Fusarium spp., a Genus of Common Plant Pathogens That Can Cause Devastating,Opportunistic Human Disease

Fusarium spp. are environmental hyaline molds that are pathogens in plants and opportunistic pathogens in humans. In immunocompetent individuals, Fusarium sp. infections primarily include keratitis, onychomycosis, and localized infections due to trauma. However, in immunocompromised patients, particularly those with hematological malignancies, members of this genus can cause devastating, invasive, and disseminated infections with high mortality. In general, these species are resistant to therapy with a variety of antifungal agents. This article reviews recent literature about human infections caused by Fusarium spp., treatment and outcomes, and methods for accurately identifying isolates recovered from clinical specimens.     

Opportunistic fusarial infections in humans

Fusarium species are common hyaline soil saprophytes and plant pathogens which have frequently been reported as etiologic agents of opportunistic infections in humans. These infections have usually been limited to superficial mycoses, but recently the number of infections of deep tissues and disseminated infections has greatly increased, especially in patients with an underlying immunosuppressive condition. The characteristic signs of these infections are disseminated skin nodules, fungemia and multiorgan involvement. Frequently, myalgia is also present. Skin involvement occurred in over 80 % of cases of disseminated infections. These lesions are significant because they are readily accessible for biopsy and culture, thus permitting an early diagnosis. The therapy and outcome are dependent on the degree of invasion of the organisms and the status of the host. Identification of the pathogen to genus level is not difficult, but identification to species level requires a greater degree of expertise. Up to now, 15 species ofFusarium have been reported to cause infections in humans and animals. Few patients with disseminated fusarial infections have survived, even after receiving an adequate dosage of amphotericin B, the only antifungal agent that has some effect against these fungi. In vitro susceptibility to amphotericin B is a poor predictor of the clinical outcome of invasive fungal infections. Recovery of the phagocytic mechanisms in the form of rising neutrophil counts appears to be mandatory for clinical resolution. The resolution of neutropenia may be aided by the use of exogenous growth factors. Outside the USA, the majority of cases of disseminated fusarial infection have been reported from Mediterranean or tropical countries.     

Negative correlation between phospholipase and esterase activity produced by Fusarium isolates

Fusarium species have emerged as one of the more outstanding groups of clinically important filamentous fungi, causing localized and life-threatening invasive infections with high morbidity and mortality. The ability to produce different types of hydrolytic enzymes is thought to be an important virulence mechanism of fungal pathogens and could be associated with the environment of the microorganism. Here, we have measured the production of two distinct lipolytic enzymes, phospholipase and esterase, by sixteen Fusarium isolates recovered from the hospital environment, immunocompromised patients'' blood cultures, foot interdigital space scrapings from immunocompromised patients, and foot interdigital space scrapings from immunocompetent patients (4 isolates each). Fourteen of these 16 isolates were identified as Fusarium solani species complex (FSSC) and two were identified as F. oxysporum species complex (FOSC). Some relevant genus characteristics were visualized by light and electron microscopy such as curved and multicelled macroconidia with 3 or 4 septa, microconidia, phialides, and abundant chlamydospores. All Fusarium isolates were able to produce esterase and phospholipase under the experimental conditions. However, a negative correlation was observed between these two enzymes, indicating that a Fusarium isolate with high phospholipase activity has low esterase activity and vice versa. In addition, Fusarium isolated from clinical material produced more phospholipases, while environmental strains produced more esterases. These observations may be correlated with the different types of substrates that these fungi need to degrade during their nutrition processes.     

Invasive infections caused by non-Aspergillus moulds identified by sequencing analysis at a tertiary care hospital in Taiwan, 2000–2008

The clinical and microbiological characteristics of 103 patients with cultures positive for non-Aspergillus moulds in the period 2000 to 2008 were described. Among these patients, 27 had proven or probable invasive infections caused by Fusarium (n = 12), Paecilomyces (n = 7), Zygomycetes (n = 5) and Scedopsorium species (n = 3). The incidence of invasive infections caused by these moulds has not increased during the study period. Lung was the most common infection site and disseminated disease was observed in three leukaemic patients. The overall mortality rate was 40.7%, and was highest in cases zygomycosis. Antifungal susceptibility varied considerably among species. Amphotericin B and posaconazole demonstrated greatest activity against these moulds.     

