Recurrent Staphylococcal Infections Research Articles

Clinical diagnosis of chronic mucocutaneous candidiasis in a patient with recurrent staphylococcal infections

Chronic mucocutaneous candidiasis is a primary immunodeficiency characterized by persistent or recurrent candidal infections of the skin, nails, or mucous membranes. It can be associated with endocrinopathies and autoimmune diseases. A 37-years-old male patient is presented who attended an immunology consultation referred from the dermatology service due to recurrent pyodermitis of several years of evolution; the physical examination also revealed signs of candidiasis in the oral mucosa and lip corners, in the eyelids of both eyes and skin in the abdominal region, which were recurrent, as well as onychomycosis in all toenails. The microbiological study of the pyodermitis lesions showed infection by staphylococcus aureus, and the lesions of the mouth, eyes, abdominal skin and nails showed the presence of Candida albicans. Delayed intradermal skin testing was performed with no T cell response to Candida and Trichophyton antigens. Complementary drugs were indicated to rule out any associated endocrine disorder

Bacterial biofilm formation and anti-biofilm strategies

Bacteria are ubiquitous prokaryotes. They are involved in biofilm formation and also have the ability to produce anti-biofilm products for biofilm mitigation. This special issue entitled: “Biofilms- community structure, applications and mitigation” of the journal Research in Microbiology was designed to discuss the flexibility of bacterial biofilms and their products under particular circumstances. Given that quorum sensing (QS) controls biofilm growth in some situations, especially for pathogenic bacteria antibiotic evading strategies. In Gram-negative bacteria, N-acyl homoserine lactones are the major quorum sensing signaling molecules. Another approach to prevent bacterial biofilm formation may be to inhibit the QS-regulated activities using quorum quenching (QQ). In this context, QS inhibitors and QS enzymes are important because they, respectively, interfere with signal creation, perception, or degradation and chemical modification. There have been numerous reports of QQ enzymes from bacteria. Treatment failure and recurrent staphylococcal infections are also brought on by biofilm development, which boosts an organism's ability to withstand antibiotics and is thought to be a virulence factor in patients. However, polyphenol quercetin antibiofilm activity is naturally available against drug-resistant Staphylococcus aureus.

P20 Job syndrome: hyper IgE syndrome in a young girl with an acneiform rash

Abstract Hyper IgE syndrome (HIES1) is a rare, autosomal dominant, primary immunodeficiency characterized by eczema, recurrent staphylococcal skin infections, pneumonia, increased serum IgE and eosinophilia. It is caused by a heterozygous mutation in the STAT3 gene on chromosome 17q21 with variable expressivity. Nonimmunological findings including characteristic facies, hyperextensibility, long-bone fractures, aneurysms, craniosynostosis and dental abnormalities. We present the case of an 11-year-old girl referred to dermatology with an acneiform facial rash. Examination was consistent with papulo-pustular scarring acne of the face and back. Her history was also significant for recurrent MSSA bacterial lymphadenitis requiring incision and drainage over the proceeding 3 years. Her past medical history was significant for the development of moderate-severity infantile acne at 2 weeks of age, mild childhood eczema, recurrent childhood otitis media Staphylococcus infections resulting in grommet insertion, primary tooth retention requiring extraction and a fractured wrist at age 9 years. Because of the burden of infection the patient was referred to immunology in Crumlin. Investigations revealed mild neutropenia, marginally elevated IgA and IgM, normal eosinophils, marginally elevated IgE, normal lymphocyte subsets, intact complement pathways and normal oxidative burst test. Next-generation sequencing was significant for STAT3 gene mutation consistent with HIES. As there is no family history this likely represents a de novo mutation. The patient is currently on prophylactic azithromycin and low-dose isotretinoin with good effect. This case represents a patient with both immunological and nonimmunological features of HIES1, marginally elevated IgE, absence of eosinophils and negative family history.

Hyper IgE syndrome with congenital hypothyroidism: a rare association

Hyper IgE syndrome (HIES) is a rare immunodeficiency syndrome, with autosomal dominant inheritance, caused mainly due to STAT 3 mutation. The affected children usually present with atopic dermatitis, recurrent staphylococcal infections, phenotypic characteristics and increased IgE levels. Though, there is a case report of autoimmune thyroiditis in HIES, congenital hypothyroidism is not reported. Here we report a case of HIES with typical phenotypic features with congenital hypothyroidism that presented to us with recurrent infections, atopic dermatitis and pneumatocele of right lung. Child was subsequently managed with antibiotics, levothyroxine and lobectomy.

