Application of Antibiotic Loaded Calcium Sulfate as Prophylaxis for Patients With Non Modifiable Risk Factors for Periprosthetic Joint Infections
Phase: PHASE4
Conditions: Infection
Sponsor: Hospital Regional Tlalnepantla

 
 
 
 
 
Approval number by the ethics committee: 207C041050020m/ceis/p.i./0348/2019  
 
 
 
 
 
Protocol Title: 
 
 
 
 
Application of antibiotic loaded calcium sulfate as 
prophylaxis for patients with risk factors for 
periprosthetic joint infections. 
 
 
 
 
 
 
August 5th 2020, Tlalnepantla. Mexico  
 
 
 
 

 

 
Title: Application of antibiotic loaded calcium sulfate as prophylaxis for patients with 
risk factors for periprosthetic joint infections. 
 
INTRODUCTION 
 
Total hip arthroplasty is one of the most widely recognized orthopedic surgeries in 
the world. Since its inception this technique has achieved remarkable success thanks to the 
excellent results in restoring function, eliminating pain, innovations in implant design, and 
improved quality of life. A devastating complications in this indication is peri-prosthetic 
infection. 
 
There are many variables to consider when evalauting the risk of peri-prosthetic 
joint infection (PJI), including the types of implants, surgical technique, postoperative 
management and not least of all the patient. When assessing patients with hip and knee 
osteoarthritis or pertrochanteric fractures, socioeconomic status can introduce a significant 
risk of infection, that can be physically debilitating for the patient, challenging for 
clinicians and have an adverse economic impact for Health Institutes. (1) 
 
 
In Mexico as in many developing countries, the necessary infrasctructure to provide 
widespread adequate healthcare is not available, but it is imperative to attempt to offer the 
best treatment available. This is how joint replacement, as a surgical technique, has to be 
approached daily in our institutions. In most cases comprehensive assessments of the 
patient are made, but despite this, there are chronic degenerative diseases, such as diabetes 
and obesity, that are difficult to control. These factors are not an impediment to 
contraindicate surgery, however they increase the risk of complications. Comorbidities like 
these are defined as non-modifiable risk factors of patients undergoing articular 
replacement surgery that increase the risk of infection rate. (2) 
 
 
In order to reduce the risk of periprosthetic infection the application of local 
antibiotic at the surgical site, in addition to systemic antibiotics may be a promising 
concept. The local placement of antibiotics can result in high local concentrations, far 
higher than the levels that can be achived through systemic administration, the risk of 
elevated resulting systemic levels remains low (3)(4)(5). The reported use of local 
antibiotics at the surgical site range from direct placement of antibiotics at the surgical 
site(6)(7)(8)(9) to the combination of atibiotics with carrier materials in an attempt to 
prolong the level and duration of antibiotic(10)(11)(12). The use of calcium sulfate as a 
carrier for antibiotics has a history almost as long as that of antibiotics, with one of the first 
reported such uses dating back to 1953(13). Since this time, reports of the use of calcium 
sulfate in combination with amtibiotics in the treatment of osteomielitis have persisted  
(14–18)  (19–23). 
 
 
Modern commercially available formulations of calcium sulfate offer a versatility 
for mixing with a wide range of antibiotics (24), and in-vitro data indicates elevated 
antibiotic levels for up to 6 weeks (25), at levels that are capable of maintaining 
antimicrobial efficacy under conditions of high bacterial challenge (26–28). The application 

of calcium sulfate has shown promising outcomes in peri-prosthetic joint revisión (29,30), 
but there is limited clinical data available regarding its use prophylactically. 
 
The aim of this study was to evaluate local antibiotic loaded calcium sulfate as 
prophylaxis in patients undergoing hip and knee joint replacement with non-modifiable risk 
factors. 
 
