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The article focuses on the birth and subsequent health concerns of a newborn delivered to a mother with an uncomplicated prenatal course. Topics include the infant's feeding regimen, initial discharge with a presumptive diagnosis, and his presentation to the emergency department with symptoms such as fever and hematochezia.

Background: Antibiotic consumption is a driver for the increase of antimicrobial resistance. The objective of this study is to analyze variations in antibiotic consumption and its appropriate use in Brazil from 2014 to 2019. Methods: We conducted a time series study using the surveillance information system database (SNGPC) from the Brazilian Health Regulatory Agency. Antimicrobials sold in retail pharmacies were evaluated. All antimicrobials recorded for systemic use identified by the active ingredient were eligible. Compounded products and formulations for topic use (dermatological, gynecological, and eye/ear treatments) were excluded. The number of defined daily doses (DDDs)/1,000 inhabitants/day for each antibiotic was attributed. The number of DDDs per 1,000 inhabitants per day (DDIs) was used as a proxy for consumption. Results were stratified by regions and the average annual percentage change in the whole period studied was estimated. We used the WHO Access, Watch, and Reserve (AWaRe) framework to categorize antimicrobial drugs. Results: An overall increase of 30% in consumption from 2014 to 2019 was observed in all Brazilian regions. Amoxicillin, azithromycin and cephalexin were the antimicrobials more consumed, with the Southeast region responsible for more than 50% of the antibiotic utilization. Among all antimicrobials analyzed 45.0% were classified as watch group in all Brazilian regions. Conclusion: We observed a significant increase in antibiotics consumption from 2014 to 2019 in Brazil restricted to the Northeast and Central West regions. Almost half of the antibiotics consumed in Brazil were classified as watch group, highlighting the importance to promote rational use in this country. [ABSTRACT FROM AUTHOR]

Excessive use of azithromycin (AZM) is associated with resistance and negative impacts on the environment. Therefore, this study aimed to develop an electrochemical sensor for AZM. The screen‐printed carbon electrode (SPCE) modified with boron‐doped diamond nanoparticle (BDDNP) and reduced‐graphene oxide (rGO) was successfully applied to measure the AZM concentration. The morphology of the modified electrode was characterized by scanning electron microscopy‐energy dispersive X‐ray (SEM‐EDX). Furthermore, the effect of electrochemical parameters, such as signal per background, scan rate, and selectivity was determined. The results showed that under optimum conditions, the plot of AZM demonstrated linearity in the range of 30–100 μM with a limit of detection (LOD) at 1.6 μM. The repeatability and recovery were also investigated, and the sensor was applied to real samples obtained from hospital wastewater. A remarkable 93.27 % recovery rate and excellent precision were recorded with an %RSD of 2.41 %. This study underscores the potential of SPCE modified with rGO/BDDNP for accurate and reliable measurement of AZM levels, showcasing great applicability in addressing the challenges associated with monitoring AZM in various environmental settings. [ABSTRACT FROM AUTHOR]

The chemical stability of azithromycin (AZM) may be compromised depending on the imposed thermo-oxidative conditions. This report addresses evidence of this process under varying conditions of temperature (20–80 °C), exposure time to UV radiation (1–3 h irradiation at 257 nm), and air saturation (1–3 h saturation with atmospheric air at 1.2 L min−1 and 15 kPa) through electrochemical measurements performed with a thermoactivated cerium molybdate (Ce2(MoO4)3)/multi-walled carbon nanotubes (MWCNT)-based composite electrode. Thermal treatment at 120 °C led to coordinated water elimination in Ce2(MoO4)3, improving its electrocatalytic effect on antibiotic oxidation, while MWCNT were essential to reduce the charge-transfer resistance and promote signal amplification. Theoretical–experimental data revealed remarkable reactivity for the irreversible oxidation of AZM on the working sensor using phosphate buffer (pH = 8) prepared in CH3OH/H2O (10:90%, v/v). Highly sensitive (230 nM detection limit) and precise (RSD < 4.0%) measurements were recorded under these conditions. The results also showed that AZM reduces its half-life as the temperature, exposure time to UV radiation, and air saturation increase. This fact reinforces the need for continuous quality control of AZM-based pharmaceuticals, using conditions closer to those observed during their transport and storage, reducing impacts on consumers' health. [ABSTRACT FROM AUTHOR]

Objective(s): Tubal factor infertility (TFI) is common female infertility responsible for a large portion of female factor infertility. This study reveals the effect of the quercetin of Huoxuehuayu Tongluo Decoction with azithromycin on the pregnancy rate and inflammation of TFI female rats. Materials and Methods: Female Sprague Dawley rats were constructed into the TFI model and treated with quercetin, Huoxuehuayu Tongluo Decoction, and combination therapy (quercetin and azithromycin). Pregnancy rate and litter size were measured. Network pharmacology was applied to analyze the interaction between Huoxuehuayu Tongluo Decoction and TFI. The combination of quercetin and IL-6 was analyzed by molecular docking. HE staining and electron microscopy were used to observe the histopathology and ultrastructure of fallopian tube tissues. The TNF-α, IL-1β, IL- 6, IL-8, and MPO levels were detected by ELISA. The activation of JAK/STAT, MAPK, and NF-κB p65 pathways was detected by western blot or immunohistochemistry. Results: Quercetin was the main active component of Huoxuehuayu Tongluo Decoction, and could bind to IL-6 in TFI. Target genes were enriched in the IL-17 signaling pathway, JAK-STAT signaling pathway, inflammatory disease, etc. Under the quercetin and azithromycin combination therapy, both rat pregnancy rates and litter sizes increased significantly. quercetin and azithromycin alleviated the symptoms of hydrosalpinx and inflammatory damage in fallopian tube tissues. The phosphorylation of JAK/STAT and MAPK pathways and NF-κB p65 translocation to the nucleus were significantly inhibited by the quercetin and azithromycin therapy. Conclusion: Quercetin and azithromycin combination therapy inhibited inflammation and phosphorylation of JAK/STAT and MAPK pathways to improve TFI inflammation and pregnancy function. [ABSTRACT FROM AUTHOR]

Contaminated lake water and fish can be sources of bacterial pathogens of public health concern, including pathogenic E. coli. Within Ethiopia, specifically, Central Oromia, raw fish consumption is a common practice. Although there are few reports on occurrence of E. coli O157 in fish destined for human consumption and children under five years, information on the transmission pathways of E. coli O157 and other sorbitol non-fermenting (SN-F) E. coli from water-to-fish-to-human, and their virulence factors and antimicrobial resistant determinants along the fish supply chain is lacking. The study aimed to investigate the occurrence, molecular characteristics, and antimicrobial susceptibility of E. coli O157 and other SN-F E. coli strains in fish, lake water and humans in central Oromia, Ethiopia. A total of 750 samples (450 fish samples, 150 water samples, 150 human stool samples) were collected from five lakes and three health facilities. The samples were processed following the standard protocol recommended by European Food Safety Authority and Kirby–Bauer disc diffusion method for detection of the bacteria, and antimicrobial susceptibility tests, respectively. Molecular characterization of presumptive isolates was performed using Whole-Genome Sequencing (WGS) for serotyping, determination of virulence factors, antimicrobial resistance traits, and genetic linkage of the isolates. Overall, 3.9% (29/750) of the samples had SN-F E. coli; of which 6.7% (n = 10), 1.8% (n = 8) and 7.3% (n = 11) were retrieved from water, fish, and diarrheic human patients, respectively. The WGS confirmed that all the isolates were SN-F non-O157: H7 E. coli strains. We reported two new E. coli strains with unknown O-antigen from fish and human samples. All the strains have multiple virulence factors and one or more genes encoding for them. Genetic relatedness was observed among strains from the same sources (water, fish, and humans). Most isolates were resistant to ampicillin (100%), tetracycline (100%), cefotaxime (100%), ceftazidime (100%), meropenem (100%), nalidixic acid (93.1%) and sulfamethoxazole/trimethoprim (79.3%). Majority of the strains were resistant to chloramphenicol (58.6%) and ciprofloxacin (48.3%), while small fraction showed resistance to azithromycin (3.45%). Isolates had an overall MDR profile of 87.5%. Majority, (62.1%; n = 18) of the strains had acquired MDR traits. Genes encoding for mutational resistance and Extended-spectrum beta-lactamases (ESBL) were also detected. In conclusion, our study revealed the occurrence of virulent and MDR SN-F E. coli strains in water, fish, and humans. Although no genetic relatedness was observed among strains from various sources, the genomic clustering among strains from the same sources strongly suggests the potential risk of transmission along the supply chain at the human–fish-environment interface if strict hygienic fish production is not in place. Further robust genetic study of the new strains with unknown O-antigens, and the epidemiology of SN-F E. coli is required to elucidate the molecular profile and public health implications of the pathogens. [ABSTRACT FROM AUTHOR]

