Azithromycin Therapy Research Articles

Mycoplasma pneumoniae-associated Mucositis: A Recently Described Entity.

Mycoplasma pneumoniae (MP) is a common cause of respiratory infections and can be associated with extrapulmonary complications. MP mucositis has recently been described as a distinct endemic clinical entity called Mycoplasma pneumoniae-induced rash and mucositis (MIRM). The authors present the case of a 46-year-old man with atypical pneumonia associated with exuberant mucositis, conjunctival hyperaemia and positive serological assays for MP IgM. The patient was treated with azithromycin and systemic corticosteroid therapy. Supportive care including pain management, intravenous hydration and mucosal care was also given. There was complete resolution of the pneumonia and mucositis. The presence of atypical pneumonia with mucosal involvement without cutaneous lesions and a favourable clinical evolution led to the diagnosis of MIRM.LEARNING POINTSMycoplasma pneumoniae infection can be associated with mucocutaneous lesions. A new entity called Mycoplasma pneumoniae-induced rash and mucositis (MIRM) has been recently described. The mucocutaneous involvement associated with MIRM is predominantly mucositis with scarce or absent cutaneous expression.The clinical presentation, pathophysiology and disease outcomes of MIRM distinguish it from Stevens-Johnson syndrome/toxic epidermal necrolysis and erythema multiform.MIRM has an overall favourable prognosis as the majority of patients recover without sequalae and recurrence is rare.

Long-term macrolide treatment for the prevention of acute exacerbations in COPD: a systematic review and meta-analysis.

BackgroundAcute exacerbation of COPD (AECOPD) is associated with an increased hospitalization and mortality. Azithromycin and erythromycin are the recommended drugs to reduce the risk of exacerbations. However, the most suitable duration of therapy and drug-related adverse events are still a matter of debate. The aim of this meta-analysis was to assess the current evidence regarding the efficacy and safety of long-term macrolide treatment for COPD.Materials and methodsWe comprehensively searched PubMed, Embase, the Cochrane Library, and the Web of Science and performed a systematic review and cumulative meta-analysis of all randomized controlled trials (RCTs) and retrospective studies.ResultsEleven RCTs and one retrospective study including a total of 2,151 cases were carried out. Long-term macrolide treatment significantly reduced the total number of cases with one or more exacerbations (OR=0.40; 95% CI=0.24–0.65; P<0.01) and the rate of exacerbations per patient per year (risk ratio [RR]=0.60; 95% CI=0.45–0.78; P<0.01). Subgroup analyses showed that the minimum duration for drug efficacy for both azithromycin and erythromycin therapy was 6 months. In addition, macrolide therapy could improve the St George Respiratory Questionnaire (SGRQ) total score (P<0.01) but did not achieve the level of clinical significance. The frequency of hospitalizations was not significantly different between the treatment and control groups (P=0.50). Moreover, chronic azithromycin treatment was more likely to increase adverse events (P<0.01).ConclusionProphylactic azithromycin or erythromycin treatment has a significant effect in reducing the frequency of AECOPD in a time-dependent manner. However, long-term macrolide treatment could increase the occurrence of adverse events and macrolide resistance. Future large-scale, well-designed RCTs with extensive follow-up are required to identify patients in whom the benefits outweigh risks.

Early target attainment of azithromycin therapy in children with lower respiratory tract infections.

Early target attainment is the key factor influencing the outcome of antimicrobial therapy. The objective of the present study was to evaluate the relationship between azithromycin concentrations during the first 24-48 h of therapy and the clinical outcome in order to optimize antimicrobial therapy. All children with lower respiratory tract infections receiving intravenous azithromycin monotherapy were included. The relationship between azithromycin trough concentrations during the first 24-48 h and the effectiveness and safety was explored. Data from 44 children [mean (SD) age = 5.25 (3.72) years] were available for final analysis. Children with trough concentrations >0.25 mg/L (n = 8) had a more significant improvement in antibacterial efficacy in terms of decreased C-reactive protein (P = 0.006) and the percentage of neutrophils (P = 0.043) compared with children with trough concentrations ≤0.25 mg/L (n = 36). No drug-related adverse events were shown to have a causal association with azithromycin therapy. Our study showed the clinical benefits of early target attainment of azithromycin therapy. A target trough concentration of 0.25 mg/L in the first 24-48 h of hospitalization was required to ensure better antibacterial efficacy.

