Cryptococcal tonsillitis in a patient with chronic lymphocytic leukemia: an unusual manifestation of cryptococcal disease

We present a case of chronic tonsillitis in a patient with chronic lymphocytic leukemia. Despite empiric radiation and antibiotic therapy, the patient's sore throat and tonsillar enlargement persisted. Excisional biopsy of the involved tonsil revealed the presence of Cryptococcus neoformans. Blood cultures also yielded cryptococcus. Specific antifungal therapy resulted in cure. To our knowledge, this is the first case report of cryptococcal infection of the tonsil. This case illustrates the pitfalls of empiric therapy in an immunosuppressed host.     

Mycological-diagnostic assessment of the efficacy of amphotericin B + flucytosine to control Cryptococcus neoformans in AIDS patients

Abstract: Optimal diagnostic data (microscopy, culture and serology) on 15 cases of Cr. neoformans infection in AIDS patients served as a basis for the preliminary subdivision of the stages of cryptococcosis: Primary (minor involvement of the lungs only) and secondary (hematogenous dissemination with involvement of various organs) stages. Cr. neoformans counts in body fluids and antigen titres in serum and CSF proved to be useful criteria to assess the stage of infection. The efficacy of the combination therapy with amphotericin B + flucytosine seems to be related to the stage of infection. From the mycological point of view, the standard combination of 0.3–0.5 mg/kg BW/d amphotericin B and 150 mg/kg BW/d flucytosine proved to be effective. Data on sensitivity of the agent to amphotericin B and flucytosine are presented in a summarized form. The subjects of duration of therapy, relapse and resistance to flucytosine are commented by means of examples. It should be the aim of an optimal therapy of cryptococcosis to diagnose this mycotic disease in its primary stage. Zusammenfassung: Anhand von 15 Fällen wird versucht, die Cr. neoformans-Infektion AIDS-Kranker in das Primärstadium (alleiniger und geringer Befall der Lunge) und das Sekundärstadium (hämatogene Dissemination mit Befall verschiedener Organe) einzuteilen. Die Keimzahl von Cr. neoformans in Körperflüssigkeiten und der Cr. neoformans-Antigentiter in Serum und Liquor dienten hierbei als die beiden wesentlichen Kriterien zur Einschätzung des Stadiums der Infektion und seiner Therapierbarkeit. Aus mykologischer Sicht erwies sich die Standardkombination von Amphotericin B (0,3–0,5 mg/kg KG täglich) + Flucytosin (150 mg/kg KG täglich) als wirksam. Anhand von Beispielen wird zu den Themen: Dauer der Therapie, Rezidiv und Flucytosin-Resistenz Stellung genommen. über die Empfindlichkeit der Cr. neoformans-Stämme gegen Amphotericin B und Flucytosin (Ancotil ) wird zusammenfassend berichtet. Voraussetzung für eine optimale Therapierbarkeit der Kryptokokkose scheint die Diagnostik dieser Mykose in ihrem Primärstadium zu sein.     

Isolated cryptococcosis of the adrenal gland

A case of isolated adrenal cryptococcosis is reported. A patient with a history of diabetes mellitus had symptoms of left flank pain. Roentgenological and sonographic findings of the adrenal gland were indicative of a malignant tumour. Tissue obtained from surgery showed fungal granuloma and a poorly encapsulated cryptococcal organism was identified by special stains. A post-operative serum cryptococcal antigen test was positive, and the patient was successfully treated with surgery and a course of amphotericin B. After a 7-month follow-up period, there is no evidence of recurrence or dissemination.     

