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David P Nichols - One of the best experts on this subject based on the ideXlab platform.
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impact of Azithromycin on the clinical and antimicrobial effectiveness of tobramycin in the treatment of cystic fibrosis
Journal of Cystic Fibrosis, 2017Co-Authors: David P Nichols, James F Chmiel, Milene T Saavedra, Jennifer L Taylorcousar, Lisa Saiman, Carrie Happoldt, Preston E Bratcher, Silvia M Caceres, Kenneth C Malcolm, Jerry A NickAbstract:Abstract Background Concomitant use of oral Azithromycin and inhaled tobramycin occurs in approximately half of US cystic fibrosis (CF) patients. Recent data suggest that this combination may be antagonistic. Methods Test the hypothesis that Azithromycin reduces the clinical benefits of tobramycin by analyses of clinical trial data, in vitro modeling of P. aeruginosa antibiotic killing, and regulation of the MexXY efflux pump. Results Ongoing administration of Azithromycin associates with reduced ability of inhaled tobramycin, as compared with aztreonam, to improve lung function and quality of life in a completed clinical trial. In users of Azithromycin FEV 1 (L) increased 0.8% during a 4-week period of inhaled tobramycin and an additional 6.4% during a subsequent 4-week period of inhaled aztreonam (P In vitro , Azithromycin selectively reduced the bactericidal effects tobramycin in cultures of clinical strains of P. aeruginosa , while up regulating antibiotic resistance through MexXY efflux. Conclusions Azithromycin appears capable of reducing the antimicrobial benefits of tobramycin by inducing adaptive bacterial stress responses in P. aeruginosa , suggesting that these medications together may not be optimal chronic therapy for at least some patients.
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Azithromycin may antagonize inhaled tobramycin when targeting pseudomonas aeruginosa in cystic fibrosis
Annals of the American Thoracic Society, 2014Co-Authors: Jerry A Nick, Samuel M Moskowitz, James F Chmiel, Anna V Forssen, Milene T Saavedra, Jennifer L Taylorcousar, Lisa Saiman, David P NicholsAbstract:Rationale: Recent studies of inhaled tobramycin in subjects with cystic fibrosis (CF) find less clinical improvement than previously observed. Nonhuman data suggest that in some strains of Pseudomonas aeruginosa, Azithromycin can antagonize tobramycin. Objectives: We tested the hypothesis that concomitant Azithromycin use correlates with less improvement in key outcome measures in subjects receiving inhaled tobramycin while not affecting those receiving a comparative, nonaminoglycoside inhaled antibiotic. Methods: We studied a cohort of 263 subjects with CF enrolled in a recent clinical trial comparing inhaled tobramycin with aztreonam lysine. We performed a secondary analysis to examine key clinical and microbiologic outcomes based on concomitant, chronic Azithromycin use at enrollment. Measurements and Main Results: The cohort randomized to inhaled tobramycin and reporting Azithromycin use showed a significant decrease in the percent predicted FEV1 after one and three courses of inhaled tobramycin when compared with those not reporting Azithromycin use (28 d: −0.51 vs. 3.43%, P < 0.01; 140 d: −1.87 vs. 6.07%, P < 0.01). Combined Azithromycin and inhaled tobramycin use was also associated with earlier need for additional antibiotics, lesser improvement in disease-related quality of life, and a trend toward less reduction in sputum P. aeruginosa density. Subjects randomized to inhaled aztreonam lysine had significantly greater improvement in these outcome measures, which were unaffected by concomitant Azithromycin use. Outcomes in those not using Azithromycin who received inhaled tobramycin were not significantly different from subjects receiving aztreonam lysine. Azithromycin also antagonized tobramycin but not aztreonam lysine in 40% of P. aeruginosa clinical isolates tested in vitro. Conclusions: Oral Azithromycin may antagonize the therapeutic benefits of inhaled tobramycin in subjects with CF with P. aeruginosa airway infection.
