Antibiotic treatment for<i>Burkholderia cepacia</i>complex in people with cystic fibrosis experiencing a pulmonary exacerbation

Horsley, Alex; Jones, Andrew M.

doi:10.1002/14651858.cd009529.pub2

Cited by 27 publications

(10 citation statements)

References 60 publications

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“…These reports emphasise the need for prolonged treatment with IV and aerosolised antibiotic combinations which include ceftazidime, ciprofloxacin, tobramycin, temocillin and trimethoprim-sulphamethoxazole [26] , [27] . At present, there is insufficient data to support the use of any specific antibiotic regimen against Bcc infection [28] , [29] . There is an even greater need to have alternative therapies with the recent alarming report of a clinical trial of inhaled aztreonam that failed to treat CF patients with Burkholderia spp.…”

Section: Introductionmentioning

confidence: 99%

Garlic Revisited: Antimicrobial Activity of Allicin-Containing Garlic Extracts against Burkholderia cepacia Complex

et al. 2014

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The antimicrobial activities of garlic and other plant alliums are primarily based on allicin, a thiosulphinate present in crushed garlic bulbs. We set out to determine if pure allicin and aqueous garlic extracts (AGE) exhibit antimicrobial properties against the Burkholderia cepacia complex (Bcc), the major bacterial phytopathogen for alliums and an intrinsically multiresistant and life-threatening human pathogen. We prepared an AGE from commercial garlic bulbs and used HPLC to quantify the amount of allicin therein using an aqueous allicin standard (AAS). Initially we determined the minimum inhibitory concentrations (MICs) of the AGE against 38 Bcc isolates; these MICs ranged from 0.5 to 3% (v/v). The antimicrobial activity of pure allicin (AAS) was confirmed by MIC and minimum bactericidal concentration (MBC) assays against a smaller panel of five Bcc isolates; these included three representative strains of the most clinically important species, B. cenocepacia. Time kill assays, in the presence of ten times MIC, showed that the bactericidal activity of AGE and AAS against B. cenocepacia C6433 correlated with the concentration of allicin. We also used protein mass spectrometry analysis to begin to investigate the possible molecular mechanisms of allicin with a recombinant form of a thiol-dependent peroxiredoxin (BCP, Prx) from B. cenocepacia. This revealed that AAS and AGE modifies an essential BCP catalytic cysteine residue and suggests a role for allicin as a general electrophilic reagent that targets protein thiols. To our knowledge, we report the first evidence that allicin and allicin-containing garlic extracts possess inhibitory and bactericidal activities against the Bcc. Present therapeutic options against these life-threatening pathogens are limited; thus, allicin-containing compounds merit investigation as adjuncts to existing antibiotics.

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Section: Introductionmentioning

confidence: 99%

Garlic Revisited: Antimicrobial Activity of Allicin-Containing Garlic Extracts against Burkholderia cepacia Complex

et al. 2014

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“…Treatment of these infections is difficult (6)(7)(8)(9) due to their numerous mechanisms of antimicrobial resistance, including efflux pumps, chromosomally encoded ␤-lactamases, decreased outer membrane permeability, intracellular survival, and biofilm formation (10)(11)(12). However, newer inhalational antibiotic therapies have the ability to deliver very high concentrations of drug to the lung, which may be able to overcome some of these mechanisms.…”

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confidence: 99%

In Vitro Efficacy of High-Dose Tobramycin against Burkholderia cepacia Complex and Stenotrophomonas maltophilia Isolates from Cystic Fibrosis Patients