Background: The objective of this network meta-analysis was to compare rates of clinical response and mortality for empiric oral antibiotic regimens in adults with mild-moderate community-acquired pneumonia (CAP). Methods: We searched PubMed, Cochrane, and the reference lists of systematic reviews and clinical guidelines. We included randomized trials of adults with radiologically confirmed mild to moderate CAP initially treated orally and reporting clinical cure or mortality. Abstracts and studies were reviewed in parallel for inclusion in the analysis and for data abstraction. We performed separate analyses by antibiotic medications and antibiotic classes and present the results through network diagrams and forest plots sorted by p-scores. We assessed the quality of each study using the Cochrane Risk of Bias framework, as well as global and local inconsistency. Results: We identified 24 studies with 9361 patients: six at low risk of bias, six at unclear risk, and 12 at high risk. Nemonoxacin, levofloxacin, and telithromycin were most likely to achieve clinical response (p-score 0.79, 0.71, and 0.69 respectively), while penicillin and amoxicillin were least likely to achieve clinical response. Levofloxacin, nemonoxacin, azithromycin, and amoxicillin-clavulanate were most likely to be associated with lower mortality (p-score 0.85, 0.75, 0.74, and 0.68 respectively). By antibiotic class, quinolones and macrolides were most effective for clinical response (0.71 and 0.70 respectively), with amoxicillin-clavulanate plus macrolides and beta-lactams being less effective (p-score 0.11 and 0.22). Quinolones were most likely to be associated with lower mortality (0.63). All confidence intervals were broad and partially overlapping. Conclusion: We observed trends toward a better clinical response and lower mortality for quinolones as empiric antibiotics for CAP, but found no conclusive evidence of any antibiotic being clearly more effective than another. More trials are needed to inform guideline recommendations on the most effective antibiotic regimens for outpatients with mild to moderate CAP. [ABSTRACT FROM AUTHOR]

We have developed an innovative thin-film nanocomposite membrane that contains cellulose acetate (CA) with small amounts of TiO2-decorated graphene oxide (GO) (ranging from 0.5 wt.% to 2 wt.%) sandwiched between two polytetrafluoroethylene (PTFE)-like thin films. The PTFE-like films succeeded in maintaining the bulk porosity of the support while increasing the thermal and chemical robustness of the membrane and boosting the catalytic activity of TiO2 nanoparticles. The membranes exhibited a specific chemical composition and bonding, with predominant carbon–oxygen bonds from CA and GO in the bulk, and carbon–fluorine bonds on their PTFE-like coated sides. We have also tested the membranes' photocatalytic activities on azithromycin-containing wastewaters, demonstrating excellent efficiency with more than 80% degradation for 2 wt.% TiO2-decorated GO in the CA-GO-TiO2/PTFE-like membranes. The degradation of the azithromycin formulation occurs in two steps, with reaction rates being correlated to the amount of GO-TiO2 in the membranes. [ABSTRACT FROM AUTHOR]

Background: In November 2019, the world faced a pandemic called SARS-CoV-2, which became a major threat to humans and continues to be. To overcome this, many plants were explored to find a cure. Methods: Therefore, this research was planned to screen out the active constituents from Artemisia annua that can work against the viral main protease Mpro as this non-structural protein is responsible for the cleavage of replicating enzymes of the virus. Twenty-five biocompounds belonging to different classes namely alpha-pinene, beta-pinene, carvone, myrtenol, quinic acid, caffeic acid, quercetin, rutin, apigenin, chrysoplenetin, arteannunin b, artemisinin, scopoletin, scoparone, artemisinic acid, deoxyartemisnin, artemetin, casticin, sitogluside, beta-sitosterol, dihydroartemisinin, scopolin, artemether, artemotil, artesunate were selected. Virtual screening of these ligands was carried out against drug target Mpro by CB dock. Results: Quercetin, rutin, casticin, chrysoplenetin, apigenin, artemetin, artesunate, sopolin and sito-gluside were found as hit compounds. Further, ADMET screening was conducted which represented Chrysoplenetin as a lead compound. Azithromycin was used as a standard drug. The interactions were studied by PyMol and visualized in LigPlot. Furthermore, the RMSD graph shows fluctuations at various points at the start of simulation in Top1 (Azithromycin) complex system due to structural changes in the helix-coil-helix and beta-turn-beta changes at specific points resulting in increased RMSD with a time frame of 50 ns. But this change remains stable after the extension of simulation time intervals till 100 ns. On other side, the Top2 complex system remains highly stable throughout the time scale. No such structural dynamics were observed bu the ligand attached to the active site residues binds strongly. Conclusion: This study facilitates researchers to develop and discover more effective and specific therapeutic agents against SARS-CoV-2 and other viral infections. Finally, chrysoplenetin was identified as a more potent drug candidate to act against the viral main protease, which in the future can be helpful. [ABSTRACT FROM AUTHOR]

Lefamulin is a first-in-class systemic pleuromutilin antimicrobial and potent inhibitor of bacterial translation, and the most recent novel antimicrobial approved for the treatment of community-acquired pneumonia (CAP). It exhibits potent antibacterial activity against the most prevalent bacterial pathogens that cause typical and atypical pneumonia and other infectious diseases. Early studies indicate additional anti-inflammatory activity. In this study, we further investigated the immune-modulatory activity of lefamulin in the influenza A/H1N1 acute respiratory distress syndrome (ARDS) model in BALB/c mice. Comparators included azithromycin, an anti-inflammatory antimicrobial, and the antiviral oseltamivir. Lefamulin significantly decreased the total immune cell infiltration, specifically the neutrophils, inflammatory monocytes, CD4+ and CD8+ T-cells, NK cells, and B-cells into the lung by Day 6 at both doses tested compared to the untreated vehicle control group (placebo), whereas azithromycin and oseltamivir did not significantly affect the total immune cell counts at the tested dosing regimens. Bronchioalveolar lavage fluid concentrations of pro-inflammatory cytokines and chemokines including TNF-α, IL-6, IL-12p70, IL-17A, IFN-γ, and GM-CSF were significantly reduced, and MCP-1 concentrations were lowered (not significantly) by lefamulin at the clinically relevant 'low' dose on Day 3 when the viral load peaked. Similar effects were also observed for oseltamivir and azithromycin. Lefamulin also decreased the viral load (TCID50) by half a log10 by Day 6 and showed positive effects on the gross lung pathology and survival. Oseltamivir and lefamulin were efficacious in the suppression of the development of influenza-induced bronchi-interstitial pneumonia, whereas azithromycin did not show reduced pathology at the tested treatment regimen. The observed anti-inflammatory and immune-modulatory activity of lefamulin at the tested treatment regimens highlights a promising secondary pharmacological property of lefamulin. While these results require confirmation in a clinical trial, they indicate that lefamulin may provide an immune-modulatory activity beyond its proven potent antibacterial activity. This additional activity may benefit CAP patients and potentially prevent acute lung injury (ALI) and ARDS. [ABSTRACT FROM AUTHOR]

Background: Randomized controlled trials found that twice-yearly mass azithromycin administration (MDA) reduces childhood mortality, presumably by reducing infection burden. World Health Organization (WHO) issued conditional guidelines for mass azithromycin administration in high-mortality settings in sub-Saharan Africa given concerns for antibiotic resistance. While prolonged twice-yearly MDA has been shown to increase antibiotic resistance in small randomized controlled trials, the objective of this study was to determine if macrolide and non-macrolide resistance in the gut increases with the duration of azithromycin MDA in a larger setting. Methods and findings: The Macrolide Oraux pour Réduire les Décès avec un Oeil sur la Résistance (MORDOR) study was conducted in Niger from December 2014 to June 2020. It was a cluster-randomized trial of azithromycin (A) versus placebo (P) aimed at evaluating childhood mortality. This is a sub-study in the MORDOR trial to track changes in antibiotic resistance after prolonged azithromycin MDA. A total of 594 communities were eligible. Children 1 to 59 months in 163 randomly chosen communities were eligible to receive treatment and included in resistance monitoring. Participants, staff, and investigators were masked to treatment allocation. At the conclusion of MORDOR Phase I, by design, all communities received an additional year of twice-yearly azithromycin treatments (Phase II). Thus, at the conclusion of Phase II, the treatment history (1 letter per 6-month period) for the participating communities was either (PP-PP-AA) or (AA-AA-AA). In Phase III, participating communities were then re-randomized to receive either another 3 rounds of azithromycin or placebo, thus resulting in 4 treatment histories: Group 1 (AA-AA-AA-AA-A, N = 51), Group 2 (PP-PP-AA-AA-A, N = 40), Group 3 (AA-AA-AA-PP-P, N = 27), and Group 4 (PP-PP-AA-PP-P, N = 32). Rectal swabs from each child (N = 5,340) were obtained 6 months after the last treatment. Each child contributed 1 rectal swab and these were pooled at the community level, processed for DNA-seq, and analyzed for genetic resistance determinants. The primary prespecified outcome was macrolide resistance determinants in the gut. Secondary outcomes were resistance to beta-lactams and other antibiotic classes. Communities recently randomized to azithromycin (groups 1 and 2) had significantly more macrolide resistance determinants than those recently randomized to placebo (groups 3 and 4) (fold change 2.18, 95% CI 1.5 to 3.51, Punadj < 0.001). However, there was no significant increase in macrolide resistance in communities treated 4.5 years (group 1) compared to just the most recent 2.5 years (group 2) (fold change 0.80, 95% CI 0.50 to 1.00, Padj = 0.010), or between communities that had been treated for 3 years in the past (group 3) versus just 1 year in the past (group 4) (fold change 1.00, 95% CI 0.78 to 2.35, Padj = 0.52). We also found no significant differences for beta-lactams or other antibiotic classes. The main limitations of our study were the absence of phenotypic characterization of resistance, no complete placebo arm, and no monitoring outside of Niger limiting generalizability. Conclusions: In this study, we observed that mass azithromycin distribution for childhood mortality among preschool children in Niger increased macrolide resistance determinants in the gut but that resistance may plateau after 2 to 3 years of treatment. Co-selection to other classes needs to be monitored. Trial registration: NCT02047981https://classic.clinicaltrials.gov/ct2/show/NCT02047981. Thuy Doan and co-workers explore the impact of mass azithromycin distribution on the antibiotic resistance in the gut of Nigerien pre-school children. Author summary: Why was this study done?: Mass azithromycin distributions to children aged 1 to 59 months in sub-Saharan countries improve childhood mortality. Prolonged mass azithromycin distributions may be necessary until a definitive solution is found for child mortality. However, mass azithromycin distributions also select for antibiotic resistance. Here, we compare communities randomized to different treatment histories to assess how antibiotic resistance changes over several years. What did the researchers do and find?: MORDOR was a cluster-randomized trial of azithromycin versus placebo aimed at evaluating childhood mortality. Randomization was performed at the village level. We conducted a sub-study of the MORDOR trial to track changes to antibiotic resistance in the gut, and 5,340 children from 150 villages were included. Rectal swabs were obtained, pooled, and sequenced for antibiotic resistance. We found that macrolide resistance determinants were increased in the gut of children whose villages were treated with twice-yearly azithromycin administration within the past 2 years compared to those who were treated with placebo. Longer periods of treatment with azithromycin were not associated with increased macrolide resistance and no changes to non-macrolide resistance determinants were detected. The main limitations of this study include the lack of phenotypic resistance assessment, the absence of a treatment arm where communities received a placebo for all 5 years, and that interpretations are limited to the community level in the Dosso region of Niger. What do these findings mean?: These findings are consistent with prior smaller studies showing that twice-yearly azithromycin treatment, at the dose recommended to improve childhood mortality, selects for macrolide resistance. However, resistance may plateau after several years, rather than continuing to increase. Non-macrolide resistance determinants were not significantly different between treatment arms, although p-values and confidence intervals need to be interpreted with caution. These findings suggest that careful surveillance for antibiotic resistance should be continued for mass drug distribution for childhood mortality. [ABSTRACT FROM AUTHOR]

