Cryptococcal Meningitis in Patient with Chronic Myeloid Leukemia

Objective: This study aimed to report the case of a female patient with chronic myeloid leukemia affected by cryptococcal meningitis. Case report: ML, white, 48 years old, female sex, previously diagnosed with chronic myeloid leukemia that has been refractive to the use of imatinib and who has recently begun using nilotinib, was admitted complaining of sudden and disabling migraine in the last 1 month associated with asthenia, adinamia, anorexia, disinterest for daily activities, dizziness, nausea, and vomiting. She evolved with ataxia, and started to stroll with help and showed decrease of muscular strength in her upper limbs. She also presented episodes of decrease of consciousness, with look fixation, no respond to sound stimulation, and short-term hearing loss. The cerebrospinal fluid showed presence of Cryptococcus sp. and, therefore, we began treatment with intravenous liposomal amphotericin B in the dose of 3 mg/kg/day, for 6 weeks. A new cerebrospinal fluid analysis, at the end of treatment, also showed rare structures that are compatible with Cryptococcus sp. As sequelae, she continued with hearing loss in her right ear and enhancement in her right auditory canal, seen in the magnetic resonance imaging. After stabilization and clinical improvement, she was discharged. After 3 weeks, she was hospitalized again with degeneration of the condition, and died due to intracranial hypertension secondary to cryptococcal infection. Final Considerations: This report reinforces the need of reflecting on fungi pathologies, especially in immunosuppressant patients, as well as the importance of early diagnosing and making a fast intervention, with the aims of providing quality of life and comfort to the patient and of minimizing neurological sequelae to the patient.

Cryptococcal antigen testing of lung tissue homogenate improves pulmonary cryptococcosis diagnosis:Two case reports

BACKGROUND Pulmonary cryptococcosis(PC)is an opportunistic infectious disease of the respiratory system.Lung tissue biopsies,culture of respiratory samples(e.g.,sputum,lung tissue,pleural fluid,and bronchoalveolar lavage fluid),and cryptococcal antigen(CrAg)testing are helpful for a definitive diagnosis.However,these tests are sometimes falsely negative.PC is often misdiagnosed or underdiagnosed owing to the absence of obvert symptoms,poor imaging specificity,and false-negative laboratory tests.CASE SUMMARY We report two female patients who underwent computed tomography-guided percutaneous needle pulmonary biopsy of a lung nodule for a confirmed diagnosis.In both patients,the CrAg test on the lung biopsy tissue homogenate was positive,while the serum CrAg test was negative.Combined with the lung tissue pathology,we made the diagnosis of PC.Antifungal therapy was effective in both patients.CONCLUSION Given the findings of our cases and the literature review,lung tissue homogenate CrAg testing can be helpful in improving the diagnosis of PC.

Cryptococcal Meningitis of the HIV-Infected Person in Lomé: About 102 Cases over 10 Years

Objective: To describe the clinical, epidemiological and evolutionary aspects of cryptococcal meningitis. Methods: This was a retrospective descriptive study on all HIV-infected patients who had been hospitalized for cryptococcal meningitis between 2006 and 2016 in the principal structures for the care of HIV infected person in Lomé. The diagnosis of meningitis was clinical and confirmed by the presence of cryptococci on Chinese ink or the detection of CSFsoluble antigens. All patients have made the CD4 rate assay and received an antifungal treatment based on fluconazole or Amphotericin B, followed later by antiretroviral triple therapy. Results: A total of 102 patients infected with cryptococcal meningitis (62 men for 40 women) were found. The sex ratio was 1.55. The median age was 34 years with extremes of 15 to 49 years. Clinically, headache was the symptomatic symptom in 100% of cases, prone to long runs and weight loss respectively in the proportions of 45% and 65%. The mean CD4 cell count was 65 ± 22 cells per mm3. The duration of hospital stay was short (less than 7 days) for the deceased. A total of 62 patients were able to receive treatment, 40 of them with fluconazole and 22 with Amphotericin B. The mortality was very high (65%), 25% were lost to follow-up, and 9.5% still in live 3 months after admission to the hospital. Conclusion: Cryptococcal meningitis has a very reserved prognosis. It is to be feared in cases of severe immunosuppression, hence the early detection of HIV for optimal management is important.

