Antibiotic Azithromycin Research Articles

Application of QuEChERS extraction and LC–MS/MS for determination of pharmaceuticals in sewage sludges sampled across the Czech Republic

AbstractThe use of pharmaceuticals entails a significant risk of environmental contamination. Wastewater treatment plants (WWTPs) are considered to be the main contributors to contamination as they ineffectively eliminate these compounds from wastewater. Simultaneously, they produce solid waste, sludge, which often contains a variety of retained pollutants, including pharmaceuticals. Since sewage sludge is frequently applied to agricultural soil due to its rich nutrient content, pollutants are introduced into the environment in this way. Only a few studies have been carried out on the topic of the analysis of pharmaceuticals in sludge. Therefore, information on the occurrence of pharmaceuticals in sludge is limited. The present study employed quick, easy, cheap, effective, rugged and safe (QuEChERS) extraction and liquid chromatography coupled with tandem mass spectrometry (LC–MS/MS) analysis to establish a simple and reliable procedure for determining 16 pharmaceuticals (antibiotics, anticonvulsants, antidepressants and β-blockers) in sewage sludge. The method has been thoroughly validated, and parameters such as linear range, accuracy, precision, matrix effects and detection and quantification limits were assessed. Our method achieved low limits of quantification (0.5–9.0 µg kg−1) and satisfactory recoveries (51–101%). Forty sludge samples from different WWTPs across the Czech Republic were analysed. Fourteen compounds were detected and quantified in most samples, with antidepressants having the highest detection frequency and overall content. Sertraline, with a mean concentration of 521.0 µg kg−1, was notably prevalent alongside its metabolite norsertraline (mean concentration 204.9 µg kg−1). The antibiotic azithromycin was also found at higher levels (mean concentration 185.1 µg kg−1).

Introducing nickel nanoparticles on boron-doped diamond electrode for realizing high performance electrochemical detection of azithromycin

The broad-spectrum antibiotic azithromycin (AZI) has been widely applied to suppress bacteria and fight infection. However, excessive use of AZI can cause serious side effects. It is greatly desirable to develop efficient and sensitive sensor devices for environmental monitoring and analysis of AZI. In this study, we develop the nickel (Ni) nanoparticle-modified boron-doped diamond (NiNPs-BDD) electrode to achieve high-performance electrochemical detection of AZI. The NiNPs-BDD electrode has square pits with Ni particles embedded in the pits, which provides higher sensitivity compared to unmodified BDD. The promoting performance is attributed to the synergistic effect of pitted features and Ni NPs on BDD electrode. The NiNPs-BDD electrode presents linear detection ranges in the wide concentration scales of 0.1–8 µM and 8–100 µM, and its limit of detection is 0.086 µM. In addition, the NiNPs-BDD electrode shows excellent repeatability, stability, and reproducibility with respect to most conventional electrodes.

Solubility Enhancement of BCS Class II Antibiotic (Azithromycin) by Solid Dispersion Technique by Using Skimmed Milk

Azithromycin has a low water solubility; Hence, dissolution represents a rate-limiting process. The goal of the present investigation is to improve azithromycin dissolution and solubility rate. The purpose of this study was to create, characterize, and test the dissolving characteristics of an Azithromycin solid dispersion with skimmed milk. Formulated tablet of optimized batch compared with marketed formulation and study its drug release and make a formulation that gives the highest rate of solubility. This experiment was conducted utilizing the solid dispersion method. The rationale for solid dispersion is that it produces better results than other methods while costing less. Skimmed milk is used as a carrier to increase the solubility of azithromycin. Azithromycin purity is certified using assessment tests such as HPLC assay, UV spectroscopy, FTIR, and DSC. Azithromycin solid dispersion (Azithromycin in skimmed milk) SD2 consistently performs well in all physiochemical tests as compared to all batches. The designed tablet F2 batch releases the drug more effectively than the marketed one. Azithromycin’s solubility was successfully enhanced by utilizing the solid dispersion method with skimmed milk. Batch SD 2 gives the highest results in all parameters like solubility. Preformulation study, mainly in tablet formulation, also it gives the highest solubility.