Pharmacokinetic data for injectable azithromycin in children remain limited. This study aims to develop and validate a population pharmacokinetic model of azithromycin for injection in children under 6 years old and optimize its dosage regimen in this population. We prospectively enrolled patients under 6 years old who received azithromycin for injection at Beijing Friendship Hospital, Capital Medical University. Demographic information, clinical characteristics, and venous blood samples were collected in accordance with the research protocol. Azithromycin concentrations were determined using a validated UPLC-MS/MS method. The population pharmacokinetic model was structured using Phoenix NLME. The adequacy and robustness of the model was evaluated using VPC and bootstrap. We optimized azithromycin's dosing regimen for injection through Monte Carlo simulations. We included 254 plasma concentration data from 148 patients to establish the model. The clearance and volume were 1.27 L/h/kg and 45.6 L/kg, respectively. The covariates included were weight and age. VPC plots and nonparametric bootstrap showed that the final PPK model was reliable and robust. Based on Monte Carlo simulation, we derived a simple and practical dosing scheme. The results provided reference for individualized dosing in this population. The individualized dosing scheme based on Monte Carlo simulation can optimize clinical decision-making and guide personalized therapy. [ABSTRACT FROM AUTHOR]

Purpose: Campylobacter is a frequent cause of enteric infections with common antimicrobial resistance issues. The most recent reports of campylobacteriosis in Italy include data from 2013 to 2016. We aimed to provide national epidemiological and microbiological data on human Campylobacter infections in Italy during the period 2017–2021. Methods: Data was collected from 19 Hospitals in 13 Italian Regions. Bacterial identification was performed by mass spectrometry. Antibiograms were determined with Etest or Kirby-Bauer (EUCAST criteria). Results: In total, 5419 isolations of Campylobacter spp. were performed. The most common species were C. jejuni (n = 4535, 83.7%), followed by C. coli (n = 732, 13.5%) and C. fetus (n = 34, 0.6%). The mean age of patients was 34.61 years and 57.1% were males. Outpatients accounted for 54% of the cases detected. Campylobacter were isolated from faeces in 97.3% of cases and in 2.7% from blood. C. fetus was mostly isolated from blood (88.2% of cases). We tested for antimicrobial susceptibility 4627 isolates (85.4%). Resistance to ciprofloxacin and tetracyclines was 75.5% and 54.8%, respectively; resistance to erythromycin was 4.8%; clarithromycin 2% and azithromycin 2%. 50% of C. jejuni and C. coli were resistant to ≥ 2 antibiotics. Over the study period, resistance to ciprofloxacin and tetracyclines significantly decreased (p < 0.005), while resistance to macrolides remained stable. Conclusion: Campylobacter resistance to fluoroquinolones and tetracyclines in Italy is decreasing but is still high, while macrolides retain good activity. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance in Neisseria gonorrhoeae (NG) is increasing worldwide. Second-line treatments with macrolides or fluoroquinolones are an option for NG infections in some cases following the STI guideline recommendations. In our study, we compared the gradient diffusion test using EUCAST 2024 breakpoints with a new molecular method using the Allplex™ NG&DR assay (Seegene®) including A2059G/C2611 mutations (23S rRNA) associated with high/moderate-level macrolide resistance and S91F mutation (gyrA) relationship with fluoroquinolone resistance in NG isolates (n = 100). We calculated the sensitivity, specificity, and correlation of the molecular test for fluoroquinolone using the gradient diffusion as the reference method. In twenty-three strains was not detected any mutation associated with macrolides or fluoroquinolone resistance. No A2059G/C2611T mutations were detected, and the S91F mutations were detected in 77 out of the 100 isolates screened. Twenty-three NG isolates were reported to be resistant to azithromycin (ECOFF: >1 mg/L), and 78 NG isolates were resistant to ciprofloxacin (MIC: >0.06 mg/L). The molecular method showed a sensitivity of 96.1% and, a specificity of 90.9% for fluoroquinolone susceptibility, but the statistical analysis between the molecular test and gradient diffusion test was not statistically significant for fluoroquinolone resistance (p = 1). Statistical analysis was not performed for macrolides because of the absence of positive RT-PCR results. According to our data, Allplex™ assay cannot replace the gradient diffusion test for macrolide resistance. However, the assay could be used to test fluoroquinolone resistance in NG isolates as a replacement for phenotypic methods. [ABSTRACT FROM AUTHOR]

Aim Materials and Methods Results Conclusions To evaluate the effectiveness of a flapless surgical approach in the treatment of peri‐implantitis and to explore the factors influencing its outcome.The present retrospective study evaluated patients with at least one implant diagnosed with peri‐implantitis and treated with a flapless surgical access, with or without systemic antimicrobials, curettage and, when needed, prostheses modification. Clinical and radiographic parameters were assessed at baseline and at 3 months and at least 12 months. The primary outcome was disease resolution (≤1 bleeding sites, probing depth [PD] ≤5 mm, no bone loss >0.5 mm). Multilevel regression analyses were used to identify predictors influencing the probability of attaining disease resolution.One hundred and seventeen patients with 338 implants were included. Disease resolution was attained in 54.4% of the 338 implants receiving flapless surgical access. At the end of the follow‐up period, 111 patients (94.9%) with 295 implants (87.3%) did not require any further treatment, with 81.4% of these implants presenting PD ≤ 5 mm. History of periodontitis and PD at baseline were identified as negative predictors, while compliance with supportive peri‐implant care, a machined surface and the adjunctive use of systemic azithromycin or metronidazole were identified as positive predictive factors for disease resolution.A flapless surgical approach led to disease resolution in 54.4% of the implants with peri‐implantitis. Several risk/protective predictors for disease resolution were identified. [ABSTRACT FROM AUTHOR]

Airway mucus hypersecretion is an important pathophysiological and clinical manifestation of a variety of chronic airway diseases, and is an independent risk factor affecting the prognosis and outcome of the disease. Azithromycin can effectively prevent or reduce the acute exacerbation of chronic airway diseases and inhibit the hypersecretion of airway mucus in chronic airway diseases. However, the specific mechanism is not completely clear, which may be related to the inhibition of the synthesis and secretion of mucin MUC5AC and the inhibition of bacterial biofilm formation. This article summarizes the possible mechanism of azithromycin in inhibiting airway mucus hypersecretion and its application in chronic airway diseases, in order to provide reference for the follow-up study and clinical application of azithromycin. [ABSTRACT FROM AUTHOR]

Azithromycin (AZM) is efficient for treatment of chronic Pseudomonas aeruginosa biofilm lung infections, despite of resistance in conventional susceptibility testing. It has been shown that planktonic P. aeruginosa are more susceptible to AZM when tested in RPMI 1640 medium. The aim of the study was to test the susceptibility to AZM of P. aeruginosa biofilms in LB vs RPMI 1640 media. We investigated the effect of AZM on planktonic and biofilms of (WT) P. aeruginosa (PAO1), the hypermutable (ΔmutS) and the antibiotic‐resistant phenotype(ΔnfxB) mutants. The effect of AZM on young and mature biofilms was investigated in the modified Calgary Biofilm Device by estimation of the minimal biofilm inhibitory concentration (MBIC). The AZM MBIC90 in LB/RPMI1640 on young biofilms treated for 24 h was 16/4 μg/mL for PAO1, 32/8 μg/mL for ΔmutS, and 256/16 μg/mL for ΔnfxB, while in mature biofilms was 256/2 μg/mL for PAO1 and ΔmutS and 16/1 μg/mL for ΔnfxB. The effect of AZM was improved when the treatment was prolonged to 72 h, supporting the intracellular accumulation of AZM. An increased susceptibility of P. aeruginosa biofilms to AZM was observed in RPMI 1640 than in LB medium. Our results might improve susceptibility testing and dosing of AZM for treatment of biofilm infections. [ABSTRACT FROM AUTHOR]

