zithromax and Pneumonia

The goal of the study was to analyze the clinical characteristics of Legionella cases caused by Legionella micdadei and explore the diagnosis and treatment.. The pathogen was identified by routine isolation and culture, biochemical identification, serum agglutination test, mass spectrometry identification, and routine PCR. Combined with the related literature review, the clinical diagnosis and treatment of Legionella micdadei were analyzed.. The patient suffered from pulmonary infection caused by Legionella micdadei. After treatment with moxi-floxacin for 2 weeks, the body temperature dropped and the shadow of the lung was completely absorbed after 2 months. Combined with literature analysis, 8 cases of Legionella micetidis, including 7 males and 1 female, aged from 27 to 57 years old, 6 cases with basic diseases, which were treated with azithromycin, erythromycin or levofloxacin, and all of them achieved good therapeutic effect.. The detection of Legionella should be strengthened in patients with pneumonia whose symptoms have no obvious improvement after antibiotic treatment. Azithromycin, erythromycin or levofloxacin are effective in the treatment of Legionella spp.

Topics: Adult; Azithromycin; Erythromycin; Female; Humans; Legionella; Legionellaceae; Legionellosis; Levofloxacin; Male; Middle Aged; Pneumonia

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; I. 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.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Azithromycin; Clarithromycin; Community-Acquired Infections; Erythromycin; Humans; Pneumonia; Randomized Controlled Trials as Topic

Tanreqing injection (TRQ) is a traditional Chinese medicine injection. The goal of this study was to assess the clinical efficacy and safety of TRQ injection in combination with azithromycin or ceftriaxone, as well as azithromycin or ceftriaxone alone, in treating Streptococcus pneumoniae pneumonia (SPP).. The randomized controlled trial (RCT) of TRQ injection combined with antibiotics versus antibiotics alone in the treatment of SPP was retrieved from Chinese and English databases (the control group was treated with antibiotics alone, while the experimental group received TRQ injection combined with antibiotics). The retrieval period was from the database's inception through February 2022. The data was extracted using the Cochrane Collaboration Network Quality Evaluation Standards, the methodological quality of the included literature was assessed, and the outcome indicators were calculated using RevMan5.4.1 software.. A total of 25 RCTs were collected, including 2057 patients. TRQ injection combined with antibiotics significantly improved clinical efficacy and reduced defervescence time, lung rale disappearance time, cough disappearance time, disappearance time of chest pain, and average hospitalization time when compared to control group, according to meta-analysis results (p < 0.05).. In the treatment of SPP, TRQ injection combination with antibiotics can significantly improve the total effect rate when compared to standard western medicine. Due to the low quality of the randomized controlled trials included in this investigation, more high-quality, multi-center, large-sample, prospective, randomized, double-blind clinical studies are needed to confirm the aforementioned conclusions.

Topics: Anti-Bacterial Agents; Azithromycin; Ceftriaxone; Drugs, Chinese Herbal; Humans; Pneumonia; Randomized Controlled Trials as Topic; Streptococcus pneumoniae

To systematically evaluate the clinical efficacy of modified Xiebai Powder or modified Xiebai Powder combined with Western medicine in the treatment of pneumonia and explore its potential mechanism of action.. Meta-analysis was used to screen the eligible literature on randomized controlled trials (RCTs) about Xiebai Powder in the treatment of pneumonia, and Review Manager 5.3 software was used for statistical analysis of the data. Based on the results of the meta-analysis, the active ingredients in Xiebai Powder and their therapeutic targets, disease-related targets, and intersection targets were screened using methods of network pharmacology, and their biological processes and key signaling pathways were analyzed using bioinformatics tools. Molecular docking was carried out to verify and predict the mechanisms for Xiebai Powder combined with Western medicine in the treatment of pneumonia.. A total of 16 papers were screened out, with a total of 1,465 patients. The results of the meta-analysis showed that modified Xiebai Powder or modified Xiebai Powder combined with Western medicine were superior to conventional Western medicine in terms of clinical efficacy, shortening the disappearance time of symptoms (body temperature, cough, and pulmonary rales) and reducing the level of C-reactive protein, and the incidence of adverse reactions was significantly reduced. A total of 40 active ingredients in Xiebai Powder and 285 therapeutic targets of Xiebai Powder combined with azithromycin after deduplication were screened out from the database. KEGG enrichment analysis showed that Xiebai Powder combined with azithromycin might play a role in the treatment of pneumonia through the IL-17 signaling pathway, tumor necrosis factor signaling pathway, C-type lectin receptor signaling pathway, Toll-like receptor signaling pathway, and HIF-1 signaling pathway.. Modified Xiebai Powder or modified Xiebai Powder combined with azithromycin has better effects in treating pneumonia, and modified Xiebai Powder combined with azithromycin may play a role in treating pneumonia through several pathways such as the IL-17 signaling pathway.

Topics: Azithromycin; C-Reactive Protein; Drugs, Chinese Herbal; Humans; Interleukin-17; Lectins, C-Type; Medicine, Chinese Traditional; Molecular Docking Simulation; Pneumonia; Powders; Toll-Like Receptors; Tumor Necrosis Factors

Stevens-Johnson syndrome (SJS) is an acute blistering disease of the skin and mucous membranes. SJS in children is not common but potentially serious disease. But the epidemiology of SJS in China is not well defined.. A 6-year-old boy was initially diagnosed as pneumonia admitted to hospital after admission, and the body appears red rash with blisters, skin damage, lip debaucjed, repeated high fever, and rapid progression.. SJS often results from an allergy reaction response to a range of drugs. It is a clinical diagnosis suggested by fever and malaise followed by an extensive painful, nonblanching, macular rash that commonly progresses to blistering or sloughing, and mucositis.. The boy was treated with continuous renal replacement therapy, anti-infection therapy, high-dose glucocorticoid treatment, and symptomatic treatment.. The patient was recovered after 33 days of treatment.. The current treatment is mainly symptomatic treatment, and for the patient, it is important to make skin care related well, included early out blisters at effusion, reducing skin ulceration of the mucosa area, keeping skin clean, removing mucosa secretion and blood clots, doing eye care related, preventing the complications, ensuring adequate intake of nutrition and warm and so on.

Topics: Anti-Bacterial Agents; Azithromycin; Child; Humans; Male; Pneumonia; Skin Care; Stevens-Johnson Syndrome

Acute lower respiratory tract infections (LRTI) range from acute bronchitis and acute exacerbations of chronic bronchitis to pneumonia. Approximately five million people die from acute respiratory tract infections annually. Among these, pneumonia represents the most frequent cause of mortality, hospitalisation and medical consultation. Azithromycin is a macrolide antibiotic, structurally modified from erythromycin and noted for its activity against some gram-negative organisms associated with respiratory tract infections, particularly Haemophilus influenzae (H. influenzae).. To compare the effectiveness of azithromycin to amoxycillin or amoxycillin/clavulanic acid (amoxyclav) in the treatment of LRTI, in terms of clinical failure, incidence of adverse events and microbial eradication.. We searched CENTRAL (2014, Issue 10), MEDLINE (January 1966 to October week 4, 2014) and EMBASE (January 1974 to November 2014).. Randomised controlled trials (RCTs) and quasi-RCTs, comparing azithromycin to amoxycillin or amoxycillin/clavulanic acid in participants with clinical evidence of an acute LRTI, such as acute bronchitis, pneumonia and acute exacerbation of chronic bronchitis.. The review authors independently assessed all potential studies identified from the searches for methodological quality. We extracted and analysed relevant data separately. We resolved discrepancies through discussion. We initially pooled all types of acute LRTI in the meta-analyses. We investigated the heterogeneity of results using the forest plot and Chi(2) test. We also used the index of the I(2) statistic to measure inconsistent results among trials. We conducted subgroup and sensitivity analyses.. We included 16 trials involving 2648 participants. We were able to analyse 15 of the trials with 2496 participants. The pooled analysis of all the trials showed that there was no significant difference in the incidence of clinical failure on about days 10 to 14 between the two groups (risk ratio (RR), random-effects 1.09; 95% confidence interval (CI) 0.64 to 1.85). A subgroup analysis in trials with acute bronchitis participants showed significantly lower clinical failure in the azithromycin group compared to amoxycillin or amoxyclav (RR random-effects 0.63; 95% CI 0.45 to 0.88). A sensitivity analysis showed a non-significant reduction in clinical failure in azithromycin-treated participants (RR 0.55; 95% CI 0.25 to 1.21) in three adequately concealed studies, compared to RR 1.32; 95% CI 0.70 to 2.49 in 12 studies with inadequate concealment. Twelve trials reported the incidence of microbial eradication and there was no significant difference between the two groups (RR 0.95; 95% CI 0.87 to 1.03). The reduction of adverse events in the azithromycin group was RR 0.76 (95% CI 0.57 to 1.00).. There is unclear evidence that azithromycin is superior to amoxycillin or amoxyclav in treating acute LRTI. In patients with acute bronchitis of a suspected bacterial cause, azithromycin tends to be more effective in terms of lower incidence of treatment failure and adverse events than amoxycillin or amoxyclav. However, most studies were of unclear methodological quality and had small sample sizes; future trials of high methodological quality and adequate sizes are needed.

Topics: Acute Disease; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Azithromycin; Bronchitis; Drug Therapy, Combination; Humans; Pneumonia; Randomized Controlled Trials as Topic; Respiratory Tract Infections; Treatment Failure

Chronic allograft dysfunction, manifesting as bronchiolitis obliterans syndrome (BOS), is the major cause of morbidity and mortality in human lung transplant recipients. While alloimmunity has a definite role, there is increasing interest in overall allograft injury and subsequent inflammation and remodeling. This review deals with nonalloimmune factors that may potentiate alloimmune injury. We discuss infection and reflux/aspiration as examples of allograft injury, which may lead to chronic loss of graft function and BOS. Surgical and nonsurgical treatments aimed at preventing these insults and improving survival are considered. The need for further evidence, including randomized-controlled trials, to evaluate the role of medical and surgical therapies is emphasized by the current literature.

Topics: Azithromycin; Bronchiolitis Obliterans; Gastroesophageal Reflux; Gram-Negative Bacterial Infections; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lung Diseases; Lung Transplantation; Pneumonia; Pneumonia, Aspiration; Transplantation, Homologous

Acute lower respiratory tract infections (LRTI) range from acute bronchitis and acute exacerbations of chronic bronchitis to pneumonia. Approximately five million people die of acute respiratory tract infections annually. Among these, pneumonia represents the most frequent cause of mortality, hospitalization and medical consultation. Azithromycin is a new macrolide antibiotic, structurally modified from erythromycin and noted for its activity against some gram-negative organisms associated with respiratory tract infections, particularly Haemophilus influenzae (H. influenzae).. To compare the effectiveness of azithromycin to amoxycillin or amoxycillin/clavulanic acid (amoxyclav) in the treatment of LRTI, in terms of clinical failure, incidence of adverse events and microbial eradication.. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2007 Issue 2), MEDLINE (January 1966 to July 2007), and EMBASE (January 1974 to July 2007).. Randomized and quasi-randomized controlled trials, comparing azithromycin to amoxycillin or amoxycillin/clavulanic acid in participants with clinical evidence of acute LRTI: acute bronchitis, pneumonia, and acute exacerbation of chronic bronchitis were studied.. The criteria for assessing study quality were generation of allocation sequence, concealment of treatment allocation, blinding, and completeness of the trial. All types of acute LRTI were initially pooled in the meta-analyses. The heterogeneity of results was investigated by the forest plot and Chi-square test. Index of I-square (I(2)) was also used to measure inconsistent results among trials. Subgroup and sensitivity analyses were conducted.. Fifteen trials were analysed. The pooled analysis of all trials showed that there was no significant difference in the incidence of clinical failure on about day 10 to 14 between the two groups (relative risk (RR), random-effects 1.09; 95% confidence interval (CI) 0.64 to 1.85). Sensitivity analysis showed a reduction of clinical failure in azithromycin-treated participants (RR 0.55; 95% CI 0.25 to 1.21) in three adequately concealed studies, compared to RR 1.32; 95% CI 0.70 to 2.49 in 12 studies with inadequate concealment. Twelve trials reported the incidence of microbial eradication and there was no significant difference between the two groups (RR 0.95; 95% CI 0.87 to 1.03). The reduction of adverse events in the azithromycin group was RR 0.76 (95% CI 0.57 to 1.00).. There is unclear evidence that azithromycin is superior to amoxicillin or amoxyclav in treating acute LRTI. In patients with acute bronchitis of a suspected bacterial cause, azithromycin tends to be more effective in terms of lower incidence of treatment failure and adverse events than amoxicillin or amoxyclav. Future trials of high methodological quality are needed.

Topics: Acute Disease; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Azithromycin; Bronchitis; Drug Therapy, Combination; Humans; Pneumonia; Randomized Controlled Trials as Topic; Respiratory Tract Infections; Treatment Failure

Acute fibrinous and organizing pneumonia, a recently described form of diffuse acute lung injury, sometimes affects adults with inflammatory myopathy. We describe a child with juvenile dermatomyositis who had development of acute fibrinous and organizing pneumonia. There does not appear to be a successful method of treatment, particularly in severe cases with respiratory failure.

Topics: Acute Disease; Adolescent; Anti-Bacterial Agents; Anti-Inflammatory Agents; Azithromycin; Dermatomyositis; Dyspnea; Fatal Outcome; Fatty Liver; Female; Humans; Pneumonia; Prednisone

Community-acquired pneumonia (CAP) is a major cause of morbidity and mortality worldwide. Non-compliance with therapy may be associated with deterioration in the patient's condition, treatment failure, and increased use and cost of healthcare resources such as the requirement for additional drugs and hospital admission. Adherence to the prescribed regimen is affected by a number of variables including dosing interval, treatment duration, adverse effects, and palatability in pediatric patients. Accumulating evidence suggests that short-course antimicrobial therapy may be at least as effective as, and in some cases may be more effective than, traditional longer therapies (7-14 days) even in hospital-acquired pneumonia. Given the unique pharmacokinetic properties of azithromycin, attempts have been made to condense the traditional total dose over a 3-5-day period into single-dose therapy with the aim of improving treatment compliance. The results of two phase III CAP trials indicate that a single 2.0 g dose of azithromycin microspheres is a suitable alternative to 7 days of either clarithromycin XL or levofloxacin.

Topics: Anti-Bacterial Agents; Azithromycin; Clarithromycin; Clinical Trials, Phase III as Topic; Community-Acquired Infections; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Levofloxacin; Male; Microspheres; Ofloxacin; Pneumonia; Time Factors; Treatment Outcome

To describe the pharmacology, efficacy, and safety data of the use of single-dose azithromycin for respiratory tract infections in children and adults.. A MEDLINE search (1990-September 2003) was performed to identify all pertinent studies and review articles. When appropriate information was not available in the literature, data were obtained from the product manufacturers or abstracts from international conferences.. All available studies were reviewed to provide pharmacokinetic, pharmacodynamic, efficacy, and safety data on use of single-dose azithromycin for respiratory tract infections.. Several studies have demonstrated that shorter regimens of azithromycin (1500 mg over 3 day vs 5 day or single dose vs 3 day) provide higher serum exposures compared with the longer regimens. This makes it possible to give the same dose over a shorter period of time and achieve the same efficacy with the potential for enhanced adherence. Single-dose azithromycin 30 mg/kg was approved in 2003 for treatment of acute otitis media (AOM) in children. Studies have demonstrated that, when administering azithromycin as a single dose, its efficacy and safety are comparable to that of other standard regimens for AOM. Single-dose regimens for treatment of respiratory tract infections in adults have not been studied widely, with only 2 studies being conducted for treatment of community-acquired pneumonia and one study for treatment of tonsillitis; all demonstrated at least equal efficacy with the single-dose regimen compared with comparators given for longer periods of time.. Available data regarding single-dose azithromycin are promising. Although use of this regimen in children is warranted based on studies to date, additional large-scale trials are needed prior to mainstream use of the regimen in adults.

Topics: Adult; Anti-Bacterial Agents; Azithromycin; Child, Preschool; Community-Acquired Infections; Humans; Otitis Media; Pneumonia; Randomized Controlled Trials as Topic; Respiratory Tract Infections; Safety

The spectrum of acute lower respiratory tract infection ranges from acute bronchitis and acute exacerbations of chronic bronchitis to pneumonia. Annually approximately five million people die of acute respiratory tract infections. Among these, pneumonia represents the most frequent cause of mortality, hospitalization and medical consultation. Azithromycin is a new macrolide antibiotic, structurally modified from erythromycin and is noted for its activity against some gram-negative organisms associated with respiratory tract infections, particularly Haemophilus influenzae (H. influenzae).. To compare the effectiveness of azithromycin to amoxycillin or amoxycillin/clavulanic acid (amoxyclav) in the treatment of LRTI, in terms of clinical failure, incidence of adverse events and microbial eradication.. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 4, 2003), MEDLINE (January 1966 to January Week 3, 2004), and EMBASE (January 1988 to 2003).. Randomised and quasi-randomised controlled trials, which compared azithromycin to amoxycillin or amoxycillin/clavulanic acid in patients with clinical evidence of acute LRTI: acute bronchitis, pneumonia, and acute exacerbation of chronic bronchitis were studied.. The criteria for assessing study quality were generation of allocation sequence, concealment of treatment allocation, blinding, and completeness of the trial. All types of acute lower respiratory tract infections were initially pooled in the meta-analyses. Funnel plot was used to examine publication bias. The heterogeneity of results was investigated by the forest plot and Chi-square test. Index of I(2) was also used to measure inconsistency results among trials. Subgroup analysis was conducted for age, types of respiratory tract infection and types of antibiotic in control groups. Sensitivity analysis was conducted under the condition of trial size and concealment of treatment allocation.. Fourteen trials with 2,521 enrolled patients used 2,416 patients in the analysis. A total of 1,350 patients received azithromycin and 1,066 received amoxicillin or amoxicillin-clavulanic acid. The pooled analysis of all trials showed that there was no significant difference in the incidence of clinical failure on about day 10 to 14 after therapy started between the two groups (relative risk (RR) (random effects) 0.96; 95% CI 0.58 to 1.57). Sensitivity analysis showed that a reduction of clinical failure in azithromycin-treated patients (RR 0.52; 95% CI 0.24 to 1.12) in three adequately concealed studies, compared to RR 1.14 (95% CI 0.62 to 2.08) in eleven studies with inadequate concealment. Eleven trials reported the incidence of microbial eradication and there was no significant difference between the two groups (RR 0.98; 95% CI 0.91 to 1.07). The reduction of adverse events in azithromycin group was RR 0.75 (95% CI 0.56 to 1.00).. There is unclear evidence that azithromycin is superior to amoxicillin or amoxicillin-clavulanic acid in treating acute LRTI. Future trials with high methodological quality are needed.