Insight into the corrosion inhibition mechanism of mild steel St1 in 2 M H2SO4 electrolyte by azithromycin

Mild steel is essential in modern industry due to its favorable mechanical properties and economic availability. However, its high susceptibility to corrosion, especially in acidic environments, poses a significant challenge, reducing service life, increasing operating costs, and raising the risk of failures. This study investigates the corrosion inhibition mechanism of mild steel St1 in a 2 M H2SO4 solution at various temperatures using the broad-spectrum antibiotic azithromycin (AZM). Experimental results indicate that AZM presence increases the polarization resistance of mild steel in the acidic solution. AZM acts as a mixed-type inhibitor, influencing the kinetics of both cathodic and anodic processes. The introduction of 200 mM AZM leads to an increase in the polarization resistance of the steel electrode in 2 M H2SO4 by up to 2.4 times. The inhibition mechanism involves forming a protective layer of protonated AZM forms on the negatively charged Fe surface. These protonated forms can also adsorb on cathodic areas, competing with hydronium ions (H3O+) and thereby inhibiting hydrogen evolution processes. The protective effect of AZM diminishes with increasing temperature of the corrosive environment, as confirmed by Monte Carlo simulations showing decreased adsorption energies for AZM and its protonated forms at higher temperatures. An assessment of the protective effect of 200 mM AZM showed that an increase in the temperature of the corrosive environment from 293 to 333 K leads to a decrease in the protective effect by almost 5.6 times. Quantum chemical calculations determined the reactivity of AZM and its protonated forms, identifying the molecular groups involved in the adsorption mechanism.

Synthesis, characterization, and evaluation of antibacterial and antifungal activities of CuO-ZnO-Co3O4 nanocomposites

The co-precipitation method was used to prepare CuO, ZnO, Co3O4 nanoparticles and CuO-ZnO-Co3O4 nanocomposite. The structural, morphological, and optical properties of the prepared samples were studied using X-ray diffraction (XRD), total reflection X-ray fluorescence (TXRF), transmission electron microscopy (TEM), selected area electron diffraction (SAED), diffuse reflectance spectroscopy (DRS), and zeta potential. XRD analysis revealed that the crystal structures of CuO, ZnO, and Co3O4 nanoparticles are monoclinic, hexagonal, and cubic, with average crystallite sizes of 30.8 nm, 31.8 nm, and 32.8 nm, respectively. For CuO-ZnO-Co3O4 nanocomposites, the corresponding sizes were 24.9 nm, 13.6 nm, and 16.1 nm. The optical bandgaps of CuO, ZnO, Co3O4 nanoparticles, and CuO-ZnO-Co3O4 nanocomposites were 1.5 eV, 3.14 eV, 1.2 eV, and 1.3 eV, respectively. In this study, the antibacterial activity of CuO-ZnO-Co3O4 nanocomposite against Gram-negative bacteria (E. coli, Klebsiella, pseudomonas, and Salmonella) and Gram-positive bacteria (Staphylococcus aureus) was investigated and compared with the antibiotic Azithromycin. In addition, the effect of the nanocomposite on fungi was studied and compared with the antifungal Mystatin.

New Zein Protein Composites with High Performance in Phosphate Removal, Intrinsic Antibacterial, and Drug Delivery Capabilities.

