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Background: Methicillin-resistant Staphylococcus aureus (MRSA) is a significant public health problem. This study investigated the antimicrobial properties and mechanisms of berberine (BBR), a plant alkaloid, against MRSA, evaluating its potential to enhance antibiotic therapy. Results: Berberine only demonstrated variable but significant inhibitory effects on 50 clinical MRSA strains. When combined with antibiotics, synergistic effects were observed only with amikacin in 6 of the 50 MRSA strains. BBR disrupted MRSA cell wall integrity, leading to leakage of cellular contents. Network pharmacology analysis revealed that BBR targets multiple pathways essential for bacterial survival. Conclusion: The study confirmed the potent antimicrobial activity of berberine against MRSA and its capability to act synergistically with traditional antibiotics. Berberine's impact on cell wall integrity and bacterial survival pathways highlights its potential as an adjunct therapy in MRSA treatment. [ABSTRACT FROM AUTHOR]

Background: Antibiotics are a key commodity for global health, and inadequate access is a major contributor to global mortality. COVID-19 has refocused attention on global pharmaceutical value chains and the need for sustainable and secure production and supply of key products, including antibiotics. Production of antibiotics and their active pharmaceutical ingredients is capital- and technology-intensive, however, and value chains are dominated by a limited number of countries. China is known to be one of the largest producers, but its position in global value chains has not previously been analyzed. This is important for discussions about equitable and resilient global supplies, including through global instruments such as the pandemic treaty. Methods: This study utilizes data from the International Trade Center database to analyze global and Chinese export trade patterns in the antibiotic industry from 2002 to 2021, along with trends in comparative advantage. The antibiotic trade data included in this study covers different antibiotic products, including some tuberculosis drugs, while other types of antimicrobial drugs (such as antivirals, antiparasitics) are excluded. Results: The export share of antibiotic ingredients from China increased from 9.0% in 2002 to 44.5% in 2021. China is the largest exporter of antibiotic ingredients (with a strong comparative advantage). Additionally, the export share of antibiotic medicines increased from 0.5% in 2002 to 6.5% in 2021, making it the 7th largest exporter of antibiotic medicines (though with a comparative disadvantage). The proportion of antibiotic medicines in China's exports is gradually increasing, though the country's antibiotic industry is expected to remain in the upstream-to-midstream segments of the global supply chain in the short term. China's export market for antibiotic medicines is fragmented, focusing on developing countries, though European (17.9% in 2021) and North American markets (13.1% in 2021) are increasing in importance. China's weight in global antibiotic exports, particularly of antibiotic ingredients, creates dependencies for countries reliant on China, and for Chinese companies reliant on certain overseas markets. Conclusions: China is central to global antibiotic manufacturing. Policies promoting the reshaping of global supply chains and reshoring of critical medicines will likely create challenges for Chinese exporters, though are unlikely to alter the global supply structure in the short term. This has implications for Chinese policymakers, including strengthening innovation, quality, international competitiveness, and diversifying markets. Equally, China's huge manufacturing capability, cost advantages, and rapid scientific and technological progress, make the country an inevitable and important part of future arrangements to ensure equitable global antibiotic access. As the Chinese government considers its global health policy in the post-COVID-19 era, antibiotics may provide an area where China can play a distinctive role. [ABSTRACT FROM AUTHOR]

Understanding the impact of antibiotics on bacterial metabolism is crucial for elucidating their mechanisms of action and developing more effective therapeutic strategies. β-lactam antibiotics, distinguished by their distinctive β-lactam ring structure, are widely used as antimicrobial agents. This study investigates the global metabolic alterations induced by three β-lactam antibiotics-meropenem (a carbapenem), ampicillin (a penicillin), and ceftazidime (a cephalosporin)-in Escherichia coli. Our comprehensive metabolic profiling revealed significant perturbations in bacterial metabolism, particularly in pathways such as glutathione metabolism, pantothenate and CoA biosynthesis, pyrimidine metabolism, and purine metabolism. Antibiotic treatment markedly increased reactive oxygen species levels, with meropenem reaching nearly 200 ± 7%, ampicillin at 174 ± 11%, and ceftazidime at 152 ± 7%. Additionally, β-lactam antibiotics elevated 8-OHdG levels to 4.73 ± 0.56-fold for meropenem, 2.49 ± 0.19-fold for ampicillin, and 3.19 ± 0.34-fold for ceftazidime; 8-OHG levels increased to 5.57 ± 0.72-fold for meropenem, 3.08 ± 0.31-fold for ampicillin, and 4.45 ± 0.66-fold for ceftazidime, indicating that oxidative stress enhances oxidative damage to bacterial DNA and RNA. Notably, we observed a selective upregulation of specific amino acids associated with cellular repair mechanisms, indicating a metabolic adaptation to counteract oxidative damage. These findings illustrate that β-lactam antibiotics induce a complex metabolic perturbations associated with ROS production, potentially compromising critical cellular components. This study enhances our understanding of the intricate relationship between antibiotic action and bacterial metabolism, providing valuable insights for developing effective strategies against antibiotic-resistant pathogens. [ABSTRACT FROM AUTHOR]

Spinal implant infections are a serious complications of instrumented spinal fusion surgeries, carrying high morbidity and complex management challenges. Early postoperative infections may manifest with wound-healing issues, back pain, and fevers. Magnetic resonance imaging (MRI) is the preferred imaging modality, but can be limited by metal artifacts. For cases with stable implants, surgical debridement with implant retention combined with at least 12 weeks of antibiotics is currently considered appropriate treatment. Staphylococcal infections are ideally treated with biofilm-active antibiotics. Suppressive antibiotic therapy can be considered when surgical debridement has been delayed or is incomplete, and for those who are poor surgical candidates for another surgery. Chronic infections may present insidiously with implant failure or pseudarthrosis; implant removal or revision is generally pursued. As current guidance is heavily based on the periprosthetic joint infection literature and low-level studies on spinal implant infections, further research on optimizing diagnostic and treatment approaches is needed. [ABSTRACT FROM AUTHOR]

Research into new antibiotics is becoming increasingly important as antibiotic resistance increases worldwide. The genus Streptomyces in particular is able to produce a wide range of antimicrobial products due to the large number of biosynthetic gene clusters (BGCs) in its genome. However, not all BGCs are expressed under laboratory conditions. In this work, deletion of the gene wblA, encoding a global regulator of natural product biosynthesis and morphogenesis in Streptomyces, led to the production of a novel natural product, olikomycin A, in Streptomyces ghanaensis ATCC 14672. Complete structure elucidation revealed that olikomycin A belongs to a class of calcium‐dependent antibiotics known as non‐ribosomal peptide synthetase (NRPS)‐encoded acidic lipopeptides. These compounds exhibit remarkable antimicrobial activity in the presence of calcium. Insights into olikomycin A biosynthesis were provided by whole genome sequencing and gene inactivation studies, while bioactivity assays showed strong inhibition of the growth of multidrug‐resistant Gram‐positive pathogens via disrupting cell membrane integrity. Olikomycin A shows an antibiotic profile similar to that of daptomycin, which is already in clinical use. [ABSTRACT FROM AUTHOR]

Background and Objectives: The incidence of multidrug-resistant, Gram-negative organisms, isolated as the etiological agents of infections is ascending. The advent of novel antibiotics poses significant challenges, necessitating the optimization and utilization of extant antimicrobial agents. Cefoperazone, a third-generation cephalosporin and ß-lactam antimicrobial, when combined with sulbactam, an irreversible ß-lactamase inhibitor, mitigates the vulnerability of cefoperazone to ß-lactamase-producing organisms. Nonetheless, regional data on the susceptibility patterns for this pharmacological combination remains scarce. The primary objective of this investigation was to assess the efficacy of the cefoperazone-sulbactam combination against prevalent Gram-negative bacteria isolated from blood cultures. Materials and Methods: A total of 700 Gram-negative isolates, comprising Escherichia coli, Klebsiella pneumoniae, Acinetobacter species, and Pseudomonas aeruginosa, were procured using the BacT/Alert 3D system. The identification and susceptibility testing for cefoperazone-sulbactam were performed using the VITEK Compact ID and AST system. Comparative analysis was conducted against other tested antibiotics. Results: The study revealed that cefoperazone-sulbactam exhibited commendable in-vitro activity against Gram-negative pathogens isolated from blood, surpassed only by colistin and tigecycline. Conclusion: Cefoperazone-sulbactam demonstrates robust activity against the most frequently encountered clinical pathogens, suggesting its potential as an efficacious therapeutic agent. The findings underscore the imperative for ongoing surveillance of resistance patterns and trends among commonly used antimicrobials. [ABSTRACT FROM AUTHOR]

