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A total of 78 patients received the study medication, 59 of whom had sufficient data available for efficacy analysis. Overall, a good clinical response with azithromycin was achieved in 49 patients (83.1%) and a microbiological response was achieved in 78.3%. Azithromycin resistance, based on CLSI criteria, was demonstrated in 85.7% (12/14) of S. pneumoniae isolates, and the presence of ermB genes was found in 50.0% (7/14). However, among patients in whom S. pneumoniae was isolated (n=17), a good clinical response was achieved in 76.5% (13/17), and the microbiological response rate was 64.3% (9/14). Furthermore, 6 of 7 patients in whom high-level resistance was documented (MICs >256 microg/mL and carrying ermB genes) exhibited good clinical responses. Azithromycin was well tolerated; adverse events, mainly of a gastrointestinal nature, were recorded in 6 patients (7.7%).
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The percentage of azithromycin resistant Neisseria gonorrhoeae strains is increasing in Poland and the antibiotic should not be used in monotherapy as gonorrhoea patients. It should only be used in combination with ceftriaxone or cefixime.
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Both treatments were well-tolerated, with the majority of adverse events being GI in nature. Favorable clinical outcomes in clinically evaluable patients were demonstrated in 89% of patients receiving azithromycin and in 92% of patients receiving levofloxacin by day 4 of therapy. At day 24, the posttherapy visit, favorable responses were approximately 82% and 86%, respectively, for patients in the two treatment groups. The bacterial eradication rates of respiratory pathogens were 96% for azithromycin and 85% for levofloxacin.
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Etravirine (formerly TMC125) is a non-nucleoside reverse transcriptase inhibitor (NNRTI) with activity against wild-type and NNRTI-resistant strains of HIV-1. Etravirine has been approved in several countries for use as part of highly active antiretroviral therapy in treatment-experienced patients. In vivo, etravirine is a substrate for, and weak inducer of, the hepatic cytochrome P450 (CYP) isoenzyme 3A4 and a substrate and weak inhibitor of CYP2C9 and CYP2C19. Etravirine is also a weak inhibitor of P-glycoprotein. An extensive drug-drug interaction programme in HIV-negative subjects has been carried out to assess the potential for pharmacokinetic interactions between etravirine and a variety of non-antiretroviral drugs. Effects of atorvastatin, clarithromycin, methadone, omeprazole, oral contraceptives, paroxetine, ranitidine and sildenafil on the pharmacokinetic disposition of etravirine were of no clinical relevance. Likewise, etravirine had no clinically significant effect on the pharmacokinetics of fluconazole, methadone, oral contraceptives, paroxetine or voriconazole. No clinically relevant interactions are expected between etravirine and azithromycin or ribavirin, therefore, etravirine can be combined with these agents without dose adjustment. Fluconazole and voriconazole increased etravirine exposure 1.9- and 1.4-fold, respectively, in healthy subjects, however, no increase in the incidence of adverse effects was observed in patients receiving etravirine and fluconazole during clinical trials, therefore, etravirine can be combined with these antifungals although caution is advised. Digoxin plasma exposure was slightly increased when co-administered with etravirine. No dose adjustments of digoxin are needed when used in combination with etravirine, however, it is recommended that digoxin levels should be monitored. Caution should be exercised in combining rifabutin with etravirine in the presence of certain boosted HIV protease inhibitors due to the risk of decreased exposure to etravirine. Although adjustments to the dose of clarithromycin are unnecessary for the treatment of most infections, the use of an alternative macrolide (e.g. azithromycin) is recommended for the treatment of Mycobacterium avium complex infection since the overall activity of clarithromycin against this pathogen may be altered when co-administered with etravirine. Dosage adjustments based on clinical response are recommended for clopidogrel, HMG-CoA reductase inhibitors (e.g. atorvastatin) and for phosphodiesterase type-5 inhibitors (e.g. sildenafil) because changes in the exposure of these medications in the presence of co-administered etravirine may occur. When co-administered with etravirine, a dose reduction or alternative to diazepam is recommended. When combining etravirine with warfarin, the international normalized ratio (INR) should be monitored. Systemic dexamethasone should be co-administered with caution, or an alternative to dexamethasone be found as dexamethasone induces CYP3A4. Caution is also warranted when co-administering etravirine with some antiarrhythmics, calcineurin inhibitors (e.g. ciclosporin) and antidepressants (e.g. citalopram). Co-administration of etravirine with some antiepileptics (e.g. carbamazepine and phenytoin), rifampicin (rifampin), rifapentine or preparations containing St John's wort (Hypericum perforatum) is currently not recommended as these are potent inducers of CYP3A and/or CYP2C and may potentially decrease etravirine exposure. Antiepileptics that are less likely to interact based on their known pharmacological properties include gabapentin, lamotrigine, levetiracetam and pregabalin. Overall, pharmacokinetic and clinical data show etravirine to be well tolerated and generally safe when given in combination with non-antiretroviral agents, with minimal clinically significant drug interactions and no need for dosage adjustments of etravirine in any of the cases, or of the non-antiretroviral agent in the majority of cases studied.
