Combination Of Amphotericin Research Articles

Disseminated Histoplasmosis in a Patient with Myelofibrosis on Ruxolitinib: A Case Report and Review of the Literature on Ruxolitinib-Associated Invasive Fungal Infections.

Ruxolitinib, a selective inhibitor of Janus kinases, is a standard treatment for intermediate/high-risk myelofibrosis (MF) but is associated with a predisposition to opportunistic infections, especially herpes zoster. However, the incidence and characteristics of invasive fungal infections (IFIs) in these patients remain uncertain. In this report, we present the case of a 59-year-old woman with MF who developed disseminated histoplasmosis after seven months of ruxolitinib use. The patient clinically improved after ten weeks of combined amphotericin B and azole therapy, and ruxolitinib was discontinued. Later, the patient received fedratinib, a relatively JAK2-selective inhibitor, without relapse of histoplasmosis. We also reviewed the literature on published cases of proven IFIs in patients with MF who received ruxolitinib. Including ours, we identified 28 such cases, most commonly due to Cryptococcus species (46%). IFIs were most commonly disseminated (39%), followed by localized lung (21%) infections. Although uncommon, a high index of suspicion for opportunistic IFIs is needed in patients receiving JAK inhibitors. Furthermore, the paucity of data regarding the optimal management of IFIs in patients treated with JAK inhibitors underscore the need for well-designed studies to evaluate the epidemiology, pathobiology, early diagnosis, and multimodal therapy of IFIs in patients with hematological malignancies receiving targeted therapies.

Expert consensus on diagnosis and treatment of severe COVID-19 associated pulmonary aspergillosis and mucormycosis

The incidence and mortality of COVID-19 associated pulmonary aspergillosis (CAPA) are high in critically ill patients. Although COVID-19 associated mucormycosis (CAPM) is relatively rare, its severity and often a delayed diagnosis or misdiagnosis lead to its high mortality. The diagnosis and treatment of CAPA and CAPM in critically ill patients are challenging. Early diagnosis and a standardized therapy are the two most important factors for a good outcome. Therefore, a working group of experts from Chinese Thoracic Society and Chinese Association of Chest Physicians Critical Care Group was organized to develop this consensus based on the current medical evidence and clinical practice, in order to improve the ability of clinical treatment for critically ill patients with CAPA and CAPM. The working group drafted a preliminary text based on the literature and clinical practice experience. Following two rounds of discussion, 16 final recommendations were made, with the recommendation strength divided into recommend, suggest and not recommend.-Utilization of chest images and bronchoscopy1. Chest CT, rather than chest X-ray, is recommended for possible CAPA or CAPM patients to provide diagnostic evidence and localization for bronchoscopy to obtain microbiological specimens. A diagnosis of CAPA could not be made on the basis of positive signs on chest CT alone. Chest contrast CT or pulmonary artery CT (CTPA) is recommended in patients with probable CAPM.2. In the case of possible CAPA or CAPM, it is recommended that bronchoscopy and BALF collection for microbiological examinations be pereformed as soon as possible.-The selection strategies of microbiological examinations3. Microscopic examination, culture, GM testing and PCR for aspergillus Spp. of BALF are recommended in patients with probable CAPA. Fungal staining and culture of BALF are suggested for possible CAPM. Selected appropriate specimens for molecular biological detection are suggested in critically ill patients and possible CAPM.-Diagnostic critieria4. The revised ECMM/ISHAM consensus statement is recommended as the diagnostic criteria for CAPA and the Delphi consensus statement is recommended as the diagnostic criteria for CAPM.-Appropriate time for antifungal therapy5. Prophylactic therapy of CAPA with amphotericin B or its liposomes is suggested for patients with severe COVID-19, especially those with risk factors for CAPA.6. It is recommended to start the empirical anti-Aspergillus therapy as soon as possible for possible CAPA, and obtain the microbiological evidence for aspergillosis at the same time.7. Prophylactic therapy for CAPM is not recommended for severe COVID-19 patients.8. Early initiation of empirical therapy for possible CAPM is recommended, and microbiological evidence should be obtained at the same time.-Clinical applications for antifungal agents9.Voriconazole or isavuconazole are recommended as initial treatment for CAPA. Amphotericin B liposomes are suggested as the initial treatment for CAPM. Isavuconazole or posaconazole may be an option in patients with renal insufficiency or amphotericin B liposome intolerance/unavailability.10. In CAPA patients with tracheobronchitis, antifungal drug inhalation is recommended in addition to systemic antifungal medication.11. Combination therapy is not recommended as initial therapy for CAPA, but may be used as a salvage therapy strategy. Triazole or amphotericin B in combination with caspofungin or micafungin is recommended; whereas amphotericin B in combination with triazole is not recommended. For CAPM patients with extensive lesions, rapid progression or poor general condition, a combination of amphotericin B liposome with isavuconazole or posaconazole is suggested.-Response assessment and treatment duration12. It is recommended that treatment response be assessed comprehensively according to the clinical symptoms/signs, imaging and microbiological examination of patients. CAPA can be evaluated in combination with the dynamic change in serum GM.13. The recommended treatment duration of CAPA is at least 6-12 weeks. A total course of at least 3-6 months is suggested for CAPM, and the sequential treatment should be considered according to the response to 4-6 weeks of intravenous therapy.-How to adjust the anti-inflammatory therapy14. In patients with severe COVID-19 combined with possible or probable filamentous fungal infection, it is suggested that of anti-inflammatory therapy be stopped or reduced appropriately, taking into account of the severity of the infection and inflammation of the disease course. The combination of baritinib and/or tozzizumab based on glucocorticoids is not suggested in these patients.-How to treat the underlying diseases15. In patients with diabetes, strict glycaemic control is suggested. In patients with long-term use of glucocorticoids and/or immunosuppressants, it is suggested to reduce the intensity of immunosuppression. Granulocyte colony-stimulating factor is suggested to use to improve the circulating granulocyte levels in patients with granulocyte deficiency due to various causes.-When an operation should be considered16. In patients with CAPA, surgery is not recommended unless large blood vessels, pericardium, or chest wall are involved, or the patient has recurrent or massive hemoptysis. For CAPM patients, early surgical removal of lesions after diagnosis is recommended. Surgery is a high-risk procedure in patients with severe COVID-19, and a multidisciplinary team discuss is suggested.

