George Cierny, MD; REOrthopaedics in San Diego

In acute pediatric osteomyelitis  and osteomyelitis of the spine (verbetral osteomyelitis; sacroiliitis) in all ages,  surgery is not always necessary to affect cure.  In other forms of acute osteomyelitis  (infection following open fracture; surgical site infections following trauma or reconstructive surgery) and nearly all forms of the chronic disease, treatment will have to combine various aspects of surgery (with antibiotics) to result in cure .
The treatment of a refractory (chronic) osteomyelitis is governed by its pathophysiolgy —– it is a ‘biofilm disease’.    Unlike the mobile (planktonic), environmentally sensitive microbes found in an acute infection, chronic wound pathogens are sessile and resilient, transformed into colony-forming units by environmental triggers (quorum-sensing) and the successful attachment to ‘unprotected’ surfaces within the wound (inert materials; non-viable tissues or organisms, etc.).    Thereafter, individual cells become colony-forming units that mature (2-4 weeks) to secrete and maintain a mucopolysaccharide “slime” that protects them from host defenses and the penetration of most antimicrobial agents .   To cure this biofilm infection, a LIVE, CLEAN WOUND is paramount: the biofilm-colony its attachment surfaces must be completely excised.

The type of surgery will depend on the duration of the infection (acute or chronic), the contents of the wound (extent of necrosis; substrate surfaces), the anatomic site, the health and well-being (impairment) of the host, and the experience of the healthcare team.

However, surgery, as a form of treatment, is not available to everyone. Patients who are very ill may not be able to endure the extensive surgery and recovery. In these cases, doctors may use antibiotics for long periods in an attempt to suppress (rather than cure) the infection.  Then, if the infection persists and, again, threatens the patient’s well-being, lesser morbid procedures, such as amputation of all or part of an infected limb, may be necessary.  

Surgical treatment options  – Drain the infected area: Opening up the area around the infected bone allows the surgeon to drain any pus or fluid that has accumulated in response to the infection.  This is usually applied in the acute setting to decrease strain on host defenses and amplify the effects of antibiotics.  Remove the attached, biofilm-colony:  In a procedure called debridement, the surgeon removes the diseased bone and tissue. In some cases, foreign objects, such as surgical plates or screws, used in previous surgeries, may also be removed. Restore the bone and soft-tissue envelope: Your surgeon may fill any empty space left by the debridement procedure with a piece of bone or other tissue, such as skin or muscle, from another part of your body. Sometimes temporary fillers containing antibiotics (antibiotic depots) are placed in the space until the infection is cured and the patient is healthy enough to undergo a definitive reconstruction. Bone grafts and tissue flaps help the body recruit new blood vessels into the site and form new bone.  Protect against instability: Immediately following debridement, the surgeon may use an external fixatation device (external fixator) to hold and protect the bone from further injury.  This method limits the amount of implanted, foreign material (metal) in the still-contaminated wound by attaching thin wires or pins (that pass through the limb) to a frame positioned around the limb (outside the skin).  The fixator can be the only method used throughout treatment or, after a course of local antibiotic therapy, replaced with internal methods of fixation such as metal plates, rods or screws.

PREVENTING HOSPITAL ACQUIRED INFECTIONS:   The translation of basic epidemiologic evidence into successful prevention has led to several successes in hospital-acquired infection prevention research over the past decade.  First is the use of alcohol-based hand rubs in clinical practice.

I.  Hand Hygiene:  Before the past decade, the major method of decontamination of the hands was the use of soap and water. The limitations of this procedure included the time it took to do, the number of sinks and the location of sinks in the hospital defined the optimal adherence to policy, and repeat use of detergents can be very irritating to the skin.

In 2002, the Centers for Disease Control and Prevention [CDC] through the Healthcare and Infection Control Practices Advisory Committee firmly established alcohol-based hand rubs at the center of hand hygiene practices, recommending them for routine decontamination of hands in all clinical situations except when the hands are visibly soiled.    Application of the rub takes seconds, the compounds are non-irritating and the dispensers are small, inexpensive and accessible wherever needed.  By 2008 84% of all US hospitals surveyed indicated that they had adopted alcohol-based hand rub and number of studies have shown dramatic increases in adherence to hand hygiene.  - Mody L, et al; Adoption of Alcohol-Based Handrub by United States Hospitals: a National Survey. Infect Control Hosp Epidemiol., 2008; 29:1177-1180.

II. Central Line catheter infections:  In the 2000s, there were 2 separate reports of large collaborative regional demonstration projects that focused on improved implementation of existing recommendations to prevent central line-associated blood stream infections (CLABSI) among patients in intensive care units (ICUs), first in southwestern Pennsylvania (2005) and then in Michigan (2006). Both studies demonstrated ~70% reductions in CLABSI rates across a wide variety of facility and ICU types, suggesting that the preventable fraction of these infections was perhaps much larger than we had originally thought.  The protocol was a 5-step process:  1) hand hygiene by the person inserting the device.  2) maximal barrier precautions.  3) chlorhexidine gluconate for antisepsis applied to the site of the insertion.  4) avoidance of femoral central line insertion.  5) removal of the central line as soon as possible /when no longer needed.

The results of these 2 studies have changed expectations of CLABSI prevention programs. The earlier single-center reports were viewed by many as somehow aberrant, the result of special circumstances and/or resources that could exist only in those particular, reporting facilities. These regional studies demonstrated that better implementation of existing recommendations can have a major impact across a wide spectrum of hospital settings —– dramatic success was possible, and not just under special circumstances.

III. DECOLONIZATION OF PATIENTS: Another innovative advance is the role of “source control” in preventing infection, particularly with the use of chlorhexidine bathing of patients. Based on data suggesting that colonization of a patient’s skin is an important source of spread for epidemiologic imported bacteria, it was hypothesized that daily bathing with a skin antiseptic (chlorhexidine gluconate) would decrease the burden of the patient’s skin contamination, indirectly decrease contamination in the environment, decrease transmission by healthcare worker, and play a role in decreased transmission of resistant pathogens and the incidence of both surgical site infections and CLABSI.  Today, data strongly suggest that daily chlorhexidine bathing can significantly reduce contamination of the patient’s skin, the environment, and healthcare workers’ hands, and an impact on methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococcus (VRE) acquisition has been documented.  - Barta R, Cooper BS, Whitely C, Patel AK, Wyncoll D, Edgeworth JD.  Efficacy and limitation of a chlorhexidine-based decolonization strategy in preventing transmission of methicillin-resistant Staphylococcus aureus in an intensive care unit. Clin Infect Dis. 2010;50:210-217.

