A randomized controlled non-inferiority trial of placebo versus macrolide antibiotics for Mycoplasma pneumoniae infection in children with community-acquired pneumonia: trial protocol for the MYTHIC Study.

BACKGROUND: Mycoplasma pneumoniae is a major cause of community-acquired pneumonia (CAP) in school-aged children. Macrolides are the first-line treatment for this infection. However, it is unclear whether macrolides are effective in treating M. pneumoniae CAP, mainly due to limitations in microbiological diagnosis of previous studies. The extensive global use of macrolides has led to increasing antimicrobial resistance. The overall objective of this trial is to produce efficacy data for macrolide treatment in children with M. pneumoniae CAP. METHODS: The MYTHIC Study is a randomized, double-blind, placebo-controlled, multicenter, non-inferiority trial in 13 Swiss pediatric centers. Previously healthy ambulatory and hospitalized children aged 3-17 years with clinically diagnosed CAP will be screened with a sensitive and commercially available M. pneumoniae-specific IgM lateral flow assay from capillary blood. Mycoplasma pneumoniae infection in screened patients will be verified retrospectively by respiratory PCR (reference test) and IgM antibody-secreting cell enzyme-linked immunospot (ELISpot) assay (confirmatory test for distinguishing between carriage and infection). Patients will be randomized 1:1 to receive a 5-day treatment of macrolides (azithromycin) or placebo. The co-primary endpoints are (1) time to normalization of all vital signs, including body temperature, respiratory rate, heart rate, and saturation of peripheral oxygen (efficacy), and (2) CAP-related change in patient care status (i.e., admission, re-admission, or intensive care unit transfer) within 28 days (safety). Secondary outcomes include adverse events (AEs), as well as antimicrobial and anti-inflammatory effects. For both co-primary endpoints, we aim to show non-inferiority of placebo compared to macrolide treatment. We expect no macrolide effect (hazard ratio of 1, absolute risk difference of 0) and set the corresponding non-inferiority margins to 0.7 and -7.5%. The "at least one" success criterion is used to handle multiplicity with the two co-primary endpoints. With a power of 80% to reject at least one null hypothesis at a one-sided significance level of 1.25%, 376 patients will be required. DISCUSSION: This trial will produce efficacy data for macrolide treatment in children with M. pneumoniae CAP that might help to reduce the prescription of antibiotics and therefore contribute to the global efforts toward reducing antimicrobial resistance. TRIAL REGISTRATION: ClinicalTrials.gov, NCT06325293. Registered on 24 April 2024.

Adverse events associated with azithromycin and clarithromycin in adults aged ≥65: a disproportionality analysis of the FDA Adverse Event Reporting System (FAERS) database.

BACKGROUND: Azithromycin and clarithromycin are commonly used to treat community-acquired pneumonia in adults aged ≥ 65, such as mycoplasma pneumonia. This study aims to evaluate adverse events (AEs) associated with azithromycin and clarithromycin in this age group by analyzing the FDA Adverse Event Reporting System (FAERS), providing insights for clinical use and management of AEs in this population. RESEARCH DESIGN AND METHODS: We retrieved reports of AEs related to azithromycin and clarithromycin from the FAERS database. Disproportionality analysis was conducted using the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-Gamma Poisson Shrinkage (MGPS) to identify AEs associated with azithromycin and clarithromycin in adults aged ≥ 65. RESULTS: A total of 2,019 adverse event reports were retrieved for azithromycin, and 2,392 for clarithromycin. Off-label use (n = 349) and drug interactions (n = 487) were the most reported AEs in adults aged ≥ 65 for azithromycin and clarithromycin, respectively. Prolonged QT interval showed the strongest signal among AEs for azithromycin in this age group. Drug interaction-related medication errors had the strongest signal for clarithromycin. Seven signals not explicitly included in the azithromycin package insert were identified in adults aged ≥ 65. Fourteen signals not explicitly included in the clarithromycin package insert were identified. CONCLUSIONS: Among adults aged ≥ 65, cardiac-related adverse events are more closely associated with azithromycin than with clarithromycin. Conversely, AEs related to drug interactions and psychiatric symptoms are more associated with clarithromycin. Additionally, clinicians should be vigilant regarding AEs not specified in the package inserts. The findings of this study may help optimize the selection of azithromycin and clarithromycin based on patient circumstances and assist clinicians in focusing on relevant AEs for early intervention.