Azithromycin therapy reduces cardiac inflammation and mitigates adverse cardiac remodeling after myocardial infarction: Potential therapeutic targets in ischemic heart disease.

IntroductionAcute myocardial infarction (MI) is a primary cause of worldwide morbidity and mortality. Macrophages are fundamental components of post-MI inflammation. Pro-inflammatory macrophages can lead to adverse cardiac remodeling and heart failure while anti-inflammatory/reparative macrophages enhance tissue healing. Shifting the balance between pro-inflammatory and reparative macrophages post-MI is a novel therapeutic strategy. Azithromycin (AZM), a commonly used macrolide antibiotic, polarizes macrophages towards the anti-inflammatory phenotype, as shown in animal and human studies. We hypothesized that AZM modulates post-MI inflammation and improves cardiac recovery.Methods and resultsMale WT mice (C57BL/6, 6–8 weeks old) were treated with either oral AZM (160 mg/kg/day) or vehicle (control) starting 3 days prior to MI and continued to day 7 post-MI. We observed a significant reduction in mortality with AZM therapy. AZM-treated mice showed a significant decrease in pro-inflammatory (CD45+/Ly6G-/F4-80+/CD86+) and increase in anti-inflammatory (CD45+/Ly6G-/F4-80+/CD206+) macrophages, decreasing the pro-inflammatory/anti-inflammatory macrophage ratio in the heart and peripheral blood as assessed by flow cytometry and immunohistochemistry. Macrophage changes were associated with a significant decline in pro- and increase in anti-inflammatory cytokines. Mechanistic studies confirmed the ability of AZM to shift macrophage response towards an anti-inflammatory state under hypoxia/reperfusion stress. Additionally, AZM treatment was associated with a distinct decrease in neutrophil count due to apoptosis, a known signal for shifting macrophages towards the anti-inflammatory phenotype. Finally, AZM treatment improved cardiac recovery, scar size, and angiogenesis.ConclusionAzithromycin plays a cardioprotective role in the early phase post-MI through attenuating inflammation and enhancing cardiac recovery. Post-MI treatment and human translational studies are warranted to examine the therapeutic applications of AZM.

Acute Exacerbations of Chronic Obstructive Pulmonary Disease With a Low Procalcitonin Concentration: Impact of Antibiotic Therapy

Patients admitted with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) often are prescribed antibiotics. Studies have shown that the use of procalcitonin (PCT) to guide the decision to initiate antibiotic therapy in AECOPD has resulted in less antibiotic use and similar outcomes compared with standard of care. We evaluated patients with AECOPD and low PCT concentrations to determine whether antibiotic therapy was associated with improved outcomes. We retrospectively evaluated adult patients admitted with AECOPD who had a peak PCT concentration <0.25 µg/mL. Patients were evaluated based on their antibiotic exposure: ≤24 hours vs >24 hours. We also evaluated outcomes based upon the duration of azithromycin therapy: ≤24 hours vs >24 hours. The primary outcome was all-cause 30-day readmissions. Secondary outcomes included length of stay (LOS) and COPD-related 30-day readmissions. One hundred sixty-one and 195 patients received ≤24 hours vs >24 hours of antibiotic therapy, respectively. The cohort with ≤24 hours of antibiotics had a shorter LOS (2.8 vs 3.7 days; P = .01). There were no differences in all-cause 30-day readmissions (15.5% vs 17.4%; P = .63) or COPD-related 30-day readmissions (11.2% vs 12.3%; P = .74). Additionally, patients receiving ≤24 hours of azithromycin had a shorter LOS (3.0 vs 3.8 days; P = .002) and there were no differences in all-cause 30-day readmissions (16.2% vs 17.1%; P = .82) or COPD-related 30-day readmissions (11.9% vs 11.6%; P = .94). For adult patients hospitalized with nonsevere AECOPD and low PCT concentrations, antibiotic therapy beyond 24 hours did not improve outcomes.

