Photodegradation of a Broad-Spectrum Antibiotic Azithromycin Using H2O2 under Ultraviolet Irradiation.

The photodegradation of azithromycin present was carried out in water using H2O2 under UV irradiation. The reaction variables considered in this study were the amount of H2O2 solution and the initial concentration of azithromycin to evaluate the performance of the photodegradation process. The azithromycin degradation was not observed in the dark during stirring for 20 min. The study showed an efficient photodegradation of azithromycin using H2O2 as an oxidant in the presence of UV irradiation. The azithromycin degradation was altered significantly by the pH of the irradiated solution. The degradation was low at an acidic pH and showed an increasing trend as the pH changed to basic. The azithromycin degradation increased with a higher amount (higher concentration) of H2O2. The degradation of azithromycin decreased with a higher concentration of azithromycin in the reacting solution. The highest degradation of AZT was achieved in 1 h using a 1.0 ppm AZT solution containing 3 mL of H2O2. The experimental data obtained were well-fitted to zero-order reaction kinetics. The results of this study were found quite excellent. They showed 100% degradation in 1 h when compared with those reported in the literature, both with photocatalysis using nanomaterials and photolysis using light irradiation and/or H2O2. The UV/H2O2 system was found to be quite efficient for the photodegradation of azithromycin, and this system can be applied to degrade other organic pollutants present in industrial wastewater.

Post Covid telogen effluvium: the diagnostic value of serum ferritin biomarker and the preventive value of dietary supplements. a case control study.

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.

Cost-effectiveness of resistance-guided therapy for Mycoplasma genitalium in Australia.

The recommended first-line treatment for Mycoplasma genitalium infections is azithromycin. However, the prevalence of macrolide resistance for M. genitalium has increased to more than 50% worldwide. In 2013, Australia introduced a resistance-guided therapy (RGT) strategy to manage M. genitalium infections. This study assesses the cost-effectiveness of the RGT approach compared to no RGT (i.e., without macrolide resistance profile test) in women, men who have sex with men (MSM), and men who have sex with women (MSW) in Australia. We constructed dynamic transmission models of M. genitalium infections in women, MSM, and MSW in Australia, each with a population of 100,000. These models compared the costs and quality-adjusted life-years (QALYs) gained between RGT and no RGT scenarios from a healthcare perspective over ten years. All costs are reported in 2022 Australian dollars (Australian $). In our model, RGT is cost saving in women and MSM, with the incremental net monetary benefit of $1.3 million and $17.9 million, respectively. In MSW, the RGT approach is not cost-effective, with an incremental cost-effectiveness ratio of -$106.96 per QALY gained. RGT is cost saving compared to no RGT for M. genitalium infections in women and MSM, supporting its adoption as the national management strategy for these two population groups.

Antimicrobial Susceptibility and Characteristics of Neisseria gonorrhoeae Isolates from Puerto Rico, 2012-2017.

OBJECTIVE: Monitoring the susceptibility patterns of Neisseria gonorrhoeae is essential for the continuing compliance with current treatment recommendations. Puerto Rico conducts susceptibility tests on N. gonorrhoeae; however, trends on antimicrobial resistance in the island have not been reported since the mid 80's. METHODS: We performed a secondary analysis of a national data repository on the antimicrobial susceptibility of N. gonorrhoeae isolates between 2012 and 2017; a period of time when the CDC recommended a single dose of ceftriaxone and azithromycin for the treatment of uncomplicated gonorrhea. Data on susceptibility to eight antibiotics using the standard disk diffusion method was obtained for 30.0% (84/276) of the samples collected from the Sexually Transmitted Disease clinics in Puerto Rico. We also performed patient demographic analyses linked to resistance. RESULTS: Rates of resistance to ceftriaxone and azithromycin were 0% and 4.0% (2/50), respectively. The percentage of isolates resistant to antimicrobials no longer recommended in Puerto Rico, such as tetracycline, ciprofloxacin, and penicillin, was 86.0% (43/50), 76.0% (38/50), and 38.0% (19/50), respectively. Prevalence of resistant N. gonorrhoeae was higher among men who have sex with men, MSM (79%, 37/47). DISCUSSION: Lack of resistance to ceftriaxone and slow emergence of azithromycin resistance was identified from 2012-2017. It is imperative to continue the surveillance for emerging patterns of resistance, especially for ceftriaxone, as it is part of the current treatment guidelines. Therefore, protocols for culture based surveillance, including sample transport and processing, should be strengthened to ensure quality assured epidemiology of gonococcal resistance in Puerto Rico.

