Search

Aim: The incidence of Staphylococcus aureus bacteremia (SAB) increases with advancing age with higher mortality reported in older adults. We aimed to describe the clinical presentation, management and outcomes of older patients with SAB., Methods: We analyzed data from a retrospectively collected database including 1692 patients with SAB, and compared 1158 older patients (≥65 years) with 534 younger patients (<65 years) in terms of clinical features, management of infection, and outcomes., Results: Older patients were significantly less likely to be febrile on presentation, with 37.5 % (415/1106) of older patients presenting with normal body temperature [versus 29.2 % (152/520) of younger patients]. Older patients were however, more likely to have leukocytosis, septic shock, lower heart rate and lower diastolic blood pressure compared with younger patients. Management of older patients included significantly less imaging studies, performance of transesophageal echocardiogram (TEE) and infectious diseases consultation. TEE was performed less in older patients [124/726 (17.1 %) versus 72/285 (25.3 %)]. Mortality was significantly higher in older patients [550/1158 (47.5 %) versus 124/534 (23.2 %)], with predictors for mortality for the entire cohort in multivariate analysis including older age, higher Charlson comorbidity index, female sex, impaired functional capacity, pneumonia or primary bacteremia, and non-performance of TEE., Conclusions: Mortality rates in older patients with SAB are higher compared with younger patients. Several diagnostic and therapeutic procedures in the management of SAB were less likely to be performed in older patients in our cohort. These may have implications on outcome and should not be dismissed on the basis of age alone.

Acute septic arthritis is a condition with the potential for joint destruction, physeal damage, and osteonecrosis, which warrants urgent identification and treatment. The organism most frequently responsible is Staphylococcus aureus; however, our understanding of pathogens continues to evolve as detection methods continue to improve. MRI has improved our ability to detect concurrent infections and is a useful clinical tool where available. The treatment course involves intravenous antibiotics followed by transition to oral antibiotics when clinically appropriate. The recommended surgical treatment of septic arthritis is open arthrotomy with decompression of the joint, irrigation, and debridement and treatment of concurrent infections., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Early innovations in the delivery of peritoneal dialysis (PD) markedly improved its acceptability and lowered peritonitis rates. The standard osmotic agent was, and continues to be dextrose, an agent that is not ideal as it is readily absorbed. The development of icodextrin-containing dialysis fluid has allowed a long dwell time to provide more effective ultrafiltration. The development of a smaller, more easily used automated cycler, led to an increase in the proportion of patients on the cycler as opposed to CAPD. Recently, new cyclers with better teaching tools and ease of use and communication with the training team have come on the market; data on outcomes using these cyclers are not yet available. Peritonitis continues to be a serious complication of PD although improvements in connectology and research on Staphylococcus aureus carriage have decreased peritonitis risk. Peritonitis rates continue to vary tremendously from one program to another, which may be in part due to failure to follow best demonstrated practices in training, care of the l catheter exit site, and prevention of peritonitis. Peritonitis rates should be expressed as episodes per year at risk and as organism-specific rates to allow comparisons from one program to another, from one period to another and from a program to the published literature. The term technique failure is misused in PD. Patients leave PD for a host of reasons including transplantation. Transfer from PD to hemodialysis can be planned and have an excellent outcome or can be delayed or done emergently and have a less optimal outcome. The life plan of the patient with ESRD needs to be not only considered but also periodically revised as circumstances and patient wishes change., (© 2017 Wiley Periodicals, Inc.)

Antibodies are potent components of the immune repertoire and have been successfully exploited to treat bacterial infections. Recently an antibody-antibiotic conjugate (AAC) that combines key attributes of an antibody and antibiotic has been shown to be efficacious against Staphylococcus aureus infection. An AAC has three components: an antibiotic payload to kill bacteria, an antibody to target delivery of the payload to bacteria, and a linker attaching the payload to the antibody. With increasing understanding of the biology and pathophysiology of S. aureus, this article highlights how this knowledge has led to the design principles of an efficacious AAC, and discusses how the AAC platform could be translationally applied to treat other perilous infectious diseases., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Aim: We aimed to describe the clinical epidemiology of Staphylococcus aureus bacteraemia (SAB) at a large, tertiary/quaternary children's hospital in Australia., Methods: We performed a retrospective chart review of SAB cases at the Children's Hospital at Westmead (CHW) over 5 years; 2006-2011. We compared frequency, clinical profile and outcomes of SAB with published data from CHW; 1994-1998. We compared health-care associated with community-associated (HCA-SAB and CA-SAB; defined epidemiologically) and methicillin-resistant with methicillin susceptible S. aureus (MRSA and MSSA)., Results: We identified 174 episodes of paediatric SAB with an average annual admission rate of 1.3/1000 which has not increased compared with a decade earlier. Half of the cases (49%) were CA-SAB; 18% were MRSA. The proportion of CA-MRSA bacteraemia (22%) has increased. The proportion of SAB associated with central venous access devices (CVADs; 40%) has increased. CA-SAB cases were more likely to present with a tissue focus of disease (e.g. osteo-articular, pneumonia) and often required surgery. HCA-SAB less frequently required surgery, a minority is MRSA, and vascular device intervention (removal, sterilisation) is common. Six cases (4%) of infective endocarditis (IE) were identified; three with a history of congenital heart disease, two with CVADs in situ. There were no deaths in this cohort., Conclusions: Over an 18-year period, the proportion of SAB due to CA-MRSA and SAB associated with CVADs has increased. Categorisation of SAB as HCA and CA reveals two broad phenotypes of paediatric SAB. SAB in children is infrequently associated with IE. The health-care burden of paediatric SAB is considerable', but mortality is low., (© 2016 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