Hyper‐IgE syndrome presenting with early life craniosynostosis in monozygotic twin sisters

<scp>Hyper‐IgE</scp> syndrome presenting with early life craniosynostosis in monozygotic twin sisters

Solution Structural Studies of Pre-amyloid Oligomer States of the Biofilm Protein Aap

Staphylococcus epidermidis is a commensal bacterium on human skin that is also the leading cause of medical device-related infections. The accumulation-associated protein (Aap) from S. epidermidis is a critical factor for infection via its ability to mediate biofilm formation. The B-repeat superdomain of Aap is composed of 5 to 17 Zn2+-binding B-repeats, which undergo rapid, reversible assembly to form dimer and tetramer species. The tetramer can then undergo a conformational change and nucleate highly stable functional amyloid fibrils. In this study, multiple techniques including analytical ultracentrifugation (AUC) and small-angle X-ray scattering (SAXS) are used to probe a panel of B-repeat mutant constructs that assemble to distinct oligomeric states to define the structural characteristics of B-repeat dimer and tetramer species. The B-repeat region from Aap forms an extremely elongated conformation that presents several challenges for standard SAXS analyses. Specialized approaches, such as cross-sectional analyses, allowed for in-depth interpretation of data, while explicit-solvent calculations via WAXSiS allowed for accurate evaluation of atomistic models. The resulting models suggest mechanisms by which Aap functional amyloid fibrils form, illuminating an important contributing factor to recurrent staphylococcal infections.

Job’s Syndrome With a Family History of Kawasaki Disease: A Case Presentation and Review of Literature

Background: Job’s syndrome or hyper-immunoglobulin E (IgE) syndrome (HIES) is an extremely rare primary immunodeficiency disease with an approximate annual incidence of less than 1/1000000. It is characterized by recurrent cold staphylococcal infections, unusual eczematous dermatitis, severe lung infections, and extensively high concentrations of the serum antibody IgE. Case Presentation: A typical case of Job’s syndrome with a family history of Kawasaki disease is presented in this study aiming at identifying the clinical features, investigational procedures, and management strategy, as well as evaluating the role of the ear, nose, and throat specialist and highlighting the probable relation between Job’s syndrome and Kawasaki disease. Conclusions: In general, early detection with proper care can prevent the progression of Job syndrome. In addition, the initiated treatment at the first signs of infection is mandatory for preventing long-term complications. There is a probable relation between Job and Kawasaki which requires more consideration.

1606. Distinct Effectiveness of Oritavancin Against Tolerance-Induced Staphylococcus aureus

BackgroundWithin a sufficiently large bacterial population, some members will naturally adopt an alternate, metabolically-active state that favors small molecule synthesis over cell division. In Staphylococcus aureus this process can be sharply accelerated by multiple factors present during infection including nutrient limitation, host cationic peptide exposure and polymorphonuclear neutrophil internalization. These isogenic “tolerant” subpopulations have variable responses during antibiotic exposure and can remain viable in the presence of typically bactericidal concentrations. Survivors of antibiotic exposure can restart cell division upon cessation of antibiotics and cause relapse or recurrent infection. In this study we determine the ability of typical and atypical antistaphylococcal therapies to reduce the viability of tolerant Staphylococcus aureus bacteria.Methods S. aureus strain ATCC29213 as well as four clinical isolates (two MSSA, two MRSA) were selected for analysis. Overnight cultures were diluted in pre-warmed broth (MHB50) to 1×106 cfu/mL. Tolerance was induced by exposure to mupirocin (low [0.032 µg/mL] or high [3.2 µg/mL]) for 30 min. Tolerant cultures were exposed to vancomycin (35 µg/mL), cefazolin (25 µg/mL), daptomycin (7 µg/mL), telavancin (10 µg/mL), dalbavancin (6 µg/mL) or oritavancin (14 µg/mL) and viability was assessed by dilution plating at pre-defined time points (0, 2, 6, 24, 48 h). The minimum duration for 3-log viability reduction from baseline (MDK99.9) and culture viability at 48h were calculated independently for each of three biological replicates.ResultsThe rate of bacterial killing (MDK99.9) was reduced for all study antibiotics by the addition of mupirocin in a dose-dependent manner. In contrast to all other regimens, including lipoglycopeptide comparators, oritavancin was the only antimicrobial agent that maintained a similar extent of bacterial killing against tolerant staphylococci.ConclusionAntimicrobial tolerant staphylococci exhibit a decreased rate of killing by antistaphylococcal agents. However, oritavancin remained effective at maintaining a similar extent of killing. Further studies to investigate the role of otritavancin against recurrent or relapse staphylococcal infection is warranted.Disclosures All Authors: No reported disclosures

