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Shigella spp. are common enteric pathogens in captive non-human primates. Treatment of symptomatic infections involves supportive care and antibiotic therapy, typically with an empirical choice of antibiotic.Twenty-four clinically ill, Shigella PCR-positive animals were randomly assigned to one of four treatment groups: single-dose ceftiofur crystalline free acid (CCFA), single-dose azithromycin gavage, a 5-day tapering azithromycin dose, or 7-day course of enrofloxacin. We hypothesized that all antimicrobial therapies would have similar efficacy.Animals in all groups cleared Shigella, based on fecal PCR, and had resolution of clinical signs 2 weeks after treatment. Eight out of nine clinically ill and PCR-positive animals tested negative by fecal culture.Single-dose CCFA, single-dose azithromycin, and a 5-day tapering course of azithromycin all performed as well as a 7-day course of enrofloxacin in eliminating Shigella infection. Fecal PCR may be a better diagnostic than culture for Shigella.

Chloroquine and azithromycin were developed in combination for the preventive treatment of malaria in pregnancy, and more recently were proposed as coronavirus disease 2019 (COVID-19) treatment options. Billions of doses of chloroquine have been administered worldwide over the past 70 years but concerns regarding cardiotoxicity, notably the risk of torsades de pointes (TdP), remain. This investigation aimed to characterize the pharmacokinetics and electrocardiographic effects of chloroquine and azithromycin observed in a large previously conducted healthy volunteer study. Healthy adult volunteers (n = 119) were randomized into 5 arms: placebo, chloroquine alone (600 mg base), or chloroquine with either 500 mg, 1,000 mg, or 1,500 mg of azithromycin all given daily for 3 days. Chloroquine and azithromycin levels, measured using liquid-chromatography tandem mass spectrometry, and electrocardiograph intervals were recorded at frequent intervals. Time-matched changes in the PR, QRS, and heart rate-corrected JT, and QT intervals were calculated and the relationship with plasma concentrations was evaluated using linear and nonlinear mixed-effects modeling. Chloroquine and azithromycin pharmacokinetics were described satisfactorily by two- and three-compartment distribution models, respectively. No drug–drug interaction between chloroquine and azithromycin was observed. Chloroquine resulted in concentration-dependent prolongation of the PR, QRS, JTc and QTc intervals with a minimal additional effect of azithromycin. QRS widening contributed ~ 28% of the observed QT prolongation. Chloroquine causes significant concentration-dependent delays in both ventricular depolarization and repolarization. Co-administration of azithromycin did not significantly increase these effects. The arrhythmogenic risk of TdP associated with chloroquine may have been substantially overestimated in studies which did not separate electrocardiograph QRS and JT prolongation.

The study evaluated the pharmacokinetic features of azithromycin (AZM) in 15 freshwater crocodiles (Crocodylus siamensis) in Thailand. The crocodiles were administered a single intramuscular (i.m.) injection of AZM at three different dosages of 2.5, 5, and 10 mg/kg body weight (b.w.). Blood samples were collected at pre-assigned times up to 168 h. The plasma concentrations of AZM were measured using a validated liquid chromatography-tandem mass spectrometry method. The plasma concentration of AZM were quantifiable for up to 168 h after i.m. administration at the three different dosages. A non-compartmental model was used to fit the plasma concentration of AZM versus the time curve for each crocodile. The elimination half-life values of AZM were 33.70, 38.11, and 34.80 h following i.m. injection after dosages of 2.5, 5, and 10 mg/kg b.w., respectively. There were no significant differences among groups. The results indicated that the overall rate of elimination of AZM in freshwater crocodiles was relatively slow. The maximum concentration and area under the curve from zero to the last values of AZM increased in a dose-dependent fashion. The average binding percentage of AZM to plasma protein was 48.66%. Based on the pharmacokinetic data, the susceptibility break-point and the surrogate PK-PD index (T MIC), the intramuscular administration of AZM at a dose of 10 mg/kg b.w. might be appropriate for the treatment of susceptible bacterial infections (MIC 4 μg/ml) in freshwater crocodiles.

Background and objective Low-dose long-term azithromycin is recommended in clinical practice guidelines for obstructive airway diseases (OADs), however, an optimal therapeutic regimen is not yet established. This study aimed to understand the patterns of azithromycin use in OADs, characterise the patients who received it, and evaluate its safety and efficacy using real-world data. METHODS: We audited 91 patients who had received azithromycin for at least 4 weeks for the management of asthma, chronic obstructive pulmonary disease (COPD) or non-cystic fibrosis bronchiectasis. RESULTS: The mean age was 65±18 years, 60% were female, and 48% were ex-smokers. The majority had asthma (75%) either alone (50%) or in combination with COPD (12%) or bronchiectasis (13%). Most (64%) reported cough or sputum at baseline. The most common treatment regimen was azithromycin 250mg daily (73%) for more than 1 year (57%), with only seven adverse events. There was a significant reduction in the proportions of patients requiring emergency department visits (48% versus 32%; p