Cryptococcal meningitis and cerebral vasculitis in a patient with primary intestinal lymphangiectasia: a case report.

Primary intestinal lymphangiectasia (Waldmann's disease) is a rare exudative enteropathy without precisely assessed infectious risk. We report the case of a 49-year-old male patient with meningitis and cerebral vasculitis due to Cryptococcus neoformans complicating Waldmann's disease diagnosed 12years ago. The treatment combined liposomal amphotericin B, 3mg/kg daily plus flucytosine 25mg/kg/6h, both intravenously during 15days, then fluconazole 800mg daily during 8weeks, and finally 200mg daily indefinitely. Dexamethasone 0.4mg/kg daily during the first week was gradually decreased over 2months. The outcome was good, and the patient is still followed 3years later without any recurrence.

In Vitro Activity of Isavuconazole and Amphotericin B in Association against Mucorales.

Mucormycoses can be treated with the combination of Amphotericin B and Isavuconazole. This study evaluates the effects of these drugs in vitro against 59 strains representing 12 Mucorales. In vitro testing of the two drugs together and alone was performed using the MIC Test strip "Epsilon test synergy-method" (ETSM), which is more standard in clinical practice than microbroth dilution testing. Amphotericin B and Isavuconazole have synergistic/additive effects against L. corymbifera, R. arrhizus and M. circinelloides. Different effects have been shown for other Mucorales. ETSM can help the clinical management of mucormycosis from a practical point of view, due to its feasibility in the laboratory.

