Fungal Infections In Transplant Recipients Research Articles

Navigating the Intersection: Fungal Infections in Transplant Recipients During COVID-19.

Navigating the Intersection: Fungal Infections in Transplant Recipients During COVID-19.

Fungal infections in transplant recipients: pros and cons of immunosuppressive and antimicrobial treatment

Fungal infections in transplant recipients: pros and cons of immunosuppressive and antimicrobial treatment

Role of New Antifungal Agents in the Treatment of Invasive Fungal Infections in Transplant Recipients: Isavuconazole and New Posaconazole Formulations.

Invasive fungal infections are a major cause of morbidity and mortality among solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients. Transplant patients are at risk for such invasive fungal infections. The most common invasive fungal infections are invasive candidiasis in the SOT and invasive aspergillosis in the HSCT. In this article, we will discuss the epidemiology of invasive fungal infections in the transplant recipients and susceptibility patterns of the fungi associated with these infections. Additionally, the pharmacology and clinical efficacy of the new antifungal, isavuconazole, and the new posaconazole formulations will be reviewed. Isavuconazole is a new extended-spectrum triazole that was recently approved for the treatment of invasive aspergillosis and mucormycosis. Advantages of this triazole include the availability of a water-soluble intravenous formulation, excellent bioavailability of the oral formulation, and predictable pharmacokinetics in adults. Posaconazole, a broad-spectrum triazole antifungal agent, is approved for the prevention of invasive aspergillosis and candidiasis in addition to the treatment of oropharyngeal candidiasis. Posaconazole oral suspension solution has shown some limitations in the setting of fasting state absorption, elevated gastrointestinal pH, and increased motility. The newly approved delayed-release oral tablet and intravenous solution formulations provide additional treatment options by reducing interpatient variability and providing flexibility in these set of critically ill patients. This review will detail these most recent studies.

Invasive fungal infections in transplant recipients.

Invasive fungal infections are an important cause of morbidity and mortality in hematopoietic stem cell transplant and solid organ transplant recipients. Evolving transplant modalities and techniques, complex and extensive immunosuppressant strategies, and the increased use of broad spectrum antifungal prophylaxis has greatly impacted the epidemiology and temporal pattern of invasive fungal infections in the transplant population. The goal of this article is to provide an up-to-date review of the most commonly encountered invasive fungal infections seen in transplant recipients, including epidemiology, risk factors, clinical features, diagnostic dilemmas, management and their overall influence on outcomes.

Breakthrough Rhinocerebral Mucormycosis in a Liver Transplant Patient Receiving Caspofungin

Zygomycetes are among the most frequent causes of non- Aspergillus mycelial fungal infections in transplant recipients. We have described a single case of breakthrough zygomycosis. A young Japanese woman presented because of idiopathic fulminant hepatitis and renal failure. On the third day of admission, she underwent orthotopic liver transplantation. A considerable amount of red blood cells and fresh frozen plasma were transfused during surgery. On posttransplant day 2, Candida albicans was isolated from respiratory secretions; prophylactic caspofungin was prescribed. During the next 6 days, C albicans was isolated from tracheal secretions, surgical wound, and exudates and stools. Ventilator-associated pneumonia was diagnosed day 4. Her renal function did not improve during the postoperative period; the patient continued on hemodialysis. On day 28, a dark blue eschar due to zygomycosis was detected on the skin of the nose. Tracheal and nasal exudates yielded Rhizopus sp. The patient died 12 hours later due to multiorgan failure with hypothermia. The fatal evolution in this case may be related to a presumed brain infarction after progressive vessel fungal invasion. The presented case had 2 risk factors related to zygomycosis. A high index of suspicion is required in transplant recipients with risk factors for zygomycosis. Early diagnosis and surgery with appropriate systemic fungal drugs (amphotericin B) are mandatory to improve the prognosis.

Prophylaxis against pulmonary viral and fungal infections in solid organ transplant recipients

Pulmonary viral and fungal infections in solid organ transplant recipients are one of the most common and potentially life-threatening infections. Understanding the strategies used for prophylaxis and prevention of these infections is critical for the health and well-being of transplant recipients. Prophylactic measures range from simple patient education to complex chemoprophylactic interventions; however, a multifaceted approach is most often required. This article focuses on strategies to prevent pulmonary viral and fungal infections in transplant recipients, with an emphasis on recent evidence that may influence practice guidelines.

