ER-30346 is a novel oral triazole with a broad spectrum of potent activity against a wide range of fungi. In the present study, we investigated the therapeutic effects of oral ER-30346 on experimental local infections caused by Aspergillus fumigatus, Candida albicans, and Cryptococcus neoformans and compared them with those of itraconazole and fluconazole. In experimental murine models of pulmonary aspergillosis, candidiasis, and cryptococcosis, ER-30346 reduced the numbers of CFU in the lungs significantly compared with the numbers of CFU in the lungs of the controls (P < 0.05). ER-30346 was as effective as or more effective than itraconazole against pulmonary aspergillosis. Against pulmonary candidiasis and cryptococcosis, ER-30346 was more effective than itraconazole and was as effective as fluconazole. ER-30346 was also effective against pulmonary candidiasis caused by fluconazole-resistant C. albicans. In mice with intracranial cryptococcosis, ER-30346 reduced the numbers of CFU in the brains significantly compared with the numbers of CFU in the brains of the controls (P < 0.05) and was more effective than itraconazole and as effective as fluconazole. In an experimental model of oral candidiasis in rats, ER-30346 reduced the numbers of CFU in oral swabs significantly compared with the numbers of CFU in oral swabs from the controls (P < 0.05) and was more effective than itraconazole and as effective as fluconazole. Thus, ER-30346 shows efficacy in murine aspergillosis, candidiasis, and cryptococcosis models. Further studies are needed to determine the potential of ER-30346 for use in the treatment of these infections.
Congenital cystic adenomatoid malformation, currently referred as congenital pulmonary airway malformation (CPAM), is one of the rare lung malformations seen in adults. We report a case of a 59-year-old male with a chronic cough and hemoptysis that was not amenable to bronchial embolization. Further work up revealed cystic changes with fungal ball and type 1 CPAM. Patients with this condition who survive to adulthood usually suffer from recurrent respiratory bacterial infections. Only three cases of fungal involvement have ever been described. We present a fatal case, as well as the oldest patient.
CPAM; aspergillosis; embolization
Organising pneumonia is a distinct histopathological entity characterized by intra-alveolar buds of granulation tissue, called Masson bodies, which mainly comprise of activated fibroblasts and loose connective tissue. This histopathologic pattern has been described in idiopathic cases, characterizing cryptogenic organising pneumonia as well as in the context of pulmonary infection, drug-induced pneumonitis and following lung transplantation. Although distinct as a clinical and pathological entity, community organising pneumonia may present with atypical clinical and pathological features, such as intra-alveolar fillings of fibrin balls and organising tissue that resembles acute respiratory distress syndrome or diffuse alveolar damage. The latter characteristics constitute a recently described anatomoclinical entity called acute fibrinous and organising pneumonia.
Here, we describe a rare case of acute fibrinous and organising pneumonia, in an otherwise healthy 65-year-old Greek woman who complained of dry cough, fever, weight loss and progressive dyspnoea. She had never been a smoker. Her clinical symptoms showed a rapid deterioration in the two weeks before admission, despite a course of oral antibiotics. After excluding infection and malignancy with routine laboratory tests and flexible bronchoscopy, high resolution computed tomography and video assisted thoracoscopic lung biopsy were performed. Diagnosis was based on radiological features typical of community organising pneumonia coupled with pathologic features characteristic of acute fibrinous and organising pneumonia. The patient was treated with corticosteroids and showed excellent clinical and radiological response three months after treatment initiation.
Acute fibrinous and organising pneumonia is an extremely rare pathologic entity, often misdiagnosed as typical community organising pneumonia. To our knowledge, this is the seventh case of acute fibrinous and organising pneumonia in the literature, with no identifiable cause or association in a female patient, with no underlying lung disease or known exposures and with an unremarkable previous medical history. We highlight the need for careful review of lung biopsies from patients with clinical and radiologic characteristics typical of community organising pneumonia. Although it remains uncertain whether fibrin alters the favourable prognosis and treatment response of community organising pneumonia, it becomes obvious that a thorough pathologic review, apart from establishing the diagnosis of acute fibrinous and organising pneumonia, may predict a more unfavorable outcome therefore alerting the clinician to administer more aggressive and prolonged therapeutic regimens.