Invasive fungal rhinosinusitis associated with COVID-19: Course changes and prognosis predictors

BackgroundThis study aimed to analyze the behavior of acute invasive fungal rhinosinusitis (AIFRS) associated with COVID-19 infection as there has been an increase in the rate of AIFRS cases in the last two years, and many reports connected this rising with the COVID-19 infection. We studied most factors that may impact the prognosis as a trial to find the most affecting factors to improve the outcomes. MethodsIt was a retrospective observational study that included cases from four tertiary referral institutions between November 2020 to February 2022. We included sixty-six patients who suffered from AIFRS associated with confirmed COVID-19. We observed the prognosis of all included patients with a six-month follow-up. We correlated the prognosis with many factors, such as demographic data, medical conditions, blood investigations, the features of fungal infections, and management. ResultsForty-two patients (64%) survived after the AIFRS associated with COVID-19, and twenty-two patients (36%) died. High doses of corticosteroids with prolonged use were the main factors that affected the behavior of the AIFRS associated with COVID-19. HbA1c was a good predictor of the prognosis; a level less than 9.35% may indicate survival with 87.5% sensitivity. ConclusionsAccording to this multi-center study, the mortality of the AIFRS associated with COVID-19 was high. The behavior was affected by glycemic control, the type of fungal species, and the type of antifungal therapy. Early surgical debridement, a combination of Amphotericin B with Voriconazole, and anticoagulants helped improve the prognosis.

Invasive mucormycosis in a tertiary care hospital in the western region of Saudi Arabia: 11-year retrospective chart review from 2009 to 2019

BackgroundMucormycosis is a life-threatening, invasive fungal disease that mostly affects immunocompromised hosts. In this study, we aimed to assess the clinical presentations and outcomes of patients with mucormycosis in a tertiary care hospital in the western region of Saudi Arabia. MethodsA retrospective chart review of patients diagnosed with mucormycosis was conducted from January 2009 to December 2019 at King Abdulaziz Medical City, a tertiary care facility in Jeddah, Saudi Arabia. We aimed to assess and analyze the characteristics of patients with mucormycosis, their clinical presentations, and treatment outcomes. ResultsFifteen cases were identified as proven or probable mucormycosis according to the revised European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria. Most cases (n = 11, 73.3 %) were categorized as proven, whereas four cases (26.7 %) were categorized as probable. The median patient age was 29.5 years (range, 6–79 years). The most common underlying etiology was hematological malignancies (7 cases), followed by diabetes mellitus (5 cases), and trauma from a motor vehicle accident (4 cases). Cutaneous mucormycosis was the predominant presentation, as noted in seven cases (46.6 %), followed by rhino-orbito-cerebral mucormycosis in four cases (26.7 %), and pulmonary mucormycosis in two cases (13.3 %). Rhizopus (six cases) and Mucor (four cases) were the two main fungal isolates. Eight patients were treated with amphotericin B lipid complex (53.3 %) alone, and three patients were treated with a combination of amphotericin B lipid complex and posaconazole. Overall, 11 (73.3 %) patients died, two of whom died before a confirmed diagnosis. ConclusionThe mortality among patients with mucormycosis was high. Relatively better survival was observed among cutaneous cases. A combination of new diagnostic technologies, optimized use of available antifungal options, development of new antifungal agents, and consistent implementation of public health policies may help reduce mortality rates from mucormycosis in Saudi Arabia.

Invasive fungal rhinosinusitis associated with COVID-19: Course changes and prognosis predictors

BackgroundThis study aimed to analyze the behavior of acute invasive fungal rhinosinusitis (AIFRS) associated with COVID-19 infection as there has been an increase in the rate of AIFRS cases in the last two years, and many reports connected this rising with the COVID-19 infection. We studied most factors that may impact the prognosis as a trial to find the most affecting factors to improve the outcomes. MethodsIt was a retrospective observational study that included cases from four tertiary referral institutions between November 2020 to February 2022. We included sixty-six patients who suffered from AIFRS associated with confirmed COVID-19. We observed the prognosis of all included patients with a six-month follow-up. We correlated the prognosis with many factors, such as demographic data, medical conditions, blood investigations, the features of fungal infections, and management. ResultsForty-two patients (64%) survived after the AIFRS associated with COVID-19, and twenty-two patients (36%) died. High doses of corticosteroids with prolonged use were the main factors that affected the behavior of the AIFRS associated with COVID-19. HbA1c was a good predictor of the prognosis; a level less than 9.35% may indicate survival with 87.5% sensitivity. ConclusionsAccording to this multi-center study, the mortality of the AIFRS associated with COVID-19 was high. The behavior was affected by glycemic control, the type of fungal species, and the type of antifungal therapy. Early surgical debridement, a combination of Amphotericin B with Voriconazole, and anticoagulants helped improve the prognosis.