Surface Roughness Examination of Glass Ionomer Restorative Cements Treated with Acidic and Basic Pediatric Medications: An In Vitro Study.

Background: Consumption of different types of beverages and liquid drugs can affect of the surface properties of restorative material. This may lead to an increased probability of dental caries and periodontal inflammation. Aim: This study evaluated and compared the effect of amoxicillin suspension (AMS) and azithromycin suspension (AZS) on the surface roughness (SR) of silver-reinforced glass ionomer (SGI) and nano resin-modified glass ionomer (NGI). Material and Methods: Thirty disks (2 mm height × 4 mm diameter) of each glass ionomer (GI) type were prepared and subdivided into three groups (n = 10), which were separately exposed to AMS, AZS, and artificial saliva (AS). SR was evaluated by atomic force microscopy before and after three-immersion protocols repeated over a 3-week duration with 2-day intervals. In each protocol, the GI samples were exposed weekly to AMS three times daily, AZS once daily, and a full day to AS. Results: This study demonstrated, for the first time, the effect of a basic drug (AZS) on the SR of GIs. Intra- and inter-group comparisons showed significant changes (P ˂ 0.05) in the SR pattern of the GIs after immersion cycles in AZS, AMS, and AS. However, the acidic medication (AMS) exhibited significantly higher changes in SGI than in NGI. Conclusions: The SR of NGIs and SGIs can be significantly affected by the use of AMS and AZS suspensions. SGI demonstrated higher SR deterioration than NGI after immersion cycles in AMS.

An added value of Azithromycin: mitigation of Doxorubicin associated oxidative damage and genotoxicity in normal human bronchial epithelium cells.

Doxorubicin, a well-known and widely used antineoplastic agent with direct ROS-accumulating activity, has proven effective in treating various cancer types. However, its non-specific cytotoxicity towards non-cancerous cells prompts concerns regarding potential adverse effects. Azithromycin is an antibiotic for treating bacterial infections and an anti-inflammatory agent, particularly beneficial in managing respiratory conditions like bronchitis and sinusitis. Despite azithromycin's well-documented antibacterial properties, its potential cellular/genomic protective effects remain unexplored. As an in vitro model, BEAS-2B cells (normal human bronchial epithelium cells) were employed in the present study to assess whether azithromycin possesses any protective properties against doxorubicin-induced cellular toxicity. Cells in pre-treatment culture were treated to various amounts of azithromycin (3.125, 6.25, 12.5, 25, and 50 µg/mL) in combination with doxorubicin at IC50 (0.08 µg/mL). Doxorubicin at 0.08 µg/mL highlighted cytotoxicity, oxidative stress, and genotoxicity. Azithromycin at 25 and 50 µg/mL markedly modulated oxidative stress and genomic damage by decreasing the ROS and LPO amounts, and suppressing DNA fragmentation in the comet assay parameters. Consequently, azithromycin may be regarded as a cytomodulating, antigenotoxic, and antioxidant agent.

Preliminary human health risk assessment of antibiotic exposures in human waste handling occupations.

Exposure to biosolids in human waste handling occupations is associated with a risk for illness due to microbial infections. Although several years of exposure to biosolids might be hypothesized to be a prophylaxis against infection, the risks associated with infections from antibiotic-resistant organisms can also be a potential concern. Therefore, this study aimed to conduct a screening level risk assessment by deriving occupational exposure limits (OELs) characterizing the risks of adverse health effects among workers in human waste handling occupations with a focus on exposure to two pharmaceuticals commonly found in biosolids: ciprofloxacin (CIP) and azithromycin (AZ). Epidemiological and exposure studies of workers exposed to biosolids were identified through searches of major scientific databases. Screening OELs (sOELs) for these antibiotics were derived using a standardized methodology. The airborne concentrations of CIP and AZ antibiotics were determined using an exposure factors approach. The health-based exposure limits (i.e., sOELs) and the acceptable daily exposure (ADE) values for both of these antibiotics were derived as 80 µg/m3 and 12 µg/kg-day, respectively. An exposure factor approach suggested that inhalation route exposures to CIP and AZ are well below the sOELs and ADE daily doses, and likely too low to cause direct adverse health effects through antibiotic inhalation. A critical review of epidemiological studies on different occupations handling biosolids showed that the workers in industries with potential biosolids exposure have experienced an increased incidence of microbial-exposure-related illness. The health effects seen in the workers have been attributed to bacterial, viral, and protozoan infections. To the extent that bacteria are the pathogen of concern, it is not clear whether these bacteria are resistant to antibiotics commonly found in biosolids. It is also unclear whether the presence of antibiotics or antibiotic-resistant bacteria increases the susceptibility of these workers. Additional studies will provide more definitive estimates of inhalation and dermal exposures to CIP and AZ and could verify the exposure estimates in this study based on the literature and common exposure factors.