Background Bacterial pathogens cause substantial diarrhea morbidity and mortality among children living in endemic settings, yet antimicrobial treatment is only recommended for dysentery or suspected cholera. Methods AntiBiotics for Children with severe Diarrhea was a 7-country, placebo-controlled, double-blind efficacy trial of azithromycin in children 2–23 months of age with watery diarrhea accompanied by dehydration or malnutrition. We tested fecal samples for enteric pathogens utilizing quantitative polymerase chain reaction to identify likely and possible bacterial etiologies and employed pathogen-specific cutoffs based on genomic target quantity in previous case-control diarrhea etiology studies to identify likely and possible bacterial etiologies. Results Among 6692 children, the leading likely etiologies were rotavirus (21.1%), enterotoxigenic Escherichia coli encoding heat-stable toxin (13.3%), Shigella (12.6%), and Cryptosporidium (9.6%). More than one-quarter (1894 [28.3%]) had a likely and 1153 (17.3%) a possible bacterial etiology. Day 3 diarrhea was less common in those randomized to azithromycin versus placebo among children with a likely bacterial etiology (risk difference [RD]likely, −11.6 [95% confidence interval {CI}, −15.6 to −7.6]) and possible bacterial etiology (RDpossible, −8.7 [95% CI, −13.0 to −4.4]) but not in other children (RDunlikely, −0.3% [95% CI, −2.9% to 2.3%]). A similar association was observed for 90-day hospitalization or death (RDlikely, −3.1 [95% CI, −5.3 to −1.0]; RDpossible, −2.3 [95% CI, −4.5 to −.01]; RDunlikely, −0.6 [95% CI, −1.9 to.6]). The magnitude of risk differences was similar among specific likely bacterial etiologies, including Shigella. Conclusions Acute watery diarrhea confirmed or presumed to be of bacterial etiology may benefit from azithromycin treatment. Clinical Trials Registration NCT03130114. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 burdens healthcare systems worldwide, yet specific drug-based treatments are still unavailable. Understanding the effects of SARS-CoV-2 on host molecular pathways is critical for providing full descriptions and optimizing therapeutic targets. The present study used Nuclear Magnetic Resonance-based metabolic footprinting to characterize the secreted cellular metabolite levels (exometabolomes) of Vero E6 cells in response to SARS-CoV-2 infection and to two candidate drugs (Remdesivir, RDV, and Azithromycin, AZI), either alone or in combination. SARS-CoV-2 infection appears to force VE6 cells to have increased glucose concentrations from extra-cellular medium and altered energetic metabolism. RDV and AZI, either alone or in combination, can modify the glycolic-gluconeogenesis pathway in the host cell, thus impairing the mitochondrial oxidative damage caused by the SARS-CoV-2 in the primary phase. RDV treatment appears to be associated with a metabolic shift toward the TCA cycle. Our findings reveal a metabolic reprogramming produced by studied pharmacological treatments that protects host cells against virus-induced metabolic damage, with an emphasis on the glycolytic-gluconeogenetic pathway. These findings may help researchers better understand the relevant biological mechanisms involved in viral infection, as well as the creation of mechanistic hypotheses for such candidate drugs, thereby opening up new possibilities for SARS-CoV-2 pharmacological therapy. [ABSTRACT FROM AUTHOR]

Introduction Antimicrobial resistance in Neisseria gonorrhoeae compromises gonorrhoea treatment and rapid antimicrobial susceptibility testing (AST) would be valuable. We have developed a rapid and accurate flow cytometry method (FCM) for AST of gonococci. Methods The 2016 WHO gonococcal reference strains, and WHO Q, R and S (n  = 17) were tested against seven clinically relevant antibiotics (ceftriaxone, cefixime, azithromycin, spectinomycin, ciprofloxacin, tetracycline and gentamicin). After 4.5 h incubation of inoculated broth, the fluorescent dye Syto™ 9 was added, followed by FCM analysis. After gating, the relative remaining population of gonococci, compared with unexposed growth control samples, was plotted against antimicrobial concentration, followed by non-linear curve regression analysis. Furthermore, the response at one single concentration/tested antibiotic was evaluated with the intention to use as a screening test for detection of resistant gonococci. Results A dose-dependent response was seen in susceptible isolates for all tested antimicrobials. There was a clear separation between susceptible/WT and resistant/non-WT isolates for ceftriaxone, cefixime, spectinomycin, ciprofloxacin and tetracycline. In contrast, for azithromycin, only high-level-resistant isolates were distinguished, while resistant isolates with MICs of 4 mg/L were indistinguishable from WT (MIC ≤ 1 mg/L) isolates. For gentamicin, all tested 17 isolates were WT and FCM analysis resulted in uniform dose–response curves. Using a single antibiotic concentration and a 50% remaining cell population cut-off, the overall sensitivity and specificity for resistance detection were 93% and 99%, respectively. Conclusions By providing results in <5 h for gonococcal isolates, FCM-based AST can become a rapid screening method for antimicrobial resistance or antimicrobial susceptibility in gonococci. [ABSTRACT FROM AUTHOR]

Background: Prior research has raised concerns regarding the use of macrolides and their association with an increased risk of cardiovascular events. Methods: We conducted a cohort study, where we explored the cardiovascular risks associated with the treatment of COPD patients using macrolide antibiotics–namely azithromycin, clarithromycin, and roxithromycin—with amoxicillin serving as a reference. The study focused on COPD patients in an outpatient setting and included a thorough 3-year follow-up. Patients were categorized into four groups based on their treatment. The primary analysis utilized an adjusted Cox model, supplemented by sensitivity analysis through inverse probability of treatment weighting. Results: No significant differences were found in major adverse cardiovascular events (MACE—stroke, acute myocardial infarction, cardiovascular death) between the macrolide groups, and the amoxicillin/hazard ratios (HR) were azithromycin HR = 1.01, clarithromycin HR = 0.99, and roxithromycin HR = 1.02. Similarly, sensitivity analysis showed no disparities in all-cause mortality and cardiovascular death among the groups. Conclusions: Overall, the study revealed no evidence of increased risk of MACE, all-cause mortality, or cardiovascular death in COPD patients treated with these macrolides compared to amoxicillin over a 3-year period. [ABSTRACT FROM AUTHOR]

Following a national population-based trachoma survey in Malawi one round of azithromycin mass drug administration (MDA) was carried out, with a post-MDA impact survey showing TF prevalence below 5% and considered eliminated as a public health problem. However, active trachoma was still present in over 200 children. We assessed whether water, sanitation, and hygiene (WASH) factors were associated with ongoing presence of TF in children aged 1–9 years following MDA. A secondary analysis was performed on a sub-set of the post-MDA impact survey data for children aged 1–9 years. We used a logistic regression analysis, adjusted for clustering at the household and village level. Among 16,142 children aged 1–9 years, 209 (1.3%) had TF after MDA. Factors associated with a significantly lower odds of TF after MDA were living in a household with a handwashing facility (aOR: 0.37) and living in a household where water for washing is located further away from the home (30 min away aOR: 0.39, p =.034, or more than 1 h away aOR: 0.31, p =.018) compared with water in the yard. The inverse association between a domestic handwashing facility and TF is consistent with previous findings, but the association of increasing distance to collect water for washing with a reduced risk of TF was unexpected and may reflect the impact of drought and unmeasured behavioural factors related to water usage. A more comprehensive collection of sociodemographic and WASH factor information in population-based trachoma surveys will provide insight into achieving and maintaining low levels of trachoma. [ABSTRACT FROM AUTHOR]

This review article explores the effectiveness of antibacterial drugs that inhibit protein synthesis in treating pythiosis, a difficult-to-treat infection caused by Pythium insidiosum. The article highlights the susceptibility of P. insidiosum to antibacterial drugs, such as macrolides, oxazolidinones, and tetracyclines. We examine various studies, including in vitro tests, experimental infection models, and clinical case reports. Based on our synthesis of these findings, we highlight the potential of these drugs in managing pythiosis, primarily when combined with surgical interventions. The review emphasizes the need for personalized treatment strategies and further research to establish standardized testing protocols and optimize therapeutic approaches. [ABSTRACT FROM AUTHOR]

The rapid expansion of telemedicine has highlighted challenges and opportunities to improve antibiotic use and effectively adapt antibiotic stewardship best practices to outpatient telemedicine settings. Antibiotic stewardship integration into telemedicine is essential to optimize antibiotic prescribing for patients and ensure health care quality. We performed a narrative review of published literature on antibiotic prescribing and stewardship in outpatient telemedicine to inform the adaptation of the Core Elements of Outpatient Antibiotic Stewardship framework to outpatient telemedicine settings. Our narrative review suggests that in-person antibiotic stewardship interventions can be adapted to outpatient telemedicine settings. We present considerations for applying the Core Elements of Outpatient Antibiotic Stewardship to outpatient telemedicine which builds upon growing evidence describing care delivery and quality improvement in this setting. Additional applied implementation research is necessary to inform the application of effective, sustainable, and equitable antibiotic stewardship interventions across the spectrum of outpatient telemedicine. [ABSTRACT FROM AUTHOR]