Discussion: One area of controversy is the role of active surveillance, or what the value is of actively screening patients for MRSA.  . Most of the studies done in the past were typically small, single-institution studies, and often with quasi-experimental, pre- vs post- design. The results from those studies leave the conclusions open to interpretation and raise the issues of potential confounding or bias. With that said, even more rigorously done, recent studies have come to different conclusions.   Clearly, more work needs to be done.  - Harbarth S, Fankhauser C, Schrenzel J, et al. Universal screening for methicillin-resistant Staphylococcus aureus at hospital admission and nosocomial infection in surgical patients. JAMA. 2008;299:1149-1157. CONCLUSION: A universal, rapid MRSA admission screening strategy did not reduce nosocomial MRSA infection in a surgical department with endemic MRSA prevalence but relatively low rates of MRSA infection. – Robicsek A, Beaumont JL, Paule SM, et al. Universal surveillance for methicillin-resistant Staphylococcus aureus in 3 affiliated hospitals. Ann Intern Med. 2008;148:409-418.  CONCLUSION: The introduction of universal admission surveillance for MRSA was associated with a large reduction in MRSA disease during admission and 30 days after discharge.

IV. Catheter-Associated Urinary Tract Infections:  Wald and colleagues  looked at catheter-associated UTIs [urinary tract infections] — morbidity and mortality associated with the device.  There is good evidence that getting the catheter out by postoperative day 2 makes a real difference. – Wald HL, Ma A, Bratzler DW, Kramer AM. Indwelling urinary catheter use in the postoperative period: analysis of the national surgical infection prevention project data. Arch Surg. 2008;143:551-557.

IF YOU HAVE DIABETES, A JOINT REPLACEMENT OR ARTHRITIS…. YOU’RE AT INCREASED  RISK FOR A BONE INFECTION?  George Cierny, MD, and Doreen DiPasquale, MD; *BottomLine Health, 2010; Vol 24(3), pp9-11

* Bottom Line/Health interviewed George Cierny, MD, and Doreen DiPasquale, MD, physician-partners at REOrthopaedics in San Diego.  Dr. Cierny is an international lecturer in orthopedic surgery who has published more than 100 scien­tific papers and/or book chapters in the field of musculoskeletal pathology and infection. Dr.Di­Pasquale, an orthopedic-trauma surgeon, is former resi­dency program director at George Washington University in Washington, DC, and National Na­val Medical Center in Bethesda, Maryland.

—————- When most people think of bone problems, broken bones and osteoporosis (re­duced bone density and strength) come to mind. But our bones also can be the site of infections that can sometimes go unrecognized for months or even years. This is especially the case if the only symptoms of bone infection (a condition known as osteo­myelitis) are ones that are commonly mis­taken for common health problems, such as ordinary back pain or fa­tigue. What you need to know…

ARE YOU AT RISK? Older adults (age 70 and older), people with diabetes or arthritis and anyone with a weakened immune sys­tem (due to chronic disease, such as cancer, for example) are among those at greatest risk for osteo­myelitis.   Anyone who has an artificial joint (such as a total hip replacement or total knee replacement) or metal implants attached to a bone also is at increased risk for osteomyelitis and should discuss the use of anti­biotics before any type of surgery, including routine dental and oral surgery. Bacteria in the mouth can enter the bloodstream and cause a bone infection.

TYPES OF BONE INFECTIONS: Before the advent of joint-­replacement surgery, most bone in­fections were caused by injuries that expose the bone to bacteria in the en­vironment (such as those caused by a car accident) or a broken bone…or an infection elsewhere in the body, such as pneumonia or a urinary tract infection, that spreads to the bone through the bloodstream. Now: About half the cases of osteo­myelitis are complications of surgery in which large metal implants are used to stabilize or replace bones and joints (such as in the hip or knee).   

Osteomyelitis is divided into three main categories, depending on the origin of the infection… Blood-born osteomyelitis occurs when bacteria that originate else­where in the body migrate to and in­fect bone. People with osteoarthritis or rheumatoid arthritis are prone to blood-borne infections in their af­fected joints due to injury to cells in the lining of the joints that normally prevent bacteria from entering the bloodstream. Contiguous-focus osteomyelitis oc­curs when organisms— usually bacte­ria, but at times fungal species —infect bone tissue. These cases usually occur in people with diabetes, who will often de­velop pressure sores on the soles of their feet or ­buttocks due to poor cir­culation and impaired immunity.   Post-traumatic osteomyelitis: Trau­ma or surgery to a bone and/or sur­rounding tissue can open the area to bacteria and other microbes. The use of prosthetic joints, surgical screws, pins or plates also makes it easier for bacteria to enter and in­fect the bone.  Important: any of the three types of bone infections described above can lead to chronic osteomyelitis, an initially low-grade infection that can persist for months or even years with few or no symptoms. Eventu­ally it gets severe enough to liter­ally destroy bone. Left untreated, the affected bone may have to be amputated.

DIFFICULT TO DIAGNOSE – When osteomyelitis first develops (acute osteomyelitis), the symptoms —such as pain, swelling and tender­ness—are usually the same as those caused by other infections. If the initial infection is subtle (low-grade) or doesn’t resolve completely with treatment, it can result in chronic osteomyelitis. In this case, you may have no symptoms or symp-toms that are not specific.  For example, some one who has had surgery might blame discomfort on delayed recovery, not realizing what they have a bone infection.  A surprising finding: When we stud­ied the histories of more than 2,000 osteomyelitis patients, we found that most of those with chronic infections had relatively little pain from the in­fection itself. About 28% of those who required surgery for infection had normal white blood cell counts—suggesting that, over time, the body adjusts to lingering infections.  If a doctor suspects that you may have osteomyelitis because of chron­ic pain…swelling…possibly fever…fatigue…or other symptoms, he/she will usually order special laboratory tests that detect the formation of an­tibodies and/or cellular signaling compounds. If the results indicate the presence of infection, he/she may then order an X-ray, a magnetic reso­nance imaging (MRI) scan or a nuclear scan(bone scan). These and other imaging tests can readily detect damaged­ bone tissue and re­veal the presence of infection.

BEST TREATMENT OPTIONS   About 60% to 70% of people with acute osteomyelitis can be cured with antibiotics (or anti­fungal agents, if a fungal infection is present) if treat­ment begins early enough to prevent the infection from becoming chronic. In these cases, patients exhibit symp­toms…test positive for infection…and readily respond to drug treatments. Most patients can be cured with a four- to six-week course of antibiotics. Fungal infections are more resistant to treatment—antifungal drugs may be needed for several months.

