[Lomentospora prolificans Fungemia in a Patient With T-Cell Large Granular Leukemia: A Rare Pathogen in Türkiye]. / T-hücreli Büyük Granüler Lösemili Bir Hastada Lomentospora prolificans Fungemisi: Türkiye'de Nadir Bir Etken.

Scedosporium/Lomentospora is an opportunistic fungal pathogen found worldwide. While Scedosporium apiospermum and Scedosporium boydii are commonly observed globally, Lomentospora prolificans, which mainly affects immunosuppressed individuals, is rarely encountered and is more prevalent in arid climates, particularly in Australia and Spain. L.prolificans is a fungus commonly found in environmental sources such as contaminated water and soil. This species is known as an opportunistic pathogen that can cause deep-seated fungal infections, especially in immunosuppressed individuals. In this case report, a fatal case of L.prolificans fungemia in a patient with T-cell large granular leukemia during profound neutropenia was presented. The patient admitted to the hospital with prolonged fever, neutropenia, and shortness of breath. Antibiotherapy was administered to the patient for febrile neutropenia, but the fever persisted and his clinical status rapidly deteriorated. L.prolificans was isolated from the blood culture, and considering its antifungal resistance, combination therapy of voriconazole and terbinafine was initiated. However, the patient died of septic shock and multiple organ failure. In conclusion, although L.prolificans infections are rare, they can be life-threatening, especially in immunosuppressed individuals. Diagnosis and treatment of such infections may be difficult, therefore rapid diagnostic methods and appropriate treatment protocols should be developed. Consideration of infections caused by rare fungal pathogens in patients with risk factors may be critical for patient care. The literature review revealed that the first case of L.prolificans fungemia from Türkiye was reported in 2023. This case presentation represents the second reported case. However, in our case, L.prolificans fungemia occurred in 2018, it can be considered that L.prolificans may have been an invasive fungal pathogen of significant concern in Türkiye much earlier than previously documented.

A fatal neonatal case of fungemia due to Exophiala dermatitidis-case report and literature review.

BACKGROUND: Systemic infections caused by the black yeast-like fungus Exophiala dermatitidis are rare, but are associated with high mortality especially in immunocompromised patients. We report the first case of E. dermatitidis fungemia in a premature extremely low birth weight (ELBW) neonate who succumbed despite antifungal therapy with liposomal amphotericin (AMB) and fluconazole. A systematic review of all fungemia cases due to E. dermatitidis was also conducted aiming for a better understanding of the risk factors, treatment strategies and outcomes. CASE PRESENTATION: A male, ELBW premature neonate, soon after his birth, developed bradycardia, apnoea and ultimately necrotizing enterocolitis with intestinal perforation requiring surgical intervention. Meanwhile, he had also multiple risk factors for developing bloodstream infection, such as intubation, mechanical ventilation, central venous catheter (CVC), parenteral nutrition, empirical and prolonged antibiotic use. His blood cultures were positive, firstly for Acinetobacter junii and then for Klebsiella pneumoniae together with E. dermatitidis while on fluconazole prophylaxis and antibiotic empiric therapy. Despite the treatment with broad spectrum antibiotics, liposomal AMB and fluconazole, the newborn succumbed. A literature review identified another 12 E. dermatitidis bloodstream infections, mainly in patients with hematologic malignancies and solid organ transplant recipients (61%), with overall mortality 38% despite CVC removal and antifungal therapy. CONCLUSIONS: Due to the rarity of E. dermatitidis infections, little is known about the characteristics of this yeast, the identification methods and the optimal therapy. Identification by common biochemical tests was problematic requiring molecular identification. Resolution of neonatal fungemia is difficult despite proper antifungal therapy especially in cases with multiple and severe risk factors like the present one. Therapeutic intervention may include CVC removal and treatment for at least 3 weeks with an azole (itraconazole or fluconazole after susceptibility testing) or AMB monotherapy but not echinocandins or AMB plus azole combination therapy.

Disseminated nontuberculous mycobacteriosis and fungemia after second delivery in a patient with MonoMAC syndrome/GATA2 mutation: a case report.