Introduction: The use of oral azithromycin (AZI) as a preventive measure against postpartum infections of planned vaginal births has garnered a lot of interest in recent years and has been the subject of many randomized controlled trials (RCTs). However, the results from these trials have not been consistent. Therefore, we aim to perform a systematic review and meta‐analysis to determine whether the use of a single‐dose of oral AZI is clinically significant. Methods: We systematically searched PubMed, Embase, and Cochrane Central for RCTs from May to June 2023, comparing a single dose of oral AZI with placebo in patients undergoing planned vaginal delivery at a minimum of 28 weeks of gestational age. The main outcomes were puerperal and neonatal sepsis. Statistical analyses were performed using Review Manager 5.4.1 (Cochrane Collaboration). Heterogeneity was assessed with I2 statistics. Results: Four RCTs were included (mothers, n = 42 235; newborns n = 42 492). Approximately 49.8% of mothers received a single dose of oral AZI for sepsis prophylaxis. Compared with placebo, AZI significantly reduced the incidence of puerperal sepsis (risk ratio [RR], 0.65 [95% confidence interval (CI), 0.55–0.77]; P < 0.001), mastitis or breast abscess (RR, 0.58 [95% CI, 0.42–0.79]; P < 0.001), endometritis (RR, 0.65 [95% CI, 0.54–0.77]; P < 0.001), wound infection (RR, 0.81 [95% CI, 0.69–0.96]; P = 0.013), infection rate (RR, 0.62 [95% CI, 0.51–0.76]; P < 0.001), and fever (RR, 0.50 [95% CI, 0.28–0.89]; P = 0.018) in mothers. No statistically significant differences were identified between groups regarding maternal all‐cause mortality and the use of prescribed postpartum antibiotics. Similarly, no statistical differences were noted in the neonatal group regarding sepsis, infection rate, and all‐cause mortality. Conclusion: AZI appears to be an effective preventive measure against many postpartum infections in mothers but a substantial impact on neonatal outcomes has not yet been conclusively observed. Synopsis: Administration of azithromycin has been shown to prevent postpartum infections and sepsis in mothers undergoing vaginal delivery. [ABSTRACT FROM AUTHOR]

Azithromycin is a macrolide antibiotic that is commonly prescribed to treat infections of the skin, soft tissues, and the upper and lower respiratory tracts. Many antibiotics, including azithromycin, are overprescribed, leading to elevated concentrations of these drugs in bodies of water; this phenomenon is referred to as antibiotic pollution. Antibiotic pollution is increasingly concerning, due to its implications for the development of antibiotic resistance and its potential ecotoxicity. Rapid detection of azithromycin in wastewater could be important for addressing antibiotic pollution. This research highlights the development of a direct electrochemical surface-enhanced Raman spectroscopy method for the detection of azithromycin in synthetic wastewater. The coupling of electrochemistry and surface-enhanced Raman spectroscopy allowed enhanced detection of azithromycin and its derivatives in wastewater. To the best of our knowledge, this is the first report of direct detection of azithromycin using electrochemical surface-enhanced Raman spectroscopy. This novel detection method has promising application in future research concerning antibiotic pollution. [ABSTRACT FROM AUTHOR]

COVID-19 pandemic changed the face of global health and brought about new issues in global health security and economy. The World Health Organization published guidelines for clinical management of COVID-19 four months after declaration of COVID-19 as a pandemic. Scholarly reviews and studies from member states within WHO AFRO reveals significant deviation from the WHO published protocols on COVID-19. Assessment of national treatment protocols of 30 of 47 WHO AFRO member states showed widespread inappropriate use of antimicrobial agents for patients, which may worsen the global and concerning threat of antimicrobial resistance. There is need for adopting interventions that optimize antimicrobial use in the context of pre- and post-pandemic preparedness to ensure long-term effectiveness and sustainability for antimicrobials. Treatment guidelines are to be adopted or adapted depending on best clinical evidence available. Non-compliance with guidelines might lead to mismanagement of infectious diseases with attendant negative consequences including antimicrobial resistance and misdirection of critical resources and supplies amongst others. [ABSTRACT FROM AUTHOR]

Telogen effluvium is characterized by excessive hair shedding usually following a stressful event. Ferritin has been used in clinical practice as a biomarker of nonanemic iron deficiency in cases of telogen effluvium. During the years of the COVID19 pandemic, telogen effluvium was reported as a part of post covid manifestations. As ferritin was also a biomarker for inflammation in cases with covid infection, this study was designed to evaluate the value of ferritin in cases with postcovid telogen effluvium one hundred patients recovering from covid 19 for 4–12 weeks were included in the study, detailed drug and laboratory history was obtained and serum ferritin level was measured. the mean serum level of ferritin among telogen effluvium patients was significantly lower than controls (68.52 ± 126 and 137 ± 137.597 ug/L respectively). Patients with telogen effluvium used significantly more azithromycin and ivermectin and significantly less vitamin C, D, lactoferrin and zinc than the controls Although serum ferritin is lower among telogen effluvium patients, it was still higher than the cutoff value for diagnosing nonanemic iron deficiency, we suggest that it will not be a good biomarkers in these cases. Our secondary outcomes showed that dietary supplements used during active infection such as vitamin C, D, lactoferrin and zinc might have a preventive value on postcovid hair loss, while azithromycin and ivermectin could have a negative long term effect on telogen effluvium. [ABSTRACT FROM AUTHOR]

Background: Mycoplasma genitalium is an emerging pathogen, which has been linked to cervicitis, urethritis and pelvic inflammatory disease (PID). With the advent of multiplex polymerase chain reaction (PCR) panels for sexually transmitted infections, it is increasingly being identified in pregnant women. Objectives: The aim was to review international guidelines, which had explicit recommendations for treatment of M. genitalium infection in pregnancy and breastfeeding. Search Strategy: PubMed, EMBASE and Cochrane databases were reviewed with no age, species, language or date restrictions. Selection Criteria: Studies were included if they had an explicit recommendation for treatment of M. genitalium in pregnancy. Studies were excluded if there was no recommendation in pregnancy, if they referred to other international guideline recommendations or were historical versions of guidelines. Data Collection and Analysis: References were manually reviewed and 50 papers were selected for review. Only four guidelines were included in the final analysis and they were from Europe, UK, Australia and Aotearoa New Zealand. Main Results: All studies recommended azithromycin as first‐line treatment, and advised against moxifloxacin use. The dosing schedule of azithromycin, varied between guidelines, as did the utility/safety of pristinamycin for macrolide resistant infections. Safety data was generally reassuring for azithromycin but inconsistent for pristinamycin. Conclusions: Azithromycin is the first‐line treatment for macrolide susceptible or unknown resistance infections, but there is a lack of consistency regarding dosing of azithromycin or the utility/safety of pristinamycin for macrolide resistant infections in pregnancy/lactation. Synopsis: While international guidelines recommend azithromycin as first‐line treatment for M. genitalium infections in pregnancy, there are inconsistencies around second‐line treatment options and azithromycin dosing. [ABSTRACT FROM AUTHOR]

The efficacy of macrolides in the management of asthma has been studied but remains controversial. We conducted a systematic review and meta-analysis of macrolides in the management of adult patients with asthma. Randomized controlled trials of macrolides used in adult patients with asthma were searched for in MEDLINE, EMBASE, PsycINFO, Cochrane Library, CINAHL, and Igaku Chuo Zasshi databases to evaluate the efficacy and safety of macrolides. Seventeen reports with macrolide treatment durations ranging from 6 to 48 weeks were included. Macrolides did not reduce exacerbations requiring hospitalization, severe exacerbations, or rescue use of short-acting beta-2 agonist inhalers; improve lung function; decrease peripheral blood or sputum neutrophil counts; or decrease fractional exhaled nitric oxide compared to placebo. Macrolides statistically improved asthma control and quality of life but by less than the minimal clinically important difference. Peripheral blood eosinophil counts as well as serum and sputum eosinophilic cationic protein concentrations were significantly decreased with macrolides compared to placebo. The improvement of asthma symptoms and airway hyperresponsiveness varied by study. The safety profile of macrolides was comparable to that of placebo. Although macrolides have some useful clinical aspects, there is not sufficient evidence to recommend their use in the management of adult patients with asthma. [ABSTRACT FROM AUTHOR]