Mimicry has evolved in a wide range of organisms and encompasses diverse tactics for defence, foraging, pollination and social parasitism. Here, I report an extraordinary case of egg mimicry by a fungus, whereby the fungus gains competitor-free habitat in termite nests. Brown fungal balls, called ‘termite balls’, are frequently found in egg piles of Reticulitermes termites. Phylogenetic analysis illustrated that termite-ball fungi isolated from different hosts (Reticulitermes speratus, Reticulitermes flavipes and Reticulitermes virginicus) were all very similar, with no significant molecular differences among host species or geographical locations. I found no significant effect of termite balls on egg survivorship. The termite-ball fungus rarely kills termite eggs in natural colonies. Even a termite species (Reticulitermes okinawanus) with no natural association with the fungus tended termite balls along with its eggs when it was experimentally provided with termite balls. Dummy-egg bioassays using glass beads showed that both morphological and chemical camouflage were necessary to induce tending by termites. Termites almost exclusively tended termite balls with diameters that exactly matched their egg size. Moreover, scanning electron microscopic observations revealed sophisticated mimicry of the smooth surface texture of eggs. These results provide clear evidence that this interaction is beneficial only for the fungus, i.e. termite balls parasitically mimic termite eggs.
egg recognition; mimicry; termites; sclerotia; insect–fungus interaction
Necrotizing or invasive aspergillary infection of the lungs has previously been considered a rare condition affecting only the debilitated or seriously ill. Four patients with necrotizing pulmonary aspergillosis are described, and the mycological and histopathological findings are discussed. The diagnosis in the first patient was not made until necropsy, following death from fulminating pulmonary infection. Of three patients treated with natamycin, two made a satisfactory recovery; the other died later from bronchial carcinoma. Previous multiple antibiotic therapy in each case may have been a contributory factor to infection with Aspergillus fumigatus. We suggest that fungal infection of the lungs should be actively sought in patients with pulmonary disease, especially in those receiving multiple antibiotic or corticosteroid therapy.
A patient is reported who had biliary tract obstruction secondary to infection of the common bile duct with Candida albicans, with the formation of a fungus ball. Treatment consisted of surgical removal of the fungus ball and drainage. Chemotherapy was not necessary. Ureteral obstruction through fungus ball formation, and even pulmonary fungus ball formation, has been attributed to candida, but this is the first case reported, to our knowledge, of bile duct obstruction.
Following the recent transfer of all accepted species of Penicillium subgenus Biverticillium to Talaromyces (including Talaromyces marneffei, formerly Penicillium marneffei), Penicillium species are becoming increasingly rare causal agents of invasive infections. Herein, we present a report of a type 2 diabetes patient with a fungus ball in the respiratory tract caused by Penicillium capsulatum.
A 56-year-old Chinese female gardener with a 5-year history of type 2 diabetes presented at the Shanghai Changzheng Hospital with fever, a cough producing yellow-white sputum, and fatigue. The therapeutic effect of cefoxitin was poor. An HIV test was negative, but the β-D-glucan test was positive (459.3 pg/ml). Chest radiography revealed a cavitary lesion in the left upper lobe, and a CT scan showed globate cavities with a radiopaque, gravity-dependent ball. The histopathologic features of the tissue after haematoxylin-eosin staining showed septate hyphae. The fungus was isolated from the gravity-dependent ball and identified as Penicillium capsulatum based on the morphological analysis of microscopic and macroscopic features and on ribosomal internal transcribed spacer sequencing. After surgery, the patient was cured with a sequential treatment of fluconazole 400 mg per day for 90 days and caspofungin 70 mg per day for 14 days.
Although the prognosis is often satisfactory, clinicians, mycologists and epidemiologists should be aware of the possibility of infection by this uncommon fungal pathogen in diabetes patients, since it may cause severe invasive infections in immunocompromised hosts such as diabetes and AIDS patients.
Fungal ball; Pulmonary infections; Penicillium capsulatum
A case of isolated candidal fungal balls in the
common bile duct causing obstructive jaundice and
cholangitis is described. There were no predisposing
factors. The fungal balls were removed from the
common bile duct and a transduodenal sphincteroplasty
was performed. Microscopic analysis yielded
colonies of candida. Postoperative period was uneventful.
At follow-up no evidence of candida
infection was evident. He is now 3 years post-surgery
and is well.
Chronic obstructive pulmonary disease (COPD) exacerbations admitted in intensive care units (ICUs) occur rarely due to fungal respiratory tract infections, but may occur when associated co-morbidities like diabetes mellitus coexist. Candida ciferrii is a new agent, recently was isolated from lung infections but usually resistant to fluconazole. Here, we report a rare case of pneumonia due to fluconazole sensitive Candida ciferrii in a COPD patient with known diabetes, admitted in our ICU.