Determining the in vitro susceptibility of Neisseria gonorrhoeae isolates from 8 cities in Guangdong Province through an improved microdilution method

A microdilution method for the antibiotic susceptibility testing of Neisseria gonorrhoeae was established and improved, and the antibiotic resistance of N. gonorrhoeae samples isolated from 8 cities of Guangdong in 2016 was determined. The improved microdilution method was compared with the agar dilution method recommend by the World Health Organization (WHO) Western Pacific Region by testing the susceptibility of 100 clinical N. gonorrhoeae isolates. The essential agreement (EA), categorical agreement (CA), very major error (VME), major error (ME), and minor error (MIE) levels of the two methods were analyzed; the acceptable performance rates were measured as follows: ≥90% for EA or CA, ≤3% for VME or ME, and ≤7% for MIE. The EA, CA, VME, ME, and MIE of each method for 7 antibiotics, penicillin, tetracycline, ciprofloxacin, spectinomycin, ceftriaxone, cefixime, and azithromycin, were 96%–100%, 94%–100%, 0%–3%, 0%–2%, and 0%–6%, respectively. The Wilcoxon signed-rank test results indicated 94%–100% agreement between the 2 methods after excluding off-scale values (P > 0.05). The susceptibility of 634 N. gonorrhoeae strains to the 7 antibiotics above were tested through the microdilution method. The resistant rates of the isolates against ciprofloxacin, tetracycline, penicillin, and azithromycin were 99.8%, 88.3%, 53.8%, and 11%, and the percentages of the isolates with decreased susceptibility to ceftriaxone (minimum inhibitory concentration [MIC] ≥0.125 μg/mL) and cefixime (MIC ≥0.25 μg/mL) were 2.1% and 12%, respectively, in Guangdong. Among 8 cities, Shenzhen had the highest rates of resistance against penicillin (77.8%) and decreased susceptibility against ceftriaxone (5.6%). Zhuhai had the highest rates of decreased susceptibility against cefixime (30.1%), and Jiangmen had the highest azithromycin-resistant isolates (16.8%). The findings from this study indicated that the improved microdilution method is an alternative for testing the antimicrobial susceptibility of N. gonorrhoeae. The resistance rates of N. gonorrhoeae against penicillin, tetracycline, and ciprofloxacin were high. While ceftriaxone, cefixime, and spectinomycin remained effective against N. gonorrhoeae, their effectiveness seemed to be decreasing over time. Azithromycin therapy requires timely susceptibility test results.

An 85-Year-Old Man With Recurrent Fever and Multiple Splenic Infarcts.

An 85-Year-Old Man With Recurrent Fever and Multiple Splenic Infarcts.

Long-term azithromycin therapy to reduce acute exacerbations in patients with severe chronic obstructive pulmonary disease.

According to clinical trials, azithromycin taken daily for 1 year, decreased exacerbations of chronic obstructive pulmonary disease (COPD). Effectiveness evaluation of long-term azithromycin to reduce exacerbations in severe COPD patient on optimal therapy in real-life practice. We conducted a retrospective observational study of severe COPD patients who were prescribed azithromycin (PA)(250 mg, at least 3 times weekly for at least 6 months). Comparison group included severe COPD patients not prescribed azithromycin (NPA). Data were extracted from clinical chart review. Study included 126 PA and 69 NPA patients. They had severe airflow obstruction, mostly emphysema and one-third bronchiectasis. A predominant feature in the PA group was respiratory tract colonization with Pseudomonas aeruginosa. The mean number of exacerbations per patient per year in the PA group was 3.2 ± 2.1 before initiating azithromycin, and 2.3 ± 1.6 during following year on therapy (p < 0.001). Patients in the NPA group had 1.7 ± 1.3 and 2.5 ± 1.7 exacerbations during first and second follow-up year respectively (p < 0.001). Exacerbation changes from pre to post differed between groups (p < 0.001). Decrease in emergency visits and hospital admissions was significant in PA group. Exacerbation reductions and patient proportions having ≥2 exacerbations extended to the second year of treatment. These data showed that long-term azithromycin reduces exacerbation numbers in severe COPD patients, and benefits persist beyond one year. Desirable effects are more likely to outweigh the risks and adverse events in patients colonized with Pseudomonas aeruginosa.

