Resistance to tobramycin and colistin in isolates of Pseudomonas aeruginosa from chronically colonized patients with cystic fibrosis under antimicrobial treatment

Valenza, Giuseppe; Radike, Kerstin; Schoen, Christoph; Horn, Stephan; Oesterlein, Anett; Frosch, Matthias; Abele‐Horn, Marianne; Hebestreit, Helge

doi:10.3109/00365548.2010.509333

Cited by 15 publications

(12 citation statements)

References 18 publications

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“…A correlation with antibiotic usage irrespective of patient age (49) or with time after colonization (6) has also been proposed. In contrast, other studies following the evolution of antibiotic susceptibility in successive isogenic isolates from a single patient suggest that resistance can occur either sporadically (50) or without correlation with the time of isolation (51). In these cases, the presence of mutator variants seems to predetermine the risk of developing resistance over time (6).…”

Section: Discussionmentioning

confidence: 92%

Antimicrobial Susceptibility of Pseudomonas aeruginosa Isolated from Cystic Fibrosis Patients in Northern Europe

Mustafa

Chalhoub

Denis

et al. 2016

Antimicrob Agents Chemother

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f Pseudomonas aeruginosa is a major cause of morbidity and mortality in cystic fibrosis patients. This study compared the antimicrobial susceptibilities of 153 P. aeruginosa isolates from the United Kingdom (UK) (n ‫؍‬ 58), Belgium (n ‫؍‬ 44), and Germany (n ‫؍‬ 51) collected from 118 patients during routine visits over the period from 2006 to 2012. MICs were measured by broth microdilution. Genes encoding extended-spectrum ␤-lactamases (ESBL), metallo-␤-lactamases, and carbapenemases were detected by PCR. Pulsed-field gel electrophoresis and multilocus sequence typing were performed on isolates resistant to >3 antibiotic classes among the penicillins/cephalosporins, carbapenems, fluoroquinolones, aminoglycosides, and polymyxins. Based on EUCAST/CLSI breakpoints, susceptibility rates were <30%/<40% (penicillins, ceftazidime, amikacin, and ciprofloxacin), 44 to 48%/48 to 63% (carbapenems), 72%/72% (tobramycin), and 92%/78% (colistin) independent of patient age. Sixty percent of strains were multidrug resistant (MDR; European Centre for Disease Prevention and Control criteria). Genes encoding the most prevalent ESBL (BEL, PER, GES, VEB, CTX-M, TEM, SHV, and OXA), metallo-␤-lactamases (VIM, IMP, and NDM), or carbapenemases (OXA-48 and KPC) were not detected. The Liverpool epidemic strain (LES) was prevalent in UK isolates only (75% of MDR isolates). Four MDR sequence type 958 (ST958) isolates were found to be spread over the three countries. The other MDR clones were evidenced in <3 isolates and localized in a single country. A new sequence type (ST2254) was discovered in one MDR isolate in Germany. Clonal and nonclonal isolates with different susceptibility profiles were found in 20 patients. Thus, resistance and MDR are highly prevalent in routine isolates from 3 countries, with meropenem, tobramycin, and colistin remaining the most active drugs.

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Section: Discussionmentioning

confidence: 92%

Antimicrobial Susceptibility of Pseudomonas aeruginosa Isolated from Cystic Fibrosis Patients in Northern Europe

Mustafa

Chalhoub

Denis

et al. 2016

Antimicrob Agents Chemother

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“…Several surveys have examined the susceptibility patterns of P. aeruginosa isolated from CF patients 61–65. Resistance rates have been demonstrated to be quite high for some antibiotics commonly used for P. aeruginosa treatment, but still very low for colistin 63,64,66. Reasons for the rare occurrence of colistin resistance might be the fact that colistin self-promotes its penetration of the cell envelope and causes irreversible disruption of the cytoplasmic membrane, and, further, that P. aeruginosa cannot modify the lipid A target of its LPS, where colistin binds to.…”

Section: Resistance Rates To Colistin Compared With Other Antibioticsmentioning

confidence: 99%

Colistimethate sodium for the treatment of chronic pulmonary infection in cystic fibrosis: an evidence-based review of its place in therapy

Koerner-Rettberg¹,

Ballmann²

2014

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Chronic bacterial respiratory-tract infections are a major driving force in the pathogenesis of cystic fibrosis (CF) lung disease and promote chronic lung-function decline, destruction, and progression to respiratory failure at a premature age. Gram-negative bacteria colonizing the airways in CF are a major problem in CF therapy due to their tendency to develop a high degree of resistance to antibiotic agents over time. Pseudomonas aeruginosa is the dominating bacterial strain infecting the CF lung from early childhood on, and multiresistant strains frequently develop after years of therapy. Colistin has been used for treating pulmonary bacterial infections in CF for decades due to its very good Gram-negative activity. However, drawbacks include concerns regarding toxicity when being applied systemically, and the lack of approval for application by inhalation in the USA for many years. Other antibiotic substances for systemic use are available with good to excellent Gram-negative and anti-Pseudomonas activity, while there are only three substances approved for inhalation use in the treatment of chronic pulmonary infection with proven benefit in CF. The emergence of multiresistant strains leaving nearly no antibiotic substance as a treatment option, the limited number of antibiotics with high activity against P. aeruginosa, the concerns about increasing the risk of antibiotic resistance by continuous antibiotic therapy, the development of new drug formulations and drug-delivery devices, and, finally, the differing treatment strategies used in CF centers call for defining the place of this “old” drug, colistimethate, in today’s CF therapy. This article reviews the available evidence to reflect on the place of colistimethate sodium in the therapy of chronic pulmonary infection in CF.

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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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Resistance to tobramycin and colistin in isolates of Pseudomonas aeruginosa from chronically colonized patients with cystic fibrosis under antimicrobial treatment

Cited by 15 publications

References 18 publications

Antimicrobial Susceptibility of Pseudomonas aeruginosa Isolated from Cystic Fibrosis Patients in Northern Europe

Antimicrobial Susceptibility of Pseudomonas aeruginosa Isolated from Cystic Fibrosis Patients in Northern Europe

Colistimethate sodium for the treatment of chronic pulmonary infection in cystic fibrosis: an evidence-based review of its place in therapy

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

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