In vitro activity of immunosuppressive agents against Cryptococcus neoformans

IntroductionInfections caused by Cryptococcus neoformans are a major cause of fungal mortality in HIV-infected/AIDS patients and in those receiving organ transplants. We evaluated the in vitro activity of tacrolimus and cyclosporine in combination with amphotericin B and fluconazole against C. neoformans. MethodsMICs were determined against a total of 30 clinical isolates of C. neoformans by the microdilution method following the CLSI M27-A3 guidelines and by the checkerboard method. ResultsTacrolimus and cyclosporine A showed in vitro activity against cryptococcal isolates. The combination of amphotericin B with cyclosporine A or tacrolimus was synergistic against 90% and 30% of isolates, respectively. Synergism was also observed with the combination of fluconazole with cyclosporine A or tacrolimus, against 70% and 20% of isolates, respectively. ConclusionsThe synergistic interactions between the calcineurin inhibitors and antifungal drugs against C. neoformans isolates, could potentially have a role in devising novel therapeutic strategies for this opportunistic mycosis.

Improved In Vitro Anti-Mucorales Activity and Cytotoxicity of Amphotericin B with a Pegylated Surfactant.

The aim of this study was to evaluate the effect of the combination of amphotericin B (AmB) and various non-ionic surfactants on the anti-Mucorales activity of AmB, the toxicity of the combination on eukaryotic cells and the modification of AmB aggregation states. Checkerboards were performed on five genera of Mucorales (12 strains) using several combinations of different surfactants and AmB. These data were analyzed by an Emax model. The effect of surfactants on the cytotoxic activity of AmB was then evaluated for red blood cells and two eukaryotic cell lines by absorbance and propidium iodide internalization. Finally, the effect of polyethylene glycol (15)-hydroxystearate (PEG15HS) on the aggregation states of AmB was evaluated by UV-visible spectrometry. PEG15HS increased the efficacy of AmB on four of the five Mucorales genera, and MICs of AmB were decreased up to 68-fold for L. ramosa. PEG15HS was the only surfactant to not increase the cytotoxic activity of AmB. Finally, the analysis of AmB aggregation states showed that the increased efficacy of AmB and the absence of toxicity are related to an increase in monomeric and polyaggregated forms of AmB at the detriment of the dimeric form. In conclusion, PEG15HS increases the in vitro efficacy of AmB against Mucorales at low concentration, without increasing its toxicity; this combination could therefore be evaluated in the treatment of mucormycosis.

Invasive infections due to Magnusiomyces capitatus: case report and review of its prevalence in China

ABSTRACT Magnusiomyces capitatus is an emerging opportunistic yeast, thus far mainly reported from the Western world where fungemia is the most frequent presentation in immunocompromised patients with high mortality. We described a rare case of Magnusiomyces capitatus infection from our hospital in China and reviewed six further cases published to date in Chinese literature. It is noted that half more of the cases (4/7) presented with fungemia in younger, immunosuppressed patients, whereas the remaining cases were with pneumonia in elderly, immunocompetent patients. All seven Chinese cases had favourable outcome with antifungal therapy. Based on the limited in vitro and clinical data, a combination of amphotericin B either with 5-fluorocytosine or voriconazole for fungemia in immunocompromised patients, and although fluconazole is not recommended as first-line therapy in the guideline, in our study, fluconazole alone or with 5-fluorocytosine for local pulmonary infection in immunocompetent patients is effective with good outcome.