A metagenomic library consisting of 15,000 clones was constructed from the mangrove sediment. An antimicrobially active clone from the metagenomic library PS49 was identified by function- based screening. This paper presents the results of the biochemical characterization and metagenomic library screening of the marine-derived antibiotic, 8-demethoxy-10-deoxysteffimycin. Plasmid libraries were constructed, and clones were produced using a metagenomic approach. Out of 15,000 clones, 81 clones were screened for antimicrobial activity, and five potential clones were selected. The activity of one clone was characterized and named as PS49. The bioactive compounds from the selected clone were checked for antimicrobial, antioxidant, and anticancer activities. The clone PS49 was tested against various pathogens including bacteria and fungi and it showed inhibitory effects against all the tested pathogens. The antimicrobially active fractions were then crystallized and subjected to spectroscopic analysis such as FTIR, NMR and LC–MS analysis. The substance from clone PS49 has finally been recognized, and the compound from clone PS49 has been identified as 8-demethoxy-10-deoxysteffimycin. The substances isolated from the PS49 clone exhibited strong anticancer activity against skin cancer-cell lines SK-MEL2. The compounds showed a reduction in cell viability with an increase in the compound concentration. The compounds obtained from clone PS49 showed an IC50 value of 85 µg/ml. [ABSTRACT FROM AUTHOR]

Purpose: The optimal duration of antibiotic therapy for fracture-related infection (FRI) has not been well defined. Our aim was to assess the recurrence rate of infection in patients who underwent six, 12, or 24 weeks of antibiotic therapy following surgical treatment for FRI one year after antibiotic discontinuation. Additionally, complications were monitored. Methods: Patients with FRI underwent surgical treatment, and antibiotic therapy was initiated. The patients were divided into groups at the 6th and 12th weeks of antibiotic therapy. The primary endpoint was the recurrence of deep or superficial infection at 90 days and one year after the end of antimicrobial therapy. Results: There was no difference in the recurrence of infection 90 days or one year after stopping antibiotic therapy among patients treated for six, 12, or 24 weeks (p = 0.98 and p = 0.19, respectively). The overall recurrence rate of infection 90 days after stopping antibiotic therapy was 4.9% (8/163), and one year after discontinuation of antibiotic therapy was 9.8% (16/163). There was a statistically significant difference in the incidence of adverse effects among the three groups (chi-square; p = 0.01). Adverse effects were more common in the group treated for 24 weeks than in the groups treated for 6 weeks (z score, p = 0.017) or 12 weeks (z score, p = 0.005). Conclusion: Antibiotic therapy longer than 6 weeks did not reduce the recurrence of FRI after one year of follow-up. Additionally, antibiotic treatment for 24 weeks increases adverse events such as skin reactions and acute renal failure. [ABSTRACT FROM AUTHOR]

Statement of the Problem: Dentin adhesion is challenging and needs modifications. Newly introduced nature-derived materials may be a useful solution in improving dentin adhesion. The use of natural antimicrobial agents for pretreating prepared dentin surfaces before restoration has become of interest. Purpose: The present study investigated the effect of natural compounds on the shear bond strength (SBS) of resin composite adhesively bonded to dentin. Materials and Method: Sixty extracted human molar teeth were randomly divided into six groups (n= 10); Group I: two-step etch and rinse adhesive system, Adper Single Bond 2 (SB2) (experimental control), Group II: 2.5% Chitosan+etch+SB2, Group III: 15% Neem (Azadirachta indica)+etch+SB2, Group IV: 15% Tulsi (Ocimum sanctum)+etch+SB2, Group V: 2% Aloe vera+etch+SB2, and group VI: 2% Chlorhexidine (CHX)+etch+SB2. Resin composite (Z350, 3M ESPE USA) was placed over the prepared dentin surfaces and was light cured. Data analysis was performed using One-way ANOVA and post hoc Tukey's test (p< 0.05). Results: Neem specimens showed the highest mean SBS, statistically greater than the control (p= 0.042). Other experimental groups showed no significant differences in SBS comparison to the control. The mean SBS values of 2.5% Chitosan, 15% Neem, 15% Tulsi, and 2% Aloe vera were significantly higher than 2% CHX (p= 0.046, p= 0.001, p= 0.010 and p =0.002 respectively). Conclusion: Dentin pretreatment with Neem may improve the bond strength of a two-step etch and rinse adhesive system. The application of Chitosan, Tulsi, Aloe vera, and CHX did not demonstrate significantly different SBS values from that of the Control, although CHX was lower. [ABSTRACT FROM AUTHOR]

The misuse of antimicrobial agents in healthcare and animal farming has led to their release into the environment through wastewater, contributing to the emergence of resistant bacteria. This study analyzed selected antimicrobial concentration and antimicrobial resistance (AMR) risk in the Little Akaki River wastewater. Samples collected from March to December 2019, June 2020, and August 2022 were processed using solid phase extraction with a hydrophilic-lipophilic balance (HLB) cartridge and analyzed through ultra-high-performance liquid chromatography (UHPLC) with mass spectrometry. Risk quotients (RQ) were calculated as the ratio of measured environmental concentrations (MEC) to predicted no-effect concentrations (PNEC). Ciprofloxacin concentrations ranged from 5.62 to 9.34 µg/L, cefotaxime from 1.89 to 64.79 µg/L, and sulfamethoxazole from 29.11 to 248.77 µg/L, with higher concentrations observed during the wet season. MECs for ciprofloxacin, cefotaxime, and sulfamethoxazole exceeded their PNECs (RQ > 2), indicating a high risk of resistance development. Sulfamethoxazole posed the greatest risk due to its consistently elevated levels. In contrast, erythromycin concentrations remained below the PNEC, suggesting minimal resistance risk. These findings highlight the urgent need for wastewater treatment strategies to mitigate AMR risks in aquatic environments. [ABSTRACT FROM AUTHOR]

Objectives: Multidrug-resistant Pseudomonas aeruginosa (MDR-PA) is a life-threatening infection with limited treatment options. This is the first meta-analysis of recently published data to compare the clinical outcomes of ceftazidime-avibactam (CAZ-AVI) with other antimicrobial agents in treating MDR-PA infections. Design: Systematic review and meta-analysis. Data sources: PubMed, Embase and the Cochrane Library have been systematically reviewed, for publications in the English language, from database inception to July 2023. Eligibility criteria for selecting studies: Studies comparing CAZ-AVI outcomes with other antimicrobial agents were included. In-hospital mortality & 30-day mortality were assessed as the main outcomes. Data extraction and synthesis: Literature screening, data extraction, and the quality evaluation of studies were conducted by two researchers independently, with disagreements resolved by another researcher. The Newcastle–Ottawa Scale was used to assess the bias risk for the included studies. Review Manager V.5.4 was employed for the meta-analysis. Results: The meta-analysis included four retrospective studies, enrolling 1934 patients. The CAZ-AVI group demonstrated significantly lower in-hospital mortality (risk ratio (RR) = 0.60, 95% CI:0.37–0.97, I2 = 74%, p = 0.04) in three studies with 1444 patients and lower 30-day mortality, in 438 patients from three studies (RR = 0.54, 95% CI:0.28–1.05, I2 = 67%, p = 0.07). No significant difference in clinical success, microbiological success, length of hospital, and ICU stay was observed. Conclusions: This meta-analysis demonstrated that CAZ-AVI treatment significantly lowered in-hospital mortality compared with other antimicrobial agents in MDR-PA infections. However, the analysis only included a few observational studies and high-quality, randomized controlled trials are needed to investigate further the scope of CAZ-AVI in MDR–PA infections. [ABSTRACT FROM AUTHOR]

