Improving Diagnosis of Pulmonary Mucormycosis: Leads From a Contemporary National Study of 114 Cases.

BACKGROUND: Pulmonary mucormycosis (PM) is a life-threatening invasive mold infection. Diagnosis of mucormycosis is challenging and often delayed, resulting in higher mortality. RESEARCH QUESTION: Are the disease presentation of PM and contribution of diagnosis tools influenced by the patient's underlying condition? STUDY DESIGN AND METHODS: All PM cases from six French teaching hospitals between 2008 and 2019 were retrospectively reviewed. Cases were defined according to updated European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria with the addition of diabetes and trauma as host factors and positive serum or tissue PCR as mycologic evidence. Thoracic CT scans were reviewed centrally. RESULTS: A total of 114 cases of PM were recorded, including 40% with disseminated forms. Main underlying conditions were hematologic malignancy (49%), allogeneic hematopoietic stem cell transplantation (21%), and solid organ transplantation (17%). When disseminated, main dissemination sites were the liver (48%), spleen (48%), brain (44%), and kidneys (37%). Radiologic presentation included consolidation (58%), pleural effusion (52%), reversed halo sign (26%), halo sign (24%), vascular abnormalities (26%), and cavity (23%). Serum quantitative polymerase chain reaction (qPCR) was positive in 42 (79%) of 53 patients and BAL in 46 (50%) of 96 patients. Results of transthoracic lung biopsy were diagnostic in 8 (73%) of 11 patients with noncontributive BAL. Overall 90-day mortality was 59%. Patients with neutropenia more frequently displayed an angioinvasive presentation, including reversed halo sign and disseminated disease (P < .05). Serum qPCR was more contributive in patients with neutropenia (91% vs 62%; P = .02), and BAL was more contributive in patients without neutropenia (69% vs 41%; P = .02). Serum qPCR was more frequently positive in patients with a > 3 cm main lesion (91% vs 62%; P = .02). Overall, positive qPCR was associated with an early diagnosis (P = .03) and treatment onset (P = .01). INTERPRETATION: Neutropenia and radiologic findings influence disease presentation and contribution of diagnostic tools during PM. Serum qPCR is more contributive in patients with neutropenia and BAL examination in patients without neutropenia. Results of lung biopsies are highly contributive in cases of noncontributive BAL.

Case Report: Immune Checkpoint Blockade Plus Interferon-Γ Add-On Antifungal Therapy in the Treatment of Refractory Covid-Associated Pulmonary Aspergillosis and Cerebral Mucormycosis.

Invasive fungal diseases (IFD) still cause substantial morbidity and mortality, and new therapeutic approaches are urgently needed. Recent data suggest a benefit of checkpoint inhibitors (ICI). We report the case of a diabetic patient with refractory IFD following a SARSCoV-2 infection treated by ICI and interferon-gamma associated with antifungal treatment.

Learning curve for radiofrequency ablation of benign thyroid nodules.

Objective: To evaluate the effect of operator experience on the treatment outcomes of radiofrequency ablation (RFA) for benign thyroid nodules (BTN). Methods: Data from the 90 first RFA procedures of a single operator in treating benign thyroid nodules were prospectively collected and retrospectively analyzed. Patients were divided into 3 groups according to their chronological treatment rank: patients 1-30 (G1), 31-60 (G2) and 61-90 (G3). Clinical symptoms, volume reduction ratio (VRR), technique efficacy (TE) defined as a VRR > 50% and ablation ratio (AR) were compared between the three groups at 6 months follow-up. All complications and side effects were recorded. Results: No significant difference was observed in improvement of clinical symptoms after the RFA procedure between the three groups, with higher satisfaction however for pressure symptoms than for esthetic complaints (complete resolution 87.5% and 52.6%, respectively). In groups 1, 2 and 3, TE was 60%, 93.3%, 76.7%, VRR 54%, 65%, 60% and AR 13.1%, 34%, 34.6%, respectively. Thus, all ultrasound efficacy parameters (TE, VRR, AR) improved significantly between G1 and G2, with no difference between G2 and G3. Solely did AR improve in nodules ≤ 30 mL between G2 and G3 to reach a median value of 94.4% in G3 versus 57.1% in G2 and 13.7% in G1. Maximum values of TE and VRR (95.6% and 68%, respectively) were seen in nodules ≤ 30 mL in G2 at 6 months follow-up, with no improvement in G3 (84.2% and 63%, respectively). Both baseline volume and energy per volume were independently associated with VRR and AR. Three minor complications were recorded which all recovered totally after conservative treatment. Conclusion: There was a measurable learning curve in RFA for benign thyroid nodules regarding efficacy until 90 patients. VRR and AR can be used as proficiency markers. Only three transient complications occurred confirming the safety of the procedure.