Fusariosis, a complex infection caused by a high diversity of fungal species refractory to treatment

In recent years the number of opportunistic invasive fusariosis has increased significantly, the main factors involved in these infections being reviewed here. In spite of the extensive literature published the advances in the management of disseminated fusariosis have been very poor and it remains a severe infection, refractory to treatment and with a high mortality rate. There are no ideal therapies and the presence of neutropenia has a critical part to play in the outcome of the infection. At least 70 species have been involved in fusariosis. Fusarium solani species complex is responsible for nearly 60 % of the cases and F. oxysporum species complex for approximately 20 % of them. Most of the infections are caused by four species, i.e. F. petroliphilum, F. keratoplasticum and other two unnamed phylogenetic species. The efficacy of amphotericin B and voriconazole, the most used antifungal drugs, for treating invasive fusariosis are controversial but in general the percentage of patients cured in the different clinical trials is low. Infections by Fusarium verticillioides seem to have the best prognosis. The recent release of complete genome sequences of the most clinically relevant species and the emergence of fungal genomics offer excellent opportunities for examining the multifactorial processes of Fusarium pathogenicity. Using knockout mutants of genes encoding sequence-specific proteins, several virulence factors have been characterized.     

The interface between COVID-19 and bacterial healthcare-associated infections

BackgroundA wide range of bacterial infections occur in coronavirus disease 2019 (COVID-19) patients, particularly in those with severe coronaviral disease. Some of these are community-acquired co-infections.ObjectiveTo review recent data that indicate the occurrence of hospital-onset bacterial infections, including with antibiotic-resistant isolates, in COVID-19 patients.SourcesUsing PubMed, the literature was searched using terms including: ‘COVID-19’; ‘SARS-CoV-2’; ‘bacterial infection’; ‘healthcare-associated infection’; ‘antibiotic resistance’; ‘antimicrobial resistance’; ‘multi-drug resistance’; ‘Streptococcus’; ‘Staphylococcus’; ‘Pseudomonas’; ‘Escherichia’; ‘Klebsiella’; ‘Enterococcus’; ‘Acinetobacter’; ‘Haemophilus’; ‘MRSA’; ‘VRE’; ‘ESBL’; ‘NDM-CRE’; ‘CR-Ab’; ‘VRSA’; ‘MDR’.ContentThere is a growing number of reports of bacterial infections acquired by patients with severe COVID-19 after hospital admission. Antibiotic-resistant pathogens found to cause healthcare-associated infections (HAIs) in COVID-19 patients include methicillin-resistant Staphylococcus aureus, New Delhi metallo-β-lactamase-producing carbapenem-resistant Enterobacterales, carbapenem-resistant Acinetobacter baumannii, extended-spectrum β-lactamase Klebsiella pneumoniae and vancomycin-resistant enterococci. COVID-19 has impacted bacterial HAIs in a number of ways with an increase in the incidence of New Delhi metallo-β-lactamase-producing carbapenem-resistant Enterobacterales and carbapenem-resistant A. baumannii reported at some hospital sites compared with before the pandemic. Recommended guidelines for antimicrobial stewardship in COVID-19 patient treatment are discussed regarding minimization of empiric broad-spectrum antibiotic use. Other studies have reported a decrease in methicillin-resistant S. aureus and vancomycin-resistant enterococci cases, which has been attributed to enhanced infection prevention and control practices introduced to minimize intra-hospital spread of COVID-19.ImplicationsPoorer outcomes have been observed in hospitalized COVID-19 patients with an antibiotic-resistant infection. Although heightened IPC measures have been accompanied by a reduction in some HAIs at specific sites, in other situations, COVID-19 has been associated with an increase in bacterial HAI incidence. Further research is needed to define the cost–benefit relationship of maintaining COVID-19-related infection prevention and control protocols beyond the pandemic to reduce the burden of HAIs. In addition, the longer-term impact of high usage of certain broad-spectrum antibiotics during the COVID-19 pandemic requires evaluation.     

Intérêt de la caspofungine dans le traitement d'une infection disséminée à Fusarium solani ?