Synergistic Anticandidal Effects of Six Essential Oils in Combination with Fluconazole or Amphotericin B against Four Clinically Isolated Candida Strains.

The development of opportunistic pathogenic Candida strains insensitive to several classes of antifungals has emerged as a major health care problem during the last years. Combinational therapy of natural products (e.g., essential oils, EOs) with conventional antifungals has been suggested as a promising alternative to overcome this medical problem. The present study investigates the potential antifungal activity of EOs extracted from some selected medicinal plants, alone and in combination with two common conventional antifungals (fluconazole and amphotericin B) against four clinical Candida isolates. MIC assays indicated that EOs induced strong anticandidal activities with MIC values ranging from 0.162 to 4.950 mg/mL. The combination of amphotericin B with Thymus leptobotrys, Origanum compactum and Artemisia herba alba EOs provided a synergistic effect against C. krusei only, with MIC gain of four-fold, and additive effect against remaining strains (MIC gain = two-fold). Interesting synergistic interactions were observed by combining all studied EOs with fluconazole, with reduction rates of their MICs ranging from 16 to 512-fold. This synergistic effect was very pronounced with the combination of T. leptobotrys EO and fluconazole. These findings indicate that studied EOs can be used as anti-candidals in combination with antifungals, particularly fluconazole, to counteract the emergence of resistant Candida spp.

In Vitro Interaction and Killing-Kinetics of Amphotericin B Combined with Anidulafungin or Caspofungin against Candida auris

Treatment of invasive infections caused by Candida auris is challenging due to the limited therapeutic options. The combination of antifungal drugs may be an interesting and feasible approach to be investigated. The aim of this study was to examine the in vitro activity of amphotericin B in combination with anidulafungin or caspofungin against C. auris. In vitro static time–kill curve experiments were conducted for 48 h with different combinations of amphotericin B with anidulafungin or caspofungin against six blood isolates of C. auris. The antifungal activity of 0.5 mg/L of amphotericin B was limited against the six isolates of C. auris. Similarly, echinocandins alone had a negligible effect, even at the highest tested concentrations. By contrast, 1 mg/L of amphotericin B showed fungistatic activity. Synergy was rapidly achieved (8 h) with 0.5 mg/L of amphotericin B plus 2 mg/L of anidulafungin or caspofungin. These combinations lead to a sustained fungistatic effect, and the fungicidal endpoint was reached against some C. auris isolates. Additionally, ≥0.5 mg/L of either of the two echinocandins with 1 mg/L of amphotericin B resulted in fungicidal effect against all C. auris isolates. In conclusion, combinations of amphotericin B with anidulafungin or caspofungin provided greater killing with a lower dose requirement for amphotericin B compared to monotherapy, with synergistic and/or fungicidal outcomes.

Combined effect of furanone fluconazole and amphotericin B against biofilms formed from Cryptococcus neoformans.

It is of interest to document the combined effect of furanone fluconazole and amphotericin B against the biofilm formed by Cryptococcus neoformans. The MIC values of amphotericine B and Fluconazole were observed as 20µg/ml and 60µg/ml, respectively. The MIC for the Combination (Amphotericin B/ Fluconazole) was found to be at (15/20) µg/ml drug concentration. Thus, data shows the combined effect of furanone fluconazole and amphotericine B derivative against C. neoformans.

Therapeutic Modalities in Post Kala-azar Dermal Leishmaniasis: A Systematic Review of the Effectiveness and Safety of the Treatment Options.