Neglected Mycobacterium Avium Complex Infection in a Patient with Prolonged Pneumonia.

BACKGROUND: Non-tuberculous mycobacterial pulmonary infections (NTM-PD) are becoming increasingly common in clinical practice, and early detection and accurate determination of the infecting pathogen is crucial for subsequent treatment. We report a case of NTM-PD in a healthy middle-aged female with Mycobacterium tuberculosis complex group (MAC) infection confirmed by mNGS examination. METHODS: Appropriate laboratory tests, chest CT scan, bronchoscopic alveolar lavage fluid (BALF) examination, and macrogenomic next-generation sequencing (mNGS) were performed to establish the diagnosis. RESULTS: Chest CT showed multiple inflammatory lesions in the right middle lobe, and BALF sent for mNGS finally confirmed the diagnosis of MAC infection. After symptomatic treatment with azithromycin combined with ethambutol and rifampicin, the patient improved and was discharged from the hospital. CONCLUSIONS: In patients with pulmonary infections, pathogens should be clarified early to determine the diagnosis. mNGS of BALF samples have high specificity in detecting pathogens of infectious diseases, especially complex mixed infectious disease pathogens.

ß-lactamase expression induces collateral sensitivity in Escherichia coli.

Major antibiotic groups are losing effectiveness due to the uncontrollable spread of antimicrobial resistance (AMR) genes. Among these, ß-lactam resistance genes -encoding ß-lactamases- stand as the most common resistance mechanism in Enterobacterales due to their frequent association with mobile genetic elements. In this context, novel approaches that counter mobile AMR are urgently needed. Collateral sensitivity (CS) occurs when the acquisition of resistance to one antibiotic increases susceptibility to another antibiotic and can be exploited to eliminate AMR selectively. However, most CS networks described so far emerge as a consequence of chromosomal mutations and cannot be leveraged to tackle mobile AMR. Here, we dissect the CS response elicited by the acquisition of a prevalent antibiotic resistance plasmid to reveal that the expression of the ß-lactamase gene blaOXA-48 induces CS to colistin and azithromycin. We next show that other clinically relevant mobile ß-lactamases produce similar CS responses in multiple, phylogenetically unrelated E. coli strains. Finally, by combining experiments with surveillance data comprising thousands of antibiotic susceptibility tests, we show that ß-lactamase-induced CS is pervasive within Enterobacterales. These results highlight that the physiological side-effects of ß-lactamases can be leveraged therapeutically, paving the way for the rational design of specific therapies to block mobile AMR or at least counteract their effects.

Meta-analysis of combined azithromycin and inhaled budesonide treatment for Chinese pediatric patients with mycoplasma pneumonia.

BACKGROUND: Budesonide, capable of reducing vascular permeability, suppressing mucus secretion, and alleviating edema and spasms, is widely used in China for combined infectious disease treatment. This study assesses budesonide's efficacy and safety as an adjunct to azithromycin in pediatric Mycoplasma pneumonia management in China, aiming to establish a strong theoretical foundation for its clinical application. METHODS: We conducted a comprehensive search for qualifying studies across 5 English databases and 4 Chinese databases, covering publications until October 31, 2023. Endpoint analyses were performed using standard software (Stata Corporation, College Station, TX). This study was conducted in compliance with the guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. RESULTS: A total of 24 randomized controlled trials were involved in the current study, including 2034 patients. Our findings indicate that the combination of budesonide with azithromycin for the treatment of pediatric Mycoplasma pneumonia delivers superior therapeutic efficacy (Intravenous: odds ratio [OR], 0.156, P < .001; Sequential: OR, 0.163, P = .001; Oral: OR, 0.139, P < .001), improved pulmonary function (Forced expiratory volume in 1 second: weighted mean differences [WMD], -0.28, P = .001; Peak expiratory flow: WMD, -0.554, P = .002; Forced vital capacity: WMD, -0.321, P < .001), diminished lung inflammation (IL-6: WMD, 4.760, P = .002; c-reactive protein: WMD, 5.520, P < .001; TNF-α: WMD, 9.124, P < .001), reduced duration of fever, faster resolution of cough and rales, all without increasing the occurrence of adverse events. CONCLUSION: The combination of budesonide and azithromycin demonstrates enhanced therapeutic effectiveness, promotes improved pulmonary function, shortens the duration of symptoms, and effectively mitigates the overexpression of inflammatory factors like c-reactive protein, TNF-α, and IL-6, all without an associated increase in adverse reactions in pediatric mycoplasma pneumonia.

