Case series of dogs with blastomycosis managed with high-flow nasal oxygen therapy (2019-2023): 19 cases.

Objective: To describe the clinical presentation, progression, treatment, and outcome of dogs with blastomycosis treated with high-flow nasal oxygen therapy (HFNOT). Design: Retrospective case review. Setting: University veterinary teaching hospital. Animals: Nineteen client-owned dogs with strongly suspected or confirmed blastomycosis treated with HFNOT. Measurements and main results: The medical records of dogs with strongly suspected or confirmed blastomycosis between October 2019 and May 2023 that received HFNOT were evaluated. Nineteen dogs were included. Nine dogs were started directly on high-flow nasal oxygen therapy. The remaining 10 dogs first received traditional oxygen therapy and were then transitioned to HFNOT 3-142 h later. Of the 19 dogs, 1 survived to discharge from hospital, 12 were euthanized due to progression of disease, and 6 died during the hospitalization period. Conclusions and clinical importance: The prognosis for survival of dogs with severe blastomycosis requiring therapy beyond traditional oxygen methods was poor to grave in this population. This is the first known documented report of HFNOT use in dogs with confirmed or suspected blastomycosis.

Construction of Candida albicans Adhesin-Exposed Synthetic Cells for Preventing Systemic Fungal Infection.

The development of efficient fungal vaccines is urgent for preventing life-threatening systemic fungal infections. In this study, we prepared a synthetic, cell-based fungal vaccine for preventing systemic fungal infections using synthetic biology techniques. The synthetic cell EmEAP1 was constructed by transforming the Escherichia coli chassis using a de novo synthetic fragment encoding the protein mChEap1 that was composed of the E. coli OmpA peptide, the fluorescence protein mCherry, the Candida albicans adhesin Eap1, and the C-terminally transmembrane region. The EmEAP1 cells highly exposed the mChEap1 on the cell surface under IPTG induction. The fungal vaccine was then prepared by mixing the EmEAP1 cells with aluminum hydroxide gel and CpG. Fluorescence quantification revealed that the fungal vaccine was stable even after 112 days of storage. After immunization in mice, the vaccine resided in the lymph nodes, inducing the recruitment of CD11c+ dendritic cells. Moreover, the vaccine strongly activated the CD4+ T splenocytes and elicited high levels of anti-Eap1 IgG. By the prime-boost immunization, the vaccine prolonged the survival time of the mice infected by the C. albicans cells and attenuated fungal colonization together with inflammation in the kidneys. This study sheds light on the development of synthetic biology-based fungal vaccines for the prevention of life-threatening fungal infections.

Optimization of a commercial Histoplasma galactomannan EIA test in a population from an endemic area of histoplasmosis in southern Brazil.

BACKGROUND: Since 2020 the World Health Organization (WHO) recommends Histoplasma antigen detection for the diagnosis of disseminated histoplasmosis (DH) in people living with HIV (PLHIV). OBJECTIVE: Here we aimed to optimise the IMMY's Clarus® Histoplasma GM enzyme immunoassay (EIA), evaluating the best cut-off in the semi-quantitative (SQ-HGM EIA), also known as 'calibrator cut-off procedure'. METHODS: The optimization was done using the quantitative standard procedure (Q-HGM EIA), also known as 'standard curve procedure', as reference test. A retrospective study from an endemic area of DH in southern Brazil was carried out including 264 patients investigated for DH using the test. Receiver Operator Characteristic curve was plotted, and sensitivity and specificity of the SQ-HGM EIA were calculated. RESULTS: The study included 24 positive (values ≥ 0.20 ng/ml) and 240 negative patients by the Q-HGM EIA. According to the manufacturer SQ-HGM EIA protocol, the new SQ-HGM EIA cut-off of 0.8 EIA units was validated, resulting in sensitivity and specificity of 88% and 98.7%, respectively. CONCLUSION: Our study pioneers and brings important data about the optimization of the Histoplasma antigen testing for the diagnosis of DH in a population from Southern Brazil. This optimization also reduced the amount of reagents used, lowering the cost associated with testing.

