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Original article
Endophthalmitis caused by Fusarium: An emerging problem in patients with corneal trauma. A case series
Endoftalmitis por Fusarium: un problema emergente en pacientes con traumatismo corneal. Serie de casos
José Luis Barrios Andrésa,
Corresponding author
, Leyre Mónica López-Soriab, Ana Alastruey Izquierdoc, Jaime Echevarría Ecenarrod, Raquel Feijoó Lerad, Jesus Garrido Fierroe, Francisco Javier Cabrerizo Nuñeze, Andrés Canut Blascoa
a Microbiology Service, Araba University Hospital, Vitoria-Gasteiz, Araba, Spain
b Microbiology Service, Cruces University Hospital, Barakaldo, Bizkaia, Spain
c Mycology Reference Laboratory, National Center for Microbiology, Instituto de Salud Carlos III, Madrid, Spain
d Ophthalmology Service, Cruces University Hospital, Barakaldo, Bizkaia, Spain
e Ophthalmology Service, Araba University Hospital, Vitoria-Gasteiz, Araba, Spain
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Although fungal eye infections are fortunately not common&#44; an immunocompromised condition or the use of increasing number of drugs in patients with ophthalmologic disorders may cause these infections to become an emerging problem&#46; Some of these ophthalmologic drugs&#44; such as corticosteroids&#44; long-term treatment&#44; or the use of broad-spectrum antibiotics in damaged corneas&#44; may be risk factors for the development of fungal endophthalmitis &#40;FE&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">9&#44;13&#44;25</span></a> The origin and etiology of this disease can vary&#44; with <span class="elsevierStyleItalic">Fusarium</span> being one of the most important etiologic agents in exogenous FE &#40;directly from an external source such as keratitis&#44; trauma&#44; or intraocular surgery&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">21&#44;25</span></a> A dysfunctional epithelial barrier is required for <span class="elsevierStyleItalic">Fusarium</span> to colonize the corneal stroma&#46; Once inside the stroma&#44; this microorganism produces an intense inflammatory reaction that breaks down internal barriers&#44; thus leading to rapid tissue degradation and the characteristic clinical features of endophthalmitis&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">13</span></a> In this case series&#44; we aim to identify clinical findings characteristic of <span class="elsevierStyleItalic">Fusarium</span> infection that may enable a prompt diagnosis and a more efficient management of this ophthalmologic condition&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Patients and methods</span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Patient 1</span><p id="par0010" class="elsevierStylePara elsevierViewall">A 79-year-old woman&#44; wearer of soft contact lenses&#44; was sent to our casualty department by her general practitioner&#46; She complained of having had redness and discomfort of the eyes for the past 15 days which did not improve with topical tobramycin and oral azithromycin&#46; A central corneal ulcer with associated stromal infiltrate was found to be the cause&#46; A corneal sample was taken and the initial result was positive for coagulase-negative <span class="elsevierStyleItalic">Staphylococcus</span>&#46; As there was a strong suspicion of fungal infection&#44; treatment with fortified topical antibiotics and topical voriconazole was prescribed&#46; Ten days later the infection progressed to endophthalmitis&#44; therefore posterior vitrectomy and a penetrating keratoplasty was performed&#46; Samples of the cornea&#44; vitreous humor&#44; and crystalline capsule were sent for microbiological analysis&#44; and <span class="elsevierStyleItalic">Fusarium solani</span> species complex was obtained in culture &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; Antifungal susceptibility testing was performed using the EUCAST method and the MICs were as follows&#58; amphotericin B&#44; 1<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;ml&#59; caspofungin&#44; &#62;16<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;ml&#59; itraconazole&#44; &#62;8<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;ml&#59; voriconazole&#44; &#62;8<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;ml&#59; posaconazole&#44; 8<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;ml&#44; and terbinafine&#44; &#62;16<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;ml&#46; Despite changing the treatment to amphotericin B&#44; the graft failed and developed an exudative retinal detachment&#46; At this point no additional interventions were considered to be necessary&#46; The eye currently remains free from infection but in a state of phthisis bulbi &#40;phthisis bulbi is the end-stage ocular response to trauma and&#47;or severe ocular disease&#46; The presentation is that of a very soft&#44; atrophic&#44; blind&#44; and shrunken eye with disorganization of the intraocular structures&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Patient 2</span><p id="par0015" class="elsevierStylePara