Antibiotics

The threat from antimicrobial resistance (AMR) continues to grow. Japan’s National Action Plan on Antimicrobial Resistance, which was formulated in 2016 and targets six areas, has already had a major impact on the countermeasures implemented against AMR. Particular advances have been made in AMR-related surveillance, and we now know the situation regarding antimicrobial use and antimicrobial-resistant bacteria in the country. Educational and awareness-raising activities for medical professionals and the general public have been actively implemented and seem to have contributed to a gradual move toward an appropriate use of antimicrobials. However, there is still insufficient understanding of the issue among the general public. Determining how to use surveillance results and implementing further awareness-raising activities are crucial to address this. Tasks for the future include both raising awareness and the promotion of AMR research and development and international cooperation. The government’s next Action Plan, which will detail future countermeasures against AMR based on the outcomes of and tasks identified in the current Action Plan, has been delayed due to the COVID-19 pandemic and is urgently awaited. Full article

Cellulose acetate (CA) is a synthetic compound that is derived from the acetylation of cellulose. CA is well known as it has been used for many commercial products such as textiles, plastic films, and cigarette filters. In this research, antibacterial CA composites were produced by addition of aluminum nitride (AlN) at different weight percentage, from 0 wt. % to 20 wt. %. The surface characterization was performed using laser microscope, Raman and FTIR spectroscopy. The mechanical and thermal properties of the composite were analyzed. Although the mechanical strength tended to decrease as the concentration of AlN increased and needed to be optimized, the melting temperature (T_m) and glass transition temperature (T_g) showed a shift toward higher values as the AlN concentration increased leading to an improvement in thermal properties. AlN additions in weight percentages >10 wt. % led to appreciable antibacterial properties against S. epidermidis and E. coli bacteria. Antibacterial CA/AlN composites with higher thermal stability have potential applications as alternative materials for plastic packaging in the food industry. Full article

The emergence of multi-drug resistant E. coli is an important matter of increasing considerable concern to global public health. The aim of this study was to investigate the incidence, antibiotic resistance pattern and phylogroups of E. coli isolates obtained from raw milk, vegetable salad and ground meat samples collected from Qazvin Province (Iran). Culture-based techniques, Kirby-Bauer disk diffusion susceptibility testing and PCR assays were used to determine the incidence rate, antimicrobial resistance pattern and phylogenetic groups of the E. coli isolates. The E. coli isolates were highly resistant to amoxicillin (79.1%), trimethoprim-sulfamethoxazole (70.8%), amoxicillin-clavulanic acid (62.5%), tetracycline (54.1%), chloramphenicol (54.1%), nitrofurantoin (54.1%), ampicillin (45.8%), streptomycin (45.8%), and kanamycin (33.3%); and completely susceptible to norfloxacin and azithromycin and 70.8% of the isolates were multi-drug resistant. Most E. coli isolates (46%) belonged to phylogroup A. Novel, practical, efficient food safety control and surveillance systems of multi-drug resistant foodborne pathogens are required to control the foodborne pathogen contamination. Full article

Staphylococcus aureus (S. aureus) is an important pathogen that causes clinical mastitis in goats and produces infections difficult to cure. Different antimicrobials as fluoroquinolones have been used against S. aureus. However, the studies developed to evaluate the bacterial drug interaction only have used the MIC as a single reference point with artificial growth media. The aims of this study were to describe the effect of marbofloxacin on S. aureus isolated from mastitis goats’ milk by different approaches as the minimum inhibitory and bactericidal concentrations (MIC and MBC) in cation adjusted Mueller–Hinton broth (CAMHB), serum and milk of goats at two inoculum sizes of 10⁵ and 10⁸ CFU/mL, the determination and analysis of the time kill curves (TKC) by non-linear mixed effect models in each growth medium and inoculum size, as well as the estimation of their pharmacokinetics/pharmacodynamics (PK/PD) cutoff values. The results obtained indicate that MIC values were higher and increases 2,4-fold in serum and 3,6-fold in milk at high inoculum, as well as the EC₅₀ values determined by each pharmacodynamics model. Finally, the PK/PD cutoff values defined as fAUC₂₄/MIC ratios to achieve clinical efficacy were highly dependent on inoculum and growth medium, with median values of 60–180, especially at high inoculum in milk, suggesting that further studies are necessary to evaluate and optimize the best therapeutic strategies for treating S. auerus in lactating goats. Full article