Economic Impact of Periprosthetic Infections 
 
In 2012 in the United States, the annual cost in the treatment of patients with peri-
prosthetic infection was analyzed, at 566 million Dollars, and it is expected to exceed 1.62 
billion Dollars by 2020. It is expected that by the year 2020, the number of PJI cases for hip 
and knee is projected to be in excess of 65,000.(31) 
 
The cost of secondary revision surgery to a peri-prosthetic infection is $60,000 
Dollars higher than the revision surgery due to aseptic loosening. This increase is due to the 
longer hospital stay, prolonged antibiotic therapy, number of surgical interventions for 
remission of the infection, etc.(32) Likewise, an increase in the number of infections of 
surgical sites by methicillin-resistant organisms has been proven, increasing even more 
costs related to antibiotic therapy. (33) 
 
In the United States, the cost of Hospitalization for peri-prosthetic infection is 
$107,264 Dollars; the cost for the treatment of infections was $110,459 Dollars per patient. 
The day of hospitalization is $3,473 Dollars and the cost of a revision arthroplasty is 
$36,607 Dollars. (32) At present in the United States, the increase in costs related to peri-
prosthetic infections is surpassing the developments in prevention (34). 
 
 
In 2018 in Mexico at the institutional level, the average hospitalization day was 
$7,757.00 Mexican pesos; the cost per surgical procedure was $ 21,004.00, a follow-up 
orthopedic clinical evaluation of $1,160.00; The cost of the revision implant reached 
$116,132.00 pesos. The average number of days of hospitalization for a patient with PJI 
was 60 days and the number of surgical procedures required varies with a minimum of 5. In 
this case, the cost of antibiotic therapy or the rest of the medications administered during 
their hospitalization it was not estimated. (35,36) 
 
Several studies have shown that the identification of risk factors, decolonization and 
administration of prophylactic antibiotics leads to a substantial reduction of peri-prosthetic 
infections and with this, the cost involved in this condition. (32) 
 
Diagnosis and Classifications: 
 
Current methods for the Diagnosis of peri-prosthetic infections.  
 
A gold standard has yet to be established for the diagnosis of peri-prosthetic 
infections, so the current diagnosis is based on a combination of clinical suspicion, 
serological studies, results in cultures, histology and molecular biology techniques. 
 

Acute Phase Reactants: 
 
The CRP rises after the arthroplasty procedure, in which its maximum peak is on the 
2nd day and it can be normalized until 42 days postoperatively; however, after the 3rd day 
the CRP continues to increase and can be used as a marker for peri-prosthetic infection. In 
the same way, the ESR increases to its maximum peak on the 5th postoperative day and its 
values decrease to normal until 3 months (37–44)(45) 
 
In this way, having the values of acute phase reactants that suggest a peri-prosthetic 
infection, we will be able to analyze the algorithm proposed by the American Academy of 
Orthopaedic Surgeons for the diagnosis of peri-prosthetic infections. In which the cut-off 
value for CRP is 93mg/L and for ESR of 44mm/hr. with an 88% risk of infection. If we 
find both reactants increased above this figure for more than 5 days after the arthroplasty, a 
culture of synovial fluid can be taken to assess the leukocytes which, with a value of 12,800 
or more, have an 89% risk infection percentage. With both positive studies we can have the 
accurate diagnosis of peri-prosthetic infection in 100%. (46) 
 
Classification: 
 
Peri-prosthetic infections are classified according to the time of presentation of 
symptoms. The most recent classification stages infections in three areas: Early, acute 
hematogenous and chronic. Early infections are manifested during the first 3 months after 
surgery, the acute hematogenous infections with evolution of symptoms no greater than 3 
weeks, and the chronic infections persist for more than 3 months and require a different 
treatment. When it comes to early and acute hematogenous infections, debridement and 
retention of the implant are still aceptable treatments. (47) 
 
Biofilm in Prosthetic Implants 
 
Although biomedical implants such as prosthetics have revolutionized medicine, 
they have also increased the risk of infections; in fact, it is considered that infections are the 
most frequent and severe complicataions.(48) Orthopaedic implant infections, especially 
prostheses, are particularly problematic since they remain in the body. Orthopaedic 
infections related to the implant are primarily caused by Staphylococcus aureus and 
secondly, by Staphylococcus epidermidis.(49) 
 
In devascularized sites, implants act as a substrate for bacterial attachement and 
biofilm formation.(50,51). These biofilms require a large concentration of antibiotics for 
their elimination, typically at higher concentrations that can be achieved through systemic 
antibiotic administration (26). Debridement can physically removed most bacteria, but even 
with a thorough debridment technique some bacterial colonies can be established in poorly 
vascularized regions or on implants and result in infection recurrences.  This is why it is not 
recommended to apply osteosynthesis and endoprosthesis in newly debrided tissue.  
 
