among environmental samples was observed in abattoir wastewater with 95.24% resistance to chloramphenicol while least resistance was observed in borehole isolates with 0.00% resistance to Gentamicin, Amikaicin, Meropenem and Aztreonam. According to the findings of this study also, there is no significant difference in habouring virulence genes among the isolates of the different sources. All the multidrug resistant isolates were found to habour both algD and LasB genes. In conclusion, P. aeruginosa was found in all of the studied sources and widespread of algD and LasB genes in the multidrug resistant isolates from all the sources.

Whole-genome sequencing analysis of multidrug-resistant Serratia marcescens isolates in an intensive care unit in Brazil.

Serratia marcescens is an opportunistic pathogen found ubiquitously in the environment and associated with a wide range of nosocomial infections. This multidrug-resistant bacterium has been a cause of concern for hospitals and healthcare facilities due to its ability to spread rapidly and cause outbreaks. Next generation sequencing genotyping of bacterial isolates has proven to be a valuable tool for tracking the spread and transmission of nosocomial infections. This has allowed for the identification of outbreaks and transmission chains, as well as determining whether cases are due to endogenous or exogenous sources. Evidence of nosocomial transmission has been gathered through genotyping methods. The aim of this study was to investigate the genetic diversity of carbapenemase-producing S. marcescens in an outbreak at a public hospital in Cuiaba, MT, Brazil. Ten isolates of S. marcenses were sequenced and antibiotic resistance profiles analyzed over 12 days. The isolates were clonal and multidrug resistant. Gentamycin and tigecycline had sensitivity in 90% and 80% isolates, respectively. Genomic analysis identified several genes that encode β-lactamases, aminoglycoside-modifying enzymes, efflux pumps, and other virulence factors. Systematic surveillance is crucial in monitoring the evolution of S. marcescens genotypes, as it can lead to early detection and prevention of outbreaks.

A Gram-negative-selective antibiotic that spares the gut microbiome.

Infections caused by Gram-negative pathogens are increasingly prevalent and are typically treated with broad-spectrum antibiotics, resulting in disruption of the gut microbiome and susceptibility to secondary infections1-3. There is a critical need for antibiotics that are selective both for Gram-negative bacteria over Gram-positive bacteria, as well as for pathogenic bacteria over commensal bacteria. Here we report the design and discovery of lolamicin, a Gram-negative-specific antibiotic targeting the lipoprotein transport system. Lolamicin has activity against a panel of more than 130 multidrug-resistant clinical isolates, shows efficacy in multiple mouse models of acute pneumonia and septicaemia infection, and spares the gut microbiome in mice, preventing secondary infection with Clostridioides difficile. The selective killing of pathogenic Gram-negative bacteria by lolamicin is a consequence of low sequence homology for the target in pathogenic bacteria versus commensals; this doubly selective strategy can be a blueprint for the development of other microbiome-sparing antibiotics.

In vitro antimalarial therapeutic interventions using various combinations of antibiotics and standard antimalarials against multi drug resistant Indian field isolates of Plasmodium falciparum

Resistance to antimalarials is considered to be major cause of increased malaria morbidity and mortality. Present study was undertaken to explore an effective drug combination against selected mutant parasite various combinations using standard antimalarials {Chloroquine diphosphate (CQ), Quinine (QUIN), Mefloquine (MQ), Piperaquine (PPQ), Artemether (ARTM), Arteether (ARTE), Dihydro-artemisinin (DHA), Lumefantrine (LUME)and Atovaquone (ATQ)} belonging to three different classes and two antibiotics, Azithromycin (AZI) and Doxycycline (DOXY) have been tried against K1 (chloroquine-resistant) and 3D7 (chloroquine-sensitive) strains as well as selected arteether torelant parasite (MZRI-R) and field isolates (MZRI &amp; MZRII) of P. falciparum. SYBR Green I fluorescence (MSF) assay was used to determine IC50 values. Results of present studies highlighted that all the combinations used exhibited additive effect with varying intensity depending upon the drug ratios used. We also observed that combination of ARTM plus LUME was more advantageous than DOXY plus DHA/CQ and AZI plus CQ/ATQ for treatment of multidrug resistant parasites whereas combinations of LUME plus PPQ, ATQ plus DOXY/AZI can be used for treatment of CQ resistant parasite.

