Selective gut decontamination with nalidixic acid or trimethoprim-sulfamethoxazole for infection prophylaxis in neutropenic cancer patients: relationship of efficacy to antimicrobial spectrum and timing of administration.

Eighty-four cancer patients at risk of infection because of neutropenia were randomized to receive nalidixic acid as an alternative to trimethoprim-sulfamethoxazole (TMP-SMX) for infection prophylaxis. Infections were documented significantly earlier and more often among patients who entered the trial with neutrophil counts of less than 0.1 X 10(9)/liter. TMP-SMX recipients experienced fewer microbiologically documented infections and bacteremias and were free of infection for a higher proportion of days with severe neutropenia (less than 0.1 X 10(9)/liter) than nalidixic acid recipients. Gram-negative bacillary and Staphylococcus aureus infections accounted for the major differences. Although the majority of aerobic gram-negative bacilli were eliminated from the feces after 1 week of prophylaxis with either agent, TMP-SMX was proved superior to nalidixic acid in this regard and was associated with acquired drug resistance by gram-negative bacilli less frequently. Both agents selected for colonization and subsequent infection by gram-positive cocci. Our data suggest that prophylaxis is most likely to be effective if administered to patients for at least 1 week before they become severely neutropenic. Nalidixic acid used as a single agent in doses of 4 g daily, however, cannot be recommended as an alternative to TMP-SMX for infection prophylaxis in neutropenic cancer patients.     

Neutropenia Associated with Long-Term Ceftaroline Use

Ceftaroline is a fifth-generation cephalosporin with potent antimicrobial activity against Gram-positive and Gram-negative pathogens. Neutropenia is a rare serious adverse event for the class of cephalosporins; however, we observed several cases of severe neutropenia in our outpatient infectious disease practice believed to be associated with ceftaroline use. The aim of this study was to determine the incidence of neutropenia among patients receiving ceftaroline therapy for more than 7 days. We conducted a retrospective cohort analysis of patients admitted to an 800-bed regional medical center between June 2012 and December 2014 who received ceftaroline for more than 7 days to assess the incidence of developing clinically significant neutropenia. Demographic and patient care data points as well as underlying admitting and chronic diagnoses were retrospectively collected from the medical record. Clinically significant neutropenia was defined as an absolute neutrophil count (ANC) less than 1,500 cells/mm³. Analysis was performed to determine the incidence, severity, and outcome of neutropenia following ceftaroline administration. A total of 39 patients were included in the cohort. The median duration of therapy was 27 days. Seven patients (18%) developed neutropenia while on ceftaroline therapy. Four (10%) of the neutropenic patients had an ANC of <500 cells/mm³. The median first neutropenic day was day 17, with the median ANC nadir of 432 cells/mm³ on day 24. We determined that extended ceftaroline infusion is associated with the development of neutropenia. We recommend obtaining a complete blood count (CBC) with differential at the onset of therapy and weekly thereafter. Should the ANC fall below 2,500 cells/mm³, then twice-weekly CBCs should be monitored for the duration of ceftaroline therapy, and therapy should be discontinued if the ANC falls to 1,500 cells/mm³ or less.     

Granulocyte transfusion therapy for infections in candidates and recipients of HPC transplantation: a comparative analysis of feasibility and outcome for community donors versus related donors

BACKGROUND: Feasibility, response to granulocyte transfusion therapy, and clinical outcome were compared among HPC transplant recipients enrolled in a prospective study of a community blood bank-based unrelated donors program, a prospective granulocyte study using family donors, and matched control patients without granulocyte transfusion therapy. STUDY DESIGN AND METHODS: Overall, 40 patients (327 collections) received granulocyte concentrates from unrelated donors, 34 patients (219 collections) received granulocyte concentrates from related donors, and 74 patients served as controls. Study entry criteria for patients included an absolute neutrophil count (ANC) of less than 200 per microL and documented invasive fungal or bacterial infections. RESULTS: There was a median delay of 3 days (range, 0-14) in patients receiving transfusions from unrelated donors between day of diagnosis of infection and start of granulocyte transfusion therapy as compared with a median delay of 5 days (range, 0-25) in patients receiving transfusions from related donors (p = 0.01). The ANC increment after the first, second, and seventh transfusions in patients who had community donors was significantly higher or comparable to patients who had family donors. Overall, clinical outcome was comparable between the three patient groups. Kaplan-Meier analysis revealed no difference between all cohorts in overall 6-month survival (p = 0.28, log-rank) or event-free survival (p = 0.17, log-rank). CONCLUSION: These results suggest that future efficacy trials should consider inclusion of unrelated community donors for timely institution of granulocyte transfusion therapy.     

