Antibiotics, Volume 13, Issue 5 (May 2024) – 49 articles

Carbapenemase-producing enterobacterales (CPE) poses an increasing threat in hospitals worldwide. Recently, the prevalence of different carbapenemases conferring carbapenem resistance in enterobacterales changed in our country, including an increase in New Delhi Metallo-beta-lactamase (NDM)-CPE. We conducted a comparative historical study of adult patients colonized with Klebsiella pneumoniae carbapenemase (KPC)-CPE (July 2016 to June 2018, a historical cohort) vs. NDM-CPE (July 2016 to January 2023). We identified patients retrospectively through the microbiology laboratory and reviewed their files, extracting demographics, underlying diseases, Charlson Comorbidity Index (CCI) scores, treatments, and outcomes. This study included 228 consecutive patients from whom a CPE rectal swab screening was obtained: 136 NDM-CPE positive and 92 KPC-CPE positive. NDM-CPE-colonized patients had a shorter hospitalization length and a significantly lower 30-day post-discharge mortality rate (p = 0.002) than KPC-CPE-colonized patients. Based on multivariate regression, independent risk factors predicting CPE-NDM colonization included admission from home and CCI < 4 (p < 0.001, p = 0.037, respectively). The increase in NDM-CPE prevalence necessitates a modified CPE screening strategy upon hospital admission tailored to the changing local CPE epidemiology. In our region, the screening of younger patients residing at home with fewer comorbidities should be considered, regardless of a prior community healthcare contact or hospital admission. Full article

Valley surface water is considered a focal public health concern owing to the presence of multi-drug-resistant bacteria. The distribution of antimicrobial resistance (AMR) bacteria in the surface water is affected by the presence of multiple factors, including antibiotics coming from wastewater discharge or other contaminant sources such as pharmaceuticals, biocides, and heavy metals. Furthermore, there is evidence suggesting that high levels of antibiotic resistance genes (ARGs) can be transferred within bacterial communities under the influence of heavy metal stress. Hence, the primary aim of this study is to investigate the presence of heavy metals and bacterial ARGs in upstream as well as downstream locations of Wadi Hanifah Valley in Riyadh, Saudi Arabia. Sample collection was conducted at eighteen surface water sites within the valley in total. The selection of ARGs was associated with the most common antibiotics, including β-lactam, tetracycline, erythromycin, gentamicin, sulphonamide, chloramphenicol, vancomycin, trimethoprim, and colistin antibiotics, which were detected qualitatively using polymerase chain reaction (PCR) technology. The tested antibiotic resistance genes (ARGs) included (bla_NDM-1 (for the antibiotic class Beta-lactamases), mecA (methicillin-resistant Staphylococcus aureus), tet(M) and tet(B) (for the antibiotic class Tetracycline), ampC (for the antibiotic class Beta-lactamases), vanA (for the antibiotic class vancomycin), mcr-1 (for the antibiotic class colistin), erm(B) (for the antibiotic class erythromycin), aac6′-Ie-aph2-Ia (for the antibiotic class Gentamicin), sulII (for the antibiotic class sulphonamide), catII (for the antibiotic class Chlorophincol), and dfrA1 (for the antibiotic class trimethoprim). Moreover, an assessment of the levels of heavy metals such as lithium (Li), beryllium (Be), chromium (Cr), cobalt (Co), arsenic (As), cadmium (Cd), tin (Sn), mercury (Hg), and lead (Pb) was conducted by using inductively coupled plasma mass spectrometry (ICPMS). According to our findings, the concentrations of sulphonamide, erythromycin, and chloramphenicol ARGs (erm(B), sulII, and catII) were observed to be the most elevated. Conversely, two ARGs, namely mecA and mcr-1, were not detected in the samples. Moreover, our data illustrated a significant rise in ARGs in the bacteria of water samples from the upstream sites as compared with the water samples from the downstream sites of Wadi Hanifah Valley. The mean concentration of Li, Be, Cr, Co, As, Cd, Sn, Hg, and Pb in the water samples was estimated to be 37.25 µg/L, 0.02 µg/L, 0.56 µg/L,0.32 µg/L, 0.93 µg/L, 0.01 µg/L, 200.4 µg/L, 0.027 µg/L, and 0.26 µg/L, respectively, for the selected 18 sites. Furthermore, it was revealed that the concentrations of the screened heavy metals in the water samples collected from various sites did not surpass the maximum limits set by the World Health Organization (WHO). In conclusion, this study offers a concise overview of the presence of heavy metals and ARGs in water samples obtained from the Wadi Hanifah Valley in Riyadh, KSA. Such findings will contribute to the ongoing monitoring and future risk assessment of ARGs spread in surface water. Full article

