Antifungal stewardship: What we need to know.

Antimicrobial stewardship refers to a well-coordinated program which promotes the scientific and rational use of antimicrobials, reduces the chances of drug resistance and improves patient outcomes. A comprehensive English language literature search was done across multiple databases (PubMed, EMBASE, MEDLINE and Cochrane) for the period 1990-2022, revealing a large volume of reports of growing resistance to established antifungal therapies, against a backdrop of irrational and unscientific prescriptions. As a result of this, antifungal stewardship, a new kid on the block, has recently garnered attention. This review article is an attempt to summarise the basic concept of stewardship programs, highlighting the dire need to implement the same in the present situation of antifungal resistance and treatment failure.

Molecular epidemiology and clinical-laboratory aspects of chromoblastomycosis in Mato Grosso, Brazil.

INTRODUCTION: Chromoblastomycosis is a disease caused by melanized fungi, primarily belonging to the genera Fonsecaea and Cladophialophora, mainly affecting individuals who are occupationally exposed to soil and plant products. This research aimed to determine the clinical, epidemiological and laboratory characteristics of chromoblastomycosis in the state of Mato Grosso, Brazil. MATERIALS AND METHODS: Patients diagnosed with chromoblastomycosis treated at the Júlio Müller University Hospital, Cuiabá, Brazil, from January 2015 to December 2020, whose isolates were preserved in the Research Laboratory of the Faculty of Medicine of the Federal University of Mato Grosso. Isolates were identified by partly sequencing the Internal Transcribed Spacer (ITS) and ß-tubulin (BT2) loci. AFLP fingerprinting was used to explore the genetic diversity. Susceptibility to itraconazole, voriconazole, 5-fluorocytosine, terbinafine and amphotericin B was determined by the broth microdilution technique. RESULTS: Ten patients were included, nine were male (mean age = 64.1 years). Mean disease duration was 8.6 years. Lesions were mainly observed in the lower limbs. Predominant clinical forms were verrucous and scarring. Systemic arterial hypertension and type II diabetes mellitus were the predominant comorbidities. Leprosy was the main concomitant infectious disease. Fonsecaea pedrosoi was the unique aetiological agent identified with moderate genetic diversity (H = 0.3934-0.4527; PIC = 0.3160-0.3502). Antifungal agents with the highest activity were terbinafine, voriconazole and itraconazole. CONCLUSION: Chromoblastomycosis is affecting the poor population in rural and urban areas, mainly related to agricultural activities, with F. pedrosoi being the dominant aetiologic agent. All isolates had low MICs for itraconazole, voriconazole and terbinafine, confirming their importance as therapeutic alternatives for chromoblastomycosis.

Mycetoma in north-western Yemen: Clinico-epidemiological and histopathological study.

Background Mycetoma is widespread in Yemen; however, there are only a few documented reports on the entity from this geographical area. Methods A prospective study of 184 cases of mycetoma (male 145 and female 39) from different regions of north-western Yemen was conducted between July 2000 and May 2014. Clinical profile was recorded in a standardized protocol. The diagnosis was based on clinical features, X-ray studies, examination of grains, and histopathology. Results Eumycetoma was diagnosed in 129, caused by Madurella mycetomatis in 124, Leptosphaeria senegalensis in one and pale grain fungus in four, whereas actinomycetoma occurred in 55, caused by Streptomyces somaliensis in 29, Actinomadura madurai in nine, Actinomadura pelletieri in one, and Nocardia in sixteen. Eumycetoma cases were treated with prolonged course of antifungal drugs, mostly ketoconazole, with itraconazole being used in four patients, along with excision or debulking. Results were better when antifungal drugs were given two to three months before surgery and in those who received itraconazole. Actinomycetoma cases were initially treated with co-trimoxazole monotherapy; later streptomycin was added in 30 cases. Six patients who did not show adequate improvement and two others from the start were treated with modified Welsh regimen and with good results. Limitations Identification of different causative agents was done by histopathology and could not be reconfirmed by culture. Conclusion Mycetoma is widespread in north-western Yemen with a higher incidence of eumycetoma and a majority of the cases were caused by Madurella mycetomatis. Modified Welsh regimen in actinomycetoma and itraconazole with excision in eumycetoma showed the best results.

Chromoblastomycosis in Latin America and the Caribbean: Epidemiology over the past 50 years.

