sirolimus and Staphylococcal-Infections

Coronary stent infection is exceedingly rare despite the widespread use of percutaneous coronary intervention (PCI). The utilization of drug-eluting stents (DES) may have a higher theoretical risk of infection due to their local immunosuppressant effect. Vigilance in suspecting stent infection is important, as the associated mortality rate is approximately 50%. We discuss the case of a patient who presented with an infected DES 2 weeks after implantation which led to spontaneous Type II coronary perforation. The perforation was sealed with prolonged balloon inflation, and the patient was treated with intravenous antibiotics. This is the first reported case of a patient with a stent infection who presented with a spontaneous coronary perforation.

Topics: Aged, 80 and over; Angioplasty, Balloon, Coronary; Coronary Artery Disease; Drug-Eluting Stents; Echocardiography; Fatal Outcome; Female; Humans; Immunosuppressive Agents; Prosthesis-Related Infections; Rupture, Spontaneous; Sirolimus; Staphylococcal Infections

The objective of this study was to analyze how Staphylococcus epidermidis SCV and WT strains manipulate the PI3K/Akt/mTOR signaling pathway. Six S. epidermidis strains with normal phenotype (WT) and six S. epidermidis strains with SCV phenotype were isolated in parallel from six patients with the prosthetic hip joint infections. THP-1 activated cells were incubated with or without PI3K inhibitor-wortmannin or with mTOR inhibitor-rapamycin. Next, macrophages were exposed to S. epidermidis WT and SCV strains. After 4 h incubation, bacterial survival inside macrophages as well as PI3K-mTOR activation was analyzed. SCV strains of S. epidermidis increased the level of Akt phosphorylation, compared to uninfected macrophages and to their parental WT forms. Wild type variants of S. epidermidis phosphorylated Akt at similar or lower levels as control uninfected cells. Next, the induction of mTOR target, phosphorylated ribosomal protein S6, was measured in bacteria-infected macrophages. The level of phosphorylation was significantly reduced when the cells were exposed to WT strains of S. epidermidis. In contrast, the SCV strains activated S6 protein mostly at a level comparable to the control cells. Rapamycin inhibited mTOR activation as the number of p-S6 positive cells decreased in the tested cases. To conclude, the SCV strains activate the PI3K-Akt signaling pathway in opposite to WT strains. This fact however did not influence the increase in the number of live SCV bacteria as compared to the WT strains. Knowing that the PI3K-Akt pathway is involved in proinflammatory cytokines suppression, SCVs seem to use this pathway to reduce the inflammatory response during the infection.

Topics: Androstadienes; Cell Line; Humans; Macrophages; Microbial Viability; Phenotype; Phosphatidylinositol 3-Kinases; Phosphorylation; Prosthesis-Related Infections; Proto-Oncogene Proteins c-akt; Signal Transduction; Sirolimus; Staphylococcal Infections; Staphylococcus epidermidis; TOR Serine-Threonine Kinases; Wortmannin

Purpose Patients undergoing hematopoietic cell transplantation are treated with multiple medications, potentially complicated by drug-drug interactions. Drug interactions with sirolimus, voriconazole, and rifampin are particularly difficult because of the complex and simultaneous enzyme inhibition and induction mechanisms. We report a hematopoietic cell transplantation patient receiving sirolimus and voriconazole who was given rifampin while being treated for presumed methicillin-resistant Staphylococcus aureus meningitis. Summary A 31 year-old female received a nonmyeloablative allogeneic umbilical cord hematopoietic cell transplantation for myelodysplastic syndrome transformed to acute myeloid leukemia (AML). Her graft versus host disease and antifungal prophylaxis included sirolimus and voriconazole, respectively. Therapeutic drug monitoring prior to admission revealed a stable outpatient sirolimus regimen of 0.4 mg orally daily (trough goal 3-12 mcg/L). She was admitted to the inpatient hematopoietic cell transplantation service and diagnosed with methicillin-resistant Staphylococcus aureus bacteremia and presumed bacterial meningitis 217 days after transplant. Intravenous rifampin and vancomycin were initiated and voriconazole was changed to micafungin. Sirolimus trough concentrations were undetectable two days after starting rifampin. Therapeutic sirolimus concentrations were achieved four days later, at a sirolimus dose of 16-18 mg orally daily. Rifampin was discontinued after nine days and the sirolimus dose was adjusted accordingly, maintaining therapeutic levels throughout follow-up. The patient suffered a flare of chronic skin graft versus host disease requiring etanercept, high-dose systemic steroids, and topical steroids. Conclusion To the best of our knowledge, this is the first report describing the management of sirolimus during the transition from voriconazole inhibition to rifampin induction. Clinicians should be aware of potential drug-drug interactions.