For chronic osteomyelitis, surgical debridement (the removal of dam­aged tissue and bone using such in­struments as a scalpel, dental burrs and/or chisels) usually is necessary. Reasons: dam­aged bone can lose its blood supply, die and remain in the body without living cells or circu­lation. Such “dead bone” is invulnerable to the effects of antibiotics and provides safe haven to organisms attached to its surface.  To address this, the surgeon, after debridement, may insert a slow-release antibiotic depot (antibiotic beads) that release antibiotic for up to a month. This approach can increase drug concentrations up to 100 times more than oral antibiotic therapy and help to eliminate the sequestered microorganisms.   Using these and other innovations, the REOrthopaedics  center in Southern California now posts an overall success rate of 95%.    Nevertheless,  up to 6% of patients who are otherwise healthy may require a second or even a third operation to completely cure the infec­tion;  and, iIn patients suffering from diabetes or oth­er disorders affecting wound healing (compromised hosts) , the percentage may be as high as 25%.    To improve your chances of a full recovery from chronic osteomyeli­tis following treatment: eat well, maintain healthy blood sugar levels, stay active after treat­ment (to promote blood circulation, prevent blood clots and help main­tain an appetite) and don’t use to­bacco products.

_{Copyright © 2009 by Boardroom Inc., 281 Tresser Blvd., Stamford, Connecticut 06901-3229.                          www.BottomLineSecrets.com}

Article:

EARLIER DEBRIDEMENT AND ANTIBIOTIC ADMINISTRATION DECREASE INFECTION:   Maj. Brown KV, Walker JA, Cortz DS et al.  J. Surg. Ortho.p Advances, 2010;  Vol 19(1): 18-22.    Goals: ascertain the effects of 1) earlier debridement (debridement alone or in combination with locally delivered antibiotics) and 2) the use of local antibiotic-depots on bacterial load following contamination of open fractures.  A contaminated, critical sized, rat femur, defect model was used.  Results: early debridement and early administration of local antibiotics resulted in lower bacterial loads in bone.  There was a significant increase in the rate of infection between 2 and 6 hours and a further increase between 6 and 24 hours when treatment was limited to debridement (alone) as well as when debridement was combined with local antibiotics.  Treatment with local antibiotics resulted in a significant reduction in infection at 2 and 6 h hours compared to debridement, alone.          

Dr. Cierny’S  comments:  Surgical antibiotic prophylaxis refers to the administration of antibiotics to patients without clinical evidence of infection in the operative field.  The objectives of prophylaxis are to prevent naturally occurring organisms in one site from proliferation in a normally sterile site; to prevent organisms contaminating a normally sterile site from producing diseases; and to prevent infection by exogenous organism.  In order to achieve this goal, the surgeon must recognize the high-risk patient, operate in an effective and efficient manner, and keep abreast of local hospital flora and sensitivity patterns.  Antibiotic prophylaxis is indicated in the surgical patient when there is an unacceptable incidence of infection or when the incidence of infection is low but such an infection would be devastating or lethal.  Prophylaxis accounts for approximately 30% of the antibiotic administration on surgical services in the United States.  In most instances, these antibiotics are not justified and may lead to multiple problems, including the selection of resistant organisms.  However, when the theory and practice of surgical antibiotic prophylaxis are correctly applied, the patient benefits.

            The pathogenesis of a surgical wound infection lends itself to a rational approach to surgical antibiotic prophylaxis.  The first step is bacterial contamination of surgically manipulated tissue.  Bacterial contamination, a component of every surgical wound, arises from two sources: exogenous contamination from the operative theater; or endogenous contamination from the skin, respiratory, or urogenital tracts of the patient.  Whether or not the bacterial contamination produces infection depends on the number and the virulence of the organisms, the adequacy of the patient’s defenses, and the condition of the disrupted (injured) tissue.

The first response to surgical injury and subsequent bacterial contamination is local inflammation.  Small vessels leak plasma, and leukocytes emerge in response to local leukotactic substances, migrate into the contaminated area, and begin phagocytosis.  Inflammation continues, wound induration develops, local macrophages and vascular components proliferate, and the stage is set for wound maturation.  The early local inflammatory phase is virtually identical to what is called the “decisive period” as defined by Burke (see below).  If inflammation is not appropriate and phagocytosis is overwhelmed, the patient will develop an infection.  Necrosis, ischemia, hemorrhage, and the presence of debris and/or foreign bodies impair the local host-defense mechanisms and decrease the number of bacterial organisms required to cure infection. The overall integrity of the host is important because a compromised host is at increased risk for infection. 

If an appropriate antimicrobial agent is present in adequate concentrations, a wound infection in the contaminated tissue is less likely.  The antibiotics must be in the tissues during the early, “decisive period” to effectively present bacterial invasion and proliferation.  If given later, when the bacteria are well established, the antibiotics will have no prophylactic effect.  Similarly, if the compromised host can be protected with prophylactic antibiotics until the local defense mechanisms are capable of eradication local bacterial invasion, the subsequent stages of wound healing can proceed normally.

The concept of a “decisive period” was first recognized when Burke (1961) administered an anti-Staphylococcal antibiotic one to three hours after inoculation of S. aureus into the dermis of a guinea pig model …. early antibiotic administration would reduce the size of the lesion.  However, if the anti-Staphylococcal antibiotic was given three hours after dermal infection, the antibiotic was less effective in reducing the size of the lesion.  Clinical studies have subsequently demonstrated, conclusively,  that antibiotic administered one hour before the surgery significantly decreases the incidence of postoperative infection when compared to placebo.  However, if the antibiotic is begun one to four hours after the operation, there is no reduction in the postoperative infection rate.

The correlation between the frequency of infection and the density of microorganisms present in a homogenized sample taken from the wound closure site has been established. Since it is not immediately possible to determine the microbial density of every surgical wound, a system for categorizing a surgical wound based on the probability and degree of microbiologic contamination has been developed.  The accuracy with which this clinical classification predicts the incidence of wound infection for general and orthopaedic surgery is well established.

Clean surgical procedures account for 75% of all operations.  These procedures are performed under ideal and sterile operating room conditions.  The procedures are generally elective and no entry is made into the oropharyngeal cavity or the lumen of the respiratory, alimentary, or genitourinary tract.  Inflammation is not encountered and no break in surgical technique occurs.  The incidence of wound infection in clean procures is less than 5%.

