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Listeria monocytogenes is a Gram-positive bacillus widespread in nature and responsible for human and animal infections. Listeriosis is a severe and rare infection transmitted orally and vertically, frequently in the context of an underlying immunosuppression. L. monocytogenes is able to cross several barriers: intestinal mucosa, placenta and blood-brain barrier. Listeriosis is associated with a range of clinical presentations: ranging from acute gastroenteritis, septicaemia, central nervous system and maternofetal infections. Diagnosis is based on the isolation of L. monocytogenes from blood and cerebrospinal fluid cultures. Treatment relies on the synergic combination amoxicillin and gentamicin, with a mortality rate up to 30% despite adequate therapy.

The pathogenesis of cryptococcosis, including the events leading to the production of meningoencephalitis, is still largely unknown. Evidence of a transcellular passage ofCryptococcus neoformansacross the blood-brain barrier (BBB) and subsequent BBB disruption exists, but the paracellular passage of free yeasts and the role of monocytes in yeast dissemination and brain invasion (Trojan horse method) remain uncertain. We used our model of disseminated cryptococcosis, in which crossing of the BBB starts 6 h after intravenous inoculation, to study paracellular passage of the BBB. We prepared bone marrow-derived monocytes (BMDM) infected in vitro withC. neoformans(BMDM yeasts) and free yeasts and measured fungal loads in tissues. (i) Spleen and lung CFU were >2-fold higher in mice treated with BMDM yeasts than in those treated with free yeasts for 1 and 24 h (P< 0.05), while brain CFU were increased (3.9 times) only at 24 h (P< 0.05). (ii) By comparing the kinetics of brain invasion in naïve mice and in mice with preestablished cryptococcosis, we found that CFU were lower in the latter case, except at 6 h, when CFU from mice inoculated with BMDM yeasts were comparable to those measured in naïve mice and 2.5-fold higher than those in mice with preestablished cryptococcosis who were inoculated with free yeasts. (iii) Late phagocyte depletion obtained by clodronate injection reduced disease severity and lowered the fungal burden by 40% in all organs studied. These results provide evidence for Trojan horse crossing of the BBB byC. neoformans, together with mechanisms involving free yeasts, and overall for a role of phagocytes in fungal dissemination.

Two commercially available adjuvants, Gerbu LQ 3000 and Montanide ISA 50V, were assessed as potential replacements for Freund's adjuvant by evaluating their efficacy in the production of polyclonal antibodies to veterinary drugs in rabbits. The aim was to find an adjuvant that could produce a similar (or enhanced) immune response in the host animal without the undesirable side effects associated with Freund's complete and incomplete adjuvant. The assessment involved the examination of each injection site and the characterisation of the resultant antibodies with regards to antibody titre and sensitivity. It was found that the rabbits immunised with Gerbu adjuvant produced some of the most sensitive antibodies. However, titres were relatively low and adverse effects at injection sites were relatively common. Montanide adjuvant produced no adverse effects and the related antibodies were found to be of adequate sensitivity when compared to those from rabbits immunised with Freund's. It was concluded that Montanide ISA 50V could be considered as a suitable replacement to Freund's for the production of polyclonal antibodies, to low molecular weight compounds in rabbits.

