Broad Spectrum Research Articles

Chloramphenicol Interferes with 50S Ribosomal Subunit Maturation via Direct and Indirect Mechanisms.

Chloramphenicol (CAM), a well-known broad-spectrum antibiotic, inhibits peptide bond formation in bacterial ribosomes. It has been reported to affect ribosome assembly mainly through disrupting the balance of ribosomal proteins. The present study investigates the multifaceted effects of CAM on the maturation of the 50S ribosomal subunit in Escherichia coli (E. coli). Using label-free quantitative mass spectrometry (LFQ-MS), we observed that CAM treatment also leads to the upregulation of assembly factors. Further cryo-electron microscopy (cryo-EM) analysis of the ribosomal precursors characterized the CAM-treatment-accumulated pre-50S intermediates. Heterogeneous reconstruction identified 26 distinct pre-50S intermediates, which were categorized into nine main states based on their structural features. Our structural analysis highlighted that CAM severely impedes the formation of the central protuberance (CP), H89, and H58 during 50S ribosomal subunit maturation. The ELISA assay further demonstrated the direct binding of CAM to the ribosomal precursors, suggesting that the interference with 50S maturation occurs through a combination of direct and indirect mechanisms. These findings provide new insights into the mechanism of the action of CAM and provide a foundation for a better understanding of the assembly landscapes of the ribosome.

Monitoring concentration of quinolones in human serum by fluorescence and colorimetric analysis based on red carbon dots

Bacterial infections are common and predominant concern after surgical operation despite surgical techniques have improved significantly. Monitoring of antibiotics concentration can provide critical feedback in clinical treatment so as to achieve rapid and effective treatment and avoid bacterial resistance. Quinolones (QNs) are synthetic broad-spectrum antibiotics to treat bacterial infections. In this work, we developed a high-yield (50.67 %) red-emitting carbon dots (R-CDs) as fluorescence probe for sensing of three quinolone antibiotics, ofloxacin (OFL), gatifloxacin (GAT), and ciprofloxacin (CIP). R-CDs were prepared in 30 min using tartaric acid and o-phenylenediamine as precursors via an economical and efficient microwave-assisted method. At excitation of 339 nm, R-CDs show sensing performance towards OFL, GAT, CIP. Ofloxacin can be detected in the range of 0.25–30 μM with limit of detection (LOD) of 27.01 nM. Detection concentration range of gatifloxacin is between 0.25–40 μM and LOD is 23.73 nM. Ciprofloxacin can be detected in the range of 0.75–35 μM with LOD of 75.23 nM. A smartphone-assisted analysis platform was developed based on colorimetric phenomenon which applicable in three quinolones concentration monitoring in human serum. This research setup an efficient and promising therapeutic drug monitoring method for clinical treatment and widen the applications of carbon dots.

Primary Healthcare Physicians' Insufficient Knowledge Is Associated with Antibiotic Overprescribing for Acute Upper Respiratory Tract Infections in China: A Cross-Sectional Study.

Overuse of antibiotics in healthcare remains prevalent and requires urgent attention in China, particularly in primary healthcare (PHC) facilities. This study aimed to describe the patterns of antibiotic prescriptions for acute upper respiratory tract infections (URTIs) in PHC facilities in China and to investigate how PHC physicians' knowledge influences their antibiotic prescribing behavior. A cross-sectional survey linking physician questionnaire responses and their prescription data was conducted in Shaanxi Province, China. The proportions of URTI visits that received at least one antibiotic, combined antibiotics, and broad-spectrum antibiotics were the main outcomes reflecting antibiotic prescribing behavior. Multivariate mixed-effects logistic regressions were applied to analyze the relationship between PHC physicians' knowledge about antibiotics and their antibiotic prescribing behavior. A total of 108 physicians filled out the questionnaires between February 2021 and July 2021, and a sample of 11,217 URTI visits attended by these physicians from 1 January 2020 to 31 December 2020 were included in the analysis. The overall mean score of our respondents on the knowledge questions was 5.2 (total score of 10). Over sixty percent (61.2%; IQR 50.2-72.1) of the URTI visits received antibiotics. The percentages of URTI visits prescribed with combined and broad-spectrum antibiotics were 7.8% (IQR 2.3-10.2) and 48.3% (IQR 36.7-58.7), respectively. Third-generation cephalosporins were the most frequently used antibiotics. Physicians with lower antibiotic knowledge scores were more inclined to prescribe antibiotics (p < 0.001), combined antibiotics (p = 0.001), and broad-spectrum antibiotics (p < 0.001). Physicians' insufficient knowledge was significantly associated with antibiotic overprescribing. Professional training targeting physicians' knowledge of antibiotics is urgently needed to improve the rational use of antibiotics in grassroots healthcare facilities in China.

