Infectious complications after simultaneous pancreas-kidney transplantation

Simultaneous pancreas-kidney transplantation (SPKT) improves long-term survival of insulin-dependent diabetes mellitus patients with diabetic nephropathy. The increasing success of SPKT is a result of improved surgical technique, better organ preservation, potent antirejection therapy, and effective use of antibiotics to prevent and treat infectious complications. However, morbidity and mortality following SPKT remain high mainly owing to infection. From 1988 to 2004, the 51 patients who underwent SPKT were 32 women and 19 men of mean age 34 +/- 4 years old with diabetes and end-stage renal disease. The mean duration of diabetes mellitus was 23 +/- 4 years. The incidence of HCV and HBV infections were 19.6% and 13.7%, respectively. Preoperative work-up included identification and elimination prior to surgery of potential sources of infection. All patients prior to SPKTx had been treated by dialysis (26 +/- 20 months). The kidneys were always placed into the left retroperitoneal space first; at the same time the pancreatic grafts were prepared on the back table. The reconstruction of the superior mesenteric and the splenic arteries was performed using a Y graft of donor iliac artery to the common or external donor's iliac artery. The pancreas was transplanted intraperitoneally to the right iliac vessels. The portal vein was sutured to the common or external iliac vein and the arterial conduit of donor iliac artery. In 20 of the patients, bladder drainage and in 31, enteric drainage was used for the pancreatic juice exterioration. Patients received immunosuppression with a calcineurin inhibitor (tacrolimus or cyclosporin), mycophenolic acid or azathioprine, and steroids. Antibody induction (alternatively anti-IL-2 monoclonal antibody or ATG) was used in last 38 patients. Antibacterial (tazobactam) and antifungal (fluconazole) as well as antiviral (gancyclovir) prophylactic treatment was given to all patients for 7 to 10 days after transplantation. Thirty-eight recipients are alive, 26 with function of both grafts; 8 with functioning kidney grafts; and 4 with nonfunctioning grafts on dialysis treatment from 1 to 14 years after transplantation. Thirteen patients (24.5%) died during the first year after transplantation. Infectious complications were the main cause of death. Systemic infections accounted for the death of five patients and CNS infection for death of another five patients. Three patients died with functioning grafts due to cardiopulmonary disorders (myocardial infarction, pulmonary embolus) early in the postoperative period. A total of 102 infections were diagnosed in 51 patients during the posttransplant course. Twenty-one episodes of CMV infection (systemic 20, duodenal site 1), 73 bacterial infections (systemic 13, pulmonary 13, urinary tract 15, intestinal 8, wound 23), and 8 fungal infections (central nervous system 5, gastrointestinal tract 3). Some patients had more than one type of infection. Overall mortality in the investigated group was 24.5%. Infectious complications were the main cause of death (77%), including systemic infection (38.5%) and CNS infection (38.5%). The predominant etiology of the systemic infections was bacterial. The etiology of CNS infections was fungal. In conclusion, infectious complications are the main cause of morbidity and mortality following SPKT. The early diagnosis of infection, particularly fungal complications, is necessary. The administration of broad-spectrum prophylactic antibiotics, antifungal, and antiviral agents is recommended.     

Association of fungal infection and increased mortality in liver transplant recipients

