First case report of acute cholangitis secondary to Cronobacter sakazakii.

INTRODUCTION: Cronobacter sakazakii is an opportunistic Gram-negative, rod-shaped bacterium which may be a causative agent of meningitis in premature infants and enterocolitis and bacteremia in neonates and adults. While there have been multiple cases of C. sakazakii infections, there have been no acute cholangitis cases reported in humans. CASE PRESENTATION: An 81-year-old male with a past medical history of basal cell carcinoma, alcoholic liver cirrhosis, transjugular intrahepatic portosystemic shunt procedure, complicated by staphylococcus bacteremia, pituitary tumor, glaucoma, and hypothyroidism presented to the emergency room with the complaint of diffuse and generalized 10/10 abdominal pain of 1 day's duration. There was a concern for pancreatitis, acute cholangitis, and possible cholecystitis, and the patient underwent a percutaneous cholecystostomy tube placement. Blood cultures from admission and biliary fluid cultures both grew C. sakazakii. The patient was treated with a carbapenem and clinically improved. CONCLUSIONS: The case study described a patient with multiple medical comorbidities that presented with C. sakazakii bacteremia and cholangitis. While this bacterium has been implicated in other infections, we believe this is the first time the bacteria is being documented to have caused acute cholangitis.

Mucormycosis with cutaneous involvement. A retrospective study of 115 cases at a tertiary care hospital in Mexico.

BACKGROUND/OBJECTIVES: Cutaneous mucormycosis is an emerging opportunistic mycosis caused by Mucorales. It can be divided into primary caused by trauma and secondary by extension of rhino-cerebral and disseminated cases. The objective is to present a retrospective study of cases of mucormycosis with cutaneous involvement. METHODS: A retrospective and descriptive study was carried out. Mucormycosis patients were included and divided into two groups: a) Primary Cutaneous and b) Secondary Cutaneous. Mycological tests were performed; the agents were identified by morphology and molecular studies (PCR and sequencing); some cases underwent histopathology. Clinical data and response to treatment were collected. RESULTS: 115 cases were included, 18 of primary, and 97 of secondary cutaneous mucormycosis. Primary cutaneous mucormycosis was most associated with adhesive bands (44.4%) and trauma from traffic accidents (33.3%). The principal clinical form was extensive and deep necrotic ulcers. Secondary cutaneous mucormycosis cases were rhino-cerebral with uncontrolled diabetes (81.4%) The most frequent clinical presentation was necrosis of the eyelid and the nose (65.9%). In both groups, the principal agent was Rhizopus arrhizus, 38.8% and 74.2% respectively. The most effective treatment was the combination of amphotericin B with surgical debridement. The clinical and mycological cure was achieved in 31.0% of primary cases, and 44.4% for secondary cases. CONCLUSION: Primary cutaneous mucormycosis is caused by implantation of the Mucorales due to trauma or rupture of the cutaneous barrier-breach, and secondary cutaneous mucormycosis develops as part of the rhino-cerebral process. The response to treatment depends on the extension and depth, as well as the predisposing factors.

Anticytokine autoantibodies leading to infection: early recognition, diagnosis and treatment options.

PURPOSE OF REVIEW: The current review gives a concise and updated overview of the relative new field of anticytokine autoantibodies (ACAA) and associated infections with a focus on recent findings regarding clinical manifestions, diagnostic and treatments. RECENT FINDINGS: Several recent case reports of unusual presentations of patients with neutralizing autoantibodies to IFN-γ and granulocyt macrophage colony-stimulating factor and expand the spectrum of clinical manifestations and suggest that anticytokine-mediated acquired immunodeficiency causing susceptibility to infection may be underdiagnosed. There is an expanding geographical distribution of antigranulocyt macrophage colony-stimulating factor associated Cryptococcus gattii infection. The spectrum of identified infections in patients with neutralizing antibodies to IFN-γ has a strong endemic component. Rituximab or cyclophophamide in addition to antimycobacterials could be a treatment options in refractory cases. NF-κB2 deficiency may be associated with a complex pattern of high titre neutralizing ACAA similar to autoimmune polyglandular syndrome type I and Thymoma. New technique for the detection of anticytokine antibodies are presented. Quantiferon testing, which is widely available for TB-diagnostic, may be repurposed to detect anti-IFN-γ autoantibodies. We propose that this test could be as well used to show if they are neutralizing. SUMMARY: ACAA are an emerging cause of acquired immunodeficiency which is likely underdiagnosed. Recent case reports document expanding spectra of clinical manifestations. NF-κB2 deficiency may be associated with a complex anti cytokine autoantibody pattern.

