Guideline
Cystic Fibrosis- Management of
Burkholderia cepacia
complex infections
Key messages
in
Burkholderia cepacia infections are associated with significant adverse outcomes
Cystic Fibrosis patients
Spread of infection can be limited by strict infection control measures.
Early and aggressive combination antibiotic therapy may prevent chronic
infection.
.
1
Scope
Trust wide
2
Aim
To optimise the management of Burkholderia cepacia infections in
paediatric patients with Cystic Fibrosis (CF)
3
Introduction
Burkholderia cepacia complex (Bcc) is a group of environmental bacteria
which have been shown to be of increasing importance to CF patients in
recent years. They are highly virulent and easily transmissible between CF
patients. Infection is associated with increased morbidity, accelerated
decline in lung function and shortened life expectancy. Some patients
develop a rapidly progressive, invasive and often fatal disease (“cepacia
syndrome”). However clinical outcome is variable and patients may have
transient infection or can remain stable for many years. Currently there
are 17 established species (geonomovars) within the Bcc, of which B.
cenocepacia has the greatest potential for virulence in CF patients. B.
cenocepacia and
B. multivorans account for 90% of isolates from CF sputum. Infection can
be acquired by person to person transmission or from the environment[1]
4
Responsibilities
All staff: Adhere to standard infection control recommendations when caring
for patients with CF.
Clinicians: Liaise with microbiologists and decide on appropriate
management on a case-by-case basis.
Secretarial staff/outpatient department: Ensure that patients with confirmed
Bcc are booked into separate clinics, or at the end of normal clinics.
5
Definitions
Burkholderia cepacia complex: A group of closely related species of bacteria
belonging to the group Burkholderia.
Cepacia syndrome: Rapid and life threatening outcome of Bcc infection,
usually with a fulminant clinical picture and very poor prognosis
Genomovar: Term used to define species which are indistinguishable by
standard microbiological or biochemical tests but are phylogenetically
differentiable.
6
Management of patients who are infected with Bcc
6.1
Laboratory identification
Accurate identification of Bcc from sputum specimens is of the utmost
importance. However Bcc species are prone to misidentification. All new
isolates suspected as Bcc should be sent to the reference laboratory (Health
Protection Agency, Colindale) for further specialised analysis and subtyping
and the final results discussed with the microbiologists. Virulence and crossinfection potential differ among strains. [1]
6.2
Patient counselling
Following a confirmed report of the first growth of Bcc, a senior clinician
should discuss with parents in detail the implications. All parents, and if
possible the child, should be aware of their Bcc status.
6.3
Antibiotic treatment
Most organisms within the Bcc complex exhibit high levels of resistance to
anti-pseudomonal antibiotics and treatment options may be limited.
Antibiotic therapy should be directed by in vitro sensitivities where available.
The most consistently active agents appear to be ceftazidime, piperacillintazobactam, meropenem, imipenem, ciprofloxacin, cotrimoxazole, and
tetracyclines[3]. Although Bcc are typically resistant to aminoglycosides,
high peak concentrations of tobramycin (e.g. when given nebulised) inhibit
the majority of strains. Combinations of two or three antibiotics have been
shown to exhibit synergy against Bcc. However routine use of synergy
testing to guide therapy is currently not recommended.
6.3.1
Management of first isolate
Some isolates of Bcc can be successfully eradicated with early aggressive
therapy before chronic infection becomes established. In view of the
potentially serious implications of chronic infection, eradication should be
attempted in all first isolates of Bcc. Although definitive evidence is lacking,
the consensus approach is to treat with three intravenous antibiotics (eg:
tobramycin plus meropenem plus ceftazidime) for two weeks, followed by
three months of nebulised tobramycin (TOBI®,Bramitob®)[4]. There have
been a few reports which suggest that eradication can be enhanced by giving
aerosolised amiloride and tobramycin in combination. This is not standard
practice yet but might be considered after a consultant decision on a caseby-case basis [7].