BACKGROUND: Invasive fungal infection is associated with increased morbidity and mortality following orthotopic liver transplantation (OLTx). Understanding the risk factors associated with fungal infection may facilitate identification of high-risk patients and guide appropriate initiation of antifungal therapy. OBJECTIVES: The aim of this study was to determine the incidence of fungal infections, identify the most common fungal pathogens, and determine the risk factors associated with fungal infections and mortality in OLTx recipients. METHODS: Medical records from 96 consecutive OLTx in 90 American veterans (88 males, 2 females; mean age 48 years, range 32 to 67) performed from January 1994 to December 1997 were retrospectively reviewed for fungal infection in the first 120 days after transplantation. Infection was defined by positive cultures from either blood, urine (<105 CFU/mL), cerebrospinal or peritoneal fluid, and/or deep tissue specimens. Superficial fungal infection and asymptomatic colonization were excluded from study. All patients received cyclosporine, azathioprine, and prednisone as maintenance immunosuppressive therapy. Fungal prophylaxis consisted of oral clotrimazole (10 mg) troches, five times per day during the study period. RESULTS: Thirty-five patients (38%) had documented infection with one or more fungal pathogens, including Candida albicans (25 of 35; 71%), C torulopsis (7 of 35; 20%), C tropicalis (2 of 35; 6%), non-C albicans (2 of 35; 6%), Aspergillus fumigatus (4 of 35; 11%), and Cryptococcus neoformans (1 of 35; 3%). The crude survival for cases with or without fungal infection was 68% and 87%, respectively (P <0.0001). The median intensive care unit stay and overall duration of hospitalization were significantly longer for patients with fungal infection (P <0.01). The mean time interval from transplantation to the development of fungal infection was 15 days (range 4 to 77) with a mean survival time from fungal infection to death of 21 days (range 3 to 64). Fungal infections occurred significantly more often in patients with renal insufficiency (serum creatinine >2.5 mg/dL), biliary/vascular complications, and retransplantation. CONCLUSIONS: Fungal infections were associated with increased morbidity and mortality following OLTx, with Candida albicans being the most common pathogen. Treatment strategies involving antifungal prophylaxis for high-risk patients and earlier initiation of antifungal therapy in cases of presumed infection are warranted.     

Central nervous system infections in transplantation

Opinion statement Central nervous system (CNS) infections are a rare but serious complication of transplantation. An appropriate diagnostic workup should be streamlined with stratification of infection risk by length and degree of immune suppression, lesion localization, and timing. Polymerase chain reaction has high sensitivity and specificity for rapid identification of viral infections and should be used when available. Early diagnosis is imperative, and biopsy should be pursued if a diagnosis is not readily obtained with noninvasive testing. Treatment is pathogen specific. Combination antifungal therapy should be considered for cerebral aspergillosis. Zygomycetes and related invasive fungi require surgical resection and high-dose antifungal therapy. Viral meningoencephalitis therapy should be continued until resolution of clinical signs and symptoms, and viral clearance is verified with repeat cerebrospinal fluid analysis. Cytomegalovirus encephalitis requires ongoing maintenance therapy until clearance of viremia or antigenemia. Bacterial meningitis is uncommon in transplantation and should be treated with 21 days of antibiotics. CNS bacterial abscesses, including nocardiosis, should be surgically drained if feasible and treated until resolution of clinical and radiographic evidence of infection.     

Fungal infections in neutropenic cancer patients

Invasive fungal infections are important causes of morbidity and mortality in cancer patients with prolonged neutropenia following chemotherapy. Recent trends indicate a change toward infections by Aspergillus species, non-albicans species of Candida, and previously uncommon fungal pathogens. These have decreased susceptibility to current antifungal agents. In the last decade there has been much effort to find solution for these changing trends. This article reviews current approaches to prevention and treatment of opportunistic fungal infections in postchemotherapy neutropenic patients and discusses future antifungal approaches and supportive methods.     

Fungal arthritis: A challenging clinical entity

There has been an increasing incidence of fungal infections in recent years. Rarely joints are also affected by fungal infections. Mainly, these infections develop in prosthetic joints, but sometimes native joints are also involved. Candida infections are mostly reported, but patients may also develop infections secondary to nonCandida fungi, especially Aspergillus. Diagnosis and management of these infections is challenging and may involve multiple surgical interventions and prolonged antifunga...     