Les recommandations pour le traitement des candiduries symptomatiques reposent sur l’utilisation du fluconazole, antifongique ayant une bonne diffusion au niveau de l’appareil urinaire. Le probleme du choix du traitement se pose lors de candiduries a Candida glabrata , espece de sensibilite diminuee voire resistante au fluconazole. Une alternative au fluconazole pourrait etre la 5-fluorocytosine (5-FC), du fait de son efficacite in vitro vis-a-vis de C. glabrata et de sa bonne diffusion urinaire. Cependant, une bitherapie est necessaire lors de l’utilisation de la 5-FC en raison de l’apparition rapide de resistance. Nous rapportons ici deux observations de cystite a C. glabrata chez deux patients transplantes de rein traites par une bitherapie antifongique associant 5-FC et caspofungine. Tous deux ont developpe en moins de 3 semaines une resistance de haut niveau a la 5-FC (CMI > 32 μg/mL). Le mecanisme moleculaire de resistance a la 5-FC des souches de C. glabrata a ete etudie. Nous avons sequence les genes FUR1 , FCY1 et FCY2 , qui codent pour les 3 enzymes impliquees dans la resistance de C. glabrata a la 5-FC pour chaque couple de souches (sensible et resistante a la 5-FC) de chaque patient. Nous avons mis en evidence que la resistance etait secondaire a l’apparition d’un codon STOP au niveau du gene FUR1 par deux mecanismes differents. Chez le premier patient, il s’agissait de l’apparition d’une mutation ponctuelle (codon 122 : GAG-->TAG) et chez le second patient d’une duplication d’une sequence de 29pb (insertion au niveau du codon 60) par un mecanisme de derapage replicatif entrainant un decalage du cadre de lecture avec apparition d’un codon STOP. Les genes FCY1 et FCY2 ne presentaient que des mutations silencieuses (polymorphisme). Conclusions Nous decrivons ici deux mecanismes differents a l’origine de l’apparition d’un codon stop dans le gene FUR1 , qui code pour une uracil phosphoribosyl transferase, responsables d’une resistance de haut niveau a la 5-FC. L’acquisition d’une resistance a la 5-FC a ete extremement rapide chez ces deux patients au cours du traitement par 5-FC et caspofungine, suggerant que la concentration de caspofungine dans les urines etait faible. Ces 2 observations d’echec de traitement d’une infection urinaire par une bitherapie par 5-FC et echinocandine suggerent que cette association, malgre une bonne activite fongicide in vitro, ne peut etre utilisee comme traitement alternatif au fluconazole.

A survey of the presence of residues of anticoccidials was performed. Three hundred and twenty egg samples, purchased in eight different European countries, were analysed for the presence of nine different compounds: dimetridazole, diclazuril, halofuginone, robenidine, nicarbazin, narasin, salinomycin, lasalocid and monensin. Analyses were performed by LC-MS/MS. Of the samples analysed, 114 (35.6%) contained one or more of the nine anticoccidials in concentrations ranging from 0.1 to 63 microg kg-1. Salinomycin and lasalocid account for more than 60% of all positive samples. Almost 90% of all positive samples contained less than 2 microg kg-1. Results were put into perspective of the farming method and country of origin.

In this work, coumarins were screened on thrombin (THR) and factor Xa (FXa), two of the most promising targets for the development of anticoagulant drugs. This allowed us to highlight compound 30, characterized by a 2,5-dichlorophenyl ester in the 3-position and a chloromethyl moiety in the 6-position, as a very potent THR inhibitor (ki/KI= 37,000 M(-1) s(-1)). Moreover, this compound exhibits good selectivity over FXa (168-fold) and trypsin (54-fold). The mechanism of inactivation was investigated in this series and significantly differs from that previously observed with alpha-chymotrypsin. Indeed, the addition of hydrazine on the THR-inhibitor complex promotes a partial induced THR reactivation. This reactivation, confirmed by LC/MS, showed the resurgence of the native THR and a new dihydrazide complex. Docking experiments were then efficiently used to explain the trends observed in the enzymatic assays as well as to corroborate the postulated inhibition mechanism. Finally, the cell permeability of our derivatives was estimated using a computational approach.

Sarcoidosis is a granulomatous disorder with a well-known T helper (Th) type 1 cell commitment and a key pathogenic role of interferon (IFN)-gamma. However, little is known about the influence of type 1 IFNs, such as IFN-alpha and IFN-beta, on the course of previous sarcoidosis. The aim of this study was to determine whether type 1 IFNs can safely be used in patients with sarcoidosis for severe associated disease. The present study examined a series of four patients with sarcoidosis, treated by IFN-alpha or IFN-beta for viral hepatitis (three cases) or multiple sclerosis (one case). IFN was initiated soon after apparent recovery (three cases) or during a worsening phase of sarcoidosis (one case). Hydroxychloroquine was added in the case with active disease. Patients received interferon for 6-24 months and had close monitoring during and after IFN therapy. Interestingly, no recurrence or exacerbation of sarcoidosis had occurred at 4 yrs of follow up. Two patients were cured from viral hepatitis, whilst treatment for another failed. No neurological progression was observed in the remaining patient. This series suggests that, despite the T helper type 1 phenotype of sarcoid granulomatous reaction, type 1 interferons do not exacerbate sarcoidosis in remission and this makes their use possible if indicated. However, their effect in persistent forms of the disease needs further evaluation.