Cesarean scar defect (CSD) is a long-term outcome of cesarean section (CS) and associated with numerous gynecological and obstetric problems. Previous studies indicate that infection may be a risk factor for CSD. Adjunctive azithromycin was shown to reduce the risk of postoperative infection in patients undergoing non-elective primary cesarean delivery in labor or after the rupture of membranes compared with standard antibiotic prophylaxis. This study investigated the protective effect of adjunctive azithromycin in combination with single-dose cephalosporin against CSD in women undergoing non-elective cesarean delivery.A randomized, double-blind, controlled clinical trial was conducted in a University hospital in Shanghai, China. A total of 242 women who underwent their first non-elective CS were randomly assigned to receive 1500 mg cefuroxime sodium plus 500 mg intravenous azithromycin (n = 121; experimental group) or 1500 mg cefuroxime sodium plus a placebo (n = 121; placebo group). The primary outcome was CSD prevalence, as determined by transvaginal ultrasound and saline infusion sonohysterography within 6 months of delivery. Secondary outcomes were changes in infectious indicators (eg hypersensitive C-reactive protein and procalcitonin), postoperative morbidity, and use of postoperative antibiotics. We also examined the operative procedure, pathogenic microorganism cultures, and fetal outcomes. Outcomes were compared between groups with the chi-squared test, Fisher's exact test, or Student's t test.Between May 2018 and May 2021, 121 women were randomized to each arm. Because the sonographic follow up was disrupted by the coronavirus disease 2019 pandemic and strict management policies, we merged the follow-up time points (6 weeks and 6 months) into a single time period (6 weeks to 6 months); 104 and 108 women in the experimental and placebo groups, respectively, completed the first sonographic follow up. CSD was diagnosed by sonography in 34/104 (32.7%) and 50/108 (46.3%) patients in the experimental and placebo groups, respectively (relative risk 0.71, 95% confidence interval 0.50-0.99; p = 0.043). Characteristics of CSD and short-term infection outcomes did not differ between groups.A single dose of intravenous 500 mg azithromycin adjunctive to single-dose cefuroxime prophylaxis significantly reduced the incidence of CSD in women undergoing non-elective CS.

Azithromycin is a common first-line antibiotic for respiratory infection; however, there is conflicting evidence regarding risk of cardiovascular death. We assessed cardiovascular and noncardiovascular mortality associated with azithromycin versus amoxicillin-clavulanate among US Veterans treated for nonear-nose-throat respiratory infection ("respiratory") or ear-nose-throat infection indication.Electronic health record data from the US Veterans Health Administration database were used to identify Veterans (30-74 years) with outpatient dispensings of oral azithromycin versus amoxicillin-clavulanate for respiratory or ear-nose-throat infection (January 01, 2000-December 31, 2014). Outcomes assessed were risk of cardiovascular death and noncardiovascular death within 1-5 and 6-10 days postdispensing. Inverse probability of treatment-weighted proportional hazards models and binomial regression models were used to estimate hazard ratios (HRs) and compute risk differences (RD) per million courses of therapy. Cardiac death (subset of cardiovascular death) was assessed in sensitivity analyses.There were 629 345 azithromycin and 168 429 amoxicillin-clavulanate dispensings for respiratory indications, 143 783 azithromycin, and 203 142 amoxicillin-clavulanate dispensings for ear-nose-throat indications. For respiratory indications, azithromycin was not associated with a significantly different risk of cardiovascular death versus amoxicillin-clavulanate within 1-5 days postdispensing (HR [95% confidence interval (CI)]: 1.12 [0.63, 2.00]; RD [95% CI]: 11 [-43, 64] deaths/million courses of therapy). No elevated risk for azithromycin was found for ear-nose-throat indications. Pooled results for both indications via meta-analysis showed no association between antibiotics and cardiovascular mortality. There was no significant difference in risk of noncardiovascular or cardiac death between antibiotics postdispensing.Azithromycin was not associated with elevated risk of cardiovascular or noncardiovascular death versus amoxicillin-clavulanate among US Veterans.

To describe the use of hydroxychloroquine (HCQ), azithromycin (AZI) and low-molecular-weight-heparins (LMWH) by sex among elderly residents in nursing homes (NHs) of Tuscany region (Italy) during the first pandemic peak.A population-based drug utilization study was performed linking the Tuscany Administrative Databases (TAD) to the regional COVID-19 registry. Among elderly patients (≥ 65 years old) registered in TAD on 1st December 2019, new users of HCQ, AZI and LMWH that started the treatment during NHs stay (i.e., no dispensing of the same drug during the previous 6 months) were respectively identified in each month of observation period (December 2019-May 2020). The percentage of subjects diagnosed with COVID-19 (COVID-19+) on, or before, the date of first dispensing of the drug of interest was described. Results were stratified by sex (male = M; female = F).New users of HCQ, AZI and LMWH were 62, 300, and 1215, respectively. About 95% of HCQ new users received the drug in April (M = 20; F = 40) of which 11 of men (55%) and 25 of women (62%) were COVID-19+; AZI new users in April (M = 32; F = 83) were two-fold compared to February, of which 10 of men (31%) and 30 of women (36%) were COVID-19+; LMWH new users showed a peak in April (M = 74; F = 142), when 31% of men and 34% of women were COVID-19 + .New users showed a peak during the first pandemic wave and females were over two-fold compared to men. HCQ was often prescribed in absence of COVID-19 diagnosis. During future global emergencies drug prescriptions should better be monitored in frail populations, especially in case of drugs with uncertain efficacy and safety.

This study aimed to characterize adverse drug reactions (ADRs) to hydroxychloroquine in the setting of Covid-19, occurring in Italy in the period March-May 2020. The analysis of the combination therapy with azithromycin or/and lopinavir/ritonavir as well as a comparison with ADRs reported throughout 2019 was performed. ADRs collected by the Italian National Network of Pharmacovigilance were analysed for their incidence, seriousness, outcome, co-administered drugs, MedDRA classification. 306 reports were gathered for the quarter of 2020: 54 % non-serious and 46 % serious, and half of the latter required either the hospitalisation or its prolongation. However most of them were either completely recovered (26 %) or in the process of recovery (45 %), except for 9 fatal cases. Throughout 2019, 38 reports were collected, 53 % non-serious and 47 % serious, but no death had been reported. Diarrhea, prolonged QT interval and hypertransaminasemia were the most frequently ADRs reported in 2020, significantly higher than 2019 and specific for COVID-19 subjects treated with hydroxychloroquine. The logistic regression analyses demonstrated that the likelihood of serious ADR, QT prolongation and diarrhea significantly increased with hydroxychloroquine dosage. Co-administration of lopinavir/ritonavir and hydroxychloroquine showed a positive correlation with diarrhea and hypertransaminasemia and a negative relationship with the ADR seriousness. The combination therapy with azithromycin was another independent predictor of a serious ADR. Off-label use of hydroxychloroquine for COVID-19, alone or in combination regimens, was associated with increased incidence and/or seriousness of specific ADRs in patients with additional risk factors caused by the infection. This article is protected by copyright. All rights reserved.