Intraventricular cryptococcoma successfully treated with liposomal amphotericin B and voriconazole: a case report

Cryptococcal infections of the central nervous system (CNS) are infrequent in immunocompetent hosts and usually present as meningitis. However, fungal masses called cryptococcoma can sometimes be formed. We report a case in which intraventricular cryptococcoma in an immunocompetent patient was completely cured using liposomal amphotericin B (L-AMB) and voriconazole (VRCZ). A 56-year-old previously healthy man was admitted to our hospital with fever, headache and bilateral hand tremor lasting over three weeks. Cerebrospinal fluid (CSF) studies on admission showed meningitis with a white blood cell count of 228 cells/μL: mononuclear leukocytes, 96%; polymorphonuclear leukocytes, 4%; proteins, 157 mg/dL; and glucose, 50 mg/dL. Magnetic resonance imaging (MRI) showed a small, homogeneously enhanced lesion in the right lateral ventricle, and 18F-fluoro-2-deoxy-D-glucose and 11C-methionine positron emission tomography revealed abnormal uptake corresponding to the lesion. To reach a definitive diagnosis, surgical excision of the lesion was performed. Histopathological examination of the specimen showed moderate lymphocyte infiltration and numerous fungal spores, and periodic acid-Schiff and Grocott staining revealed the presence of Cryptococcus neoformans (C.neoformans) within the granuloma, leading to a diagnosis of CNS cryptococcoma. The patient underwent treatment with intravenous L-AMB for 2 weeks and oral VRCZ for 10 months. CSF cultures were negative for C.neoformans and no recurrences were identified on MRI. CNS cryptococcoma is a rare infection that may occur in patients with no known history of immunosuppression. This pathology can be difficult to distinguish from brain tumor, so early pathological diagnosis from an excised specimen is very important. Furthermore, administration of L-AMB and VRCZ may be effective in treating cases of CNS cryptococcoma.     

Successful,Combined Long-term Treatment of Cerebral Candidiasis and Aspergillosis in a Liver Transplant Recipient: A Case Report

Invasive fungal infections, of which the most common are candidiasis and aspergillosis, are among the most important and fatal complications in solid organ transplantation. They continue to be a significant cause of morbidity and mortality in patients with involvement of the central nervous system (CNS) because of the poor CNS penetration of antifungal medications. Voriconazole yields fungicidal drug concentrations in the CNS, but its use is limited in solid organ transplant patients because of its metabolic interactions with immunosuppression. Here we report a case of invasive fungal infection in the CNS after an emergency liver transplantation due to hepatitis B virus–related acute liver failure. The patient was managed successfully with a long-term conservative medical treatment.     

Surgical lung biopsy for diffuse pulmonary disease: experience of 196 patients

OBJECTIVE: Surgical lung biopsy is considered the final method of diagnostic modality in patients with undiagnosed diffuse pulmonary disease. Nevertheless, the effect of surgical lung biopsy on the diagnosis, treatment, and outcome of the patient still remains controversial. This study reviewed the experiences of surgical lung biopsies in 196 consecutive patients during the past 7 years. METHODS: Surgical lung biopsy was performed after achievement of general anesthesia through video-assisted thoracoscopic surgery or a 7-cm minithoracotomy. Biopsy specimens were swabbed for aerobic and anaerobic bacterial, fungal, and mycobacterial cultures. The sections of specimens were routinely stained with hematoxylin and eosin, and acid-fast, Gomori methenamine silver, Gram stain, or other special stains were added if necessary. RESULTS: The pathologic diagnosis after surgical lung biopsy included infection (30.6%), interstitial pneumonia or fibrosis (21.9%), diffuse alveolar damage (17.3%), neoplasm (13.3%), autoimmune diseases (8.2%), and others (8.2%). After surgical lung biopsy, 165 (84.2%) patients had changes in their therapy, 124 (63.3%) patients had clinical improvement of their conditions, and 119 (60.7%) patients survived to hospital discharge. Comparison between immunocompromised and immunocompetent patients showed that diagnosis of infection was significantly higher ( P < .01) in the former group (41.2% vs 20.2%). In addition, there was no significant difference in the distribution of diagnosis and rate of change in therapy between the respiratory failure and nonrespiratory failure groups. However, the rates of response to therapy and patient survival were significantly lower in the respiratory failure group (51.2% and 41.5%) than in the nonrespiratory failure group (71.9% and 78.1%, P < .05). There was no surgical mortality directly related to the procedure. The surgical morbidity rate was 6.6%. CONCLUSION: Surgical lung biopsy is a safe and accurate diagnostic tool for diffuse pulmonary disease. For a large proportion of the patients, change of therapy and then clinical improvement can be achieved after surgical lung biopsy. Surgical lung biopsy should be considered earlier in patients with undiagnosed diffuse pulmonary disease, especially when the respiratory condition is deteriorating.     