The mechanism of biofilm formation in smooth or coated implants has been broadly 
studied, determining the facilities that bacteria have for their adhesion in avascular implants 

with porous coatings, and how difficult or impossible it is to eliminate them from these 
surfaces.(52) 
 
Because antibiotic concentrations at sublethal doses cause persistence and resistance 
of the infection, the concentrations of the antibiotic to be administered as well as the 
method used must be taken into account. This is because infections in implants are located 
in avascular zones; therefore methods of antibiotic release at minimal inhibitory 
concentrations have been sought locally. 
 
Antibiotic Release: 
 
Polymethylmethacrylate (PMMA) has been used for many years as a local antibiotic 
release method, either in the form of spacers or in pre-filled beads.(10),(53)   
 
However, it has been shown that this method is not effective for the elimination of 
biofilm, since between 90 and 95% of the antibiotic remains trapped in the cement and only 
small amounts of antibiotic are released from the surface, releasing moderate 
concentrations. During the first hours after implantation, 90% of the pre-filled beads and 
50% of the spacers are covered with biofilms at the time of extraction associated with the 
induction of bacterial resistance by their limited antibiotic concentration.(23–26). Small 
colony variants (SCV) require up to 100 times more than minimal inhibitory concentrations 
and for pathogens embedded in the biofilm, up to 1000 times the minimum inhibitory 
concentrations (MIC) for their elimination. This suggests that neither the systemic 
antibiotic therapy nor the antibiotics released by PMMA are useful for the elimination of 
the biofilm. (54,55) 
 
In order to eliminate the residual biofilm, local antibiotic release is required to 
provide high concentrations of antibiotic for prolonged periods of time. Most of the related 
pathogens in bone infections are Gram-positive susceptible to Vancomycin; most of the 
Gram negative are susceptible to tobramycin, showing less cytotoxicity and adverse effects. 
(56) 
 
 
 

 
Risk Factors 
 
It has been proven that the non-modifiable risk factors of patients undergoing 
Articular Replacement Surgery increase the risk of infection rate. According to a meta-
analysis based on 14 studies from January 1980 to March 2014, the following were 
identified as risk factors for developing a peri-prosthetic infection: Body mass index, 
Diabetes Mellitus, corticosteroid therapy, hypoalbuminemia, rheumatoid arthritis, blood 
transfusion, presence of secretion in any wound, wound dehiscence, superficial infection in 
surgical site, coagulopathy, immunodeficiency, history of nosocomial infection, prolonged 
surgery time and previous surgery of the region. (57) 
 
Risk Factors 
Characteristics 
1 
Body Mass Index  
>40 kg/m2 
2 
Wound Drain, dehiscence or another 
surgical active infection 
Any active wound that is draining 
before the joint replacement  
3 
History of Nosocomial Infection 
Any infection acquired in the 
Hospital 
4 
Prolonged surgical time 
Greater than 120 minutes and 
every 15 minutes of extra 
surgery increases a 9% risk of 
infection. 
5 
Decompensated 
Type 
2 
Diabetes 
Mellitus 
HbA1C > 7 
6 
Serum albumin 
< 3.4 g/dl 
7 
Rheumatoid Arthritis 
In treatment or not. 
8 
Blood transfusion 
Transoperative Bleeding 
During the 24 hours after 
surgery. 
Greater than 1000cc 
9 
History of Prosthetic Surgery 
Prosthetic Revision Surgery or history 
of a knee or hip primary  prosthetic 
surgery 
10 
Immunosuppression 
Lymphocytes < 1,500 
11 
Malignancy 
History of any malignant tumor. 
12 
Corticosteroid Therapy 
>1 month of continuous 
treatment 
Table 1. Main non-modifiable risk factors for periprosthetic joint infections. 
 