Vitamin C, doxycycline, and azithromycin (VDA) targeted changes in cellular senescence-related genes in human adipose-derived mesenchymal stem cells.

Objectives: Adipose-derived Mesenchymal stem cells (ASCs) have garnered attention for their regenerative potential; therefore, their cellular senescence-related gene expression remains crucial in therapeutic contexts. Nowadays, combination therapies have shown promising results in reducing senescent cells. This study investigated the effects of vitamin C, doxycycline, and azithromycin co-treatment on the key cellular senescence-associated genes in ASCs. Materials and Methods: Human ASCs were cultured and treated for 24 hr with vitamin C, doxycycline, azithromycin, and a combination of three drugs. Total RNAs were extracted, and the expression of p21, p16, Nanog, Oct4, and Sox2 genes was assessed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Additionally, cell cycle alterations were analyzed via flow cytometry after treatment with these compounds. Results: Notably, vitamin C treatment resulted in a significant down-regulation of p21 gene expression (P<0.01), implicating the potential role of vitamin C in promoting cell cycle progression. Doxycycline treatment led to a significant up-regulation of p21 and p16 gene expression (P<0.05), as it has previously been shown to induce cell cycle arrest. Similarly, azithromycin treatment predominantly increased p21 expression (P<0.05). Besides, cell cycle analysis revealed that each compound had changed the distribution of cells across different phases of the cell cycle. Conclusion: The combined use of all three drugs yielded intricate interactions, suggesting a complex yet promising approach to future research. According to our findings, the major difference in the combination drug-treated group (VDA) can be explained by the neutralizing effect of these three components in the environment.

Efficacy and safety of long-term macrolide therapy for non-cystic fibrosis bronchiectasis: A systematic review and meta-analysis.

BACKGROUND: Long-term macrolide therapy for non-cystic fibrosis bronchiectasis (NCFB) can play a significant role. However, such data are insufficient regarding the efficacy against severe exacerbation and adverse effects, including the emergence of macrolide-resistant pathogens and prolonged macrolide use beyond 1 year. METHODS: Randomized controlled trials (RCTs) and prospective observational studies comparing the efficacy and safety of macrolides and placebo in adult patients with NCFB were screened on April 10, 2024. The primary outcome was severe exacerbation frequency. RESULTS: Ten RCTs ≤1 year study durations were included. Most studies mainly included patients with a history of >2 exacerbations. Macrolides had a tendency to reduce the frequency of severe exacerbations compared with placebo (odds ratio = 0.54, 95% confidence interval (CI) = 0.25-1.18). Macrolides significantly reduced the frequency of exacerbations (rate ratio = 0.58, 95% CI = 0.48-0.69), prolonged the time to first exacerbation (rate ratio = 0.41, 95% CI = 0.30-0.55), improved the changes in SGRQ scores [mean difference (MD) = -3.99, 95% CI = -4.63-3.44] and percent predicted forced expiratory volume in 1 s (MD = -2.30, 95% CI = 0.26-4.33), and reduced sputum volume (gram) (MD = -7.44, 95% CI = -9.15-5.74). Additionally, macrolides did not increase drug-related adverse events leading to discontinuation. Qualitative SR of pathogens indicated macrolides might increase the number of macrolide-resistant oropharyngeal and sputum pathogens and the emergence of Pseudomonas aeruginosa. CONCLUSIONS: Our results support macrolide therapy for patients with NCFB. Studies with an observation period of >1 year or those focusing on patients with/without a minimal exacerbation history are required to determine the long-term effects on patients with NCFB.

Novel Sustained Release Azithromycin Resinate Fabricated by One-Pot Ion-exchange Performed in Hydro-alcoholic Solution.