Primary Cutaneous Aspergillosis in an Immunocompetent Patient: A Case Report from a Tertiary Care Hospital in Chennai.

Aspergillosis is a systemic fungal infection that commonly affects immunocompromised individuals and, less frequently, immunocompetent individuals. It is the most common opportunistic fungal disease after candidiasis. This is primarily a pulmonary infection and can also involve other body sites like paranasal sinuses and cutaneous tissues. Aspergillus fumigatus , Aspergillus niger , and Aspergillus flavus are the common species infecting humans. Primary cutaneous aspergillosis (PCA) is usually caused by A. flavus and A. fumigatus . It is commonly seen in immunocompromised patients such as those suffering from diabetes, malignancies, tuberculosis, human immunodeficiency virus, or patients on long-term steroids and antibiotics. In this article, we report a case of PCA, in the immediate postoperative period, following a road traffic accident, in an immunocompetent patient. This posed a diagnostic challenge to the treating physicians. A. flavus was confirmed with 10% potassium hydroxide mount, lactophenol cotton blue, and growth on Sabouraud dextrose agar from tissue culture sample. Antifungal treatment was initiated with oral itraconazole 200 mg after performing antifungal susceptibility testing based on Clinical and Laboratory Standards Institute guidelines. The patient's condition improved and was discharged. Thus, early detection of PCA combined with medical and surgical intervention can successfully eradicate infection and help in preventing disseminated aspergillosis.

Amphiphilic hyperbranched polyglycerol nanoarchitectures for Amphotericin B delivery in Candida infections.

Although Amphotericin B (AMB) is considered the most effective anti-mycotic agent for treating Candida infections, its clinical use is limited due to its high toxicity. To address this issue, we developed cholesterol-based dendritic micelles of hyperbranched polyglycerol (HPG), including cholesterol-cored HPG (Chol-HPG) and cholesterol end-capped HPG (HPG@Chol), for AMB delivery. The findings suggested that the presence of cholesterol moieties could control AMB loading and release properties. Dendritic micelles inhibited AMB hemolysis and cytotoxicity in HEK 293 and RAW 264.7 cell lines while increasing antifungal activity against C. albicans biofilm formation. Furthermore, significantly lower levels of renal and liver toxicity biomarkers compared to Fungizone® ensured AMB-incorporated dendritic micelle biosafety, which was confirmed by histopathological evaluations. Overall, the Chol-HPG and HPG@Chol dendritic micelles may be a viable alternative to commercially available AMB formulations as well as an effective delivery system for other poorly soluble antifungal agents.

Natural products targeting the synthesis of ß(1,3)-D-glucan and chitin of the fungal cell wall. Existing drugs and recent findings.