Characteristic analysis of diffuse leptomeningeal glioneuronal tumor misdiagnosed as cryptococcal meningitis in adolescent female

Diffuse leptomeningeal glioneuronal tumor(DLGNT)in adolescent female is rare and easy to be misdiagnosed due to its nonspecificity.This article described the characteristics of an adolescent female DLGNT patient with no history of tumor whose first symptoms are headache and vision loss,and analyzed the causes why DLGNT is easy to be misdiagnosed as cryptococcal meningitis.Treatment remedies:the adolescent female presented with progressive exacerbations of headache,vomiting and vision loss after general treatment.Dynamic monitoring of routine biochemical changes in cerebrospinal fluid(CSF)found abnormal high CSF pressure and protein,repeated examination of antibodies and acid-fast bacilli were negative,and high-throughput pathogen gene examination excluded viral meningitis,tuberculous meningitis and other diseases.To save the optic nerve,the Ommaya capsule was implanted to reduce the intracranial pressure.After diagnostic antifungal treatment,the patient’s condition did not improve.To identify the etiology,extensive meningeal enhancement was eventually detected by enhanced magnetic resonance imaging(MRI),and highly atypical tumor cells were identified by repeated examination of fresh CSF cytology.Post treatment evaluating:for DLGNT,consult oncology.Meningeal biopsy and PET-CT(positron emission tomographycomputed tomography)examination were recommended,and intrathecal chemotherapy and whole-brain radiotherapy were performed according to the examination results.But the patient’s family refused to have a meningeal biopsy and asked to be released from the hospital.Conclusions:the adolescent female without a history of tumor can not rule out the disease,and cryptococcal meningitis also has meningeal enhancement.The gold standard for the diagnosis of DLGNT is to find cancer cells.There is no effective cure for DLGNT,the timely placement of Ommaya sac can significantly improve the quality of the patient’s life,and the active adoption of targeted therapy is expected to extend the patient’s survival.

Successful Treatment with Triple Therapy of Amphotericin B, Voriconazole and Flucytosine on an AIDS Patients with Severe Cryptococcal Meningitis

A 35-year-old man(body weight=63 kg)with AIDS complaining fever and headache after having commenced anti-retroviral therapy(ART)for a week was admitted to our hospital.Five lumbar punctures performed during38 days could not confirm a cryptococcal meningitis(CM)based on staining or culture methods for cerebrospinal fluid(CSF).The disease quickly progressed with serious hearing/vision impairment and frequent onset of seizure and coma after being treated with corticosteroids for five days,and then CM was confirmed.Subsequent lumbar puncture showed elevated intracranial pressure as high as 870 mm H2O,even though treated with standard antifungal regimens for CM.His disease was finally controlled by a new triple therapy with amphotericin B(0.7mg?kg-1?day-1,intravenously),flucytosine(100 mg/kg perday,orally in four divided doses),and voriconazole(200mg every 12 hours)and ART containing lamivudine(300 mg/day),stavuding(30 mg,twice a day)and efavirenz(300 mg,orally every night).Although it is rare,negative CSF stain or culture for cryptococci in AIDS patients with CM can persist for a long time.Corticosteroids should be used cautiously when an effective anti-fungal therapy is not administered.Triple therapy with amphotericin B,flucytosine and voriconazole may be selectively applied in severe CM.Voriconazole can be co-administered with efavirenz with modified dosing.