Staphylococcus aureus and Hyper-IgE Syndrome.

Hyper-immunoglobulin E syndrome (HIES) is a primary immunodeficiency disease characterized by recurrent Staphylococcus aureus (S. aureus) infections, eczema, skeletal abnormalities and high titers of serum immunoglobulin E. Although the genetic basis of HIES was not known for almost a half century, HIES most frequently exhibits autosomal dominant trait that is transmitted with variable expressivity. Careful genetic studies in recent years identified dominant-negative mutations in human signal transducer and activator of transcription 3 (STAT3) gene as the cause of sporadic and dominant forms of HIES. The STAT3 mutations were localized to DNA-binding, SRC homology 2 (SH2) and transactivating domains and disrupted T helper 17 (TH17) cell differentiation and downstream expression of TH17 cytokines IL-17 and IL-22. Deficiency of IL-17 and IL-22 in turn is responsible for suboptimal expression of anti-staphylococcal host factors, such as neutrophil-recruiting chemokines and antimicrobial peptides, by human keratinocytes and bronchial epithelial cells. TH17 cytokines deficiency thereby explains the recurrent staphylococcal lung and skin infections of HIES patients.

Distinct Effectiveness of Oritavancin against Tolerance-Induced Staphylococcus aureus.

Within a sufficiently large bacterial population, some members will naturally adopt an alternate, metabolically-active state that favors small molecule synthesis over cell division. These isogenic “tolerant” subpopulations have variable responses during antibiotic exposure and can remain viable in the presence of typically bactericidal concentrations. In this study, we determine the ability of typical and atypical antistaphylococcal therapies to reduce the viability of mupirocin-induced tolerant Staphylococcus aureus bacteria. Overall, tolerance-induced staphylococci exhibited a markedly decreased rate and extent of killing following antibiotic exposure. However, oritavancin remained effective at maintaining a similar extent of killing. Further studies to investigate the role of oritavancin against recurrent or relapse staphylococcal infection are warranted.

The role of the msaABCR operon in implant-associated chronic osteomyelitis in Staphylococcus aureus USA300 LAC

BackgroundThe msaABCR operon regulates several staphylococcal phenotypes such as biofilm formation, capsule production, protease production, pigmentation, antibiotic resistance, and persister cells formation. The msaABCR operon is required for maintaining the cell wall integrity via affecting peptidoglycan cross-linking. The msaABCR operon also plays a role in oxidative stress defense mechanism, which is required to facilitate persistent and recurrent staphylococcal infections. Staphylococcus aureus is the most frequent cause of chronic implant-associated osteomyelitis (OM). The CA-MRSA USA300 strains are predominant in the United States and cause severe infections, including bone and joint infections.ResultsThe USA300 LAC strain caused significant bone damage, as evidenced by the presence of severe bone necrosis with multiple foci of sequestra and large numbers of multinucleated osteoclasts. Intraosseous survival and biofilm formation on the K-wires by USA300 LAC strains was pronounced. However, the msaABCR deletion mutant was attenuated. We observed minimal bone necrosis, with no evidence of intramedullary abscess and/or fibrosis, along reduced intraosseous bacterial population and significantly less biofilm formation on the K-wires by the msaABCR mutant. microCT analysis of infected bone showed significant bone loss and damage in the USA300 LAC and complemented strain, whereas the msaABCR mutant’s effect was reduced. In addition, we observed increased osteoblasts response and new bone formation around the K-wires in the bone infected by the msaABCR mutant. Whole-cell proteomics analysis of msaABCR mutant cells showed significant downregulation of proteins, cell adhesion factors, and virulence factors that interact with osteoblasts and are associated with chronic OM caused by S. aureus.ConclusionThis study showed that deletion of msaABCR operon in USA300 LAC strain lead to defective biofilm in K-wire implants, decreased intraosseous survival, and reduced cortical bone destruction. Thus, msaABCR plays a role in implant-associated chronic osteomyelitis by regulating extracellular proteases, cell adhesions factors and virulence factors. However additional studies are required to further define the contribution of msaABCR-regulated molecules in osteomyelitis pathogenesis.