Herein, poly(N-(4-aminophenyl)methacrylamide)-carbon nano-onions [abbreviated as PAPMA-CNOs (f-CNOs)] integrated gallic acid cross-linked zein composite fibers (ZG/f-CNOs) were developed for the removal/recovery of phosphate from wastewater along with controlled drug delivery and intrinsic antibacterial characteristics. The composite fibers were produced by Forcespinning followed by a heat-pressure technique. The obtained ZG/f-CNOs composite fibers presented several favorable characteristics of nanoadsorbents and drug carriers. The composite fibers exhibited excellent adsorption capabilities for phosphate ions. The adsorption assessment demonstrated that composite fibers process highly selective sequestration of phosphate ions from polluted water, even in the presence of competing anions. The ZG/f-CNOs composite fibers presented a maximum phosphate adsorption capacity (qmax) of 2500 mg/g at pH 7.0. This represents the most efficient phosphate adsorption system among all of the reported nanocomposites to date. The isotherm studies and adsorption kinetics of the adsorbent showed that the adsorption experiments followed the pseudo-second-order and Langmuir isotherm model (R2 = 0.9999). After 13 adsorption/desorption cycles, the adsorbent could still maintain its adsorption efficiency of 96-98% at pH 7.0 while maintaining stability under thermal and chemical conditions. The results mark significant progress in the design of composite fibers for removing phosphates from wastewater, potentially aiding in alleviating eutrophication effects. Owing to the f-CNOs incorporation, ZG/f-CNOs composite fibers exhibited controlled drug delivery. An antibiotic azithromycin drug-encapsulated composite fibers presented a pH-mediated drug release in a controlled manner over 18 days. Furthermore, the composite fibers displayed excellent antibacterial efficiency against Gram-positive and Gram-negative bacteria without causing resistance. In addition, zein composite fibers showed augmented mechanical properties due to the presence of f-CNOs within the zein matrix. Nonetheless, the robust zein composite fibers with inherent stimuli-responsive drug delivery, antibacterial properties, and phosphate adsorption properties can be considered promising multifunctional composites for biomedical applications and environmental remediation.

Effect of the mixed micelles of zwitterionic-anionic surfactant on efficiency of antibiotic azithromycin dihydrate

The study highlights the importance of mixed micelles in enhancing the binding and solubilization properties of partially water-soluble medications, using zwitterionic cocoamidopropyl betaine (CAPB) and anionic sodium tetradecyl sulfate surfactants. Surface tension and fluorescence spectroscopy evaluated the critical micelle concentration (CMC) of CAPB-STS mixed micelle. The thermodynamic parameters were assessed using Clint, Rubingh, and Motomura’s approach, which showed a synergistic interaction between the CAPB and STS. UV spectroscopy technique was used to evaluate the applicability of mixed micelle to enhance the solubility and binding constant (Kb) of antibiotic azithromycin dihydrate (AZI). Kb values of AZI were increased from 2.301 to 3.415 and molar solubilization ratio (MSR) values of AZI were increased from 0.228 to 0.801 by decreasing αCAPB from 0.9 to 0.1. The result indicated that zwitterionic CAPB was an electrostatic interaction consisting of both attractive (−CH2COO¯ group) and repulsive (−N+ group) interactions with AZI (−NH+ group), causing AZI molecules to reside in the Stern layer. While STS consisted of a negative −SO4¯ head group, it caused increased electrostatic interaction, and AZI penetrated the palisade layer of mixed micelles. At 7.00 mmolL-1 concentration of αCAPB 0.1, the solubility of AZI in water was increased to 2.77 mmol/L from 0.0032 mmol/L. Additionally, after 8 h, the controlled release of AZI in PBS at pH 7.4 was 95.58 % and decreased up to 30.77 % at αCAPB 0.1 mixed micelles. The observation of controlled AZI release from αCAPB 0.9 to 0.1 indicates that AZI molecules were strongly bound to mixed micelles by both hydrophobic and electrostatic interactions. In the end, a mixed micelle of CAPB-STS could serve as a useful drug-solubilizing agent in pharmaceutical applications.