Cryptococcal meningitis: an analysis among 5521 consecutive organ transplant recipients

Abstract: Cryptococcal meningitis has been reported to be an important cause of morbidity and mortality in renal transplant recipients. However, additional studies of recipients of other organ transplants suggested that these patients might be at low risk for cryptococcal meningitis. We examined the incidence and clinical features of cryptococcal meningitis among different groups of organ transplant patients at the University of Pittsburgh Medical Center. From January 1989 through July 1999, 28 patients were diagnosed with cryptococcal meningitis among 5521 transplant recipients. These included liver (11/2539), heart (8/372), kidney (7/2122), lung (1/432), and small bowel (1/56) recipients. The incidence of cryptococcal meningitis was higher in heart and small bowel recipients compared to other transplant populations ( P  = 0.005). The cryptococcal meningitis-related mortality in transplant recipients was 50% and was associated with altered mental status ( P  = 0.001), absence of headache ( P  = 0.02), and liver failure ( P  = 0.002). Multivariable analysis indicated that liver failure was the only independent risk factor for poor prognosis ( P  = 0.043). All cases of liver failure occurred among liver transplant recipients. Cryptococcal meningitis is associated with significant mortality among organ transplant recipients. The presence of allograft failure in liver transplant recipients with cryptococcal meningitis may be an indicator of poor prognosis in this patient population.     

Criptococosis meníngea en pacientes con diabetes y sida

IntroductionCryptococcal meningitis is a severe AIDS-related infectious disease, with a high mortality rate. Diabetes mellitus (DM) is a metabolic disorder very common worldwide. Infectious diseases in diabetic patients are always more severe than in non-diabetic ones.The aim of this study was to compare the outcome of a group of HIV-positive patients with DM and cryptococcal meningitis with a similar group HIV-positive patients with cryptococcal meningitis, but without DM.Material and methodsA total of 182 clinical records of HIV-positive patients suffering cryptococcal meningitis were reviewed, and 28 of them with similar clinical and epidemiological characteristics, were chosen. They included 14 patients with DM (group A) and the remaining 14 who did not suffer this metabolic disorder (group B).ResultsOnly 21.4% (3/14 cases) of group A patients had negative CSF cultures after 10 weeks of treatment. In group B patients, 78.5% (11/14 cases) achieved negative CSF cultures before 10 weeks.A higher overall mortality rate was observed in the diabetic patients (85.7%, 12/14 cases) than in the non-diabetic group (21.4%, 3/14 cases).All CSF isolates were identified as Cryptococcus neoformans, and all strains were susceptible in vitro to amphotericin B and fluconazole.ConclusionsCryptococcal meningitis in diabetic patients was associated with a poor clinical outcome and a high mortality rate. A longer treatment induction period is suggested in order to improve the outcome of cryptococcal meningitis in diabetic patients.     

艾滋病合并肺隐球菌感染的影像学诊断与鉴别诊断

肺隐球菌感染是艾滋病患者重要的机会性感染,也是其重要的死因之一,早期诊断与治疗是改善预后的重要因素,影像学作为无创性检查,在隐球菌感染的早期诊断与鉴别诊断中具有重要意义。对于非艾滋病患者合并隐球菌感染的影像学改变已经有了普遍认识,但是关于艾滋病患者相关的隐球菌影像学特征,文献报道较少,至今未有特征性的影像学表现得到影像学医生的公认。笔者通过文献复习,结合我们确诊的艾滋病相关隐球菌肺部感染病例的回顾性分析,发现还是有一定特征性改变,其中单发结节合并中心空洞是最常见的征象。掌握这些特征对艾滋病合并隐球菌感染的早期诊断有很大帮助。     

Monitoring and impact of fluconazole serum and cerebrospinal fluid concentration in HIV‐associated cryptococcal meningitis‐infected patients

