BAPTIST: Broad-spectrum Antibiotic Prophylaxis in Tumor and Infected Orthopedic Surgery

Sponsor

Balgrist University Hospital (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05502380

Collaborator

(none)

414

Enrollment

Arms

27.5

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

The perioperative antibiotic prophylaxis is evidence-based in orthopedic surgery. While its duration ranges from a single dose to three doses throughout the world, the choice of the prophylactic agents is undisputed. Worldwide, the surgeons use 1st or 2nd-generation cephalosporins (or vancomycin in some cases).

However, there are particular clinical situation with a high risk of antibiotic-resistant surgical site infections (SSI); independently of the duration of adminis-tered prophylaxis. These resistant SSI's occur in contaminated wounds, or during surgery under current therapeutic antibiotics, and base on "selection" by antibiotics used for therapy or for prophylaxis.

Condition or Disease	Intervention/Treatment	Phase
Surgical Site Infection Microbial Colonization Antibiotic Resistant Infection	Drug: Standard antibiotic prophylaxis	Phase 3

Detailed Description

The perioperative antibiotic prophylaxis is evidence-based for the majority of orthopedic surgeries. While the debate of its duration and timing (single-dose versus triple-dose; before or after the intraoperative microbiological sampling) may continue, no clinicians doubt on the efficiency of the recommended prophylactic agents; that are mostly 1st or 2nd-generation cephalosporins, co-amoxiclav or other exceptional agents in cases of (pseudo)-allergy. However. and traditionally, up to the half of all detected pathogens of orthopedic SSI's are not covered by the prior prophylactic regimens: e.g. SSIs due to methicillin-resistant cocci or non-fermenting Gram-negative rods in orthopedic surgery.

Additionally, orthopedic surgeons operating selected patient populations (neoplasms, open fractures, postoperative wound dehiscence9, diabetic foot infections or already infected body sites) experience a high risk of prophylactic-resistant pathogens, or pathogens resistant to current therapeutic antibiotics regimens. At least 10% of all new intraoperative tissue samples, during iterative surgical debridement, yield (new) pathogens unknown to the clinicians.

This is due to selection by prophylactic or therapeutic antibiotics, which only kill the previously detected pathogens, but left over newly introduced contaminants, remnant parts of partially-diagnosed polymicrobial infections; ultimately leading to a new SSIs occurring during therapy for the first infection at the orthopedic site. This selection is unpredictable involving both Gram-positive skin pathogens as well as (multi) resistant Gram-negative rods.From a microbiological point of view, only a maximal Gram-negative coverage, alongside with a large Gram-negative coverage, would cover these selections.

The literature is in-existing how to prevent these selections. Most clinicians just continue with the standard prophylactic recommendation, or the current thera-peutic antibiotic regimen. Theoretically, clinicians cannot exclude that these selected patient populations eventually might profit from a broad-spectrum prophylaxis.

The BAPTIST trials only concern the perioperative antibiotic prophylaxis in selected situations of orthopedic surgery: tumor surgery, debridement for postoperative dehiscent wounds, debridement under antibiotics, open fractures, skin colonization with multidrug-resistant bacteria, plus, as a control; spine surgery in selected multimorbid patients. The investigators alternately randomize the standard prophylaxis (or by continuing the current antibiotic treatment) to the additional broad-spectrum single-shot of vancomycin 1g IV & single-shot of gentamicin 5 mg/kg intravenously; before an eventual intraoperative sampling. End-of-Treatment (EOT) and/or Test-of-Cure (TOC) occur latest at the 6-week's surgical control visit. The rest of the hospital stay, treatment, the use of negative-pressure vacuum therapy, other interventions, local antibiotic therapies; therapies or procedure are at the discretion of the treating clinicians.

The investogators will randomize surgical interventions defined by the inclusion criteria in a prospective-alternating scheme (1:1) according to the scheduled position in the operating theatres. The anesthetists (or the nurses at the hospitalization units) the will administer the standard prophylaxis (or the therapeutic antibiotics) alone, or with the addition of the single-shot broad-spectrum prophylaxis regimen composed of vancomycin and gentamicin. In case of clinical suspicion of infection or massive contamination, the surgeons will perform at least three microbiological intraoperative tissue samples. Each surgery counts as an independent event. If a patient is debrided several times, he/she can have different prophylaxis regimens during each of the interventions. After the prophylactic regimen, the clinicians are free to continue with a targeted or empirical therapeutic antibiotic regimen. The antibiotic therapy per se is not an objective of this current trials.

The treatment period includes the following daily study visits:

Visit 1 - Enrollment (Day 1)
EOT (end of microbiological cultures) - Day 14 (+/- 3 days)
TOC (clinical surgical control) - Day 42 (+/- 14 days)
Follow-up (telephone) for implant-related surgery - 1 year (+/- 2 months)

Study Design

Study Type:

Interventional

Anticipated Enrollment :

414 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

At enrollment (Day 1), the investigator will prescribe the preoperative antibiotic prophylaxis based on instructions provided in the protocol according to the patient's randomization. Patients will be randomized in the ratio 1:1 into the investigational group (broad-spectrum prophylaxis) and the control group (usual prophylaxis). Each patient can be included several times with one episode for each surgical interven-tion in the operating theatre. The initial consent form is valid during 1 month and will be renewed in case of another inclusion following a delay of 1 month after the initial signature of the patient.At enrollment (Day 1), the investigator will prescribe the preoperative antibiotic prophylaxis based on instructions provided in the protocol according to the patient's randomization. Patients will be randomized in the ratio 1:1 into the investigational group (broad-spectrum prophylaxis) and the control group (usual prophylaxis). Each patient can be included several times with one episode for each surgical interven-tion in the operating theatre. The initial consent form is valid during 1 month and will be renewed in case of another inclusion following a delay of 1 month after the initial signature of the patient.

