tacrolimus and Gram-Positive-Bacterial-Infections

Activated hepatic macrophages can provoke massive liver necrosis following endotoxin stimulation through microcirculatory disturbances due to sinusoidal fibrin deposition in rats pretreated with heat-killed Propionibacterium acnes. In these rats, FK506 (tachlorinus) administered 24 h before and at the time of endotoxin injection, significantly attenuated liver injury compared with the rats given no FK506. The effect of FK506 on hepatic macrophage activation and its action sites were studied in Propionibacterium acnes-treated rats. When rats received Propionibacterium acnes intravenously, hepatic-mRNA expression of interferon-gamma-inducing factor and interleukin-2 and splenic-mRNA expression of interferon-gamma were significantly increased compared with normal rats. Hepatic-mRNA expression of CD14, a receptor for lipopolysaccharide and its binding protein complex, was also increased preceding the expressions of the three cytokines in the liver and spleen. FK506 administration attenuated hepatic-mRNA expression of interleukin-2 and both superoxide anions as well as tumour necrosis factor-alpha production by hepatic macrophages, but did not change CD14-mRNA expression in Propionibacterium acnes-treated rats. It is suggested that a cytokine network through interferon-gamma-inducing factor, interferon-gamma and interleukin-2 may operate during activation of hepatic macrophages in rats treated with heat-killed Propionibacterium acnes, while CD14 expression on the cells may increase independently of this network. FK506 seems to attenuate such activation by suppressing hepatic interleukin-2 expression, without affecting CD14 expression on the cells.

Topics: Animals; Cytokines; Gram-Positive Bacterial Infections; Immunosuppressive Agents; Liver; Macrophages; Propionibacterium acnes; Rats; Tacrolimus

To determine whether myalgias/arthralgias occurring in cancer patients who receive quinupristin/dalfopristin are associated with biliary tract dysfunction.. We studied 56 patients with vancomycin-resistant enterococcal infections who were treated with quinupristin/dalfopristin 7.5 mg/kg every 8 h for a mean duration of 12 days (range 2-52 days). Liver function tests, including a test for alkaline phosphatase, were performed before, during and after the end of therapy. All patients were followed for 1 month after completion of therapy.. Thirty-eight (68%) of the 56 patients responded. Myalgias/arthralgias were the leading adverse events occurring in 20 (36%) of the patients. Patients with myalgias/arthralgias had significantly higher levels of alkaline phosphatase (mean 318.7 IU/L) during the mid-term therapy cycle compared with patients without any joint or muscular pain (mean 216.3 IU/L, P = 0.05). In addition, 3/18 (16.6%) patients with myalgias/arthralgias had more than five-fold the normal levels of alkaline phosphatase, which did not occur in any of the other patients who did not develop myalgias/arthralgias (P = 0.04). All myalgias/arthralgias resolved after the discontinuation of quinupristin/dalfopristin. By univariate analysis, other factors associated with myalgias/arthralgias were relapse of haematological malignancy (P = 0.01), receiving tacrolimus within 1 month prior to treatment (P = 0.04) and receiving methotrexate during antimicrobial therapy (P = 0.05).. Myalgias/arthralgias occur frequently in cancer patients receiving quinupristin/dalfopristin and may be associated with biliary tract dysfunction, as measured by alkaline phosphatase or other factors that could lead to intra-hepatic cholestasis, such as relapse of haematological malignancy or treatment with tacrolimus or methotrexate.

Topics: Aged; Alkaline Phosphatase; Anti-Bacterial Agents; Antimetabolites, Antineoplastic; Antineoplastic Agents; Arthralgia; Biliary Tract Diseases; Enterococcus; Female; Gram-Positive Bacterial Infections; Humans; Immunosuppressive Agents; Liver Function Tests; Male; Methotrexate; Middle Aged; Muscular Diseases; Neoplasms; Pain; Recurrence; Risk Factors; Tacrolimus; Virginiamycin

The clinical course and outcomes of immunocompromised patients, such as transplant recipients, with COVID-19 remain unclear. It has been postulated that a substantial portion of the disease burden seems to be mediated by the host immune activation to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Herein, we present a simultaneous heart-kidney transplant (SHKT) recipient who was hospitalized for the management of respiratory failure from volume overload complicated by failure to thrive, multiple opportunistic infections, and open non-healing wounds in the setting of worsening renal dysfunction weeks prior to the first case of SARS-CoV-2 being detected in the state of Connecticut. After his third endotracheal intubation, routine nucleic acid testing (NAT) for SARS-CoV-2, in anticipation of a planned tracheostomy, was positive. His hemodynamics, respiratory status, and ventilator requirements remained stable without any worsening for 4 weeks until he had a negative NAT test. It is possible that the immunocompromised status of our patient may have prevented significant immune activation leading up to clinically significant cytokine storm that could have resulted in acute respiratory distress syndrome and multisystem organ failure.

Topics: Antibiotics, Antineoplastic; Bacteremia; BK Virus; Cardiomyopathy, Dilated; Cardiotoxicity; COVID-19; COVID-19 Nucleic Acid Testing; Doxorubicin; Graft Rejection; Gram-Positive Bacterial Infections; Heart Transplantation; Humans; Immunocompromised Host; Immunosuppressive Agents; Incidental Findings; Kidney Failure, Chronic; Kidney Transplantation; Male; Malnutrition; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Mycophenolic Acid; Opportunistic Infections; Polyomavirus Infections; Postoperative Complications; Prednisone; Renal Dialysis; SARS-CoV-2; Staphylococcal Infections; Surgical Wound Infection; Tacrolimus; Tracheostomy; Tumor Virus Infections; Vancomycin-Resistant Enterococci; Viremia; Water-Electrolyte Imbalance

To explore the etiopathogenesis, therapy and incidence of pulmonary infection in kidney transplantation recipients taking new immunosuppressant.. The clinical data from 752 kidney transplant recipients were retrospectively analyzed, who were divided into 3 groups according to the immunosuppressants administered, namely group A (CsA+MMF+Pred, n=226), group B (FK506+MMF+Pred, n=386) and group C (FK506+Rap+Pred, n=140). The incidence and mortality of pulmonary infection were recorded and the analysis of etiopathogenesis, diagnosis and therapy of pulmonary infection were carried out in the 3 groups.. Fifty-three patients acquired post-transplant pulmonary infection. The incidence of pulmonary infection was 7.08% (16/226) in group A, 7.25% (28/386) in group B and 6.43% (9/140) in group C. One patient died in group A and 2 in group B. Among the 53 patients, 24 had simple bacterial infection, 9 had cytomegalovirus infection, 1 had mycotic infection, 17 had combined infection, and 2 had unidentified pathogen infection. Of the pathogenic bacteria detected, 68.35% were Gram-negative.. Gram-negative bacteria are most likely responsible for pulmonary infection after kidney transplantation, which most possibly occurs within 6 months after kidney transplantation. Early diagnosis and early treatment are critical for decreasing the mortality of severe pneumonia and for improving the survival rate of the patients and grafts.

Topics: Adolescent; Adult; Aged; Cyclosporine; Cytomegalovirus Infections; Female; Gram-Positive Bacterial Infections; Humans; Immunosuppressive Agents; Kidney Transplantation; Lung Diseases; Male; Middle Aged; Tacrolimus