BACKGROUND: Heterozygous mutations in the transcription factor GATA2 result in a wide spectrum of clinical phenotypes, including monocytopenia and Mycobacterium avium complex (MAC) infection (MonoMAC) syndrome. Patients with MonoMAC syndrome typically are infected by disseminated nontuberculous mycobacteria, fungi, and human papillomavirus, exhibit pulmonary alveolar proteinosis during late adolescence or early adulthood, and manifest with decreased content of dendritic cells (DCs), monocytes, and B and natural killer (NK) cells. CASE PRESENTATION: A 39-year-old woman was diagnosed with MonoMAC syndrome postmortem. Although she was followed up based on the symptoms associated with leukocytopenia that was disguised as sarcoidosis with bone marrow involvement, she developed disseminated nontuberculous mycobacterial infection, fungemia, and MonoMAC syndrome after childbirth. Genetic testing revealed a heterozygous missense mutation in GATA2 (c.1114G > A, p.A372T). Immunohistochemistry and flow cytometry showed the disappearance of DCs and decreased frequency of NK cells in the bone marrow, respectively, after childbirth. CONCLUSIONS: To the best of our knowledge, this is the first study reporting that MonoMAC syndrome can be exacerbated after childbirth, and that immunohistochemistry of bone marrow sections to detect decreased DC content is useful to suspect MonoMAC syndrome.

Trichosporon asahii superinfections in critically ill COVID-19 patients overexposed to antimicrobials and corticosteroids.

OBJECTIVES: To investigate the occurrence of Trichosporon asahii fungemia among critically ill COVID-19 patients. METHODS: From 1 July to 30 September 2020, cases of T asahii fungemia (TAF) in a Brazilian COVID-19 referral centre were investigated. The epidemiology and clinical courses were detailed, along with a mycological investigation that included molecular species identification, haplotype diversity analysis and antifungal susceptibility testing. RESULTS: Five critically ill COVID-19 patients developed TAF in the period. All five patients had common risk conditions for TAF: central venous catheter at fungemia, previous exposure to broad-spectrum antibiotics, prior echinocandin therapy and previous prolonged corticosteroid therapy. The average time of intensive care unit hospitalisation previous to the TAF episode was 23 days. All but one patient had voriconazole therapy, and TAF 30-day mortality was 80%. The five T asahii strains from the COVID-19 patients belonged to 4 different haplotypes, mitigating the possibility of skin origin and cross-transmission linking the 5 reported episodes. The antifungal susceptibility testing revealed low minimal inhibitory concentrations for azole derivatives. CONCLUSIONS: Judicious prescription of antibiotics, corticosteroids and antifungals needs to be discussed in critically ill COVID-19 patients to prevent infections by hard-to-treat fungi like T asahii.

Real-Time Therapeutic Drug Monitoring-Based Pharmacokinetic/Pharmacodynamic Optimization of Complex Antimicrobial Therapy in a Critically Ill Morbidly Obese Patient. Grand Round/A Case Study.

The authors present the case of a critically ill morbidly obese patient (body mass index, 51.2 kg/m) who suffered from methicillin-resistant Staphylococcus epidermidis, and Candida albicans bloodstream infections. Initial treatment with caspofungin and daptomycin was deemed inappropriate, because blood cultures remained positive for both isolates after 14 days. The clinical pharmacological consultant suggested adding fluconazole and ceftobiprole to the ongoing antimicrobial therapy, and starting a real-time therapeutic drug monitoring program of daptomycin, ceftobiprole, and fluconazole, aimed at optimizing plasma exposures. Punctual minimum inhibitory concentration knowledge on the clinical isolates allowed attainment of the desired pharmacodynamic efficacy targets. Within few days, the patient greatly improved, as blood cultures became negative, and the inflammatory markers decreased to near normal values. This is a proof-of-concept of the importance of a therapeutic drug monitoring-based multidisciplinary approach in the proper management of complex antimicrobial therapy in special populations.

Cryptococcal meningitis in an immunocompetent patient.