Nosocomial fungal infections in surgical patients. Older age as factor of risk and early presumptive and systemic therapy versus prophylactic therapy

Objective of our study has been to verify if the age is a factor of additional risk for the opportunistic fungal infections and if prophylactic therapy cause real advantages in terms of reduction of morbidity, mortality and times of hospitalization. To such we report the experience of the Operational Unity of Emergency Surgery of the Hospital of Relief National and High Specialization of Caserta relatively to the patients submitted to intervention of great abdominal surgery. In the year 2000 antifungal therapy has been administered to 20 patient (of which 18 over 65 years) on the escort of an laboratory diagnosis; in the year 2001 we have administered prophylactic therapy to 53 high-risk patient (of which 48 over 65). In the group of patients essays with preventive therapy the middle hospitalization has been slightly inferior with a reduction of around 2 days of refuge for the elderly patients and of around 1.5 days in the youngest patients. Mortality in the elderly patients has been reduced from 38% of the year 2000 at 23% of the year 2001. Our data confirm that the age is an important factor of risk for the fungal infections in the surgical departments and we believe to a prophylactic therapy can be of benefit in well selected patient, although an ordinary application of antifunfal therapy can not have recommended without an laboratory diagnosis because to emerge of new resistances to the medicines.     

Preemptive prophylaxis with a lipid preparation of amphotericin B for invasive fungal infections in liver transplant recipients requiring renal replacement therapy

BACKGROUND: Posttransplant renal replacement therapy has been shown to be an independently significant risk factor for invasive fungal infections after liver transplantation. We assessed the efficacy of a lipid preparation of amphotericin B as prophylaxis for invasive fungal infections, directed toward liver transplant recipients requiring renal replacement therapy. METHODS: A total of 148 patients transplanted between 1990 and 1997 received no antifungal prophylaxis. Since 1997, 38 patients underwent liver transplantation; antifungal prophylaxis with a lipid preparation of amphotericin B was used in patients requiring renal replacement therapy. RESULTS: Fifteen percent (22 of 148) of the patients transplanted before 1997 required renal replacement therapy. In this cohort, the incidence of invasive fungal infections (36% vs. 7%, P=0.0007) and invasive aspergillosis (14% vs. 2%, P=0.02) was significantly higher in patients who required renal replacement therapy compared with those who did not. Since 1997, 29% (11 of 38) of the patients required renal replacement therapy and received antifungal prophylaxis. Invasive fungal infections occurred in 36% (8 of 22) of the patients who received no prophylaxis (patients before 1997), and 0% (0 of 11, P=0.03) in those who received antifungal prophylaxis (since 1997). Antifungal prophylaxis was independently associated with protection from fungal infection (P=0.017). No reduction in mortality with antifungal prophylaxis was documented. CONCLUSION: Prophylaxis with a lipid preparation of amphotericin B was associated with a significant reduction in invasive fungal infections in high-risk liver transplant recipients, i.e., those requiring renal replacement therapy. However, no beneficial effect on survival could be documented.     

Cerebral aspergillosis. Apropos of 4 cases

Four patients with aspergillosis of the central nervous system collected in less than two years are reported. Three patients had hematologic malignancies (acute myelogenous leukemia, Hodgkin's disease) and were treated with corticosteroids and chemotherapy. One patient received antimicrobial agents fort a post operative meningitis (after acoustic neuroma surgery). Analysis of these cases and review of literature available us to point out the increased frequency of invasive and cerebral aspergillosis particularly in immunocompromised hosts treated by cytotoxic drugs or broad spectrum antibiotic therapy. Diagnosis is very difficult because: --there are non specific radiologic features for aspergillus granuloma, abscess, aneurysm or meningitis, --blood and cerebrospinal fluid cultures are invariably negative, --serologic tests have limited value in immunosuppressed patients (poor capacity to elaborate antibodies). Diagnosis can be made only by surgical biopsy who isolate fungal elements. However diagnosis in greatest cases is only made at autopsy. Treatment consist by antifungal drugs administered intravenously and surgery when it is possible. Prognosis of cerebral aspergillosis is very poor and mortality rate very high about 70%.     