Cryptococcal Antigenaemia among Treatment-Naïve Adult HIV-Infected Nigerian Patients

Background: There is a high burden of HIV-related cryptococcal meningitis in Sub-Saharan Africa and it is a leading cause of morbidity and early mortality among severely immunocompromised patients. Objectives of the Study: This study was carried out to determine the prevalence of cryptococcal antigen (CrAg) and the relationship of positivity to CD4+ve T cell counts and WHO clinical stage among severely immunocompromised treatment naive adult HIV-infected Nigerian patients. Methods: This was a hospital based cross sectional and prospective study carried out among newly diagnosed and confirmed HIV infected patients. Bio data of consenting consecutive subjects was collected by the attending physician using structured questionnaire. Rapid point of care lateral flow assay kits (IMMY, USA) was used to screen plasma samples from subjects strictly following manufacturer’s instructions. Data were analysed with statistical package for social sciences (spss 15.0) software. Results were presented in simple tables with frequencies and percentages while statistical significance was taken to be p value ≤ 0.05. Results: Of 432 subjects, there were 184 (42.6%) males and 248 (57.4%) females in the study. The median CD4 count of the subjects was 74 (range 6 - 1264) cells/ul. Seven (1.6%) of the subjects were positive for cryptococcal antigen (CrAg) and all were females (100%). Six (85.7%) of CrAg positives had CD4+ T cell count less than 100 cells, while 1 (14.3%) had count above 200cells/ul. The WHO clinical stage of studied patients was;stage I 163 (37.7%), stage II 132 (30.6%) stage III 95 (22.0%) and stage IV 42 (9.7%). Among the CrAg positive subjects, 3 (42.9%) were in WHO clinical stage l while 4 (57.1%) were in stage II disease. Conclusion: The observed overall prevalence of CrAg positivity among studied patients was low but occurred most frequently among the severely immunocompromised subjects. Advancement in WHO clinical stage was not a predicting risk factor for cryptococcal antigenaemia in studied adult HIV infected patients.

Extent of Lung Involvement and Serum Cryptococcal Antigen Test in Non-Human Immunodeficiency Virus Adult Patients with Pulmonary Cryptococcosis

Background： Serum cryptococcal antigen （CrAg） test is the most used noninvasive method to detect cryptococcal infection. However, false-negative CrAg test is not uncommon in clinical practice. Then, the aim of this study was to investigate the factors associated with false-negative CrAg test among non-human immunodeficiency virus （HIV） adult patients with pulmonary cryptococcosis and its clinical features. Methods： One hundred and fourteen non-HIV adult patients with pulmonary cryptococcosis, proven by biopsy, were retrospectively reviewed. Finally, 85 patients were enrolled; 56 were CrAg positive （CrAg＋ group） and 29 were negative （CrAg- group）. It was a cross-sectional study. Then, baseline characteristics, underlying diseases, clinical symptoms, laboratory findings, and chest radiological findings were reviewed and analyzed. Chi-square test was used to analyze categorical variable. Odds ratio （OR） was used to measure correlation. Student＇s t-test was obtained to analyze continuous variable. Results： No difference in baseline characteristics, underlying diseases, clinical symptoms, and laboratory findings were found between two groups （P 〉 0.05 in all）. Nevertheless, diffuse extent lesion was 82.1% in CrAg＋ group and 10.3% in CrAg- group （χ2 = 40.34, P〈 0.001; OR = 39.87）. Conclusions： Among patients with limited pulmonary involvement, a negative serum CrAg does not preclude the diagnosis of pulmonary cryptococcosis. However, among patients with extensive pulmonary involvement, serum CrAg is a useful diagnostic tool for pulmonary cryptococcosis. Furthermore, we also noticed that the untypical and mild presentations with extensive pulmonary lesion might be the features of pulmonary cryptococcosis, which needs further investigation.

Treatment of cryptococcal meningitis with low-dose amphotericin B and flucytosine