Topics: Acute Disease; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Azithromycin; Bronchitis; Drug Therapy, Combination; Humans; Pneumonia; Randomized Controlled Trials as Topic; Treatment Failure

The treatment of community-acquired pneumonia (CAP) in children is empirical, being based on the knowledge of the etiology of CAP at different ages. As a result of currently available methods in everyday clinical practice, a microbe-specific diagnosis is not realistic in the majority of patients. Even the differentiation between viral, 'atypical' bacterial (Mycoplasma pneumoniae or Chlamydia pneumoniae) and 'typical' bacterial (Streptococcus pneumoniae) CAP is often not possible. Moreover, up to one-third of CAP cases seem to be mixed viral-bacterial or dual bacterial infections. Recent serologic studies have confirmed that S. pneumoniae is an important causative agent of CAP at all ages. M. pneumoniae is common from the age of 5 years onwards, and C. pneumoniae is common from the age of 10 years onwards. In addition to age, the etiology and treatment of CAP are dependent on the severity of the disease. Pneumococcal infections are predominant in children treated in hospital, and mycoplasmal infections are predominant in children treated at home.In ambulatory patients with CAP, amoxicillin (or penicillin V [phenoxymethylpenicillin]) is the drug of choice from the age of 4 months to 4 years, and at all ages if S. pneumoniae is the presumptive causative organism. Macrolides, preferably clarithromycin or azithromycin, are the first-line drugs from the age of 5 years onwards. In hospitalized patients who need parenteral therapy for CAP, cefuroxime (or penicillin G [benzylpenicillin]) is the drug of choice. Macrolides should be administered concomitantly if M. pneumoniae or C. pneumoniae infection is suspected. Radiologic findings and C-reactive protein (CRP) levels offer limited help for the selection of antibacterials; alveolar infiltrations and high CRP levels indicate pneumococcal pneumonia, but the lack of these findings does not rule out bacterial CAP. Most guidelines recommend antibacterials for 7-10 days (except azithromycin, which has a recommended treatment duration of 5 days). If no improvement takes place within 2 days, therapy must be reviewed.

Topics: Adolescent; Ampicillin; Anti-Bacterial Agents; Azithromycin; Child; Child, Preschool; Community-Acquired Infections; Humans; Infant; Pneumonia; Randomized Controlled Trials as Topic; Severity of Illness Index

We carried out a meta-analysis of randomized controlled trials of azithromycin compared with other antibiotics in the treatment of lower respiratory tract infections, including acute bronchitis (five comparisons including 1372 patients), acute exacerbations of chronic bronchitis (13 comparisons including 1342 patients) and community-acquired pneumonia (18 comparisons with 1664 patients). For the first two indications, azithromycin did not offer any statistically significant reduction in clinical failures [random effects odds ratios 0.84, 95% confidence interval (CI) 0.54-1.31 and 0.64, 95% CI 0.31-1.32, respectively] and absolute risk differences were small. For community-acquired pneumonia, azithromycin significantly reduced clinical failures by about one-third (random effects odds ratio 0.63, 95% CI 0.41-0.95). The absolute incremental benefit was approximately one clinical failure prevented per 50 treated patients with community-acquired pneumonia. There was no significant heterogeneity for different comparators and for bacterial versus atypical pneumonias. Azithromycin was discontinued because of adverse events in only 23 of 3487 patients (0.7%). Although results should be interpreted cautiously as most trials were open-label and susceptible to bias, the meta-analysis indicates that, compared with antibiotics with traditional pharmacokinetics that require more prolonged courses, azithromycin offers no significant advantage for bronchitis, but may be more effective in community-acquired pneumonia.

Topics: Anti-Bacterial Agents; Azithromycin; Bronchitis; Chi-Square Distribution; Chronic Disease; Community-Acquired Infections; Confidence Intervals; Humans; Odds Ratio; Pneumonia; Randomized Controlled Trials as Topic; Respiratory Tract Infections

Histone methylation modification plays an irreplaceable role in the wheezing diseases. The aim of this study was to explore whether azithromycin (AZM) attenuates post-inflammatory wheezing through inhibiting hypermethylation of histone H3K27me3 mediated by EZH2.. A randomized controlled trial was conducted on 227 children who underwent fiber-optic bronchoscopy, and bronchoalveolar lavage fluid (BALF) was collected for analyses. The expressions of IL-6, IL-2, NF-κB P65, EZH2 and H3K27me3 in the BALF of wheezing cases were significantly increased when compared with levels in non-wheezing cases (P < 0.05), while IL-10 was decreased (P < 0.05). AZM attenuated the overexpression of NF-κB P65, EZH2 and H3K27me3 in wheezing cases (P < 0.05) and shortened the time of wheezing in wheezing cases (P < 0.05). An in vitro model of inflammation was established using rat alveolar macrophages induced by lipopolysaccharide (LPS). AZM, SN50 (a NK-κB inhibitor) and GSK126 (an EZH2 inhibitor) attenuated the overexpression of EZH2, NF-κB P65 and H3K27me3 induced by LPS in rat alveolar macrophages (P < 0.05). AZM, SN50 and GSK126 normalized the decreased expression of IL-10 induced by LPS in the same samples (P < 0.05). Co-immunoprecipitation results showed that H3K27me3 interacted with EZH2 and NF-κB P65, and immunofluorescence data showed that AZM and SN50 inhibited LPS-induced NF-κB P65 nuclear translocation in rat alveolar macrophages.. Histone H3K27me3 hypermethylation mediated by EZH2 may be involved in wheezing after pulmonary inflammation. AZM attenuated wheezing after pulmonary inflammation by inhibiting NF-κB P65-related hypermethylation of H3K27me3 mediated by EZH2.

Topics: Animals; Azithromycin; DNA Methylation; Enhancer of Zeste Homolog 2 Protein; Histones; Interleukin-10; Lipopolysaccharides; NF-kappa B; Pneumonia; Rats

The MORDOR study, a masked, community-level randomized clinical trial conducted in Niger, Malawi and Tanzania (2015 to 2017), showed that biannual administration of single-dose azithromycin to preschool children reduced all-cause mortality. We sought to evaluate its impact on causes of death in children aged 1-59 months in Tanzania. A random sampling of 614 communities was conducted in Kilosa District, Tanzania, with simple random assignment of communities to receive either azithromycin or placebo. In these communities, a census was carried out every 6 months and children aged 1-59 months received biannual (every 6 months), single-dose azithromycin (~20mg/kg) or placebo depending on community assignment, over a 2-year period. Mortality was determined at the time of the biannual census. For child deaths, a verbal autopsy was performed to ascertain the cause using a standardized diagnostic classification. A total of 190- (0.58 /100 person-years) and 200 deaths (0.59/100 person-years) were reported in the azithromycin and placebo arms, respectively. Malaria, pneumonia and diarrhea, accounted for 71% and 68% of deaths in the respective arms. Overall, the mortality was not different by treatment arm, nor were the distribution of causes of death after adjusting for community clustering. The cause-specific mortality for diarrhea/pneumonia was no different over time. In children aged 1-5 months, 32 deaths occurred in the placebo arm and 25 deaths occurred in the azithromycin arm; 20 (62.5%) deaths in the placebo- and 10 (40%) in the azithromycin arm were attributed to diarrhea or pneumonia. Neither differences in the number of deaths nor the diarrhea/pneumonia attribution was statistically significant after adjusting for community clustering. In conclusion, azithromycin was not associated with a significant decline in deaths by specific causes compared to placebo. The non-significant lower rates of diarrhea or pneumonia in children <6 months who received azithromycin merit further investigation in high-mortality settings. Trial registration: NCT02048007.

Topics: Anti-Bacterial Agents; Antibiotic Prophylaxis; Azithromycin; Cause of Death; Child, Preschool; Diarrhea; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Infant; Infant, Newborn; Malaria; Malawi; Male; Niger; Pneumonia; Tanzania; Treatment Outcome

In Asia, an estimated one million deaths are caused by communityacquired pneumonia (CAP) each year. Despite the high mortality in elderly people, a large number of CAP patients have been treated and survived with optimal life expectancy. A few studies have been done on adult CAP therapeutic approaches in Asia. Moreover, differences have been noted between these studies and European data. We aimed to investigate the efficacy of oral Levofloxacin (TAVANEX), 750 mg, once daily for five days versus parenteral Ceftriaxone 1gr BD, plus oral Azithromycin (250 mg, once daily) for seven to ten days (standard regimen) in CAP treatment.. We conducted a prospective randomized trial among 150 patients with CAP in Qaem Hospital of Alborz city from December 2016 to June 2017. A group of CAP patients were randomized in two treatment groups. One group was treated with oral Levofloxacin (TAVANEX), 750 mg, once daily for five days and the other group with parenteral Ceftriaxone 1gr BD plus oral Azithromycin (250 mg, once daily) for seven to ten days (standard regimen). The efficacy and side effects of the assigned drugs were compared between two groups. The probability level for statistical significance was set at P ≤ 0.05.. The body temperature (P value=0.09), WBC count (P value=0.15), respiratory sounds (P value=0.18) and admission duration (P value=0.15) showed no significant differences after treatment between two groups. There was no report of hospital mortality, clinical deterioration and antibiotic escalation during hospital admission in both groups of study. In standard regimen group, only two (2.7%) patients had skin rash while in Levofloxacin group one case (1.3%) had skin rash, two patients (2.7%) had gastrointestinal problems and three (4%) patients showed central nervous system (CNS) complications. In both groups, the reticulonodular pattern was more frequently observed in Chest X-ray. Although standard regimen group (n=27, 36%) showed more consolidation than patients in Levofloxacin group (n=22, 29.3%), and the ground glass pattern was observed more in Levofloxacin group.. We concluded that monotherapy with oral Levofloxacin was as effective as treatment with Ceftriaxone plus Azithromycin combination in patients with CAP who required hospitalization.

Topics: Administration, Intravenous; Administration, Oral; Adult; Aged; Anti-Bacterial Agents; Asia; Azithromycin; Ceftriaxone; Community-Acquired Infections; Drug Administration Schedule; Drug Therapy, Combination; Female; Hospitalization; Humans; Levofloxacin; Male; Middle Aged; Pneumonia; Prospective Studies; Treatment Outcome

This randomised, open-label, non-inferiority study was designed to demonstrate that a 3-day course of oral azithromycin 1 g once daily was at least as effective as a standard 7-day course of oral amoxicillin-clavulanate 875/125 mg twice daily in the treatment of outpatients with community-acquired pneumonia (Fine class I and II). In total, 267 patients with clinically and radiologically confirmed community-acquired pneumonia were randomly assigned to receive either the azithromycin (n=136) or the amoxicillin-clavulanate (n=131) regimen. At screening, 60/136 (58.8%) and 61/131 (62.9%) respectively had at least one pathogen identified by sputum culture, PCR, or serology. The primary endpoint was the clinical response in the intent-to-treat population at the end of therapy (day 8 to 12). Clinical success rates were 126/136 (92.6%) for azithromycin and 122/131 (93.1%) for amoxicillin-clavulanate (treatment difference: - 0.48%; 95% confidence interval: - 5.66%; 4.69%). Clinical and radiological success rates at follow-up (day 22-26) were consistent with the end of therapy results, no patient reporting clinical relapse. Bacteriological success rates at the end of therapy were 32/35 (91.4%) for azithromycin and 30/33 (90.9%) for amoxicillin-clavulanate (treatment difference: 0.52%; 95% confidence interval - 10.81%; 11.85%). Both treatment regimens were well tolerated: the overall incidence of adverse events was 34/136 (25.0%) for azithromycin and 22/132 (16.7%) for amoxicillin-clavulanate. In both treatment groups, the most commonly reported events were gastrointestinal symptoms. Azithromycin 1g once daily for 3 days is at least as effective as amoxicillin-clavulanate 875/125 mg twice daily for 7 days in the treatment of adult patients with community-acquired pneumonia.

Topics: Adolescent; Adult; Aged; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Azithromycin; Community-Acquired Infections; Female; Humans; Male; Middle Aged; Pneumonia; Treatment Outcome

This study compared patients with moderate-to-severe community-acquired pneumonia (CAP) requiring hospitalisation, who received initial therapy with either intravenous ceftriaxone plus intravenous azithromycin, followed by step-down to oral azithromycin (n = 135), with patients who received intravenous ceftriaxone combined with either intravenous clarithromycin or erythromycin, followed by step-down to either oral clarithromycin or erythromycin (n = 143). Clinical and bacteriological outcomes were evaluated at the end of therapy (EOT; day 12-16) or at the end of study (EOS; day 28-35). At baseline, mean APACHE II scores were 13.3 and 12.6, respectively, with >50% of patients classified as Fine Pneumonia Severity Index (PSI) category IV or V. Clinical success rates (cure or improvement) in the modified intent-to-treat (MITT) population at EOT were 84.3% in the ceftriaxone/azithromycin group and 82.7% in the ceftriaxone/clarithromycin or erythromycin group. At EOS, MITT success rates (cure only) were 81.7% and 75.0%, respectively. Equivalent success rates in the clinically evaluable population were 83% and 87%, respectively, at EOT, and 79% and 78%, respectively, at EOS. MITT bacteriological eradication rates were 73.2% and 67.4%, respectively, at EOT, and 68.3% vs. 60.9%, respectively, at EOS. Mean length of hospital stay (LOS) was 10.7 and 12.6 days, and the mean duration of therapy was 9.5 and 10.5 days, respectively. The incidence of infusion-related adverse events was 16.3% and 25.2% (p 0.04), respectively. An intravenous-to-oral regimen of ceftriaxone/azithromycin was at least equivalent in efficacy and safety to the comparator regimen and appeared to be a suitable treatment option for hospitalised patients with CAP.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anti-Bacterial Agents; Azithromycin; Ceftriaxone; Clarithromycin; Community-Acquired Infections; Drug Therapy, Combination; Erythromycin; Female; Hospitalization; Humans; Injections, Intravenous; Male; Middle Aged; Pneumonia; Prospective Studies; Random Allocation; Treatment Outcome

This randomized, double-blind, noninferiority study was designed to demonstrate that a single 2.0-g oral dose of a novel microsphere formulation of azithromycin was at least as effective as 7 days of levofloxacin, 500 mg/day, in the treatment of adult patients with mild to moderate community-acquired pneumonia (Fine classes I, II, and III). In total, 427 subjects were randomly assigned to receive either a single 2.0-g dose of azithromycin microspheres (n = 213) or a 7-day regimen of levofloxacin (n = 214). At baseline, 219 of 423 (51.8%) treated subjects had at least one pathogen identified by culture, PCR, or serology. The primary end point was the clinical response (cure or failure) in the "clinical per protocol" population at test of cure (days 13 to 24). Clinical cure rates were 89.7% (156 of 174) for azithromycin microspheres and 93.7% (177 of 189) for levofloxacin (treatment difference, -4.0%; 95% confidence interval, -9.7%, 1.7%). Bacteriologic success at test of cure in the "bacteriologic per protocol" population was 90.7% (97 of 107) for azithromycin microspheres and 92.3% (120 of 130) for levofloxacin (treatment difference, -1.7%; 95% confidence interval, -8.8%, 5.5%). Both treatment regimens were well tolerated; the incidence of treatment-related adverse events was 19.9% and 12.3% for azithromycin and levofloxacin, respectively. A single 2.0-g dose of azithromycin microspheres was at least as effective as a 7-day course of levofloxacin in the treatment of mild to moderate community-acquired pneumonia in adult outpatients.