Clean-contaminated surgical procedures involve entry into the oropharyngeal cavity or the lumen of the respiratory, alimentary, or genitourinary tract without significant contamination from these sites.  Clean wounds are included in this category when there is a major break in the surgical technique. Clean- contaminated surgical procures occur in approximately 15% of all surgical operations and wound infection is reported in approximately 10% of these cases.  Since the mucosa of the oropharyngeal , respiratory, alimentary and genitourinary tracts harbor diffuse and dense microbiologic flora, some contamination of the wound is e inevitable.  Antibiotic prophylaxis is indicated in these patients and should be appropriately tailored to the flora expected in the particular region of surgery.  Clean surgery on a compromised host ( ) or transoral fixation of lesions involving the first and second cervical vertebra are examples of clean-contaminated procedures.

Contaminated-dirty surgery includes surgery through traumatic wounds, operative procedures with a major break in sterile technique and operations into a site of active infection.  The infection rate is between 20% and 40% in surgery involving these patients.  Antibiotic “prophylaxis”, in these circumstances, is directed at the prevention of infection in the soft-tissue planes and wounds previously uncontaminated by bacteria.  As such, the antibiotic(s) used  may be modified by the preoperative Gram stain or culture results stemming from biopsies of exposed granulating surfaces and/or wounds, themselves.  Surgery of open fractures is an example of contaminated-dirty surgery.  The risk of subsequent infection increases with the amount of tissue devitalization, the extent of contamination and the systemic compromise of the host. 

Final comment:  There are few controlled trials to scientifically support a practice mandating emergency-debridement of all open fractures  (< 6hrs). However, it is in agreement that 1) all open fractures require immediate, systemic antibiotic coverage and 2) that additional coverage with a local antibiotic-depot (antibiotic beads ) will reduce the incidence even further when treating  severe open injuries (Seligson D, Henry SL) when used in conjunction with systemic coverage.   BEST PRACTICE:  all methods of treatment should impact outcomes within the  “decisive period”:  immediate antibiotic coverage; host resuscitation; the earliest possible debridement; avoidance of large surgical implants; adequate (and safe) methods of stabilization; soft-tissue coverage within 7 days of injury –  Primary_versus_Delayed_Soft_Tissue_Coverage_for.8 .

Review Article:  Warner M et al; Comparison of Vacuum-assisted Closure to the Antibiotic Bead Pouch for the Treatment of Blast Injury of the Extremity. ORTHOPEDICS, 2010; 33: pp77-87.

A retrospective study of 24 patients suffering blast injuries to the lower extremities.  Prior to closure, half were initially treated with VAC (vacuum assisted closure) and half with an antibiotic bead pouch. The same surgeons performed all surgeries. Findings: VAC-therapies produced more late Methicillin-resistant Staphylococcus aureus (MRSA) infections (30% vs 0%), more unanticipated returns to the operating room (4:12 vs 0:12), required more surgeries to affect closure (at ~12days vs ~8days)and cost ~$1,000 more /patient once a $23,000 investment was made to purchase a single, VAC machine (KCI; SanAntonio, TX).

 Dr. Cierny comments: Although several studies have suggested that VAC will decrease the need for free tissue transfer in like/like wounds following trauma^1,2, others found no significant difference in time to closure³, an increase the amount of S aureus in the wound bed,⁴ a statistically significant increase in colony count during use,⁵ and infection /nonunion rates similar to historical controls (suggesting no benefit to the use of VAC over conventional dressings.⁶   Hallock⁷ contended that VAC does not prolong the time allowed for successful definitive wound closure and Stewart and Keating⁸ found VAC not as good as early soft tissue coverage (for acute wounds).  Although Morris⁹ found weak evidence to suggest that negative pressure therapy is superior to saline dressings when healing chronic wounds, Stannard et al¹⁰ , in a prospective, randomized study of 62 open fractures, found patients treated with NPWT one-fifth as likely to develop an infection compared with patients randomized to controls treated with wet-to-dry dressings until closure.

The consensus:  NPWT is more comfortable /convenient for the patient and healthcare team, effectively decompressing (displacing)  the inevitable need (energy) for complex and sequential reconstructions.  Despite its controversies, the use of external fixation and NPWT in the treatment of blast injuries and gunshot wounds resulting in open fractures with severe soft tissue injuries has become the mainstay of damage control orthopaedics.    In our experience, however,  15%-20% of patients with refractory infections following long-term  NPWT protocols have had retained sponge-fragments (gossypiboma) discovered in their wounds at the time of debridement and all of these fragements grew ‘culture positive’ for the primary, wound pathogen(s).   For us, NPWT is extremely helpful in managing acute /peri-operative wounds.   However, we find it of limited value in the chronic-wound scenario unless the wound has first been rendered 100% live and is no longer in need of any further reconstruction (ie; bone grafts, tendon repairs, etc.).   GC  02/20/10 .

Bibliography (1-10): -1- Herscovici D Jr, Sanders RW, Scaduto JM, Infante A, DiPasquale T. Vacuum-assisted wound closure (VAC therapy) for the management of patients with high-energy soft tissue injuries. J Orthop Trauma. 2003; 17(10):683-688. -2- Dedmond BT, Kortesis B, Punger K, et al. Sub-atmospheric pressure dressings in the temporary treatment of soft tissue injuries associated with type III open tibial shaft fractures in children. J Pediatr Orthop. 2006; 26(6):728-732. -3- Song DH, Wu LC, Lohman RF, Gottleib LJ, Franczyk MPT. Vacuum assisted closure for the treatment of sternal wounds: the bridge between débridement and definitive closure. Plast Reconstr Surg. 2003; 111(1):92-97. -4- Mouës CM, van den Bemd GJ, Heule F, Hovius SE. Comparing conventional gauze therapy to vacuum-assisted closure wound therapy: a prospective randomized trial. J Plast Reconstr Aesthet Surg. 2007; 60(6):672-681. -5- Weed T, Ratliff C, Drake DB. Quantifying bacterial bioburden during negative pressure wound therapy: does the wound VAC enhance bacterial clearance? Ann Plast Surg. 2004; 52(3):276-279.  -6-Dedmond BT, Kortesis B, Punger K, et al. The use of negative-pressure wound therapy (NPWT) in the temporary treatment of soft-tissue injuries associated with high-energy open tibial shaft fractures. J Orthop Trauma. 2007; 21(1):11-17.  -7- Hallock GG. To VAC or not to VAC? Ann Plast Surg. 2007; 59(4):473-474. -8- Stewart KJ, Wilson Y, Keating JF. Suction dressings are no substitute for flap cover in acute open fractures. Br J Plast Surg. 2001; 54(7):652-653. -9- Morris GS, Brueilly KE, Hanzelka H. Negative pressure wound therapy achieved by vacuum-assisted closure: Evaluating the assumptions. Ostomy Wound Manage. 2007; 53(1):52-57. -10- Stannard JP, Wolgas DA, Stewart R, et al; Negative Pressure wound therapy after severe open fractures: a rospecive randomized study.  J. Orthop. Trauma, 2009; 23(8): 552-557.