Azithromycin removal using pine bark, oak ash and mussel shell

Adsorption is considered an interesting option for removing antibiotics from the environment because of its simple design, low cost, and potential efficiency. In this work we evaluated three by-products (pine bark, oak ash, and mussel shell) as bio-adsorbents for the antibiotic azithromycin (AZM). Furthermore, they were added at doses of 48 t ha−1 to four different soils, then comparing AZM removal for soils with and without bio-adsorbents. Batch-type experiments were used, adding AZM concentrations between 2.5 and 600 μmol L−1 to the different bio-adsorbents and soil + bio-adsorbent mixtures. Regarding the bio-adsorbents, oak ash showed the best adsorption scores (9600 μmol kg−1, meaning >80% retention), followed by pine bark (8280 μmol kg−1, 69%) and mussel shell (between 3000 and 6000 μmol kg−1, 25–50% retention). Adsorption data were adjusted to different models (Linear, Freundlich and Langmuir), showing that just mussel shell presented an acceptable fitting to the Freundlich equation, while pine bark and oak ash did not present a good adjustment to any of the three models. Regarding desorption, the values were always below the detection limit, indicating a rather irreversible adsorption of AZM onto these three by-products. Furthermore, the results showed that when the lowest concentrations of AZM were added to the not amended soils they adsorbed 100% of the antibiotic, whereas when the highest concentrations of AZM were spread, the adsorption decreased to 55%. However, when any of the three bio-adsorbents was added to the soils, AZM adsorption reached 100% for all the antibiotic concentrations used. Desorption was null in all cases for both soils with and without bio-adsorbents. These results, corresponding to an investigation carried out for the first time for the antibiotic AZM, can be seen as relevant in the search of low-cost alternative treatments to face environmental pollution caused by this emerging contaminant.

Keratin Formed Bioadhesive Ophthalmic Gel for the Bacterial Conjunctivitis Treatment.

Keratin has the potential to function as the gel matrix in an ophthalmic formulation for the encapsulation of the macrolide antibiotic azithromycin. The quality of this formulation was thoroughly evaluated through various analyses, such as in vitro release assessment, rheological examination, intraocular retention studies in rabbits, assessment of bacteriostatic efficacy, and safety evaluations. It is worth mentioning that the gel demonstrated shear thinning properties and exhibited characteristics of an elastic solid, thereby confirming its structural stability. The gel demonstrated a notable affinity for mucosal surfaces in comparison to traditional azithromycin aqueous solutions. In vitro release testing revealed that drug release transpired via diffusion mechanisms, following a first-order kinetic release pattern. Additionally, the formulated gel exhibited remarkable antibacterial efficacy against Staphylococcus aureus and Pseudomonas aeruginosa in bacteriostatic evaluations. Lastly, safety assessments confirmed that the gel eye drops induced minimal irritation and displayed no apparent cytotoxicity, indicating their good safety and biocompatibility for ocular application. Thus, these findings indicated that the prepared azithromycin gel eye drops complied with the requisite standards for ophthalmic preparations.

Azithromycin disrupts apicoplast biogenesis in replicating and dormant liver stages of the relapsing malaria parasites Plasmodium vivax and Plasmodium cynomolgi

The control and elimination of malaria caused by Plasmodium vivax is hampered by the threat of relapsed infection resulting from the activation of dormant hepatic hypnozoites. Currently, only the 8-aminoquinolines, primaquine and tafenoquine, have been approved for the elimination of hypnozoites, although their use is hampered by potential toxicity. Therefore, an alternative radical curative drug that safely eliminates hypnozoites is a pressing need. This study assessed the potential hypnozoiticidal activity of the antibiotic azithromycin, which is thought to exert antimalarial activity by inhibiting prokaryote-like ribosomal translation within the apicoplast, an indispensable organelle. The results show that azithromycin inhibited apicoplast development during liver-stage schizogony in P. vivax and Plasmodium cynomolgi, leading to impaired parasite maturation. More importantly, this study found that azithromycin is likely to impair the hypnozoite's apicoplast, resulting in the loss of this organelle. Subsequently, using a recently developed long-term hepatocyte culture system, this study found that this loss likely induces a delay in the hypnozoite activation rate, and that those parasites that do proceed to schizogony display liver-stage arrest prior to differentiating into hepatic merozoites, thus potentially preventing relapse. Overall, this work provides evidence for the potential use of azithromycin for the radical cure of relapsing malaria, and identifies apicoplast functions as potential drug targets in quiescent hypnozoites.