Cryptococcal meningitis is a fungal infection that is most commonly thought of as an opportunistic infection affecting immunocompromised patients, classically patients with Human Immunodeficiency (HIV) infection. It is associated with a variety of complications including disseminated disease as well as neurologic complications including intracranial hypertension, cerebral infarcts, vision loss and other neurologic deficits. It is diagnosed by lumbar puncture with CSF studies, including fungal culture and cryptococcal antigen testing. We present a case of cryptococcal meningitis and fungemia in a previously healthy male patient who presented after multiple emergency department visits with persistent headache. After multiple visits, he underwent a lumbar puncture consistent with cryptococcal infection, and he was admitted to the hospital for initiation of antifungal therapy. His workup revealed no known underlying condition leading to immune compromise.

Candidal Prosthetic Hip Infection in a Patient with Previous Candidal Sepsis - A Case Report.

A 60 year-old woman with hip dysplasia battled with duodenal cancer that was complicated with Candida tropicalis sepsis. Two years later, the patient underwent a total hip arthroplasty (THA). She complained of a persisting low-grade fever and local heat on the THA scar. Arthrocentesis of the hip was performed and the Candida tropicalis was detected. Debridement and polyethylene liner/modular head exchange were performed 28 days after the primary THA. Fluconazole was administrated for one year. The patient reported no symptoms five years later. It was found that periprosthetic infection could be prevented by implant preservation surgery.

Fungaemia in haematological malignancies: SEIFEM-2015 survey.

BACKGROUND: Fungal infections are still a relevant challenge for clinicians involved in the cure of patients with cancer. We retrospectively reviewed charts of hospitalized patients with haematological malignancies (HMs), in which a documented fungaemia was diagnosed between January 2011 and December 2015 at 28 adult and 6 paediatric Italian Hematology Departments. METHODS: During the study period, we recorded 215 fungal bloodstream infections (BSI). Microbiological analyses documented that BSI was due to moulds in 17 patients (8%) and yeasts in 198 patients (92%), being Candida spp identified in 174 patients (81%). RESULTS: Mortality rates were 70% and 39% for mould and yeast infections, respectively. Infection was the main cause of death in 53% of the mould and 18% of the yeast groups. At the multivariate analysis, ECOG ≥ 2 and septic shock were significantly associated with increased mortality, and removal of central venous catheter (CVC) survival was found to be protective. When considering patients with candidemia only, ECOG ≥ 2 and removal of CVC were statistically associated with overall mortality. CONCLUSIONS: Although candidemia represents a group of BSI with a good prognosis, its risk factors largely overlap with those identified for all fungaemias, even though the candidemia-related mortality is lower when compared to other fungal BSI. Management of fungal BSI is still a complex issue, in which both patients and disease characteristics should be focused to address a personalized approach.

Severe Sepsis in Pediatric Liver Transplant Patients: The Emergence of Multidrug-Resistant Organisms.

OBJECTIVES: To describe characteristics of liver transplant patients with severe sepsis in the PICU. DESIGN: Retrospective descriptive analysis. SETTING: Tertiary children's hospital PICU. PATIENTS: Liver transplant recipients admitted January 2010 to July 2016 for pediatric severe sepsis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Between January 2010 and July 2016, 173 liver transplants were performed, and 36 of these patients (21%) were admitted with severe sepsis (54 episodes total). Median age at admission was 2 years (1-6.5 yr), 47.2% were male. Bacterial infections were the most common (77.8%), followed by culture negative (12.9%) and viral infections (7.4%). Fungal infections accounted for only 1.9%. Median time from transplant for viral and culture negative infections was 18 days (8.25-39.75 d) and 25 days (9-41 d), whereas 54.5 days (17-131.25 d) for bacterial infections. Bloodstream and intra-abdominal were the most common bacterial sites (45% and 22.5%, respectively). Multidrug-resistant organisms accounted for 47.6% of bacterial sepsis. Vancomycin-resistant Enterococcus and extended-spectrum beta-lactamase producers were the most frequently identified multidrug-resistant organisms. Patients with multidrug-resistant organism sepsis demonstrated higher admission Pediatric Logistic Organ Dysfunction scores (p = 0.043) and were noted to have an odds ratio of 3.8 and 3.6 for mechanical ventilation and multiple organ dysfunction syndrome, respectively (p = 0.047 and p = 0.044). Overall mortality was 5.5% (n = 2 patients), with both deaths occurring in multidrug-resistant organism episodes. CONCLUSIONS: We report that multidrug-resistant organisms are increasingly being identified as causative pathogens for sepsis in pediatric liver transplant recipients and are associated with significantly higher odds for mechanical ventilation and higher organ failure. The emergence of multidrug-resistant organism infections in pediatric liver transplant patients has implications for patient outcomes, antibiotic stewardship, and infection prevention strategies.