Infective Endocarditis (IE) is an endocardial infection usually caused by bacteria that affects not only the native heart valves but also, with increasing frequency intravascular implanted devices and congenital heart diseases. Despite medical advances, IE remains a life-threatening disease with substantial morbidity and mortality. In Africa, its diagnosis and treatment are still a major challenge in clinical practice. The objective of this work was to study the epidemiological, clinical features, diagnostic techniques currently used in medical practice and the range of micro-organisms that are responsible. This was a retrospective study done at Principal Hospital of Dakar. We include all patients who were admitted with clinical manifestations of definite or possible IE according to the extended DUKE criteria between January 1 st , 2005 and December 31 st , 2014. We collected and analyzed epidemiological, clinical, paraclinical and outcomes data of 42 patients. Hospital prevalence of IE was 0.078% (42/53711). The mean age was 27.5+/- 18 years with a sex ratio (M/F) of 0.55. IE were more common in patients with damaged or abnormal heart valves (78.6%) and in thoses with underlying structural defects (14.3%). The most common presenting symptoms were fever (90%) and cardiac murmurs (81%). Extracardiac clinical manifestations were very rare. The usual laboratory parameters of inflammation were elevated in 90% of patients. Blood cultures were negative in 50% of cases and positive in 21.4%. The main organism found was Staphylococcus aureus. Echocardiography found vegetations in 95.2% of cases, chamber enlargement in 73.8% and mitral regurgiation in 83.3%. Broad-spectrum penicillins including ampicillin and gentamycine were used for all patients. Major complications were heart failure (47.6%). Strokes and cerebral abcess (23.8%) and Vascular emboli 14.3%. Hospital mortality was 31%. IE remains a life-threatening disease with hight mortality despites improved techniques of diagnosis and modern antibiotics., Competing Interests: The authors declare no competing interests.

The bacterial spectrum in chronic rhinosinusitis (CRS) is clinically relevant. This study aimed to compare two sampling techniques and to characterise Staphylococcus aureus isolated from CRS patients. Bacterial specimens were collected from the nares and maxillary sinus in 42 CRS patients and from the nares in 57 healthy controls. Maxillary sinus sampling was performed in two ways in each patient: with a cotton-tipped aluminium swab through the enlarged sinus ostium, and with a protected brush. S. aureus was characterised by DNA-sequencing of the repeat region of the S. aureus protein A gene, spa typing. The protected brush technique was superior to the cotton-tipped aluminium swab in reducing contamination rate. However, the two sampling methods were consistent in terms of clinically relevant bacterial findings, and the easy-to-handle cotton-tipped swab can still be recommended when culturing the maxillary sinus. Patients showed a significantly higher presence of S. aureus in the nares compared with healthy controls, and healthy controls showed a significantly higher presence of coagulase-negative staphylococci in the nares compared with patients. The spa types were identical for the nares and maxillary sinus in all patients except one. The sampling techniques showed equivalent results, indicating a low risk of unnecessary antibiotic treatment when using the easy-to-handle cotton-tipped aluminium swab. The high rate of identical spa types of S. aureus isolated from the nares and maxillary sinus of CRS patients might indicate colonisation of the maxillary sinus from the nares., Competing Interests: Compliance with ethical standardsConflict of interestBo Söderquist has been a consultant for Pfizer and Janssen-Cilag.Ethical approvalAll procedures performed in this study were in accordance with the ethical standards of the national research committee and with the 1964 Helsinki declaration. The study was approved by the regional ethical review board in Uppsala, Sweden.

Acute peritonitis remains the most common complication of peritoneal dialysis (PD), with coagulase-negative staphylococci (CoNS) reported to account for more than 25% of peritonitis episodes (1). Staphylococcus capitis is a gram-positive, catalase-positive CoNS that was originally identified as a commensal on the skin of the human scalp (2). Advancement of microbiological technologies for bacterial identification enables diagnosis of previously unknown causes of acute peritonitis. This is the first reported case of acute peritonitis in a PD patient caused by S. capitis., (Copyright © 2017 International Society for Peritoneal Dialysis.)

