tacrolimus and Peritonitis

Four months after receiving an orthotopic liver transplant, a 51-year-old man was admitted for progressive liver failure and severe hepatocellular necrosis thought to be due to tacrolimus. During his hospitalization he experienced bloodstream infections including fungemia due to Trichosporon mucoides and prolonged undulating fever despite antifungal and antibacterial treatment. He underwent removal of the allograft and implantation of another liver. Fever continued postoperatively until therapy with posaconazole was initiated. Initiation of posaconazole led to clinical improvement until the patient's demise from bacteremic vancomycin-resistant enterococcal peritonitis. Trichosporonosis appears to be an emerging fungal infection among immunocompromised individuals (including both hematological and solid organ transplant recipients). T. mucoides is a rare cause of systemic infection. When it occurs, trichosporonosis usually is associated with hematological malignancies and, to the best of our knowledge, has not been previously reported in a liver transplant recipient. The optimal treatment is not well defined. We report here the first case using posaconazole for treatment of trichosporonosis in a liver transplant recipient caused by T. mucoides.

Topics: Antifungal Agents; Enterococcus faecium; Fatal Outcome; Fungemia; Humans; Immunosuppressive Agents; Liver Transplantation; Male; Middle Aged; Mycoses; Peritonitis; Postoperative Complications; Tacrolimus; Triazoles; Trichosporon; Vancomycin; Vancomycin Resistance

Bowel perforation is an uncommon but serious complication of peritoneoscopic peritoneal dialysis (PD) catheter insertion. The approach to diagnosis of bowel perforation utilizing this technique has not been previously published. The authors report their experience with the diagnosis and management of bowel perforation in the context of peritoneoscopic placement of PD catheters.. The authors retrospectively reviewed the records of 750 PD catheters inserted over a 12-year period (January 1991 to May 2003) utilizing peritoneoscopic technique.. Six (0.8%) patients experienced bowel perforation during the procedure. The diagnosis was made immediately during the procedure in 5 (83%) of the 6 patients. Of these 5, peritoneoscopy confirmed intrabowel position of the cannula by visualizing bowel mucosa (n = 3) and hard stool (n = 1). The fifth patient showed extrusion of fecal matter upon trocar withdrawal before peritoneoscopy. All 5 had emanation of foul-smelling gas through the cannula. Bowel rest and broad-spectrum intravenous antibiotics were initiated. Of the 5, 1 required surgery, whereas the others were discharged home after 3 days. The sixth patient had fever, severe peritoneal irritation, and polymicrobial peritonitis the morning after the procedure. In this patient, no evidence of bowel injury was noted during the procedure except for brief emanation of foul-smelling gas. He required surgical intervention.. Bowel perforation can be diagnosed immediately in most patients undergoing peritoneoscopic PD catheter insertion. A majority of these patients can be treated medically. The surgical team should be consulted if the patient shows clinical deterioration or has signs of peritoneal irritation.

Topics: Abdomen, Acute; Adult; Aged; Anti-Bacterial Agents; Catheterization; Combined Modality Therapy; Diabetic Nephropathies; Drug Therapy, Combination; Feces; Female; Gases; Humans; Immunosuppressive Agents; Intestinal Perforation; Kidney Failure, Chronic; Laparoscopy; Lung Transplantation; Male; Middle Aged; Peritoneal Dialysis; Peritonitis; Postoperative Complications; Retrospective Studies; Surgical Instruments; Tacrolimus

Topics: Adult; Ascites; Chronic Disease; Cyclophosphamide; Female; Humans; Lupus Erythematosus, Systemic; Mycophenolic Acid; Peritonitis; Prednisolone; Severity of Illness Index; Tacrolimus; Tomography, X-Ray Computed; Treatment Outcome

Topics: Arthroplasty, Replacement, Hip; Cecal Diseases; Female; Hepatitis C, Chronic; Humans; Immunosuppressive Agents; Intestinal Perforation; Liver Cirrhosis; Liver Transplantation; Middle Aged; Periprosthetic Fractures; Peritonitis; Tacrolimus; Therapeutic Irrigation

