Activity of quinupristin/dalfopristin against Staphylococcus epidermidis in biofilms: a comparison with ciprofloxacin (original) (raw)
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Interaction between biofilms formed by Staphylococcus epidermidis and quinolones
Diagnostic Microbiology and Infectious Disease, 2001
The interaction between pefloxacin, ciprofloxacin, norfloxacin, and ofloxacin and biofilms formed by Staphylococcus epidermidis (20 clinical isolates) was studied. In the presence of 1/2-MIC and 1/8-MIC of quinolones, the optical density of the biofilms was reduced to 22-24% and 65-74% of the controls, respectively. Treatment of preformed biofilms with quinolones in concentrations ranging from 12.5 g/ml to 400 g/mL caused reduction in the optical density of the adherent biofilms to 45-77% of the control. In an in vitro model of vascular catheter colonization, subinhibitory concentrations ( 1 ⁄2, 1 ⁄4 and 1/8 MIC) of fluoroquinolones reduced the number of adherent bacteria to 24 -28%, 48 -55% and 58 -76% of the controls, respectively. The vascular catheter segments precolonized with Staphylococcus epidermidis for 24 h and exposed to the fluoroquinolones in 8 -16 times MIC (100 g/mL) for 2 h showed no growth of adherent cells. The activity of pefloxacin in reducing the bacterial adhesion and eradicating the preformed biofilms was demonstrated by scanning electron microscope. These data show that subinhibitory concentrations of ciprofloxacin, norfloxacin, pefloxacin, and ofloxacin inhibit the adhesion of Staphylococcus epidermidis to plastic surfaces and vascular catheters. Higher concentrations of fluoroquinolones were able to eradicate the preformed biofilms on vascular catheters.
In vitro Activity of Daptomycin, Linezolid and Rifampicin on Staphylococcus epidermidis Biofilms
Current Microbiology, 2011
Owing to their massive use, Staphylococcus epidermidis has recently developed significant resistance to several antibiotics, and became one of the leading causes of hospital-acquired infections. Current antibiotics are typically ineffective in the eradication of bacteria in biofilmassociated persistent infections. Accordingly, the paucity of effective treatment against cells in this mode of growth is a key factor that potentiates the need for new agents active in the prevention or eradication of biofilms. Daptomycin and linezolid belong to the novel antibiotic therapies that are active against gram-positive cocci. On the other hand, rifampicin has been shown to be one of the most potent, prevalent antibiotics against S. epidermidis biofilms. Therefore, the main aim of this study was to study the susceptibility of S. epidermidis biofilm cells to the two newer antimicrobial agents previously mentioned, and compare the results obtained with the antimicrobial effect of rifampicin, widely used in the prevention/treatment of indwelling medical device infections. To this end the in vitro activities of daptomycin, linezolid, and rifampicin on S. epidermidis biofilms were accessed, using these antibiotics at MIC and peak serum concentrations. The results demonstrated that at MIC concentration, rifampicin was the most effective antibiotic tested. At peak serum concentration, both strains demonstrated similar susceptibility to rifampicin and daptomycin, with colony-forming units (CFUs) reductions of approximately 3-4 log 10 , with a slightly lower response to linezolid, which was also more strain dependent. However, considering all the parameters studied, daptomycin was considered the most effective antibiotic tested, demonstrating an excellent in vitro activity against S. epidermidis biofilm cells. In conclusion, this antibiotic can be strongly considered as an acceptable therapeutic option for S. epidermidis biofilm-associated infections and can represent a potential alternative to rifampicin in serious infections where rifampicin resistance becomes prevalent.
The aim of the present study is to determine the activities of three kinds of antibiotics against Staphylococcal biofilm and planktonic cultures in vitro, and to indicate the enhancement of biofilm formation in response to stress factors such as glucose and sub-inhibitory concentrations of antibiotics by using scanning electron microscope. Biofilm forming staphylococci were identified by using the modified microtiter plate method. And the effect of different concentrations of several antibiotics (including ciprofloxacin, gentamycin and amoxicillin-clavulanic acid) on eight isolates was determined. The result showed that out of 86 Staphylococcal isolates, eight strains were found to be strong biofilm forming. Sub-MIC of the antimicrobial agents used increased the biofilm formation in some isolates. However, the preformed biofilm was very difficult to remove with most isolates even with multiples of the MIC. The biofilm MBC reached 46 times the planktonic MBC in some isolates. Scanning electron micrographs of staphylococcus aureus isolate (45S) were made in order to confirm the enhanced biofilm formation in the presence of glucose and sub-MIC of ciprofloxacin and it was found that the slime layer production increases in the presence of glucose and low concentration of ciprofloxacin.