Determining an energy threshold for optimal volume reduction of benign thyroid nodules treated by radiofrequency ablation.

OBJECTIVES: Radiofrequency ablation (RFA) is effective in reducing the volume of benign thyroid nodules. However, what parameters can influence the response to RFA is still unclear. The present study aimed to (1) investigate which ultrasound and technical parameters are potential determinants of the volumetric reduction; (2) develop a dose-response model, and (3) analyze the effects of RFA on ultrasound features. METHODS: In this retrospective study, three institutions treated patients with benign thyroid nodules according to the same protocol. The technical parameters were power and energy. The 1-year volume reduction ratio (VRR) was the reference standard of the response. The correlations of different parameters with VRR were analyzed and the association between several parameters and a VRR above 50% studied by uni- and multivariate analyses. The probit regression estimated the probability to achieve an effective response. RESULTS: One hundred fifteen patients were enrolled. The median power was 50 W and median total delivered energy 27,531 J. At 1-year follow-up, the median VRR was 64.0% and 87 (75.7%) nodules showed a VRR above 50%. Among all parameters, only baseline volume, total energy, and energy per volume were independently associated to a VRR > 50% (p = 0.001, p = 0.0178, p < 0.001 respectively). The probit regression analysis demonstrated that delivering 756 J/ml and 2670 J/ml gave a probability of VRR > 50% in 50% and 99% of patients, respectively. CONCLUSIONS: Considering the baseline nodular volume and delivering the adequate energy per volume allow optimizing technical and clinical success. KEY POINTS: • The effectiveness of radiofrequency ablation in treating benign thyroid nodules is negatively correlated to the volume of the nodule and positively correlated to the energy delivered per volume. • When planning the treatment, the total energy to deliver can be calculated by using a simple formula: nodular volume × 2670 J.

Aspergillus felis in Patient with Chronic Granulomatous Disease.

We report a case of Aspergillus felis infection in a patient with chronic granulomatous disease who had overlapping features of invasive pulmonary aspergillosis and allergic bronchopulmonary aspergillosis. Identifying the species responsible for aspergillosis by molecular methods can be crucial for directing patient management and selection of appropriate antifungal agents.

Why are so many cases of invasive aspergillosis missed?

Invasive aspergillosis (IA) incidence is increasing in several countries like France, and numerous cases are indeed missed and still only diagnosed at autopsy as evidenced by recently published data. Such missed diagnoses are obviously encountered when appropriate diagnostic tools are not available especially in low resource areas or when biologists have not been trained enough in medical mycology (i.e., microscopic examination and culture in most of those areas). Besides logistical issues, which are indeed critical, IA may not be recognized because clinicians failed to consider that risk factors are evolving with the IA burden now observed among patients with chronic lymphoid malignancies or receiving new biotherapies, with diabetes mellitus or liver cirrhosis and/or acute alcoholic hepatitis, with patients from the intensive care unit (ICU) and among patients with some predisposing primary immune deficiencies now reaching the adult's age. This is also the case for human immunodeficiency virus (HIV)-infected patients who failed to meet the classical definitions of IA. From the radiology perspective, new entities of IA have also emerged which absolutely need to be recognized especially bronchial-based-IA among allogeneic stem cell transplant recipients. Finally, from the laboratory side, contribution and limits of indirect blood biomarkers should be integrated to the clinical life in order not to miss IA cases. To conclude, several diagnostic tools should be combined and a constant dialog between laboratory and clinics is crucial to appropriately diagnose IA.