Topics: Adult; Aged; Anti-Bacterial Agents; Azithromycin; Chemistry, Pharmaceutical; Community-Acquired Infections; Double-Blind Method; Female; Humans; Incidence; Levofloxacin; Male; Microspheres; Middle Aged; Ofloxacin; Outpatients; Pneumonia; Serologic Tests; Time Factors; Treatment Outcome

Community-acquired pneumonia (CAP) is a major cause of morbidity and mortality worldwide. The inability or failure of many subjects to adhere to standard antibiotic regimens, which may last up to 10 days, results in suboptimal antibiotic treatment. Treatment with a single-dose antibiotic regimen may improve compliance with prescribed therapy. A novel microsphere formulation of azithromycin provides a single-dose regimen while maintaining tolerability.. To compare the efficacy and safety of a single 2.0-g dose of azithromycin microspheres to that of an extended-release formulation of clarithromycin (1.0 g/d for 7 days) for the treatment of adults with mild-to-moderate CAP.. A phase III, multinational, multicenter, randomized, double-blind, double-dummy study, comparing single-dose azithromycin microspheres to extended-release clarithromycin, both administered orally.. Subjects with mild-to-moderate CAP (Fine class I and II) were included. The primary end point was clinical response at the test-of-cure (TOC) visit (days 14 to 21) in the clinical per protocol (CPP) population. The bacteriologic response at the TOC visit was assessed in subjects with a baseline pathogen.. A total of 501 subjects were randomized, and 499 were treated. Clinical cure rates at the TOC visit in the CPP population were 92.6% (187 of 202 subjects) for azithromycin microspheres and 94.7% (198 of 209 subjects) for extended-release clarithromycin. Overall pathogen eradication rates were 91.8% (123 of 134 subjects) for azithromycin microspheres and 90.5% (153 of 169 subjects) for extended-release clarithromycin. Both agents were well tolerated. The incidence of treatment-related adverse events was 26.3% with azithromycin microspheres and 24.6% with extended-release clarithromycin. Most adverse events were mild to moderate in severity.. A single 2.0-g dose of azithromycin microspheres was as effective and well tolerated as a 7-day course of extended-release clarithromycin in the treatment of adults with mild-to-moderate CAP.

Topics: Adult; Aged; Anti-Bacterial Agents; Azithromycin; Clarithromycin; Community-Acquired Infections; Delayed-Action Preparations; Double-Blind Method; Female; Humans; Male; Microspheres; Middle Aged; Pneumonia

Topics: Administration, Oral; Adult; Anti-Bacterial Agents; Azithromycin; Clarithromycin; Community-Acquired Infections; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Pneumonia; Prospective Studies

Community-acquired pneumonia (CAP) is associated with considerable morbidity and mortality in both developed and developing countries. Despite research into the optimal management of this condition, there remains great variation in how patients with CAP are treated. A study was performed to assess the results of CAP treatment using a clinical pathway that incorporated admission guidelines, standard treatment orders with oral levofloxacin or cefuroxime axetil plus azithromycin, and an algorithm for oxygen therapy and discharge. The study involved seven centers enrolling 7,734 patients, 55% of whom were treated as outpatients and the remainder were admitted. Overall mortality was 8%, and increasing severity of illness, as assessed by pneumonia severity risk score, was associated with early mortality (within five days of admission) and late mortality (five or more days following admission). The use of the clinical pathway was associated with a reduction in early mortality. The use of levofloxacin alone or with cefuroxime axetil plus azithromycin was associated with decreased mortality compared with the use of other antibiotics.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Ambulatory Care; Anti-Infective Agents; Azithromycin; Cefuroxime; Community-Acquired Infections; Critical Pathways; Drug Therapy, Combination; Female; Humans; Levofloxacin; Longitudinal Studies; Male; Middle Aged; Ofloxacin; Oxygen Inhalation Therapy; Pneumococcal Infections; Pneumonia; Pneumonia, Bacterial; Treatment Outcome

Changing etiologic patterns and the growing problem of antimicrobial resistance, particularly an increase in macrolide-resistant pneumococcal bacteremia, are causing physicians to adopt new approaches to the treatment of community-acquired pneumonia (CAP).. The relative efficacy and tolerability of levofloxacin monotherapy and azithromycin and ceftriaxone combination therapy were assessed in hospitalized adults with moderate to severe CAP.. This Phase IV, multicenter, open-label, randomized trial compared 2 treatment regimens: (1) levofloxacin 500 mg PO or IV q24h, and (2) azithromycin 500 mg IV q24h for > or = 2 days plus ceftriaxone 1 g IV q24h for 2 days, followed by an optional transition to azithromycin 500 mg PO q24h at the investigator's discretion. The total duration of therapy was to be a minimum of 10 days in both treatment groups. Ceftriaxone was included in the initial azithromycin regimen to ensure coverage against pneumococcal bacteremia.. Of 236 patients in the intent-to-treat population, completion or withdrawal information was available for 110 patients in the levofloxacin group and 114 in the azithromycin group. Baseline demographic and disease characteristics were comparable between groups. At the end of treatment, the clinical success rate (cured + improved) in clinically evaluable patients was 94.1% in the levofloxacin group and 92.3% in the azithromycin group. The respective posttherapy microbiologic eradication rates were 89.5% and 92.3%. Levofloxacin was as well tolerated as azithromycin, with an incidence of drug-related adverse events (AEs) for all body systems of 5.3% and 9.3%, respectively. None of the drug-related AEs were considered serious [corrected].. In this study in hospitalized patients with moderate to severe CAP, levofloxacin monotherapy was at least as effective as a combination regimen of azithromycin and ceftriaxone in providing coverage against the current causative pathogens in CAP. In addition, levofloxacin was as well tolerated as the combination of azithromycin and ceftriaxone.

Topics: Adult; Aged; Aged, 80 and over; Azithromycin; Ceftriaxone; Community-Acquired Infections; Drug Therapy, Combination; Female; Humans; Levofloxacin; Male; Middle Aged; Ofloxacin; Pneumonia; Severity of Illness Index

To conduct a cost-effectiveness analysis of IV-to-oral regimens of azithromycin vs cefuroxime with or without erythromycin in the treatment of patients hospitalized with community-acquired pneumonia (CAP).. Of the 268 evaluable patients enrolled into a randomized, multicenter clinical trial of adults, 266 patients had sufficient data to be included in this cost-effectiveness analysis. One hundred thirty-six patients received azithromycin, and 130 patients received cefuroxime with or without erythromycin.. A pharmacoeconomic analysis from the hospital provider perspective was conducted. Health-care resource utilization was extracted from the clinical database and converted to national reference costs. Decision analysis was used to structure and characterize outcomes. Sensitivity analyses were performed, and statistics were applied to the cost-effectiveness ratios.. The clinical success and adverse event rates and antibiotic-related length of stay were 78%, 11.8%, and 5.8 days for the azithromycin group and 75%, 20.7%, and 6.4 days for the group receiving cefuroxime with or without erythromycin, respectively. Geometric mean treatment costs were 4,104 US dollars (95% confidence interval [CI], 3,874 to 4,334 US dollars) for the azithromycin group, and 4,578 US dollars (95% CI, 4,319 to 4,837 US dollars) for the group receiving cefuroxime with or without erythromycin (p = 0.06). The cost-effectiveness ratios were 5,265 US dollars per expected cure for the azithromycin group, and 6,145 US dollars per expected cure for group receiving cefuroxime with or without erythromycin (p = 0.05).. Despite a higher per-dose purchase price, overall costs with azithromycin tended to be lower due to decreased duration of therapy, lower preparation and administration costs, and reduced hospital length of stay. As empiric therapy, azithromycin monotherapy was cost-effective compared to cefuroxime with or without erythromycin for patients hospitalized with CAP who have no underlying cardiopulmonary disease, and no risk factors for either drug-resistant pneumococci or enteric Gram-negative pathogens.

Topics: Administration, Oral; Adult; Aged; Azithromycin; Cefuroxime; Community-Acquired Infections; Confidence Intervals; Cost-Benefit Analysis; Drug Therapy, Combination; Economics, Pharmaceutical; Erythromycin; Female; Humans; Infusions, Intravenous; Male; Middle Aged; Pneumonia; Probability; Sensitivity and Specificity

To compare the efficacy and safety of azithromycin dihydrate monotherapy with those of a combination of cefuroxime axetil plus erythromycin as empirical therapy for community-acquired pneumonia in hospitalized patients.. Patients were enrolled in a prospective, randomized, multicenter study. The standard therapy of cefuroxime plus erythromycin was consistent with the American Thoracic Society, Canadian Community-Acquired Pneumonia Consensus Group, and Infectious Disease Society of America consensus guidelines. The doses were intravenous azithromycin (500 mg once daily) followed by oral azithromycin (500 mg once daily), intravenous cefuroxime (750 mg every 8 hours), followed by oral cefuroxime axetil (500 mg twice daily), and erythromycin (500-1000 mg) intravenously or orally every 6 hours. Randomization was stratified by severity of illness and age. Patients who were immunosuppressed or residing in nursing homes were excluded.. Data from 145 patients (67 received azithromycin and 78 received cefuroxime plus erythromycin) were evaluable. Streptococcus pneumoniae and Haemophilus influenzae were isolated in 19% (28/145) and 13% (19/145), respectively. The atypical pathogens accounted for 33% (48/145) of the etiologic diagnoses; Legionella pneumophila, Chlamydia pneumoniae, and Mycoplasma pneumoniae were identified in 14% (20/ 145), 10% (15/145), and 9% (13/145), respectively. Clinical cure was achieved in 91% (61/67) of the patients in the azithromycin group and 91% (71/78) in the cefuroxime plus erythromycin group. Adverse events (intravenous catheter site reactions, gastrointestinal tract disturbances) were significantly more common in patients who received cefuroxime plus erythromycin (49% [30/78]) than in patients who received azithromycin (12% [8/67]) (P<.001).. Treatment with azithromycin was as effective as cefuroxime plus erythromycin in the empirical management of community-acquired pneumonia in immunocompetent patients who were hospitalized. Azithromycin was well tolerated.

Topics: Anti-Bacterial Agents; Azithromycin; Cefuroxime; Cephalosporins; Community-Acquired Infections; Drug Therapy, Combination; Erythromycin; Humans; Microbial Sensitivity Tests; Pneumonia; Prospective Studies

The purpose of this study was to evaluate intravenous (i.v.) azithromycin followed by oral azithromycin as a monotherapeutic regimen for community-acquired pneumonia (CAP). Two trials of i.v. azithromycin used as initial monotherapy in hospitalized CAP patients are summarized. Clinical efficacy is reported from an open-label randomized trial of azithromycin compared to cefuroxime with or without erythromycin. Bacteriologic and clinical efficacy results are also presented from a noncomparative trial of i.v. azithromycin that was designed to give additional clinical experience with a larger number of pathogens. Azithromycin was administered to 414 patients: 202 and 212 in the comparative and noncomparative trials, respectively. The comparator regimen was used as treatment for 201 patients; 105 were treated with cefuroxime alone and 96 were given cefuroxime plus erythromycin. In the comparative trial, clinical outcome data were available for 268 evaluable patients with confirmed CAP at the 10- to 14-day visit, with 106 (77%) of the azithromycin patients cured or improved and 97 (74%) of the comparator patients cured or improved. Mean i.v. treatment duration and mean total treatment duration (i.v. and oral) for the clinically evaluable patients were significantly (P < 0.05) shorter for the azithromycin group (3.6 days for the i.v. group and 8.6 days for the i.v. and oral group) than for the evaluable patients given cefuroxime plus erythromycin (4.0 days for the i.v. group and 10.3 days for the i.v. and oral group). The present comparative study demonstrates that initial therapy with i.v. azithromycin for hospitalized patients with CAP is associated with fewer side effects and is equal in efficacy to a 1993 American Thoracic Society-suggested regimen of cefuroxime plus erythromycin when the erythromycin is deemed necessary by clinicians.

Topics: Administration, Oral; Adolescent; Adult; Aged; Anti-Bacterial Agents; Azithromycin; Community-Acquired Infections; Female; Hospitalization; Humans; Infusions, Intravenous; Male; Microbial Sensitivity Tests; Middle Aged; Penicillin Resistance; Pneumonia; Streptococcus pneumoniae

Lower respiratory tract infection (LRTI) is one of the major health problems in developing countries such as Indonesia. According to the National Household Health Survey conducted by the Ministry of Health in 1992, LRTIs still rank fourth as the main cause of death in Indonesia. The problem of LRTIs could be simply managed as long as the causative organism can be identified and the proper antibiotic known. In some occasions, it is not quite so easy to identify the causative micro-organism, especially in lower tract infections. There are several methods of obtaining specimens from LRTIs for cultures. The easiest, most simple way is to collect expectorated sputum. Unfortunately, because of the high rate of contamination by upper respiratory tract flora, this method is not reliable. Recognizing the difficulties with routine expectorated sputum cultures, two alternative approaches have been suggested. One approach is to bypass potential expectorated sputum 'contaminants' in the oropharynx by transtracheal aspiration or transthoracic aspiration. The second approach is to modify the usual technique of processing expectorated sputum by either washing techniques or by quantitative cultures. Azithromycin and clarithromycin are chemically related to macrolide erithromycin. Both antibiotics retain the traditional macrolide spectrum of activity against gram-positive and atypical pneumonia pathogens, while demonstrating improved activity against gram-negative bacteria. The American Thoracic Society (ATS) recommended the use of macrolide for outpatients with community-acquired pneumonia, without comorbidity and 60 years of age or younger. A total of 34 outpatients with acute LRTIs were open-comparative, randomly allocated to treatment with the new macrolide in Persahabatan Hospital, Jakarta, 1996. The purposes of this study were: (i) to identify the causative micro-organisms; and (ii) to evaluate the clinical efficacy of the new macrolide in these infections. Azithromycin 500 mg was given orally once a day for 3 days and was administered 1 h before or 2 h after every meal. Clarithromycin 500 mg was given orally every 12 h for 10 days. The diagnosis of the patients were: 16 with pneumonia, 10 with acute bronchitis and 8 with acute exacerbation of chronic bronchitis. In this study of 34 patients, the sputum specimens were washed with N acetylcysteine before culture and we could only detect micro-organisms in one patient. Before treatment, we found 47 strains in 33 (97.05

Topics: Administration, Oral; Adult; Anti-Bacterial Agents; Azithromycin; Bronchitis; Clarithromycin; Female; Humans; Klebsiella pneumoniae; Male; Pneumonia; Respiratory Tract Infections; Specimen Handling; Sputum; Staphylococcus aureus; Streptococcus; Streptococcus pneumoniae

The efficacies and safeties of a 3-day, 3-dose course of azithromycin (10 mg/kg of body weight per day) and a 10-day, 30-dose course of erythromycin (40 mg/kg/day) for the treatment of acute lower respiratory tract infections in children were compared in an open randomized multicenter study. Sixty-eight of 85 evaluable patients (80%) had radiologically proven pneumonia, and 20% had bronchitis. Treatment success defined as cure or major improvement was achieved in 42 of 45 (93%) azithromycin recipients versus 36 of 40 (90%) erythromycin recipients. Adverse events were reported in 12 of 45 and 6 of 40 of the patients treated with azithromycin and erythromycin, respectively, a difference which was not statistically significant. In conclusion, a 3-day course of azithromycin is as effective as a 10-day course of erythromycin in the treatment of community-acquired lower respiratory tract infections in children, with comparable safety and acceptability profiles. This shorter treatment course might have a beneficial effect on compliance, especially in the pediatric age group.

Topics: Adolescent; Anti-Bacterial Agents; Azithromycin; Bronchitis; Child; Child, Preschool; Community-Acquired Infections; Erythromycin; Follow-Up Studies; Humans; Pneumonia; Prospective Studies; Respiratory Tract Infections

An open, randomized, multicentre study compared the efficacy and safety of 3-day azithromycin with 10-day roxithromycin for the treatment of atypical pneumonia. Azithromycin was administered 500 mg once daily to 90 and roxithromycin 150 mg bid to 60 patients. Causative pathogens were identified by serological methods. In the azithromycin treatment group, Mycoplasma pneumoniae was identified in 65, Chlamydia spp. in 9 and Coxiella burnetti in 1 patient. In the roxithromycin treatment group, M. pneumoniae was identified in 39, Chlamydia spp. in 9 and C. burnetti in 3 patients. 89 azithromycin and 53 roxithromycin patients were eligible for efficacy analysis. Clinical cure rate was 98.9% in the azithromycin and 94.3% in the roxithromycin treatment group. Adverse events were observed in 3 patients in each group. Azithromycin appears to be as effective as roxithromycin for the treatment of atypical pneumonia. The 3-day azithromycin regimen may offer an additional advantage over 10-day roxithromycin by virtue of its more convenient administration.

Topics: Adolescent; Adult; Aged; Azithromycin; Chlamydia; Chlamydia Infections; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Mycoplasma pneumoniae; Pneumonia; Pneumonia, Mycoplasma; Q Fever; Roxithromycin; Treatment Outcome

A total of 51 patients with acute exacerbation of chronic bronchitis and pneumonia were enrolled: 27 treated with azithromycin (500 mg once a day for 3 days), and 24 with roxithromycin (150 mg every 12 hours for 7 days). The two regimens were equally effective, with clinical cure in 80% and 72% of patients respectively. Bacteriological eradication on day 19-23 was obtained in 7/11 cases (64%) and in 6/13 cases (46%) in the two groups, respectively. No side effects occurred in patients treated with azithromycin, while they occurred in the roxithromycin group (2 vomiting and 1 gastritis). Clinical and bacteriological efficacy, excellent tolerability, simplified dosage (single daily dose) and short-course (3 days) therapeutic regimen make azithromycin, in our experience, efficacious for the treatment of acute exacerbation of chronic bronchitis and community-acquired pneumonia.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Azithromycin; Bacterial Infections; Bronchitis; Chronic Disease; Drug Administration Schedule; Erythromycin; Female; Humans; Male; Middle Aged; Pneumonia; Prospective Studies; Roxithromycin; Treatment Outcome

The efficacy and safety of azithromycin and clarithromycin in lower respiratory tract infection (LRTI) were compared in an open, multicentre study. Five hundred and ten adult patients with a diagnosis of LRTI, including acute bronchitis, acute infective exacerbations of chronic bronchitis (AIECB) or pneumonia were enrolled. The patients were randomly assigned to receive either azithromycin (n = 252) as a single daily dose of 500 mg for three days, or clarithromycin (n = 258) 250 mg twice daily for ten days. In AIECB patients, baseline comparisons of the two treatment groups showed that there were no differences in the number of previous episodes of infection or in the incidence of current or past smokers. The overall clinical efficacy was found to be similar in each treatment group on day 10 to 14, with a satisfactory response (cured or improved) in 94% of azithromycin- and 97% of clarithromycin-treated patients. At follow-up evaluation (day 18 to 22), 97% of azithromycin- and 100% of clarithromycin-treated patients who had improved at day 10 to 14, showed satisfactory outcomes. Bacteriological efficacy was similar in both treatment groups, with eradication of 100% vs 95% of isolates in the azithromycin and clarithromycin groups, respectively. In AIECB, 100% of pathogens were eradicated by azithromycin, although one patient was clinically assessed as failed. Clarithromycin eradicated 93% of pathogens in this group; all patients being assessed as cured or improved. Both drugs were well tolerated, with 9% and 6% of patients reporting adverse events with azithromycin and clarithromycin, respectively. These adverse events were largely gastrointestinal in origin. It was concluded that a three-day course of azithromycin is as effective and well tolerated as a ten-day course of clarithromycin in adults with acute LRTIs.

