Antibiotic treatment for Burkholderia cepacia complex in people with cystic fibrosis experiencing a pulmonary exacerbation

Horsley, Alex; Jones, Andrew M.

doi:10.1002/14651858.cd009529

Cited by 12 publications

(17 citation statements)

References 38 publications

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“…68 Further complicating treatment is the lack of evidence that any specific antimicrobial treatment regimen is effective in treating B cepacia complex pulmonary exacerbations. 70…”

Section: Burkholderia Cepacia Complex and Related Organismsmentioning

confidence: 99%

Infections in Patients with Cystic Fibrosis

Gilligan

2014

Clinics in Laboratory Medicine

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Survival has improved in patients with cystic fibrosis (CF), in part because of aggressive antimicrobial management. Two multidrug-resistant environmental bacteria, the Burkholderia cepacia group and nontuberculous mycobacteria, have emerged. Improving genomic and proteomic technologies are allowing better identification of bacteria and fungi found in the CF lung and detection of viral agents that may be associated with pulmonary exacerbations. Anaerobic bacteria and Streptococcus angionsus group organisms may play a role in chronic CF lung infections. The diversity of organisms declines perhaps as a result of aggressive antimicrobial therapy, and an apex predator, Pseudomonas aeruginosa, may emerge in many patients with CF.

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“…68 Further complicating treatment is the lack of evidence that any specific antimicrobial treatment regimen is effective in treating B cepacia complex pulmonary exacerbations. 70…”

Section: Burkholderia Cepacia Complex and Related Organismsmentioning

confidence: 99%

Infections in Patients with Cystic Fibrosis

Gilligan

2014

Clinics in Laboratory Medicine

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“…2 Within this group of species, Burkholderia multivorans is among the most commonly identified species isolated from CF respiratory specimens. This species has been associated with “cepacia syndrome”, a rapidly progressive necrotizing pneumonia.…”

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confidence: 99%

Overcoming an Extremely Drug Resistant (XDR) Pathogen: Avibactam Restores Susceptibility to Ceftazidime for Burkholderia cepacia Complex Isolates from Cystic Fibrosis Patients

et al. 2017

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Burkholderia multivorans is a significant health threat to persons with cystic fibrosis (CF). Infections are difficult to treat as this pathogen is inherently resistant to multiple antibiotics. Susceptibility testing of isolates obtained from CF respiratory cultures revealed that single agents selected from different antibiotic classes were unable to inhibit growth. However, all isolates were found to be susceptible to ceftazidime when combined with the novel non-β-lactam β-lactamase inhibitor, avibactam (all minimum inhibitor concentrations (MICs) were ≤8 mg/L of ceftazidime and 4 mg/L of avibactam). Furthermore, a major β-lactam resistance determinant expressed in B. multivorans, the class A carbapenemase, PenA was readily inhibited by avibactam with a high k2/K of (2 ± 1) × 106 μM−1 s−1 and a slow koff of (2 ± 1) × 10−3 s−1. Mass spectrometry revealed that avibactam formed a stable complex with PenA for up to 24 h and that avibactam recyclized off of PenA, re-forming the active compound. Crystallographic analysis of PenA–avibactam revealed several interactions that stabilized the acyl–enzyme complex. The deacylation water molecule possessed decreased nucleophilicity, preventing decarbamylation. In addition, the hydrogen-bonding interactions with Lys-73 were suggestive of a protonated state. Thus, Lys-73 was unlikely to abstract a proton from Ser-130 to initiate recyclization. Using Galleria mellonella larvae as a model for infection, ceftazidime–avibactam was shown to significantly (p < 0.001) improve survival of larvae infected with B. multivorans. To further support the translational impact, the ceftazidime–avibactam combination was evaluated using susceptibility testing against other strains of Burkholderia spp. that commonly infect individuals with CF, and 90% of the isolates were susceptible to the combination. In summary, ceftazidime–avibactam may serve as a preferred therapy for people that have CF and develop Burkholderia spp. infections and should be considered for clinical trials.

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“…One of the reasons is that individuals with Burkholderia cepacia complex infection have historically been excluded from efficacy trials of inhaled antibiotics [5, 8, 9]. …”

Section: Discussionmentioning

confidence: 99%

Eradication ofBurkholderia cepaciaUsing Inhaled Aztreonam Lysine in Two Patients with Bronchiectasis

Iglesias

Artiles

Cabanillas

et al. 2014

Case Reports in Pulmonology

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There are not many articles about the chronic bronchial infection/colonization in patients with underlying lung disease other than cystic fibrosis (CF), especially with non-CF bronchiectasis (NCFBQ). The prevalence of B. cepacia complex is not well known in NCFBQ. The vast majority of published clinical data on Burkholderia infection in individuals with CF is comprised of uncontrolled, anecdotal, and/or single center experiences, and no consensus has emerged regarding treatment. We present two cases diagnosed with bronchiectasis (BQ) of different etiology, with early pulmonary infection by B. cepacia complex, which was eradicated with inhaled aztreonam lysine.

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Antibiotic treatment for Burkholderia cepacia complex in people with cystic fibrosis experiencing a pulmonary exacerbation

Cited by 12 publications

References 38 publications

Infections in Patients with Cystic Fibrosis

Infections in Patients with Cystic Fibrosis

Overcoming an Extremely Drug Resistant (XDR) Pathogen: Avibactam Restores Susceptibility to Ceftazidime for Burkholderia cepacia Complex Isolates from Cystic Fibrosis Patients

Eradication ofBurkholderia cepaciaUsing Inhaled Aztreonam Lysine in Two Patients with Bronchiectasis

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