Exploring diflunisal as a synergistic agent against Staphylococcus aureus biofilm formation.

Staphylococcus aureus is a bacterial pathogen of considerable significance in public health, capable of inducing a diverse range of infectious diseases. One of the most notorious mechanisms used by S. aureus to survive and colonize the site of infection is its ability to form biofilms. Diflunisal, a non-steroidal anti-inflammatory drug (NSAID), is a known inhibitor of the Agr system in S. aureus, which is key in regulating biofilm formation. This study evaluated the effect of broad-spectrum antibiotics in combination with diflunisal on S. aureus biofilm density. Eight antibiotics were tested independently at different concentrations and in combination with diflunisal to assess their effect on S. aureus biofilm formation. When using the antibiotics alone and with diflunisal, a significant control effect on biofilm formation was observed (p < 0.05), irrespective of diflunisal presence, but did not achieve a complete biofilm growth inhibition. Over time, diflunisal influenced biofilm formation; however, such an effect was correlated with antibiotic concentration and exposure time. With amikacin treatments, biofilm density increased with extended exposure time. In the case of imipenem, doripenem, levofloxacin, and ciprofloxacin, lower doses and absence of diflunisal showed higher control over biofilm growth with longer exposure. However, in all cases, diflunisal did not significantly affect the treatment effect on biofilm formation. In the absence of antibiotics, diflunisal significantly reduced biofilm formation by 53.12% (p < 0.05). This study suggests that diflunisal could be a potential treatment to control S. aureus biofilms, but it does not enhance biofilm inhibition when combined with antibiotics.

Adoption of clinical pharmacist roles in primary care: Longitudinal evidence from English general practice.

Over the last decade, the number of clinical pharmacists working within multidisciplinary teams in English general practice has expanded Aim: This study examines changes in quality of prescribing after the adoption of clinical pharmacists in English general practices. Two-way fixed effects regression was used to compare differences in prescribing indicators in general practices in England with and without pharmacists following implementation between September 2015 and December 2019 Results: Between September 2015 and December 2019, the proportion of practices employing a clinical pharmacist increased from 236/ 7,623 (3.10%) to 1,402/ 6,836 (20.51%). Clinical pharmacist implementation resulted in statistically significant reductions in total costs of medicines per 1,000 patients (-0.85% ,95% CI -1.50%, -0.21%), the total number of opioid prescriptions per 1,000 patients (- 1.06%, 95% CI -1.82%, -0.29%), and the average daily quantity (ADQs) of anxiolytics per 1,000 patients (-1.26%, 95% CI -2.40%, -0.12%). Clinical pharmacist implementation also resulted in reductions in the total number of prescriptions per 1,000 patients (-0.58%, 95% CI -1.30%, 0.13%), and the total number of antibiotic prescriptions per 1,000 patients (-0.51%, 95% CI -1.30%, 0.27%) that trended towards statistical significance. There were no statistically significant differences in the share of broad-spectrum versus narrow-spectrum antibiotics (0.02%, 95% CI -0.07%, 0.11%) and the oral morphine equivalence of high-dose opioids (>120mg per 24 hours) per 1,000 patients (1.19%, 95% CI -0.46%, 2.85%). Our analysis is limited by aggregate data at the practice-level but supports the hypothesis that clinical pharmacist implementation results in improvements in prescribing quality.