Synergy of different antibiotic combinations in biofilms of Staphylococcus epidermidis
Journal of Antimicrobial Chemotherapy, 2001
The in vitro effect of nine antibiotic combinations was investigated in Staphylococcus epidermidis biofilms using ATP-bioluminescence for viable bacterial cell quantification. Four slime-producing (SP) strains were used to form biofilms 6, 24 and 48 h old. These biofilms were exposed for 24 h to antibiotics at 4 ؋, 2 ؋, 1 ؋ and 0.5 ؋ MIC. Combinations involving tetracycline together with another antibiotic were the most efficient at the biofilm age and concentration range under study. The combination vancomycin-rifampicin produced the highest bactericidal effect on 6 h biofilms at 4 ؋ MIC, but this effect decreased dramatically in older biofilms. To detect possible antibiotic synergy in combinations that had a significant killing effect, antibiotics were studied not only in combination but also individually. Synergic effects were observed in all the combinations tested. Differences between the effect in combination and the sum of individual antibiotic effects (degree of synergy) were significant (mostly P < 0.001) and exceeded 1 log 10 cfu/mL in the majority of cases. In 48 h biofilms, antibiotics caused a significant bactericidal effect when applied in combination, but never when used individually. These results indicate that the biofilm test applied allows the detection of synergy between antibiotics and suggests that this assay could be useful in clinical and extensive synergy studies on S. epidermidis biofilms.
American Journal of Medicine, 1998
This report summarizes the activities of quinupristin/ dalfopristin (Q/D) and appropriate comparator antibiotics, including ciprofloxacin, erythromycin, gentamicin, rifampin, teicoplanin, and vancomycin, against selected gram-positive pathogens, including Enterococcus faecium, Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, Streptococcus agalactiae, and Streptococcus pyogenes. The study pathogens were obtained from 2 sources: (1) clinical isolates taken from patients participating in Q/D worldwide Phase III comparative and noncomparative (emergency-use program) clinical trials; and (2) other isolates collected from the laboratories of 45 geographically distinct medical centers around the world. Q/D was highly active, with minimum inhibitory concentrations (MICs) ≤1.0 g/mL against most isolates, including those known to be resistant to methicillin, vancomycin, or erythromycin. Q/D was active (MICs ≤1 g/mL) against 95% of the vancomycin-resistant E. faecium strains, for example, whereas ciprofloxacin was active against 6%. Q/D was equally active against methicillin-susceptible or -resistant S. aureus strains (MIC 90 ؍ 1 g/mL), as was vancomycin (MIC 90 ؍ 2 g/mL), whereas ciprofloxacin was much less active against methicillin-resistant strains than against methicillin-susceptible strains (MIC 90 ؍ 32 vs 1 g/mL). Given its spectrum of activity, Q/D may provide a viable option for the treatment of severe respiratory and skin and skin-structure infections caused by gram-positive bacteria, especially when strains with known or suspected resistance to other commonly used antibiotics are present. Am J Med. 1998;104(5A): 34S-42S.
Journal of Orthopaedic Research, 2009
Infection of medical implanted material is associated with considerable morbidity and costs. In the following work, we investigated the effects of vancomycin, daptomycin, fosfomycin, tigecycline, and ceftriaxone on biofilms formed by Staphylococcus epidermidis isolates causative for implant infection and catheter-associated bacteremia. Biofilms were studied using the static microtiter plate model and incubated with the antibiotics increasing the concentration from 1Â to 128Â the minimal inhibitory concentration (MIC) of the respective isolate tested. To quantify the reduction of the biomass, the optical density ratio (ODr) of stained biofilms and the number of growing bacteria were determined. Incubation of the staphylococcal biofilms with the antibiotics decreased the biofilm ODr (at baseline ¼ 1) for ceftriaxone (0.83 AE 0.48) but minimally only for fosfomycin (0.96 AE 0.64), daptomycin (1.05 AE 0.59), tigecycline (1.18 AE 0.66), and vancomycin (0.98 AE 0.44) at exceedingly high concentrations of 128 Â MIC. The significant reduction of the bacterial growth was not achieved for all antibiotics, not even at the highest concentrations tested. Using higher doses of the antibiotics may be of some value in the treatment of biofilm-associated infections, although effects are seen only at clinically unachievable doses. However, to eradicate the staphylococcal biofilm, additional measures like debridement and/or removal of the implant are needed. ß
Infection and Drug Resistance
Background: Community-acquired urinary tract infections are associated with significant morbidity, and uropathogenic Escherichia coli (UPEC) alone causes 90% of urinary tract infections. This bacterium retains a diverse armament of virulence factors including fimbria, hemolysins, and siderophores production. In a post invasion scenario, formation of intracellular communities mimic biofilm-like characteristics and are linked to recurrent urinary tract infections. We investigated the effects of different frontline antibiotics on the formation, inhibition, and eradication of biofilms of virulent UPEC strains. Materials and Methods: A total of 155 UPEC strains were scrutinized for various virulence factors including gelatinase, cell surface hydrophobicity, hemagglutination, and serum bactericidal activity. Biofilm formation was confirmed by three different methods: Congo red agar, test tube, and tissue culture plate method. Biofilm inhibition and eradication assays were performed according to the standard protocols. Topographical analysis of biofilms was done by scanning electronic microscopy (SEM). Results: Out of 155 strains, 113 (73%) were strong biofilm formesr, while 37 (24%) produced biofilms at moderate level. Significant differences were observed between MICs of planktonic cells (MIC-p) and MICs of UPEC biofilms (MIC-b). Among tested frontline antibiotics, levofloxacin successfully inhibited biofilms at a concentration of 32 µg/mL, while trimethoprim eradicated biofilms at higher concentrations (512-1024 µg/mL). Ciprofloxacin treatment at sub-MIC level significantly enhanced biofilm formation (P<0.05). Conclusion: The majority of UPEC strains are strong biofilm formers and show higher tolerance towards frontline antibiotics in biofilm form. We observed significant inhibitory effects of levofloxacin (32 µg/mL) on UPEC biofilms, while treatment with sub-minimal concentrations of ciprofloxacin significantly enhanced biofilm formation. Out of all tested antibiotics, trimethoprim (512-1024 µg/mL) eradicated UPEC biofilms.