Objectives The aim of the present study was to assess fluconazole pharmacokinetic measures in serum and cerebrospinal fluid (CSF); and the correlation of these measures with clinical outcomes of invasive fungal infections. Methods A randomized trial was conducted in HIV‐infected patients receiving three different regimens of fluconazole plus amphotericin B (AmB) for the treatment of cryptococcal meningitis. Regimens included fluconazole 400 mg/day+AmB (AmB+Fluc400) or fluconazole 800 mg/day+AmB (AmB+Fluc800) (14 days followed by fluconazole alone at the randomized dose for 56 days); or AmB alone for 14 days followed by fluconazole 400 mg/day for 56 days. Serum (at 24 h after dosing) and CSF samples were taken at baseline and days 14 and 70 (serum only) for fluconazole measurement, using gas–liquid chromatography. Results Sixty‐four treated patients had fluconazole measurements: 11 in the AmB group, 12 in the AmB+Fluc400 group and 41 in the AmB+Fluc800 group. Day 14 serum concentration geometric means were 24.7 mg/L for AmB+Fluc400 and 37.0 mg/L for AmB+Fluc800. Correspondingly, CSF concentration geometric means were 25.1 mg/L and 32.7 mg/L. Day 14 Serum and CSF concentrations were highly correlated with AmB+Fluc800 (P<0.001, r=0.873) and AmB+Fluc400 (P=0.005, r=0.943). Increased serum area under the curve (AUC) appears to be associated with decreased mortality at day 70 (P=0.061, odds ratio=2.19) as well as with increased study composite endpoint success at days 42 and 70 (P=0.081, odds ratio=2.25 and 0.058, 2.89, respectively). Conclusion High fluconazole dosage (800 mg/day) for the treatment of HIV‐associated cryptococcal meningitis was associated with high serum and CSF fluconazole concentration. Overall, high serum and CSF concentration appear to be associated with increased survival and primary composite endpoint success.     

特发性CD4+T淋巴细胞减少症伴播散性皮肤隐球菌病

患者女，23岁，左锁骨、腰部右侧及左膝部出现肿块并溃疡4个月，组织病理检查示组织中大量浆细胞及异物巨细胞；PAS染色显示大量散在或成团的孢子，经鉴定证实为新生隐球菌，连续T淋巴细胞亚群分析显示CD4^ T淋巴细胞明显减少，占总T淋巴细胞数20％以下．无人类免疫缺陷病毒(HIV)感染，诊断为特发件CD4^ T淋巴细胞减少症伴播散性皮肤隐球菌病．主要给予两性霉素B治疗，1个月后溃疡愈合．     

Cryptococcal meningitis in HIV‐infected patients: a longitudinal study in Cambodia

Objective To describe the frequency of diagnosis of cryptococcosis among HIV‐infected patients in Phnom Penh, Cambodia, at programme entry, to investigate associated risk factors, and to determine the incidence of cryptococcal meningitis. Methods We analysed individual monitoring data from 11 970 HIV‐infected adults enrolled between 1999 and 2008. We used Kaplan–Meier naïve methods to estimate survival and retention in care and multiple logistic regression to investigate associations with individual‐level factors. Results Cryptococcal meningitis was diagnosed in 12.0% of the patients: 1066 at inclusion and 374 during follow‐up. Incidence was 20.3 per 1000 person‐years and decreased over time. At diagnosis, median age was 33 years, median CD4 cell count was 8 cells/μl, and 2.4% of patients were receiving combined antiretroviral therapy; 38.7% died and 34.6% were lost to follow‐up. Of 750 patients alive and in care after 3 months of diagnosis, 85.9% received secondary cryptococcal meningitis prophylaxis and 13.7% relapsed in median 5.7 months [interquartile range 4.1–8.8] after cryptococcal meningitis diagnosis (relapse incidence = 5.7 per 100 person‐years; 95%CI 4.7–6.9). Cryptococcal meningitis was more common in men at programme entry (adjusted OR = 2.24, 95% CI 1.67–3.00) and fell with higher levels of CD4 cell counts (P < 0.0001). Conclusions Cryptococcal meningitis remains an important cause of morbidity and mortality in Cambodian HIV‐infected patients. Our findings highlight the importance of increasing early access to HIV care and cryptococcal meningitis prophylaxis and of improving its diagnosis in resource‐limited settings.