In this paper, the binding mode of original pyridinic compounds structurally related to nimesulide, a preferential cyclooxygenase (COX)-2 inhibitor, is analyzed by docking simulations in order to understand structure-activity relationships of this family. Structural modifications are proposed to reverse the selectivity of the more active inhibitor of the series characterized by a preferential activity on COX-1. On the basis of these modifications, a new compound with a bromo substituent was designed and showed a COX-2 selective inhibition.

Three related compounds containing a pyrazole moiety with vicinal phenyl rings featuring a methyl­sulfonyl substituent are described, namely 3-methyl-1-[4-(methyl­sulfonyl)­phenyl]-5-phenyl-1H-pyrazole, C17H16N2O2S, ethyl 1-[4-(methyl­sul­fonyl)­phenyl]-5-phenyl-1H-pyrazole-3-carboxyl­ate, C19H18N2O4S, and 1-[4-(methyl­sulfonyl)­phenyl]-3-[3-(morpholino)­phenoxy­methyl]-5-phenyl-1H-pyrazole, C27H27N3O4S. The design of these compounds was based on celecoxib, a selective cyclo­oxy­genase-2 (COX-2) inhibitor, in order to study the influence of various substituents on COX-2 and 5-lipoxy­genase (5-LOX) inhibition.

Introduction – objectifs Notre service accueille des femmes enceintes presentant des pathologies infectieuses. Elles necessitent une surveillance et une prise en charge specifiques, source d’inquietudes ou de questionnements de la part de l’equipe paramedicale vis-a-vis de sa pratique de soin. Nous avons voulu les identifier et tenter de les reduire. Nos objectifs etaient : 1. d’evaluer les representations et difficultes ressenties par le personnel paramedical face a la prise en charge de femmes enceintes hors de la maternite ; 2. d’identifier les besoins de formation et d’echanges pour optimiser cette prise en charge. Materiels et methodes Etude infirmiere par un auto-questionnaire qualitatif etabli apres un entretien semi-directif aupres d’une infirmiere et d’une aide-soignante, teste aupres d’une autre infirmiere et d’une autre aide-soignante, puis soumis au reste de l’equipe paramedicale. Resultats Le questionnaire a porte sur l’ensemble de l’equipe (n = 29) et objective des questionnements sur : — la capacite a evaluer la viabilite foetale/les urgences obstetricales (30 %) ; — la capacite a repondre a l’inquietude maternelle (45 %) ; — le besoin de stages en maternite, de formation sur des points infectiologiques et obstetricaux specifiques (90 %). Conclusion Cette etude a permis un auto-diagnostic libre et complet des difficultes reelles ou percues liees a la prise en charge de femmes enceintes hors de la maternite. Une formation va etre menee, impliquant obstetriciens, infectiologues, psychologue avec stages en Obstetrique. Une reevaluation par le meme questionnaire sera menee ensuite pour apprecier les benefices de cette action. Nous voulons dans l’avenir etudier d’autres groupes patients dans un projet infirmier annuel d’auto-evaluation des soins et de formation.

The title compound, C(12)H(12)N(2)O(3)S, is a strict pyridine analogue of nimesulide, a selective inhibitor of cyclooxygenase-2. The structure is characterized by a pyridinium ring with a deprotonated sulfonamide group. An intermolecular charge-assisted hydrogen bond between these two groups is observed within the crystal packing, linking the molecules into an infinite chain running along the b-axis direction.

International audience; We describe a patient with confirmed novel H1N1 (swine-like) influenza A virus who had daily nasal swabs tested during oseltamivir therapy. Nasal shedding remained positive for 2 days and became negative on day 3. This report presents the first available data on the kinetics of shedding of this novel virus under antiviral therapy.