BACKGROUND: During the last three decades systemic fungal infections associated to immunosuppressive therapies have become a serious healthcare problem. Clinical development of new antifungals is an urgent requirement. Since fungal but not mammalian cells are encased in a carbohydrate-containing cell wall, which is required for the growth and viability of fungi, the inhibition of cell wall synthesizing machinery, such as ß(1,3)-D-glucan synthases (GS) and chitin synthases (CS) that catalyze the synthesis of ß(1-3)-D-glucan and chitin, respectively, represent an ideal mode of action of antifungal agents. Although the echinocandins anidulafungin, caspofungin and micafungin are clinically well-established GS inhibitors for the treatment of invasive fungal infections, much effort must still be made to identify inhibitors of other enzymes and processes involved in the synthesis of the fungal cell wall. PURPOSE: Since natural products (NPs) have been the source of several antifungals in clinical use and also have provided important scaffolds for the development of semisynthetic analogues, this review was devoted to investigate the advances made to date in the discovery of NPs from plants that showed capacity of inhibiting cell wall synthesis targets. The chemical characterization, specific target, discovery process, along with the stage of development are provided here. METHODS: An extensive systematic search for NPs against the cell wall was performed considering all the articles published until the end of 2020 through the following scientific databases: NCBI PubMed, Scopus and Google Scholar and using the combination of the terms "natural antifungals" and "plant extracts" with "fungal cell wall". RESULTS: The first part of this review introduces the state of the art of the structure and biosynthesis of the fungal cell wall and considers exclusively those naturally produced GS antifungals that have given rise to both existing semisynthetic approved drugs and those derivatives currently in clinical trials. According to their chemical structure, natural GS inhibitors can be classified as 1) cyclic lipopeptides, 2) glycolipids and 3) acidic terpenoids. We also included nikkomycins and polyoxins, NPs that inhibit the CS, which have traditionally been considered good candidates for antifungal drug development but have finally been discarded after enduring unsuccessful clinical trials. Finally, the review focuses in the most recent findings about the growing field of plant-derived molecules and extracts that exhibit activity against the fungal cell wall. Thus, this search yielded sixteen articles, nine of which deal with pure compounds and seven with plant extracts or fractions with proven activity against the fungal cell wall. Regarding the mechanism of action, seven (44%) produced GS inhibition while five (31%) inhibited CS. Some of them (56%) interfered with other components of the cell wall. Most of the analyzed articles refer to tests carried out in vitro and therefore are in early stages of development. CONCLUSION: This report delivers an overview about both existing natural antifungals targeting GS and CS activities and their mechanisms of action. It also presents recent discoveries on natural products that may be used as starting points for the development of potential selective and non-toxic antifungal drugs.

Prophylactic antigen-specific T-cells targeting seven viral and fungal pathogens after allogeneic haemopoietic stem cell transplant.

OBJECTIVES: Adoptive immunotherapy using donor-derived antigen-specific T-cells can prevent and treat infection after allogeneic haemopoietic stem cell transplant (HSCT). METHODS: We treated 11 patients with a prophylactic infusion of 2 × 107 cells per square metre donor-derived T-cells targeting seven infections (six viral and one fungal) following HSCT. Targeted pathogens were cytomegalovirus (CMV), Epstein-Barr virus (EBV), adenovirus, varicella zoster virus, influenza, BK virus (BKV) and Aspergillus fumigatus. RESULTS: T-cell products were successfully generated in all patients with 10 products responsive to 6 or 7 infections. T-cell infusions were associated with increases in antigen-experienced activated CD8+ T-cells by day 30. CMV, EBV and BKV reactivation occurred in the majority of patients and was well controlled except where glucocorticoids were administered soon after T-cell infusion. Three patients in that circumstance developed CMV tissue infection. No patient required treatment for invasive fungal infection. The most common CMV and EBV TCR clonotypes in the infusion product became the most common clonotypes seen at day 30 post-T-cell infusion. Donors and their recipients were recruited to the study prior to transplant. Grade III/IV graft-versus-host disease developed in four patients. At a median follow-up of 390 days post-transplant, six patients had died, 5 of relapse, and 1 of multi-organ failure. Infection did not contribute to death in any patient. CONCLUSION: Rapid reconstitution of immunity to a broad range of viral and fungal infections can be achieved using a multi-pathogen-specific T-cell product. The development of GVHD after T-cell infusion suggests that infection-specific T-cell therapy after allogeneic stem cell transplant should be combined with other strategies to reduce graft-versus-host disease.

Retrospective analysis of the effects of Blastomyces antigen concentration in urine and radiographic findings on survival in dogs with blastomycosis.