Antimicrobial stewardship involves a delicate balance between the risk of undertreating individuals and the potential societal burden of overprescribing antimicrobials. This balance is especially crucial in neonatal care. In this observational study, the usefulness of biomarkers of infectious diseases (calprotectin, procalcitonin (PCT), C-reactive protein (CRP), and white blood cells (WBCs) were evaluated in 141 febrile infants aged 28–90 days presenting to an emergency department. Since our focus was on the usefulness of serum calprotectin, this biomarker was not part of clinical decision-making. A significant difference was observed in the levels of all biomarkers, related to final discharge diagnosis and disposition status. The difference in levels related to antibiotic prescription was significant for all biomarkers but WBCs. The performance of calprotectin in the detection of bacterial infections (AUC (95% CI): 0.804 (0.691, 0.916)) was comparable to the performance of both PCT (0.901 (0.823, 0.980)) and CRP (0.859 (0.764, 0.953)) and superior to the WBC count (0.684 (0.544, 0.823)). Procalcitonin and CRP demonstrated a statistically significantly higher specificity relative to calprotectin. In this cohort, antibiotic use did not always correlate to a definite diagnosis of confirmed bacterial infection. The sample size was limited due to associated challenges with recruiting febrile infants. Hence, there is a need for adequate diagnostic tools to help discriminate between various kinds of infections. This study suggests serum calprotectin, procalcitonin, and CRP may serve as valuable biomarkers to differentiate between types of infection, in addition to clinical input and decision-making. Full article

This study aimed to assess the efficacy of a novel prophylactic scheme of fosfomycin trometamol in patients undergoing elective HoLEP (holmium laser enucleation of the prostate) or TURP (transurethral resection of the prostate) procedures for treating benign prostatic hyperplasia. Patients affected by benign prostatic hyperplasia and undergoing elective HoLEP or TURP procedures during the period February 2022–June 2023 were prospectively enrolled. Two 3 g oral fosfomycin trometamol doses 12 h apart were administered at 8.00 p.m. on day −1 (i.e., the day before HoLEP or TURP procedure) and at 8.00 a.m. on day 0 (i.e., the day of the surgical procedure). The following outcomes were assessed: prevalence of fever occurring in the first 48 h after surgical procedure; prevalence of urological complications occurring after the surgical procedure; prevalence of proven urinary tract infections (UTIs) and/or bloodstream infections (BSIs) at 14 days post-procedure; and prevalence of emergency department admission for UTI-related sepsis at 14 days post-procedure. Univariate analysis comparing patients with and without proven UTI, BSI, or emergency department admission at 14 days post-procedure was carried out. Overall, 96 patients (median age 70 years) undergoing HoLEP (82.3%) or TURP (17.7%) were prospectively included. Median (IQR) time of surgical procedure after the morning fosfomycin dose was 226.5 min (range 88.5–393.75 min). Fever in the post-surgical 48 h occurred in 3/96 patients (3.1%). Prevalence of proven UTI at 14 days was as low as 1.0% (1/96), whereas no patient had proven BSI or UTI-related sepsis requiring emergency department admission at 14 days. Our findings support the contention that a prophylactic scheme based on two doses of fosfomycin trometamol 12 h apart before surgical intervention may represent a valuable strategy for preventing infectious complications in urologic patients undergoing HoLEP or TURP. Larger definitive confirmatory studies are warranted. Full article

Acinetobacter baumannii has emerged as a pressing challenge in clinical practice, mainly due to the development of resistance to multiple antibiotics, including colistin, one of the last-resort treatments. This review highlights all the possible mechanisms of colistin resistance and the genetic basis contributing to this resistance, such as modifications to lipopolysaccharide or lipid A structures, alterations in outer membrane permeability via porins and heteroresistance. In light of this escalating threat, the review also evaluates available treatment options. The development of new antibiotics (cefiderocol, sulbactam/durlobactam) although not available everywhere, and the use of various combinations and synergistic drug combinations (including two or more of the following: a polymyxin, ampicillin/sulbactam, carbapenems, fosfomycin, tigecycline/minocycline, a rifamycin, and aminoglycosides) are discussed in the context of overcoming colistin resistance of A. baumannii infections. Although most studied combinations are polymyxin-based combinations, non-polymyxin-based combinations have been emerging as promising options. However, clinical data remain limited and continued investigation is essential to determine optimal therapeutic strategies against colistin-resistant A. baumannii. Full article

