Ceftriaxone as Home IV for Staph Infections
Ceftriaxone as Home IV for Staph Infections
Patients who are admitted to hospital with serious infections, such as those in bone, joints
 or spine, require a long course of intravenous (IV) antibiotics. After an initial treatment
 course in hospital or through a dedicated outpatient antibiotic program many patients can
 complete their treatment course at home. Such infections are often caused by bacteria called
 Staphylococci, and currently there are three antibiotic options used routinely. A fourth
 antibiotic, ceftriaxone, is a promising alternative; it is also effective against
 Staphylococci, and is more convenient, less costly and easier to give at home, however, it
 has not been studied thoroughly in a prospective manner. This study will compare ceftriaxone
 to routinely used antibiotics (cloxacillin, cefazolin or daptomycin) to see if ceftriaxone is
 equally as safe and efficacious in curing deep-seated Staphylococcal infections in patients
 receiving home IV antibiotics. Patients with deep-seated infections caused by
 methicillin-susceptible Staphylococcus aureus (MSSA) or coagulase-negative Staphylococcal
 species will be randomly assigned home IV treatment with ceftriaxone OR one of the three
 other antibiotics before leaving the hospital. Patients will then receive usual care from an
 Infectious Disease physician and Home IV team. The study team will assess whether cure has
 been achieved by the end of the IV treatment, follow-up at 6 months to see if patients remain
 infection-free, and record any side-effects of treatment. The overall goal is to determine
 whether ceftriaxone can be considered non-inferior to usual antibiotic treatment in treating
 Staphylococcal infections in a home IV setting.
The use of ceftriaxone for deep-seated Staphylococcal infections requiring prolonged IV
 treatment is a practice that has already evolved both locally and globally despite the
 absence of high-quality clinical data. Retrospective studies that support the use of
 ceftriaxone for this indication, including those that currently inform Infectious Diseases
 Society of America (IDSA) guidelines, unanimously agree that prospective, randomized data is
 urgently needed. Our study is the next natural step in the research process and would greatly
 add to the body of evidence informing this practice by addressing current knowledge gaps. On
 a clinical level, demonstrating non-inferiority of ceftriaxone would allow its use in a
 population of patients currently ineligible for outpatient antibiotic treatment or in cases
 where broader, more expensive agents are currently employed. This would facilitate more rapid
 discharge from hospital, lead to substantial cost savings, and have a considerable impact on
 antimicrobial stewardship. Most importantly, it would improve the quality of life of patients
 by allowing them to be treated at home in cases when multi-dose home IV administration is a
 barrier to discharge. This study would address the need to support and harmonize current
 practice at Island Health, increase the level of evidence in current guidelines and improve
 patient care both locally and globally.

 This is a prospective, randomized, controlled, unblinded trial with a pragmatic design. The
 goal is to assess whether the intervention is non-inferior to standard therapies in achieving
 the primary outcome. Patients will be drawn from inpatient populations and patients treated
 through an outpatient antibiotic therapy clinic who are eligible for further IV treatment
 through a home intravenous therapy program. Patients meeting inclusion criteria as described
 will be asked to participate and informed consent obtained. Once informed consent is obtained
 patients will be randomized to receive ceftriaxone or standard therapies (cloxacillin,
 cefazolin, daptomycin) as determined by the treating infectious diseases physician. Patients
 will have deep-seated infections such as:

 -  Osteomyelitis

 -  Native Joint Septic Arthritis

 -  Prosthetic Joint Septic Arthritis

 -  Central Nervous System Infection

 -  Deep Tissue Infection

 -  Diabetic Foot Infection

 Infections will be confirmed to have been caused by methicillin-sensitive Staphylococcus
 aureus or a coagulase-negative Staphylococcal species through microbiological testing.
 Susceptibility testing will ensure that the isolate is susceptible to the study drug and at
 least one of the standard therapies.

