Cryptococcal Meningitis in Kidney Transplant Recipients: A Two-Decade Cohort Study in France (original) (raw)
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Open forum infectious diseases, 2017
Cryptococcosis is the third most common invasive fungal infection in solid organ transplant (SOT) recipients. There are no nationally representative data describing the incidence, risk factors, and outcomes of cryptococcosis after SOT. We assembled a large cohort of adult SOT recipients using Classification of Diseases, Ninth Revision, Clinical Modification billing data from Healthcare Cost and Utilization Project State Inpatient Databases of Florida (2006-2012), New York (2006-2011), and California (2004-2010). Demographics, comorbidities, death, and cryptococcal infections coded during hospitalization were identified. A total of 42634 adults with SOT were identified during the study period. Cryptococcal disease was identified in 0.37% (n = 158), 44% of which had meningitis (n = 69). Median time to diagnosis of cryptococcosis was 464 days (range, 4-2393). The median time to onset of cryptococcosis was earlier for lung (191 days; range, 7.5-1816), heart (195 days; range, 4-1061), an...
Medical Mycology Case Reports, 2021
Cryptococcosis is the third most common invasive fungal infection in solid organ transplant recipients. We describe three cases of neuro-meningeal cryptococcosis occurring among kidney transplant (KT) patients, and discuss the diagnostic and therapeutic challenges in this context. Median time from KT to infection was 6 months [range: 3-9]. The most common clinical manifestations at diagnosis were fever (2/3), headache (2/3), and confusion (2/3); none had extra-neurological involvement. CrAg was positive in all cases at diagnosis both in serum and cerebrospinal fluid (CSF). For two patients, analysis of previous samples showed that CrAg was detected in plasma up to 4 weeks before diagnosis. All patients received induction treatment with liposomal amphotericin-B (L-AmB) and flucytosine for a median duration of 10 days [range: 7-14], followed by fluconazole maintenance therapy. Acute kidney injury secondary to LAmB therapy was observed in only one case, but all patients had a tacrolimus overdose following initiation of maintenance therapy due to drug-drug interactions between fluconazole and tacrolimus. Among KTR, early detection of Cryptococcus meningitis using serum CrAg is possible. Close monitoring of renal function during treatment is essential due to the nephrotoxicity of LAmB , but also drug-drug interactions between fluconazole and calcineurin inhibitors.
Transplantation Proceedings, 2011
Fungal infections of the central nervous system are rare and are more frequently encountered in immunocompromised patients. Cryptococcocal infection is the most common opportunistic fungal infection after Candida and Aspergillus in organ transplant recipients. Atypical manifestations and nonspecific neuroradiological findings due to the lack of inflammatory response in these immunocompromised patients are responsible for a delay in diagnosis. This diagnosis should be considered even in atypical neurological signs, and additional tests (cerebrospinal fluid examination, magnetic resonance, etc) that may help to suggest the correct diagnosis should be used. We report a case of cryptococcal meningitis in a renal transplant recipient, which was misdiagnosed for several months because of an atypical presentation of headaches without fever or neurological signs. From the Departments of Nephrology (S.Y., N.E., K.C., M.K., J.H.) and Infectious Diseases (I.M., M.B.J.), CHU Hedi Chaker, Sfax, Tunisia.
Cryptococcal meningitis in renal transplant patients associated with environmental exposure
Transplant Infectious Disease, 1999
Fungal infections in renal transplant recipients are less common than bacterial infections; however, the morbidity from fungal infections is high. There is limited information in the literature concerning post-transplantation cryptococcal infection due to environmental exposure of patients living in high-risk areas. We report three patients who were diagnosed with cryptococcal meningitis after kidney transplantation. Cryptococcal titers prior to transplant surgery were negative in all three patients. These patients all lived in rural areas and demonstrated evidence of environmental exposure leading to subsequent cryptococcal meningitis. All patients had exposure to pigeon and chicken excreta and, after treatment, two patients are alive and well with excellent allograft function. The third patient has marginal renal function but is currently not on dialysis. Early diagnosis is essential for salvage from these potentially lethal infections. Intense headache was a prominent feature in the clinical presentation of our patients, and should signal the need for early sampling and culture of spinal fluid. Meningismus was not present in any of our patients, even when other systemic symptoms were identified. We recommend a high index of suspicion posttransplantation for all patients who may have environmental or occupational exposure to cryptococcus. If infection is detected quickly and treatment instituted promptly, patient recovery and allograft survival are possible. Long-term therapy with fluconazole, a non-nephrotoxic agent, should permit eradication of the infection with preservation of kidney function.