Enhancement in the antibacterial activity of Rifaximin by delivery through gelatin nanoparticles

Objectives Bacterial infections are a noteworthy global health concern that necessitates the development of new strategies to enhance the potency and efficacy of antibiotics. Rifaximin (RFX), a broad-spectrum antibiotic, exhibits promising antibacterial activity against several bacterial strains. However, its insolubility and impermeability impede the exploitation of its full potential. The objective of the current study is to overcome the inherent caveats of RFX to exploit its maximum potential. Significance The exploitation of the full potential of antibiotics is necessary for reduction in their dosage and to minimize antibiotic pollution. This is a preliminary study aiming for maximum utilization of RFX at the target site and reduction in its release in unmetabolized form. Methods Gelatin is a biopolymer that has gained significant attention for biomedical applications owing to its inherent biocompatibility and biodegradability. In this study, bovine gelatin nanoparticles (BGNPs) were fabricated by the self-assembly method for their application as a carrier of RFX to enhance its antibacterial activity. The study employs a comprehensive range of experimental techniques to characterize the fabricated BGNPs such as DLS, Zeta Potential, FT-IR, AFM, SEM-EDX, and UV-Vis spectrophotometry. Results The average size of the fabricated BGNPs was 100 nm with a zeta potential value of −15.3 mV. The loading of RFX on BGNPs rendered an increase in its size to 136 nm with a zeta potential value of −16 mV. In-vitro assays and microscopic analyses were conducted to compare the antibacterial efficacy of RFX and RFX@BGNPs. An excellent loading capacity followed by sustained release of RFX from RFX@BGNPs rendered a significant enhancement in its pharmaceutical efficacy. The release of RFX from RFX@BGNPs followed the Higuchi and Korsmeyer-Peppas models. The antibacterial efficacy of RFX against Staphylococcus aureus has doubled by delivery through RFX@BGNPs, assessed by inhibitory and biofilm inhibitory assays. The enhancement in the antibacterial efficiency was further endorsed by SEM and microscopic imaging of the control and treated bacterial colonies. Conclusion The study demonstrates an enhancement in the antimicrobial efficacy of RFX by its delivery in the form of RFX@BGNPs to exploit its full potential for practical applications.

Optimization of the Central α-Amino Acid in Cystobactamids to the Broad-Spectrum, Resistance-Breaking Antibiotic CN-CC-861.

Cystobactamids have a unique oligoarylamide structure and exhibit broad-spectrum activity against Gram-negative and Gram-positive bacteria. In this study, the central α-amino acid of the cystobactamid scaffold was modified to address the relevance of stereochemistry, hydrogen bonding and polarity by 33 derivatives. As demonstrated by three matched molecular pairs, l-amino acids were preferred over d-amino acids. A rigidification to a six-membered system stabilized the bioactive conformation for the on-target Escherichia coli gyrase, but did not improve antimicrobial activity. Compound CN-CC-861, carrying a propargyl side chain, had more than 16-fold lower minimal inhibitory concentration (MIC) values against Enterococcus faecalis, Staphylococci and Acinetobacter strains, compared to known analogues. Moreover, CN-CC-861 retained activity against multidrug-resistant enterococci, displayed strong bactericidal activity, moderate-low frequencies of resistance and in vivo efficacy in a neutropenic thigh infection model with E. coli. Overall, the findings will guide the design of new promising structures with higher activities and broader spectrum.

Highly efficient and broad-spectrum antibacterial carbon dots combat antibiotic resistance

Bacterial infections have become a major global public health issue, particularly with the emergence of multidrug-resistant strains. Therefore, developing non-antibiotic antimicrobial agents is crucial for treating drug-resistant bacterial infections. Building on previous research into natural products as novel antibacterial agents, this study synthesized curcumin-derived carbon dots using curcumin and ethylenediamine as raw materials through a hydrothermal method. The resulting carbon dots not only improved the water solubility and stability of curcumin but also exhibited highly efficient broad-spectrum antibacterial activity. Detailed investigations into the antibacterial performance and mechanisms of the carbon dots were conducted through experiments such as minimum inhibitory concentration (MIC) determination, live/dead bacterial staining, morphological studies, nucleic acid concentration detection, and reactive oxygen species (ROS) detection. The results indicated that the carbon dots significantly damaged the structural integrity of bacteria and generated large amounts of ROS. They exhibited remarkable antibacterial effects against Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus, and effectively inhibited drug-resistant MRSA. Their antibacterial efficacy was notably superior to that of broad-spectrum antibiotics such as chloramphenicol and Sulfadiazine. This study highlights the potential application of curcumin-derived carbon dots in combating bacterial infections and provides valuable insights for developing novel antibacterial agents derived from natural products.