Drug-resin complexes usually form in the aqueous phase. For poorly water-soluble drugs, low drug loading limits the use of resin in drug formulation. In this study, we used a new method to prepare azithromycin resinates, improving the drug loading rate, shortening the preparation time and simplifying the process. We used hydro-alcoholic solution as the drug loading solvent and the ion exchange resin as the carrier, and this method enabled the resin to adsorb both the retardant and the drug. The sustained release effect of retardant Eudragit RL, RS100 was analyzed. Drug loading efficiency, release profiles, morphology, physicochemical characterization and pharmacokinetic study were assessed. Preparation of drug resinate by batch method resulted in 14% higher drug loading of azithromycin and 3.5 h shorter loading time as compared to pure water for hydroalcoholic solution as drug loading solvent. Raman mappings demonstrated that the retardant with higher molecular weight was more likely to adsorb to the outer layer of the resin compared to the drug. The in vitro release and in vivo pharmacokinetic study of azithromycin resinates showed a sustained release profile with few gastrointestinal adverse effects. Therefore, the addition of ethanol not only improved the efficiency of drug loading but also showed sustained-release effect with one-pot preparation of azithromycin resinates.

Impact of oral azithromycin and intermittent preventive treatment with sulfadoxine-pyrimethamine regimen on child mortality in Sierra Leone: trial protocol for a randomised, two-arm, double-blinded, placebo-controlled clinical trial (ICARIA).

BACKGROUND: Azithromycin has been shown to be beneficial in preventing infectious diseases, including malaria, infectious diarrhoea and pneumonia. A cluster randomised control trial on azithromycin MDA in children in Niger, Malawi and Tanzania found a reduction in all-cause under-five (U5) mortality in communities who received azithromycin compared to placebo. However, the reduction was largest and statistically significant only in Niger. The purpose of this trial is to evaluate the impact of azithromycin plus intermittent preventive treatment in infants (IPTi), recently renamed by the World Health Organisation as perennial malaria chemoprevention (PMC), with sulfadoxine-pyrimethamine (SP) on all-cause mortality up to 18 months of age in children living in areas of high mortality burden through the Expanded Program on Immunisation (EPI) in Sierra Leone. METHODS: The Improving Care through Azithromycin Research for Infants in Africa (ICARIA) trial is a phase III two-arm, individually randomised, double-blinded, placebo-controlled trial administering oral AZI (20 mg/kg bodyweight) at three time points to children attending EPI visits in Sierra Leone. A total of 20,560 infants attending the first EPI contact at around 6 weeks of age are recruited and randomised to AZI or placebo in a 1:1 ratio. The second and third AZI/placebo doses are given at 9 and 15 months of age. The primary outcome of the trial is all-cause mortality rate at 18 months of age assessed through mortality surveillance. Other trial outcomes include the impact on antimicrobial resistance, and on the immune response to certain key routine EPI immunisations, the safety of the intervention, the prevalence of SP resistance markers and the feasibility, and acceptability of adding AZI to the EPI programme. DISCUSSION: The trial will provide the evidence needed to inform policy regarding the adoption and large-scale implementation of AZI in areas of high-mortality burden in sub-Saharan Africa. TRIAL REGISTRATION: ClinicalTrials.gov NCT04235816. Registered on 22 January 2020. Pan-African Clinical Trials Registry PACTR202004540256535. Registered on 14 April 2020.

A Comparative Clinical Evaluation of Subgingivally Delivered 0.5% Azithromycin Gel and 1% Chlorhexidine Gel as an Adjunct to Scaling and Root Planing in the Treatment of Chronic Periodontitis.

Background: Chronic periodontitis is a prevalent inflammatory condition affecting the supporting structures of teeth. Adjunctive therapies to scaling and root planing (SRP) play a crucial role in enhancing treatment outcomes. This study aimed to compare the clinical effectiveness of subgingivally delivered 0.5% azithromycin gel and 1% chlorhexidine gel as adjuncts to SRP in the management of chronic periodontitis. Materials and Methods: A comparative clinical evaluation was conducted involving 60 participants diagnosed with chronic periodontitis. They were randomly assigned to two groups: Group A received subgingival application of 0.5% azithromycin gel after SRP, whereas Group B received 1% chlorhexidine gel in a similar manner. Clinical parameters including probing pocket depth (PPD), clinical attachment level (CAL), and gingival index (GI) were recorded at baseline and 3-month follow-up. Results: Both groups demonstrated significant improvements in clinical parameters after treatment. However, Group A exhibited a greater reduction in PPD (mean decrease of 2.5 mm) compared with Group B (mean decrease of 1.8 mm). Similarly, Group A showed a higher gain in CAL (mean gain of 2.3 mm) compared with Group B (mean gain of 1.5 mm). In addition, a significant reduction in GI was observed in both groups, with Group A showing slightly better outcomes. Conclusion: Subgingivally delivered 0.5% azithromycin gel demonstrated superior clinical efficacy as an adjunct to SRP in the treatment of chronic periodontitis compared with 1% chlorhexidine gel. The findings suggest that azithromycin gel may serve as a promising therapeutic option in managing periodontal disease.