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Azithromycin may antagonize inhaled tobramycin when targeting pseudomonas aeruginosa in cystic fibrosis
Annals of the American Thoracic Society, 2014Co-Authors: Jerry A Nick, Samuel M Moskowitz, James F Chmiel, Anna V Forssen, Milene T Saavedra, Jennifer L Taylorcousar, Lisa Saiman, David P NicholsAbstract:Rationale: Recent studies of inhaled tobramycin in subjects with cystic fibrosis (CF) find less clinical improvement than previously observed. Nonhuman data suggest that in some strains of Pseudomonas aeruginosa, Azithromycin can antagonize tobramycin. Objectives: We tested the hypothesis that concomitant Azithromycin use correlates with less improvement in key outcome measures in subjects receiving inhaled tobramycin while not affecting those receiving a comparative, nonaminoglycoside inhaled antibiotic. Methods: We studied a cohort of 263 subjects with CF enrolled in a recent clinical trial comparing inhaled tobramycin with aztreonam lysine. We performed a secondary analysis to examine key clinical and microbiologic outcomes based on concomitant, chronic Azithromycin use at enrollment. Measurements and Main Results: The cohort randomized to inhaled tobramycin and reporting Azithromycin use showed a significant decrease in the percent predicted FEV1 after one and three courses of inhaled tobramycin when compared with those not reporting Azithromycin use (28 d: −0.51 vs. 3.43%, P < 0.01; 140 d: −1.87 vs. 6.07%, P < 0.01). Combined Azithromycin and inhaled tobramycin use was also associated with earlier need for additional antibiotics, lesser improvement in disease-related quality of life, and a trend toward less reduction in sputum P. aeruginosa density. Subjects randomized to inhaled aztreonam lysine had significantly greater improvement in these outcome measures, which were unaffected by concomitant Azithromycin use. Outcomes in those not using Azithromycin who received inhaled tobramycin were not significantly different from subjects receiving aztreonam lysine. Azithromycin also antagonized tobramycin but not aztreonam lysine in 40% of P. aeruginosa clinical isolates tested in vitro. Conclusions: Oral Azithromycin may antagonize the therapeutic benefits of inhaled tobramycin in subjects with CF with P. aeruginosa airway infection.
Jerry A Nick - One of the best experts on this subject based on the ideXlab platform.
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impact of Azithromycin on the clinical and antimicrobial effectiveness of tobramycin in the treatment of cystic fibrosis
Journal of Cystic Fibrosis, 2017Co-Authors: David P Nichols, James F Chmiel, Milene T Saavedra, Jennifer L Taylorcousar, Lisa Saiman, Carrie Happoldt, Preston E Bratcher, Silvia M Caceres, Kenneth C Malcolm, Jerry A NickAbstract:Abstract Background Concomitant use of oral Azithromycin and inhaled tobramycin occurs in approximately half of US cystic fibrosis (CF) patients. Recent data suggest that this combination may be antagonistic. Methods Test the hypothesis that Azithromycin reduces the clinical benefits of tobramycin by analyses of clinical trial data, in vitro modeling of P. aeruginosa antibiotic killing, and regulation of the MexXY efflux pump. Results Ongoing administration of Azithromycin associates with reduced ability of inhaled tobramycin, as compared with aztreonam, to improve lung function and quality of life in a completed clinical trial. In users of Azithromycin FEV 1 (L) increased 0.8% during a 4-week period of inhaled tobramycin and an additional 6.4% during a subsequent 4-week period of inhaled aztreonam (P In vitro , Azithromycin selectively reduced the bactericidal effects tobramycin in cultures of clinical strains of P. aeruginosa , while up regulating antibiotic resistance through MexXY efflux. Conclusions Azithromycin appears capable of reducing the antimicrobial benefits of tobramycin by inducing adaptive bacterial stress responses in P. aeruginosa , suggesting that these medications together may not be optimal chronic therapy for at least some patients.
