Infections in liver transplant recipients.
Explore the source record for details and available documents.
Anti-Infective Agents↗
Biomedical subjects
D J Winston
Publications and source records attributed to D J Winston.
Fluconazole prophylaxis of fungal infections in patients with acute leukemia. Results of a randomized placebo-controlled, double-blind, multicenter trial.
OBJECTIVE: To evaluate the efficacy and safety of fluconazole for prevention of fungal infections. DESIGN: A randomized, placebo-controlled, double-blind, multicenter trial. PATIENTS: Adults (257) undergoing chemotherapy for acute leukemia. INTERVENTION: Patients were randomly assigned to receive either fluconazole (400 mg orally once daily or 200 mg intravenously every 12 hours) or placebo. The study drug was started at initiation of chemotherapy and continued until recovery of neutrophil count, development of proven or suspected invasive fungal infection, or the occurrence of a drug-related toxicity. MEASUREMENTS: Fungal colonization, proven superficial or invasive fungal infection, empiric antifungal therapy with amphotericin B, drug-related side effects, and mortality. MAIN RESULTS: Fluconazole decreased fungal colonization (83 of 122 [68%] placebo patients compared with 34 of 119 [29%] fluconazole patients colonized at end of prophylaxis, P < 0.001) and proven fungal infections (27 of 132 [21%] placebo patients compared with 11 of 123 [9%] fluconazole patients infected, P = 0.02). Superficial fungal infections occurred in 20 of 132 (15%) placebo patients but in only 7 of 123 (6%) fluconazole patients (P = 0.01), whereas invasive fungal infections developed in 10 of 132 (8%) placebo patients and in 5 of 123 (4%) fluconazole patients (P = 0.3). Fluconazole was especially effective in eliminating colonization and infection by Candida species other than Candida krusei (66 of 122 [64%] placebo patients colonized at end of prophylaxis compared with 11 of 119 [9%] fluconazole patients, P < 0.001; 22 of 132 [17%] placebo patients infected compared with 7 of 123 [6%] fluconazole patients, P = 0.005). Aspergillus infections were infrequent in both fluconazole (3 cases) and placebo groups (3 cases). The use of amphotericin B, the incidence of drug-related side effects, and overall mortality were similar in both study groups. CONCLUSION: Prophylactic fluconazole prevents colonization and superficial infections by Candida species other than Candida krusei in patients undergoing chemotherapy for acute leukemia and is well tolerated. Fluconazole could not be clearly shown to be effective for preventing invasive fungal infections, reducing the use of amphotericin B, or decreasing the number of deaths.
Acute Disease↗
Ganciclovir prophylaxis of cytomegalovirus infection and disease in allogeneic bone marrow transplant recipients. Results of a placebo-controlled, double-blind trial.
OBJECTIVE: To evaluate the efficacy and safety of ganciclovir for prevention of cytomegalovirus (CMV) infection and disease. DESIGN: A randomized, placebo-controlled, double-blind trial. SETTING: University-affiliated bone marrow transplant center. PATIENTS: Cytomegalovirus-seropositive allogeneic bone marrow transplant recipients. INTERVENTIONS: Random assignment to receive either a placebo or ganciclovir at a dose of 2.5 mg/kg body weight every 8 hours for 1 week before transplant and then at a dose of 6 mg/kg once per day, Monday through Friday, after transplant when the post-transplant neutrophil count reached 1.0 x 10(9)/L. MEASUREMENTS: Cytomegalovirus infection (positive culture, seroconversion, positive histologic findings), CMV disease (pneumonia, gastroenteritis, the wasting syndrome), and study-drug toxicity. RESULTS: Cytomegalovirus infection developed in 25 of 45 placebo patients (56%) but in only 8 of 40 ganciclovir patients (20%) (P < 0.001). Cytomegalovirus disease may also have occurred less often in the ganciclovir patients (4 of 40 patients [10%] versus 11 of 45 patients [24%]; P = 0.09). The probability of CMV disease occurring within the first 120 days after transplantation was 0.29 among the placebo patients but only 0.12 among ganciclovir patients (P = 0.06). Reversible neutropenia was the only appreciable toxicity related to ganciclovir and required interruption of the study drug after transplant in 25 of 43 ganciclovir patients (58%) and in 13 of 47 placebo patients (28%) (P = 0.005). Overall survival was similar in both the placebo patients (29 of 45 [64%]) and ganciclovir patients (28 of 40 [70%]; P > 0.2). CONCLUSIONS: Prophylactic ganciclovir, started before transplant and continued after recovery of the post-transplant neutrophil count, reduces the incidence and severity of CMV infection in CMV-sero-positive bone marrow transplant recipients but is frequently associated with neutropenia.
