Biofilm Formation in Staphylococcus Epidermidis Associated Implant Infections

Staphylococcal Infections Clinical Trial

Official title:

Biofilm Formation Increases Treatment Failure in Staphylococcus Epidermidis Device-related Osteomyelitis in Human Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02640937
• Other study ID #: 12063
• Status: Completed
• Phase: N/A
• First received: December 16, 2015
• Last updated: December 22, 2015
• Start date: November 2011
• Est. completion date: November 2015

Study information

• Verified date: December 2015
• Source: BG Unfallklinik
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Ethics Commission
• Study type: Observational

Clinical Trial Summary

This was a prospective study performed between November 2011 and September 2013. Patients with a confirmed S. epidermidis infection after fracture fixation or prosthetic joint infection were included. Exclusion criteria included infections involving external fixation pins, infections without any implanted hardware and culture positive patients not displaying any clinical sign of infection. The following surgical parameters were documented: affected bone or joint; type of implant; time between implantation of the device and onset of symptoms. Personal characteristics and patients`health status were also documented. Any revision surgeries involving the site of interest and all isolated pathogens were recorded throughout the course of treatment and follow-up.

A follow up examination was performed an average of 26 months after discharge. Primary outcome at follow up was cure. Cure was define by the authors as: missing local (at site of interest) or systemic signs of infection, terminated surgical and systemic therapy and restoration of joint or limb function.

At the first surgical procedure after enrolment, at least four deep bone biopsies were taken from the interface between implant and affected bone. Identification and antibiotic susceptibility testing of all growth was performed. Multi-drug-resistance (MDR) was defined according to the definitions of the European Committee of Antimicrobial Susceptibility Testing (EUCAST). Biofilm formation was analysed and quantified in microtitre plate assays according to protocol of Stepanovic et al.(see references).

Description:

This was a prospective study performed between November 2011 and September 2013. All patients provided informed written consent prior to inclusion in the study. Inclusion criteria were deep S. epidermidis infections after fracture fixation or prosthetic joint surgery. Fracture fixation infections includes fractures involving the long bones as well as the pelvis and the spine. Bacterial growth at the site of interest in combination with either pseudarthrosis, implant-loosening/failure or local and systemic signs of surgical site infection were required for inclusion. Exclusion criteria included infections involving external fixation pins, infections without any implanted hardware and culture positive patients not displaying any clinical sign of infection.

Upon entry into the study, the following surgical parameters were documented: affected bone or joint; type of implant; time between implantation of the device and onset of symptoms. Personal characteristics were also documented and included: gender; age; body mass index (BMI); smoker/non-smoker; overall medical condition (Charlson comorbidity index); and chronic immunosuppressive conditions (Diabetes mellitus, chronic alcoholism, Child`s class C cirrhosis, neoplasia, transplantation, AIDS and steroid medication). Any revision surgeries involving the site of interest and all isolated pathogens were recorded throughout the course of treatment and follow-up.

A follow up examination was performed an average of 26 months after discharge. Primary outcome at follow up was cure. Cure was define by the authors as: missing local (at site of interest) or systemic signs of infection and terminated surgical and systemic therapy.

At the first surgical procedure after enrolment, at least four deep bone biopsies were taken from the interface between implant and affected bone. The tissue samples were placed in a sterile container with thioglycollate liquid medium (bioMérieux, Hazelwood, MO, USA). The samples were cultured for ten days at 37°C and examined each day macroscopically. Any growth was inoculated onto a blood agar plate (bioMérieux, Hazelwood, MO, USA) for further growth and subsequent identification. In all cases, additional swabs and soft tissue samples may have been taken as per clinical routine, however, only samples adjacent to the implant were used for diagnosis in this study.

Identification and antibiotic susceptibility testing of all growth was performed using a Vitek2 (bioMerieux Vitek Inc, Hazelwood, MO, USA). Multi-drug-resistance (MDR) was defined according to the definitions of the European Committee of Antimicrobial Susceptibility Testing (EUCAST). Oxacillin resistance was used as an indicator for methicillin resistant S. epidermidis (MRSE).

Biofilm formation was analysed and quantified in microtitre plate assays according to the well-established protocol of Stepanovic et al.(see references). This method traditionally assigns isolates to one of four categories: non-biofilm-formers and weak, moderate or strong biofilm-formers.

The key variables with regards to bacterial phenotype were: biofilm formation; methicillin resistance; and multidrug resistance. The primary outcome measure was whether the infection was "cured" or not. Primary outcome parameters were calculated as a function of all patients for whom data was complete. Statistical comparison was restricted to the lower extremity cohort since the other patients are not scored for many of the functional outcome measures and as such incomplete.

Univariate logistic regression models were used to determine the influence of each prognostic factor (obesity, smoking, diabetes mellitus, chronic immune suppression, open fracture (initially), early onset infection, biofilm formation, methicillin resistance, MDR and Charlson comorbidity index) on cure. P-values <0.05 were considered significant. Statistical analyses were performed using SAS software (Version 9.2; Cary, NC, USA).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 124
• Est. completion date: November 2015
• Est. primary completion date: September 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• infections after fracture fixation or prosthetic joint surgery

• Affected bone or joint: Long bones of the lower extremity; hip joint, knee joint;

• Bacterial growth of S. epidermidis at the site of interest

• Written consent

• Age: 18 and older

Exclusion Criteria:

• no prove of bacterial growth at site of interest

• missing consent

• infections involving external fixation pins, infections without any implanted hardware.

Study Design

Observational Model: Case-Only, Time Perspective: Prospective

Related Conditions & MeSH terms

• Infection
• Staphylococcal Infections

Locations

Country	Name	City	State
Germany	BG Unfallklinik Murnau	Murnau	Bavaria

Sponsors (1)

Lead Sponsor	Collaborator
BG Unfallklinik

Country where clinical trial is conducted

Germany, 

References & Publications (1)

Stepanovic S, Vukovic D, Hola V, Di Bonaventura G, Djukic S, Cirkovic I, Ruzicka F. Quantification of biofilm in microtiter plates: overview of testing conditions and practical recommendations for assessment of biofilm production by staphylococci. APMIS. 2007 Aug;115(8):891-9. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cure	Cure was define by the authors as: missing local (at site of interest) or systemic signs of infection and terminated surgical and systemic antibiotic therapy. All Parameters had to be positive to fulfill the outcome parameter "cure".If one of the mentioned parameters was negative, outcome was defined as "not cured". Local signs of infection were defined as the appearance of: redness, tenderness, swelling or persisting wound drainage.	24 month	No