There are other risk factors such as: age over 65 years, kidney failure, liver failure, 
smoking, drug and alcohol abuse, prolonged drainage, etc.; however, the fact that they are 
representative for an infection has not been corroborated. (58,59) 
 
Although there are multiple studies on periprosthetic infections, there is still no one 
that proves the percentage represented by each risk factor; however, it has been 
corroborated that these comorbidities have a significant risk factor for periprosthetic 
infections. (1) 

 
Calcium Sulfate Vs. PMMA 
 
Polymethyl methacrylate (PMMA) loaded with antibiotic has been used for a long 
time as a carrier and release method, either as a spacer or as beads, increasing the local 
levels of antibiotic in the surgical site. However, its limited clinical benefit has been 
proven. Once the antibiotics have been released from the nonabsorbable layer of cement, it 
becomes a foreign body susceptible to bacterial colonization and biofilm formation, which 
is why it is essential to perform a new surgical procedure for its extraction.(60–62). PMMA 
has a high setting temperatura wich means that thermosensitive antibiotics cannot be 
combined with it. 
 
Calcium sulphate as a vehicle for antibiotic release is completely absorbed within 4 
to 8 weeks, completely releasing the  full antibiotic load. Due to its low setting temperature, 
it has the potential to be mixed with thermosensitive antibiotic. As it is fully absorbed there 
is no residual material that can act as nidus for bacterial attachment and biofilm formation. 
Clacium sulfate also presents a minimal risk to damage components of joint prosthesis 
when implanted into or adjacent to the articulating surfaces. In  contrast, PMMA is 
designed as a cement for prosthetic implantation and this characteristics can be impaired by 
its combination with high quantities of antibiotic, pontentially leading to early loosening. 
 
 
 
Calcium Sulphate Vs. PMMA Comparison 
Features 
Calcium Sulfates 
PMMA 
Gradual 
release 
of 
the 
antibiotic 
YES 
NO 
Total 
release 
of 
the 
antibiotic 
YES 
NO 
Nidus 
for 
bacterial 
attachment 
NO 
YES 
Requires its Extraction 
NO 
YES 
Works with heat-sensitive 
antibiotics 
YES 
NO 
Serves as a spacer 
NO 
YES 
Effective for dead space 
management 
YES 
YES 
Table 2. Correlation between antibiotic loaded Calcium Sulfate versus PMMA. 
 
 
 

 
RESEARCH QUESTION 
 
Is there a difference in the incidence of periprosthetic infection in patients with risk factors 
and the application of prophylactic antibiotic loaded calcium sulfate versus patients with 
risk factors without prophylactic treatment? 
 
HYPOTHESIS 
 
 
H0 . There is no significant difference in the incidence of periprosthetic joint infection 
between patients who received local prophylaxis versus conventional prophylaxis. 
 
H1.- The incidence of periprosthetic infection in patients with non-modifiable risk factors 
and prophylactic application of antibiotic loaded calcium sulfate is lower than in patients 
without prophylactic treatment with calcium sulfate.  
 
JUSTIFICATION 
 
Medical Justification 
 
Peri-prosthetic infections, although rare, are devastating. They can occur at any time 
after the surgical treatment; however, most are diagnosed within the first 2 years after the 
surgical treatment. Once an infection occurs, the mortality in the person suffering from it 
increases from 2.7 to 18%, this far exceeds the mortality rate that occurs in patients who 
undergo a revision arthroplasty. 
 
A peri-prosthetic infection is not only overhelming for patients and doctors, but also 
health institutions. When a patient becomes infected, treatment costs are usually 4 times 
more expensive than the costs generated in the initial procedure. 
 
If a peri-prosthetic infection causes so much damage, it would be prudent to take 
action to prevent it. The truth is that there are various strategies developed by different 
national and international agencies to prevent and treat infections, and yet there are still 
cases of infection. 
 