Candidiasis and aspergillosis are the most frequent fungal infections in onco-hematology. However, during the last 20 years, the emergence of previously exceptional species including Fusarium has been observed. Hematopoietic stem cell transplant recipients are logically the most exposed patients to these infections. New antifungal molecules have been made available to clinicians in the past few years, though their indication in these rare infections and their efficacy in combination often remain difficult to demonstrate. In this report, we examine the clinical case of a 3 year-old child who presented disseminated infection with Fusarium solani during induction treatment for acute lymphoblastic leukemia. During this infection, associations containing caspofungin were shown to be efficient. This was the second known case of Fusarium infection with a positive outcome with this molecule, which may now be considered as one of the antifungal agents that could be used against this microorganism. The optimum duration of treatment and the best combination for this mycosis remain to be defined.     

Diversity of Fusarium species causing invasive and disseminated infections

IntroductionInvasive fusariosis (IF) is considered an emerging fungal disease and an important problem worldwide that increasingly affects immunocompromised individuals. There is currently concern about establishing the genetic diversity and phylogenetic relationship of the species Fusarium causing invasive fusariosis.Materials and MethodsThe aim of this study was to characterize the molecular profile and morphological characteristics of Fusarium species isolated from 21 patients with invasive fusariosis. Multilocus sequence typing was performed for molecular identification of the following genes: the second largest subunit of the RNA polymerase gene (RPB2) and elongation factor 1 alpha (EF-1α). The morphological features of different species were carefully described and revised by experienced mycologists.ResultsMorphological and molecular analyses revealed that the F. solani species complex (FSSC) and F. oxysporum species complex (FOSC) were the most common species isolated from patients with invasive fusariosis; FSSC-2 h (5), FSSC-1 (2) and FOSC-183 (2) were the most frequent haplotypes. The macroscopic characterization revealed great variation in the tonalities of the FSSC colonies and particularities amongst the species in relation to the macroconidia structures, while the FOSC was more homogeneous and presented shades from white to lilac.ConclusionsOur study characterized the diversity, haplotypes, and morphological aspects of Fusarium species and the haplotypes prevalent in patients with invasive fusariosis. FSSC and FSSC-2 h were the predominant species and haplotype, respectively. Although we have described interesting morphological aspects in Fusarium species, particularly haplotypes, their identification cannot rely on phenotypical aspects. Molecular biology techniques are necessary and should be introduced for routine use in mycology laboratories.     

Molecular identification of Fusarium species complexes: Which gene and which database to choose in clinical practice?

Identification of Fusarium at the level of the species complex is difficult with phenotypic methods, so it is necessary to use molecular sequencing methods. This study presents, for 33 isolates distributed among the four major species complexes, the performance of five identification schemes involving ITS (internal transcribed spacer), EF1α (translation elongation factor 1 alpha), RPB1 (largest subunit of RNA polymerase) and RPB2 (second largest subunit of RNA polymerase) genes and two databases: GenBank and Fusarium MLST (MultiLocus Sequence Typing). In our practice, the identification of the fungus from a culture is performed with EF1α and from a primary sample with ITS, using in both cases the specific database Fusarium MLST.     

Seasonality in Gram-negative and healthcare-associated infections

To assess seasonal variations in Gram-negative and healthcare-associated infections (HCAIs), a literature search was performed with combinations of the keywords ‘seasonality’, ‘seasonal variations’, ‘Gram-negative bacilli’, ‘infections’, ‘nosocomial infections’, and ‘health care associated infections’, to retrieve articles published in English in peer-reviewed journals from 1 January 1970 to 29 February 2012. Seasonality was demonstrated for infections, mostly bloodstream infections (BSIs), caused by Acinetobacter spp., Escherichia coli, Enterobacter cloacae, Klebsiella spp., and Pseudomonas aeruginosa, with higher rates of infection during the summer months in North America, Europe, the Middle East, Australia, and Asia. Correlations were observed between temperature increase and rates of BSI for Acinetobacter spp., P. aeruginosa, E. coli, Klebsiella pneumoniae, and extended-spectrum β-lactamase-producing Enterobacteriaceae. A significant correlation between lower urinary tract infections and higher temperature and decreased relative humidity could explain the seasonality of some BSIs. Regarding HCAI, seasonality is intrinsically present in most viral respiratory and gastrointestinal infections, because viruses are introduced into hospitals during seasonal community outbreaks. Other HCAIs subject to seasonal variations include surgical wound infections, with winter peaks in the USA and summer peaks in Finland, central-line-associated BSIs in haematology/oncology paediatric outpatients, and dialysis-associated peritonitis. In summary, seasonal variations have been shown for infections caused by many Gram-negative bacilli, as well as for a few HCAIs, but many studies remain to be performed in order to better understand the mechanisms of these variations.     