Objective Coagulase-negative staphylococci are among the most frequently isolated microorganisms in blood cultures. The aim of this study was to assess [1] the clinical characteristics of methicillin-resistant, coagulase-negative staphylococci bacteremia and [2] the susceptibility of the isolated bacteria to glycopeptides. Methods We retrospectively reviewed the medical records of 70 patients from whom methicillin-resistant coagulase-negative staphylococci had been isolated at Osaka City University Hospital between January 2010 and December 2013. We evaluated the patients' background, severity and prognosis of the disease, and the susceptibility of the isolated methicillin-resistant coagulase-negative staphylococci to glycopeptides. Results Out of the 70 patients tested, 28 (40.0%) had leukemia, and 36 (51.4%) had been treated for febrile neutropenia. Infection with Staphylococcus epidermidis accounted for 78.6% of patients. Thirty-nine cases (55.7%) were related to intravascular catheters, and 39 (55.7%) were treated using teicoplanin as a first-line therapy. The 30-day mortality rate was 4.3%. Regarding susceptibility, 20% of all isolates were non-susceptible to teicoplanin. According to multivariate analyses, it was observed that premedication using glycopeptides was independently associated with teicoplanin non-susceptibility (p=0.03; hazard ratio = 5.64; 95% confidence interval, 1.16-26.76). Conclusion Our results suggest that clinicians must use glycopeptides appropriately to prevent the development of further antibiotic resistance in methicillin-resistant coagulase-negative staphylococci.

Introduction: Bacterial cellulitis post-Cesarean section is rare. Negative pressure wound therapy (NPWT) is widely used in various medical specialities; its effectiveness in obstetrics however remains the topic of debate-used predominantly as an adjunct to secondary intention specific to high-risk patient groups. Its application in the treatment of actively infected wounds post-Cesarean is not well documented. Here, we document NPWT in the treatment of an unusually severe case of bacterial cellulitis with abdominal abscess postpartum. We provide a unique photographic timeline of wound progression following major surgical debridement, documenting the effectiveness of 2 different NPWT systems (RENASYS GO and PICO, Smith & Nephew). We report problems encountered using these NPWT systems and "ad-hoc" solutions to improve efficacy and patient experience.A 34-year-old primiparous Caucasian female with no prior history or risk factors for infection and a normal body mass index (BMI) presented with severe abdominal pain, swelling, and extensive abdominal redness 7 days postemergency Cesarean section. Examination revealed extensive cellulitis with associated abdominal abscess. Staphylococcus aureus was identified in wound exudates and extensive surgical debridement undertaken day 11 postnatally due to continued febrile episodes and clinical deterioration, despite aggressive intravenous antibiotic therapy. Occlusive NPWT dressings were applied for a period of 3 weeks before discharge, as well as a further 5 weeks postdischarge into the community.NPWT was well tolerated and efficacious in infection clearance and wound healing during bacterial cellulitis. Wound healing averaged 1 cm per week before NPWT withdrawal; cessation of NPWT before full wound closure resulted in significantly reduced healing rate, increased purulent discharges, and skin irritation, highlighting the efficacy of NPWT. Five-month follow-up in the clinic found the wound to be fully healed with no additional scarring beyond the boundaries of the original Cesarean incision. The patient was pleased with treatment outcomes, reporting no lasting pain or discomfort from the scar., Conclusions: This report represents the first documented use of NPWT to aid healing of an actively infected, open wound following extensive surgical debridement 10 days post-Cesarean section, confirming both the efficacy and tolerability of NPWT for the treatment of severe bacterial cellulitis in obstetric debridement., Competing Interests: The authors declare they have no competing financial interests.

Congenital coronary artery fistulas (CAFs) are infrequent congenital coronary artery anomalies. Complications such as left-to-right shunt, congestive heart failure, myocardial infarction, pericardial effusion, aneurysm formation, rupture, hemopericardium, pulmonary hypertension, infective endocarditis (IE), syncope, stroke, and sudden death may occur with a variable low frequency. To describe the clinical characteristics of patients with CAFs complicated by IE. A search was conducted through PubMed using the terms "CAFs" and "IE." Papers with a full description of the fistula characteristics and detailed data regarding bacterial endocarditis were included for evaluation. In the overall group of reviewed subjects (n = 25, 9 females), the mean patient age was 42.5 years (range: 16 and 87). The right coronary artery (RCA) and left coronary artery (LCA) contributed equally to fistula formation. Terminations into the right heart side occurred in 19 (76%) fistulas. The majority of the fistulas (92%) were unilateral. The cultured microorganism was Streptococcus in 14 (56%) and Staphylococcus in 4 (16%) of the reviewed subjects. Echocardiographic single or multiple valvular regurgitation was found in 8 (32%) of the reviewed subjects. Small and large intracardiac vegetations were detected in 18 patients (72%). Antibiotic therapy was initiated in 20 (80%) subjects and 16 fistulas were treated surgically. During surgery, spontaneous closure of the fistula was observed in one patient. Percutaneous therapeutic embolization (PTE) was successfully performed in two subjects. CAFs complicated by IE may affect all age groups with a slight male preponderance. Unilateral fistulas, either arising from the right or left coronary artery, are predominant, draining mainly into the right heart side. It is emphasized that antibiotic prophylaxis is strongly advised for pediatric and adult patients with congenital CAFs., (© 2016 Wiley Periodicals, Inc.)