The article:  What is Osteomyelomyelitis? What Causes Osteomyelitis?” in Medical News Today: 10 Feb 2010-0:00PST

Dr. Cierny comments:

TYPES OF OSTEOMYELITIS: ‘Acute’,’ sub-acute’ and ‘chronic’ are time-related terms that parallel the fundamental principles and mechanisms  inherent to wound colonization by microorganisms.  Early in the course of infection, microorganisms are mobile (plankonic) and vulnerable to antibiotics and host defenses.   If the fracture is live and stable, the infection may resolve following adequate wound decompression, antimicrobials and the elimination of dead space (the acute wound).  After 2-3 weeks,  reactions between surface macromolecules begin forming at pathogen-substrate interfaces (sub-acute), resulting in a resilient “microzone’ of attachment in 4-6weeks that is precursor to a microbial-based, mucopolysaccharide “slime” that encompasses the entire colony.   Within the bio-slime (biofilm) microbial nutrition and growth are enhanced, protected from host defenses and the penetration /effects of antimicrobials.  The result is a profound compromise to the host: wound healing and fracture repair are impaired due to toxins produced by the pathogens and the by-products of host efforts to unsuccessfully destroy the biofilm colony. Curative treatment of such a biofilm-infection (chronic /refractory) requires both anti-microbial therapy and surgical removal of the entire biofilm burden.

WHAT ARE THE SIGNS AND SYMPTOMS OF OSTEOMYELITIS? See: http://www.osteomyelitis.com/html/osteomyelitis.html

WHAT ARE THE RISK FACTORS FOR OSTEOMYELITIS? 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; surgical implants 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, injury and pre-existing health conditions compromise the host response.   The goals of treatment are three-fold: timely intervention; creation/maintenance of a clean, manageable wound; adequate and durable fracture fixation.

Surgical Site Infections (infection following elective surgery) are more common in compromised hosts,( ), long procedures (SSI) and operations where in a large surgical implant is used (substrat surfaces; see above).  OSTEOMYELITIS: CIERNY/MADER HOST STATUS  OSTEOMYELITIS: CIERNY/MADER CLASSIFICATION SYSTEM 

DIAGNOSIS OF OSTEOMYELITIS:   MALNUTRITION;   WHAT BLOOD TESTS ARE USED TO DIAGNOSE OSTEOMYELITIS?    DO POSITIVE CULTURES ALWAYS MEAN A BONE INFECTION IS PRESENT?   WHEN DO I NEED A NUCLEAR SCAN?

TYPES OF BONE INFECTIONS:   There are really only three etiologic categories of bone infection, not five:  hematogenous (blood-born) osteomyelitis;  contiguous-focus osteomyelitis;  and post-traumatic osteomyelitis.  Osteomyelitis due to vascular insufficiency is a form of contiguous focus infection since the lack of oxygen leads to breakdown of the integument (skin), ulceration and eventual exposure ( and contamination) of the underlying bone (a contiguous focus).  Ischemic compromise can  occur in patients with peripheral vascular disease, disruption of major bood vessels, diabetes (foot ulcers) and patients developing bed (decubitus) ulcers.

The categorization of bone infection into etiologic types,  however, does not help with establishing a treatment strategy or prognosis.  To do this, the chronology (see above), patient’s health and anatomic localization of the infection (in the bone itself) must be brought together into a staging system similar to those used for various forms of cancer.    For example, vertebral osteomyelitis is a regional localization of infection (the spine) as opposed to an anatomic localization (configuration) of the disease in the spinal bone (s) itself.  Spine infections occur following: blood-born contamination (hematogenous) to the marrow part of the bone or to the disc between the vertebral bodies;  as a contiguous focus infection (sacral decubitus ulcers); or following trauma (ie; post-operative, surgical site infections ).   Treatment will depend on the etiology, the timing (acute, subacute, chronic) and the extent to which the infection involves the bone (on the surface, in the marrow, fracture with instability, etc.).  That is why the CIERNY/MADER Clinical Staging System (1985)  is now accepted internationally as the gold standard for classifying bone infection in adults (all types, all etiologies, all locations) as it articulates the natural history of the disease with treatment and outcomes.

The Orthopaedic Supervisory of Sharp Memorial Hospital in San Diego has asked the Infection Prevention and Clinical Epidemiology Department to periodically distribute individual, surgeon specific, surgical site infection (SSI) rates.  Practices proven to minimize the risk of post-operative SSI include:  1) asking patients to shower or bathe with chlorhexidine(Hibiclens) for several days pre-op; 2) the administration of prophylactic antibiotics within 1 hour of incision (2 hours for Vancomycin); 3) using electric clippers (not a razor) to remove hair at the operative site if it will interfere with wound closure; 4)to identify and treat all infections remote to the surgical site before elective operation.

Pre-operative colonization screening for Methicillin-sensitive (MSSA) and Methicillin-resistant (MRSA) Staphylococcus aureus, the application of 2% nasal Mupirocin (Bactroban) in the anterior nares twice a day for 5 days for those colonized and assuring that patients colonized with MRSA receive the appropriate preoperative prophylaxis are further strategies to reduce risk .

The attached figure compares the SSI rates of REOrthopaedics physicians to the SMH aggregate rates and rates generated by the National Healthcare Safety Network (NHSN) at the CDC in Atlanta.  As seen, Dr. Cierny and Dr. DiPasqaule have a 0.00%  post-operative SSI rate following 55 consecutive hip and knee arthroplasties performed 2006-2008. The Risk index is scored from 0-3 points (the higher the risk index, the higher the score), with one point each for: a) wound class of contaminated or dirty; b) ASA score of III, IV or V; c) duration of surgery >2 hours.  NHSN rates reflect the National Healthcare Safety Network Report: a data summary for 2006-2008 (AJIC: Nov 2008; 609-626).  SMH = Sharp Memorial Hospital; San Diego, Calfiornia.  REO = REOrthopaedics, Inc in San Diego, CA; Drs.George Cierny, MD and Doreen DiPasquale, MD.   

 Dr. Cierny’s comments:  Unfortunately, this registry does not differentiate between primary vs revision arthroplasties or clean vs infected arthropasties performed at Sharp Memorial Hospital.   All of the REOrthopaedics’ cases began, initially, as peri-prosthetic total joint infections (54: 2-stage revisions vs 1: primary exchange). 