Species distribution, antifungal susceptibility pattern and associated factors of Candida blood stream infections in Sri Lanka from 2018 to 2022

Introduction: Candidemia can be life-threatening in immunocompromised individuals thus, prompt diag-nosis and treatment with antifungal agents is mandatory for successful outcome.Surveillance data on species distribution, antifungal susceptibility and associated factors of candidemia is utmost important to decide on empiric antifungal therapy, to impose infection control measures as well to promote antifungal stewardship in a country.Therefore, this study was aimed at retrospective review of data on candidemia at Mycology Reference Laboratory in Sri Lanka for 5 years duration to identify the species causing candidemia, their antifungal susceptibility pattern and associated factors.Results: A twofold rise in candidemia cases were seen during this 5-year duration compared to previous 7 years (2011-2017). Predominant species causing candidemia was C. tropicalis (35%) followed by C. parapsilosis (33%). C. albicans was the 3rd commonest species causing candidemia in Sri Lanka.There were 3% C. glabrata cases, 2% C. guilliermondii and 1% C. famata and C. krusei cases. Importantly two sequencing confirmed C. auris cases were identified for the first time in Sri Lanka in 2021.Overall good antifungal susceptibility was seen for both fluconazole and amphotericin B and there were only 7%and 1.6% resistance respectively.Long term hospital stay (47%) was commonly seen in this study group followed by use of broad-spectrum antibiotics (24%) and involvement of gastro-intestinal tract (21%).Conclusion: Candida tropicalis is the commonest species causing candidemia in Sri Lanka. Common Candida species had good susceptibility to antifungals. Long term hospital stay was associated with candidemia in majority of patients.

Scrotoschisis: Management Challenges and Review of Literature.

Scrotoschisis (extracorporeal testicular ectopia) is a rare congenital defect of the scrotal sac associated with the extrusion of one or both testicles. The exact mechanism causing the anomaly is largely unknown. This is a report of two infants aged 3 and 4 days, respectively, presented with infected unilateral extracorporeal testicular ectopia. Both infants had orchidopexy and repair of the scrotal defect following debridement of the infected defects and administration of broad-spectrum parenteral antibiotics. The infants have remained well at 3 years of follow-up. The isolated unilateral disease was described by several authors. Delayed presentation in scrotoschisis results in superimposed infection which complicates surgical management resulting in a prolonged hospital stay.

Residue depletion profiles and withdrawal intervals of florfenicol and its metabolite florfenicol amine in plasma and milk of lactating goats after repeated subcutaneous administrations

Florfenicol is a broad-spectrum and bacteriostatic antibiotic with a time-dependent killing action. It is commonly used to treat respiratory diseases in goats in an extra-label manner. This study aimed to determine the plasma pharmacokinetics and milk residue depletion profiles and calculate the milk withdrawal interval (WDI) of florfenicol and its main metabolite florfenicol amine in lactating goats. Five healthy lactating goats were administered with 40 mg/kg florfenicol by subcutaneous injection, twice, 96 h apart. Plasma and milk samples were collected up to 864 h post the first injection. Non-compartmental analysis was used to estimate the plasma pharmacokinetic parameters. Milk WDIs were calculated using the U.S. Food and Drug Administration (FDA) method and European Medicines Agency (EMA) method. A Monte Carlo simulation was performed to generate simulated data for five virtual animals to meet the data requirement of the FDA method. The calculated milk WDIs based on florfenicol, florfenicol amine, and the combined (the sum of florfenicol and florfenicol amine) were 720.28, 690.45, and 872.69 h after the last injection using the FDA method. In conclusion, this study improves our understanding on the plasma pharmacokinetics and milk residue depletion kinetics of florfenicol and florfenicol amine in lactating ruminants after subcutaneous injections.

Appropriate antimicrobial prescribing for bacteriuria before urological procedures: A room for improvement