Orthopedic infections are challenging pathologies that impose a heavy burden on patients and the healthcare system. Antimicrobial therapy is a critical component of the successful management of orthopedic infections, but its effectiveness depends on patient-, surgery-, drug-, and hospital-related factors. The dramatic increase in the emergence of multidrug-resistant microbial strains necessitates new clinical approaches in order to prevent or limit this phenomenon and to ensure a favorable therapeutic outcome. The present paper reviews the currently available antimicrobial strategies in the management of orthopedic infections, highlighting their clinical use related to the occurrence of microbial resistance. Some approaches for reducing antibiotic resistance emergence in orthopedics are also presented. The use of antibiotics tailored to the microorganism's sensitivity profile, patient factors, and pharmacokinetic profile in terms of monotherapy or combinations, the understanding of microbial pathogenicity and resistance patterns, strict control measures in healthcare facilities, the development of new antimicrobial therapies (drugs, devices, technologies), and patient education for improving compliance and tolerance are some of the most important tools for overcoming microbial resistance. [ABSTRACT FROM AUTHOR]

Immunotherapy is a novel treatment approach for malignant tumors, which has opened a new journey of anti-tumor therapy. Although some patients will show a positive response to immunotherapy, unfortunately, most patients and cancer types do not achieve an ideal response to immunotherapy. Therefore, it is urgent to search for the pathogenesis of sensitized immunotherapy. This review indicates that Fusobacterium nucleatum, Coprobacillus cateniformis, Akkermansia muciniphila, Bifidobacterium, among others, as well as intestinal microbial metabolites are closely associated with resistance to anti-tumor immunotherapy. While natural products of pectin, inulin, jujube, anthocyanins, ginseng polysaccharides, diosgenin, camu-camu, and Inonotus hispidus (Bull).Fr. P. Karst, Icariside I, Safflower yellow, Ganoderma lucidum, and Ginsenoside Rk3, and other Chinese native medicinal compound prescriptions to boost their efficacy of anti-tumor immunotherapy through the regulation of microbiota and microbiota metabolites. However, current research mainly focuses on intestinal, liver, and lung cancer. In the future, natural products could be a viable option for treating malignant tumors, such as pancreatic, esophageal, and gastric malignancies, via sensitizing immunotherapy. Besides, the application characteristics of different types, sources and efficacy of natural products in different immune resistance scenarios also need to be further clarified through the development of future immunotherapy-related studies. [ABSTRACT FROM AUTHOR]

Burkholderia thailandensis has emerged as a nonpathogenic surrogate for Burkholderia pseudomallei, the causative agent of melioidosis, and an important Gram-negative model bacterium for studying the biosynthesis and regulation of secondary metabolism. We recently reported that subinhibitory concentrations of trimethoprim induce vast changes in both the primary and secondary metabolome of B. thailandensis. In the current work, we show that the folate biosynthetic enzyme FolE2 is permissive under standard growth conditions but essential for B. thailandensis in the presence of subinhibitory doses of trimethoprim. Reasoning that FolE2 may serve as an attractive drug target, we screened for and identified ten inhibitors, including dehydrocostus lactone (DHL), parthenolide, and ß-lapachone, all of which are innocuous individually but form a chemical-synthetic lethal combination with subinhibitory doses of trimethoprim. We show that DHL is a mechanism-based inhibitor of FolE2 and capture the structure of the covalently inhibited enzyme using X-ray crystallography. In vitro, the combination of subinhibitory trimethoprim and DHL is more potent than Bactrim, the current standard of care against melioidosis. Moreover, unlike Bactrim, this combination does not affect the growth of most commensal and beneficial gut bacteria tested, thereby providing a degree of specificity against B. pseudomallei. Our work provides a path for identifying antimicrobial drug targets and for utilizing binary combinations of molecules that form a toxic cocktail based on metabolic idiosyncrasies of specific pathogens. [ABSTRACT FROM AUTHOR]

The introduction of antibiotics in the beginning of the 20th century was one of the most important scientific breakthroughs in history. However, in recent decades, the growing threat of antimicrobial resistance (AMR) has shown the limitations of the current research and development programs for new antimicrobial drugs. In the last decade, 20 antibiotics, 7 β-lactam/β-lactamase inhibitor (BL/BLI) combinations and 4 non-traditional antibacterial drugs have been launched worldwide. Methods: This study aimed to assess the time to patient access for new antibacterial drugs in countries in the European Union and the European Economic Area (EU/EEA). Time differences in marketing authorization from the U.S. Food and Drug Agency (FDA) and the European Medicines Agency (EMA) were also described, as well as the availability of each drug in the countries in the EU/EEA according to the national competent authorities. Results: Substantial differences between countries were observed, with no or only one new drug available in some countries. Conclusions: Improving pricing and reimbursement timelines and fostering collaboration between national health authorities and market authorization holders can enhance timely and equitable patient access to new antibacterial treatments in Europe. Equitable and sustainable access to antibacterial drugs is a cornerstone in the battle against AMR. [ABSTRACT FROM AUTHOR]

Background: MSSA and MRSA strains are challenging human pathogens that can develop resistance to antibiotics, highlighting the need for alternative antimicrobial agents. Plant metabolites, particularly volatile phytochemicals, may offer promising antimicrobial properties. The aim was to evaluate the antimicrobial and antibiofilm efficacy of various commercial volatile phytochemicals from the terpene and terpenoid groups against reference MSSA and MRSA strains, focusing on synergistic effects in both binary combinations and combinations with antibiotics. Methods: The microdilution method was used to determine the minimum inhibitory concentrations (MICs) for antibiotics and phytochemicals. The checkerboard method assessed synergistic interactions between phytochemicals and between phytochemicals and antibiotics, while the time-kill method was used to confirm these results. Biofilm quantification was performed using the microtiter plate method to evaluate the effects of phytochemicals, antibiotics, and their binary combinations on the eradication of 48-h-old biofilms. Results: Carvacrol and thymol demonstrated the strongest anti-staphylococcal activity, while other terpene compounds showed weaker effects. In binary combinations, carvacrol and thymol exhibited synergy against one MSSA strain (FICI = 0.50) and with tetracycline and chloramphenicol (FICI = 0.28–0.50). Synergy was also noted with streptomycin sulfate against one MRSA strain (FICI = 0.31–0.50) and with other antibiotics, including gentamicin (FICI = 0.25–0.50) and oxacillin (FICI = 0.44). Additionally, effective combinations achieved over 50% biofilm removal at both minimum inhibitory and sub-inhibitory concentrations. Conclusions: Results showed that synergy varies based on strain sensitivity to chemical agents, highlighting their potential for personalized therapy. Despite the difficulty in removing preformed biofilms, the findings highlight the importance of combined treatments to enhance antibiotic effectiveness. [ABSTRACT FROM AUTHOR]

Background/Objectives: The search for new antimicrobial molecules is important to expand the range of available drugs, as well as to overcome the drug resistance of pathogens. One of the promising sources of antibacterial and antifungal metabolites is basidial fungi, which have wide biosynthetic capabilities. Methods: The review summarized the results of studying the antimicrobial activity of extracts and metabolites from basidiomycetes published from 2018–2023. Results: In all studies, testing for antibacterial and antifungal activity was carried out in in vitro experiments. To obtain the extracts, mainly the fruiting bodies of basidiomycetes, as well as their mycelia and culture liquid were used. Antimicrobial activity was found in aqueous, methanol, and ethanol extracts. Antimicrobial metabolites of basidiomycetes were isolated mainly from the submerged culture of basidiomycetes. Metabolites active against Gram-positive and Gram-negative bacteria and mycelial and yeast-like fungi were identified. Conclusions: Basidiomycete extracts and metabolites have shown activity against collectible strains of bacteria and fungi and multi-resistant and clinical strains of pathogenic bacteria. The minimum inhibitory concentration (MIC) values of the most active metabolites ranged from 1 to 16.7 µg/mL. [ABSTRACT FROM AUTHOR]

In an effort to expand the spectrum of the antibacterial activity of pleuromutilin, a series of amine- and polyamine-linked analogues were prepared and evaluated for activities against a panel of microorganisms. Simple C-22-substituted amino esters or diamines 16, 17, 18, and 22, as well as two unusual amine-linked bis-pleuromutilin examples 20 and 23, displayed variable levels of activity towards Staphylococcus aureus ATCC 25923 and methicillin-resistant S. aureus, but with no detectable activities towards Gram-negative bacteria. Fortunately, the incorporation of a longer-chain triamine or polyamine (spermine) at C-22 did afford analogues (30, 31) that exhibited activity towards both S. aureus ATCC 25923 and Escherichia coli ATCC 25922 with MIC 6.1–13.4 µM. Spermine–pleuromutilin analogue 31 was also able to enhance the action of doxycycline towards Pseudomonas aeruginosa ATCC 27853 by eight-fold, highlighting it as a useful scaffold for the development of new antibacterial pleuromutilin analogues that exhibit a broader spectrum of activity. [ABSTRACT FROM AUTHOR]

