Background Primary antifungal prophylaxis with mold-active azoles is used to prevent invasive fungal infections in patients with high-risk hematological disorders; however, breakthrough infections occur, and the reasons for treatment failure are still not fully understood. To help inform clinical decisions, we sought to define microbiological, clinical, and pharmacological characteristics of proven and probable breakthrough invasive fungal infections (bIFIs) in patients with high-risk hematological disorders receiving voriconazole or posaconazole prophylaxis. Methods We performed a systematic review of the literature following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The search strategy was last conducted on 19 April 2023. Results We assessed 5293 studies for eligibility, and 300 were selected for data extraction. These studies described 1076 cases of bIFIs occurring under voriconazole (42.5%) or posaconazole (57.5%). The most commonly found pathogens were Aspergillus (40%), Mucorales (20%), Candida (18%), and Fusarium (9%) species. Mucorales were more frequent among voriconazole-emerging cases, whereas Aspergillus and Fusarium were more prevalent among posaconazole-emerging cases. Definitive, putative, or probable antifungal resistance was found in 31% of cases. Therapeutic drug monitoring showed subtherapeutic azole concentration in 32 of 90 (36%) cases. Infection-related mortality was reported in 117 cases and reached 35%. Conclusions In our systemic review, the most common bIFIs were aspergillosis, mucormycosis, candidiasis, and fusariosis. Antifungal resistance explains only a minority of cases. Subtherapeutic prophylaxis was frequent but rarely reported. Prospective studies are needed to better understand these infections and to establish optimal management.

Background The burden of mucormycosis has increased with the expansion of risk groups and improved diagnosis. Although diabetes mellitus has been the leading risk factor for mucormycosis globally, the emergence of risk groups such as hemato-oncology patients, allogeneic bone marrow transplantation and solid organ transplantation have shifted the epidemiology of mucormycosis. There is a paucity of literature describing the burden, clinical presentation, treatment and outcomes of mucormycosis in Canada. CANMUS (Canadian Mucormycosis Study)is a national registry with broad geographical representation ,that will assess the epidemiology and clinical outcomes of Canadian patients affected by mucormycosis. Here we assess the outcomes at 6 and 12 weeks of therapy and last clinical assessment. Methods This retrospective registry involving 15 centers across Canada, from 1/1/2009 to 1/31/2020 using pathology/microbiology records to identify proven cases of mucormycosis in patients ≥18 years of age. Patient medical record data were collected and reported in a web-based data management program (REDCap). Descriptive statistics analyzed both categorical and continuous data. Cox proportional hazards models were used to explore risk factors for 6 and 12-week survival. Logistical regression was employed to investigate factors associated with positive clinical outcomes (defined as partial or complete response versus stable disease or progression). Results Interim data was available on 108 patients. The mean age was 53 (range 20-91) and 55.6% were male patients. The leading diagnostic risk factor for mucormycosis was hematological malignancy (50.9%, of which AML comprised 54.5%) followed by diabetes mellitus (25%). The most common sites of infection were: pulmonary (42.6%) rhino-sinus and/or orbital and/or cerebral (22.2%) and cutaneous (18%). The distribution of pathogens was: Mucor spp. (45.2%), Rhizopus spp. (34.5%) and Lichtheimia spp. (10.7%). Clinical response (composite of complete and partial responses) at 6 and 12 weeks was 31% and 29%, respectively. Survival analyses will be presented using hazard ratios and confidence intervals (CI). Logistic regression of factors associated with a positive clinical response will also be presented. Conclusions The epidemiology of mucormycosis in Canada is evolving. Hematological malignancies rather than diabetes are the major predisposing risk factor for mucormycosis with Mucor spp. being the predominant pathogen. Despite modest advances in therapies, outcomes remain poor.