Effect of Small Doses of Azithromycin on Pulmonary Ventilation Function and Inflammatory Factors IL-6, IL-13 in Children with Bronchial Asthma.

OBJECTIVE: To observe the effect of low-dose azithromycin on pulmonary ventilation function and inflammatory factors IL-6, IL-13 in children with bronchial asthma. METHODS: A total of 80 children with asthma in Pediatric Medicine affiliated to Taizhou Women and Children's Hospital of Wenzhou Medical University from January 2019 to December 2022 were selected and divided into control group (42 cases) and study group (38 cases). The control group regularly inhaled Salmeterol Xinafoate and Fluticasone Propionate inhalation, while the study group was additionally given low-dose azithromycin. After four weeks of treatment, pulmonary function tests including FEV1, FVC were performed and inflammatory indicators including CRP, FeNO, IL-6, IL-13 were measured. The occurrence of adverse reactions during treatment was recorded. RESULTS: Pulmonary function tests including FEV1%, FEV1/FVC% were improved in all subjects, and the improvement of pulmonary function was more significant in the study group (P<0.05). The levels of CRP, FeNO, IL-6 and IL-13 were decreased in the two groups, especially in the study group (P<0.05). There was no significant difference in the incidence of adverse drug reactions between the two groups (P>0.05). CONCLUSION: Low-dose azithromycin can significantly improve the pulmonary function in children with bronchial asthma, reduce the levels of inflammatory factors, control airway mucus secretion and inflammation, and can be used to treat chronic lung diseases such as bronchial asthma.

Hyaluronic Acid-Modified Micelles of Azithromycin and Quercetin Against Infections Caused by Methicillin-Resistant Staphylococcus Aureus.

Introduction: Resistance of intracellular pathogens is a challenge in microbial therapy. Methicillin-resistant Staphylococcus aureus (MRSA), which is able to persist inside the cells of infected tissues, is protected from attack by the immune system and many antimicrobial agents. To overcome these limitations, nano-delivery systems can be used for targeted therapy of intracellular MRSA. Methods: Hyaluronic acid-modified azithromycin/quercetin micelles (HA-AZI/Qe-M) were synthesized by thin film hydration. The micelles were characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS) and Fourier transform infrared spectroscopy (FTIR), and the drug loading (DL) and encapsulation efficiency (EE) were detected by high performance liquid chromatography (HPLC). The uptake ability of RAW264.7 cells was investigated, and its distribution in mice was evaluated by in vivo imaging. The inhibitory effect of the micelles against MRSA in vitro and its ability to eliminate intracellular bacteria were evaluated. Bacterial muscle-infected mice were constructed to evaluate the therapeutic effect of the micelles on bacterial infections in vivo and the biocompatibility of the micelles was investigated. Results: HA-AZI/Qe-M had suitable physical and chemical properties and characterization. In vitro antibacterial experiments showed that HA-AZI/Qe-M could effectively inhibit the growth of MRSA, inhibit and eliminate the biofilm formed by MRSA, and have an excellent therapeutic effect on intracellular bacterial infection. The results of RAW264.7 cells uptake and in vivo imaging showed that HA-AZI/Qe-M could increase the cellular uptake, target the infection site, and prolong the treatment time. The results of in vivo antibacterial infection experiments showed that HA-AZI/Qe-M was able to ameliorate the extent of thigh muscle infections in mice and reduce the expression of inflammatory factors. Conclusion: HA-AZI/Qe-M is a novel and effective nano-drug delivery system that can target intracellular bacterial infection, and it is expected to be safely used for the treatment of MRSA infection.

Magnetic graphene oxide-zinc oxide nanocomposite for enhanced photocatalytic degradation of azithromycin under normal sunlight.