This review focuses on the genetic and biotechnological aspects of the biosynthesis of ramoplanin (Rmp), enduracidin (End), and other related lipodepsipeptide antibiotics, herein named collectively ramoplanin and ramoplanin-related lipodepsipeptide (RRLDPs). These compounds exhibit a promising antimicrobial activity against Gram-positive bacterial pathogens, showing no cross-resistance with vancomycin. Rmp is in clinical development for human treatment and End has been used as animal growth promoter for decades. Other RRLDPs as ramoplanose and janiemycin had been poorly investigated in the past, whereas new molecules as chersinamycin have been recently discovered, attracting a renewed interest in this class of antibiotics. Nowadays, sequence and annotation of the biosynthetic gene clusters (BGCs) of Rmp, End, and several other RRLDPs are available, and researchers are focused on understanding the biosynthetic logic behind the production of these compounds. Interestingly, producers of Rmp and chersinamycin belong to the so-called "non-common" actinomycetes from the family Micromonosporaceae, whereas End is produced by different members of the genus Streptomyces. To the best of our knowledge, no reviews summarize and systematize the current information on the biosynthesis of RRLDPs. Therefore, in this review, we aim to fill this gap. We first describe and compare the BGCs for known RRLDPs, giving an insight on how they were discovered and developed. Next, we review the biosynthetic pathways of these antibiotics, as well as the regulation of their biosynthesis. Then, we focus on the production processes of RRLDPs, demonstrating how cultivation and nutritional factors influence their production. Finally, we provide a short outline of future directions in studying RRLDPs. [ABSTRACT FROM AUTHOR]

The relevance of active research lies in the need to develop new technologies to improve drug delivery methods for the effective treatment of wound healing. Additionally, the potential application of organogels in other areas of biomedicine, such as creating medical patches with controlled drug delivery, indicates a wide range of possibilities for using this technology. This study focuses on developing controlled drug delivery systems using organogels as carriers for ceftriaxone and ofloxacin. By selecting optimal formulations, organogels were created to immobilize the drugs, facilitating their effective and sustained release. The swelling behavior of the hydrogels was studied, showing a swelling coefficient between 16 and 32%, indicating their ability to absorb liquid relative to their weight. Drug release studies demonstrated that ceftriaxone was released 1.8 times slower than ofloxacin, ensuring a more controlled delivery. Microbiological tests confirmed that the organogels containing ofloxacin exhibited antimicrobial activity against Escherichia coli, Bacillus subtilis, and Staphylococcus aureus. However, it was a challenge to estimate activity for the model antibiotic ceftriaxone due to bacterial resistance to it. Organogel poly(vinyl alcohol) (PVA)-DMSO–alginate modifications with surfactant cetylpyridinium bromide led to the formation of a polyelectrolyte complex on the interphase, allowing further enhanced the prolonged release of the drugs. The research identified that the optimal compositions for sustained drug release were organogels with compositions PVA (10%)-PVP (1%) DMSO (50%) and PVA (10%)-DMSO (50%) formulations, illustrating the transparent nature of these organogels making them suitable for ophthalmological application. Various organogels compositions (PVA-DMSO, PVA-poly(vinylpyrrolidone)-DMSO, PVA-DMSO–alginate, PVA-DMSO-PLGA, PVA-DMSO–drug–surfactant) loaded with ceftriaxone, ofloxacin, and surfactant were prepared and characterized, highlighting their potential use in antibiotic patches for wound healing. These organogels illustrate promising results for localized treatment of infections in wounds, cuts, burns, and other skin lesions. [ABSTRACT FROM AUTHOR]

Background and Aims: Urinary tract infections (UTIs) are prevalent among hospitalized patients, constituting the most frequent health‐care infections. Uropathogenic Escherichia coli (UPEC) is leading causative agent of UTIs. The present study was aimed to examine the susceptibility of UPEC isolates obtained from nosocomial cases to antibiotics, as well as their biofilm formation capability and frequency of virulence genes. Methods: A total of 100 UPEC isolates were collected from nosocomial UTIs at Imam Reza Hospitals in Tabriz, Iran, spanning from April 2022 to January 2023. The antimicrobial susceptibility patterns were evaluated using the disk diffusion method, along with the detection of broad‐spectrum β‐lactam enzymes (ESBLs) and carbapenemases. The ability of isolates to form biofilms was assessed using the microtiter‐plate method, while the PCR method was employed to identify the presence of virulence genes. Results: The highest resistance was observed toward piperacillin (82%), followed by aztreonam and ciprofloxacin (81%), while the lowest resistance was found against piperacillin/tazobactam (12%) and meropenem (9%). ESBLs were detected in 62% of the isolates. The microtiter‐plate results revealed strong, moderate, and weak biofilm formation abilities in 32%, 33%, and 24% of the isolates, respectively. The most prevalent virulence gene was fimA (74%) followed by hlyF (68%), papA (44%), papC (32%), iroN (26%), and cnf (20%). Conclusion: The elevated levels of resistance to multiple antimicrobial agents, coupled with the co‐presence of virulence genes and biofilm formation abilities, contribute to the persistence of UPEC‐related infections, particularly in hospitalized patients. These findings underscore the necessity of implementing an effective program to control nosocomial UTIs caused by UPEC in the healthcare centers. [ABSTRACT FROM AUTHOR]

Background: Lack of access to timely, detailed antibiotic use data has limited ambulatory antibiotic stewardship efforts. Antibiotic utilization is tracked across ambulatory care sites and emergency departments (ED) within a large integrated health system. Methods: This is a retrospective cohort analysis from June 1, 2019 to May 31, 2020 comparing antibiotic prescribing for all patients with ICD-10 diagnosis codes for cystitis, otitis media, pharyngitis, sinusitis, and upper respiratory tract infections (URTIs) among five ambulatory care departments across northeast Ohio and southeast Florida locations: ED, Urgent Care (UC), On-Demand Telehealth (TEL), Pediatrics (PED), and Primary Care (PC). Results: A total of 261,947 encounters were included (ED:56,766, UC:92,749, TEL:8,783, PED:29,151, PC:74,498) for the treatment of cystitis (30,932), otitis media (22,094), pharyngitis (59,964), sinusitis (53,693), or URTI (95,264). The population was 63% female with a median age of 34.2 years [12.8-56.3]. A total of 17% of patients had documented penicillin allergies and 18% of patients with pharyngitis received Group A Streptococcus (GAS) testing. Antibiotics were prescribed in 44% of encounters (ED:21,746 [38%], UC:45,652 [49%], TEL:4,622 [53%], PED:10,909 [37%], PC:33,547 [45%]; P < 0.001). Guideline concordant antibiotics were prescribed in 65% of encounters (ED:14,338 [66%], UC:31,532 [69%], TEL:3,869 [84%], PED:8,212 [75%], PC:17,263 [51%]; P < 0.001). Conclusions: Observed rates of antibiotic and guideline concordant antibiotic prescribing were similar to national published rates of antibiotic prescribing in the ambulatory setting. The variability in antibiotic prescribing demonstrates opportunities for targeted outpatient stewardship efforts. Timely antibiotic tracking tools can facilitate ambulatory antimicrobial stewardship activities. [ABSTRACT FROM AUTHOR]

Antibacterial bone cements (ABCs), such as antibiotic-loaded bone cements (ALBCs), have been widely utilized in clinical treatments. Currently, bone cements loaded with vancomycin, gentamicin, tobramycin, or clindamycin are approved by the US Food and Drug Administration. However, traditional ALBCs exhibit drawbacks like burst release and bacterial resistance. Therefore, there is a demand for the development of antibacterial bone cements containing novel agents to address these defects. In this review, we provide an overview and prospect of the new antibacterial agents that can be used or have the potential to be applied in bone cement, including metallic antibacterial agents, pH-switchable antibacterial agents, cationic polymers, N-halamines, non-leaching acrylic monomers, antimicrobial peptides and enzymes. Additionally, we have conducted a preliminary assessment of the feasibility of bone cement containing N-halamine, which has demonstrated good antibacterial activities. The conclusion of this review is that the research and utilization of bone cement containing novel antibacterial agents contribute to addressing the limitations of ALBCs. Therefore, it is necessary to continue expanding the research and use of bone cement incorporating novel antibacterial agents. This review offers a novel perspectives for designing ABCs and treating bone infections. [ABSTRACT FROM AUTHOR]