Aerococcus urinae is a urinary pathogen with well-described resistance to fluoroquinolones. This study aimed to validate the gradient diffusion (GD) method (Etest) on cation-adjusted Mueller-Hinton agar with 5% sheep blood for testing the susceptibilities of Aerococcus urinae to the antimicrobial agents ciprofloxacin and levofloxacin and to compare the Etest to the broth microdilution (BMD) method from CLSI document M45-A3. Agar dilution (AD), as recommended by EUCAST, was used as an alternative reference method to arbitrate discrepancies or address technical issues. Aerococcus urinae isolates from urinary specimens were prospectively collected between June 2016 and December 2017 from six hospitals in Quebec, Canada, and identifications were confirmed using Vitek MS with the IVD 3.0 database. Of the 207 isolates tested using BMD, 37 (17.9%) showed trailing and 19 (9.2%) showed insufficient growth; these were tested using AD. Also, 38 isolates (18.4%) for ciprofloxacin and 13 isolates (6.3%) for levofloxacin showed a lack of essential or categorical agreement between the Etest and BMD and were also tested by AD. By use of a combined reference method (BMD or AD), the susceptibility rates of Aerococcus urinae were 82.6% and 81.6% for ciprofloxacin and levofloxacin, respectively. Categorical agreement between GD and the combined reference methods was 95.2% for ciprofloxacin and 97.1% for levofloxacin, with no very major error identified. Major and minor error rates were 0.6% and 4.3% for ciprofloxacin and 1.2% and 1.9% for levofloxacin. Overall, antimicrobial susceptibility testing (AST) using the Etest on sheep blood agar showed good agreement with the reference methods and can be considered by clinical laboratories wishing to perform AST on Aerococcus urinae isolates.

Highlight Musculoskeletal cystic echinococcosis can present as an isolated disease mimicking neoplasia. Along with albendazole therapy, complete excision avoiding cyst rupture is essential to prevent disease dissemination and hypersensitivity reactions. Conventional epidemiology and molecular typing can help differentiate between domestic and sylvatic strains of echinococcosis in the traveler and migrant population.

Rapid T cell reconstitution following hematopoietic stem cell transplantation (HSCT) is essential for protection against infections and has been associated with lower incidence of chronic graft-versus-host disease (cGVHD), relapse, and transplant-related mortality (TRM). While cord blood (CB) transplants are associated with lower rates of cGVHD and relapse, their low stem cell content results in slower immune reconstitution and higher risk of graft failure, severe infections, and TRM. Recently, results of a phase I/II trial revealed that single UM171-expanded CB transplant allowed the use of smaller CB units without compromising engraftment (www.clinicaltrials.gov, NCT02668315). We assessed T cell reconstitution in patients who underwent transplantation with UM171-expanded CB grafts and retrospectively compared it to that of patients receiving unmanipulated CB transplants. While median T cell dose infused was at least 2 to 3 times lower than that of unmanipulated CB, numbers and phenotype of T cells at 3, 6, and 12 months post-transplant were similar between the 2 cohorts. T cell receptor sequencing analyses revealed that UM171 patients had greater T cell diversity and higher numbers of clonotypes at 12 months post-transplant. This was associated with higher counts of naive T cells and recent thymic emigrants, suggesting active thymopoiesis and correlating with the demonstration that UM171 expands common lymphoid progenitors in vitro. UM171 patients also showed rapid virus-specific T cell reactivity and significantly reduced incidence of severe infections. These results suggest that UM171 patients benefit from rapid T cell reconstitution, which likely contributes to the absence of moderate/severe cGVHD, infection-related mortality, and late TRM observed in this cohort.

Abstract Background Aerococcus urinae is frequently identified by MALDI-TOF in urinary specimens. It is generally susceptible to β-lactams, but its susceptibility pattern to fluoroquinolones (FQ) remains unpredictable. The goal of this study was to evaluate the performance of the gradient diffusion method (Etest®) to determine FQ susceptibility compared with broth microdilution (BMD) and agar dilution (AD). Methods Prospectively collected isolates of A. urinae from urinary tract specimens originating from 5 hospitals in Quebec city and Montreal were identified by MALDI-TOF (Vitek-MS). All isolates were tested using BMD according to CLSI guidelines, and also with Etest® strips on MH agar w/ 5% sheep blood. Isolates showing trailing, insufficient growth or discordance between both methods were further tested by agar dilution (MH agar w/5% horse blood + β-NAD) according to EUCAST guidelines. Breakpoints were interpreted using CLSI M45-A3. Combined results of BMD and AD were then compared with Etest. Results Of the 207 isolates of A. urinae tested, 37 showed trailing (17,8%) and 19 (9,2%) insufficient growth with the BMD method and were retested using AD. Moreover, 38 isolates (ciprofloxacin) and 13 isolates (levofloxacin) showed either lack of categorical or essential agreement between Etest and BMD and were also retested using AD to arbitrate discrepancies. Susceptibility profiles combining BMD and AD are presented in Table 1. As suggested in EUCAST guidelines, readings were much clearer and growth was better with AD compared with BMD. The categorical agreement of the Etest® with BMD+AD was 95% for ciprofloxacin and 97% for levofloxacin. Essential agreement was 95% for ciprofloxacin and 97% for levofloxacin. No very major errors were identified. Two major errors were identified for levofloxacin (1,2%) and one for ciprofloxacin (0.6%). Conclusion Gradient diffusion method using Etest® strips on MH agar w/ sheep blood is a valid method to determine susceptibility to FQ for urinary tract isolates. As a reference method, AD provides clearer endpoints and better growth than BMD for FQ susceptibility testing. Disclosures All authors: No reported disclosures.

