Report of the UK Cystic Fibrosis Trust Antibiotic Working Group

Unfortunately most organisms within the B.cepacia complex exhibit high levels of resistance toantipseudomonal antibiotics, including inherent resistance to colistin. 21–23 Some UK centres havereported pan-resistance in >80% of patient isolates. 24 In general environmental strains are moresusceptible than clinical strains. 25;26 Resistance can be observed in all genomovars, 27 although somestudies have suggested that resistance may be highest with B.dolosa. 26 The most consistently activeagents in vitro appear to be ceftazidime, piperacillin-tazobactam, meropenem, imipenem,ciprofloxacin, trimethoprim, cotrimoxazole, and tetracyclines. 23;26;28–32 Levels of resistance toaminoglycosides are high. There are also anecdotal reports of the use of temocillin for treating Bccexacerbations, although the clinical improvements observed were relatively modest. 33 [3]Some combinations of two or three antibiotics have shown synergy against Bcc. 34 In this studymeropenem in particular was shown to be bactericidal in combination with ceftazidime, amikacin orminocycline against >70% of isolates. Combinations of tobramycin plus meropenem plus a thirdagent were synergistic against >80% of isolates. However, other studies, using different laboratorymethods, have failed to demonstrate such levels of synergy. 32 In this later study of 2,621 Bcc isolatesfrom 1,257 persons with CF, synergy was observed against less than 20% of isolates for two-drugcombinations. The clinical significance of synergy is also questionable. A randomised, double-blind,controlled trial of selection of treatment for exacerbations caused by multi-resistant bacteria(including Bcc) failed to show a benefit for those regimens selected on the basis of synergy testingversus those chosen on the basis of routine susceptibility tests. 35 [1+]There are anecdotal reports that some isolates of Bcc, particularly B.multivorans, can be successfullyeradicated with early aggressive antibiotic therapy before chronic infection becomes established.36Patients were treated with a regimen of three intravenous antibiotics (e.g. tobramycin plus meropenemplus ceftazidime) for two weeks. There is also anecdotal evidence that eradication can be enhanced bygiving aerosolized amiloride and tobramycin in combination. 37 [3]Little data exist on optimum therapeutic approaches to the management of ‘cepacia syndrome’.Interestingly one study of Bcc bacteraemia suggested persons with CF were less likely to die within 14days of bacteraemia than those with other co-morbid factors. 38 The same study also suggested thattreatment with cotrimoxazole was associated with reduced mortality. [2-] There are also anecdotalreports that administration of corticosteroids in conjunction with antibiotic therapy may improvesurvival 39 and combined intravenous and nebulised antibiotics have been used. 40 [3]7.1.2 Recommendations for the treatment of Burkholderia cepacia complex• Antimicrobial therapy should be directed by in vitro sensitivities where available [C].• Combination therapy should be used for treatment of Bcc exacerbations and ‘cepacia syndrome’[C].• The routine use of synergy testing to guide therapy of Bcc cannot be recommended at this time[A].• The use of eradication therapy for all new growths of Bcc should be considered [D].Cystic Fibrosis Trust 7.1.2March 2009