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Azithromycin may antagonize inhaled tobramycin when targeting pseudomonas aeruginosa in cystic fibrosis
Annals of the American Thoracic Society, 2014Co-Authors: Jerry A Nick, Samuel M Moskowitz, James F Chmiel, Anna V Forssen, Milene T Saavedra, Jennifer L Taylorcousar, Lisa Saiman, David P NicholsAbstract:Rationale: Recent studies of inhaled tobramycin in subjects with cystic fibrosis (CF) find less clinical improvement than previously observed. Nonhuman data suggest that in some strains of Pseudomonas aeruginosa, Azithromycin can antagonize tobramycin. Objectives: We tested the hypothesis that concomitant Azithromycin use correlates with less improvement in key outcome measures in subjects receiving inhaled tobramycin while not affecting those receiving a comparative, nonaminoglycoside inhaled antibiotic. Methods: We studied a cohort of 263 subjects with CF enrolled in a recent clinical trial comparing inhaled tobramycin with aztreonam lysine. We performed a secondary analysis to examine key clinical and microbiologic outcomes based on concomitant, chronic Azithromycin use at enrollment. Measurements and Main Results: The cohort randomized to inhaled tobramycin and reporting Azithromycin use showed a significant decrease in the percent predicted FEV1 after one and three courses of inhaled tobramycin when compared with those not reporting Azithromycin use (28 d: −0.51 vs. 3.43%, P < 0.01; 140 d: −1.87 vs. 6.07%, P < 0.01). Combined Azithromycin and inhaled tobramycin use was also associated with earlier need for additional antibiotics, lesser improvement in disease-related quality of life, and a trend toward less reduction in sputum P. aeruginosa density. Subjects randomized to inhaled aztreonam lysine had significantly greater improvement in these outcome measures, which were unaffected by concomitant Azithromycin use. Outcomes in those not using Azithromycin who received inhaled tobramycin were not significantly different from subjects receiving aztreonam lysine. Azithromycin also antagonized tobramycin but not aztreonam lysine in 40% of P. aeruginosa clinical isolates tested in vitro. Conclusions: Oral Azithromycin may antagonize the therapeutic benefits of inhaled tobramycin in subjects with CF with P. aeruginosa airway infection.
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Azithromycin may antagonize inhaled tobramycin when targeting pseudomonas aeruginosa in cystic fibrosis
Annals of the American Thoracic Society, 2014Co-Authors: Jerry A Nick, Samuel M Moskowitz, James F Chmiel, Anna V Forssen, Milene T Saavedra, Jennifer L Taylorcousar, Lisa Saiman, David P NicholsAbstract:Rationale: Recent studies of inhaled tobramycin in subjects with cystic fibrosis (CF) find less clinical improvement than previously observed. Nonhuman data suggest that in some strains of Pseudomonas aeruginosa, Azithromycin can antagonize tobramycin. Objectives: We tested the hypothesis that concomitant Azithromycin use correlates with less improvement in key outcome measures in subjects receiving inhaled tobramycin while not affecting those receiving a comparative, nonaminoglycoside inhaled antibiotic. Methods: We studied a cohort of 263 subjects with CF enrolled in a recent clinical trial comparing inhaled tobramycin with aztreonam lysine. We performed a secondary analysis to examine key clinical and microbiologic outcomes based on concomitant, chronic Azithromycin use at enrollment. Measurements and Main Results: The cohort randomized to inhaled tobramycin and reporting Azithromycin use showed a significant decrease in the percent predicted FEV1 after one and three courses of inhaled tobramycin when compared with those not reporting Azithromycin use (28 d: −0.51 vs. 3.43%, P < 0.01; 140 d: −1.87 vs. 6.07%, P < 0.01). Combined Azithromycin and inhaled tobramycin use was also associated with earlier need for additional antibiotics, lesser improvement in disease-related quality of life, and a trend toward less reduction in sputum P. aeruginosa density. Subjects randomized to inhaled aztreonam lysine had significantly greater improvement in these outcome measures, which were unaffected by concomitant Azithromycin use. Outcomes in those not using Azithromycin who received inhaled tobramycin were not significantly different from subjects receiving aztreonam lysine. Azithromycin also antagonized tobramycin but not aztreonam lysine in 40% of P. aeruginosa clinical isolates tested in vitro. Conclusions: Oral Azithromycin may antagonize the therapeutic benefits of inhaled tobramycin in subjects with CF with P. aeruginosa airway infection.
Chienching Hung - One of the best experts on this subject based on the ideXlab platform.
