10-year experience in patients operated for acute invasive fungal rhinosinusitis. / Experiencia de 10 años en pacientes operados por rinosinusitis fúngica invasiva aguda.

INTRODUCTION: Acute invasive fungal rhinosinusitis (AIFRS) is rare but has high mortality. It is more frequent in immunocompromised patients with multiple comorbidities, which make their management more difficult. The aim of this study is to describe a cohort of patients operated due to AIFRS, their clinical characteristics, mortality, aetiological agent and efficacy of diagnostic tests. MATERIAL AND METHOD: Non-concurrent prospective study of patients with AIFRS who were operated between 2005 and 2015 in our centre. RESULTS: Thirty-two patients were included, 62.5% (20/32) men, with an average age of 39.4 years (16-65 years). Overall mortality was 71.9%; acute mortality 46.9% and late mortality 25%. Haematological malignancies were the most common underlying disease, present in 84.4% (27/32) of cases, followed by diabetes mellitus in 9.4% (3/32). On diagnosis, 62.5% (20/32) of patients were neutropenic, 80% (16/20) of them with febrile neutropenia. Fever was the most frequent symptom, present in 65.6% (21/32) of patients, followed by facial pain or headache in 53.1% (17/32). Aspergillus was identified in 37.5% (12/32) of cases and Rhizopus in 31.3% (10/32). There was no association between the analysed variables and increased risk of mortality. CONCLUSIONS: AIFRS is an aggressive disease with a high mortality rate, therefore a timely diagnosis is fundamental. It is necessary to optimise suspicion criteria for an early diagnosis in order to improve the prognosis.

Multiresistent opportunistic talaromycosis in a patient with ovarian cancer.

BACKGROUND: Talaromycosis (penicillinosis) is multiresistent opportunistic mycosis. The infection can be inapparent and it can simmulate malignant tumor dissemination in some patients. CASE: We present a case of 33-years-old patient with mucinous adenocarcinoma of left ovary, initially FIGO IIC. The patient had had hysterectomy, bilateral adnexectomy, omentectomy and port-site metastasis extirpation. Six cycles of 1st chemother-apy paclitaxel and carboplatin had been administered to patient follow-ing the surgery. Positron emission tomography / computed tomography (PET/CT) scan after the treatment, had shown metabolic activity infiltrat-ing both lung apexes, supposedly with no dis-ease correlation, and hypermetabolic foci in spleen, suspicious of be-ing metastases. Pa-cient showed no clinical symp-toms, nor markers of inflammation elevation. Initially elevated serum tumor markers CA125 and CA72-4 had decreased after the treatment. Bronchoalveolar lavage cytology described presence of inflammatory infiltration with fungiform-ing hyphae - most probably an aspergillosis. Mannan and galactomannan serology was negative. In regard to splenectomy plans, treatment with voriconazol was initiated empirically. Result of fungi cultivation out of bronchoalveolar lavage was finalized later, show-ing sporadic presence o Penicillium sp. with resistance to antimycotic treatment except for amphotericin B. Liposomal amphotericin B treatment was administered in two cures, 28 days in total. Immunomodulatory treatment of secondary cellular immunodeficiency and vaccination against encapsulated bacteria was given to the patient. Splenectomy was performed 6 months after the end of chemother-apy treatment. Histopathology showed chronic granulomatous inflammation without mycotic hyphae, with no evidence of tumor cells. After the splenectomy, patient was treated by surgical incision and drainage and by klindamycin for intraabdominal abscess in left hypogastric area. CONCLUSION: Patient is under follow up by oncologist, immunologist and gynecologist 12 months after the splenectomy, she is surveilled by PET/CT and serum tumor markers. Talaromycosis can be clinically inapparent in spite of its dissemination. It can be present in diffuse, granulomatous and mixed form. Therapeutic agent is sometimes limited to amphotericin B due to its resistence. Liposomal form of amphotericin B is recommended regard-ing its pharmacokinetic properties. In case of dissemination, administration period of more than 14 days is recommended, even in inapparent form. Immunomodulatory treatment is recommended due to opportunistic infection.

Invasive Curvularia Infection in Pediatric Patients With Hematologic Malignancy Identified by Fungal Sequencing.