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In four of seven patients, M genitalium in post-treatment urine had an A-to-G transition at nucleotide position 2071 or 2072, corresponding to 2058 or 2059 in the 23S rRNA gene of Escherichia coli. In one of the four strains, Pro81Ser in the ribosomal protein L4 accompanied the mutation in the 23S rRNA gene. The genotyping of M genitalium DNAs suggested that these four post-treatment strains were selected from the respective closely related or identical pretreatment strains without macrolide resistance-associated mutations by the treatment.
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During 2009-11, 434 Streptococcus pneumoniae, 307 Haemophilus influenzae and 140 Moraxella catarrhalis were collected from eight centres and during 2013-14, 208 S. pneumoniae, 185 H. influenzae and 80 M. catarrhalis were collected from five centres. Penicillin-non-susceptible isolates remained stable at ∼66% over both time periods but susceptibility decreased significantly for amoxicillin/clavulanic acid (or amoxicillin) and cefaclor. For H. influenzae, the proportion of β-lactamase-positive isolates and β-lactamase-negative ampicillin-resistant strains (CLSI definition) was higher in 2013-14 (25.4% and 7.0%, respectively) than in 2009-11 (16.3% and 3.6%, respectively), with decreased ampicillin and cephalosporin susceptibility. By 2009-11 and 2013-14, only amoxicillin/clavulanic acid (amoxicillin), levofloxacin, penicillin (intravenously) and chloramphenicol inhibited >70% of S. pneumoniae. During 2013-14, M. catarrhalis showed increasing resistance, with cefaclor and levofloxacin susceptibility decreasing significantly. However, amoxicillin/clavulanic acid, cefuroxime and levofloxacin continued to inhibit >90% of isolates.
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Aggregatibacter actinomycetemcomitans resists killing by neutrophils and is inhibited by azithromycin (AZM) and amoxicillin (AMX). AZM actively concentrates inside host cells, whereas AMX enters by diffusion. The present study is conducted to determine whether AZM is more effective than AMX at enhancing phagocytic killing of A. actinomycetemcomitans by neutrophils.
Biofilm production is an important mechanism for bacterial survival and its association with antimicrobial resistance represents a challenge for the patient treatment. In this study we evaluated the in vitro action of macrolides in combination with anti-pseudomonal agents on biofilm-grown Pseudomonas aeruginosa recovered from cystic fibrosis (CF) patients.
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Antimicrobial susceptibility was analyzed for 354 typhoidal Salmonella isolates collected during 1999-2012 in the Netherlands. In 16.1% of all isolates and in 23.8% of all isolates that showed increased MICs for ciprofloxacin, the MIC for azithromycin was increased. This resistance may complicate empirical treatment of enteric fever.
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In this prospective study we compared the efficiency of azithromycin and amoxicillin-clavulanate in treatment of acute sinusitis in children. Seventy patients were included in the age between 5 and 15 years. Beside ENT and pediatricians examination, nasal and throat smear on culture and antibiogram is taken from all the patients, as well as, X-ray of paranasal sinuses and laboratory findings, followed by check-up of nasal and throat smear and X-ray of paranasal sinuses. Azithromycin in single daily dose of 10 mg/kg during three days showed same efficiency as amoxicillin-clavulanate given three times per day in dose of 45 mg/kg during ten days.
Azithromycin loaded microspheres with blends of poly-l-lactide and ploy-D,L-lactide-co-glycolide as matrices were prepared by the atmosphere-solvent evaporation (ASE) and reduced pressure-solvent evaporation (RSE) method. Both the X-ray diffraction spectra and DSC thermographs demonstrated that poly-L-lactide existed in a crystalline form in the ASE microspheres, while an amorphous form was present in the RSE formulations. Besides, solvent removal at atmosphere gave microspheres of porous and rough surfaces, but smooth surfaces appeared in the RSE microspheres. The incorporation efficiency as well as the burst release (cumulative release in the first 24h) in the ASE formulations was 39.94 ± 1.18% and 23.96 ± 2.01% respectively, yet the encapsulation efficiency of the microspheres fabricated under 385 mmHg was high up to 57.19 ± 3.81% and the burst release was 4.12 ± 0.15%. The in vitro drug release studies indicated that the ASE microspheres presented a zero-order profile; while the RSE formulations followed first-order kinetics. Other factors including solidification time, temperature, drug to polymer ratio and pH value of the continuous phase could also influence the physicochemical characteristics and release profiles of microspheres. In conclusion, the overall improvement of microspheres in appearance, encapsulation efficiency and controlled drug release through the RSE method could be easily fulfilled under optimal preparation conditions.