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comparison of serological responses to single dose Azithromycin 2 g versus benzathine penicillin g in the treatment of early syphilis in hiv infected patients in an area of low prevalence of macrolide resistant treponema pallidum infection
Journal of Antimicrobial Chemotherapy, 2016Co-Authors: Chiajui Yang, Hungjen Tang, Suiyuan Chang, Szumin Hsieh, Kuanyeh Lee, Yuanti Lee, Wanghuei Sheng, Shangping Yang, Chienching HungAbstract:Objectives Effectiveness of single-dose Azithromycin (2 g) in the treatment of early syphilis among HIV-infected patients has rarely been evaluated in the era of combination ART. Methods Consecutive HIV-infected patients with early syphilis, who received 2 g single-dose Azithromycin or 2.4 MU benzathine penicillin G, between 2007 and 2014, were prospectively observed. Genotypic resistance to macrolides was determined in Treponema pallidum isolates identified from clinical specimens using PCR assays. Rapid plasma reagin (RPR) titres were determined at baseline and every 3 months after treatment. Primary outcome was a decline of RPR titre by ≥4-fold at 12 months after treatment. Results During the study period, 162 HIV-infected patients with early syphilis received benzathine penicillin G and 237 patients received Azithromycin. At 12 months follow-up, the serological response rate for penicillin and Azithromycin groups was 61.1% and 56.5% (P = 0.41), respectively; respective response rate was 61.1% and 65.9% (P = 0.49) if we only included patients infected with T. pallidum not harbouring macrolide resistance in the Azithromycin group. In multivariate analysis, RPR titres ≥1:32 (OR 2.56; 95% CI 1.55-4.21) and prior syphilis (OR 0.54; 95% CI 0.35-0.81) were predictors of serological response. Most common adverse effects of Azithromycin included diarrhoea (52.7%), nausea (22.4%), abdominal pain (18.6%), bloating (17.7%) and lassitude/somnolence (27.4%). Conclusions In the setting of a low prevalence of macrolide-resistant T. pallidum, 2 g single-dose Azithromycin achieved a similar serological response to benzathine penicillin G in HIV-infected patients with early syphilis. Major adverse effects of Azithromycin were gastrointestinal symptoms and lassitude/somnolence.
Lisa Saiman - One of the best experts on this subject based on the ideXlab platform.
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impact of Azithromycin on the clinical and antimicrobial effectiveness of tobramycin in the treatment of cystic fibrosis
Journal of Cystic Fibrosis, 2017Co-Authors: David P Nichols, James F Chmiel, Milene T Saavedra, Jennifer L Taylorcousar, Lisa Saiman, Carrie Happoldt, Preston E Bratcher, Silvia M Caceres, Kenneth C Malcolm, Jerry A NickAbstract:Abstract Background Concomitant use of oral Azithromycin and inhaled tobramycin occurs in approximately half of US cystic fibrosis (CF) patients. Recent data suggest that this combination may be antagonistic. Methods Test the hypothesis that Azithromycin reduces the clinical benefits of tobramycin by analyses of clinical trial data, in vitro modeling of P. aeruginosa antibiotic killing, and regulation of the MexXY efflux pump. Results Ongoing administration of Azithromycin associates with reduced ability of inhaled tobramycin, as compared with aztreonam, to improve lung function and quality of life in a completed clinical trial. In users of Azithromycin FEV 1 (L) increased 0.8% during a 4-week period of inhaled tobramycin and an additional 6.4% during a subsequent 4-week period of inhaled aztreonam (P In vitro , Azithromycin selectively reduced the bactericidal effects tobramycin in cultures of clinical strains of P. aeruginosa , while up regulating antibiotic resistance through MexXY efflux. Conclusions Azithromycin appears capable of reducing the antimicrobial benefits of tobramycin by inducing adaptive bacterial stress responses in P. aeruginosa , suggesting that these medications together may not be optimal chronic therapy for at least some patients.