elsevierViewall">A 56-year-old woman&#44; wearer of soft contact lenses&#44; was admitted to our department complaining about redness and discomfort in both eyes for the past 48<span class="elsevierStyleHsp" style=""></span>h&#46; She had been using anesthetic drops since the onset of the symptoms&#46; Slit lamp examination showed bilateral conjunctival inflammation&#44; a central corneal erosion&#44; and stromal keratitis in the left eye&#46; Treatment with topical ciprofloxacin was initiated and a conjunctival exudate sample was taken for microbiological examination&#46; After clinical worsening&#44; the treatment was changed to topical vancomycin and ceftazidime on the second day&#46; Five days later&#44; the patient showed bilateral central infiltrates with severe anterior chamber inflammation and hypopyon in both eyes&#46; Due to the rapid evolution of the eye infection despite intensive treatment with antibiotics&#44; and given the clinical suspicion of fungal endophthalmitis&#44; antimicrobial treatment was extended to include topical voriconazole&#46; The microbiological cultures were positive for <span class="elsevierStyleItalic">Fusarium oxysporum</span> species complex and voriconazole was replaced with topical 5&#37; natamycin&#46; Due to progressive stromal melting&#44; further surgical management with intracameral ceftazidime&#44; vancomycin&#44; voriconazole&#44; and an amniotic membrane graft was performed&#46; A keratoplasty on the left eye to re-establish the corneal architecture was performed &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>A&#41;&#46; Keratoplasty and phacoemulsification with intraocular lens implantation was carried out on the right eye two months after the onset of symptoms&#46; The same procedure had to be repeated on the left eye nine months later &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>B&#41;&#46; The evolution was good and a transparent keratoplasty with no signs of rejection was observed in both eyes in subsequent medical checks&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Patient 3</span><p id="par0020" class="elsevierStylePara elsevierViewall">A 66-year-old male with posterior polymorphous corneal dystrophy had received in his right eye six previous failed penetrating keratoplasties&#44; cataract surgery&#44; and one trabeculectomy for glaucoma&#46; He had also undergone four previous failed keratoplasties&#44; cataract surgery&#44; limbal allograft transplantation&#44; and trabeculectomy in his left eye&#46; In September 2007&#44; the patient underwent Boston type I keratoprosthesis surgery on his right eye&#44; reaching a BCVA &#40;best corrected visual acuity&#41; of 20&#47;40&#46; During follow-up he developed cystic macular edema&#44; which was successfully treated with intravitreous steroids and bevacizumab&#46; In August 2008 he developed cornea melting in the inferior hemicornea&#44; which was unsuccessfully treated with topical medroxyprogesterone and tetracyclines&#44; therefore a new Boston keratoprosthesis type I for aphakia was repeated in October 2008&#44; achieving a BCVA of 20&#47;60 despite his glaucoma &#40;disc excavation 5&#47;6&#41;&#46; In December 2008&#44; he developed vitritis&#44; which was treated with pars plana vitrectomy&#44; with the microbiological conclusion that the vitritis was sterile&#46; The patient was prescribed oral prednisone&#44; topical vancomycin bid&#44; topical tobramycin bid&#44; topical dexamethasone bid&#44; Combigan<span class="elsevierStyleSup">&#174;</span> bid &#40;for glaucoma&#41;&#44; and topical medroxyprogesterone tid&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Two months later&#44; the patient presented a corneal feather infiltrate &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41; suggestive of a vitreous fungal infection&#46; Samples of the cornea and vitreous humor were cultured and the patient started with topical 1&#37; voriconazole six times a day as well as vancomycin and topical medroxyprogesterone&#46; Two days later a new pars plana vitrectomy was performed&#44; removing the Boston keratoprosthesis and inserting a penetrating keratoplasty&#46; The cultures yielded filamentous colonies of a fungus that was identified as <span class="elsevierStyleItalic">F&#46; oxysporum</span> species complex&#46; The patient initiated oral voriconazole and topical voriconazole&#44; vancomycin&#44; tobramycin&#44; cyclosporine A&#44; and ketorolac&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">Seven days later&#44; with a new fungal infiltrate in the keratoplasty and on the basis of the susceptibility testing results &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#44; the patient started systemic and topical amphotericin B&#44; which controlled the endophthalmitis but&#44; unfortunately&#44; the eye developed phthisis bulbi&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Identification of fungal isolates</span><p id="par0035" class="elsevierStylePara elsevierViewall">Fungal isolates were identified as <span class="elsevierStyleItalic">Fusarium</span> spp&#46; based