Spectrum of Pulmonary Aspergillosis in Hyper-IgE Syndrome with Autosomal-Dominant STAT3 Deficiency.

BACKGROUND: Autosomal-dominant signal transducer and activator of transcription 3 (STAT3) deficiency predisposes to recurrent bacterial pneumonia, complicated by bronchiectasis and cavitations. Aspergillosis is a major cause of morbidity in these patients. However, its diagnosis, classification, and treatment are challenging. OBJECTIVE: We aimed to assess the prevalence and describe the clinical, mycological, and radiological presentation and related therapy and outcome of Aspergillus infections of the respiratory tract in the STAT3-deficient patients of the National French cohort. METHODS: We performed a retrospective study of all pulmonary aspergillosis cases in STAT3-deficient patients (n = 74). Clinical and mycological data were collected up to October 2015 and imaging was centralized. RESULTS: Twenty-one episodes of pulmonary aspergillosis in 13 (17.5%) STAT3-deficient patients were identified. The median age at first episode was 13 years (interquartile range, 10-26 years). Ninety percent of patients had previous bronchiectasis or cavitations. Infections were classified as follows: 5 single aspergilloma, 9 chronic cavity pulmonary aspergillosis, 5 allergic bronchopulmonary aspergillosis-like disease, and 2 mixed forms of concomitant allergic bronchopulmonary aspergillosis-like disease and chronic cavity pulmonary aspergillosis. No invasive aspergillosis cases were identified. Aspergillus species were isolated in 71% of episodes and anti-Aspergillus antibodies in 93%. Eleven episodes were breakthrough infections. Antifungal treatment was prolonged, with a median of 13 months, and 6 patients (7 episodes) required surgery, with a high rate of postsurgical complications. One patient died and 6 had a relapse. CONCLUSIONS: Chronic and allergic forms of aspergillosis occurred in 17.5% of STAT3-deficient patients, mostly in lung cavities. Almost half had recurrences, despite prolonged antifungal treatment and/or surgery.

Successful Treatment of Saksenaea sp. Osteomyelitis by Conservative Surgery and Intradiaphyseal Incorporation of Amphotericin B Cement Beads.

Osteoarticular mucormycosis cases are quite rare and challenging infections that are mostly due to direct inoculation during traumatic injury among immunocompetent patients. Classic management includes a combination of aggressive surgical debridement, which may lead to amputation, and long-term systemic liposomal amphotericin B therapy. This article describes the successful treatment of Saksenaea sp. osteomyelitis in a patient with diabetes mellitus, using a combination of systemic antifungal therapy and conservative surgery with insertion of amphotericin-impregnated cement beads.

Imaging of Human Neurolisteriosis: A Prospective Study of 71 Cases.