During the Covid-19 pandemic and its aftermath, there has been a sudden surge in the production and consumption of macrolide antibiotics. This surge has had a significant impact on water quality, leading to concentrations exceeding acceptable limits. To address this concerning issue, a magnetic graphene oxide-zinc oxide nanocomposite (MZG) was synthesized using a straightforward wet chemical synthesis method. The synthesized catalyst was then subjected to comprehensive characterization using sophisticated techniques including HRTEM, XRD, FTIR, Raman spectroscopy, BET, XPS, VSM, DRS, and TGA. Subsequently, the MZG photocatalyst's efficacy was evaluated through a series of experiments aimed at degrading azithromycin drug residues in water. These techniques divulged substantial information about the morphology, polycrystallinity, size (in nm range), functional groups, defects, surface area (132.9 m2/g), elemental composition (C, O, Fe and Zn), super paramagnetism (Ms 69.78 emu/g), suitable bandgap (2.8 eV) and thermal stability of the material, respectively. The optimized concentration of MZG photocatalyst demonstrated remarkable potential for photocatalytic degradation, particularly towards higher concentrations of 50 ppm azithromycin. It achieved an impressive degradation efficiency of 96.04 % in water when exposed to normal sunlight for just 1 h. Kinetic studies revealed a first-order reaction rate, with a notably higher rate constant (k = 0.0533 min⁻1) compared to other photocatalysts. Furthermore, MZG had shown better recyclabilty up to four cycles with minimal loss of photocatalytic acitvity to only 9%. Thus, it proves to be both effective and cost-efficient, capable of functioning under visible radiation. This makes it suitable for industrial applications aimed at removing azithromycin drugs and promoting a safer and more sustainable environment.

Case report: a co-occurring case of severe Mycoplasma pneumoniae pneumonia and Anti-IgLON5 antibody-associated encephalitis in a pediatric patient.

This case report details the clinical course of a 16-year-old female student with Mycoplasma pneumoniae infection complicated by autoimmune encephalitis, spanning from 6 February 2022, to 12 April 2022, with a one-year follow-up. The patient presented with a two-week history of cough and fever, followed by altered consciousness and neuropsychiatric symptoms, including hyperactivity and incoherent speech. Despite normal brain MRI findings, cerebrospinal fluid (CSF) analysis confirmed Mycoplasma pneumoniae with titers of, and positive IgLON5 antibodies. Initial treatment included azithromycin, ceftriaxone, and acyclovir, followed by mechanical ventilation and ECMO due to respiratory failure. The antibiotic regimen was switched to intravenous omadacycline based on genetic testing results. Autoimmune encephalitis was managed with intravenous methylprednisolone, intravenous immunoglobulin (IVIG), and plasma exchange. The patient's condition improved, and she was discharged on 12 March 2022, with normal cognitive and behavioral functions. However, she was readmitted one month later due to cognitive decline and sleep disturbances, with a Mini-Mental State Examination (MMSE) score of 20/30 and a modified Rankin Scale (mRS) score of 3. At the one-year follow-up, her MMSE score had improved to 28/30, and her mRS score was 1. This case underscores the importance of comprehensive diagnostic approaches and personalized treatment strategies in managing complex cases of mycoplasma-related infections and associated autoimmune conditions.

Macrolide-loaded nanofibrous inserts with polycaprolactone and cellulose acetate base for sustained ocular delivery: Pharmacokinetic study in Rabbit's eye.

The present study aimed to prepare nanofibrous inserts for sustained ocular drug delivery of Azithromycin (AZM) toward conquering the obstacles of conventional topical drug delivery. Nanofibers were fabricated by electrospinning using polycaprolactone (PCL) and cellulose acetate (CA) which are biocompatible and biodegradable polymers. Prepared nanofibers were evaluated in terms of physicochemical, morphological properties, pharmacokinetic study and ocular irritation. SEM images revealed average diameters of about 160 nm and 190 nm for CA and PCL nanofibers, respectively. These ocular drug delivery systems were strong, flexible, and stable under humid and dry conditions. Quantification was performed using microbiological assay by M. luteus as a microorganism. While PCL-based nanofibrous inserts released AZM in a two-step manner initiated by a burst release via Peppas kinetical model, CA-based inserts showed a gradual release profile without any burst release which followed the first-order model. Results showed that these inserts were non-cytotoxic and non-irritating. The nanofibers showed antibacterial efficacy against Escherichia coli and Staphylococcus aureus. In addition, according to a pharmacokinetic study in Rabbit's Eye, a higher Cmax and lower Tmax were achieved by PCL nanofibers compared to CA-based ones. The pharmacokinetic study of nanofibers in rabbit eyes showed that all formulations were able to maintain the effective concentration of AZM for about 6 days. In conclusion, the prepared nanofibers can be effectively utilized for prolonged ocular delivery of AZM in the treatment of conjunctival infections.

