Antibiotic-resistant Infections Research Articles

Adipose-derived stem cells and antibiotics: A novel synergistic approach for treating implant-related osteomyelitis

ABSTRACT Implant-related osteomyelitis poses a significant challenge in orthopedic practice, particularly due to the increasing prevalence of antibiotic-resistant infections and biofilm-associated complications. This article focused on exploring the potential of combination therapy with adipose-derived stem cells (ADSCs) and antibiotics to overcome these challenges, thereby enhancing treatment efficacy. A systematic synthesis of the results of recent in vivo studies, predominantly those using rat models, was performed. Studies that evaluated the effectiveness of ADSCs combined with antibiotics against common pathogens in implant-related osteomyelitis, particularly Staphylococcus aureus and methicillin-resistant Staphylococcus epidermidis, were selected. A significant reduction in symptoms such as swelling, abscess formation, and bacterial burden in the ADSCs + antibiotic-treated group was observed in all studies. In addition, microcomputed tomography revealed reduced osteolysis, indicating enhanced bone preservation. Furthermore, histological examination revealed improved tissue structure and altered immune response, signifying the dual role of ADSCs in enhancing antibiotic action and modulating the immune system. This review highlights the promising role of the concurrent use of ADSCs and antibiotics in the treatment of implant-related osteomyelitis. This novel therapeutic strategy has the potential to revolutionize the management of complex orthopedic infections, especially those resistant to conventional treatments. However, further research is required to translate the results of animal studies into clinical applications and to develop optimized treatment protocols for human use.

Development of Penicillin-Based Carbonic Anhydrase Inhibitors Targeting Multidrug-Resistant Neisseria gonorrhoeae.

The development of antibacterial drugs with new mechanisms of action is crucial in combating the rise of antibiotic-resistant infections. Bacterial carbonic anhydrases (CAs, EC 4.2.1.1) have been validated as promising antibacterial targets against pathogens such as Helicobacter pylori, Neisseria gonorrhoeae, and vancomycin-resistant enterococci. A multitarget strategy is proposed to design penicillin-based CA inhibitor hybrids for tackling resistance by targeting multiple bacterial pathways, thereby resensitizing drug-resistant strains to clinical antibiotics. The sulfonamide derivatives potently inhibited the CAs from N. gonorrhoeae and Escherichia coli with KI values in the range of 7.1-617.2 nM. Computational simulations with the main penicillin-binding protein (PBP) of N. gonorrhoeae indicated that these hybrid derivatives maintained the mechanism of action of the lead β-lactams. A subset of derivatives showed potent PBP-related antigonococcal effects against multidrug-resistant N. gonorrhoeae strains, with several compounds significantly outperforming both the lead β-lactam and CA inhibitor drugs (MIC values in the range 0.25 to 0.5 μg/mL).

Bacteriophage cocktail shows no toxicity and improves the survival of Galleria mellonella infected with Klebsiella spp.

Klebsiella spp. are causative agents of healthcare-associated infections in patients who are immunocompromised and use medical devices. The antibiotic resistance crisis has led to an increase in infections caused by these bacteria, which can develop into potentially life-threatening illnesses if not treated swiftly and effectively. Thus, new treatment options for Klebsiella are urgently required. Phage therapy can offer an alternative to ineffective antibiotic treatments for antibiotic-resistant bacteria infections. The aim of the present study was to produce a safe and effective phage cocktail treatment against Klebsiella pneumoniae and Klebsiella oxytoca, both in liquid in vitro culture and an in vivo Galleria mellonella infection model. The phage cocktail was significantly more effective at killing K. pneumoniae and K. oxytoca strains compared with monophage treatments. Preliminary phage cocktail safety was demonstrated through application in the in vivo G. mellonella model: where the phage cocktail induced no toxic side effects in G. mellonella. In addition, the phage cocktail significantly improved the survival of G. mellonella when administered as a prophylactic treatment, compared with controls. In conclusion, our phage cocktail was demonstrated to be safe and effective against Klebsiella spp. in the G. mellonella infection model. This provides a strong case for future treatment for Klebsiella infections, either as an alternative or adjunct to antibiotics.IMPORTANCEKlebsiella infections are a concern in individuals who are immunocompromised and are becoming increasingly difficult to treat with antibiotics due to their drug-resistant properties. Bacteriophage is one potential alternative therapy that could be used to tackle these infections. The present study describes the design of a non-toxic phage cocktail that improved the survival of Galleria mellonella infected with Klebsiella. This phage cocktail demonstrates potential for the safe and effective treatment of Klebsiella infections, as an adjunct or alternative to antibiotics.