Antimicrobial stewardship programs (ASP) are an essential strategy to combat antimicrobial resistance. This study aimed to measure the impact of an ASP multidisciplinary team (MDT) escalating intervention on improvement of clinical, microbiological, and other measured outcomes in hospitalised adult patients from medical, intensive care, and burns units. The escalating intervention reviewed the patients’ cases in the intervention group through the clinical pharmacists in the wards and escalated complex cases to ID clinical pharmacist and ID physicians when needed, while only special cases required direct infectious disease (ID) physicians review. Both non-intervention and intervention groups were each followed up for six months. The study involved a total of 3000 patients, with 1340 (45%) representing the intervention group who received a total of 5669 interventions. In the intervention group, a significant reduction in length of hospital stay (p < 0.01), readmission (p < 0.01), and mortality rates (p < 0.01) was observed. Antibiotic use of the WHO AWaRe Reserve group decreased in the intervention group (relative rate change = 0.88). Intravenous to oral antibiotic ratio in the medical ward decreased from 4.8 to 4.1. The presented ASP MDT intervention, utilizing an escalating approach, successfully improved several clinical and other measured outcomes, demonstrating the significant contribution of clinical pharmacists atimproving antibiotic use and informing antimicrobial stewardship. Full article

Despite the availability of evidence-based guidelines, antibiotics for cellulitis remain inappropriately prescribed. This evidence–practice gap is more evident in low-resource settings, such as rural hospitals. This implementation study developed and introduced a cellulitis management plan to improve antibiotic prescribing for cellulitis in three health services in regional Australia. Appropriateness of antibiotic prescribing for cellulitis at Day 1 was the primary outcome measure. Adults with ICD-10-AM codes for lower-limb cellulitis admitted as inpatients of the three health services between May and November 2019 (baseline, n = 165) and March and October 2020 (post-implementation, n = 127) were included in the assessment. The uptake of the cellulitis management plan was 29.1% (37/127). The appropriateness of antibiotic prescribing for cellulitis at Day 1 was similar at baseline (78.7%, 144/183) and in the intention-to-treat post-implementation group (81.8%, 126/154) [95% CI −5.6% to 11.3%, p = 0.50]. Commencement of the cellulitis management plan resulted in a non-statistically significant increase in antibiotic appropriateness at Day 1 compared to when a cellulitis management plan was not commenced (88.1% vs. 79.5%; 95% CI −5.6% to 19.8%; p = 0.20) Evaluation of more real-world strategies to address evidence–practice gaps, such as the appropriateness of antibiotic prescribing for cellulitis, is required. Full article

Even though people worldwide tend to consume probiotic products for their beneficial health effects on a daily basis, recently, concerns were outlined regarding the uptake and potential intestinal colonisation of the bacteria that they carry. These bacteria are capable of executing horizontal gene transfer (HGT) which facilitates the movement of various genes, including antimicrobial resistance genes (ARGs), among the donor and recipient bacterial populations. Within our study, 47 shotgun sequencing datasets deriving from various probiotic samples (isolated strains and metagenomes) were bioinformatically analysed. We detected more than 70 ARGs, out of which rpoB mutants conferring resistance to rifampicin, tet(W/N/W) and potentially extended-spectrum beta-lactamase (ESBL) coding TEM-116 were the most common. Numerous ARGs were associated with integrated mobile genetic elements, plasmids or phages promoting the HGT. Our findings raise clinical and public health concerns as the consumption of probiotic products may lead to the transfer of ARGs to human gut bacteria. Full article

Isotretinoin (INN), a drug used to treat severe acne, has anti-inflammatory and antibacterial properties. INN may affect periodontal pathogenic bacteria, so we aimed to study the effect of INN on intraoral microbial profiles of periodontal disease and healthy periodontium. Our case-control study divided 180 subjects into six groups according to periodontal health status and INN usage as follows: healthy periodontium receiving INN (HINN; n = 30); those with generalized plaque-induced gingivitis receiving INN (GINN; n = 30); and those with stage I generalized periodontitis receiving INN (PINN; n = 30). Subjects not taking INN, were categorized in the same manner: those with a healthy periodontium (HC; n = 30); those with generalized plaque-induced gingivitis (GC; n = 30); and those with generalized periodontitis stage I (PC; n = 30). Plaque samples were collected to determine the prevalence of four periodontal pathogens (Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, and Fusobacterium nucleatum) in each study group using real-time polymerase chain reaction. Data were analyzed using IBM SPSS software, and multiple regression analysis was performed for each parameter tested in each group at a significance level of 0.05. All INN groups showed significantly lower levels of P. gingivalis, T. forsythia, and T. denticola and higher levels of F. nucleatum (p < 0.001). INN had an observable antimicrobial effect on the periodontal pathogen count in patients with plaque-induced gingivitis and chronic periodontitis. INN may have a potential additive antimicrobial value in the treatment of periodontal disease. Full article