Post-kala-azar dermal Leishmaniasis (PKDL) is one of the important neglected tropical diseases, which has a tremendous epidemiological significance, being the reservoir of kala-azar. Relapse and resistance to treatment along with the lack of a drug of choice and consensus treatment guideline pose a significant problem in the management of PKDL. The aim of this article was to review the available therapeutic options for PKDL, with special emphasis on their pharmaco-dynamics, pharmaco-kinetics, effectiveness, safety, tolerability, and cost factor. A comprehensive English language literature search was done for therapeutic options in PKDL across multiple databases (PubMed, EMBASE, MEDLINE, and Cochrane) for keywords (alone and in combination). MeSH as well as non-MeSH terms such as “Kala-azar,” “Leishmaniasis” AND “Treatment,” “Management,” “Antimony Sodium Gluconate,” “Meglumine Antimoniate,” “Amphotericin B,” “Paromomycin,” “Miltefosine” were taken into consideration. Among 576 relevant articles, 15 were deemed relevant to this review. These articles were evaluated using “Oxford Centre for Evidence-Based Medicine (OCEBM)” AND “strength of recommendation taxonomy” (SORT) with respect to the level of evidence and grade of recommendation. The review includes 15 studies. The use of sodium stibogluconate is being discouraged because of multiple documented reports of treatment failure. Liposomal amphotericin B is emerging as a favorable option, owing to its superiority in terms of effectiveness and safety profile. Miltesfosine is the drug of choice in India because of the ease of oral administration and minimal risk of toxicity. Isolated Paromomycin alone is not effective in PKDL; however, combination therapy with sodium stibogluconate is found to be safe and effective. Combination of amphotericin B and miltefosine is one of the excellent options. Immunotherapy with combination of alum-precipitated autoclaved Leishmania major (Alum/ALM) vaccine + Bacille Calmette-Gu´erin (BCG) has shown promising results. Kala-azar continues to haunt the tropical countries and PKDL being its reservoir is threatening its elimination. With the availability of drugs such as liposomal amphotericin B and miltefosine, apart from the advent of immunotherapy, the future of treatment of this condition looks promising.

Candida auris Urinary Tract Infections and Possible Treatment.

Candida auris is a globally emerging pathogen that has been identified in urinary tract infections (UTIs) worldwide. The novel pathogen is characterized by common misidentification, difficult eradication, and multidrug resistance. To date, there is a paucity of data to guide the optimal management of C. auris UTIs. This review provides an overview of C. auris as an etiologic agent of UTIs, a comprehensive review of published data on C. auris UTIs, and a proposed treatment algorithm based on patient clinical status, the presence or absence of clinical infection, comorbidities, infection, and therapy history. Echinocandin and liposomal amphotericin B are recommended as first-line agents for most patients with C. auris isolated in the urine, with a focus on infection control measures and appropriate follow-up criteria. A variety of combination therapies, flucytosine, and amphotericin B bladder irrigations are offered as potential alternatives in the event of infection persistence or recurrence. The treatment approach centers on the aggressive treatment of C. auris in most patients, with the goal of preventing subsequent invasive spread, multi-drug resistance, and ultimate mortality. Published literature on C. auris urinary isolation and treatment is imperative for the future evolution of evidence-based treatment recommendations for this unique pathogen of concern.

Mucormycosis with cutaneous involvement. A retrospective study of 115 cases at a tertiary care hospital in Mexico.

Cutaneous mucormycosis is an emerging opportunistic mycosis caused by Mucorales. It can be divided into primary caused by trauma and secondary by extension of rhino-cerebral and disseminated cases. The objective is to present a retrospective study of cases of mucormycosis with cutaneous involvement. A retrospective and descriptive study was carried out. Mucormycosis patients were included and divided into two groups: a) Primary Cutaneous and b) Secondary Cutaneous. Mycological tests were performed; the agents were identified by morphology and molecular studies (PCR and sequencing); some cases underwent histopathology. Clinical data and response to treatment were collected. 115 cases were included, 18 of primary, and 97 of secondary cutaneous mucormycosis. Primary cutaneous mucormycosis was most associated with adhesive bands (44.4%) and trauma from traffic accidents (33.3%). The principal clinical form was extensive and deep necrotic ulcers. Secondary cutaneous mucormycosis cases were rhino-cerebral with uncontrolled diabetes (81.4%) The most frequent clinical presentation was necrosis of the eyelid and the nose (65.9%). In both groups, the principal agent was Rhizopus arrhizus, 38.8% and 74.2% respectively. The most effective treatment was the combination of amphotericin B with surgical debridement. The clinical and mycological cure was achieved in 31.0% of primary cases, and 44.4% for secondary cases. Primary cutaneous mucormycosis is caused by implantation of the Mucorales due to trauma or rupture of the cutaneous barrier-breach, and secondary cutaneous mucormycosis develops as part of the rhino-cerebral process. The response to treatment depends on the extension and depth, as well as the predisposing factors.