Curvularia is a saprophytic dematiaceous mold and a rare human pathogen. Here, we report three severely immunocompromised pediatric patients who developed invasive Curvularia infection. Diagnosis was achieved or confirmed in all cases by fungal ribosome sequencing, which hastened species identification and targeted treatment for the patients reported. There are no treatment guidelines for invasive Curvularia infection, though we report three patients who were cured of their infection through a combination of surgical resection and various anti-fungal therapies, indicating a relatively low virulence and good prognosis in comparison to other angioinvasive molds.

Surgical Treatment of Multifocal Pulmonary Mucormycosis.

Mucormycosis is a devastating opportunistic fungal infection to which the immunosuppressed are particularly vulnerable. We report the case of a 60-year-old man who was found to have multifocal pulmonary mucormycosis 10 weeks after concomitant heart and kidney transplantation. Despite appropriate antifungal therapy, the infection progressed rapidly and soon involved critical pulmonary vasculature. He successfully underwent staged operative resection of his pulmonary mucormycosis without recurrence of infection. Although surgical debridement of pulmonary mucormycosis is typically reserved for localized disease, this case demonstrates that surgical intervention should be considered as an adjunct to antifungal therapy in multifocal disease.

Successful Sequential Liver and Hematopoietic Stem Cell Transplantation in a Child With CD40 Ligand Deficiency and Cryptosporidium-Induced Liver Cirrhosis.

BACKGROUND: Hematopoietic stem cell transplantation (HSCT) is curative in patients with primary immunodeficiencies. However, pre-HSCT conditioning entails unacceptably high risks if the liver is compromised. The presence of a recurrent opportunistic infection affecting the biliary tree and determining liver cirrhosis with portal hypertension posed particular decisional difficulties in a 7-year-old child with X-linked CD40-ligand deficiency. We aim at adding to the scanty experience available on such rare cases, as successful management with sequential liver transplantation (LT) and HSCT has been reported in detail only in 1 young adult to date. METHODS: A closely sequential strategy, with a surgical complication-free LT, followed by reduced-intensity conditioning, allowed HSCT to be performed only one month after LT, preventing Cryptosporidium parvum recolonization of the liver graft. RESULTS: Combined sequential LT and HSCT resolved the cirrhotic evolution and corrected the immunodeficiency so that the infection responsible for the progressive sclerosing cholangitis did not recur. CONCLUSIONS: Hopefully, this report of the successful resolution of a potentially fatal combination of immunodeficiency and chronic opportunistic infection with end-stage organ damage in a child will encourage others to adapt a sequential transplant approach to this highly complex pathology. However, caution is to be exercised to carefully balance the risks intrinsic to transplant surgery and immunosuppression in primary immunodeficiencies.

Necrotizing fasciitis resulting in fatal lung aspergillosis: Uncommon pathogenesis. A case report.

We present a fatal case of Aspergillus-associated lung failure in a patient with necrotizing fasciitis. The cause of the fasciitis was a retroperitoneal perforation of a colon carcinoma. Being already a rare condition, the fasciitis did not manifest as Fournier's gangrene like similar described cases illustrate, but instead travelled along the fasciae and subcutaneous fat tissue cranially into the thoracic cavity, ultimately leading to a disseminated infection of the lungs. The lethal outcome was thus caused by respiratory failure at a time when the primary focus was already successfully treated, contrary to typical cases of necrotizing fasciitis. This case report depicts the importance of acknowledging opportunistic fungal infections in the practice of emergency surgery. Contributing factors, pathogenesis and possible prevention measures are discussed.

Surgery of a nocardia lung abscess presenting as a tension pyopneumothorax.

While some cases of nocardial pneumonia develop secondary empyema, tension pyopneumothorax is a very rare and lethal complication. A 74-year-old man who exhibited thrombocytopenia during steroid therapy for autoimmune hepatitis, presented to our department with a nocardial tension pyopneumothorax. He underwent a left lower lobectomy after chest drainage, and was discharged without any complication other than reoperation to remove a postoperative hematoma.

Mucormycosis: an unusual cause of gastric perforation and severe bleeding in immunocompetent patients

Mucormycosis is a rare and often fatal opportunistic infection that especially occurs in immunocompromised patients. Primary gastrointestinal infection is uncommon and accounts for only approximately 7% of all cases of mucormycosis but it is associated with an 85% mortality rate due to perforation and massive bleeding. Very few cases of gastrointestinal mucormycosis in an immunocompetent host have been reported. We describe a case of gastric necrosis and massive bleeding due to fulminant invasive mucormycosis (AU)

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Successful Treatment of Rhino-Orbital-Cerebral Mucormycosis in a Child With Leukemia.

