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• Automatic software is able to measure bronchus-artery (BA) dimensions on chest CT. • A large number of BA-pairs can be analyzed on chest CTs in infants aged 1–3 years with CF. • Azithromycin-treated infants with CF show a reduction in bronchial wall thickness. • Reduced arterial diameter suggests azithromycin's effect on small airways disease and associated lung perfusion. • Automatic measurements of bronchial dimensions add clinically relevant information. COMBAT-CF showed that children aged 0–3 years treated with azithromycin did clinically better than placebo but there was no effect on CT-scores. We reanalysed CTs using an automatic bronchus-artery (BA) analysis. Inspiratory and expiratory CTs at 12 and 36 months were analysed. BA-analysis measures BA-diameters: bronchial outer wall (B out), bronchial inner wall (B in), artery (A), and bronchial wall thickness (B wt) and computes BA-ratios: B out /A and B in /A for bronchial widening, B wt /A and B wa /B oa (bronchial wall area/bronchial outer area) for bronchial wall thickening. Low attenuation regions (LAR) were analysed using an automatic method. Mixed-effect model was used to compare BA-outcomes at 36 months between treatment groups. 228 CTs (59 placebo; 66 azithromycin) were analysed. The azithromycin group had lower B wa /B oa (p = 0.0034) and higher B in /A (p = 0.001) relative to placebo. B out /A (p = 0.0088) was higher because of a reduction in artery diameters which correlated to a reduction in LAR. Azithromycin-treated infants with CF show a reduction in bronchial wall thickness and possibly a positive effect on lung perfusion. [ABSTRACT FROM AUTHOR]

Azithromycin is used for children with cystic fibrosis (CF) for its immunomodulatory and anti-inflammatory action. This study investigated the short-term alterations in QTc interval associated with azithromycin prophylaxis in pediatric patients with CF. This study included 121 patients with mild CF, of whom 76 received azithromycin (patient group) and 45 did not receive azithromycin (control group). The patient and control groups were categorized according to age as under 12 years of age and over 12 years of age. The first presentation measured all the patient and control groups at basic QTc time intervals. The QTc intervals of all patients were then remeasured systemically at 1, 3, and 6 months. Age categories and QTc intervals that were calculated at each month in the patient and control groups were compared statistically. A statistically significant difference was detected in the patient group between the initial QTc interval time and the electrocardiogram (ECG) findings in the first and third months after prophylaxis treatment (p < 0.001; p = 0.01). However, no statistically significant difference was detected in the sixth month (p > 0.05) in all groups. Almost all of the children's QTc intervals were within normal range and within the safety zone (under 0.44 s). No statistically significant difference was detected in the control group between the initial ECG and the QTc intervals measured at 1, 3, and 6 months. Short-term use of azithromycin prophylaxis in pediatric patients with mild CF slightly increased the QTc interval in the first and third months of follow-up. Nevertheless, all QTc interval changes fell within the safety zone. Notably, 1 month of follow-up treatment should be performed to check for any alteration in the QTc interval. If increased QTc interval duration is not detected in the first month, azithromycin prophylaxis can be safely prescribed. [ABSTRACT FROM AUTHOR]

The pandemic of SARS-CoV-2 worldwide with successive emerging variants urgently calls for small-molecule oral drugs with broad-spectrum antiviral activity. Here, we show that carrimycin, a new macrolide antibiotic in the clinic and an antiviral candidate for SARS-CoV-2 in phase III trials, decreases the efficiency of programmed –1 ribosomal frameshifting of coronaviruses and thus impedes viral replication in a broad-spectrum fashion. Carrimycin binds directly to the coronaviral frameshift-stimulatory element (FSE) RNA pseudoknot, interrupting the viral protein translation switch from ORF1a to ORF1b and thereby reducing the level of the core components of the viral replication and transcription complexes. Combined carrimycin with known viral replicase inhibitors yielded a synergistic inhibitory effect on coronaviruses. Because the FSE mechanism is essential in all coronaviruses, carrimycin could be a new broad-spectrum antiviral drug for human coronaviruses by directly targeting the conserved coronaviral FSE RNA. This finding may open a new direction in antiviral drug discovery for coronavirus variants. Carrimycin binds directly to the coronavirus FSE RNA pseudoknot to interrupt the translational switch of viral proteins from ORF1a to ORF1b, synergistically reducing viral replication in combination with RdRp and 3CLpro inhibitors. [Display omitted] [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]

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]

Clinical chorioamnionitis, the most common infection-related diagnosis in labor and delivery units, is an antecedent of puerperal infection and neonatal sepsis. The condition is suspected when intrapartum fever is associated with two other maternal and fetal signs of local or systemic inflammation (eg, maternal tachycardia, uterine tenderness, maternal leukocytosis, malodorous vaginal discharge or amniotic fluid, and fetal tachycardia). Clinical chorioamnionitis is a syndrome caused by intraamniotic infection, sterile intraamniotic inflammation (inflammation without bacteria), or systemic maternal inflammation induced by epidural analgesia. In cases of uncertainty, a definitive diagnosis can be made by analyzing amniotic fluid with methods to detect bacteria (Gram stain, culture, or microbial nucleic acid) and inflammation (white blood cell count, glucose concentration, interleukin-6, interleukin-8, matrix metalloproteinase-8). The most common microorganisms are Ureaplasma species, and polymicrobial infections occur in 70% of cases. The fetal attack rate is low, and the rate of positive neonatal blood cultures ranges between 0.2% and 4%. Intrapartum antibiotic administration is the standard treatment to reduce neonatal sepsis. Treatment with ampicillin and gentamicin have been recommended by professional societies, although other antibiotic regimens, eg, cephalosporins, have been used. Given the importance of Ureaplasma species as a cause of intraamniotic infection, consideration needs to be given to the administration of antimicrobial agents effective against these microorganisms such as azithromycin or clarithromycin. We have used the combination of ceftriaxone, clarithromycin, and metronidazole, which has been shown to eradicate intraamniotic infection with microbiologic studies. Routine testing of neonates born to affected mothers for genital mycoplasmas could improve the detection of neonatal sepsis. Clinical chorioamnionitis is associated with decreased uterine activity, failure to progress in labor, and postpartum hemorrhage; however, clinical chorioamnionitis by itself is not an indication for cesarean delivery. Oxytocin is often administered for labor augmentation, and it is prudent to have uterotonic agents at hand to manage postpartum hemorrhage. Infants born to mothers with clinical chorioamnionitis near term are at risk for early-onset neonatal sepsis and for long-term disability such as cerebral palsy. A frontier is the noninvasive assessment of amniotic fluid to diagnose intraamniotic inflammation with a transcervical amniotic fluid collector and a rapid bedside test for IL-8 for patients with ruptured membranes. This approach promises to improve diagnostic accuracy and to provide a basis for antimicrobial administration. [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]

• In a systematic review, no significant differences regarding mortality, hospital length of stay or clinical complications were identified when comparing fluoroquinolones vs macrolides administration in hospitalized patients with moderate severity Legionella pneumonia. • When data from the three cohorts with severe pneumonia were pooled together, mortality with fluoroquinolones alone was statistically superior to macrolides alone (72.8 % vs 30.7 %, p value 0.027). • A randomized controlled trial in severe pneumonia is an unmet clinical need to determine if one class of antibiotic is superior to another or whether a combination therapy regimen provides any significant clinical benefit over monotherapy. The optimal antimicrobial regimen for adults with respiratory failure due to Legionella pneumonia remains controversial. A systematic review was performed to assess the impact on outcomes comparing quinolones versus macrolides. A literature search was conducted in PubMed, Cochrane Library and Web of Science between 2012 and 2022. It yielded 124 potentially articles and ten observational studies met the inclusion criteria. A total of 4271 patients were included, 2879 (67 %) were male. A total of 1797 (42 %) subjects required intensive care unit (ICU) admission and 942 (52 %) mechanical ventilation. Fluoroquinolones and macrolides alone were administered in 1397 (33 %) and 1500 (35 %) subjects, respectively; combined therapy in 204 (4.8 %) patients. Overall mortality was 7.4 % (319 patients), with no difference between antibiotics. When data from the three studies with severe pneumonia were pooled together, mortality with fluoroquinolones alone was statistically superior to macrolides alone (72.8 % vs 30.8 %, p value 0.027). Hospital length of stay and complications were comparable. Our findings suggest that macrolides and quinolones were comparable for hospitalized Legionella pneumonia. However, in severe pneumonia, a randomized clinical trial is an unmet clinical need. PROSPERO registration number: CRD42023389308. [ABSTRACT FROM AUTHOR]