Human Papillomavirus-Associated Invasive Condylomas in a Man with Immunosuppressive Comorbidities.

Human papilloma virus (HPV) infections are one of the most common sexually transmitted diseases. We present the case of a 77-year-old Caucasian male with enormous genital warts of the penis, scrotum, groins and anus. Lesions were excised by electrosurgery. The histological examination revealed Condylomata gigantea as well as an invasive perianal squamous cell carcinoma. Mucosal "low-risk" HPV type 6 was detected. The patient had a history of an immunosuppressing disease. During the 4-year follow-up, multiple relapses occurred. Thus, particularly in immunosuppressed patients, early prophylactic HPV vaccination seems to be indicated for use in the prevention of HPV-associated mutilating and life-threatening disease. Vaccination should also protect from "low-risk" HPV.

Fifteen minute consultation: Fever in children being treated for cancer.

Fever is a common symptom in children receiving treatment for cancer. Clinicians and families are most concerned about febrile neutropenia, though non-neutropenic fever often causes more challenging treatment dilemmas. This article provides a structured approach to the initial assessment, examination, investigation and risk assessment of children with fever during treatment for childhood cancer. Non-neutropenic fever in children with cancer is not well researched. There are no systematic reviews of its management and no National Institute for Health and Care Excellence (NICE) (or other international) guidance about what to do. Features to consider when managing non-neutropenic fever are discussed. Febrile neutropenia, meanwhile, is an oncological emergency and requires management using standard sepsis principles including administration of broad-spectrum antibiotics. Relevant NICE guidance provides a clear structure for treatment. Ongoing management depends on the response to initial treatment.

[Customised infectiology - Immunogenetics]. / Infectiologie sur mesure - 1.Immunogénétique des maladies infectieuses†: premiers pas.

Recent discoveries in innate immunity together with improvements in the analysis of the human genome have led to the identification of factors that make certain individuals more susceptible to infections than other. We know understand why herpes simplex virus I, a virus with a minor burden in most individuals, is responsible for devastating encephalitis in children unable to detect primo-infection of neural cells. A growing number of patients are treated with immunosuppressive drugs in the field of oncology, organ transplantation and immunology. In such patients, opportunistic infections such invasive aspergillosis are clearly associated with genetic polymorphisms. Medical immune suppression represents a possible model for personalized approaches, in which infections could be prevented by individualized prophylactic strategies based on genetic testing.

Les progrès de la connaissance du système immunitaire inné et des techniques d'analyse du génome humain ont permis d'identifier des facteurs qui rendent certains individus susceptibles aux agents infectieux. C'est ainsi que l'on comprend depuis quelques années pourquoi le virus de l'herpès simplex I peut causer des encéphalites dévastatrices chez des enfants dont l'immunité est incapable de détecter la primo-infection. De plus en plus de patients subissent des traitements immunosuppresseurs dans le domaine de l'oncologie, des greffes d'organes ou de l'immunologie. Chez ces patients, certaines infections opportunistes, comme l'aspergillose pulmonaire invasive, sont clairement associées à des polymorphismes génétiques. L'immunosuppression Med représente un modèle possible d'infectiologie personnalisée, où les infections pourraient être prévenues par des prophylaxies individualisées, basées sur des tests génétiques.

[Combined application of NPWT-therapy and reamberin infusion in treatment of lower limb trophic ulcer (clinical case)]. / Sochetannoe primenenie NPWT-terapii i infuzii reamberina v lechenii troficheskoi iazvy nizhnei konechnosti (klinicheskoe nabliudenie).

A clinical case of successful combined use of NPWT-therapy and Reamberin infusion in the treatment of a non-healing (over 5 months) trophic ulcer of the lower limb in an elderly patient is presented. It was manifested that introduction of antioxidant/antihypoxant drug reamberin on the background of NPWT-therapy in patient with slow healing wounds has a positive effect on metabolic processes, resulting in more active and rapid cleansing of wound surface from opportunistic microflora by the 5th day of therapy. Absence of adverse effects to drug application allows to recommend its inclusion in the complex treatment scheme in patients with this pathology.

Biofilm formation - what we can learn from recent developments.