Introduction Prophylactic antibiotic (ATB) administration has been shown to reduce febrile episodes and infections in neutropenic patients undergoing high dose chemotherapy or hematopoietic stem cell transplant (HSCT) in large meta-analyses (Gafter-Gvili, Cochrane, 2012; Kimura, J Infect Dis, 2014). This practice is supported by current guidelines in high-risk patients including those undergoing HSCT. However, ATB use has also been associated with adverse outcomes such as decreased microbiota diversity (Taur, Blood, 2014) and increased resistance (Magesic, Transpl Inf Dis, 2014). Recently, our group participated in a multicenter retrospective cohort of patients undergoing allogeneic (a) HSCT that demonstrated an increased incidence of acute graft versus host disease (aGVHD) and lower overall survival in patients receiving antibioprophylaxis (Routy, Oncoimmunology, 2017). To assess the impact of omitting prophylactic ATB, we used the sample from one of the participating centers (Hôpital Maisonneuve-Rosemont) to compare the incidence of bacteraemia and mortality in aHSCT patients who received prophylactic ATB during the pre-engraftment period to those who did not. Methods This retrospective study included patients undergoing aHSCT for hematological malignancy between January 2005 and December 2012 at our center. Exclusion criteria were prior aHSCT, syngenic and haploidentical HSCT. Antibioprophylaxis with fluoroquinolones or trimethoprim-sulfamethoxazole (TMP-SMX)was administered at initiation of the conditioning regimen in patients receiving a myeloablative (MA) and reduced intensity conditioning regimen and discontinued after engraftment. It was omitted in patients with fluoroquinolone or penicillin allergy and in patients receiving a non-myeloablative regimen. Prophylactic ATB were substituted for therapeutic ATB during episodes of febrile neutropenia and documented infection. Bacteraemia occurring during the pre-engraftment period (30 days or less after stem cell infusion) were recorded. Results A total of 377 patients were included, of which 182 (48%) received prophylactic ATB and 195 (52%) did not. In the ATB group, 141 patients received ciprofloxacin, 17 moxifloxacin and 24 TMP-SMX. Baseline characteristics differed in both groups. The ATB group had a younger mean age with 45.2 ±12.3 years compared to 49.5 ±11.3 years (p<0.001) and a higher intensity conditioning regimen with 74% receiving a MA regimen compared with 36% (p<0.001). The incidence of bacteraemia was similar in both groups with 14.3% (95% CI 9.2-19.4%) in those receiving prophylactic ATB compared to 12.3% (95% CI 7.7-17.0%) in those who did not (OR 1.19, 95% CI 0.7-2.2, p 0.57). Expectedly, gram negative bacteremia was less likely (OR 0.24, 95% CI 0.07-0.84, p 0.026) in the ATB group, representing 11.5% of all bacteraemia compared to 52.2%. The incidence of bacteraemia was also reduced by prophylactic ATB in patients receiving a MA conditioning regimen (OR 0.48, 95% CI 0.25-0.96, p 0.036). There was no mortality associated to infectious causes during the pre-engraftment period in either group. Two patients died during the pre-engraftment period, one from hepatic failure and the other from acute respiratory distress syndrome in the context of veno-occlusive disease. Both were in the group that did not receive prophylactic ATB and received MA conditioning. Discussion In this study, the omission of prophylactic ATB did not increase the incidence of bacteraemia in patients undergoing aHSCT. However, the administration of prophylactic ATB did reduce bacteremia in those receiving MA conditioning regimens, as well as gram negative bacteraemia in all patients. Nevertheless, there was no impact on treatment related mortality at day 30 after stem cell infusion. Thus, the benefit of prophylactic ATB must be weighed against the higher risk of aGVHD and shorter overall survival observed in this sample in earlier studies (Routy, Oncoimmunology, 2017) and with the potential risk of selection and resistance. The limitations of this study include its retrospective design, the heterogenicity between the two groups and its omission of febrile episodes and infections without bacteraemia. Further data, preferably from a large prospective, randomised trial, would be useful to reassess the benefits and risks of prophylactic antibiotics in aHSCT. Lachance: ExCellThera: Patents & Royalties: Royalities from sales of UM171.