Adolescent↗
Intravenous immunoglobulin and CMV-seronegative blood products for prevention of CMV infection and disease in bone marrow transplant recipients.
The efficacy of i.v. immunoglobulin plus CMV-seronegative blood products or CMV-seronegative blood products alone for prevention of CMV infection, symptomatic CMV disease, other infections and GVHD after BMT was evaluated in a randomized, controlled trial. Fifty-one CMV-seronegative allogeneic BMTs with a CMV-seronegative or CMV-seropositive marrow donor were randomly assigned to receive either i.v. immunoglobulin (1.0 g/kg once weekly for 120 days after transplant) plus CMV-seronegative blood products or CMV-seronegative blood products alone. CMV infection occurred in 2 of 25 patients (7%) receiving i.v. immunoglobulin plus CMV-seronegative blood and in 2 of 23 patients (9%) receiving CMV-seronegative blood alone. All CMV infections were asymptomatic and characterized by viral excretion with or without CMV seroconversion. There were no cases of CMV-related interstitial pneumonia. Grade > or = II GVHD was less frequent in patients given i.v. immunoglobulin (5 of 25 patients (20%) vs. 11 of 23 patients (48%), p = 0.04). The number of bacterial and fungal infections was similar in both groups. Fewer non-CMV viral infections (9 of 27 patients (33%) vs. 15 of 24 patients (63%), p = 0.03) and fewer deaths associated with infection (1 of 27 patients (4%) vs. 5 of 24 patients (21%), p = 0.07) occurred in recipients of immunoglobulin. Neither survival nor risk of leukemia relapse was changed by the immunoglobulin. The high doses of i.v. immunoglobulin were well tolerated. These results suggest that CMV-seronegative blood products alone prevent most CMV infections and CMV disease in CMV-seronegative allogeneic BMT recipients, even when the marrow donor is CMV-seropositive.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Prophylaxis and treatment of infection in the bone marrow transplant recipient.