Background Amphotericin B （0.7 mg/kg） with flucytosine is the standard treatment for cryptococcal meningitis.However,the long treatment course can induce adverse reactions in patients; therefore,reducing the dose may decrease such reactions.We performed a retrospective analysis of treatment effects and adverse reactions when amphotericin B （0.4 mg/kg or 0.7 mg/kg per day） and flucytosine were used together to treat HIV-negative patients with cryptococcal meningitis.Methods Retrospective analysis was conducted on inpatients at the First Affiliated Hospital,College of Medicine,Zhejiang University （January 2005 to December 2009）.Low- or high-dose amphotericin B （0.4 or 0.7 mg/kg per day,respectively） plus flucytosine was used.The negative conversion rate of Cryptococcus in the cerebrospinal fluid （CSF）,patient mortality,and the incidence of side effects for the two groups （low- vs.high-dose） were compared immediately after treatment and 2 and 10 weeks later.Data were analyzed by the Student＇s t test,chi-square tests using SPSS 12.0 statistical soitware.Results Two weeks post-treatment,Cryptococcus negative CSF rates were 78% （18/23） in the low-dose group and 87% （13/15） in the high-dose group （P=0.28）.Ten weeks post-treatment,both groups were negative.The mortality rate was 8% （2/25） in the low-dose group and 17% （3/18） in the high-dose group （P=-0.25）.There was a statistically significant difference in the incidence of adverse events between the groups,48% （12/25） and 78% （14/18） in the low- and high-dose groups,respectively （P=0.04）.Adverse events that required a change in treatment program in the low-dose group were 12% （3/25） compared to 39% （7/18） in the high-dose group （P=-0.04）.Conclusion Low-dose treatment regimens were better tolerated

Comparison and Correlation of Magnetic Resonance Imaging and Clinical Severity in Nonhuman Immunodeficiency Virus Patients with Cryptococcal Infection of Central Nervous System

Background:The incidence of cryptococcal meningitis among immunocompetent patients increases,especially in China and imaging plays an important role.The current study was to find the correlation between magnetic resonance imaging (MRI)manifestation and clinical severity in nonhuman immunodeficiency virus patients with cryptococcal infection of central nervous system (CNS). Methods:A total of 65 patients with CNS cryptococcal infection from August 2014 to October 2016 were retrospectively included in this study.All the patients had MRI data and clinical data.The patients were divided into two groups according to whether the patients were confirmed with identifiable underlying disease.Comparison and correlation of MRI and clinical data in both groups were investigated using independent sample t-test,Chi-square test,Mann-Whitney test and Spearman rank correlation analysis. Results:In all 65 patients,41 cases (41/65,63.1%;Group 1)had normal immunity and 24 cases (24/65,36.9%;Group 2)had at least one identifiable underlying disease.Fever,higher percentage of neutrophil (NEUT)in white blood cell (WBC),and increased cell number of cerebral spinal fluid (CSF)were much common in patients with underlying disease (Group 1 vs.Group 2:Fever:21/41 vs.21/24,x^2 =8.715,P =0.003;NEUT in WBC:73.15%vs.79.60%,Z=-2.370,P =0.018;cell number of CSF:19 vs.200,Z=-4.298,P <0.001;respectively).Compared to the patients with normal immunity,the lesions are more common in the basal ganglia among patients with identifiable underlying disease (Group 1 vs.Group 2:20/41 vs.20/24,x^2 =7.636,P =0.006).The number of the involved brain areas in patients with identifiable underlying disease were well correlated with the number of cells and pressure of CSF (r =-0.472,P =0.031,r =0.779,P =0.039;respectively). Conclusions:With the increased number of the involved brain areas in patients with identifiable underlying disease,the body has lower immunity against the organism which might result in higher intracranial pressure and more severe clinical status.

Voriconazole in an infant with cryptococcal meningitis

Cryptococcus neoformans （C. neoformans） is the most common cause of fungal meningitis worldwide.1 Cryptococcal meningitis is an opportunistic infection commonly found in immunocompromised hosts, especially HIV-infected adults. It also occurs in apparently immunocompetent individuals. Rarely has it been reported in children, and it is almost nonexistent in infants. Voriconazole is a member of a second generation of antifungal triazoles with broad spectrum antifungal activity, oral and parenteral bioavailability and a favorable safety profile in adults.3 This patient shows improved in vitro activity against C. neoformans when compared to fluconazole and it has been used successfully in about half the patients with refractory cryptococcosis.4 However, the efficacy and safety of voriconazole as a antifungal agent in children with cryptococcal meningitis have not been well assessed, This report described cryptococcal meningitis in a 13-day-old premature neonate who recovered without overt toxicity after voriconazole was added to an antifungal regimen that included amphotericin B and flucytosine. We focused on the response of this child with cryptococcal meningitis to voriconazole.

