• Paecilomyces variotii is a common environmental mold found in composts, soils, wood, food products, indoor air, and carpet dust. It produces heat-resistant ascospores that can contaminate heat-treated foods and juices. This mostly infects various parts of the body like lungs, eye, skin, bone, blood, and CNS. If not treated they can be fatal. 
• The distribution and prevalence rates of P. variotii infections need better documentation as they often misidentified as other fungi. Cases have been reported globally. P. variotii infections are more prevalent in tropical and subtropical areas due to the favorable environmental conditions. The incidence rate is likely to increase with the immunocompromised patients and invasive medical devices. These infections are rare but this has potential life-threatening in those with indwelling devices or immunocompromised individuals. The overall mortality rate is about 28.8%. 

• Kingdom: Fungi 
• Phylum: Ascomycota 
• Class: Eurotiomycetes 
• Order: Eurotiales 
• Family: Thermoascaceae 
• Genus: Paecilomyces 
• Species: P. variotii 

The species P. variotii belongs to the Paecilomyces genus and Thermoascaceae family. 

The structure of Paecilomyces variotii can be summarized into five key points: 

• The fungus produces colonies that resemble powdery to suede-like materials which may be either yellow-brown or sand-colored. 
• This possesses loosely branched, irregularly brush-like conidiophores with phialides at the tips. 
• The phialides are swollen at the base and tapering to a sharp point at the tip. 
• Hyaline are single-celled conidia which are typically carried in chains with the youngest at the base. 
• This fungus also produces brown and thick-walled chlamydospores which can be single or in short chains. 

• This fungus with high antigenic variability can produce various antigens or substances that induce immunological reactions depending on environmental conditions or host that potentially explaining its ability to cause infections in various hosts like plants, animals, and humans. 

The pathogenesis of Paecilomyces variotii is not fully understood but it is believed to involve several factors: 

• This pathogen can enter the human body through inhalation, ingestion, trauma, surgery, or indwelling devices which causes the infection through spores, contaminated aerosols, food, water, or direct injection. 
• P. variotii invades various tissues and organs producing proteases, lipases, and phospholipases to degrade host cell membranes. It can also produce biofilms on medical equipment by protecting it from host defenses and antifungal drugs. 
• It can stimulate both innate and adaptive immune responses in the host by activating macrophages, neutrophils, and dendritic cells and triggering cytokine release. 
• The infection triggers inflammation, stimulates T cell differentiation, and induces antibody secretion. However, these immune responses may not be sufficient to clear the infection which leading to tissue damage and inflammation. 
• This pathogen exhibits resistance to antifungal drugs like amphotericin B, fluconazole, voriconazole, and caspofungin due to various factors including higher drug efflux, altered drug target, increased ergosterol biosynthesis, and increased stress response. 

Host defenses, immune mechanisms, and mechanisms are crucial to fight against infections caused by fungi like P. variotii that includes: 

• Innate immunity is the initial defense mechanism involving the physical barriers like cells and mucous membranes. It involves macrophages, neutrophils, and dendritic cells that recognize the phagocytose fungal spores and produces pro-inflammatory cytokines like TNF-α, IL-1β, IL-6, and IL-8, to recruit more immune cells and activate adaptive immunity. 
• Adaptive immunity is the second line of defense involving specific and memory responses which are mediated by T cells, B cells, and natural killer cells. These cells differentiate into different subsets and secrete antibodies or cytotoxic molecules to target and eliminate fungus. 

The host defenses against P. variotii infection in immunocompromised patients or those with indwelling devices may not be sufficient and cause tissue damage and inflammation necessitating to the use of antifungal drugs like posaconazole, itraconazole, or amphotericin B. 

The clinical manifestations of P. variotii infection includes: 

• Peritonitis is a stomach lining inflammation linked to peritoneal dialysis causing symptoms like abdominal pain, fever, and cloudy dialysate fluid. 
• Pneumonia caused by spores or aerosols presenting symptoms like cough, fever, and sputum production which potentially revealing nodules or cavities. 
• Endophthalmitis linked to trauma, surgery, or injection causing symptoms like eye pain, blurred vision, and light sensitivity. 
• Skin and soft-tissue infections are inflammations of the skin and underlying tissues often linked to wounds, burns, or implants. 
• Osteomyelitis is a bone-related inflammation often linked to trauma, surgery, or implants which are characterized by bone pain, and reduced mobility. 
• Bloodstream infections often linked to catheters or intravenous lines that involves the spread of fungus into the blood and causing symptoms like fever, low blood pressure, and organ failure. 
• CNS infections involve fungus invasion into the brain or spinal cord which is linked to trauma, surgery, or disseminated infections. 

Diagnosing P. variotii infection can be a challenging due to its potential confusion with other fungi or contamination. Some methods for diagnosis include: 

• It is diagnosed through culture from various specimens like blood, sputum, urine, tissue, or eye samples. The organism snowballs on Sabouraud’s dextrose agar by producing yellow-brown or sand-colored colonies. Staining the culture with lactophenol cotton blue or calcofluor white which reveals its microscopic morphology and including lemon-shaped conidia or conidiophores with pointy phialides. 
• Molecular techniques like PCR, sequencing, MALDI-TOF MS, and real-time PCR are used for rapid and accurate identification of P. variotii when the culture is negative or inconclusive. These techniques can detect DNA or protein signatures from blood, tissue, or eye samples with 18S rDNA, ITS, and 28S rDNA regions that are being most commonly used as targets. 
• Histopathology is a method used to detect the presence and extent of tissue invasion by P. variotii in few cases of endophthalmitis, osteomyelitis, or skin and soft-tissue infections. It appears as septate, branching, irregular hyphae with occasional conidia or chlamydospores. 

The prevention strategies for P. variotii infection includes: 

• It can contaminate in heat-treated foods and juices due to its heat-resistant ascospores. Proper storage, handling, and consumption can prevent ingestion. Cleaning and disinfecting wounds, burns, or implants can also prevent skin and soft tissue infections. 
• P. variotii can form biofilms on medical equipment like prosthetic valves, implants, and catheters thereby protecting it from host defenses and antifungal drugs. Therefore, removing or replacing these devices can prevent or treat infection. 
• It can cause severe and fatal infections especially in those with indwelling devices or those who are immunocompromised. 

Monitoring health status and seeking medical attention if symptoms occur that may improve the outcome of an infection. x`

• Characterization and outcome of invasive infections due to Paecilomyces variotii: analysis of patients from the FungiScope® registry and literature reports | Journal of Antimicrobial Chemotherapy | Oxford Academic (oup.com) 
• Paecilomyces variotii as an Emergent Pathogenic Agent of Pneumonia (hindawi.com)