BACKGROUND: The Blastomyces antigen concentration in urine (BACU) test is used to diagnose blastomycosis and monitor treatment in dogs. It is unknown if a higher BACU is associated with shorter survival. OBJECTIVES: To determine if the magnitude of BACU before treatment is associated with survival in dogs with blastomycosis. ANIMALS: Fifty-two dogs with blastomycosis. METHODS: Retrospective case review. BACU, radiographic lung severity (RLS) score (0-4 scale), and survival time up to 1 year after diagnosis were obtained through medical record review of dogs with Blastomyces dermatitidis. RESULTS: The overall survival was: discharge, 87%; 1 week, 85%; 2 months, 74%; and 6 months, 69%. BACU correlated with RLS score (rs = 0.33, P = .02). BACU and RLS scores were lower in survivors to 2 months than nonsurvivors (average BACU difference of 2.5 ng/mL, 95% confidence interval [CI]: 0.2-4.8 ng/mL, P = .04; median RLS difference of 2; range, 0-4, P = .02). Dogs with BACU <5 ng/mL and dogs with mild (0-1) RLS scores had a greater proportion surviving than those with BACU >5 ng/mL (P = .03) and dogs with severe (3-4) RLS scores (P = .04). All dogs with a BACU <5 ng/mL or mild RLS score were alive at last follow-up (median, 365 days; range, 44-365 days). In all, 68.1% of other dogs survived to 2 months (95% CI, 54.8%-84.8%). CONCLUSIONS AND CLINICAL IMPORTANCE: Dogs with lower BACU and RLS scores have improved survival; however, it is unclear what specific cutoffs should be used for prognosis.

Oral nystatin prophylaxis to prevent systemic fungal infection in very low birth weight preterm infants: a randomized controlled trial.

BACKGROUND: Systemic fungal infection (SFI) is one of leading causes of morbidity and mortality in very low birth weight (VLBW) preterm infants. Because early diagnosis of SFI is challenging due to nonspecific manifestations, prophylaxis becomes crucial. This study aimed to assess effectiveness of oral nystatin as an antifungal prophylaxis to prevent SFI in VLBW preterm infants. METHODS: A prospective, open-labelled, randomized controlled trial was performed in a neonatal intensive care unit (NICU) of an academic hospital in Indonesia. Infants with a gestational age ≤ 32 weeks and/or birth weight of ≤ 1500 g with risk factors for fungal infection were assessed for eligibility and randomized to either an intervention group (nystatin) or control group. The intervention group received 1 ml of oral nystatin three times a day, and the control group received a dose of 1 ml of sterile water three times a day. The incidence of fungal colonization and SFI were observed and evaluated during the six-week study period. Overall mortality rates and nystatin-related adverse drug reactions during the study period were also documented. RESULTS: A total of 95 patients were enrolled. The incidence of fungal colonization was lower among infants in nystatin group compared to those in control group (29.8 and 56.3%, respectively; relative risk 0.559; 95% confidence interval 0.357-0.899; p-value = 0.009). There were five cases of SFI, all of which were found in the control group (p-value = 0.056). There was no difference in overall mortality between the two groups. No adverse drug reactions were noted during the study period. CONCLUSIONS: Nystatin is effective and safe as an antifungal prophylactic medication in reducing colonization rates in the study population. Whilst the use of nystatin showed a potential protective effect against SFI among VLBW preterm infants, there was no statistical significant difference in SFI rates between groups. TRIAL REGISTRATION: NCT03390374. Registered 4 January 2018 - Retrospectively registered.

Isolation of Aspergillus caninus (Synonym: Phialosimplex caninus) from a Canine Iliac Lymph node.

Aspergillus caninus (synonym: Phialosimplex caninus) is an anamorphic fungus species associated with systemic infections in dogs that has been transferred from the genus Phialosimplex to Aspergillus. Here, we report the first case of canine A. caninus infection in Japan. A castrated Japanese Shiba Inu (6 years old; weight, 12.5 kg) was referred to the Yamaguchi University Animal Medical Center, Yamaguchi, Japan, in June 2017 showing vitality loss and depression. Computed tomography revealed iliac and splenic hilum lymphopathies, and histologic examination of an iliac lymph node by biopsy revealed granulomatous lesions with numerous oval to round yeast-like fungal cells. Aspergillus caninus was isolated from the biopsy samples, and in vitro susceptibility tests of the isolate to the antifungal drugs amphotericin B (AMB), fluconazole (FLZ), itraconazole (ITZ), voriconazole (VRZ), and micafungin (MCF) were performed by the E-test method. The isolate from this dog exhibited a minimal inhibitory concentration of < 0.002 µg/ml to AMB, > 256 µg/ml to FLZ, < 0.002 µg/ml to ITZ, < 0.002 µg/ml to VRZ, and < 0.002 µg/ml to MCF, indicating that the isolate was not susceptible to FLZ and susceptible to AMB, ITZ, VRZ, and MCF. Since the response of the patient dog to ITZ and VRZ treatments was poor, more aggressive management using combination therapies of ITZ with other antifungals may be necessary for treating canine A. caninus infection in dogs.