Azithromycin (AZI) is increasingly used for childhood asthma despite limited and inconsistent data. We aimed to evaluate the efficacy and safety of AZI in childhood asthma.We searched seven databases to include randomized controlled trials (RCTs) of AZI in the treatment of childhood asthma. Four reviewers independently screened the records. Risk of Bias 2 was used to assess the quality of RCTs. Risk ratios with 95% confidence interval (CI) from dichotomous outcomes, and mean difference (MD) with 95% CI from continuous outcomes were pooled.We included 19 eligible reports from 17 studies. The prevalence of exacerbations in AZI + budesonide (BUD) + βAZI may be beneficial in improving some clinical symptoms and lung functions in older asthma children (over 6 years old) with persistent asthma. But it still requires further research.

Background Typhoid and paratyphoid (enteric fever) are febrile bacterial illnesses common in many low‐ and middle‐income countries. The World Health Organization (WHO) currently recommends treatment with azithromycin, ciprofloxacin, or ceftriaxone due to widespread resistance to older, first‐line antimicrobials. Resistance patterns vary in different locations and are changing over time. Fluoroquinolone resistance in South Asia often precludes the use of ciprofloxacin. Extensively drug‐resistant strains of enteric fever have emerged in Pakistan. In some areas of the world, susceptibility to old first‐line antimicrobials, such as chloramphenicol, has re‐appeared. A Cochrane Review of the use of fluoroquinolones and azithromycin in the treatment of enteric fever has previously been undertaken, but the use of cephalosporins has not been systematically investigated and the optimal choice of drug and duration of treatment are uncertain. Objectives To evaluate the effectiveness of cephalosporins for treating enteric fever in children and adults compared to other antimicrobials. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL, MEDLINE, Embase, LILACS, the WHO ICTRP and ClinicalTrials.gov up to 24 November 2021. We also searched reference lists of included trials, contacted researchers working in the field, and contacted relevant organizations. Selection criteria We included randomized controlled trials (RCTs) in adults and children with enteric fever that compared a cephalosporin to another antimicrobial, a different cephalosporin, or a different treatment duration of the intervention cephalosporin. Enteric fever was diagnosed on the basis of blood culture, bone marrow culture, or molecular tests. Data collection and analysis We used standard Cochrane methods. Our primary outcomes were clinical failure, microbiological failure and relapse. Our secondary outcomes were time to defervescence, duration of hospital admission, convalescent faecal carriage, and adverse effects. We used the GRADE approach to assess certainty of evidence for each outcome. Main results We included 27 RCTs with 2231 total participants published between 1986 and 2016 across Africa, Asia, Europe, the Middle East and the Caribbean, with comparisons between cephalosporins and other antimicrobials used for the treatment of enteric fever in children and adults. The main comparisons are between antimicrobials in most common clinical use, namely cephalosporins compared to a fluoroquinolone and cephalosporins compared to azithromycin. Cephalosporin (cefixime) versus fluoroquinolones Clinical failure, microbiological failure and relapse may be increased in patients treated with cefixime compared to fluoroquinolones in three small trials published over 14 years ago: clinical failure (risk ratio (RR) 13.39, 95% confidence interval (CI) 3.24 to 55.39; 2 trials, 240 participants; low‐certainty evidence); microbiological failure (RR 4.07, 95% CI 0.46 to 36.41; 2 trials, 240 participants; low‐certainty evidence); relapse (RR 4.45, 95% CI 1.11 to 17.84; 2 trials, 220 participants; low‐certainty evidence). Time to defervescence in participants treated with cefixime may be longer compared to participants treated with fluoroquinolones (mean difference (MD) 1.74 days, 95% CI 0.50 to 2.98, 3 trials, 425 participants; low‐certainty evidence). Cephalosporin (ceftriaxone) versus azithromycin Ceftriaxone may result in a decrease in clinical failure compared to azithromycin, and it is unclear whether ceftriaxone has an effect on microbiological failure compared to azithromycin in two small trials published over 18 years ago and in one more recent trial, all conducted in participants under 18 years of age: clinical failure (RR 0.42, 95% CI 0.11 to 1.57; 3 trials, 196 participants; low‐certainty evidence); microbiological failure (RR 1.95, 95% CI 0.36 to 10.64, 3 trials, 196 participants; very low‐certainty evidence). It is unclear whether ceftriaxone increases or decreases relapse compared to azithromycin (RR 10.05, 95% CI 1.93 to 52.38; 3 trials, 185 participants; very low‐certainty evidence). Time to defervescence in participants treated with ceftriaxone may be shorter compared to participants treated with azithromycin (mean difference of −0.52 days, 95% CI −0.91 to −0.12; 3 trials, 196 participants; low‐certainty evidence). Cephalosporin (ceftriaxone) versus fluoroquinolones It is unclear whether ceftriaxone has an effect on clinical failure, microbiological failure, relapse, and time to defervescence compared to fluoroquinolones in three trials published over 28 years ago and two more recent trials: clinical failure (RR 3.77, 95% CI 0.72 to 19.81; 4 trials, 359 participants; very low‐certainty evidence); microbiological failure (RR 1.65, 95% CI 0.40 to 6.83; 3 trials, 316 participants; very low‐certainty evidence); relapse (RR 0.95, 95% CI 0.31 to 2.92; 3 trials, 297 participants; very low‐certainty evidence) and time to defervescence (MD 2.73 days, 95% CI −0.37 to 5.84; 3 trials, 285 participants; very low‐certainty evidence). It is unclear whether ceftriaxone decreases convalescent faecal carriage compared to the fluoroquinolone gatifloxacin (RR 0.18, 95% CI 0.01 to 3.72; 1 trial, 73 participants; very low‐certainty evidence) and length of hospital stay may be longer in participants treated with ceftriaxone compared to participants treated with the fluoroquinolone ofloxacin (mean of 12 days (range 7 to 23 days) in the ceftriaxone group compared to a mean of 9 days (range 6 to 13 days) in the ofloxacin group; 1 trial, 47 participants; low‐certainty evidence). Authors' conclusions Based on very low‐ to low‐certainty evidence, ceftriaxone is an effective treatment for adults and children with enteric fever, with few adverse effects. Trials suggest that there may be no difference in the performance of ceftriaxone compared with azithromycin, fluoroquinolones, or chloramphenicol. Cefixime can also be used for treatment of enteric fever but may not perform as well as fluoroquinolones. We are unable to draw firm general conclusions on comparative contemporary effectiveness given that most trials were small and conducted over 20 years previously. Clinicians need to take into account current, local resistance patterns in addition to route of administration when choosing an antimicrobial.