 
 

 
Social Justification 
 
Peri-prosthetic infection has an incidence in the United States of America of 0.69% 
and 1.09% for total hip arthroplasty (THA) and 0.74% and 1.38% for total knee 
arthroplasty (TKA), respectively. The projection for the future is for these figures to 
increase, which would mean that the health system could be significantly affected. There is 
also a relationship between peri-prosthetic infections and mortality.(63)  
 
The Institute of Social Security for the State of Mexico and Municipalities 
(ISSEMyM, as in Spanish), is an institute that has a large population of beneficiaries with a 
diagnosis of osteoarthritis and hip fracture, and many of these patients will undergo 
articular replacement surgery. The purpose of this study is that these patients do not suffer 
from a peri-prosthetic infection, and therefore, avoid not only the human suffering, but the 
high expense that is generated when treating this pathology. 
 
OBJECTIVES 
 
General Objective:  
 
To compare the incidence of early periprosthetic infection in patients with non modifiable 
risk factors and prophylactic antibiotic loaded calcium sulphate (“Study” group) versus 
patients without antibiotic loaded calcium sulphate (“Control” group). 
 
Specific Objectives: 
 
- To know the incidence of early periprosthetic infection in patients with non-modifiable 
risk factors to present infection.  
 
- To create a Control Group and an Study Group for the application of antibiotic loaded 
calcium sulphate as a prophylactic treatment in patients with non-modifiable risk factors for 
peroposthetic infection. 
periprosthetic infection. 
 
- To perform statistical analysis for the control group and the experimental group. 
 
Secondary objectives: 
 
- Establish differences in the cost benefit of prophylaxis with or without antibiotic loaded 
calcium sulphate beads by length of hospital stay. 
 
 
 

 
PARTICIPANTS ELIGIBILITY CRITERIA  
Inclusion Criteria: 
 
- All patients who come to the Tlalnepantla Regional Hospital with hip or knee 
osteoarthritis and hip fracture that requieres joint replacement.  
- All patients who have any of the Non-Modifiable Risk Factors prior to surgery or during      
  transoperative period. (Table 1) 
- Patients entitled to the ISSEMyM 
- Patients over 60 years old (64) 
- Patients with a cardiopulmonary assessment prior to their surgical treatment 
- Patients who undergo primary non-cemented Hip and Cemented Knee Joint Replacement. 
- Patients who do not have an active system infection. 
 
Exclusion Criteria: 
 
- Patients who are not beneficiaries of the ISSEMyM 
- Patients who do not have the diagnosis of Hip or knee osteoarthritis 
- Patients under 60 years old (64) 
- Patients with hip fractures that requires an internal fixation. 
- Patients with active systemic infection 
- Patients with Renal or Hepatic Insufficiency 
- Patients who do not have any of the risk factors for periprosthetic infection. (Table 1) 
 
Elimination Criteria: 
 
- Patients that lose their validity of institutional rights and do not follow up the treatment. 
- Patients who die during the study due to other causes not related to the orthopedic 
procedure. 
- Patients who for any reason do not give continuity to the treatment or do not follow 
medical indications. 
 
 
 

 
METHODS AND PATIENTS 
Study Design 
This was a prospective, longitudinal and randomized controlled trial. The study was 
performed at the department of Orthopedics at The Hospital Regional Tlalnepantla 
(Mexico) and approved by the ethics and research committee.  
 