The main objective of this project was to compare in the field conditions two strategies of re‐nutrition of children with moderate acute malnutrition (MAM) aged from 6 to 24 months, targeting the microbiota in comparison with a standard regimen. A three‐arm, open‐label, pragmatic randomised trial was conducted in four countries (Niger, CAR, Senegal and Madagascar). Children received for 12 weeks either fortified blended flour (FBF control) = arm 1, or FBF + azithromycin (oral suspension of 20 mg/kg/day daily given with a syringe) for the first 3 days at inclusion = arm 2 or mix FBF with inulin/fructo‐oligosaccharides (6 g/day if age ≥12 months and 4 g if age <12 months) = arm 3. For each arm, children aged from 6 to 11 months received 100 g x 2 per day of flours and those aged from 12 to 24 months received 100 g × 3 per day of FBF. The primary endpoint was nutritional recovery, defined by reaching a weight‐for‐height z‐score (WHZ) ≥ −1.5 within 12 weeks. Overall, 881 children were randomised (297, 290 and 294 in arm 1, arm 2 and arm 3, respectively). Three hundred and forty‐four children were males (39%) and median/mean age were 14.6/14.4 months (SD = 4.9, IQR = 10.5–18.4). At inclusion, the three arms were comparable for all criteria, but differences were observed between countries. Overall, 44% (390/881) of the children recovered at week 12 from MAM, with no significant difference between the three arms (41.4%, 45.5% and 45.9%, in arm 1, arm 2 and arm 3, respectively, p = 0.47). This study did not support the true advantages of adding a prebiotic or antibiotic to flour. When using a threshold of WHZ ≥ −2 as an exploratory endpoint, significant differences were observed between the three arms, with higher success rates in arms with antibiotics or prebiotics compared to the control arm (66.9%, 66.0% and 55.2%, respectively, p = 0.005). Key messages: Re‐nutrition of children with MAM is still a concern as the duration of recovery is always long and recurrences are frequent.Literature suggests that prebiotics and antibiotics show potentially useful properties to speed this process of recovery.However, in this open‐label study, prebiotics and antibiotics did not lead to advantages on the recovery rates defined by reaching the WHZ (−1.5) cut‐off. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study was to assess the long‐term effects of topical azithromycin on signs, symptoms and self‐management of meibomian gland dysfunction (MGD). Methods: Forty participants were assessed for MGD and its effect on the fluorescein tear break‐up time (FTBUT). Participants were treated with topical azithromycin twice daily for 2 weeks and then once daily for a further 2 weeks. One year after treatment, 31 participants completed a survey assessing pre‐ and post‐treatment effect on symptoms, lifestyle and self‐treatment methods. Results: Following treatment, there was a significant reduction in MGD grading from a median of grade 2 to grade 0 (z = 4.40, p < 0.0001) and an increase in FTBUT from a median of 3–8 s (z = 4.75, p < 0.0001). One year afterwards, the survey showed a significant improvement in symptoms (sensitivity to light, grittiness, burning, blurred vision, all p < 0.03) and reduction in required self‐treatments (lid wipes, tear substitutes, both p < 0.03). There was also a reduced impact on lifestyle (reading, night driving, computer use and watching television, all p < 0.0001) and in all environmental conditions (all p < 0.0001). Conclusions: This study confirms the positive effect of topical azithromycin on MGD and shows it has a long‐term impact on symptoms, self‐treatment methods and lifestyle. This has implications for both chair time and healthcare costs when managing patients with MGD. Pending further clinical trials in a larger population with different demographics, topical azithromycin should be considered by all eyecare practitioners as a viable pharmacological treatment when managing MGD. [ABSTRACT FROM AUTHOR]

Objective: This systematic review and meta-analysis investigated whether the use of azithromycin during labour or caesarean section reduces the incidence of sepsis and infection among mothers and newborns. Data sources: We independently searched the PubMed, Web of Science, Cochrane Library and EMBASE databases for relevant studies published before February, 2024. Methods: We included RCTs that evaluated the effect of prenatal oral or intravenous azithromycin or placebo on intrapartum or postpartum infection incidence. We included studies evaluating women who had vaginal births as well as caesarean sections. Studies reporting maternal and neonatal infections were included in the current analysis. Review Manager 5.4 was used to analyse 6 randomized clinical trials involving 44,448 mothers and 44,820 newborns. The risk of bias of each included study was assessed using the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions.Primary outcomes included the incidence of maternal sepsis and all-cause mortality and neonatal sepsis and all-cause mortality; secondary outcomes included maternal (endometritis, wound and surgical site infections, chorioamnionitis, and urinary tract infections) and neonatal outcomes (infections of the eyes, ears and skin). A random-effects model was used to test for overall effects and heterogeneity. Results: The pooled odds ratios (ORs) were as follows: 0.65 for maternal sepsis (95% CI, 0.55–0.77; I2, 0%; P <.00001); 0.62 for endometritis (95% CI, 0.52–0.74; I2, 2%; P <.00001); and 0.43 for maternal wound or surgical site infection (95% CI, 0.24–0.78; P <.005); however, there was great heterogeneity among the studies (I2, 75%). The pooled OR for pyelonephritis and urinary tract infections was 0.3 (95% CI, 0.17–0.52; I2, 0%; P <.0001), and that for neonatal skin infections was 0.48 (95% CI, 0.35–0.65; I2, 0%, P <.00001). There was no significant difference in maternal all-cause mortality or incidence of chorioamnionitis between the two groups. No significant differences were observed in the incidence of neonatal sepsis or suspected sepsis, all-cause mortality, or infections of the eyes or ears. Conclusion: In this meta-analysis, azithromycin use during labour reduced the incidence of maternal sepsis, endometritis, incisional infections and urinary tract infections but did not reduce the incidence of neonatal-associated infections, except for neonatal skin infections. These findings indicate that azithromycin may be potentially beneficial for maternal postpartum infections, but its effect on neonatal prognosis remains unclear. Azithromycin should be used antenatally only if the clinical indication is clear and the potential benefits outweigh the harms. [ABSTRACT FROM AUTHOR]

Background Nontyphoidal Salmonella causes an estimated 1.35 million US infections annually. Antimicrobial-resistant strains are a serious public health threat. We examined the association between resistance and the clinical outcomes of hospitalization, length-of-stay ≥3 days, and death. Methods We linked epidemiologic data from the Foodborne Diseases Active Surveillance Network with antimicrobial resistance data from the National Antimicrobial Resistance Monitoring System (NARMS) for nontyphoidal Salmonella infections from 2004 to 2018. We defined any resistance as resistance to ≥1 antimicrobial and clinical resistance as resistance to ampicillin, azithromycin, ceftriaxone, ciprofloxacin, or trimethoprim-sulfamethoxazole (for the subset of isolates tested for all 5 agents). We compared outcomes before and after adjusting for age, state, race/ethnicity, international travel, outbreak association, and isolate serotype and source. Results Twenty percent of isolates (1105/5549) had any resistance, and 16% (469/2969) had clinical resistance. Persons whose isolates had any resistance were more likely to be hospitalized (31% vs 28%, P =.01) or have length-of-stay ≥3 days (20% vs 16%, P =.01). Deaths were rare but more common among those with any than no resistance (1.0% vs 0.4%, P =.01). Outcomes for patients whose isolates had clinical resistance did not differ significantly from those with no resistance. After adjustment, any resistance (adjusted odds ratio 1.23, 95% confidence interval 1.04–1.46) remained significantly associated with hospitalization. Conclusions We observed a significant association between nontyphoidal Salmonella infections caused by resistant pathogens and likelihood of hospitalization. Clinical resistance was not associated with poorer outcomes, suggesting that factors other than treatment failure (eg, strain virulence, strain source, host factors) may be important. [ABSTRACT FROM AUTHOR]

Background: The prevalence of macrolide-resistant Mycoplasma pneumoniae has increased considerably. Treatment in children has become challenging. This study aimed to evaluate the efficacy of doxycycline therapy for macrolide-resistant Mycoplasma pneumoniae pneumonia in children at different periods. Methods: We retrospectively analyzed the data of patients with macrolide-resistant Mycoplasma pneumoniae pneumonia hospitalized between May 2019 to August 2022. According to treatment, patients were divided into three groups: oral doxycycline treatment alone (DOX group), changed from intravenous azithromycin to oral doxycycline (ATD group), and intravenous azithromycin treatment alone (AZI group). ATD group cases were separated into two sub-groups: intravenous azithromycin treatment<3 days (ATD1 group) and ≥ 3 days (ATD2 group). Clinical symptoms were compared in each group and adjusted by Propensity score matching (PSM) analysis. Results: A total of 106 were recruited in this study. 17 (16%) were in DOX group, 58 (55%) in ATD group, and 31(29%) in AZI group. Compared with ATD group and AZI group, the DOX group showed shorter hospitalization duration and fever duration after treatment, while higher rate of chest radiographic improvement. After using PSM analysis, shorter days to hospitalization duration (P = 0.037) and to fever duration after treatment (P = 0.027) in DOX + ATD1 group than in ATD2 group was observed. A higher number of patients in the DOX + ATD1 group achieved defervescence within 72 h (P = 0.031), and fewer children received glucocorticoid adjuvant therapy (P = 0.002). No adverse reactions associated with doxycycline was observed during treatment. Conclusions: Children receiving early oral doxycycline had a shorter duration of fever and hospitalization in macrolide-resistant Mycoplasma pneumoniae patients. [ABSTRACT FROM AUTHOR]

• Azithromycin preserves adult hippocampal neurogenesis in LPS-treated mice. • Azithromycin reduces time spent immobile by LPS-treated mice during the Porsolt test. • Azithromycin reverses the hippocampal pro-inflammatory phenotype caused by LPS. • Azithromycin promotes synaptic integration. 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. [ABSTRACT FROM AUTHOR]

Antimicrobial Resistance (AMR) in bacteria is a growing public health concern in the US and around the world threatening the continual use of antimicrobials. In pigs, the oral route, either in-feed or in-water, is by far the most common route of administration of antimicrobials. Because the distribution of the antibiotic in the gut and the dosages are different, the impact of in-feed vs. in-water administration of antibiotics on the prevalence of pathogens, such as Salmonella, and the development of AMR are likely to be different. Therefore, a study was conducted to compare in-feed vs. in-water administrations of chlortetracycline (CTC) and/or tiamulin on the fecal prevalence and AMR profiles of Salmonella in nursery piglets. A total of 1296 weaned piglets, housed in 48 pens (27 piglets per pen), were assigned randomly to six treatment groups: Control (no antibiotic), in-feed CTC, in-water CTC, in-feed tiamulin, in-water tiamulin, or in-feed CTC and tiamulin. Fecal samples (n = 1440) were collected randomly from five piglets from each pen during the pre-treatment (days 7, 0), treatment (days 7, 14), and post-treatment (days 21, 28) phases. Salmonella enterica isolation and identification were completed by culture and PCR methods. The microbroth dilution method with SensititreTM (ThermoFisher Scientific, Lenexa, KS, USA) plates was used to determine the antimicrobial susceptibility and resistance of Salmonella strains. The susceptibility and resistance were interpreted based on the Clinical and Laboratory Standards Institute guidelines. The overall prevalence of Salmonella was 3.0% (43/1440). All isolates belonged to Salmonella enterica subsp. enterica serovar Typhimurium. Salmonella isolates were susceptible to azithromycin and resistant (100%) to ampicillin, streptomycin, sulfisoxazole, tiamulin, and tetracycline. Neither antibiotic, CTC or tiamulin, nor the route of administration, in-feed or in-water, had an effect (p > 0.05) on the occurrence of resistant Salmonella in the feces of piglets. [ABSTRACT FROM AUTHOR]

The article presents a case of pediatric Mycobacterium abscessus mastoiditis resistant to standard treatments, emphasizing the importance of considering M. abscessus in treatment-resistant chronic otitis media and mastoiditis, especially in children with tympanostomy tubes. Topics include challenges in diagnosing M. abscessus infections, treatment strategies, and the effectiveness of tigecycline in multidrug regimens.