Due to current advances and growing experience in the management of coronavirus Disease 2019 (COVID‐19), the outcome of COVID‐19 patients with severe/critical illness would be expected to be better in the second wave compared with the first wave. As our hospitalization criteria changed in the second wave, we aimed to investigate whether a favorable outcome occurred in hospitalized COVID‐19 patients with only severe/critical illness. Among 642 laboratory‐confirmed hospitalized COVID‐19 patients in the first wave and 1121 in the second wave, those who met World Health Organization (WHO) definitions for severe or critical illness on admission or during follow‐up were surveyed. Data on demographics, comorbidities, C‐reactive protein (CRP) levels on admission, and outcomes were obtained from an electronic hospital database. Univariate analysis was performed to compare the characteristics of patients in the first and second waves. There were 228 (35.5%) patients with severe/critical illness in the first wave and 681 (60.7%) in the second wave. Both groups were similar in terms of age, gender, and comorbidities, other than chronic kidney disease. Median serum CRP levels were significantly higher in patients in the second wave compared with those in the first wave [109 mg/L (interquartile range [IQR]: 65–157) vs. 87 mg/L (IQR: 39–140); p, Highlights Even though a lower mortality rate in the second wave has been reported in previous studies, including all hospitalized COVID‐19 patients, we found similar AQ4demographics and outcomes among hospitalized COVID‐19 patients with severe/critical illness in the first and second wave.

A sensitive, specific and rapid liquid chromatographic-tandem mass spectrometric (LC-MS/MS) method was developed and validated to quantify azithromycin concentrations in human plasma. Azithromycin (AZI) is the most common outpatient prescribed antibiotic in the US and clinical studies have demonstrated the efficacy and safety of AZI in many bacterial infections. To support a clinical study, we developed a high-throughput LC-MS/MS method to process up to 250 samples per day to quantify AZI in human plasma. Samples were prepared by solid-phase extraction. Separation was achieved with an ACE C

Drug‐induced liver injury (DILI) should be considered in all patients with recent elevation of liver tests without obvious etiology and normal hepatobiliary imaging. There is currently no biomarker that is helpful in diagnosis which relies on clinical and laboratory findings. Diagnosis is dependent on temporal relationship with a recently started drug or herbal and dietary supplement and elevated liver tests with exclusion of competing etiologies. The implicated agent should be discontinued and the patient should be observed closely. This is particularly important in patients with jaundice who have approximately 10% risk of liver related mortality and/or need for liver transplantation. There is no specific therapy for DILI which is only symptomatic such as for itching. Patients with jaundice and coagulopathy usually require hospitalization.

Only a handful of US Food and Drug Administration (FDA) Emergency Use Authorizations exist for drug and biologic therapeutics that treat severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2) infection. Potential therapeutics include repurposed drugs, some with cardiac liabilities. We report on a chronic preclinical drug screening platform, a cardiac microphysiological system (MPS), to assess cardiotoxicity associated with repurposed hydroxychloroquine (HCQ) and azithromycin (AZM) polytherapy in a mock phase I safety clinical trial. The MPS contained human heart muscle derived from induced pluripotent stem cells. The effect of drug response was measured using outputs that correlate with clinical measurements, such as QT interval (action potential duration) and drug‐biomarker pairing. Chronic exposure (10 days) of heart muscle to HCQ alone elicited early afterdepolarizations and increased QT interval past 5 days. AZM alone elicited an increase in QT interval from day 7 onward, and arrhythmias were observed at days 8 and 10. Monotherapy results mimicked clinical trial outcomes. Upon chronic exposure to HCQ and AZM polytherapy, we observed an increase in QT interval on days 4–8. Interestingly, a decrease in arrhythmias and instabilities was observed in polytherapy relative to monotherapy, in concordance with published clinical trials. Biomarkers, most of them measurable in patients’ serum, were identified for negative effects of monotherapy or polytherapy on tissue contractile function, morphology, and antioxidant protection. The cardiac MPS correctly predicted clinical arrhythmias associated with QT prolongation and rhythm instabilities. This high content system can help clinicians design their trials, rapidly project cardiac outcomes, and define new monitoring biomarkers to accelerate access of patients to safe coronavirus disease 2019 (COVID‐19) therapeutics.