IPIAD- an augmentation regimen added to standard treatment of pancreatic ductal adenocarcinoma using already-marketed repurposed drugs irbesartan, pyrimethamine, itraconazole, azithromycin, and dapsone.

This short note presents the data and rationale for adding five generic non-oncology drugs from general medical practice to gemcitabine, nab-paclitaxel, a current standard cytotoxic chemotherapy of pancreatic ductal adenocarcinoma. The regimen, called IPIAD, uses an angiotensin receptor blocker (ARB) irbesartan indicated for treating hypertension, an old antimicrobial drug pyrimethamine indicated for treating toxoplasmosis or malaria, an old antifungal drug itraconazole, an old broad spectrum antibiotic azithromycin and an old antibiotic dapsone. In reviewing selected growth driving systems active in pancreatic ductal adenocarcinoma then comparing these with detailed data on ancillary attributes of the IPIAD drugs, one can predict clinical benefit and slowing growth of pancreatic ductal adenocarcinoma by this augmentation regimen.

Azithromycin preserves adult hippocampal neurogenesis and behavior in a mouse model of sepsis

The mammalian hippocampus can generate new neurons throughout life. Known as adult hippocampal neurogenesis (AHN), this process participates in learning, memory, mood regulation, and forgetting. The continuous incorporation of new neurons enhances the plasticity of the hippocampus and contributes to the cognitive reserve in aged individuals. However, the integrity of AHN is targeted by numerous pathological conditions, including neurodegenerative diseases and sustained inflammation. In this regard, the latter causes cognitive decline, mood alterations, and multiple AHN impairments. In fact, the systemic administration of Lipopolysaccharide (LPS) from E. coli to mice (a model of sepsis) triggers depression-like behavior, impairs pattern separation, and decreases the survival, maturation, and synaptic integration of adult-born hippocampal dentate granule cells. Here we tested the capacity of the macrolide antibiotic azithromycin to neutralize the deleterious consequences of LPS administration in female C57BL6J mice. This antibiotic exerted potent neuroprotective effects. It reversed the increased immobility time during the Porsolt test, hippocampal secretion of pro-inflammatory cytokines, and AHN impairments. Moreover, azithromycin promoted the synaptic integration of adult-born neurons and functionally remodeled the gut microbiome. Therefore, our data point to azithromycin as a clinically relevant drug with the putative capacity to ameliorate the negative consequences of chronic inflammation by modulating AHN and hippocampal-related behaviors.

Solvent-Free Method for Masking the Bitter Taste of Azithromycin Dihydrate Using Supercritical Fluid Technology

ABSTRACT Introduction and purpose The unpleasant extremely bitter taste of the orally administered broad-spectrum antibiotic azithromycin decreases patient compliance, especially in pediatrics. This issue can be overcome by decreasing drug interaction with the tasting buds using insoluble polymers at salivary pH (6.8 -7.4), like the cationic polymer Eudragit EPO. Supercritical fluid technology is a green synthesis method for preparing pharmaceutical preparations that replace organic solvents with safe supercritical CO2. This study aimed to mask the bitter taste of azithromycin using the supercritical fluid method and a pH-sensitive Eudragit EPO polymer. Methods: A foaming process was investigated for preparing a formulation (TEST), which comprises treating the polymer with supercritical carbon dioxide (CO2) fluid to prepare a taste-masked dosage form without employing organic solvents or flavors. Results: The use of the supercritical technique at 40 °C and 10 MPa for two hours allowed the manufacturing of solvent-free polymeric foam with azithromycin dispersions; the average calculated percentage of apparent volume change was 62.5 ± 5.9% with an average pore diameter of 34.879 Å. The formulated sample showed low drug release in simulated salivary fluid while keeping its crystalline nature. Moreover, clinical studies on healthy subjects showed that the formula successfully masked azithromycin's bitter taste. Conclusions: Overall, it has been shown herein that the supercritical fluid technology foaming method is promising in masking the bitter taste of bitter ingredients.