Adjunctive therapy with azithromycin for moderate and severe acute respiratory distress syndrome: a retrospective, propensity score-matching analysis of prospectively collected data at a single center

Effective pharmacological therapy has not been established for patients with acute respiratory distress syndrome (ARDS). Macrolides are antibiotics with potent immunomodulatory and anti-inflammatory effects that may be beneficial in ARDS treatment. The objective of this study was to determine the adjunctive effect of azithromycin on survival for patients with ARDS. This single-center, retrospective cohort evaluation of hospitalized patients with moderate or severe ARDS was conducted to assess the impact of intravenous azithromycin on clinical outcomes using a propensity score analysis. All data were collected prospectively as part of ongoing research on the utility of high-resolution computed tomography in ARDS. The primary outcome was 90-day mortality, and the secondary analysis assessed the effect of azithromycin on time to successful discontinuation of mechanical ventilation and 28-day mortality. Of 191 eligible patients with severe or moderate ARDS, 62 were treated with azithromycin. The 62 patients treated with azithromycin and 62 not treated with azithromycin were matched and analysed. Azithromycin use was associated with a statistically significant improvement in 90-day survival rate (Hazard ratio [HR], 0.49; 95% confidence interval [CI], 0.27–0.87; P = 0.015) and a shorter time to successful discontinuation of mechanical ventilation (HR, 1.74; 95% CI, 1.07–2.81; P = 0.026). The 28-day mortality rate tended to be higher in the azithromycin cohort than in the non-azithromycin cohort, but this was not statistically significant. Adjunctive intravenous azithromycin therapy was effective in patients with moderate or severe ARDS. Further prospective randomized controlled trials are needed to confirm this result.

ADVERSE EVENTS ASSOCIATED WITH ANTIBIOTIC THERAPY IN PEDIATRIC PRACTICE. THE ROLE OF PRE- AND PROBIOTICS IN THE PREVENTION OF ANTIBIOTIC-ASSOCIATED DIARRHEA

The era of antibiotics began in the mid-twentieth century, which resulted in changing the basic views on the treatment of infectious diseases and significantly increased the life expectancy among individuals on average by 20 to 30 years. The widespread uncontrolled use of antibacterial drugs has led to development of resistance to antibiotics and a number of adverse events, one of which is diarrhoea. Diarrhoea is caused by the use of antibiotics in 6–7% of cases. Pre- and probiotics are used to prevent diarrhoea. A study of the efficacy and safety of Ecomed (a powder to prepare a suspension containing 100 mg/5 ml azithromycin manufactured by AVVA RUS JSC (Russia) in combination with prebiotics lactulose) in comparison with azithromycin without lactulose was conducted in children with acute bacterial rhinosinusitis. A total of 100 patients were included in the study (50 boys and 50 girls) aged 3 to 14 years, who were divided into 2 groups: the main group consisted of 50 children (mean age 6.16 ± 2.78 years) who received Ecomed for 3 days; the control group of 50 children (mean age 6.9 ± 3.24 years) who received azithromycin for 3 days. The observation period was 2 months. During the observation period, the gastrointestinal tract state was evaluated for such symptoms as flatulence, bloating, frequency of bowel movements and consistency of feces. Feces were collected from children of both groups for gene sequencing by the 16s rRNA method during 4 visits: visit 1: before therapy, visit 2: 3 days after start of the therapy (end of the therapy), visit 3: 17 days after start of the therapy, visit 4: 60 days after start of the therapy. The study showed a significant difference between the microbiota profiles against the background of therapy with azithromycin and Ecomed. It was established that the total share of micro-organisms exposed to the drugs accounted for approximately 20–25%. The use of azithromycin provoked the development of intestinal dysbiosis according to the criteria for the deviation of the microbiota families, genera and species profile from the initial state, and according to the diagnostic signs of clinical symptomatology. An important observation was the fact that even after 2 months the dysbiotic state did not return to normal. The use of Ecomed containing a combination of azithromycin and lactulose reduced dysbiosis of the intestinal microbiota exposed to azithromycin. The main advantages were that opportunistic microorganisms had been prevented from growing against the background of azithromycin therapy and useful and other microorganisms had been preserved.