The presence of azithromycin in the human plasma of pediatric patients was determined with a UHPLC-MS/MS assay. Sample preparation was done by protein precipitation, and the separation was achieved on a C18 column by the gradient mixture of the mobile phase A (0.1% acetic acid and 3 mM ammonium acetate in water) and the mobile phase B (0.1% acetic acid and 3 mM ammonium acetate in the solution of acetonitrile, methanol, and water, 47.5/47.5/5, V/V/V). The multiple reaction monitoring mode was adopted to monitor the precursor-to-product ion transitions of m/z 749.6 → m/z 591.5 for azithromycin and m/z 753.6 → m/z 595.5 for azithromycin

Objective To assess economic and social drivers of dispensing antibiotics without prescription by community pharmacies in Nepal. Method A survey was conducted among 111 pharmacy owners and managers in five districts. Information on demographic and economic characteristics of the pharmacies (e.g. revenue and profits from antibiotics) and their inclination to sell antibiotics without a physician's prescription under various scenarios (e.g. diarrhoea in a child) was collected. Univariate analysis was conducted to assess the demographic and economic characteristics. Bivariate analysis was conducted to examine the relationship between dispensing antibiotics without prescription and economic and social factors. Results Azithromycin and amoxicillin were the most commonly dispensed antibiotics. The proportions of pharmacies reporting that they would 'most likely' or 'likely' dispense antibiotics without prescription to adult patients ranged from 36.9% (sore throat) to 67.6% (cough). The proportions for paediatric patients ranged from 62.2% (sore throat) to 80.2% (cough or diarrhoea). There was no consistent relationship between the likelihood of dispensing antibiotics and revenues, profits or the number of patients. Instead, dispensing behaviour was influenced by the pressure from the patient; the respondents were more likely to dispense antibiotics when the patient specifically asked for 'an antibiotic' rather than for 'a medicine', and 68.5% respondents ranked 'customer satisfaction' as the most important factor motivating their work. Conclusions In Nepal, inappropriate sale of antibiotics by community pharmacists is high, particularly for paediatric patients. Additional research is needed to establish key drivers of this behaviour and to help design effective approaches to reducing AMR.

Azithromycin (AZM) has a therapeutic effect on diabetes, but there is no report on whether AZM has a therapeutic effect on diabetic nephropathy (DN) and its specific mechanism. Cell survival was detected by CCK-8. The expression of the inflammatory factors TNF-α, IL-1β, and IL-6 was determined by ELISA. The expression of inflammatory proteins MCP-1, NLPR3, and ASC was detected by western blot. The expression of MDA, LDH, and SOD was detected by the appropriate kit. Apoptosis was detected by flow cytometry and apoptosis-related proteins Bcl-2, Bax, Caspase-3, 6, 9, and Cleaved caspase-3, 6, 9 were detected by western blot. In addition, the expression of STAT1 was detected by western blot. AZM can increase the activity of high glucose-induced podocytes (p < .05). After high glucose induction, the expression of TNF-α, IL-1β, and IL-6 was increased and the expression of MCP-1, NLPR3, and ASC proteins was also increased (p < .001). When AZM was added, the expression of all the above-mentioned proteins was decreased (p < .001). In addition, MDA, LDH, and SOD were increased after high glucose induction, while decreased after AZM treatment (p < .001). AZM can inhibit apoptosis and the expression of Bax and Cleaved caspase-3, 6, 9, and promote the expression of Bcl-2 (p < .001). Furthermore, the expression of STAT1 was increased after high glucose induction, while the expression of STAT1 was decreased after AZM action (p < .01). By adding a STAT1 agonist IFN-γ, the effects of AZM on inflammation, oxidative stress, and apoptosis of high glucose-induced podocytes were inhibited (p < .05). AZM inhibited inflammation, oxidative stress, and apoptosis of high glucose-induced podocytes by inhibiting STAT1 pathway.

Soil characteristics in certain regions may favor the growth of Mycobacterium avium complex (MAC), leading to regional differences in epidemiology. Laboratory abnormalities classically have reflected the disseminated nature of the disease with profound anemia out of proportion to neutropenia or thrombocytopenia, and elevated transaminases and alkaline phosphatase. Either because of improved diagnosis or concurrent antiretroviral therapy, these laboratory abnormalities may be less common among patients with disseminated Mycobacterium avium complex (DMAC) diagnosed in the present day than among those diagnosed earlier in the human immunodeficiency virus (HIV)/AIDS epidemic. One study has suggested that interferon (IFN)-ү release assays, which do not cross-react with MAC, may be useful to make the distinction between nontuberculous mycobacterial lymphadenitis. If highly active antiretroviral therapy (HAART) is ineffective, due to HIV multidrug resistance, for example, or CD4 lymphocyte improvement is delayed in a particular individual, MAC prophylaxis is still an important adjunct to care and is cost-effective. Dyspnea on initial presentation and presence of coexisting lung disease have been associated with increased mortality among patients with MAC pulmonary disease. In studies conducted for a course of clarithromycin monotherapy and a course of azithromycin monotherapy, gastrointestinal side effects were common, and changes in hearing were not infrequent. These two studies strongly suggested that clarithromycin and azithromycin have clinical utility for treatment of pulmonary MAC. DMAC is almost exclusively seen in patients with latestage AIDS and can be treated with the combination of either clarithromycin or azithromycin in combination with ethambutol, with or without rifabutin or a fluoroquinolone.

Background Atovaquone and azithromycin (A&A) with supportive care improve survival rates in cats with cytauxzoonosis. Resistance to atovaquone via parasite cytochrome b gene (cytb) mutations occurs in other Apicomplexan protozoans but is not described in Cytauxzoon felis. Objective To serially characterize the C. felis cytb sequences from a cat that remained persistently infected after A&A treatment. Animal A cat with naturally occurring C. felis infection. Methods Case report of the anemic cat persistently infected with C. felis before, during and after A&A treatment. Cytauxzoon felis cytb genes were amplified and sequenced before, during and after A&A treatment. Results Cytauxzoon felis was detected before, during and after A&A treatment including samples collected 570 days after treatment. After A&A treatment, the cat's anemia improved slightly. Cytb sequencing revealed only wild-type cytb methionine (M128) in samples collected before treatment. In samples collected after treatment, the cytb coded for isoleucine (M128I) and valine (M128I) at 2- and 4-months after treatment. These M128I and M128V mutations persisted even after a repeat treatment course with a higher dose atovaquone combined with the standard dose of azithromycin. Conclusions and clinical importance This report documents C. felis atovaquone resistance associated with M128 cytb mutations. This study suggests parasites with mutations of cytb M128 can be selected and impart resistance to A&A treatment even with higher atovaquone dosing.

