Abstract
Summary Statement
Combination of antibiotics with N-acetylcisteine and sub-MIC concentration of erythromycin was evaluated in two collection and 16 clinical strains of staphylococci isolated from PJI. The results were strain-dependent, so it evidences the necessity of perform individual studies of biofilm susceptibility.
Objectives
Staphylococci are the most common cause of prosthetic joint infections (PJI) (1), making the treatment of this disease difficult due to the increased resistance to antibiotics of biofilms. Combination between antibiotics and other compounds could be a good alternative. The aim of this study was to evaluate the effect of the combination of two compounds with nine antibiotics in biofilms formed by staphylococcal strains isolated from PJI.
Methods
16 clinical strains (8 S. aureus and 8 S. epidermidis) isolated from patients with PJI as well as 2 collection strains (S. aureus 15981 and S. epidermidis ATCC 35984) were tested against 9 antibiotics (rifampin, vancomycin, tigecycline, clindamycin, cotrimoxazole, ciprofloxacin, cloxacillin, daptomycin and fosfomycin) in combination with NAC 1024 μg/mL and erythromycin at subinhibitory concentration (0.12 μg/mL), which was established after the determination of MIC according to EUCAST recommendations. The Calgary Biofilm Device (CBD) was used to determine the susceptibility of the biofilms to these combinations. The Minimal Biofilm Eradication Concentration (MBEC) for the all the antibiotics alone was determined in a previous study. All the experiments were performed by triplicate.
Results
All the S. aureus strains showed homogeneous results, and the addition of NAC or erythromycin at the tested concentrations has not a clear effect in the antibiotic susceptibility of the biofilm, although combination of tigecycline with NAC seems even to increase the MBEC in most cases. Almost all clinical strains were MRSA. Regarding S. epidermidis strains, the results were strain-dependant. The combination with NAC seems to increase the MBEC for rifampin and tigecycline in some strains. However, there was a slight MBEC decrease with cotrimoxazole, ciprofloxacin, cloxacillin, daptomycin and fosfomycin. Erythromycin combinations resulted to be successful only in a few cases, and there is no an apparent relationship between erythromycin resistance and combination results. It is especially remarkable that one strain (P-23.2) showed a slight decrease of the MBEC combining both substances with most of the antibiotics tested.
Conclusion
None of the combinations tested was clearly effective against biofilms for all strains of both species. This heterogeneity showed the necessity of making an individual study of each strain. The search of new strategies to fight against PJI is mandatory and further investigation is needed.
