Continuous alternating inhaled antibiotics for chronic pseudomonal infection in cystic fibrosis

Flume, Patrick A.; Clancy, John; Retsch‐Bogart, George; Tullis, D. Elizabeth; Bresnik, Mark; Derchak, P.A.; Lewis, Sandra A; Ramsey, Bonnie W.

doi:10.1016/j.jcf.2016.05.001

Cited by 51 publications

(35 citation statements)

References 17 publications

(17 reference statements)

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“…More recently, the use of continuous therapy either with a single agent or as alternating therapy, has increased in an effort to prevent exacerbations and decline in lung function [34]. A 28-week, multicenter, randomized, double-blind, placebo-controlled trial was conducted to evaluate the use of continuous alternating therapy with TSI and aztreonam compared to intermittent TSI alone [35]. The trial faced difficulty with enrolling patients and did not achieve statistical significance but suggested a potential benefit in reduction of pulmonary exacerbations (by 25%), rates of hospitalization (by 35%), treatment with non-study antibiotics and median time to first exacerbation (175 days vs. 140 days).…”

Section: Cystic Fibrosismentioning

confidence: 99%

Inhaled Antibiotic Therapy in Chronic Respiratory Diseases

Maselli

Keyt

Restrepo

2017

IJMS

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The management of patients with chronic respiratory diseases affected by difficult to treat infections has become a challenge in clinical practice. Conditions such as cystic fibrosis (CF) and non-CF bronchiectasis require extensive treatment strategies to deal with multidrug resistant pathogens that include Pseudomonas aeruginosa, Methicillin-resistant Staphylococcus aureus, Burkholderia species and non-tuberculous Mycobacteria (NTM). These challenges prompted scientists to deliver antimicrobial agents through the pulmonary system by using inhaled, aerosolized or nebulized antibiotics. Subsequent research advances focused on the development of antibiotic agents able to achieve high tissue concentrations capable of reducing the bacterial load of difficult-to-treat organisms in hosts with chronic respiratory conditions. In this review, we focus on the evidence regarding the use of antibiotic therapies administered through the respiratory system via inhalation, nebulization or aerosolization, specifically in patients with chronic respiratory diseases that include CF, non-CF bronchiectasis and NTM. However, further research is required to address the potential benefits, mechanisms of action and applications of inhaled antibiotics for the management of difficult-to-treat infections in patients with chronic respiratory diseases.

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Section: Cystic Fibrosismentioning

confidence: 99%

Inhaled Antibiotic Therapy in Chronic Respiratory Diseases

Maselli

Keyt

Restrepo

2017

IJMS

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“…However, there are evolving practices by clinicians of adopting a continuous alternating regimen in clinical practice (e.g., a month of TOBI alternating with a month of Coliracin or Aztreonam). This practice is based on the clinical impression that the month off has disadvantages over the month on therapy (36). Theoretically, on/off treatment evaluations may help in identifying patients who deteriorate over the month off treatment.…”

Section: Discussionmentioning

confidence: 99%

Intermittent inhaled tobramycin and systemic cytokines response in CF patients with Pseudomonas aeruginosa

Toukan

Gur

Hakim

et al. 2018

CIM

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Introduction: CF pulmonary guidelines recommend alternate therapy (one month on, one month off) with inhaled tobramycin for chronic Pseudomonas aeruginosa colonization in cystic fibrosis (CF). Tobramycin-inhaled powder (TIP™) is increasingly replacing time-consuming nebulizer therapy. It is unclear whether laboratory parameters change during the month off period compared with the month on therapy. Purpose: Our aim was to assess whether spirometry, lung clearance index and circulating inflammatory markers differ between on/off treatment periods. Materials and methods: A prospective pilot study evaluating CF patients treated with TIP, on two consecutive months (on/off) therapy. The evaluations were performed at the end of a month off therapy (1-2 days before the initiation of TIP) and after 28 days of treatment with TIP (1-2 days after the end of the treatment cycle). Results: Nineteen CF patients (10 males) with a mean age of 18.7±9.7 years and BMI (body mass index) of 19.62±3.53 kg/m2 were evaluated. After a month off treatment with TIP, spirometry parameters and lung clearance index remained unchanged. IL-6 increased significantly (p=0.022) off treatment. There was a non-significant change in the other inflammatory cytokines off therapy [hs-CRP, IL-8,TNF-α, α1-antitrypsin (α1AT) and neutrophilic elastase]. Conclusions: The results of lung function parameters support the relative stability of CF patients during the month off therapy; however, the difference in serum IL-6 raises the possibility of ongoing higher degrees of inflammation during the month off therapy with TIP. The small sample size and the multiple parameters evaluated preclude firm conclusions; therefore, larger multicenter studies are needed to assess the on/off treatment strategy.

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“…The escalation of underlying standard of care in CF limits the broad applicability of placebo-controlled efficacy trials (55). A postapproval study of continuous alternating therapy of inhaled aztreonam and tobramycin versus inhaled tobramycin and placebo was stopped early because of enrollment difficulties in a patient population increasingly managed with multiple inhaled antibiotics; patients and their providers were reluctant to participate in a placebo-controlled trial, potentially due to concerns about worsening symptoms and lung function in the absence of inhaled antibiotics (56). Comparative effectiveness research is an appealing alternative to traditional controlled trials aimed to answer clinical questions through pragmatic trials with limited inclusion/exclusion criteria, or via observational data such as patient registries (57,58).…”

Section: Challenges To Clinical Trial Design For Future Therapeuticsmentioning

confidence: 99%