Considerable progress has been made in the prophylaxis and treatment of infections in the bone marrow transplant recipient. Much of this progress is related to the availability of many new antimicrobial agents and biological products, as well as to an improved understanding of the pathogenesis of infections. Because of the expense associated with many of these agents and products, defensive strategies against infections must consider not only effectiveness but also cost (Table 16.9). It is now possible that a marrow transplant recipient could receive as many as five or six different prophylactic agents. While the use of an oral fluoroquinolone or oral fluconazole for prevention of serious bacterial and fungal infections is relatively inexpensive, the price of intravenous immune globulin and GM-CSF is considerably higher. Their routine use in all patients may not be economical. The results from ongoing trials comparing different dosing regimens of intravenous immune globulin and selectively using GM-CSF or G-CSF only in patients with suspected or documented infection will be important (80,173). On the other hand, the cost of providing CMV-seronegative blood products or prophylactic ganciclovir is justified by the high morbidity and mortality of CMV interstitial pneumonia in allotransplants. The low incidence of CMV disease in syngeneic transplants and autotransplants, however, makes CMV prophylaxis unnecessary. Similarly, in view of a recent controlled trial showing no benefit of intravenous immune globulin for prophylaxis of infections, intravenous immune globulin is also not needed in autotransplants. Trimethoprim-sulfamethoxazole is cheap prophylaxis for Pneumocystis carinii pneumonia, but the very low mortality from herpes simplex infection makes acyclovir a very expensive prophylaxis. Treatment options for the infected bone marrow transplant recipient have also become broader. The decline of Pseudomonas aeruginosa and other gram-negative bacillary infections and the availability of newer, more potent beta-lactam drugs makes monotherapy an appropriate and more cost-effective regimen for empiric therapy of many febrile patients. The introduction of fluconazole, itraconazole, and other newer antifungals offers promise for improving antifungal therapy, but these agents should not take the place of amphotericin B in a critically ill patient with suspected or documented fungal infection until results of ongoing controlled trials show equivalent efficacy. The role of biological response modifiers like macrophage colony-stimulating factor in the treatment of fungal infections also needs to be defined. Development of clinically applicable serologic tests for early detection of specific Candida or Aspergillus antigen is badly needed to help guide antifungal therapy.(ABSTRACT TRUNCATED AT 400 WORDS)
Agranulocytosis↗
Ganciclovir for cytomegalovirus after heart transplantation.
Explore the source record for details and available documents.
Cytomegalovirus Infections↗
A controlled trial of fluconazole to prevent fungal infections in patients undergoing bone marrow transplantation.
BACKGROUND AND METHODS: Superficial and systemic fungal infections are a major problem among severely immunocompromised patients who undergo bone marrow transplantation. We performed a double-blind, randomized, multicenter trial in which patients receiving bone marrow transplants were randomly assigned to receive placebo or fluconazole (400 mg daily). Fluconazole or placebo was administered prophylactically from the start of the conditioning regimen until the neutrophil count returned to 1000 per microliter, toxicity was suspected, or a systemic fungal infection was suspected or proved. RESULTS: By the end of the treatment period, 67.2 percent of the 177 patients assigned to placebo had a positive fungal culture of specimens from any site, as compared with 29.6 percent of the 179 patients assigned to fluconazole. Among these, superficial infections were diagnosed in 33.3 percent of the patients receiving placebo and in 8.4 percent of the patients receiving fluconazole (P less than 0.001). Systemic fungal infections occurred in 28 patients who received placebo as compared with 5 who received fluconazole (15.8 percent vs. 2.8 percent, P less than 0.001). Fluconazole prevented infection with all strains of candida except Candida krusei. Fluconazole was well tolerated, although patients who received it had a higher mean increase in alanine aminotransferase levels than patients who received placebo. Although there was no significant difference in overall mortality between the groups, fewer deaths were ascribed to acute systemic fungal infections in the group receiving fluconazole than in the group receiving placebo (1 of 179 vs. 10 of 177, P less than 0.001). CONCLUSIONS: Prophylactic administration of fluconazole to recipients of bone marrow transplants reduces the incidence of both systemic and superficial fungal infections.
Bone Marrow Transplantation↗
Beta-lactam antibiotic therapy in febrile granulocytopenic patients. A randomized trial comparing cefoperazone plus piperacillin, ceftazidime plus piperacillin, and imipenem alone.
