Meropenem and Ciprofloxacin Dosing in Septic Shock

Patients with septic shock may have altered volume of distribution and metabolism of antibiotics which are crucial medications for treating infections. The aim of the study is to investigate the blood concentrations of Meropenem and Ciprofloxacin, two commonly used antibiotics, in patients with septic shock. The hypothesis is that standard dosing may produce insufficient levels of antibiotics in patients with septic shock.

Sepsis may induce changes in renal function, increased capillary leakage and frequently blood-flow stasis in the peripheral tissues leading to an increase in the water space and diffusion distances. Significant changes have been observed in the distribution volume of certain antibiotics in patients with sepsis. The increased volume of distribution of water-soluble drugs is caused by a capillary leak syndrome that results in a net movement of fluid from the intravascular compartment into tissues. This capillary leak syndrome has been well described in patients with sepsis and may result in low trough serum concentrations. This, in turn, may result in a slow antibiotic penetration of tissues and a low tissue antibiotic concentration. Treatment failure may result if antibiotic choice or doses are incorrect and there is a lack of information which describes how to alter drug dosing in response to this increased volume of distribution in sepsis. Previous research has shown that some intensive care unit (ICU) patients have larger than normal between subject variability in drug clearance and volumes that can be attributed to supranormal renal clearances.

Aims of the present study:

1. To evaluate present meropenem and ciprofloxacin dosing and achieved plasma concentrations in relation to bacterial susceptibility.
2. To evaluate how to accurately dose meropenem and ciprofloxacin in patients with sepsis The overall hypothesis for this project is that some patients admitted to ICU with severe sepsis are undertreated with meropenem and ciprofloxacin using the dosing based on that recommended by the Product Information

Eligibility Criteria:
Inclusion Criteria:

* Age \>18 years and \<90 years
* Clinical indication for therapy of one of the study antibiotics Meropenem or Ciprofloxacin in patients diagnosed at or during admission to ICU with septic shock
* Sepsis will be defined as:

  * Clinical suspicion of infection and/or Positive culture results
  * Systemic inflammatory response syndrome (SIRS) as defined by 2 or more of the following:
  * Core temperature \< 36o C or \> 38o C
  * Tachycardia as defined by a heart rate \> 90 beats per minute
  * Tachypnoea as defined by a respiratory rate greater than 20 breaths per minute OR a PaCO2 less than 32 mmHg during spontaneous ventilation OR the requirement for mechanical ventilation.
  * A white blood cell count \> 12 X 109 / L OR \< 4 X 109 / L OR greater than 10 % immature (band) forms.
* Septic shock will be defined as:

  * Sepsis with persistent hypotension, systolic blood pressure \< 90 mmHg or mean arterial pressure \< 65 despite adequate fluid resuscitation
  * Requirement of inotropic support.
* Normal renal function as defined by:

  * Serum creatinine \<170 mmol/L

Exclusion Criteria:

* Pre-existing renal impairment as defined by:

  * Serum creatinine above normal limits ( defined as \>500mmol/L)

    * Need for renal replacement therapy
    * History of allergy to study antibiotic
    * Pregnancy