Pathogenic free-living amoebae: Epidemiology and clinical review

Free-living amoebae are widely distributed in soil and water. Small number of them was implicated in human disease: Acanthamoeba spp., Naegleria fowleri, Balamuthia mandrillaris and Sappinia diploidea. Some of the infections were opportunistic, occurring mainly in immunocompromised hosts (Acanthamoeba and Balamuthia encephalitis) while others are non opportunistic (Acanthamoeba keratitis, Naegleria meningoencephalitis and some cases of Balamuthia encephalitis). Although, the number of infections caused by these amoebae is low, their diagnosis was still difficult to confirm and so there was a higher mortality, particularly, associated with encephalitis. In this review, we present some information about epidemiology, ecology and the types of diseases caused by these pathogens amoebae.     

It's Bordetella,It's Alcaligenes… No,It's Achromobacter! Identification,Antimicrobial Resistance,and Clinical Significance of an Understudied Gram-Negative Rod

Gram-negative non-fermentative bacilli, such as Achromobacter spp., can be opportunistic pathogens in nosocomial settings. Widely found in nature, Achromobacter spp. cause a broad spectrum of diseases and are best known as emerging opportunistic pathogens in the lungs of cystic fibrosis patients. Importantly, Achromobacter infections represent a diagnostic and clinical challenge. First, clinical laboratories cannot routinely identify Achromobacter isolates reliably to the species level outside of creating and curating a custom mass spectrometry database or using Achromobacter-specific genotypic molecular methods. Additionally, Achromobacter spp. infections are often difficult to treat owing to numerous intrinsic, and to a lesser extent acquired, antimicrobial resistance mechanisms. Treatment decisions are further complicated by discordance between CLSI and EUCAST breakpoints for antimicrobial susceptibility testing of Achromobacter isolates, and collaboration to harmonize these is necessary. Further studies are also needed to define the clinical spectrum of disease and pathogenic potential of many Achromobacter species.     

Resistance of Candida to azoles and echinocandins worldwide

BackgroundRecently there has been an increase in Candida infections worldwide. A handful of species in the genus Candida are opportunistic pathogens and have been known to cause infections in immunocompromised or otherwise impaired hosts. These infections can be superficial, affecting the skin or mucous membrane, or invasive, which can be life-threatening. Azoles and echinocandins are antifungal drugs used globally to treat Candida infections. However, resistance to these antifungal drugs has increased in many of the Candida species, and the effects this has in the clinical setting can be seen.ObjectivesHere, we discuss the mechanisms that Candida albicans, Candida dubliniensis, Candida glabrata, Candida parapsilosis, Candida tropicalis and Candida auris are implementing to increase resistance to azoles and echinocandins, and how they are affecting clinical, or hospital, settings worldwide.SourcesDifferent studies and papers describing the mechanisms of antifungal drugs and Candida species evolution to becoming resistant to these drugs were looked at for this review.ContentWe discuss the mechanisms that azoles and echinocandins use against Candida species to treat infections, as well as the evolution of these fungi to become resistant to these drugs, and the effect this has in the clinical settings around the globe.ImplicationsIncreased resistance to azoles and echinocandins by Candida species is an increasingly serious problem in clinical settings worldwide. Understanding the mechanisms used against antifungal drugs is imperative for patient treatment.     