Objectives Data supporting routine infectious diseases (ID) consultation in gram-negative bloodstream infection (GN-BSI) are limited. We evaluated the association between ID consultation and mortality in patients with GN-BSI in a retrospective population-wide cohort study in Ontario using linked health administrative databases. Methods Hospitalized adult patients with GN-BSI between April 2017 and December 2021 were included. The primary outcome was time to all-cause mortality censored at 30 days, analyzed using a mixed effects Cox proportional hazards model with hospital as a random effect. ID consultation 1–10 days after the first positive blood culture was treated as a time-varying exposure. Results Of 30 159 patients with GN-BSI across 53 hospitals, 11 013 (36.5%) received ID consultation. Median prevalence of ID consultation for patients with GN-BSI across hospitals was 35.0% with wide variability (range 2.7%–76.1%, interquartile range 19.6%–41.1%). In total, 1041 (9.5%) patients who received ID consultation died within 30 days, compared to 1797 (9.4%) patients without ID consultation. In the fully adjusted multivariable model, ID consultation was associated with mortality benefit (adjusted hazard ratio [HR] 0.82, 95% confidence interval [CI].77–.88, P <.0001; translating to absolute risk reduction of −3.8% or number needed to treat [NNT] of 27). Exploratory subgroup analyses of the primary outcome showed that ID consultation could have greater benefit in patients with high-risk features (nosocomial infection, polymicrobial or non-Enterobacterales infection, antimicrobial resistance, or non-urinary tract source). Conclusions Early ID consultation was associated with reduced mortality in patients with GN-BSI. If resources permit, routine ID consultation for this patient population should be considered to improve patient outcomes. [ABSTRACT FROM AUTHOR]

Infection of native tissues or implanted devices is common, but clinical diagnosis is frequently difficult and currently available noninvasive tests perform poorly. Immunocompromised individuals (for example transplant recipients, or those with cancer) are at increased risk. No imaging test in clinical use can specifically identify infection, or accurately differentiate bacterial from fungal infections. Commonly used [18F]fluorodeoxyglucose (18FDG) positron emission computed tomography (PET/CT) is sensitive for infection, but limited by poor specificity because increased glucose uptake may also indicate inflammation or malignancy. Furthermore, this tracer provides no indication of the type of infective agent (bacterial, fungal, or parasitic). Imaging tools that directly and specifically target microbial pathogens are highly desirable to improve noninvasive infection diagnosis and localization. A growing field of research is exploring the utility of radiometals and their chelators (siderophores), which are small molecules that bind radiometals and form a stable complex allowing sequestration by microbes. This radiometal-chelator complex can be directed to a specific microbial target in vivo, facilitating anatomical localization by PET or single photon emission computed tomography. Additionally, bifunctional chelators can further conjugate therapeutic molecules (e.g., peptides, antibiotics, antibodies) while still bound to desired radiometals, combining specific imaging with highly targeted antimicrobial therapy. These novel therapeutics may prove a useful complement to the armamentarium in the global fight against antimicrobial resistance. This review will highlight current state of infection imaging diagnostics and their limitations, strategies to develop infection-specific diagnostics, recent advances in radiometal-based chelators for microbial infection imaging, challenges, and future directions to improve targeted diagnostics and/or therapeutics. [ABSTRACT FROM AUTHOR]

Oral antimicrobials remain the mainstay of long-term treatment for many infections. Meanwhile, the use of oral agents is becoming commonplace for the treatment of several pediatric infections once managed exclusively with parenteral therapies. Unfortunately, antimicrobials are associated with several laboratory toxicities, particularly when high doses or combination therapies are used, but there is a paucity of data on optimal laboratory monitoring strategies. In this ID Consultant article, we offer a summary of the 3 most common laboratory-based toxicities seen with long-term use of oral antimicrobials—drug-induced kidney injury, liver injury, and hematological toxicities—and we provide our recommended approach to monitoring. [ABSTRACT FROM AUTHOR]

Elysia crispata (Sacoglossa, Gastropoda) is a tropical sea slug known for its ability to incorporate functional chloroplasts from a variety of green macroalgae, a phenomenon termed kleptoplasty. This sea slug, amenable to laboratory cultivation, produces mucus, a viscous secretion that serves diverse purposes including protection, locomotion, and reproduction. In this study, we profiled the antimicrobial, antioxidant, and anti-inflammatory activities of the mucus of this sea slug. Results revealed inhibitory activity against several bacterial strains, more pronounced for Gram–negative bacteria. Particularly interesting was the strong inhibitory effect against Pseudomonas aeruginosa, a bacterial species classified by the WHO as a high-priority pathogen and associated with high-risk infections due to its frequent multidrug-resistant profile. Similar inhibitory effects were observed for the mucus native protein extracts, indicating that proteins present in the mucus contributed significantly to the antimicrobial activity. The mucus also showed both antioxidant and anti-inflammatory activities. The latter activities were associated with the low molecular weight (<10 kDa) fraction of the mucus rather than the native protein extracts. This study opens the way to further research on the biotechnological applications of the mucus secreted by this unique marine organism, particularly as an antimicrobial agent. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus (SA) is a leading cause of bloodstream infection. The liver represents the sentinel immune organ for clearance of bloodstream pathogens and eradication of intracellular SA from liver-resident macrophages (Kupffer cells, KCs) eliminates the likely pathogenic reservoir that contributes to persistent bacteraemia. Objectives We assessed antimicrobial activity at phagolysosome-mimicking pH, intracellular penetration, and SA eradication within KCs in vitro for clinically prescribed antistaphylococcal agents alone or in combination: vancomycin, daptomycin, ceftaroline, ceftobiprole, oritavancin, oxacillin, cefazolin; rifampin and fosfomycin. Methods pH-adjusted broth microdilution assays, intracellular bioaccumulation assays, and intracellular killing assays against clinical bloodstream isolates were performed using a murine KC line with study agents. Results Rifampin and β-lactams exhibited enhanced activity [2- to 16-fold minimum inhibitory concentrations (MIC) decrease] at phagolysosomal pH while vancomycin, oritavancin, daptomycin and fosfomycin demonstrated reduced activity (2- to 32-fold MIC increase in order of least to greatest potency reduction). All agents evaluated had poor to modest intracellular to extracellular concentration ratios (0.024–7.8), with exceptions of rifampin and oritavancin (intracellular to extracellular ratios of 17.4 and 78.2, respectively). Finally, we showed that the first-line treatment for SA bacteraemia (SAB), vancomycin, performed worse than all other tested antibiotics in eradicating intracellular SA at human C max concentration (0.20 log cfu decrease), while oritavancin performed better than all other agents alone (2.05 versus 1.06–1.36 log cfu decrease). Conclusions Our findings raise concerns about the efficacy of commonly prescribed antibiotics against intracellular SA reservoirs and emphasize the need to consider targeting pathogen eradication from the liver to achieve early control of SAB. [ABSTRACT FROM AUTHOR]