Masking:

Single (Care Provider)

Masking Description:

The microbiologists culturing the pathogens of eventual surgical site infections are blinded to the prior prophylaxis during the index surgery

Primary Purpose:

Prevention

Official Title:

Broad-spectrum Antibiotic Prophylaxis in Tumor and Infected Orthopedic Sur-gery - the Prospective-randomized, Microbiologist-blinded, Stratified, Superiority Trials - BAPTIST Trials

Anticipated Study Start Date :

Sep 15, 2022

Anticipated Primary Completion Date :

Dec 31, 2023

Anticipated Study Completion Date :

Dec 31, 2024

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Standard prophylaxis arm The standard prophylaxis consists of one to three intravenous doses of cefuroxime 1.5 g intravenously; or cefuroxim 3g if obesity > 120 kg or a BMI > 35 kg/m2; or vancomycin 1 g or clindamycin 600 mg in case of intolerance to cephalosporins In patients alrady under current therapuetic antibiotic therapy, continuation of that therapuetic antibiotic regimen	Drug: Standard antibiotic prophylaxis One to three intravenous doses of cefuroxime 1.5 g intravenously; or 3g if obesity; or vancomycin 1 g or clindamycin 600 mg; if allergy. Continuation of eventual current therapeutic antibiotc regimens for any infection
Experimental: Innovative prophylaxis arm Additional single-shot perioperative antibiotic prophylaxis with Broad-spectrum prophylaxis: vancomycin 1 g & gentamicin 5 mg/kg.	Drug: Standard antibiotic prophylaxis One to three intravenous doses of cefuroxime 1.5 g intravenously; or 3g if obesity; or vancomycin 1 g or clindamycin 600 mg; if allergy. Continuation of eventual current therapeutic antibiotc regimens for any infection

Arm

Intervention/Treatment

Active Comparator: Standard prophylaxis arm

The standard prophylaxis consists of one to three intravenous doses of cefuroxime 1.5 g intravenously; or cefuroxim 3g if obesity > 120 kg or a BMI > 35 kg/m2; or vancomycin 1 g or clindamycin 600 mg in case of intolerance to cephalosporins In patients alrady under current therapuetic antibiotic therapy, continuation of that therapuetic antibiotic regimen

Drug: Standard antibiotic prophylaxis

One to three intravenous doses of cefuroxime 1.5 g intravenously; or 3g if obesity; or vancomycin 1 g or clindamycin 600 mg; if allergy. Continuation of eventual current therapeutic antibiotc regimens for any infection

Experimental: Innovative prophylaxis arm

Additional single-shot perioperative antibiotic prophylaxis with Broad-spectrum prophylaxis: vancomycin 1 g & gentamicin 5 mg/kg.

Drug: Standard antibiotic prophylaxis

Outcome Measures

Primary Outcome Measures

Incidence of Surgical Site Infections (SSI) at 6 weeks for surgeries without implant; and 1 year for surgeries with implant [6 weeks postoperatively, or 1 year postoperatively in case of implant-related orthopedic surgery]
Assessment of SSI at the clinical controls according to clinical criteria in the literature (pus, discharge, pain, inflammation, several deep tissue microbiological cultures

Secondary Outcome Measures

Proportion of antibiotic-resistant pathogens in the deep surgical site of the study patients; in relation to the prior antibiotic prophylaxis or the current therapeu-tic antibiotic therapy [6 weeks postoperatively, or 1 year postoperatively in case of implant-related orthopedic surgery]
Assessments of antibiotic resistance of pathogens according to standard susceptibilty testing in the Microbiological Laboratory
Incidence of revision surgery for non-infections reasons within 6 weeks [6 weeks postoperatively]
Unplanned revision surgery in the operating theatre for any reasons
Proportion of the change of antibiotic therapy based on intraoperative findings [6 weeks postoperatively]
Asssesment in the medical files. Have therapeutic antibiotics been changed according to new intraoperative bacterial culture findings
Incidence of dverse events and global costs of therapeutic antibiotics (if any) [6 weeks postoperatively, or 1 year postoperatively in case of implant-related orthopedic surgery]
If there is therapeutic antibiotc treatment necessary, the investigators assess the drugs, the adverse events and the global costs related to the antibiotc treatment. The costs are the global (overall) hospitalizations costs in Swiss Francs.
Incidence of non-SSI infections within 6 weeks (e.g. urine infections) [6 weeks postoperatively]
Assessment of all nosocomial and community-acquired infections ocrruging in the immediate postoperative period and relate them to prior perioperative antibiotic prophylaxis
Incidence of skin and body colonization with Gram-negative multi-resistant bacteriaweeks (if there are any samples) [4-6 weeks postoperatively]
Assessment of the impact of the priorantibiotic prophylaxis on the body colonization with multiresistant bacteria of concern for infection control

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria

Age ≥ 18 years
Surgery under current or recent therapeutic antibiotics (antibiotic-free window <14 days and past antibiotic prescription >4 days)
Surgery for open fractures and wounds; including 2nd and 3rd looks
Potentially contaminated wound revision in the operating theatre
Tumor (oncologic) surgery (if prior radiotherapy and/or bone involvement)
Spine surgery with ASA-Score >= 3 points, sacral involvement, or re-vision surgery
Known skin colonization with multidrug-resistant Gram-negative bacteria

Exclusion Criteria:

Inability to understand the study procedure for linguistic or cognitive rea-sons
Surgery without intraoperative microbiological samples
Allergy or major intolerance to vancomycin and/or gentamicin
Anticipated clinical follow-up of less than 6 weeks after inclusion
Pregnant or breastfeeding women
Known carriage of multiresistant Gram-negative bacteria in the urine or anal region