on the characteristics of colonies grown on potato-dextrose agar &#40;PDA&#41; at 35<span class="elsevierStyleHsp" style=""></span>&#176;C and microscopic examination with lactophenol cotton blue stain&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Identification of the species was done by molecular methods&#46; The isolate was cultured in GYEP medium &#40;0&#46;3&#37; yeast extract&#44; 1&#37; peptone&#59; Difco&#44; Soria Melguizo SA&#44; Madrid&#44; Spain&#41; with 2&#37; glucose &#40;Sigma Aldrich Qu&#237;mica&#44; Madrid&#44; Spain&#41; for 24&#8211;48<span class="elsevierStyleHsp" style=""></span>h at 30<span class="elsevierStyleHsp" style=""></span>&#176;C&#46; Genomic DNA was extracted using a previously described procedure&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">12</span></a> DNA segments comprising a region of elongation factor alpha &#40;EF&#945;&#41; and the internal transcribed spacers &#40;ITS&#41; were amplified using the primers EF1 &#40;5&#8242;-ATGGGTA AGARGACAAGAC-3&#8242;&#41;&#44; EF2 &#40;5&#8242;-GGARGTACCAGTS ATCATGTT-3&#8242;&#41;&#44; ITS1 &#40;5&#8242;-TCCGTAGGTGAACCTGCG G-3&#8242;&#41;&#44; and ITS4 &#40;5&#8242;-TCCTCCGCTTATTGATATGC-3&#8242;&#41; in a GeneAmp 9700 PCR system &#40;Applied Biosystems&#44; Madrid&#44; Spain&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0200"><span class="elsevierStyleSup">14&#44;24</span></a> The reaction mixtures contained 0&#46;5<span class="elsevierStyleHsp" style=""></span>&#956;M of each primer&#44; 0&#46;2<span class="elsevierStyleHsp" style=""></span>&#956;M of each deoxynucleoside triphosphate&#44; 5<span class="elsevierStyleHsp" style=""></span>&#956;l PCR buffer &#40;Applied Biosystems&#41;&#44; 2&#46;5<span class="elsevierStyleHsp" style=""></span>U Taq DNA polymerase &#40;AmpliTaq&#59; Applied Biosystems&#41;&#44; and 25<span class="elsevierStyleHsp" style=""></span>ng DNA in a final volume of 50<span class="elsevierStyleHsp" style=""></span>&#956;l&#46; The samples were amplified in a GeneAmp 9700 PCR system &#40;Applied Biosystems&#41; using the following cycling conditions&#58; 1 initial cycle of 5<span class="elsevierStyleHsp" style=""></span>min at 94<span class="elsevierStyleHsp" style=""></span>&#176;C&#44; followed by 35 cycles of 30<span class="elsevierStyleHsp" style=""></span>s at 94<span class="elsevierStyleHsp" style=""></span>&#176;C&#44; 45<span class="elsevierStyleHsp" style=""></span>s at 47<span class="elsevierStyleHsp" style=""></span>&#176;C &#40;EF&#945;&#41; or 56<span class="elsevierStyleHsp" style=""></span>&#176;C &#40;ITS&#41;&#44; and 2<span class="elsevierStyleHsp" style=""></span>min at 72<span class="elsevierStyleHsp" style=""></span>&#176;C&#44; with a final cycle of 5<span class="elsevierStyleHsp" style=""></span>min at 72<span class="elsevierStyleHsp" style=""></span>&#176;C&#46; The reaction products were analyzed on a 0&#46;8&#37; agarose gel and purified with illustra ExoProStar 1-Step &#40;VWR International Eurolab&#44; Spain&#41; following the manufacturer&#39;s recommendations&#46; Sequencing reactions were performed with 5<span class="elsevierStyleHsp" style=""></span>&#956;l of the PCR product&#44; 1<span class="elsevierStyleHsp" style=""></span>&#956;l of primers &#40;EF1&#44; EF2&#44; ITS1&#44; or ITS4&#41;&#44; and 4<span class="elsevierStyleHsp" style=""></span>&#956;l of DNA using a sequencing kit &#40;BigDye Terminator Cycle Sequencing Ready Reaction&#44; Applied Biosystems&#41; in a final volume of 10<span class="elsevierStyleHsp" style=""></span>&#956;l&#46; Sequences were assembled and edited using the SeqMan II and EditSeq software &#40;Lasergene package&#59; DNAstar&#44; Inc&#46;&#44; Madison&#44; WI&#41;&#46; Sequence analysis was performed by comparing the DNA sequences with EF&#945; sequences from <span class="elsevierStyleItalic">Fusarium</span> strains obtained from the GenBank database &#40;<a id="intr0005" class="elsevierStyleInterRef" href="http://www.ncbi.nih.gov/Genbank/">http&#58;&#47;&#47;www&#46;ncbi&#46;nih&#46;gov&#47;Genbank&#47;</a>&#41;&#46; The sequences were submitted to GenBank database with accession numbers&#58; KY688091&#44; KY688092 and KY688093 for ITS and KY886147&#44; KY886148 and KY886149 for EF&#46; The strains were stored in the collection of filamentous fungi of the National Center for Microbiology with the numbers CNM-CM5601&#44; CNM-CM6230 and CNM-CM7600&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Antifungal susceptibility testing</span><p id="par0045" class="elsevierStylePara elsevierViewall">The in vitro susceptibilities to antifungal drugs were determined using the broth dilution method&#44; following the EUCAST method&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">3</span></a><span class="elsevierStyleItalic">Aspergillus fumigatus</span> ATCC 2004305 and <span class="elsevierStyleItalic">Aspergillus flavus</span> ATCC 2004304 were used as quality-control strains&#46; The antifungal agents used in the study were amphotericin B &#40;range 16&#8211;0&#46;03<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;ml&#41; &#40;Sigma