In the presence of a positive preoperative urine culture, the prescription of a preoperative antibiotic therapy is recommended. The choice of antibiotic therapy and prescription are usually made by the urologist or the general practitioner (GP). The objective of the treatment is urinary sterilization rather than parenchymal treatment, and the treatment choice is key to reduce selective pressure and antimicrobial resistance. The objective of this study was to evaluate prescription patterns made by urologists and GPs, then to compare the antibiotics chosen by urologists or GPs to the “ideal” treatment defined by infectious diseases specialists. We retrospectively reviewed all positive preoperative urine cultures obtained between November 2022 and July 2023. Data pertaining to antibiotic prescriptions, including the duration of treatment, antibiotic class, and prescriber were collected. An infectious disease specialist conducted a blind review of each urine culture, providing recommendations for the most appropriate antibiotic based on their assessment. In cases of disagreement, a second infectious disease specialist conducted a similar evaluation. Out of 196 preoperative antibiotic prescriptions, 40 (20%) differed from the recommendations provided by the infectious disease specialist, with 39 involving the use of overly broad-spectrum antibiotics. Both infectious disease specialists yielded congruent recommendations in all cases. Notably, in 50% of these instances, the preoperative antibiotic treatment duration unduly exceeded 48hours. A statistically significant increase (4.84days vs. 2.99days) in preoperative treatment duration was observed when a GP was the prescriber (P<0.001). There is room for improvement of urologists’ antibiotic prescription practices to reduce the ecological impact on the patient's microbiota and on a global scale. The delegation to GPs resulted in unjustified longer treatment durations and should be avoided without dedicated training. Level of evidence4.

Micronization of ciprofloxacin by the Supercritical Antisolvent (SAS) Technique

Ciprofloxacin is a broad-spectrum antibiotic that is proposed for pulmonary administration. In this work micronization of ciprofloxacin was performed by the Supercritical Antisolvent Technique (SAS) using ciprofloxacin base (CIP) in ethanol/acetic acid and ciprofloxacin hydrochloride salt (CIP·HCl) in methanol at 40–60 ºC and 100–150 bar. Yields ranged from 40 % to 90 %. CIP precipitated incorporating acetate whilst CIP·HCl precipitated as the AH1 anhydrous form. CIP and CIP·HCl particles exhibited an acicular morphology (0.2–0.9 μm wide × 1–4 μm long). Micronization adding lactose, PVP K-10 and K-30 modified the precipitate morphology. CIP·HCl:lactose and CIP·HCl:PVP K-30 at a 4:1 drug:excipient mass ratio precipitated like flakes. CIP·HCl:PVP K-10 precipitated as submicron globular particles suitable for oral formulation. Increasing the PVP content, the morphology changed to sheets and flakes, which could be used for pulmonary administration. The antibacterial activity of the samples for Staphylococcus epidermidis was confirmed.

The role of intestinal microbiota in physiologic and body compositional changes that accompany CLA-mediated weight loss in obese mice

ObjectiveObesity continues to be a major problem, despite known treatment strategies such as lifestyle modifications, pharmaceuticals, and surgical options, necessitating the development of novel weight loss approaches. The naturally occurring fatty acid, 10,12 conjugated linoleic acid (10,12 CLA), promotes weight loss by increasing fat oxidation and browning of white adipose tissue, leading to increased energy expenditure in obese mice. Coincident with weight loss, 10,12 CLA also alters the murine gut microbiota by enriching for microbes that produce short chain fatty acids (SCFAs), with concurrent elevations in fecal butyrate and plasma acetate. MethodsTo determine if the observed microbiota changes are required for 10,12 CLA-mediated weight loss, adult male mice with diet-induced obesity were given broad-spectrum antibiotics (ABX) to perturb the microbiota prior to and during 10,12 CLA-mediated weight loss. Conversely, to determine whether gut microbes were sufficient to induce weight loss, conventionally-raised and germ-free mice were transplanted with cecal contents from mice that had undergone weight loss by 10,12 CLA supplementation. ResultsWhile body weight was minimally modulated by ABX-mediated perturbation of gut bacterial populations, adult male mice given ABX were more resistant to the increased energy expenditure and fat loss that are induced by 10,12 CLA supplementation. Transplanting cecal contents from donor mice losing weight due to oral 10,12 CLA consumption into conventional or germ-free mice led to improved glucose metabolism with increased butyrate production. ConclusionsThese data suggest a critical role for the microbiota in diet-modulated changes in energy balance and glucose metabolism, and distinguish the metabolic effects of orally delivered 10,12 CLA from cecal transplantation of the resulting microbiota.

