Anthony G. Gristina

Adhesive colonization of biomaterials and antibiotic resistance

This study addresses the problem of antibiotic resistance in adhesive, biomaterial-centred infections. It is suggested that this anionic, extracapsular, polysaccharide slime produced by bacteria protects them from antibiotics and sequesters critical ions from the surface of biomaterials. Biofilm-enclosed bacteria on the surface of stainless steel substrata in a test chamber were challenged with incremental levels of tobramycin. In this setting, the minimum inhibitory concentration and minimum bactericidal level of tobramycin for Staphylococcus epidermis were well above normal.

In vitro and in vivo comparative colonization of Staphylococcus aureus and Staphylococcus epidermidis on orthopaedic implant materials

Clinically, Staphylococcus aureus appears to be the dominant organism associated with infected metal implants, whereas coagulase-negative staphylococcal strains are more frequently isolated from infected polymer implants. We reproduced this trend experimentally in vitro and in vivo. Discs of a titanium alloy, poly(methyl methacrylate) and ultra-high molecular weight polyethylene were exposed to a clinical isolate of Staphylococcus aureus or either of two strains of Staphylococcus epidermidis. Within 1 h Staphylococcus aureus was always the most rapid colonizer regardless of biomaterial. However, after 8 to 24 h, Staphylococcus aureus was present in higher numbers on metal and Staphylococcus epidermidis on polymers. Moreover, the exopolysaccharide produced by Staphylococcus epidermidis appeared to offer an effective protection against host defences in vivo.

Implant failure and the immuno-incompetent fibro-inflammatory zone.

Biomaterial implants are surrounded by an immuno-incompetent, fibro-inflammatory, integration-deficient zone within which stimulation of cellular immune responses results in superoxide radical and cytokine-mediated tissue damage with increased susceptibility to infection or aseptic loosening. Three important questions that pertain to surgical implants are (1) What are the mechanisms that cause abnormal inflammatory responses in the absence of infection and result in interface cellular disorganization and device failure? (2) What causes host defenses to be compromised to the extent that normal flora organisms like Staphylococcus epidermidis, with little or no virulence potential, can cause life-threatening infections at the implant-host interface? (3) What is the nature of surface regions of biomaterials that facilitate bacterial adherence? Pathogenic strains of S. epidermidis and Staphylococcus aureus have an affinity for biomaterial surfaces and are capable of initiating infection. Binding may be nonspecific and glue-like rather than a receptor-ligand event as for S. aureus and matrix proteins. This study indicates bacterial binding to sites of higher vanadium concentration at grain boundaries and mixed phases in titanium alloys. Repeated macrophage priming by biomaterial particulates results in the production of reactive oxygen intermediates, macrophage exhaustion, and adjacent tissue damage. A cytokine cascade is also initiated. A self-perpetuating enlarging immuno-incompetent fibro-inflammatory zone develops about implants, which features tissue cell damage, increased susceptibility to infection, and results in septic or aseptic failure of the implant. These effects are clearly exemplified by fibrosis about breast implants and osteolysis at the interface of total joint replacements.

Antibiotic resistance of biomaterial-adherent coagulase-negative and coagulase-positive staphylococci.

Whether or not bacterial populations are massively enclosed in slime, it appears that antibiotic resistance, when compared to suspension organisms, is related to surface adhesion and to the specific material of the substratum. These findings are of significance in the understanding and treatment of biomaterial-localized infections.

Surgical biomaterials and differential colonization by Staphylococcus epidermidis

The data presented in this communication demonstrate preferential colonization of certain biomaterials by Staphylococcus epidermidis. Using a laminar flow biomaterial colonization chamber and surgical-grade biomaterials (stainless steel, aluminium ceramic, methyl methacrylate and high-density polyethylene), the pattern of colonization was quantitated using plate count techniques and electron microscopy. Under comparable conditions, methyl methacrylate was colonized by S. epidermidis in greater numbers than the other biomaterials. Increased bacterial colonization and slime production on methyl methacrylate was time-dependent and 15 times higher than on stainless steel and aluminium and four times higher than on high-density polyethylene. The data reveal that certain biomaterials may promote infection by favouring colonization by potential pathogens. This variable should be explored extensively in an in vivo setting because of its implication in clinical infections.