The eligibility criteria for this study were: being over 60 years of age, having one or 
more non-modifiable risk factors, patients who underwent for total hip or knee joint 
replacement between June 2019 and May 2020. The exclusion criteria taken into 
consideration were: Patients with an active systemic infection, kidney or liver failure, 
known allergies to vancomycin or cephalosporins. All patients who met the selection 
criteria were invited to be part of the study, detailing that they could have a systemic or 
local prophylactic therapy according to the group assigned to the roasting. Those who 
accepted signed a letter of informed consent agreeing to join the study. Apendix 1 
Patients were randomized with the randomizer app v0.2.6-beta and assigned into 
one of both control or study group. 
Subjects enrolled in the control group received a prophylactic dose of 750 mgs of 
cetriaxone 20 minutes before joint replacement surgery and every 8 hours for 24 hours. 
Regarding the patients assigned to the study group, none received parenteral antibiotic 
prophylaxis. At the operating room and before the final implantation of the prosthesis, the 
purified calcium sulfate beds impregnated with 3g of vancomycin were applied locally. For 
the local prophylaxis it was used: Stimulan Kit (Biocomposites Ltd, United Kingdom) 
which includes 10 cc (20 g) of calcium sulphate hemihydrate powder, a pre-mixing solution 
bulb, mould of 3, 4.8 and 6 mm sizes of beads and spatula. 3g of vancomycin powder was 
mixed with each 10 cc of calcium sulphate in the mixing bowl, after 30 seconds the 
resulting paste was applied to the moulds using the spatula and allowed to set for 10 to 15 
minutes. In hip joints the 3 mm beads were applied and pulverized on the previosly reamed 
acetabular cavity. For the proximal femur, the pearls were inserted into the canal and the 
final components were placed by impactation, ending the pulverization of the beads in the 
interface areas. The remaining beads were applied to the soft tissue around the prosthesis. 
Instead for the knee joint, the 4.8mm beads were applied inside the femoral and tibial canal, 
the remaining beads were placed into the soft tissue around the prosthesis. Antibiotic-
loaded polymethylmethacrylate cement was not used in any subject.  
After surgery, CRP and ERS biomarkers were analyzed at day 5 and weeks 4, 8, and 
12 to determine acute periprosthetic infection. A CRP > 93mg/L and ERS >44mm/h were 
the cutoff value for infection risk. If CRP were elevated alone or with ESR, then the 
synovial fluid were obtain and analyzed. A threshold of Leucocytes > 12,800 cells/μL 
and/or positive culture was defined as acute periprosthetic joint infection. The information 
obtained from patients is noted on the data collection sheet. Apendix 2 and 3 
The primary outcome of this study was to determine the relationship between 
prophylaxis with local calcium sulfate beads in patients with non-modifiable risk factors for 
PJI and its evolution without infection compared with a control group. The secondary 

outcome was to know the institutional economic cost according to the length of hospital 
stay.  
Prospectively recorder data included: patient demographics; biomarkers values 
before and after surgery, diagnosis and if it was knee or hip replacement, risk factor for PJI, 
Synovial fluid analysis, length of hospital stay, and the need for periprosthetic joint 
infection treatment. 
Statistical Analysis.  
According to our biostatistics department and the sample size determination 
estimated by STATS 2.0 Software, this trial requiered enrollment of  76 patients to obtain a 
statistically valid meaningful.  
The presence of periprosthetic infection in both groups was evaluated by chi-square 
and Lambda tests for dichotomous nominal and qualitative variables with longitudinal 
direction and relative risk test. Demographic variables were tested by central trend 
measures,  t-student for independiente continuous variables and chi-square for categorical 
variables. Statical analysis was performed using SPSS Statistics 26 IBM  software. A p 
value <0.05 was considered to reject the null hypothesis. 
 
Results. 
Eigthy seven subjects were enrolled to the study in the period between June 2019 to May 
2020, Four of them were excluded (all 4 patients lost institutional validity so postopertive 
follow-up was no obtain). A total of 83 patients were evaluated, for the female we obtained 
44 cases (53%) and for male 39 cases (46.9%).  We randomly assigned subjects in two 
groups for the longitudinal design study. All the patients had at least one of the main risk 
factors for presenting periprosthetic infection. Forty subjects (48%) were enrolled  for the 
control group and received conventional intravenous prohpylactic antibiotic therapy for a 
total of 24 hours.  For the study group 43 patients (51.8%) received local antibiotic therapy 
with calcium sulfate beads mixed with vancomycin during the surgery. An average age of 
77.3 years was found for the control group (61 to 90 years) versus 75.9 (62 to 89) years in 
the study group. BMI was the main risk factor found for both groups (16 patients 19.28%) 
follow by the decompensated type 2 diabetes (15 patients 18.07%). Both knee and hip 
prostheses were applied. A total of 38 knees (52.5% for control group versus 39.5% for the 
study group) and 45 hips were treated (47.5% and 60.5% for control and study groups 
respectively).  There was no difference in demographic variables for both groups p>0.05.  
Although the prophylactic treatment was applied in both groups, the presence of early 
periprosthetic infection was found in 37.3%. In 31 subjects enrolled to the control group, 
67.5% developed acute PJI, while the study group had 9.3%. Variable analysis identified 
that local prophylaxis with calcium sulfate beads compared to conventional prophylaxis, 
can further prevent the presence of acute knee or hip periprosthetic infection in patients 
with non-modifiable risk factors (p=0.022) with a 0.13 of relative risk . Lenght of stay was 
also shorter in the study group  at 4.6 days (range: 2-23 days) compared to 15.25 days in 
the control group (range: 2-32 days; p<0.001). 