Outcome of Levofloxacin in the Treatment of Lower Respiratory Tract Infection

Background: Levofloxacin, a broad-spectrum fluoroquinolone antibiotic, is commonly used in treating lower respiratory tract infections (LRTIs) like pneumonia and chronic bronchitis. Its effectiveness lies in its ability to inhibit bacterial DNA gyrase, leading to bacterial cell death. Clinical outcomes of levofloxacin in LRTI treatment have generally been positive, with high rates of bacterial eradication and symptom resolution. Objective: The present research aimed to determine whether levofloxacin is an effective and safe option for treating lower respiratory tract infections. Method: From January 2022 to January 2023, researchers analyzed data from 120 patients with a lower respiratory tract infection at a tertiary hospital. Sixty patients were split evenly between a control group and an observation group. Levofloxacin was administered at the standard dosage to the control group and at a significantly higher dose to the observation group. Both the clinical efficacy and adverse reaction rates were compared and contrasted between the two groups statistically. Results: The cure rate in the observation group was 53.33 percent, which was substantially greater than the cure rate in the control group, which was 36.67 percent. There is a statistically significant difference between them (P 0.05). The overall efficacy rate of the observation group was 93.33%, significantly higher than that of the control group (73.33%). There is a statistically significant difference between them (P 0.05). There was no statistically significant difference (P&gt;0.05) between the two groups due to the low incidence of adverse responses in both the observation and control groups. Conclusion: This research demonstrates that large dosages of levofloxacin have a stronger clinical curative impact on treating lower respiratory infections than lesser doses. It is worthwhile to promote the widespread adoption of this technique since it has the potential to greatly enhance the quality of patient care

Emphysematous Pyelonephritis: Nephrectomy is not necessary, a narrative review

Emphysematous pyelonephritis (EPN) is a severe, life-endangering, necrotising, gas-producing infection affecting the kidney and perinephric tissue. It is associated with renal loss, high morbidity, and mortality. Diabetes, obstructive uropathy, female gender and hypertension are the most common risk factors. Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis are the most common pathogens causing Emphysematous pyelonephritis. EPN presents as a clinical triad of fever, flank pain, and nausea. Non-contrast CT scan is the mainstay of early diagnosis of EPN. It is diagnosed by demonstrating gas in renal parenchyma and perinephric tissue. Huang and Sang's classification is used for the classification and management of EPN. Treatment of EPN progressed from early nephrectomy to minimally invasive treatments including newer and advanced antibiotics and percutaneous drainage along with Percutaneous nephrostomy and DJ stenting. Early nephrectomy was the treatment of choice in the last century however newer studies suggest conservative treatment is associated with renal preservation, decreased morbidity and mortality. The initial use of broad-spectrum antibiotics such as Third-or fourth generation cephalosporins and carbapenems is recommended. Emergency drainage is indicated with a larger-sized pigtail catheter as pus is thick and frequent blockage of tubes is common. Nephrectomy should be done for those patients who fail to respond to conservative therapy i.e., antibiotics and percutaneous drainage. This review aims to provide comprehensive, evidence-based recommendations for the diagnosis and management of this life-threatening urological infection Emphysematous pyelonephritis. Keywords: Emphysematous pyelonephritis, Diabetes, Antibiotics, Conservative, Percutaneous drainage, Nephrectomy

Neonatal Infectious Disease: A Major Contributor to Infant Mortality Requiring Advances in Point-of-Care Diagnosis.

Neonatal infectious disease continues to result in high rates of infant morbidity and mortality. Early- and late-onset disease represent difficult to detect and difficult to treat illnesses, particularly when antimicrobial resistant pathogens are present. Newborns are immunodeficient and are at increased risk of vertical and horizontal infection, with preterm infants increasingly susceptible. Additional risk factors associated with infection include prolonged use of a central catheter and/or ventilation, congenital abnormalities, admittance to intensive care units, and the use of broad-spectrum antibiotics. There is increasing recognition of the importance of the host microbiome and dysbiosis on neonatal infectious disease, including necrotising enterocolitis and sepsis in patients. Current diagnostic methods rely on blood culture, which is unreliable, time consuming, and can result in false negatives. There is a lack of accurate and reliable diagnostic tools available for the early detection of infectious disease in infants; therefore, efficient triage and treatment remains challenging. The application of biomarkers, machine learning, artificial intelligence, biosensors, and microfluidics technology, may offer improved diagnostic methodologies. Point-of-care devices, such diagnostic methodologies, may provide fast, reliable, and accurate diagnostic aids for neonatal patients. This review will discuss neonatal infectious disease as impacted by antimicrobial resistance and will highlight novel point-of-care diagnostic options.

Antibiotic Prescribing Trends in Dentistry during Ten Years' Period-Croatian National Study.