Rhino-orbital-cerebral mucormycosis (ROCM) is a rare fulminant opportunistic fungal infection that despite relevant treatment has high mortality. We present a case of a 3-year-old girl with acute lymphoblastic leukemia and ROCM, who was treated successfully with excessive surgery, systemic antifungal treatment with amphotericin B (AmB), posaconazole, and terbinafine as well as hyperbaric oxygen. Surgery included, beside extracranial and intracranial removal of infected areas, endoscopic sinus and skull base surgery with local AmB installation and in addition placement of an Ommaya reservoir for 114 intrathecal administrations of AmB. In addition, we review the literature of ROCM in pediatric patients with hematological diseases.

Treatment of mucormycosis in transplant patients: role of surgery and of old and new antifungal agents.

PURPOSE OF REVIEW: Mucormycosis is an opportunistic mold infection whose management is difficult, as there is a paucity of evidence-based data. We summarize the latest advances in diagnosis and management of mucormycosis in transplant recipients. RECENT FINDINGS: There is promise for improvement in nonculture-based diagnostics with new biomarkers of Mucorales DNA that can be used for early diagnosis, and monitoring of response. Antifungal treatment consists of high-dose lipid formulations of amphotericin B or isavuconazole as the first-line therapy and posaconazole as salvage therapy. The new, pharmacokinetically more reliable formulations of posaconazole (intravenous, extended-release tablets) are welcomed improvements. Yet, the role of combination therapy is still uncertain. Surgery had a significant role in selected cases, such as in patients with rhinosinusitis form of mucormycosis, which nowadays can be performed with minimal invasive technique. SUMMARY: Mucormycosis remain a life-threatening opportunistic mold infection among transplant patients. Early diagnosis, prompt treatment with effective antifungals in combination with surgery if feasible is essential. Immune adjunct therapy and improvement of early diagnostics are important areas for future research. There are good prospects of progress in diagnostics and management of mucormycosis in transplant patients.

Cytomegalovirus Infection in Ulcerative Colitis is Related to Severe Inflammation and a High Count of Cytomegalovirus-positive Cells in Biopsy Is a Risk Factor for Colectomy.

BACKGROUND AND AIMS: Cytomegalovirus [CMV] infection often reactivates in the course of inflammatory bowel disease, but the significance of this remains disputable. Our aim was to evaluate whether severity of CMV colitis is associated with colectomy risk in ulcerative colitis [UC] patients. The secondary aim was to evaluate agreement between immunohistochemistry [IHC] and blood CMV polymerase chain reaction [PCR]. METHODS: UC patients with CMV assessment of the colon, hospitalised in a referral unit between 2005 and 2012 were retrospectively identified. The course and severity of the disease were analysed, with inflammation graded histologically across the range 0-3. The numbers of CMV IHC-positive cells per biopsy section were counted, and results for blood CMV PCR were also retrieved. Data on colectomies were also collected. RESULTS: Of 141 patients, 95 were analysed, with 33 found to be CMV IHC-positive and 62 negative. The colectomy risk was significantly higher in patients with ≥ 5 IHC-positive cells, as opposed to those with none or less than 5 [p = 0.014] with median follow-up of 1.9 and 3.2 years, respectively. The CMV IHC-positive patients had lower haemoglobin [median 11.0g/dl vs 12.0; p = 0.028] and albumin [median 29.5g/l vs 33.1; p = 0.038] levels and more intense histological inflammation [p = 0.020] compared with CMV IHC-negative patients. There was substantial agreement between IHC and blood PCR [Cohen's kappa coefficient 0.72]. CONCLUSIONS: Five or more CMV IHC-positive cells per biopsy section were indicative of a greater colectomy risk. CMV infection was related to more severe inflammation. Blood CMV PCR is a useful tool in UC.

Survival following lung resection in immunocompromised patients with pulmonary invasive fungal infection.