Although biofilms have been observed early in the history of microbial research, their impact has only recently been fully recognized. Biofilm infections, which contribute to up to 80% of human microbial infections, are associated with common human disorders, such as diabetes mellitus and poor dental hygiene, but also with medical implants. The associated chronic infections such as wound infections, dental caries and periodontitis significantly enhance morbidity, affect quality of life and can aid development of follow-up diseases such as cancer. Biofilm infections remain challenging to treat and antibiotic monotherapy is often insufficient, although some rediscovered traditional compounds have shown surprising efficiency. Innovative anti-biofilm strategies include application of anti-biofilm small molecules, intrinsic or external stimulation of production of reactive molecules, utilization of materials with antimicrobial properties and dispersion of biofilms by digestion of the extracellular matrix, also in combination with physical biofilm breakdown. Although basic principles of biofilm formation have been deciphered, the molecular understanding of the formation and structural organization of various types of biofilms has just begun to emerge. Basic studies of biofilm physiology have also resulted in an unexpected discovery of cyclic dinucleotide second messengers that are involved in interkingdom crosstalk via specific mammalian receptors. These findings even open up new venues for exploring novel anti-biofilm strategies.

Adjunctive interferon-γ immunotherapy in a pediatric case of Aspergillus terreus infection.

Aspergillus terreus causes invasive aspergillosis (IA) in immunocompromised patients. Treatment is complicated by intrinsic resistance to amphotericin B and thereby contributing to a high mortality. Therefore, we conducted in vitro studies to investigate the effectivity of adjunctive recombinant interferon-γ immunotherapy. We describe a pediatric patient with A. terreus IA who received adjunctive recombinant interferon-γ (rIFNγ) immunotherapy. In vitro studies were conducted to investigate the capacity of rIFNγ to improve antifungal host defense in terms of fungal killing ability and the release of pro-inflammatory cytokines in cells of the patient as well as healthy controls. An 8-year-old female pediatric patient with leukemia developed A. terreus IA. She clinically deteriorated and had high serum galactomannan levels despite broad antifungal therapy. Therefore, adjunctive immune stimulatory therapy with rIFNγ was initiated. After 3 weeks of treatment, galactomannan levels decreased and the patient clinically showed improvement. Addition of rIFNγ boosted the capacity of monocytes of healthy volunteers to mount TNFα and IL-1ß cytokine responses to Escherichia coli LPS, and increased TNFα response to both A. terreus and Aspergillus fumigatus. Monocytes isolated from the patient's blood demonstrated a similar augmented cytokine induction in response to rIFNγ. In addition, rIFNγ increased the capacity of monocytes from healthy volunteers as well as monocytes from the patient to kill A. terreus spores. Adjuvant immunotherapy with rIFNγ might be a promising additional treatment strategy that could be used to improve outcome in patients with refractory invasive A. terreus infections or other resistant invasive Aspergillus infections.

Scedosporium and Lomentospora: an updated overview of underrated opportunists.

Species of Scedosporium and Lomentospora are considered as emerging opportunists, affecting immunosuppressed and otherwise debilitated patients, although classically they are known from causing trauma-associated infections in healthy individuals. Clinical manifestations range from local infection to pulmonary colonization and severe invasive disease, in which mortality rates may be over 80%. These unacceptably high rates are due to the clinical status of patients, diagnostic difficulties, and to intrinsic antifungal resistance of these fungi. In consequence, several consortia have been founded to increase research efforts on these orphan fungi. The current review presents recent findings and summarizes the most relevant points, including the Scedosporium/Lomentospora taxonomy, environmental distribution, epidemiology, pathology, virulence factors, immunology, diagnostic methods, and therapeutic strategies.

Opportunistic fungal infection in children and management.

PURPOSE OF REVIEW: An opportunistic mycosis is a fungal agent of low pathogenicity that specifically infects immunocompromised hosts. Advances in transplantation, preterm care, immunosuppressive therapies and intensive care, have lead to the emergence of pediatric patients with serious immunodeficiency who are vulnerable to nonpathogenic fungi. RECENT FINDINGS: The advent of the use of biologic agents in pediatric disease as well as the advances in care of preterm and immunosuppressed patients opens up a new cohort of patients at risk of opportunistic mycotic infections. Recent cases of cutaneous histioplasmosis as the presenting sign of hyper-IgM syndrome and the case of cutaneous blastomycosis in a patient treated with infliximab underscore the need to have a high clinical suspicion for deep fungal infections in immunosuppressed patients. SUMMARY: The current review will focus on the cutaneous manifestations of cutaneous infections by Aspergillus, Blastomyces, histoplasmosis, and mucormycosis. Greater understanding of these diseases and high-quality research in identification and treatment can enhance care of patients in the coming future.

The Child with Recurrent Mycobacterial Disease.