Prescribing antibiotics is a regular part of daily dental practice. Antibiotics have a significant but a limited role in general dental practice due to the threat of emergence of antimicrobial resistance (AMR). As such, the aim of this study was to assess prescribing trends in dental antibiotics use from 2014-2023 in Croatia. Data on antibiotic prescribing practices for this study were provided by the Croatian Health Insurance Fund. The analysis included the number of prescriptions, packages, cost, and the World Health Organization's defined daily dose per 1000 inhabitants (DID) per day as an objective utilization for comparison. Over the 10-year period, dentists in Croatia prescribed an annual average of 357,875 antibiotic prescriptions, representing an annual average of 78.7% of all dental prescriptions. The most commonly prescribed antibiotic was the combination of amoxicillin and the beta-lactamase inhibitor clavulanic acid, which made up 58.54% of antibiotics and 46.1% of all dental prescriptions. This was followed by amoxicillin (12.61%), clindamycin (12.58%), and metronidazole (9.96%). The trend showed two discontinuations, the first for the pandemic years, and the second caused by disruption in amoxicillin production. The rise in the use of broad-spectrum antibiotics needs to be addressed and regulated to ensure patients and dentists understand that antibiotics are not a substitute for dental treatment. Dentists should always begin treatment with narrow-spectrum antibiotics regardless of possible exceptional circumstances.

Evaluating Antibiotic Misuse and Cost Analysis Among Hospitalized Dengue Virus-Infected Adults: Insights From a Retrospective Cohort Study.

Dengue is a prevalent cause of acute febrile illness, predominantly in Asia, where it necessitates supportive care without the need for antibiotics. This study aimed to evaluate antibiotic usage and analyze hospitalization costs among adults infected with the dengue virus. This retrospective cohort study was conducted at the Hospital for Tropical Diseases, Thailand, in 2022. Two independent reviewers assessed all adult cases with confirmed dengue from 2016 to 2021. Determinants of inappropriateness were analyzed using Poisson regression. The study included 249 participants with over half presenting with severe dengue or dengue with warning signs upon admission. The cumulative incidence of antibiotic use was 9.3% (95% CI, 8.23-10.47), predominantly involving empirical treatment strategies. Ceftriaxone and doxycycline were the most frequently prescribed antibiotics. Notably, patients who received empirical antibiotics showed no definite or presumed bacterial infections. Among those who received definite strategies, inappropriate durations, including both short treatments and the overuse of broad-spectrum antibiotics, were observed. A private ward admission was identified as a significant predictor of inappropriate use, with an incidence rate ratio of 4.15 (95% CI, 1.16-14.82) compared with intensive care unit admission. Direct medical costs did not differ significantly between appropriate and inappropriate uses. The incidence of antibiotic use among dengue cases was moderate; however, inappropriate use by indication was observed. Antimicrobial stewardship strategies should be encouraged, particularly in patients with dengue with warning signs admitted to a general or private ward. Direct medical costs between appropriate and inappropriate use were comparable.

An Engineered Nisin Analogue with a Hydrophobic Moiety Attached at Position 17 Selectively Inhibits Enterococcus faecium Strains.

Antibiotic resistance is one of the most challenging global public health concerns. It results from the misuse and overuse of broad-spectrum antibiotics, which enhance the dissemination of resistance across diverse bacterial species. Antibiotics like nisin and teixobactin do not target an essential protein and employ a dual mode of action antibacterial mechanism, thereby being less prone to induce resistance. There is a need for the development of a potent narrow-spectrum dual-mode-acting antibiotic against human pathogens. Using nisin, a lantibiotic with potent antimicrobial activity against many pathogens, as a template, the unnatural amino acid azidohomoalanine was introduced at selected positions and subsequently modified using click chemistry with 14 alkyne-moiety containing tails. A novel nisin variant, compound 47, featuring a benzyl group-containing tail, exhibited potent activity against various (drug-resistant) E. faecium strains with an MIC value (3.8 mg/L) similar to nisin, whereas its activity toward other pathogens like Staphylococcus aureus and Bacillus cereus was significantly reduced. Like nisin, the mode of action of compound 47 results from the inhibition of cell wall synthesis by binding to lipid II and nisin-lipid II hybrid-pore formation in the outer membrane. The resistance of compound 47 against proteolytic degradation is markedly enhanced compared to nisin. Like nisin, compound 47 was hardly hemolytic even at a very high dose. Collectively, a modified nisin variant is presented with significantly enhanced target organism specificity and stability.