Rare Fungal Infection Linked to a Case of Juvenile Arthritis.

Juvenile arthritis with unknown disease etiology is also known as juvenile idiopathic arthritis. Symptoms include joint pain, swelling, and stiffness, and standard treatment involves immunosuppressant medication. Here we present a case of juvenile idiopathic arthritis with severe malnutrition and worsening of symptoms, which restrained a nine-year-old girl to a wheelchair with minimal movement capacity and low energy during standard immunosuppressant therapies over the course of three years. Our innovative Pathogen Blood Test combining cytology-based microscopy and genetic analysis using a pan-fungal primer assay and sequencing identified a systemic fungal infection with Sagenomella species, closely related to Aspergillus, and a soil-dwelling highly pathogenic fungus, which had previously been linked to a fatal veterinary case of arthritis and malnutrition. Our test results encouraged a radical change of the patient's treatment plan, including cessation of the regular immunosuppressants, including steroids, over six months. The patient made a progressive recovery, including complete reversion of the previously swollen and painful joints, development of a good appetite, and return to liveliness. Within the year of change from immunosuppressants to immune-supportive integrative nutritional therapies, including regular intravenous vitamin C, and oral vitamin D, as well as gentle aqua- and physiotherapy, the patient started to gain weight including muscle mass and regained strength and movement in the hands, arms, and legs. She was able to walk again within 18 months. Her mood and energy levels continued to improve and she was able to return to school full-time.

Cost-effectiveness of amphotericin B formulations in the treatment of systemic fungal infections.

Amphotericin formulations, indicated for invasive fungal infections (IFIs), vary in effectiveness, safety and costs. In Brazil, only the conventional formulation is provided by the Public Health System. The aim of this study was to perform a cost-effectiveness analysis comparing conventional amphotericin B (CAB), liposomal amphotericin B (LAB) and amphotericin B lipid complex (ABLC). Therefore, a decision tree was developed. The model began with high-risking patients on suspicion or confirmation of IFI. The analysis was conducted under the perspective of the Brazilian Public Health System. Model health states were defined according to medication use and clinical evolution. Clinical efficacy (cure) and transition probabilities were derived from the literature. Resource use was estimated from Brazilian data. Time horizon followed the maximum treatment time determined in the patient information leaflets (3 or 6 weeks). One-way and probabilistic-sensitivity analyses were conducted. The conventional formulation was the most cost-effective. No dominance was observed; however, high incremental cost-effectiveness ratios were obtained for LAB (USD 313 130) and ABLC (USD 1 711 280). Sensitivity analyses demonstrated the robustness of the results. CAB is the most cost-effective treatment, followed by LAB and ABLC. Although CAB presents critical safety aspects, the high acquisition costs of the other formulations prevent their large-scale use in Brazil.

Size matters - how the immune system deals with fungal hyphae.

Fungal hyphae constitute a special challenge for the immune system, since they are too large to be phagocytosed. This review summarizes our current knowledge on those immune cells that are able to attack and eliminate hyphae and we discuss the different means that are employed by these cells in order to kill hyphae.

High level of ß-(1,3)-d-glucan antigenaemia in cystic fibrosis in the absence of invasive fungal disease.

ß-(1,3)-d-glucan (BDG) is used to rule out invasive fungal disease (IFD) but its usefulness in cystic fibrosis (CF) has not been evaluated. We measured serum BDG in CF patients with no clinical suspicion of IFD. Samples from 46 adult CF patients during a stable period and during pulmonary exacerbation were tested. The association of BDG with clinical variables was analyzed. Three hundred and three non-CF patients with suspected IFD were used as comparators. Both samples were negative in 52% of CF patients, whereas 67% of comparators had only negative results (P=0.08). CF patients with pancreatic insufficiency and CF-related diabetes had fewer negative results (P<0.05 for both). Negative results were more common in older CF patients (P<0.05). Use of antibiotics, presence of fungi in sputum and CF liver disease did not impact BDG levels. In conclusion, patients with CF experience significant BDG antigenaemia in the absence of IFD.