Topics: Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; Azithromycin; Bacterial Infections; Bronchitis; Clarithromycin; Drug Administration Schedule; Erythromycin; Female; Humans; Male; Middle Aged; Pneumonia; Respiratory Tract Infections

The clinical efficacy and tolerance of a three-day course of azithromycin was evaluated in patients with community-acquired pneumonia in an open, non-comparative pilot study. Sixty-six patients with clinical and radiological findings of pneumonia were treated with a total dose of 1.5 g azithromycin (500 mg once-daily for three days). Of these 66 patients, 40 were evaluable clinically and microbiologically. Of the remaining 26 patients, 22 had no organisms isolated at baseline, and could only be evaluated clinically; two patients were lost to follow-up; and two patients were protocol violators. Of the 40 patients in whom aetiological agents were identified, 39 (98%) had a satisfactory clinical response (34 cured, five improved), including all eight patients diagnosed as having Legionella pneumophila pneumonia on the basis of serology. One patient with recurrent Haemophilus influenzae infection on day 8 was considered a failure. Total severity score for overall signs and symptoms was reduced significantly from a baseline level by day 2 (P = 0.0001). Bacteriological eradication was achieved in 32 of 33 (97%) isolates including 27 of 27 Streptococcus pneumoniae, the most frequently isolated pathogen. All six patients with pneumococcal bacteraemia were cured clinically by day 14, and blood cultures were negative for four of these patients within 48 h. Treatment-related side effects were reported in 4 of 66 (6%) patients, but were all mild. Laboratory abnormalities were observed in 5 of 62 (8%) patients: elevated liver enzymes (2), elevated creatine levels (1), haematological test abnormalities (2), including one patient with severe eosinophilia.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Azithromycin; Drug Administration Schedule; Erythromycin; Female; Humans; Male; Middle Aged; Pilot Projects; Pneumonia

Forty-eight patients with acute bronchitis and four with pneumonia were randomly assigned to receive five doses (500 mg on day 1, plus 250 mg/day on days 2-5) of azithromycin; 54 patients with acute bronchitis and four with pneumonia were assigned 30 doses (625 mg every eight hours for ten days) of amoxicillin/clavulanic acid (CA). The two regimens were equally effective, with clinical improvement or cure in 92% and 87% of patients respectively, bacteriological cure in 89% and 86%, with 91% and 89% of pathogens eliminated. Minor side effects occurred in 6% and 12% of patients in the two groups, respectively. No major abnormalities in laboratory safety parameters were seen in either group.

Topics: Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Azithromycin; Bronchitis; Clavulanic Acids; Drug Administration Schedule; Drug Therapy, Combination; Erythromycin; Female; Humans; Male; Middle Aged; Pneumonia; Pseudomonas aeruginosa; Streptococcus pneumoniae

This was a randomized, third-party-blinded, multicenter study that compared once-daily azithromycin (500 mg on day 1, followed by 250 mg on days 2-5) to cefaclor (500 mg three times daily for 10 days) in the treatment of patients with acute bronchitis or pneumonia. A total of 546 patients were entered into the study and 272 patients were evaluable for efficacy analysis. Of these, 249 (176 azithromycin, 73 cefaclor) had bronchitis and 23 (15 azithromycin, 8 cefaclor) had pneumonia. The combined clinical cure and improvement rate, as determined by the investigator, was 96% for azithromycin and 94% for cefaclor, with 88% bacteriologic eradication in both treatment groups. The elimination of Haemophilus influenzae was significantly better with azithromycin (94.5%) than with cefaclor (61.1%) (p less than 0.001; Fisher's exact two-tail test). The two antibiotics were well tolerated during this study; the incidence of side effects reported was similar for azithromycin and cefaclor. Approximately two thirds of the side effects were mild. Only minor abnormalities in the screening laboratory tests were noted. This study shows that a 5-day course of once-daily azithromycin is as effective as a 10-day three times daily course of cefaclor in the treatment of patients with acute lower respiratory tract infections.

Topics: Azithromycin; Bronchitis; Cefaclor; Erythromycin; Haemophilus Infections; Humans; Klebsiella Infections; Moraxella catarrhalis; Neisseriaceae Infections; Pneumonia; Prospective Studies; Sputum; Staphylococcal Infections; Streptococcal Infections

In this randomised, double-blind study carried out in 28 centres, azithromycin (500 mg single dose on day 1, followed by 250 mg once-daily on days 2-5) was compared with cefaclor (500 mg t.i.d. for 10 days) in the treatment of acute bacterial pneumonia. A total of 119 patients entered the study, and of these 71 were evaluable and included in the efficacy analysis. The overall satisfactory clinical response was 97.3% for azithromycin patients and 100% for cefaclor patients. The clinical cure rates of azithromycin and cefaclor were 46.9% and 41.0%, respectively; improvement was seen in an additional 46.9% of azithromycin-treated patients and in 59.0% of the cefaclor group. The bacteriological eradication rates were 80.4% and 92.6%, respectively. These rates of clinical and bacteriological efficacy, were not statistically different. Both antibiotics were well tolerated during the study; only two patients (one on each study drug) discontinued medication due to adverse events. The overall incidence of side effects was 18.9% (10 of 53 patients) for azithromycin- and 12.1% (eight of 66 patients) for cefaclor-treated patients. Gastrointestinal disturbances were the most commonly reported side effects (nine of 10 azithromycin-treated patients and six of eight cefaclor-treated patients). In addition, two cefaclor patients reported headache. All azithromycin side effects were mild or moderate in severity, but there were two severe occurrences in the cefaclor group (1 nausea, 1 vomiting) the later leading to discontinuation.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acute Disease; Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Azithromycin; Bacterial Infections; Cefaclor; Double-Blind Method; Drug Administration Schedule; Erythromycin; Female; Humans; Male; Middle Aged; Pneumonia

This open, randomised clinical study, conducted from June 1988 to December 1989, included 84 patients with clinical and radiological findings of atypical pneumonia. All patients were treated with a total dose of 1.5 g azithromycin, a new azalide antibiotic. In Group I, azithromycin was administered for three days (500 mg once daily). In Group II, azithromycin was administered for five days (250 mg b.i.d. on day 1, followed by 250 mg once daily on days 2 to 5). Causative pathogens were identified by serological methods. Of the 41 patients in Group I, Mycoplasma pneumoniae, Chlamydia psittaci and Coxiella burnetti were identified in 19, 4 and 3 patients, respectively. In Group II there were 43 patients; Mycoplasma pneumoniae was identified in 24, Chlamydia psittaci in 4 and Coxiella burnetti in 3. Only patients with known causative pathogens were included in the evaluation of clinical efficacy. All patients were clinically cured by day 5; most of the patients became afebrile within 48 h of starting treatment. Side effects were observed in one patient in Group I and in one patient in Group II. The results suggest that a 1.5 g total dose of azithromycin is equally effective when administered as a three- or five-day regimen for the treatment of atypical pneumonia.

Topics: Adult; Azithromycin; Chlamydia Infections; Drug Administration Schedule; Erythromycin; Female; Humans; Male; Middle Aged; Phagocytes; Pneumonia; Pneumonia, Mycoplasma; Q Fever

An open, randomized, multicentre study compared the efficacy and safety of the prototype, azalide, azithromycin, and erythromycin in the treatment of atypical pneumonias. Azithromycin was administered for five days at a dosage of 250 mg bd on day 1 and 250 mg once daily on days 2 to 5. Erythromycin was given for ten days at 500 mg qid. Causative pathogens were identified by serological methods. Of 57 patients treated with azithromycin, Mycoplasma pneumoniae and Chlamydia psittaci were identified in 31 and eight patients, respectively. Of 44 patients treated with erythromycin, M. pneumoniae and C. psittaci were identified in 24 and eight patients, respectively. There were no therapeutic failures in either treatment group. Side effects were observed in one of 57 patients on azithromycin and in six of 44 patients on erythromycin. Azithromycin appears to be as effective as erythromycin in the treatment of atypical pneumonias and better tolerated.

Topics: Adolescent; Adult; Aged; Azithromycin; Child; Chlamydophila psittaci; Erythromycin; Female; Humans; Male; Middle Aged; Mycoplasma pneumoniae; Pneumonia; Pneumonia, Mycoplasma

In an open, multicenter randomized clinical trial on patients with acute pneumonia, 5-day therapy using a new oral macrolide antibiotic, azithromycin (Az), was compared with standard 10-day therapy using another macrolide, josamycin (J). Eighty-nine patients were treated (46 Az, 43 J); both groups were comparable, except in terms of the sex ratios. The causative agent was determined in 31 cases; streptococcal pneumonia was the most common diagnosis (48%). Cure rates were 93% for J and 80% for Az (p greater than 0.30), as judged by a fall in body temperature and an improvement in clinical condition and in radiographic findings. Among 6 failures, there were 4 cases of empyema (1 J, 3 Az). Of 6 deaths, 2 were pneumonia-dependent (1 J and 1 Az, Haemophilus and Streptococcus pneumoniae, respectively). We conclude that 5-day Az is as effective as 10-day J and that such short-course therapy is an advantage in the treatment of pneumonia caused by macrolide susceptible pathogens.

Topics: Adult; Aged; Aged, 80 and over; Azithromycin; Drug Administration Schedule; Drug Tolerance; Erythromycin; Female; Humans; Josamycin; Male; Middle Aged; Multicenter Studies as Topic; Pneumonia; Randomized Controlled Trials as Topic

The potential antimicrobial and anti-inflammatory effectiveness of azithromycin against severe influenza is yet unclear. We retrospectively investigated the effect of intravenous azithromycin administration within 7 days of hospitalization in patients with influenza virus pneumonia and respiratory failure. Using Japan's national administrative database, we enrolled and classified 5066 patients with influenza virus pneumonia into severe, moderate, and mild groups based on their respiratory status within 7 days of hospitalization. The primary endpoints were total, 30-day, and 90-day mortality rates. The secondary endpoints were the duration of intensive-care unit management, invasive mechanical ventilation, and hospital stay. The inverse probability of the treatment weighting method with estimated propensity scores was used to minimize data collection bias. Use of intravenous azithromycin was proportional to the severity of respiratory failure (mild: 1.0%, moderate: 3.1%, severe: 14.8%). In the severe group, the 30-day mortality rate was significantly lower with azithromycin (26.49% vs. 36.65%,

Topics: Azithromycin; Hospitalization; Humans; Influenza, Human; Orthomyxoviridae; Pneumonia; Propensity Score; Respiratory Insufficiency; Retrospective Studies

Community-acquired pneumonia (CAP) is a significant source of hospital admissions and mortality. Atypical organisms are implicated in up to 40% of cases of CAP diagnoses. We studied the difference in outcomes of severe CAP patients treated with doxycycline versus azithromycin in addition to β-lactam therapy.. This was a prospective observational cohort study from March 2020 to July 2022 in a medical ICU (MICU) of an academic quaternary medical center. Adults ≥18 years admitted to the MICU receiving doxycycline or azithromycin in addition to β-lactam therapy for the treatment of CAP were included for analysis. The primary outcomes were in-hospital and 30 day mortality. Secondary outcomes were ICU and hospital length-of-stay, 30 day readmission, days of mechanical ventilation, escalation and duration of antibiotics, adverse effects such as Clostridioides difficile infection and QTc prolongation.. Sixty-three patients were in the azithromycin group and eighty-six patients in the doxycycline group. Both groups had similar APACHE IV and CURB-65 scores. The mean Charlson Comorbidity Index score was higher for the doxycycline group compared with the azithromycin group (P = 0.04). There was no statistically significant difference in in-hospital and 30 day mortality between the groups (P = 0.53, P = 0.57). There were no significant differences in any of the secondary outcomes.. MICU patients with severe CAP who received doxycycline versus azithromycin in addition to β-lactam treatment showed no significant differences in outcomes. These data offer support for inclusion of doxycycline as an alternative regimen in current IDSA recommendations.

Topics: Adult; Anti-Bacterial Agents; Azithromycin; beta-Lactams; Community-Acquired Infections; Critical Illness; Doxycycline; Drug Therapy, Combination; Humans; Pneumonia; Prospective Studies; Treatment Outcome

Certain macrolide antibiotics, azithromycin included, possess anti-inflammatory properties that are considered fundamental for their efficacy in the treatment of chronic inflammatory diseases, such as diffuse pan-bronchiolitis and cystic fibrosis. In this study, we disclose a novel azithromycin analog obtained via Barton-McCombie oxidation during which an unprecedented epimerization on the cladinose sugar occurs. Its structure was thoroughly investigated using NMR spectroscopy and compared to the natural epimer, revealing how the change in configuration of one single stereocenter (out of 16) profoundly diminished the antimicrobial activity through spatial manipulation of ribosome binding epitopes. At the same time, the anti-inflammatory properties of parent macrolide were retained, as demonstrated by inhibition of LPS- and cigarette-smoke-induced pulmonary inflammation. Not surprisingly, the compound has promising developable properties including good oral bioavailability and a half-life that supports once-daily dosing. This novel anti-inflammatory candidate has significant potential to fill the gap in existing anti-inflammatory agents and broaden treatment possibilities.

Topics: Animals; Anti-Bacterial Agents; Anti-Inflammatory Agents; Azithromycin; Bacteria; Bacterial Infections; Cells, Cultured; Humans; Macrolides; Mice, Inbred BALB C; Models, Molecular; Oxidation-Reduction; Pneumonia

Azithromycin is prescribed for atypical antimicrobial cover in severe community-acquired pneumonia. Inappropriate azithromycin administration incurs unnecessary financial costs, exacerbates antimicrobial resistance and risks QTc interval prolongation leading to cardiac arrhythmias. The present study demonstrated that a majority of patients were prescribed azithromycin without having electrocardiograms to assess the QTc interval and without meeting criteria for severe community-acquired pneumonia based on CURB-65 score.

Topics: Anti-Bacterial Agents; Azithromycin; Community-Acquired Infections; Electrocardiography; Humans; Long QT Syndrome; Pneumonia

We aimed to investigate the effectiveness of an antibiotic stewardship program (ASP) on antibiotic prescription in children with community-acquired pneumonia (CAP). Antibiotic purchasing data were collected for children aged 3 months to 18 years diagnosed with CAP from November 2016 to April 2017 (pre-intervention period) and from November 2017 to April 2018 (post-intervention period). The intervention was a 1-day seminar for primary care pediatricians on the diagnosis and treatment of CAP in children according to national guidelines. There was a substantial decrease in the use of azithromycin after the intervention. In younger children, there was a 42% decrease, alongside an increased use of amoxicillin (

Topics: Amoxicillin; Anti-Bacterial Agents; Antimicrobial Stewardship; Azithromycin; Child; Community-Acquired Infections; Humans; Pneumonia

Novel antibiotic combinations may act synergistically to inhibit the growth of multidrug-resistant bacterial pathogens but predicting which combination will be successful is difficult, and standard antimicrobial susceptibility testing may not identify important physiological differences between planktonic free-swimming and biofilm-protected surface-attached sessile cells. Using a nominally macrolide-resistant model Klebsiella pneumoniae strain (ATCC 10031) we demonstrate the effectiveness of several macrolides in inhibiting biofilm growth in multi-well plates, and the ability of azithromycin (AZM) to improve the effectiveness of the antibacterial last-agent-of-choice for K. pneumoniae infections, colistin methanesulfonate (CMS), against biofilms. This synergistic action was also seen in biofilm tests of several K. pneumoniae hospital isolates and could also be identified in polymyxin B disc-diffusion assays on azithromycin plates. Our work highlights the complexity of antimicrobial-resistance in bacterial pathogens and the need to test antibiotics with biofilm models where potential synergies might provide new therapeutic opportunities not seen in liquid culture or colony-based assays.