Diversity and antimicrobial susceptibility patterns of clinical and environmental Salmonella enterica serovars in Western Saudi Arabia.

The diverse environmental distribution of Salmonella makes it a global source of human gastrointestinal infections. This study aimed to detect Salmonella spp. and explore their diversity and antimicrobial susceptibility patterns in clinical and environmental samples. Pre-enrichment, selective enrichment, and selective plating techniques were adopted for the Salmonella detection whereas the API 20E test and Vitek Compact 2 system were used to confirm the identity of isolates. Salmonella serovars were subjected to molecular confirmation by 16S rDNA gene sequencing. Disc diffusion method and Vitek 2 Compact system determined the antibiotic susceptibility of Salmonella serovars. Multiple antibiotic resistance index (MARI) was calculated to explore whether Salmonella serovars originate from areas with heavy antibiotic usage. Results depicted low Salmonella prevalence in clinical and environmental samples (3.5%). The main detected serovars included Salmonella Typhimurium, S. enteritidis, S. Infantis, S. Newlands, S. Heidelberg, S. Indian, S. Reading, and S. paratyphi C. All the detected Salmonella serovars (27) exhibited multidrug resistance to three or more antimicrobial classes. The study concludes that the overall Salmonella serovars prevalence was found to be low in environmental and clinical samples of Western Saudi Arabia (Makkah and Jeddah). However, antimicrobial susceptibility patterns of human and environmental Salmonella serovars revealed that all isolates exhibited multidrug-resistance (MDR) patterns to frequently used antibiotics, which might reflect antibiotic overuse in clinical and veterinary medicine. It would be suitable to apply and enforce rules and regulations from the One Health approach, which aim to prevent antibiotic resistance infections, enhance food safety, and improve human and animal health, given that all Salmonella spp. detected in this investigation were exhibiting MDR patterns.

Long-Term Outcomes Associated With β-Lactam Allergies

β-lactam (BL) allergies are the most common drug allergy worldwide, but most are reported in error. BL allergies are also well-established risk factors for adverse drug events and antibiotic-resistant infections during inpatient health care encounters, but the understanding of the long-term outcomes of patients with BL allergies remains limited. To evaluate the long-term clinical outcomes of patients with BL allergies. This longitudinal retrospective cohort study was conducted at a single regional health care system in western Pennsylvania. Electronic health records were analyzed for patients who had an index encounter with a diagnosis of sepsis, pneumonia, or urinary tract infection between 2007 and 2008. Patients were followed-up until death or the end of 2018. Data analysis was performed from January 2022 to January 2024. The presence of any BL class antibiotic in the allergy section of a patient's electronic health record, evaluated at the earliest occurring observed health care encounter. The primary outcome was all-cause mortality, derived from the Social Security Death Index. Secondary outcomes were defined using laboratory and microbiology results and included infection with methicillin-resistant Staphylococcus aureus (MRSA), Clostridium difficile, or vancomycin-resistant Enterococcus (VRE) and severity and occurrence of acute kidney injury (AKI). Generalized estimating equations with a patient-level panel variable and time exposure offset were used to evaluate the odds of occurrence of each outcome between allergy groups. A total of 20 092 patients (mean [SD] age, 62.9 [19.7] years; 12 231 female [60.9%]), of whom 4211 (21.0%) had BL documented allergy and 15 881 (79.0%) did not, met the inclusion criteria. A total of 3513 patients (17.5%) were Black, 15 358 (76.4%) were White, and 1221 (6.0%) were another race. Using generalized estimating equations, documented BL allergies were not significantly associated with the odds of mortality (odds ratio [OR], 1.02; 95% CI, 0.96-1.09). BL allergies were associated with increased odds of MRSA infection (OR, 1.44; 95% CI, 1.36-1.53), VRE infection (OR, 1.18; 95% CI, 1.05-1.32), and the pooled rate of the 3 evaluated antibiotic-resistant infections (OR, 1.33; 95% CI, 1.30-1.36) but were not associated with C difficile infection (OR, 1.04; 95% CI, 0.94-1.16), stage 2 and 3 AKI (OR, 1.02; 95% CI, 0.96-1.10), or stage 3 AKI (OR, 1.06; 95% CI, 0.98-1.14). Documented BL allergies were not associated with the long-term odds of mortality but were associated with antibiotic-resistant infections. Health systems should emphasize accurate allergy documentation and reduce unnecessary BL avoidance.