Phenotypic and Genotypic Antibiotic Resistance Patterns of Clinical Shigella Isolates from Tehran, Iran

Background: The emergence of multidrug-resistant (MDR) Shigella is a health concern in both developed and developing countries. The indiscriminate use of antibiotics without considering resistance patterns has led to the emergence of resistant strains. Objectives: This study aimed to investigate the phenotypic and genotypic patterns of antibiotic resistance and virulence gene distribution in Shigella isolates from patients in Tehran, Iran. Methods: In this cross-sectional study, 60 Shigella isolates were collected from patients referred to Milad Hospital and Pasargad Laboratory in Tehran. The isolates were gathered over four months, from February 2023 to June 2023. After biochemical and genetic confirmation of the isolates, the disk diffusion method was employed to determine antibiotic resistance patterns. The distribution of beta-lactamase genes (blaCTX-M1, blaCTX-M2, blaCTX-M8, blaSHV, blaTEM, and blaOXA) and virulence genes (ial, virF, invE, sigA, and pic) was investigated in Shigella isolates using the multiplex PCR method. SPSS statistical software version 22 was used for data analysis. Results: Thirty-six percent of isolates were found to be MDR. The highest rate of resistance was against tetracycline (90%) and ampicillin (80%). The lowest resistance rate was against azithromycin (1.9%) and amikacin (7.1%). The blaCTX-M1 and blaCTX-M8 genes were more prevalent, detected in 38.3% and 50% of the isolates, respectively. However, the blaSHV and blaCTX-M2 genes were not detected in any of the isolates. Additionally, 32% of the MDR isolates harbored both the blaCTX-M1 and blaCTX-M8 genes simultaneously. The distribution of virulence genes ial, virF, invE, sigA, and pic in the studied isolates was 28.3%, 85%, 68.3%, 81.7%, and 15%, respectively. Conclusions: The present study emphasizes the increasing trend of MDR Shigella isolates. Therefore, serious measures are needed to prevent the spread of resistant genes. Furthermore, the detection of virulence factors could help in controlling shigellosis, which is a significant global health issue.

Prevalence of Antibiotic Resistance and Virulence Genes in Escherichia coli Carried by Migratory Birds on the Inner Mongolia Plateau of Northern China from 2018 to 2023.

(1) Background: Antibiotic resistance in bacteria is an urgent global threat to public health. Migratory birds can acquire antibiotic-resistant and pathogenic bacteria from the environment or through contact with each other and spread them over long distances. The objectives of this study were to explore the relationship between migratory birds and the transmission of drug-resistant pathogenic Escherichia coli. (2) Methods: Faeces and swab samples from migratory birds were collected for isolating E. coli on the Inner Mongolia Plateau of northern China from 2018 to 2023. The resistant phenotypes and spectra of isolates were determined using a BD Phoenix 100 System. Conjugation assays were performed on extended-spectrum β-lactamase (ESBL)-producing strains, and the genomes of multidrug-resistant (MDR) and ESBL-producing isolates were sequenced and analysed. (3) Results: Overall, 179 isolates were antibiotic-resistant, with 49.7% MDR and 14.0% ESBL. Plasmids were successfully transferred from 32% of ESBL-producing strains. Genome sequencing analysis of 91 MDR E. coli strains identified 57 acquired resistance genes of 13 classes, and extraintestinal pathogenic E. coli and avian pathogenic E. coli accounted for 26.4% and 9.9%, respectively. There were 52 serotypes and 54 sequence types (STs), including ST48 (4.4%), ST69 (4.4%), ST131 (2.2%) and ST10 (2.2%). The international high-risk clonal strains ST131 and ST10 primarily carried blaCTX-M-27 and blaTEM-176. (4) Conclusions: There is a high prevalence of multidrug-resistant virulent E. coli in migratory birds on the Inner Mongolian Plateau. This indicates a risk of intercontinental transmission from migratory birds to livestock and humans.