Comparison between solvent evaporation and supercritical CO2 technology in taste-masking of Azithromycin bitter-taste using pH-sensitive Eudragit EPO or Eudragit S100 polymers

Despite the broad spectrum of the antibiotic Azithromycin, its extremely bitter taste after oral dosing decreases patient compliance. This bitter taste can be masked by minimizing Azithromycin interaction with the tasting buds using polymers that are insoluble at salivary pH (6.8–7.4), like the cationic polymers Eudragit EPO and Eudragit S100. The purpose of this study was to employ two different techniques (solvent evaporation (SE) and supercritical fluid technology (SFT)) for encapsulating Azithromycin into Eudragit microparticles to mask its bitter taste. The formulations were characterized using Fourier-transform infrared spectroscopy (FTIR(, powder X-ray diffraction (PXRD), Differential scanning calorimetry (DSC), and scanning electron microscope (SEM). Also, the Azithromycin in vitro release and in vivo assessment of bitter taste masking were conducted. The present work showed promising results in veiling the bitter taste of Azithromycin. Taste panel scores for the in vivo clinical taste study of the formulation prepared using SE was 0.3 after 30 seconds compared to Azithromycin, resulting in a score of 3 owing to its palpable bitter taste. Whereas drug-Eudragit EPO showed no interaction, FTIR results indicated azithromycin interaction with Eudragit S100. The formulation prepared by the SE method and Eudragit EPO showed efficient taste masking, within-matrix encapsulation, lower drug release in simulated salivary fluid (SSF, <2% released over 60 seconds), and loss of Azithromycin’s crystallinity. On the contrary, SFT had higher encapsulation efficiency (91%) but faster in vitro release (6% released over 60 seconds). Thus, SE was better than SFT in Azithromycin taste masking using Eudragit EPO.

Azithromycin targets the CD27 pathway to modulate CD27hi T-lymphocyte expansion and type-1 effector phenotype.

Macrolide antibiotic azithromycin is widely used in clinical practice to treat respiratory tract infections and inflammatory diseases. However, its mechanism of action is not fully understood. Given the involvement of the CD27 pathway in the pathophysiology of various T-lymphocyte-mediated inflammatory, autoimmune, and lymphoproliferative diseases, we examined the impact of AZM on CD27 regulation and potential consequences on CD4+ and CD8+ T-cell phenotypes. Using cellular immunology approaches on healthy donors' peripheral blood mononuclear cells, we demonstrate AZM-mediated downregulation of surface CD27 expression as well as its extracellular release as soluble CD27. Notably, AZM-exposed CD27high (hi) cells were defective in their ability to expand compared to CD27intermediate (Int) and CD27low (lo) subsets. The defective CD27hi subset expansion was found to be associated with impaired cell proliferation and cell division. At the molecular level, the CD27hi subset exhibited lower mTOR activity than other subsets. Functionally, AZM treatment resulted in marked depletion of helper CD4+ (Th1) and cytotoxic CD8+ T-lymphocyte (Tc1)-associated CXCR3+CD27hi effector cells and inhibition of inflammatory cytokine IFN-γ production. These findings provide mechanistic insights on immunomodulatory features of AZM on T-lymphocyte by altering the CD27 pathway. From a clinical perspective, this study also sheds light on potential clinical benefits observed in patients on prophylactic AZM regimens against various respiratory diseases and opens avenues for future adjunct therapy against Th1- and Tc1-dominated inflammatory and autoimmune diseases.

