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. 2012 Sep 8:12:196.
doi: 10.1186/1471-2180-12-196.

Macrolides decrease the minimal inhibitory concentration of anti-pseudomonal agents against Pseudomonas aeruginosa from cystic fibrosis patients in biofilm

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Macrolides decrease the minimal inhibitory concentration of anti-pseudomonal agents against Pseudomonas aeruginosa from cystic fibrosis patients in biofilm

Larissa Lutz et al. BMC Microbiol. .

Abstract

Background: Biofilm production is an important mechanism for bacterial survival and its association with antimicrobial resistance represents a challenge for the patient treatment. In this study we evaluated the in vitro action of macrolides in combination with anti-pseudomonal agents on biofilm-grown Pseudomonas aeruginosa recovered from cystic fibrosis (CF) patients.

Results: A total of 64 isolates were analysed. The biofilm inhibitory concentration (BIC) results were consistently higher than those obtained by the conventional method, minimal inhibitory concentration, (MIC) for most anti-pseudomonal agents tested (ceftazidime: P = 0.001, tobramycin: P = 0.001, imipenem: P < 0.001, meropenem: P = 0.005). When macrolides were associated with the anti-pseudomonal agents, the BIC values were reduced significantly for ceftazidime (P < 0.001) and tobramycin (P < 0.001), regardless the concentration of macrolides. Strong inhibitory quotient was observed when azithromycin at 8 mg/L was associated with all anti-pseudomonal agents tested in biofilm conditions.

Conclusions: P. aeruginosa from CF patients within biofilms are highly resistant to antibiotics but macrolides proved to augment the in vitro activity of anti-pseudomonal agents.

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Figures

Figure 1
Figure 1
Azithromycin and clarithromycin action on biofilm inhibitory concentration (BIC) of non-susceptible P. aeruginosa isolates combined with anti-pseudomonal agents. Detailed legend: CAZ - ceftazidime, CIP - ciprofloxacin, TOB - tobramycin, IPM - imipenem, MEM - meropenem, CLR - clarithromycin, AZM – azithromycin. Results are expressed as median of BIC. Solid lines represent association with AZM; dashed lines represent association with CLR.
Figure 2
Figure 2
Inhibitory Quotient (IQ) of combinations of macrolide antibiotics to anti-pseudomonal agents against P. aeruginosa isolates. Detailed legend: CAZ 2AZM – ceftazidime with 2 mg/L of azithromycin, CAZ 8AZM - ceftazidime with 8 mg/L of azithromycin, CAZ 2CLR - ceftazidime with 2 mg/L of clarithromycin, CAZ 8CLR - ceftazidime with 8 mg/L of clarithromycin, CIP 2AZM – ciprofloxacin with 2 mg/L of azithromycin, CIP 8AZM - ciprofloxacin with 8 mg/L of azithromycin, CIP 2CLR - ciprofloxacin with 2 mg/L of clarithromycin, CIP 8CLR - ciprofloxacin with 8 mg/L of clarithromycin, TOB 2AZM – tobramycin with 2 mg/L of azithromycin, TOB 8AZM - tobramycin with 8 mg/L of azithromycin, TOB 2CLR - tobramycin with 2 mg/L of clarithromycin, TOB 8CLR - with 8 mg/L of clarithromycin, IPM 2AZM – imipenem with 2 mg/L of azithromycin, IPM 8AZM - imipenem with 8 mg/L of azithromycin, IPM 2CLR - imipenem with 2 mg/L of clarithromycin, IPM 8CLR - imipenem with 8 mg/L of clarithromycin, MEM 2AZM – meropenem with 2 mg/L of azithromycin, MEM 8AZM – meropenem with 8 mg/L of azithromycin, MEM 2CLR – meropenem with 2 mg/L of clarithromycin, MEM 8CLR – meropenem with 8 mg/L of clarithromycin. STRONG IQ (Black bar) means that there was a reduction in biofilm inhibitory concentration (BIC) when macrolides combination was tested and the isolates changed its profile from “Resistant” to “Susceptible”; WEAK IQ (Grey bar) means that there was a reduction in BIC value when the isolate profile changed from “Resistant” to “Intermediate”.

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