To evaluate the efficacy and tolerability of a single dose of oral cefixime 800 mg plus oral doxycycline 100 mg twice a day for 7 days, compared with a recommended single dose of ceftriaxone plus single dose of oral azithromycin, for treatment of uncomplicated urogenital, rectal, or pharyngeal gonorrhoea. A noninferiority, open-label, multicentre randomized controlled trial was conducted in Prague, Czech Republic. Some 161 patients, 18–65 years of age diagnosed with uncomplicated urogenital, rectal, or pharyngeal gonorrhoea by nucleic acid amplification test (NAAT) were randomized to treatment with single dose of cefixime 800 mg plus doxycycline 100 mg twice a day for 1 week or a single dose of ceftriaxone 1 g intramuscularly plus single dose of azithromycin 2 g. The primary outcome was the number of participants with negative culture and NAAT at 1 week and 3 weeks, respectively, after treatment initiation. In all, 161 patients were randomized and 152 were included in per-protocol analyses. All 76 (100%; 95% CI, 0.95–1.00) patients treated with ceftriaxone plus azithromycin achieved negative cultures and NAAT after treatment. In the cefixime plus doxycycline arm at week 1, culture was negative in all 76 (100%) patients; at week 3, culture was negative in 70 of the 76 patients (92%; 95% CI, 0.84–0.97) and NAAT negative in 66 of the 76 patients (87%; 95% CI, 0.77–0.94). At week 3, culture and NAAT were negative in 65 of the 76 patients (86%; 95% CI, 0.76–0.93). Per-protocol risk difference was 14.5%; 95% CI, 6.56–22.38. All treatment failures observed in the cefixime arm were pharyngeal gonorrhoea cases. The combination of cefixime and doxycycline did not achieve noninferiority to ceftriaxone and azithromycin for treatment of gonorrhoea when including pharyngeal gonorrhoea. It did, however, show high efficacy for urogenital and rectal gonorrhoea. [ABSTRACT FROM AUTHOR]

The encapsulation efficiency and the loading capacity of azithromycin (AZI) were succesfully enhanced by modifying chitosan nanoparticle (NCh) with Anredera cordifolia leaf extract (ACLE), as demonstrated in this study. The prominent secondary metabolites in ACLE could establish a new chemical bonds with NCh's amino groups and partly improved the hydrophobicity of NCh, which leads to excellent AZI encapsulation efficiency and loading capacity of 95.24 ± 1.30% and 55.74 ± 1.03%, respectively. TEM characterization demonstrated that the AZI-loaded ACLE-NCh nanoparticles were uniformly distributed with a particle size of 24.6 ± 2.9 nm. According to the result of in vitro drug release studies, AZI-loaded ACLE-NCh releases 1.12 ± 0.33% at a pH of 1.6 for 2 h, 82.05 ± 2.26% at a pH of 6.8 for 6 h, and 93.44 ± 1.94% at a pH of 7.4 for 24 h. It is remarkable that the encapsulation activityu of AZI-loaded ACLE-NCh is more effective due to the better interaction between NCh and AZI resulting from the increased hydrophobicity of modified NCh. Moreover, this work provides novel findings on the significant contribution of NCh modified by plant extracts, which has the potential as a carrier for azithromycin. [Display omitted] • Nanochitosan was capable of serving as an azithromycin drug carrier. • The encapsulation efficiency and the loading capacity of azithromycin were succesfully enhanced by modifying nanochitosan with Anredera cordifolia leaf extract. • The azithromycin-loaded modified nanochitosan demonstrated outstanding controlled release behavior at various pH. [ABSTRACT FROM AUTHOR]

• Gingival CD68+/CD163 + macrophage ratio increased in chronic periodontitis. • Azithromycin decreased the CD68+/CD163 + macrophage ratio in periodontal tissues. • Azithromycin can modulate gingival macrophages' functional role in periodontitis. The growing interest in the possibilities of macrophages modulation with therapeutic purposes promotes new approaches for periodontitis treatment. The aim of this randomized controlled open clinical study was to evaluate the early clinical and immunological effects of the long-course azithromycin as an adjunct to scaling and root planing in periodontitis. 50 patients (with stage I-III, grade A/B periodontitis) and 22 periodontally healthy volunteers as the reference group were recruited. Following scaling and root planing (SRP), the patients were randomly assigned to one of two treatment modalities: SRP only (n = 25) and adjunct azithromycin (Az) treatment (n = 25). The patients were monitored at baseline, and 30 ± 5 days after therapy. Clinical attachment loss (CAL), periodontal probing depth (PPD) and bleeding on probing (BoP) were evaluated. Secondary outcome measures included mean changes in single-positive CD68 + and CD163 + macrophages (Mφs) density and ratio, evaluated by immunohistochemistry, and IL1-β, IL-6, IL-10, TGF-β levels, detected by ELISA. At 1 month both groups showed significant improvements of CAL, PPD and BoP, without significant added benefit in terms of CAL, PPD and BoP of Az. But Az increased the density of CD68 + and CD163 + Mφs (P < 0.0001), decreased the CD68+/CD163 + ratio (P = 0.043), decreased IL-1β (P < 0.01), IL-6 (P < 0.001) levels, and increased IL-10 (P < 0.0001) and TGF-β (P < 0.001) levels compared to SRP and periodontitis at baseline. The long course of Az demonstrated modulation of CD68 + and CD163 + Mφs towards M2 polarization, which may play a significant role in achieving favorable long-term treatment outcomes. ClinicalTrials.gov [ABSTRACT FROM AUTHOR]

Dysbiotic bacterial communities within the vagina are associated with Chlamydia trachomatis infection. We compared the effect of treatment with azithromycin and doxycycline on the vaginal microbiota in a cohort of women with a urogenital C. trachomatis infection randomly assigned to one of these treatments (Chlazidoxy trial). We analysed vaginal samples from 284 women (135 in the azithromycin group and 149 in the doxycycline group) collected at baseline and 6 weeks after treatment initiation. The vaginal microbiota was characterized using 16S rRNA gene sequencing and classified into community state types (CSTs). At baseline, 75% (212/284) of the women had a high-risk microbiota (CST-III or CST-IV). A cross-sectional comparison 6 weeks after treatment showed that 15 phylotypes were differentially abundant, but this difference was not reflected at the CST (p 0.772) or diversity level (p 0.339). Between baseline and the 6-week visit, α-diversity (p 0.140) and transition probabilities between CSTs were not significantly different between the groups, and no phylotype was differentially abundant. In women with urogenital C. trachomatis infection, the vaginal microbiota does not seem to be affected by azithromycin or doxycycline 6 weeks after treatment. Because the vaginal microbiota remains susceptible to C. trachomatis infection (with CST-III or CST-IV) after antibiotic treatment, women remain at risk of reinfection, which could originate from unprotected sexual intercourse or untreated anorectal C. trachomatis infection. This last consideration advocates for the use of doxycycline instead of azithromycin because of its higher anorectal microbiological cure rate. [ABSTRACT FROM AUTHOR]

Azithromycin has been adopted as a component of the COVID-19 management protocol throughout the global healthcare settings but with a questionable if not downright unsubstantiated evidence base. In order to amalgamate and critically appraise the conflicting evidence around the clinical efficacy of Azithromycin (AZO) vis a vis COVID-19 management outcomes, a meta-analysis of meta-analyses was carried out to establish an evidence-based holistic status of AZO vis a vis its efficacy as a component-in-use of the COVID-19 management protocol. A comprehensive systematic search was carried out through PubMed/Medline, Cochrane and Epistemonikos with a subsequent appraisal of abstracts and full-texts, as required. The Quality of Reporting of Meta-analyses (QUOROM) checklist and the Assessment of Multiple Systematic Reviews (AMSTAR) methodology were adopted to assess the methodological quality of the included meta-analyses. Random-effects models were developed to calculate summarized pool Odds Ratios (with 95% confidence interval) for the afore determined primary and secondary outcomes. AZO, when compared with best available therapy (BAT) including or excluding Hydroxychloroquine, exhibited statistically insignificant reduction in mortality [(n= 27,204 patients) OR= 0.77 (95% CI: 0.51-1.16) (I2= 97%)] , requirement of mechanical ventilation [(n= 14,908 patients) OR= 1.4 (95% CI: 0.58-3.35) (I2= 98%)] , induction of arrhythmia [(n= 9,723 patients) OR= 1.21 (95% CI: 0.63-2.32) (I2= 92%)] and QTc prolongation (a surrogate for torsadogenic effect) [(n= 6,534 patients) OR= 0.62 (95% CI: 0.23-1.73) (I2= 96%)]. The meta-analysis of meta-analyses portrays AZO as a pharmacological agent that does not appear to have a comparatively superior clinical efficacy than BAT when it comes to COVID-19 management. Secondary to a very real threat of anti-bacterial resistance, it is suggested that AZO be discontinued and removed from COVID-19 management protocols. [ABSTRACT FROM AUTHOR]

