Factors related to outcome of early and delayed prosthetic joint infections.

UNLABELLED: In this prospective study, we evaluate the impact of adherence to a diagnostic and therapeutic protocol on prosthetic joint infections (PJI) diagnostic accuracy and outcome. PATIENTS AND METHODS: Patients with early or delayed PJI referred over a 5-year period were included. Diagnosis was based on characteristic clinical signs, radiographic findings and microbiological evidence. Antibiotics were chosen on the basis of microbiological findings, and drugs active against methicillin-resistant staphylococci were administered if no microbiological evidence had been obtained. RESULTS: Inclusion criteria were met in 159 cases (median age 64 years, males 45%). 56 were early infections and 103 delayed infections. Comorbidities were reported in 99 (62%) cases. Positive cultures were obtained in 122/159 (77%), coagulase-negative staphylococci were cultured in 20%, Staphylococcus aureus in 28%, and Pseudomonas aeruginosa in 7%. In early infections, cure rate after debridement and antibiotic therapy was 80%. In delayed infections, cure rate after two-stage exchange was 85%. Of 28 patients with delayed infection treated with antibiotics without surgery, only 8 (29%) infections were suppressed 48 weeks after treatment discontinuation. Rifampin afforded a better outcome. CONCLUSION: Appropriate diagnostic and surgical procedures and microbiologically driven antibiotic therapy including rifampin are recommended to improve diagnostic accuracy and outcome.

Mechanism of cytokine inhibition of beta-adrenergic agonist stimulation of cyclic AMP in rat cardiac myocytes. Impairment of signal transduction.

Studies conducted in our laboratory have demonstrated that activated immune cells produce a soluble inhibitor(s) of cardiac myocyte contractile and cyclic AMP (cAMP) responses to beta-adrenergic stimulation. To examine the mechanism of this effect, metabolic assays were conducted on cultured rat cardiac myocytes incubated in the presence and absence of supernatants harvested from rat activated splenocyte cultures. Intracellular cAMP accumulation in response to isoproterenol was inhibited by up to 74% in a dose-dependent fashion by conditioned media containing soluble cytokines from activated immune cells. By use of myocyte cultures in which contaminating nonmyocyte proliferation was inhibited by nonlethal irradiation, this phenomenon was shown to be independent of mitogenic effects. Isobutylmethylxanthine, a phosphodiesterase inhibitor, did not ablate cytokine-induced inhibition of cAMP accumulation. Parameters of beta-adrenergic receptor binding and affinity were also unaffected. cAMP suppression was maintained after cholera toxin stimulation of cAMP production via stimulatory G protein ADP-ribosylation. cAMP inhibition was not apparent when cells were stimulated with forskolin, a direct adenylate cyclase activator. Importantly, pertussis toxin treatment significantly ablated cytokine-induced cAMP inhibition. Thus, interference with agonist-occupied beta-adrenergic receptor coupling to adenylate cyclase to produce cAMP and subsequent contractile responses is induced by a factor(s) elaborated by activated immune cells. This interference occurs at the level of signal transduction across the membrane, can be overridden by pertussis toxin, and may involve changes in the coupling of the stimulatory/inhibitory G proteins to adenylate cyclase. These results demonstrate a novel mechanism of cytokine-induced myocyte dysfunction and may have important pathophysiological ramifications in immune-mediated myocardial diseases.