A Mimic of Hepatic Encephalopathy: Two Cases of Cryptococcal Meningitis in North America

In the non-human immunodeficiency virus infected population,cryptococcosis occurs primarily in people who are functionally immunosuppressed,including patients who have undergone solid organ transplantation requiring immunosuppressive medications,are on corticosteroids,or have renal failure or cirrhosis.Cryptococcal meningitis poses a particular challenge in the setting of cirrhosis because its clinical presentation can mimic hepatic encephalopathy.Here,we describe two patients with decompensated cirrhosis,both with a known history of hepatic encephalopathy who had lumbar punctures and were found to have cryptococcal meningitis.The first patient had a subacute fluctuating change in mental status,while the second patient had progressive subacute headaches,gait disturbance,and hearing loss.Both patients were treated with amphotericin B and flucytosine induction,but only the second survived to maintenance therapy.These cases demonstrate the importance of having a high index of suspicion for cryptococcal meningitis in cirrhosis and having a low threshold for performing a lumbar puncture when altered mental status or other neurologic complaints are not fully explained by hepatic encephalopathy.We also provide a brief review of the pathobiology of cryptococcal infection in cirrhosis and highlight the challenges in therapy.

Antifungal therapy for treatment of cryptococcal meningitis

Objective To compare the curative effects of three different antifungal regimens in the treatment of cryptococcal meningitis Methods Twenty two patients were divided into 3 groups: Group Ⅰ was given intravenous amphotericin B alone or combination with flucytosine therapy Group Ⅱ received intravenous fluconazole alone or combination with flucytosine The treatment of Group Ⅲ was divided into two steps, where the patients received intrathecal amphotericin B plus intravenous amphotericin B with or without intravenous fluconazole until the mycological culture of cerebrospinal fluid (CSF) turned negative, followed by oral fluconazole or itraconazole as maintenance therapy until direct microscopic examination of CSF showed negative once a week for three consecutive weeks Results Of the twenty two patients, 17 (77 3%) were cured, 2 (9 1%) improved, 3 (13 6%) died, and one (4 5%) relapsed Of the 8 patients in Group Ⅰ, 5 were cured, 2 improved, one died and one relapsed; Of the 4 patients in Group Ⅱ, 2 were cured, and 2 died; All the 10 patients in Group Ⅲ were cured without any recurrence Conclusion The two step therapeutic regimen may be suited to the treatment of cryptococcal meningitis

Metataxonomics of Internal Transcribed Spacer amplicons in cerebrospinal fluid for diagnosing and genotyping of cryptococcal meningitis

Background:Cryptococcal meningitis is a severe infectious disease associated with high morbidity and mortality.Rapidity and accuracy of diagnosis contribute to better prognosis,but readily available tools,such as microscopy,culture,and antigens do not perform well all the time.Our study attempted to diagnose and genotype cryptococcus in the cerebrospinal fluid(CSF)samples from patients with cryptococcal meningitis using the approach of metataxonomics of Internal Transcribed Spacer(ITS)amplicons.Methods:The CSF samples were collected from 11 clinically suspected cryptococcal meningitis patients and four non-infectious controls.Samples were recruited from the First Affiliated Hospital of Fujian Medical University Hospital,Fuzhou Fourth Hospital and the 476th Hospital of Chinese People's Liberation Army from December 2017 to December 2018.ITS1 ribosomal deoxyribonucleic acid(rDNA)genes of 15 whole samples were amplified by universal forward primer ITS1(CTTGGTCATTTAGAGGAAGTAA)and reverse primer ITS2(GCTGCGTTCTTCATCGATGC),sequenced by Illumina MiSeq Benchtop Sequencer.The results were confirmed by sanger sequencing of ITS1 region and partial CAP59 gene of microbial isolates from 11 meningitic samples.Pair-wise comparison between infectious group and control group was conducted through permutational multivariate analysis(PERMANOVA)in R software.Results:The 30,000 to 340,000 high-quality clean reads were obtained from each of the positively stained or cultured CSF samples and 8 to 60 reads from each control.The samples from 11 infected patients yielded detectable cryptococcal-specific ITS1 DNA with top abundance(from 95.90%to 99.97%),followed by many other fungal groups(each<1.41%).ITS genotype was defined in 11 CSF samples,corresponding to ITS type 1,and confirmed by Sanger sequencing.A statistically significant difference(r2=0.65869,P=0.0014)between infectious group and control group was observed.Conclusions:The metataxonomics of ITS amplicons facilitates the diagnosis and genotype of cryptococcus in CSF samples,which may provide a better diagnostic approach of cryptococcal infection.

