Evaluation of combinations of putative anti-biofilm agents and antibiotics to eradicate biofilms of Staphylococcus aureus and Pseudomonas aeruginosa

Abstract

32OBJECTIVES: To evaluate potential anti-biofilm agents for their ability to enhance the 33 activity of antibiotics for local treatment of localised biofilm infections. 34 METHODS: Staphylococcus aureus and Pseudomonas aeruginosa in vitro biofilm models 35were developed. The putative antibiotic enhancers N-acetylcysteine, acetylsalicylic acid, 36 sodium salicylate, rhDNase I, Dispersin B, hydrogen peroxide, and Baby Shampoo were 37 tested for their anti-biofilm activity alone and their ability to enhance the activity of antibiotics 38 for seven or 14 days, against five-day-old biofilms. The antibiotic enhancers were paired with 39 rifampicin and clindamycin against S. aureus and gentamicin and ciprofloxacin against P. 40 aeruginosa. Isolates from biofilms that were not eradicated were tested for antibiotic 41 resistance. 42 RESULTS: Antibiotic levels 10xMIC and 100xMIC significantly reduced biofilm but did not 43 consistently eradicate it. Antibiotics at 100xMIC with 10% Baby Shampoo for 14 days was 44 the only treatment to eradicate both staphylococcal and pseudomonal biofilms. RhDNase I 45 significantly reduced staphylococcal biofilm. Emergence of resistance of surviving isolates 46 was minimal and was often associated with Small Colony Variant phenotype. 47 CONCLUSIONS: Baby Shampoo enhanced the activity of antibiotics and several other 48 promising anti-biofilm agents were identified. Antibiotics with 10% Baby Shampoo eradicated 49 biofilms produced by both organisms. Such a combination might be useful in local treatment 50 of localised biofilm infections. 51 52 Introduction 53Biofilms are an important cause of persistent and chronic infections such as otitis 54 media with effusion (OME), 1,2 prosthetic joint infections, 3 colonisation of other indwelling 55 devices, 4 and infections after trauma, either following the injury itself or the surgical 56 treatment. 5 The biofilm mode of growth has many strategies for persistence and in this state, 57 only essential processes remain active, and therefore many target sites for antibiotics are 58 down-regulated leading to reduced susceptibility to antibiotics. 6,7 Biofilm eradication requires 59 10-1,000 times the MIC of antibiotics normally needed to inhibit the planktonic form. 8,9 Such 60 high levels of antibiotics would be difficult to achieve safely when administered 61 3 Methods 85The antibiotic enhancers were tested against two biofilm -forming bacteria, 86Staphylococcus aureus and Pseudomonas aeruginosa, grown as biofilms on silicone discs. 87The agents were paired with rifampicin and clindamycin against S. aureus, and gentamicin 88 and ciprofloxacin against P. aeruginosa. These antibiotics were chosen based on the 89 isolates' susceptibilities, routine clinical use, and their known anti-biofilm activity. 29,30 91 Biofilm Model 92The two strains of S. aureus and P. aeruginosa strains were isolated from 93 clinical biofilm infections (from the middle ear effusion of patients undergoing surgery for 94 treatment of OME). Biofilms were grown on auto...

Francisella novicida and F. philomiragia biofilm features conditionning fitness in spring water and in presence of antibiotics

“…In this context, the precise role of eDNA, a common feature of Francisella EPS, in biofilm formation and stability should be thoroughly addressed. However, our data already indicate that treatment of these biofilms with DNase I and EDTA, two compounds already approved for human use [62,63] may enhance the ability of antibiotics to clear infections, especially when ciprofloxacin is used. Finally, this study suggests that the functional role of biofilms could be intrinsically linked to their EPS composition with a proteinase K resistant and carbohydrate-rich matrix [54] hence more prone to promote the survival of Francisella spp.…”

Activity of Antibiotics against Pseudomonas aeruginosa in an In Vitro Model of Biofilms in the Context of Cystic Fibrosis: Influence of the Culture Medium

“…While the selection of SCVs by aminoglycosides was described a long time ago in different species, including S. aureus (28), P. aeruginosa (29), or Enterobacteriaceae (30), less is known about those selected by fluoroquinolones. They were described in Salmonella enterica as a transient response to stress (31), but also in P. aeruginosa biofilms grown in TSB (32) or in ASM(Ϫ) (33). No specific auxotrophism could be determined for these SCVs (33).…”

The Concept of an Ideal Antibiotic: Implications for Drug Design

“…The production of biofilms in cystic fibrosis patients is an additional concern, because antibiotics cannot successfully penetrate to affect the planktonic phase of growth in these cells, contributing to the morbidity and mortality of the disease [87]. Some antibiotics (such as rifampin) can penetrate and break up this extracellular polymeric matrix produced by bacteria, which is why they are usually used in combination with other drugs to enhance their efficacy [85,88,89].…”