Aerococcus urinae is an emerging urinary pathogen frequently identified by MALDI-TOF. It is generally susceptible to β-lactams, however, its susceptibility pattern to fluoroquinolones (FQ) remains variable. The goals of this study were (i) to evaluate the performance of the gradient diffusion method (Etest®) to determine FQ resistance compared with broth microdilution (BMD) and (ii) to estimate the resistance rate of A. urinae toward FQ in Quebec hospitals. Two hundred seven consecutive isolates of A. urinae from urinary tract specimens originating from five hospitals in Quebec and Montreal were identified by MALDI-TOF (Vitek-MS and Bruker). All isolates were tested with the BMD and gradient diffusion methods. BMD was carried out in triplicate and was conducted in accordance with CLSI guidelines (M45-A3). Isolates with insufficient growth at 24 hours were reincubated and evaluated at 48 hours. The gradient diffusion method was carried out using Etest® strips on MH agar with 5% sheep blood. Of the 207 isolates of A. urinae, 52 (25%) gave uninterpretable results using the BMD method (insufficient growth = 20; trailing = 32). We obtained the following results for the remaining 155 isolates: BMD readings were often complicated by noticeably poor growth. The categorical agreement of the Etest® was 83% for ciprofloxacin and 95% for levofloxacin. Four very major errors were identified in a preliminary manner on 11% (4/35) of the ciprofloxacin-resistant isolates and 11%(4/35) of the levofloxacin-resistant isolates. Agar dilution will be done to confirm these results. In our experience, the method recommended by the CLSI for A. urinae susceptibility testing of FQ presented several problems, including insufficient growth and difficult reading. The Etest® appears to be a promising method for susceptibility testing of FQ for urinary tract isolates, but will first require a further comparison with agar dilution methods. In our study, the rate of FQ non-susceptibility of A. urinae was 27% for levofloxacin and 33% for ciprofloxacin. Therefore, FQ cannot be empirically recommended for the treatment of urinary tract infections caused by A. urinae. J. M. Leduc, Biomérieux: Investigator, Research grant.

BACKGROUND:Clostridium difficile infection (CDI) is a significant complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Our primary objective was to determine risk factors for the development of CDI during the first year following allo-HSCT.METHODS:A matched case-control study nested in a cohort of allo-HSCT at a single hospital in Montréal, Québec, Canada, was conducted from 2002 through 2011.RESULTS:Sixty-five of 760 patients who underwent allo-HSCT between 2002 and 2011 developed CDI, representing an incidence of 8.6%. We selected 123 controls matched for year of transplant for risk factor analyses. In the multivariable analysis, receipt of trimethoprim-sulfamethoxazole (TMP-SMX) prior to transplantation (adjusted odds ratio [aOR] 0.07, 95% confidence interval [CI] 0.02-0.27), mucositis (aOR 5.90, 95% CI 2.08-16.72), and reactivation of cytomegalovirus (CMV) (aOR 6.17, 95% CI 2.17-17.57) and of other Herpesviridae viruses (aOR 3.04, 95% CI 1.13-8.16) were the variables that remained statistically associated with CDI. High-risk antibiotic use in the late post-transplant period (aOR 7.63, 95% CI 2.14-27.22) was associated with development of late CDI.CONCLUSION:This study revealed reactivation of CMV and other Herpesviridae viruses as novel risk factors for CDI. Administration of TMP-SMX prior to transplantation was independently associated with a decreased risk of CDI. Early and late CDI after HSCT may have distinct risk factors.