How does malnutrition affect outcomes of patients with musculoskeletal infection?”     Good nutrition is essential for normal wound healing and host defense against infection.  A lack of proteins, fats, vitamins and minerals creates a welcome environment for invading bacteria:  1) decreased production of new blood vessels to heal wounds, potentiate antimicrobial effectiveness and thereby prevent infection; 2) lack of proteins to seal and heal wounds, stop bleeding and kill bacteria (antibodies against bacteria and viruses);  3) impotent white blood cells (natural  killer cells ) to destroy invaders.   In our protocols and staging system, patients with obesity and/or mal-nutrition are considered B-hosts with co-morbidities affecting wound healing and treatment outcomes.

 How can I be obese and still be malnourished?  Concomitant  obesity and malnutrition can offend occur if the obesity is linked to: 1)  the consumption of empty calories in a diet of processed, fast  foods lacking minerals and containing additives to prolong shelf life; 2) bariatric patients following bariatric surgery where absorption is altered; 3) dietary deficiencies in folate, selenium, zinc and vitamins A, B-12, B-1, C, D and E.  Obesity, for these purposes, is defined as a Mean Body Index (BMI) > 40.   Our treatment center has introduced many innovations in treatment that have improved outcomes for all B-hosts.

How do you diagnose mal-nutrition?  Common measurements of nutritional status include: laboratory tests (serum albumin, transferring, pre-albumin and total lymphocyte count); body measurements such as BMI, tricps skin fold thickness (fat reserves) and a  mid-humeral circumference (protein reserves).  

Can I still be operated if I am malnourished?  In order to prevent post-operative wound complications (healing) and infection (SSI), surgery is often delayed until a mal-nourished patient can first be restored to good health and nutrition.  However, in the case of a serious infection or tumor, when a delay of surgery cannot be advised, alternative and sometimes more circuitous methods must be employed to reach a similar goal (TREATMENT OUTCOMES: slide #4).  

BLOOD TESTS TO DIAGNOSE OSTEOMYELITIS / BONE and SOFT TISSUE  INFECTIONS - 

The Erythrocyte Sedimentation Rate (ESR):   When inflammation is present in the body, proteins are produced by the liver and the immune system under many abnormal conditions, such as an infection, an autoimmune disease, and/or cancer.  The increased presence of these proteins will cause red blood cells to stick together in solution (whole blood) and, therefore, settle out of solution more slowly than when these proteins are absent or in lower concentrations.   The Erythrocyte Sedimentation Rate (ESR) is, therefore, a non-specific test to indicate thickening of the blood due and can be used to rule in or rule out disease processes that, when present, stimulate production of these proteins (see below discussion of acute phase proteins).   Since there are many possible causes of an elevated sedimentation rate, this blood test is done with other tests to confirm a diagnosis such as a chronic osteomyelitis.  Once a sed rate (ESR) blood test is conducted, the course of a disease or the effectiveness of treatment can be monitored.

C-reactive protein (CRP): CRP is believed to play another important role in innate immunity, as an early defense system against infection.  It is a protein found in the blood, the levels of which rise in response to inflammation due to trauma, infection or serious illnesses; it is an “acute-phase protein” synthesized by the liver.  It is not related to C-peptide or protein C.   A rise in C-RP is due to a rise in the plasma concentration of IL-6(see below), which is produced predominantly by macrophages and fat cells.   CRP binds to microbes and is thought to enhance the process of phagocytosis (cellular ingestion/digestion) of bacteria by macrophages.  

When signaled, the CRP level rises above normal limits within 6 hours, and peaks at 48 hours.  Thereafter, its level is determined by the rate of production (and hence the severity of the precipitating cause).  Measuring and charting C-reactive protein values can prove useful in determining the presence of disease, disease progress and/or the effectiveness of various treatments.

Acute-phase proteins:  a class of proteins whose plasma concentrations increase (positive acute-phase proteins) or decrease (negative acute-phase proteins) in response to inflammation. This response is called the acute-phase reaction (also called acute-phase response).  In response to injury, local inflammatory cells (neutrophils, granulocytes and macrophages) secrete a number of cytokines; cytokines are chemical signals between cells that have an effect on other cells, the most most notable of which are the interleukins IL-1, IL-6 and IL-8 and tumor-necrosis factor alpha (TNF- α).   

Interleukin-6 (IL-6) is both a pro-inflammatory and anti-inflammatory cytokine.  It is secreted by T-cells and macrophages to stimulate immune response to trauma, especially burns or other tissue damage leading to inflammation. IL-6 has been shown to be required for resistance against certain bacteria (i.e.; Streptococcus pneumoniae).  IL-6, one of the most important mediators of fever and of the acute phase response, can be secreted in response to specific microbial molecules referred to as pathogen associated molecular patterns (PAMPs).  These PAMPs bind to highly important group of detection molecules of the innate immune system called pattern recognition receptors (PRRs) which signal cascades giving rise to inflammatory cytokine production.

 At our Osteomyelitis Treatment Center in Sand Diego, CA we use the ESR, CRP and IL-6 blood tests in the diagnosis of bone and soft tissue infections as well as in the follow up following treatment results and peri-prosthetic total joint infections.

RECENT REVIEW: ANTIBIOTIC DEPOTS:

1) Does antibiotic elution from PMMA beads deteriorate after 1-year shelf storage?   Balsamo LH; Whiddon DR; Simpson RB; Bone and Joint/Sports Medicine Institute, Naval Medical Center Portsmouth, Portsmouth, VA.  Clin Orthop Relat Res, 2007; 462:195-9.

-Tobramycin-impregnated antibiotic beads were manufactured using a bead mold. The antibiotic was either hand-mixed into the polymethylmethacrylate powder (1.2 g/40 g) or came premixed from the factory (1 g/40 g). Packages of beads were gas-sterilized and stored at room temperature. Beads were tested at 0, 1, 2, 3, 6, and 12 months and antibiotic levels in the eluent from each day of the month measured.  

There was no difference in the amount of antibiotic elution between beads tested immediately after manufacture and beads manufactured and stored for 6 or 12 months. Beads with hand-mixed antibiotics eluted higher levels of antibiotics than the beads prepared with factory-mixed antibiotics. We conclude antibiotic beads can be made, sterilized, and used after 1 year of storage with no deleterious effect on antibiotic elution characteristics.  DR. CIERNY’S COMMENTS:  THIS KIND OF LONGITUDINAL STUDY IS LONG OVERDUE AND WILL BRING FURTHER EFFICIENCY TO THE PROCESSING OF HAND-MADE ANTIBIOTIC BEAD PREPARATIONS AND THEIR STORAGE.  ANTIBIOTIC BEADS; TREATMENT OF OSTEOMYELTIS AND BONE INFECTIONS 

2) Comparative study of antibiotic-containing polymethylmetacrylate capsules and beads. Borzsei L; Mintal T; Horvath A; Koos Z; Kocsis B; Nyarady.  J Department of Traumatology and Hand Surgery, Faculty of Medicine, University of Pecs, Hungary. Chemotherapy 2006;52(1):1-8.    