Lower respiratory tract infections are frequently treated with antibiotics, despite a viral cause in many cases. It remains unknown whether low procalcitonin concentrations can identify patients with lower respiratory tract infection who are unlikely to benefit from antibiotics. We aimed to compare the efficacy and safety of azithromycin versus placebo to treat lower respiratory tract infections in patients with low procalcitonin. We conducted a randomised, placebo-controlled, double-blind, non-inferiority trial at five health centres in the USA. Adults aged 18 years or older with clinically suspected non-pneumonia lower respiratory tract infection and symptom duration from 24 h to 28 days were eligible for enrolment. Participants with a procalcitonin concentration of 0·25 ng/mL or less were randomly assigned (1:1), in blocks of four with stratification by site, to receive over-encapsulated oral azithromycin 250 mg or matching placebo (two capsules on day 1 followed by one capsule daily for 4 days). Participants, non-study clinical providers, investigators, and study coordinators were masked to treatment allocation. The primary outcome was efficacy of azithromycin versus placebo in terms of clinical improvement at day 5 in the intention-to-treat population. The non-inferiority margin was –12·5%. Solicited adverse events (abdominal pain, vomiting, diarrhoea, allergic reaction, or yeast infections) were recorded as a secondary outcome. This trial is registered with ClinicalTrials.gov , NCT03341273. Between Dec 8, 2017, and March 9, 2020, 691 patients were assessed for eligibility and 499 were enrolled and randomly assigned to receive azithromycin (n=249) or placebo (n=250). Clinical improvement at day 5 was observed in 148 (63%, 95% CI 54 to 71) of 238 participants with full data in the placebo group and 155 (69%, 61 to 77) of 227 participants with full data in the azithromycin group in the intention-to-treat analysis (between-group difference –6%, 95% CI –15 to 2). The 95% CI for the difference did not meet the non-inferiority margin. Solicited adverse events and the severity of solicited adverse events were not significantly different between groups at day 5, except for increased abdominal pain associated with azithromycin (47 [23%, 95% CI 18 to 29] of 204 participants) compared with placebo (35 [16%, 12 to 21] of 221; between-group difference –7% [95% CI –15 to 0]; p=0·066). Placebo was not non-inferior to azithromycin in terms of clinical improvement at day 5 in adults with lower respiratory tract infection and a low procalcitonin concentration. After accounting for both the rates of clinical improvement and solicited adverse events at day 5, it is unclear whether antibiotics are indicated for patients with lower respiratory tract infection and a low procalcitonin concentration. National Institute of Allergy and Infectious Diseases, bioMérieux. [ABSTRACT FROM AUTHOR]

WHO recommends mass drug administration (MDA) of the antibiotic azithromycin for children aged 1–11 months in areas with high rates of infant and child mortality. Notwithstanding the substantial potential benefits of lowering childhood mortality, MDA raises understandable concerns about exacerbating antibiotic resistance. In this study, we aimed to evaluate the use of MDA using both quantitative and ethical considerations. We performed a series of literature searches between July 2019 and June 2022. We first compared MDA with other uses of antibiotics using the standard metric of 'number needed to treat', and five additional criteria: (1) other widely accepted uses of anti-infectives (2) absolute use (i.e. total number), of antibiotics, (3) risk-benefit trade-off, (4) availability of short-term alternatives, and (5) the precedent for implementing similar interventions. We found that MDA falls well within a justifiable range when compared with widely accepted uses of antibiotics in terms of the number needed to treat. The other five criteria we considered provided further support for the use of MDA to prevent childhood mortality. Although better data on antibiotic use and resistance are needed, efforts to reduce antibiotic use and resistance should not start with halting MDA of azithromycin in the areas with the highest rates of childhood mortality. Improving data to inform this decision is critical. However, on the basis of the best evidence available, we believe that concerns regarding resistance should not thwart MDA; instead, MDA should be accompanied by robust plans to monitor its efficacy and changes in resistance levels. Similar considerations could be included in a framework for evaluating the benefits of antibiotics against the risk of resistance in other contexts. [ABSTRACT FROM AUTHOR]

Porphyromonas gingivalis (P. gingivalis) is viewed as a keystone microorganism in the pathogenesis of periodontal and peri -implant diseases. Hyaluronic acid (HA) is believed to exert antimicrobial activity. The aim of this study is to assess the in-vitro growth and biofilm formation of P. gingivalis under HA and compare the effect of HA to that of azithromycin (AZM) and chlorhexidine (CHX). In each material, the minimum inhibitory concentration (MIC), 50% MIC, 25% MIC, and 12.5% MIC were tested. The growth of P. gingivalis was evaluated by absorbance spectrophotometry after 48 h. A biofilm inhibition assay was performed on a 72-hour culture by washing planktonic bacterial cells, fixing and staining adherent cells, and measuring the variation in stain concentrations relative to the untreated control using absorbance spectrophotometry. The results show that the overall growth of P. gingivalis after 48 h was 0.048 ± 0.030, 0.008 ± 0.013, and 0.073 ± 0.071 under HA, AZM, and CHX, respectively, while the untreated control reached 0.236 ± 0.039. HA was also able to significantly reduce the biofilm formation of P. gingivalis by 64.30 % ± 22.39, while AZM and CHX reduced biofilm formation by 91.16 %±12.58 and 88.35 %±17.11, respectively. High molecular-weight HA significantly inhibited the growth of P. gingivalis. The overall effect of HA on the growth of P. gingivalis was similar to that of CHX but less than that of AZM. HA was also able to significantly reduce the biofilm formation of P. gingivalis. However, the ability of HA to prevent the biofilm formation of P. gingivalis was generally less than that of both AZM and CHX. [ABSTRACT FROM AUTHOR]

To determine whether gestational use of all or specific macrolides (azithromycin, clarithromycin, roxithromycin or erythromycin) lead to an increase in rates of overall major congenital malformations, organ-specific malformations, and other adverse pregnancy outcomes in infants. PubMed/MEDLINE, Cochrane Central Register of Controlled Trials and Reprotox® databases were searched. Dichotomous outcomes or calculated log odds ratios and standard errors from observational studies are combined using the random-effects method in Review Manager 5.3. No significant increased risks for major congenital malformation (OR 1.06 [95% CI 0.99, 1.13]) and congenital heart defect (OR 1.05 [95% CI 0.92, 1.19]) following all macrolides use during the first trimester were detected. Prenatal azithromycin use was associated with a significantly increased risk of major congenital malformations in the analysis of cohort studies (OR 1.21 [95% CI 1.08–1.36]). This significance was also present in the sensitivity analysis. There were no statistically significant associations between the risk of organ specific malformations and all or specific macrolide exposures except for the decreased risk in hypospadias following erythromycin use in the meta-analysis of case-control studies (OR 0.38 [95% CI 0.18, 0.81]. Also, a significant 1.5-fold increased risk for spontaneous abortion following macrolide use was detected. A slight yet significantly increased rate of major congenital malformation with azithromycin exposure during pregnancy may be associated with maternal confounders. Nevertheless, level II ultrasound can be suggested following maternal azithromycin use during the first trimester. Future studies should take into account the inclusion of a disease-matched control group and accurate classification of the malformations. • Concerns regarding pregnancy outcomes following maternal macrolide use exists. • No increased risk for major malformations following maternal all macrolide exposure. • 1.5-fold increased risk for miscarriage following all macrolide use was present. • Maternal confounders cannot be ruled out in the azithromycin analyses. • Further studies with better disease-matched control groups are needed. [ABSTRACT FROM AUTHOR]