Use of granulocyte transfusion in early period in life-threatening infections of pediatric hematology and oncology patients: A single-center experience

Despite all the developments in medicine, infections continue to be one of the most important causes of mortality in pediatric hematology and oncology patients. The more severe the degree of neutropenia develops after intensive chemotherapy in cancer patients, and the longer the neutropenia duration, the higher the risk of infection. Granulocyte transfusion (GT) is used as supportive therapy in cases where the bone marrow needs time to recover in invasive bacterial or fungal infections along with severe neutropenia. The patients who had granulocyte transfusions in our clinic between June 2019 and June 2020 were reviewed retrospectively. A total of 15 units of granulocyte concentrate were used in 11 febrile neutropenia attacks of 9 patients. The demographic characteristics of the patients and features belonging to the period of GT were recorded. In our study, the clinical response rate after GT was 90.9 %, while the hematological response rate was 40 %. Most of the patients were treated succesfully, the mortality rate was 9%. We think that the most critical factor for success with GTs is determining the neutropenic patient in particular with a combination of high-risk malignancy and acute life-threatening infection for using GT. Also, early use of GT in those patients who do not recover despite appropriate antimicrobial and supportive treatment may contribute to improvement of the clinical conditon in a shorter period of time and reduction of repeated GTs.     

Granulocyte transfusion therapy in paediatric patients with severe neutropenic infection

The data of 10 children who developed 13 high-risk febrile neutropenia with/without microbiologically documented severe infection, while being treated for a hematologic disorder were investigated retrospectively. The 24th hour post-transfusion neutrophil and platelet counts increased significantly, compared to the baseline values (p = 0.034, p = 0.025). Except three granulocyte transfusions (GTs) after which oliguria and/or mild respiratory distress developed, the transfusions were well tolerated. The clinical response, hematologic response and infection related mortality rates were 69.2%, 53.8% and 30.8%, respectively. Although our study includes limited number of patients, we can conclude that GT seems beneficial for children with severe sepsis during neutropenia.     

Recent developments in human cytomegalovirus diagnosis

Since the early 1990s, great efforts have been made in the field of human cytomegalovirus (HCMV) diagnosis. Besides HCMV diagnosis in immunosuppressed patients (solid organ transplant recipients, hematopoietic stem cell transplant patients and AIDS patients), diagnosis in connection with congenital HCMV infection is of great interest. This review focuses on the development and clinical utility of serological assays, as well as on virological tests (molecular and nonmolecular assays). Interpretation of these tests is strongly dependent on the patient group (solid organ transplant recipients and hematopoietic stem cell transplant patients) and whether the tests are used for screening, risk stratification or diagnosis. Furthermore, a better understanding of HCMV infection has led to new approaches in HCMV diagnosis and monitoring. Thus, assays for viral resistance testing and assays for monitoring the HCMV-specific cellular immune response are increasingly important for the guidance of antiviral therapy.     

Successful neutrophil engraftment supported by granulocyte transfusion in adult allogeneic transplant patients with peri-transplant active infection

Active infection at the time of allogeneic hematopoietic stem cell transplantation (HSCT) is a risk for non-relapse mortality (NRM) after HSCT. Granulocyte transfusion (GTX) has been used to prevent or treat life-threatening infections in patients with severe neutropenia. However, data are limited on the clinical benefits of GTX during HSCT. We retrospectively analyzed the transplant outcomes of HSCT patients who had undergone GTX between 2012 and 2020. Altogether, 20 patients with documented infection had received 55 GTXs during HSCT. No adverse events were observed during the GTX infusion. The average number of granulocytes was 0.40 (range, 0.10–1.59) × 10⁹/kg. The median neutrophil increment one day after GTX was 515 (range, ?6 to 6630)/μl, which was significantly correlated with the infused granulocyte dose (p = 0.0007). A total of 17 of 20 patients achieved neutrophil engraftment. The number of infused granulocytes tended to higher in clinical responders (p = 0.12), and patients receiving ≥ 0.5 × 10⁹/kg showed trend toward to better transplant outcomes (GTX-high vs. GTX-low, 1-year OS; 33% vs. 11%, p = 0.19. 1-year NRM; 44% vs.77%, p = 0.11). The type of red blood sedimenting agents was significantly correlated with the amounts of granulocyte collection. In conclusion, GTX, especially with a high amount of containing granulocytes, could be a safe bridging therapy for neutrophil engraftment after HSCT in patients with active infection.     