Recurrent staphylococcal abscess in an adolescent with hyperimmunoglobulin E syndrome: A rare presentation

Hyperimmunoglobulin E syndrome (HIES) more commonly referred to as Job’s syndrome, is an infrequent primary immunodeficiency disorder. It can be inherited either by autosomal dominant or recessive mode with each one having distinct varied clinical presentation. The distinguishing clinical features include recurrent infections, dermatitis, and elevated serum immunoglobulin E (IgE) levels. We report a case of an adolescent female who presented with recurrent staphylococcal infection with axillary lymphadenitis, positive family history, and abnormal facial features mainly broad forehead, facial asymmetry, and peripheral blood eosinophilia with significantly high serum IgE levels, suggestive of autosomal dominant HIES.

RECURRENT STAPHYLOCOCCAL ABSCESS IN AN ADOLESCENT WITH HYPERIMMUNOGLOBULIN E SYNDROME: A RARE PRESENTATION

Hyperimmunoglobulin E syndrome (HIES) more commonly referred to as Job’s syndrome, is an infrequent primary immunodeficiency disorder. It can be inherited either by autosomal dominant or recessive mode with each one having distinct varied clinical presentation. The distinguishing clinical features include recurrent infections, dermatitis, and elevated serum immunoglobulin E (IgE) levels. We report a case of an adolescent female who presented with recurrent staphylococcal infection with axillary lymphadenitis, positive family history, and abnormal facial features mainly broad forehead, facial asymmetry, and peripheral blood eosinophilia with significantly high serum IgE levels, suggestive of autosomal dominant HIES.

Evasion of host defenses by intracellular Staphylococcus aureus.

Staphylococcus aureus is one of the leading causes of hospital and community-acquired infections worldwide. The increasing occurrence of antibiotic resistant strains and the high rates of recurrent staphylococcal infections have placed several treatment challenges on healthcare systems. In recent years, it has become evident that S. aureus is a facultative intracellular pathogen, able to invade and survive in a range of cell types. The ability to survive intracellularly provides this pathogen with yet another way to evade antibiotics and immune responses during infection. Intracellular S. aureus have been strongly linked to several recurrent infections, including severe bone infections and septicemias. S. aureus is armed with an array of virulence factors as well as an intricate network of regulators that enable it to survive, replicate and escape from a number of immune and nonimmune host cells. It is able to successfully manipulate host cell pathways and use it as a niche to multiply, disseminate, as well as persist during an infection. This bacterium is also known to adapt to the intracellular environment by forming small colony variants, which are metabolically inactive. In this review we will discuss the clinical evidence, the molecular pathways involved in S. aureus intracellular persistence, and new treatment strategies for targeting intracellular S. aureus.

Darier Disease – A Clinical Illustration of Its High Variable Expressivity

Darier disease (DD), also known as dyskeratosis follicularis, is a rare genodermatosis classically characterized by persistent hyperkeratotic papules and plaques affecting the seborrheic areas. Due to its variable expressivity, it can present with very discrete clinical features for many years, leading to diagnostic errors and incorrect treatments.We report an unusual case of Darier disease in a 69-year-old male patient in which the classical features of DD had a remarkably late onset. This patient had a several decades’ history of small, recurrent, scattered papules, limited to the face, for which he had received multiple diagnostic interpretations, such as acne or recurrent staphylococcal skin infection. We established the diagnosis of DD with superinfected lesions, and initiated treatment with intravenous antibiotics and oral retinoids. Results were extremely satisfactory in a very short time.This case shows an extremely unusual clinical course of Darier disease and is illustrative for the variable expressivity of the disease. It highlights the need to take dyskeratosis follicularis into account in patients with a longstanding history of persistent, hyperkeratotic papules, from unknown origin, even in the absence of the classical clinical findings.

