Multiple Combination Bactericidal Antibiotic Testing for Patients with Cystic Fibrosis Infected with Burkholderia cepacia

Abstract

Most Burkholderia cepacia strains are resistant to many, or all, of the antibacterial agents commonly used in cystic fibrosis (CF), and selection of appropriate antibiotics for treatment of pulmonary exacerbations is therefore difficult. We developed a technique for rapid in vitro testing of multiple antibiotic combinations for B. cepacia isolates. For each of 119 multi-drug-resistant isolates of B. cepacia, our multiple combination bactericidal test (MCBT) studied the bactericidal activity of 10 to 15 antimicrobial agents using 225 +/- 97 single, double, and triple antibiotic combinations. Of the 119 isolates, 50% were resistant to all single antibiotics tested, 8% were resistant to all two-drug antibiotic combinations, but all were inhibited by at least one bactericidal triple-drug combination. When used alone, meropenem, ceftazidime and high-dose tobramycin (200 microg/ml) were bactericidal against only 47, 15, and 14% of in vitro isolates, respectively. Using a double antibiotic combination improved bactericidal activity; meropenem-minocycline, meropenem-amikacin, and meropenem-ceftazidime combinations were bactericidal against 76, 73, and 73% of isolates, respectively. However, 47% of isolates demonstrated antagonism (growth of an organism when a second antibiotic was added to a bactericidal single antibiotic). Triple antibiotic combinations that contained tobramycin, meropenem, and an additional antibiotic were most effective, and were bactericidal against 81 to 93% of isolates. We conclude that triple-antibiotic combinations are more likely than double and single antibiotic combinations to be bactericidal against B. cepacia in vitro. MCBT testing is a useful technique to help clinicians decide on appropriate nonantagonistic combination antibiotic therapy for patients with CF infected with B. cepacia.

Exopolysaccharides from Burkholderia cenocepacia Inhibit Neutrophil Chemotaxis and Scavenge Reactive Oxygen Species

“…Innate resistance to antibiotics (31) and an ability to spread from patient to patient (32) make these bacteria especially problematic clinically. As of yet, little is known about virulence determinants that make BCC particularly virulent for CF and CGD patients, whereas posing little or no threat to the population in general (2).…”

Challenging and emerging pathogens in cystic fibrosis

“…There is a general consensus that isolates identified through commercial test systems as belonging to the B. cepacia complex, Step 2: repeat step 1 for 5 days 105 . In a study on 119 multi-drug resistant B. cepacia isolates, multi combination bactericidal testing (mcbt) showed that triple antibiotic combinations containing tobramycin, meropenem and a third additional antibiotic were most effective 106 . These combinations were bactericidal against 81-93% of isolates.…”

An Effect of Biofield Treatment on Multidrug-resistant Burkholderia cepacia: A Multihost Pathogen

“…However, some pathogenic strains of B. cepacia are resistant to above drugs combination and are difficult to treat. So, other treatment modalities must be adopted like multiple combination bactericidal therapy to assess whether greater effect can be achieved when more than two drugs are given together [7]. Recently, an alternate system called biofield treatment is reported to alter the susceptibility of microorganism towards existing medicines [8].…”