Brucine Sulfate, a Novel Bacteriostatic Agent in 3D Printed Bone Scaffold Systems.

Bacterial infection is a common complication in bone defect surgery, in which infection by clinically resistant bacteria has been a challenge for the medical community. Given this emerging problem, the discovery of novel natural-type inhibitors of drug-resistant bacteria has become imperative. Brucine, present in the traditional Chinese herb Strychnine semen, is reported to exert analgesic and anti-inflammatory effects. Brucine's clinical application was limited because of its water solubility. We extracted high-purity BS by employing reflux extraction and crystallization, greatly improved its solubility, and evaluated its antimicrobial activity against E. coli and S. aureus. Importantly, we found that BS inhibited the drug-resistant strains significantly better than standard strains and achieved sterilization by disrupting the bacterial cell wall. Considering the safety concerns associated with the narrow therapeutic window of BS, a 3D BS-PLLA/PGA bone scaffold system was constructed with SLS technology and tested for its performance, bacteriostatic behaviors, and biocompatibility. The results have shown that the drug-loaded bone scaffolds had not only long-term, slow-controlled release with good cytocompatibility but also demonstrated significant antimicrobial activity in antimicrobial testing. The above results indicated that BS may be a potential drug candidate for the treatment of antibiotic-resistant bacterial infections and that scaffolds with enhanced antibacterial activity and mechanical properties may have potential applications in bone tissue engineering.

Analysis of Antibiotics in Milk from Smallholder Farmers from Kenya Shows Traces Above the Recommended Maximum Residue Limits

Antimicrobial resistance (AMR) is rising globally and is likely to cause more deaths because of antibiotic-resistant microbial infections and antibiotic residues in animal foods and products as a result of misuse of antibiotics in dairying. Thus, we determined the presence and quantities of sulfonamide, tetracycline, and beta-lactam drug residues in milk sampled in Nyandarua, Meru, and Kiambu counties in Kenya using the Charm TRIO® test kit and liquid chromatography (LC) coupled to the triple quadrupole mass spectroscopy (MS) (LC-MS/MS). The TRIO® test kit showed dicloxacillin as the most prevalent at 9.3%, followed by penicillin and cloxacillin at 3.7% each, and nafcillin at 0.9% among the beta-lactams. Among the tetracyclines, demeclocycline and tigecycline were the most prevalent at 10.3% each, followed by oxytetracycline at 9.3%, chlortetracycline at 7.5%, and doxycycline at 3.7%, while sulfaquinoxaline was the only sulfonamide drug detected at 4%. The LC-MS/MS detected the presence of all the tested β-lactam and tetracycline antimicrobial traces and all sulfonamide drugs except sulfamerazine in all three counties. All the tetracycline antibiotics recorded between 3 and 10.5% of antibiotic residues above the recommended Maximum Residue Levels (MRLs) in milk across all three counties, with beta-lactam antibiotics recording between 2 and 33.3%, indicating their misuse in the three counties. Sulfaquinoxaline was the only sulfonamide detected in milk samples above the recommended MRLs, indicating sulfonamides are less used in those counties. Therefore, it is important to enforce a regulatory framework to control antibiotic use in livestock to minimize potential health risks related to their traces in the foods.

Current and emerging strategies to curb antibiotic-resistant urinary tract infections.

