Oral Antibiotic Treatment at Home Instead of Intravenous Treatment in Hospital for Resistant Gram Positive Infections

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

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.

Study Overview

• Status: Completed
• Conditions: Staphylococcal Infections; Gram-positive Bacterial Infections
• Intervention / Treatment: Drug: linezolid

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

• Study Type: Interventional
• Enrollment (Actual): 211
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, W12 0NN
    • Imperial College London

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Patients who fulfilled the study criteria; IV to oral switch inclusion criteria used; Clinical statusTemperature less than 38°C for 24 hoursWhite cell count normalisingNo unexplained tachycardia (Heart rate less than 100 beats per minute)Sensitivity received (if microbiology positive); Oral absorptionPatient tolerates oral fluidsNo medical problems leading to reduced oral absorption (e.g. vomiting, diarrhoea, and gastrointestinal surgery)No surgical operation scheduled within next 36 hours IV to oral switch exclusion criteria used; Continuing sepsisTemperature less than 36°C or more than 38°CWhite cell count less than 4 × 109/L or more than 12 × 109/LUnexplained tachycardia (Heart rate greater than 100 beats per minute in last 12 hours); Oral route compromisedVomiting or severe diarrhoeaOther ongoing or potential absorption problem

Drug: linezolid; Linezolid is an antimicrobial with activity against MRSA that can be given orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To identify the percentage of patients currently prescribed IV glycopeptides who could be discharged earlier if an oral agent was used	Period between IV oral switch and discharge, at least 24 hours

Secondary Outcome Measures

Outcome Measure	Time Frame
To estimate the number of inpatient days that could be saved	Period between IV oral switch and discharge, at least 24 hours
To identify the groups of patients most likely to be suitable for earlier discharge if an oral agent was used	Period between IV oral switch and discharge, at least 24 hours
To identify the additional number of days of IV antibiotic treatment that could be prevented by using an oral agent in hospitalised patients	Period between IV oral switch and discharge, at least 24 hours

Collaborators and Investigators

• Sponsor: Imperial College London
• Collaborators: Hammersmith Hospitals NHS Trust
• Investigators: Principal Investigator: Kathleen B Bamford, MB BCh BAO, Imperial College London

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2005
• Primary Completion (Actual): June 1, 2007
• Study Completion (Actual): June 1, 2007

Study Registration Dates

• First Submitted: July 12, 2007
• First Submitted That Met QC Criteria: July 12, 2007
• First Posted (Estimated): July 13, 2007

Study Record Updates

• Last Update Posted (Actual): October 26, 2023
• Last Update Submitted That Met QC Criteria: October 25, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: vancomycin; linezolid; glycopeptides; methicillin resistant staphylococcus aureus; resistant gram positive infections
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Bacterial Infections and Mycoses; Infections; Communicable Diseases; Bacterial Infections; Staphylococcal Infections; Gram-Positive Bacterial Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; Protein Synthesis Inhibitors; Linezolid
• Other Study ID Numbers: BAMK1021; 05/q0406/106