Stereotactic biopsy in the era of advanced neuroimaging. Does the minimal therapeutic gain justify its current wide use?

OBJECTIVE: This study reviewed the contribution of stereotactic brain biopsy in the management and final outcome of a series of patients with presumed inoperable lesions. PATIENTS AND METHODS: Sixty-nine consecutive patients underwent a CT-guided lesion biopsy (n = 67) or abscess/cyst aspiration (n = 2) using the Cosman-Roberts-Wells (CRW) frame. RESULTS: A definitive specific diagnosis was made in 53 of 67 patients (79 %). The remaining procedures did not provide a diagnosis because of failure to obtain appropriate specimen (11 patients), findings consistent with non-specific inflammation (2 patients) or uneventful surgical complication requiring termination of the procedure (1 patient). A total of 55 patients (80 %) died due to the malignant nature of the lesion, most within six months after the biopsy. The preoperative imaging diagnosis was consistent with the histological diagnosis in 60 patients (87 % accuracy). The perioperative morbidity and mortality were nil and most of the patients were discharged within twenty-four hours. CONCLUSIONS: The stereotactic biopsy did not alter either the therapeutic management or the mortality due to the natural course of the lesion. These findings indicate that the current principle of mandatory histological diagnosis in virtually all non-resectable brain lesions should be re-evaluated taking into account parameters such as: age, medical/neurological status, neuroimaging characteristics, patients' best interest and health care financial shortages.     

Burn Wound Infections: Current Status

Pseudomonas aeruginosa . Even so, effective topical antimicrobial chemotherapy and early burn wound excision have significantly reduced the overall occurrence of invasive burn wound infections. Individual patients, usually those with extensive burns in whom wound closure is difficult to achieve, may still develop a variety of bacterial and nonbacterial burn wound infections. Consequently, the entirety of the burn wound must be examined on a daily basis by the attending surgeon. Any change in wound appearance, with or without associated clinical changes, should be evaluated by biopsy. Quantitative cultures of the biopsy sample may identify predominant organisms but are not useful for making the diagnosis of invasive burn wound infection. Histologic examination of the biopsy specimen, which permits staging the invasive process, is the only reliable means of differentiating wound colonization from invasive infection. Identification of the histologic changes characteristic of bacterial, fungal, and viral infections facilitates the selection of appropriate therapy. A diagnosis of invasive burn wound infection necessitates change of both local and systemic therapy and, in the case of bacterial and fungal infections, prompt surgical removal of the infected tissue. Even after the wounds of extensively burned patients have healed or been grafted, burn wound impetigo, commonly caused by Staphylococcus aureus , may occur in the form of multifocal, small superficial abscesses that require surgical débridement. Current techniques of burn wound care have significantly reduced the incidence of invasive burn wound infection, altered the organisms causing the infections that do occur, increased the interval between injury and the onset of infection, reduced the mortality associated with infection, decreased the overall incidence of infection in burn patients, and increased burn patient survival.     

Fungal infections in renal transplant recipients.

Infection continues to be a major source of morbidity and the major source of mortality in renal transplant recipients who are susceptible to opportunistic infections. We recently reviewed all renal transplant recipients who had fungi cultured during a three year period. C. albicans and T. glabrata were cultured most frequently. Deep fungal infections occurred in many patients and were frequently observed late in the course of bacterial and viral infections. Ten patients had fungemia, and primary fungal pneumonia occurred in eight patients. Three patients had fungal infection of the central nervous system. Three of eight patients with fungal pneumonia and eight of ten patients with fungemia died as a result of their fungus infections. These patients frequently had poor renal function and were receiving high steroid doses or had recently been treated for kidney rejection. One patient with fungal pneumonia and six patients with fungemia had the fungus cultured from a superficial site. Several patients developed fungal infections late in the course of viral or bacterial infections. Amphotericin-B and 5-fluorocytosine remain the mainstays of antifungal therapy.     