Deceptively asymptomatic cryptococcaemia in a renal transplant recipient: the lull before a storm
BMJ Case Reports, 2019
Cryptococcal infection constitutes around 3% of opportunistic infections in solid organ transplant recipients. Most common organ affected in renal transplant recipients (RTRs) is central nervous system and usually presents with chronic meningoencephalitis (CME). Ischaemic stroke as a consequence of cryptococcal meningoencephalitisis rare and possibly due to the involvement of intracranial vessel by exudates causing vasculitis-related thrombosis. In this context, we describe an unusual case of asymptomatic cryptococcaemia in an RTR, progressing on to acute ischaemic stroke secondary to acute CME with near complete neurological recovery following timely diagnosis, early and appropriate antifungal treatment. The index case attempts to re-emphasise the significance of mandatory screening required to exclude the possibility of dissemination of cryptococcaemia in RTRs besides highlighting the requirement of prolonged induction phase with combination therapy, particularly in presence of st...
Treatment of cryptococcal meningitis in liver transplantation
Infection, 1998
lnvasive fungal infections occur in 7-24% of liver transplant recipients and account for 20-30% of all major infections in these patients . Cryptoeoccosis is a relative rare but serious opportunistic disease after liver transplantation, with an incidence of 0.3-5 % and a mortality rate of 20-100% [4, 5 I. Looking at the clinical experience of Singh et al. . in 57% of cases reported, cryptococcosis develops in a median period of 292 days after liver transplantation and usually occurs in patients over 60 years of age. They often have pneumonia and subacute meningoencephalitis, coexisting in approximately 50% of cases, and cutaneous lesions . Jabbour et al. report an incidence of cryptococcal meningoencephalitis in 0.26% of eases: in the ten patients observed, the mean age was 46.1 years (range. 37-60 years) and the infection developed in a median period of 3.5 months after liver transplantation. As regards the therapy of cryptococcal meningoencephalitis, the most common and effective treatment in non-AIDS patients is a 6-week course of 0.2~0.5 mg/kg/day of amphotericm B i.v., plus 150 mg of flucytosine in four divided oral doses daily. Nevertheless, in solid organ transplantation the use of liposomal amphotericin B is recommended because the drug presents a low nephrotoxicity, also if associated with cyclosporine, and reaches much higher serum and tissue concentrations . -['he necessity of preventing relapses of infecuon using a longterm suppressive therapy with fluconazole/itraconazole, as described in AIDS patients, is controversial but a maintenance treatment is indicated in all the patients with persistent elevation ot cryptococcal antigen liter and/or positive cultures or in the presence of cryptococcosis of the brain [7]. We report a case of cryptocoecal meningitis that developed 1 year after liver transp1.antat~on and was treated with an aggressive regimen of liposomal amphotericin B for 5 weeks. Thereafter, itraconazole was used for 1 year as long-term suppressive therapy.
