USING CLINDAMYCIN IN BONE CEMENT:

This question came up in a discussion regarding the treatment of osteomyelitis (bone infections) and/or treatment of peri-prosthetic total joint infections caused by anaerobic bacteria.  The experience using Clindamycin (Cleocin) to impregnate bone cements has been limited due to its liquid (non-miscible) form and the availability of more user-friendly agents to treat anerobes.  You can, however, whip liquids (and therefore drugs) into a freshly mixed batch of polymethyl-methacrylate (PMMA) and capture enough agents to effectively work in prophylaxis but (probably) not in treatment for active infection. References include: JBJS,2005; 87A: 268-272;  J Arthroplasty Vol.24 (1); 125-130.
My preference:  Powdered Claforan (Cephotaxime): covers Bacteroides species (including Bacteroides fragilis), Clostridium species, and anaerobic cocci (including Peptostreptococcus species and Peptococcus species) and Fusobacterium species (including F. nucleatum).  If you are dealing with a Penicillin allergy you may be limited to this drug.  But, if not, these derivatives can be used: Oxacillian, Zosyn, Primaxim (Imipenem and Cilastatin) and other  -penems in powder form.

Methods:  The amount you mix, per pack of cement will, of course, vary according to use of the depot and the pathogens treated ( ie; 3gr Vanc + 3.375gr Zosyn ).   Here are the rules: 1) first mix dry ingrediants and then add the monomer;  2) Active bone infections:  25-30cc of finely-sifted, antibiotic powder /pk /PMMA;  it is always better to make 0.8cm antibiotic-beads than to use large blocks of antibiotic-cement due to their superior surface area /elution kinetics. 3) Prophylaxis:  I usually mix around 12-15cc antibiotic /pk /PMMA (variable/depending).

Bone Infection Following Treatment for Open Fracture Injuries

            Open fractures create “the perfect storm” for infection to complicate injury:  the initial wound is contaminated and injury to soft tissues potentiates an on going exposure to pathogens (bacteria); surgical implants (plates, screws and rods) and dead bone fragments grant ‘safe-haven’ to proliferating microbes; ischemia, dead space and foreign bodies impede local immunity and the delivery of antibiotics; shock, crush-injury and pre-existing health conditions compromise the host response.    As a result, osteomyelitis (bone infection) and fracture non-union are the most common complications following treatment for open fractures.  Once a bone infection is diagnosed, the goals of treatment are three-fold:  timely intervention; creation and maintenance of a live, clean, manageable wound; adequate and durable fracture fixation.   

Strategies to Minimize Complications:

1) After treatment for an open fracture, follow patients closely: culture all wound drainage; serially check CBC, ESR and CRP values; manage wound-healing disturbances aggressively, especially in compromised hosts (B-hosts).  

2) Treat the bone infection as either an ‘early’ or a ‘late’ process, based on the time lapsed since index-contamination (early < 4weeks).   http://www.osteomyelitis.com/pdf/treatment_protocol.pdf

3) Base antimicrobial therapy on multiple tissue specimens and pathogen sensitivities and use bactericidal antibiotics whenever possible.

4) Reverse all amenable, host co-morbidities and optimize the host response throughout treatment. http://www.osteomyelitis.com/pdf/staging-paper.pdf

5)  Select ‘low-risk’ methods when treating ‘high-risk’ patients ( see  Cierny III, G., DiPasquale, D. Treatment of Chronic Infection. in the Symposium: Extremity War Injuries: state of the art and future directions. JAAOS , Vol 14, No. 10, 105-110, October 2006. 

Jordan,

Dr. Cierny has not written an article specifically addressing acid-fast bacterial(AFB), peri-prosthetic infections. In our experience, the type of organism is not indicative of the prognosis so long as there is adjunctive treatment with a bactericidal antimicrobial.

There have only been 5 Mycobacterial(AFB)infections in our 1996-2009 series of 194 infected total joint arthroplasties: 1 total shoulder; 1 total elbow; 2 total hips; 2 total knees.  4 of these were successfully treated(80%).  The one treatment failure relapsed with a Oxacillin-resistant, Staphylococcus epidermidis(ORRE vs MRSE)—– all final cultures and permanent histological sections(pathology) were negative for the organism, Mycobacterium abscessus(AFB).

The experience is more extensive in our registry of 2013 cases of chronic osteomyelitis excluding those cases associated with a total joint arthroplasty.  Here, the success rate is 92% (33/36).

http://www.osteomyelitis.com/html/treatment_results4.html

http://www.google.com/search?hl=en&q=Staphylococcus+epidermidis.++&btnG=Google+Search&rlz=1W1GGLJ_en&aq=f&oq=&aqi

Sincerely,

G. Cierny,MD  /Orthopaedic Infection, Reconstruction and Oncology 

—–Original Message—–
From: jordan
Sent: Tuesday, August 18, 2009 8:31 AM
To: George Cierny
Subject: Response from: Osteomyelitis.com

The information below has been submitted via the “Quick Contact – Osteomyelitis.com” form located at:

http://www.osteomyelitis.com/html/prosthetic.html 

——————————————————————–

Greeting:         jordan

Home Phone:       Phone

Comment:          Has Dr Ceirny written any articles on AFB infections in total joint replacements?