Ratjen

Yau

Wettlaufer

et al. 2015

Antimicrob Agents Chemother

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f Burkholderia cepacia complex and Stenotrophomonas maltophilia infections are associated with poor clinical outcomes in persons with cystic fibrosis (CF). The MIC 50 based on planktonic growth and the biofilm concentration at which 50% of the isolates tested are inhibited (BIC 50 ) of tobramycin were measured for 180 B. cepacia complex and 101 S. maltophilia CF isolates and were 100 g/ml for both species. New inhalation devices that deliver high tobramycin levels to the lung may be able to exceed these MICs. As individuals with cystic fibrosis (CF) age, they are increasingly infected in their lungs with multidrug-resistant Gramnegative organisms such as Burkholderia cepacia complex and Stenotrophomonas maltophilia, which are associated with poor clinical outcomes (1-5). Treatment of these infections is difficult (6-9) due to their numerous mechanisms of antimicrobial resistance, including efflux pumps, chromosomally encoded ␤-lactamases, decreased outer membrane permeability, intracellular survival, and biofilm formation (10-12). However, newer inhalational antibiotic therapies have the ability to deliver very high concentrations of drug to the lung, which may be able to overcome some of these mechanisms. One of the new inhalational antibiotics available is tobramycin inhalation powder (TIP), delivered by the Podhaler device, which can achieve up to 1.5-to 2-fold higher sputum tobramycin concentrations (up to 2,000 g/g) than tobramycin inhalation solution (TIS) (13). It is not known whether these higher tobramycin concentrations can overwhelm the efficient efflux pumps known to be present in B. cepacia complex and S. maltophilia (14)(15)(16).In order to determine whether the known pulmonary concentrations of inhaled high-dose tobramycin powder can overcome these inhibitory concentrations, the aim of this study was to measure the inhibitory concentrations of tobramycin for a large collection of B. cepacia complex and S. maltophilia isolates, grown planktonically and in a biofilm, from pediatric and adult CF patients.B. cepacia complex isolates (n ϭ 180) were prospectively collected from sputum samples from CF patients from four study sites, The Hospital for Sick Children (n ϭ 10), St. Michael's Hospital (n ϭ 36), the Cystic Fibrosis Foundation Burkholderia cepacia Research Repository at the University of Michigan (n ϭ 16), and the Canadian Burkholderia cepacia Complex Research and Referral Repository at the University of British Columbia, Vancouver (n ϭ 118). S. maltophilia isolates (n ϭ 101) were obtained from pediatric CF patients at The Hospital for Sick Children in Toronto (n ϭ 67) and from adult CF patients (n ϭ 34) at St. Michael's Hospital in Toronto. All the isolates used in this study were independent strains (1 isolate/patient). Antimicrobial susceptibility testing was performed on isolates grown planktonically by broth microdilution using Clinical and Laboratory Standards Institute (CLSI) guidelines (17). Antimicrobial susceptibility testing was also performed on isolates grown as a biofilm using a mo...

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“…Bcc consists of 18 different genetically related Gram-negative, non-spore-forming species (2). Infection with Bcc leads to a spectrum of clinical manifestations, ranging from asymptomatic carriage in respiratory secretions to necrotizing pneumonia (1,3,4). Burkholderia cenocepacia isolates are frequently virulent, transmissible, and innately resistant to multiple drug classes (1,5).…”

Section: N the Cystic Fibrosis (Cf) Patient Population Infection Withmentioning

confidence: 99%

Clinafloxacin for Treatment of Burkholderia cenocepacia Infection in a Cystic Fibrosis Patient

Balwan

Nicolau

Wungwattana

et al. 2016

Antimicrob Agents Chemother

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Antibiotic treatment forBurkholderia cepaciacomplex in people with cystic fibrosis experiencing a pulmonary exacerbation

Cited by 27 publications

References 60 publications

Garlic Revisited: Antimicrobial Activity of Allicin-Containing Garlic Extracts against Burkholderia cepacia Complex

Garlic Revisited: Antimicrobial Activity of Allicin-Containing Garlic Extracts against Burkholderia cepacia Complex

In Vitro Efficacy of High-Dose Tobramycin against Burkholderia cepacia Complex and Stenotrophomonas maltophilia Isolates from Cystic Fibrosis Patients

Clinafloxacin for Treatment of Burkholderia cenocepacia Infection in a Cystic Fibrosis Patient

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