Abstract 3215 Introduction: The International Sickle Cell Disease Observatory (ISCDO) is an international group, established in 2011, including representatives from countries where sickle cell disease (SCD) is highly prevalent, in order to collect and share information of SCD patient's to improve patients care and quality of life, to define common guidelines, to develop advanced targeted approaches and transfer innovative practices worldwide. One of the first ISCDO study is a survey of pregnancy in SCD in France and Brazil. Context: Pregnancy in SCD has been associated with complications and adverse outcomes with an increased incidence of vaso-occlusive, infectious, obstetrical and neonatal complications. Recently, in Paris (France) and Belo Horizonte (BH) (Brazil), integrated care sickle-obstetric units were created, associating sickle cell haematologist, obstetrician and infectious disease specialists, experienced in the care of these high risk pregnancies. Our aim is to compare in two different geographic institutions the prognostic and evolution of SCD in pregnant women with the prospective goal to build up a clinical score in order to better determine appropriate treatment. Methods: We conducted a retrospective study on 253 pregnancies (120 Paris, 133 BH) characterized by 147 Hb SS, 91 Hb SC, 14 Hb SBeta, 2 Hb SD hemoglobinopathy. An e-crf was developed, to screen: the pre-pregnancy, the ante-partum rates of SCD-specific and infectious complications. We compared the obstetrical and the newborns health parameters and complications, the rate of Caesarean section, the perinatal and the maternal mortality in both countries. Results and Discussion: In both populations, 60% of women had a maternal age between 21–30 years old (yo). However, in Brazil there was a higher rate of young pregnant women (14–20 yo) (4% Paris; 20% BH) while in France, patients were older (>31 yo) (36% Paris; 18% BH). In the history of SCD women followed in Paris we noticed that: -Most of these patients had a severe form of SCD with 53% who had experienced an acute chest syndrome and 9% with a symptomatic cerebral vasculopathy, several infectious complications with 26% of pyelonephritis, -A high level of obstetrical complications with 35% of miscarriage and 10% of intrauterine foetal death. The patients followed in Paris during their pregnancy, were treated according to the French guidelines published in 2009. According to these guidelines 67% of patients were transfused and 17% patients were not transfused because of a post-transfusion reaction history. Caesarean section was performed in most cases in both populations (79% in Paris with 23% performed in emergency; 66% in BH). In both populations, there was 1 materno-foetal death. Furthermore, in BH, 15 perinatal deaths and 7 patient deaths were observed. In the Paris' group, there was no other perinatal death and 1 maternal death following a post-transfusional reaction after delivery. The key difference between the 2 study groups concerns the foetal/neonatal morbidity and mortality. These results lead us to compare the 2 health care structures to try to find out the medical guidelines to significantly reduce the frequency of these severe clinical events. In Paris, we introduce oxygenotherapy at home during pregnancy (2l/min) in patients who were transfused because of severe SCD symptomatology (33 patients) and who could not anymore be transfused because of a severe post-transfusion reaction history (11 patients). For these subgroups of patients, we found that 40% of them didn't experience any VOC complications, or preeclampsia. The introduction of oxygenotherapy at home during pregnancy might have a positive impact in reducing the occurrence of a number life threatening complications in these high risk pregnant woman especially when they cannot be appropriately transfused. This study is the first initial step of an international effort by the ISCDO to optimise the treatment of SCD pregnant women, to harmonize the guidelines in different countries and develop new methods of diagnosis and treatment. By improving care and the sharing knowledge of these pregnancies, we would like to increase worldwide access to the development of directed family cord blood banks in families with SCD and the access to hematopoietic stem cell transplant and other innovative therapies in developing and emerging countries where SCD is highly prevalent. Disclosures: No relevant conflicts of interest to declare.

International audience; BACKGROUND: In October 2009, the French government organized a national-wide, free of charge vaccination campaign against pandemic H1N1 influenza virus, especially targeting pregnant women, a high risk group for severe illness. The study objective was to evaluate pandemic flu vaccine uptake and factors associated with non-vaccination in a population of pregnant women. METHODOLOGY/PRINCIPAL FINDINGS: In a prospective cohort conducted in 3 maternity hospitals in Paris, 882 pregnant women were randomly included between October 12, 2009 and February 3, 2010, with the aim to study characteristics of pandemic influenza during pregnancy. At inclusion, socio-demographic, medical, obstetrical factors and those associated with a higher risk of flu exposition and disease-spreading were systematically collected. Pandemic flu vaccine uptake was checked until delivery. 555 (62.9%) women did not get vaccinated. Determinants associated with non-vaccination in a multivariate logistic regression were: geographic origin (Sub-Saharan African origin, adjusted Odd Ratio aOR = 5.4[2.3-12.7], North African origin, aOR = 2.5[1.3-4.7] and Asian origin, aOR = 2.1[1.7-2.6] compared to French and European origin) and socio-professional categories (farmers, craftsmen and tradesmen, aOR = 2.3[2.0-2.6], intermediate professionals, aOR = 1.3[1.0-1.6], employees and manual workers, aOR = 2.5[1.4-4.4] compared to managers and intellectual professionals). The probability of not receiving pandemic flu vaccine was lower among women vaccinated against seasonal flu in the previous 5 years (aOR = 0.6[0.4-0.8]) and among those who stopped smoking before or early during pregnancy (aOR = 0.6[0.4-0.8]). Number of children less than 18 years old living at home, work in contact with children or in healthcare area, or professional contact with the public, were not associated with a higher vaccine uptake. CONCLUSIONS/SIGNIFICANCE: In this cohort of pregnant women, vaccine coverage against pandemic 2009 A/H1N1 flu was low, particularly in immigrant women and those having a low socio-economic status. To improve its effectiveness, future vaccination campaign for pregnant women should be more specifically tailored for these populations.