Biodegradable functional polycarbonate micelles for controlled release of amphotericin B.

Amphotericin B (AmB), a poorly soluble and toxic antifungal drug, was encapsulated into polymeric micelles self-assembled from phenylboronic acid-functionalized polycarbonate/PEG (PEG-PBC) and urea-functionalized polycarbonate/PEG (PEG-PUC) diblock copolymers via hydrogen-bonding, boronate ester bond, and/or ionic interactions between the boronic acid group in the micellar core and amine group in AmB. Three micellar formulations were prepared: AmB/B micelles using PEG-PBC, AmB/U micelles using PEG-PUC and AmB/B+U mixed micelles using 1:1molar ratio of PEG-PBC and PEG-PUC. The average particle sizes of the micelles were in the range of 54.4-84.8nm with narrow size distribution and zeta potentials close to neutral. UV-Vis absorption analysis indicated that AmB/B micelles significantly reduced AmB aggregation status due to the interactions between AmB and the micellar core, while Fungizone® and AmB/U micelles had no effect. AmB/B+U mixed micelles exerted an intermediate effect. Both AmB/B micelles and AmB/B+U mixed micelles showed sustained drug release, with 48.6±2.1% and 59.2±1.8% AmB released respectively after 24hunder sink conditions, while AmB/U micelles displayed a burst release profile. All AmB-loaded micelles showed comparable antifungal activity to free AmB or Fungizone®, while AmB/B micelles and AmB/B+U mixed micelles were much less hemolytic than other formulations. Histological examination showed that AmB/B and AmB/B+U micelles led to a significantly lower number of apoptotic cells in the kidneys compared to Fungizone®, suggesting reduced nephrotoxicity of the micellar formulations in vivo. These phenylboronic acid-functionalized polymeric micelle systems are promising drug carriers for AmB to reduce non-specific toxicities without compromise in antifungal activity. STATEMENT OF SIGNIFICANCE: There is a pressing need for a novel and cost-effective delivery system to reduce the toxicity induced by the antifungal agent, amphotericin B (AmB). In this study, phenylboronic acid-functionalized polycarbonate/PEG diblock copolymers were used to fabricate micelles for improved AmB-micelle interaction via the manipulation of hydrogen-bonding, boronate ester bond, ionic and hydrophobic interactions. Compared to free AmB and Fungizone®, the resultant micellar systems displayed improved stability while reducing non-specific toxicities without a compromise in antifungal activity. These findings demonstrate the potential of biodegradable functional polycarbonate micellar systems as promising carriers of AmB for the treatment of systemic fungal infections.

Coccidioidomicosis cutánea: Comunicación de seis casos mexicanos / Cutaneous coccidioidomycoses: Six mexican cases report

Coccidioidomycosis is a systemic airborne mycosis that may involve secondarily other organs through systemic dissemination. Fungi Coccidioides immitis and C. posadasii are the etiologic agents. The former is ubiquitous from the area of California in North America, and the latter is found elsewhere in the world. Primary cutaneous infection is rare. We present six Mexican male cases, residents of Tijuana B.C. Three of them with primary pulmonary infection and further cutaneous dissemination, and three cases of primary cutaneous coccicioidomycosis. In half the cases C. posadasii was isolated. The clinical suspicion is basic for reaching the diagnosis, and we must always keep in mind that the cutaneous manifestations are widely varied and that the lesions are more severe when systemic dissemination occurs.