Chromoblastomycosis is a chronic disease caused by melanized fungi that mainly affect individuals performing soil-related labor. The objective of this study was to analyze the epidemiological and clinical characteristics of chromoblastomycosis in Latin America and the Caribbean by an extensive literature review. An integrative review was performed of English, French, Portuguese, and Spanish publications in LILACS, SciELO, PubMed, SCOPUS and Web of Science databases covering the period 1969-2019. A total of 1211 articles were identified, of which 132 were included in the review, covering 2081 patients, 80.3% were males, the mean age was 56.1 years. The mean duration of the disease was 10.8 years. The lesions were mainly described in the lower limbs (60%). The most frequent clinical forms were verrucous (46.4%) and tumorous (21.7%). Major disease symptoms and signs consisted of itching and pain. Bacterial infection and functional limitation were important complications. Immunosuppression post-kidney transplantation was the most frequent comorbidity while leprosy was the main concomitant infectious disease. Fonsecaea pedrosoi and Cladophialophora carrionii were the predominant etiological agents. Majority of the cured cases were treated with itraconazole as monotherapy or in combination with other antifungals, surgery or cryosurgery. Chromoblastomycosis affects hundreds of rural workers in Latin America and the Caribbean, causing disability and personal, family and economic losses. It is important to prioritize epidemiological surveillance and early diagnosis of this disease in order to reveal its real prevalence and direct resources to preventive actions, diagnosis and early treatment. LAY SUMMARY: Chromoblastomycosis is a slowly progressing chronic disease caused by melanized fungi. We collected data from South America and the Caribbean covering 1969-2019, the 132 articles included 2081 patients, mean disease duration was 10.8 years. Fonsecaea pedrosoi and Cladophialophora carrionii predominated.

A case of disseminated subcutaneous phaeohyphomycosis caused by Exserohilum rostratum with CARD9 mutation.

Phaeohypomycosis is a rare cutaneous and subcutaneous fungal infection caused by dematiaceous fungi. They have a widespread global distribution occasionally affecting humans. A 26-year-old woman presented with multiple skin lesions over her face and extremities for last 7 years, unresponsive to systemic amphotericin B and itraconazole. Further investigations revealed CARD9 mutation and phaeohyphomycosis caused by the pigmented fungus Exserohilum rosatratum. Lesions subsequently improved with oral flucytosine and itraconazole.

The unprecedented epidemic-like scenario of dermatophytosis in India: III. Antifungal resistance and treatment options.

One of the canonical features of the current outbreak of dermatophytosis in India is its unresponsiveness to treatment in majority of cases. Though there appears to be discordance between in vivo and in vitro resistance, demonstration of in vitro resistance of dermatophytes to antifungals by antifungal susceptibility testing is essential as it may help in appropriate management. The practical problem in the interpretation of antifungal susceptibility testing is the absence of clinical breakpoints and epidemiologic cutoff values. In their absence, evaluation of the upper limit of a minimal inhibitory concentration of wild type isolates may be beneficial for managing dermatophytosis and monitoring the emergence of isolates with reduced susceptibility. In the current scenario, most of the cases are unresponsive to standard dosages and duration of treatment recommended until now. This has resulted in many ex-cathedra modalities of treatment that are being pursued without any evidence. There is an urgent need to carry out methodical research to develop an evidence base to formulate a rational management approach in the current scenario.

Lobomycosis in Soldiers, Colombia.

Lobomycosis is a disease that is endemic to the Amazon rainforest and is caused by the still uncultured fungus Lacazia loboi. This disease occurs in loggers, farmers, miners, fishermen, and persons living near coastal rivers of this region. We report 6 soldiers in Colombia in whom lobomycosis developed after military service in the Amazon area. The patients had nodular and keloid-like lesions on the face, neck, trunk, and limbs. The duration of illness ranged from 2 years to 15 years. The initial diagnosis was leishmaniasis on the basis of clinical manifestations and direct smear results, but biopsies confirmed the final diagnosis of lobomycosis. Treatment with surgical excision, itraconazole and clofazimine was satisfactory. However, the follow-up time was short. Healthcare professionals responsible for the diagnosis and treatment of skin diseases need to be able to recognize the clinical signs of lobomycosis and differentiate them from those of cutaneous leishmaniasis.

Septic shock due to Candida famata (Debaryomyces hansenii) candidemia in an ICU immunocompetent trauma-patient.

Sepsis related to Candida famata (C. famata) fungemia is extremely rare in immunocompetent patients. Moreover, septic shock has not been reported due to this yeast. A previously healthy young multi-trauma male, presented septic shock from C. famata, after he had been admitted in the Intensive Care Unit (ICU) due to haemorrhagic shock. Risk factors for candidemia in ICU patients are the presence of a central venous catheter (CVC), Total Parenteral Nutrition (TPN), use of broad-spectrum antimicrobials, immunosuppression and the length of ICU stay. The presence of CVCs, prior use of antibiotics, prolonged hospitalization, disruption of skin flora and immunocompromised states have been identified as predisposing risk factors for C. famata fungemia. It is worth noting that the present case concerns a non-immunocompromised patient, but long ICU stay and brain injury may indicate a state of immunoparalysis. Identification of the yeast was performed by partial amplification and sequencing of the 26S ribosomal DNA gene [hypervariable region D1/D2; partial sequencing of the act1 gene confirmed the identity of the strain as Debaryomyces hansenii (GenBank submission ID: 1688297)] The patient quickly recovered from sepsis after initiation of amphotericin B and was discharged on the 60th day.