Physiological changes in animals exposed to elevated ambient temperature are characterized by the redistribution of blood toward the periphery to dissipate heat, with a consequent decline in blood flow and oxygen and nutrient supply to splanchnic tissues. Metabolic adaptations and gut dysfunction lead to oxidative stress, translocation of lumen contents, and release of proinflammatory mediators, activating a systemic inflammatory response. This review discusses the activation and development of the inflammatory response in heat-stressed models. Full article

In Japan, there is concern regarding the relation between the inappropriate use of antibiotics and antibiotic resistance (AMR). Increased bacterial resistance is due in part to the inappropriate use of antimicrobial agents. The support of the pharmacist becomes important, and there is growing interest in antimicrobial stewardship to promote the appropriate and safe use of antimicrobials needed for the optimal selection of drugs, doses, durations of therapy, therapeutic drug monitoring (TDM), and implementations of cost containment strategies in Japan. Pharmacists should strive to disseminate the concept of “choosing wisely” in relation to all medicines, implement further interventions, and put them into practice. In this article, we present data for antimicrobial stewardship and Japan’s AMR action plan, focusing on how pharmacists should be involved in enabling physicians to choose antimicrobials wisely. Full article

Antimicrobial resistance (AMR) remains one of the greatest public health-perturbing crises of the 21st century, where species have evolved a myriad of defence strategies to resist conventional therapy. The production of extended-spectrum β-lactamase (ESBL), AmpC and carbapenemases in Gram-negative bacteria (GNB) is one such mechanism that currently poses a significant threat to the continuity of first-line and last-line β-lactam agents, where multi-drug-resistant GNB currently warrant a pandemic on their own merit. The World Health Organisation (WHO) has long recognised the need for an improved and coordinated global effort to contain these pathogens, where two factors in particular, international travel and exposure to antimicrobials, play an important role in the emergence and dissemination of antibiotic-resistant genes. Studies described herein assess the resistance patterns of isolated nosocomial pathogens, where levels of resistance were detected using recognised in vitro methods. Additionally, studies conducted extensively investigated alternative biocide (namely peracetic acid, triameen and benzalkonium chloride) and therapeutic options (specifically 1,10-phenanthroline-5,6-dione), where the levels of induced endotoxin from E. coli were also studied for the latter. Antibiotic susceptibility testing revealed there was a significant association between multi-drug resistance and ESBL production, where the WHO critical-priority pathogens, namely E. coli, K. pneumoniae, A. baumannii and P. aeruginosa, exhibited among the greatest levels of multi-drug resistance. Novel compound 1,10-phenanthroline-5,6-dione (phendione) shows promising antimicrobial activity, with MICs determined for all bacterial species, where levels of induced endotoxin varied depending on the concentration used. Tested biocide agents show potential to act as intermediate-level disinfectants in hospital settings, where all tested clinical isolates were susceptible to treatment. Full article

Despite decades of intensive research on bacteriophage lambda, a relatively uncharacterized region remains between the exo and xis genes. Collectively, exo-xis region genes are expressed during the earliest stages of the lytic developmental cycle and are capable of affecting the molecular events associated with the lysogenic-lytic developmental decision. In Shiga toxin-producing E. coli (STEC) and enterohemorragic E. coli (EHEC) that are responsible for food- and water-borne outbreaks throughout the world, there are distinct differences of exo-xis region genes from their counterparts in lambda phage. Together, these differences may help EHEC-specific phage and their bacterial hosts adapt to the complex environment within the human intestine. Only one exo-xis region protein, Ea8.5, has been solved to date. Here, I have used the AlphaFold and RoseTTAFold machine learning algorithms to predict the structures of six exo-xis region proteins from lambda and STEC/EHEC phages. Together, the models suggest possible roles for exo-xis region proteins in transcription and the regulation of RNA polymerase. Full article

Lipid transfer proteins (LTPs) are among the most promising plant-exclusive antimicrobial peptides (AMPs). They figure among the most challenging AMPs from the point of view of their structural diversity, functions and biotechnological applications. This review presents a current picture of the LTP research, addressing not only their structural, evolutionary and further predicted functional aspects. Traditionally, LTPs have been identified by their direct isolation by biochemical techniques, whereas omics data and bioinformatics deserve special attention for their potential to bring new insights. In this context, new possible functions have been identified revealing that LTPs are actually multipurpose, with many additional predicted roles. Despite some challenges due to the toxicity and allergenicity of LTPs, a systematic review and search in patent databases, indicate promising perspectives for the biotechnological use of LTPs in human health and also plant defense. Full article