International Journal of Antimicrobial Agents, 2009
Both bacteria and the matrix are essential for the development of biofilms. Antimicrobials should therefore be tested against both components. The aim of this study was to determine the structure-activity relationships of different antibiotics against biofilm-forming Staphylococcus aureus and Pseudomonas aeruginosa strains using in vitro biofilm discriminatory assays. Only four of twelve antibiotics showed efficacy against S. aureus biofilms. Rifampicin had a 50% inhibitory activity both against the matrix and bacteria at 16× the minimum bactericidal concentration (MBC). Polymyxin B killed nearly all bacteria at 8× MBC, but left the matrix undisturbed. Both P. aeruginosa biofilms responded differently to antibiotic treatment. Rifampicin showed the greatest activity, with 100% killing of microorganisms combined with 91% destruction of the matrix at the MBC. In conclusion, rifampicin showed the highest activity on biofilm matrix and bacteria in S. aureus and P. aeruginosa biofilms. Our results also indicated that biofilm viable mass was more susceptible to treatment than the biofilm matrix, which is mainly responsible for biofilm persistence. Future research should specifically focus on compounds destroying the matrix that can be used as an adjunct to antibiotic therapy.
In vitro additive effects of dalbavancin and rifampicin against biofilm of Staphylococcus aureus
Scientific Reports, 2021
Dalbavancin is a novel glycopeptide antibiotic approved for the treatment of acute bacterial skin and skin structure infections (ABSSSIs). It is characterized by a potent activity against numerous Gram-positive pathogens, a long elimination half-life and a favorable safety profile. Most recently, its application for the treatment of periprosthetic joint infections (PJIs) was introduced. The aim of this study was to proof our hypothesis, that dalbavancin shows superior efficacy against staphylococcal biofilms on polyethylene (PE) disk devices compared with vancomycin and additive behavior in combination with rifampicin. Staphylococcus aureus biofilms were formed on PE disk devices for 96 h and subsequently treated with dalbavancin, vancomycin, rifampicin and dalbavancin-rifampicin combination at different concentrations. Quantification of antibacterial activity was determined by counting colony forming units (CFU/ml) after sonification of the PE, serial dilution of the bacterial suspension and plating on agar-plates. Biofilms were additionally life/dead-stained and visualized using fluorescence microscopy. Dalbavancin presented superior anti-biofilm activity compared to vancomycin. Additive effects of the combination dalbavancin and rifampicin were registered. Dalbavancin combined with rifampicin presents promising anti-biofilm activity characteristics in vitro. Further in vivo studies are necessary to establish recommendations for the general use of dalbavancin in the treatment of PJIs. Periprosthetic joint infection (PJI) is a persistent problem in orthopedic surgery and treatment remains challenging. The most common pathogens in PJI are coagulase-negative staphylococci (CNS) and Staphylococcus aureus 1. Septic re-revision rates of up to 40.2% within two years after primary arthroplasty were described 2. Vancomycin is a well-known and established antibiotic used to combat CNS and methicillin-resistant S. aureus (MRSA) in PJI 3. While rifampicin is well known for its biofilm active characteristics 4 , vancomycin shows at least inconsistent activity against biofilm. On the one hand a time-dependend eradication of mature S. aureus biofilms could be demonstrated, on the other hand 15 mg/l vancomycin achieved bactericidal activity against only low-biofilm-procuding strains 5,6. Thus vancomycin susceptibility seems to be heavily strain dependend 7. Dalbavancin is a bactericidal lipoglycopeptide antibiotic FDA-approved in 2014 for the treatment of acute bacterial skin and skin-structure infections (ABSSSIs) 8. Compared to other glycopeptides (e.g. vancomycin), it exhibits a favourable overall safety profile and is characterized by a long elimination half-life, which makes it a suitable candidate for outpatient treatment 9. Based on these advantages, dalbavancin has been introduced recently as an option for treating PJI 10. Among the few in vivo studies in rodents that have so far investigated the activity of dalbavancin against biofilms, initial results appear to be promising 11,12. However, only few studies investigated the synergism and/or additive effects of dalbavancin and rifampicin to date. Therefore, we aimed to determine the efficacy of dalbavancin combined with rifampicin against S. aureus biofilms on polyethylene (PE) disks in comparison to both compounds alone and to vancomycin.