Viral and fungal infections after liver transplantation--part II.

Viral and fungal infections in liver transplant recipients are important to recognize and treat early because of their association with substantial morbidity and mortality. Some viruses, such as cytomegalovirus and human herpesvirus 6, have immunomodulatory properties and can facilitate other infections, including fungal infections. Cytomegalovirus has long been recognized as an important virus in transplantation, but in the past decade other viruses have also received attention in the medical literature because of their association with particular clinical syndromes. Although human herpesvirus 6 has been associated with fever, rash, and encephalitis, a direct cause-and-effect relationship is still lacking. Human herpesvirus 8 has been found to be the cause of Kaposi sarcoma. Molecular techniques (e.g., pp65 antigenemia and polymerase chain reaction) that have been introduced for routine diagnosis of viruses have facilitated the diagnosis of asymptomatic viral infections and the institution of preemptive therapy. Nonetheless, the diagnosis of invasive fungal infections in liver transplant recipients is often delayed and thus associated with high mortality. Despite the use of new antifungal agents in clinical practice and the reduced incidence of fungal infections because of antifungal prophylaxis regimens, mortality has not decreased. Future patient outcomes may improve with early identification of patients who have risk factors for invasive fungal infections and with the development of new molecular diagnostic techniques for early detection.     

The surgical management of fungal pulmonary infections in children with acute myelogenous leukemia

Infections are the primary cause of complications and death in patients with acute myelogenous leukemia. Current aggressive treatment protocols have improved patient survival but produce extended periods of profound neutropenia during which the patients are particularly susceptible to opportunistic infections. Candida and Aspergillus species are the most common of the fungi causing invasive infections in these patients. In a group of 77 previously untreated children with acute myelogenous leukemia begun on treatment from March 1976 to June 1984, four patients developed localized fungal infections of the lung. These initially appeared as pulmonary infiltrates on chest roentgenograms during periods of severe neutropenia (three during remission induction and one after intensive consolidation therapy). Endobronchial cultures failed to identify the infectious organism in all cases. Computerized axial tomography best defined the cavitary nature of the lesions in 2 patients. All four patients underwent surgical resection, both to establish a diagnosis (three patients) and as part of therapy. There was no operative morbidity. The organisms involved were Aspergillus (2), Torulopsis (1), and Penicillium (1). Three patients were cured of their fungal infections. The fourth patient failed to enter remission and died of a cerebral fungal abscess that developed shortly after thoracotomy. We report these cases to encourage early surgical intervention in leukemics with a localized pulmonary process consistent with a fungal infection. Resection of the primary focus obviates the risk of life threatening pulmonary hemorrhage or dissemination of the fungus and allows for early reinstitution of chemotherapy which is vital to these patients' survival.     

真菌感染性胰腺坏死的临床分析：附46例报告

目的:分析真菌感染性胰腺坏死(IPN)的发病情况以及外科治疗与临床转归。方法:回顾2010年1月—2018年7月间中南大学湘雅医院胰胆外科连续收治的145例IPN患者的临床资料,对其中真菌性IPN病例进行重点分析。结果:145例IPN中,真菌性IPN共46例(31.7%);年代分布分析显示,近2年(2017—2018)真菌性IPN所占比例最高,达40.7%;46例患者均为念珠菌感染,主要为白色念珠菌(25例次),其次为光滑念珠菌(14例次)和热带念珠菌(7例次)。46例患者中,41例采取升阶梯治疗,5例采取降阶梯治疗。真菌性IPN患者的外科干预总次数159次,平均外科干预次数明显高于非真菌性IPN患者(3.5次/例vs. 2.7次/例,P0.05)。全组IPN患者的病死率为22.1%(32/145),其中真菌性IPN患者的病死率为17.3%(8/46),非真菌性IPN患者为24.2%(24/99),两者差异无统计学意义(P0.05)。46例患者中,4例患者合并真菌血症,合并真菌血症者的病死率较非真菌血症的病死率明显增高[75%(3/4)vs.14.3%(5/42),P0.05]。结论:真菌性IPN的发病率呈上升趋势。虽然真菌感染并不增加IPN患者的病死率,但往往需要更多的外科干预,且当合并真菌血症时,患者的病死率明显升高。因此,合理选用抗真菌药物及彻底的感染源控制是治疗真菌性IPN的关键。     