BACKGROUND Medication use is important to collect accurately in medically complex patients in both clinical and research settings. AIM We assessed patient-level agreement for medication use between self-reported survey and electronic health record (EHR) for children with cystic fibrosis (CF). METHODS Our retrospective cross-sectional study focused on children with CF ages 6-20 years from Seattle Children's Hospital in Washington state, USA (N = 85). A self- or parent-reported survey included questions on current use of specific medications and antibiotic use in the past 2 months. We compared survey data with data abstracted from the individual's EHR and derived Cohen's Kappa statistics to estimate the level of agreement between the two methods. RESULTS Self-reported medication use was generally higher in the survey than in the EHR. The level of agreement ranged from slight for probiotics (74.1% agreement; 95% confidence interval [CI]: 64.6%-83.6%; kappa: 0.07), pancreatic enzymes (80% agreement; 95% CI: 71.3%-88.7%; kappa: 0.12), and vitamin D (55.3% agreement; 95% CI: 44.5%-66.1%; kappa: 0.20) to moderate for chronic azithromycin (80% agreement; 95% CI: 7.13%-88.7%; kappa: 0.50), proton pump inhibitors (76.5% agreement; 95% CI: 67.3%-85.7%; kappa: 0.46), and oral antibiotics (70.6% agreement; 95% CI: 60.7%-80.5%; kappa: 0.42). CONCLUSION There is considerable heterogeneity in level of agreement in medication use between self-reported survey and EHR data for children with CF. Standardized approaches are needed to improve the accuracy of medication data collected in clinical practice and research.

Increased use of azithromycin (AZ) in treating infections associated with coronavirus disease 2019 (COVID‐19) and reports of increased incidence of prolonged corrected QT (QTc) interval associated with AZ used with hydroxychloroquine prompted us to review the latest evidence in the literature, present additional analyses of human cardiovascular (CV) electrophysiology studies, and to describe sequential steps in research and development that were undertaken to characterize the benefit‐risk profile of AZ. Combined QTc findings from electrocardiograms taken during oral and i.v. pharmacokinetic‐pharmacodynamic studies of AZ suggest that clinically meaningful QTc prolongation is unlikely. Findings from several observational studies were heterogeneous and not as consistent as results from at least two large randomized controlled trials (RCTs). The QTc findings presented and observational data from studies with large numbers of events are not consistent with either a proarrhythmic action of AZ or an increase in frequency of CV deaths. Well‐powered RCTs do not suggest a presence of increased risk of CV or sudden cardiac death after short‐term or protracted periods of AZ usage, even in patients at higher risk from pre‐existing coronary disease.

BACKGROUND Refractory chronic rhinosinusitis (CRS) remains a significant burden for patients, often leaving them with few therapeutic options that provide low-morbidity, long-term, and meaningful symptomatologic and endoscopic disease improvement. Macrolides have long been thought to offer both an immunomodulatory and antimicrobial effect. Our objective was to evaluate the efficacy of low-dose, long-term azithromycin in a carefully selected high-risk population failing appropriate medical therapy of budesonide nasal irrigations (BNIs) and endoscopic sinus surgery (ESS). METHODS A double-blind, randomized, placebo-controlled trial was completed in a single tertiary-care center assessing the addition of 250 mg azithromycin, 3 times per week for 16 weeks, in adults failing ESS and high-volume BNIs. Associated comorbidities, as well as symptomatologic, microbiologic, and serologic values, were systematically collected. RESULTS A total of 128 patients were enrolled and underwent ESS followed by BNI. At the 4-month post-ESS visit, 48 patients showed disease persistence and were randomized to azithromycin or placebo. Overall, azithromycin, when compared with placebo, did not show a statistically significant difference in disease clearance (54% vs 33%, respectively; p = 0.146), although patients with disease clearance who were on azithromycin showed significantly better 22-item Sino-Nasal Outcome Test score improvements than patients on placebo (18 vs -0.9, respectively; p = 0.046). In a subgroup analysis excluding aspirin-exacerbated respiratory disease (AERD) patients, azithromycin significantly improved disease clearance when compared with placebo (71% vs 35%, respectively; p = 0.031), with a number needed to treat of 3 (2.8). CONCLUSION Low-dose azithromycin is a therapeutic option with few side effects. Its use can show favorable clinical outcomes in this difficult-to-treat population, especially if patients are AERD-negative.

The COVID‐19 pandemic has dramatically challenged care for cancer patients, especially those with active treatment that represent a vulnerable population for SARS‐CoV‐2 infection. Aggressive lymphoid neoplasms, such as diffuse large B‐cell lymphoma and high‐grade B‐cell lymphoma, need to be treated without delay in order to get the best disease outcome. Because of that, our clinical practice was changed so as to minimize risk of SARS‐CoV‐2 infection while continuing haematological treatment. In this report, we analyse the management of front‐line therapy in 18 patients during COVID‐19 outbreak, as well as the results of the implemented measures in their outcome.