——————————————————————–

Westin Hotel; San Diego, CA 

MEETING HIGHLIGHTS:

-Diagnosis of Peri-prosthetic Total Joint Infection: The role of a Simple, Yet Unrecognized, Enzyme.  J. Parvizi, MD; Rothman Institute; Philadelphia, PA

Testing for a leukocyte esterase enzyme in neutrophils is a valuable addition to the diagnostic armamentarium of prosthetic joint infection.  The use of the reagent strips used to test urine samples had a sensitivity of 100% and specificity of 88%.

-Peri-prosthetic Infection with Propronibacterium Acnes: Different from Conventional Arthroplasty Infections.  E.Yu, MD: Mayo Clinic; Rochester, MN

P. acnes PPI have non-specific symptoms (pain=76%) and radiographic findings at presentation. 29 patients (20 hips; 9 knees): ESR <25 in 46% and path negative for acute inflammation in >60%.  P. acnes a common organism to cause re-infection in the series (43%).

-Prosthetic Joint Infection in Patients with solid Organ Transplantation. A. Duggal, MD:  Cleveland Clinic, Cleveland, OH

13 patient series disclosing 62% poly-microbial infections.  Seven patients (50%) had a recurrence of PPI in the same joint and 4 (57%) with a different pathogen altogether. Organisms included Enterococcus, Streptococcus, Staphylococcus, Klebsiella, Acinetobacter, Campylobacter and fungi.   Three of the infections were  delayed (late) beyond 2 years.

-Microbiology of Bone and Joint Infections in Injecting Drug Abusers. C. Zalavras, MD: USC, Los Angeles, CA.

Pathogens predominantly caused by Gram-positive bacteria with an increase of ORSA(MSSA).  Incidence of Pseudamonas is down to 7% while  but anaerobes were up (13%).

-Impact of sarA on Antibiotic Susceptibility in Staphylocococcal Biofilm-Associated infections. M. Smeltzer, MS: Univ. Arkansas; Little Rock, AR.

The purpose of the experiments were to assess the impact of the sarA locus on antibiotic susceptibility in the specific contest of a Staphylococcus aureus biofilm.    When the Staphylococcal accessory regulator (sarA) was altered, there was impact on the susceptibility of established Staphylococcus aureus biofilms to treatment with Daptomycin in vivo.  This effect was more notable in the CA-MRSA than the MSSA colonies.

-Aseptic vs Septic Total Hip Arthroplasty Revisions: Comparing the Results.  C. Romano, MD: Instituto Ortopedico Galeazzi; Milan, Italy.

Two-stage revision for infected hip prostheses, using a preformed, antibiotic-loaded cement spacer and un-cemented revision prosthesis, offers a success rate equivalent to non-infected revisions, at higher financial and physical costs (complications). 

-Comparing OsteoSet and Stimulan as Antibiotic-loaded, Calcium Sulfate Beads in the Management of Musculoskeletal Infection.  G.Cierny, D. DiPasquale: REOrthopaedics; San Diego, California. 

A series of 28 CASO4 antibiotic-loaded bead implantations to treat deep, musculoskeletal infections (osteomyelitis (bone infections), infected non-unions, infected total joint arthroplasties, infected fractures): 14 OsteoSet (Wright  Medical, Memphis) and 14 Stimulan (BioComposites, NC).  The out comes for the two groups were equal save for a 29% incidence of wound healing disturbances in the OsteoSet group vs 0% in the Stimulan Group.  The OsteoSet kits were user  friendly with a limited antibiotic carriage capacity; the Stimulan kits were awkward to use but with considerable versatility regarding antibiotic carriage, including Amphoteracin-B, Azithromycin and Clindamycin.

-Pliable Antibiotic in Situ Loaded Chitosan Film for Infectyion Prevention: A Preliminary In-vitro Characterization Evaluation.  J Keaton, WO Haggard: Univ. Memphis Biomed. Engineering, TN

The ability of 80LA film variations to adhere to fracture fixation alloys and elute large amounts ABx shows chitosan film’s potential for traumatic injury infection    prevention.  ABX activity against Staphylococcus aureus was successfully shown to be unaffected by the film variations, loading, and elution processes in a 72 hour period.

-A Nano-therapeutic Approach to Combating Staphylococcus aureus Biofilms-Associated Infection.  M Smeltzer, MS: Univ. Arkansas; Little Rock, AR.

A preliminary step toward developing integrated nano-medicine, which combines nano-therapeutic with simultaneous nano-diagnositics for guiding and optimization of thermal-based laser treatment.  The paper demonstrated that this photothermal (PT) technique is a powerful tool that can be used to monitor thermal and accompanied effects at broad temperature ranges from a few degrees (diagnostics) to several hundred or thousand degrees (therapeutics). 

-We Haven’t Yet Defeated the Biofilm: Diagnosis and Vaccine Development.  M. Shirtliff, PhD: Univ. Maryland; Baltimore, MD

Targeting single-locus capsular and biofilm vaccines have not worked due to transient and non-uniform expressions.   Multi-locus vaccines now show promise.   “Partners in Slime” - Staph gains access to host’s micro-circulation by attaching to epithelial-penetrating hyphae of Candida species; questions raised as to implications regarding colonization /decolonization protocols.