Emergence of fusarioses in a university hospital in Turkey during a 20-year period

Fusarium species have started appearing increasingly as the main cause of infections, particularly in immunocompromised patients. In this study, we aimed to present the first epidemiological data from Turkey, analyze fusariosis cases that have been monitored in a university hospital during the past 20 years, identify the responsible Fusarium species, and determine antifungal susceptibilities. A total of 47 cases of fusariosis was included in the study. Fusarium isolates were identified by multilocus sequence typing (MLST). Antifungal susceptibility was tested by the broth microdilution method according to the Clinical and Laboratory Standards Institute (CLSI) methodology. Of the Fusarium infections, 23.4 % were superficial, 44.7 % were locally invasive, and 31.9 % were disseminated. A significant increase was observed over the years. The Fusarium fujikuroi species complex (FFSC) proved to be the most frequent agent group (17 cases; 51.5 %), followed by the Fusarium solani species complex (FSSC) (14 cases; 42.4 %), the Fusarium dimerum species complex (FDSC), and the Fusarium oxysporum species complexes (FOSC) (one case each). Amphotericin B had the highest in vitro activity against all species. Voriconazole and posaconazole showed interspecies variability across and within Fusarium species complexes. In conclusion, our data support the fact that regional differences exist in the distribution of the Fusarium species and that species-specific differences are observed in antifungal susceptibility patterns. The monitoring of local epidemiological data by determining fungal identity and susceptibility are of importance in guiding the clinical follow-up of patients.     

Profilaktyka i leczenie zakażeń u chorych na przewlekłą białaczkę limfocytową

Infections have a significant impact on the clinical course of chronic lymphocytic leukemia and are the leading cause of patients’ death. Severe and recurrent infections are associated with impaired immunity connected with the pathogenesis of the disease, older age of patients and immunosuppressive therapy. The infections caused by encapsulated bacteria (Streptococcus pneumoniae, Haemophilus influenzae) dominate in untreated patients, while in patients under therapy, infections are caused by Staphylococcus aureus and Gram-negative bacteria such as: Pseudomonas aeruginosa, Escherichia coli and Klebsiella pneumoniae, opportunistic infections are also frequent. It is important not only to treat the infections, but also their appropriate prevention. The article discusses various methods for prevention of infections, including vaccinations.     

Ureaplasma: Current perspectives

Ureaplasma species are the most prevalent genital Mycoplasma isolated from the urogenital tract of both men and women. Ureaplasma has 14 known serotypes and is divided into two biovars- Ureaplasma parvum and Ureaplasma urealyticum. The organism has several genes coding for surface proteins, the most important being the gene encoding the Multiple Banded Antigen (MBA). The C-terminal domain of MBA is antigenic and elicits a host antibody response. Other virulence factors include phospholipases A and C, IgA protease and urease. Besides genital tract infections and infertility, Ureaplasma is also associated with adverse pregnancy outcomes and diseases in the newborn (chronic lung disease and retinopathy of prematurity). Infection produces cytokines in the amniotic fluid which initiates preterm labour. They have also been reported from renal stone and suppurative arthritis. Genital infections have also been reported with an increasing frequency in HIV-infected patients. Ureaplasma may be a candidate ‘co factor’ in the pathogenesis of AIDS. Culture and polymerase chain reaction (PCR) are the mainstay of diagnosis. Commercial assays are available with improved turnaround time. Micro broth dilution is routinely used to test antimicrobial susceptibility of isolates. The organisms are tested against azithromycin, josamycin, ofloxacin and doxycycline. Resistance to macrolides, tetracyclines and fluoroquinolones have been reported. The susceptibility pattern also varies among the biovars with biovar 2 maintaining higher sensitivity rates. Prompt diagnosis and initiation of appropriate antibiotic therapy is essential to prevent long term complications of Ureaplasma infections. After surveying PubMed literature using the terms ‘Ureaplasma’, ‘Ureaplasma urealyticum’ and ‘Ureaplasma parvum’, relevant literature were selected to provide a concise review on the recent developments.     