CHRONIC RHINITIS WITH BRONCHITIS INDICATION IN MALE PERSIAN CAT

Cats are animals that are often used as pets. Cats are prone to disease in their respiratory system. The aim of this study was to examine the case of respiratory tract diseases that often occur in cats are rhinitis and bronchitis, namely inflammation of one or more bronchi. Examination was carried out on a pet at the Veterinary Internal Medicine Laboratory, Faculty of Veterinary Medicine, Udayana University. The animal examined was a 4 years old male Persian cat with a body weight of 3 kg, with complaints of runny nose and sneezing. The results of clinical examination showed that the cat experienced bradycardia, hypothermia and bradypnea, swelling and redness of the nose. The results of the hematological examination showed the occurrence of hypochromic macrocytic anemia and radiographic examination showed inflammation of the bronchi which was characterized by a bronchial pattern and also pulmonary vein distension which was indicated by a vascular pattern. Case animals were diagnosed with chronic rhinitis with indications of bronchitis and were treated with the antibiotic azithromycin (10 mg/kg BW; q24 hours; PO), the anti-inflammatory drug meloxicam (0.1 mg/kg BW; q24 hours; PO), and bromhexine hydrochloride (1 mg/ kg BW; q24 hours; PO) and change of feed to wet feed. Treatment of case cats for 10 days showed better clinical conditions as indicated by a decrease in the frequency of sneezing and no runny nose was found. To treat rhinitis, the selection of an antibacterial agent should ideally be based on the results of a culture of runny nose and further observation is needed because an indication of bronchitis was found on the radiographic examination results.

Risk Factors for Pediatric Acute Chest Syndrome Utilizing Machine Learning Techniques

Introduction: Acute chest syndrome (ACS) causes significant morbidity and mortality in both adult and pediatric sickle cell disease (SCD). Fifty to thirty percent of all pediatric SCD admissions develop ACS, with each episode potentially causing irreversible lung damage. Although there are some known risk factors for developing ACS (e.g., history of asthma), often this complication occurs unexpectedly. Our hypothesis was that a machine learning model could be developed to predict progression to ACS. Methods: A retrospective cohort study was designed to develop this prediction model. Data was abstracted from the electronic health record (EHR) from a single institution for all pediatric SCD admissions from 0-21 years old between June 1, 2016, and December 31, 2022. Inputs into the model included demographics (e.g., age, genotype), vital signs (e.g., heart rate, oxygen saturation), laboratory values (e.g., hemoglobin, neutrophil count), medication orders (e.g., albuterol, oxycodone) and additional co-morbidities (e.g., asthma, obstructive sleep apnea). The inputs had maximum and minimum values based on normal ranges by age. The output was a diagnosis of ACS as a continuous dependent variable to develop a continuous likelihood estimation score from 0 to 1. A positive output of ACS was defined as 2 doses of the antibiotic azithromycin and a chest x-ray ordered in the same encounter. The negative output included all patients who did not meet criteria for a positive output as defined above. Both positive and negative cohorts for ACS were included in the model. The time of ACS diagnosis was when the first dose of azithromycin was ordered. All ACS encounters were verified by chart review. A random forest model was implemented using Sklearn Python library. Different depth of trees was experimented between 1 to 24. A prediction for ACS was calculated every 6 hours after admission to the inpatient setting. Eighty percent of the data was used for training and twenty percent for testing. Results: Two thousand two hundred and sixty encounters were included in the negative cohort and 512 encounters were included in the positive cohort. One thousand four hundred and fourteen (51%) were male patients and 1358 were female patients (49%). The maximum depth of the tree was determined to be 10. Sixty-five percent of the positive cohort developed ACS 24 hours after the admission time. The median time that the random forest model predicted ACS was 18 hours before the diagnosis was determined in the chart. The model had a sensitivity of 80% and specificity of 64% at the cutoff point of 0.17. The area under the receiver operating characteristic (ROC) curve was 71%. The model's negative predictive value was 92% and the positive predictive value was 36% of diagnosing ACS. The features that were important predictors in the model were age, height, weight, pulse, respiratory rate, presence of hypoxia, temperature, neutrophil count, hemoglobin, absolute reticulocyte count and reticulocyte percent. Conclusion: A machine learning model demonstrated markers of hemolysis and vital sign changes were important to predict ACS in pediatric patients. This is the first model utilizing machine learning techniques in pediatric SCD to predict ACS. Detecting patients who are a higher risk for ACS could impact treatment options and approach to inpatient management.

