The use of macrolides in treatment of upper respiratory tract infections

Wierzbowski, Aleksandra; Hoban, Daryl J.; Hisanaga, Tamiko; DeCorby, Mel; Zhanel, George G.

doi:10.1007/s11882-006-0056-x

Cited by 21 publications

(15 citation statements)

References 54 publications

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“…Inappropriate or overuse of antibiotics is a major factor in the development of antibiotic resistance . In the case of macrolides, countries with a high consumption have experienced a rapid increase in macrolide resistance among common RTI pathogens, including M. pneumoniae . This is particularly concerning in China, where high rates of prescription (80%–90%) of antibiotics for colds, pharyngitis and acute bronchitis have been reported, with macrolides being among the most commonly used drugs .…”

Section: Resultsmentioning

confidence: 99%

Overview of antimicrobial options for Mycoplasma pneumoniae pneumonia: focus on macrolide resistance

Cao

Yin

et al. 2015

Clinical Respiratory J

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Section: Resultsmentioning

confidence: 99%

Overview of antimicrobial options for Mycoplasma pneumoniae pneumonia: focus on macrolide resistance

Cao

Yin

et al. 2015

Clinical Respiratory J

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“…Macrolides are effective against most aerobic and anaerobic Gram-positive organisms and many Gram-negative bacteria (35,37). They are used for treating respiratory tract and soft tissue infections (23,38). Macrolides, such as clarithromycin, inhibit protein synthesis in bacteria by reversibly binding to the 50S ribosomal subunits (38).…”

mentioning

confidence: 99%

“…They are used for treating respiratory tract and soft tissue infections (23,38). Macrolides, such as clarithromycin, inhibit protein synthesis in bacteria by reversibly binding to the 50S ribosomal subunits (38). Clarithromycin is also known as the most effective chemotherapy against Mycobacterium avium complex (MAC) (39).…”

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confidence: 99%

Efficacy and Safety of Liposomal Clarithromycin and Its Effect on Pseudomonas aeruginosa Virulence Factors

Alhajlan

Alhariri

Omri

2013

Antimicrob Agents Chemother

116

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We investigated the efficacy and safety of liposomal clarithromycin formulations with different surface charges against clinical isolates of Pseudomonas aeruginosa from the lungs of cystic fibrosis (CF) patients. The liposomal clarithromycin formulations were prepared by the dehydration-rehydration method, and their sizes were measured using the dynamic-light-scattering technique. Encapsulation efficiency was determined by microbiological assay, and the stabilities of the formulations in biological fluid were evaluated for a period of 48 h. The MICs and minimum bactericidal concentrations (MBCs) of free and liposomal formulations were determined with P. aeruginosa strains isolated from CF patients. Liposomal clarithromycin activity against biofilm-forming P. aeruginosa was compared to that of free antibiotic using the Calgary Biofilm Device (CBD). The effects of subinhibitory concentrations of free and liposomal clarithromycin on bacterial virulence factors and motility on agar were investigated on clinical isolates of P. aeruginosa. The cytotoxicities of the liposome preparations and free drug were evaluated on a pulmonary epithelial cell line (A549). The average diameter of the formulations was >222 nm, with encapsulation efficiencies ranging from 5.7% to 30.4%. The liposomes retained more than 70% of their drug content during the 48-h time period. The highly resistant strains of P. aeruginosa became susceptible to liposome-encapsulated clarithromycin (MIC, 256 mg/liter versus 8 mg/liter; P < 0.001). Liposomal clarithromycin reduced the bacterial growth within the biofilm by 3 to 4 log units (P < 0.001), significantly attenuated virulence factor production, and reduced bacterial twitching, swarming, and swimming motilities. The clarithromycin-entrapped liposomes were less cytotoxic than the free drug (P < 0.001). These data indicate that our novel formulations could be a useful strategy to enhance the efficacy of clarithromycin against resistant P. aeruginosa strains that commonly affect individuals with cystic fibrosis.