Progressive disseminated histoplasmosis with concomitant disseminated nontuberculous mycobacterial infection in a patient with AIDS from a nonendemic region (California).

BACKGROUND: Opportunistic infections, while well studied in the AIDS population, continue to have variable and surprising presentations. Here, we present a case of disseminated histoplasmosis with disseminated nontuberculous mycobacterial infection in a 50 year old man with long standing AIDS living in a non-endemic area. CASE PRESENTATION: Patient presented with a constellation of symptoms, and imaging of the chest showed a pulmonary mass with cavitation, multiple nodules, and ground glass opacities. Further investigations revealed granulomatous lung nodules and fungemia consistent with Histoplasma capsulatum, and coinfection with disseminated nontuberculous mycobateria in a nonendemic area. CONCLUSIONS: Immunocompromised patients risk co-inhabitation by multiple infectious organisms. Some of these organisms may preside in the host for years prior to reactivation. Clinicians in non endemic areas should therefore be careful to not overlook specific organisms based on a lack of a recent travel history. Physicians in nonendemic areas should become more familiar with the clinical findings and diagnostic approach of infectious such as Histoplasmosis, to ensure earlier recognition and treatment in immunocompromised individuals.

Risk factors and clinical outcomes of breakthrough yeast bloodstream infections in patients with hematological malignancies in the era of newer antifungal agents.

Although yeast bloodstream infections (BSIs) are increasingly being reported in patients with hematological malignancies undergoing antifungal therapy, clinical information regarding breakthrough infections is scarce. The aim of this study was to determine the risk factors for and clinical outcomes of breakthrough yeast BSIs in patients with hematological malignancies in the era of newer antifungal agents. Between 2011 and 2014, all consecutive patients with hematological malignancies who developed yeast BSIs were included in a case-control study wherein breakthrough infections (cases) and de novo infections (controls) were compared. Of 49 patients with yeast BSIs, 21 (43%) met the criteria for breakthrough infections. The proportions of Candida krusei and Candida tropicalis in the cases and controls were significantly different (32% [7/22] vs. 3% [1/29], P = .015; 5% [1/22] vs. 38% [11/29], P = .007, respectively). Acute leukemia, presence of a central venous catheter and neutropenia in the 3 days prior to BSI were significant risk factors for breakthrough infections. Six-week mortality rates was 33% [7/21] in the cases and 43% [12/28] in the controls (P = .564). Refractory neutropenia and the Pitt bacteremia score were independent predictors of 6-week mortality. In conclusion, breakthrough infections accounted for a significant proportion of yeast BSIs in patients with hematological malignancies. However, these infections did not increase the risk of death by themselves. Our results suggest that current clinical management of breakthrough yeast BSIs, which includes switching to a different antifungal class and prompt catheter removal is reasonable.

Rapid emergence of cryptococcal fungemia, Mycobacterium chelonae vertebral osteomyelitis and gastro intestinal stromal tumor in a young HIV late presenter: a case report.