A 38-year-old female from Montreal, Canada, consulted for sudden, painless vision loss in her left eye 5 days before presentation. Her medical history was known for bipolar disease, hypothyroidism, and clinically diagnosed truncal tinea versicolor (Fig. 1). Her history was largely unremarkable except for occasional ingestion of beef tartar. She denied any chills or fever and was afebrile upon physical examination. At initial visit, her visual acuity was 20/20 OD and counting fingers OS. Slit-lamp examination of the left eye showed 1+ cells and 1+ flare in the anterior chamber as well as 2+ vitreous cells and 1+ vitreous haze as per the Standardization of Uveitis Nomenclature working group grading scheme.1Chorich III, L.J. Kisovic D.D. Foster C.S. Diagnosis of uveitis.in: Foster C.S. Vitale A.T. Diagnosis and treatment of uveitis. 2nd ed. Jaypee Brothers Medical Publishers, New Delhi2013: 101-122Crossref Google Scholar Dilated fundus examination revealed an exophytic white lesion in the macula (Fig. 2). A clinical diagnosis of panuveitis caused by probable ocular toxoplasmosis OS was established. Baseline uveitis workup was initiated while empirical therapy with pyrimethamine (25 mg PO daily), folinic acid (10 mg PO every second day), and clindamycin (300 mg PO QID) was started on the day of the initial presentation. The patient also received routine topical uveitis treatment (prednisolone 1% q1hr, dexamethasone ointment 0.1% qHS, and homatropine 2% BID) in her left eye and oral prednisone 60 mg daily, started 48 hours after the initiation of antiprotozoal treatment. Her initial workup was notable for mild absolute eosinophilia and negative Toxoplasma gondii serology (immunoglobin [Ig]M and IgG). Results of screening for HIV, syphilis, cytomegalovirus (IgG), and tuberculosis (interferon-gamma release assay) were negative. Baseline workup was done for sarcoidosis even though the clinical picture was more suggestive of an infectious etiology; both chest x-ray and angiotensin-converting enzyme level were within normal limits. After 2 weeks of clinical stability, the patient's vision deteriorated and the fundus lesion had worsened significantly. Prednisone was suspended and a diagnostic vitrectomy was performed promptly. Calcofluor-white stain showed presence of pseudohyphae in the vitreous a few hours after the vitrectomy (Fig. 3). The vitreal culture subsequently confirmed Candida albicans growth the next day. Upon further questioning, in addition to her chronic skin lesions, the patient also reported chronic white buccal lesions, as well as recurrent vulvovaginitis. Furthermore, on review of systems, she described symptoms suggesting left-sided neglect for the last few weeks. On subsequent investigations, direct examination of skin lesion scrapings showed pseudohyphae consistent with Candida species, and buccal culture grew Candida albicans. Serum (1 to >3) β-D-glucan, a marker of invasive fungal infection, was elevated at >500 pg/mL though blood cultures remained negative. Cerebral magnetic resonance imaging (MRI) showed multiple active right parietal microabscesses (Fig. 4) and an old frontal lesion suggesting previous infection. Spinal MRI was consistent with spondylodiscitis at the level of L4–L5. The diagnosis was established as chronic mucocutaneous candidiasis (CMCC) complicated by invasive candidiasis, with the eye as the presenting infection site. Intravenous liposomal amphotericin B (5 mg/kg/day) was started but had to be stopped 2 weeks later due to renal toxicity. This was followed by oral fluconazole (800 mg daily) for 1 year, leading to complete resolution of mucocutaneous symptoms and of the cerebral and spinal lesions on subsequent MRIs. The daily dose of fluconazole was then reduced to 400 mg daily for the following 6 months before further being tapered to 200 mg daily. She will likely continue on this prophylactic dosage for life. In addition to the systemic treatments, the patient also received 4 weekly intravitreal antifungal injections (amphotericin B, 5 μg/0.1 mL, n = 1; voriconazole, 100 μg/0.1 mL, n = 3) OS, quieting down the panuveitis. However, her visual acuity stayed at counting fingers as