Objective: This study proposed to assess the effect of Cryptocarya moschata extract on single and mixed biofilms formed on denture base and reline acrylic resin. Materials and Methods: Single and mixed biofilms of Candida albicans and Streptococcus mutans were formed on the samples and treated with C. moschata extract; Nystatin solution at 100,000 IU/mL or Penicillin antibiotic solution at 100,000 IU/mL; or PBS solution. Antimicrobial activity was analyzed by counting colony‐forming units, metabolism assay, assessment of protein components of the biofilm matrix, and of cell viability using confocal laser scanning microscopy (CLSM). Data were submitted to ANOVA and Tukey's post‐test (α = 0.05). Results: Cryptocarya moschata extract reduced cell viability of C. albicans and S. mutans single and mixed biofilms formed on samples. For all types of biofilms in the C. moschata group, there was a log reduction of the biofilm, proven by the Alamar Blue assay. Analyzing the extracellular matrix protein components, groups treated with the extract exhibited a lower level of fluorescence compared to the PBS groups. Reduction in thickness biofilm and viable cells was perceptible in the C. moschata group when assessing through CLSM. Conclusion: Cryptocarya moschata extract reduced the single and mixed biofilms of C. albicans and S. mutans on acrylic resins. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to determine the feasibility of capturing antimicrobial usage data from prisons for inclusion in the Antimicrobial Use and Resistance in Australia (AURA) surveillance system and to analyse 2021 and 2022 South Australian (SA) usage data for notable trends. Methods: Monthly antimicrobial supply data for eight SA prisons were collected. Antimicrobial volume was converted into the World Health Organization metric, defined daily doses (DDD). Usage rates were calculated relative to prison occupied bed days (OBD). Results: Annual usage of systemic antimicrobials across eight SA prisons totalled 26,448 DDD and 23,526 DDD in 2021 and 2022 respectively. Antibacterials accounted for 80.6% of all antimicrobials dispensed during the study period. The average antibacterial usage rate in female prisons was higher on average than in male prisons. The state-wide systemic antibacterial usage rate in SA prisons declined by 11.3% from 23.8 DDDs/1000 OBD in 2021 to 21.1 DDDs/1000 OBD. Doxycycline, amoxicillin, flucloxacillin, amoxicillin-clavulanic acid, and cefalexin accounted for 72% of the total systemic antibacterial usage rate. Variation in the oral and topical antifungal agents used and the rate of use was observed between prisons. Conclusions: This SA pilot study demonstrates the feasibility of including prisons in routine national antimicrobial surveillance using similar methodology to hospital surveillance. The contributing facilities comprised 6.1% of all Australian prison beds, and extrapolation of the results suggests that the identified gap in surveillance may equate to over 400,000 DDD per annum in prisons nationwide, equating to approximately 5% of hospital inpatient antimicrobial usage. What is known about the topic? Surveillance of antimicrobial use is a useful tool to identify overuse or inappropriate use and enable targeted interventions to optimise antimicrobial prescribing and reduce the risk of antimicrobial resistance. What does this paper add? The methodology currently used to monitor antimicrobial use in Australian hospitals could be utilised to conduct facility-level surveillance in Australian prisons and would provide a mechanism to benchmark use between facilities and identify unexpected or inappropriate use. What are the implications for practitioners? Surveillance of antimicrobial use in prisons would support prison healthcare workers to monitor use over time, identify any increasing or unexpected trends in use, and target educational interventions to ensure compliance with antimicrobial prescribing guidelines. [ABSTRACT FROM AUTHOR]

Antimicrobial peptides (AMPs), sourced from various organisms, including aquatic life, are promising alternatives to combat antibiotic resistance. Their investigation is essential amid global antibiotic resistance concerns. The invaluable impact of antibiotics on human health, having saved numerous lives, is currently at risk. The growing global incidence of antibiotic-resistant bacteria poses a serious challenge to their ability to effectively treat various illnesses. This situation demands immediate attention and the exploration of alternative medical solutions. One of the most promising alternatives to antibiotics is antimicrobial peptides (AMPs), which can treat bacterial infections, particularly those brought by multi-drug-resistant pathogens. With a particular focus on their antimicrobial properties, this systematic review aims to evaluate and classify recent AMPs isolated from aquatic organisms. This review advances knowledge of these aquatic life-derived AMPs' potential as alternatives to conventional antibiotics by examining their unique antibacterial characteristics and modes of action. A systematic review of articles published in English between 2014 and 2024 was carried out in the Science Direct, PubMed NCBI and Google Scholar databases using keywords and inclusion and exclusion criteria. A total of 33 potential AMPs isolated from aquatic organisms had been reported, and 21 of the AMPs were reported to have functional antimicrobial activities. Continuous research and study of natural substances, particularly AMPs, remain critical in pursuing alternatives to conventional antibiotics for effective treatments in combating antibiotic resistance. Therefore, ongoing research holds significant importance in identifying and harnessing the potential of AMPs for future medical applications. [ABSTRACT FROM AUTHOR]

Background: This study aimed to evaluate the profile of antimicrobial consumption in patients assisted by a palliative care (PC) team during the COVID-19 pandemic. Methods: A retrospective observational study was conducted in a quaternary hospital. Patients assisted by the PC team in 2020 were selected. The clinical and demographic characteristics, as well as the outcomes, were assessed using electronic records. Results: A total of 181 patients were included in the study, of whom 93.4% had used antimicrobials and 24.3% had had COVID-19. COVID-19 patients were more likely to receive at least one course of antimicrobial therapy. Patients who received polytherapy in the first course of treatment were more likely to die and to be still receiving antimicrobials at death. There was no significant difference in the length of hospital stay, new hospitalization in 12 months, nor the time to death among patients who received monotherapy or polytherapy during the first course of antimicrobial therapy. Conclusions: There was a large amount of PC patients receiving antimicrobial therapy during the COVID-19 pandemic. SARS-CoV-2-positive patients were more likely to receive antimicrobial therapy. [ABSTRACT FROM AUTHOR]

Purpose: Very low birth weight (VLBW) infants are at a risk of spontaneous focal intestinal perforation (FIP). Treatment includes supportive care, antibiotics, and drainage with/without surgery. Broad-spectrum antibiotic agents like carbapenems are applied frequently, although their use is not well-supported by the limited evidence of causal pathogens. We hypothesize that the use of carbapenems may not be necessary in VLBW infants with FIP. Our primary objective was to evaluate the antimicrobial use in VLBW infants with FIP in a cohort of the German Neonatal Network (GNN). The secondary objective was to characterize a subset in detail as a benchmark for future targets of stewardship. Methods: Data on VLBW infants with FIP was collected prospectively within the GNN, a collaboration of 68 neonatal intensive care units (NICU). With regards to the primary objective, patient characteristics and antimicrobial treatment were extracted from the predefined GNN database. To address our secondary objective, an additional on-site assessment of laboratory and microbiological culture results were performed. Results: In the GNN cohort, 613/21,646 enrolled infants (2.8%) developed FIP requiring surgery. They were frequently treated with carbapenems (500/613 (81.6%)) and vancomycin (497/613 (81.1%)). In a subset of 124 VLBW infants, 77 (72.6%) had proof of gram-positive bacteria in the abdominal cavity, coagulase-negative staphylococci (CoNS) predominantly. Despite the low prevalence of gram-negative bacteria (n = 6 (4.8%)), the combination of meropenem and vancomycin was prescribed most frequently (n = 96 (78.0%)). Conclusion: The use of carbapenems as broad-spectrum antimicrobials agents might not be justified in most VLBW infants with FIP. Knowledge on the development of the neonatal gut microbiota, local resistance patterns and individual microbiological findings should be taken into consideration when implementing antimicrobial stewardship programs (ASPs). [ABSTRACT FROM AUTHOR]

Background Bone infections with Staphylococcus aureus are notoriously difficult to treat and have high recurrence rates. Local antibiotic delivery systems hold the potential to achieve high in situ antibiotic concentrations, which are otherwise challenging to achieve via systemic administration. Existing solutions have been shown to confer suboptimal drug release and distribution. Here we present and evaluate an injectable in situ-forming depot system termed CarboCell. The CarboCell technology provides sustained and tuneable release of local high-dose antibiotics. Methods CarboCell formulations of levofloxacin or clindamycin with or without antimicrobial adjuvants cis-2-decenoic acid or cis-11-methyl-2-dodecenoic acid were tested in experimental rodent and porcine implant-associated osteomyelitis models. In the porcine models, debridement and treatment with CarboCell-formulated antibiotics was carried out without systemic antibiotic administration. The bacterial burden was determined by quantitative bacteriology. Results CarboCell formulations eliminated S. aureus in infected implant rat models. In the translational implant-associated pig model, surgical debridement and injection of clindamycin-releasing CarboCell formulations resulted in pathogen-free bone tissues and implants in 9 of 12 and full eradication in 5 of 12 pigs. Conclusions Sustained release of antimicrobial agents mediated by the CarboCell technology demonstrated promising therapeutic efficacy in challenging translational models and may be beneficial in combination with the current standard of care. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance in agriculture is a global concern that is growing every day. As a result, there is increasing interest in investigating different approaches to disease control in both plants and animals. Research on the identification and synthesis of antimicrobial compounds derived from plants and microbes has exploded in the last few years. The purpose of this review is to give a broad overview of the current knowledge regarding antimicrobials derived from plants and microbes and their possible uses in agricultural practises. It discusses a number of topics, such as the origins of these antimicrobial agents, how they work, and how well they work to fight infections in plants and animals. Furthermore, the difficulties pertaining to their execution and potential outcomes are examined. [ABSTRACT FROM AUTHOR]