 
DISCUSSION  
 
Our Health Mexico Institute, it's a representation of most hospitals in developing 
conuntries. In wich up to 800 patients a week, are attend for external consultation in the 
Orthopedic’s department. This is not exclusive to orthopedic services; as most of other 
specializations are over saturated. This problem is the result of lack of adequate 
management and control over chronic degenerative disorders. In this way, it has been 
observed that a high number of patients that have had joint replacement surgery but do not 
have an adecuate control of their chronic conditions, have .an increase risk of ingfection. 
This is due to risk factors that can not be measured, in the short or médium term. Despite all 
this; in many cases joint replacement surgery is needed, in order to give the patient a better 
quality of life. It has been demostrated that there’s an increase risk of infection in patients 
with unmodifiable risk factors(65–67)(68). Once the infection has been diagnosed, the 
treatment that follows is complex and not without complications; in patients who also have 
risk factor or comorbidities, the treatment becomes even more difficult and expensive.  
 
In this study we have found that the local antibiotic prophylaxis can influence to a 
greater degree in the prevention of periprosthetic infections, mainly in patients with non 
modifiable high risk factors sucha as: high body mass index (BMI); as well as lack of 
metabolic control of type 2 diabetes.(69–71) The application of local antibiotics has been 
studied in several occasions, yet the direct application of bone prosthesis interphase hasn’t 
been well established. In this study however, we have managed to identified benefitial 
results in the application of local antibiotics in relation to the prosthesis components and 
the surrounded tissue. 
 
 
Periprosthetic infections continue to be a problem with devastating consequences 
for the surgeon, the patient and the health system. Based in our study, medicated calcium 
sulfate beads as a local release method of prophylactic antibiotic therapy, represents a 
possibility in the reduction of 86.6% the presence of periprostethic infections in patients 
with non-modifiable risk factors and their association with complications and economic 
cost. Unfortunately, this study was based on patients with the presence of acute 
periprosthetic infection, and there are no long-term results yet. However, it would be 
expected to have similar results. Likewise it was performed both in knee and hip prosthesis, 
so a deeper study is required for each type of prosthesis and each risk factor. 
 
Conclusions 
 
Medicated calcium sulfate beads as a local antibiotic prophylaxis method in patinets 
with non-modibiable risk factors undergoing hip or knee replacement adds adecuate 
protection, reducing the risk of developing acute preiposthetic joint infection. However, 
more studies are required to corroborate these results in a long term basis.  
 
 
 

 
GRAPHS AND TABLES 
 
 
 
 
 
 
 
 
0.00%
20.00%
40.00%
60.00%
80.00%
100.00%
120.00%
Control Group
Study Group
Total
PJI 
With Infection
Without Infection
0
2
4
6
8
10
12
14
16
18
Control group
Study group
Total
Lenght of hospital stay 