OBJECTIVE: To compare the efficacy, toxicity, and cost-effectiveness of double beta-lactam therapy with monotherapy. DESIGN: A randomized, controlled trial. PATIENTS: Febrile, granulocytopenic patients (429). INTERVENTIONS: Patients were randomly assigned to receive iv cefoperazone (3 g every 12 hours) plus piperacillin (75 mg/kg body weight every 6 hours), ceftazidime (2 g every 8 hours) plus piperacillin (75 mg/kg every 6 hours), or imipenem alone (1.0 g or 0.5 g every 6 hours). Patients also received prophylactic vitamin K. MEASUREMENTS: Clinical improvement, eradication of the infecting organism, and toxicity in 403 evaluable patients with one or more infections. MAIN RESULTS: Cefoperazone and ceftazidime, when given in combination with piperacillin, were equally effective (response rates of 75% (104 of 138 patients) and 74% (101 of 137 patients), respectively). Monotherapy with imipenem had a response rate of 82% (111 of 136 patients) and was as effective as double beta-lactam therapy. Overall antibiotic-related toxicity was minimal, although seizures were associated with high doses of imipenem. Seizures occurred in 3 of 29 patients (10.3%) who were receiving 4 g/d of imipenem, in 3 of 136 patients (2.2%) who were receiving cefoperazone plus piperacillin, in 0 of the 132 patients who were receiving ceftazidime plus piperacillin, and in 1 of 106 patients (0.9%) who were receiving 2 g/d of imipenem (P less than 0.005). The 2-g daily dose of imipenem was as effective as the 4-g daily dose. Diarrhea was more frequent in patients receiving cefoperazone, whereas nausea occurred more often with imipenem. No antibiotic-related hemorrhage or nephrotoxicity was observed. Superinfections caused by beta-lactam-resistant, gram-negative bacilli were uncommon but occurred more frequently with double beta-lactam therapy than with imipenem monotherapy (11 of 268 patients compared with 1 of 135 patients; P = 0.06). Xanthomonas maltophilia superinfections occurred only in patients receiving imipenem (3 of 135 patients compared with 0 of 268 patients; P = 0.03). Imipenem monotherapy was the least expensive therapy. CONCLUSIONS: Cefoperazone and ceftazidime were equally effective when used in combination antibiotic therapy with piperacillin. Twice-daily cefoperazone is less expensive than ceftazidime given three times daily. Monotherapy with imipenem, at a daily dose of 2 g, is as efficacious as double beta-lactam therapy and costs less than combination therapy.
Adolescent↗
Prevention and treatment of cytomegalovirus infection and disease after bone marrow transplantation in the 1990s.
There is substantial progress in preventing and treating cytomegalovirus (CMV) infections and CMV-related disease after allogeneic bone marrow transplantation. In CMV-seronegative recipients, use of CMV-seronegative blood products eliminates most CMV infections. Effective prophylaxis for CMV-seropositive recipients is being studied. Preliminary results of controlled trials of prophylactic ganciclovir show reduced CMV-related interstitial pneumonia. Intravenous immunoglobulin (i.v.IG) may further reduce risk of interstitial pneumonia in both CMV-seronegative and -seropositive recipients by decreasing graft-versus-host disease. CMV infection is a lesser problem after autotransplant. Consequently, prophylaxis with CMV-screened blood products, i.v.IG, and antiviral drugs is not necessary. Treatment of CMV-related interstitial pneumonia remains problematic. Best results to date are with ganciclovir and high-dose i.v.IG.
Bone Marrow Transplantation↗
Cytomegalovirus infection and interstitial pneumonia after bone marrow transplantation.
Explore the source record for details and available documents.
Bone Marrow Transplantation↗
Ofloxacin versus vancomycin/polymyxin for prevention of infections in granulocytopenic patients.