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“…Macrolides are currently used as a first-line treatment for respiratory tract infections (RTIs), including community-acquired pneumonia, acute exacerbations of chronic bronchitis, acute sinusitis, pharyngitis/tonsillitis, and otitis media (5,37). The extensive clinical usage of macrolides has resulted in the rapid emergence of macrolide resistance, particularly among streptococci, staphylococci, and enterococci (1,13,38).…”

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confidence: 99%

Pharmacokinetics of EDP-420 after Multiple Oral Doses in Healthy Adult Volunteers and in a Bioequivalence Study

Jiang

2009

Antimicrob Agents Chemother

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EDP-420 (also known as EP-013420, or S-013420) is a first-in-class bridged bicyclolide currently in clinical development for the treatment of respiratory tract infections (RTI) and has previously shown favorable pharmacokinetic (PK) and safety profiles after the administration of single oral doses of a suspension to healthy volunteers. Here we report its PK profile after the administration of multiple oral doses of a suspension to healthy adults. Bioequivalence between suspension and capsule formulations, as well as the effect of food, is also reported. The most important PK features of EDP-420 observed in these clinical studies are its long half-life of 17 to 18 h and its high systemic exposure, which support once-daily dosing and treatment durations potentially shorter than those of most other macrolide antibiotics. EDP-420 is readily absorbed following oral administration in both suspension and capsule formulations. In the multiple-oral-dose study, steady state was achieved on day 1 by using a loading dose of 400 mg/day, followed by 2 days of 200 mg/day. A high-fat meal had no effect on the bioavailability of EDP-420 administered in a capsule formulation. EDP-420 was well tolerated, with no serious or severe adverse events reported, and no subject was discontinued from the study due to an adverse event. Based on its human PK and safety profiles, together with its in vitro/in vivo activities against common respiratory pathogens, EDP-420 warrants further development, including trials for clinical efficacy in the treatment of RTI.Macrolides are currently used as a first-line treatment for respiratory tract infections (RTIs), including community-acquired pneumonia, acute exacerbations of chronic bronchitis, acute sinusitis, pharyngitis/tonsillitis, and otitis media (5, 37). The extensive clinical usage of macrolides has resulted in the rapid emergence of macrolide resistance, particularly among streptococci, staphylococci, and enterococci (1, 13, 38). Thus, there is an urgent need to develop new antibiotics with activity against a broad spectrum of pathogens (especially resistant strains) commonly encountered in community-acquired RTIs. The design of EDP-420 (formerly known as EP-013420, or S-013420) was undertaken in response to this unmet medical need.EDP-420 represents a novel structural class of bridged bicyclolide antibacterial agents (36) (the structure is shown in Fig. 1). It exhibits potent in vitro activities against RTI pathogens, including multidrug-resistant streptococci and the atypical pathogens (e.g., Chlamydia pneumoniae, Mycoplasma pneumoniae, and Legionella pneumophila) (4, 10, 19, 24, 27-32, 34, 39). In vivo, EDP-420 has also demonstrated efficacy against Streptococcus pneumoniae, Streptococcus pyogenes, Staphylococcus aureus, and Mycobacterium avium in mouse protection tests, against S. pneumoniae and Haemophilus influenzae in a rat lung infection model, and against penicillin-and quinoloneresistant pneumococci in a rabbit meningitis model (2-4, 22, 23, 25, 32-34). The nonclinical pharmacok...

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The use of macrolides in treatment of upper respiratory tract infections

Cited by 21 publications

References 54 publications

Overview of antimicrobial options for Mycoplasma pneumoniae pneumonia: focus on macrolide resistance

Overview of antimicrobial options for Mycoplasma pneumoniae pneumonia: focus on macrolide resistance

Efficacy and Safety of Liposomal Clarithromycin and Its Effect on Pseudomonas aeruginosa Virulence Factors

Pharmacokinetics of EDP-420 after Multiple Oral Doses in Healthy Adult Volunteers and in a Bioequivalence Study

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