Sequential high-recovery nanofiltration and electrochemical degradation for the treatment of pharmaceutical wastewater.

The presence of antibiotics in aquatic ecosystems poses a significant concern for public health and aquatic life, owing to their contribution to the proliferation of antibiotic-resistant bacteria. Effective wastewater treatment strategies are needed to ensure that discharges from pharmaceutical manufacturing facilities are adequately controlled. Here we propose the sequential use of nanofiltration (NF) for concentrating a real pharmaceutical effluent derived from azithromycin production, followed by electrochemical oxidation for thorough removal of pharmaceutical compounds. The NF membrane demonstrated its capability to concentrate wastewater at a high recovery value of 95 % and 99.7 ± 0.2 % rejection to azithromycin. The subsequent electrochemical oxidation process completely degraded azithromycin in the concentrate within 30 min and reduced total organic carbon by 95 % in 180 min. Such integrated treatment approach minimized the electrochemically-treated volume through a low-energy membrane approach and enhanced mass transfer towards the electrodes, therefore driving the process toward zero-liquid-discharge objectives. Overall, our integrated approach holds promises for cost-effective and sustainable removal of trace pharmaceutical compounds and other organics in pharmaceutical wastewater.

Neonatal outcomes in term and preterm infants following adjunctive azithromycin antibiotic prophylaxis for non-elective cesarean delivery.

OBJECTIVE: It is currently unknown whether adjunctive azithromycin prophylaxis at the time of non-elective cesarean has differential effects on neonatal outcomes in the context of prematurity. The objective of this study was to compare whether neonatal outcomes differ in term and preterm infants exposed to adjunctive azithromycin prophylaxis before non-elective cesarean delivery. STUDY DESIGN: A planned secondary analysis of a multi-center randomized controlled trial that enrolled women with singleton pregnancies ≥24 weeks gestation undergoing non-elective cesarean delivery (during labor or ≥4 h after membrane rupture). Women received standard antibiotic prophylaxis and were randomized to either adjunctive azithromycin (500 mg) or placebo. The primary composite outcome was neonatal death, suspected or confirmed neonatal sepsis, and serious neonatal morbidities (NEC, PVL, IVH, BPD). Secondary outcomes included NICU admission, neonatal readmission, culture positive infections and prevalence of resistant organisms. Odds ratios (OR) for the effect of azithromycin versus placebo were compared between gestational age strata (preterm [less than 37 weeks] versus term [37 weeks or greater]). Tests of interaction examined homogeneity of treatment effect with gestational age. RESULTS: The analysis includes 2,013 infants, 226 preterm (11.2%) and 1,787 term. Mean gestational ages were 34 and 39.5 weeks, respectively. Within term and preterm strata, maternal and delivery characteristics were similar between the azithromycin and placebo groups. There was no difference in the odds of composite neonatal outcome between those exposed to azithromycin versus placebo in preterm neonates (OR 0.82, 95% CI 0.48-1.41) and in term neonates (OR 1.06, 95% CI 0.77-1.46), with no difference between gestational age strata (p = 0.42). Analysis of secondary outcomes also revealed no differences in treatment effects within or between gestational age strata. CONCLUSION: Exposure to adjunctive azithromycin antibiotic prophylaxis for non-elective cesarean delivery does not increase neonatal morbidity or mortality in term or preterm infants. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov, NCT01235546.

Azithromycin sequential therapy plus inhaled terbutaline for Mycoplasma Pneumoniae pneumonia in children: a systematic review and meta-analysis.

BACKGROUND: An improper host immune response to Mycoplasma pneumoniae generates excessive inflammation, which leads to the impairment of pulmonary ventilation function (PVF). Azithromycin plus inhaled terbutaline has been used in the treatment of Mycoplasma pneumoniae pneumonia (MPP) in children with impaired pulmonary function, but previous randomized controlled trials (RCTs) showed inconsistent efficacy and safety. This study is aimed to firstly provide a systematic review of the combined therapy. METHODS: This study was registered at the International Prospective Register of Systematic Reviews (PROSPERO CRD42023452139). A PRISMA-compliant systematic review and meta-analysis was performed. Six English and four Chinese databases were comprehensively searched up to June, 2023. RCTs of azithromycin sequential therapy plus inhaled terbutaline were selected. The revised Cochrane risk of bias tool for randomized trials (RoB2) was used to evaluate the methodological quality of all studies, and meta-analysis was performed using Stata 15.0 with planned subgroup and sensitivity analyses. Publication bias was evaluated by a funnel plot and the Harbord' test. Certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation recommendations. RESULTS: A total of 1,938 pediatric patients from 20 RCTs were eventually included. The results of meta-analysis showed that combined therapy was able to significantly increase total effectiveness rate (RR = 1.20, 95%CI 1.15 to 1.25), forced expiratory volume in one second (SMD = 1.14, 95%CIs, 0.98 to 1.29), the ratio of forced expiratory volume in one second/forced vital capacity (SMD = 2.16, 95%CIs, 1.46 to 2.86), peak expiratory flow (SMD = 1.17, 95%CIs, 0.91 to 1.43). The combined therapy was associated with a 23% increased risk of adverse reactions compared to azithromycin therapy alone, but no significant differences were found. Harbord regression showed no publication bias (P = 0.148). The overall quality of the evidence ranged from moderate to very low. CONCLUSIONS: This first systematic review and meta-analysis suggested that azithromycin sequential therapy plus inhaled terbutaline was safe and beneficial for children with MPP. In addition, the combined therapy represented significant improvement of PVF. Due to lack of high-quality evidence, our results should be confirmed by adequately powered RCTs in the future.

