Outpatient Treatment of <i>Pseudomonas aeruginosa</i> Bronchial Colonization with Long‐term Inhaled Colistin, Tobramycin, or Both in Adults without Cystic Fibrosis

Berlana, David; Llop, Jordi; Manresa, F.; Jódar, R.

doi:10.1592/phco.31.2.146

Cited by 29 publications

(26 citation statements)

References 57 publications

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“…The tolerability of alternating therapy with inhaled antibiotics, the clinical effects of the treatment with inhaled tobramycin and/or colistin, and the treatment compliance were of interest. Our study is the first study to investigate the safety and efficacy of sequentially inhaled tobramycin and colistin treatment in CF patients [13]. We noted that the novel treatment regimen is safe and led to a significant increase in lung function in subgroup analyses.…”

Section: Discussionmentioning

confidence: 83%

Sequential Inhalational Tobramycin-Colistin-Combination in CF-Patients with Chronic P. Aeruginosa Colonization - an Observational Study

Riethmüller

Herrmann

Graepler-Mainka

et al. 2016

Cell Physiol Biochem

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Background/Aims: In cystic fibrosis (CF), chronic microbial lung infections are difficult to treat and cause morbidity and increased mortality. Methods: In a multicentre, open-label, exploratory, non-interventional study, inhaled tobramycin (300 mg twice daily) and colistin (1 million I.U. twice daily) were sequentially combined with the aim to investigate the effect on 41 CF patients with chronic P. aeruginosa infections for six months (mean age 24 ± 10.8y). Results: Six patients had adverse events that were assessed as being related to treatment. Mucus production and coughing both decreased in 39%, whereas FEV₁ absolute and relative to baseline increased by 4.9% and 9.1%, respectively (p = 0.004) in 29 patients, who were definitely treated sequentially. Efficacy of the therapy was rated ‘excellent' or ‘good' by the physicians in 80.5% of the patients. Conclusions: The results indicate that treatment with inhaled antibiotics, sequentially combined, was very well tolerated by most patients and may have a beneficial effect, even if transitory on lung function and respiratory symptoms.

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Section: Discussionmentioning

confidence: 83%

Sequential Inhalational Tobramycin-Colistin-Combination in CF-Patients with Chronic P. Aeruginosa Colonization - an Observational Study

Riethmüller

Herrmann

Graepler-Mainka

et al. 2016

Cell Physiol Biochem

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“…However, there has been a significant increase in the prevalence of aminoglycoside resistance in P. aeruginosa isolated from CF patients in recent years [5]. Both intravenous [25] and inhaled [26], [27] tobramycin therapy has been associated with a trend towards higher MICs and resistance amongst P. aeruginosa isolates. In addition, long term tobramycin therapy has been shown to be a risk factor for the development of multi-drug resistant P. aeruginosa in CF [28].…”

Section: Discussionmentioning

confidence: 99%

Resistance Development of Cystic Fibrosis Respiratory Pathogens When Exposed to Fosfomycin and Tobramycin Alone and in Combination under Aerobic and Anaerobic Conditions

et al. 2013

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Although antibiotics from different classes are frequently prescribed in combination to prevent the development of resistance amongst Cystic Fibrosis (CF) respiratory pathogens, there is a lack of data as to the efficacy of this approach. We have previously shown that a 4∶1 (w/w) combination of fosfomycin and tobramycin (F∶T) has excellent activity against CF pathogens with increased activity under physiologically relevant anaerobic conditions. Therefore, the aim of this study was to determine whether F∶T could delay or prevent the onset of resistance compared to either fosfomycin or tobramycin alone under aerobic and anaerobic conditions. The frequency of spontaneous mutants arising following exposure to fosfomycin, tobramycin and F∶T was determined for clinical Pseudomonas aeruginosa and MRSA isolates under aerobic and anaerobic conditions. The effect of sub-inhibitory concentrations of fosfomycin, tobramycin and F∶T on the induction of resistance was also investigated, with the stability of resistance and fitness cost associated with resistance assessed if it developed. P. aeruginosa and MRSA isolates had a lower frequency of spontaneous mutants to F∶T compared to fosfomycin and tobramycin under both aerobic and anaerobic conditions. There was a maximum two-fold increase in F∶T MICs when P. aeruginosa and MRSA isolates were passaged in sub-inhibitory F∶T for 12 days. In contrast, sequential resistance to fosfomycin and tobramycin developed quickly (n = 3 days for both) after passage in sub-inhibitory concentrations. Once developed, both fosfomycin and tobramycin resistance was stable and not associated with a biological fitness cost to either P. aeruginosa or MRSA isolates. The results of this study suggest that F∶T may prevent the development of resistance compared to fosfomycin or tobramycin alone under aerobic and physiologically relevant anaerobic conditions. F∶T may be a potential treatment option in CF patients chronically colonised by MRSA and/or P. aeruginosa.

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“…This study suffered from several limitations, including ambiguous inclusion criteria, observational design, differences in dosages and adjunctive antibiotic use that were not accounted for, and results that conflict with many previously reported results, including a treatment-emergent resistance rate of 48% for tobramycin. Most importantly, the outcomes for patients with bronchiectasis and those with COPD were reported together (228).…”

Section: Non-cf Bronchiectasismentioning

confidence: 99%

Inhaled Antibiotics for Gram-Negative Respiratory Infections

et al. 2016

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SUMMARYGram-negative organisms comprise a large portion of the pathogens responsible for lower respiratory tract infections, especially those that are nosocomially acquired, and the rate of antibiotic resistance among these organisms continues to rise. Systemically administered antibiotics used to treat these infections often have poor penetration into the lung parenchyma and narrow therapeutic windows between efficacy and toxicity. The use of inhaled antibiotics allows for maximization of target site concentrations and optimization of pharmacokinetic/pharmacodynamic indices while minimizing systemic exposure and toxicity. This review is a comprehensive discussion of formulation and drug delivery aspects,in vitroand microbiological considerations, pharmacokinetics, and clinical outcomes with inhaled antibiotics as they apply to disease states other than cystic fibrosis. In reviewing the literature surrounding the use of inhaled antibiotics, we also highlight the complexities related to this route of administration and the shortcomings in the available evidence. The lack of novel anti-Gram-negative antibiotics in the developmental pipeline will encourage the innovative use of our existing agents, and the inhaled route is one that deserves to be further studied and adopted in the clinical arena.

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Outpatient Treatment of Pseudomonas aeruginosa Bronchial Colonization with Long‐term Inhaled Colistin, Tobramycin, or Both in Adults without Cystic Fibrosis

Cited by 29 publications

References 57 publications

Sequential Inhalational Tobramycin-Colistin-Combination in CF-Patients with Chronic P. Aeruginosa Colonization - an Observational Study

Sequential Inhalational Tobramycin-Colistin-Combination in CF-Patients with Chronic P. Aeruginosa Colonization - an Observational Study

Resistance Development of Cystic Fibrosis Respiratory Pathogens When Exposed to Fosfomycin and Tobramycin Alone and in Combination under Aerobic and Anaerobic Conditions

Inhaled Antibiotics for Gram-Negative Respiratory Infections

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