zithromax and Hemolysis

Topics: Azithromycin; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Diabetes Mellitus; Glucosephosphate Dehydrogenase Deficiency; Hemolysis; Humans; Hydroxychloroquine; Male; Methemoglobinemia; Middle Aged; Obesity, Morbid; Pandemics; Pneumonia, Viral; SARS-CoV-2

While the COVID-19 epidemic occurred since December 2019, as of end April 2020, no treatment has been validated or invalidated by accurate clinical trials. Use of hydroxychloroquine has been popularised on mass media and put forward as a valid treatment option without strong evidence of efficacy. Hydroxychloroquine (HCQ) has its own side effects, some of which are very serious like acute haemolysis in glucose-6-phosphate dehydrogenase (G6PD) deficient patients. Side effects may be worse than the disease itself. Belgian national treatment guidelines recommend the use of HCQ in mild to severe COVID-19 disease. As opinions, politics, media and beliefs are governing COVID-19 therapy, performance of randomised controlled blinded clinical trials became difficult. Results of sound clinical trials are eagerly awaited. We report a case of acute haemolysis leading to admission in intensive care unit and renal failure in a patient with uncovered G6PD deficiency.

Topics: Aged; Azithromycin; Betacoronavirus; Blood Transfusion; Continuous Renal Replacement Therapy; Coronavirus Infections; COVID-19; Drug Therapy, Combination; Enzyme Inhibitors; Glucosephosphate Dehydrogenase Deficiency; Haptoglobins; Hemolysis; Humans; Hydroxychloroquine; Hypoxia; Male; Nasopharynx; Pandemics; Pneumonia, Viral; Respiratory Distress Syndrome; SARS-CoV-2; Severe acute respiratory syndrome-related coronavirus

Poly(lactide-co-glycolide) (PLGA) copolymers are promising synthetic materials in the biomedical field. However, in wound management, their hydrophobic properties limit their further application because of their poor adhesion to the surface of moist wounds. Furthermore, the lack of hemostatic materials with sustainable anti-infection and immunoregulation functions remains a highly significant clinical problem, as commercially available hemostatic products, such as Arista™, Celox™ and QuikClot™, do not have sufficient infection prevention and immunoregulation properties. Herein, we employ electrospinning, ammonia dissociation and surface grafting techniques to develop a series of PLGA-based hemostatic materials, including a PLGA electrospun fibrous membrane, PLGA-NH2 fibrous particles and PLGA-hyaluronic acid fibrous fragments (PLGA-HA FFs). Notably, we load azithromycin on the PLGA-HA FFs to endow them with anti-infection and immunoregulation properties. The hemostatic mechanism analysis demonstrates that the PLGA-HA FFs show superior hemostasis performance compared to traditional gauzes. The results show that the PLGA-HA FFs can act as a versatile platform with high encapsulation of azithromycin (83.03% ± 2.81%) and rapid hemostasis (28 ± 2 s) as well as prominent cytocompatibility towards L929 cells, RAW 264.7 cells and red blood cells. We believe that the current research proposes a possible strategy to synthesize materials that achieve not only safe and effective hemostasis, but also have anti-infection and immunoregulation properties for the development of further hemostatic products.

Topics: Animals; Anti-Bacterial Agents; Azithromycin; Cell Line; Cell Survival; Drug Carriers; Electricity; Hemolysis; Humans; Hyaluronic Acid; Immunologic Factors; Materials Testing; Mice; Platelet Adhesiveness; Polylactic Acid-Polyglycolic Acid Copolymer; Rats; Rats, Sprague-Dawley; RAW 264.7 Cells; Staphylococcus aureus

Biofilms formed by pathogenic bacteria are one of the most important reasons for multidrug resistance. One of the major limitations in the biofilm treatment is the existence of intensive matrices, which greatly block the diffusion of antimicrobial agents. In the current study, we designed poly(aspartamide)-derived micelles self-assembled from cationic copolymers with azithromycin-conjugated and pH-sensitive copolymers, followed by loading cis-aconityl-d-tyrosine (CA-Tyr) via electrostatic interactions. In response to the acidic microenvironment of the biofilm matrix, the hydrophilic transition of the pH-sensitive copolymers and the removal of CA-Tyr led to a sharp decrease in micelle size from 107 nm to 54 nm and a rapid shift in their zeta potential from -11.7 mV to +26.4 mV, which facilitated the penetration of the micelles into biofilms. The acid-labile release of d-tyrosine disintegrated the biofilm matrix, and the lipase-triggered release of azithromycin eradicated the bacteria in the biofilms. An in vitro test was performed on pre-established P. aeruginosa biofilms in microwells, while biofilms grown on catheters were surgically implanted in rats for in vivo evaluation. The results demonstrated the capabilities of the size/surface charge-adaptive micelles in the intensive infiltration in the biofilm matrix and spatiotemporal release of biofilm dispersion and antibacterial agents for the comprehensive treatment of biofilm-relevant infections.