Background: Neurolisteriosis ranks among the most severe neurological infections. Its radiological features have not been thoroughly studied. We describe here the neuroradiological features of neurolisteriosis and assess their prognostic value. Methods: Patients with microbiologically proven neurolisteriosis were enrolled from November 2009 to October 2013 in MONALISA study. Magnetic resonance and computed tomography images were studied by 2 independent neuroradiologists. Predictors of 3-month mortality were determined using logistic regression. Results: Seventy-one patients were included; 42 were men (59%). Mean age was 64 years. Sixty patients (85%) reported signs of encephalitis, with clinical brainstem involvement in 16 (23%). Images were abnormal in 87% of cases (62/71). Main neuroradiological images were meningeal enhancement (25/71, 35%), abscess(es), or nodular image(s) evocative of abscess (10/71, 14%), hemorrhages (11/71, 15%), contrast-enhancing ventricles, or hydrocephalus (7/71, 10%). White-matter images (42/71, 59%), dilated Virchow-Robin spaces (22/71, 31%), and cerebral atrophy were also reported (34/71, 48%). Brainstem involvement (meningeal enhancement, abscess) was reported in only 7/71 cases (10%). Three-month survival was lower in patients with hydrocephalus or contrast-enhancing ventricles (1/7 [14%] than without [47/64, 73%], P = .005) and in patients with parenchymal images (abscess[es], nodule[s]\, or white matter images; 25/46 [54%] vs 23/25 without [92%], P = .004). Parenchymal images were associated with lower 3-month survival in the multivariable model (odds ratio 5.60, 95% confidence interval [1.42-29.6], P = .02). Conclusions: Neurolisteriosis presents as a combination of neuroradiological images, none being specific. Radiological signs of rhombencephalitis are uncommon, whereas, unexpectedly, hemorrhagic images are frequent. The negative prognostic value of parenchymal neuroradiological images was evidenced. Clinical Trials Registration: NCT01520597.

Clinical Assessment of a Nocardia PCR-Based Assay for Diagnosis of Nocardiosis.

The diagnosis of nocardiosis, a severe opportunistic infection, is challenging. We assessed the specificity and sensitivity of a 16S rRNA Nocardia PCR-based assay performed on clinical samples. In this multicenter study (January 2014 to April 2015), patients who were admitted to three hospitals and had an underlying condition favoring nocardiosis, clinical and radiological signs consistent with nocardiosis, and a Nocardia PCR assay result for a clinical sample were included. Patients were classified as negative control (NC) (negative Nocardia culture results and proven alternative diagnosis or improvement at 6 months without anti-Nocardia treatment), positive control (PC) (positive Nocardia culture results), or probable nocardiosis (positive Nocardia PCR results, negative Nocardia culture results, and no alternative diagnosis). Sixty-eight patients were included; 47 were classified as NC, 8 as PC, and 13 as probable nocardiosis. PCR results were negative for 35/47 NC patients (74%). For the 12 NC patients with positive PCR results, the PCR assay had been performed with respiratory samples. These NC patients had chronic bronchopulmonary disease more frequently than did the NC patients with negative PCR results (8/12 patients [67%] versus 11/35 patients [31%]; P = 0.044). PCR results were positive for 7/8 PC patients (88%). There were 13 cases of probable nocardiosis, diagnosed solely using the PCR results; 9 of those patients (69%) had lung involvement (consolidation or nodule). Nocardia PCR testing had a specificity of 74% and a sensitivity of 88% for the diagnosis of nocardiosis. Nocardia PCR testing may be helpful for the diagnosis of nocardiosis in immunocompromised patients but interpretation of PCR results from respiratory samples is difficult, because the PCR assay may also detect colonization.

Prognosis of Invasive Aspergillosis in Kidney Transplant Recipients: A Case-Control Study.

BACKGROUND: Invasive aspergillosis (IA) is a major cause of invasive fungal infection in kidney transplant recipients (KTR), and it has a high mortality rate. However, its impact on patients and graft survival has not been well defined in the current era of voriconazole first-line therapy. METHODS: We retrospectively collected all cases of KTR-associated IA occurring at Necker Enfants Malades Hospital, Paris, from 2003 to 2013. These cases were compared with a group of controls (1:3) who were matched by age, year of kidney transplantation, and sex. The characteristics of IA were also studied. RESULTS: Sixteen patients developed IA after KTR. Most IA cases were limited to the lungs (81.3%), with mild respiratory symptoms in only 53% of the patients. The patients were administered voriconazole (n = 15, 94%) and/or posaconazole (n = 2, 13%). The 12-week and 1-year postinfection survival rates were 94% and 81%, respectively. Compared with the controls (n = 46), patients and death-censored graft survivals rates were significantly lower after IA (P = 0.017 and 0.001, respectively). In the patients with IA, the occurrences of cardiovascular diseases before transplantation (P < 0.0001), delayed graft function (P < 0.0001), and infectious complications (0.0018) were significantly more frequent. CONCLUSIONS: Even with voriconazole therapy, the prognosis of patients with IA after kidney transplantation is still poor. When the patients survive to IA, they have a high risk of graft loss.