Clinical and Safety Outcomes of Long-Term Azithromycin Therapy in Severe COPD Beyond the First Year of Treatment

Exacerbations of COPD (ECOPD) are a major cause of mortality and morbidity. Continuous cyclic azithromycin (CC-A) reduces the exacerbation rate, but it is unknown whether it remains effective and safe beyond the first year. This study was a retrospective analysis of patients with severe COPD (Global Initiative for Chronic Obstructive Lung Disease grade D) with≥ 4 moderate to severe ECOPD who received CC-A (500mg three times per week) as add-on therapy. Patients treated over 24months were considered long-term continuous cyclic azithromycin (LT-CC-A) users, andECOPD, hospitalizations, and length of hospital stays during the first, second, and third years were compared with the previous 12months. Microbiologic monitoring, assessment of macrolide resistance, and analysis of side effects were maintained throughout the study period. A total of 109 patients with severe COPD treated with CC-A (39 for≥ 24months) comprised the LT-CC-A group (35.8%). This group presented average reductions in ECOPD from baseline of 56.2%at 12months, 70%at 24months, and 41%at 36months, paralleled by respective reductions in hospitalizations of 62.6%, 75.8%, and 39.8%. ECOPD due to common microorganisms fell by 12.5%and 17.3%at 12 and 24months of LT-CC-A, respectively, with a 50%increase in macrolide resistance. Pseudomonas aeruginosa ECOPD rose by 7.2%and 13.1%at these two time points. CC-A therapy was well tolerated with few side effects: digestive disorders in the short term (7.1%) and hearing loss in the long term (5.1%). LT-CC-A therapy over a 24- to 36-month period in patients with COPD (Global Initiative for Chronic Obstructive Lung Disease grade D) achieved sustained reductions in ECOPD and hospitalizations of > 50%with few adverse events, although macrolide resistance increased.

Effect of Low Dose Azithromycin Towards The Long Period of Clinical Improvement, Level of IL-8 And Sputum Neutrophil of Pneumonia Patients

Backgrounds: Pneumonia is an acute inflammation of the lung parenchyma caused by microorganisms. Inflammation is an immune response that occurs when bacterial infection. The immune response that occurs will induce alveolar macrophages secrete IL-8 which mediates the movement of neutrophils into the alveolar to release reactive oxygen species (ROS) and protease. Low-dose azithromycin has anti-inflammatory effects that are used on a chronic inflammatory disease of the lung, so its use in pneumonia interesting to do. This study aimed to determine the effect of low-dose azithromycin towards the long period of clinical improvement, level of IL-8 and sputum neutrophil of pneumonia patients.&#x0D; Methode: This research is an experimental study with pretest and post-test design. Subjects were patients with pneumonia who were treated at the Hospital Dr. Moewardi Surakarta in July - August 2016. Samples were taken by consecutive sampling as many as 30 patients. treatment group (n = 15) received additional therapy of azithromycin 250 mg / day and the control group (n = 15) received additional placebo. &#x0D; Result: Supplementation of low-dose azithromycin was significantly reduced levels of IL-8 (reduction = -90.31 ± 89.30; P=0.002) and sputum neutrophil (reduction = -35.73 ± 25.25; P=0.0001) in pneumonia patients. There is a statistically significant difference (P=0.0001) of the long period of clinical improvement between treatment groups (3.87 + 0.64 days) and control (5,60+ 0.91 days). &#x0D; Conclusion: Supplementation 250 mg/day of azithromycin during hospitalization led to decreased levels of IL-8 serum, sputum neutrophil, and affect the long period of clinical improvement in pneumonia patients. (J Respir Indo 2018; 38(1): 39-47)

The timing of azithromycin treatment is not associated with the clinical prognosis of childhood Mycoplasma pneumoniae pneumonia in high macrolide-resistant prevalence settings.

BackgroundMycoplasma pneumoniae infection is a major cause of community-acquired pneumonia in children. We performed a retrospective study to evaluate the clinical impact of the timing of azithromycin treatment in children with Mycoplasma pneumoniae pneumonia in high macrolide-resistant prevalence settings.Methods and findingsA total of 623 patients were enrolled in this study and were divided into 2 groups according to the timing of azithromycin therapy. Children who received azithromycin within 3 days (72 hours) after the onset of Mycoplasma pneumoniae pneumonia were classified into the early azithromycin treatment group (n = 174), whereas the late azithromycin treatment group (n = 449) comprised children treated with azithromycin more than 72 hours after symptom onset. We evaluated clinical prognosis according to demographic, clinical and laboratory characteristics. Although the early azithromycin treatment group exhibited a longer fever duration after azithromycin administration (7.17±4.12 versus 4.82±3.99 days, P<0.01), the total fever duration exhibited no significant difference (9.02±4.58 versus 9.57±4.91 days, P = 0.212). After azithromycin therapy, the two groups exhibited no significant differences with respect to improvements in the laboratory and radiological findings (all P>0.05).ConclusionThe timing of azithromycin treatment is not associated with the clinical prognosis of Mycoplasma pneumoniae pneumonia in children in high macrolide-resistant Mycoplasma pneumoniae prevalence settings.