FJ6, N-methyl-N-(4-nitro-2-phenoxy­phenyl)­methanesulfon­amide, C14H14N2O5S, is an analogue of nimesulide, a selective inhibitor of cyclo­oxy­genase-2. The structure of the title compound has been characterized to understand its inactivity towards cyclo­oxy­genase-2.

Cryptococcus neoformans is a common life-threatening human fungal pathogen. The size of cryptococcal cells is typically 5 to 10 µm. Cell enlargement was observed in vivo, producing cells up to 100 µm. These morphological changes in cell size affected pathogenicity via reducing phagocytosis by host mononuclear cells, increasing resistance to oxidative and nitrosative stress, and correlated with reduced penetration of the central nervous system. Cell enlargement was stimulated by coinfection with strains of opposite mating type, and ste3 a Δ pheromone receptor mutant strains had reduced cell enlargement. Finally, analysis of DNA content in this novel cell type revealed that these enlarged cells were polyploid, uninucleate, and produced daughter cells in vivo. These results describe a novel mechanism by which C. neoformans evades host phagocytosis to allow survival of a subset of the population at early stages of infection. Thus, morphological changes play unique and specialized roles during infection., Author Summary Cryptococcus neoformans is a common life-threatening opportunistic human fungal pathogen. C. neoformans grows as a budding yeast in vitro with typical cell sizes ranging from 5 to 10 µm in diameter. Early reports suggested the presence of enlarged cells in human infections yet the identity of these cells and their role in virulence remained uncharacterized. Changes in cellular morphology are also observed in the mouse inhalation model of cryptococcosis. These enlarged “titan” cells accounted for 20% of the cells in the lungs. Titan cell formation was found to be regulated by a G-protein coupled receptor (GPCR) signal transduction pathway associated with pheromone sensing. Analysis of titan cells revealed uninucleate, polyploid cells that reproduced by budding, suggesting alterations in the regulation of cell growth and mitosis. Titan cell formation also affected host-pathogen interactions by reducing phagocytosis by host mononuclear cells and was correlated with reduced dissemination within the host. These results describe a novel mechanism by which C. neoformans undergoes morphogenesis to evade host phagocytosis, leading to the hypothesis that titan cell formation allows survival of a subset of the population and plays a unique and specialized role during infection.

Dual COX-2/5-LO inhibitors are described as potential new therapeutic agents for inflammatory diseases. A surprisingly potent effect of a 5-LO pharmacophoric group on the COX-2 inhibition is presented as well as pharmacological in vitro and in vivo results.

Dual COX/5-LOX (cyclooxygenase/5-lipoxygenase) inhibitors constitute a valuable alternative to classical non-steroidal anti-inflammatory drugs (NSAIDs) and selective COX-2 inhibitors for the treatment of inflammatory diseases. Indeed, these latter present diverse side effects, which are reduced or absent in dual-acting agents. In this review, COX and 5-LOX pathways are first described in order to highlight the therapeutic interest of designing such compounds. Various structural families of dual inhibitors are illustrated.

The design of selective COX-2 inhibitors is a new approach to obtain potent, anti-inflammatory drugs but with less side effects. Several families of such inhibitors were reported in literature. In this review, the drug design processes used to understand their binding mode and the origin of selectivity of these compounds are described.