Host reactions to biomaterials and their evaluation

Publisher Summary The complications of medical devices are based on biomaterials–tissue interactions that include both the effects of the implant on the host tissues and the effects of the host on the implant. All implants interact to some extent with the tissue environment in which they are placed. This chapter summarizes the biomaterials–tissue interactions encountered most frequently. It describes several of the most important interaction mechanisms in clinical and experimental implants and medical devices, including inflammation, foreign body reaction, immunological sequelae, systemic toxicity, blood–surface interactions, thrombosis, device-related infection, and tumorigenesis. The chapter also illustrates host defense or immune mechanisms that are invariably disrupted by the implantation of biomaterials and tissue transplants. The mechanisms of such disruption are unknown. The quality of the immune and defense responses defines susceptibility to and the specificity and outcome of infection. Spontaneous bacteremia, trauma, and surgery are common contributors to infection

Musculoskeletal injuries in theatrical dance students

Three hundred and fifty-two injuries in 185 theatrical dance students at the North Carolina School of the Arts were diagnosed and treated from September 1981 through May 1982, the most recent academic year. The total number of dancers enrolled in the school was 218; thus, 84.9% of the dance students were evaluated for an injury by a physician, with 87.8% of the injuries sustained during dance. Approximately one-fourth of the dance-related inju ries involved the foot or ankle. The injuries were usually not severe, and proved amenable to treatment by con servative measures.

Spontaneous septic arthritis complicating rheumatoid arthritis.

Thirteen cases (in twelve patients) of septic arthritis complicating rheumatoid arthritis are reported. One ankle, one metacarpopophalangeal joint, one shoulder, and ten knees were involved. Staphylococcus aureus was cultured from twelve joints and Escherichia coli, from one. Treatment consisted of repeated needle aspirations in two patients, arthrotomy with Penrose drainage in six, and arthrotomy with through-and-through irrigation in four. Needle aspiration was the least effective therapy. The authors recommend as the treatment of choice: systemic antibiotic therapy and immediate arthrotomy followed by through-and-through irrigation with fluid containing the appropriate antibiotics.

Inhibition of bacterial adhesion by antibacterial surface pretreatment of vascular prostheses

Polytetrafluoroethylene grafts were pretreated with oxacillin, with the cationic detergent benzalkonium, or with both substances, either at room temperature or at 90 degrees C. Inhibition zones ranging from 6.4 to 15.2 mm formed around all grafts incubated on Staphylococcus aureus-streaked agar plates except control disks and those treated with oxacillin. Treated grafts were exposed in vitro to S. aureus in high concentration, followed by distilled water lavage. The graft surface was then stained with ruthenium red to stain polysaccharides and studied by scanning and transmission electron microscopy. Colonization of the graft surface by adhesive bacteria was demonstrated in all cases, although it was less prevalent on grafts pretreated with benzalkonium bound at 90 degrees C.

Altered oxidative responses and antibacterial activity of adult rabbit alveolar macrophages exposed to poly(methyl methacrylate)

The effect of poly(methyl methacrylate) (PMMA) on the oxidative responses and antibacterial activity of adult rabbit alveolar macrophages (AM) was studied. PMMA beads (ca. 0.3 micron diameter) elicited an acute respiratory burst within 6-8 min after the addition of the beads. In contrast. Teflon beads of comparable size (ca. 0.2 micron diameter) did not elicit an oxidative burst of AM. An oxidative response was elicited only by those PMMA samples that had affinity for AM adherence. Incubation of AM with PMMA beads reduced the subsequent phorbol myristate acetate (PMA)-elicited oxidative burst by more than 80%. The Staphylococcus epidermidis--RP12 killing capacity of AM was greatly increased when PMMA beads (ca. 0.3 micron) were added to the challenge dose of bacteria. Pre-incubation of freshly harvested AM with PMMA beads, which greatly reduced subsequent PMA-elicited chemiluminescent (CL) responses did not significantly affect the RP12 killing capacity of AM. Our data also suggest that killing of the RP12 strain of S. epidermidis does not involve reactive oxygen intermediates.