Rising rates of antibiotic resistance in uropathogenic bacteria compromise patient outcomes and prolong hospital stays. Consequently, new strategies are needed to prevent and control the spread of antibiotic resistance in uropathogenic bacteria. Over the past two decades, sizeable clinical efforts and research advances have changed urinary tract infection (UTI) treatment and prevention strategies to conserve antibiotic use. The emergence of antimicrobial stewardship, policies from national societies, and the development of new antimicrobials have shaped modern UTI practices. Future UTI management practices could be driven by the evolution of antimicrobial stewardship, improved and readily available diagnostics, and an improved understanding of how the microbiome affects UTI. Forthcoming UTI treatment and prevention strategies could employ novel bactericidal compounds, combinations of new and classic antimicrobials that enhance bacterial killing, medications that prevent bacterial attachment to uroepithelial cells, repurposing drugs, and vaccines to curtail the rising rates of antibiotic resistance in uropathogenic bacteria and improve outcomes in people with UTI.

Nanoantibiotics: A Tool Against Antimicrobial Resistance

Antimicrobial Resistance (AMR), is one of the biggest emerging threats to human health and healthcare systems. Experts are suggesting that the post-antibiotic era, in which microbial infections and minor injuries will again become fatal, is near. A report published by the Antibiotics Resistance Collaborators, in the Lancet,reported that 1.27 million people died due to antibiotic-resistant bacterial infections in 2019.1 Deaths could reach 10 million by 2050 if the problem is not addressed. Antimicrobial resistance arises as a natural adaptation of microorganisms to environmental challenges. One typical self-defense mechanism is by producing enzymes that inactivate antimicrobial agents. Bacteria can also become resistant to β-lactams by producing β-lactamase, and by altering binding sites for antimicrobials agents (resistance to glycopeptide antibiotic agents), expressing multidrug efflux pumps such as tigecycline resistance to Acinetobacter baumannii, and limiting cell permeability for antibiotics such as Acinetobacter baumannii and pseudomonas aeruginosa.2,3th In the early 20 century, infectious diseases were the major cause of death. The advent of antibiotics led to a significant decrease in mortality.4 However, antibiotics resistance has now reached a threshold that is invalidating commonly used antibiotic agents. Currently the attempts to manage microbial resistance to antibiotics include the development of novel antimicrobial agents. However, there is no guarantee that the introduced new antimicrobial agents would be able to cope with the microbial resistance effectively andefficiently.5 Apart from developing new antibiotics, the chemical modification of existing antimicrobial agents is emerging as an upcoming strategy to combat antimicrobial resistance.4-6 Research on the effect of antibiotic associated nanoparticles on bacterial function is being conducted with the hope that advances in nanotechnology will lead to strategies for reconfiguration of presently available antibiotic molecules.Several nanomaterials have been identified as alternates for combating antimicrobial resistant strains. Each metallic and ceramic nanomaterials and more specifically their nanoparticles have their own peculiar antimicrobial properties. Studies have reported that these nanoparticles can be surface-functionalized withantimicrobial agents or molecules to further enhance their antimicrobial efficacy.6 Engineering antibiotics into nanoscale or functionalizing nanoparticles with antibiotic agents allows them to penetrate microbial cells and reach their target sites with precision and accuracy. Studies have shown that in contrast to free antibiotics, tailored functionalized nanoparticles and small antibiotic molecules have improved binding affinities andtarget specificity.6 Currently, these nanotechnology-based solutions have reported some problems like cytotoxicity, targeted selectivity, and bulk production. However, with concrete planning and a cohesive approach from academia, industry, and government, the development of nanoantibiotics drugs of unique shapes and sizes, high surface areas, ability to carry antibiotic drugs to target sites, and protein disruption will help overcome antimicrobial resistance. Editor-in-Chief How to cite this: Alamgir W, Adnan H. Nanoantibiotics: A Tool Against Antimicrobial Resistance. Life and Science. 2024; 5(2): 130-131. doi: http://doi.org/10.37185/LnS.1.1.657

Novel pentafluorosulfanyl-containing triclocarban analogs selectively kill Gram-positive bacteria.

The rise of antibiotic resistance among bacterial pathogens poses a significant threat to global health, underscoring the urgent need for novel antimicrobial agents. This study presents research on a promising class of novel compounds with potent antibacterial properties against Gram-positive bacteria, notably Staphylococcus aureus and MRSA. What sets these novel analogs apart is their superior efficacy at substantially lower concentrations compared with commonly used antibiotics like ciprofloxacin and gentamycin. Importantly, these compounds act by disrupting the bacterial cell membrane, offering a unique mechanism that could potentially circumvent existing resistance mechanisms. Preliminary safety assessments also highlight their potential for therapeutic use. This study not only opens new avenues for combating antibiotic-resistant infections but also underscores the importance of innovative chemical approaches in addressing the global antimicrobial resistance crisis.