La coccidioidomicosis es una micosis con vía de entrada inhalatoria que puede tener manifestaciones secundarias en otros órganos, y diseminación sistèmica. Se han identificado como agentes etiológicos a Coccidioides immitis y C. posadasii, El primero está presente en California de Norteamérica y el segundo en cualquier otra región del mundo. La infección cutánea primaria es una presentación poco común. Presentamos seis casos clínicos mexicanos, de sexo masculino, residentes de la ciudad de Tijuana, B.C. Tres de ellos con infección pulmonar primaria y diseminación cutánea y tres cutáneos primarios. En la mitad de los casos se logró aislar C. posadasii. La sospecha clínica es fundamental para llegar al diagnóstico ya que las manifestaciones cutáneas son muy variadas, y ante diseminación sistèmica las lesiones cutáneas son más graves.

Serum and urine Blastomyces antigen concentrations as markers of clinical remission in dogs treated for systemic blastomycosis.

BACKGROUND: Serum and urine Blastomyces antigen concentrations can be used to diagnose blastomycosis in dogs. OBJECTIVES: Blastomyces antigen concentrations correlate with clinical remission in dogs during antifungal treatment, and detect disease relapse after treatment discontinuation. ANIMALS: 21 dogs with newly diagnosed blastomycosis monitored until clinical remission (Treatment Phase), and 27 dogs monitored over 1 year from the time of antifungal discontinuation or until clinical relapse (After Treatment Phase). METHODS: Prospective study. Dogs were monitored monthly during treatment and every 3 months after treatment discontinuation, with a complete history, physical exam, chest radiographs, and ocular exam. Urine and serum Blastomyces antigen concentrations were measured at each visit using a quantitative enzyme immunoassay. RESULTS: At enrollment in the Treatment Phase, Blastomyces antigen was positive in all 21 urine samples (100% sensitivity; 95% CI 85-100%), and in 18 of 20 serum samples (90% sensitivity; 95% CI 70-97%). At 2-4 months of treatment, urine antigen was more sensitive for clinically detectable disease (82%; CI 60-94%) than serum antigen (18%; CI 6-41%). The sensitivity of the urine test for clinical relapse was 71% (CI 36-92%), with close to 100% specificity (CI 84-100%) during after treatment surveillance in this population. CONCLUSIONS: Urine Blastomyces antigen testing has high sensitivity for active disease at the time of diagnosis and during treatment, and moderate sensitivity but high specificity for clinical relapse. Urine testing should be useful at the time of diagnosis, when treatment discontinuation is being considered, and anytime there is poor clinical response or suspicion of relapse.

Clinical Study of Neonatal Systemic Fungal Infection

PURPOSE: We evaluared the risk factors, clinical characteristic, diagnosis and treatment of neonatal systemic fungal infection in 28 cases in order to find ways to prevent development of and to improve the prognosis of neonatal systemic fungal infection METHODS: From November 1994 to August 1996, 28 premature infants who were diagnosed as systemic fungal infection at Ilsin Christian Hospital NICU were analyzed retrospectively. RESULTS: 1) The mean gestational age was 30.7 weeks(27-35.5weeks) and the mean birth weight was 1528g(975-2980g). 2) The risk factors associated with the development of neonatal systemic fungal infection included long-term use of broad-spectrum antibiotics, prolonged hyperalimentation, prolonged use of aminophylline and steroid, and endotracheal intubation. 3) The most common presenting clinical manifestations were temperature instability, feeding intolerance, and apnea. 4) In laboratory studies, blood, urine, and CSF culture positivity was 92.8%, 92.8%, and 10.7%, respectively and renal and cranial sonogram were helpful to evaluate the renal and CNS involvement. 5) The principal treatment was intravenous amphotericin B administration for 4 weeks. The side effects, such as renal toxicity, hepatotoxicity, hypokalemia, and vomiting, developed but were reversible. 6) The mortality rate was 7.1%, and ventriculo-peritoneal shunts was performed in 3 cases who had fungal meningitis for the management of postmeningitic hydrocephalus. CONCLUSION: For was beformedin the diagnosis of neonatal systemic fungal infection is very difficult and the mortality is high, we recommend that antifungal therapy be initiated in clinically ill infants who are not responsive to antibiotic therapy and have negative culture findings and have some of the risk factors associated with systemic fungal infection.