Curcumin is a polyphenolic compound present in turmeric with extensive uses in cooking foods and biomedical applications. However, due to its hydrophobic nature, it is poorly soluble in water and its bioavailability is very low on oral administration in organisms. In this study, we investigated the dietary curcumin nanospheres in a weaned piglet model based on the growth, serum biochemistry, proteomics, fecal coliform bacteria, and malodors in the feces of piglets. A total of 135 weaned piglets (Duroc × [Yorkshire × Landrace]) with an average initial body weight of 7.0 ± 1.0 kg (28 ± 1 days of age) were randomly distributed in 9 pens (15 pigs in each pen) fed the dietary curcumin nanospheres (CN) at 0 (control), 0.5 (T1), and 1.0 mL (T2) CN/kg of diet in triplicates for 21 days. At the end of the feeding trial, the results showed piglets fed 1.0 mL CN/kg diet had significantly higher growth performance and feed utilization than control diet (without CN). However, there were no significant differences in growth and feed utilization between piglets fed T1 and T2 diets. Serum glucose, gamma-glutamyl transferase, total bilirubin, amylase, and lipase contents were unaffected in piglets fed the experimental diets. Interestingly, piglets fed T1 and T2 diets showed significantly lower total cholesterol levels than control diet. In serum proteomics, a total of 103 differentially expressed proteins (DEPs) were identified in the piglets fed control, T1, and T2 diets, of which 14 DEPs were upregulated and 4 DEPs were downregulated. Fecal coliform bacteria and ammonia gas were significantly reduced in piglets fed T1 and T2 diets. Overall, the results indicated dietary supplementation of CN could enhance the growth, feed utilization, and immunity—and reduce fecal pathogenic bacteria as well as ammonia gas emissions—in weaned piglets. Full article

The biofilm production of Pseudomonas aeruginosa (PA) is central to establishing chronic infection in the airways in cystic fibrosis. Epithelial cells secrete an array of innate immune factors, including antimicrobial proteins and lipids, such as human beta defensin 2 (HBD2) and cholesteryl lineolate (CL), respectively, to combat colonization by pathogens. We have recently shown that HBD2 inhibits biofilm production by PA, possibly linked to interference with the transport of biofilm precursors. Considering that both HBD2 and CL are increased in airway fluids during infection, we hypothesized that CL synergizes with HBD2 in biofilm inhibition. CL was formulated in phospholipid-based liposomes (CL-PL). As measured by atomic force microscopy of single bacteria, CL-PL alone and in combination with HBD2 significantly increased bacterial surface roughness. Additionally, extracellular structures emanated from untreated bacterial cells, but not from cells treated with CL-PL and HBD2 alone and in combination. Crystal violet staining of the biofilm revealed that CL-PL combined with HBD2 effected a significant decrease of biofilm mass and increased the number of larger biofilm particles consistent with altered cohesion of formed biofilms. These data suggest that CL and HBD2 affect PA biofilm formation at the single cell and community-wide level and that the community-wide effects of CL are enhanced by HBD2. This research may inform future novel treatments for recalcitrant infections in the airways of CF patients. Full article

The purpose of this study was to explore the value of using cefepime and ceftazidime in treating patients with COVID-19. A total of 370 (162 males) patients, with RT-PCR-confirmed cases of COVID-19, were included in the study. Out of them, 260 patients were treated with cefepime or ceftazidime, with the addition of steroids to the treatment. Patients were divided into three groups: Group 1: patients treated with cefepime (124 patients); Group 2: patients treated with ceftazidime (136 patients); Group 3 (control group): patients treated according to the WHO guidelines and the Egyptian COVID-19 management protocol (110 patients)/ Each group was classified into three age groups: 18–30, 31–60, and >60 years. The dose of either cefepime or ceftazidime was 1000 mg twice daily for five days. Eight milligrams of dexamethasone were used as the steroidal drug. Careful follow-ups for the patients were carried out. In vitro and in silico M^pro enzyme assays were performed to investigate the antiviral potential of both antibiotics. The mean recovery time for Group 1 was 12 days, for Group 2 was 13 days, and for Group 3 (control) was 19 days. No deaths were recorded, and all patients were recovered without any complications. For Group 1, the recovery time was 10, 12, and 16 days for the age groups 18–30, 30–60, and >60 years, respectively. For Group 2, the recovery time was 11, 13, and 15 days for the age groups 18–30, 30–60, and >60 years, respectively. For Group 3 (control), the recovery time was 15, 16, and 17 days for the age groups 18–30, 30–60, and >60 years, respectively. Both ceftazidime and cefepime showed very good inhibitory activity towards SARS CoV-2′s M^pro, with IC₅₀ values of 1.81 µM and 8.53 µM, respectively. In conclusion, ceftazidime and cefepime are efficient for the management of moderate and severe cases of COVID-19 due to their potential anti-SARS CoV-2 activity and low side effects, and, hence, the currently used complex multidrug treatment protocol can be replaced by the simpler one proposed in this study. Full article