Increasing Antibiotic-Resistant Infections With Inpatient Endoscopic Retrograde Cholangioscopies (ERCP) Is Associated With Higher Mortality in the United States: A Cross-sectional Cohort Study.

This study aims to investigate associated mortality with inpatient endoscopic retrograde cholangiopancreatography (ERCP) with and without resistant infections. The co-primary objective compares frequencies of inpatient ERCP with resistant infections to overall hospitalizations with resistant infections. The risks of inpatient antibiotic-resistant organisms are known, but the associated mortality for inpatient ERCP is unknown. We aim to use a national database of hospitalizations and procedures to understand trends and mortality for patients with antibiotic-resistant infections during inpatient ERCP. The largest publicly available all-payer inpatient database in the United States (National Inpatient Sample) was used to identify hospitalizations associated with ERCPs and antibiotic-resistant infections for MRSA, VRE, ESBL, and MDRO. National estimates were generated, frequencies were compared across years, and multivariate regression for mortality was performed. From 2017 to 2020, national weighted estimates of 835,540 inpatient ERCPs were generated, and 11,440 ERCPs had coincident resistant infections. Overall resistant infection, MRSA, VRE, and MDRO identified at the same hospitalization of inpatient ERCPs were associated with higher mortality (OR CI(95%): Overall: 2.2(1.77-2.88), MRSA: 1.90 (1.34-2.69), VRE: 3.53 (2.16-5.76), and MDRO: 2.52 (1.39-4.55)). While overall hospitalizations with resistant infections have been decreasing annually, there has been a yearly increase in admissions requiring ERCPs with simultaneous resistant infections ( P =0.001-0.013), as well as infections with VRE, ESBL, and MDRO ( P =0.001-0.016). Required Research Practices for Studies Using the NIS scoring was 0, or the most optimal. Inpatient ERCPs have increasing coincident resistant infections and are associated with higher mortality. These rising infections during ERCP highlight the importance of endoscopy suite protocols and endoscopic infection control devices.

Antimicrobial combination effects against multidrug-resistant Acinetobacter baumannii and Pseudomonas aeruginosa strains: A cross-sectional study.

Emergence of multidrug resistance in non-fermenting Gram-negative bacilli is a threat to public health. Combination therapy is a strategy for the treatment of antibiotic-resistant infections. In this cross-sectional study, a total of 63 nonduplicate clinical isolates of Acinetobacter baumannii and Pseudomonas aeruginosawere collected from various specimens. Identification of bacterial isolates was performed by phenotypic and molecular tests. Antibiotic susceptibility patterns and detection of β-lactamase genes were determined using the broth microdilution and polymerase chain reaction (PCR) techniques, respectively. Then, the combined effects analysis was determined by the checkerboard method. Based on the status of resistance to carbapenems (imipenem and meropenem), 25 isolates of each genus were selected for further investigation. For A. baumannii, bla OXA-23, bla OXA-58, and bla OXA-48 genes were positive in 21 (84%), 17 (68%), and 11 (44%) of isolates, respectively. In P. aeruginosa isolates, bla VIM was the most common gene (44%) and other genes including bla IMP, bla NDM, and bla OXA-23 were found in nine (36%), six (24%), and three (12%) isolates, respectively. Meropenem (MER)-tigecycline (TIG) had a significant synergistic effect against 20 (80%) A. baumannii (pvalue < 0.001). This combination was also efficient against 5 (20%) P. aeruginosa isolates. Moreover, the other combination, tigecycline-amikacin (TIG-AMK) was effective against 10 (40%) A. baumannii isolates. The combination of colistin (COL) and MER showed a significant synergistic effect against 21 (84%) A. baumannii (pvalue < 0.001) and 17 (68%) P. aeruginosa isolates (pvalue < 0.001). The MER-TIG and COL-MER combinations are promising options against resistant bacteria. Our study could be helpful for the development of a new treatment recommendation.