Prophylactic use of hyperimmunoglobulin for cytomegalovirus infection in heart transplantation

Cytomegalovirus (CMV) infection in solid organ recipients can endanger the immunosuppressed patient and increase vulnerability to secondary infections and the high risk of rejection triggered by the viral disease. The effect of passive immunization against CMV was examined in 69 heart transplant patients. The patients received weekly administrations of 1 ml/kg of CMV hyperimmunoglobulin from the day of transplantation until the 30th postoperative day. Forty-four of the patients were monitored clinically and serologically up to the 120th postoperative day. Nine patients showed clinical and serologic signs of CMV infection; in 15 the only evidence of CMV infection was a rise in antibody titers. The remaining 20 patients showed no clinical or serologic signs of CMV infection. Three patients who were seronegative preoperatively remained seronegative until the end of the observation period. The results indicate a potential therapeutic benefit of hyperimmunoglobulin prophylaxis to prevent infectious complications due to CMV in heart transplant patients.     

Febrile neutropenia and Fusobacterium bacteremia: clinical experience with 13 cases

OBJECTIVES: To assess the disease spectrum of Fusobacterium bacteremia in our neutropenic patients and review the literature. METHODS: This was a 6.5-year retrospective study in which all the records of neutropenic patients with Fusobacterium bacteremia were analyzed. RESULTS: Fusobacterium bacteremia was found in 13 neutropenic patients, 10 with hematological malignancies and 3 with solid tumors. The standard clinical presentation was that of primary bacteremia with benign evolution under antibiotics with anaerobic coverage. Most patients presented with oral mucositis as the probable portal of entry. Coinfection with other germs was documented in four patients. No patient had a localized infection documented. Most patients were receiving ciprofloxacin chemoprophylaxis. None of the patients had catheter-related infection. All tested strains were susceptible to all standard anaerobic agents. Fusobacterium spp. were responsible for 5% of bacteremias in neutropenic patients in our hospital during the last 6.5 years. CONCLUSION: Fusobacterium bacteremia is a possible cause of febrile neutropenia, especially in the setting of quinolone prophylaxis and oral mucositis after intense chemotherapeutic regimens. We think that its benign outcome if there is no localized infection detected does not justify the use of antianaerobic prophylaxis. Combination of beta-lactams and beta-lactamase inhibitors is a safe and reasonable treatment.     

An autopsy case of disseminated mucormycosis in a neutropenic patient receiving chemotherapy for the underlying solid malignancy

Mucormycosis is a rare, opportunistic infection caused by fungi of the order Mucorales, class Zygomycetes. These fungi produce fatal opportunistic infections in immunocompromised patients, especially in those with severe neutropenia. Recently, mucormycosis has become more widespread, because potent, myelosuppressive chemotherapies are performed more often than before. Nevertheless, this infection rarely occurs in patients with solid malignancies. Here, we describe an autopsy case of disseminated mucormycosis in a neutropenic patient who was receiving chemotherapy for an underlying solid malignancy. A 31-year-old Japanese man received cytotoxic chemotherapy with etoposide for the pulmonary metastasis of a secondary malignant fibrous histiocytoma. This patient had long been treated with chemotherapeutic agents for this solid cancer and for the preceding eosinophilic granuloma, both of which were highly resistant to the therapy. During the treatment with etoposide, his neutrophil count declined to less than 100/μl. He presented with high fever and severe dyspnea. Pneumonia was highly suspected. The chemotherapy was discontinued, and granulocyte colony-stimulating factor was administered. Although the neutrophil count recovered, the pneumonia progressed. The patient experienced respiratory failure and died 17 days after the onset of this episode. An autopsy revealed dissemination of mucormycosis not only in the lungs but also in the liver, the spleen, the kidney, and in the digestive tract. The therapy-related severe neutropenia, and the probable impairment of the immune system, because of the previous chemotherapies, would have been responsible for this fatal infection. Received: March 23, 2001 / Accepted: July 30, 2001     