Background: It is known that patients who acquired methicillin-resistant Staphylococcus aureus (MRSA) in hospitals suffer and feel as plague. Moreover, the patient interaction with nurses and physicians is described as frightening. Little is known about patient experiences after having acquired CA-MRSA concerning care and everyday life., Aim: To reveal and interpret otherwise healthy patients' lived experiences of receiving care and their everyday life after having acquired community MRSA (CA-MRSA)., Methods: A phenomenological hermeneutic approach guided by Ricouer was conducted. Interviews with twelve patients were transcribed verbatim into a text. The text was analysed in three phases: naive understanding, structural analysis and comprehensive understanding to reveal a possible being in the world. In this study, this referred to what it means to be infected with CA-MRSA., Results: The findings indicate that patients who acquired MRSA experience a changed body image. They suffer from ignorant and frightened behavior from healthcare workers, social contacts, and also of being bullied by colleagues. Despite this, patients assume great responsibility for protecting others. However, knowledgeable staff alleviate suffering and bring peace of mind to the patients., Conclusions: Preventing patient's feelings of being a pest, an outsider living with fear, requires urgent education and understanding about resistant bacteria and how to meet an infected patient. The results describing patients, affected with MRSA, may contribute and touch the readers to better understanding of patient's changed body image and suffering and how to mitigate these feelings., (© 2016 Nordic College of Caring Science.)

Purpose: Vancomycin (VCM) is used in the treatment of methicillin-resistant Staphylococcus aureus infection. The dosage of VCM must be adjusted by using therapeutic drug monitoring because of the drug's narrow therapeutic concentration window. Although optimal administration based on population pharmacokinetic (PPK) analysis and/or a Bayesian method has improved prediction accuracy, serum concentrations of VCM in patients with sepsis often deviate significantly from predicted values. We investigated factors influencing prediction errors with PPK analysis in VCM dosing., Methods: This retrospective cohort study included patients treated with VCM. Their clinical data were recorded, and there were 27 nonseptic patients and 68 septic patients. VCM concentrations were predicted by using PPK analysis and data compared with observed concentrations., Findings: Patients with sepsis had a higher mean absolute error than nonseptic patients, indicating a deviation of VCM concentrations from predicted values in the septic patients. To determine factors influencing prediction errors, we classified patients with sepsis into 3 subgroups according to the mean absolute error value (2.17) for the nonseptic patients: "lower" group (prediction errors, below -2.17), "upper" group (>2.17), and "no change" group (-2.17 to 2.17). In a comparison of clinical characteristics of the 3 groups, significant differences were found in the duration of systemic inflammatory response syndrome (SIRS), SIRS score, disseminated intravascular coagulation score, and levels of creatinine clearance (CrCl), hemoglobin, and diastolic blood pressure. Multiple logistic regression analysis identified SIRS duration and CrCl as factors associated with VCM concentrations in the lower and/or upper groups of septic patients. Shorter and longer SIRS duration were associated with VCM concentrations in the lower group and the upper group, respectively, compared with predicted values in patients with sepsis. According to receiver-operating characteristic curve analysis, the optimal cutoff value of SIRS duration for the lower group was 2 days; for the upper group, it was 6 days. VCM clearance in patients with an SIRS duration <2 days was higher than that for patients with an SIRS duration ≥6 days., Implications: SIRS duration was identified as influencing VCM concentration in patients with sepsis. This study has 2 limitations. First, we performed blood sampling only for trough concentrations. Repeated blood sampling for both peak and trough concentrations should be performed for more accurate pharmacokinetic evaluation in critically ill patients. Second, we determined CrCl by using the Cockcroft-Gault formula, which may not be accurate in critically ill patients. Modifying VCM dosing according to SIRS duration will improve prediction accuracy of VCM concentration based on therapeutic drug monitoring., (Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.)

Background: Staphylococcus aureus is an important pathogen in cystic fibrosis (CF). However, it is not clear which factors are associated with worse lung function in patients with persistent S. aureus airway cultures. Our main hypothesis was that patients with high S. aureus density in their respiratory specimens would more likely experience worsening of their lung disease than patients with low bacterial loads., Methods: Therefore, we conducted an observational prospective longitudinal multi-center study and assessed the association between lung function and S. aureus bacterial density in respiratory samples, co-infection with other CF-pathogens, nasal S. aureus carriage, clinical status, antibiotic therapy, IL-6- and IgG-levels against S. aureus virulence factors., Results: 195 patients from 17 centers were followed; each patient had an average of 7 visits. Data were analyzed using descriptive statistics and generalized linear mixed models. Our main hypothesis was only supported for patients providing throat specimens indicating that patients with higher density experienced a steeper lung function decline (p<0.001). Patients with exacerbations (n = 60), S. aureus small-colony variants (SCVs, n = 84) and co-infection with Stenotrophomonas maltophilia (n = 44) had worse lung function (p = 0.0068; p = 0.0011; p = 0.0103). Patients with SCVs were older (p = 0.0066) and more often treated with trimethoprim/sulfamethoxazole (p = 0.0078). IL-6 levels positively correlated with decreased lung function (p<0.001), S. aureus density in sputa (p = 0.0016), SCVs (p = 0.0209), exacerbations (p = 0.0041) and co-infections with S. maltophilia (p = 0.0195) or A. fumigatus (p = 0.0496)., Conclusions: In CF-patients with chronic S. aureus cultures, independent risk factors for worse lung function are high bacterial density in throat cultures, exacerbations, elevated IL-6 levels, presence of S. aureus SCVs and co-infection with S. maltophilia., Trial Registration: ClinicalTrials.gov NCT00669760., Competing Interests: The authors have declared that no competing interests exist.