Topics: Animals; Anti-Bacterial Agents; Azithromycin; Biofilms; Cell Line; Cell Survival; Drug Carriers; Erythrocytes; Female; Hemolysis; Humans; Hydrogen-Ion Concentration; Mice; Micelles; Polymers; Pseudomonas aeruginosa; Rats; Rats, Wistar; Static Electricity; Tyrosine

Novel, safe, efficient and cost effective nano-carriers from renewable resources have got greater interest for enhancing solubility and bioavailability of hydrophobic dugs.. This study reports the synthesis of a novel biocompatible non-phospholipid human metabolite "Creatinine" based niosomal delivery system for Azithromycin improved oral bioavailability.. Synthesized surfactant was characterized through spectroscopic and spectrometric techniques and then the potential for niosomal vesicle formation was evaluated using Azithromycin as model drug. Drug loaded vesicles were characterized for size, polydispersity index (PDI), shape, drug encapsulation efficiency (EE), in vitro release and drug-excipient interaction using zetasizer, atomic force microscope (AFM), LC-MS/MS and FTIR. The biocompatibility of surfactant was investigated through cells cytotoxicity, blood hemolysis and acute toxicity. Azithromycin encapsulated in niosomes was investigated for in vivo bioavailability in rabbits.. The vesicles were spherical with 247 ± 4.67 nm diameter hosting 73.29 ± 3.51% of the drug. Surfactant was nontoxic against cell cultures and caused 5.80 ± 0.51% hemolysis at 1000 µg/mL. It was also found safe in mice up to 2.5 g/kg body weight. Synthesized surfactant based niosomal vesicles revealed enhanced oral bioavailability of Azithromycin in rabbits.. The results of the present study confirm that the novel surfactant is highly biocompatible and the niosomal vesicles can be efficiently used for improving the oral bioavailability of poor water soluble drugs.

Topics: Animals; Antibiotics, Antineoplastic; Azithromycin; Biological Availability; Cells, Cultured; Creatinine; Drug Delivery Systems; Drug Stability; Hemolysis; Humans; Liposomes; Mice; Particle Size; Surface-Active Agents

Ocular and parenteral application potentials of azithromycin-containing, non-phospholipid-based cationic nanosized emulsion in comparison to the phospholipid-based anionic and neutral-charged nanosized emulsions were investigated. Various physical, chemical, nonclinical toxicity and antimicrobial activity studies (mean droplet diameter, surface charge, creaming index, entrapment efficiency, accelerated, long-term and freeze-thaw cycling stabilities, TLC study, modified hen's egg chorioallantoic membrane (HET-CAM) test, in vitro hemolysis test, in vitro and in vivo myotoxicity, and in vitro antimicrobial activity) were conducted for assessing the potentials of these three types of emulsions. Following autoclave sterilization, all of these emulsions exhibited a nanometer range mean particle diameter (200 ± 29 to 434 ± 13 nm). While the anionic and cationic emulsions did show high negative (-34.2 ± 1.23 mV) and positive zeta potential (42.6 ± 1.45 mV) values, the neutral-charged emulsion did not. Even with 5 freeze-thaw cycles, the cationic emulsion remained stable whereas other two emulsions underwent phase-separation. The hen's egg chorioallantoic membrane test revealed an irritation score value that was higher for the anionic emulsion than for cationic or neutral-charged emulsion. A significantly higher % hemolysis value was also noticed for the anionic emulsion when compared to the % hemolysis value of cationic emulsion (ANOVA, P ‹ 0.05). However, all of the emulsions showed a lesser intracellular creatine kinase (CK) release/plasma CK level in comparison to the positive control (phenytoin) indicating their lesser myotoxicity at the injection site . When compared to anionic and neutral-charged emulsions, the possible controlled drug release from cationic emulsion delayed the in vitro antimicrobial action against H.influenzae and S.pneumoniae.

Topics: Administration, Ophthalmic; Animals; Anti-Bacterial Agents; Azithromycin; Chickens; Chorioallantoic Membrane; Creatine Kinase; Drug Stability; Emulsions; Erythrocytes; Haemophilus influenzae; Hemolysis; Hemorrhage; Infusions, Parenteral; Lipids; Male; Muscle, Skeletal; Poloxamer; Rats; Rats, Sprague-Dawley; Sheep; Streptococcus pneumoniae; Surface Properties