The use of Filgrastim in AIDS-related neutropenia

Neutropenic individuals are at high risk for bacterial and fungal infections. Filgrastim (r-metHuG-CSF, NEUPOGEN) has been shown to improve chemotherapy-induced neutropenia significantly. Because a high incidence of HIV-infected patients have neutropenia, often associated with myelosuppressive antiretroviral medication, Filgrastim is frequently used as a treatment strategy for this HIV-associated neutropenia. This review summarizes published work related to the use of Filgrastim in HIV-infected patients. Literature bases (EMBASE, MEDLINE, Int. Pharm. Abs., SciSearch, and Aidsline) from 1970 to 1998 were searched for articles describing the relationship of Filgrastim and ANC to bacterial infection rates, bacterial infection outcome, and overall survival. Thirty-five related articles were identified during this search. Filgrastim appears to have a significant role in increasing peripheral ANC and enhancing neutrophil function in patients with HIV infection and AIDS. This may translate into a clinical benefit of delivery of full-dose myelosuppressive antiretroviral therapy and decreased susceptibility to infections and increased survival in this patient population.     

High levels of circulating cytomegalovirus DNA reflect visceral organ disease in viremic immunosuppressed patients other than marrow recipients.

Although viremia is a hallmark of disseminated cytomegalovirus (CMV) infection, not all viremic patients have visceral organ CMV disease. We used blot hybridization with a cloned subgenomic probe to quantitate viral DNA in blood leukocytes of 60 viremic patients (25 with solid organ transplants, 20 with AIDS, and 15 marrow recipients) who had different clinical manifestations of CMV infection. The results are expressed as pg of viral DNA/10 micrograms of leukocyte DNA. Patients with AIDS or with solid organ transplants who had CMV visceral organ disease had the largest amounts of viral DNA in their granulocytes (median 632 and 237 pg, respectively). These amounts were significantly greater than those in similar viremic patients without CMV visceral disease (17 and 21 pg; P < 0.005 and 0.002, respectively). All patients in the study with > 150 pg of CMV DNA in their granulocytes had visceral CMV disease. The amounts of viral DNA in granulocytes of AIDS and organ transplant patients with CMV retinitis were low (median 22 pg). Marrow transplant patients were unique in that the amounts of CMV DNA in granulocytes were low whether CMV visceral organ disease was present (17 pg) or absent (14 pg). We conclude that high levels of circulating CMV DNA in viremic AIDS and solid organ transplant patients reflect viral involvement of visceral organs but not the retina. In marrow recipients, the severity of CMV disease, even when fatal, is not reflected quantitatively in peripheral blood leukocytes.     

A randomized, crossover comparison of standard-dose versus low-dose lenograstim in the prophylaxis of post-chemotherapy neutropenia

The aim of this trial was to compare the severity of neutropenia, the frequency of hospital admission for fever or infection, and the use of antibiotics among patients treated with a standard dose of lenograstim (263 microg/day of Euprotin) and others treated with half of this dose (131.5 microg/day) and the cost-effectiveness of each of the two doses. In this single-center study, 44 patients with solid tumors, who were all receiving standard-dose chemotherapy regimens following previous neutropenia or were at high risk of neutropenia, were randomized to receive lenograstim at a dose of 263 microg or 131.5 microg daily in the first cycle and then crossed over to the alternate dose for the following cycle. Crossover to the alternate dose was repeated for patients who received more than two cycles. Lenograstim was administered from day +5 to day +14. The absolute neutrophil count (ANC) was assessed on days +5, +8, +12 and +15 of each cycle. Statistical analysis was performed using a general lineal model for repeated samples. In all, 120 cycles were administered, with a median of 3 cycles (range 1-6). Only 4 patients received only 1 cycle. No statistically significant difference (P=0.324) in ANC was observed between standard-dose (mean 5.3, 10.7, 8.3, 11.4 x 10(9)/l) and low-dose (5.0, 8.6, 5.4, 7.5 x 10(9)/l) treatment at days +5, +8, +12 and + 15. Neutropenia grade III-IV was more common in patients receiving the low than in those receiving the standard dose of lenograstim (20% vs 12%, respectively), but the difference did not reach statistical significance (P=0.1). The incidence of fever and frequency of hospital admission were not affected by the dose of lenograstim: 3 patients presented with fever with the standard dose (all of those were admitted to hospital) and 2 patients with the low dose (1 was admitted). ANC in both groups (standard and low doses) was independent of chemotherapy line (first versus second or more). Lenograstim at a dose of 131.5 microg/day is as effective as the standard dose in limiting the severity of neutropenia and in preventing episodes of fever and hospital admissions after chemotherapy for solid tumors. The lower dose of lenograstim is cost-effective in neutropenia prophylaxis. Starting its administration on day +5 reduces costs while maintaining efficacy.     