PURPOSE OF REVIEW: Many genetic conditions predispose affected individuals to opportunistic infections. A number of immunodeficiency diseases, including genetic defects termed Mendelian susceptibility to mycobacterial disease (MSMD), permit infection from many different strains of mycobacteria that would otherwise not cause disease. These include tuberculous and nontuberculous mycobacteria, and bacille Calmette-Guérin vaccine (BCG). Patients may present with infections from other organisms that depend on macrophage function for containment. Defects in multiple genes in the IL-12 and NFKB signaling pathways can cause the MSMD phenotype, some of which include IL12RB1, IL12B, IKBKG, ISG15, IFNGR1, IFNGR2, CYBB, TYK2, IRF8, and STAT1. RECENT FINDINGS: Multiple autosomal recessive and dominant, and 2 X-linked recessive gene defects resulting in the MSMD phenotype have been reported, and others await discovery. This review presents the known gene defects and describes clinical findings that result from the mutations. If MSMD is suspected, a careful clinical history and examination and basic immunodeficiency screening tests will narrow the differential diagnosis. A specific diagnosis requires more sophisticated laboratory investigation. Genetic testing permits a definitive diagnosis, permitting genetic counseling. Mild cases respond well to appropriate antibiotic therapy, whereas severe disease may require hematopoietic stem cell transplantation.

Successful treatment of pulmonary mucormycosis in two pediatric hematopoietic stem cell transplant patients.

Pulmonary mucormycosis diagnosed immediately after hematopoietic stem cell transplantation frequently portends a poor prognosis. However, here we describe two cases in children that were treated successfully to highlight the efficacy of a multidisciplinary approach. Despite diagnosis in the immediate post-transplant period and requirement for ongoing immunosuppression to prevent or treat GVHD, both are long-term survivors due to early surgical debridement with transfusion support and prompt initiation of targeted antifungal therapy. In the absence of evidence-based treatment guidelines, survival of pulmonary mucormycosis is achievable even in high-risk patients with a multidisciplinary team to guide management.

Viral infections directly involved in kidney allograft function.

Modern immunosuppressive therapy has dramatically reduced the incidence of acute rejection and improved graft survival in kidney transplant patients. However, infectious complications remain an important issue. Amongst the various pathogens, viruses such as adenovirus and polyomavirus BK can directly cause acute or chronic graft dysfunction. Adenovirus mainly causes haemorrhagic cystitis and tubulointerstitial nephritis in kidney transplant patients. While patients show apparent clinical symptoms such as fever, dysuria, gross haematuria, frequency and urgency of urination, and most patients show acute graft dysfunction, these symptoms and graft dysfunction are reversible. Polyomavirus BK infection, however, is asymptomatic but graft outcome is poor if the patient develops tissue-invasive nephropathy confirmed by graft biopsy. Recently, an attempt to create a pathological classification for predicting the clinical course has been made by the Banff Working Group on Polyomavirus Nephropathy. With regards to treatment, the basic strategy is a reduction of calcineurin inhibitor and/or antimetabolites, and the effectiveness of several adjunct treatments has been investigated in several clinical trials. There are other unresolved issues, such as the diagnosis of subsequent acute rejection, the definition of remission, methods of resuming immunosuppression and long-term follow-up. Most of all, development of effective vaccines and novel drug discovery are necessary to prevent the development and progression of BKV-associated nephropathy.

Brain abscess caused by Micrococcus luteus in a patient with systemic lupus erythematosus: case-based review.

Central nervous system infections, which are rarely seen in systemic lupus erythematosus (SLE), have considerably high mortality but they are difficult to distinguish from neuropsychiatric manifestation of lupus. This article reports the case of a patient with SLE with brain abscess which developed during immunosuppressive therapy for lupus nephritis. The patient completely recovered without neurological sequelae by open surgical drainage and 12-week antibiotic therapy. It is recommended that CNS infections must be excluded in patients with SLE, particularly who are receiving immunosuppressive therapy.

Mycobacterium longobardum Infection in the Hand.

Mycobacterium longobardum is a slow-growing, nontuberculous mycobacterium that was first characterized in 2012. We report a case of M. longobardum infection in the right middle finger of a diabetic man. He underwent surgery for a presumed diagnosis of an epidermal inclusion cyst. Molecular diagnosis of the surgical specimens demonstrated M. longobardum through RNA polymerase ß-subunit encoding gene sequencing. After surgery, the patient was treated with antibiotics and eventually cured of the infection. To the best of our knowledge, this is only the second reported case of a pathogenic M. longobardum infection worldwide and the first such case in the hand. The purposes of this case study are to alert treating providers to consider nontuberculous mycobacterium infection when an inflammatory process persists, discuss signs and symptoms of the disease, and provide general treatment guidelines.