Staphylococcus aureus is both a commensal organism and also an important opportunistic human pathogen, causing a variety of community and hospital-associated pathologies, such as bacteremia-sepsis, endocarditis, pneumonia, osteomyelitis, arthritis and skin diseases. The resurgence of S. aureus during the last decade in many settings has been facilitated not only by bacterial antibiotic resistance mechanisms but also by the emergence of new S. aureus clonal types with increased expression of virulence factors and the capacity to neutralize the host immune response. Prevention of the spread of S. aureus infection relies on the use of contact precautions and adequate procedures for infection control that so far have not been fully effective. Prevention using a prophylactic vaccine would complement these processes, having the potential to bring additional, significant progress toward decreasing invasive disease due to S. aureus.

Introduction: Mean annual ambient temperature is a replicated environmental modifier of cystic fibrosis (CF) lung disease with warmer temperatures being associated with lower lung function. The mechanism of this relationship is not completely understood. However, Pseudomonas aeruginosa, a pathogen that infects the lungs of CF individuals and decreases lung function, also has a higher prevalence in individuals living in warmer climates. We therefore investigated the extent to which respiratory pathogens mediated the association between temperature and lung function., Methods: Thirteen respiratory pathogens observed on CF respiratory cultures were assessed in multistep fashion using clustered linear and logistic regression to determine if any mediated the association between temperature and lung function. Analysis was performed in the CF Twin-Sibling Study (n=1730; primary population); key findings were then evaluated in the U.S. CF Foundation Data Registry (n=15,174; replication population)., Results: In the primary population, three respiratory pathogens (P. aeruginosa, mucoid P. aeruginosa, and methicillin-resistant Staphylococcus aureus) mediated the association between temperature and lung function. P. aeruginosa accounted for 19% of the association (p=0.003), mucoid P. aeruginosa for 31% (p=0.001), and MRSA for 13% (p=0.023). The same three pathogens mediated association in the replication population (7%, p<0.001; 7%, p=0.002; and 4%, (p=0.002), respectively)., Conclusions: Three important respiratory pathogens in CF mediate the association between lower lung function and warmer temperatures. These findings have implications for understanding regional variations in clinical outcomes, and interpreting results of epidemiologic studies and clinical trials that encompass regions with different ambient temperatures., Competing Interests: The authors have no competing interest with any organization(s) with a financial interest in the subject matter. Declaration of Interests: No conflicts of interest exist., (Copyright © 2016 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

In the global perspective of antibiotic resistance, it is urgent to find potent topical antibiotics for the use in human and animal infection. Healing of equine wounds, particularly in the limbs, is difficult due to hydrostatic factors and exposure to environmental contaminants, which can lead to heavy bio-burden/biofilm formation and sometimes to infection. Therefore, antibiotics are often prescribed. Recent studies have shown that honeybee-specific lactic acid bacteria (LAB), involved in honey production, and inhibit human wound pathogens. The aim of this pilot study was to investigate the effects on the healing of hard-to-heal equine wounds after treatment with these LAB symbionts viable in a heather honey formulation. For this, we included ten horses with wound duration of >1 year, investigated the wound microbiota, and treated wounds with the novel honeybee LAB formulation. We identified the microbiota using MALDI-TOF mass spectrometry and DNA sequencing. In addition, the antimicrobial properties of the honeybee LAB formulation were tested against all wound isolates in vitro. Our results indicate a diverse wound microbiota including fifty-three bacterial species that showed 90 % colonization by at least one species of Staphylococcus. Treatment with the formulation promoted wound healing in all cases already after the first application and the wounds were either completely healed (n = 3) in less than 20 days or healing was in progress. Furthermore, the honeybee LAB formulation inhibited all pathogens when tested in vitro. Consequently, this new treatment option presents as a powerful candidate for the topical treatment of hard-to-heal wounds in horses., Competing Interests: Therefore, the authors declare no competing interests regarding this work.