Characterization of azithromycin-resistant Shigella flexneri serotype 2a isolates using whole genome sequencing in Ontario from 2016 to 2018.

Azithromycin-resistant shigellosis is increasing globally. This retrospective analysis of Shigella flexneri serotype 2a isolates from 2016 to 2018 in Ontario found nearly half were azithromycin (47.7%, 72/151) and ciprofloxacin (50.7%, 77/152) resistant. Moreover, 34.7% (25/72) of azithromycin-resistant isolates were also ciprofloxacin-resistant. Four isolates were ceftriaxone-resistant, although all azithromycin-resistant isolates were ceftriaxone-susceptible. Overall, 83.6% (127/152) of all S. flexneri 2a isolates were recovered from males and 97.2% (70/72) of the azithromycin-resistant cases were males. Among the azithromycin-resistant cases, some (8/72) reported international travel. Phylogenetic analysis of azithromycin-resistant isolates revealed two large male-dominated clusters, and one cluster may have been due to importation of resistant strain. Comparison of plasmids isolated from the clusters in Ontario revealed the presence of incFII plasmid with high percentage of similarity to plasmids present in global outbreaks affecting mostly males including men who have sex with men (MSM). These two large azithromycin-resistant clusters are suggestive of an outbreak among MSM, though disease exposure or sexual orientation of patients was unknown. The presence of plasmid-borne azithromycin resistance in ciprofloxacin-resistant isolates is a public health concern. Antimicrobial surveillance is important for patient management, understanding the spread of novel resistance types in local communities which sometimes is introduced by travel. We found ongoing multidrug-resistant outbreaks spanning multiple years affecting males. Reduction of future outbreaks in high-risk communities like MSM requires consorted information flow between laboratory, public health, and physicians. We impart genomic and antimicrobial characteristics of multidrug S. flexneri 2a which may serve as reference by clinicians and public health.IMPORTANCEOral ciprofloxacin and azithromycin are generally considered as the first-line therapy of shigellosis. Here, we report the emergence and transmission of azithromycin and ciprofloxacin-resistant S. flexneri serotype 2a among male adults in Ontario during 2016-2018. The percentage of azithromycin and ciprofloxacin resistance among S. flexneri 2a is higher compared to previous reports from Canada and United States. Here, we show the genetic basis of the antimicrobial resistance among these unique groups of S. flexneri 2a isolates. We describe a domestically acquired azithromycin-resistant and ciprofloxacin-resistant S. flexneri 2a lineage in Ontario. Combining whole-genome sequencing (WGS) data with travel-associated data helped in understanding dissemination and transmission. We employed WGS, which not only helped us in understanding the genetic-relationship between isolates but also mine information regarding plasmids. In the future, linking WGS, travel-related data, and clinical data can provide enhanced contact tracing and improve public-health management.

Anti-infective therapies for Pythium insidiosum keratitis.

INTRODUCTION: Pythium insidiosum keratitis (PIK) is a rapidly progressing ocular disease predominantly found in tropical and subtropical regions. Characterized by severe corneal damage and high morbidity, this infection poses significant challenges in diagnosis and management, necessitating effective anti-infective therapies. AREAS COVERED: This report delves into the pathophysiology, clinical and microbiological diagnosis, and detailed insights into the anti-infective therapy for PIK, outlining current diagnostic challenges that complicate treatment. We review existing anti-infective therapies, including their efficacy and limitations, and discuss the role of surgical interventions in managing advanced cases. The report also highlights ongoing research into novel treatment approaches and the critical need for developing targeted therapies. EXPERT OPINION: Despite advances in understanding PIK, treatment remains complex due to pathogen resistance and diagnostic hurdles. Future research should focus on innovative anti-infective strategies, improved diagnostic techniques, and global surveillance to enhance therapeutic outcomes. Collaboration between ophthalmologists, microbiologists, and pharmacologists is essential to advance treatment protocols and improve patient prognosis.

Effectiveness of Oral Azithromycin in Treating Enteric Fever: A Hospital-Based Study on Pediatric Patients.