Efficacy of ertapenem in severe hidradenitis suppurativa: a pilot study in a cohort of 30 consecutive patients.

OBJECTIVES: Hidradenitis suppurativa (HS) is an inflammatory skin disease typically localized in the axillae and inguinal and perineal areas. In the absence of standardized medical treatment, severe HS patients present chronic suppurative lesions with polymicrobial anaerobic abscesses. Wide surgery is the cornerstone treatment of severe HS, but surgical indications are limited by the extent of lesions. Intravenous broad-spectrum antibiotics may help control HS, but their efficacy is not documented. This study was designed to assess the efficacy of a 6 week course of ertapenem (1 g daily) and of antibiotic consolidation treatments for 6 months (M6) in severe HS. PATIENTS AND METHODS: Thirty consecutive patients with severe HS were retrospectively included in this study. The clinical severity of HS was assessed using the Sartorius score, which takes into account the number and severity of lesions. RESULTS: The median (IQR) Sartorius score dropped from 49.5 (28-62) at baseline to 19.0 (12-28) after ertapenem (P < 10(-4)). Five patients were lost to follow-up thereafter. At M6 the Sartorius score further decreased for the 16 patients who received continuous consolidation treatments, since 59% of HS areas reached clinical remission at M6 (i.e. absence of any inflammatory symptoms, P < 10(-4)). Nine patients interrupted or received intermittent consolidation treatments due to poor observance or irregular follow-up. Their Sartorius score stopped improving or returned to baseline. No major adverse event occurred. CONCLUSIONS: Ertapenem can dramatically improve severe HS. Consolidation treatments are needed to further improve HS and are mandatory to prevent relapses. Combined with surgery, optimized antibiotic treatments may be promising in severe HS.

Nocardia Arthritis: 3 Cases and Literature Review.

Nocardia are Gram-positive filamentous bacteria responsible for infections ranging from opportunistic life-threatening disseminated diseases to chronic skin and soft-tissue infections.Even if virtually all organs can be infected, articular involvement is rare. Therefore, we report 3 recent cases and performed a literature review of cases of Nocardia arthritis in order to describe clinical features, therapeutic challenges, and outcome of these patients.Among 34 patients (31 in the literature plus our 3 cases), 21 (62%) were due to hematogenous dissemination, 9 (26%) were due to direct bacterial inoculation through the skin, and in 4 cases, the mechanism of infection was unknown. Four out of these 34 cases occurred on prosthetic joints.Whereas hematogenous infections mostly occurred in immunocompromised hosts (17 of 21, 81%), direct inoculation was mostly seen in immunocompetent patients.Eighty-two percent of patients (28 out of 34) received trimethoprim-sulfamethoxazole-containing regimens and median antibiotic treatment duration was 24 weeks (range, 12-120) for hematogenous infections and 12 weeks (range, 6-24) for direct inoculations. Outcome was favorable in 27 cases despite unsystematic surgical management (17 cases) without sequelae in 70% of the cases.Nocardia arthritis is rare but its management is complex and should rely on a combined approach with rheumatologist, infectious diseases expert, and surgeon.

Chronic Invasive Aspergillus Sinusitis and Otitis with Meningeal Extension Successfully Treated with Voriconazole.