Primary Cutaneous Fungal Infections in Solid Organ Transplantation: A Case Series

Cutaneous fungal infections in solid-organ transplant patients present in a variety of nonspecific ways, requiring a high index of suspicion to diagnose correctly. In the present series of four transplant recipients, subsequent primary cutaneous fungal infections presented as papules, plaques, ulcers and subcutaneous nodules. Transplantations included one cardiac, two renal and one renal-pancreatic transplant. Fungal infections were limited to the skin; there was no evidence of disseminated disease in any case. The pathogens isolated were Scedosporium apiospermum (Pseudallescheria boydii), Alternaria species, Aspergillus fumigatus, and a coelomycete in the Coniothyrium-Microsphaeropsis complex of dark molds. Individuals were successfully treated with surgical debridement, antifungal agents, and reduction of immunosuppressive therapy. All patients and allografts survived. Accurate diagnosis, aggressive surgery and appropriate antifungal therapy, combined with close outpatient follow-up, optimize the likelihood of a cure in a transplant population.     

Invasive fungal infections in renal transplant recipients

Invasive fungal infections are a significant and often lethal problem in transplant patients. Infections caused by geographically limited endemic fungi are infrequent, and Aspergillus species, Mucorales species, Candida species, and Cryptococcus neoformans are the opportunistic fungi responsible for most such infections. The symptoms of systemic fungal infections are nonspecific, particularly in their early stages. The high rates of mortality and graft loss owing to fungal infections render early diagnosis and treatment imperative in immunosuppressed patients. Current methods for the diagnosis of systemic fungal infections include imaging procedures, endoscopic methods and biopsies, microscopic and culture techniques, antibody and antigen-based serologic testing, and the detection (via polymerase chain reaction) of fungal deoxyribonucleic acid in blood or bronchoalveolar lavage fluid, as well as the careful analysis of signs and symptoms. Antifungal therapy should be initiated early in patients with a suspected fungal infection (even before laboratory findings have confirmed that diagnosis) and should be administered with appropriate adjustment of immunosuppressive regimens. To manage fungal infections in patients with renal failure, optimizing the pharmacokinetics of antifungal drugs to reduce the risk of nephrotoxicity is crucial.     

Incidence of systemic fungal infection and related mortality following severe burns

Advancements in burn care therapy have extended survival of seriously burned patients, exposing burn patients to increased risk of infectious complications, notably fungal infections. We performed a 12-year review of autopsied patients with severe burns for the presence of fungal infection at the US Army Institute of Surgical Research Burn Center between February 1991 and November 2003. The primary goal was to identify the relationship between fungal element noted in autopsy and mortality, and to determine contributing factors that increase a patient's susceptibility to fungal infection. A total of 228 deaths (6.1%) resulted from the 3751 admissions of which 97 underwent autopsy. Fungal elements were identified on histopathology in 44% (43 of 97) of autopsied patients with an attributable mortality of 33% (14 of 43). Aspergillus and Candida were the most frequently recovered fungi, but Aspergillus was recovered in 13 of the 14 cases with fungus identified as an attributable cause of death. The most common sites of infections with attributable mortality were wounds (86%) and the pulmonary system (14%). Total body surface area (TBSA) burn and length of stay (survival after burn) were identified as contributing factors for the incidence of fungal element in autopsy on ROC curve analysis. More severely injured patients with greater %TBSA burn injury and full-thickness burns require a longer recovery period resulting in a longer hospital stay. The propensity for fungal infection increases the longer the wound is present. Therefore, the development of products to close the wound more rapidly, improvement in topical antifungal therapy with mold activity for treating wounds, and implementation of appropriate systemic antifungal therapy may improve outcome for severely injured burn victims susceptible to fungal infections.