Scorpion venom peptides are generally classified into two main groups: the disulfide bridged peptides (DBPs), which usually target membrane-associated ion channels, and the non-disulfide bridged peptides (NDBPs), a smaller group with multifunctional properties. In the past decade, these peptides have gained interest because most of them display functions that include antimicrobial, anticancer, haemolytic, and anti-inflammatory activities. Our current study focuses on the short (9–19 amino acids) antimicrobial linear scorpion peptides. Most of these peptides display a net positive charge of 1 or 2, an isoelectric point at pH 9–10, a broad range of hydrophobicity, and a Grand Average of Hydropathy (GRAVY) Value ranging between −0.05 and 1.7. These features allow these peptides to be attracted toward the negatively charged phospholipid head groups of the lipid membranes of target cells, a force driven by electrostatic interactions. This review outlines the antimicrobial potential of short-chained linear scorpion venom peptides. Additionally, short linear scorpion peptides are in general more attractive for large-scale synthesis from a manufacturing point of view. The structural and functional diversity of these peptides represents a good starting point for the development of new peptide-based therapeutics. Full article

Chlamydial infections and diseases caused by filarial nematodes are global health concerns. However, treatment presents challenges due to treatment failures potentially caused by persisting Chlamydia and long regimens against filarial infections accompanied by low compliance. A new treatment strategy could be the targeting of the reduced peptidoglycan structures involved in cell division in the obligate intracellular bacteria Chlamydia and Wolbachia, the latter being obligate endosymbionts supporting filarial development, growth, and survival. Here, cell culture experiments with C. trachomatis and Wolbachia showed that the nucleoside antibiotics muraymycin and carbacaprazamycin interfere with bacterial cell division and induce enlarged, aberrant cells resembling the penicillin-induced persistence phenotype in Chlamydia. Enzymatic inhibition experiments with purified C. pneumoniae MraY revealed that muraymycin derivatives abolish the synthesis of the peptidoglycan precursor lipid I. Comparative in silico analyses of chlamydial and wolbachial MraY with the corresponding well-characterized enzyme in Aquifex aeolicus revealed a high degree of conservation, providing evidence for a similar mode of inhibition. Muraymycin D2 treatment eradicated persisting non-dividing C. trachomatis cells from an established penicillin-induced persistent infection. This finding indicates that nucleoside antibiotics may have additional properties that can break bacterial persistence. Full article

Outpatient parenteral antimicrobial therapy (OPAT) aims to deliver intravenous antimicrobials to medically stable patients with complex infections outside of a hospital setting. There is good evidence to demonstrate the safety and efficacy of OPAT in the literature. Anecdotally, the feedback from patients has been positive, but only a few studies evaluate this topic in detail. The aim of this qualitative study was to examine patients’ experiences with and feedback on the OPAT service in Bristol, United Kingdom, which was established in 2021. A total of 92 patient feedback surveys were reviewed retrospectively, and thematic analysis was undertaken. Feedback from OPAT patients in our centre was overwhelmingly positive. The key themes identified were benefits to the patients, their friends, and family, and positive feedback about OPAT staff. The mean overall satisfaction score for OPAT was 9.6 out of 10. Areas to improve included communication between the OPAT and parent teams, improving OPAT capacity, and expansion of the service. Full article

This study aimed to characterize the impact of extracorporeal membrane oxygenation (ECMO) on the pharmacokinetics (PK) of meropenem in neonates and children and to provide recommendations for meropenem dosing in this specific population of patients. Therapeutic drug monitoring (152 meropenem plasma concentrations) data from 45 patients (38 received ECMO) with a body weight (BW) of 7.88 (3.62–11.97) kg (median (interquartile range)) and postnatal age of 3 (0–465) days were collected. The population PK analysis was performed using NONMEM V7.3.0. Monte Carlo simulations were performed to assess the probability of target achievement (PTA) for 40% of time the free drug remained above the minimum inhibitory concentration (fT > MIC) and 100% fT > MIC. BW was found to be a significant covariate for the volume of distribution (Vd) and clearance (CL). Additionally, continuous renal replacement therapy (CRRT) was associated with a two-fold increase in Vd. In the final model, the CL and Vd for a typical patient with a median BW of 7.88 kg that was off CRRT were 1.09 L/h (RSE = 8%) and 3.98 L (14%), respectively. ECMO did not affect meropenem PK, while superimposed CRRT significantly increased Vd. We concluded that current dosing regimens provide acceptably high PTA for MIC ≤ 4 mg/L for 40% fT > MIC, but individual dose adjustments are needed for 100% fT > MIC. Full article

Rapid detection of antimicrobial resistance is crucial for early initiation of appropriate therapy. The aim of this study was to investigate whether resistance to colistin, the last-resort antibiotic, in carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates can be detected accurately and rapidly by flow cytometry (FCM). The VITEK 2 automated system was used to identify 85 K. pneumoniae strains and to determine their resistance to carbapenems. The minimum inhibitory concentration (MIC) values for colistin in 85 CRKP strains were determined by broth microdilution (BMD), which is the reference method. In addition, FCM was used, combined with DiBAC₄(3) fluorescent stain, to determine colistin susceptibility. The MIC₅₀ value of the strains, 80% of which were resistant to colistin by the BMD method, was 16 mg/L, and the MIC₉₀ value was 32 mg/L. When FCM was compared with the reference method, it was determined that the specificity was 94.1%, sensitivity was 100% of FCM, and Cohen’s kappa value was 0.96. Colistin susceptibility results with FCM were obtained within an average of 2 h. These findings suggest that FCM holds great promise as a rapid and reliable alternative method for detecting colistin resistance in CRKP strains. Full article