IL-1α and MMP-9 Tear Levels of Patients with Active Ocular Rosacea before and after Treatment with Systemic Azithromycin or Doxycycline

Aims: The purpose of this paper was to determine the lacrimal concentration of IL-1α and MMP-9 in patients with active ocular rosacea before and after systemic treatment with azithromycin or doxycycline. Methods: After 4 weeks of therapy with azithromycin (500 mg/day, 3 days a week PO) or doxycycline (200 mg/day PO), lacrimal samples were analyzed using an enzyme-linked immunosorbent assay multiplex. Results: There was a significant difference between baseline IL-1α (37.9 pg/mL) and MMP-9 (26.7 ng/mL) in rosacea eyes compared to controls (0.001 pg/mL for IL-1α and 0.2 ng/mL for MMP-9) (p < 0.001). IL-1α decreased from 47.0 pg/mL before azithromycin to 23.5 pg/mL after treatment (p = 0.024), but not after doxycycline therapy. On the contrary, baseline MMP-9 tear levels (10.28 ng/mL) decreased after treatment (8.36 pg/mL) with doxycycline (p = 0.054) but not with azithromycin. There was a strong clinical correlation of higher baseline IL-1α tear levels between patients who responded to doxycycline therapy and those who failed (p = 0.043). Patients unresponsive to azithromycin had significantly higher baseline MMP-9 levels than those with doxycycline (p = 0.040). Conclusions: While IL-1α levels decreased after azithromycin therapy, MMP-9 did so after doxycycline treatment. Baseline cytokine tear levels tend to be markedly elevated in patients with antibiotic failure, suggesting their potential role as therapeutic biomarkers for the disease.

Case Report of Pathognomonic Findings of Severe Colchicine Effect in the Esophagus, a Rarely Reported Site of Colchicine Effect

Colchicine, a medication commonly used to treat gout, interferes with the cell cycle and can injure rapidly reproducing cells, including proliferative cells in gastrointestinal mucosa, primarily in the small bowl. Esophageal injury is rarely reported, and when reported is typically mild. A case is reported of severe injury to esophageal mucosa secondary to colchicine. A 47-year-old male with a medical history of systemic lupus erythematosus, intermittently treated with corticosteroids for 2 years, recently treated with azithromycin therapy for upper respiratory infection and hydroxychloroquine for polyarthritis, presented with dyspnea and severe substernal chest pain, exacerbated by deep inspiration, and ameliorated by leaning forward. Physical examination revealed an afebrile man with stable vital signs and no friction rub. Laboratory tests revealed Hb=12.6 g/dl, creatinine=1.33 mg/dl, CRP=3.4 mg/dl, ESR=51 mm/hr, D-Dimer=1140 ng/ml, and troponin level was within normal limits. EKG revealed PR segment depression and upwardly concave ST elevation, findings suggestive of pericarditis. Echocardiogram revealed no pericardial effusion. CT angiogram of chest was negative for pulmonary embolus, but showed prominent distal esophagus wall. Patient was admitted for acute pericarditis, likely viral versus lupus pericarditis. Patient treated with prednisone 50 mg/ day and colchicine 0.6 mg twice daily with significant symptomatic improvement. Esophagogastroduodenoscopy revealed LA grade C reflux esophagitis and nonbleeding small gastric ulcers. He was treated with an oral proton pump inhibitor and discharged home. Pathological examination of esophageal biopsies revealed mild chronic gastritis at the gastroesophageal junction, with cytotoxic colchicine effect, but no intestinal metaplasia, dysplasia, or H. pylori infection. Colchicine prevents tubulin protein polymerization, prevents mitotic spindle formation and causes mitotic arrest during metaphase. The pathognomonic histopathologic finding is ring mitoses accompanied by increased glandular cell apoptosis and epithelial pseudostratification. Small bowel is the most severely affected site in the GI tract by colchicine, but in the present case the esophagus was significantly affected, a highly uncommon finding. Colchicine toxicity typically manifests soon after therapy initiation; in the current case endoscopic biopsies were performed one day after receiving 3 doses of colchicine therapy. The irregular arrangement of nuclei, increase in mitotic figures, and hyperchromatism of nuclei are pathognomonic of colchicine, but this finding can occasionally mimic dysplasia. Nontoxic doses of colchicine do not cause mucosal changes, except in areas with increased cell proliferation, such as a hyperplastic polyp, where nontoxic levels of colchicine can cause mitotic arrest and ring figures, and mimic a sessile serrated adenoma. These pathologic findings should be assessed in conjunction with clinical presentation to avoid missing the diagnosis of colchicine toxicity.Figure: Esophagogastroduodenoscopy showing deep linear erosions in distal esophagus. The lesions are unlikely from Mallory-Wiess tear in the absence of antecedent vomiting.Figure: Medium power photomicrograph of esophageal squamous mucosa showing brisk mitotic activity involving almost the entire thickness of the epithelium. Right inset shows high power view of characteristic ring mitosis associated with colchicine effect.Figure: Medium power photomicrograph of gastric cardial epithelium at gastroesophageal junction showing brisk mitotic activity in columnar epithelial cells. Right inset shows a high power view of numerous mitotic figures.