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Azithromycin may antagonize inhaled tobramycin when targeting pseudomonas aeruginosa in cystic fibrosis
Annals of the American Thoracic Society, 2014Co-Authors: Jerry A Nick, Samuel M Moskowitz, James F Chmiel, Anna V Forssen, Milene T Saavedra, Jennifer L Taylorcousar, Lisa Saiman, David P NicholsAbstract:Rationale: Recent studies of inhaled tobramycin in subjects with cystic fibrosis (CF) find less clinical improvement than previously observed. Nonhuman data suggest that in some strains of Pseudomonas aeruginosa, Azithromycin can antagonize tobramycin. Objectives: We tested the hypothesis that concomitant Azithromycin use correlates with less improvement in key outcome measures in subjects receiving inhaled tobramycin while not affecting those receiving a comparative, nonaminoglycoside inhaled antibiotic. Methods: We studied a cohort of 263 subjects with CF enrolled in a recent clinical trial comparing inhaled tobramycin with aztreonam lysine. We performed a secondary analysis to examine key clinical and microbiologic outcomes based on concomitant, chronic Azithromycin use at enrollment. Measurements and Main Results: The cohort randomized to inhaled tobramycin and reporting Azithromycin use showed a significant decrease in the percent predicted FEV1 after one and three courses of inhaled tobramycin when compared with those not reporting Azithromycin use (28 d: −0.51 vs. 3.43%, P < 0.01; 140 d: −1.87 vs. 6.07%, P < 0.01). Combined Azithromycin and inhaled tobramycin use was also associated with earlier need for additional antibiotics, lesser improvement in disease-related quality of life, and a trend toward less reduction in sputum P. aeruginosa density. Subjects randomized to inhaled aztreonam lysine had significantly greater improvement in these outcome measures, which were unaffected by concomitant Azithromycin use. Outcomes in those not using Azithromycin who received inhaled tobramycin were not significantly different from subjects receiving aztreonam lysine. Azithromycin also antagonized tobramycin but not aztreonam lysine in 40% of P. aeruginosa clinical isolates tested in vitro. Conclusions: Oral Azithromycin may antagonize the therapeutic benefits of inhaled tobramycin in subjects with CF with P. aeruginosa airway infection.
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Azithromycin may antagonize inhaled tobramycin when targeting pseudomonas aeruginosa in cystic fibrosis
Annals of the American Thoracic Society, 2014Co-Authors: Jerry A Nick, Samuel M Moskowitz, James F Chmiel, Anna V Forssen, Milene T Saavedra, Jennifer L Taylorcousar, Lisa Saiman, David P NicholsAbstract:Rationale: Recent studies of inhaled tobramycin in subjects with cystic fibrosis (CF) find less clinical improvement than previously observed. Nonhuman data suggest that in some strains of Pseudomonas aeruginosa, Azithromycin can antagonize tobramycin. Objectives: We tested the hypothesis that concomitant Azithromycin use correlates with less improvement in key outcome measures in subjects receiving inhaled tobramycin while not affecting those receiving a comparative, nonaminoglycoside inhaled antibiotic. Methods: We studied a cohort of 263 subjects with CF enrolled in a recent clinical trial comparing inhaled tobramycin with aztreonam lysine. We performed a secondary analysis to examine key clinical and microbiologic outcomes based on concomitant, chronic Azithromycin use at enrollment. Measurements and Main Results: The cohort randomized to inhaled tobramycin and reporting Azithromycin use showed a significant decrease in the percent predicted FEV1 after one and three courses of inhaled tobramycin when compared with those not reporting Azithromycin use (28 d: −0.51 vs. 3.43%, P < 0.01; 140 d: −1.87 vs. 6.07%, P < 0.01). Combined Azithromycin and inhaled tobramycin use was also associated with earlier need for additional antibiotics, lesser improvement in disease-related quality of life, and a trend toward less reduction in sputum P. aeruginosa density. Subjects randomized to inhaled aztreonam lysine had significantly greater improvement in these outcome measures, which were unaffected by concomitant Azithromycin use. Outcomes in those not using Azithromycin who received inhaled tobramycin were not significantly different from subjects receiving aztreonam lysine. Azithromycin also antagonized tobramycin but not aztreonam lysine in 40% of P. aeruginosa clinical isolates tested in vitro. Conclusions: Oral Azithromycin may antagonize the therapeutic benefits of inhaled tobramycin in subjects with CF with P. aeruginosa airway infection.