-PMMA capsules were produced with a pressing machine designed and laid out by us. The characteristics of antibiotic penetration from this novel carrier were compared to those of standard-made, PMMA beads. METHODS: The time-dependent outflow of amikacin, clindamycin, pefloxacin, piperacillin + tazobactam, amoxicillin + clavulanic acid and cefotaxime was examined from the capsules and the beads with standard microbiological techniques using the Micrococcus luteus ATCC9341 test strain. The diameter of the inhibitory zones was measured after 24 h incubation at 37 degrees C and converted to mug/ml antibiotic concentrations. RESULTS AND CONCLUSIONS: Our results revealed that all antibiotics showed longer-lasting and higher concentration outflow from the PMMA capsules than from the beads. Therefore, these capsules can provide a more promising new opportunity for specific local antimicrobial treatment in cases of chronic suppurative bone and soft tissue injuries. In these cases the polymerization has already been completed and the heat does not influence the structure of the antibiotics; therefore, it can be inserted into the capsules in powder or solution form. [Copyright 2006 S. Karger AG, Basel.].   DR. CIERNY’S COMMENTS:   THE PROBLEM, HERE, IS THAT THIS REQUIRES A PRESSING OUTSIDE THE OPERATING ROOM, AGAIN BRINGING OUR FOCUS BACK TO THE 2008 USP CHAPTER 797 REVISION PERTAINING TO COMPOUNDING, STERILE PREPARATIONS, ETC.  IN THE PAST, SUCH PREPARATIONS HAVE NOT PASSED FDA OR HOSPITAL REGULATIONS AND ARE UNLIKELY TO DO SO IN THE NEAR FUTURE.  ANTIBIOTIC BEADS, TREATMENT OF OSTEOMYELITIS AND BONE INFECTIONS 

3) Two-stage revision hip arthroplasty for infection: comparison between the interim use of antibiotic-loaded cement beads and a spacer prosthesis.  Hsieh PH; Shih CH; Chang YH; Lee MS; Shih HN; Yang WE. Department of Orthopedic Surgery, Chang Gung Memorial Hospital, Kweishian, Taoyuan, Taiwan. J Bone Joint Surg Am 2004 Sep;86-A(9):1989-97.

-The results associated with the interim use of antibiotic-loaded cement beads were compared with those associated with the interim use of an antibiotic-loaded cement prosthesis in an outcomes study of two-stage revisions following a peri-prosthetic total hip infection.  METHODS: 128 consecutive PPI-THA patients were followed clinically and radiographically for an average of 4.9 years. Cement beads were implanted following resection arthroplasty in the first 70 hips, and a custom cement prosthesis was implanted in the subsequent 58. RESULTS: There was no evidence of recurrent infection in 122 patients (95.3%); the infection-free rates in both groups were similar. The use of a spacer prosthesis was associated with a higher hip score, a shorter hospital stay, and better walking capacity in the interim period; a decreased operative time, less blood loss, and a lower transfusion requirement at the time of reimplantation; and fewer postoperative dislocations. CONCLUSIONS: The present study supports the safety and efficacy of the routine use of an antibiotic-loaded cement prosthesis in the interim between the stages of a two-stage revision procedure for the treatment of an infection at the site of a hip arthroplasty.   DR. CIERNY’S COMMENTS:  IT IS IMPORTANT TO NOTE HERE THAT THESE AUTHORS USED ONLY HIGH-DOSE ANTIBIOTIC COCKTAILS IN BOTH GROUPS AND THAT THE PROSTALAC IMPLANT WAS A CEMENT-ON-CEMENT ARTICULATION, CAPABLE OF ELUTING ADEQUATE LEVELS INTO THE JOINT, ITSELF.    ALTHOUGH THE CONCENTRATIONS OF ANTIBIOTICS IN THE JOINT AND DRAIN FLUIDS WERE NOT DOCUMENTED IN THIS STUDY, THESE SAME AUTHORS HAVE  SUBSEQUENTLY PUBLISHED THIS DATA ELSEWHERE (J Arthroplasty, 2009; 24(1):125-30) AND BELOW IN PAPER #4 OF THIS REVIEW.    THIS IS ONE OF THE FIRST STUDIES TO  CONFIRM EQUANIMITY OF THE TWO METHODS.    PERI-PROSTHETIC TOTAL JOINT INFECTIONS; INFECTED TOTAL HIP ARTHROPLASTY.

4) Liquid Gentamicin in bone cement spacers: in vivo antibiotic release and systemic safety in two-stage revision of infected hip arthroplasty. Hsieh PH; Huang KC; Tai CL.  Department of Orthopedics, Chang Gung Memorial Hospital, Taoyuan, Taiwan. J Trauma, 2009; 66(3):804-8.    

-This study investigated the application of liquid gentamicin in bone cement  to treat musculoskeletal infections. METHODS: Forty-two patients undergoing two-stage revision hip arthroplasty for periprosthetic infection were managed with an interim cement spacer loaded with liquid gentamicin (480 mg per 20 mL pack of cement monomer) with or without vancomycin (3.0 g per 40 g pack cement polymer). Serum and aliquots of drainage collected after the first-stage surgery; joint fluid obtained at the time of the second-stage surgery were analyzed for antibiotic concentrations and bioactivity. RESULTS: Antibiotic levels in joint fluid peaked on the first day after implantation of the spacer and then gradually declined during the first week, with levels of gentamicin and vancomycin reached 43.6 mg/L +/- 12.3 mg/L and 485.5 mg/L +/- 103.5 mg/L, respectively. Bioassay confirmed the antimicrobial activity of the released antibiotics.  At a mean 87 days after implantation, antibiotic concentrations in joint fluid remained clinically effective (gentamicin, 5.1 mg/L +/- 2.2 mg/L and vancomycin, 21.6 mg/L +/- 8.5 mg/L). CONCLUSIONS: Incorporation of liquid gentamicin in bone cement spacers led to effective drug delivery with systemic safety. Substantial health care dollars could be saved by the use of liquid gentamicin in bone cement to treat musculoskeletal infections.   DR. CIERNY’S COMMENTS:  I HAVE CONTACTED THE AUTHORS TO ASK HOW THEY WERE ABLE TO INCORPORATE SO MUCH LIQUID INTO THEIR CEMENT CONSTRUCTS.  DR. HSIEH REPLIED THAT THEY FIRST MIX THE 12CC OF GENTAMICIN (480MG) WITH THE LIQUID MONOMER.  AFTER THE POWDERS ARE MIXED (VANCOMYCIN +  POLYMER),  THE WET AND DRY BATCHES ARE MIXED, TOGETHER.   SIMPLEX HAS PROVEN SUPERIOR TO PALECOS CEMENT IN THIS CAPACITY.  TREATMENT OF OSTEOMYELITIS AND BONE INFECTIONS; PERI-PROSTHETIC TOTAL JOINT INFECTIONS