Abdominal sepsis due to intestinal leakage of endogenous gut bacteria is a life-threatening condition. In healthy individuals, T lymphocytes have essential functions in balancing the immune response to the commensal gut flora.. To determine how T lymphocytes shape the process of diffuse faecal peritonitis.. In colon ascendens stent peritonitis (CASP), a clinically relevant mouse model of diffuse peritonitis, the kinetics of systemic T cell activation were investigated by assessment of activation markers. CD4(+) T cells were then depleted with monoclonal antibodies, and survival, bacterial dissemination and cytokine concentrations were measured. T cell receptor signalling was blocked with tacrolimus.. In diffuse peritonitis, CD4(+) T cells, both Foxp3(-) and Foxp3(+), became systemically involved within hours and upregulated CTLA-4 and other activation markers. Depletion of the CD4(+) T cells enhanced local bacterial clearance from the peritoneal cavity, reduced bacterial dissemination and improved survival. This was accompanied by increased immigration of granulocytes and macrophages into the peritoneum, indicating that CD4(+) T cells inhibit the local innate immune response. Blockade of T cell receptor (TCR) signalling by tacrolimus did not influence the survival in this peritonitis model, showing that the inhibitory effects of the CD4(+) T lymphocytes were independent of TCR-mediated antigen recognition.. In diffuse peritonitis caused by commensal gut bacteria the CD4(+) T lymphocytes exert a net negative effect on the local anti-bacterial defence, and thereby contribute to bacterial dissemination and poor outcome.

Topics: Abdomen; Animals; Bacteria; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes; Cell Communication; Immunosuppressive Agents; Mice; Peritonitis; Receptors, Antigen, T-Cell; Sepsis; Tacrolimus

The metabolism of tacrolimus is influenced by several medications when they are given concurrently. We report the interaction between tacrolimus and chloramphenicol in a renal transplant recipient.. An adolescent with vancomycin-resistant Enterococcus was given standard doses of chloramphenicol. Tacrolimus trough levels increased, and the dose was adjusted to maintain the target trough level. Pharmacokinetic studies were obtained during chloramphenicol administration and 14 days after its discontinuation.. Toxic levels of tacrolimus were seen on the second day of chloramphenicol administration, requiring an 83% reduction in the tacrolimus dose. The dose-adjusted area under the curve value for tacrolimus was 7.5-fold greater while the patient was on chloramphenicol. These data are consistent with inhibition of tacrolimus clearance by chloramphenicol. Chloramphenicol interferes with tacrolimus metabolism. Careful monitoring of tacrolimus trough levels during concomitant chloramphenicol therapy is recommended to avoid toxicity.

Topics: Adolescent; Anti-Bacterial Agents; Bacterial Infections; Chloramphenicol; Dose-Response Relationship, Drug; Drug Interactions; Enterococcus; Female; Humans; Immunosuppressive Agents; Kidney Transplantation; Peritonitis; Postoperative Complications; Tacrolimus

An 8-month-old child with an immunodeficiency disorder characterized by abnormal lymphocyte function and by low IgG and IgA levels had combined liver and small bowel transplantation under tacrolimus and steroid immunosuppression for the treatment of short gut syndrome and hepatic cirrhosis. The patient developed an early postoperative episode of Pneumocystis carinii pneumonia, and a subsequent surgical complication, prompting discontinuance of tacrolimus. A skin rash eventually shown to be graft-versus-host disease (GVHD) developed in the flank on the 12th post-transplant day and gradually became generalized. Peritonitis, sepsis, multisystem organ failure including the liver allograft led to death on the 23rd post-operative day. The mechanisms leading to post-transplant GVHD under the specific circumstances in this case are discussed.