Chloroquine and hydroxychloroquine are quinoline derivatives used to treat malaria. To date, these medications are not approved for the treatment of viral infections and there are no well‐controlled, prospective, randomized clinical studies or evidence to support their use in patients with Coronavirus Infectious Disease‐2019 (COVID‐19). Nevertheless, chloroquine and hydroxychloroquine are being studied alone or in combination with other agents to assess their effectiveness in the treatment or prophylaxis for COVID‐19. The effective use of any medication involves an understanding of its pharmacokinetics (PK), safety and mechanism of action. This work provides basic clinical pharmacology information relevant for planning and initiating COVID‐19 clinical studies with chloroquine or hydroxychloroquine, summarizes safety data from healthy volunteer studies, and summarizes safety data from Phase 2 and Phase 2/3 clinical studies in patients with uncomplicated malaria, including a Phase 2/3 study in pediatric patients following administration of azithromycin and chloroquine in combination. In addition, this work presents data describing the proposed mechanisms of action against the severe acute respiratory distress syndrome (ARDS) coronavirus–2 (SARS‐CoV‐2) and summarizes clinical efficacy to date.

Background Diabetes increases the risk of infections as well as coronary heart disease (CHD). Whether infections increase the risk of CHD and how this applies to individuals with diabetes is unclear. Objectives To investigate the association between bacterial infections and the risk of CHD in type 1 diabetes. Methods Individuals with type 1 diabetes (n = 3781) were recruited from the Finnish Diabetic Nephropathy Study (FinnDiane), a prospective follow-up study. CHD was defined as incident events: fatal or non-fatal myocardial infarction, coronary artery bypass surgery or percutaneous coronary intervention, identified through national hospital discharge register data. Infections were identified through national register data on all antibiotic purchases from outpatient care. Register data were available from 1.1.1995-31.12.2015. Bacterial lipopolysaccharide (LPS) activity was measured from serum samples at baseline. Data on traditional risk factors for CHD were collected during baseline and consecutive visits. Results Individuals with an incident CHD event (n = 370) had a higher mean number of antibiotic purchases per follow-up year compared to those without incident CHD (1.34 [95% CI: 1.16-1.52], versus 0.79 [0.76-0.82],P

The emergence of coronavirus disease 2019 (COVID‐19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has become a major global public health concern. Although SARS‐CoV‐2 causes primarily respiratory problems, concurrent cardiac injury cannot be ignored since it may be an independent predictor for adverse outcomes. Cardiac arrhythmias are often observed in patients with COVID‐19, especially in severe cases, and more likely contribute to the high risk of adverse outcomes. Arrhythmias should be regarded as one of the main complications of COVID‐19. Mechanistically, a number of ion channels can be adversely affected in COVID‐19, leading to alterations in cardiac conduction and/or repolarization properties, as well as calcium handling, which can predispose to cardiac arrhythmogenesis. In addition, several antimicrobials that are currently used as potential therapeutic agents for COVID‐19, such as chloroquine, hydroxychloroquine and azithromycin, have uncertain benefit, and yet may induce electrocardiographic QT prolongation with potential ventricular pro‐arrhythmic effects. Continuous electrocardiogram monitoring, accurate and prompt recognition of arrhythmias are important. The present review focuses on cardiac arrhythmias in patients with COVID‐19, its underlying mechanisms, and proposed preventive and therapeutic strategies., Diagnosis and management of coronavirus disease 2019 (COVID‐19) related arrhythmias. Arrhythmias are the main complications of COVID‐19. Tachycardia, atrioventricular/intraventricular conduction block, ST‐T changes, QT interval prolongation, and even malignant arrhythmias are observed in COVID‐19 patients. Continuous electrocardiogram monitoring, accurate and prompt recognition, and ppropriate treatments of arrhythmias are important. COVID‐19, Coronavirus disease 2019; ECG, Electrocardiogram; MCOT, Mobile continuous telemetry monitor.

BACKGROUND The sinonasal microbiome is believed to play an important role in the pathophysiology of refractory chronic rhinosinusitis (CRS). We evaluated changes in the microbiome following a 4-month course of low-dose azithromycin. Assessing microbiome alterations following such a treatment may help identify underlying mechanisms of this drug. METHODS A total of 48 adults with refractory CRS were enrolled in a double-blind, randomized, placebo-controlled trial. Patients were randomized to 250 mg of azithromycin or placebo 3 times weekly for 4 months. During this time, daily budesonide saline irrigations were continued. Sinonasal swabs were collected by endoscopically-assisted method prior to treatment initiation and at the end of it, and sent for 16S ribosomal RNA gene sequencing. High-resolution ANCHOR pipeline was used to infer and annotate putative species. The 2 patient groups were compared using DESeq2 differential abundance analysis. RESULTS From initiation to the end of azithromycin treatment, patients showed a significant difference in beta diversity analysis (p = 0.0004) along with a significant decrease in 71 different operational taxonomic units (OTUs) of Staphylococcus aureus (false discovery rate [FDR] < 0.05) obtained from the differential abundance analysis. This was not observed in placebo-treated patients. By the end of treatments, azithromycin-treated patients had a significant decrease in 29 different OTUs of S. aureus (FDR < 0.05) when compared to placebo. CONCLUSION A 4-month course of 250 mg of azithromycin 3 times weekly in patients with refractory CRS significantly decreases S. aureus abundance in the sinonasal microbiome. Considering the pathogenic role of S. aureus in the refractory CRS population, azithromycin may constitute an additional therapeutic option to help control this disease.

