METHODS: The antibacterial activity of four NSAIDs (aspirin, ibuprofen, diclofenac and mefenamic acid) were tested against ten pathogenic bacterial strains using the microdilution broth method. The interaction between NSAIDs and antibiotics (cefuroxime/chloramphenicol) was estimated by calculating the fractional inhibitory concentration (FICI) of the combination.
RESULTS: Aspirin, ibuprofen and diclofenac exhibited antibacterial activity against the selected pathogenic bacteria. The interaction between ibuprofen/aspirin with cefuroxime was demonstrated to be synergistic against methicillin-sensitive S. aureus (MSSA) and the MRSA reference strain, whereas for MRSA clinical strains additive effects were observed for both NSAIDs and cefuroxime combinations. The combination of chloramphenicol with ibuprofen/aspirin was synergistic against all of the tested MRSA strains and displayed an additive effect against MSSA. A 4-8192-fold reduction in the cefuroxime minimum inhibitory concentration (MIC) and a 4-64-fold reduction of the chloramphenicol MIC were documented.
CONCLUSIONS: Overall, the NSAIDs ibuprofen and aspirin showed antibacterial activity against strains of S. aureus. Although individually less potent than common antibiotics, these NSAIDs are synergistic in action with cefuroxime and chloramphenicol and could potentially be used as adjuvants in combating multidrug-resistant MRSA.
METHOD: We created an iontophoresis cell; 3% CF was inserted within medullary segment of goat bone and sealed from external saline solution. The cell operated at the following voltages 30, 60 and 90 V and at the following durations 5, 10, 15, 20, 25 and 30 min. Information regarding optimal conditions for its application was then obtained. After which, correlation between voltages and time with CF concentration in the bone was analysed. A bioavailability test was also conducted to observe the optimal rate of CF elution from the graft.
RESULT: The optimal condition for the impregnation process is 3% CF at 90 V for 10 min. Bone graft impregnated with CF at optimal conditions can elute above minimum inhibitory concentration of the CF against MRSA for 21 days.
CONCLUSION: CF iontophoresis was found feasible for allograft impregnation. The technique is simple, inexpensive and reproducible clinically. Iontophoresis offers a novel solution to reduce the rate of perioperative infection in reconstructive surgery involving use of bone graft.
METHODS: PMMA pellets were prepared with three separate concentrations of each of the two antibiotics tested. They were tested to determine the effect of increasing concentration of antibiotics on the biomechanical properties of PMMA and antibiotic activity by measuring the zone of inhibition and broth elution assay.
RESULTS: Ceftaroline PMMA at 3 wt%, three-point bending was 37.17 ± 0.51 N ( p < 0.001) and axial loading was 41.95 N ± 0.51 ( p < 0.001). At 5-wt% vancomycin-PMMA, three-point bending was 41.65 ± 0.79 N ( p = 0.02) and axial loading was 49.49 ± 2.21 N ( p = 0.01). Stiffness of ceftroline-loaded PMMA in low and medium concentration was significantly higher than the vancomycin. The zone of inhibition for ceftaroline was higher than vancomycin. Ceftaroline at 3 wt% eluted up to 6 weeks (0.3 ± 0.1 μg/ml) above the minimum inhibitory concentration (MIC) and vancomycin at 2.5 wt% eluted up to 3 weeks, same as MIC, that is, 0.5 ± 0.0 μg/ml.
CONCLUSIONS: Ceftaroline, loaded at similar concentrations as vancomycin into PMMA, is a more potent alternative based on its more favourable bioactivity and elution properties, while having a lesser effect on the mechanical properties of the cement. The use of 3-wt% ceftaroline as antibiotic laden PMMA against MRSA is recommended. It should be noted that this was an in vitro study and to determine the clinical efficacy would need prospective, controlled and randomized studies.