Aldrich Qu&#237;mica&#41;&#44; itraconazole &#40;range 8&#8211;0&#46;015<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;ml&#41; &#40;Janssen Pharmaceutica SA&#44; Madrid&#44; Spain&#41;&#44; voriconazole &#40;range 8&#8211;0&#46;015<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;ml&#41; &#40;Pfizer SA&#44; Madrid&#44; Spain&#41;&#44; posaconazole &#40;range 8&#8211;0&#46;015<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;ml&#41; &#40;Schering-Plough Research Institute&#44; Kenilworth&#44; NJ&#41;&#44; terbinafine &#40;range 16&#8211;0&#46;03<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;ml&#41; &#40;Novartis&#44; Basel&#44; Switzerland&#41;&#44; and caspofungin &#40;range 16&#8211;0&#46;03<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;ml&#41; &#40;Merck &#38; Co&#46;&#44; Inc&#46;&#44; Rahway&#44; NJ&#41;&#46;</p></span></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Discussion</span><p id="par0050" class="elsevierStylePara elsevierViewall">Fungal keratitis and its more serious associated consequences&#44; such as FE&#44; are a major health problem in rural regions of tropical countries&#44; whereas the prevalence of these infections is much lower in warm climate countries&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">25</span></a> However&#44; we must not overlook the possibility of this etiologic agent due to the severity and poor visual outcomes of these infections&#46; Although <span class="elsevierStyleItalic">Fusarium</span> spp&#46; is the leading cause of exogenous FE secondary to keratitis&#44;<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">7&#44;19&#44;25</span></a> several predisposing factors&#44; such as corneal trauma or disruption of the ocular barriers&#44; are necessary for an infection to progress&#46; As corneal damage is a leading factor&#44; the use of contact lenses is of particular relevance&#46; The frequent use of these devices&#44; the hygiene required for the proper care of the lenses and&#44; occasionally&#44; low clinical suspicion&#44; may lead to a diagnosis of FE being overlooked&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">19</span></a> Although the origin of two of the cases herein was the use of contact lenses&#44; the patients did not receive antifungal therapy from the beginning as some fungal infections may be clinically undistinguishable from bacterial endophthalmitis&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">22</span></a> As such&#44; the specific treatment was only administrated once the clinical situation had worsened&#46; Surgery is another factor that clearly alters the structure of the eye and may represent a risk factor for this condition&#46; We have to take into account that fungi were isolated in 21&#46;8&#37; of cultures in cases with postoperative endophthalmitis&#46;<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">2&#44;7</span></a> The emergence of these surgery-related infections greatly complicates the health of the patient&#44; and outbreaks of FE due to <span class="elsevierStyleItalic">Fusarium</span> following surgery can sometimes appear&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">5</span></a> Our third case reflects this finding&#44; with concomitant steroid and immunomodulator treatment probably increasing the risk of infection with these fungi&#46; More rarely&#44; outbreaks of fungal endophthalmitis may be associated with intraocular use of contaminated products&#44; so physicians should be aware of the use of such compounds&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">17</span></a> A warning in this regard may come from the Microbiology Laboratory&#44; although there are several barriers to submitting a prompt report&#46; Thus&#44; although <span class="elsevierStyleItalic">Fusarium</span> is one of the most common causes of keratitis and FE&#44; with <span class="elsevierStyleItalic">F&#46; solani</span> and <span class="elsevierStyleItalic">F&#46; oxysporum</span> being the most prevalent species&#44;<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">7&#44;15&#44;16</span></a> identification may be difficult without experience as this polymorphic fungus could be misidentified or confused with contaminant molds&#46; FE is a destructive intraocular infection that has extremely poor visual prognosis&#44; especially when the <span class="elsevierStyleItalic">Fusarium</span> genus is involved&#44; even after appropriate antifungal treatment&#46; Therefore&#44; rapid communication between the Microbiology Laboratory and practitioners in high suspicion cases should be facilitated as any delay in applying the right treatment may have fatal consequences&#46;<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">9&#44;22</span></a> In our cases&#44; despite a rapid beginning of the antifungal treatment&#44; only one patient preserved an acceptable degree of vision following a rigorous and difficult treatment&#46; Unfortunately&#44; the remaining cases had a much worse outcome&#44; thus confirming the poor prognosis of