Azithromycin is becoming an effective alternative medicine against antibiotic resistant Escherichia coli (E. coli), and in parallel, is frequently detecting in wastewater and fresh water media. The current study aimed to evaluate the presence of azithromycin resistance genes (AzRGs) in E. coli isolated from urban wastewater for which there is a serious lack of information. For this, the samples were collected from four vital points of an urban wastewater treatment plant (WWTP), analyzed for physicochemicfial parameters, and identified for the azithromycin resistant isolates. The isolates were then subjected to 13 other extensively used antibiotics (from seven different classes), including amikacin, aztreonam, ceftazidime, ciprofloxacin, cefepime, ceftriaxone, cefotaxime, doxycycline, gentamicin, imipenem, norfloxacin, tetracycline, and trimethoprim/sulfamethoxazole; detected for AzRGs, phylogenic group, and molecular typing. The results clearly showed that: a) except for amikacin in all samples and gentamicin in effluent samples, E. coli isolates were resistant to all other the antibiotics studied in the mean respective values of 53.8%, 90.4%, 50%, 40.4%, 86.5%, 86.5%, 63.5%, 13.5%, 73.1%, 46.2%, 65.4%, 69.2%; b) for 75% of them (i.e. except for amikacin, gentamicin, and trimethoprim/sulfamethoxazole), the antibiotic resistance prevalence in effluent samples were significantly higher than that of sludge (p-value = 0.011), aeration (p-value = 0.023), and even influent (p-value = 0.038) samples, suggesting that WWTP facilities acquiring the resistance gene; c) The high values of multiple antibiotic resistance (MAR) index in almost all of the isolates (0.21–0.91) were categorized them in high-risk group, though the values were not found to be influenced by WWTP. Surprisingly, from 10 AzRGs, only two genes of mph(A) and erm(B) were detected in 100% and 67.3% of the isolates, respectively. The prevalence of erm(B) was significantly influenced by MAR index (p-value = 0.004), which MAR in turn, influenced by physicochemical parameters of wastewater in the relative effectiveness of COD (36%) > EC (29%) > TS (16%) > TDS (9%) > temperature (6%) > pH (4%), as modeled using artificial neural network (ANN) approach (R2 = 0.85 and MSE = 0.006302). The phylogenetic group A (59.6%) and clusters of III and V with 23 and 18 isolates, respectively, were dominant among the isolates which both showed a high correlation with MAR indices and therefore erm(B) prevalence. These results were interesting as highlight the effect of WWTP on acquiring antibiotic resistance and AzRGs prevalence in E. coli. Therefore, defining new strategies for relieving the challenge is of great importance. [Display omitted] • WWTP plays a facilitating role in acquiring antibiotic resistance in E.coli. • Almost all of the isolates were in the high-risk categories (multiple antibiotic resistance; MAR > 0.2). • WWTP showed no significant effect on MAR indices. • Two genes of mph(A) and erm(B) were detected in 100 % and 67.3 % of the isolates, respectively. • The prevalence of erm(B) genes was found to be highly correlated with MAR index, which in turn, was impressed by wastewater physicochemical parameters. • The phylogenetic group A and clusters of III and V were dominant among the isolates which both showed a high correlation with MAR index and therefore erm(B) prevalence. [ABSTRACT FROM AUTHOR]

Azithromycin is an alternative to treat invasive non-typhoidal Salmonella (iNTS) infections. We determined its epidemiological cut-off (ECOFF) and compared azithromycin susceptibility testing methods for iNTS. We used EUCAST ECOFFinder to determine the minimum inhibitory concentrations (MIC; obtained by broth microdilution) ECOFF and corresponding disk zone diameters of 515 iNTS from blood cultures in Democratic Republic of Congo, Burkina Faso, Rwanda, and Cambodia. Transferable resistance mechanisms were determined by polymerase chain reaction. We compared azithromycin susceptibility testing by semi-automated broth microdilution (customized Sensititre panel; reference), agar dilution, gradient tests (bioMérieux, Liofilchem, HiMedia; read at 80% (MIC80%) and 100% inhibition (MIC100%)), and disk diffusion (Rosco, Oxoid, BD, Liofilchem) for 161 wild- and 198 non–wild-type iNTS. Azithromycin MIC ECOFF was 16 mg/L corresponding to a 12 mm zone diameter; mphA was detected in 192/197 non–wild- and 0/47 wild-type iNTS. Categorical agreement was excellent (≥98%) for all methods. Essential agreement was very good for agar dilution (>90%) but moderate for gradient tests (MIC80%: 52% to 71% and MIC100%: 72% to 91%). Repeatability was good for all methods/brands. Interreader agreement was high for broth microdilution and agar dilution (all ≤1 twofold dilution difference) and disk diffusion (>96% ≤3 mm difference) but lower for gradient tests (MIC80% & MIC100%: 83% to 94% ≤1 twofold dilution difference). Azithromycin ECOFF of iNTS was 16 mg/L, i.e. equal to Salmonella Typhi. Disk diffusion is an accurate, precise, and user-friendly alternative for agar dilution and broth microdilution. Reading gradient tests at 100% instead of 80% inhibition improved accuracy and precision. [ABSTRACT FROM AUTHOR]

• Decrease in high sensitivity C-reactive protein (hsCRP) from baseline to week 39 in the OPTIMIZE clinical trial was significantly larger in the azithromycin treated group than placebo. • No difference between the groups was seen in hsCRP at 78 weeks compared to baseline. • Calprotectin, myeloperoxidase, absolute neutrophil count and total white blood cell count showed no differences between groups at any time point. • The findings are consistent with a transient systemic immunomodulatory effect of azithromycin in children with new pseudomonas. Chronic azithromycin improves outcomes in cystic fibrosis (CF), but its mechanism of action is unclear. The OPTIMIZE trial demonstrated improvement in time to first pulmonary exacerbation in children with new Pseudomonas treated with azithromycin. Azithromycin effect on systemic markers of inflammation over 18 months was assessed by change from baseline for high-sensitivity C-reactive protein, myeloperoxidase, calprotectin and absolute neutrophil count in the OPTIMIZE population. Subjects treated with chronic azithromycin or placebo had samples collected at baseline, 39 and 78 weeks of treatment. In 129 subjects, a significant decrease in high-sensitivity C-reactive protein was present at 39 weeks in the azithromycin group compared to placebo, but no significant difference between the groups at 78 weeks. No differences in change from baseline in myeloperoxidase, calprotectin or absolute neutrophil count were present at either time point. This supports the concept of a transient immunomodulatory effect for chronic azithromycin therapy in children with CF. [ABSTRACT FROM AUTHOR]

• The beneficial effect of azithromycin in patients with COVID-19 is debated • Azithromycin was associated with a 1.5-fold higher risk of hospitalization in patients with COVID-19 • Results did not indicate any significant risk reduction in the other studied outcomes • Results raise concerns on risks associated with inappropriate use of azithromycin Previous studies ruled out the benefits of azithromycin for treatment of patients with COVID-19 who are hospitalized. However, the effects of azithromycin for treatment of patients with positive SARS-CoV-2 test results in the community remains a matter of debate. This study aimed to assess whether azithromycin, when used in subjects with positive test results for SARS-CoV-2, is associated with a reduced risk of hospitalization, in-hospital COVID-19 outcomes, and death. Two study cohorts were selected. Cohort A included subjects with positive test results for SARS-CoV-2 between February 20, 2020 and December 10, 2020; cohort B included subjects infected with SARS-CoV-2 and hospitalized between February 20, 2020 and December 31, 2020. We compared the risk of hospitalization, intensive care unit access, need for mechanical ventilation, and death in azithromycin users versus nonusers. A clustered Fine-Gray analysis was employed to assess the risk of hospitalization; logistic and Cox regressions were performed to assess the risk of intensive care unit access, mechanical ventilation, and death. In cohort A, among 4861 azithromycin users and 4861 propensity-matched nonusers, azithromycin use was associated with higher risk of hospitalization (hazard ratio [HR] 1.59, 95% confidence interval [CI] 1.45-1.75) compared with nonuse. In cohort B, among 997 subjects selected in both groups, azithromycin use was not significantly associated with intensive care unit access (odds ratio [OR] 1.22, 95% CI 0.93-1.56), mechanical ventilation (OR 1.30, 95% CI 0.99-1.70), 14-day mortality (HR0.88, 95% CI 0.74-1.05), or 30-day mortality (HR 0.89, 95% CI 0.77-1.03). Our findings confirm the lack of benefits of azithromycin treatment among community patients infected with SARS-CoV-2, raising concern on potential risks associated with its inappropriate use. [ABSTRACT FROM AUTHOR]

The treatment of drug-resistant bacterial infections attributed to the overuse of antibiotics still remains a serious challenge globally. Herein, zwitterionic charge switchable meso-silica/polypeptide hybrid nanoparticles (MSPNs) were prepared for the synergistic chemo-photodynamic therapy in the treatment of drug-resistant bacterial infections. Subsequently, azithromycin (AZT) and methylene blue (MB) were loaded in the MSPNs to form the combined chemo-photodynamic therapeutic nanoparticles (MSPNs-AZT/MB) for the treatment of methicillin-resistant Staphylococcus aureus (MRSA). Remarkably, the as-prepared MSPNs-AZT/MB exhibited a negative surface charge of −5.2 mV at physiological pH while switching into positive surface charge of 24.7 mv in an acidic environment, leading to enhanced binding with bacterial surface. The lipase-triggered AZT release up to 77.9 % was achieved, and the loaded MB demonstrated efficient singlet oxygen (1O 2) generation for photodynamic therapy. The in vitro experimental results displayed an excellent antibacterial effect against MRSA in both planktonic and biofilm phenotypes. Additionally, the as-prepared MSPNs-AZT/MB exhibited synergistic and enhanced antibacterial infection effect up to 94 % comparing to monotherapy in a mice model. Considering the above advantages, the as-prepared combined chemo-photodynamic therapeutic nanoparticles showed promising biocompatibility and clinical potential for the efficient therapy of drug-resistant bacteria. [ABSTRACT FROM AUTHOR]