Asymptomatic cryptococcal antigenemia in HIV-infected patients:a review of recent studies

The prevalence of asymptomatic cryptococcal antigenemia(ACA)in human immunodeficiency virus(HIV)infected individuals has been observed to be elevated.The prevalence of ACA ranges from 1.3%to 13%,with different rates of prevalence in various regions of the world.We reviewed studies conducted internationally,and also referred to two established expert consensus guideline documents published in China,and we have concluded that Chinese HIV-infected patients should undergo cryptococcal antigen screening when CD4+T-cell counts fall below 200 cells/μL and that the recommended treatment regimen for these patients follow current World Health Organization guidelines,although it is likely that this recommendation may change in the future.Early screening and optimized preemptive treatment for ACA is likely to help decrease the incidence of cryptococcosis,and is lifesaving.Further studies are warranted to explore issues related to the optimal management of ACA.

Clinical features and treatment outcomes of human immunodeficiency virus-associated cryptococcal meningitis:a 2-year retrospective analysis

Background:Cryptococcal meningitis(CM)is one of the most common opportunistic infections caused by Cryptococcus neoformans in human immunodeficiency virus(HIV)-infected patients,and is complicated with significant morbidity and mortality.This study retrospectively analyzed the clinical features,characteristics,treatment,and outcomes of first-diagnosed HIV-associated CM after 2-years of follow-up.Methods:Data from all patients(n=101)of HIV-associated CM hospitalized in Shanghai Public Health Clinical Center from September 2013 to December 2016 were collected and analyzed using logistic regression to identify clinical and microbiological factors associated with mortality.Results:Of the 101 patients,86/99(86.9%)of patients had CD4 count<50 cells/mm^3,57/101(56.4%)were diagnosed at≥14 days from the onset to diagnosis,42/99(42.4%)had normal cerebrospinal fluid(CSF)cell counts and biochemical examination,30/101(29.7%)had concomitant Pneumocystis(carinii)jiroveci pneumonia(PCP)on admission and 37/92(40.2%)were complicated with cryptococcal pneumonia,50/74(67.6%)had abnormalities shown on intracranial imaging,amongst whom 24/50(48.0%)had more than one lesion.The median time to negative CSF Indian ink staining was 8.50 months(interquartile range,3.25-12.00 months).Patients who initiated antiretroviral therapy(ART)before admission had a shorter time to negative CSF Indian ink compared with ART-naïve patients(7 vs.12 months,χ^2=15.53,P<0.001).All-cause mortality at 2 weeks,8 weeks,and 2 years was 10.1%(10/99),18.9%(18/95),and 20.7%(19/92),respectively.Coinfection with PCP on admission(adjusted odds ratio[AOR],3.933;95%confidence interval[CI],1.166-13.269,P=0.027)and altered mental status(AOR,9.574;95%CI,2.548-35.974,P=0.001)were associated with higher mortality at 8 weeks.Conclusion:This study described the clinical features and outcomes of first diagnosed HIV-associated CM with 2-year follow-up data.Altered mental status and coinfection with PCP predicted mortality in HIV-associated CM.

