High Concentrations Of Ciprofloxacin Research Articles

The lack of long-term suppressive effect of ciprofloxacin on murine bone marrow.

In order to investigate the long-term effect of therapy with ciprofloxacin on haemopoietic cells, we administered ciprofloxacin orally in a daily dosage of 150 mg/kg/day in three divided doses for 11 days to syngeneic mice. A control group of mice was treated with saline. On the second, sixth, tenth and sixteenth day of ciprofloxacin therapy complete blood counts (cbc) and determination of haemopoietic progenitor cells (cfu-gm) from the tibial and femoral bone marrow were performed and followed by the transplantation of the bone marrow into lethally irradiated syngeneic mice. Bone marrow engraftment was evaluated ten days following transplantation by counting the visible colonies formed on the spleen surface (cfu-s) and by measuring the incorporation of 125I by the spleen and by the femurs of the transplanted mice. The results revealed that there was no statistical significance between the control and the ciprofloxacin treated mice in cbc, cfu-gm and cfu-s parameters. It is concluded that the suppressive effect of ciprofloxacin on haemopoietic cells appears only with very high concentrations of ciprofloxacin and is short-term and reversible.

Mechanism of ciprofloxacin resistance in Pseudomonas aeruginosa.

We studied the mechanism(s) of resistance to ciprofloxacin arising in a clinical strain of Pseudomonas aeruginosa and in a laboratory-derived isolate of that strain. Higher concentrations of ciprofloxacin were required to interfere with DNA synthesis in resistant isolates compared with the parent strain, a finding indicating a relative insensitivity of DNA gyrase to ciprofloxacin. Reduced uptake of ciprofloxacin was seen in one isolate and may have contributed to its ciprofloxacin resistance but was not associated with alterations in outer or cytoplasmic membrane proteins, a result suggesting that such changes are not required to decrease uptake of fluoroquinolones into cells. No evidence for plasmid-mediated resistance was found, and no ciprofloxacin-inactivating activity was detected in sonic extracts of resistant organisms. In these isolates, resistance to ciprofloxacin was likely the result of more than one mutation, because single-step mutations conferring such high-level resistance were not found in the parent strain.

Population analyses of the susceptibility to ciprofloxacin of eight clinical strains of Pseudomonas aeruginosa.

Population analyses of the susceptibility to ciprofloxacin of eight strains of Pseudomonas aeruginosa, including mucoid strains and strains resistant to aminoglycosides or anti-Pseudomonas beta-lactams, were carried out. All strains were sensitive as judged by the broth-dilution technique, but four strains were found to yield resistant mutants with a frequency of less than 10(-6). Two strains yielded mutants homogeneously sensitive to ciprofloxacin at a level 8-16 times the MIC of the parent strains. Two other strains yielded mutants resistant to different higher concentrations of ciprofloxacin. One of these mutants was examined for production of ciprofloxacin-inactivating enzyme; no enzyme production could be detected. Cross-resistance was found with another quinolone antibiotic, ofloxacin, but not with aminoglycosides or beta-lactam antibiotics.