 
Table 3. Outcomes and P Value for non modifiable risk factors associated with PJI 
Variable/Groups
Control group n= 40
Study n=43
Total  n= 83/  100%
p Value
Age
77.3 years (61-90)
    75.9 years (62-89)
76.6 years +/- 8.5
0.2
Gender
0.721
Male
18 (45%)
21 (48.8%)
39 (46.9%)
Female
22 (55%)
22 (51.2%)
44 (53%)
Non modifiable risk factors
%
%
%
0.427
BMI
6
15
10
23.26
16
19.28
Wound Drain, dehiscence or surgical activ
4
10
2
4.65
6
7.23
H istory of nosocomial infection
3
7.5
3
6.98
6
7.23
Prolonged surgical time
4
10
3
6.98
7
8.43
Decompensated Type 2 Diabetes Mellitus
7
17.5
8
18.60
15
18.07
Serum Albumin
4
10
1
2.33
5
6.02
Rheumatoid Arthritis
5
12.5
2
4.65
7
8.43
Blood transfusion Transoperative Bleeding
5
12.5
7
16.28
12
14.46
H istory of prosthetic surgery
1
2.5
3
6.98
4
4.82
Immunosuppression
1
2.5
0
0.00
1
1.20
Malignancy
0
0
3
6.98
3
3.61
Corticosteroid Therapy
0
0
1
2.33
1
1.20
Joint Prosthesis
0.236
Knee
21 (52.5%)
17 (39.5%)
38 (45.7%)
H ip
19 (47.5%)
26 (60.5%)
45 (54.3%)
Lenght of hospital stay
15.25 days (2-32 days)
4.6 days (2-23)
9.77 days +/- 9.37
<0.001
Periprosthetic Joint Infection
0.022
With Infection
27 (67.5%)
4 (9.3%)
31 (37.3%)
Without Infection
13 (32.5%)
39 (90.7%)
52 (62.7%)
 
 
 

 
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Appendix 1 
INFORMED CONSENT FORM 
 
HOSPITAL REGIONAL TLALNEPANTLA ISSEMYM 
Place:  TLALNEPANTLA ESTADO DE MEXICO 
 
Date: 
 
Name: 
 
According to the Official Mexican Law NOM-004-SSA3-2012, of the medical clinical file, published in the 
Official Gazette of the Federation, this written and signed document is presented by the patient and / or 
legal representative, by means of which he accepts, under due information, the risks and benefits 
expected.  
As a patient I agree to participate in the research protocol entitled: Application of antibiotic loaded in 
calcium sulfate beads as prophylaxis of patients with risk factors for peri-prosthetic infection. Where I am 
explained possibility of being randomized in the study group, calcium sulfate loaded with 3 gr of 
vancomycin will be applied during the prosthetic application as the interface between the acetabulum and 
the metal cup and between the femoral canal and the porous stem in the hip replacement, for the 
articulation of the knee, calcium sulfate will be applied in the femoral and tibial canal and in the soft ridged 
tissue. For the control group, the use of 1 gr of ceftriaxone 30 minutes before surgery is used as a protocol 
for antibiotic prophylaxis. I DECLARE: 1.- That I have received the invitation to participate as a research 
subject without having been subjected to inappropriate influences or intimidation. 2.- I know the reasons 
why I was elected, that my participation is voluntary and that I have the freedom to refuse and withdraw at 
any time without any penalty. 3.- that the purpose of the project has been explained to me and that I have 
enough information about the risks and benefits during my procedure. 4.- I have understood the possibility 
of anaphylaxis to the medication, risk of peri-prosthetic infection, and that I may require complementary 
treatments due to problems inherent to the medical practice, as well as the reasonable benefits that can 
be expected. 5.- I can access information about the results obtained during the study and that I will not 
receive any remuneration for participating in this study other than the reasonable benefits explained from 
the handling. 6.- The responsible researcher has explained to me that I will not be identified in the 
presentations or publications that derive from this study and that the data related to my privacy will be 
handled confidentially. 
Agree  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
NAME AND SIGNATURE 
 
 
 
 FIRST WITNESS NAME AND SIGNATURE 
 
 
 
 
 
 
 
 
 
SECOND WITNESS NAME AND SIGNATURE  

Apendix 2 
 
Name 
 
ISSEMyM ID: 
 
Age: 
 
Surgery Date 
 
Diagnosis 
 
Treatment  
 
Another diagnosis 
 
 
Random group 
 
Risk Factors  
 
 
 
 
CRP 
 
Preop 
5 days 
4 weeks 
8 weeks 
12 weeks 
 
 
 
 
 
ESR 
Preop 
5 days 
4 weeks 
8 weeks 
12 weeks 
 
 
 
 
 
Leucocytes 
in 
sinovial fluid  
 
Tissue or sinovial 
fluid culture 
 
Periprosthetic 
joint 
infection 
(Yes/No) 
 
 
 
 

 
Apendix 3 
Economics 
 
 
 
 
 
 
               Study  
 
       Control 
Time in surgery room  
 
 
Lenght of hospital stay in days