Current diagnosis and treatment of cryptococcal meningitis without acquired immunodeficiency syndrome

Cryptococcal meningitis(CM)is a central nervous system infectious disease caused by Cryptococcus.It is the most common fungal infection in the central nervous system,accounting for about 48%of fungal infection.The disease occurs mainly in acquired immunodeficiency syndrome(AIDS)patients and concentrates in the immunocompromised people without AIDS.There are nearly one million new cases of CM each year,and about 70%of them died.In China,CM occurs mainly in people without AIDS and there is an increasing trend in recent years.Early diagnosis and treatment is the key to reducing morbidity and mortality associated with CM.The diagnosis mainly depends on laboratory examination such as morphological examination,fungal culture and antigen detection.History,clinical manifestation and imaging examination are the important parts of auxiliary examination.The initial combined antifungal treatment is emphasized,and the principle of fractional treatment including induction,consolidation and maintenance therapy should be followed.The high intracranial pressure must be reduced actively at the same time.In addition,it is proved that the novel immunotherapy combined with antifungal agents can improve the curative effect and limit the chance of antimicrobial resistance.Large-scale clinical trials are needed for further study.

Cryptococcus infection with asymptomatic diffuse pulmonary disease in an immunocompetent patient:A case report

BACKGROUND Cryptococcus presenting as an opportunistic pathogen mainly affects immunocompromised patients,but the disseminated form of infection is rare among immunocompetent populations.The partial radiographic characteristics of pulmonary cryptococcosis mimic lung carcinoma,leading to unnecessary open chest exploratory surgery,and the lack of a gold-standard noninvasive diagnostic increases the risk of misdiagnosis.Positron emission tomography/computed tomography(PET/CT),a sensitive method for distinguishing malignant tumors,coupled with cryptococcal latex agglutination test showing a high positive rate may overcome these issues.CASE A 36-year-old man presented for general examination,without health complaints.Routine CT showed multiple pulmonary nodules and a mass with high maximum standardized uptake value.Initially,we suspected primary malignancy with hematogenous metastasis.Although his routine fungal analysis had been negative,subsequent CT-guided percutaneous core needle biopsy and histopathology examination indicated a diagnosis of pulmonary cryptococcosis.Fluconazole(200 mg/d)antifungal drug treatment was initiated,and 1 mo later the pulmonary mass had reduced in size markedly(on chest CT scan)without any complications.CONCLUSION Serologic and PET/CT examinations may not rule out cryptococcosis,and percutaneous lung puncture is critical under all circumstances.

Pathogen Analysis of Central Nervous System Infections in a Chinese Teaching Hospital from 2012-2018: A Laboratory-based Retrospective Study

Central nervous system (CNS) infections are associated with high mortality rates. The clinical presentation of many CNS infections by different pathogens is difficult to distinguish, but the definite diagnosis of the etiology is critical for effective therapy and prognosis. The aim of this study was to explore the etiology of CNS infections with definite diagnoses based on data from a clinical microbiology laboratory in Tongji Hospital, a teaching hospital in China, obtained over a six-year period. We conducted a retrospective study on all cerebrospinal fluid (CSF) specimens submitted to our clinical microbiology laboratory from September, 2012 to December, 2018. The etiology of CNS infections caused by Cryptococcus neoformans, Mycobacterium tuberculosis and common bacteria was analyzed. Antimicrobial susceptibility testing was conducted on all isolates. The results showed that 1972 cases of CNS infections were identified from 18 300 CSF specimens. Common bacterial meningitis (BM), cryptococcal meningitis (CM) and tuberculous meningitis (TM) accounted for 86.3%(677/785), 9.4%(74/785) and 4.3%(34/785) respectively of cases over the six-year period. BM was the most common among the different age groups, followed by CM. Of the TM cases, 44.1%(15/34) were distributed within the age group of 15-34 years, whereas for CM cases, 52.7%(39/74) occurred within the 35-54-year age group, and the age distribution of BM cases was fairly even. Among the bacterial pathogens isolated, Staphylococcus epidermidis was the most common, accounting for 12.5%(98/785), followed by Acinetobacter baumannii (ABA) and Staphylococcus aureus (SAU), accounting for 11.8%(93/785) and 7.6%(60/785) respectively. The resistance rates to antibiotics were >75%, with the exception of the resistance rate of ABA to tegafycline, which was <3%. More than 60% of SAU strains displayed resistance to penicillin, oxacillin, ampicillin/sulbactam, cefazolin, cefuroxime, gentamycin, tobramycin, erythromycin and levofloxacin, whereas more than 90% of SAU strains showed susceptibility to trimethoprim/ sulfamethoxazole, tegafycline, vancomycin, teicoplanin and linezolid. For C. neoformans, the susceptibility rates to amphotericin B, 5-fluorocytosine, fluconazol and voriconazole were >95%. Analysis of samples from patients with CNS infection in a clinical microbiology laboratory at a teaching hospital in China over a six-year period indicated that the most common etiological agents were the bacteria ABA and SAU. The antibiotic resistance levels of ABA were found to be high and of concern, whereas isolates of C. neoformans were found to be sensitive to antifungal antibiotics.