OBJECTIVES: Pulmonary invasive fungal infections (IFIs) are associated with high mortality in patients being treated for haematological malignancy. There is limited understanding of the role for surgical lung resection and outcomes in this patient population. METHODS: This is a retrospective cohort of 50 immunocompromised patients who underwent lung resection for IFI. Patient charts were reviewed for details on primary malignancy and treatment course, presentation and work-up of IFI, reasons for surgery, type of resection and outcomes including postoperative complications, mortality, disease relapse and survival. Analysis was also performed on two subgroups based on year of surgery from 1990-2000 and 2001-2014. RESULTS: The median age was 39 years (range: 5-64 years). Forty-seven patients (94%) had haematological malignancies and 38 (76%) underwent haematopoietic stem cell transplantation (HSCT). Surgical indications included haemoptysis, antifungal therapy failure and need for eradication before HSCT. The most common pathogen was Aspergillus in 34 patients (74%). Wedge resections were performed in 32 patients (64%), lobectomy in 9 (18%), segmentectomy in 2 (4%) and some combination of the 3 in 7 (14%) for locally extensive, multifocal disease. There were 9 (18%) minor and 14 (28%) major postoperative complications. Postoperative mortality at 30 days was 12% (n = 6). Acute respiratory distress syndrome was the most common cause of postoperative death. Overall 5-year survival was 19%. Patients who had surgery in the early period had a median survival of 24 months compared with 5 months for those who had surgery before 2001 (P = 0.046). At the time of death, 15 patients (30%) had probable or proven recurrent IFI. Causes of death were predominantly related to refractory malignancy, fungal lung disease or complications of graft versus host disease (GVHD). Patients who had positive preoperative bronchoscopy cultures had a trend towards worse survival compared with those with negative cultures (hazard ratio: 1.80, P = 0.087). CONCLUSIONS: Surgical resection of IFI in immunocompromised patients is associated with high perioperative mortality. Long-term survival is limited by recurrent malignancy, persistent fungal infection and GVHD but has improved in recent years. Selection for surgical resection is difficult in this patient population, but should be carefully considered in those who are symptomatic, or have failed antifungal treatment.

Potential burden of antibiotic resistance on surgery and cancer chemotherapy antibiotic prophylaxis in the USA: a literature review and modelling study.

BACKGROUND: The declining efficacy of existing antibiotics potentially jeopardises outcomes in patients undergoing medical procedures. We investigated the potential consequences of increases in antibiotic resistance on the ten most common surgical procedures and immunosuppressing cancer chemotherapies that rely on antibiotic prophylaxis in the USA. METHODS: We searched the published scientific literature and identified meta-analyses and reviews of randomised controlled trials or quasi-randomised controlled trials (allocation done on the basis of a pseudo-random sequence-eg, odd/even hospital number or date of birth, alternation) to estimate the efficacy of antibiotic prophylaxis in preventing infections and infection-related deaths after surgical procedures and immunosuppressing cancer chemotherapy. We varied the identified effect sizes under different scenarios of reduction in the efficacy of antibiotic prophylaxis (10%, 30%, 70%, and 100% reductions) and estimated the additional number of infections and infection-related deaths per year in the USA for each scenario. We estimated the percentage of pathogens causing infections after these procedures that are resistant to standard prophylactic antibiotics in the USA. FINDINGS: We estimate that between 38·7% and 50·9% of pathogens causing surgical site infections and 26·8% of pathogens causing infections after chemotherapy are resistant to standard prophylactic antibiotics in the USA. A 30% reduction in the efficacy of antibiotic prophylaxis for these procedures would result in 120,000 additional surgical site infections and infections after chemotherapy per year in the USA (ranging from 40,000 for a 10% reduction in efficacy to 280,000 for a 70% reduction in efficacy), and 6300 infection-related deaths (range: 2100 for a 10% reduction in efficacy, to 15,000 for a 70% reduction). We estimated that every year, 13,120 infections (42%) after prostate biopsy are attributable to resistance to fluoroquinolones in the USA. INTERPRETATION: Increasing antibiotic resistance potentially threatens the safety and efficacy of surgical procedures and immunosuppressing chemotherapy. More data are needed to establish how antibiotic prophylaxis recommendations should be modified in the context of increasing rates of resistance. FUNDING: DRIVE-AB Consortium.

A Hemophagocytic Lymphohistiocytosis Case with Newly Defined UNC13D (c.175G>C; p.Ala59Pro) Mutation and a Rare Complication.