Prescription sequence symmetry analysis (PSSA) is used to detect adverse event signals using administrative claims databases. In this study, we investigated whether PSSA can be applied to gauge the effects of PCV13 vaccination on antibiotic prescription rates in elderly patients. We studied prescription records of patients aged 65 or older between 1 January 2014 and 31 December 2020, from the Helsana Swiss claims database. PSSA was performed to explore the relationship between 13-valent pneumococcal conjugate vaccine (PCV13) and six antibiotics recommended by the Swiss Society of Infectious Diseases for community-acquired pneumonia treatment (amoxicillin-clavulanate, azithromycin, clarithromycin, doxycycline, levofloxacin, and moxifloxacin), three additional antibiotics (amoxicillin, ciprofloxacin, and fosfomycin), and ten control drugs. Amoxicillin-clavulanate, clarithromycin, and levofloxacin were more likely to be prescribed before than after vaccination, for all time windows between 25 and 104 weeks. Adjusted sequence ratio (ASR) values ranged from 0.599 to 0.614, 0.508 to 0.568, and 0.514 to 0.752, respectively. Lower prescription rates after vaccination were also observed for azithromycin (all time windows between 38 and 104 weeks, ASR 0.705–0.739) and moxifloxacin (all time windows between 52 and 104 weeks, ASR 0.658–0.772). PCV13 did not have statistically significant associations with doxycycline, amoxicillin, ciprofloxacin, fosfomycin, or any of the ten controls. The lower prescription rate of antibiotics for community-acquired pneumonia after vaccination could be attributed to a protective effect of PCV13. This novel application of PSSA can be used to compare the real-world impact of other vaccines on drug consumption. [Display omitted] [ABSTRACT FROM AUTHOR]

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe drug reaction where patients present with fever, morbilliform rash and multiorgan manifestations, which may include acute renal failure, acute respiratory distress syndrome and eosinophilic myocarditis. We present a case of a 60‐year‐old woman with acute heart failure, DRESS syndrome features and human herpesvirus 6 reactivation in the absence of a drug trigger. She was diagnosed with eosinophilic myocarditis and successfully treated with corticosteroid therapy. [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate the impact of dietary zinc supplementation in pre-weaned dairy calves on the phenotypic antimicrobial resistance (AMR) of fecal commensal bacteria. A repository of fecal specimens from a random sample of calves block-randomized into placebo (n = 39) and zinc sulfate (n = 28) groups collected over a zinc supplementation clinical trial at the onset of calf diarrhea, calf diarrheal cure, and the last day of 14 cumulative days of zinc or placebo treatment were analyzed. Antimicrobial susceptibility testing was conducted for Enterococcus spp. (n = 167) and E. coli (n = 44), with one representative isolate of each commensal bacteria tested per sample. Parametric survival interval regression models were constructed to evaluate the association between zinc treatment and phenotypic AMR, with exponentiated accelerated failure time (AFT) coefficients adapted for MIC instead of time representing the degree of change in AMR (MIC Ratio, MR). Findings from our study indicated that zinc supplementation did not significantly alter the MIC in Enterococcus spp. for 13 drugs: gentamicin, vancomycin, ciprofloxacin, erythromycin, penicillin, nitrofurantoin, linezolid, quinupristin/dalfopristin, tylosin tartrate, streptomycin, daptomycin, chloramphenicol, and tigecycline (MR = 0.96–2.94, p > 0.05). In E. coli, zinc supplementation was not associated with resistance to azithromycin (MR = 0.80, p > 0.05) and ceftriaxone (MR = 0.95, p > 0.05). However, a significant reduction in E. coli MIC values was observed for ciprofloxacin (MR = 0.17, 95% CI 0.03–0.97) and nalidixic acid (MR = 0.28, 95% CI 0.15–0.53) for zinc-treated compared to placebo-treated calves. Alongside predictions of MIC values generated from these 17 AFT models, findings from this study corroborate the influence of age and antimicrobial exposure on phenotypic AMR. [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate the impact of dietary zinc supplementation in pre-weaned dairy calves on the phenotypic antimicrobial resistance (AMR) of fecal commensal bacteria. A repository of fecal specimens from a random sample of calves block-randomized into placebo (n = 39) and zinc sulfate (n = 28) groups collected over a zinc supplementation clinical trial at the onset of calf diarrhea, calf diarrheal cure, and the last day of 14 cumulative days of zinc or placebo treatment were analyzed. Antimicrobial susceptibility testing was conducted for Enterococcus spp. (n = 167) and E. coli (n = 44), with one representative isolate of each commensal bacteria tested per sample. Parametric survival interval regression models were constructed to evaluate the association between zinc treatment and phenotypic AMR, with exponentiated accelerated failure time (AFT) coefficients adapted for MIC instead of time representing the degree of change in AMR (MIC Ratio, MR). Findings from our study indicated that zinc supplementation did not significantly alter the MIC in Enterococcus spp. for 13 drugs: gentamicin, vancomycin, ciprofloxacin, erythromycin, penicillin, nitrofurantoin, linezolid, quinupristin/dalfopristin, tylosin tartrate, streptomycin, daptomycin, chloramphenicol, and tigecycline (MR = 0.96–2.94, p > 0.05). In E. coli, zinc supplementation was not associated with resistance to azithromycin (MR = 0.80, p > 0.05) and ceftriaxone (MR = 0.95, p > 0.05). However, a significant reduction in E. coli MIC values was observed for ciprofloxacin (MR = 0.17, 95% CI 0.03–0.97) and nalidixic acid (MR = 0.28, 95% CI 0.15–0.53) for zinc-treated compared to placebo-treated calves. Alongside predictions of MIC values generated from these 17 AFT models, findings from this study corroborate the influence of age and antimicrobial exposure on phenotypic AMR. [ABSTRACT FROM AUTHOR]

Key Points: Question: Does twice-annual mass azithromycin distribution prevent all-cause childhood mortality among children in Burkina Faso aged 1 to 59 months in the setting of seasonal malaria chemoprevention distribution? Findings: In this randomized trial of twice-yearly mass azithromycin distribution, 498 deaths were recorded over 60 592 person-years (8.2 deaths/1000 person-years) in the azithromycin group compared with 588 deaths over 58 547 person-years (10.0 deaths/1000 person-years) in the placebo group. The difference was not statistically significant. Meaning: Communities with mass azithromycin distribution had lower child mortality than controls, although the difference was not statistically significant. The study may have been underpowered to detect a clinically relevant difference. Importance: Repeated mass distribution of azithromycin has been shown to reduce childhood mortality by 14% in sub-Saharan Africa. However, the estimated effect varied by location, suggesting that the intervention may not be effective in different geographical areas, time periods, or conditions. Objective: To evaluate the efficacy of twice-yearly azithromycin to reduce mortality in children in the presence of seasonal malaria chemoprevention. Design, Setting, and Participants: This cluster randomized placebo-controlled trial evaluating the efficacy of single-dose azithromycin for prevention of all-cause childhood mortality included 341 communities in the Nouna district in rural northwestern Burkina Faso. Participants were children aged 1 to 59 months living in the study communities. Interventions: Communities were randomized in a 1:1 ratio to receive oral azithromycin or placebo distribution. Children aged 1 to 59 months were offered single-dose treatment twice yearly for 3 years (6 distributions) from August 2019 to February 2023. Main Outcomes and Measures: The primary outcome was all-cause childhood mortality, measured during a twice-yearly enumerative census. Results: A total of 34 399 children (mean [SD] age, 25.2 [18] months) in the azithromycin group and 33 847 children (mean [SD] age, 25.6 [18] months) in the placebo group were included. A mean (SD) of 90.1% (16.0%) of the censused children received the scheduled study drug in the azithromycin group and 89.8% (17.1%) received the scheduled study drug in the placebo group. In the azithromycin group, 498 deaths were recorded over 60 592 person-years (8.2 deaths/1000 person-years). In the placebo group, 588 deaths were recorded over 58 547 person-years (10.0 deaths/1000 person-years). The incidence rate ratio for mortality was 0.82 (95% CI, 0.67-1.02; P =.07) in the azithromycin group compared with the placebo group. The incidence rate ratio was 0.99 (95% CI, 0.72-1.36) in those aged 1 to 11 months, 0.92 (95% CI, 0.67-1.27) in those aged 12 to 23 months, and 0.73 (95% CI, 0.57-0.94) in those aged 24 to 59 months. Conclusions and Relevance: Mortality in children (aged 1-59 months) was lower with biannual mass azithromycin distribution in a setting in which seasonal malaria chemoprevention was also being distributed, but the difference was not statistically significant. The study may have been underpowered to detect a clinically relevant difference. Trial Registration: ClinicalTrials.gov Identifier: NCT03676764 This cluster randomized placebo-controlled trial examines the efficacy of single-dose azithromycin for prevention of all-cause childhood mortality in rural Burkina Faso. [ABSTRACT FROM AUTHOR]