Candida ciferrii; chronic obstructive pulmonary disease; fluconazole sensitive; pneumonia
Aspergillus causes a variety of clinical syndromes in the lung including tracheobronchial aspergillosis, invasive aspergillosis, chronic necrotizing pulmonary aspergillosis, allergic bronchopulmonary aspergillosis, and aspergilloma. Aspergilloma usually results from ingrowths of colonized Aspergillus in damaged bronchial tree, pulmonary cyst or cavities of patients with underlying lung diseases. There are a few reports on endobronchial aspergilloma without underlying pulmonary lesion. We have experienced a case of endobronchial aspergilloma associated with foreign body developed in an immunocompetent patient without underlying lung diseases. A 59-year-old man is being hospitalized with recurring hemoptysis for 5 months. X-ray and computed tomography scans of chest showed a nodular opacity in superior segment of left lower lobe. Fiberoptic bronchoscopy revealed an irregular, mass-like, brownish material which totally obstructed the sub-segmental bronchus and a foreign body in superior segmental bronchus of the lower left lobe. Histopathologic examinations of biopsy specimen revealed fungal hyphae, characteristic of Aspergillus species.
Aspergillosis; Foreign Bodies; Immunocompetence
Concha bullosa is the pneumatization of the concha and is one of the most common variations of the sinonasal anatomy. The histopathological changes caused by the infections which arise from the impaired aeration of conchal cavity are frequently found. Fungus ball of the nasal cavity is an extremely rare, fungal infection with only three cases reported previously. In this paper, we present the fourth fungus ball case which developed within a concha bullosa and presented with anosmia.
The clinical, radiographic, pathological, and environmental features of a case of extensive aluminium fibrosis of the lungs are reported in a man of 49 years of age who had worked for 13½ years in the ball-mill room of an aluminium powder factory.
It is noteworthy that his symptoms were referable to the central nervous system, and that he died from terminal broncho-pneumonia following rapidly progressive encephalopathy, associated with epileptiform attacks. He had no presenting pulmonary symptoms, and ϰ-ray examination of the chest showed only slight abnormalities. Radiographic examination of the chests of 53 other workers in the same factory, and clinical examination with lung function tests of 23 of them revealed no other definite cases of aluminium fibrosis of the lung, nor any other cases with neurological signs and symptoms.
Estimations of the aluminium contents of the body tissues such as the lungs, brain, liver, and bone are also recorded. When compared with normal values, it was found that the lungs and brain contained about 20 times and the liver 122 times more than normal. As a contribution to the study of the aluminium content of normal tissues, and as a control series for the results given by Tipton, Cook, Steiner, Foland, McDaniel, and Fentress (1957), and Tipton, Cook, Foland, Rittner, Hardwick, and McDaniel (1958, 1959), the aluminium content of eight “normal” brains was estimated and in all cases it was found to be less than 0·6 μg. Al/g. wet weight.
The results of a survey of the dust concentrations in the factory are also given.
The use of aluminium compounds in the experimental production of epilepsy in primates is reviewed, and it is suggested that the neurological signs and symptoms with epileptiform convulsions which occurred in this case might have been related to aluminium intoxication. We hold the view, however, that the interstitial and nodular fibrosis found in the lungs was undoubtedly associated with the inhalation and retention of aluminium dust.
Invasive fungal infection is common in the present day NICUs - generally manifesting as candiduria or candida sepsis. Fungal balls in the kidneys are very uncommon and most are amenable to higher antifungal agents. However, we had a child who did not respond to such measures and ultimately needed a surgical removal of the fungal ball in his kidney.
We report this case along with a review of literature to highlight about this uncommon, but an important cause of persistent sepsis in pre-term infants and to review the treatment options including a surgical removal.
Invasive candidiasis; pre-term infants; renal fungal balls
Chronic necrotizing pulmonary aspergillosis is an uncommon subacute form of Aspergillus infection. It typically occurs in immunocompromised individuals and in those with underlying lung disease. This interesting case highlights the occurrence of this entity of aspergillosis in an immunocompetent middle-aged woman with atypical radiological findings. To the best of our knowledge this is the first case report of chronic necrotizing pulmonary aspergillosis presenting with pleural effusion.
Our patient was a 64-year-old Malay woman with a background history of epilepsy but no other comorbidities. She was a lifelong non-smoker. She presented to our facility with a six-month history of productive cough and three episodes of hemoptysis. An initial chest radiograph showed bilateral pleural effusion with bibasal consolidation. Bronchoscopy revealed a white-coated endobronchial tree and bronchoalveolar lavage culture grew Aspergillus niger. A diagnosis of chronic necrotizing pulmonary aspergillosis was made based on the clinical presentation and microbiological results. She responded well to treatment with oral itraconazole.