Azithromycin reduces hemoglobin-induced innate neuroimmune activation

Neonatal intraventricular hemorrhage (IVH) releases blood products into the lateral ventricles and brain parenchyma. There are currently no medical treatments for IVH and surgery is used to treat a delayed effect of IVH, post-hemorrhagic hydrocephalus. However, surgery is not a cure for intrinsic brain injury from IVH, and is performed in a subacute time frame. Like many neurological diseases and injuries, innate immune activation is implicated in the pathogenesis of IVH. Innate immune activation is a pharmaceutically targetable mechanism to reduce brain injury and post-hemorrhagic hydrocephalus after IVH. Here, we tested the macrolide antibiotic azithromycin, which has immunomodulatory properties, to reduce innate immune activation in an in vitro model of microglial activation using the blood product hemoglobin (Hgb). We then utilized azithromycin in our in vivo model of IVH, using intraventricular blood injection into the lateral ventricle of post-natal day 5 rat pups. In both models, azithromycin modulated innate immune activation by several outcome measures including mitochondrial bioenergetic analysis, cytokine expression and flow cytometric analysis. This suggests that azithromycin, which is safe for neonates, could hold promise for modulating innate immune activation after IVH.

Fabrication of 3D-Printed Contact Lens Composed of Polyethylene Glycol Diacrylate for Controlled Release of Azithromycin.

Since three-dimensional (3D)-printed tablets were approved by the United States Food and Drug Administration (FDA), 3D printing technology has garnered increasing interest for the fabrication of medical and pharmaceutical devices. With various dosing devices being designed for manufacture by 3D printing, 3D-printed ophthalmic formulations to release drugs have been one such target of investigation. In the current study, 3D-printed contact lenses designed for the controlled release of the antibiotic azithromycin were produced by vat photopolymerization, and the effect of the printer ink composition and a second curing process was investigated. The azithromycin-loaded contact lenses were composed of the cross-linking reagent polyethylene glycol diacrylate (PEGDA), PEG 400 as a solvent, a photoinitiator, and azithromycin. The 3D-printed contact lenses were fabricated successfully, and formulations with lower PEGDA concentrations produced thicker lenses. The mechanical strength of the PEGDA-based contact lenses was dependent on the amount of PEGDA and was improved by a second curing process. Drug release from 3D-printed contact lenses was reduced in the samples with a second curing process. The azithromycin-loaded contact lenses exhibited antimicrobial effects in vitro for both Gram-positive and -negative bacteria. These results suggest that 3D-printed contact lenses containing antibiotics are an effective model for treating eye infections by controlling drug release.

Quantum chemical investigation of predominant conformation of the antibiotic azithromycin in water and DMSO solutions: thermodynamic and NMR analysis.

Azithromycin (AZM) is a macrolide-type antibiotic used to prevent and treat serious infections (mycobacteria or MAC) that significantly inhibit bacterial growth. Knowledge of the predominant conformation in solution is of fundamental importance for advancing our understanding of the intermolecular interactions of AZM with biological targets. We report an extensive density functional theory (DFT) study of plausible AZM structures in solution considering implicit and explicit solvent effects. The best match between the experimental and theoretical nuclear magnetic resonance (NMR) profiles was used to assign the preferred conformer in solution, which was supported by the thermodynamic analysis. Among the 15 distinct AZM structures, conformer M14, having a short intramolecular C6-OH … N H-bond, is predicted to be dominant in water and dimethyl sulfoxide (DMSO) solutions. The results indicated that the X-ray structure backbone is mostly conserved in solution, showing that large flexible molecules with several possible conformations may assume a preferential spatial orientation in solution, which is the molecular structure that ultimately interacts with biological targets.