Lack of Pharmacokinetic Interaction Between Anidulafungin and Tacrolimus

The safety and pharmacokinetics of anidulafungin coadministered with tacrolimus were investigated using a single-sequence, open-label design. Healthy volunteers received 5 mg tacrolimus orally on days 1 and 13 of the study. Anidulafungin (200 mg) was administered intravenously on day 4, followed by 100-mg doses on days 5 through 13. Key pharmacokinetic parameters, including C(max), AUC, t((1/2)), CL, and V(ss), were derived from concentration-time data. The 90% confidence intervals (CIs) of the ratios of mean pharmacokinetic parameters of anidulafungin plus tacrolimus to each drug alone were well within the 80% to 125% bioequivalence range, indicating no pharmacokinetic interaction. This ratio was 101.6 (90% CI: 92.77-111.22) for tacrolimus AUC(0-infinity) and 107.2 (90% CI: 105.1-109.4) for anidulafungin AUC(ss). The 2 drugs were well tolerated, and no drug-related serious adverse events were reported. Because of its lack of pharmacokinetic interaction with key immunosuppressive agents, anidulafungin is an important option for the prevention and treatment of invasive fungal infections in transplant recipients.

Fungal Infections in Transplant Recipients Receiving Alemtuzumab

Recently, we have used an anti-T-cell agent, alemtuzumab, as induction or conversion therapy to achieve a calcineurin (CNI) and steroid-free immunosuppressive regimen. We identified recipients who developed systemic fungal infections after the initiation of alemtuzumab and looked at their outcomes. The study population consisted of all pancreas transplant recipients who received alemtuzumab. Only invasive fungal infections were included in the analysis (eg, fungemia, meningitis, or pneumonia; fungal urinary tract infections were excluded). The organism was confirmed by culture, histopathology, or latex antigen test. Between February 2003 and February 2004, a total of 121 pancreas transplant recipients received alemtuzumab-56 as part of induction, and 65 as part of conversion. Of these, 8 (6.6%) developed an invasive fungal infection; 2 (3.6%) recipients as part of induction therapy and 6 (9.2%) as part of conversion therapy. Mean recipient age was 42.1 years. The mean length of time from alemtuzumab administration (first dose) to the diagnosis of the fungal infection was 115.9 days (range 5 to 318). The organisms identified initially were: Cryptococcus, Histoplasma, Aspergillus, and Candida. Overall, 3 (38%) of the eight patients died during ongoing treatment of their fungal infection: two from sepsis, one due to myocardial infarction. The other five recipients were treated successfully and have functioning grafts. The initial therapeutic agents used included: amphotericin B/liposomal AMB ( n = 6), voriconazole ( n = 3), capsofungin ( n = 2), and fluconazole ( n = 1). The use of alemtuzumab as induction or conversion therapy in pancreas transplant recipients may predispose patients to the development of systemic fungal infections. It would be important to determine what the most appropriate prophylaxis regimen would be for these patients.

Invasive aspergillosis in solid-organ transplantation: report of eight cases and review of the literature

Abstract Invasive fungal infections are life-threatening complications in solid-organ transplantation. Although the rate of fungal infections in transplant recipients is lower than that of other infections, the mortality rate is higher. The most frequent fungi isolated from these kinds of infections are Candida spp. and Aspergillus spp. We retrospectively evaluated the clinical and laboratory findings in eight patients who were treated for invasive aspergillosis (IA) at our center. This report describes these cases and discusses the relevant literature.

Invasive aspergillosis in solid-organ transplantation: report of eight cases and review of the literature.

Invasive fungal infections are life-threatening complications in solid-organ transplantation. Although the rate of fungal infections in transplant recipients is lower than that of other infections, the mortality rate is higher. The most frequent fungi isolated from these kinds of infections are Candida spp. and Aspergillus spp. We retrospectively evaluated the clinical and laboratory findings in eight patients who were treated for invasive aspergillosis (IA) at our center. This report describes these cases and discusses the relevant literature.

Fungal infections in transplant recipients.