Enterococci are part of the natural flora of the gastrointestinal tract of mammals, including humans, birds and invertebrates. They can cause infection, mainly among hospitalized patients, as well as acquire and transfer antimicrobial resistance genes. The present study allowed the isolation of 98 Enterococcus (73.47% E. faecium, 23.47% E. faecalis, 3.06% E. avium) strains from 120-day-old healthy chickens that had never been treated with antimicrobials. Their antimicrobial resistance was evaluated by the agar disk diffusion method; high-level aminoglycoside (streptomycin and gentamicin) and vancomycin resistance were established using the microbroth dilution method. The highest percentages of resistant isolates were detected with quinupristin–dalfopristin (88.78%), rifampicin (64.29%), tetracyclines (45.92%), and enrofloxacin (41.84%). High percentages of susceptible strains were found with teicoplanin (100%), amoxicillin–clavulanic acid (97.96%), nitrofurantoin (94.90%), ampicillin (92.86%), chloramphenicol (90.82%), and linezolid (88.78%). About 60% of the strains were classified as MDR (multidrug-resistant). Moreover, PCR was carried out to investigate genes encoding for tetracyclines resistance determinants: tet(M), tet(L), tet(O), tet(K), and Int-Tn. Genes were detected in 68 (69.38%) strains: 36 were shown to be resistant with the agar disk diffusion method, while 28 were intermediate, and 2 were susceptible. The present study showed that chickens never treated with antimicrobials potentially harbor enterococci having phenotypic and genotypic characters of antimicrobial resistance. Full article

Co-infection with carbapenem-resistant Klebsiella pneumoniae (CRKP) and Pseudomonas aeruginosa (CRPA) is associated with poor outcomes and historically relied on combination therapy with toxic agents for management. However, several novel β-lactam/β-lactamase inhibitor combination agents have been developed, offering potential monotherapy options. Here, we compare the in vitro activity of ceftazidime-avibactam (CZA), imipenem-relebactam (IRL), and meropenem-vaborbactam (MVB) against both CRKP and CRPA clinical isolates. Minimum inhibitory concentrations (MICs) for each agent were determined using broth microdilution. Carbapenemase gene detection was performed for representative isolates of varying carbapenem resistance phenotypes. IRL demonstrated excellent activity against CRKP and CRPA with susceptibility rates at 95.8% and 91.7%, respectively. While CZA and MVB showed comparable susceptibility to IRL against CRKP (93.8%), susceptibility of CRPA to CZA was modest at 79.2%, whereas most CRPA strains were resistant to MVB. Of the 35 CRKP isolates tested, 91.4% (32/35) carried a bla_KPC gene. Only 1 of 37 (2.7%) CRPA isolates tested carried a bla_VIM gene, which conferred phenotypic resistance to all three agents. None of the CRKP strains were cross-resistant to all three agents. Source of infection and co-infection did not significantly influence antimicrobial activity for IRL and CZA; none of the CRPA isolates from co-infected patients were susceptible to MVB. Our results suggest that novel β-lactam agents with antipseudomonal activity and stability against carbapenemases, such as IRL and CZA, offer potential monotherapy options for the treatment of co-infection involving both CRKP and CRPA, but not MVB. Full article

This review delves into using natural antimicrobials in the dairy industry and examines various sources of these compounds, including microbial, plant, and animal sources. It discusses the mechanisms by which they inhibit microbial growth, for example, by binding to the cell wall’s precursor molecule of the target microorganism, consequently inhibiting its biosynthesis, and interfering in the molecule transport mechanism, leading to cell death. In general, they prove to be effective against the main pathogens and spoilage found in food, such as Escherichia coli, Staphylococcus aureus, Bacillus spp., Salmonella spp., mold, and yeast. Moreover, this review explores encapsulation technology as a promising approach for increasing the viability of natural antimicrobials against unfavorable conditions such as pH, temperature, and oxygen exposure. Finally, this review examines the benefits and challenges of using natural antimicrobials in dairy products. While natural antimicrobials offer several advantages, including improved safety, quality, and sensory properties of dairy products, it is crucial to be aware of the challenges associated with their use, such as potential allergenicity, regulatory requirements, and consumer perception. This review concludes by emphasizing the need for further research to identify and develop effective and safe natural antimicrobials for the dairy industry to ensure the quality and safety of dairy products for consumers. Full article