BACKGROUND To better understand the mechanisms of infection with nontuberculous mycobacteria (NTM) in patients with cystic fibrosis (CF), we explore different risk factors associated with NTM positivity in a meta-analysis. METHODS Studies published before 31 July 2019 were selected from MEDLINE. Combined odds ratios (ORs) were calculated by pooling the ORs of each study. The weighted mean difference (WMD) was used for continuous numerical measurements. Summary data were pooled using fixed- or random-effects models according to the presence of heterogeneity (P 50%). RESULTS Nineteen studies with a total of 23 418 patients, of whom 1421 (6%) were diagnosed as NTM positive, were included. Older age was significantly associated with NTM positivity (WMD = 2.12, 95% confidence interval [CI]: 1.11-3.13; P

BACKGROUND: Emerging micro‐pollutants (EMPs) in water have received much attention due to their potential hazards to human health and ecological security. Ferrate has been researched in recent years to remove both particulate and dissolved impurities (including EMPs) from water, and its promising performance has been attributed to the high oxidation capacity and coagulation functions. However, limited research has compared ferrate with coagulation alone in the treatment of EMPs, which is one of the major objectives of this study. RESULTS: Three emerging micro‐pollutants (EMPs), imidacloprid (IMP), bisphenol‐S (BS), and azithromycin (AZM) were chosen for this study. In all cases, ferrate outperformed to ferric chloride in the removal of the EMPs. For a given ferrate dose of 0.05 mM, 99% of BS, 85% of AZM, and 78% of IMP were removed for a start concentration of 10 μg L⁻¹. However, if the start concentration was 1000 μg L⁻¹, removal efficiency was decreased to 82% for BS, 62% for AZM, and 22% for IMP. pH 5 was favorable to the EMP removal by ferrate for the study conditions. Although higher removals of IMP, BS, and AZM were achieved by ferrate in comparison to those by ferric chloride, only 20% DOC removal was achieved by the ferrate. The formation of various oxidation products in the degradation process resulted in the disparity of the solution toxicity; that of BS was reduced but those of IMP and AZM increased after ferrate treatment. Nevertheless, the toxicity of ferric chloride treated samples was all increased. CONCLUSION: Ferrate has higher efficiency comparing with FeCl₃ to remove IMP, BS, and AZM. Degradation of the EMPs by ferrate was more efficient in acidic conditions (pH 5) and at the EMPs' lower initial concentrations for the given conditions. IMP was more resistant to the ferrate treatment compared to BS and AZM under the same conditions. Overall, 20% DOC reduction was achieved by ferrate for pH 5. Finally, the toxicity of BS can be reduced but those of IMP and AZM were increased after ferrate treatment, whilst the toxicity of ferric chloride treated samples was all increased. © 2020 Society of Chemical Industry

Background Invasive aspergillosis is a well-known complication of severe influenza pneumonia with acute respiratory distress syndrome (ARDS). However, recent studies are reporting emergence of aspergillosis in severe COVID-19 pneumonia, named as COVID-19-associated pulmonary aspergillosis (CAPA). Methods A retrospective observational study was conducted in patients with severe COVID-19 pneumonia from February 2020 to April 2020. Patients ≥18 years of age with clinical features and abnormal chest imaging with confirmed COVID-19 by RT-PCR for SARS-CoV-2 were included. CAPA was diagnosed based on clinical parameters, radiological findings and mycological data. Data were recorded on a structured proforma, and descriptive analysis was performed using Stata ver 12.1. Results A total of 147 patients with confirmed COVID-19 and 23 (15.6%) patients requiring ICU admission were identified. Aspergillus species were isolated from tracheal aspirates of nine (39.1%) patients, and of these, five patients (21.7%) were diagnosed with CAPA and four (17.4%) had Aspergillus colonisation. The mean age of patients with CAPA was 69 years (Median age: 71, IQR: 24, Range: 51-85), and 3/5 patients were male. The most frequent co-morbid was diabetes mellitus (4/5). The overall fatality rate of COVID-19 patients with aspergillosis was 44% (4/9). The cause of death was ARDS in all three patients with CAPA, and the median length of stay was 16 days (IQR: 10; Range 6-35 days). Conclusion This study highlights the need for comparative studies to establish whether there is an association of aspergillosis and COVID-19 and the need for screening for fungal infections in severe COVID-19 patients with certain risk factors.

Azithromycin (AZ) is a broad‐spectrum macrolide antibiotic with a long half‐life and a large volume of distribution. It is primarily used for the treatment of respiratory, enteric, and genitourinary bacterial infections. AZ is not approved for the treatment of viral infections, and there is no well‐controlled, prospective, randomized clinical evidence to support AZ therapy in coronavirus disease 2019 (COVID‐19). Nevertheless, there are anecdotal reports that some hospitals have begun to include AZ in combination with hydroxychloroquine or chloroquine (CQ) for treatment of COVID‐19. It is essential that the clinical pharmacology (CP) characteristics of AZ be considered in planning and conducting clinical trials of AZ alone or in combination with other agents, to ensure safe study conduct and to increase the probability of achieving definitive answers regarding efficacy of AZ in the treatment of COVID‐19. The safety profile of AZ used as an antibacterial agent is well established.1 This work assesses published in vitro and clinical evidence for AZ as an agent with antiviral properties. It also provides basic CP information relevant for planning and initiating COVID‐19 clinical studies with AZ, summarizes safety data from healthy volunteer studies, and safety and efficacy data from phase II and phase II/III studies in patients with uncomplicated malaria, including a phase II/III study in pediatric patients following administration of AZ and CQ in combination. This paper may also serve to facilitate the consideration and use of a priori–defined control groups for future research.

Introduction Management of drug-influenced gingival enlargement is challenging, and surgery is most often indicated. However, because of a unique mechanism of action, azithromycin helps in the management of gingival enlargement caused by cyclosporine. An incidental observation of the effect of azithromycin in the cyclosporine-influenced gingival enlargement by physicians in 1995 led to series of basic investigations and clinical trials confirming this observation and providing a non-surgical treatment modality. Case presentation In this report, successful management of cyclosporine-influenced gingival enlargement in a 39-year-old renal transplant patient with the use of azithromycin without any surgical intervention is presented. Conclusion Use of azithromycin for managing cyclosporine-influenced gingival enlargement is a useful alternative or adjunct to surgical management. It is hoped that this report will raise further awareness of this non-surgical modality in patients taking cyclosporine.