Detection of multiple hypervirulent Klebsiella pneumoniae strains in a New York City hospital through screening of virulence genes

ObjectivesThe ‘hypervirulent’ variant of Klebsiella pneumoniae (hvKp) is a predominant cause of community-acquired pyogenic liver abscess in Asia, and is an emerging pathogen in Western countries. hvKp infections have demonstrated ‘metastatic’ dissemination in immunocompetent hosts, an unusual mode of infection associated with severe complications. Two cases alerted us to the possible presence of hvKp at our hospital, both involving elderly Hispanic males who presented with recurrent fever, bacteraemia, epigastric pain and liver abscesses/phlegmon, thus prompting an assessment of hvKp prevalence.MethodsA surveillance of K. pneumoniae blood, body fluid and wound isolates was conducted using real-time PCR to detect virulence-associated genes (uni-rmpA, iucA and peg344). Positive isolates were further characterized by wzi gene sequencing to determine capsular types (K-type) and by multilocus sequence typing and pulsed-field gel electrophoresis to determine strain relatedness.ResultsFour-hundred and sixty-three K. pneumoniae isolates, derived from 412 blood, 21 body fluids and 30 abdominal wound specimens, were screened over a 3-year period. Isolates included 98 multidrug-resistant strains. Eighteen isolates from 17 patients, including two from the index patient, screened positive for all three virulence genes. Sixteen of 18 positive isolates had K-types associated with hvKp, and isolates from different patients were unrelated strains, indicating likely community acquisition. Of 13 patients with significant morbidity, five died; eight patients had co-existing hepatobiliary disease, and six had diabetes mellitus.ConclusionsMultiple strains of hvKp are emerging in New York City and are associated with high mortality relative to multidrug-resistant and classical Klebsiella infections. Co-existing hepatobiliary disease appears to be a potential risk factor for these infections.     

Autologous Stem Cell Transplantation for Multiple Myeloma: Growth Factor Matters

Engraftment syndrome (ES) is a known complication of autologous hematopoietic stem cell transplant during neutrophil recovery. There is a limited amount of data available comparing the incidence of ES with post-transplant granulocyte colony-stimulating factor versus granulocyte macrophage colony-stimulating factor (GM-CSF), specifically in patients with multiple myeloma. Our retrospective review of 156 patients at a single center showed that GM-CSF was associated with a higher incidence of ES compared with G-CSF (32% versus 8% of patients, P < .001) and that development of ES was associated with a 32.9% (P < .001) longer hospital stay. This suggests that the choice of growth factor could possibly contribute to the development of ES and the associated costs of increased medical care.     

In vitro susceptibility and multilocus sequence typing of Fusarium isolates causing keratitis

Fungal keratitis is recognized as a significant cause of ocular morbidity and blindness especially in developing countries. In this study, we aimed to present the molecular identification and susceptibility of Fusarium isolates causing fungal keratitis in a university hospital in southern Brazil. The samples were identified using the second largest subunit of the RNA polymerase gene (RPB2) and the translation elongation factor 1-alpha (TEF1), while the antifungal susceptibility was tested by the broth microdilution method according to the Clinical and Laboratory Standards Institute (CLSI) methodology. The majority of the isolates belonged to the Fusarium solani species complex (F. solani, F. keratoplasticum and F. falciforme) and Fusarium oxysporum species complex. Antifungal susceptibility has shown that amphotericin B and natamycin were the most effective antifungals across all isolates, followed by voriconazole. Variation among Fusarium complexes in their antifungal sensitivities was observed in our study. The identification of Fusarium species from human samples is important not only from an epidemiological viewpoint, but also for choosing the appropriate antifungal agent for difficult-to-treat Fusarium infections such as keratitis.     

A rare case of idiopathic cluster of differentiation 4+ T-cell lymphocytopenia presenting with disseminated tubercular infection

Idiopathic cluster of differentiation 4⁺ (CD4⁺) T-cell lymphocytopenia is a rare heterogeneous clinical syndrome characterized by low absolute CD4 counts on two different occasions without any evidence of other known cause of immunodeficiency including human immunodeficiency virus (HIV), infections or drugs associated with fall in CD4⁺ count. Also referred to as severe unexplained HIV seronegative immune suppression by the World Health Organization, it was first described by Centers for Disease Control in 1992 in patients with opportunistic infections who were negative for HIV but had low CD4 counts. Patients typically present with opportunistic infections, malignancies, or autoimmune disorders. There have been case reports on opportunistic infections such as cryptococcal meningitis or non-Mycobacterium tuberculosis infections in these patients. However, no case of disseminated M. tuberculosis has been reported as such in Indian literature. We present a case of disseminated tuberculosis with low CD4 counts without any evidence of HIV infection.