Relationship Between Biophysical Properties of Antimicrobial Peptides (AMPs) and their Associated Drug Efficacies

Antibiotic resistance is a growing global health threat. One consequence is that patients with cystic fibrosis (CF) are prone to developing antibiotic resistant lung infections caused by multiple strains of bacteria, including Pseudomonas aeruginosa. Due to the limited number of treatment options for patients with chronic antibiotic resistant infections, there is a need for finding new antibiotics that allow for effective eradication of bacterial infections, such as those in the CF lung. Many antimicrobial peptides (AMPs) have been annotated in databases and are considered as potential alternatives for current antibiotics. However, in many instances, the suitability of AMPs as drug molecules has not been extensively explored. Here, we propose that certain molecular properties of AMPs favor high antibiotic efficacy. Using information from AMP databases, we combined statistical analyses and machine learning techniques to identify relationships between various biophysical properties of AMPs and their drug efficacies. Analyses from classification and regression trees (CART) and random forests suggest that net charge and maximum average hydrophobic moment are the most important properties in determining if a peptide is useful against P. aeruginosa infections in CF patients. Maximum average hydrophobic residue, average alpha helix propensity score, hydrophobic proportion, and peptide length still contribute to this determination but to lesser degrees. Cation-pi interactions, on the other hand, do not appear to factor into this decision at all. Based on these properties, our current work is focused on designing and experimentally testing new peptides that may have activity against P. aeruginosa infections.

Investigation of the Antibacterial Synergistic Activity of Fosfomycin-Teicoplanin Combination in Methicillin-Resistant Staphylococcus aureus Strains Isolated from Various Clinical Sample

The aim of this study was to investigate the detection of teicoplanin and fosfomycin antibiotic susceptibility of methicillin-resistant Staphylococcus aureus (MRSA) strains by different methods and to evaluate the antibacterial synergistic effect of teicoplanin-fosfomycin combination by using checkerboard assay and time kill curve assay. Forty-five MRSA strains isolated from clinical samples in routine medical microbiology laboratory of Göztepe Prof. Dr. Süleyman Yalçın City Hospital were included in the study. In the first stage of the combination study, minimum inhibitory concentrations (MIC) were investigated by broth microdilution for teicoplanin and by both broth microdilution and agar dilution methods for fosfomycin. The combination of teicoplanin and fosfomycin was tested by the checkerboard method in 45 MRSA strains and combination effect was determined according to fractional inhibitory concentration index (ΣFIC) calculation. The synergistic effect and bactericidal activity of antibiotic combination were studied against a randomly selected strain from the strains used in the study by using time-kill method for 24 hours. As a result of teicoplanin and fosfomycin antibiotic susceptibility studies, all isolates were found to be susceptible to both antibiotics according to the susceptibility breakpoints determined by the European Committee on Antimicrobial Susceptibility Testing (EUCAST). A synergistic effect was found in 22 (49%), additive effect in 22 (49%) and indifferent effect in one (2%) of the 45 strains studied with the checkerboard method. The mean ΣFIC of 45 isolates was found to be 0.5. In the combination study of the antibiotics of the isolate that was studied with time-kill method, synergism was detected for 1/8 MIC concentrations at 12th hour and 24th hour and synergism at 1/4 MIC concentration at sixth hour, 12th hour and 24th hour. In the combination study of 1/4 MIC concentrations of antibiotics, bactericidal effect was detected at sixth hour and this effect was observed to disappear at 12th and 24th hours. High rate of synergistic antibacterial effect of teicoplanin-fosfomycin combination on MRSA isolates was demonstrated as a result of in vitro tests. Such studies conducted on antibiotic-resistant bacterial infections will provide clinicians different treatment options and will contribute to increasing survival. As a result of this study, provided that it is supported by future clinical studies, it can be stated that the teicoplanin-fosfomycin combination may be an effective treatment option in community and hospital-acquired infections caused by MRSA.

Use of the Naturally Occurring Bacteriophage Grouping Model for the Design of Potent Therapeutic Cocktails.