The radiological findings in chronic necrotizing pulmonary aspergillosis can be very diverse. This case illustrates that this condition can be a rare cause of bilateral pleural effusion.
Prostate cancer has a high tendency to spread to bone. Pulmonary metastasis and generalized lymphadenopathy commonly develop after pelvic and bone involvement have already occurred. Few patients with prostate cancer present initially with symptomatic metastatic lung lesions and lymphadenopathy without any other concomitant distant dissemination.
We report a case of a 73-year-old white male who sought medical help for symptoms of cough, hemoptysis, and dyspnea. A chest X-ray was done revealing multiple "cannon ball" infiltrates involving all segments of the lung parenchyma. Fine-needle aspiration cytology under computed tomography guidance of a subpleural lesion revealed adenocarcinomatous cells. Despite the absence of any detectable osseous lesions and with the presence of multiple hilar, mediastinal, para-aortic, and pelvic lymphadenopathy, the patient had a complete work-up in search for the primary adenocarcinoma. His prostate specific antigen was 146 ng/ml and a prostatic biopsy done, revealing an acinar prostatic adenocarcinoma. A tru-cut biopsy of a lung lesion under computed tomography guidance showed a metastatic prostatic adenocarcinoma positive for prostate specific antigen stain.
This case sheds light on an unusual metastatic pattern of prostatic adenocarcinoma. It also emphasizes the importance of including prostate cancer in the differential diagnosis of men with adenocarcinoma of unknown origin.
Invasive fungal infections are on the rise. Amphotericin B and azole antifungals have been the mainstay of antifungal therapy so far. The high incidence of infusion related toxicity and nephrotoxicity with amphotericin B and the emergence of fluconazole resistant strains of Candida glabrata egged on the search for alternatives. Echinocandins are a new class of antifungal drugs that act by inhibition of β (1, 3)-D- glucan synthase, a key enzyme necessary for integrity of the fungal cell wall.
Caspofungin was the first drug in this class to be approved. It is indicated for esophageal candidiasis, candidemia, invasive candidiasis, empirical therapy in febrile neutropenia and invasive aspergillosis. Response rates are comparable to those of amphotericin B and fluconazole. Micafungin is presently approved for esophageal candidiasis, for prophylaxis of candida infections in patients undergoing hematopoietic stem cell transplant (HSCT) and in disseminated candidiasis and candidemia. The currently approved indications for anidulafungin are esophageal candidiasis, candidemia and invasive candidiasis.
The incidence of infusion related adverse effects and nephrotoxicity is much lower than with amphotericin B. The main adverse effect is hepatotoxicity and derangement of serum transaminases. Liver function may need to be monitored. They are, however, safer in renal impairment. Even though a better pharmacoeconomical choice than amphotericin B, the higher cost of these drugs in comparison to azole antifungals is likely to limit their use to azole resistant cases of candidial infections and as salvage therapy in invasive aspergillosis rather than as first line drugs.
Anidulafungin; candidemia; caspofungin; echinocandins; esophageal candidiasis; invasive aspergillosis; invasive candidiasis; micafungin
Immunocompromised patients who develop invasive filamentous mycotic infections can be efficiently treated if rapid identification of the causative fungus is obtained. We report a case of fatal necrotic pneumonia caused by combined pulmonary invasive mucormycosis and aspergillosis in a 66 year-old renal transplant recipient. Aspergillus was first identified during the course of the disease by cytological examination and culture (A. fumigatus) of bronchoalveolar fluid. Hyphae of Mucorales (Rhizopus microsporus) were subsequently identified by culture of a tissue specimen taken from the left inferior pulmonary lobe, which was surgically resected two days before the patient died. Histological analysis of the lung parenchyma showed the association of two different filamentous mycoses for which the morphological features were evocative of aspergillosis and mucormycosis. However, the definitive identification of the associative infection was made by polymerase chain reaction (PCR) performed on deparaffinized tissue sections using specific primers for aspergillosis and mucormycosis. This case demonstrates that discrepancies between histological, cytological and mycological analyses can occur in cases of combined mycotic infection. In this regard, it shows that PCR on selected paraffin blocks is a very powerful method for making or confirming the association of different filamentous mycoses and that this method should be made available to pathology laboratories.