Clinical diagnosis,treatment,and medical identification of specific pulmonary infection in naval pilots:Four case reports

BACKGROUND Specific pulmonary infection could seriously threaten the health of pilots and their companions.The consequences are serious.We investigated the clinical diagnosis,treatment,and medical identification of specific pulmonary infections in naval pilots.CASE SUMMARY We analyzed the medical waiver and clinical data of four pilots with specific pulmonary infections,who had accepted treatment at the Naval Medical Center of Chinese People’s Liberation Army between January 2020 and November 2021,including three cases of tuberculosis and one of cryptococcal pneumonia.All cases underwent a series of comprehensive treatment courses.Three cases successfully obtained medical waiver for flight after being cured,while one was grounded after reaching the maximum flight life after being cured.CONCLUSION Chest computed tomography scanning should be used instead of chest radiography in pilots’physical examination.Most pilots with specific pulmonary infection can be cured and return to flight.

Cryptococcus neoformans,a global threat to human health

Background Emerging fungal pathogens pose important threats to global public health. The World Health Organization has responded to the rising threat of traditionally neglected fungal infections by developing a Fungal Priority Pathogens List (FPPL). Taking the highest-ranked fungal pathogen in the FPPL,Cryptococcus neoformans, as a paradigm, we review progress made over the past two decades on its global burden, its clinical manifestation and management of cryptococcal infection, and its antifungal resistance. The purpose of this review is to drive research efforts to improve future diagnoses, therapies, and interventions associated with fungal infections.Methods We first reviewed trends in the global burden of HIV-associated cryptococcal infection, mainly based on a series of systematic studies. We next conducted scoping reviews in accordance with the guidelines described in the Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for Scoping Reviews using PubMed and ScienceDirect with the keywordCryptococcus neoformans to identify case reports of cryptococcal infections published since 2000. We then reviewed recent updates on the diagnosis and antifungal treatment of cryptococcal infections. Finally, we summarized knowledge regarding the resistance and tolerance ofC. neoformans to approved antifungal drugs.Results There has been a general reduction in the estimated global burden of HIV-associated cryptococcal meningitis since 2009, probably due to improvements in highly active antiretroviral therapies. However, cryptococcal meningitis still accounts for 19% of AIDS-related deaths annually. The incidences of CM in Europe and North America and the Latin America region have increased by approximately two-fold since 2009, while other regions showed either reduced or stable numbers of cases. Unfortunately, diagnostic and treatment options for cryptococcal infections are limited, and emerging antifungal resistance exacerbates the public health burden.Conclusions The rising threat ofC. neoformans is compounded by accumulating evidence for its ability to infect immunocompetent individuals and the emergence of antifungal-resistant variants. Emphasis should be placed on further understanding the mechanisms of pathogenicity and of antifungal resistance and tolerance. The development of novel management strategies through the identification of new drug targets and the discovery and optimization of new and existing diagnostics and therapeutics are key to reducing the health burden.