Bacitracin Methylene Disalicylate (BMD), as a feed additive to poultry diets, enhances digestion, prevents Salmonella enteritidis (SE) colonization, and treats current infections. The objective of this study was to utilize a quantitative proteomic approach to determine the effect of BMD feed additive on broiler chickens challenged with SE in the spleen proteome. At 1 d of age, chicks were randomly allocated into four groups: control with and without SE challenge (CON, n = 60; CON-SE, n = 60), BMD with and without SE challenge (BMD, n = 60; BMD-SE, n = 60). Birds in the CON-SE and BMD-SE treatment were administered SE inoculum by oral gavage. On day three and day seven post-gavage, the spleen was collected aseptically from birds in each treatment group (CON, n = 4/day; CON-SE, n = 4/day; BMD, n = 4/day; BMD-SE, n = 4/day). Proteomic analysis by liquid chromatography-tandem mass spectrometry (LC-MS/MS) showed an increased abundance of 115 proteins and decreased of 77 due to the BMD. Proteins that decreased in abundance were enriched for fibrinogen complex and extracellular space, whereas proteins that increased in abundance were enriched for proteasome-mediated ubiquitin-dependent protein catabolic process and mitochondrion. Analysis of the interaction between BMD and the Salmonella challenge found 230 differentially abundant proteins including proteins associated with RNA binding, spliceosome, protein transport, and cell adhesion among the upregulated proteins, and those associated with protein folding, carbon metabolism, biosynthesis of nucleotide sugars, response to oxidative stress, positive regulation of NIK/NF-kappaB signaling, and inflammatory response among the downregulated proteins. The impact of BMD treatment on spleen proteome indicates an anti-apoptotic effect. BMD also modified the response of the spleen to the SE challenge with a marked decrease in proteins that prompt cytokine synthesis and an increase in proteins involved in the selective removal of unfolded proteins. Full article

This study investigated the effects of an antibiotic cocktail on intestinal microbial composition, mechanical barrier structure, and immune functions in early broilers. One-day-old healthy male broiler chicks were treated with a broad-spectrum antibiotic cocktail (ABX; neomycin, ampicillin, metronidazole, vancomycin, and kanamycin, 0.5 g/L each) or not in drinking water for 7 and 14 days, respectively. Sequencing of 16S rRNA revealed that ABX treatment significantly reduced relative Firmicutes, unclassified Lachnospiraceae, unclassified Oscillospiraceae, Ruminococcus torques, and unclassified Ruminococcaceae abundance in the cecum and relative Firmicutes, Lactobacillus and Baccillus abundance in the ileum, but significantly increased richness (Chao and ACE indices) and relative Enterococcus abundance in the ileum and cecum along with relatively enriched Bacteroidetes, Proteobacteria, Cyanobacteria, and Enterococcus levels in the ileum following ABX treatment for 14 days. ABX treatment for 14 days also significantly decreased intestinal weight and length, along with villus height (VH) and crypt depth (CD) of the small intestine, and remarkably increased serum LPS, TNF-α, IFN-γ, and IgG levels, as well as intestinal mucosa DAO and MPO activity. Moreover, prolonged use of ABX significantly downregulated occludin, ZO-1, and mucin 2 gene expression, along with goblet cell numbers in the ileum. Additionally, chickens given ABX for 14 days had lower acetic acid, butyric acid, and isobutyric acid content in the cecum than the chickens treated with ABX for 7 days and untreated chickens. Spearman correlation analysis found that those decreased potential beneficial bacteria were positively correlated with gut health-related indices, while those increased potential pathogenic strains were positively correlated with gut inflammation and gut injury-related parameters. Taken together, prolonged ABX application increased antibiotic-resistant species abundance, induced gut microbiota dysbiosis, delayed intestinal morphological development, disrupted intestinal barrier function, and perturbed immune response in early chickens. This study provides a reliable lower-bacteria chicken model for further investigation of the function of certain beneficial bacteria in the gut by fecal microbiota transplantation into germ-free or antibiotic-treated chickens. Full article

Acute pancreatitis (AP) is a common but often self-limiting disease in the majority of patients. However, in the minority, who may progress to moderately severe or severe AP, high mortality risk has been reported. Infected pancreatitis necrosis (IPN) in necrotising pancreatitis has been shown to result in more than twice the mortality rate compared with in sterile pancreatic necrosis. This raises the question on whether prophylactic antibiotics (PABs) should be given in subgroups of AP to prevent superimposed infection to improve survival outcomes. Despite numerous randomised controlled trials (RCTs), meta-analyses, and guidelines on the management of AP, there is a lack of strong evidence to suggest the use of PABs in AP. Additionally, use of PABs is associated with antimicrobial resistance. Considerable heterogeneity exists and limits the interpretation of results—subgroup of AP benefitting from PAB use, choice/class of PAB, and timing of administration from symptom onset and duration of PAB use. Only a minority of existing meta-analyses suggest mortality benefits and reduction in IPN. The majority of existing guidelines do not recommend the use of PABs in AP. More research is required to make more definitive conclusions. Currently, PAB should only be administered after multidisciplinary discussions led by pancreatology experts. Full article