Fungi are ubiquitous and the respiratory tract is exposed to aerosolized spores of both fungi that are "pathogenic" even in the normal host, such as Cryptococus neoformans, and those that are "opportunistic", such as Candida and Aspergillus species, among others. Although these latter species may occasionally form fungal balls or induce allergic phenomena in the normal host, they produce more invasive diseases in immunosuppressed patients. Among these diseases, pseudomembranous aspergillosis has recently been described. The diagnostic approach to these entities, and, in particular, the thin dividing line between colonization and infection are addressed, along with the diagnostic value of the various procedures. New prophylactic regimens are reviewed such as the possibility of using amphotericin aerosols in combination with systemic azole administration. The authors would emphasize the importance of restoring lung defences by not only decreasing immunosuppressive regimens but also considering the use of newly available recombinant cytokines such as growth factors, to reduce neutropenia, for instance, in addition to antifungal drugs when infection is diagnosed. However, immunomodulation procedures are far from being well established.

Microbiological diagnosis of invasive fungal infections in transplant recipients.

Invasive fungal infections remain an important cause of morbidity and mortality in transplant recipients. Since conventional diagnostic tools such as culture lack sensitivity and specificity, alternative diagnostic assays have been developed. Among the most promising techniques are the detection of fungal DNA and serology. Fungal DNA can be detected with high sensitivity and specificity when performed with specimens from sterile sites such as blood. Polymerase chain reaction (PCR) assays can be used to detect a broad range of fungal pathogens and combined with species identification. Multicenter diagnostic studies are needed to establish the diagnostic value of PCR but lack of standardization hampers such studies. The serodiagnosis of invasive fungal infections has become an important tool in the management of invasive fungal infections. Especially the detection of circulating galactomannan has been shown to be a sensitive marker for invasive aspergillosis. Both serology and PCR can be used to monitor the response to antifungal therapy. The optimal use of non-culture-based methods is in prospective screening of patients at high risk. Since the incidence of disease greatly influences the positive predictive value, screening should take place only in those patients at very high risk for invasive fungal disease.

Primary prophylaxis reduces fungal infections in transplant recipients

Primary prophylaxis reduces fungal infections in transplant recipients

Prophylaxis Against Fungal Infections in Transplant Recipients

Although the morbidity and mortality associated with invasive fungal infections in transplant recipients is high, the optimal approach to antifungal prophylaxis is controversial. Most fungal infections occur shortly after the trans- plantation during maximum immunosuppression and are caused by Candida or Aspergillus spp. Nonspecific strategies for prevention do not differ from those used in other patients at risk. They consist mainly of a reduction in risk factors, such as removal of plants from around the patient, separation of the patient from the vicinity of construction sites or improvement in hospital care by isolation and careful nursing of the patient, with strict hygiene. A more controversial issue is primary antifungal chemoprophylaxis, since there are few well designed trials of this intervention, and most of the patients studied have had haematological diseases. Orally administered antifungal drugs that are not absorbed through the gastrointestinal tract have not shown any evidence of a prophylactic effect to date. Controlled trials of systemically administered or orally absorbed drugs in specific transplant recipients have, however, proved effective. In allogeneic and autologous bone marrow transplants, fluconazole 400 mg/day was effective when administered from the conditioning treatment period through the neutropenic period. In liver transplant recipients, either fluconazole 400 mg/day for 10 weeks or liposomal amphotericin B 1 mg/kg/day for 5 days significantly reduced the incidence of invasive fungal infections. However, one must be aware of the risk of fluconazole-resistant fungi and the possibility of selection. In patients with a history of previous fungal infection, secondary prophylaxis may be of value, although data are limited. For recipients of transplants other than bone marrow or liver, there are insufficient data to recommend general prophylaxis.

Use of macrophage colony-stimulating factor in the treatment of fungal infections.

Management of fungal infections is a major medical problem. The risk of developing a fungal infection is higher for patients who are undergoing dose-intensive therapy, are immunocompromised, have neutropenia, are receiving prophylactic antibiotics, have other infections, have invasive catheters, or have a history of severe trauma or burns. Survival is decreased among patients who develop fungal infection in these situations. In view of the high morbidity and mortality associated with fungal infections in transplant recipients, cytokines that enhance cell function, such as macrophage colony-stimulating factor (M-CSF), have been investigated. M-CSF enhances cytotoxicity, superoxide production, phagocytosis, chemotaxis, and secondary cytokine production in monocytes and macrophages. Animal models and clinical data suggest efficacy of M-CSF in controlling fungal infection.