INTRODUCTION: The efficacy and safety of oral ofloxacin were compared with those of vancomycin/polymyxin for prophylaxis of bacterial infections in granulocytopenic patients undergoing chemotherapy for hematologic malignancy. PATIENTS AND METHODS: Antimicrobial prophylaxis was begun at the time of initiation of chemotherapy. Thirty patients received ofloxacin tablets (300 mg orally every 12 hours) plus a nystatin suspension. Thirty-two patients received vancomycin capsules (500 mg orally every eight hours) and polymyxin capsules (100 mg orally every eight hours) plus a nystatin suspension. RESULTS: In the group of patients receiving ofloxacin, there were a lower number of acquired gram-negative bacillary organisms per patient (0.13 versus 1.37, p less than 0.00005), fewer patients with documented infection (11 of 30 versus 21 of 32, p = 0.04), and fewer cases of gram-negative septicemia (zero of 30 versus five of 32, p = 0.05). Ofloxacin was also better tolerated (24 of 30 versus 10 of 32 patients highly compliant, p = 0.01) and associated with fewer gastrointestinal side effects (one of 30 versus nine of 32 patients with gastrointestinal side effects, p = 0.01) than vancomycin/polymyxin. However, except for a reduction of Staphylococcus aureus colonization and infection by ofloxacin, neither ofloxacin nor vancomycin/polymyxin was effective in eliminating colonization or infection with viridans group streptococci, coagulase-negative staphylococci, or other gram-positive organisms. Only three isolates of ofloxacin-resistant gram-negative bacteria (Pseudomonas fluorescens, Pseudomonas putida, and Enterobacter aerogenes) were isolated from surveillance cultures, but none caused infection. CONCLUSION: These results suggest that oral ofloxacin is a more tolerable and efficacious alternative to vancomycin/polymyxin for prevention of serious gram-negative bacillary infections in granulocytopenic patients. More effective prophylaxis of gram-positive infections, however, is still needed.
Adolescent↗
Bone marrow transplantation for severe aplastic anemia. Effect of a preparative regimen of cyclophosphamide-low-dose total-lymphoid irradiation and posttransplant cyclosporine-methotrexate therapy.
Twenty-nine patients with severe aplastic anemia were entered into a study of pre- and posttransplant immunosuppressive therapy for bone marrow transplantation. Four of twenty-five previously transfused recipients prepared with cyclophosphamide 200 mg/kg and total-lymphoid irradiation 3 Gy experienced graft failure, indicating that this regimen was inadequate to ensure sustained engraftment. Posttransplant treatment with cyclosporine and methotrexate resulted in an actuarial incidence for grade greater than or equal to 2 graft-versus-host disease of 22 +/- 16%. Actuarial survival was 78 +/- 15%. These data indicate that more effective treatment is necessary to prevent graft failure, but since many patients can be successfully retransplanted, overall survival is comparable to other recent studies.
Adolescent↗
Tolerance and efficacy of ganciclovir in the treatment of cytomegalovirus infections in immunosuppressed patients.
Explore the source record for details and available documents.
Acyclovir↗
Current approaches to management of infections in bone marrow transplants.
Infections continue to be common complications of bone marrow transplantation, but recent advances have improved their outcome. Oral chemoprophylaxis with the fluoroquinolones has reduced gram-negative infections during periods of granulocytopenia, while new triazole drugs show promise for improving antifungal prophylaxis. Similarly, recombinant hematopoietic growth factors may reduce infections by shortening the period of post-transplant granulocytopenia. The efficacy of double beta-lactam antibiotic therapy or monotherapy with imipenem has obviated the need to use aminoglycosides in the empiric treatment of febrile patients receiving cyclosporine or other nephrotoxic agents. Treatment of post-transplant interstitial pneumonia associated with cytomegalovirus (CMV) remains problematic, but recent results using the combination of ganciclovir plus intravenous immune globulin have been favorable. In CMV-seronegative patients, CMV infections and pneumonia can be prevented or modified by using CMV-seronegative blood products and intravenous immune globulin. Intravenous immune globulin also has the additional benefits of modifying graft versus host disease and preventing late bacterial infections after marrow engraftment. In CMV-seropositive patients, prophylactic ganciclovir may prevent CMV reactivation and pneumonia and is the subject of an ongoing controlled clinical trial.
Bone Marrow Transplantation↗
Controlled trials of double beta-lactam therapy with cefoperazone plus piperacillin in febrile granulocytopenic patients.
