Effect of a Short Course of Clarithromycin Therapy on Sputum Production in Patients With Chronic Airway Hypersecretion

Tagaya, Etsuko; Tamaoki, Jun; Kondo, Mitsuko; Nagai, Atsushi

doi:10.1378/chest.122.1.213

Cited by 81 publications

(48 citation statements)

References 9 publications

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“…Macrolide CLM already showed clinical effectiveness in treating diffuse panbronchiolitis and has been studied as therapy for other respiratory diseases [23–25]; CLM effects in CF patients were also evaluated in different studies, although with contrasting outcomes [19–22]. Like AZM, low-dose CLM has no bactericidal activity against P. aeruginosa , but we observed that it can lower the amount of virulence factors secreted by P. aeruginosa and reduce the associated host inflammatory response in both WT and CF mice.…”

Section: Discussionmentioning

confidence: 99%

“…Although the comparison of the outcomes of these studies is limited by the different treatment regimens, doses, drug formulations and clinical factors evaluated, low-dose CLM seems to be more effective, as supported also by its low-dose benefits in the treatment of diffuse panbronchiolitis which shares many similarities in clinical and pathological characteristics with CF [19–23]. Moreover, CLM treatment was shown to decrease lung inflammatory processes and chronic airways hypersecretion in non-CF patients with bronchiectasis [24,25]. Pertaining to its anti-pseudomonal effects, CLM has no bactericidal activity against P. aeruginosa , like other macrolides, but can interfere with protein synthesis and inhibit protease expression, twitching motility and biofilm maturation, promoting biofilm permeability and favoring penetration of other antimicrobial agents like ciprofloxacin and tobramycin, also used in CF therapy [26–28].…”

Section: Introductionmentioning

confidence: 99%

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Inhibition of Pseudomonas aeruginosa secreted virulence factors reduces lung inflammation in CF mice

et al. 2018

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Background: Cystic fibrosis (CF) lung infection is a complex condition where opportunistic pathogens and defective immune system cooperate in developing a constant cycle of infection and inflammation. The major pathogen, Pseudomonas aeruginosa, secretes a multitude of virulence factors involved in host immune response and lung tissue damage. In this study, we examined the possible anti-inflammatory effects of molecules inhibiting P. aeruginosa virulence factors.Methods: Pyocyanin, pyoverdine and proteases were measured in bacterial culture supernatant from different P. aeruginosa strains. Inhibition of virulence factors by sub-inhibitory concentrations of clarithromycin and by protease inhibitors was evaluated. Lung inflammatory response was monitored by in vivo bioluminescence imaging in wild-type and CFTR-knockout mice expressing a luciferase gene under the control of a bovine IL-8 promoter.Results: The amount of proteases, pyocyanin and pyoverdine secreted by P. aeruginosa strains was reduced after growth in the presence of a sub-inhibitory dose of clarithromycin. Intratracheal challenge with culture supernatant containing bacteria-released products induced a strong IL-8-mediated response in mouse lungs while lack of virulence factors corresponded to a reduction in bioluminescence emission. Particularly, sole inactivation of proteases by inhibitors Ilomastat and Marimastat also resulted in decreased lung inflammation.Conclusions: Our data support the assumption that virulence factors are involved in P. aeruginosa pro-inflammatory action in CF lungs; particularly, proteases seem to play an important role. Inhibition of virulence factors production and activity resulted in decreased lung inflammation; thus, clarithromycin and protease inhibitors potentially represent additional therapeutic therapies for P. aeruginosa-infected patients.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Inhibition of Pseudomonas aeruginosa secreted virulence factors reduces lung inflammation in CF mice

et al. 2018

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“…However, an increasing body of evidence suggests that clarithromycin possesses considerable antiinflammatory and immunomodulatory properties, recommending its administration for the treatment of chronic inflammatory conditions like diffuse panbronchiolitis and cystic fibrosis (11,21,26). Its immunomodulatory properties are observed in vitro at concentrations close to 10 g/ml (14).…”

mentioning

confidence: 99%

Immunomodulatory Clarithromycin Treatment of Experimental Sepsis and Acute Pyelonephritis Caused by Multidrug-Resistant Pseudomonas aeruginosa