Streptococcus pneumoniae and chronic endobronchial infections in childhood.

Streptococcus pneumoniae (pneumococcus) is the main cause of bacterial pneumonia worldwide and has been studied extensively in this context. However, its role in chronic endobronchial infections and accompanying lower airway neutrophilic infiltration has received little attention. Severe and recurrent pneumonia are risk factors for chronic suppurative lung disease (CSLD) and bronchiectasis; the latter causes considerable morbidity and, in some populations, premature death in children and adults. Protracted bacterial bronchitis (PBB) is another chronic endobronchial infection associated with substantial morbidity. In some children, PBB may progress to bronchiectasis. Although nontypeable Haemophilus influenzae is the main pathogen in PBB, CSLD and bronchiectasis, pneumococci are isolated commonly from the lower airways of children with these diagnoses. Here we review what is known currently about pneumococci in PBB, CSLD and bronchiectasis, including the importance of pneumococcal nasopharyngeal colonization and how persistence in the lower airways may contribute to the pathogenesis of these chronic pulmonary disorders. Antibiotic treatments, particularly long-term azithromycin therapy, are discussed together with antibiotic resistance and the impact of pneumococcal conjugate vaccines. Important areas requiring further investigation are identified, including immune responses associated with pneumococcal lower airway infection, alone and in combination with other respiratory pathogens, and microarray serotyping to improve detection of carriage and infection by multiple serotypes. Genome wide association studies of pneumococci from the upper and lower airways will help identify virulence and resistance determinants, including potential therapeutic targets and vaccine antigens to treat and prevent endobronchial infections. Much work is needed, but the benefits will be substantial.

A novel ceftazidime/avibactam, rifabutin, tedizolid and moxifloxacin (CARTM) regimen for pulmonary Mycobacterium avium disease.

To compare the efficacy of ceftazidime/avibactam plus tedizolid-based combination regimens with the standard therapy of azithromycin, ethambutol and rifabutin for the treatment of pulmonary Mycobacterium avium complex (MAC) disease. We mimicked the human pulmonary concentration-time profiles of ceftazidime/avibactam and tedizolid in combination, ceftazidime/avibactam, rifabutin, tedizolid and moxifloxacin (CARTM), and the standard regimen and examined microbial kill in triplicate hollow-fibre system model of intracellular pulmonary MAC (HFS-MAC) units. The tedizolid and moxifloxacin doses used were non-optimized; the tedizolid dose was that associated with bacteriostasis. Drugs were administered daily for 28 days. Each HFS-MAC was sampled in the central and peripheral compartment to ascertain that the intended drug exposures had been achieved. The peripheral compartments were sampled at regular intervals over the 28 days to quantify the burden of MAC. MAC-infected macrophages in the HFS-MAC achieved multi-fold higher intracellular versus extracellular concentrations of rifabutin, moxifloxacin, ceftazidime/avibactam. The non-optimized ceftazidime/avibactam plus tedizolid dual therapy held the bacterial burden at the same level as day 0 (stasis) throughout the 28 days. The standard therapy reduced the bacterial load 2 log10 cfu/mL below stasis on day 14 but started failing after that. The CARTM regimen achieved 3.2 log10 cfu/mL kill below stasis on day 21, but had started to fail by day 28. The CARTM regimen promises to have kill rates better than standard therapy. Experiments to identify exposures of each of the four drugs associated with optimal effect in the CARTM combination are needed in order to design a short-course chemotherapy regimen.

