Introduction

Fusarium species is a well-known plant pathogen,seen in an immunocompetent patient with soil and water worldwide[1].Fusarium species cause a broad spectrum of infections in humans,including superficial infections,as well as locally invasive and disseminated infections[2].It causes invasive infections in immunocompromised patients,especially in bone marrow transplantation and long-term steroid therapy patients[1].There has been a marked increase in opportunistic infection by fungal pathogens involving the urinary tract over the past decade[3].Fungal urinary tract infections are most commonly caused by Candida species followed by Cryptococcus,Coccidioides,Aspergillus,Histoplasma and Curvularia species[3].However,Fusarium species has rarely been previously reported as pathogenic fungi in the urinary tract in the English literature[4].

一方面，以往继续教育供给主体少，继续教育资源建设者主要解决资源有无问题，侧重于资源数量的建设；另一方面，以往生产力发展水平稍低，用人单位对劳动者的职业技能和职业素养没有过多要求，基本能胜任工作岗位要求即可，但现阶段生产力得到迅速发展，劳动者既有的职业技能和职业素养逐渐难以胜任日益专业化、精细化的岗位技能要求。内外因素共同影响下，迫使继续教育供给者转变资源建设思路，从数量为重变质量优先。

Case report

A 77 year old male,with type 2 diabetes mellitus for 25 years,complained of dysuria,weakness and decreased appetite for 6 days and fever for one day.

He was diagnosed with chronic kidney disease 15 years ago and received conservative management.There was no history of burning micturition or abdominal pain or haematuria.On examination,the patient was alert,and febrile;his pulse was 100 per minute,and his blood pressure 140/90 mmHg.Systemic examination did not reveal any abnormality.

Laboratory investigations

Fig.1　Urine microscopy&culture.A:Urine routine microscopy showing hyaline septate hyphae and fusiform macroconidia;B:SDA showing velvety pale yellow to peach colonies on obverse and pale yellow on reverse.High power magnification 40×.

His laboratory findings included hemoglobin 8.0 mg/dL(normal range 14.5-16.5 gms/dL),total leucocyte count 8,000/mm3(normal references 4,000-11,000/mm3)with differential count of polymorphonuclear cells 70%,lymphocytes 24%,eosinophils 3%,and monocytes 3%.His blood tests for HIV/HBsAg were negative,fasting blood sugar was 230 mg/dL(normal references 60-110 mg/dL),urea 59 mg/dL(normal references 20-40 mg/dL)and creatinine 2.1 mg/dL(normal references 0.6-1.2 mg/dL).Urine microscopic examination showed occasional leucocytes,septate hyphae and many sickled shaped to fusiform macroconidia with 3-5 septa(Fig.1A).RBCs or organisms were not present.Periodic acid Schiff(PAS)stain was performed on deposit from centrifuged urine sample and showed PAS positive multiple sickled shaped fungal elements in each field.A provisional diagnosis of fungal infection was done due to presence of septate fungal hyphae and fusiform macroconidia in urine wet mount preparation on two occasions.On the basis of urine examination,Fusariosis of the urinary tract was suspected and informed to the clinician.Urine was cultured using standard techniques for the isolation of aerobic bacteria on Blood agar and MacConkey agar.Fungal culture was done on Sabouraud dextrose agar(SDA)supplemented with gentamicin and chloramphenicol.Two slants of SDA for fungal cultures were incubated at 25 °C and 37 °C.Blood culture was performed to rule out bacteremia and fungemia.Urine culture was negative for bacteria but was positive for fungus after 3-4 days of incubation.On SDA,the isolate produced floccose colonies with sparse to abundant aerial mycelia,initially white,becoming peach/pale orange with both at 25 °C and 37 °C(Fig.1B).The reverse of the colony was pale yellow to orange with no pigment.On lactophenol cotton blue preparation of growth,septate hyphae and sickle/banana shaped macroconidia with 3-4 septae were seen(Fig.2A).For confirmation of fungal identification,slide culture was done,which showed septate branched hyphae that produced microcondia and macroconidia.Conidiophores were short with single lateral monophialide(Fig.2B).Macroconidia were fusiform,slightly curved to straight,pointed and mostly had three septa.Microconidia were abundant but never in chains,mostly non-septate,oval to ellipsoidal,straight or often curve(Fig.3A).Chlamydospores were terminal,hyaline,smooth or rough-walled(Fig.3B).Thus,the isolate was identified as Fusarium oxysporum on the basis of characteristic- floccose pale orange colored colonies,short,single conidiophore with lateral monophialides,fusiform,slightly curved to almost straight macroconidia,oval-ellipsoid non-septate microconidia,terminal oval chlamydospores.[4]Fusariosis of the urinary tract due to Fusarium oxysporum was con firmed.Blood culture was negative for bacteria as well as for fungus.

Fig.2　Microscopic pictures of fungal growth.A:LPCB mount showing septate hyphae and sickle shaped macroconidia(3-8×11-17 μm)with 3-4 septae under 40× magnification.B:Septate branched hyphae with lateral monophialide conidiophore under 40×power.

After inception of microbiology report of fungal growth,antifungal treatment was started.On the basis of efficacy and safety considerations,the patient was started on voriconazole 200 mg orally every 24 hours.

Clinical improvement occurred after initiation of antifungal treatment,and thus was continued for 4 weeks.On follow-up after 4 weeks,urine microscopy was normal.

Fig.3　SDA slide culture.A:Microconidia mostly non-septate,oval to ellipsoidal on SDA slide culture;B:Chlamydospores are terminal,hyaline,smooth or rough-walled,5-13µm seen on slide culture.

