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Treatment of Methicillin-sensitive Staphylococcus Aureus (MSSA) (CLINDOS)

A

Assistance Publique - Hôpitaux de Paris

Status

Completed

Conditions

Osteoarticular Infection

Treatments

Drug: association of LEVOFLOXACIN+ CLINDAMYCIN
Drug: association of RIFAMPIN + CLINDAMYCIN

Study type

Interventional

Funder types

Other

Identifiers

NCT01500837
K000000

Details and patient eligibility

About

Background:

One of the leading causes of peri-operative osteoarticular infections (OAI) is Staphylococcus aureus. Treatment usually requires surgical debridement in association with appropriate antibiotic therapy. After surgery, an intravenous (IV) antibiotic therapy is routinely indicated for 10 to 15 days, followed by a minimal one-month oral treatment. In this protocol, the latter includes clindamycin in combination with rifampin or levofloxacin. Clindamycin is considered a good option in staphylococcal infections, because of its action against biofilm formation and bacterial adherence, its high level of joint and bone penetration and its good tolerance. Rifampin, a potent cytochrome P-450 inducer, enhances the elimination of a large number of drugs. Therefore, an influence of rifampin on clindamycin pharmacokinetics must be considered.

Objectives:

The primary objective is to compare the influence of rifampin and levofloxacin respectively on the pharmacokinetics of clindamycin in a randomized series of peri-operative staphylococcal OAI. The investigators then seek to determine the optimal drug association with regard to infection control and drug tolerance.

Study design:

Monocentric, randomized, open label, comparative study

Study period:

From November 2010 to October 2011.

Materials and Methods:

Following surgical debridement and after 10 to 15 days of IV antibiotherapy, patients are randomly assigned either to the "clindamycin/rifampin" arm either to the "clindamycin/levofloxacin" arm, according to the antimicrobial susceptibility testing. Peak and trough serum concentrations of clindamycin are measured at day-1, day-15 and day-30 of oral treatment. Rifampin and levofloxacin serum concentrations are measured at the same intervals to monitor patient compliance.

Full description

Background:

One of the leading causes of peri-operative osteoarticular infections (OAI) is Staphylococcus aureus. Treatment usually requires surgical debridement in association with appropriate antibiotic therapy. After surgery, an intravenous (IV) antibiotic therapy is routinely indicated for 10 to 15 days, followed by a minimal one-month oral treatment. In this protocol, the latter includes clindamycin in combination with rifampin or levofloxacin. Clindamycin is considered a good option in staphylococcal infections, because of its action against biofilm formation and bacterial adherence, its high level of joint and bone penetration and its good tolerance. Rifampin, a potent cytochrome P-450 inducer, enhances the elimination of a large number of drugs. Therefore, an influence of rifampin on clindamycin pharmacokinetics must be considered.

Objectives:

The primary objective is to compare the influence of rifampin and levofloxacin respectively on the pharmacokinetics of clindamycin in a randomized series of peri-operative staphylococcal OAI. The investigators then seek to determine the optimal drug association with regard to infection control and drug tolerance. Study design: monocentric, randomized, open label, comparative study

Study period:

From November 2010 to October 2011.

Materials and Methods:

Following surgical debridement and after 10 to 15 days of IV antibiotherapy, patients are randomly assigned either to the "clindamycin/rifampin" arm either to the "clindamycin/levofloxacin" arm, according to the antimicrobial susceptibility testing. Peak and trough serum concentrations of clindamycin are measured at day-1, day-15 and day-30 of oral treatment. Rifampin and levofloxacin serum concentrations are measured at the same intervals to monitor patient compliance. Infection cure is evaluated clinically, with periodic X-rays and CRP dosage in serum.

Enrollment

23 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

  • subject over 18 years with a IOA with GERME sensitivity to three antibiotics,
  • Patient in orthopedic unit of HEGP,
  • Patient who received and understood the information and who signed consent,

Exclusion criteria

  • Known allergy to one of three antibiotics and / or excipients,
  • Pregnancy or during lactation,
  • Congenital galactosemia, malabsorption of glucose and galactose, or lactase deficiency,
  • History of tendinopathy with fluoroquinolones,
  • G6PD deficiency,
  • porphyria,
  • subject receiving a protease inhibitor,
  • subject receiving anticoagulants
  • Malabsorption syndrome,
  • subject unable to follow the protocol (organizational problem, intellectual disability, ...).

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

23 participants in 2 patient groups

RIFAMPIN
Active Comparator group
Description:
CLINDAMYCIN + RIFAMPIN
Treatment:
Drug: association of RIFAMPIN + CLINDAMYCIN
LEVOFLOXACIN
Active Comparator group
Description:
CLINDAMYCIN + LEVOFLOXACIN
Treatment:
Drug: association of LEVOFLOXACIN+ CLINDAMYCIN

Trial contacts and locations

1

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Data sourced from clinicaltrials.gov

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