• Sludge disintegration rate increased with the dosage of K 2 FeO 4. • K 2 FeO 4 pretreatment can effectively increase SCFA yield. • Acetic acid is the predominate acidogenic product after K 2 FeO 4 pretreatment. • K 2 FeO 4 promoted the release and subsequent biodegradation of antibiotics. During the acidogenic fermentation converting waste activated sludge (WAS) into short-chain fatty acids (SCFA), hydrolysis of complex organic polymers is a limiting step and the transformation of harmful substances (such as antibiotics) during acidogenic fermentation is unknown. In this study, potassium ferrate (K 2 FeO 4) oxidation was used as a pretreatment strategy for WAS acidogenic fermentation to increase the hydrolysis of sludge and destruct the harmful antibiotics. Pretreatment with K 2 FeO 4 can effectively increase the SCFA production during acidogenic fermentation and change the distribution of SCFA components. With the dosage of 0.2 g/g TS, the maximum SCFA yield was 4823 mg COD/L, which is 28.3 times that of the control group; acetic acid accounts for more than 90% of the total SCFA. The higher dosage (0.5 g/g TS) can further increase the proportion of acetic acid, but inhibit the overall performance of SCFA production. Apart from the promotion of hydrolysis and acidogenesis, K 2 FeO 4 pretreatment can also simultaneously oxidizes and degrades part of the antibiotics in the sludge. When the dosage is 0.5 g/g TS, the degradation efficacy of antibiotics is the most significant, and the contents of ofloxacin, azithromycin, and tetracycline in the sludge are reduced by 69%, 42%, and 50%, respectively. In addition, K 2 FeO 4 pretreatment can also promote the release of antibiotics from sludge flocs, which is conducive to the simultaneous degradation of antibiotics in the subsequent biological treatment process. Graphical abstract [Display omitted] [ABSTRACT FROM AUTHOR]

Objectives: Enteric fever is predominantly managed as an outpatient condition in endemic settings but there is little evidence to support this approach in non-endemic settings. This study aims to review the outcomes of outpatients treated for enteric fever at the Hospital of Tropical Diseases in London, UK.Methods: We conducted a retrospective analysis of all patients with confirmed enteric fever between August 2009 and September 2020. Demographic, clinical, laboratory and microbiological data were collected and compared between the inpatient and outpatient populations. Outcomes investigated were complicated enteric fever, treatment failure and relapse.Results: Overall, 93 patients (59% male, median age 31) were identified with blood and/or stool culture confirmed enteric fever and 49 (53%) of these were managed as outpatients. The commonest empirical treatment for outpatients was azithromycin (70%) and for inpatients was ceftriaxone (84%). Outpatients were more likely than inpatients to receive only one antibiotic (57% vs 19%, p < 0.01) and receive a shorter duration of antibiotics (median 7 vs 11 days, p <0.01). There were no cases of complicated disease or relapse in either the inpatient or outpatient groups. There was one treatment failure in the outpatient group. Azithromycin was well-tolerated with no reported side effects.Conclusions: Our findings suggest that outpatient management of uncomplicated imported enteric fever is safe and effective with the use of oral azithromycin. Careful monitoring of patients is recommended as treatment failure can occur. [ABSTRACT FROM AUTHOR]

• This combinational therapy: • Improved the clinical status of septic mice based on MSS scoring system. • Reduced bacterial loads in the peritoneum of septic mice leading to effective control of infection. • Showed a strong anti-inflammatory effect by decreasing the serum TNF-α levels and neutrophil-to-lymphocyte ratio (NLR) • Reduced tissue damage and inflammation in lung, liver, and kidney organs determined by H&E staining and serum biochemical parameters. Sepsis is a syndrome that occurs following an infection and marked by severe inflammatory responses, and if not treated in time, it can lead to multi-organ failure syndrome and death. This study examines the effects of a novel combination therapy using azithromycin and mesenchymal stem cell-derived extracellular vesicles (EVs) on a cecal ligation and puncture (CLP) model of sepsis. Human Wharton's jelly-mesenchymal stem cells were cultured, characterized, and used to extract EVs. The CLP sepsis model was induced in mice, followed by treatments: saline, AZM, EVs, and combination therapy (A+E). Clinical sepsis scores were recorded 24 h post-treatment. Serum, peritoneal fluid, and organ tissues (kidney, liver, lung) were collected and analyzed for biochemical parameters (AST ALT, and creatinine), inflammatory markers, bacterial load, and histopathological changes. The A+E combined treatment improved the clinical scores of septic mice. The administration of A+E reduced bacterial loads in the peritoneum of septic mice, contributing to effective control of infection. Inflammatory markers of neutrophils-to-lymphocytes ratio (NLR) and TNF-α serum levels were significantly lower in the combinational therapy group, indicating significant anti-inflammatory effect of this combination. Additionally, combination of AZM and EVs alleviated organ damage mainly within liver, kidneys and lungs. Based on histopathological assessments and biochemical parameters, there was diminished tissue damage as well as reduced inflammation, which is correlated with improved functions of these vital organs. The combined use of azithromycin and EVs offers a promising therapeutic approach for sepsis by effectively controlling infection and modulating the inflammatory response. [ABSTRACT FROM AUTHOR]

We compared the ability of one emergent (Sagittaria montevidensis), two floating (Salvinia minima and Lemna gibba), and one heterophyllous species (Myriophyllum aquaticum) to simultaneously remove sulfamethoxazole, sulfadiazine, ciprofloxacin, enrofloxacin, norfloxacin, levofloxacin, oxytetracycline, tetracycline, doxycycline, azithromycin, amoxicillin, and meropenem from wastewater in a mesocosm-scale constructed wetland over 28 days. Antibiotic concentrations in plants and effluent were analyzed using an LC-MS/MS to assess the removal rates and phytoremediation capacities. M. aquaticum did not effectively mitigate contamination due to poor tolerance and survival in effluent conditions. S. minima and L. gibba demonstrated superior efficiency, reducing the antibiotic concentrations to undetectable levels within 14 days, while S. montevidensis achieved this result by day 28. Floating macrophytes emerge as the preferable choice for remediation of antibiotics compared to emergent and heterophyllous species. Antibiotics were detected in plant tissues at concentrations ranging from 0.32 to 29.32 ng g−1 fresh weight, highlighting macrophytes' ability to uptake and accumulate these contaminants. Conversely, non-planted systems exhibited a maximum removal rate of 65%, underscoring the persistence of these molecules in natural environments, even after the entire experimental period. Additionally, macrophytes improved effluent quality regardless of species by reducing total soluble solids and phosphate concentrations and mitigating ecotoxicological effects. This study underscores the potential of using macrophytes in wastewater treatment plants to enhance overall efficiency and prevent environmental contamination by antibiotics, thereby mitigating the harmful impact on biota and antibiotic resistance. Selecting appropriate plant species is crucial for successful phytoremediation in constructed wetlands, and actual implementation is essential to validate their effectiveness and practical applicability. [Display omitted] • Macrophytes exposed to real multi-contaminated WWTP effluent. • Varied phytoremediation capacity observed among morphotypes. • Floating macrophytes outperform emergent and heterophyllous. • Macrophytes enhance WWTP efficiency in antibiotic reduction. • Lab studies need validation under natural conditions for phytoremediation. [ABSTRACT FROM AUTHOR]

[Display omitted] • AZM promotes M2 polarization of LPS-exposed RAW264.7 macrophages. • AZM attenuates LPS-triggered ferroptosis in MLE-12 cells. • AZM inactivates the NF-κB signaling by downregulating Mettl3. Azithromycin (AZM) has been proposed as a potential therapeutic drug in acute pulmonary injury due to its immunomodulatory and anti-inflammatory properties. However, its therapeutic mechanism remains not fully understood. LPS was used to stimulate MLE-12 cells and RAW264.7 macrophages. Analyses of viability and apoptosis were performed by CCK-8 assay and flow cytometry, respectively. Protein analysis was performed by immunoblotting, and mRNA expression was tested by quantitative PCR. The secretion levels of TNF-α and IL-6 were detected by ELISA. MDA, GSH, ROS and Fe2+ contents were analyzed using assay kits. Administration of AZM or depletion of methyltransferase-like 3 (Mettl3) could attenuate LPS-triggered apoptosis, inflammation and ferroptosis in MLE-12 alveolar cells, as well as enhance M2 polarization of LPS-stimulated RAW264.7 macrophages. In LPS-exposed MLE-12 and RAW264.7 cells, AZM reduced Mettl3 protein expression and inactivated the NF-κB signaling through downregulation of Mettl3. Furthermore, Mettl3 restoration abated AZM-mediated anti-apoptosis, anti-inflammation and anti-ferroptosis effects in LPS-exposed MLE-12 cells and reversed AZM-mediated M2 polarization enhancement of LPS-exposed RAW264.7 macrophages. Our study indicates that AZM can promote M2 polarization of LPS-exposed RAW264.7 macrophages and attenuate LPS-triggered injury of MLE-12 alveolar cells by inactivating the Mettl3-mediated NF-κB pathway. [ABSTRACT FROM AUTHOR]