Hematopoietic colony-stimulating factors for neutropenic patients in the ICU

OBJECTIVE: To assess whether adjunct hematopoietic colony-stimulating factor (H-CSF) accelerates neutrophil recovery and improves survival. DESIGN: A retrospective study. SETTING: Medical/surgical intensive care unit (ICU). PATIENTS: 30 neutropenic patients admitted to the ICU and treated with H-CSF. Controls were the preceding 30 neutropenic patients not treated with H-CSF. MEASUREMENTS AND RESULTS: Patient admission characteristics were reviewed. Endpoints were neutrophil recovery ( > 1.0 x 10(9)/l), length of ICU stay and survival. Depth and duration of neutropenia (0.267 +/- 0.04 x 10(9)/l for 12 +/- 1.7 days vs 0.293 +/- 0.05 x 10(9)/l for 15 +/- 1.9 days; p = 0.67 and 0.21), and the Acute Physiology and Chronic Health Evaluation II and organ system failure scores were similar. Systemic candidiasis was lower in the H-CSF group (20 vs 3 %; p > 0.05). In 11 (36.6 %) and 10 (33.3 %) patients neutrophil count recovered ( > 1.0 x 10(9)/l); H-CSF did not reduce the duration of neutropenia (7.8 +/- 1.4 vs 5.7 +/- 1.3 days; p = 0. 28), the length of ICU stay (7.8 +/- 1.1 vs 8.9 +/- 1.5 days; p = 0. 55) or improve survival (23 vs 10 %; p = 0.168). CONCLUSION: H-CSF for treatment of neutropenia in patients admitted to the ICU did not accelerate neutrophil recovery or improve survival.     

Itraconazole is not effective for the prophylaxis of fungal infections in patients with neutropenia

 Fungal infections are a major problem among patients with hematological malignancies. To evaluate the efficacy of itraconazole (200 mg twice daily) in the prophylaxis of fungal infections in neutropenic patients, we conducted a prospective trial. A total of 61 patients with acute leukemia (113 cytotoxic chemotherapy episodes) were enrolled in the study. One patient in the itraconazole group was excluded because itraconazole was not taken due to gastrointestinal hemorrhage. Because the duration of neutropenia (neutrophil count, <0.5 × 10⁹/l) did not reach 7 days, 3 (1 patient) and 13 (4 patients) cytotoxic chemotherapy episodes in the itraconazole and control groups, respectively, were excluded. After these exclusions, the study population consisted of 31 patients (54 cytotoxic chemotherapy episodes) who had taken itraconazole and 24 patients (43 cytotoxic chemotherapy episodes) who had not taken itraconazole. Prophylactic treatment was initiated on the first day of chemotherapy and was continued until the end of the neutropenic period (absolute neutrophil count, >1 × 10⁹/l) unless a systemic fungal infection was documented or suspected. Thirteen episodes (24%) in the itraconazole group and 7 episodes (16%) in the control group proceeded to intravenous amphotericin B (P > 0.05). Fungal infections occurred in 9 episodes (17%) in the itraconazole group and in 5 episodes (12%) in the control group (P > 0.05). Overall mortality was five deaths in the itraconazole group and two in the control group. These deaths were not due to clinically documented fungal infection. In our study, efficacy of itraconazole in the prophylaxis of fungal infections in neutropenic patients was not detected. Received: March 25, 2002 / Accepted: October 1, 2002     

Imipenem/cilastatin as initial therapy for febrile neutropenic patients

Imipenem 2 g daily was administered intravenously to 40 evaluable patients with neutropenia and fever. Twenty-three patients had acute leukaemia and 17 malignant lymphoma. The overall response rate was 70.0%. Of the 14 patients with documented infection, 9 (64.3%) responded. Poorer responses were observed in patients with pneumonia (40%) or pseudomonal infection (50%). The response rate was significantly higher among patients with increasing neutrophil counts during therapy (P less than 0.02). Fungal infection was a common cause of treatment failure. Gastrointestinal side effects and skin rashes were occasionally seen. No patient developed central nervous system toxicity. Imipenem is a practical alternative to antibiotic combinations for management of neutropenic infection. However, careful monitoring is essential in the subgroups of patients with pneumonia or pseudomonal infections, who may require modifications of therapy.     