Giamarellos‐Bourboulis¹,

Adamis

Laoutaris³

et al. 2004

Antimicrob Agents Chemother

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Clarithromycin was administered intravenously to 55 rabbits to evaluate its effect on experimental sepsis caused by multidrug-resistant Pseudomonas aeruginosa. Acute pyelonephritis was induced after ligation of the right ureter and injection of 10 8 CFU of the test isolate per kg of body weight into the renal pelvis. The animals were divided into six groups: group A, controls; group B, rabbits that received one intravenous dose of 80 mg of clarithromycin per kg concomitantly with bacterial challenge; group C, rabbits that received two doses of clarithromycin, the second one of which was given 2 h after the first one; group D, rabbits that received 15 mg of amikacin per kg; group E, rabbits that received one dose of clarithromycin and amikacin; and group F, rabbits that received two doses of clarithromycin and amikacin. Serum endotoxin levels were estimated by the QCL-1000 Limulus amoebocyte lysate assay, tumor necrosis factor alpha (TNF-␣) levels were measured by a bioassay, and malondialdehyde (MDA) levels were measured by the thiobarbiturate assay. Viable bacterial counts in various tissue samples were also assessed. The mean survival times of the animals in groups A, B, C, D, E, and F were 4.50, 7.69, 4.07, 4.55, 11.55, and 11.60 days, respectively (P ‫؍‬ 0.033 for group D versus group F, P ‫؍‬ 0.006 for group D versus group E, P ‫؍‬ not significant for group B versus group E, P ‫؍‬ 0.042 for group C versus group F). Serum endotoxin levels were similar between groups at all sampling times; TNF-␣ and MDA levels in groups B, C, E, and F decreased significantly over follow-up. The numbers of viable bacterial cells in the infected kidney were similar among the groups; those in the liver, spleen, lungs, and mesenteral lymph nodes were significantly decreased in groups B, E, and F compared to those in groups A and D. It is concluded that a prolongation of survival in animals with experimental sepsis caused by multidrug-resistant P. aeruginosa was achieved after coadministration of clarithromycin and amikacin and that the increased survival was probably attributable to the immunomodulatory properties of clarithromycin.Clarithromycin is a macrolide classically known to possess an antimicrobial spectrum that includes gram-positive cocci and atypical pathogens (23). However, an increasing body of evidence suggests that clarithromycin possesses considerable antiinflammatory and immunomodulatory properties, recommending its administration for the treatment of chronic inflammatory conditions like diffuse panbronchiolitis and cystic fibrosis (11,21,26). Its immunomodulatory properties are observed in vitro at concentrations close to 10 g/ml (14). On the basis of that finding, intravenous administration of clarithromycin leading to the same levels in blood might be beneficial for the treatment of an acute inflammatory state like sepsis.Pseudomonas aeruginosa is a common pathogen that is involved in nosocomial sepsis and that is often characterized nowadays by multidrug resistance (18). In the present study, intravenous clar...

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“…In addition, in a study of patients with chronic bronchitis or bronchiectasis, seven days of treatment with clarithromycin (400 mg/day) decreased sputum production. 55 The percentage of patients in whom it decreased >30% (so-called responders) was 38%. During treatment with clarithromycin, the sputum solid composition increased, while chloride concentration decreased in responders, but not in non-responders.…”

Section: Use Of Macrolides In Patients With Copdmentioning

confidence: 99%

Non-antimicrobial activity of macrolides: therapeutic potential in chronic inflammatory airway disorders

Feldman

Anderson²

2009

Southern African Journal of Epidemiology and Infection

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Effect of a Short Course of Clarithromycin Therapy on Sputum Production in Patients With Chronic Airway Hypersecretion

Cited by 81 publications

References 9 publications

Inhibition of Pseudomonas aeruginosa secreted virulence factors reduces lung inflammation in CF mice

Inhibition of Pseudomonas aeruginosa secreted virulence factors reduces lung inflammation in CF mice

Immunomodulatory Clarithromycin Treatment of Experimental Sepsis and Acute Pyelonephritis Caused by Multidrug-Resistant Pseudomonas aeruginosa

Non-antimicrobial activity of macrolides: therapeutic potential in chronic inflammatory airway disorders

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