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Twenty-four healthy men aged 19-41 years.
Food and Drug Administration (FDA, USA)-approved category B antibiotics are commonly prescribed to treat infections during pregnancy. The aim of this study was to investigate antibiotic-induced changes in gut microbiota (GM) that occur during pregnancy. The 16S rRNA amplicon deep-sequencing method was used to analyze the effect of category B antibiotics (azithromycin, amoxicillin and cefaclor) on GM during pregnancy using a rat model. The GM composition was substantially modulated by pregnancy and antibiotics administration. Firmicutes, Bacteroidetes, Proteobacteria, Chlamydiae, Actinobacteria, and Cyanobacteria were the dominant phyla. Antibiotic treatment during pregnancy increased the relative abundance of Proteobacteria and reduced Firmicutes. The genera Shigella, Streptococcus, Candidatus Arthromitus, and Helicobacter were significantly (p < 0.05) more abundant during pregnancy. Antibiotics significantly (p < 0.05) reduced the relative abundance of Lactobacillus but increased that of Enterobacter. There was a significant (p < 0.05) decrease in Lactobacillus sp., Lactobacillus gallinarum and Lactobacillus crispatus during pregnancy. Antibiotic treatment reduced bacterial diversity; the lowest number of operational taxonomic units (OTUs) were detected in the cefaclor-treated groups. Antibiotics significantly (p < 0.05) promoted weight gain during pregnancy, and increased relative abundance of Shigella sonnei, Enterococcus hormaechei, and Acinetobacter sp. GM perturbations were accompanied by increases in Proteobacteria abundance and weight gain in pregnancy following antibiotic treatment.
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Two ATCC strains and two clinical strains of Ureaplasma were evaluated in vitro for antibiotic minimum inhibitory concentration (MIC). In addition, FVB albino mice pups infected with Ureaplasma were randomly assigned to saline, erythromycin, or azithromycin therapy and survival, quantitative blood culture, and growth were evaluated.
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The anti-inflammatory and immunomodulatory effects of macrolides include the ability to decrease mucus secretion and inhibit inflammatory mediators in chronic rhinosinusitis. Nevertheless, their mechanisms of action remain to be determined. Here we have investigated the effects of macrolide antibiotics (clarithromycin, azithromycin and josamycin; representating the 14-, 15- and 16-membered macrolides) on endogenous steroids in human sinonasal epithelial cells and mouse nasal mucosa.
Enteric fever (typhoid and paratyphoid) remains a threat to British troops overseas and causes significant morbidity and mortality. We report the case of a soldier who developed typhoid despite appropriate vaccination and field hygiene measures, which began 23 days after returning from a deployment in Sierra Leone. The incubation period was longer than average, symptoms started 2 days after stopping doxycycline for malaria chemoprophylaxis and initial blood cultures were negative. The Salmonella enterica serovar Typhi eventually isolated was resistant to amoxicillin, co-amoxiclav, co-trimoxazole and nalidixic acid and had reduced susceptibility to ciprofloxacin. He was successfully treated with ceftriaxone followed by azithromycin, but 1 month later he remained fatigued and unable to work. The clinical and laboratory features of enteric fever are non-specific and the diagnosis should be considered in troops returning from an endemic area with a febrile illness. Multiple blood cultures and referral to a specialist unit may be required.
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The MIC at which 90% of the isolates were inhibited and the minimal chlamydiacidal concentration at which 90% of the isolates were killed by cethromycin were both 0.016 mg/L (range 0.016-0.031 mg/L). Cethromycin was the most active antibiotic tested in this study.
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To determine the effectiveness and safety of interventions aimed at preventing MAC infection in adults and children with HIV infection.
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This paper reports the development of a new method for the focused ultrasound extraction of Cr and Mn from pharmaceutical formulations and their determination by electrothermal atomic absorption spectrometry (ETAAS). The method was optimized by evaluating the influence of several variables such as the sonication power and time, concentration of HCl in the extractant solution and mass of sample employed in the extraction procedure. The curves of pyrolysis and atomization were constructed for both analytes in order to evaluate the effect of the matrix on the measurement of Cr and Mn. Quantitative extraction of both Cr and Mn was achieved when 25-150 mg of the sample were sonicated for 30 min at 50% power with 5 ml of a 1 moll(-1) HCl solution. The developed method was successfully applied in the determination of Cr and Mn in samples of pharmaceutical formulations containing different active principles such as ciprofloxacin, cephalexin, azithromycin, amlodipine and methionine. There was no statistical (95% confidence level, paired t-test) difference between the results obtained by the proposed method and the results obtained after total digestion of the samples.