this disease&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">13</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Fusarium</span> is one of the most drug-resistant fungi&#44; with <span class="elsevierStyleItalic">F&#46; solani</span> being the most resistant species in this group&#46;<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">1&#44;9</span></a> Our cases involved two <span class="elsevierStyleItalic">F&#46; oxysporum</span> and one <span class="elsevierStyleItalic">F&#46; solani</span> strains&#44; in agreement with other cases in the literature&#46;<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">7&#44;9</span></a> When <span class="elsevierStyleItalic">Fusarium</span> is identified as the cause of FE&#44; the multi-resistant condition of this mold and the poor tissue penetration of topical antifungal agents make treatment very difficult&#46; Amphotericin B&#44; which has a low minimum inhibitory concentration &#40;MIC&#41; in vitro&#44; has traditionally been the prescribed antifungal therapy&#46;<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">1&#44;4&#44;9</span></a> However&#44; intravitreal injection can cause retinal necrosis&#44; the number of necessary injections is not standardized&#44; and refractory cases may be observed&#46;<a class="elsevierStyleCrossRefs" href="#bib0255"><span class="elsevierStyleSup">25&#44;26</span></a> Although natamycin has been successfully used to treat endophtalmitis by <span class="elsevierStyleItalic">Fusarium</span>&#44; an intravitreal formulation is not usually available and voriconazole has a varying activity against these molds&#46;<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">7&#44;26</span></a> However&#44; despite its high MIC&#44; voriconazole may be a treatment option as it achieves good aqueous and vitreous concentration &#40;53&#37; and 38&#37;&#44; respectively&#41; with oral administration&#46; Furthermore&#44; intravitreal inoculation of voriconazole &#40;25<span class="elsevierStyleHsp" style=""></span>mg&#47;l&#41; is effective in refractory endophthalmitis and the topical formulation has good stability and activity over 21 days&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">8</span></a> In light of the above&#44; topical voriconazole is increasingly being used by ophthalmologists&#44; even as a first-line antifungal therapy&#46;<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">6&#44;10&#44;25</span></a> However&#44; despite several doubts regarding its benefits&#44; combined antifungal therapy is usually recommended as an empirically acceptable option to ensure the activity of at least one agent&#46;<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">11&#44;20&#44;23</span></a> Furthermore&#44; combined therapy should be started as soon as the suspicion becomes high&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">18</span></a> Likewise&#44; it is clear that such therapy should involve two different types of antifungals and different routes of access in FE&#46; Thus&#44; the simultaneous use of topical&#44; intravitreous&#44; and systemic drugs is recommended due to the severity of the disease and its poor prognosis&#46; The use and combination of antifungals varied in our case series&#44; with widespread use of voriconazole&#44; although combined therapy was started once the diagnosis had been confirmed&#46; A systemic approach with amphotericin B was only used in one case&#44; although this compound does not achieve therapeutic concentrations in the eye and the final outcome was poor&#44; mainly due to the fact that the patient was in an advanced disease state&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">25</span></a> It should be noted that visual outcomes depend on the severity of the infection at presentation&#44; and the prognosis of FE will depend upon the virulence of the organism&#44; the extent of intraocular involvement&#44; and the timing and mode of interventions&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">7</span></a> In light of the above&#44; a rapid reaction is required when the infection is suspected and&#44; in the majority of cases&#44; multidisciplinary measures should be included in the treatment as antimicrobial therapy is not usually sufficient if FE is already established&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Conflict of interest</span><p id="par0060" class="elsevierStylePara elsevierViewall">The authors declare no conflict of interest&#46;</p></span></span>"
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            0 => "<span class="elsevierStyleItalic">Fusarium</span>"
            1 => "Endophthalmitis"
            2 => "Corneal trauma"
            3 => "Contact lenses"
            4 => "<span class="elsevierStyleItalic">Fusarium oxysporum</span>"
            5 => "<span class="elsevierStyleItalic">Fusarium solani</span>"
            6 => "<span class="elsevierStyleItalic">Fusarium</span> treatment"
            7 => "Keratoplasty"
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            0 => "<span class="elsevierStyleItalic">Fusarium</span>"