Prolonged mass azithromycin distributions and macrolide resistance determinants among preschool children in Niger: A sub-study of a cluster-randomized trial (MORDOR).

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: NCT02047981 https://classic.clinicaltrials.gov/ct2/show/NCT02047981.

Concomitantly Diagnosed Disseminated M kansasii Infection and Hairy Cell Leukemia With Review of Pathophysiology.

The association between Hairy Cell Leukemia (HCL) and non-tuberculous mycobacterial infections (NTMs) is well described, most notably Mycobacterium kansasii. The exact pathophysiology is not known. We report a case of a 31-year-old male with concomitantly diagnosed HCL and disseminated M kansasii infection who presented with rash, pancytopenia, and bulky axillary lymphadenopathy. The M kansasii was initially diagnosed through use of cell-free DNA detection and confirmed by bone marrow and lymph node cultures. Hairy Cell Leukemia was diagnosed with peripheral flow cytometry and confirmed via the same bone marrow sample. His HCL was put into remission with a single course of cladribine and rituximab chemotherapy; however, his M kansasii infection persisted for 6 months despite aggressive antimicrobial and surgical therapy. It was finally controlled using high-dose rifampin in combination with azithromycin and ethambutol. This case highlights the known link between HCL and M kansasii. Furthermore, it hints at potential causes beyond chemotherapy-induced immunocompromise. Notable possibilities include HCL cells acting as sanctuary sites for M kansasii to evade the immune system, and subclinical M kansasii infections causing NLRP3 inflammasome overactivation to trigger the oncogenic transformation to HCL. More research into the pathophysiologic link between HCL and M kansasii infections would allow for more effective prevention, diagnosis, and treatment of these severe atypical infections which are the major cause of morbidity in the cladribine era of HCL treatment.

The topical azithromycin meibomian gland dysfunction survey: The effect of topical azithromycin on signs and symptoms of meibomian gland dysfunction.

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.

Legionella Serositis: A Rare Presentation.

BACKGROUND: Legionella has a higher prevalence in India than in the world. Legionaries' disease most commonly involves the lungs but because of increased awareness, extrapulmonary manifestations are also being diagnosed more frequently. CASE DESCRIPTION: We present a case of a young female with acute onset of fever and chest pain. On initial investigation, an electrocardiogram (ECG) reported widespread pulse rate (PR) depression suggestive of pericarditis which was confirmed by ECG. High-resolution computed tomography (HRCT) thorax suggested mild bilateral pleural effusion with normal lung parenchyma. elevated erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) added to the diagnosis of serositis. Serological study for atypical organisms was remarkable for positive immunoglobulin M (IgM) for Legionella. She was treated with a high dose of steroids and azithromycin successfully. CONCLUSION: Isolated extrapulmonary presentation of legionaries disease is often overlooked and is common. So it should be always included in the diagnostic armamentarium as treatment is highly efficacious if started early.

Do asymptomatic STEC-long-term carriers need to be isolated or decolonized? New evidence from a community case study and concepts in favor of an individualized strategy.