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Azithromycin is used as an alternative medicine in patients with syphilis who are intolerant to penicillin. Nevertheless, the report of treatment failure of azithromycin for patients with syphilis has raised concerns in China in the past years. In this study, 178 patients with early syphilis, who were treated in sexually transmitted infections clinics in four cities in Guangxi Zhuang Autonomous Region were enrolled to investigate the regional prevalence of Treponema pallidum strain resistant to azithromycin. Nested PCR was performed to amplify the 23S ribosomal RNA (23SrRNA) gene. The point mutation of A2058G in 23SrRNA, which confers Treponema pallidum resistance to azithromycin, was measured by endonuclease digestion of PCR amplification products using MboII. A2058G point mutation was detected in 91.0% (162/178; 95% CI, 86.8%, 95.2%) of the specimens, but no difference in prevalence of azithromycin resistance was found between the patients who had taken antibiotics before enrollment and the patients who had not (91.8% vs. 89.4%), nor between the patients with and without past sexually transmitted infections (87.1% vs. 93.1%). We concluded that azithromycin may not be suitable for syphilis as a treatment option in Guangxi Zhuang Autonomous Region because of the extremely high prevalence of resistance in the general syphilis population.
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Activities of clarithromycin, erythromycin, and azithromycin against 120 pneumococci from the United States were tested by agar dilution MIC. All three compounds yielded MICs at which 90% of the isolates were inhibited (MIC90S) of < or = 0.125 micrograms/ml against penicillin-susceptible and -intermediate strains, but MIC90S against resistant strains were > 128.0 micrograms/ml. All erythromycin-resistant strains were also resistant to clarithromycin and azithromycin. Clarithromycin yielded MICs which were generally one or two dilutions lower than those of the other two compounds for all strains. The respective bacteriostatic and bactericidal values (micrograms per milliliter) for two susceptible, two intermediate, and two resistant strains were 0.004 to 0.03 and 0.016 to 0.03 (0.004 to 0.03/0.016 to 0.03) (clarithromycin), 0.008 to 0.06/0.016/0.016 to 0.125 (erythromycin), and 0.016 to 0.06/0.03 to 0.125 (azithromycin); clarithromycin yielded the lowest values. All compounds were uniformly bactericidal after 24 h only; erythromycin was bactericidal at eight times the MIC, and azithromycin and clarithromycin were both bactericidal at two time the MIC. The relevance of these in vitro differences requires clarification by clinical trials.
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S. agalactiae isolates of the serotypes Ia, Ib, III, and V are common in Beijing. Among the S. agalactiae isolates, the macrolide and clindamycin resistance rates are extremely high. Most of the erythromycin-resistant isolates carry ermB.
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A high prevalence of CT infections was identified among Philadelphia public high school students. This program demonstrated the effectiveness of a school-based screening program to identify and treat these infections.
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Linear immunoglobulin A (IgA) bullous dermatosis (LABD) is a rare autoimmune disorder characterized by vesiculobullous mucocutaneous eruptions. LABD also has been reported as a drug-induced reaction. Idiopathic LABD and drug-induced LABD are clinically indistinguishable and can resemble bullous pemphigoid, dermatitis herpetiformis, or bullous erythema multiforme. LABD is diagnosed with direct immunofluorescence (DIF), and idiopathic LABD can be distinguished from drug-induced LABD with a careful medication history. We present the case of a 54-year-old man with drug-induced LABD after ingestion of rimantadine, zanamivir, and azithromycin for presumed influenza. The patient's bullous eruption resolved with discontinuation of the offending medications and treatment with prednisone and pentoxifylline.
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The prevalence of active and latent yaws infection fell rapidly and substantially 12 months after high-coverage mass treatment with azithromycin, with the reduction perhaps aided by subsequent activities to identify and treat new cases of yaws. Our results support the WHO strategy for the eradication of yaws. (Funded by Newcrest Mining and International SOS; YESA-13 ClinicalTrials.gov number, NCT01955252.).
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Azithromycin is an effective, safe and well-tolerated treatment for children with acute otitis media.
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To guide interpretation of gonorrhea tests of cure using nucleic acid amplification testing, this study examined the persistence of Neisseria gonorrhoeae DNA following treatment for pharyngeal and rectal gonorrhea.
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Development of single dose antibiotic treatments for chancroid has been followed by drug-resistant Haemophilus ducreyi in endemic areas. We examined the activity and interactions of antimicrobial agents and combinations against H. ducreyi.
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On the basis of serum and ELF concentrations, clarithromycin achieved pharmacodynamic targets against a greater proportion of S. pneumoniae isolates than did azithromycin. Clinical studies are needed to determine the efficacy of these agents against pneumococci that demonstrate in vitro resistance using current susceptibility breakpoints.