Topics: Anti-Bacterial Agents; Azithromycin; Biofilms; Colistin; Humans; Klebsiella Infections; Klebsiella pneumoniae; Mesylates; Microbial Sensitivity Tests; Pneumonia; Polymyxin B

Klebsiella pneumoniae is known as one of the most principal opportunistic human pathogens. Although antibiotics such as the first-line agent azithromycin (AZM) usually are efficient for the treatment of K. pneumonia-related infections, growing threat from antibiotic resistance has become a major challenge. Various preparations based on traditional Chinese medicine (TCM) clinical experience have been developed to help combat such a global public health threat, including Xiyanping injection (XYP) that is made from the natural product andrographolide with potent heat-clearing and toxin-resolving functions.. The present study aimed to demonstrate the therapeutic potential, as well as the action of mechanism of AZM in combination with XYP against K. pneumonia infection in rats.. Pneumonia model of K. pneumoniae infection in rats was established and subjected to various treatments. The lung histopathological lesions were evaluated. ELISA and Griess techniques were used to determine the level of crucial cytokines. The protein expressions of MAPKs and NF-κB pathways were analyzed by Western blotting.. The combination in vivo could significantly inhibit the proliferation of K. pneumoniae in lung, improve the pathological changes of lung and reduce inflammatory factors in lung homogenate and bronchoalveolar lavage fluid, mainly by inactivating MAPKs and NF-κB signaling pathways. Combination therapy caused one-fold increase in apparent distribution volume of AZM in rats after multiple dosing, along with a significant increase of AZM level in lungs but obvious decrease in livers.. The combination therapy of AZM and XYP showed increased antibacterial and anti-inflammatory properties, indicating that it might be used to treat K. pneumoniae infection.

Topics: Animals; Anti-Bacterial Agents; Azithromycin; Humans; Klebsiella pneumoniae; Lung; Medicine, Chinese Traditional; NF-kappa B; Pneumonia; Rats

In 2013, the US Food and Drug Administration issued a warning regarding the use of azithromycin and the risk of fatal dysrhythmias after a 14-year retrospective analysis showed increased risk of cardiovascular-related death in patients who had taken a 5-day course of azithromycin compared with those who took amoxicillin, ciprofloxacin, or no antibiotics. At the authors' institution, pneumonia is the most common diagnosis for which azithromycin is used as a treatment for patients who are hospitalized.. To compare corrected QT (QTc) interval measurements on electrocardiogram (ECG) before and after inpatient azithromycin treatment for pneumonia.. The authors retrospectively reviewed the medical records of 642 patients age 18 years and older who were diagnosed with pneumonia and treated with azithromycin at an academic teaching hospital between January 1, 2017 and December 31, 2017. Patients who had an ECG performed both before and after azithromycin treatment were included and divided into 2 groups: those who had 1 dose of azithromycin (Group 1) and those who had 2 doses (Group 2). Patients were excluded if they had a baseline QTc interval on initial ECG greater than or equal to 500 ms, any signs of ischemia or myocardial infarction, any initial dysrhythmia or underlying ECG abnormalities, or absence of pre- and post-ECG results. Outcomes measures included a comparison of QTc intervals on ECG before and after azithromycin, and an analysis of the percentage of patients with a QTc interval measurement greater than 500 ms on ECG after azithromycin treatment. Our primary outcome measurement was the QTc interval measurement on ECG before and after azithromycin in patients treated with azithromycin for community acquired pneumonia. Our secondary outcome measurement was the percentage of patients with a QTc interval measurement of greater than 500 ms on ECG after azithromycin treatment. A Wilcoxon signed-rank test was used to evaluate repeated QTc measures of our primary outcome in Group 1 and Group 2. Our secondary outcome was reported as a percentage of total patients with a QTc interval of greater than 500 ms after azithromycin doses on ECG.. Of 642 patients, 142 had available pre- and post-EGC results available; 100 were included in Group 1 (1 dose) and 42 in Group 2 (2 doses). Mean QTc interval differences after 1 dose of azithromycin exhibited an increase compared to baseline values (424 vs 477 ms). A Wilcoxon signed-rank test indicated a significant QTc prolongation after 1 dose of azithromycin (mean rank, 43.76; Z=-4.921; P<.001). QTc interval differences after 2 doses of azithromycin did not reach statistical significance when compared to baseline values (422 vs 444 ms). A total of 10 patients (10%) in Group 1 and 4 patients (9.5%) in Group 2 had a QTc interval >500 ms after azithromycin. There were no documented dysrhythmias during hospitalization in this study period.. QTc interval increases were observed during inpatient azithromycin therapy for pneumonia, but were not found to be associated with cardiac dysrhythmias during hospitalization.

Topics: Adolescent; Azithromycin; COVID-19; Electrocardiography; Humans; Inpatients; Long QT Syndrome; Pneumonia; Retrospective Studies

Topics: Acetaminophen; Adult; Ampicillin; Anti-Bacterial Agents; Azithromycin; Cefpodoxime; Ceftizoxime; Ceftriaxone; Dexamethasone; Drug Therapy, Combination; Fatigue; Female; Headache; Humans; Meningitis, Aseptic; Pneumonia; Tomography, X-Ray Computed; Treatment Outcome; Vancomycin; Young Adult

To assess a persuasive multimodel approach to decreasing unnecessary intravenous (IV) clarithromycin use for community-acquired pneumonia (CAP) in Canterbury District Health Board (CDHB) hospitals.. In December 2013, CDHB guidelines for empiric treatment of CAP changed to prioritise oral azithromycin over IV clarithromycin. The multimodel approach we used to implement this change included obtaining stakeholder agreement, improved guidelines access, education and pharmacist support. The impact of the intervention was evaluated by comparing macrolide usage and expenditure for the four years pre- and post-intervention.. Mean annual clarithromycin IV use decreased by 72% from 6.4 to 1.8 defined daily doses (DDDs) per 1,000 occupied bed days (OBDs) post-intervention, while oral azithromycin increased by 833% (4.2 to 39.2 DDDs per 1,000 OBDs). Concurrently, oral clarithromycin use decreased by 91% (32.9 to 2.9 DDDs per 1,000 OBDs), and roxithromycin by 71% (17.0 to 5.0 DDDs per 1,000 OBDs). Mean annual total macrolide use decreased by 21% (68.2 to 53.9 DDDs per 1,000 OBDs), while expenditure decreased by 69% mainly through avoided IV administration.. A persuasive multimodel approach to support adoption of CAP guidelines produced a sustained decrease in IV clarithromycin use, which may have clinical benefits such as reduced occurrence of catheter-related complications.

Topics: Administration, Intravenous; Administration, Oral; Anti-Bacterial Agents; Antimicrobial Stewardship; Azithromycin; Clarithromycin; Community-Acquired Infections; Dosage Forms; Guideline Adherence; Hospitals; Humans; New Zealand; Pneumonia

Approximately 21 human cases of infection with Mycobacterium conceptionense have been reported. However, most cases were outside the United States, and optimal treatment remains uncertain. We report a case of M. conceptionense pneumonitis in a patient with HIV/AIDS in the United States. The patient was cured with azithromycin and doxycycline.

Topics: AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Antiretroviral Therapy, Highly Active; Azithromycin; Doxycycline; Drug Therapy, Combination; Humans; Male; Middle Aged; Mycobacteriaceae; Mycobacterium Infections; Pneumonia; United States

Topics: Adult; Azithromycin; Cytochrome P-450 CYP2C19; Cytochrome P-450 CYP2D6; Drug Interactions; Heart Failure; Humans; Male; Pharmacogenetics; Pneumonia; Polymorphism, Genetic; Venlafaxine Hydrochloride

Legionnaires' disease is a recognised but rare cause of rhabdomyolysis. It can be further complicated with renal impairment. In this case report, we describe a previously healthy, semiactive 50-year-old man who within days was reduced to having periods of dyspnea after minutes of walking in addition to near fatal acute renal failure. He was found to have the rare triad of

Topics: Acute Kidney Injury; Anti-Bacterial Agents; Azithromycin; Diagnosis, Differential; Humans; Legionella pneumophila; Legionnaires' Disease; Male; Middle Aged; Pneumonia; Rhabdomyolysis; Treatment Outcome

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.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Azithromycin; Female; Hospital Mortality; Humans; Lung; Male; Pneumonia; Propensity Score; Prospective Studies; Respiration, Artificial; Retrospective Studies; Severe Acute Respiratory Syndrome

Topics: Alanine Transaminase; Anti-Bacterial Agents; Azithromycin; Child; Child, Preschool; Chromatography, Liquid; Community-Acquired Infections; Female; Humans; Male; Microbial Sensitivity Tests; Monte Carlo Method; Pneumonia; Prospective Studies; Tandem Mass Spectrometry

BACKGROUND Severe pneumonia requiring admission to an intensive care unit carries high morbidity and mortality. Evidence-based management includes early administration of empiric antibiotics against plausible bacterial pathogens while awaiting results of microbiologic cultures. However, in over 60% of pneumonia cases, no causative pathogen is identified with conventional diagnostic techniques. In this case report, we demonstrate how direct-from-sample sequencing of bacterial DNA could have identified the multiple culprit pathogens early in the disease course to guide appropriate antibiotic management. CASE REPORT A previously healthy, 21-year-old man presented with neck pain and fever and rapidly developed acute respiratory distress syndrome (ARDS) requiring mechanical ventilation. He was started on broad-spectrum antibiotics and was found to have septic thrombophlebitis of the left internal jugular vein (Lemierre syndrome), with blood cultures growing Fusobacterium necrophorum. While his antibiotics were narrowed to piperacillin-tazobactam monotherapy, his clinical condition worsened, but repeated efforts to define an additional/alternative respiratory pathogen resulted in negative cultures. He eventually developed bilateral empyemas growing Mycoplasma hominis. Once azithromycin was added to the patient's regimen, he improved dramatically. Retrospective sequencing of consecutive endotracheal aspirates showed Fusobacterium as the dominant pathogen early in the course, but with significant and increasing Mycoplasma abundance several days prior to clinical detection. CONCLUSIONS Had sequencing information been available to the treating clinicians, the causative pathogens could have been detected earlier, guiding appropriate antibiotic therapy and perhaps preventing his clinical complications. Real-time bacterial DNA sequencing has the potential to shift the diagnostic paradigm in severe pneumonia.

Topics: Anti-Bacterial Agents; Azithromycin; DNA, Bacterial; Fusobacterium necrophorum; Humans; Lemierre Syndrome; Male; Mycoplasma hominis; Mycoplasma Infections; Piperacillin, Tazobactam Drug Combination; Pneumonia; Sequence Analysis, DNA; Young Adult

Scrub typhus is a re-emerging mite-borne rickettsiosis, which continues to be underdiagnosed, with lethal consequences. The present study was conducted to determine the seasonality, clinical presentation and predictors of mortality in patients with scrub typhus at a tertiary care teaching hospital in northern India.. Scrub typhus was suspected in patients attending the hospital as per the standard case definition and serological evidence was obtained by performing an IgM ELISA.. A total of 284 patients with scrub typhus from urban and rural areas were seen, predominantly from July to November. The most common clinical presentation was a bilateral community-acquired pneumonia (CAP), which resembled pneumonia due to atypical pathogens and often progressed to acute respiratory distress syndrome (ARDS). An acute undifferentiated febrile illness (AUFI) or a febrile illness associated with altered sensorium, aseptic meningitis, shock, abdominal pain, gastrointestinal bleeding or jaundice was also seen. Eschars were seen in 17 per cent of patients, and thrombocytopenia, transaminitis and azotaemia were frequent. There were 24 deaths (8.5%) caused predominantly by ARDS and multi-organ dysfunction. The mortality in patients with ARDS was high (37%). ARDS [odds ratio (OR)=38.29, 95% confidence interval (CI): 9.93, 147.71] and acute kidney injury (OR=8.30, 95% CI: 2.21, 31.21) were the major predictors of death.. The present findings indicate that scrub typhus may be considered a cause of CAP, ARDS, AUFI or a febrile illness with multisystem involvement, in Uttarakhand and Uttar Pradesh, especially from July to November. Empiric therapy of CAP may include doxycycline or azithromycin to ensure coverage of underlying unsuspected scrub typhus.

Topics: Adult; Azithromycin; Community-Acquired Infections; Doxycycline; Female; Humans; India; Male; Middle Aged; Orientia tsutsugamushi; Pneumonia; Respiratory Distress Syndrome; Scrub Typhus

The development of low-density polymeric microparticles may be a useful approach to deliver antibiotics such as azithromycin into the lung.. The aim of this study was to develop azithromycin-loaded low density polycaprolactone microparticles by the double emulsion/solvent evaporation method.. Microparticles were prepared and characterized according to their physicochemical properties, drug loading, and drug release profiles. A full 2. The resulting particles presented drug loading up to 23.1% (wt%) and mean geometric diameters varying from 4.0 µm to 15.4 µm. Bulk and tapped densities were low, resulting in good or excellent flow properties. SEM images showed spherical particles with a smooth surface. However, hollow inner structures were observed, which may explain the low values of bulk density. The estimated aerodynamic diameters ranged from 2.3 µm to 8.9 µm. The in silico pulmonary deposition profiles indicated, for some formulations, that a significant fraction of the particles would be deposited in the deeper lung regions.. Statistical analysis demonstrated that not only drug loading but also the aerodynamic diameter of the microparticles is greatly affected by the preparation conditions. Overall, the results indicated that the low-density azithromycin-loaded microparticles with a relatively high respirable fraction may be obtained for the local treatment of lung infections.

Topics: Administration, Inhalation; Anti-Bacterial Agents; Azithromycin; Community-Acquired Infections; Computer Simulation; Drug Carriers; Drug Compounding; Drug Liberation; Lung; Microscopy, Electron, Scanning; Models, Biological; Models, Chemical; Particle Size; Pneumonia; Polyesters; Surface Properties; X-Ray Diffraction

While ceftriaxone 1 g q24h is commonly used for hospitalized patients with community-acquired pneumonia (CAP), the prescribing information recommends 2-4 g a day to treat methicillin-susceptible Staphylococcus aureus (MSSA). Similarly, recent pharmacodynamic analyses suggest shortcomings of 1 g q24h against the bulk of the MSSA. We evaluated the outcomes of empiric ceftriaxone 1 g q24h ± azithromycin in patients with MSSA pneumonia, as compared with Streptococcus pneumoniae. Adult patients admitted to Hartford Hospital from 1/2005 to 12/2014 with respiratory culture for MSSA or S. pneumoniae were considered for inclusion. Non-ICU, CAP patients were included. Early clinical failure (ECF) was defined as persistent signs/symptoms or change of antibiotic due to poor response at 72-96 h. A multivariate analysis was performed to evaluate predictors of ECF. Over the study period, 403 MSSA and 227 S. pneumoniae positive respiratory cultures were identified. The majority of patients were excluded due to the following: no signs/symptoms of pneumonia, hospital-acquired pneumonia, alternative antibiotics, and polymicrobial infection. Thirty-nine patients met inclusion/exclusion criteria. All but three patients in the S. pneumoniae group received ceftriaxone + azithromycin. ECF was greater in the MSSA group (53 vs. 4 %, P = 0.003), as was length of stay (7.5 ± 5.4 vs. 4.6 ± 3.3 days, P = 0.006). When controlling for disease severity and macrolide non-susceptibility in a multivariate analysis, MSSA was significantly correlated with ECF (OR 12.3, 95 % CI 0.8-188.8). Poor clinical outcomes were observed in patients empirically treated with ceftriaxone ± azithromycin for MSSA CAP. Despite the popularity of ceftriaxone 1 g q24h, these data suggest this dose or compound may be inadequate for CAP caused by MSSA.

Topics: Aged; Azithromycin; Ceftriaxone; Community-Acquired Infections; Drug Therapy, Combination; Female; Hospitalization; Humans; Length of Stay; Male; Middle Aged; Pneumonia; Staphylococcus aureus; Streptococcus pneumoniae; Treatment Outcome

The objective of this study was to measure plasma cytokine levels and blood neutrophil functions as well as clinical outcomes in hospitalized patients with community-acquired pneumonia (CAP) treated with or without macrolide use--a known modulator of inflammatory response.. Subjects with CAP had peripheral blood analyzed for some neutrophil functions (degranulation of secretory vesicles and specific granules, respiratory burst response and phagocytosis) and ten cytokine levels measured in serum and sputum supernatants. Neutrophil function in healthy volunteers was also measured for reference. Values were measured on the day of enrollment, days 2-4 and 5-7, depending on a patient's length of stay. Early and late clinical outcomes were also evaluated. All values were compared between those treated with or without a macrolide.. A total of 40 subjects were in this study; 14 received macrolide treatment, and 26 did not. Neutrophil function in the macrolide group was not significantly different compared to the non-macrolide group. None of the median cytokine levels or IQRs were statistically significant between the groups. However, a trend toward decreased IL-6, IL-8, and IFN-γ levels, and favorable clinical outcomes were present in the macrolide group.. This pilot study showed no statistical difference between cytokine levels or neutrophil activity for CAP patients prescribed a macrolide containing regimen. Considering the trend of lower cytokine levels in the macrolide group when comparing the 5- to 7-day time period with the non-macrolide group, a full study with an appropriate sample size may be warranted.