Topics: Exanthema; Fatal Outcome; Female; Glucocorticoids; Graft vs Host Disease; Humans; IgA Deficiency; IgG Deficiency; Immunologic Deficiency Syndromes; Immunosuppressive Agents; Infant; Intestine, Small; Ischemia; Liver; Liver Cirrhosis; Liver Transplantation; Lymphocytes; Methylprednisolone; Multiple Organ Failure; Peritonitis; Pneumonia, Pneumocystis; Sepsis; Short Bowel Syndrome; Tacrolimus

Topics: Adolescent; Child; Child, Preschool; Female; Follow-Up Studies; Graft Survival; Humans; Immunosuppressive Agents; Infant; Intestine, Small; Male; Peritonitis; Postoperative Complications; Reoperation; Retrospective Studies; Survival Rate; Tacrolimus; Time Factors; Transplantation, Homologous

Topics: Animals; CD4-Positive T-Lymphocytes; Eosinophils; Hypersensitivity; Interferon-gamma; Lymphocyte Depletion; Male; Mice; Mice, Inbred BALB C; Neutrophils; Ovalbumin; Peritoneal Cavity; Peritonitis; Recombinant Proteins; Tacrolimus

1. The intraperitoneal (i.p.) injection of 1 or 10 micrograms ovalbumin to sensitized Balb/c mice led to an acute histamine release, firstly evidenced 1 min after the challenge and returning to basal levels 30 min thereafter. This phenomenon was unaccompanied by protein extravasation. A dose-dependent increase in the amounts of immunoreactive leukotriene (LT) C4 and LTB4 was observed in the peritoneal washing from sensitized mice 6 h after 1 or 10 micrograms ovalbumin administration. In separate experiments, the i.p. administration of 1 mg activated zymosan to non-immunized mice was followed by a marked protein extravasation, and by immunoreactive LTC4 and LTB4, but not histamine, release in mouse peritoneum 1 h after its injection. 2. Mediator release in the mice peritoneal cavity was concomitant with a transient neutrophil infiltration, which peaked at 6 h and returned to basal levels therefore. An intense eosinophil accumulation starting at 24 h, peaking at 48 h and returning to basal values at 164 h, was also observed. 3. Ovalbumin (1 microgram)-induced eosinophilia, observed at 24 h, was reduced by the pretreatment of the animals with dexamethasone (1 mg kg-1, s.c.) or with the 5-lipoxygenase inhibitor, BWA4C (20 mg kg-1, s.c.), whereas indomethacin (2 mg kg-1, s.c.) and the platelet-activating factor (PAF)-antagonist SR 27417 (10 mg kg-1, s.c.) were ineffective. These results indicate that metabolites of arachidonic acid of lipoxygenase pathway, but not cyclo-oxygenase derivatives or PAF, mediate antigen-induced eosinophil accumulation in the mouse peritoneum. 4. The histamine HI receptor antagonist drug, cetirizine (15-30 mg kg-1, s.c.) markedly reduced ovalbumin-induced eosinophil accumulation under conditions where terfenadine was ineffective, suggesting that the effect of cetirizine was not related to the inhibition of the H1 receptor effects of histamine.5. The immunosuppressive agent, FK-506 (1-2 mg kg-1, s.c.) and the protein synthesis inhibitor,cylcoheximide, when administered either in situ (0.06 ng/cavity) or systemically (5 mg kg-1, s.c.),prevented antigen-induced eosinophil accumulation in the mouse peritoneum, contributing to the concept that substances (probably cytokines) originating from lymphocytes may be involved in the modulation of the eosinophilotactic response in this model.6. The results of the present study indicate that the i.p. administration of ovalbumin to actively sensitized mice induced late eosinophil accumulation in t

Topics: Animals; Benzeneacetamides; Cetirizine; Cycloheximide; Dexamethasone; Eosinophils; Histamine Release; Hydroxamic Acids; Indomethacin; Kinetics; Leukocyte Count; Leukotriene B4; Leukotriene C4; Lipoxygenase Inhibitors; Male; Mice; Mice, Inbred BALB C; Ovalbumin; Peritoneal Cavity; Peritonitis; Platelet Activating Factor; T-Lymphocytes; Tacrolimus; Terfenadine; Thiazoles; Zymosan