Long-term azithromycin for Indigenous children with non-cystic-fibrosis bronchiectasis or chronic suppurative lung disease (Bronchiectasis Intervention Study): a multicentre, double-blind, randomised controlled trial

Valery, Patricia C.; Morris, Peter S.; Byrnes, Catherine A; Grimwood, Keith; Torzillo, Paul J.; Bauert, Paul; Masters, Ian Brent; Diaz, Abbey; McCallum, Gabrielle B.; Mobberley, Charmaine; Tjhung, Irene; Hare, Kim M.; Ware, Robert S.; Chang, Anne B.

doi:10.1016/s2213-2600(13)70185-1

Cited by 165 publications

(223 citation statements)

References 44 publications

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“…A number of studies have shown that the primary reason for the development of drug resistance is the use of antimicrobials (34), even when an antibiotic is used at the recommended dose for the approved therapeutic indication(s). In recent years, this has become particularly evident for macrolide antibiotics (6,(35)(36)(37), where, for example, Malhotra-Kumar et al (5) clearly demonstrated in a randomized, double-blind, and placebocontrolled study that following a single course of AZM, macrolide resistance increased by up to 60% and remained 14% higher even at 6 months after the end of drug therapy compared to that with the placebo. In order to better understand the pharmacokinetic/ pharmacodynamic reasons behind this drug-induced increase in antimicrobial resistance, Matzneller et al (4) determined the concentration-time course of AZM plasma (total), PMLs (total), and in the ISF of potential infection sites (muscle and subcutaneous adipose tissue) following three consecutive doses of 500 mg QD in healthy volunteers.…”

Section: Discussionmentioning

confidence: 99%

Development of a Population Pharmacokinetic Model Characterizing the Tissue Distribution of Azithromycin in Healthy Subjects

Zheng

Matzneller

Zeitlinger

et al. 2014

Antimicrob Agents Chemother

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Recent clinical trials indicate that the use of azithromycin is associated with the emergence of macrolide resistance. The objective of our study was to simultaneously characterize free target site concentrations and correlate them with the MIC 90 s of clinically relevant pathogens. Azithromycin (500 mg once daily [QD]) was administered orally to 6 healthy male volunteers for 3 days. The free concentrations in the interstitial space fluid (ISF) of muscle and subcutaneous fat tissue as well as the total concentrations in plasma and polymorphonuclear leukocytes (PMLs) were determined on days 1, 3, 5, and 10. All concentrations were modeled simultaneously in NONMEM 7.2 using a tissue distribution model that accounts for nonlinear protein binding and ionization state at physiological pH. The model performance and parameter estimates were evaluated via goodness-of-fit plots and nonparametric bootstrap analysis. The model we developed described the concentrations at all sampling sites reasonably well and showed that the overall pharmacokinetics of azithromycin is driven by the release of the drug from acidic cell/tissue compartments. The model-predicted unionized azithromycin (AZM) concentrations in the cytosol of PMLs (6.0 ؎ 1.2 ng/ml) were comparable to the measured ISF concentrations in the muscle (8.7 ؎ 2.9 ng/ml) and subcutis (4.1 ؎ 2.4 ng/ml) on day 10, whereas the total PML concentrations were >1,000-fold higher (14,217 ؎ 2,810 ng/ml). The total plasma and free ISF concentrations were insufficient to exceed the MIC 90 s of the skin pathogens at all times. Our results indicate that the slow release of azithromycin from low pH tissue/cell compartments is responsible for the long terminal half-life of the drug and thus the extended period of time during which free concentrations reside at subinhibitory concentrations.

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Section: Discussionmentioning

confidence: 99%

Development of a Population Pharmacokinetic Model Characterizing the Tissue Distribution of Azithromycin in Healthy Subjects

Zheng

Matzneller

Zeitlinger

et al. 2014

Antimicrob Agents Chemother

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“…However, the authors noted a greater incidence of macrolide-resistant bacteria in children treated with azithromycin (46% vs 11%). 17 …”

Section: Articlementioning

confidence: 99%

Prescribing azithromycin

McMullan¹,

Mostaghim²

2015

Aust Prescr

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“…52,53 These conditions overlap and children with CSLD experience similar clinical disease patterns as children with CT-confirmed BE. 49 They also respond similarly to therapies used to treat children with BE.…”

Section: Chronic Suppurative Lung Disease (Csld) and Bronchiectasis (Be)mentioning

confidence: 99%

“…49 They also respond similarly to therapies used to treat children with BE. 52,53 Also thirdly, indigenous children living in non-urban centres and children in developing countries have limited access to CT scanning to confirm BE and defining 'irreversibility' requires two CT scans, which is neither safe (increased radiation) nor feasible. Finally, there are limitations in the radiographic definitions of BE in children because HRCT definitions are derived from adult studies and are not necessarily equivalent to those in children.…”

Section: Chronic Suppurative Lung Disease (Csld) and Bronchiectasis (Be)mentioning

confidence: 99%

Lung disease in indigenous children

Chang

Brown

Toombs

et al. 2014

Paediatric Respiratory Reviews

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A c c e p t e d M a n u s c r i p t 2 EDUCATIONAL AIMSThe reader will be able to:• Discuss the common respiratory problems encountered by indigenous children.• Appreciate the similarities and differences in the aetiology, associations and management of these common respiratory problems.• Understand the many facets that impact on the clinical outcomes of common respiratory conditions affecting indigenous children.• Discuss potential intervention targets that can reduce the morbidity and mortality of respiratory diseases in indigenous children. Page 3 of 27A c c e p t e d M a n u s c r i p t 3 SUMMARY Children in indigenous populations have substantially higher respiratory morbidity than nonindigenous children. Indigenous children have more frequent respiratory infections that are, more severe and, associated with long-term sequelae. Post-infectious sequelae such as chronic suppurative lung disease and bronchiectasis are especially prevalent among indigenous groups and have lifelong impact on lung function. Also, although estimates of asthma prevalence among indigenous children are similar to non-indigenous groups the morbidity of asthma is higher in indigenous children. To reduce the morbidity of respiratory illness, best-practice medicine is essential in addition to improving socio-economic factors, (eg household crowding), tobacco smoke exposure, and access to health care and illness prevention programs that likely contribute to these issues. Although each indigenous group may have unique health beliefs and interfaces with modern health care, a culturally sensitive and community-based comprehensive care system of preventive and long term care can improve outcomes for all these conditions. This article focuses on common respiratory conditions encountered by indigenous children living in affluent countries where data is available.

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Long-term azithromycin for Indigenous children with non-cystic-fibrosis bronchiectasis or chronic suppurative lung disease (Bronchiectasis Intervention Study): a multicentre, double-blind, randomised controlled trial

Cited by 165 publications

References 44 publications

Development of a Population Pharmacokinetic Model Characterizing the Tissue Distribution of Azithromycin in Healthy Subjects

Development of a Population Pharmacokinetic Model Characterizing the Tissue Distribution of Azithromycin in Healthy Subjects

Prescribing azithromycin

Lung disease in indigenous children

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