[Display omitted] • The bioavailability of the weakly water-soluble AZI could have been enhanced by the CAPB-STS mixed micelle. • The AZI binding constant values were found maximum of 3.144 at α CAPB 0.1of mixed micelle. • Aqueous solubility of AZI 0.0032 mmol/L were enhanced up to 0.048 mmol/L in the presence of mixed micelles. • At α CAPB 0.1 mixed micelles, the controlled release of AZI in PBS at pH 7.4 was found to be 30.77%. The study highlights the importance of mixed micelles in enhancing the binding and solubilization properties of partially water-soluble medications, using zwitterionic cocoamidopropyl betaine (CAPB) and anionic sodium tetradecyl sulfate surfactants. Surface tension and fluorescence spectroscopy evaluated the critical micelle concentration (CMC) of CAPB-STS mixed micelle. The thermodynamic parameters were assessed using Clint, Rubingh, and Motomura's approach, which showed a synergistic interaction between the CAPB and STS. UV spectroscopy technique was used to evaluate the applicability of mixed micelle to enhance the solubility and binding constant (K b) of antibiotic azithromycin dihydrate (AZI). K b values of AZI were increased from 2.301 to 3.415 and molar solubilization ratio (MSR) values of AZI were increased from 0.228 to 0.801 by decreasing α CAPB from 0.9 to 0.1. The result indicated that zwitterionic CAPB was an electrostatic interaction consisting of both attractive (−CH 2 COO¯ group) and repulsive (−N+ group) interactions with AZI (−NH+ group), causing AZI molecules to reside in the Stern layer. While STS consisted of a negative −SO 4 ¯ head group, it caused increased electrostatic interaction, and AZI penetrated the palisade layer of mixed micelles. At 7.00 mmolL-1 concentration of α CAPB 0.1, the solubility of AZI in water was increased to 2.77 mmol/L from 0.0032 mmol/L. Additionally, after 8 h, the controlled release of AZI in PBS at pH 7.4 was 95.58 % and decreased up to 30.77 % at α CAPB 0.1 mixed micelles. The observation of controlled AZI release from α CAPB 0.9 to 0.1 indicates that AZI molecules were strongly bound to mixed micelles by both hydrophobic and electrostatic interactions. In the end, a mixed micelle of CAPB-STS could serve as a useful drug-solubilizing agent in pharmaceutical applications. [ABSTRACT FROM AUTHOR]

[Display omitted] Cancer treatment demands innovative approaches. Azithromycin (AZM), traditionally an antibiotic, shows promise in inhibiting cancer growth due to its anti-inflammatory and senolytic properties. Beyond its antimicrobial effects, AZM disrupts mitochondrial function in cancer cells, leading to increased reactive oxygen species (ROS) and DNA damage. This disrupts cancer cell survival pathways and induces programmed cell death. AZM has shown efficacy against various cancers, including lung, breast, and ovarian cancers. Nanoparticle (NP) delivery systems are proposed to enhance AZM's therapeutic potential. NPs offer advantages like increased surface area, biocompatibility, and targeted delivery to cancer cells. This review explores strategies for AZM delivery using various nanomaterials, including polymers, carbon-based materials, lipids, and inorganic frameworks. It also discusses the potential of combining AZM with other therapies. [ABSTRACT FROM AUTHOR]

[Display omitted] • Fe 3 O 4 @ionic salt g-C 3 N 4 was synthesized as a new adsorbent. • The adsorbent used in MDSPE of clarithromycin and azithromycin. • The adsorbent characterized by FT-IR, FE-SEM, TEM, BET, XRD, and VSM. • Box-Behnken design and RSM used for the optimization. In this study, Fe 3 O 4 @ionic salt g-C 3 N 4 was synthesized as a new adsorbent for magnetic dispersive solid phase extraction (MDSPE) of two antibiotics (clarithromycin and azithromycin) in biological samples followed by HPLC-UV. The new nanocomposite was characterized by Fourier-transform infrared (FT-IR), field emission-scanning electronic microscope (FE-SEM), transmission electron microscope (TEM), nitrogen adsorption–desorption analysis, X-ray powder diffraction (XRD), and vibrating sample magnetometer (VSM). Box-Behnken design (BBD) and response surface methodology (RSM) were used for the optimization and design of experiments. The method had a suitable linear range (1–300 µg/L), a high coefficient of determination (R2; 0.9988 and 0.9993), and a low detection limit (0.33 and 0.42 µg/L) for clarithromycin and azithromycin, respectively. The applicability of the method was evaluated by estimating the recovery of analytes from urine and blood serum samples. Recovery of more than 90.0 % and RSDs of less than 5.2 % show the acceptable accuracy and precision of the proposed method. [ABSTRACT FROM AUTHOR]

Azithromycin can effectively inhibit bacterial protein synthesis and reduce biofilm formation and quorum sensing, and thus has been preferentially used in the treatment of various infections. However, azithromycin is also among the most highly concentrated antibiotics present in wastewater due to the inappropriate use and treatment. In order to sensitively and rapidly monitor the azithromycin residues, aptamers specific to azithromycin were selected through 12 rounds of screening by using magnetic beads-SELEX (MB-SELEX). The screened aptamers were assessed for their affinity and specificity using fluorescent assay. Apt3 emerged as the optimal candidate aptamer with the dissociation constant (K d) of 235.07 nM. After secondary structure analysis and molecular docking, Apt3 was systematically truncated and subjected to single-base mutations. The optimal aptamer Apt3–27 T was identified, exhibiting the K d value of 215.84 nM and the improved specificity compared to the original aptamer. Then Apt3–27 T was utilized to construct a ratiometric fluorescent aptasensor, which exhibited the linear dynamic range of 25–400 nM and low detection limit of 9.78 nM. More importantly, the ratiometric fluorescence mechanism further improved the specificity of the biosensor, which finally can discriminate azithromycin from structurally similar erythromycin. Evaluation experiments using actual samples spiked with azithromycin showed the recovery ranging from 97.1% to 106% and the relative standard deviation ranging from 4.29% to 8.61%. The screened aptamer and constructed aptasensor offer the advantages of high affinity, high effectiveness and ease of use in actual sample detection, thereby displaying promising applications in the monitoring of azithromycin residues. [Display omitted] • DNA library-immobilized MB-SELEX was used to screen azithromycin-specific aptamers. • Truncating non-binding segments of aptamers was based on structural prediction and rational design. • Specific single-base mutations were based on molecular docking analysis. • The aptamer was used in a ratiometric fluorescent aptasensor for azithromycin. • The aptasensor has been successfully utilized for detection of azithromycin in actual samples. [ABSTRACT FROM AUTHOR]