Topics: Aged; Anti-Bacterial Agents; Azithromycin; Cell Degranulation; Community-Acquired Infections; Cytokines; Female; Hospital Mortality; Humans; Interferon-gamma; Interleukin-6; Interleukin-8; Length of Stay; Male; Middle Aged; Neutrophils; Phagocytosis; Pilot Projects; Pneumonia; Prospective Studies; Respiratory Burst

We investigated the effect of long-term treatment with azithromycin on the pathogenesis of chronic asthma with airway remodeling.. Six-week-old-BALB/c mice were sensitized with ovalbumin (OVA) combined with lipopolysaccharide (LPS) for 1 month, then challenged with OVA for 3 months. Azithromycin at 75 mg/kg was administered via oral gavage five times a week during the challenge period. Inflammatory cells, T helper 2 cytokines in bronchoalveolar lavage fluid (BAL) fluid, and airway hyperresponsiveness (AHR) were measured. Parameters related to airway remodeling were evaluated. The levels of neutrophil elastase, Interleukin (IL)-8, and BRP-39 (human homologue YKL-40) were assessed. The expression of MAPK and NF-κB signaling were investigated.. Long-term treatment with azithromycin improved AHR and airway inflammation compared with the OVA and the OVA/LPS groups. The concentrations of IL-5 and IL-13 in the OVA/LPS group decreased significantly after azithromycin administration. The levels of neutrophil elastase and IL-8, as surrogate markers of neutrophil activation, were reduced in the azithromycin group compared with the OVA/LPS group. Goblet cell hyperplasia and the smooth muscle thickening of airway remodeling were attenuated after azithromycin treatment. The expression of MAPK/NF-kappaB signal and the level of BRP-39 in the lung decreased remarkably in the OVA/LPS with azithromycin-treated group.. This study suggests that in a murine model of chronic asthma, long-term azithromycin treatment ameliorates not only airway inflammation but also airway remodeling by influencing on neutrophilc-related mediators, BRP-39 and MAPK/NF-κB signal pathways. Macrolide therapy might be an effective adjuvant therapy in a chronic, severe asthma with remodeling airway.

Topics: Animals; Anti-Bacterial Agents; Asthma; Azithromycin; Bronchial Hyperreactivity; Bronchoalveolar Lavage Fluid; Female; Interleukins; Leukocyte Elastase; Lipopolysaccharides; Mice; Mice, Inbred BALB C; Mitogen-Activated Protein Kinases; Ovalbumin; Pneumonia; T-Lymphocytes, Helper-Inducer

Studies investigating the association between macrolides and outcomes in both pulmonary and nonpulmonary critically ill patients are limited. We aimed to examine the association between azithromycin use and clinical outcomes in severe sepsis patients with and without pneumonia receiving mechanical ventilation.. A retrospective cohort of 105 patients admitted to an adult intensive care unit (ICU) with severe sepsis in an urban university hospital were included in the study. Multivariable linear regression was performed to assess the relationship between azithromycin use and the following outcomes: 28-day ICU-free days and 28-day ventilator-free days.. In univariate analysis, patients receiving azithromycin had nearly 6 more ICU-free days on average than did patients not receiving azithromycin (P = .005). The increased ICU-free days remained in multivariable analysis adjusting for age, sex, race, ICU type, and presence of shock (P = .005). In stratified analysis examining the association of azithromycin use in severe sepsis patients without pneumonia (n = 74), the results were similar to the full cohort.. Azithromycin was associated with more ICU-free days in severe sepsis patients with and without pneumonia. Further investigations are warranted to better elicit the association of macrolide use on clinical outcomes in severe sepsis patients, especially those without pneumonia.

Topics: Adult; Aged; Anti-Bacterial Agents; Azithromycin; Female; Hospitals, University; Humans; Intensive Care Units; Male; Middle Aged; Multivariate Analysis; Outcome Assessment, Health Care; Pneumonia; Respiration, Artificial; Retrospective Studies; Sepsis

The role of inflammation and immunity in COPD treatment is increasingly being recognized. The relationship between anti-inflammation/immunoregulation and emphysema in COPD lungs remains to be elucidated. The aim of this study was to investigate the effects of azithromycin (Azm) on the development of emphysema in smoking-induced COPD in rats.. Sprague-Dawley rats (n = 50) were randomly assigned to normal, COPD, saline-treated, Azm-treated, and levofloxacin-treated (Lev) groups. The effects of treatment were assessed by measuring the levels of vascular endothelial growth factor (VEGF) by enzyme-linked immunosorbent assay and measuring the numbers of neutrophil and macrophage in bronchoalveolar lavage fluid, vascular endothelial growth factor (VEGF) and VEGF receptor-2 (VEGFR2) protein expression by western blotting. Lung function measurements and histopathological evaluations (mean linear intercept and destructive index) were performed.. FEV0.3/FVC and peak expiratory flow were lower in the COPD group than in the normal group. Mean linear intercept and destructive index were lower in the Azm-treated group than in the COPD, saline-treated, and Lev-treated groups. The numbers of neutrophil and macrophage in bronchoalveolar lavage fluid were lower in the Azm-treated group than in the COPD, saline-treated, and Lev-treated groups. As confirmed by western blotting, the levels of VEGF in lung homogenates were higher in the Azm-treated group than in the COPD, saline-treated, and Lev-treated groups. VEGFR2 protein expression was higher in the Azm-treated group than in the COPD, saline-treated, and Lev-treated groups.. Azm attenuates pulmonary emphysema by partly reversing the decrease in the numbers of inflammatory cells (neutrophil and macrophage) and VEGF secretion and VEGFR2 protein expression in smoking-induced COPD in rats.

Topics: Animals; Anti-Bacterial Agents; Azithromycin; Bronchoalveolar Lavage Fluid; Disease Models, Animal; Forced Expiratory Volume; Lung; Macrophages; Male; Neutrophils; Peak Expiratory Flow Rate; Pneumonia; Pulmonary Disease, Chronic Obstructive; Pulmonary Emphysema; Rats; Rats, Sprague-Dawley; Smoking; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-2; Vital Capacity

Topics: Adolescent; Antibiotic Prophylaxis; Azithromycin; Cough; Diagnosis, Differential; Diphtheria-Tetanus-acellular Pertussis Vaccines; Disease Outbreaks; Humans; Male; Pneumonia; Whooping Cough

Chronic inflammation of the airways is a central component in lung diseases and is frequently associated with bacterial infections. Monitoring the pro-inflammatory capability of bacterial virulence factors in vivo is challenging and usually requires invasive methods.. Lung inflammation was induced using the culture supernatants from two Pseudomonas aeruginosa clinical strains, VR1 and VR2, isolated from patients affected by cystic fibrosis and showing different phenotypes in terms of motility, colony characteristics and biofilm production as well as pyoverdine and pyocyanine release. More interesting, the strains differ also for the presence in supernatants of metalloproteases, a family of virulence factors with known pro-inflammatory activity. We have evaluated the benefit of using a mouse model, transiently expressing the luciferase reporter gene under the control of an heterologous IL-8 bovine promoter, to detect and monitoring lung inflammation.. In vivo imaging indicated that VR1 strain, releasing in its culture supernatant metalloproteases and other virulence factors, induced lung inflammation while the VR2 strain presented with a severely reduced pro-inflammatory activity. The bioluminescence signal was detectable from 4 to 48 h after supernatant instillation. The animal model was also used to test the anti-inflammatory activity of azithromycin (AZM), an antibiotic with demonstrated inhibitory effect on the synthesis of bacterial exoproducts. The inflammation signal in mice was in fact significantly reduced when bacteria grew in the presence of a sub-lethal dose of AZM causing inhibition of the synthesis of metalloproteases and other bacterial elements. The in vivo data were further supported by quantification of immune cells and cytokine expression in mouse broncho-alveolar lavage samples.. This experimental animal model is based on the transient transduction of the bovine IL-8 promoter, a gene representing a major player during inflammation, essential for leukocytes recruitment to the inflamed tissue. It appears to be an appropriate molecular read-out for monitoring the activation of inflammatory pathways caused by bacterial virulence factors. The data presented indicate that the model is suitable to functionally monitor in real time the lung inflammatory response facilitating the identification of bacterial factors with pro-inflammatory activity and the evaluation of the anti-inflammatory activity of old and new molecules for therapeutic use.

Topics: Animals; Azithromycin; Bronchoalveolar Lavage Fluid; Cattle; Cytokines; Diagnostic Imaging; Female; Humans; Interleukin-8; Mice, Inbred BALB C; Mice, Transgenic; Peptide Hydrolases; Phenotype; Pneumonia; Pseudomonas aeruginosa; Pseudomonas Infections; Virulence Factors

Azithromycin is a macrolide antibiotic with anti-inflammatory and immunomodulating effects. Long-term azithromycin therapy in patients with chronic lung diseases such as cystic fibrosis has been associated with increased antimicrobial resistance, emergence of hypermutable strains, ototoxicity and cardiac toxicity. The aim of this study was to assess the anti-inflammatory effects of the non-antibiotic azithromycin derivative CSY0073.. We compared the effects of CSY0073 with those of azithromycin in experiments on bacterial cultures, Pseudomonas aeruginosa biofilm, lung cells and mice challenged intranasally with P. aeruginosa LPS.. In contrast to azithromycin, CSY0073 did not inhibit the growth of P. aeruginosa, Staphylococcus aureus or Haemophilus influenzae and had no effect on an established P. aeruginosa biofilm. Bronchoalveolar lavage (BAL) fluids and lung homogenates collected after the LPS challenge in mice showed that CSY0073 and azithromycin (200 mg·kg(-1), i.p.) decreased neutrophil counts at 24 h and TNF-α, CXCL1 and CXCL2 levels in the BAL fluid after 3 h and IL-6, CXCL2 and IL-1β levels in the lung after 3 h compared with the vehicle. However, only azithromycin reduced IL-1β levels in the lung 24 h post LPS challenge. CSY0073 and azithromycin similarly diminished the production of pro-inflammatory cytokines by macrophages, but not lung epithelial cells, exposed to P. aeruginosa LPS.. Unlike azithromycin, CSY0073 had no antibacterial effects but it did have a similar anti-inflammatory profile to that of azithromycin. Hence, CSY0073 may have potential as a long-term treatment for patients with chronic lung diseases.

Topics: Animals; Anti-Inflammatory Agents; Azithromycin; Biofilms; Bronchoalveolar Lavage Fluid; Disease Models, Animal; Dose-Response Relationship, Drug; Inflammation Mediators; Lipopolysaccharides; Lung; Mice; Mice, Inbred C57BL; Pneumonia; Pseudomonas aeruginosa; Time Factors

Recent Food and Drug Administration (FDA) guidance endorses the use of an early clinical response endpoint as the primary outcome for community-acquired bacterial pneumonia (CABP) trials. While antibiotics will now be approved for CABP, in practice they will primarily be used to treat patients with community-acquired pneumonia (CAP). More importantly, it is unclear how achievement of the new FDA CABP early response endpoint translates into clinically applicable real-world outcomes for patients with CAP. To address this, a retrospective cohort study was conducted among adult patients who received ceftriaxone and azithromycin for CAP of Pneumonia Outcomes Research Team (PORT) risk class III and IV at an academic medical center. The clinical response was defined as clinical stability for 24 h with improvement in at least one pneumonia symptom and with no symptom worsening. A classification and regression tree (CART) was used to determine the delay in response time, measured in days, associated with the greatest risk of a prolonged hospital length of stay (LOS) and adverse outcomes (in-hospital mortality or 30-day CAP-related readmission). A total of 250 patients were included. On average, patients were discharged 2 days following the achievement of a clinical response. In the CART analysis, adverse clinical outcomes were higher among day 5 nonresponders than those who responded by day 5 (22.4% versus 6.9%, P = 0.001). The findings from this study indicate that time to clinical response, as defined by the recent FDA guidance, is a reasonable prognostic indicator of real-world effectiveness outcomes among hospitalized PORT risk class III and IV patients with CAP who received ceftriaxone and azithromycin.

Topics: Adult; Aged; Anti-Bacterial Agents; Azithromycin; Ceftriaxone; Cohort Studies; Community-Acquired Infections; Endpoint Determination; Female; Hospital Mortality; Humans; Male; Middle Aged; New York; Patient Readmission; Pneumonia; Retrospective Studies; Risk Assessment; Time Factors; Treatment Outcome

Although clinical practice guidelines recommend combination therapy with macrolides, including azithromycin, as first-line therapy for patients hospitalized with pneumonia, recent research suggests that azithromycin may be associated with increased cardiovascular events.. To examine the association of azithromycin use with all-cause mortality and cardiovascular events for patients hospitalized with pneumonia.. Retrospective cohort study comparing older patients hospitalized with pneumonia from fiscal years 2002 through 2012 prescribed azithromycin therapy and patients receiving other guideline-concordant antibiotic therapy.. This study was conducted using national Department of Veterans Affairs administrative data of patients hospitalized at any Veterans Administration acute care hospital.. Patients were included if they were aged 65 years or older, were hospitalized with pneumonia, and received antibiotic therapy concordant with national clinical practice guidelines.. Outcomes included 30- and 90-day all-cause mortality and 90-day cardiac arrhythmias, heart failure, myocardial infarction, and any cardiac event. Propensity score matching was used to control for the possible effects of known confounders with conditional logistic regression.. Of 73,690 patients from 118 hospitals identified, propensity-matched groups were composed of 31,863 patients exposed to azithromycin and 31,863 matched patients who were not exposed. There were no significant differences in potential confounders between groups after matching. Ninety-day mortality was significantly lower in those who received azithromycin (exposed, 17.4%, vs unexposed, 22.3%; odds ratio [OR], 0.73; 95% CI, 0.70-0.76). However, we found significantly increased odds of myocardial infarction (5.1% vs 4.4%; OR, 1.17; 95% CI, 1.08-1.25) but not any cardiac event (43.0% vs 42.7%; OR, 1.01; 95% CI, 0.98-1.05), cardiac arrhythmias (25.8% vs 26.0%; OR, 0.99; 95% CI, 0.95-1.02), or heart failure (26.3% vs 26.2%; OR, 1.01; 95% CI, 0.97-1.04).. Among older patients hospitalized with pneumonia, treatment that included azithromycin compared with other antibiotics was associated with a lower risk of 90-day mortality and a smaller increased risk of myocardial infarction. These findings are consistent with a net benefit associated with azithromycin use.

Topics: Age Factors; Aged; Aged, 80 and over; Anti-Bacterial Agents; Azithromycin; Cardiovascular Diseases; Cohort Studies; Female; Hospitals, Veterans; Humans; Inpatients; Male; Pneumonia; Retrospective Studies; Risk; United States

Intrauterine infection with Ureaplasma spp. is strongly associated with preterm birth and adverse neonatal outcomes. We assessed whether combined intraamniotic (IA) and maternal intravenous (IV) treatment with one of two candidate antibiotics, azithromycin (AZ) or solithromycin (SOLI), would eradicate intrauterine Ureaplasma parvum infection in a sheep model of pregnancy. Sheep with singleton pregnancies received an IA injection of U. parvum serovar 3 at 85 days of gestational age (GA). At 120 days of GA, animals (n=5 to 8/group) received one of the following treatments: (i) maternal IV SOLI with a single IA injection of vehicle (IV SOLI only); (ii) maternal IV SOLI with a single IA injection of SOLI (IV+IA SOLI); (iii) maternal IV AZ and a single IA injection of vehicle (IV AZ only); (iv) maternal IV AZ and a single IA injection of AZ (IV+IA AZ); or (v) maternal IV and single IA injection of vehicle (control). Lambs were surgically delivered at 125 days of GA. Treatment efficacies were assessed by U. parvum culture, quantitative PCR, enzyme-linked immunosorbent assay, and histopathology. Amniotic fluid (AF) from all control animals contained culturable U. parvum. AF, lung, and chorioamnion from all AZ- or SOLI-treated animals (IV only or IV plus IA) were negative for culturable U. parvum. Relative to the results for the control, the levels of expression of interleukin 1β (IL-1β), IL-6, IL-8, and monocyte chemoattractant protein 2 (MCP-2) in fetal skin were significantly decreased in the IV SOLI-only group, the MCP-1 protein concentration in the amniotic fluid was significantly increased in the IV+IA SOLI group, and there was no significant difference in the histological inflammation scoring of lung or chorioamnion among the five groups. In the present study, treatment with either AZ or SOLI (IV only or IV+IA) effectively eradicated macrolide-sensitive U. parvum from the AF. There was no discernible difference in antibiotic therapy efficacy between IV-only and IV+IA treatment regimens relative to the results for the control.