            1 => "Endoftalmitis"
            2 => "Traumatismo corneal"
            3 => "Lentes de contacto"
            4 => "<span class="elsevierStyleItalic">Fusarium oxysporum</span>"
            5 => "<span class="elsevierStyleItalic">Fusarium solani</span>"
            6 => "Tratamiento de <span class="elsevierStyleItalic">Fusarium</span>"
            7 => "Queratoplastia"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Although fortunately very rare in countries with a temperate climate&#44; certain factors&#44; such as clinical or pharmacological immunosuppression&#44; may cause <span class="elsevierStyleItalic">Fusarium</span>-related fungal infections to become an emerging problem&#46; Moreover&#44; <span class="elsevierStyleItalic">Fusarium</span> is one of the most important etiological agents in exogenous endophthalmitis&#44; which is often favored by the disruption of the epithelial barriers&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Aims</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">The aim of this series of clinical cases is to identify characteristic clinical findings that may allow an early diagnosis and more efficient management of this ophthalmologic emergency&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Methods</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Three cases of endophthalmitis due to <span class="elsevierStyleItalic">Fusarium solani</span> and <span class="elsevierStyleItalic">Fusarium oxysporum</span>&#44; diagnosed in 2009&#44; 2010&#44; and 2014 in patients from two different health regions belonging to the same health system and separated by around 43 miles&#44; are presented&#46; The <span class="elsevierStyleItalic">Fusarium</span> isolates were initially identified microscopically and the species subsequently confirmed by sequencing the elongation factor alpha &#40;EF&#945;&#41; and internal transcribed spacers &#40;ITS&#41;&#46; Susceptibility to antifungal agents was determined using the EUCAST broth dilution method&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Results</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Evolution was poor as two of the three patients progressed to phthisis bulbi despite surgical measures and broad-spectrum antifungal antibiotic therapy&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Conclusions</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">It is essential to rapidly instigate multidisciplinary measures to combat suspected endophthalmitis due to <span class="elsevierStyleItalic">Fusarium</span> given the poor prognosis of this type of infection&#46;</p></span>"
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        "resumen" => "<span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Antecedentes</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Afortunadamente&#44; las infecciones por <span class="elsevierStyleItalic">Fusarium</span> son poco frecuentes en pa&#237;ses de clima templado&#59; sin embargo&#44; determinados factores como la inmunodepresi&#243;n cl&#237;nica o farmacol&#243;gica&#44; pueden convertirlas en un problema emergente&#46; <span class="elsevierStyleItalic">Fusarium</span> es uno de los microrganismos etiol&#243;gicos m&#225;s importantes de la endoftalmitis ex&#243;gena&#44; favorecida habitualmente por una rotura de las barreras epiteliales&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Objetivos</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">En esta serie de casos cl&#237;nicos queremos identificar hallazgos cl&#237;nicos caracter&#237;sticos que puedan establecer un diagn&#243;stico temprano y un tratamiento m&#225;s eficiente de esta urgencia oftalmol&#243;gica&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">M&#233;todos</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Se presentan tres casos de endoftalmitis por <span class="elsevierStyleItalic">Fusarium solani</span> y <span class="elsevierStyleItalic">Fusarium oxysporum</span> que se produjeron en los a&#241;os 2009&#44; 2010 y 2014&#44; en pacientes de dos &#225;reas de salud diferentes&#44; pero pertenecientes al mismo sistema sanitario&#44; las cuales distan 43 millas una de la otra&#46; Las cepas aisladas de <span class="elsevierStyleItalic">Fusarium</span> se identificaron inicialmente por microscopia y su identidad se confirm&#243; posteriormente mediante secuenciaci&#243;n del factor de elongaci&#243;n alfa &#40;EF&#945;&#41; y de la regi&#243;n codificadora espaciadora interna &#40;ITS&#41;&#46; La sensibilidad a los antif&#250;ngicos se llev&#243; a cabo por el m&#233;todo de diluci&#243;n en caldo del EUCAST&#46;</p></span> <span id="abst0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Resultados</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Se produjo una mala evoluci&#243;n&#44; ya que dos de los tres pacientes evolucionaron haca la atrofia ocular a pesar de las medidas quir&#250;rgicas y el tratamiento antibi&#243;tico y antif&#250;ngico de amplio espectro&#46;</p></span> <span id="abst0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Conclusiones</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Es importante actuar r&#225;pidamente con medidas multidisciplinarias ante la sospecha de una endoftalmitis por <span class="elsevierStyleItalic">Fusarium</span> por el mal pron&#243;stico de este tipo de infecciones&#46;</p></span>"