新课改的环境下，小学三、四年级的科学教师要摒弃一味只重视卷面成绩的传统认识，坚持科学实验的本质，扩展科学实践活动，加大学生动手实验的机会，丰富多样地调动学生的学习兴趣，使学生的创新能力、探究能力、及科学素养得以发展与提升。

Discussion

In the literature,Fusarium oxysporum has been reported to cause keratitis,onychomycosis,skin infection,and catheter associated fungemia[8].F.oxysporum has been isolated from hospital water system also[9].Su et al.(2007)diagnosed fusariosis in urine in an adult patient with nephrolithiasis but did not mention species.Perinephric abscess in an immunocompetent child has been described by Sidhu S et al.(2013)and who identified F.Chlamydosporum as the causative agent.

首先，今年环保力度的加大。2018年上半年政府开展了“环保回头看”的督查工作，对全国31个省区市存在的环境问题又进行了第一轮全覆盖式的督察。这意味着环保严查态势不改，化肥、化工等装置的开工会受到影响。此外，在今年年初，我国开始正式征收环境保护税，施行了38年的排污收费停征。环保税的开征增加了企业的运行成本。运行成本增加了，企业势必会提高化肥价格。其实，环保税的开征也是在倒逼企业，优胜劣汰，提升装置水平，变相地实现化肥行业的去产能。

Infections due to Fusarium species are collectively referred to as fusariosis[3].The clinical manifestations of fusariosis range from a localized infection(e.g.keratitis,onychomycosis)to disseminated infection involving skin,bloodstream,lung,eye(e.g.endophthalmitis),boneandbrain[5].Fusariumspecies are verycommon in the tropical and subtropical areas[6].Most cases of human fusariosis are caused by F.solani,F.oxysporum,and F.moniliforme but various other atypical strains are emerging as an important cause of infection,especially in patients having one or the other underlying risk factors like immunosuppression,tissue damage and neutropenia[2].Recently,a case of urinary tract infection due to Fusarium proliferatum was published in a patient of agranulocytosis[7].The diagnosis of Fusarium infection requires cultures for accurate identification.On slide culture,Fusarium species appears as septate hyaline hyphae with acute angle branching.The appearance of banana or sickle-shaped macroconidia on lactophenol preparation is a pathognomonic feature of Fusarium species.

We report a rare case of urinary tract infection due to Fusarium oxysporum in a chronic kidney disease,diabetic patient who was also diagnosed with multiple myeloma.To the best of our knowledge,this is the first case described in the literature in which localized urinary bladder fusariosis was present as a cause of urinary tract infection.Fusarium species are relatively resistant to treatment with antifungal agents.Amphotericin B is the drug of choice but high doses are needed,which,however,may increase ocurrence of side effects.Voriconazole was reported as a successful treatment of disseminated fusariosis in patients with hematooncologic malignancies or refractory fungal infections[10].

Fusariosis of the urinary tract in this patient might have resulted from ascending infection due to unknown source,probably contaminated water source or urinary catheterization.Patient responded to treatment with voriconazole with an excellent outcome and without adverse events.Demonstration of typical septate hyphae or growth of Fusarium from clinical specimens remains the gold standard for a definitive diagnosis;hence,PCR analysis of the isolate was not done.

In conclusion,urinary tract fungal infections in immunocompromised patients caused by molds other than Aspergillus have increased.Fusarium oxysporum may be an emerging pathogen in urinary tract infection,particularly in immunocompromised patients.Rapid and reliable diagnostic methods for mold identification from various specimens would increase diagnostic precision and should be adopted in routine microbiology laboratory.Judicious use of voriconazole becomes a very important tool in the treatment of this type of infections because of the safety and efficacy of the drug.

References

[1]　Kwon-Chung KJ.Bennet JE.Infections due to miscellaneous moulds:Hyalohyphomycosis[M]//Medical mycology.3rd ed.Philadelphia:Lea and Febiger,1992:752.

[2]　Sidhu S,Chander J,Singh K.Perinephric abscess caused by Fusarium chlamydosporum in an immunocompetent child:case report and identification of the morphologically atypical fungal strain[J].Indian J Pathol Microbiol,2013,56(3):312-314.

[3]　Su CC,Hsu HJ,Wu JJ,et al.Diagnosis of fusariosis in urine cytology.J Clin Pathol,2007,60(4):422-424.

[4]　Leslie JF,Summerell BA,Bullock S.Species descriptions in the fusarium laboratory manual[M].Ames,Iowa,USA:Blackwell Publishing.2006.

[5]　Garcia RR,Min Z,Narasimhan S,et al.Fusarium brain abscess:case report and literature review[J].Mycoses,2015,58(1):22-26.

[6]Nelson PE,Dignani MC,Anaissie EJ.Taxonomy,biology,and clinical aspects of Fusarium species[J].Clin Microbiol Rev,1994,7(4):479-504.

[7]　Su H,Zhang Q,Li L,et al.Urinary tract infection(UTI)caused by fusarium proliferatum in an agranulocytosis patient and a review of published reports[J].Mycopathologia,2016,181(1-2):131-135.

[8]　Raad I,Hachem R.Treatment of central venous catheter-related fungemia due to Fusarium oxysporum[J].Clin Infect Dis,1995,20(3):709-711.

[9]　Anaissie EJ,Kuchar RT,Rex JH,et al.Fusariosis associated with pathogenic fusarium species colonization of a hospital water system:a new paradigm for the epidemiology of opportunistic mold infections[J].Clin Infect Dis,2001,33(11):1871-1878.

[10]Garbino J,Uckay I,Rohner P,et al.Fusarium peritonitis concomitant to kidney transplantation successfully managed with voriconazole:case report and review of the literature[J].Transpl Int,2005,18(5):613-618.