a result of extensive macular scarring. Her right eye remained free of disease with normal visual acuity. In light of her unusual clinical presentation, the patient was referred for genetic testing, which revealed bi-allelic CARD9 mutations (manuscript in preparation). The clinical presentation of ocular candidiasis spans over a continuous spectrum. Whereas chorioretinitis involves only the chorioretinal layers, manifesting as cotton wool spots, Roth spots, retinal hemorrhages, or deep retinal focal white infiltrates, the diagnosis of Candida endophthalmitis also requires the presence of vitritis and/or fluffy vitreal lesions extending from chorioretinal infiltrates.2Oude Lashof A.M. Rothova A. Sobel J.D. et al.Ocular manifestations of candidemia.Clin Infect Dis. 2011; 53: 262-268Crossref PubMed Scopus (142) Google Scholar In addition to ocular candidiasis, the differential diagnosis of a focal chorioretinal lesion with associated vitreous cells includes toxoplasmosis, toxocariasis, tuberculosis, cat-scratch disease, onchocerciasis, cysticercosis, sarcoidosis, syphilis, and masquerade syndrome.3Moorthy R.S. Rao P.K. Read R.W. et al.Intraocular inflammation and uveitis.2013–2014 ed. American Academy of Ophthalmology, San Francisco2013Google Scholar Toxoplasmosis is by far the most common infectious cause of such lesions in both adults and children.3Moorthy R.S. Rao P.K. Read R.W. et al.Intraocular inflammation and uveitis.2013–2014 ed. American Academy of Ophthalmology, San Francisco2013Google Scholar However, when necessary, diagnostic vitrectomy should be performed for microbiological testings. Candida species are the leading cause of endogenous endophthalmitis.2Oude Lashof A.M. Rothova A. Sobel J.D. et al.Ocular manifestations of candidemia.Clin Infect Dis. 2011; 53: 262-268Crossref PubMed Scopus (142) Google Scholar Risk factors associated with ocular candidiasis overlap with those associated with invasive candidiasis in general, including surgery due to solid tumor4Blennow O. Tallstedt L. Hedquist B. Gardlund B. Duration of treatment for candidemia and risk for late-onset ocular candidiasis.Infection. 2013; 41: 129-134Crossref PubMed Scopus (22) Google Scholar and immunosuppression.5Donahue S.P. Greven C.M. Zuravleff J.J. et al.Intraocular candidiasis in patients with candidemia. Clinical implications derived from a prospective multicenter study.Ophthalmology. 1994; 101: 1302-1309Abstract Full Text PDF PubMed Scopus (215) Google Scholar In the context of established Candida infection, prolonged candidemia and specific Candida species (C. albicans and C. parasilosis) are associated with a higher risk of eye involvement.2Oude Lashof A.M. Rothova A. Sobel J.D. et al.Ocular manifestations of candidemia.Clin Infect Dis. 2011; 53: 262-268Crossref PubMed Scopus (142) Google Scholar By definition, endogenous Candida endophthalmitis occurs in association with transient or persistent candidemia, yet it remains an infrequent complication of invasive candidiasis. Even though the aforementioned wide spectrum of signs of ocular candidiasis was detected in up to 26% of patients with proven candidemia,6Krishna R. Amuh D. Lowder C.Y. Gordon S.M. Adal K.A. Hall G. Should all patients with candidaemia have an ophthalmic examination to rule out ocular candidiasis?.Eye (Lond). 2000; 14: 30-34Crossref PubMed Scopus (81) Google Scholar full-blown endophthalmitis involving the vitreous was reported in only 0% to 1.6% of patients with invasive candidiasis.2Oude Lashof A.M. Rothova A. Sobel J.D. et al.Ocular manifestations of candidemia.Clin Infect Dis. 2011; 53: 262-268Crossref PubMed Scopus (142) Google Scholar, 6Krishna R. Amuh D. Lowder C.Y. Gordon S.M. Adal K.A. Hall G. Should all patients with candidaemia have an ophthalmic examination to rule out ocular candidiasis?.Eye (Lond). 2000; 14: 30-34Crossref PubMed Scopus (81) Google Scholar Conversely, not all Candida endophthalmitis have proven candidemia at presentation. The reported rates of positive blood culture in patients diagnosed with Candida endophthalmitis are highly variable, ranging from 11% to 100% depending on the population.7Nolla-Salas J. Sitges-Serra A. Leon C. de la Torre M.V. Sancho H. Candida endophthalmitis in non-neutropenic critically ill patients.Eur J Clin Microbiol Infect Dis. 1996; 15: 503-506Crossref PubMed Scopus (22) Google Scholar, 8Essman T.F. Flynn Jr., H.W. Smiddy W.E. et al.Treatment outcomes in a 10-year study of endogenous fungal endophthalmitis.Ophthalmic Surg Lasers. 