Clostridia are uncommon causes of pleuropulmonary infection. Clostridial species infecting the pleuropulmonary structures characteristically cause a necrotizing pneumonia with involvement of the pleura. Most cases have iatrogenic causes usually due to invasive procedures into the pleural cavity, such as thoracentesis or thoracotomy, or penetrating chest injuries. Rarely clostridia pleuropulmonary infections are not related to these factors. The clinical course of pleuropulmonary clostridial infections can be very variable, but they may be rapid and fatal. We report a rare case of necrotizing pneumonia and sepsis due to Clostridium perfringens not related to iatrogenic causes or injuries in an 82 years old woman.
Necrotizing soft-tissue infections exclusively due to Candida species are rare and not usually considered in the differential diagnosis of this devastating condition. When documented previously, Candida species are generally proposed to be a saprophytic component of multibacterial synergistic infection often associated with streptococcal species. We report a case of a 51-year-old man who developed necrotizing fasciitis secondary to Candida infection following a motor vehicle accident. His clinical presentation was very similar to that of clostridial gas gangrene. The only organisms isolated from tissue culture were Candida albicans and Candida tropicalis. Histopathology confirmed yeast forms and pseudohyphae within the debrided tissue specimens. No bacteria were identified on any of the wound swabs or tissue specimens. Our report is the first that reveals Candida as the sole identifiable cause for necrotizing fasciitis following trauma. Candida should be considered in the differential diagnosis of causative organisms for necrotizing fasciitis and infective myonecrosis.
Candida albicans; Candida tropicalis; Fournier's gangrene; Myonecrosis; Necrotizing fasciitis; Trauma
Invasive pulmonary aspergillosis is the most common form of infection by Aspergillus species among immunocompromised patients. Although this infection frequently involves the lung parenchyma, it is unusual to find it limited to the tracheobronchial tree, a condition known as invasive aspergillus tracheobronchitis.
A 65 year-old Hispanic man from Bolivia with a history of chronic lymphocytic leukemia developed cough and malaise eight months after having an allogenic stem cell transplant. A computed tomography of the chest revealed an area of diffuse soft tissue thickening around the left main stem bronchus, which was intensely fluorodeoxyglucose-avid on positron emission tomography scanning. An initial bronchoscopic exam revealed circumferential narrowing of the entire left main stem bronchus with necrotic and friable material on the medial wall. Neither aspirates from this necrotic area nor bronchial washing were diagnostic. A second bronchoscopy with endobronchial ultrasound evidenced a soft tissue thickening on the medial aspect of the left main stem bronchus underlying the area of necrosis visible endoluminally. Endobronchial ultrasound-guided transbronchial needle aspiration performed in this area revealed multiple fungal elements suggestive of Aspergillus species.
We describe the first case of invasive aspergillus tracheobronchitis in which the diagnosis was facilitated by the use of endobronchial ultrasound guided trans-bronchial needle aspiration. To the best of our knowledge, we are also presenting the first positron emission tomography scan images of this condition in the literature. We cautiously suggest that endobronchial ultrasound imaging may be a useful tool to evaluate the degree of invasion and the involvement of vascular structures in these patients prior to bronchoscopic manipulation of the affected areas in an effort to avoid potentially fatal hemorrhage.
Chronic necrotizing pulmonary aspergillosis usually occurs in mildly immune-compromised hosts or those with underlying pulmonary disease. The radiographic pattern of chronic necrotizing pulmonary aspergillosis is typically a progressive upper lobe cavitary infiltrate with pleural thickening. We report here an atypical case of chronic necrotizing pulmonary aspergillosis mimicking lung cancer, which developed into a disseminated fatal disease in an older woman with no comorbidity.
An 80-year-old Japanese woman was referred to our hospital for a chest roentgenogram abnormality. Repeated fiber-optic bronchoscopy could not confirm any definite diagnosis, and she refused further examinations. Considering the roentgenogram findings and her age, she was followed-up as a suspected case of lung cancer without any treatment. Then, 10 months later, she complained of visual disturbance and was admitted to our department of ophthalmology. She was diagnosed as having endophthalmitis. After treatment with corticosteroids for 20 days, she developed acute encephalitis and died four weeks later. Autopsy revealed dissemination of Aspergillus hyphae throughout her body, including her brain.
In older patients, even if they do not have any comorbidity, chronic necrotizing pulmonary aspergillosis should be added to the differential diagnosis of solitary pulmonary lesions in a chest roentgenogram.