BACKGROUND: Highly active antiretroviral therapy has significantly changed the natural history of HIV infection, leading to a dramatic reduction of HIV-related morbidity and mortality. Late Presenters, Very Late Presenters and AIDS presenters still represent, also in Europe, including Italy, a huge challenge in terms of diagnostic and therapeutic management. CASE PRESENTATION: A 35-year-old male with a history of fever and back pain. HIV test resulted positive with a high HIV Viral Load and a very low T-CD4 number of cells (5 cells/mm3). Imaging investigations revealed multiple vertebral and pulmonary lesions together with abdominal and thoracic lymphadenopathy. Blood cultures were positive for Cryptococcus neoformans and for Staphylococcus haemolyticus. Lymphnode biopsy resulted positive in PCR for Non-Tuberculosis Mycobacteria (Mycobacterium chelonae). A gastric biopsy also revealed a GIST. The patient also had CMV DNA positive. Although we performed antiretroviral therapy and specific-therapies for each disease, he was transferred to intensive care unit where he died due to an Acute Respiratory Distress Syndrome. CONCLUSION: The reported case is unusual due to the relevant number of opportunistic diseases (both infectious and tumoral) emerging not long after the HIV infection had been diagnosed. Late presenters HIV patients and AIDS presenters still represent a challenge, which is often too complex for clinicians to deal with. In spite of proper management, the risk of suboptimal results cannot be excluded.

Fatal disseminated Trichosporon asahii fungemia in a child with acute lymphoblastic leukemia and a morbilliform eruption.

Trichosporonosis is a rare, life-threatening, opportunistic fungal infection that affects immunocompromised individuals with neutropenia, particularly those with underlying hematologic malignancies. We present the case of a 10-year-old boy with acute lymphoblastic leukemia who developed a diffuse, morbilliform eruption in the setting of fever and pancytopenia. He was found to have Trichosporon asahii fungemia with widespread visceral dissemination, and his condition rapidly deteriorated despite treatment. It is important to consider trichosporonosis in the evaluation of a critically ill individual with neutropena and a rash, because the initial cutaneous presentation may appear benign and delayed therapy results in death.

Administration of Voriconazole in Disseminated Talaromyces (Penicillium) Marneffei Infection: A Retrospective Study.

Talaromyces (Penicillium) marneffei infection is a fatal disseminated mycosis caused by the dimorphic fungus Talaromyces marneffei; the therapeutic strategies for this infectious disease are limited. The aim of this retrospective study was to evaluate the efficacy and safety of voriconazole for treating patients with disseminated T. marneffei infection with or without HIV infection in a clinical setting. Patients who intravenously received voriconazole (6 mg/kg q12 h for the first 24 h followed by 4 mg/kg q12 h) as the initial antifungal treatment were enrolled. The duration of the following antifungal treatment varied at the discretion of the investigators according to the patient responses. The primary global response was evaluated at Week 16 or at the end of treatment (EOT). Follow-up evaluations were performed at 6 months and 1 year after the EOT. Seventeen patients were enrolled in this study, but three were not evaluable because the treatment was prematurely discontinued. Among the remaining fourteen patients, ten patients had complete response and three had partial response at Week 16. Only one patient was determined to have failed response. Follow-up assessments in eleven patients showed that eight patients were cured and the remaining three patients relapsed at 6 months after the EOT. These eight patients were assessed 1 year later, and none of them had relapsed. No adverse events associated with voriconazole were recorded during the treatment. The results from our study suggest that voriconazole is an effective, well-tolerated therapeutic option for disseminated T. marneffei infection.

Pseudozyma aphidis fungaemia with invasive fungal pneumonia in a patient with acute myeloid leukaemia: case report and literature review.

Pseudozyma species rarely cause invasive diseases in humans, which are usually isolated from plants. There have been anecdotal reports regarding Pseudozyma species infections in patients with underlying diseases or in neonates. However, clinical data and the pathogenicity in humans are still insufficient. We experienced a case of Pseudozyma aphidis fungaemia with invasive fungal pneumonia that developed during reinduction chemotherapy in a 51-year-old male with acute myeloid leukaemia (AML). P. aphidis was suspected based on the morphology of the yeast isolated from the blood and was confirmed via rDNA gene sequencing analysis. The patient successfully underwent stem cell transplantation with continuing antifungal treatment and finally completely recovered from both the AML and infectious complications. Here, we report a case of P. aphidis infection that developed during neutropenia in an AML patient and review the global literature.

Rhodotorula mucilaginosa Fungemia and Pleural Tuberculosis in an Immunocompetent Patient: An Uncommon Association.