Invasive aspergillosis (IA) is a severe disseminated fungal disease that occurs mostly in immunocompromised patients. However, central nervous system IA, combining meningitis and skull base involvement, does not occur only in groups with classic risk factors for IA; patients with chronic renal failure and diabetes mellitus are also at risk for more chronic forms. In both of our proven IA cases, voriconazole monotherapy was effective without surgery, and cerebrospinal fluid and serum 1,3-ß-d-glucan test results were initially positive, in contrast to galactomannan antigen results.

Bacterial pathogens associated with hidradenitis suppurativa, France.

Hidradenitis suppurativa (HS) is a skin disease characterized by recurrent nodules or abscesses and chronic suppurating lesions. In the absence of clear pathophysiology, HS is considered to be an inflammatory disease and has no satisfactory medical treatment. Recently, prolonged antimicrobial treatments were shown to improve or resolve HS lesions. We prospectively studied the microbiology of 102 HS lesions sampled from 82 patients using prolonged bacterial cultures and bacterial metagenomics on 6 samples. Staphylococcus lugdunensis was cultured as a unique or predominant isolate from 58% of HS nodules and abscesses, and a polymicrobial anaerobic microflora comprising strict anaerobes, milleri group streptococci, and actinomycetes was found in 24% of abscesses or nodules and in 87% of chronic suppurating lesions. These data show that bacteria known to cause soft tissue and skin infections are associated with HS lesions. Whether these pathogens are the cause of the lesions or are secondary infectious agents, these findings support targeted antimicrobial treatment of HS.

Last generation triazoles for imported eumycetoma in eleven consecutive adults.

BACKGROUND: Optimal management of eumycetoma, a severely debilitating chronic progressive fungal infection of skin, disseminating to bone and viscera, remains challenging. Especially, optimal antifungal treatment and duration are ill defined. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a monocentric retrospective study of 11 imported cases of eumycetoma treated by voriconazole or posaconazole for at least 6 months. Response to treatment was assessed through evolution of clinical and magnetic resonance imaging (MRI). (1→3) ß-D-glucan (BG) and positron emission tomography using [18F] fluorodeoxyglucose (PET/CT) results were also assessed. Identified species were Fusarium solani complex (n = 3); Madurella mycetomatis, (n = 3), and Exophiala jeanselmei, (n = 1). Moreover, two coelomycetes and one phaeohyphomycetes strains without species identification were retrieved. Serum BG and PET/CT were abnormal in 7/8 and 6/6 patients tested, respectively. Patients received last generation azoles for a mean duration of 25.9±18 months. Complete response (major clinical and MRI improvement) was observed in 5/11 patients, partial response (minor MRI improvement or stable MRI findings) in 5 and failure (MRI evidence of disease progression) in one, with a 73±39 [6-132] months mean follow-up. Relapse occurred in 2 patients after treatment discontinuation. Optimal outcome was associated with fungal species, initiation of last generation triazole therapy (<65 months since first symptoms), negative serum BG and PET/CT normalization. CONCLUSIONS/SIGNIFICANCE: MRI, PET/CT and serum BG appear as promising tools to assess optimal time of antifungal treatment for eumycetoma.

Litchi-associated acute encephalitis in children, Northern Vietnam, 2004-2009.

Since the end of the 1990s, unexplained outbreaks of acute encephalitis in children coinciding with litchi harvesting (May-July) have been documented in the Bac Giang Province in northern Vietnam. A retrospective ecologic analysis of data for 2004-2009 involving environmental, agronomic, and climatic factors was conducted to investigate the suspected association between the outbreaks and litchi harvesting. The clinical, biological, and immunologic characteristics of the patients suggested a viral etiology. The ecologic study revealed an independent association between litchi plantation surface proportion and acute encephalitis incidence: Incidence rate ratios were 1.52 (95% CI 0.90-2.57), 2.94 (95% CI 1.88-4.60), and 2.76 (95% CI 1.76-4.32) for second, third, and fourth quartiles, respectively, compared with the lowest quartile. This ecologic study confirmed the suspected association between incidence of acute encephalitis and litchi plantations and should be followed by other studies to identify the causative agent for this syndrome.