Hemophagocytic lymphohistiocytosis (HLH) represents a severe hyperinflammatory condition with cardinal symptoms of prolonged fever, cytopenias, hepatosplenomegaly, and hemophagocytosis by activated, morphologically benign macrophages with impaired function of natural killer cells and cytotoxic T lymphocytes. A 2-month-old girl, who was admitted with fever, was diagnosed with HLH and her genetic examination revealed a newly defined mutation in the UNC13D (c.175G>C; p.Ala59Pro) gene. She was treated with dexamethasone, etoposide, and intrathecal methotrexate. During the second week of treatment, after three doses of etoposide, it was noticed that there was a necrotic plaque lesion on the soft palate. Pathologic examination of debrided material in PAS and Grocott staining revealed lots of septated hyphae, which was consistent with aspergillosis infection. Etoposide was stopped and amphotericin B treatment was given for six weeks. HLH 2004 protocol was completed to eight weeks with cyclosporine A orally. There was no patient with invasive aspergillosis infection as severe as causing palate and nasal septum perforation during HLH therapy. In immunocompromised patients, fungal infections may cause nasal septum perforation and treatment could be achieved by antifungal therapy and debridement of necrotic tissue.

Chronic pulmonary aspergillosis: a frequent and potentially severe disease.

INTRODUCTION: Chronic pulmonary aspergillosis is a pulmonary fungal infection with various presentations that can occur on a pre-existing cavity, often a sequel of tuberculosis. The objective of our study was to report the diagnostic and therapeutic management of pulmonary aspergilloma in our structure. PATIENTS AND METHODS: We retrospectively studied 81 cases of pulmonary aspergilloma having occurred in the respiratory diseases unit of the Casablanca Ibn Rochd hospital, over 11 years. RESULTS: We included 48 male and 33 female non-immunocompromised patients, with an average age of 51 years (27-75). A history of tuberculosis was recorded in 78 cases. Hemoptysis was the revealing symptom in 73 cases. A characteristic "bell-like" image was observed in 25 cases. The serological results were positive for aspergillus in 54 cases. The treatment was surgical in 50 cases and medical in 24 cases. Five patients died. DISCUSSION: A significant number of pulmonary aspergilloma cases were recorded in our study, occurring most frequently on sequels of tuberculosis. This disease is currently common in countries highly endemic for tuberculosis; early and adequate management is required. CONCLUSION: Aspergillosis is a frequent and potentially severe disease occurring on pre-existing lesions, most often in our context sequels of tuberculosis. Surgical resection is the reference treatment but is the cause of a significant morbidity and mortality. Preventive measures are mandatory.

Fungal necrotizing fasciitis, an emerging infectious disease caused by Apophysomyces (Mucorales).

BACKGROUND: The mucoralean fungi are emerging causative agents of primary cutaneous infections presenting in the form of necrotizing fasciitis. AIMS: The aim of this study was to investigate a series of suspected necrotizing fasciitis cases by Apophysomyces species over one-year period in a northern Indian hospital. METHODS: The clinical details of those patients suspected to suffer from fungal necrotizing fasciitis were recorded. Skin biopsies from local wounds were microscopically examined and fungal culturing was carried out on standard media. The histopathology was evaluated using conventional methods and special stains. Apophysomyces isolates were identified by their morphology and by molecular sequencing of the internal transcribed spacer (ITS) region of the ribosomal genes. Antifungal susceptibility testing was carried out following EUCAST guidelines and treatment progress was monitored. RESULTS: Seven patients were found to be suffering from necrotizing fasciitis caused by Apophysomyces spp. Six isolates were identified as Apophysomyces variabilis and one as Apophysomyces elegans. Five patients had previously received intramuscular injections in the affected area. Three patients recovered, two died and the other two left treatment against medical advice and are presumed to have died due to their terminal illnesses. Posaconazole and terbinafine were found to be the most active compounds against A. variabilis, while the isolate of A. elegans was resistant to all antifungals tested. CONCLUSIONS: Apophysomyces is confirmed as an aggressive fungus able to cause fatal infections. All clinicians, microbiologists and pathologists need to be aware of these emerging mycoses as well as of the risks involved in medical practices, which may provoke serious fungal infections such as those produced by Apophysomyces.