Unusual presentations and associations of hyper IgE Syndrome: Retrospective analysis of ten cases at tertiary care institute – With review of indian published reports

Background: Job syndrome also known as hyper IgE syndrome (HIES) is primary immunodeficiency syndrome. Autosomal dominant variant caused by mutation in signal transducer and activator of transcription-3 gene is characterized by recurrent staphylococcal skin infections, sinopulmonary infections, eczema, recurrent bone fractures, and coarse facial features. Autosomal recessive (AR) variant is because of mutation in DOCK8 gene which lacks the skeletal and dental involvement but manifest with severe viral infection and develop neurological complications. Aims: This study aims to evaluate variable presentations and associations of job syndrome. Methods: Analysis of ten cases, presented at our department between October 2015 and September 2016, with suspected HIES was done retrospectively. All cases were studied for their presentations and associations and were investigated accordingly for the same. Score for HIES was counted as per National Institutes of Health (NIH) scoring system. Indian published reports were found by internet search engine and were reviewed for unusual presentations. Results: NIH scoring was indeterminate in two patients and was highly likely for autosomal dominant-HIES in five patients. Three patients were diagnosed as AR-HIES. Two of our patients had multiple endocrinopathy, one had pyoderma gangrenosum and two patients had autoimmune disorders. Limitations: Genetic analysis was not done because of nonavailability of testing in our state and poor financial conditions of patients. It is a retrospective study. Conclusion: Our patients had unusual association in the form of multiple endocrinopathy, pyoderma gangrenosum, dermatomyositis, and all were diagnosed very much late in life. Hence, a vigilant eye for suspicion at a younger age might benefit patients.

50 Years Ago in The Journal of Pediatrics: Bacterial Interference in the Treatment of Recurrent Staphylococcal Infections in a Family

50 Years Ago in The Journal of Pediatrics: Bacterial Interference in the Treatment of Recurrent Staphylococcal Infections in a Family

CNS vasculitis and stroke as a complication of DOCK8 deficiency: a case report

BackgroundPrimary immunodeficiency disorders associated with autoimmunity are poorly understood. Central nervous system (CNS) vasculitis can complicate the courses of such entities, but it is underappreciated. Deletion of the dedicator of cytokinesis 8 (DOCK8) gene is considered to be the autosomal recessive form of hyperimmunoglobulin E syndrome which is a rare type of primary immunodeficiency disease characterized by elevated levels of IgE antibody, eczema, and recurrent staphylococcal infections. DOCK8 deletion is associated with fatal CNS vasculitis. However, descriptions of such cases and their outcomes are scarce in the literature.Case presentationThis report describes a young female with a DOCK8 gene deletion presenting acutely with squint, fatigue and visual hallucinations. The patient was diagnosed as having neuritis of the third oculomotor nerve and encephalitis, which were thought to be related to her underlying immune deficiency, however, she subsequently was diagnosed with CNS vasculitis based on brain magnetic imaging and magnetic resonance angiography findings. We provide here a comprehensive description of the patient’s clinical outcome and outline an effective treatment approach that may be useful for similar patients and includes the use of steroids and mycophenolate mofetil (MMF). The treatment was well tolerated and enabled the patient to recover most of her neurological deficits. However, despite the initial improvement, she later developed stroke.ConclusionsTo the best of our knowledge, this is the first report in the literature of a case of primary immunodeficiency complicated by CNS vasculitis demonstrating a successful outcome. Our observations indicate that the combination of MMF and steroids is an effective treatment for CNS vasculitis associated with DOCK8 deficiency. However, lack of awareness of the neurological comorbidities associated with primary immunodeficiencies and the delay in diagnosis likely contributed to the development of acute cerebral infarction. Early treatment and aggressive control of the disease’s initial inflammation is essential for preventing catastrophic stroke.

