Combination antibiotics against Pseudomonas aeruginosa, representing common and rare cystic fibrosis strains from different Irish clinics

Abstract

ObjectivesTo evaluate the effect of antibiotic combination therapy versus single therapy against cystic fibrosis strains of Pseudomonas aeruginosa identified as common and rare among patient groups in different Irish hospitals.MethodsThis study compares the susceptibility profiles of P. aeruginosa isolates from different cystic fibrosis (CF) clinics in Ireland, collected from 2004–2005. Strains were recovered in small numbers and typed by pulsed-field gel electrophoresis. Five common clonal variants were identified in five different hospitals, described as ‘common strains’. A number of ‘rare strains’ associated with any single patient were also included in the study. Certain virulence factors were determined and in vitro assays such as minimum inhibitory concentrations (MIC) and biofilm inhibitory concentrations (BIC) were employed to assess potential synergistic effects of antipseudomonal antibiotic combination therapy.ResultsThere was no distinct virulence factors associated with clinical strains that were common in comparison to those that were rare. Antibiotic combination testing revealed the majority of combinations were similar to the activity of either antibiotic used as single agents. Tobramycin-ceftazidime was the most effective combination exhibiting synergistic interactions (FIC ≤ 0.5) against certain clinical isolates of P. aeruginosa.ConclusionThe efficacy of single antibiotics and synergistic interactions of antibiotic combinations were strain specific, irrespective of virulence characteristics of P. aeruginosa. Common clonal P. aeruginosa strains do not have distinct characteristics that possibly influence persistence in the chronic CF lung. Tobramycin-ceftazidime may be successful for controlling specific P. aeruginosa strains. Further studies on representative isolates are needed to support these results.

The Antibacterial and Anti-Biofilm Activity of Metal Complexes Incorporating 3,6,9-Trioxaundecanedioate and 1,10-Phenanthroline Ligands in Clinical Isolates of Pseudomonas aeruginosa from Irish Cystic Fibrosis Patients

“…At the highest concentration of the metal-tdda-phen complexes (64 µg/mL) in combination with gentamicin (32 µg/mL), there was >90% biofilm removal for CF2 and CF3 and >83% for CF1, and the fractional inhibitory concentration (FIC) index showed a positive synergism for all three metal-tdda-phen complexes in the presence of gentamicin. A recent clinical study in Ireland on cystic fibrosis P. aeruginosa clinical isolates with the same laboratory reference strains (ATCC 27853 and PAO1) showed that tobramycin (aminoglycoside) and ceftazidime (cephalosporin) was the only effective combination to show positive synergism (FIC ≤ 0.5) against a mature biofilm of a single clinical isolate at a concentration of 64 mg/L [ 41 ]. However, as mentioned earlier, the evolving resistance to antibiotics is problematic and of concern when considering combinations of established antibiotics for the treatment of P. aeruginosa infections in CF patients.…”

An in-vitro evaluation of C-di-GMP mediated biofilm dispersal as a potential strategy to restore antimicrobial efficacy

“…3-day grown biofilms used here, showed a significant increase in the concentrations of imipenem (of up to 1000-fold) required to eradicate efficiently (MBEC 2048 µg/mL), and 5 two-fold increase for tobramycin (MBEC 64 µg/mL). These observations are in agreement with literature (Hengzhuang, Wu et al 2011, Kapoor andMurphy 2018), that a 3-day P. aeruginosa biofilm model, can be considered "mature", usually exhibiting MBEC of 100 -1000 fold higher than MBC.…”

“…CV staining has been suggested in a number of recent publications to be used as a standard proxy for biofilm susceptibility assays (Haney, Trimble et al 2018, Kapoor and Murphy 2018). It is known that CV stains both live and dead bacterial populations, and all EPS components in varying degrees.…”

Antibacterial efficacy of different combinations of clove, eucalyptus, ginger, and selected antibiotics against clinical isolates of Pseudomonas aeruginosa

“…In the present study, the antibacterial activity of selected antibiotics was screened and ciprofloxacin was found most effective which was similar to the finding of Kapoor and Murphy. [ 23 ] The methanol extract of clove exhibited higher zone of inhibition against reference strain PA01, clinical isolate 2 and clinical isolate 4. Almost similar activity of clove was reported by Pandey and Singh, Mostafa et al .…”