Objectives: A systematic review with met‐analysis was performed to summarise the evidence on the effect of intrapartum azithromycin on maternal and neonatal infections and deaths. Search strategy: PubMed, Scopus and Web of Science databases were searched in March 2023. Selection criteria: Randomised controlled trials comparing intrapartum single‐dose of azithromycin with placebo. Data collection and analysis: Maternal infections, maternal mortality, neonatal sepsis, neonatal mortality. We used the random‐effects Mantel–Haenszel method to calculate risk ratios (RR) with 95% confidence intervals (95% CI). We assessed risk of bias of the included studies and estimated the evidence certainty using the GRADE approach. Main results: After screening 410 abstracts, five studies with 44 190 women and 44 565 neonates were included. The risk of bias was low in four and had some concerns in one of the studies. The risk of endometritis was 1.5% in the azithromycin group and 2.3% in the placebo group (RR 0.64, 95% CI 0.55–0.75), and the evidence certainty was high. The respective risk for chorioamnionitis was 0.05% and 0.1% (RR 0.50, 95% CI 0.22–1.18; evidence certainty moderate). The wound infection rate was lower in the azithromycin group (1.6%) than in the placebo group (2.5%), RR 0.52 (95% CI 0.30–0.89; moderate certainty evidence). The maternal sepsis rate was 1.1% in the azithromycin group and 1.7% in the placebo group (RR 0.66, 95% CI 0.56–0.77; evidence certainty high). Mortality rates did not show evidence of a difference (0.09% versus 0.08%; RR 1.26, 95% CI 0.65–2.42; moderate certainty evidence). The neonatal mortality rate was 0.7% in the azithromycin group and 0.8% in the placebo group (RR 0.94, 95% CI 0.76–1.16; moderate certainty evidence). The neonatal sepsis rate was 7.6% in the azithromycin group and 7.4% in the placebo group (RR 1.02, 95% CI 0.96–1.09; moderate certainty evidence). Conclusions: Intrapartum administration of azithromycin to the mother reduces maternal postpartum infections, including sepsis. Impact on maternal mortality remains undecided. Azithromycin does not reduce neonatal sepsis or mortality rates. [ABSTRACT FROM AUTHOR]

Objectives Most human infections caused by Vibrio spp. do not warrant antimicrobial treatment but in severe cases, targeted antimicrobial treatment can be lifesaving. For Vibrio spp. standardized antimicrobial susceptibility testing (AST) guidelines with EUCAST methodology are lacking. In this study, we aimed to produce data suitable for EUCAST to establish clinical MIC breakpoints and zone diameter correlates for Vibrio spp. Methods An intercontinental collection (N = 524) comprising five important Vibrio spp. (V. alginolyticus , V. cholerae , V. fluvialis , V. parahaemolyticus and V. vulnificus) was organized. All isolates were subjected to broth microdilution (BMD) against 11 antimicrobial agents according to ISO 20776-1 using unsupplemented Mueller–Hinton broth on freeze-dried Sensititre panels (Thermo Scientific, UK), and most isolates (n = 371) were also tested with disc diffusion according to EUCAST methodology for non-fastidious organisms. Results Aggregated results were used to generate MIC and zone diameter distributions and to prepare graphs of MIC-zone diameter correlation. Based on these results, the EUCAST Steering Committee determined clinical susceptible (S) and resistant (R) MIC (mg/L) breakpoints (S≤/R>) for the five Vibrio spp. for piperacillin/tazobactam (1/1), cefotaxime (0.25/0.25), ceftazidime (1/1), meropenem (0.5/0.5), ciprofloxacin (0.25/0.25), levofloxacin (0.25/0.25), azithromycin (4/4), doxycycline (0.5/0.5) and trimethoprim/sulfamethoxazole (0.25/0.25). The corresponding zone diameter breakpoints were identified. Conclusions We demonstrated the validity of using standard BMD and EUCAST disc diffusion methodology for AST of five Vibrio spp. and generated suitable data to allow EUCAST to determine clinical MIC and zone diameter breakpoints for five pathogenic Vibrio spp. including both non-toxigenic and toxigenic V. cholerae. [ABSTRACT FROM AUTHOR]

Brucellosis is a momentous zoonotic disease. Unpasteurized milk and milk products are the leading sources of Brucella transmission to humans. The present research was conducted to investigate the contamination of local crumbled Kope cheeses distributed in Urmia city with Brucella species and evaluate the antibiotic -resistance pattern of the isolates. Fifty samples of local cow’s Kope cheese were randomly collected from traditional dairy retailers in different regions of Urmia by sterile conditions in 2022. The samples were cultured in Brucella enrichment broth and then in Brucella selective agar with a supplement. Molecular identification of Brucella spp. was done using specific primers by polymerase chain reaction (PCR). Antimicrobial susceptibility testing on the isolates was performed by the Kirby -Bauer disc diffusion method. Among the tested samples, two samples were contaminated with Brucella (4%). One was contaminated with B. abortus bv. 1, 2, and 4 (2%), and the other with B. melitensis (2%). The isolates were sensitive to azithromycin, imipenem, doxycycline, rifampin, and co -trimoxazole antibiotics and were resistant to ampicillin, amoxicillin -clavulanic acid, tetracycline, gentamicin, and ceftriaxone antibiotics. Also, the B. abortus strain was sensitive to ciprofloxacin, but the B. melitensis strain was resistant. The isolates showed multi -drug resistance (MDR) characteristics. From the findings, it can be concluded that Brucella contamination in local Kope cheeses distributed in Urmia city is low; However, due to the high pathogenicity of B. melitensis for humans, it is recommended to screen infected cows, vaccinate sheep and goat herds, and prevent the supply of unpasteurized milk and milk products. It is also recommended to evaluate azithromycin and imipenem antibiotics along with other common antibiotics in brucellosis. [ABSTRACT FROM AUTHOR]

The article presents a study which examined azithromycin prescriptions in children from birth to 19 years of age. Topics discussed include data collected in the study, a high prevalence of penicillin (PCN) allergy in the cohort of patients who were prescribed azithromycin, and age distribution of children who received azithromycin prescriptions during the study period.

During the initial phase of the COVID-19 pandemic, there was ongoing investigation into potentially effective treatments. Antiviral medications such as Favipiravir and Hydroxychloroquine were employed to treat COVID-19 infections. However, limited studies have examined the adverse effects of these medications on hearing, particularly at extended high frequencies. This study included 10 subjects who had received medications like Azithromycin, a combination of Favipiravir and Hydroxychloroquine, and Hydroxychloroquine alone as part of their COVID-19 treatment. These subjects had previously undergone extended high-frequency audiometry testing (from 8 to 20 kHz) as part of another project conducted by the same department before contracting COVID-19. Post-COVID-19 extended high-frequency audiometry was performed 1 month after the patients received a negative RT-PCR report. The results were then compared using a Paired t-test. A significant shift in the thresholds of high frequencies above 8–20 kHz is found in subjects who had received Favipiravir and Hydroxychloroquine medications. We observed a significant impact of COVID-19 medications on high-frequency hearing, which tends to go unnoticed in regular pure-tone audiometry evaluations. Therefore, our study emphasizes the need for regular follow-ups, including detailed audiological assessments that incorporate extended high-frequency testing, at least once every 3 months for patients who have taken medications for COVID-19 treatment. [ABSTRACT FROM AUTHOR]

Sestrins are stress-responsive proteins with antioxidant properties. They participate in cellular redox balance and protect against oxidative damage. This study investigated the effects of Sestrin2 (Sesn2) on osteoclast differentiation and function. Overexpressing Sesn2 in osteoclast precursor cells significantly inhibited receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclastogenesis. This was assessed as reduced expression of various osteoclast markers, including c-Fos, nuclear factor of activated T cells 1 (NFATc1), osteoclast-associated receptor, tartrate-resistant acid phosphatase, and cathepsin K. Conversely, downregulation of Sesn2 produced the opposite effect. Mechanistically, Sesn2 overexpression enhanced AMPK activation and the nuclear translocation of nuclear factor erythroid-derived factor 2-related factor 2 (Nrf2), promoting antioxidant enzymes. Moreover, azithromycin (Azm) induced Sesn2 expression, which suppressed RANKL-induced osteoclast differentiation. Specifically, Azm treatment reduced RANKL-induced production of reactive oxygen species in osteoclasts. Furthermore, intraperitoneal administration of Azm ameliorated RANKL-induced bone loss by reducing osteoclast activity in mice. Taken together, our results suggested that Azm-induced Sesn2 act as a negative regulator of RANKL-induced osteoclast differentiation through the AMPK/NFATc1 signaling pathway. Concisely, targeting Sesn2 can be a potential pharmacological intervention in osteoporosis. [Display omitted] • Sestrin2 inhibits RANKL – induced osteoclast differentiation. • Sestrin2 promotes AMPK activation and Nrf2 nuclear accumulation. • Sestrin2 inhibits RANKL-induced ROS production. • Azithromycin induces expression of sestrin2 on osteoclastogenesis. • Azithromycin blocks RANKL-induced bone loss in vivo. [ABSTRACT FROM AUTHOR]