Vaccination arguably remains the only long-term strategy to limit the spread of S. aureus infections and its related antibiotic resistance. To date, however, all staphylococcal vaccines tested in clinical trials have failed. In this review, we propose that the failure of S. aureus vaccines is intricately linked to prior host exposure to S. aureus and the pathogen’s capacity to evade adaptive immune defenses. We suggest that non-protective immune imprints created by previous exposure to S. aureus are preferentially recalled by SA vaccines, and IL-10 induced by S. aureus plays a unique role in shaping these non-protective anti-staphylococcal immune responses. We discuss how S. aureus modifies the host immune landscape, which thereby necessitates alternative approaches to develop successful staphylococcal vaccines. Full article

Enterococcus cecorum is associated with bacterial chondronecrosis with osteomyelitis (BCO) in broilers. Prophylactic treatment with antimicrobials is common in the poultry industry, and, in the case of outbreaks, antimicrobial treatment is needed. In this study, the minimum inhibitory concentrations (MICs) and epidemiological cutoff (ECOFF) values (CO_WT) for ten antimicrobials were determined in a collection of E. cecorum strains. Whole-genome sequencing data were analyzed for a selection of these E. cecorum strains to identify resistance determinants involved in the observed phenotypes. Wild-type and non-wild-type isolates were observed for the investigated antimicrobial agents. Several antimicrobial resistance genes (ARGs) were detected in the isolates, linking phenotypes with genotypes for the resistance to vancomycin, tetracycline, lincomycin, spectinomycin, and tylosin. These detected resistance genes were located on mobile genetic elements (MGEs). Point mutations were found in isolates with a non-wild-type phenotype for enrofloxacin and ampicillin/ceftiofur. Isolates showing non-wild-type phenotypes for enrofloxacin had point mutations within the GyrA, GyrB, and ParC proteins, while five amino acid changes in penicillin-binding proteins (PBP2x superfamily) were observed in non-wild-type phenotypes for the tested β-lactam antimicrobials. This study is one of the first that describes the genetic landscape of ARGs within MGEs in E. cecorum, in association with phenotypical resistance determination. Full article

Microplastics (MPs) and antibiotics are emerging pollutants widely found in aquatic environments, potentially causing environmental harm. MPs may act as carriers for antibiotics, affecting their environmental distribution. This study investigates the adsorption of four macrolide antibiotics and a metabolite onto two types of MPs: polyethylene terephthalate (PET) and polyethylene (PE). Results revealed a linear isotherm adsorption model, with higher adsorption to PET than to PE (R² > 0.936 for PE and R² > 0.910 for PET). Hydrophobic interactions and hydrogen bonding could be the main adsorption mechanisms, with pore filling potentially involved. Reduced particle size enhances adsorption due to the increase of active adsorption sites. This increasement is more pronounced in PE than in PET, leading to an 11.6% increase in the average adsorption of all macrolides to PE, compared to only 5.1% to PET. Dissolved organic matter inhibits adsorption (azithromycin adsorption to PE was reduced from 12% to 5.1%), while salinity enhances it just until 1% salinity. pH slightly influences adsorption, with maximal adsorption at neutral pH. Results in real samples showed that complexity of the matrix decreased adsorption. Overall, these findings indicate that PE and PET MPs can be a vector of macrolides in aquatic environments. Full article

Due to widespread overuse, pharmaceutical compounds, such as antibiotics, are becoming increasingly prevalent in greater concentrations in aquatic ecosystems. In this study, we investigated the capacity of the white-rot fungus, Coriolopsis gallica (a high-laccase-producing fungus), to biodegrade ampicillin under different cultivation conditions. The biodegradation of the antibiotic was confirmed using high-performance liquid chromatography, and its antibacterial activity was evaluated using the bacterial growth inhibition agar well diffusion method, with Escherichia coli as an ampicillin-sensitive test strain. C. gallica successfully eliminated ampicillin (50 mg L⁻¹) after 6 days of incubation in a liquid medium. The best results were achieved with a 9-day-old fungal culture, which treated a high concentration (500 mg L⁻¹) of ampicillin within 3 days. This higher antibiotic removal rate was concomitant with the maximum laccase production in the culture supernatant. Meanwhile, four consecutive doses of 500 mg L⁻¹ of ampicillin were removed by the same fungal culture within 24 days. After that, the fungus failed to remove the antibiotic. The measurement of the ligninolytic enzyme activity showed that C. gallica laccase might participate in the bioremediation of ampicillin. Full article