Longitudinal study of cryptococcosis in adult solid-organ transplant recipients
Transplant International, 2003
While studies in kidney recipients have found meningitis to be the most common clinical manifestation of cryptococcosis (Cry), it is unclear if the clinical presentation of Cry differs among various solidorgan transplant (SOT) recipients and whether the serum cryptococcal antigen (SCA) might predict the site of infection. We report the clinical manifestations and the correlation with a positive SCA among 55 consecutive SOT recipients diagnosed with Cry at the University of Pittsburgh Medical Center. These included: heart (n = 13), lung (n = 4), liver (n = 28), kidney (n = 9) and small bowel (n = 1) recipients. While there were no significant differences in the manifestations of Cry in heart and lung recipients, kidney recipients had disseminated disease as the most common presentation ( P = 0.02). In contrast, pneumonia ( P = 0.003) and meningitis ( P = 0.02) were more frequent than disseminated disease in liver recipients. Positive SCA was higher in patients with disseminated disease and meningitis than in patients with isolated pneumonia ( P = 0.0001). Significant differences in the manifestations of Cry were observed among types of SOT populations. A positive SCA may be predictive of dissemination and meningitis, but it may not be sensitive for pulmonary disease.
Longitudinal study of cryptococcosis in adult sold-organ transplant recipients
Transplant International, 2003
While studies in kidney recipients have found meningitis to be the most common clinical manifestation of cryptococcosis (Cry), it is unclear if the clinical presentation of Cry differs among various solidorgan transplant (SOT) recipients and whether the serum cryptococcal antigen (SCA) might predict the site of infection. We report the clinical manifestations and the correlation with a positive SCA among 55 consecutive SOT recipients diagnosed with Cry at the University of Pittsburgh Medical Center. These included: heart (n = 13), lung (n = 4), liver (n = 28), kidney (n = 9) and small bowel (n = 1) recipients. While there were no significant differences in the manifestations of Cry in heart and lung recipients, kidney recipients had disseminated disease as the most common presentation ( P = 0.02). In contrast, pneumonia ( P = 0.003) and meningitis ( P = 0.02) were more frequent than disseminated disease in liver recipients. Positive SCA was higher in patients with disseminated disease and meningitis than in patients with isolated pneumonia ( P = 0.0001). Significant differences in the manifestations of Cry were observed among types of SOT populations. A positive SCA may be predictive of dissemination and meningitis, but it may not be sensitive for pulmonary disease.
Cryptococcal infection in renal transplant: two case reports and a literature review
Revista Española de Quimioterapia
The first case was a 64-year-old woman with chronic kidney failure secondary to nephroangiosclerosis and nonsteroidal anti-inflammatory drug use, who received a kidney transplant in July 2017. Immunosuppressive therapy included prednisone, tacrolimus, and mycophenolate. In October 2018, the patient was admitted for a two-week history of progressive cephalea, diplopia and occasional speech problems, although the patient remained afebrile. Routine serum chemistry was normal, except for creatinine 2.75 mg/dL and a glomerular filtration (GF) of 18 mL/min. Brain CT scan was normal. Findings in cerebrospinal fluid (CSF) were consistent with lymphocytic meningoencephalitis (Table 1). Bacterial and fungal culture was negative, as were nucleic-acid amplification tests (NAATs) for bacteria, mycobacteria, virus, and fungi. Empirical treatment with acyclovir (350 mg/24 h, IV), ceftriaxone (2 g/12 h IV), and antituberculous drugs was started. Mycophenolate was suspended, whereas tacrolimus and prednisone were maintained at previous doses. After a week, the patient developed neurological deterioration. A new lumbar puncture was performed and NAAT was positive for Cryptococcus neoformans/gatti. A yeast was isolated from culture and identified as C. neoformans by mass spectrometry (MALDI-TOF). Antifungal therapy with liposomal amphotericin B (250 mg/24h IV) and fluconazole (200 mg/12 h IV) was initiated and neurologic function of the patient improved significantly. Simultaneously, tacrolimus was suspended. After 10 days of antifungal treatment, the viral load of CMV progressively increased, and ganciclovir (115 mg/24 h) was added. Tacrolimus at low doses (1mg/day) was restarted at 14 days. India-ink staining of CSF obtained by control lumbar punctures performed weekly was persistently positive and C. neoformans was isolated again from culture. Four weeks after diagnosis, the patient developed pancytopenia, which was probably linked to drug toxicity and ganciclovir was withdrawn. After this finding, the patient had fever, dyspnea, and rapid progressive general deterioration resulting in death 34 days after admission. Streptococcus pneumoniae was isolated in blood culture.