Analysis of the potential for point-of-care test to enable individualised treatment of infections caused by antimicrobial-resistant and susceptible strains of Neisseria gonorrhoeae: a modelling study

ObjectiveTo create a mathematical model to investigate the treatment impact and economic implications of introducing an antimicrobial resistance point-of-care test (AMR POCT) for gonorrhoea as a way of extending the...

Steady-State Therapy with Azithromycin or Low-Dose Prednisolone in Paediatric Cystic Fibrosis Patients: Inflammatory Markers and Disease Progression

Background: Anti-inflammatory therapy is a logical approach to slowing the inevitable lung function deterioration in cystic fibrosis (CF) patients. This study's aim was to evaluate inflammatory markers and disease progression in paediatric CF patients chronically treated with azithromycin or low-dose prednisolone. Methods: The study included 204 patients with CF and 100 healthy controls; 102 CF patients were treated with basic therapy only (without anti-inflammatory treatment; WAT), and 102 individuals received basic therapy along with azithromycin (n = 59) or low-dose prednisolone (n = 43). The median duration of therapy was 24 months (range 12-82) with azithromycin and 31 months (range 12-180) with prednisolone. A cross-sectional analysis of plasma and sputum biomarkers was performed. Results: Compared with the healthy controls, the WAT group showed elevated IFN-γ, IL-10 (total), and TGFβ₁ concentrations, and decreased TNFα (total) and adrenocorticotropic hormone (ACTH) levels (all p < 0.05). Plasma TNFα (total) concentrations in azithromycin/prednisolone patients were significantly higher than those in WAT patients and similar to those of healthy children. In contrast, IL-10 (total) levels were significantly decreased in azithromycin/prednisolone-treated patients compared with WAT patients. Children from the azithromycin group demonstrated ACTH levels similar to those of healthy controls. Azithromycin-treated patients showed a significantly reduced rate of CF-related liver disease and a significantly increased incidence of glucose metabolism disturbances. Conclusions: Steady-state anti-inflammatory treatments may have a sustained immunomodulatory action at systemic and local levels in CF patients. Further investigations are needed to assess the effects of supportive azithromycin therapy on the hypothalamic-pituitary-adrenal axis and the incidence of non-pulmonary CF complications.

A combination of irsogladine maleate and azithromycin exhibits addictive protective effects in LPS-induced human gingival epithelial cells.

This study aimed to investigate the potential effects of the combination therapy of irsogladine maleate (IM) and azithromycin (AZM) on the inflammation in lipopolysaccharide (LPS)-induced gingival epithelial cells. Human gingival epithelial cell OBA-9 was stimulated by LPS to construct the periodontitis model, followed by the treatment of irsogladine maleate (IM) or azithromycin (AZM) with different concentration. Transepithelial electrical resistance (TER) of cells in each group was analyzed, and qRT-PCR and western blotting were used to detect the expressions of inflammatory cytokines. Immunofluorescence staining was performed to detect the protein expression. The TER for cells was significantly decreased while the inflammatory cytokines expressions including IL-6, IL-8, IL-1β and TNF-α were all significantly increased by LPS compared to the control (P<0.05). However, TER was increased significantly, whereas the cytokine levels were decreased by IM or AZM, but these effects was more apparent in cells treated with IM and AZM combination (P<0.01). Moreover, E-cadherin and vimentin expressions were more positive in the IM and AZM group than in the other groups. The application of ERK and P38 MAPK inhibitors reversed the effects of LPS on cell inflammatory cytokine production and cell TER. This study revealed that the combination therapy of IM and AZM performed excellent effects on preventing the inflammatory progression of periodontitis.