The specificity of phages and their ability to evolve and overcome bacterial resistance make them potentially useful as adjuncts in the treatment of antibiotic-resistant bacterial infections. The goal of this study was to mimic a natural grouping of phages of interest and to evaluate the nature of their proliferation dynamics with bacteria. We have, for the first time, transferred naturally occurring phage groups directly from their sources of isolation to in vitro and identified 13 P. aeruginosa and 11 K. pneumoniae phages of 18 different genera, whose host range was grouped as 1.2-17%, 28-48% and 60-87%, using a large collection of P. aeruginosa (n = 102) and K. pneumoniae (n = 155) strains carrying different virulence factors and phage binding receptors. We introduced the interpretation model curve for phage liquid culturing, which allows easy and quick analysis of bacterial and phage co-proliferation and growth of phage-resistant mutants (PRM) based on qualitative and partially quantitative evaluations. We assayed phage lytic activities both individually and in 14 different cocktails on planktonic bacterial cultures, including three resistotypes of P. aeruginosa (PAO1, PA14 and PA7) and seven K. pneumoniae strains of different capsular serotypes. Based on the results, the natural phage cocktails designed and tested in this study largely performed well and inhibited PRM growth either synergistically or in proto-cooperation. This study contributes to the knowledge of phage behavior in cocktails and the formulation of therapeutic phage preparations. The paper also provides a detailed description of the methods of working with phages.

Molecular insights into quercetin-enhanced crystalline silver nanoparticles: Implications for breast cancer cell cytotoxicity and antibacterial action in Kyllinga nemoralis

Amidst the ongoing global health crisis posed by cancer and antibiotic-resistant infections, innovative solutions are in high demand. The utilization of Kyllinga nemoralis leaf (KNL) extracts for synthesizing silver nanoparticles (AgNPs) represents a novel approach, with the potential to deliver profound advancements in healthcare, benefitting society on a broad scale. Successful synthesis of AgNPs by KNL extracts for treating breast cancer cells, specifically MDA-MB-231 cells, is recorded in this report. The adsorption mechanism of quercetin (Q) on Ag and its optimized structural characteristics were computed at the DFT level. According to FTIR analysis, quercetin, one of the flavonoids found in KNL extract, acts as a reducing and stabilizing agent for the conversion of Ag+ ions to Ag0, and carboxylates serve as ligands that cap the AgNPs. The small-sized (7 nm), spherical particles, which are uniform in size and monodispersed, exhibit regulation over the size of the AgNPs due to being shielded by enough flavonoids and gallic acid absorbed into the extract. The observed negative zeta potential of −20 mV indicates the moderate stability of the AgNPs colloid. It is noted that AgNPs prepared at higher concentrations of KNL extract showed lower minimum inhibitory concentration (MIC) values (80 µg/mL) and larger inhibition zones (22 mm) against Pseudomonas aeruginosa. The cell viability rate of MDA-MB-231 cell lines decreases with increasing concentration of AgNPs. The antibacterial and anticancer activity of AgNPs is observed in a size-dependent manner. This research raises the possibility of using plant-based, small-sized AgNPs therapeutically for breast cancer and as antibacterial agents.

Selective antibacterial and antibiofilm activity of chlorinated hemicyanine against gram-positive bacteria

Antibiotic-free therapies are highly needed due to the limited success of conventional approaches especially against biofilm related infections. In this direction, antimicrobial phototherapy, either in the form of antimicrobial photothermal therapy (aPTT) or antimicrobial photodynamic therapy (aPDT), have appeared to be highly promising candidates in recent years. These are local and promising approaches for antibiotic resistant bacterial infections and biofilms. Organic small photosensitizers (PSs) are extensively preferred in antimicrobial phototherapy applications as they offer a great opportunity to combine therapeutic action (aPTT, aPDT or both) with fluorescence imaging on a single molecule. In this study, the bactericidal effect of cationic chlorinated hemicyanine (Cl-Hem)-based type I PS, which can function as a dual aPDT/aPTT agent, was investigated on both planktonic cells and biofilms of different gram-positive (E. faecalis and S. epidermidis) and gram-negative bacteria (P. aeruginosa and K. pneumoniae) with and without 640 nm laser irradiation. Cl-Hem was shown to induce a selective phototheranostic activity against gram-positive bacteria (E. faecalis and S. epidermidis). Cl-Hem exhibited both dose and laser irradiation time dependent bactericidal effect on planktonic and biofilms of S. epidermidis. These results clearly showed that highly potent Cl-Hem can treat resistant microbial infections, while allowing fluorescence detection at the same time. High biofilm reduction observed with combined aPDT/aPTT action of Cl-Hem together with its non-cytotoxic nature points out that Cl-Hem is a promising PS for antibacterial and antibiofilm treatments.