We report a case of acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) associated with toxic shock syndrome caused by burns. A one-year-old girl was admitted to our hospital for treatment of severe burns. On day 3, she exhibited a fever, generalized rash and multiple organ failure. She was diagnosed with toxic shock syndrome after burns. She had seizures with fever twice on the same day, followed by secondary seizures on day 8 and transient deterioration of the gross motor functions involved in sitting alone and rolling over. On day 9, MRI diffusion-weighted images showed bright tree appearance (BTA). We conclude that she developed AESD., (Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Mural endocarditis is a rare clinical entity with an extremely high mortality rate. It is usually predisposed by an underlying structural intracardiac abnormality. We present two cases of mural endocarditis occurring in the right atrium which were complicated by septic pulmonary embolism, one of which was predisposed by a jet lesion secondary to a coronary artery fistula. Both cases were successfully managed conservatively with excellent long-term outcomes., (Copyright © 2016 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Poly-N-acetylglucosamine (PNAG) is a major component of the Staphylococcus epidermidis biofilm extracellular matrix. However, it is not yet clear how this polysaccharide impacts the host immune response and infection-associated pathology. Faster neutrophil recruitment and bacterial clearance were observed in mice challenged intraperitoneally with S. epidermidis biofilm cells of the PNAG-producing 9142 strain than in mice similarly challenged with the isogenic PNAG-defective M10 mutant. Moreover, intraperitoneal priming with 9142 cells exacerbated liver inflammatory pathology induced by a subsequent intravenous S. epidermidis challenge, compared to priming with M10 cells. The 9142-primed mice had elevated splenic CD4(+) T cells producing gamma interferon and interleukin-17A, indicating that PNAG promoted cell-mediated immunity. Curiously, despite having more marked liver tissue pathology, 9142-primed mice also had splenic T regulatory cells with greater suppressive activity than those of their M10-primed counterparts. By showing that PNAG production by S. epidermidis biofilm cells exacerbates host inflammatory pathology, these results together suggest that this polysaccharide contributes to the clinical features associated with biofilm-derived infections., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)

Bacteria invading the mammary gland can cause pathogen-dependent differences in the permeability of the blood-milk barrier leading to the differential paracellular transfer of blood and milk components. Glucocorticoids such as prednisolone (PRED) are known to increase the integrity of the blood-milk barrier and quickly restore the decreased milk quality associated with mastitis. The objective of this study was to examine the effect of intramammary PRED on the differential permeability of the blood-milk barrier during mastitis induced by lipopolysaccharide (LPS) from Escherichia coli or lipoteichoic acid (LTA) from Staphylococcus aureus. Thirty-one dairy cows, divided into 6 groups, were injected via a teat canal with LPS, LTA, LPS and PRED, LTA and PRED, saline (control), or PRED. Milk and blood samples were collected 0 to 8h after challenge and analyzed for somatic cell count, IgG, serum albumin, and lactate dehydrogenase in milk, or α-lactalbumin in plasma. Somatic cell count was similarly elevated in LPS- and LTA-challenged quarters and was reduced to control quarter levels only in LTA-challenged quarters with PRED administration. Lactate dehydrogenase activity was highly elevated in LPS quarters and only slightly elevated in LTA quarters, but decreased to control quarter levels with PRED administration. For serum albumin and IgG, only LPS quarters showed an elevation in concentration and PRED treatment reduced the concentration to control quarter level. We found no differences in α-lactalbumin concentrations in plasma in PRED-treated cows compared with cows that only received LPS or LTA. In conclusion, the pathogen-specific appearance of blood constituents in milk during mastitis demonstrates a differential activation of the blood-milk barrier that, in turn, can be manipulated by intramammary glucocorticoids. The results show that the administration of PRED during mastitis increases the blood-milk barrier integrity but has implications in reducing the transfer of IgG that specifically occurs during E. coli mastitis. In addition, it can also reduce the number of migrating immune cells dependent on the mastitis-inducing pathogen. Potential effects of PRED on the cure of naturally occurring mastitis have to be taken into consideration., (Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Background: Staphylococcus aureus is one of the earliest bacterial pathogens to colonize the lungs of children with cystic fibrosis and is an important contributor to pulmonary exacerbations. The adaptive host response to S. aureus in cystic fibrosis remains inadequately defined and has important implications for pathogenesis and potential interventions. The objectives of this study were to determine the functional antibody response to select staphylococcal exotoxins (LukAB, alpha-hemolysin, and PVL) in children with cystic fibrosis and to evaluate the relationship of this response with pulmonary exacerbations., Methods: Fifty children with cystic fibrosis were enrolled and followed prospectively for 12months. Clinical characteristics and serologic profiles were assessed at routine visits and during pulmonary exacerbations, and functional antibody assessments were performed to measure neutralization of LukAB-mediated cytotoxicity., Results: For each antigen, geometric mean titers were significantly higher if S. aureus was detected at the time of exacerbation. For LukAB, geometric mean titers were significantly higher at exacerbation follow-up compared to titers during the exacerbation, consistent with expression during human disease, and the humoral response capably neutralized LukAB-mediated cytotoxicity. Moreover, the presence of a positive S. aureus culture during a pulmonary exacerbation was associated with 31-fold higher odds of having a LukA titer ≥1:160, suggesting potential diagnostic capability of this assay., Conclusions: The leukotoxin LukAB is expressed by S. aureus and recognized by the human adaptive immune response in the setting of pulmonary infection in cystic fibrosis. Anti-LukAB antibodies were not only predictive of positive staphylococcal culture during exacerbation, but also functional in the neutralization of this toxin., (Copyright © 2016 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

Methicillin-resistant Staphylococcus aureus is a frequent cause of hospital-associated infections, including central catheter-associated bacteremia. Vancomycin has been the drug of choice for treating this type of bacteremia for decades in patients who have no contraindications to the antibiotic. However, resistance to vancomycin is an emerging problem. Newer antibiotics approved by the Food and Drug Administration have activity against methicillin-resistant S aureus Some of the antibiotics also have activity against strains of S aureus that are intermediately susceptible or resistant to vancomycin. This article uses a case study to highlight the clinical signs of vancomycin failure and describes the indications for and appropriate use of alternative antimicrobials such as ceftaroline, daptomycin, linezolid, tigecycline, and telavancin. (Critical Care Nurse 2016;36[4]:46-57)., (©2016 American Association of Critical-Care Nurses.)