5) Persistence of bacterial growth on antibiotic-loaded beads: is it actually a problem? Anagnostakos K; Hitzler P; Pape D; Kohn D; Kelm J.  Klinik fur Orthopadie und Orthopadische Chirurgie, Universitatsklinikum des Saarlandes, Homburg/Saar, Germany. Acta Orthop, 2008; 79(2):302-7

-This Paper assessed whether bacterial adherence and growth could be determined on gentamicin- and gentamicin-vancomycin-loaded beads that had been removed after eradication of infection. MATERIAL AND METHODS: They bacteriologically examined 18 chains of antibiotic-loaded beads (11 gentamicin-loaded, 7 gentamicin-vancomycin-loaded) that had been previously implanted for infection.  Staphylococcus epidermidis, Staph-ylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA) were the most frequent organisms identified. RESULTS: In 4 cases (3 with S. epidermidis and one with MRSA), there was persistence of bacterial growth on the beads. S. epidermidis strains persisted only on gentamicin-loaded beads, while MRSA could grow on gentamicin-vancomycin-impregnated cement. In one case, the emergence of a gentamicin-resistant S. epidermidis strain was observed despite the fact that preoperative samples of S. epidermidis from this patient had been susceptible to the antibiotic.   DR. CIERNY’S COMMENTS:  PERSISTENCE OF BACTERIAL GROWTH ON BONE CEMENT REMAINS A CONCERN.   IN OUR PAPER ON PERI-PROSTHETIC TOTAL JOINT INFECTIONS, THE INCIDENCE OF POSITIVE, SONICATED CULTURES OF THE RETIRED IMPLANTS AT THE TIME OF REIMPLANTATION WAS 23% (pp.25).     THIS, AGAIN, DRIVES HOME THE MESSAGE THAT PROSTALAC COMPONENTS (ARTICULATED SPACERS) ARE MEANT FOR TEMPORARY, NOT PERMANENT IMPLANTATION.   IT IS UNCLEAR WHEN ADHERENT, INACTIVE BACTERIA  WILL RE-EMERGE AS WOUND PATHOGENS.  IN OUR PRESENT PROTOCOLS, EVERY EFFORT IS MADE TO REIMPLANT WITHIN 3 – 6MOS OF DEBRIDEMENT.   PERI-PROSTHETIC TOTAL JOINT INFECTIONS; TREATMENT OF OSTEOMYELITIS AND BONE INFECTIONS; ANTIBIOTIC BEADS

6) Vancomycin covalently bonded to titanium beads kills Staphylococcus aureus. Jose B; Antoci V; Zeiger AR; Wickstrom E; Hickok NJ. Department of Biochemistry and Molecular Biology, Thomas Jefferson University, Philadelphia, Pennsylvania.  Chem Biol, 2005; 12(9):1041-8.

-The authors designed a covalent modification to titanium implant surfaces to render them bactericidal.  Specifically, they aminopropylated titanium and extended a tether by solid phase coupling of ethylene glycol linkers, followed by solid phase coupling of vancomycin.   Vancomycin covalently attached to titanium still bound soluble bacterial peptidoglycan, reduced Staphylococcus aureus colony-forming units by 88% +/- 16% over 2 hr, and retained antibacterial activity upon a repeated challenge.   DR. CIERNY’S COMMENTS: THERE HAVE BEEN SEVERAL ARTICLES PUBLISHED ON TETHERING ANTIBIOTICS TO IMPLANT  SURFACES, SUGGESTING THE POSSIBILITY OF AN EVERLASTING PROTECTION AGAINST BIOFILM FORMATION.   ON THE OTHER HAND, THESE ANTIBIOTIC TETHERS DO LITTLE, IF ANYTHING, TO PREVENT INFECTION IN SURROUNDING SOFT TISSUES OR DEAD SPACE SINCE THERE IS NO RELEASE OF ANTIBIOTIC INTO SOLUTION.  PERI-PROSTHETIC TOTAL JOINT INFECTIONS; TREATMENT OF OSTEOMYELITIS AND BONE INFECTIONS.

7) Cierny-Mader Type III chronic osteomyelitis: the results of patients treated with debridement, irrigation, vancomycin beads and systemic antibiotics. Kinik H; Karaduman M.  Department of Orthopaedics and Traumatology, Ankara University School of Medicine, Ankara, Turkey. Int Orthop, 2008; 32(4):551-8.    

- 26 patients (19 men and 7 women; average age: 34.7 years) with Cierny-Mader(C-M) Type III osteomylelitis were treated with radical debridement, irrigation, vancomycin-impregnated custom-made beads and culture-specific systemic antibiotics.  Type III osteomyelitis is defined as a localised lesion with both medullary and cortical involvement that is stable mechanically after debridement.Those patients with metaphyseal involvement were treated with deroofing of the cortex and debridement by means of a “trough” (16 patients); those with diaphyseal involvement were treated with both intramedullary reaming and debridement from a trough (ten patients). Antibiotic cement rods were used as an additional therapy in five patients with diaphyseal involvement. Recurrence developed in three patients and was attributed to inadequate debridement; all three patients were treated again in the same manner with success. The mean follow-up is currently 3.6 years (range: 2-6 years). All of the patients have normal clinical, radiographic and laboratory parameters, and all are ambulatory and have returned to their pretreatment level of activity or better.    DR. CIERNY’S COMMENTS:   WELL DONE, INDEED!   THE CLINCIAL STAGING SYSTEM ARTICULATES THE NATURAL HISTORY OF THE DISEASE WITH TREATMENT OPTIONS AND ALLOWS COMPARISON OF TREATMENT PROTOCOLS FOR ALL TYPES OF OSTEOMYELITIS  AND  PATIENT COHORTS. TREATMENT OSTEOMYELITIS AND BONE INFECT ION; CLINICAL STAGING OF OSTEOMYELITIS