Medicinal and immunological aspects of bacteriophage therapy to combat antibiotic resistance

Bacteriophages are viruses that infect bacterial cells and use their machinery to reproduce. This unique characteristic holds immense promise for combating antibiotic-resistant bacterial infections, a growing global threat. There are two types: one of them is named temperate phages, which inject their genomic material into bacteria and integrate into the host’s genome, while the second one is entitled as lytic phages that subdue the entire metabolism of the bacterium for the synthesis of its genome and proteins, including lytic proteins involved in breaking bacterial cell membrane and release of novel phages. In addition, phage therapy can be expressed through anti-biofilm activity and by triggering innate and adaptive immune cells responses. Moreover, no adverse effects of phage therapy have been reported. However, phage therapy is still grim for many and could influence some interpretations related to immune response, bacteriophage selections, and phage resistance in the future.

Antibiotic Resistance Mechanisms and Strategies for Combating Resistance in Germany

Purpose: The aim of the study was to explore antibiotic resistance mechanisms and strategies for combating resistance in Germany Methodology: This study adopted a desk methodology. A desk study research design is commonly known as secondary data collection. This is basically collecting data from existing resources preferably because of its low cost advantage as compared to a field research. Our current study looked into already published studies and reports as the data was easily accessed through online journals and libraries. Findings: antibiotic resistance represents a complex and evolving challenge to public health in Germany. Mechanisms such as efflux pumps, mobile genetic elements, and enzymatic degradation contribute to the resilience of bacteria against antibiotics. However, strategic interventions have been identified to combat resistance effectively. Exploration of alternative therapies like bacteriophage therapy offers promising avenues for addressing antibiotic-resistant infections, especially in light of increasing resistance rates. Unique Contribution to Theory, Practice and Policy: Evolutionary theory of antibiotic resistance &amp; Game Theory in Antibiotic Stewardship may be used to anchor future studies on antibiotic resistance mechanisms and strategies for combating resistance in Germany. Implement antimicrobial stewardship programs across healthcare settings to optimize antibiotic use. These programs should involve prescriber education, antibiotic guidelines, and regular audits to promote appropriate prescribing practices and minimize unnecessary antibiotic exposure. Prioritize infection prevention measures, including hand hygiene, environmental cleaning, and infection control protocols, to reduce the spread of resistant pathogens within healthcare facilities and communities. Enact policies to regulate the use of antibiotics in human health, veterinary medicine, and agriculture. This includes restrictions on antibiotic use in food production, bans on over-the-counter antibiotic sales, and incentives for the development of new antibiotics.

Combating Multidrug Resistance: The Potential of Antimicrobial Peptides and Biofilm Challenges

The escalating crisis of antibiotic resistance represents a formidable challenge to global public health, necessitating urgent and innovative solutions. This review delves into the multifaceted nature of antibiotic resistance, emphasizing the pivotal role of biofilms and the genetic mechanisms underpinning resistance in both Gram-positive and Gram-negative bacteria. A significant focus is placed on Staphylococcus aureus, particularly methicillin-resistant S. aureus (MRSA), and its mechanisms of resistance, including the SCCmec element and the agr quorum sensing system. The review also explores the alarming rise of resistance in Gram-negative pathogens, such as E. coli and K. pneumoniae, highlighting the perilous spread of extended-spectrum β- lactamases (ESBLs) and carbapenemases. Amidst this dire landscape, antimicrobial peptides (AMPs), particularly melittin from bee venom (BV), emerge as promising agents capable of breaching microbial defenses, including those of dormant cells within biofilms, thus offering a potential strategy to circumvent traditional resistance mechanisms. The review underscores the necessity of understanding bacterial survival strategies, such as biofilm formation and genetic adaptation, to develop effective countermeasures against antibiotic-resistant infections.