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synergistic activities of macrolide antibiotics against pseudomonas aeruginosa burkholderia cepacia stenotrophomonas maltophilia and alcaligenes xylosoxidans isolated from patients with cystic fibrosis
Antimicrobial Agents and Chemotherapy, 2002Co-Authors: Lisa Saiman, Yunhua Chen, Pablo San Gabriel, Charles KnirschAbstract:Azithromycin and clarithromycin were paired with other antibiotics to test synergistic activity against 300 multidrug-resistant pathogens isolated from cystic fibrosis (CF) patients. Clarithromycin-tobramycin was most active against Pseudomonas aeruginosa and inhibited 58% of strains. Azithromycin-trimethoprim-sulfamethoxazole, Azithromycin-ceftazidime, and Azithromycin-doxycycline or Azithromycin-trimethoprim-sulfamethoxazole inhibited 40, 20, and 22% of Stenotrophomonas maltophilia , Burkholderia cepacia complex, and Achromobacter ( Alcaligenes ) xylosoxidans strains, respectively.
Edward W Hook - One of the best experts on this subject based on the ideXlab platform.
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the efficacy and safety of gentamicin plus Azithromycin and gemifloxacin plus Azithromycin as treatment of uncomplicated gonorrhea
Clinical Infectious Diseases, 2014Co-Authors: Robert D Kirkcaldy, John R Papp, Hillard Weinstock, Page C Moore, Susan S Philip, Harold C Wiesenfeld, Peter R Kerndt, Shacondra M Johnson, Khalil G Ghanem, Edward W HookAbstract:Background. Ceftriaxone is the foundation of currently recommended gonorrhea treatment. There is an urgent need for backup treatment options for patients with cephalosporin allergy or infections due to suspected cephalosporin-resistant Neisseria gonorrhoeae. We evaluated the efficacy and tolerability of 2 combinations of existing noncephalosporin antimicrobials for treatment of patients with urogenital gonorrhea. Methods. We conducted a randomized, multisite, open-label, noncomparative trial in 5 outpatient sexually transmitted disease clinic sites in Alabama, California, Maryland, and Pennsylvania. Patients aged 15–60 years diagnosed with uncomplicated urogenital gonorrhea were randomly assigned to either gentamicin 240 mg intramuscularly plus Azithromycin 2 g orally, or gemifloxacin 320 mg orally plus Azithromycin 2 g orally. The primary outcome was microbiological cure of urogenital infections (negative follow-up culture) at 10–17 days after treatment among 401 participants in the per protocol population. Results. Microbiological cure was achieved by 100% (lower 1-sided exact 95% confidence interval [CI] bound, 98.5%) of 202 evaluable participants receiving gentamicin/Azithromycin, and 99.5% (lower 1-sided exact 95% CI bound, 97.6%) of 199 evaluable participants receiving gemifloxacin/Azithromycin. Gentamicin/Azithromycin cured 10 of 10 pharyngeal infections and 1 of 1 rectal infection; gemifloxacin/Azithromycin cured 15 of 15 pharyngeal and 5 of 5 rectal infections. Gastrointestinal adverse events were common in both arms. Conclusions. Gentamicin/Azithromycin and gemifloxacin/Azithromycin were highly effective for treatment of urogenital gonorrhea. Gastrointestinal adverse events may limit routine use. These non-cephalosporin-based regimens may be useful alternative options for patients who cannot be treated with cephalosporin antimicrobials. Additional treatment options for gonorrhea are needed. Clinical Trials Registration. {"type":"clinical-trial","attrs":{"text":"NCT00926796","term_id":"NCT00926796"}}NCT00926796.
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evaluation of Azithromycin resistance in treponema pallidum specimens from madagascar
Sexually Transmitted Diseases, 2009Co-Authors: Kathlee Van Damme, Charmie Godornes, Sheila A Lukeha, Frieda Ehets, Noro Ravelomanana, Maria R Kha, Odo Randrianasolo, Ny Lovaniaina Rabenja, Mitchell S Cohe, Edward W HookAbstract:Treponema pallidum resistance to Azithromycin has been documented in the US, Canada, and Ireland. We found no evidence of resistance to Azithromycin in specimens from 141 patients with syphilitic lesions in Madagascar suggesting resistance is geographically isolated and supporting use of Azithromycin as alternative treatment for early syphilis in Madagascar.
