Clinical trial NCT00501150: Oral Antibiotic Treatment at Home Instead of Intravenous Treatment in Hospital for Resistant Gram Positive Infections
Official title: A Prospective Implementation of an IV-oral Switch Policy to Treat Proven or Suspected Infections Due to Resistant Gram Positive Bacteria in a London Hospital Trust
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Gram-positive Bacterial Infections
Staphylococcal Infections
Keywords: linezolid
vancomycin
glycopeptides
methicillin resistant staphylococcus aureus
resistant gram positive infections
Lead sponsor: Imperial College London
Sponsor class: OTHER
Collaborators: name: Hammersmith Hospitals NHS Trust
First posted: 2007-07-13
Enrollment: 211
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The main purpose of this study is to find out whether changing the hospital policy to allow switch from glycopeptide antibiotics (given by intravenous drip), to an equally effective oral antibiotic (linezolid) will enable patients who are otherwise well enough to be discharged from hospital sooner.

The secondary objectives are

1. To identify those patients who could potentially be discharged on an oral agent from those being treated with a glycopeptide, thus helping target this approach most effectively
2. To evaluate the cost involved and compare this with the costs that would have taken place if use of an oral agent and discharge had not occurred.

Detailed description: The treatment of resistant gram positive infections remains problematic, with glycopeptides remaining the mainstay of current management. Unfortunately these can only be administered by the IV route, with no useful activity when given orally for these infections. Thus while oral flucloxacillin or ampicillin are used as follow up to IV treatment in the management of infections caused by antibiotic sensitive Staphylococcus aureus or enterococcal respectively, in the case of antibiotic resistant infections the whole course of antibiotics is usually given by the IV route. To some extent this is because there is insufficient evidence to support routine use of other oral agents and means that patients with antibiotic resistant infections stay in hospital longer than those with antibiotic sensitive infections.

Linezolid is a relatively newly available antibiotic that has been shown to be as, and in some settings more effective than glycopeptides in the treatment of resistant gram positive infections including MRSA. Unfortunately Linezolid is significantly more expensive than other currently available agents making it important to evaluate the cost benefit aspects of its use in comparison to similarly effective agents.

Switching from IV to a suitable oral alternative in the management of resistant gram positive infection could potentially result in significant saving in the duration of IV therapy and would allow patients to be discharged earlier. This would provide a significant cost benefit which in the face of Linezolids equal if not superior efficacy would justify more widespread use in order to allow suitable patients to be treated at home.

The rationale behind this study is to determine the level at which this can be implemented in an NHS teaching hospital Trust. To do this we will identify patients who could potentially benefit from early discharge on oral therapy, implement this where possible and compare the actual effect on LOS with the potential identified in the earlier cohort of patients.

We propose to prospectively assess the economic and clinical impact of switching from IV glycopeptides to oral Linezolid and implementing home treatment on oral therapy policy over an 18 month period in HHT hospitals Two senior infection specialists(a Medical Microbiologist, K Bamford and an Infectious Disease physician, A Holmes) will independently review each patient together with the study pharmacist and decide if the individual is suitable for switch to an oral agent and/or discharge using standardised criteria for decision making. Patients will be studied to assess the number of attributable bed days, line use days, ward pharmacist interventions (to trigger monitoring and adjust dose) and investigations and medical complications that accrue due to IV administration following glycopeptide prescription. The various costs to the Trust which are saved when the IV glycopeptide is switched to a suitable oral alternative and early discharge implemented will be calculated

Eligibility criteria: Inclusion Criteria:

1. Prescribed five or more days glycopeptide
2. Fulfil IV-oral switch criteria (see below) with likelihood of discharge within next 48 hours.

Exclusion Criteria:

1. Renal dialysis out patients
2. Suspected or proven left sided endocarditis/osteomyelitis/prosthetic infection where the prosthesis cannot be removed
3. Per-protocol prescribing in haematology (i.e. where teicoplanin is prescribed in response to failure of fever resolution in neutropenic patients without microbiological or clinical evidence of gram positive infection).
4. Age \< 16 years
5. Pregnant or lactating female.
6. Other contraindication to linezolid
7. Clinically unlikely to be discharged within study period or at end of antibiotic therapy.

Primary outcomes:
measure: To identify the percentage of patients currently prescribed IV glycopeptides who could be discharged earlier if an oral agent was used
timeFrame: Period between IV oral switch and discharge, at least 24 hours
Secondary outcomes:
measure: To estimate the number of inpatient days that could be saved
timeFrame: Period between IV oral switch and discharge, at least 24 hours
measure: To identify the groups of patients most likely to be suitable for earlier discharge if an oral agent was used
timeFrame: Period between IV oral switch and discharge, at least 24 hours
measure: To identify the additional number of days of IV antibiotic treatment that could be prevented by using an oral agent in hospitalised patients
timeFrame: Period between IV oral switch and discharge, at least 24 hours
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Imperial College London
Study officials:
affiliation: Imperial College London
name: Kathleen B Bamford, MB BCh BAO
role: PRINCIPAL_INVESTIGATOR
References:
citation: Desai M, Franklin BD, Holmes AH, Trust S, Richards M, Jacklin A, Bamford KB. A new approach to treatment of resistant gram-positive infections: potential impact of targeted IV to oral switch on length of stay. BMC Infect Dis. 2006 Jun 8;6:94. doi: 10.1186/1471-2334-6-94.