Sepsis poses a significant global health challenge due to immune system dysregulation. This narrative review explores the complex relationship between antibiotics and the immune system, aiming to clarify the involved mechanisms and their clinical impacts. From pre-clinical studies, antibiotics exhibit various immunomodulatory effects, including the regulation of pro-inflammatory cytokine production, interaction with Toll-Like Receptors, modulation of the P38/Pmk-1 Pathway, inhibition of Matrix Metalloproteinases, blockade of nitric oxide synthase, and regulation of caspase-induced apoptosis. Additionally, antibiotic-induced alterations to the microbiome are associated with changes in systemic immunity, affecting cellular and humoral responses. The adjunctive use of antibiotics in sepsis patients, particularly macrolides, has attracted attention due to their immune-regulatory effects. However, there are limited data comparing different types of macrolides. More robust evidence comes from studies on community-acquired pneumonia, especially in severe cases with a hyper-inflammatory response. While studies on septic shock have shown mixed results regarding mortality rates and immune response modulation, conflicting findings are also observed with macrolides in acute respiratory distress syndrome. In conclusion, there is a pressing need to tailor antibiotic therapy based on the patient’s immune profile to optimize outcomes in sepsis management. Full article

Natural host defensins, also sometimes termed antimicrobial peptides, are evolutionarily conserved. They have been studied as antimicrobials, but some pharmaceutical properties, undesirable for clinical use, have led to the development of synthetic molecules with constructed peptide arrangements and/or peptides not found in nature. The leading development currently is synthetic small-molecule nonpeptide mimetics, whose physical properties capture the characteristics of the natural molecules and share their biological attributes. We studied brilacidin, an arylamide of this type, for its activity in vitro against fungi (40 clinical isolates, 20 species) that the World Health Organization has highlighted as problem human pathogens. We found antifungal activity at low concentrations for many pathogens, which indicates that further screening for activity, particularly in vivo, is justified to evaluate this compound, and other mimetics, as attractive leads for the development of effective antifungal agents. Full article

This study investigates the in vitro activity of Nα-aroyl-N-aryl-phenylalanine amides (AAPs), previously identified as antimycobacterial RNA polymerase (RNAP) inhibitors, against a panel of 25 non-tuberculous mycobacteria (NTM). The compounds, including the hit compound MMV688845, were selected based on their structural diversity and previously described activity against mycobacteria. Bacterial strains, including the M. abscessus complex, M. avium complex, and other clinically relevant NTM, were cultured and subjected to growth inhibition assays. The results demonstrate significant activity against the most common NTM pathogens from the M. abscessus and M. avium complexes. Variations in activity were observed against other NTM species, with for instance M. ulcerans displaying high susceptibility and M. xenopi and M. simiae resistance to AAPs. Comparative analysis of RNAP β and β′ subunits across mycobacterial species revealed strain-specific polymorphisms, providing insights into differential compound susceptibility. While conservation of target structures was observed, differences in compound activity suggested influences beyond drug–target interactions. This study highlights the potential of AAPs as effective antimycobacterial agents and emphasizes the complex interplay between compound structure, bacterial genetics, and in vitro activity. Full article

The use of antimicrobials in swine production is an issue that concerns the whole world due to their impact on animal and public health. This study aimed to verify the antimicrobial use in 29 commercial full-cycle farms in the midwestern region of the state of Minas Gerais, since this region is a hub of intensive pig farming in Brazil, as well as the possible correlations between the use of antimicrobials, biosecurity, and productivity. A total of 28 different drugs used for preventive purposes were described. On average, the herds used seven drugs, exposing the piglets for 116 days and totaling 434.17 mg of antimicrobials per kilogram of pig produced. Just eight active ingredients made up 77.5% of the total number of drugs used on the studied herds. Significant differences were found between the variables, biosecurity score and number of sows, antimicrobial amount and number of drugs, number of drugs and number of sows, and between productivity and biosecurity scores. The use of antimicrobials was considered excessive in the swine farms in the state of Minas Gerais compared to what was reported in Brazil and in other countries. Educational measures and better control should be proposed to reduce the preventive use of antimicrobials. Full article