METHODS: A total of 28 critically ill patients were included in this study. All data were collected from medical, microbiology and pharmacokinetic records. The clinical response was evaluated on the basis of clinical and microbiological parameters. The 24-h area under the curve (AUC0-24) was estimated from a single trough level using established equations.
RESULTS: Out of the 28 patients, 46% were classified as responders to vancomycin treatment. The trough vancomycin concentration did not differ between the responders and non-responders (15.02 ± 6.16 and 14.83 ± 4.80 μg mL-1; P = 0.929). High vancomycin minimum inhibitory concentration (MIC) was observed among the non-responders (P = 0.007). The ratio between vancomycin trough concentration and vancomycin MIC was significantly lower in the non-responder group (8.76 ± 3.43 vs. 12.29 ± 4.85 μg mL-1; P = 0.034). The mean ratio of estimated AUC0-24 and vancomycin MIC was 313.78 ± 117.17 μg h mL-1 in the non-responder group and 464.44 ± 139.06 μg h mL-1 in the responder group (P = 0.004). AUC0-24/MIC of ≥ 400 μg h mL-1 was documented for 77% of the responders and 27% of the non-responders (c2 = 7.03; P = 0.008).
CONCLUSIONS: Ratio of trough concentration/MIC and AUC0-24/MIC of vancomycin are better predictors for MRSA treatment outcomes than trough vancomycin concentration or AUC0-24 alone. The single trough-based estimated AUC may be sufficient for the monitoring of treatment response with vancomycin.
Results: We tested the isolated bacteria using a selection of antibiotics. The results showed that both the number of antibiotic resistant strains and resistance level were higher in humans than NHPs. Overall, the composition of gut microbiome and pattern of antibiotic resistance showed that there was higher similarity between MF and TC, the two NHPs, than with HS. In addition, samples with higher levels of antibiotic resistance showed lower bacterial richness. Homo sapiens had the lowest bacterial diversity and yet it had higher abundance of Bacteroides. In contrast, NHPs displayed higher bacterial richness and greater prevalence of Firmicutes such as Ruminococceae and Oscillospira.
Conclusion: Higher antibiotic susceptibility in NHPs is likely related to low direct exposure to antibiotics. The lack of resistance may also suggest limited antimicrobial resistance transmission between humans and NHP. Nonetheless, continued monitoring over a long period will help mitigate the risk of anthropozoonosis and zooanthroponosis.
HYPOTHESIS/OBJECTIVES: To determine the in vitro interaction of ionophores (narasin or monensin) with antimicrobial adjuvants (N-acetylcysteine (NAC), Tris-EDTA or disodium EDTA) against bacterial strains representing pathogens associated with canine otitis externa (OE).
ANIMAL/ISOLATES: American Type Culture Collection (ATCC) strains Staphylococcus aureus 29213, Pseudomonas aeruginosa 27853 and P. aeruginosa biofilm producer PAO1, and a clinical isolate of Proteus mirabilis from a case of canine OE were tested.
METHODS AND MATERIALS: A 2D microdilution checkerboard method was used, allowing calculation of fractional inhibitory concentration index (FICI), dose reduction index (DRI) and plotting of isobolograms.
RESULTS: The combination of narasin with either Tris-EDTA or disodium EDTA produced additive effects (FICI = 0.75) against P. aeruginosa ATCC 27853 and P. aeruginosa biofilm producer ATCC PAO1. An additive effect (FICI = 0.53-0.75) was found against S. aureus ATCC 29213 when narasin or monensin were combined with NAC. The highest DRI (32-fold) was found with monensin/NAC where the MIC of monensin was reduced from 4 to 0.125 μg/mL.
CONCLUSIONS AND CLINICAL IMPORTANCE: The combination of narasin with Tris-EDTA or disodium EDTA is a promising strategy to inhibit the intrinsic resistance elements of Gram-negative bacteria. These novel combinations potentially could be useful as a multimodal approach to treat mixed infections in canine OE.