According to the guidelines of the Clinical and Laboratory Standards Institute (CLSI), E. coli and Pseudomoras are to be deemed susceptible if the MIC is less than or equal to 1 ^g/mL. Susceptibility is defined as follows: “the isolates are inhibited by the usually achievable concentrations of antimi­crobial agent when the recommended dosage is used for the site of infection.” According to Mandell and others, ciprofloxacin 500 mg administered orally achieves a Cmax of 2.4 ^g/mL, which is approximately twice the MIC breakpoint provided by the CLSI. De Marie and others found a Cmax of 3.2 ^g/mL with ciprofloxacin 750 mg BID administered enterally, which would imply that this dose and route would achieve adequate bactericidal activity against E. coli and Pseudomonas.

However, fluoroquinolones exhibit concentration- dependent killing; therefore, the higher the concentration, the greater the rate and extent of bactericidal activity. With parenteral administration, these drugs achieve a Cmax of 6.8 ^g/mL and may exhibit greater bactericidal activity. Since data for organism-specific MIC were not reported by De Marie and others, we do not know if a Cmax of 3.2 or 6.8 ^g/mL would achieve a Cmax/MIC ratio of 10 or more for a particular organism that could be correlated with clinical outcomes. Despite this limitation, parenteral and enteral administration achieved similar AUC values. Again, without organism-specific MICs, the AUC/MIC ratio (another predictor of clinical outcomes) cannot be calculated for the patients in that trial. Therefore, it is unknown whether patients receiving ciprofloxacin 750 mg BID enterally or ciprofloxacin 400 mg BID intravenously will have similar clinical outcomes.

Implications for Practice

Because of the paucity of evidence for clinical equivalence, the choice to use ciprofloxacin 750 mg BID enterally should be based on a number of factors. Clinicians must consider the patient’s clinical status, including the acuity of the patient’s illness, signs and symptoms of clinical improvement or deterioration, and the site of infection. In particular, higher concentrations of the drug may be required for infections other than bacteremias and urinary tract infections. Apcalis Oral Jelly

Implications for Future Studies

The ideal trial would have the following characteristics: random assignment of patients receiving enteral feeds to either ciprofloxacin 400 mg BID intravenously, ciprofloxacin 500 mg BID enterally, or 750 mg BID enterally; and measurement of pertinent clinical outcomes, relevant microbiological data, and pharmacokinetic and pharmacodynamic parameters.

CONCLUSIONS

There is insufficient evidence to determine whether patients receiving enteral feeds who are given ciprofloxacin 750 mg BID enterally will achieve clinical outcomes similar to those of patients who receive ciprofloxacin 400 mg BID intravenously. There is evidence to suggest that when patients receiving continuous enteral feeds are given ciprofloxacin 750 mg BID enterally, they will achieve similar AUCs but lower Cmax concentrations relative to patients who receive ciprofloxacin 400 mg BID intravenously. canadian cialis online