The efficacy and safety of double beta-lactam therapy with cefoperazone plus piperacillin in febrile granulocytopenic patients were compared with moxalactam plus piperacillin, ceftazidime plus piperacillin, and imipenem alone in two separate clinical trials. All patients also received prophylactic vitamin K. When National Committee for Clinical Laboratory Standards breakpoints for susceptibility were used, a greater proportion of pretherapy isolates of gram-negative aerobic bacilli and gram-positive organisms were found to be susceptible to cefoperazone (94 percent) and imipenem (91 percent) than to moxalactam (84 percent), ceftazidime (85 percent), or piperacillin (85 percent). In trial I, the overall response rates for documented or possible infections were 78 percent (76 of 97 patients) for cefoperazone/piperacillin and 80 percent (72 of 90 patients) for moxalactam/piperacillin. In trial II, the overall response rates were 86 percent (25 of 29 patients) for cefoperazone/piperacillin, 74 percent (20 of 27 patients) for ceftazidime/piperacillin, and 72 percent (21 of 29 patients) for imipenem alone. There was no nephrotoxicity or hemorrhage related to the study drugs. Diarrhea was more frequent with each of the double beta-lactam regimens, whereas nausea and seizures were more common with imipenem given at a dosage of 1.0 g intravenously every six hours. Seizures occurred in three of 29 imipenem-treated patients but in none of 243 patients treated with the double beta-lactam regimens (p less than 0.001). These results suggest that cefoperazone plus piperacillin provides adequate coverage for most common bacterial pathogens and is safe and effective therapy for febrile granulocytopenic patients.
Adolescent↗
Infectious complications in liver transplantation.
Thirty-five patients received 42 liver homografts between February 1984 and August 1985. One or more infections developed in 23 patients (66%) some time after transplantation. An average of 2.5 infections per infected patient occurred. Of 37 bacterial infections, two thirds were either bacteremias or localized intra-abdominal infections. The median onset was 29 days after operation. Thirteen viral infections were identified, with a median onset of 18 days after operation. Nine fungal infections, six disseminated and three localized, were identified, with a median onset of nine days after operation. Infection was the primary cause of death in five (14%) of 35 patients. Fatal infections were evenly distributed among bacterial (two), fungal (three), and viral (two) pathogens. Despite advances in surgical techniques and the use of cyclosporine, infection after orthotopic liver transplantation is a serious problem. Certain patients can be identified as high risks for infection and require an aggressive diagnostic workup followed by early institution of antimicrobial therapy.
Adolescent↗
Acute graft-vs.-host disease and interstitial pneumonitis interrelated problems following allogeneic bone marrow transplantation: effects of intravenous immune globulin and other interventions.
Explore the source record for details and available documents.
Antibodies, Viral↗
Recombinant interferon alpha-2a for treatment of herpes zoster in immunosuppressed patients with cancer.
PURPOSE: Acyclovir and high doses of intramuscular leukocyte interferon have been shown to prevent dissemination of herpes zoster in cancer patients with localized herpes zoster. With the availability of recombinant interferon, we decided to conduct a multicenter, placebo-controlled, double-blind trial of intramuscular recombinant interferon alpha-2a to assess its efficacy and safety in the treatment of localized herpes zoster in immunosuppressed patients with cancer. PATIENTS AND METHODS: Immunosuppressed cancer patients with localized herpes zoster were randomly assigned to receive placebo, 36 X 10(6) units of recombinant interferon alpha-2a per day, or 68 X 10(6) units of recombinant interferon alpha-2a per day. Due to frequent adverse effects, the 68 X 10(6) unit dose of interferon was discontinued prior to conclusion of the trial. RESULTS: Dissemination of herpes zoster occurred in 14 of the 24 patients (58 percent) who received placebo but in only four of 24 recipients (17 percent) of 36 X 10(6) units of interferon per day (p = 0.003). Adverse effects (fever, chills, headaches, gastrointestinal irritability, fatigue, and myalgias) were more common or severe in interferon-treated patients. CONCLUSION: These results suggest that interferon modifies the severity of herpes zoster in immunosuppressed patients with cancer but is associated with frequent side effects.
Adult↗