In vitro activity of immunosuppressive agents against Cryptococcus neoformans

IntroductionInfections caused by Cryptococcus neoformans are a major cause of fungal mortality in HIV-infected/AIDS patients and in those receiving organ transplants. We evaluated the in vitro activity of tacrolimus and cyclosporine in combination with amphotericin B and fluconazole against C. neoformans. MethodsMICs were determined against a total of 30 clinical isolates of C. neoformans by the microdilution method following the CLSI M27-A3 guidelines and by the checkerboard method. ResultsTacrolimus and cyclosporine A showed in vitro activity against cryptococcal isolates. The combination of amphotericin B with cyclosporine A or tacrolimus was synergistic against 90% and 30% of isolates, respectively. Synergism was also observed with the combination of fluconazole with cyclosporine A or tacrolimus, against 70% and 20% of isolates, respectively. ConclusionsThe synergistic interactions between the calcineurin inhibitors and antifungal drugs against C. neoformans isolates, could potentially have a role in devising novel therapeutic strategies for this opportunistic mycosis.

Neonatal Candida auris infection: Management and prevention strategies - A single centre experience.

Our aim was to identify the clinical features and outcome of multidrug resistant Candida auris (CA) infection in neonates. This is a retrospective case cohort study of 17 neonates who developed sepsis caused by CA infection in a tertiary care neonatal intensive care unit over 3 years. The risk factors, clinical features, treatment and outcome were studied. The mean gestation was 32.4 ± 4.9 weeks with overall mortality of 41%. Clinical features were indistinguishable from other causes of sepsis. CA was sensitive to micafungin but resistant to fluconazole and had variable sensitivity to voriconazole and amphotericin. Survival improved to 83% when infants were treated with a combination of micafungin and amphotericin. Non-survivors were of lower birthweights and had other risk factors. The management guidelines and infection control measures are described in this largest series of neonatal CA infection. Treatment with a combination of amphotericin and micafungin improved the outcome.

Dusky violaceous necrotic plaques of the chest

Dusky violaceous necrotic plaques of the chest

Evaluation of Indolocarbazoles from Streptomyces sanyensis as a Novel Source of Therapeutic Agents against the Brain-Eating Amoeba Naegleria fowleri.

Naegleria fowleri is an opportunistic pathogenic free-living amoeba which is able to rapidly colonize the central nervous system (CNS) and causes a lethal infection known as primary amoebic meningoencephalitis (PAM). Furthermore, more than 98% of the known cases of PAM are fatal and affect mainly children under 12 and young adults. Until now, no fully effective therapeutic agents against N. fowleri are available and hence the urgent need to find novel agents to treat PAM. At present, PAM therapy is based on the combination of amphotericin B, miltefosine, among others, with unwanted toxic effects. Recently, our team isolated various indolocarbazoles (ICZs) from the culture of a mangrove strain of Streptomyces sanyensis which showed activity against kinetoplastids and the Acanthamoeba genus. Hence, in this study, the activity of the previously isolated ICZs, staurosporine (STS), 7-oxostaurosporine (7OSTS), 4′-demethylamino-4′-oxostaurosporine, and streptocarbazole B, was evaluated against two type strains of N. fowleri. Furthermore, the performed activity assays revealed that STS was the most active ICZ presenting an inhibitory concentration 50 (IC50) of 0.08 ± 0.02 µM (SI 109.3). Moreover, STS induced programmed cell death (PCD) in the treated amoebae by triggering DNA condensation, mitochondrial disfunction, cell membrane disruption, and reactive oxygen species (ROS) generation. Therefore, STS could be a promising therapeutic agent against PAM.