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          "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Early postoperative findings after tectonic penetrating keratoplasty in the left eye&#46; Corneal transplant is edematous and shows fibrotic changes&#46; Note the superior neovascularization secondary to graft failure&#46; Early postoperative findings in the right eye after the first penetrating keratoplasty&#46; Severe conjunctival infection with a dense superior infiltrate in the interface suggestive of infection&#46; The transplant appears edematous and with Descemet folds in the visual axis&#46;</p>"
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          "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Endophthalmitis in a patient with Boston type I keratoprosthesis &#40;Boston KPro&#41;&#46; The whole cornea was infiltrated &#40;keratitis&#41; and the posterior chamber was also involved &#40;endophthalmitis&#41;&#46; Prompt surgery is imperative in these patients &#40;Pars plana vitrectomy<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>remove the KPro and replace with a penetrating keratoplasty&#41;&#46;</p>"
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Caspofungin&nbsp;\t\t\t\t\t\t\n
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          "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">In vitro antifungal susceptibility of the isolates&#46;</p>"
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    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0015"
          "bibliografiaReferencia" => array:26 [
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                            0 => "A&#46; Alastruey-Izquierdo"
                            1 => "M&#46; Cuenca-Estrella"
                            2 => "A&#46; Monz&#243;n"
                            3 => "E&#46; Mellado"
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                  ]
                  "host" => array:1 [
                    0 => array:2 [
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                        ]
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                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0140"
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                            0 => "A&#46;R&#46; Anand"
                            1 => "K&#46;L&#46; Therese"
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            ]
            2 => array:3 [
              "identificador" => "bib0145"
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                            0 => "M&#46; Azor"
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                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
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                        ]
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                    ]
                  ]
                ]
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            ]
            4 => array:3 [
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                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "V&#46; Buchta"
                            1 => "A&#46; Feuermannov&#225;"
                            2 => "M&#46; V&#225;&#353;a"
                            3 => "L&#46; Ba&#353;kov&#225;"
                            4 => "R&#46; Kutov&#225;"
                            5 => "A&#46; Kub&#225;tov&#225;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
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              ]
            ]
            5 => array:3 [
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                          "etal" => false
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                            0 => "V&#46;Y&#46; Bunya"
                            1 => "K&#46;M&#46; Hammersmith"
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              "referencia" => array:1 [
                0 => array:3 [
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              ]
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            7 => array:3 [
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                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
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                  ]
                  "host" => array:1 [
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                      "doi" => "10.1128/JCM.43.10.5372-5375.2005"
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                        "fecha" => "2005"
                        "volumen" => "43"
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ISSN: 11301406
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