Background: Anorectal infections with Chlamydia trachomatis are commonly found in women. Although the efficacy of doxycycline and azithromycin is comparable in the treatment of urogenital infection, their efficacies toward anorectal infection remain unclear. We therefore aimed to compare a single dose of azithromycin with a 7-day course of doxycycline for the treatment of anorectal C trachomatis infection in women with concurrent vaginal infection.Methods: We did a multicentre, open-label, randomised, controlled, superiority trial involving four sexually transmitted infection screening centres and three pregnancy termination centres in France. We included sexually active adult women (≥18 years) with a positive C trachomatis vaginal swab who agreed to provide self-collected anorectal swabs for C trachomatis detection. Participants were randomly assigned (1:1), using block sizes of six and eight and stratification by each investigating centre, to orally receive either azithromycin (a single 1-g dose, with or without food) or doxycycline (100 mg in the morning and evening at mealtimes for 7 days [ie, 100 mg of doxycycline twice per day for 7 days]). All laboratory staff who did the bacteriological analyses, but not the participants and the investigators, were masked to the treatment groups. The primary outcome was the microbiological anorectal cure rate defined as a C trachomatis-negative nucleic acid amplification test (NAAT) result in anorectal specimens 6 weeks after treatment initiation among women who had a baseline C trachomatis-positive anorectal NAAT result. The primary analysis was done in the modified intention-to-treat population, with multiple imputation, which included all women who underwent randomisation and had a C trachomatis-positive vaginal and anorectal NAAT result at baseline. Adverse events were reported in all women who underwent randomisation. This study is registered with ClinicalTrials.gov, number NCT03532464.Findings: Between Oct 19, 2018, and April 17, 2020, we randomly assigned a total of 460 participants to either the doxycycline group (n=230) or the azithromycin group (n=230). Four (1%) of 460 participants were excluded because they refused to take doxycycline or were found to be ineligible after randomisation. Among the 456 participants, 357 (78%) had a concurrent C trachomatis-positive anorectal NAAT result at baseline; 184 (52%) of 357 were in the doxycycline group and 173 (48%) were in the azithromycin group (ie, the modified intention-to-treat population). Microbiological anorectal cure occurred in 147 (94%) of 156 participants in the doxycycline group (28 missing values) versus 120 (85%) of 142 in the azithromycin group (31 missing values; adjusted odds ratio with imputation of missing values 0·43 [95% CI 0·21-0·91]; p=0·0274). Reported adverse events possibly related to treatment were notified in 53 (12%) of 456 women: 24 (11%) of 228 in the doxycycline group and 29 (13%) of 228 in the azithromycin group. Gastrointestinal disorders were the most frequently occurring, in 43 (9%) of 456 women: 17 (8%) of 228 in the doxycycline group and 26 (11%) of 228 in the azithromycin group.Interpretation: The microbiological anorectal cure rate was significantly lower among women who received a single dose of azithromycin than among those who received a 1-week course of doxycycline. This finding suggests that doxycycline should be the first-line therapy for C trachomatis infection in women.Funding: French Ministry of Health.Translation: For the French translation of the abstract see Supplementary Materials section. [ABSTRACT FROM AUTHOR]

It is debatable whether erythromycin has similar efficacy to other macrolides in treating community-acquired pneumonia (CAP). The aim of this meta-analysis is to compare the efficacy of erythromycin with clarithromycin and azithromycin. We performed this meta-analysis of randomized controlled trials (RCTs) of adults or adolescents with CAP which compared the efficacy of erythromycin monotherapy to either azithromycin or clarithromycin. We searched PubMed and EMBASE and Cochrane Library databases and three clinical trial registries up to November 02, 2021. We evaluated heterogeneity and used random-effects models to perform risk ratios with 95% confidence intervals. We included four RCTs (total of 472 patients), which compared the clinical efficacy of erythromycin versus clarithromycin. No studies comparing monotherapy of erythromycin versus azithromycin were found. Erythromycin use was associated with significantly lower rates of clinical success (RR, 0.79; 95% CI, 0.64 to 0.98; P-value = 0.033; I2 = 20.27%), clinical cure (RR,0.67; 95% CI, 0.48 to 0.92; P-value = 0.014; I2 = 8.75%), and radiological success (RR, 0.84; 95% CI, 0.71 to 0.996; P-value = 0.045; I2 = 20.12%) than clarithromycin. Erythromycin is less effective than clarithromycin as empiric treatment of CAP in adults and adolescents. Because of this and the higher rate of adverse reactions, erythromycin should not be used in the majority of CAP patients when azithromycin and clarithromycin are available. [ABSTRACT FROM AUTHOR]

Synergistic therapy against the resurgence of bacterial pathogenesis is a modern trend for antibacterial chemotherapy. The phytochemical allicin, found in garlic extract is a commendable antimicrobial agent that can be used in synergistic combination with modern antibiotics. Determination of optimal antibacterial combination for the target species is vital for maximizing efficacy, lowering toxicity, total eradication of the bacterial cells and minimization of the risk of resistance generation. In this present investigation, Hill function-based pharmacodynamics models were employed to elaborate various time-kill kinetics parameters. The bactericidal potency of the synergistic combinations of allicin and individual antibiotic was assessed in comparison to their monotherapy application viz. using sole allicin and sole antibiotics (levofloxacin, ciprofloxacin, oxytetracycline, rifaximin, ornidazole and azithromycin) on actively growing Bacillus subtilis and Escherichia coli bacteria. Here, all the synergistic combinations showed significantly better (t -test p -value < 0.05) killing effect and biofilm reduction potential compared to their respective monotherapy application, where the highest killing effect was observed with rifaximin-allicin combination (kill rate was more than 5.5 h−1). Moreover, the average inhibition potential to protein denaturation by the synergistic combination group was significantly higher (3.4 fold) than the sole antibiotic's group manifests reduction in the dose-related toxicity. The potential of synergism between antibiotics and allicin combination demonstrated greater killing efficiency at significantly lower concentration compared to monotherapy with increased kill rates in all cases. [Display omitted] • Allicin shows synergy with the selected antibiotics. • Reduction of bactericidal concentrations ensures low dose related toxicity. • Synergy combinations increase the Hill coefficient significantly than monotherapy. • Biofilm reduction potential increases significantly with synergistic combinations. • Allicin-rifaximin combination showed maximum bactericidal potential. [ABSTRACT FROM AUTHOR]

• Hydroxychloroquine + azithromycin (HCQ + AZ) did not reduce recovery time in COVID-19 • HCQ + AZ had no effect on the risk of worsening or transfer to the intensive care unit • The use of HCQ + AZ appeared to be associated with lower mortality rates Our study aimed to assess the statistical relationship between the use of chloroquine phosphate or hydroxychloroquine plus azithromycin (CQ/HCQ + AZ) and virological recovery, disease worsening, and death among out- and inpatients with COVID-19 in Burkina Faso. This was a retrospective observational study that compared outcomes in terms of time to recovery, worsening, and death in patients who received CQ/HCQ + AZ and those who did not using a multivariable Cox or Poisson model before and after propensity matching. Of the 863 patients included in the study, about 50% (432/863) were home-based follow-up patients and 50% were inpatients. Of these, 83.3% (746/863) received at least 1 dose of CQ/HCQ + AZ and 13.7% (118/863) did not. There were no significant differences in associated time to recovery for patients receiving any CQ/HCQ + AZ (adjusted HR 1.44; 95% CI 0.76–2.71). Similarly, there was no significant association between CQ/HCQ + AZ use and worsening (adjusted IRR 0.80; 95% CI 0.50–1.50). However, compared with the untreated group, the treated group had a lower risk of death (adjusted HR 0.20; 95% CI 0.10–0.44). The study provided valuable additional information on the use of CQ/HCQ in patients with COVID-19 and did not show any harmful outcomes of CQ/HCQ + AZ treatment. [ABSTRACT FROM AUTHOR]

The epidemiology of infective endocarditis (IE) is under constant change due to the aging society and increases in antimicrobial-resistant pathogens. However, IE remains severe. This study aimed to review the current clinical characteristics of IE and the antimicrobial susceptibility of oral bacteria (OB) isolated from blood cultures to implement appropriate antimicrobial prophylaxis. We retrospectively investigated the clinical features of 180 patients with IE in whom OB and pathogens except OB (eOB) were identified as causative microorganisms via blood cultures. The susceptibility of the OB group to eight antibiotics was examined by broth microdilution. Among causative microorganisms, the isolation rate of staphylococci was slightly higher than that of OB; however, the difference was not significant (36.7% vs. 33.8%, p = 0.3203). The number of patients with underlying cardiac disease was significantly higher in the OB group than in the eOB group (53.7% vs. 34.1%, p = 0.0113). Only one ampicillin-resistant OB was detected (2.0%). OBs were significantly less susceptible to clarithromycin and azithromycin than to ampicillin (98.0% vs. 66.7% and 98.0% vs. 60.0%, p = 0.0003 and p = 0.0003, respectively). Moreover, OBs were significantly less susceptible to clarithromycin and azithromycin than to clindamycin (66.7% vs. 88.2% and 60.0% vs. 88.2%, p = 0.0301 and p = 0.0217, respectively). OBs were susceptible to ampicillin. However, the susceptibility of OBs to clarithromycin and azithromycin was significantly lower than that to ampicillin and clindamycin. These results are important and should help decisions regarding guide antimicrobial prophylaxis. [ABSTRACT FROM AUTHOR]