Topics: Administration, Intravenous; Amniotic Fluid; Animals; Anti-Bacterial Agents; Azithromycin; Chemokine CCL2; Chemokine CCL8; Female; Fetus; Interleukins; Lung; Macrolides; Pneumonia; Pregnancy; Pregnancy Complications, Infectious; Sheep; Triazoles; Ureaplasma; Ureaplasma Infections

Topics: Anti-Bacterial Agents; Azithromycin; Cardiovascular Diseases; Female; Humans; Male; Pneumonia

Topics: Anti-Bacterial Agents; Azithromycin; Cardiovascular Diseases; Female; Humans; Male; Pneumonia

Topics: Anti-Bacterial Agents; Azithromycin; Cardiovascular Diseases; Female; Humans; Male; Pneumonia

Topics: Anti-Bacterial Agents; Azithromycin; Cardiovascular Diseases; Female; Humans; Male; Pneumonia

Topics: Aged; Anti-Bacterial Agents; Azithromycin; Community-Acquired Infections; Electrocardiography; Female; Humans; Pneumonia; Renal Insufficiency

Lymphocytic airway inflammation is a major risk factor for chronic lung allograft dysfunction, for which there is no established treatment. We investigated whether azithromycin could control lymphocytic airway inflammation and improve allograft function. Fifteen lung transplant recipients demonstrating acute allograft dysfunction due to isolated lymphocytic airway inflammation were prospectively treated with azithromycin for at least 6 months (NCT01109160). Spirometry (FVC, FEV1 , FEF25-75 , Tiffeneau index) and FeNO were assessed before and up to 12 months after initiation of azithromycin. Radiologic features, local inflammation assessed on airway biopsy (rejection score, IL-17(+)  cells/mm(2) lamina propria) and broncho-alveolar lavage fluid (total and differential cell counts, chemokine and cytokine levels); as well as systemic C-reactive protein levels were compared between baseline and after 3 months of treatment. Airflow improved and FeNO decreased to baseline levels after 1 month of azithromycin and were sustained thereafter. After 3 months of treatment, radiologic abnormalities, submucosal cellular inflammation, lavage protein levels of IL-1β, IL-8/CXCL-8, IP-10/CXCL-10, RANTES/CCL5, MIP1-α/CCL3, MIP-1β/CCL4, Eotaxin, PDGF-BB, total cell count, neutrophils and eosinophils, as well as plasma C-reactive protein levels all significantly decreased compared to baseline (p < 0.05). Administration of azithromycin was associated with suppression of posttransplant lymphocytic airway inflammation and clinical improvement in lung allograft function.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Azithromycin; Bronchitis; Bronchoalveolar Lavage; C-Reactive Protein; Cytokines; Female; Follow-Up Studies; Graft Rejection; Graft Survival; Humans; Lung Diseases; Lung Transplantation; Lymphocytes; Male; Middle Aged; Pneumonia; Postoperative Complications; Prognosis; Prospective Studies; Respiratory Function Tests; Retrospective Studies; Spirometry; Transplantation, Homologous; Young Adult

Topics: Azithromycin; Bronchitis; Female; Graft Rejection; Humans; Lung Transplantation; Lymphocytes; Male; Pneumonia; Postoperative Complications

To analyze the clinical manifestations and intervention against fulminant scrub typhus-associated hemophagocytic syndrome.. The medical records for the onset time of hemophagocytic syndrome, the clinical course, the chest radiographic findings, laboratory data, antibiotic therapy, clinical outcome and its prognosis were retrospectively reviewed.. (1) Four patients were diagnosed as scrub typhus based on clinical manifestations only, while 15 patients met the criteria of laboratory diagnosis. All 19 patients with scrub typhus had hemophagocytic syndrome. Eschar lesion was identified in 12 patients, 7 patients were described as an ulcer. A seasonal pattern (78.9% from June through September in 15 patients) was observed. Clinical misdiagnosis was common (all 19 cases). There were 9 patients with admitting diagnosis of scrub typhus, 10 patients were not diagnosed as scrub typhus after admission. In 5 cases within 3 days after admission diagnosis was corrected as scrub typhus. Until discharge from the hospital, 5 cases were not diagnosed with scrub typhus. In this study, the length of time from the illness onset (beginning of fever) to the occurrence of clinical symptoms was (9 ± 4) days. (2) All 19 patients had changed AST levels (149 ± 37) U/L, albumin levels (23 ± 4) g/L, C-reactive protein levels (103 ± 51) mg/L, and platelet count (48 ± 41) × 10⁹/L; bone marrow aspiration revealed in 16 patients marked hemophagocytosis. Weil-Felix agglutination test revealed positive results in 6 of 15 cases. Diagnostic IFA results were positive for 14 patients; 19 patients had interstitial pneumonitis and 17 patients had pleural effusion. (3) Five cases with failure to diagnose the disease had ineffective antibiotics treatment (imipenem or β-lactam-based regimens). These patients did not receive appropriate treatment with antibiotics against scrub typhus. Fourteen patients with admitting diagnosis of scrub typhus were successfully treated with appropriate antibiotics, 8 cases with chloramphenicol, 3 cases with azithromycin, and in 3 patients (2 cases of azithromycin and one case of erythromycin), therapy was then switched to chloramphenicol. Four patients were treated with methylprednisolone and 10 patients with dexamethasone. (4) During their hospitalization, the clinical course in five cases with failure to diagnose the disease rapidly developed and progressed to the life-threatening MODS, four of five cases died. However, the course in 14 patients were relieved and did not progress to MODS.. The diagnosis of scrub typhus was frequently delayed, the early course of scrub typhus could be associated with hemophagocytic syndrome. Serious complications of MODS generally occur without antibiotic treatment. Scrub typhus-associated hemophagocytic syndrome should be taken into consideration among patients with acute systemic febrile illness, significant increases in levels of CRP, hypoalbuminemia, thrombocytopenia, splenomegaly, pneumonitis with pleural effusion, especially those with suspected exposure history. It was not easily recognized without careful observation and was present for a few days in each patient.

Topics: Anti-Bacterial Agents; Azithromycin; C-Reactive Protein; Clinical Laboratory Techniques; Diagnosis, Differential; Erythromycin; Humans; Imipenem; Lymphohistiocytosis, Hemophagocytic; Pneumonia; Retrospective Studies; Scrub Typhus

Acinetobacter baumannii is one of the main pathogens that cause ventilator-associated pneumonia (VAP) and is associated with a high rate of mortality. Little is known about the efficacy of macrolides against A. baumannii. In order to confirm the efficacy of azithromycin (AZM) against VAP caused by multidrug-resistant A. baumannii (MDRAB), we used a mouse model that mimics VAP by placement of a plastic tube in the bronchus. AZM (10 and 100 mg/kg of body weight) was administered subcutaneously every 24 h beginning at 3 h after inoculation. Phosphate-buffered saline was administered as the control. Survival was evaluated over 7 days. At 48 h postinfection, mice were sacrificed and the numbers of viable bacteria in lungs and bronchoalveolar lavage fluid were compared. Histopathological analysis of lung specimens was also performed. The treatment groups displayed significantly longer survival than the control group (P < 0.05). AZM did not have an antimicrobial effect. Histopathological examination of lung specimens indicated that the progression of lung inflammation was prevented in the AZM-treated groups. Furthermore, total cell and neutrophil counts, as well as cytokine levels, in bronchoalveolar lavage fluid were significantly decreased (P < 0.05) in the AZM-treated groups. AZM may have a role for the treatment of VAP with MDRAB because of its anti-inflammatory effects.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Anti-Inflammatory Agents; Azithromycin; Bacterial Load; Disease Models, Animal; Drug Administration Schedule; Drug Evaluation, Preclinical; Drug Resistance, Multiple, Bacterial; Lung; Male; Mice; Microbial Viability; Pneumonia; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated; Survival Analysis

Viral bronchiolitis is the leading cause of hospitalization in young infants. It is associated with the development of childhood asthma and contributes to morbidity and mortality in the elderly. Currently no therapies effectively attenuate inflammation during the acute viral infection, or prevent the risk of post-viral asthma. We hypothesized that early treatment of a paramyxoviral bronchiolitis with azithromycin would attenuate acute and chronic airway inflammation.. Mice were inoculated with parainfluenza type 1, Sendai Virus (SeV), and treated daily with PBS or azithromycin for 7 days post-inoculation. On day 8 and 21 we assessed airway inflammation in lung tissue, and quantified immune cells and inflammatory mediators in bronchoalveolar lavage (BAL).. Compared to treatment with PBS, azithromycin significantly attenuated post-viral weight loss. During the peak of acute inflammation (day 8), azithromycin decreased total leukocyte accumulation in the lung tissue and BAL, with the largest fold-reduction in BAL neutrophils. This decreased inflammation was independent of changes in viral load. Azithromycin significantly attenuated the concentration of BAL inflammatory mediators and enhanced resolution of chronic airway inflammation evident by decreased BAL inflammatory mediators on day 21.. In this mouse model of paramyxoviral bronchiolitis, azithromycin attenuated acute and chronic airway inflammation. These findings demonstrate anti-inflammatory effects of azithromycin that are not related to anti-viral activity. Our findings support the rationale for future prospective randomized clinical trials that will evaluate the effects of macrolides on acute viral bronchiolitis and their long-term consequences.

Topics: Animals; Anti-Inflammatory Agents; Azithromycin; Bronchiolitis, Viral; Bronchoalveolar Lavage Fluid; Chemokines; Cytokines; Disease Models, Animal; Female; Inflammation Mediators; Lung; Mice; Mice, Inbred C57BL; Parainfluenza Virus 1, Human; Pneumonia; Respirovirus Infections; Sendai virus; Time Factors; Viral Load; Weight Loss

Topics: Adult; Anti-Bacterial Agents; Azithromycin; Bronchoscopy; Female; Fluoroquinolones; Humans; Macrolides; Mycoplasma pneumoniae; Pneumonia; Radiography, Thoracic; Tetracyclines; Treatment Outcome

The 2007 American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) guidelines recommend that community-acquired pneumonia (CAP) patients admitted to hospital wards initially receive respiratory fluoroquinolone monotherapy or beta-lactam plus macrolide combination therapy. There is little evidence as to which regimen is preferred, or if differences in medical resource utilization exist between therapies. Thus, the authors compared length of hospital stay (LOS) and length of intravenous antibiotic therapy (LOIV) for patients who received initial levofloxacin 750 mg daily versus ceftriaxone 1000 mg plus azithromycin 500 mg daily ('combination therapy').. Adult hospital CAP cases from January 2005 to December 2007 were identified by principal discharge diagnosis code. Patients with a chest infiltrate and medical notes indicative of CAP were included. Direct intensive care unit admits and healthcare-associated cases were excluded. A propensity score technique was used to balance characteristics associated with initial antimicrobial therapy using multivariable regression to derive the scores. Propensity score categories, defined as propensity score quintiles, rather than propensity scores themselves, were used in the least squares regression model to assess the impact of LOS and LOIV.. A total of 495 patients from six hospitals met study criteria. Of these, 313 (63%) received levofloxacin and 182 (37%) received combination therapy. Groups were similar with respect to age, sex, most comorbidities, presenting signs and symptoms, and Pneumonia Severity Index (PSI) risk class. Patients on combination therapy were more likely to have heart failure and receive pre-admission antibiotics. Adjusted least squares mean (+/-SE) LOS and LOIV were shorter with levofloxacin versus combination therapy: LOS, 4.6 +/- 0.17 vs. 5.4 +/- 0.22 days, p < 0.01; and LOIV, 3.6 +/- 0.17 vs. 4.8 +/- 0.21 days, p < 0.01. Results for PSI risk class III or IV patients were: LOS, 5.0 +/- 0.30 vs. 5.9 +/- 0.37 days, p = 0.07; and LOIV, 3.7 +/- 0.33 vs. 5.2 +/- 0.39 days, p < 0.01. Due to the retrospective study design, limited sample size, and scope (single health-network), the authors encourage replication of this study in other data sources.. Given the LOS and LOIV reductions of 0.8 and 1.2 days, respectively, utilization of levofloxacin 750 mg daily for CAP patients admitted to the medical floor has the potential to result in substantial cost savings for US hospitals.

Topics: Adult; Aged; Anti-Bacterial Agents; Azithromycin; Ceftriaxone; Community-Acquired Infections; Drug Therapy, Combination; Female; Health Resources; Humans; Least-Squares Analysis; Levofloxacin; Male; Middle Aged; Ofloxacin; Pneumonia; Practice Guidelines as Topic; Societies, Medical; United States

Azithromycin (AZM) has been used as an anti-inflammatory agent in the treatment of cystic fibrosis (CF), particularly those with chronic infection with P. aeruginosa (PA). To investigate mechanisms associated with the beneficial effects of AZM in CF, we examined bacterial load, cytokine levels, and clearance of inflammatory cells in CF mice infected with mucoid PA and treated with AZM.. Gut-corrected Cftr(tm1Unc)-TgN(FABPCFTR)#Jaw CF mice infected with an alginate-overproducing PA CF-isolate were treated with AZM or saline and examined for survival of animals, lung bacterial load, inflammation, cytokine levels, and apoptotic cells up to 5 days post-infection.. Administration of AZM (20 mg/kg) 24 h after the infection improved 5-day survival to 95% compared with treatment with saline (56%). AZM administration was associated with significant reductions in bacterial load, decreased lung inflammation, and increased levels of IFN-gamma. AZM increased macrophage clearance of apoptotic neutrophils from the lung.. Azithromycin enhances bacterial clearance and reduces lung inflammation by improving innate immune defense mechanisms in CF mice.

Topics: Alginates; Animals; Anti-Bacterial Agents; Apoptosis; Azithromycin; Biofilms; Bronchoalveolar Lavage Fluid; Cystic Fibrosis; Cytokines; Drug Resistance, Bacterial; Female; Lung; Mice; Neutrophils; Peroxidase; Pneumonia; Pseudomonas Infections; Respiratory Mucosa; Survival Analysis

Inflammation plays a critical role in lung disease development and progression in cystic fibrosis. Azithromycin is used for the treatment of cystic fibrosis lung disease, although its mechanisms of action are poorly understood. We tested the hypothesis that azithromycin modulates lung inflammation in cystic fibrosis mice.. We monitored cellular and molecular inflammatory markers in lungs of cystic fibrosis mutant mice homozygous for the DeltaF508 mutation and their littermate controls, either in baseline conditions or after induction of acute inflammation by intratracheal instillation of lipopolysaccharide from Pseudomonas aeruginosa, which would be independent of interactions of bacteria with epithelial cells. The effect of azithromycin pretreatment (10 mg/kg/day) given by oral administration for 4 weeks was evaluated.. In naive cystic fibrosis mice, a spontaneous lung inflammation was observed, characterized by macrophage and neutrophil infiltration, and increased intra-luminal content of the pro-inflammatory cytokine macrophage inflammatory protein-2. After induced inflammation, cystic fibrosis mice combined exaggerated cellular infiltration and lower anti-inflammatory interleukin-10 production. In cystic fibrosis mice, azithromycin attenuated cellular infiltration in both baseline and induced inflammatory condition, and inhibited cytokine (tumor necrosis factor-alpha and macrophage inflammatory protein-2) release in lipopolysaccharide-induced inflammation.. Our findings further support the concept that inflammatory responses are upregulated in cystic fibrosis. Azithromycin reduces some lung inflammation outcome measures in cystic fibrosis mice. We postulate that some of the benefits of azithromycin treatment in cystic fibrosis patients are due to modulation of lung inflammation.

Topics: Animals; Anti-Inflammatory Agents; Azithromycin; Chemokine CXCL2; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Interleukin-10; Lipopolysaccharides; Lung; Macrophages; Mice; Mice, Mutant Strains; Monokines; Neutrophil Infiltration; Pneumonia; Tumor Necrosis Factor-alpha

Topics: Adult; Azithromycin; Community-Acquired Infections; Delayed-Action Preparations; Drug Interactions; Haemophilus Infections; Humans; Pneumonia; Sinusitis

BB-81384, a novel peptide deformylase (PDF) inhibitor, was characterized in terms of enzyme inhibition profile, antibacterial activity, rodent pharmacokinetics and oral efficacy in murine infection models.. MICs were determined by standard NCCLS broth microdilution. Selectivity of metalloenzyme inhibition was determined with a limited panel of enzymes via standard biochemical assays. Profiling of the pharmacokinetics and select tissue disposition in mice was determined and compared with that of the macrolide, azithromycin. In vivo murine efficacy studies using Streptococcus pneumoniae were conducted using a peritonitis model, as well as lung and thigh burden models of infection.. BB-81384 selectively inhibited PDF with an IC(50) approximately 10 nM and with MICs < 0.5 mg/L against most S. pneumoniae pathogens. Pharmacokinetic analysis revealed good oral bioavailability and moderate clearance and volume of distribution. BB-81384 partitioning to lung tissue was similar in terms of magnitude and kinetics to that of the plasma compartment. Single-administration oral efficacy in a mouse peritonitis model was evident with an ED(50) of 30 mg/kg. BB-81384 reduced the bacterial load by approximately 5 and 3 log units in organ-burden models of lung and thigh infection, respectively.. BB-81384, a novel PDF inhibitor with good activity against S. pneumoniae in vitro, was the first compound of this class to be profiled for oral pharmacokinetics and tissue disposition and to demonstrate oral anti-pneumococcal efficacy in mice.

Topics: Amidohydrolases; Amoxicillin-Potassium Clavulanate Combination; Animals; Anti-Bacterial Agents; Azithromycin; Bacteria; Drug Therapy, Combination; Enzyme Inhibitors; Kinetics; Mice; Mice, Inbred ICR; Microbial Sensitivity Tests; Muscle, Skeletal; Muscular Diseases; Neutropenia; Peritonitis; Piperazines; Pneumococcal Infections; Pneumonia; Streptococcus pneumoniae; Tissue Distribution

Topics: Anti-Bacterial Agents; Azithromycin; Community-Acquired Infections; Humans; Length of Stay; Macrolides; Pneumonia; Retrospective Studies

Current American Thoracic Society (ATS) community-acquired pneumonia treatment guidelines recommend azithromycin monotherapy for a limited subset of hospitalized patients. We evaluated the effectiveness of azithromycin monotherapy in a more generalized population of patients hospitalized with mild-to-moderate community-acquired pneumonia.. We reviewed medical records from a Veterans Affairs facility for patients admitted with community-acquired pneumonia between December 1, 1997, and June 30, 2001, comparing those receiving azithromycin monotherapy, other ATS-recommended antibiotics, and non-ATS-recommended antibiotics. We excluded patients with immunosuppression, metastatic cancer, or hospital-acquired pneumonia. Outcome measures included times to stability, meeting criteria for change to oral therapy, and eligibility for discharge; length of stay; intensive care unit transfer; and mortality. Outcomes were adjusted for pneumonia severity, skilled nursing facility status, and processes of care.. A total of 442 patients were eligible for the study (221 in the azithromycin monotherapy group, 129 in the ATS group, and 92 in the non-ATS group). Times to clinical stability and to fulfilling early switch criteria were not statistically significantly different among the 3 groups. Mean time to fulfilling early discharge criteria was 2.48 days for patients receiving azithromycin monotherapy vs 2.84 days for those receiving ATS antibiotics (P =.008) and 2.58 days for those receiving non-ATS antibiotics (P =.64). Overall mean length of stay was shorter in the azithromycin monotherapy group (4.35 days) vs the ATS (5.73 days) (P =.002) and non-ATS (6.21 days) (P<.001) groups. Mortality, intensive care unit transfer, and readmission rates were similar across the groups.. Azithromycin monotherapy is equally as efficacious as other ATS-recommended regimens for treating hospitalized patients with mild-to-moderate community-acquired pneumonia.