Antifungal prophylaxis in solid organ transplant recipients

Solid organ transplantation is life saving for thousands of patients worldwide with end-stage organ failure, but post-transplantation invasive fungal infections (IFIs) remain a significant cause of morbidity and mortality. To improve patient outcomes, investigators have explored various strategies of prevention, including the use of antifungal prophylaxis with both systemic and topical nonabsorbable agents. Often, the strategy is to identify those patients at highest risk for IFIs who would be expected to derive the most benefit from antifungal prophylaxis. Currently, data support the use of antifungal prophylaxis in liver, lung, small bowel and pancreas transplant recipients. By understanding the epidemiology of post-transplant IFIs and antifungal adverse effects, clinicians may target antifungal prophylaxis more optimally. Herein, we review antifungal prophylaxis with systemic agents among solid organ transplant recipients.     

Transfusions of granulocyte-colony-stimulating factor-mobilized granulocyte components to allogeneic transplant recipients: analysis of kinetics and factors determining posttransfusion neutrophil and platelet counts

BACKGROUND: Granulocyte-colony-stimulating factor (G-CSF) is a safe and effective agent for mobilization of neutrophils in normal donors, consistently resulting in cell yields per leukapheresis (LA) procedure that are superior to those with other agents. LA components also contain platelets, whose clinical relevance is unknown. STUDY DESIGN AND METHODS: This study describes the kinetics of and analyzes the factors determining the ANC and platelet count increments seen with each of three transfusions of granulocytes collected from HLA-matched sibling donors receiving G-CSF (n=10; maximum of 3 LA procedures/donor). The transfusions were given to recipients (n=10) on alternate days beginning. Day 1 after allogeneic bone marrow transplant (BMT). RESULTS: Significant, sustained increments in the recipient ANCs were observed after the transfusion of G-CSF-mobilized LA components. The mean peak posttransfusion increments in the ANCs were 1195, 729, and 631 per microL with transfusion of donor LA components on Days 1, 3, and 5, respectively. The length of time that the mean posttransfusion ANC was at or above the baseline (pretransfusion) value was 25 to 37 hours, depending on the post-BMT day when the component was administered. No consistent relationship was observed between LA component granulocyte dose, baseline recipient ANC, or temperature elevation and post-transfusion ANC increments. Large numbers of platelets (mean, 2.55 × 10(11)) were present in LA components, and this resulted in significant increments from baseline in the mean platelet count 1 hour after LA component transfusions. Between Days 1 and 7, the duration of severe neutropenia was shorter and the percentage of patients requiring nondonor platelet transfusions was less in study patients who received LA component transfusions than in a similar historical control group who did not. CONCLUSION: The transfusion of G-CSF-mobilized, HLA-matched LA components to allogeneic BMT recipients resulted in significant and sustained increments in the ANC and the platelet count. Within the range examined, a relationship between neutrophil dose and an increment in the ANC was not demonstrated.     

Antifungal prophylaxis in solid organ transplant recipients

Solid organ transplantation is life saving for thousands of patients worldwide with end-stage organ failure, but post-transplantation invasive fungal infections (IFIs) remain a significant cause of morbidity and mortality. To improve patient outcomes, investigators have explored various strategies of prevention, including the use of antifungal prophylaxis with both systemic and topical nonabsorbable agents. Often, the strategy is to identify those patients at highest risk for IFIs who would be expected to derive the most benefit from antifungal prophylaxis. Currently, data support the use of antifungal prophylaxis in liver, lung, small bowel and pancreas transplant recipients. By understanding the epidemiology of post-transplant IFIs and antifungal adverse effects, clinicians may target antifungal prophylaxis more optimally. Herein, we review antifungal prophylaxis with systemic agents among solid organ transplant recipients.     

Antifungal prophylaxis among allogeneic hematopoietic stem cell transplant recipients: current issues and new agents

Invasive candidiasis and invasive mold infections cause significant morbidity and mortality in the hematopoietic stem cell transplant population, in particular in recipients of allografts. The introduction of a variety of new antifungal compounds over the past decade has focused attention on prophylactic strategies as a means to decrease the burden of invasive fungal infections (IFIs). Until recently, fluconazole has been the standard agent for prophylaxis before and after engraftment. In 2005, the echinocandin micafungin received US FDA approval for prophylaxis against IFIs in stem cell transplant recipients during the neutropenic period prior to engraftment. In patients with substantial risk for invasive mold infection, many centers now use a mold-active antifungal agent (e.g., a triazole such as itraconazole, voriconazole or posaconazole, or an echinocandin) as prophylaxis after engraftment. Several recent studies have highlighted the efficacy of these newer agents in preventing IFIs in these highly immunocompromised patients. This review will discuss current issues in IFI and new agents available for prophylaxis in allogeneic hematopoietic stem cell transplant recipients.