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.

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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 .

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.

Contents: 1) Management of Bone Loss; 2) Common Decision-Making Errors in Limb Salvage; 3) Chrnic Neuropathic Pain Following Open Fractures; 4) Management of Soft-Tissue Loss After Trauma; 5) Malunions and Nonunions in the Lower Exdtremity; 7) Infection Following Open Fracture – George Cierny III, MD  pp71- 87.  In Complications in Orthopaedics: Open Fractures; Levin, L.S. (ed).   AAOS monograph Series; Amer. Acad. Orthop Surg, Rosemont, IL, 2010.  Here, Dr. Cierny presents his classification systems and treatment algorithms which are among  the principal advances in the management of infection following open fractures – osteomyelitis with micro-necrosis; osteomyelitis with macro-necrosis; fixation strategies; chronic_infection; staged treatment options.

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