Staphylococcus argenteus is a recently described staphylococcal species that is related to Staphylococcus aureus but lacks the staphyloxanthin operon. It is able to acquire both resistance markers such as the SCCmec elements and mobile genetic elements carrying virulence-associated genes from S. aureus. This includes those encoding the Panton–Valentine leukocidin (PVL), which is associated mainly with severe and/or recurrent staphylococcal skin and soft tissue infections. Here, we describe the genome sequences of two PVL-positive, mecA-negative S. argenteus sequence type (ST) 2250 isolates from the United Arab Emirates in detail. The isolates were found in a dental clinic in the United Arab Emirates (UAE). Both were sequenced using Oxford Nanopore Technology (ONT). This demonstrated the presence of temperate bacteriophages in the staphylococcal genomes, including a PVL prophage. It was essentially identical to the published sequence of phiSa2wa_st78 (GenBank NC_055048), a PVL phage from an Australian S. aureus clonal complex (CC) 88 isolate. Besides the PVL prophage, one isolate carried another prophage and the second isolate carried two additional prophages, whereby the region between these two prophages was inverted. This “flipped” region comprised about 1,083,000 bp, or more than a third of the strain’s genome, and it included the PVL prophage. Prophages were induced by Mitomycin C treatment and subjected to transmission electron microscopy (TEM). This yielded, in accordance to the sequencing results, one or, respectively, two distinct populations of icosahedral phages. It also showed prolate phages which presumptively might be identified as the PVL phage. This observation highlights the significance bacteriophages have as agents of horizontal gene transfer as well as the need for monitoring emerging staphylococcal strains, especially in cosmopolitan settings such as the UAE. Full article

The ESKAPE group (Enterococcus faecium, Staphylococcus aureus, Klebsiella Pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp.) is a group of bacteria very difficult to treat due to their high ability to acquire resistance to antibiotics and are the main cause of nosocomial infections worldwide, posing a threat to global public health. Nosocomial infections with MDR bacteria are found mainly in Intensive Care Units, due to the multitude of maneuvers and invasive medical devices used, the prolonged antibiotic treatments, the serious general condition of these critical patients, and the prolonged duration of hospitalization. Materials and Methods: During a period of one year, from January 2023 to December 2023, this cross-sectional study was conducted on patients diagnosed with sepsis admitted to the Intensive Care Unit of the Sibiu County Emergency Clinical Hospital. Samples taken were tracheal aspirate, catheter tip, pharyngeal exudate, wound secretion, urine culture, blood culture, and peritoneal fluid. Results: The most common bacteria isolated from patients admitted to our Intensive Care Unit was Klebsiella pneumoniae, followed by Acinetobacter baumanii and Pseudomonas aeruginosa. Gram-positive cocci (Enterococcus faecium and Staphilococcus aureus) were rarely isolated. Most of the bacteria isolated were MDR bacteria. Conclusions: The rise of antibiotic and antimicrobial resistance among strains in the nosocomial environment and especially in Intensive Care Units raises serious concerns about limited treatment options. Full article

The most frequent cause of periprosthetic infections (PJIs) is intraoperative contamination; hence, antibiotic prophylaxis plays a crucial role in prevention. Modifications to standard prophylaxis can be considered if there is a high incidence of microorganisms resistant to current protocols. To date, very few studies regarding microbial etiology have been published in Italy. In this single-center, retrospective study conducted at IRCCS Ospedale Galeazzi-Sant’Ambrogio in Milan, we analyzed hip, knee, and shoulder PJIs in patients undergoing first implantation between 1 January 17 and 31 December 2021. The primary aim was to derive a local microbiological case history. The secondary aim was to evaluate the adequacy of preoperative antibiotic prophylaxis in relation to the identified bacteria. A total of 57 PJIs and 65 pathogens were identified: 16 S. aureus, 15 S. epidermidis, and 10 other coagulase-negative staphylococci (CoNS), which accounted for 63% of the isolations. A total of 86.7% of S. epidermidis were methicillin-resistant (MRSE). In line with other case reports, we found a predominance of staphylococcal infections, with a lower percentage of MRSA than the Italian average, while we found a high percentage of MRSE. We estimated that 44.6% of the bacteria isolated were resistant to cefazolin, our standard prophylaxis. These PJIs could be prevented by using glycopeptide alone or in combination with cefazolin, but the literature reports conflicting results regarding the adequacy of such prophylaxis. In conclusion, our study showed that in our local hospital, our standard antibiotic prophylaxis is ineffective for almost half of the cases, highlighting the importance of defining specific antibiotic guidelines based on the local bacterial prevalence of each institution. Full article

Klebsiella pneumoniae causes severe human diseases, but its resistance to current antibiotics is increasing. Therefore, new antibiotics to eradicate K. pneumoniae are urgently needed. Bacterial toxin–antitoxin (TA) systems are strongly correlated with physiological processes in pathogenic bacteria, such as growth arrest, survival, and apoptosis. By using structural information, we could design the peptides and small-molecule compounds that can disrupt the binding between K. pneumoniae MazE and MazF, which release free MazF toxin. Because the MazEF system is closely implicated in programmed cell death, artificial activation of MazF can promote cell death of K. pneumoniae. The effectiveness of a discovered small-molecule compound in bacterial cell killing was confirmed through flow cytometry analysis. Our findings can contribute to understanding the bacterial MazEF TA system and developing antimicrobial agents for treating drug-resistant K. pneumoniae. Full article