Background: Staphylococcus aureus (SA) colonization/infection is important in the pathophysiology of childhood atopic dermatitis (AD), but the role of Staphylococcus epidermidis (SE) is unknown., Aim: To evaluate if SE co-infects with SA and is associated with more severe disease., Methods: Associations between bacteriological culture results of skin swabs (taken from the most severely affected area and at the antecubital fossa) and SCORing Atopic Dermatitis (SCORAD) score, skin hydration, transepidermal water loss (TEWL) and quality of life (QoL) were evaluated., Results: In 100 consecutive patients with AD (aged 12.4 ± 4.8 years), SE was present in 28% and 32% of the swabs taken from the most severe area and the flexural area (antecubital fossa), respectively, whereas SA was present in 69% and 55%, respectively. Binomial logistic regression showed that SE was inversely associated with SA growth in the most severely affected skin site [adjusted odds ratio (aOR) = 0.42, 95% CI 0.22-0.81; P = 0.01], frequency of emollient usage (aOR = 0.50, 95% CI 0.29-0.87; P = 0.01) and frequency of oral antihistamine usage (aOR = 0.81, 95% CI 0.65-0.10, P < 0.05), but positively associated with objective SCORAD (aOR = 1.04, 95% CI 1.00-1.02; P < 0.05). SE in the antecubital fossa was not associated with SA growth, disease severity, QoL or any clinical parameters., Conclusions: SE may not be just a commensal bystander in the skin microbiota. The organism amensalistically displaces SA and is associated with more severe disease., (© 2016 British Association of Dermatologists.)

Secreted factors of Staphylococcus aureus can activate host signaling from the epidermal growth factor receptor (EGFR). The superantigen toxic shock syndrome toxin-1 (TSST-1) contributes to mucosal cytokine production through a disintegrin and metalloproteinase (ADAM)-mediated shedding of EGFR ligands and subsequent EGFR activation. The secreted hemolysin, α-toxin, can also induce EGFR signaling and directly interacts with ADAM10, a sheddase of EGFR ligands. The current work explores the role of EGFR signaling in menstrual toxic shock syndrome (mTSS), a disease mediated by TSST-1. The data presented show that TSST-1 and α-toxin induce ADAM- and EGFR-dependent cytokine production from human vaginal epithelial cells. TSST-1 and α-toxin also induce cytokine production from an ex vivo porcine vaginal mucosa (PVM) model. EGFR signaling is responsible for the majority of IL-8 production from PVM in response to secreted toxins and live S. aureus. Finally, data are presented demonstrating that inhibition of EGFR signaling with the EGFR-specific tyrosine kinase inhibitor AG1478 significantly increases survival in a rabbit model of mTSS. These data indicate that EGFR signaling is critical for progression of an S. aureus exotoxin-mediated disease and may represent an attractive host target for therapeutics.

Background: Osteomyelitis shows a strong predilection for the tibia in the pediatric population and is a significant source of complications. The purpose of this article is to retrospectively review a large series of pediatric patients with tibial osteomyelitis. We compare our experience with that in the literature to determine any factors that may aid diagnosis and/or improve treatment outcomes., Methods: A 10-year retrospective review was performed of clinical records of all cases of pediatric tibial osteomyelitis managed at the 2 children's orthopaedic departments in the Auckland region. The Osteomyelitis Database was used to identify all cases between 1997 and 2007, at Starship Children's Hospital, and 1998 and 2008 at Middlemore's Kids First Hospital., Results: One hundred ninety-one patients fulfilled the inclusion criteria, and had a review of clinical notes and relevant investigations. The average duration of symptoms before presentation to hospital was 5.7 days. Less than 40% of patients had a recent episode of trauma. Almost 60% of patients could not bear weight on admission. Over 40% of patients had a temperature above 38°C. Erythrocyte sedimentation rate was elevated in 78% and the C-reactive protein was elevated in 90% of patients. In total, 42% of blood cultures and almost 75% of tissue cultures were positive, with Staphylococcus aureus being the most commonly cultured organism. X-rays, bone scans, and magnetic resonance imaging were all used to aid the diagnosis. About 43% of patients had surgery. Treatment length was an average of 2 weeks 6 days of intravenous antibiotics followed by 3 weeks 2 days of oral treatment. Six postsurgical complications and 46 readmissions were noted: 25 for relapse, with the remainder due to social and antibiotic-associated complications., Conclusions: Although generally diagnosed on presentation, pediatric tibial osteomyelitis can require more sophisticated investigations and prolonged management. Treatment with intravenous and oral antibiotics and surgical debridement where indicated can lead to a good clinical outcome, although complications are often noted., Level of Evidence: Level IV-Prognostic study.