Introduction: Due to the concerning increase in resistance to traditional antimicrobial drugs, new therapies to fight antibiotic-resistant microorganisms, such as plant-based compounds and nanoparticles, appear necessary. The goal of this research was to examine the antimicrobial activity of silver nanoparticles synthesized using Lycium ruthenicum extract. Methods & Materials: In this experimental study, Escherichia coli (ATCC25922), Pseudomonas aeruginosa (ATCC27853), Klebsiella pneumoniae (ATCC9997), Staphylococcus aureus (ATCC25923) and Enterococcus faecalis (ATCC29212) were studied. Aqueous extract of L. ruthenicum was prepared. Silver nanoparticles were prepared in combination with L. ruthenicumextract. The MIC of silver nanoparticles was investigated alone and in combination with the L. ruthenicumplant using the broth microdilution method for Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Staphylococcus aureus and Enterococcus faecalis. Results: The nanoparticle synthesized with the aqueous extract of the Lycium ruthenicum plant had a significant inhibitory effect on E. coli, P. aeruginosa, and S. aureus compared to the aqueous extract alone (P<0.05). Also, the highest inhibitory activity of L. ruthenicum extract was for K.pneumoniae and E. faecalis with MIC 2.5 mg / ml. On the other hand, biosynthesized silver nanoparticles against E. coli with MIC 1.25 mg / ml showed the highest inhibitory activity. In general, silver nanoparticles synthesized with L. ruthenicum extract had significant antibacterial effects on the studied bacteria, in comparison with silver nanoparticles by chemical method as well as the plant L. ruthenicum alone. Conclusion: Silver nanoparticles synthesized with L. ruthenicum extract have significant antibacterial effects, which can be used as a suitable treatment option for antibiotics due to the side effects of antibiotics after further studies on animal models. [ABSTRACT FROM AUTHOR]

Contact of aquatic microbiocenoses with antibiotics present in the environment can cause the former to develop resistance to antimicrobial drugs. Therefore, the search for methods to detect antibiotics and drug-resistant microorganisms in the environment is important. The presented paper proposes a simple procedure to assess environmental exposure to antibiotics and the presence of non-susceptible microorganisms. Medium solutions with selected antibiotics and a microbial growth indicator were applied to test plates, and were inoculated with water samples from various ecosystems. After incubation, the susceptibility of the microorganisms to antibiotics was determined and presented in chronic microbial toxic concentration (MTC) values. It was confirmed that the presented procedure enables the assessment of the antibiotic susceptibility and adaptation potential of unselected microorganisms from different aquatic ecosystems. However, the MTC values depend on the inoculum volume, the density and seasonal activity of the microorganisms, the method of inoculum preparation, and the incubation time of the test plate. The described procedure may be practically applied as a screening test to identify the presence of drug-resistant microorganisms. Additionally, it may also be suitable as a method to assess environmental exposure to antibiotics. However, prior standardisation is required before implementing this procedure in quantitative studies. [ABSTRACT FROM AUTHOR]

Penicillin was the first antibacterial drug discovered in the world. Now it has been developed to be a family of antimicrobial drugs containing β-lactam, which is widely used in clinic. This article introduces the penicillin family and its main members in the form of a live interview recording. Through a dialogue between representatives of the penicillin family and the host, the antibacterial mechanism, characteristics, and clinical applications of the penicillin family members are vividly presented to the public. It aims to promote people's awareness of the rational use of antibiotics. [ABSTRACT FROM AUTHOR]

Pactamycin (PCT), an antibiotic produced by Streptomyces pactum, is a five-membered ring aminocyclitol that is active against a variety of Gram-positive and Gram-negative microorganisms, as well as several animal tumor lines in culture and in vivo. Pactamycin targets the small ribosomal subunit and inhibits protein synthesis in bacteria, archaea, and eukaryotes, but due to its toxicity is used only as a tool for biochemical research. Prompted by the successful and well-established procedure for the derivatization of antibiotics, we modified pactamycin by tethering basic amino acids to the free primary amino group of the aminocyclitol ring. Specifically, lysine, ornithine, and histidine were conjugated via an amide bond, and the antimicrobial activity of the derivatives was evaluated both in vivo and in vitro. According to our results, their antimicrobial activity was maintained at almost equal levels, while their toxicity was reduced compared to the parent molecule. These findings suggest that the new pactamycin derivatives can be considered as promising pharmacophores for the development of new antimicrobials that are able to combat the dangerously increasing resistance of pathogens to antibiotics. [ABSTRACT FROM AUTHOR]

Nosocomial pneumonia is defined as pneumonia occurring ≥ 48 h after hospital admission in a patient without severe immunosuppression. It can occur in spontaneously breathing patients or with noninvasive ventilation (NIV) and mechanically ventilated patients. In patients with suspected ventilator-associated pneumonia (VAP) (semi)quantitative cultures of tracheobronchial aspirates or bronchoalveolar lavage fluid should be perfomed. The initial empirical antimicrobial treatment is determined by the risk for multidrug-resistant pathogens (MDRP). The advantage of combination treatment increases with the prevalence of MDRPs. The antibiotic treatment should be adapted when the microbiological results are available. After 72 h a standardized re-evaluation including the response to treatment and also checking of the suspected diagnosis of pneumonia in a structured form is mandatory. Treatment failure can occur as a primary or secondary failure and in the case of primary progression necessitates another comprehensive diagnostic work-up before any further antibiotic treatment. [ABSTRACT FROM AUTHOR]

Dapsone, initially synthesized for textile dyeing, gained recognition in the 1930s for its antibacterial properties, leading to its utilization in dermatology for leprosy and dermatitis herpetiformis. Despite US Food and Drug Administration (FDA) approval for these conditions, dapsone's off-label uses have expanded, making it a valuable option in various dermatologic conditions. This review seeks to highlight the common uses of dapsone in its FDA indications and off-label indications. Diseases in which dapsone is considered first-line therapy or adjunctive therapy are reviewed, with highlights from the resources included. An overview of dapsone's pharmacokinetics, pharmacodynamics, indications, dosages, and safety profile are also reviewed. Dapsone's versatility and safety profile make it a cost-effective treatment option in dermatology, particularly for patients with limited access to specialized medications. Ongoing clinical trials are also described exploring dapsone's efficacy in novel dermatologic uses. Dapsone has been a valuable adjunctive therapy across various dermatologic conditions for years and evidence for its use continues to expand. [ABSTRACT FROM AUTHOR]

The objectives of this article are to report 2 cases of nonsurgical endodontic treatment for the management of periapical lesions associated with large cortical bone perforations and review the literature on the clinical efficacy of nonsurgical endodontic treatment to draw insights from published case reports. Large, cyst-like periapical lesions in 2 patients were successfully treated with combined modalities of root canal treatment, antimicrobial therapy (calcium hydroxide and triple antibiotic paste [TAP]), and mineral trioxide aggregate (MTA) obturation of the canal space. In both cases, instrumentation was extended 1 mm beyond the apical foramen to facilitate drainage through the root canal, because it was assumed that the periapical lesion could be cystic. After instrumentation, TAP was placed within the canal space to aid in disinfection and healing of the dental, pulpal, and periapical conditions. In both patients, the teeth were asymptomatic and functional at follow-up examinations (case 1, 3 years; case 2, 30 months). Supporting the positive outcomes in the 2 clinical cases, the published literature suggests that the use of biocompatible materials such as MTA, which can promote the deposition of hydroxyapatite, has the potential to contribute to tissue regeneration and the healing of large periapical lesions. [ABSTRACT FROM AUTHOR]