Antimicrobial resistance (AMR) is a global crisis for human public health which threatens the effective prevention and control of ever-increasing infectious diseases. The advent of pandrug-resistant bacteria makes most, if not all, available antibiotics invalid. Meanwhile, the pipeline of novel antibiotics development stagnates, which prompts scientists and pharmacists to develop unconventional antimicrobials. Bacteriophage-derived endolysins are cell wall hydrolases which could hydrolyze the peptidoglycan layer from within and outside of bacterial pathogens. With high specificity, rapid action, high efficiency, and low risk of resistance development, endolysins are believed to be among the best alternative therapeutic agents to treat multidrug resistant (MDR) bacteria. As of now, endolysins have been applied to diverse aspects. In this review, we comprehensively introduce the structures and activities of endolysins and summarize the latest application progress of recombinant endolysins in the fields of medical treatment, pathogen diagnosis, food safety, and agriculture. Full article

According to the search for alternatives to replace antibiotics in animal production suggested in the antimicrobial resistance action plans around the world, the objective of this work was to evaluate the bactericidal effect of kaolin–silver nanomaterial for its possible inclusion as an additive in animal feed. The antibacterial activity of the C3 (kaolin–silver nanomaterial) product was tested against a wide spectrum of Gram-negative and Gram-positive bacteria (including multidrug resistant strains) by performing antibiograms, minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC), as well as growth inhibition curves against seven strains causing infections in animals. The C3 product generated inhibition halos in all the tested strains, and a higher activity against Gram-negative bacteria was found, with MBC values ranged from 7.8 µg/mL (P. aeruginosa) to 15.6 µg/mL (E. coli and Salmonella). In contrast, it was necessary to increase the concentration to 31.3 µg/mL or 250 µg/mL to eliminate 99.9% of the initial population of S. aureus ATCC 6538 and E. faecium ATCC 19434, respectively. Conversely, the inhibition growth curves showed a faster bactericidal activity against Gram-negative bacteria (between 2 and 4 h), while it took at least 24 h to observe a reduction in cell viability of S. aureus ATCC 6538. In short, this study shows that the kaolin–silver nanomaterials developed in the framework of the INTERREG POCTEFA EFA183/16/OUTBIOTICS project exhibit antibacterial activity against a wide spectrum of bacteria. However, additional studies on animal safety and environmental impact are necessary to evaluate the effectiveness of the proposed alternative in the context of One Health. Full article

Nanobiotechnology is a promising field in the development of safe antibiotics to combat the increasing trend of antibiotic resistance. Nature is a vast reservoir for green materials used in the synthesis of non-toxic and environmentally friendly nano-antibiotics. We present for the first time a facile, green, cost-effective, plant-mediated synthesis of platinum nanoparticles (PtNPs) using the extract of Combretum erythrophyllum (CE) plant leaves. The extract of CE served as both a bio-reductant and a stabilizing agent. The as-synthesized PtNPs were characterized using ultraviolet-visible (UV–Vis) absorption spectroscopy, high-resolution transmission electron microscopy (HR-TEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and dynamic light scattering (DLS) techniques. The HR-TEM image confirmed that the PtNPs are ultrasmall, spherical, and well dispersed with an average particle diameter of 1.04 ± 0.26 nm. The PtNPs showed strong antibacterial activities against pathogenic Gram-positive Staphylococcus epidermidis (ATCC 14990) at a minimum inhibitory concentration (MIC) of 3.125 µg/mL and Gram-negative Klebsiella oxytoca (ATCC 8724) and Klebsiella aerogenes (ATCC 27853) at an MIC value of 1.56 µg/mL. The CE-stabilized PtNPs was mostly effective in Klebsiella species that are causative organisms in nosocomial infections. Full article