We report an atypical case of Rhodotorula mucilaginosa fungemia coexisting with pleural tuberculosis, in an immunocompetent host. The patient was an inhaled drug abuser and worked in a fruit market. The diagnosis of Rhodotorula mucilaginosa infection was established by the isolation of the yeast in two blood cultures followed by a good response to amphotericin B treatment. Persistent evening fever and pleural effusion led to the second diagnosis-pleural tuberculosis. In the last 5 years, this was the only case of Rhodotorula mucilaginosa fungemia in our hospital and the first case in the literature that documents Rhodotorula mucilaginosa fungemia associated with pleural tuberculosis.

Rhizopus arrhizus and Fusarium solani Concomitant Infection in an Immunocompromised Host.

Neutropenic patients are at risk of the development of hyalohyphomycosis and mucormycosis. Correct identification is essential for the initiation of the specific treatment, but concomitant mold infections are rarely reported. We report one unprecedented case of concomitant mucormycosis and fusariosis in a neutropenic patient with acute myeloid leukemia. The patient developed rhino-orbital infection by Rhizopus arrhizus and disseminated infection by Fusarium solani. The first culture from a sinus biopsy grew Rhizopus, which was consistent with the histopathology report of mucormycosis. A second sinus biopsy collected later during the patient's clinical deterioration was reported as hyalohyphomycosis, and the culture yielded F. solani. Due to the discordant reports, the second biopsy was reviewed and two hyphae types suggestive of both hyalohyphomycetes and mucormycetes were found. The dual mold infection was confirmed by PCR assays from paraffinized tissue sections. Increased awareness of the existence of dual mold infections in at-risk patients is necessary. PCR methods in tissue sections may increase the diagnosis of dual mold infections. In case of sequential biopsies showing discrepant results, mixed infections have to be suspected.

Epidemiology and outcome of fungemia in a cancer Cohort of the Infectious Diseases Group (IDG) of the European Organization for Research and Treatment of Cancer (EORTC 65031).

BACKGROUND: Anti-cancer treatment and the cancer population have evolved since the last European Organisation for Research and Treatment of Cancer (EORTC) fungemia survey, and there are few recent large epidemiological studies. METHODS: This was a prospective cohort study including 145 030 admissions of patients with cancer from 13 EORTC centers. Incidence, clinical characteristics, and outcome of fungemia were analyzed. RESULTS: Fungemia occurred in 333 (0.23%; 95% confidence interval [CI], .21-.26) patients, ranging from 0.15% in patients with solid tumors to 1.55% in hematopoietic stem cell transplantation recipients. In 297 evaluable patients age ranged from 17 to 88 years (median 56 years), 144 (48%) patients were female, 165 (56%) had solid tumors, and 140 (47%) had hematological malignancies. Fungemia including polymicrobial infection was due to: Candida spp. in 267 (90%), C. albicans in 128 (48%), and other Candida spp. in 145 (54%) patients. Favorable overall response was achieved in 113 (46.5%) patients by week 2. After 4 weeks, the survival rate was 64% (95% CI, 59%-70%) and was not significantly different between Candida spp. Multivariable logistic regression identified baseline septic shock (odds ratio [OR] 3.04, 95% CI, 1.22-7.58) and tachypnoea as poor prognostic factors (OR 2.95, 95% CI, 1.66-5.24), while antifungal prophylaxis prior to fungemia (OR 0.20, 95% CI, .06-.62) and remission of underlying cancer (OR, 0.18; 95% CI, .06-.50) were protective. CONCLUSIONS: Fungemia, mostly due to Candida spp., was rare in cancer patients from EORTC centers but was associated with substantial mortality. Antifungal prophylaxis and remission of cancer predicted better survival.

Unanticipated Multiplex PCR-Based Identification of Polymicrobial Blood Culture Resulting in Earlier Isolation, Determination of Susceptibilities, and Optimization of Clinical Care.

We describe a case of polymicrobial bloodstream infection with six organisms identified by multiplex PCR that was initially thought to be a monomicrobial infection. Early recognition of specific Gram-positive, Gram-negative, and fungal organisms and resistance elements allowed significantly more rapid optimization of therapy.