Objective:To characterise major infectious complications and analyse potential risk factors in patients with Wegener granulomatosis (WG).Methods:Data from 113 patients with WG (69 male) followed at least once between January 1984 and March 2006 in our internal medicine department, were analysed retrospectively.Results:A total of 35 patients (mean (SD) age at WG diagnosis: 50.2 (13.05) years) developed 53 major infections. Infections were: bronchopneumonias (n = 19), herpes zoster recurrences (n = 9), cellulitis (n = 4), prostatitis (n = 4), spondylodiscitis and septic arthritis (n = 3), digestive tract infections (n = 2), Enterococcus faecalis or Staphylococcus aureus septicaemia (n = 2), viral hepatitis B reactivations (n = 2), post transfusion HIV infection with fatal cerebral toxoplasmosis, oesophageal candidiasis, disseminated herpes simplex and cytomegalovirus infection, cytomegalovirus retinitis, herpetic keratitis, herpetic stomatitis, Serratia sp. node suppuration and fever resolving under broad spectrum antibiotics (n = 1 each). Half of the major infectious episodes occurred within 3 years after WG diagnosis. Eight (7%) patients died, with two (2%) infection-related deaths. Patients diagnosed with WG before 1996 had a significantly higher rate of infection than those diagnosed later (48% vs 24%, p = 0.02). Cyclophosphamide and corticosteroids were independently associated with significantly higher risk of major infection (pConclusion:Cyclophosphamide and corticosteroids were associated with higher risk of infection. Despite systematic cotrimoxazole prophylaxis, major infections, mostly bronchopneumonias and herpes zoster recurrences, were still common in the course of WG.

Background Preterm prelabor rupture of membranes (PPROM) before 34 weeks of gestation complicates 1% of pregnancies and accounts for one-third of preterm births. International guidelines recommend expectant management, along with antenatal steroids before 34 weeks and antibiotics. Up-to-date evidence about the risks and benefits of administering tocolysis after PPROM, however, is lacking. In theory, reducing uterine contractility could delay delivery and reduce the risks of prematurity and its adverse short- and long-term consequences, but it might also prolong fetal exposure to inflammation, infection, and acute obstetric complications, potentially associated with neonatal death or long-term sequelae. The primary objective of this study is to assess whether short-term (48 h) tocolysis reduces perinatal mortality/morbidity in PPROM at 22 to 33 completed weeks of gestation. Methods A randomized, double-blind, placebo-controlled, superiority trial will be performed in 29 French maternity units. Women with PPROM between 220/7 and 336/7 weeks of gestation, a singleton pregnancy, and no condition contraindicating expectant management will be randomized to receive a 48-hour oral treatment by either nifedipine or placebo (1:1 ratio). The primary outcome will be the occurrence of perinatal mortality/morbidity, a composite outcome including fetal death, neonatal death, or severe neonatal morbidity before discharge. If we assume an alpha-risk of 0.05 and beta-risk of 0.20 (i.e., a statistical power of 80%), 702 women (351 per arm) are required to show a reduction of the primary endpoint from 35% (placebo group) to 25% (nifedipine group). We plan to increase the required number of subjects by 20%, to replace any patients who leave the study early. The total number of subjects required is thus 850. Data will be analyzed by the intention-to-treat principle. Discussion This trial will inform practices and policies worldwide. Optimized prenatal management to improve the prognosis of infants born preterm could benefit about 50,000 women in the European Union and 40,000 in the United States each year. Trial registration ClinicalTrials.gov identifier: NCT03976063 (registration date June 5, 2019).

International audience; Background: Mucormycosis incidence is increasing and is associated with a high rate of mortality. Although lipid-based formulations of amphotericin B are the recommended first-line treatment, only one prospective trial in a limited number of patients has been performed to evaluate this regimen. Methods: Patients with proven or probable mucormycosis were included between June 2007 and March 2011. Patients were scheduled to receive 10 mg/kg/day liposomal amphotericin B (L-AMB) monotherapy for 1 month and surgery was performed when appropriate. The primary outcome was response rate at week 4 or at the end of treatment (EOT) if before week 4, evaluated by an independent committee. ClinicalTrials.gov Identifier: NCT00467883. Results: Forty patients were enrolled. Response was analysed in 33 patients at week 4. Most patients had a haem-atological malignancy as their primary underlying disease (53%). Seventy-one percent of patients underwent therapeutic surgery. The response rate at week 4 or at EOT was 36%, with 18% partial responses and 18% complete responses. The response rate at week 12 was 45%, with 13% partial responses and 32% complete responses. Overall mortality was 38% at week 12 and 53% at week 24. Serum creatinine doubled in 16 (40%) patients and returned to normal levels within 12 weeks in 10/16 (63%). Conclusions: High-dose LAMB for mucormycosis, in combination with surgery in 71% of cases, was associated with an overall response rate of 36% at week 4 and 45% at week 12 and creatinine level doubling in 40% of patients (transient in 63%). These results may serve as the basis for future clinical trials.