Microbial resistance to antibiotics and the shortage of efficient antimicrobial agent has necessitated the search for a better antimicrobial agent from various sources. Plants secondary metabolites are the major sources for discovery of new bioactive chemical compounds. The objective of this study was to determine the antibacterial and antioxidant activities of Laurus nobilis leaf extract and its essential oil against human pathogenic microorganisms and to analyse its chemical composition. The leaf of L. nobilis (500 g) was air-dried, powdered and extracted using four different solvents. The crude extract and the essential oil were tested against four Gram-negative and two Gram-positive bacterial strains. The radical scavenging activity of the crud extract was examined using DPPH assay. Bacterial inhibition activity of the crude extract increased with increased concentration from 25 mg/mL to 200 mg/mL. The maximum inhibition zone was recorded against Enterococcus faecalis 13.33±1.52 mm, Escherichia coli 14.33±1.53 mm and Salmonella typhimurium 16.00±1.00 mm, respectively. MeOH extract (1000 µg/mL) showed superior radical scavenging property (0.02) than ascorbic acid (0.05). The analysis of the oil using GC-MS indicated the presence of 48 chemical substances accounting for 91.4 % of the total compositions. The finding of this study showed that bay leaf has considerable antimicrobial and antioxidant activities. Further evaluation of this plant is recommended with particular focus on the mechanisms of action of the antimicrobial substance. [ABSTRACT FROM AUTHOR]

The routine use of antimicrobial therapy to treat diabetic foot infections has been widely published. However, effective treatments can be interrupted with complications such as antimicrobial resistance, systemic toxicity and allergic reactions. This paper looked at 26 individual cases using calcium sulfate (Stimulan®, Biocomposites Ltd) as a carrier for delivering antimicrobials, in the form of beads, at a local level and at the site of infection. In 69% of patients, oral and parenteral antimicrobials were ceased at the point of treatment. Patients were managed under local protocols by the podiatry team to the point of wound closure. Additionally, average healing rates were seen to be significantly reduced. [ABSTRACT FROM AUTHOR]

As per the World Health Organization (WHO), antimicrobial resistance (AMR) is a natural phenomenon whereby microbes develop or acquire genes that render them resistant. The rapid emergence and spread of this phenomenon can be attributed to human activity specifically, the improper and excessive use of antimicrobials for the treatment, prevention, or control of infections in humans, animals, and plants. As a result of this factor, many antibiotics have reduced effectiveness against microbes or may not work fully. Thus, there is a pressing need for the development of new antimicrobial agents in order to counteract antimicrobial resistance. Metallic nanoparticles (MNPs) are well known for their broad antimicrobial properties. Consequently, the use of MNPs with current antibiotics holds significant implications. MNPs, including silver nanoparticles (AgNPS), zinc oxide nanoparticles (ZnONPs), copper nanoparticles (CuNPs), and gold nanoparticles (AuNPs), have been extensively studied in conjunction with antibiotics. However, their mechanism of action is still not completely understood. The interaction between these MNPs and antibiotics can be either synergistic, additive, or antagonistic. The synergistic effect is crucial as it represents the desired outcome that researchers aim for and can be advantageous for the advancement of new antimicrobial agents. This article provides a concise and academic description of the recent advancements in MNP and antibiotic conjugates, including their mechanism of action. It also highlights their possible use in the biomedical field and major challenges associated with the use of MNP–antibiotic conjugates in clinical practice. [ABSTRACT FROM AUTHOR]

The article discusses various studies on infectious diseases published in medical journals as of August 2024. Topics include cases of falsely positive HIV 1-nucleic acid amplification tests (NAAT) related to chimeric antigen receptor T-cell (CAR-T) therapy, effect of nonantibiotic s on a large number of bacterial strains, and characteristics and clinical course of listeria monocytogenes infection in recipients of hematopoietic stem cell transplants.

The emergence of antimicrobic-resistant infectious pathogens and the consequent rising in the incidence and prevalence of demises caused by or associated to infections which are not sensitive to drug treatments is one of today's major global health challenges. Antimicrobial resistance (AMR) can bring to therapeutic failure, infection's persistence and risk of serious illness, in particular in vulnerable populations such as the elderly, patients with neoplastic diseases or the immunocompromised. It is assessed that AMR will induce until 10 million deaths per year by 2050, becoming the leading cause of disease-related deaths. The World Health Organisation (WHO) and the United Nations General Assembly urgently call for new measures to combat the phenomenon. Research and development of new antimicrobial agents has decreased due to market failure. However, promising results are coming from new alternative therapeutic strategies such as monoclonal antibodies, microbiome modulators, nanomaterial-based therapeutics, vaccines, and phages. This narrative review aimed to analyse the benefits and weaknesses of alternative therapeutic strategies to antibiotics which treat multidrug-resistant bacterial infections. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to determine the use of antimicrobial drugs during the second year of the coronavirus disease 2019 (COVID19) pandemic, and evaluate the pandemic's impact on antibiotic use by comparing with the pre-pandemic period. Methodology: The study was a retrospective point prevalence study. Patients aged ≥ 18 years, who received antibiotics in our hospital between 11 February 2020. and 3 January 2022 were evaluated. The antibiotics were categorized according to the 2021 Access/Watch/Reserve (AWARe) classification. Compliance with recommendations from infectious diseases (ID) physicians, and reasons for inappropriate treatment were evaluated. Results: Among the hospitalized patients, 323 (36.4%) during the pre-pandemic days (PPD), and 361 (50.1%) during pandemic days (PD), used at least one antimicrobial drug (p < 0.001). The most frequently used antibiotics during PPD and PD were piperacillin, tazobactam, and imipenem/meropenem. The use of the "Access" group antibiotics decreased in the PD, while the use of the "Watch" and "Reserve" groups increased (p = 0.034). There was 100% (n = 209) compliance with ID consultation in the PPD, and 91.9% (n = 227) in the PD (p < 0.001). In the PPD, 64 (19.8%). of the treatments received by inpatients were inappropriate, and during the PD 100 (27.7%) were inappropriate (p = 0.016). Conclusions: The pandemic led to an increase in the overuse and inappropriate use of antimicrobial drugs, particularly in the Watch and Reserve groups, in both COVID-19 and non-COVID-19 clinics. There was a notable transition towards the increased utilization of broad-spectrum antibiotics during the pandemic. [ABSTRACT FROM AUTHOR]

Most of the Escherichia coli turned into serious pathogens or developed antibiotic resistance, mainly due to their ability to show different phenotypic traits. In order to overcome the resistance to these antibiotics, the use of essential oils (EOs) is of great significance against highly pathogenic microorganisms. This study has been made to compare the in vitro antibacterial activity and further validated the same through the molecular docking study of 13 antibiotics such as ciprofloxacin, chloramphenicol, erythromycin, ampicillin, cefotaxime, rifampicin, kanamycin, vancomycin, streptomycin, penicillin, nalidixic acid, trimethoprim, and polymyxin, and 10 EOs such as garlic, tulsi, neem, clove, thyme, peppermint, coriander, tea, lavender, and eucalyptus against the target protein (DNA gyrase) of E. coli MTCC443. E. coli Microbial Type Culture Collection 443 was found to be highly sensitive to ciprofloxacin (zone of inhibition [ZOI], 2.5 cm ±0.1) and chloramphenicol (ZOI, 1.8 cm ±0.1), whereas garlic oil (ZOI, 5.5 cm ±0.1) and coriander oil (ZOI, 4.4 cm ±0.1) were found comparatively most effective. Further, the in silico investigation observed the same; ciprofloxacin (binding affinity: −7.2 kcal/mol) and chloramphenicol (binding affinity: −6.6 kcal/mol). Penicillin (binding affinity: −4.2 kcal/mol) and polymyxin (binding affinity: −0.3 kcal/mol) were found to be least effective against the tested microbe, whereas vancomycin (binding affinity: +0.8 kcal/mol) had no effect on it. Garlic (binding affinity: −7.8 kcal/mol), coriander (binding affinity: −6.8 kcal/mol), peppermint (binding affinity: −6.2 kcal/mol), and neem (binding affinity: −6.2 kcal/mol) oil exhibited the potent antibacterial activity against E. coli MTCC443, whereas thyme (binding affinity: −6.1 kcal/mol), tea tree (binding affinity: −4.9 kcal/mol), and tulsi (binding affinity: −3.8 kcal/mol) oil were observed moderately effective. Eucalyptus (binding affinity: −2.9 kcal/mol) and lavender (binding affinity: −2.8 kcal/mol) oil were found to be the least effective among all the oils tested. The pharmacokinetics and networking were performed to the pharmacology of the potential compounds. [ABSTRACT FROM AUTHOR]