[Display omitted] • The sensitive determination of Lactobacillus Acidophilus in presence of cefixime, ofloxacin and azithromycin. • Two PLS models were developed and optimized for quantitative determination. • Traditional HPLC-PDA method was developed for simultaneous determination of cefixime and ofloxacin. • Noble HPLC-ELSD method was developed for determination of Azithromycin. • FTIR-PLS METHOD show pose less or almost no-challenges over traditional HPLC for determination of Lactobacillus Acidophilus. Fourier-transform infrared spectroscopy (FTIR) combined with multicomponent multivariate quantitative models plays a crucial role and provides a successful alternative in analyzing achromic, complex, and molecular structures with diverse properties. In the present research work, we had discussed the quantitative determination of Azithromycin, Cefixime, Ofloxacin, and Lactobacillus acidophilus using a simple, economical, and accurate FT-IR spectroscopy method combined with partial least square (PLS) analysis. The full spectrum FTIR-based PLS models were developed for randomly distributed concentration sets and cross-validated for untested concentration determination. For each analyte, the concentrations were chosen over a linearity range of 1–5 % w/w , which encompasses the concentration ratios in the market samples. The root mean PRESS value and % error for validation concentration sets was observed at 0.12, for the PLS model for full spectrum scan-randomly distributed concentration sets. Chromatographic methods for the determination of AZT, Cefixime, Ofloxacin, and Lactobacillus acidophilus was also developed. The chromatographic retention of AZT was achieved on Phenomenex Luna 5 µm C18 column with solvents A: 25 % (20 mM Ammonium Acetate (pH-5.7)) & B: 75 % (Acetonitrile) as mobile phase in isocratic mode and was developed and validated using HPLC-ELSD detection. Whereas quantitative determination of Cefixime and Ofloxacin was determined simultaneously on YMC-Triart C18 column and the gradient consisted of solvent-A (20 mM Disodium hydrogen phosphate (pH-5.5), solvent-B (Acetonitrile) & solvent-C (Methanol) using HPLC-DAD detection. The FTIR-PLS method yielded significant benefits over traditional HPLC methods, including superior accuracy and precision, ease of experimentation, and quantitative determination of "difficult to analyse" probiotics in combination with antibiotics. [ABSTRACT FROM AUTHOR]

New methods for the analysis of azithromycin (AZM) have been devised, employing direct fluorescence and spectrophotometric techniques. This research focused on the development and validation of these methods, especially based on the formation of an ion-pair complex with fluorescein isothiocyanate (FITC). The resulting complex enhanced the fluorescence intensity at a wavelength of 520 nm and the absorbance at 480 nm. The impact of different solvent compositions was investigated, with methanol and a 1:1 mixture of methanol and Milli-Q proving to be the most sensitive. The optimal FITC concentration was determined as 50 µg/ml, and the molar ratio of the AZM-FITC ion-pair complex was determined to be 1:1. Notably, an instantaneous increase in fluorescence intensity was observed, eliminating the need for incubation. The developed methods were validated for sensitivity, accuracy, and precision, with the fluorescence-based method demonstrating superior sensitivity and precision compared to the spectrophotometric method. Under optimum conditions, the fluorescence-based method achieved a linear range of 0–31.25 µg/ml with a limit of detection (LOD) of 0.41 µg/ml and a limit of quantification (LOQ) of 1.23 µg/ml., In contrast, the spectrophotometric method had an LOD of 0.82 µg/ml and an LOQ of 2.49 µg/ml. Additionally, the fluorescence-based method exhibited a narrower recovery range in artificial urine samples, suggesting higher precision in complex matrices. Overall, these methods offer rapid and sensitive AZM analysis with potential applications in diverse matrices such as biological samples post-extraction. • Residual trace azithromycin elevates antimicrobial resistance. • Direct optical detection of azithromycin in urine. • Azithromycin-fluorescein isothiocyanate ion pair complex. • Fluorescence-based detection of azithromycin using fluorescein isothiocyanate. • Spectrophotometric detection of azithromycin using fluorescein isothiocyanate. [ABSTRACT FROM AUTHOR]

Uptake and elimination kinetics, bioconcentration factors (BCFs), and metabolic transformation of 20 different pharmaceutically active compounds (PhACs), covering a wide range of therapeutic categories and physico-chemical properties, were studied using zebrafish (Danio rerio). The fish were exposed to the mixture of the selected PhACs at environmentally relevant concentrations similar to 10 µg L−1. The experiments were performed in semi-static conditions and comprised a 7-day uptake period followed by a 7-day depuration period. Most of the PhACs reached a concentration plateau within the 7-day uptake-phase which was followed by an efficient depuration, with the observed uptake (k u) and depuration rate constants (k d,) ranging between 0.002 and 3.752 L kg−1 h−1, and 0.010 to 0.217 h−1, respectively. The investigated PhACs showed low to moderate BCFs. The highest BCFs of 47.8, 28.6 and 47.6 L kg−1 were determined for sertraline, diazepam and desloratadine, respectively. A high contribution of metabolic products to the total internal concentration was observed for some PhACs such as codeine (69%), sulfamethoxazole (51%) and verapamil (87%), which has to be taken into account when assessing the bioconcentration potential. Moreover, most of the metabolites exhibited significantly longer half-lives in zebrafish than their parent compounds and affected the overall depuration kinetics. [Display omitted] • Bioconcentration of a complex pharmaceutical mixture in zebrafish was assessed. • The most bioaccumulative compounds were sertraline, diazepam and desloratadine. • Depuration was very fast, but azithromycin and desloratadine had long half-lives. • Bioconcentration factors of parent drugs were affected by biotransformation. • Most of the metabolites had longer half-lives than their parent compounds. [ABSTRACT FROM AUTHOR]

This review offers a comprehensive overview of the occurrence, fate, and ecological risk associated with six major categories of antibiotics found in influent, effluent, and sludge from urban wastewater treatment plants (WWTPs) in China. Further exploration includes examining the correlation between antibiotic residual rates in the effluents and process parameters of urban WWTPs across the country. Lastly, a nationwide and urban cluster-specific evaluation of the ecological risk posed by antibiotics in WWTPs is conducted. The findings reveal that the average concentrations of antibiotics in influent, effluent, and sludge from urban WWTPs in China are 786.2 ng/L, 311.2 ng/L, and 186.8 μg/kg, respectively. Among the detected antibiotics, 42% exhibit moderate to high ecological risk in the effluent, with ciprofloxacin, sulfamethoxazole, erythromycin, azithromycin, and tetracycline posing moderate to high ecological risks in sludge. The current biological treatment processes in WWTPs demonstrate inefficacy in removing antibiotics. Hence, there is a pressing need to develop and integrate innovative technologies, such as advanced oxidation processes. This review aims to offer a more comprehensive understanding and identify priority antibiotics for control to effectively manage antibiotic pollution within WWTPs at both national and regional levels. [Display omitted] • Investigation of antibiotic occurrence in WWTPs across China. • Compilation of Kd of antibiotics in sludge and their PNEC in effluent and sludge. • Identification of medium- and high-risk antibiotic types in effluent and sludge. • HRT, NsB and seasonal variations significantly affect antibiotic fate in WWTPs. • Comparison of antibiotic occurrence and risk in WWTPs across different regions. [ABSTRACT FROM AUTHOR]

The erm (T) gene encodes the 23 s rRNA methyltransferase and confers erythromycin resistance in Gram-positive bacteria, while has rarely been identified in Gram-negative bacteria. In this study, we identified a small IncQ1 plasmid of 6135 bp harboring the erm (T) gene in a clinical K. pneumoniae strain and confirmed the role of the erm (T) gene in mediating azithromycin resistance. This plasmid was found to be generated by incorporating the erm (T) gene from mobile elements into an IncQ1 plasmid. Our data indicated the spread of the erm (T) gene from Gram-positive bacteria to Gram-negative bacteria and the clonal spread of the ST11-KL47 type K. pneumoniae strains carrying this plasmid. Generation of this kind of multi-host plasmid will promote the dissemination of the erm (T) gene among Gram-negative bacteria and result in failures of azithromycin in treating bacterial infections. [ABSTRACT FROM AUTHOR]

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

Canine babesiosis has been increasingly diagnosed in various regions of Germany such as north-eastern Germany in recent years. A dog with several relapses of Babesia canis infection after treatment with imidocarb is described. A 9-year-old male Magyar Viszla with B. canis infection was referred after two treatments with imidocarb (dosage 2.1 mg/kg SC) because of lethargy, fever and pancytopenia (additional treatments with prednisolone and doxycycline). Merozoites were detected in the blood smear and imidocarb treatment was repeated. Clinical signs, pancytopenia and a positive B. canis PCR occurred after the 3rd (6 mg/kg SC), 4th (7.7 mg/kg SC) and 5th (7.5 mg/kg SC and doxycycline for 4 weeks in addition) imidocarb injection and thorough tick prevention with isoxazoline and permethrin products. 12 days after the 5th injection, the PCR was negative for the first time. The dog was again presented with fever 35 days after the 5th injection. The B. canis PCR was positive and laboratory examination revealed pancytopenia. Treatment with atovaquone/azithromycin for 18 days was performed and no further relapse occurred for 32 weeks. In the case of suspected imidocarb resistance in B. canis infection, treatment with atovaquone/azithromycin can be an alternative. [ABSTRACT FROM AUTHOR]