Introduction Enteric fever is prevalent in underdeveloped and developing countries. It is caused by Salmonella Typhi, which has developed resistance over the years to commonly used antimicrobials. Meropenem is an effective treatment for all complicated and uncomplicated extensively drug-resistant (XDR) bacteria, but it is administered intravenously, three times daily, by infusion, and it is quite expensive for the patient. Oral azithromycin is shown by some authors to be effective in extensively drug-resistant enteric fever. Material and methods This retrospective cross-sectional study was conducted in the outpatient department of Lady Reading Hospital Medical Teaching Institution, Peshawar. The duration of the study was one year. Data was collected after approval from the hospital's Ethical and Research Committee. All pediatric patients meeting the inclusion criteria for extensively drug-resistant enteric fever were included. Data on patient demographics, blood culture and laboratory results, treatment given, and effectiveness were documented in a specialized proforma. Statistical Package for Social Sciences (SPSS) version 23 (IBM Corp., Armonk, NY, US) was used for data analysis. Results Out of the total 106 patients, 72 (67.9%) were male and 34 (32.1%) were female. The mean age was 7.51 ± 2.75 years, with a range of 1 to 15 years. Among them, 66 (62.3%) had anemia (hemoglobin less than 11 grams per deciliter for under 5 years and 11.5 for 5-15 years old children), with a mean hemoglobin level of 10.6 ± 1.53 grams per deciliter (g/dl), ranging from 7.2 to 13.8 g/dl. Thrombocytopenia was found in 14 (13%) patients. The mean platelet count was 317 x 103 ± 164 cells per microliter, with a range of 61 x 103 to 834 x 103 cells per liter. The mean total leukocyte count was 9.71x 103 ± 4.321 cells per microliter, with a range of 2.01 x 103 to 30.40 x103 cells per microliter. However, leucopenia was seen in only 5 (4.7%) patients. In 98.1% of cases, azithromycin was found to be effective in treating enteric fever caused by extensively drug-resistant Salmonella. Conclusion Azithromycin is effective in treating extensively drug-resistant enteric fever. It can be confidently used in patients with no or mild complications with extensively drug-resistant enteric fever. Good compliance and complete dosage should be followed to avoid resistance to this drug. Blood cultures should always be sent when prescribing antibiotics, especially when suspecting enteric fever.

Gallic acid synergistically enhances the antibacterial activity of azithromycin in MRSA.

The rise of antibiotic resistance in existing pathogens has been identified as a major threat to global healthcare in the twenty-first century. This resistance has consequences such as increased cost and prolonged hospital stays, treatment failure, and ultimately increased risk of patient mortality. It is therefore imperative to develop strategies to combat drug resistance. Combined treatment of common antibiotics and natural compounds is one of the most effective methods against resistant bacterial infections. Gallic acid (GA) is a natural secondary metabolite abundantly found in plants and has significant medicinal effects in various aspects of health. In this research, the antibacterial effects of azithromycin (AZM) and GA alone and in combination with each other were investigated on planktonic and biofilm forms of methicillin-sensitive Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA), and Pseudomonas aeruginosa (P. aeruginosa). The results showed that the combination of AZM/GA had an additive effect against MSSA and P. aeruginosa and a synergistic effect against MRSA. In addition, combining these two agents significantly reduced the minimum biofilm inhibitory concentration (MBIC) of AZM and GA in the MRSA strain. Finally, the level of ROS generation in the effect of AZM plus GA was evaluated in the bacteria. Among the studied strains, ROS production was significantly increased in combination treatment compared to AZM alone in MRSA. The results show that the combination of AZM and GA has a significant effect against MRSA and can be considered as an effective treatment option.

Molecular spectroscopy, solvent effect, and DFT studies of azithromycin solvate.

Azithromycin ethanol solvate monohydrate [C38H72N2O120.5(C2H6O)H2O], abbreviated by AZM-MH-EtOH, was synthesized by slow evaporation method and investigated by powder X-ray diffraction, Raman and infrared (IR) spectroscopy combined with density functional theory (DFT) studies. Electronic and vibrational properties were properly investigated based on a theoretical study of solvation effects, using implicit solvation and solute electron density models. The electronic and vibrational studies were evaluated under aqueous, ethanolic, and vacuum conditions. The electronic structure calculations indicated that the AZM-MH-EtOH is chemically more stable in solvents compared to vacuum condition. Ultraviolet-visible (UV-vis) measurements confirmed the stability of the material in ethanolic medium, due to higher absorbance values compared to the aqueous medium. Vibrational changes were observed in the Raman and IR bands, which have connection with hydrogen bonds. The experimental vibration modes showed better accordance with the predicted modes' values under solvation effects, but a slight divergence is noticed when we compared to vibration modes obtained in vacuum. Furthermore, the results have revealed a greater affinity profile of AZM-MH-EtOH for water and ethanol solvents compared to theoretical data under vacuum condition.