1997; 28: 185-194PubMed Google Scholar Even when bloodstream infection is not demonstrated, most reports involve processes or procedures pathologically consistent with transient candidemia such as intravenous drug use,9Connell P.P. O'Neill E.C. Amirul Islam F.M. et al.Endogenous endophthalmitis associated with intravenous drug abuse: seven-year experience at a tertiary referral center.Retina. 2010; 30: 1721-1725Crossref PubMed Scopus (34) Google Scholar contaminated intravenous infusion,10Daily M.J. Dickey J.B. Packo K.H. Endogenous Candida endophthalmitis after intravenous anesthesia with propofol.Arch Ophthalmol. 1991; 109: 1081-1084Crossref PubMed Scopus (29) Google Scholar and childbirth,11Lee J.H. Kim J.S. Park Y.H. Diagnosis and treatment of postpartum Candida endophthalmitis.J Obstet Gynaecol Res. 2012; 38: 1220-1222Crossref PubMed Scopus (8) Google Scholar as well as lithotripsy of renal calculi in the presence of fungal urinary tract colonization.12Greenwald B.D. Tunkel A.R. Morgan K.M. Campochiaro P.A. Donowitz G.R. Candidal endophthalmitis after lithotripsy of renal calculi.South Med J. 1992; 85: 773-774Crossref PubMed Scopus (8) Google Scholar Reports of Candida endophthalmitis associated with superficial candidiasis such as vaginal infection or onychomycosis are rare.13Kostick D.A. Foster R.E. Lowder C.Y. Meyers S.M. McHenry M.C. Endogenous endophthalmitis caused by Candida albicans in a healthy woman.Am J Ophthalmol. 1992; 113: 593-595Abstract Full Text PDF PubMed Scopus (31) Google Scholar, 14Hassan A. Poon W. Baker M. Linton C. Muhlschlegel F.A. Confirmed Candida albicans endogenous fungal endophthalmitis in a patient with chronic candidiasis.Med Mycol Case Rep. 2012; 1: 42-44Crossref Scopus (8) Google Scholar To our knowledge, our patient is the first reported case of endophthalmitis associated with CMCC, a condition characterized by persistent or recurrent superficial candidal infection of skin, mucous membranes, and nails. Finally, this case emphasizes the importance of performing an in-depth workup and of screening for immunodeficiencies when managing atypical cases presenting with "spontaneous" deep Candida infections such as endophthalmitis. Multiple genetic mutations, including CARD9, have been reported to cause impaired Th17 immunity against Candida species, predisposing to superficial and/or deep infections.15Shoham S. Dufresne S.F. The role of genetics in host reponses to mucosal and invasive candidiasis.Curr Fungal Infect Rep. 2011; 5: 262-268Crossref Scopus (1) Google Scholar The presence of CMCC and its associated genetic susceptibilities are often overlooked but are important for several reasons. Recognition of such susceptibilities not only ensures prompt short-term and long-term treatments for patients, but also provides the opportunity for novel adjunctive therapy targeting specific mutations.16Gavino C. Cotter A. Lichtenstein D. et al.CARD9 deficiency and spontaneous central nervous system candidiasis: complete clinical remission with GM-CSF therapy.Clin Infect Dis. 2014; 59: 81-84Crossref PubMed Scopus (125) Google Scholar Furthermore, as some of these mutations are inheritable, appropriate genetic counselling would also be beneficial and necessary. The authors have no proprietary or commercial interest in any materials discussed in this article. Q.W., S.F.D., and M.-J.A. have no financial or proprietary interest to declare. D.C.V. has received an unrestricted educational grant from CSL Behring Canada; an investigator-initiated grant from Astellas Canada; and honoraria from CSL Behring Canada, Sunovion, Pfizer Canada, and Merck Canada. He has received research funding support from the McGill University Health Centre/Research-Institute and is a Chercheur-Boursier clinicien junior 1 (Fondation de recherche Santé-Québec, FRQS). This case report received no funding.