Topics: Aged; Anti-Bacterial Agents; Azithromycin; California; Cohort Studies; Community-Acquired Infections; Comorbidity; Female; Humans; Length of Stay; Male; Middle Aged; Patient Admission; Pneumonia; Retrospective Studies; Severity of Illness Index; Societies, Medical; Survival Analysis; Treatment Outcome

Topics: Aged; Anti-Bacterial Agents; Azithromycin; Delirium; Humans; Male; Pneumonia

In this report, we describe an azithromycin treatment failure in community-acquired pneumonia. During the first three days of azithromycin, the patient's symptoms worsened, and she was subsequently admitted to the hospital. Blood cultures were positive for a penicillin-susceptible, macrolide-resistant S. pneumoniae. DNA sequencing revealed an A2059G mutation in domain V of the 23S rRNA. To our knowledge, this is the first clinical report of an azithromycin failure in the treatment of S. pneumoniae resistant to macrolides by this mechanism.

Topics: Anti-Bacterial Agents; Azithromycin; Community-Acquired Infections; Drug Resistance, Bacterial; Female; Genetic Variation; Humans; Middle Aged; Pneumonia; RNA, Ribosomal, 23S; Sequence Analysis, DNA; Streptococcus pneumoniae; Treatment Failure

Topics: Anti-Bacterial Agents; Azithromycin; Ceftriaxone; Cefuroxime; Cephalosporins; Gram-Negative Anaerobic Bacteria; Gram-Negative Bacterial Infections; Humans; Infant; Male; Pneumonia

Topics: Amoxicillin; Australia; Azithromycin; Ceftriaxone; Clinical Trials as Topic; Community-Acquired Infections; Drug Therapy, Combination; Drug Utilization; Humans; Pneumonia; Sensitivity and Specificity

We examined the cost-effectiveness of sparfloxacin compared with other selected oral antimicrobials in outpatient treatment of community-acquired pneumonia (CAP) using clinical pathway-based decision analysis. Cost estimates were obtained from medical claims databases and Medicare reimbursement schedules. Probability estimates were derived from published clinical trials, the medical literature, and clinical expert opinion. Overall adjusted efficacy rates were 89% for sparfloxacin, 79.4% for azithromycin, 77.8% for clarithromycin, 73% for cefaclor, 70.8% for amoxicillin-clavulanic acid, and 69% for erythromycin. The expected total cost/CAP episode of treatment with sparfloxacin was $216.07 compared with $258.97, $297.08, $345.75, $389.80, and $395.93 for azithromycin, clarithromycin, erythromycin, amoxicillin-clavulanic acid, and cefaclor, respectively. Therapy with sparfloxacin for managing CAP is cost effective-relative to other commonly prescribed antibiotics, resulting in net cost savings.

Topics: Administration, Oral; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Anti-Infective Agents; Antitubercular Agents; Azithromycin; Cefaclor; Clarithromycin; Community-Acquired Infections; Cost-Benefit Analysis; Erythromycin; Fluoroquinolones; Humans; Models, Economic; Outpatients; Pneumonia; Treatment Outcome

The effects of treatment with azithromycin plus rifampin (A+R), amoxicillin (A), or placebo (P) on the chronic course of experimental Chlamydia pneumoniae pneumonitis in mice were assessed by culture, PCR, and immunocytochemistry as well as by degree of inflammation in lung tissue. Eradication of the pathogen was significantly more frequent and inflammation in tissue was significantly reduced after treatment with A+R compared to after treatment with A or P. Combination therapy with azithromycin plus rifampin showed favorable effects in the chronic course of C. pneumoniae pneumonitis.

Topics: Amoxicillin; Animals; Anti-Bacterial Agents; Azithromycin; Chlamydia Infections; Chlamydophila pneumoniae; Drug Therapy, Combination; Mice; Pneumonia; Rifampin

Topics: Administration, Oral; Anti-Bacterial Agents; Azithromycin; Cefuroxime; Cephalosporins; Community-Acquired Infections; Drug Administration Schedule; Drug Therapy, Combination; Erythromycin; Hospitalization; Humans; Injections, Intravenous; Multicenter Studies as Topic; Pneumonia; Randomized Controlled Trials as Topic

Topics: Anti-Bacterial Agents; Azithromycin; Cost-Benefit Analysis; Humans; Pneumonia; Respiratory Tract Infections

Topics: Anti-Bacterial Agents; Azithromycin; Child; Humans; Pneumonia

Topics: Azithromycin; Cefuroxime; Cost Savings; Drug Resistance, Microbial; Drug Therapy, Combination; Erythromycin; Humans; Outcome and Process Assessment, Health Care; Pneumonia; Practice Guidelines as Topic; Treatment Outcome; United States

The costs of i.v. erythromycin versus azithromycin (in terms of medication use and treatment of adverse effects) when these drugs were used with other antimicrobials to treat community-acquired pneumonia (CAP) were compared. The medical records of patients receiving i.v. azithromycin or erythromycin as part of combination antimicrobial therapy for the treatment of CAP at a 473-bed level 1 trauma center in Kentucky were retrospectively reviewed. Data were collected for patients treated from December 1, 1997, through March 31, 1998. Patient data collected included occurrence of phlebitis or pain at the injection site, number of line changes due to phlebitis, and culture results. Cost data collected included drug acquisition cost, pharmacy cost of drug preparation, nursing time to administer the agent, cost of drug supplies, and cost of managing complications. Three time-and-motion studies were conducted to determine technician preparation time and pharmacist verification time. The medical records of 62 patients were identified and reviewed; 50 patients were enrolled in the study (25 in the azithromycin group and 25 in the erythromycin group). The average total days of therapy was 5.1 for the azithromycin group and 5.6 for the erythromycin group. The average total cost, including the cost of complications ($4.36 per patient in the erythromycin group), was $66.46 in the azithromycin group and $96.56 in the erythromycin group. The difference in costs between the two groups was not significant. There was no significant cost difference between azithromycin- and erythromycin-containing combination antimicrobial therapy in the treatment of CAP.

Topics: Anti-Bacterial Agents; Azithromycin; Community-Acquired Infections; Erythromycin; Humans; Male; Medical Records; Middle Aged; Pneumonia; Retrospective Studies

Topics: Anti-Bacterial Agents; Azithromycin; Chlamydia Infections; Humans; Pneumonia; Pneumonia, Pneumococcal

Topics: Aged; Anti-Bacterial Agents; Attention; Azithromycin; Community-Acquired Infections; Drug Information Services; Humans; Male; Medication Errors; Nursing Staff, Hospital; Pneumonia

The efficacy of a 5-day regimen consisting of 500 mg in a single dose on the first day followed by 250 mg once daily for 4 consecutive days was compared with that of a 3-day course of azithromycin given in single daily doses of 500 mg for treatment of atypical pneumonia. Adult patients hospitalized with atypical pneumonia in the years 1990 to 1993 were studied retrospectively. For each patient, the medical history, laboratory data, the results of serological tests, chest radiographs and treatment outcome were reviewed. Out of 148 patients with atypical pneumonia, 40 were treated with azithromycin for 5 days (Group 1) and 41 for 3 days (Group 2). The success rate in Group 1 was 80% (32 patients). Eight patients did not respond to treatment: 5 had significant complement fixing antibody titers to adenovirus and in 3 the etiology was unknown. The success rate in Group 2 was 88% (36 patients). Azithromycin was ineffective in all 3 patients with adenoviral pneumonia, in 1 patient with Q fever, and in 1 patient with no identified pathogen. Azithromycin is equally effective as treatment of atypical pneumonia in adult patients if given for 3 or 5 days at the same total dose.

Topics: Administration, Oral; Adolescent; Adult; Aged; Anti-Bacterial Agents; Azithromycin; Dose-Response Relationship, Drug; Female; Humans; Male; Middle Aged; Pneumonia; Retrospective Studies

Azithromycin (AZM) in fine granules was studied for its pharmacokinetics and clinical efficacies in eight child patients with ages between 1 month and 8 years. Informed consent was received from all of their parents. AZM was administered to the patients once a day at a dose of 10 mg/kg for 3 days. The clinical efficacies of AZM in 8 patients with microbial infections (pneumonia in one, Mycoplasma pneumonia in two, acute tonsillitis in one, pertussis in one, Campylobacter enteritis in one, infectious enteritis in one, Salmonella enteritis in one) were evaluated as "excellent" in five cases, "good" in two and "not evaluable" in one. As for the microbial efficacy, isolated strains were eradicated in 2 out of 3 patients. No adverse reaction was found except for one case with abnormal laboratory change, that is mildly increased GPT value. Plasma samples were collected from 3 cases. The elimination half-life of AZM was 45.8 hours. AUC0-infinity was 12.6 micrograms.hr/ml. Urine sample was collected from one. AZM concentration in urine was 35.0 micrograms/ml during a period between 48 and 72 hours after the start of treatment.

Topics: Anti-Bacterial Agents; Azithromycin; Campylobacter Infections; Child; Child, Preschool; Enteritis; Female; Humans; Male; Pneumonia; Pneumonia, Mycoplasma; Salmonella Infections; Tonsillitis

35 children between 9 months and 12 years of ages were given 9.1 to 12.2 mg/kg of azithromycin (AZM) once a day for 3 days. In the treatment of pediatric infectious diseases, we studied pharmacokinetics, efficacy and safetiness of AZM. After administration of 10 mg/kg/day of AZM for 3 days, the elimination half-life was calculated to be 3.8 +/- 16.3 hours (n = 6, mean +/- S.D.). The excretion rate of AZM in the urine within 120 hours of administration was 9.0 +/- 2.3% (n = 5). For the evaluation of efficacy of AZM, we treated 33 cases of children with pharyngotonsillitis, bronchitis, mycoplasma bronchitis, pneumonia, mycoplasma pneumonia, atypical pneumonia, and SSTI. The efficacy rate of these cases were 93.9%. 6 strains of bacteria were identified as causative agents. All strains were eradicated upon the treatment. One case of elevated GOT and GPT and two cases of elevated GPT were observed. No clinical adverse reactions were observed. In conclusion, AZM was useful for the treatment of pediatric infectious diseases were examined.

Topics: Anti-Bacterial Agents; Azithromycin; Bronchitis; Child; Child, Preschool; Female; Half-Life; Humans; Infant; Male; Mycoplasma Infections; Pharyngitis; Pneumonia; Tonsillitis

A 39-year-old HIV positive patient developed myalgia, headache and cough 4 weeks after a tick bite. His temperature was 37.4 degrees C and a circular pale erythema was noted over the left lower leg.. C-reactive protein was raised to 120 mg/l, white blood cell count was 5860/microliter, CD4-lymphocyte count 250/microliter. The chest radiogram showed pneumonitic infiltration in the left lower lobe. There were IgM antibodies against Borrelia burgdorferi.. Left lower lobe pneumonia and chronic erythema migrans were diagnosed and he was given oral azithromycin (500 mg on the first day and 250 mg for 4 days). The pneumonia cleared up, but 2 weeks later he developed symptoms of meningitis (496 cells per microliter, 87% lymphocytes, positive Borrelia burgdorferi antibody titer), which quickly and lastingly responded to ceftriaxon (2 g daily by brief infusion for 14 days).. This immune-compromised HIV-infected patient developed disseminated borreliosis with CNS involvement 2 weeks after the occurrence of chronic erythema migrans. The initial treatment of the latter with azithromycin was unable to prevent the meningitis. It is unlikely that there was a causal connection between the borreliosis and the pneumonia.

Topics: Adult; Animals; Anti-Bacterial Agents; Antibodies, Bacterial; Azithromycin; Borrelia burgdorferi Group; Ceftriaxone; Cephalosporins; HIV Seropositivity; Humans; Immunocompromised Host; Immunoglobulin M; Insect Bites and Stings; Lyme Disease; Male; Meningitis, Bacterial; Pneumonia; Ticks

Fine granules or capsules of azithromycin (AZM) were given to 32 pediatric patients for the treatment of the following diseases: pharyngitis in three cases; tonsillitis in one; bronchitis in six; pneumonia in six; mycoplasmal pneumonia in 14; pertussis and enteritis in one, each. Effectiveness of AZM was evaluated in 30 cases and the drug was rated "excellent" in 18 patients, "good" in 11 and "fair" in one, resulting in a total efficacy rate of 96.7%. Three strains of bacteria were isolated from 3 patients as the causative organisms including: Streptococcus pneumoniae, Haemophilus influenzae and Haemophilus parainfluenzae, from three different patients, respectively. One patient complained of mild diarrhea, another patient mild urticaria. Abnormal laboratory test results were reported as follows: one patient showed a slight decrease in leukocyte count, three patients showed slight increases in eosinophils, and one patient had slight elevations in GOT and GPT. The above results suggest that AZM is a useful antibiotic drug in the treatment of pediatric patients with various bacterial infections.

Topics: Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Bronchitis; Child; Child, Preschool; Female; Humans; Infant; Male; Pharyngitis; Pneumonia; Pneumonia, Mycoplasma; Tonsillitis

The Third International Conference on the Macrolides, Azalides, and Streptogramins was held in Lisbon, Portugal. Conferees were given news on the latest advances in the development of innovative antibiotics belonging to these increasingly important groups of drugs, and learned of their expanding clinical indications. The following areas were emphasized at the conference: multiresistant gram-positive bacteremias in patients with serious underlying infections, azithromycin's effectiveness against acute community-acquired pneumonia, results of clarithromycin plus ethambutol in HIV-infected patients with MAC bacteremia, duodenal ulcers associated with Helicobacter pylori infections, and use of roxithromycin against AIDS-related cryptosporidium diarrhea.

Topics: AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Anti-Infective Agents; Azithromycin; Bacteremia; Bacterial Infections; Clarithromycin; Clofazimine; Cryptosporidiosis; Drug Therapy, Combination; Duodenal Ulcer; Ethambutol; Humans; Microbial Sensitivity Tests; Mycobacterium avium-intracellulare Infection; Pneumonia; Smoking; Virginiamycin

Topics: Acquired Immunodeficiency Syndrome; AIDS-Related Opportunistic Infections; Animals; Anti-Bacterial Agents; Azithromycin; Community-Acquired Infections; Cryptosporidiosis; Humans; Injections, Intravenous; Malaria, Falciparum; Mycobacterium avium-intracellulare Infection; Plasmodium falciparum; Pneumonia; Pneumonia, Pneumocystis; Toxoplasmosis, Cerebral

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Azithromycin; Bacterial Infections; Cefixime; Cefotaxime; Cefuroxime; Clarithromycin; Fluoroquinolones; Humans; Pneumonia

Since serious sequelae may follow streptococcal infections, eradication is viewed as necessary for successful therapy. Studies were therefore conducted to compare the effectiveness of azithromycin with other macrolide antibiotics and amoxycillin to eliminate these organisms in experimental localized infections. In a Streptococcus pneumoniae lung infection induced by transtracheal challenge, the pathogen was not recovered after therapy with azithromycin (ED50 7.9 mg/kg), while clarithromycin was not effective (ED50 > 100 mg/kg). However, in a S. pneumoniae middle ear infection, azithromycin and clarithromycin were effective (ED50 2.9 and 6.3 mg/kg, respectively) in eradicating the pathogen from this closed space infection. Against a localized Streptococcus pyogenes infection (implanted inoculated disc), azithromycin effectively eradicated the pathogen, while clarithromycin, roxithromycin and erythromycin did not. Eradication of a viridans streptococcus or Streptococcus gordonii (formerly Streptococcus sanguis) from heart tissue in experimental bacterial endocarditis was also evaluated. Azithromycin given prophylactically or therapeutically was efficacious in eliminating the viridans streptococcus and S. gordonii in the bacterial endocarditis model of infection; erythromycin was only marginally effective in the same studies. All studies provided evidence of the bactericidal action of azithromycin in vivo and demonstrated the ability of the compound to eradicate streptococcal pathogens in localized infections.

Topics: Amoxicillin; Animals; Anti-Bacterial Agents; Azithromycin; Clarithromycin; Disease Models, Animal; Endocarditis, Bacterial; Erythromycin; Female; Gerbillinae; Male; Mice; Mice, Inbred C57BL; Mice, Inbred Strains; Otitis Media; Pneumococcal Infections; Pneumonia; Rats; Roxithromycin; Streptococcal Infections; Streptococcus pyogenes

Among the atypical pneumonias observed between March 1990 and March 1991, 6 were diagnosed as being caused by Chlamydia pneumoniae of the TWAR strain. The serological diagnosis was obtained by a microimmunofluorescence test. All 6 patients had anti-TWAR antibody levels higher than 512; they were treated with a macrolide administered by the oral route and were cured without sequelae or recurrences. Four cases received a ten day course of roxithromycin 300 mg/day and one case received erythromycin 2 g/day also for 10 days. The sixth case received a short course of azithromycin 500 mg once daily for three days. In 2 other patients presenting with clinical and radiological signs of pneumonia the diagnosis of C. pneumoniae infection could not be made despite an antibody level equal or higher than 512, since the serological results showed cross-reactions between C. pneumoniae, C. trachomatis and C. psittaci antibody responses.

Topics: Aged; Azithromycin; Chlamydia Infections; Chlamydophila pneumoniae; Erythromycin; Female; Fluorescent Antibody Technique; Humans; Male; Middle Aged; Pneumonia; Prospective Studies; Roxithromycin; Serologic Tests