6.3.2
Management of exacerbations
In chronically infected patients, oral antibiotics (Ciprofloxacin/ trimethoprim/
doxycycline) can be considered for the treatment of mild exacerbations at
the discretion of the consultant. Combination therapy of two or three
antibiotics should be given for more significant respiratory
exacerbations[1,2& 5] Some patients will be chronically infected with
Psueudomonas aeruginosa as well as Bcc and initial empiric therapy for
exacerbations might have to be tailored to cover both organisms.
6.3.3
Cepacia syndrome
This is associated with poor prognosis and a high mortality. Optimum
treatment strategy is not well defined. Treatment with co-trimoxazole has
been associated with reduced mortality. Combining intravenous and
nebulised antibiotics as well as addition of corticosteroids have been shown
to be of some benefit. [1] Treatment will be decided on a case-by-case basis
by the consultant concerned.
6.4
Infection control
There is strong evidence that people with CF can acquire Bcc by direct
patient-to-patient spread in hospital or during social contact outside the
hospital. A policy of strict segregation should be followed for both inpatients
and outpatients as this approach has been shown to reduce cross-infection.
There should be evidence of at least 3 negative sputum cultures over a
period of at least 1 year before a person with CF can be considered free from
Bcc[1]
6.4.1
Outpatient clinics
There should be separate outpatient clinics for patients chronically infected
with Bcc and those who are Bcc negative. The Bcc clinics should be held on
different days or at a later time to avoid mixing of patients. Standard
hygienic measures, as per local infection control policy should be strictly
followed for these patients [1].
6.4.2
Inpatients
Bcc patients should be nursed on different wards to non Bcc patients if
possible. If not possible then they should be barrier nursed in cubicles and
stringent infection control policies applied [1].
6.4.3
Outside the hospital
Social contact between CF patents outside the hospital has some potential to
spread infection and should be avoided wherever possible. The risk of
transmission is higher with close contact of extended duration (eg: travelling
together in a car, communal sports or exercise classes)[1].
7
Monitoring compliance with and the effectiveness of
this policy
All Bcc isolates will be discussed by the CF multi-professional team in the
weekly CF clinic meeting held on Thursdays.
8
References
1]Burkholderia cepacia Complex. Suggestions for Prevention and Infection
Control. Report of the UK Cystic Fibrosis Infection Control Group. Second
Edition. September 2004
2]Antibiotic treatment for Cystic Fibrosis. Third edition. Report of the UK
Cystic Fibrosis Trust Antibiotic Group. May 2009
3] Aaron SD Ferris W, Henry DA, Speert DP, MacDonald NE. Multiple
combination bactericidal antibiotic testing for patients with Cystic fibrosis
infected with Burkhloderia cepacia. Am J Respir Crit Care Med2000: 161:
1206-12.
4]Cystic Fibrosis in Children and Adults. The Leeds Method of
Management,
2008.
5]Etherington C, Peckham DG, Conway SP, Denton M. Burkholderia
cepacia complex infection in adults with cystic fibrosis - is early
eradication possible? J Cyst Fibros 2003;2:220–1.
6]Middleton PG, Kidd TJ, Williams B. Combination aerosol therapy to
treat
Burkholderia cepacia complex. Eur Respir J 2005;26:305–8.
7]Ball R, Brownlee KG, Duff AJ, Denton M, Conway SP, Lee TW.
Can Burkholderia cepacia complex be eradicated with nebulised
Amiloride and TOBI? J Cyst Fibrosis 2010 ;9(1):73-4.
8]Kazachkov M, Lager J, LiPuma J, Barker PM. Survival following
Burkholderia cepacia sepsis in a patient with cystic fibrosis
treated with corticosteroids. Pediatr Pulmonol 2001;32:338–40.
9]Weidmann A, Webb AK, Dodd ME, Jones AM. Successful
treatment of cepacia syndrome with combination nebulised and
intravenous antibiotic therapy. J Cyst Fibros 2008;7:409–11.
9
Associated documents
Antibiotic Guideline for the care of children with cystic fibrosis
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This document complies with the Cambridge University
Hospitals NHS Foundation Trust service equality and diversity
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Issue
Author(s)
Owner
Date
Circulation
Comments
Dr A Pillai, Dr
R Aniapravan,
Dr D McShane
Dr D McShane
Addenbrooke’s
Hospital
Mar 2012
NSC CF
Network