Penicillium species are among the most common fungi present in the environment and are usually considered non-pathogenic to humans. However, in immunocompromised hosts they can be virulent pathogens and can cause death. Penicillium digitatum is a plant pathogen that commonly causes a postharvest fungal disease of citrus called green mould; it very rarely causes systemic mycosis in humans. Here, we report a case of fatal pneumonia due to P. digitatum infection, as confirmed by repeated examination of cultured sputum.
A cavity was found in the left upper lung on routine chest X-ray in a 78-year-old undernourished male who had been diagnosed at age 66 with bronchial asthma and pulmonary emphysema. No increased sputum production was present. The presence of antigen-specific precipitating antibodies to Aspergillus flavus and P. digitatum was confirmed in the patient’s serum and also later pleural fluid by using Ouchterlony double immunodiffusion testing with A. flavus and P. digitatum antigens. The patient was treated over a period of months with itraconazole, micafungin, voriconazole, amphotericin B, and antibacterials. However, the cavity enlarged, the pleural effusion increased, and the patient began producing purulent sputum. He died from progressive renal failure. From sputum culture only one fungus was isolated repeatedly on potato-dextrose agar in large quantities. This fungus was confirmed to be P. digitatum by molecular identification. Partial sequences of the beta-tubulin gene were determined by using the primers Bt2a and Bt2b for PCR amplification and sequencing and underwent a BLAST search at the National Centre for Biotechnology Information, these results confirmed that the isolated fungus was P. digitatum.
To our knowledge, this is the first report of pulmonary infection with P. digitatum. Our patient had pulmonary emphysema and was elderly, and undernourished. These factors might have facilitated the infection. In his case, antimycotics were ineffective in treating the lung involvement. Although human infection with P. digitatum is considered rare, it appears that this organism can be very virulent and resistant to antimycotics.
Penicillium digitatum; Penicillium species; Infection; Immunocompromised host; Pulmonary emphysema; Pneumonia
Necrotizing fasciitis is known to be a highly lethal infection of deep-seated subcutaneous tissue and superficial fascia. Reports of necrotizing fasciitis due to Streptococcus pneumoniae are exceedingly rare. We report a case of necrotizing fasciitis in a 62-yr-old man with liver cirrhosis and diabetes mellitus. He presented with painful swelling of left leg and right hand. On the day of admission, compartment syndrome was aggravated and the patient underwent surgical exploration. Intra-operative findings revealed necrotizing fasciitis and cultures of two blood samples and wound aspirates showed S. pneumoniae. The patient died despite debridement and proper antimicrobial treatment. To the best of our knowledge, this is the first case of fatal necrotizing fasciitis with meningitis reported in Korea. We also review and discuss the literature on pneumococcal necrotizing fasciitis.
Fasciitis, Necrotizing; Streptococcus pneumoniae; Korea
Abnormalities of the underlying bone of the paranasal sinuses have sometimes been shown in Wegener's granulomatosis (WG). We describe an interesting case of WG with extensive bone abnormalities in the sinuses mimicking fungal sinusitis. A 30-year-old woman presented with intermittent unilateral epistaxis. Biopsy was performed for the granulation tissue in the right nasal cavity, and she was diagnosed as having WG. Computed tomography (CT) revealed a ring-like calcification, mimicking a fungus ball, in the right maxillary sinus. Endoscopic sinus surgery was performed to confirm the diagnosis. A spherical bony structure, surrounded by granulation tissue, was identified in the maxillary sinus. The wall of the “bony ball” was fragile, like an egg shell. No fungus was found in the sinus. Thus, the extensive bone abnormalities were due to WG.
Staphylococcus aureus necrotizing pneumonia is a life-threatening disease that is frequently preceded by influenza infection. The S. aureus toxin Panton–Valentine leukocidin (PVL) is most likely causative for necrotizing diseases, but the precise pathogenic mechanisms of PVL and a possible contribution of influenza virus remain to be elucidated. In this study, we present a model that explains how influenza virus and PVL act together to cause necrotizing pneumonia: an influenza infection activates the lung epithelium to produce chemoattractants for neutrophils. Upon superinfection with PVL-expressing S. aureus, the recruited neutrophils are rapidly killed by PVL, resulting in uncontrolled release of neutrophil proteases that damage the airway epithelium. The host counteracts this pathogen strategy by generating PVL-neutralizing antibodies and by neutralizing the released proteases via protease inhibitors present in the serum. These findings explain why necrotizing infections mainly develop in serum-free spaces (eg, pulmonary alveoli) and open options for new therapeutic approaches.