Clinical and in vitro evidence for the antimicrobial therapy in Burkholderia cepacia complex infections

Abstract

Treatment of infections caused by Burkholderia cepacia complex (Bcc) in cystic fibrosis (CF) patients poses a complex problem. Bcc is multidrug-resistant due to innate and acquired mechanisms of resistance. As CF patients receive multiple courses of antibiotics, susceptibility patterns of strains from CF patients may differ from those noted in strains from non-CF patients. Thus, there was a need for assessing in vitro and clinical data to guide antimicrobial therapy in these patients. A systematic search of literature, followed by extraction and analysis of available information from human and in vitro studies was done. The results of the analysis are used to address various aspects like use of antimicrobials for pulmonary and non-pulmonary infections, use of combination versus monotherapy, early eradication, duration of therapy, route of administration, management of biofilms, development of resistance during therapy, pharmacokinetics–pharmacodynamics correlations, therapy in post-transplant patients and newer drugs in Bcc-infected CF patients.

Keywords:

• Burkholderia cepacia
• cystic fibrosis
• eradication
• review
• therapy

Acknowledgements

The authors are thankful to N Sharma, retired from the Regional Institute of English Chandigarh (UT) for the valuable suggestions and proof reading of the manuscript.

Financial & competing interests disclosure

V Gautam, Concept; V Gautam, N Shafiq, Planning, analysis and interpretation; NP Jaiswal, A Agarwal, A Prasad, S Singh, Literature search and data extraction; V Gautam, N Shafiq, L Singhal, Writing; M Singh, P Ray, Critical reviewing of manuscript; V Gautam, N Shafiq, L Singhal, A Prasad, S Singh, Finalization of manuscript. The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Key issues

• Burkholderia cepacia complex (Bcc) is a multidrug-resistant, Gram-negative bacillus that has emerged as a serious human pathogen with a predilection for cystic fibrosis (CF).

• Two important roadblocks in managing Bcc-infected patients are the organism’s resistance to various antimicrobials coupled with the lack of newer effective antibiotics.

• Bcc infections are often associated with rapid decline of the lung function and, in some cases, with the ‘cepacia syndrome’ characterized by necrotizing pneumonia and sepsis. Despite pulmonary exacerbation being an important concern in CF, no good-quality study could be identified.

• There was remarkable paucity of high-quality clinical studies to help in decision-making regarding antimicrobial use.

• The issues raised in this review highlight that for resolving most of these, adequately powered multicentric studies are urgently needed.

• Optimization of treatment regimens is the need of the hour as most of the information is based solely on in vitro antimicrobial susceptibility of the isolates. Pharmacokinetics–pharmacodynamics studies are needed.

• Duration of treatment is widely varied across studies.

• The treatment of Bcc may be rendered more difficult by its ability to form biofilms.

• Despite getting antimicrobial results, clinicians are faced with difficult decision-making questions.

• There is a dire necessity to undertake good-quality observational studies and controlled trials to answer the unresolved questions.

Notes