 Once the patient is randomized all other aspects of care will follow usual home IV therapy
 policies and procedures. Neither the patient nor the clinical team will be blinded to the
 study drug the patient is receiving. Duration of treatment will be decided by the treating
 infectious diseases clinician based on infection site and available guidelines. Baseline data
 will be collected by the study team at the time of randomization.

 The patient will be followed up in the usual manner by their infectious diseases physician.
 Data will be collected in a standardized manner at the pre-specified end of antibiotic
 therapy. Clinical cure (primary outcome) will be determined based on this data.

 Adverse event rates will be collected throughout the study period. At six months
 post-randomization the study team will assess for any markers of treatment failure (see
 secondary outcomes).

 Plan for statistical analysis is pre-specified in the protocol and will be completed with the
 assistance of biostatistics staff at the University of Victoria. Specific information on the
 protection of patient confidentiality and data integrity is outlined in the study protocol.
 Ethics approval has been granted by the Clinical Research Ethics Board at Vancouver Island
 Health Authority.
Inclusion Criteria:

 -  are 18 years of age or older

 -  were referred to and assessed by an Infectious Disease physician in the form of a
 clinical consult as either:

 -  an inpatient at the Royal Jubilee or Victoria General Hospitals

 -  an outpatient at the emergency department of one of the aforementioned hospitals

 -  an outpatient at the Outpatient Parenteral Antibiotic Therapy (OPAT) clinic

 -  have a clinically and/or radiographically diagnosed deep-seated MSSA or
 coagulase-negative Staphylococcal infection as defined in Table 1 of the protocol
 (Osteomyelitis, Discitis/Epidural abscess, Central Nervous System (CNS) infection,
 Abscess, Septic Arthritis (including Prosthetic Joint Infection), Diabetic foot
 infection) and the diagnosis has been made or confirmed by the Infectious Disease
 physician

 -  have had the causative pathogen confirmed microbiologically as either MSSA or CoNS
 through a laboratory sample indicative of the current site of infection

 -  are deemed to require prolonged IV antibiotic therapy and subsequently referred for
 assessment by the home IV program by the Infectious Disease physician

 -  are an appropriate candidate for the home IV program as determined by the assessing
 Home IV nurse, and are eligible for treatment with BOTH ceftriaxone AND at least one
 of the usual alternatives, namely cloxacillin, cefazolin or daptomycin

 -  provide written informed consent to participate in the study

 -  have their culture and sensitivity results finalized prior to randomization, with the
 isolate confirmed to be sensitive to all study drugs (susceptibilities are discussed
 in the "Microbiological Testing" section of the protocol)

 -  are successfully randomized to either ceftriaxone OR one of cloxacillin, cefazolin or
 daptomycin before Home IV orders are written (the choice between the three comparator
 antibiotics will be at the discretion of the treating Infectious Disease physician)

 -  receive at least one dose of the antibiotic to which they were randomized prior to
 being discharged on the home IV program

 -  are physically discharged to the home IV program for any duration

 Exclusion Criteria:

 -  younger than 18 years of age

 -  pregnant

 -  involved in another therapeutic trial

 -  are not under the care of an Infectious Disease physician

 -  are unable to provide informed consent due to language or cognitive barriers

 -  are not appropriate for Home IV therapy as determined by the assessing Home IV nurse

 -  are concurrently receiving other anti-staphylococcal antibiotics (excluding the
 synergistic use of rifampin for prosthetic joint infections) at the time of discharge
 on the home IV program

 -  have relevant cultures indicating a polymicrobial infection (except in the case of
 diabetic foot infections where they may be included if MSSA or CoNS is determined to
 be the dominant pathogen by the Infectious Disease physician and any additional
 antibiotics used do not exhibit activity against MSSA or CoNS)

 -  have concurrent or incompletely treated bacteremia with MSSA or CoNS (as defined in
 protocol)

 -  have infective endocarditis based on imaging or clinical judgement

 -  are receiving home IV antibiotics solely as palliative therapy

 -  are unable to tolerate ceftriaxone AND any ONE of the standardly used antibiotics
 (cloxacillin, cefazolin, daptomycin) because of an allergy or intolerance