Nano-ciprofloxacin/meropenem exhibit bactericidal activity against Gram-negative bacteria and rescue septic rat model.

Aim: We hypothesized that simultaneous administration of two antibiotics loaded into a nanopolymer matrix would augment their synergistic bactericidal interaction. Methods: Nanoplatforms of chitosan/Pluronic® loaded with ciprofloxacin/meropenem (CS/Plu-Cip/Mer) were prepared by the ionic gelation method, using Plu at concentrations in the range 0.5-4% w/v. CS/Plu-Cip/Mer was evaluated for antibacterial synergistic activity in vitro and in vivo. Results: CS/Plu-Cip and CS/Plu-Mer with Plu concentrations of 3% w/v and 2% w/v, respectively, exhibited ∼80% encapsulation efficiency. The MICs of pathogens were fourfold to 16-fold lower for CS/Plu-Cip/Mer than for Cip/Mer. Synergy was evidenced for CS/Plu-Cip/Mer with a bactericidal effect (at 1× MIC and sub-MICs), and it significantly decreased bacterial load and rescued infected rats. Conclusion: This study illustrates the ability of CS/Plu nanopolymer to intensify synergy between antibiotics, thereby providing a promising potential to rejuvenate antibiotics considered ineffective against resistant pathogens.

Antibiotics are used to treat bacterial infections. However, the more they are used, the less effective they become, because bacteria develop resistance to them. One strategy to overcome this is to treat bacterial infection with a combination of antibiotics that work well together. The antibiotics ciprofloxacin and meropenem are often given together to treat Pseudomonas aeruginosa, a bacterium which can cause sepsis, a type of blood poisoning. Another strategy to overcome antibiotic resistance is to load them into nanocarriers, which can change their properties. Nanocarrier-loaded antibiotics can reduce toxicity and increase effectiveness. This study investigated whether the effectiveness of this pair could be improved by loading them into nanoparticles. When these nanoparticles were given to rats with sepsis, they were significantly more effective than unloaded ciprofloxacin and meropenem combinations. These nanoparticles were also able to directly kill bacteria, rather than just prevent bacterial reproduction, as with the unloaded combination. This study demonstrates that nanocarrier loading can intensify the enhanced benefit of combined antibiotic treatments. This is a promising strategy to reuse antibiotics that have become ineffective at treating bacteria which have developed resistance.

The role of ITPA and ribavirin transporter genes polymorphisms in prediction of ribavirin-induced anaemia in chronic hepatitis C Egyptian patients.

Few data are available concerning the roles of polymorphisms of inosine triphosphatase (ITPA) gene and ribavirin (RBV) transporter genes in the prediction of RBV-induced anaemia among Egyptians with chronic hepatitis C (CHC). Genotyping of three ITPA gene variants and two variants of RBV transporter genes has been performed in 123 patients under pegylated interferon-α/ribavirin treatment. The baseline haemoglobin and ITPA rs1127354 CA/AA have been found as predictors of anaemia at 4, 8 and 12 weeks of RBV therapy. In addition, ITPA rs7270101 AC/CC and age predicted anaemia after 12 weeks of therapy. In conclusion, the ITPA variant rs1127354C>A significantly predict RBV-induced anaemia during the first 3 months of treatment and it is recommended to be assessed before RBV administration.