Randomized trial of biofilm testing to select antibiotics for cystic fibrosis airway infection

Abstract

SUMMARY Rationale In cystic fibrosis (CF), conventional antibiotic susceptibility results correlate poorly with clinical outcomes. We hypothesized that biofilm testing would more accurately reflect the susceptibilities of bacteria infecting CF airways. Methods A multi-center randomized pilot trial was conducted to assess the efficacy and safety of using biofilm susceptibility testing of Pseudomonas aeruginosa sputum isolates to guide antibiotic regimens for chronic airway infections in clinically stable adolescent and adult CF patients. Thirty-nine participants were randomized to biofilm or conventional treatment groups; 14-day courses of two antibiotics were selected according to an activity-based algorithm using the corresponding susceptibility results. Results Of the agents tested, meropenem was most active against biofilm-grown bacteria, and was included in regimens for about half of each study group. For nineteen of 39 randomized participants, randomization to the other study group would not have changed the antibiotic classes of the assigned regimen. Study groups were comparable at baseline, and had similar mean decreases in bacterial density, measured in log10 colony forming units per gram of sputum (biofilm, -2.94 [SD 2.83], versus conventional, -3.27 [SD 3.09]), and mean increases in forced expiratory volume in one second, measured in liters (0.18 [SD 0.20] versus 0.12 [SD 0.22]). Conclusions In this pilot study, antibiotic regimens based on biofilm testing did not differ significantly from regimens based on conventional testing in terms of microbiological and clinical responses. The predictive value of biofilm testing may nonetheless warrant evaluation in an adequately powered clinical trial in younger CF patients or those experiencing acute pulmonary exacerbation.

In vitro prevention of Pseudomonas aeruginosa early biofilm formation with antibiotics used in cystic fibrosis patients

“…In summary, the new BPC parameter might be useful to define the antibiotic concentration needed to prevent biofilm formation during the early stages of colonisation and potentially to establish correlations of in vitro measurements with therapeutic outcomes in which other concentration values have failed [15]. In contrast, BICs would be more useful in CF patients with chronic lung colonisation when biofilms are well established.…”

Biofilm Formation by Clinical Isolates and Its Relevance to Clinical Infections

“…Several clinical trials have included azithromycin for CF therapy with salutary effects on pulmonary function (reviewed in (Schultz 2004 )). Subsequently, the utility of biofi lm susceptibility testing to guide antimicrobial therapy for chronic pulmonary infections by P. aeruginosa was examined in a multicenter randomized pilot clinical trial (Moskowitz et al 2011 ). Twenty subjects were randomized to biofi lm-directed therapy on the basis of testing results, versus 19 whose treatments were guided by conventional planktonic susceptibility testing.…”

The clinical impact of bacterial biofilms

“…The minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of antibiotics to biofilm growing bacteria may be up to 100-1 000 fold higher than that of planktonic bacteria. Methods to test antibiotic susceptibility of biofilm growing bacteria have therefore been developed [3], but their clinical relevance with regard to prediction of successful clinical therapy has been disappointing [25]. The molecular mechanisms responsible for resistance are a mixture of conventional resistance mechanisms, which also protect planktonic growing bacteria and the specific properties of biofilms that increase the tolerance of the bacteria against antibiotics [3].…”