Yarrowia lipolytica: a beneficious yeast in biotechnology as a rare opportunistic fungal pathogen: a minireview.

Yarrowia lipolytica is one of the most studied "non-conventional" yeast species capable of synthesizing a wide group of valuable metabolites, in particular lipases and other hydrolytic enzymes, microbial oil, citric acid, erythritol and γ-decalactone. Processes based on the yeast have GRAS status ("generally recognized as safe") given by Food and Drug Administration. The majority of research communications regarding to Y. lipolytica claim that the yeast species is non-pathogenic. In spite of that, Y. lipolytica, like other fungal species, can cause infections in immunocompromised and critically ill patients. The yeast possess features that facilitate invasion of the host cell (particularly production of hydrolytic enzymes), as well as the protection of the own cells, such as biofilm formation. The aim of this study was to present well-known yeast species Y. lipolytica as a rare opportunistic fungal pathogen. Possible pathogenicity and epidemiology of this yeast species were discussed. Antifungal drugs susceptibility and increasing resistance to azoles in Y. lipolytica yeasts were also presented.

Immunotherapy for infectious diseases in haematological immunocompromise.

Opportunistic infections remain a major problem across a broad spectrum of immunocompromised haematological patient groups, with viruses, bacteria, fungi and protozoa all presenting significant challenges. Given the major difficulties in treating many of these infections with the currently available antimicrobial chemotherapeutic arsenal, and the rapid emergence of antimicrobial resistance amongst all of the microbial kingdoms, novel strategies that enable host control or elimination of infection are urgently required. Recently, major progress has been made in our understanding of host immunocompromise in the haematological patient. In addition, a wide range of novel immunomodulatory strategies for infectious diseases have been developed. Here we discuss the major and wide-ranging areas of progress that have been made for host-directed immunotherapies in the context of infectious diseases, with relevance to haematological immunocompromise.

Cytomegalovirus disease in hematopoietic stem cell transplant patients: current and future therapeutic options.

PURPOSE OF REVIEW: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has become one of the standard treatment for hematological diseases. Although the clinical outcome has improved significantly during the last decades, the morbidity and mortality after allo-HSCT are still obstacles to cure. Out of major morbidities, opportunistic virus infections such as cytomegalovirus (CMV) infection are important complications, in particular in patients who received human leukocyte antigen-mismatched HSCT. Here, we aim to summarize information about current and future therapeutic options in CMV disease after allo-HSCT. RECENT FINDINGS: Recently, not only new drugs but also adoptive T-cell therapy are tested in the setting of clinical trials. CMV prophylaxis using letermovir significantly reduced the incidence of CMV disease in comparison to placebo in a phase III clinical trial. Meanwhile, adoptive T-cell therapies which are fully adapted to good manufacturing practice (GMP) conditions are now available. A recent multicenter study in Germany showed a promising result using Streptamer-isolated T-cell therapy. SUMMARY: With the recent development of CMV-targeted therapy, treatment strategies of CMV infection would be further sophisticated in the near future. VIDEO ABSTRACT: http://links.lww.com/COID/A19.

Treatment of severe alcoholic hepatitis: past, present and future.

Alcoholic hepatitis (AH) manifests as a clinical syndrome characterized by recent jaundice and liver function deterioration in an actively drinking patient. The principal cause of AH is alcoholic steatohepatitis (ASH) defined histologically by the coexistence of steatosis, hepatocyte ballooning and satellitosis. While nonsevere AH usually responds to alcohol abstinence, severe AH, identified by Maddrey scoring ≥ 32, has a bad prognosis and is traditionally treated by a 28-day course of prednisone therapy. A recent trial, which showed no improvement of long-term survival but significant reduced mortality after 28 days of corticoid therapy compared to placebo, opens a debate on its efficacy. N-acetyl-cysteine supplementation combined with steroid therapy is also able to reduce the 28-day mortality compared to steroid alone. While guidelines recommend high-calorie intake and protein supplementation in decompensated liver diseases, intensive enteral nutrition together with corticoid treatment does not reduce mortality compared to corticoid alone in a recent study with ASH patients. Stimulation of liver regeneration through interleukin-22, granulocyte colony-stimulating factor or farnesoid X receptor agonists, inhibition of apoptosis, early liver transplantation and modulation of gut microbiota through antibiotic or faecal transplantation approaches constitute new therapeutic perspectives that are investigated in current clinical trials. Inhibition of oxidative stress, modulation of gut fungal populations and stimulation of progenitor cell proliferation and pro-regenerative inflammatory pathways constitute prospects for future human trials. For long-term survival, strategies for persistent alcohol abstinence remain the key of success, opening another large research field.