Use of Staphylococcus aureus Phage Lysate Staphage Lysate (SPL)® for the Control of Recurrent Pyoderma Eczema in Dogs with Atopic Dermatitis

Background: Recurrent staphylococcal infections are frequent in dogs with atopic dermatitis (AD). Many factors seem to contribute to making bacterial pyoderma refractory to treatment. Short-term systemic antibiotic therapy is effective for the treatment of acute symptoms, and may, along with pulsatile therapy, contribute to the long-term control of the disease. However, microbial resistance has become a growing and alarming problem. The aim of this study was to evaluate whether the use of Staphylococcus aureus Phage Lysate Staphage Lysate (SPL)®, can minimize the symptoms of recurrent pyoderma and increase the interval between acute atopic manifestations in dogs.Materials, Methods &amp; Results: Thirteen dogs with a history of Canine Atopic Dematitis (CAD) and recurrent bacterial pyoderma received SPL at increasing intervals for 23 weeks. The contents of an intact pustule of each dog was collected and submitted to microbiological analysis. Systemic antibiotic therapy was established for the first 4-6 weeks of SPL protocol, based on the antibiotic sensitivity tests. The animals included in the study underwent a therapeutic protocol receiving shots of 0.5 mL of SPL subcutaneously (SC) twice a week for the first 12 weeks; 1.0 mL of SPL (SC) once a week for four weeks; 1.0 mL of SPL (SC) once every 15 days; 1.0 mL of SPL (SC) after a three-week interval from the last dose on week 20, until final observation at week 26, with no application. The animals underwent clinical examination every week and the evaluation of pruritus was used according Rybnicek et al. During the therapeutic protocol with SPL, a significant decline in the pruritus was observed in the treated dogs (P &lt; 0.05). In week 1, the mean pruritus index was 7.33 on the Rybnicek scale; in weeks 12 and 23, the mean indices were 2.41 and 1.91. An effectiveness of 83.33% for the control of pruritus along with regression of the lesions was observed.Discussion: Before treatment, the selected animals presented worsening of the pruritus during the pyoderma eczema episodes (pruritic), resulting in the emergence of a vicious cycle where the pruritus induced the appearance of new lesions, requiring the use of antibiotics for a long period. During the therapeutic protocol with SPL, a significant decline in the pruritus was observed in the treated dogs. The control of pruritus associated with pyoderma eczema of the dogs in this study before the vaccination protocol with SPL was satisfactory when they were subjected to antibiotic therapy; however, after suspending therapy, the bacterial infections recurred, on average, after 2-4 weeks. On the other hand, with the use of SPL, the animals were recurrence-free until the end of the experimental protocol. This was attributed to the antibiotic therapy administered at the beginning of the protocol, as this led to a regression of the bacterial pyoderma and involution of the lesions. However, after suspending antibiotics, it was observed that, by the end of the study, 83.33% of the dogs still had a low level of pruritus, few or no lesions, which were considered acceptable to most owners. At this moment none of these patients needed to be subjected to antibiotic treatment. The sums of the scores for the dogs on weeks 1, 12, and 23 were 53.33, 4.41, and 3.5, respectively, indicating significant improvements of the lesions, showing that the proposed protocol with SPL was able to prevent new episodes of pyoderma.

Host factors that contribute to recurrent staphylococcal skin infection

Staphylococcus aureus is the most common cause of skin and soft tissue infections (SSTI) in the United States and elsewhere. Recurrent infections occur frequently in patients with S. aureus SSTI, underscoring the need to better understand the nature of protective immunity against these infections. Here, we review recent findings concerning the host factors that predispose to S. aureus SSTI. Recurrent infections occur in nearly half of all patients with S. aureus SSTI. Epidemiologic and environmental factors, such as exposure to healthcare, age, and household contacts with S. aureus SSTI, and contaminated household fomites are associated with recurrence. The majority of the population has evidence of antistaphylococcal antibodies, but whether these are protective remains enigmatic. In contrast, recent clinical and experimental findings clearly highlight the critical roles of innate and T cell-mediated immunity in defense against these infections. S. aureus interferes with innate and adaptive immunity by a number of recently elucidated mechanisms. Recurrent S. aureus SSTIs are common, suggesting incomplete or absent protective immunity among these patients. Our understanding of protective immunity against recurrent infections is incomplete, and further basic and translational investigation is urgently needed to design strategies to prevent and treat these infections.