Broad-spectrum Antibiotic Prophylaxis in Tumor and Infected Orthopedic Surgery

Studien-Informationen Einschlusskriterien Studien-Rationale Studien-Arme Geprüfte Regime

Rekrutierend

NCT-Nummer:
NCT05502380

Studienbeginn:
September 2022

Letztes Update:
28.02.2023

Wirkstoff:
Standard antibiotic prophylaxis

Indikation (Clinical Trials):
Infections, Communicable Diseases, Surgical Wound Infection

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 3

Sponsor:
Balgrist University Hospital

Collaborator:
-

Studienleiter

Ilker Uçkay, Professor
Principal Investigator
Balgrist University Hospital

Kontakt

Ilker Uçkay, Professor
Kontakt:
Phone: ++41 44 386 37 05
E-Mail: ilker.uckay@balgrist.ch» Kontaktdaten anzeigen

Mazda Farshad, Professor
Kontakt:
Phone: ++ 41 44 386 30 00
E-Mail: mazda.farshad@balgrist.ch» Kontaktdaten anzeigen

Studienlocations
(1 von 1)

Balgrist University Hospital
8008 Zurich
SwitzerlandRekrutierend» Google-Maps

Studien-Informationen

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)

Ein-/Ausschlusskriterien

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

Studien-Rationale

Primary outcome:

1. Incidence of Surgical Site Infections (SSI) at 6 weeks for surgeries without implant; and 1 year for surgeries with implant (Time Frame - 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:

1. 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 (Time Frame - 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

2. Incidence of revision surgery for non-infections reasons within 6 weeks (Time Frame - 6 weeks postoperatively):
Unplanned revision surgery in the operating theatre for any reasons

3. Proportion of the change of antibiotic therapy based on intraoperative findings (Time Frame - 6 weeks postoperatively):
Asssesment in the medical files. Have therapeutic antibiotics been changed according to new intraoperative bacterial culture findings

4. Incidence of dverse events and global costs of therapeutic antibiotics (if any) (Time Frame - 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.

5. Incidence of non-SSI infections within 6 weeks (e.g. urine infections) (Time Frame - 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

6. Incidence of skin and body colonization with Gram-negative multi-resistant bacteriaweeks (if there are any samples) (Time Frame - 4-6 weeks postoperatively):
Assessment of the impact of the priorantibiotic prophylaxis on the body colonization with multiresistant bacteria of concern for infection control

Studien-Arme

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

Geprüfte Regime

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

Quelle: ClinicalTrials.gov

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