Asymptomatic long-term carriers of Shigatoxin producing Escherichia coli (STEC) are regarded as potential source of STEC-transmission. The prevention of outbreaks via onward spread of STEC is a public health priority. Accordingly, health authorities are imposing far-reaching restrictions on asymptomatic STEC carriers in many countries. Various STEC strains may cause severe hemorrhagic colitis complicated by life-threatening hemolytic uremic syndrome (HUS), while many endemic strains have never been associated with HUS. Even though antibiotics are generally discouraged in acute diarrheal STEC infection, decolonization with short-course azithromycin appears effective and safe in long-term shedders of various pathogenic strains. However, most endemic STEC-strains have a low pathogenicity and would most likely neither warrant antibiotic decolonization therapy nor justify social exclusion policies. A risk-adapted individualized strategy might strongly attenuate the socio-economic burden and has recently been proposed by national health authorities in some European countries. This, however, mandates clarification of strain-specific pathogenicity, of the risk of human-to-human infection as well as scientific evidence of social restrictions. Moreover, placebo-controlled prospective interventions on efficacy and safety of, e.g., azithromycin for decolonization in asymptomatic long-term STEC-carriers are reasonable. In the present community case study, we report new observations in long-term shedding of various STEC strains and review the current evidence in favor of risk-adjusted concepts.

In Vivo Immune-Modulatory Activity of Lefamulin in an Influenza Virus A (H1N1) Infection Model in Mice.

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.

Azithromycin removal using pine bark, oak ash and mussel shell.

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

Azithromycin for Pediatric Critical Asthma: A Multicenter Retrospective Cohort Study.

OBJECTIVES: To characterize the prescribing trends and clinical outcomes related to azithromycin (AZI) among children hospitalized for critical asthma (CA). METHODS: We performed a multicenter, retrospective cohort study using the Pediatric Health Information Systems registry of children 3 to 17 years of age hospitalized in a PICU for CA from January 2011 to December 2022. We excluded for alternative indications for AZI (eg, atypical pneumonia, B. pertussis infection, acute otitis media, acute sinusitis, pharyngitis/tonsillitis, and urethritis). The primary outcome was AZI prescribing rate by hospital and calendar year (trends assessed by Joinpoint regression). Cohorts with and without AZI exposure were further characterized by demographics, CA treatments, and inpatient outcomes using descriptive and comparative (ie, χ2 and Wilcoxon rank tests) statistics. RESULTS: Of the 47 797 children studied, 9901 (20.7%) were prescribed AZI with a downward annual trend noted from 34.7% in 2011% to 12.4% in 2022 (-1.7% per year, R2 = 0.91). Median institutional AZI prescribing rate was 19.2% (interquartile range [IQR] 11.7%-28%; total range 5.6%-60%). Compared with children not prescribed AZI, those prescribed AZI were older (median 8.3 [IQR 5.7-11.6] vs 7.3 [4.9-10.8] years, P < .001) and experienced a more severe clinical trajectory with greater rates of bilevel positive airway pressure ventilation (19.7% vs 12.6%, P < .001), invasive ventilation (22.1% vs 13.5%, P < .001), extracorporeal life support (0.8% vs 0.1%, P < .001), and median length of stay (4 [IQR 3-6] vs 3 [IQR 2-4] days, P < .001). CONCLUSIONS: Between 2011 and 2022, 20.7% of children hospitalized for CA were prescribed AZI notwithstanding the absence of trial-derived efficacy or safety data for this indication and population.

In Vitro Investigation of Therapy-Induced Senescence and Senescence Escape in Breast Cancer Cells Using Novel Flow Cytometry-Based Methods.

Although cellular senescence was originally defined as an irreversible form of cell cycle arrest, in therapy-induced senescence models, the emergence of proliferative senescence-escaped cancer cells has been reported by several groups, challenging the definition of senescence. Indeed, senescence-escaped cancer cells may contribute to resistance to cancer treatment. Here, to study senescence escape and isolate senescence-escaped cells, we developed novel flow cytometry-based methods using the proliferation marker Ki-67 and CellTrace CFSE live-staining. We investigated the role of a novel senescence marker (DPP4/CD26) and a senolytic drug (azithromycin) on the senescence-escaping ability of MCF-7 and MDA-MB-231 breast cancer cells. Our results show that the expression of DPP4/CD26 is significantly increased in both senescent MCF-7 and MDA-MB-231 cells. While not essential for senescence induction, DPP4/CD26 contributed to promoting senescence escape in MCF-7 cells but not in MDA-MB-231 cells. Our results also confirmed the potential senolytic effect of azithromycin in senescent cancer cells. Importantly, the combination of azithromycin and a DPP4 inhibitor (sitagliptin) demonstrated a synergistic effect in senescent MCF-7 cells and reduced the number of senescence-escaped cells. Although further research is needed, our results and novel methods could contribute to the investigation of the mechanisms of senescence escape and the identification of potential therapeutic targets. Indeed, DPP4/CD26 could be a promising marker and a novel target to potentially decrease senescence escape in cancer.