Topics: Adult; Drug Interactions; Female; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Rifampin; Sirolimus; Staphylococcal Infections; Voriconazole

Coronary stent infection is exceedingly rare, with only 23 reported cases. We present a patient with an everolimus-coated stent infection that led to an infected pseudoaneurysm in the left anterior descending artery. Medical therapy failed and the patient underwent emergent surgical intervention; however, he died of multiorgan failure after the operation.

Topics: Aged; Aneurysm, False; Angioplasty, Balloon, Coronary; Bacteremia; Cardiac Output, Low; Coronary Stenosis; Everolimus; Fatal Outcome; Humans; Male; Prosthesis-Related Infections; Reoperation; Sirolimus; Staphylococcal Infections; Stents

Coronary artery stent infection is a rare complication of percutaneous intervention. We report a case of fulminant coronary stent infection with Staphylococcus aureus presenting as a pseudoaneurysm of the left circumflex artery following repeated implantation of drug-eluting stents in the setting of multiple episodes of recurrent in-stent restenosis. We speculate that sirolimus- and paclitaxel-eluting stents may be more likely to predispose to infection than bare metal stents because of their immunomodulating and antiproliferative effects.

Topics: Aged; Aneurysm, False; Aneurysm, Infected; Blood Vessel Prosthesis Implantation; Cardiovascular Agents; Cell Proliferation; Coronary Restenosis; Fatal Outcome; Humans; Immunosuppressive Agents; Male; Paclitaxel; Prosthesis-Related Infections; Sirolimus; Staphylococcal Infections; Staphylococcus aureus; Stents

Topics: Adolescent; Chronic Disease; Gram-Positive Bacterial Infections; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Nail Diseases; Peptostreptococcus; Sirolimus; Staphylococcal Infections; Staphylococcus aureus; Streptococcal Infections; Streptococcus milleri Group; Suppuration; Thumb

The development of infected coronary aneurismal fistula following stenting seems exceedingly rare. A sirolimus-eluting stent (SES) was implanted in a 70-year-old male patient for acute coronary syndrome. His fever persisted despite treatment with adapted antibiotics. Coronary angiography and 16-multidetector row computed tomography demonstrated the huge right coronary aneurysm forming a fistula to the right ventricle. The aneurysm was excised by surgical treatment. Histopathological examination of the resected mass revealed leucocyte infiltration at the stent site, which lead to the diagnosis of mycotic aneurysm. SESs may play a potential role in locally blunting the innate response to bacterial agents.

Topics: Aged; Anti-Bacterial Agents; Coronary Aneurysm; Fistula; Heart Ventricles; Humans; Male; Sirolimus; Staphylococcal Infections; Stents; Treatment Outcome

Topics: Aneurysm, Infected; Angioplasty, Balloon, Coronary; Coronary Aneurysm; Humans; Immunosuppressive Agents; Male; Middle Aged; Sirolimus; Staphylococcal Infections; Stents

We report a case of mycotic aneurysms due to Staphylococcus aureus infection in the left anterior descending coronary artery in a 56-year-old male after implantation of a sirolimus-eluting stent. This is an unreported complication of a drug-eluting stent.

Topics: Aneurysm, Infected; Angioplasty, Balloon, Coronary; Coronary Aneurysm; Humans; Immunosuppressive Agents; Male; Middle Aged; Sirolimus; Staphylococcal Infections; Stents

Septic complications after coronary stenting are extremely rare. The occurrence of cardiac related sepsis after rapamycin eluting stent deployment has not been previously reported. The potential role of drug eluting stents in locally blunting the innate response to bacterial agents is discussed.

Topics: Catheterization; Coronary Restenosis; Drug Implants; Fatal Outcome; Humans; Immunosuppressive Agents; Male; Middle Aged; Retreatment; Sirolimus; Staphylococcal Infections; Staphylococcus aureus; Stents

Topics: Aneurysm, Infected; Angioplasty, Balloon, Coronary; Coronary Aneurysm; Humans; Immunosuppressive Agents; Risk Factors; Sirolimus; Staphylococcal Infections; Stents