Methods: The nanoemulsions were formulated using a high-pressure homogenization technique and were characterized for their physicochemical properties.
Results: The characterizations revealed a particle size of 100.32±0.75 nm, polydispersity index of 0.18±0.01, zeta potential of -46.9±1.39 mV, viscosity of 1.24±0.34 cps, and osmolality of 285.33±0.58 mOsm/kg, indicating that the nanoemulsion has compatibility for parenteral application. CLN was physicochemically stable within 6 months of storage at 4°C, and the transmission electron microscopy revealed that the CLN droplets were almost spherical in shape. The in vitro release of CLN profile followed a sustained release pattern. The pharmacokinetic profile of CLN showed a significantly higher Cmax, area under the curve (AUC)0-
t
, prolonged half-life, and lower total plasma clearance, indicating that the systemic concentration of cefuroxime was higher in CLN-treated rats as compared to cefuroxime-free treated rats. A similar profile was obtained for the biodistribution of cefuroxime in the brain, in which CLN showed a significantly higher Cmax, AUC0-
t
, prolonged half-life, and lower clearance as compared to free cefuroxime solution.
Conclusion: Overall, CLN showed excellent physicochemical properties, fulfilled the requirements for parenteral administration, and presented improved in vivo pharmacokinetic profile, which reflected its practical approach to enhance cefuroxime delivery to the brain.
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.
Methods: This research investigated the blaKPC, and MBL genes, namely, blaIMP, blaVIM, and blaNDM-1 and their phenotypic resistance to K. pneumoniae isolated from urinary tract infections (UTI) in Bangladesh. Isolated UTI K. pneumoniae were identified by API-20E and 16s rDNA gene analysis. Their phenotypic antimicrobial resistance was examined by the Kirby-Bauer disc diffusion method, followed by minimal inhibitory concentration (MIC) determination. blaKPC, blaIMP, blaNDM-1, and blaVIM genes were evaluated by polymerase chain reactions (PCR) and confirmed by sequencing.
Results: Fifty-eight K. pneumoniae were identified from 142 acute UTI cases. Their phenotypic resistance to amoxycillin-clavulanic acid, cephalexin, cefuroxime, ceftriaxone, and imipenem were 98.3%, 100%, 96.5%, 91.4%, 75.1%, respectively. Over half (31/58) of the isolates contained either blaKPC or one of the MBL genes. Individual prevalence of blaKPC, blaIMP, blaNDM-1, and blaVIM were 15.5% (9), 10.3% (6), 22.4% (13), and 19% (11), respectively. Of these, eight isolates (25.8%, 8/31) were found to have two genes in four different combinations. The co-existence of the ESBL genes generated more resistance than each one individually. Some isolates appeared phenotypically susceptible to imipenem in the presence of blaKPC, blaIMP, blaVIM, and blaNDM-1 genes, singly or in combination.
Conclusion: The discrepancy of genotype and phenotype resistance has significant consequences for clinical bacteriology, precision in diagnosis, the prudent selection of antimicrobials, and rational prescribing. Heterogeneous phenotypes of antimicrobial susceptibility testing should be taken seriously to avoid inappropriate diagnostic and therapeutic decisions.