Aim: Clinical practice guidelines for the management of diabetic foot infections developed by the Infectious Diseases Society of America (IDSA) are commonly used worldwide. The issue of whether or not these guidelines need to be adjusted for local circumstances, however, has seldom been assessed in large prospective trials., Methods: The Turk-DAY trial was a prospective, multi-center study in which infectious disease specialists from centers across Turkey were invited to participate (NCT02026830)., Results: A total of 35 centers throughout Turkey enrolled patients in the trial. Overall, investigators collected a total of 522 specimens from infected diabetic foot wounds for culture from 447 individual patients. Among all isolates, 36.4% were gram-positive organisms, with Staphylococcus aureus the most common among these (11.4%). Gram-negative organisms constituted 60.2% of all the isolates, and the most commonly isolated gram-negative was Escherichia coli (15%). The sensitivity rates of the isolated species were remarkably low for several antimicrobials used in the mild infection group., Conclusions: Based on our findings, several of the antimicrobials frequently used for empirical treatment, including some also recommended in the IDSA guidelines, would not be optimal for treating diabetic foot infections in Turkey. Although the IDSA guideline recommendations may be helpful to guide empiric antimicrobial therapy of DFIs, they should be adjusted to local conditions., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Staphylococcus aureus, a Gram-positive bacterium colonizing nares, skin, and the gastrointestinal tract, frequently invades the skin, soft tissues, and bloodstreams of humans. Even with surgical and antibiotic therapy, bloodstream infections are associated with significant mortality. The secretion of coagulases, proteins that associate with and activate the host hemostatic factor prothrombin, and the bacterial surface display of agglutinins, proteins that bind polymerized fibrin, are key virulence strategies for the pathogenesis of S. aureus bloodstream infections, which culminate in the establishment of abscess lesions. Pathogen-controlled processes, involving a wide spectrum of secreted factors, are responsible for the recruitment and destruction of immune cells, transforming abscess lesions into purulent exudate, with which staphylococci disseminate to produce new infectious lesions or to infect new hosts. Research on S. aureus bloodstream infections is a frontier for the characterization of protective vaccine antigens and the development of immune therapeutics aiming to prevent disease or improve outcomes.

Background: Differentiating between septic arthritis and Lyme disease of the knee in endemic areas can be challenging and has major implications for patient management. The purpose of this study was to identify a prediction rule to differentiate septic arthritis from Lyme disease in children presenting with knee pain and effusion., Methods: We retrospectively reviewed the records of patients younger than 18 years of age with knee effusions who underwent arthrocentesis at our institution from 2005 to 2013. Patients with either septic arthritis (positive joint fluid culture or synovial white blood-cell count of >60,000 white blood cells/mm(3) with negative Lyme titer) or Lyme disease (positive Lyme immunoglobulin G on Western blot analysis) were included. To avoid misclassification bias, undiagnosed knee effusions and joints with both a positive culture and positive Lyme titers were excluded. Historical, clinical, and laboratory data were compared between groups to identify variables for comparison. Binary logistic regression analysis was used to identify independent predictive variables., Results: One hundred and eighty-nine patients were studied: 23 with culture-positive septic arthritis, 26 with culture-negative septic arthritis, and 140 with Lyme disease. Multivariate binary logistic regression identified pain with short arc motion, history of fever reported by the patient or a family member, C-reactive protein of >4 mg/L, and age younger than 2 years as independent predictive factors for septic arthritis. A simpler model was developed that showed that the risk of septic arthritis with none of these factors was 2%, with 1 of these factors was 18%, with 2 of these factors was 45%, with 3 of these factors was 84%, or with all 4 of these factors was 100%., Conclusions: Although septic arthritis of the knee and Lyme monoarthritis share common features that can make them difficult to distinguish clinically, the presence of pain with short arc motion, C-reactive protein of >4.0 mg/L, patient-reported history of fever, and age younger than 2 years were independent predictive factors of septic arthritis in pediatric patients. The more factors that are present, the higher the risk of having septic arthritis., Level of Evidence: Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence., (Copyright © 2016 by The Journal of Bone and Joint Surgery, Incorporated.)

Background: Few studies have examined the association between chronic methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (PA) co-infection and health outcomes despite evidence that these pathogens alone contribute to higher morbidity and mortality in cystic fibrosis (CF). This study examines outcomes among CF patients with chronic MRSA and PA co-infection compared with patients with either or neither of these organisms., Methods: CF patients attending the care center in Atlanta, GA from 2007-2013 comprised the study cohort. Chronic co-infection was defined as >50% PA+ cultures and >50% MRSA+ cultures and modeled as time-varying. The rate of decline in lung function (FEV1) and the rate of IV treatments were the main outcomes., Results: Among all patients (N=354), chronic co-infection was associated with a significantly more rapid rate of FEV1 decline compared with patients with chronic PA alone [adjusted difference: -0.60% predicted/year (-1.13, -0.08)] and chronic MRSA alone [adjusted difference: -0.89% predicted/year (-1.56, -0.22)]. Rate of IV treatments was significantly higher among patients with chronic co-infection compared with patients with chronic PA alone [adjusted IRR: 1.24 (1.01, 1.52)] and chronic MRSA alone [adjusted IRR: 1.34 (1.03, 1.74)]., Conclusions: Data from the Atlanta Care Center suggest that chronic MRSA and PA co-infection may be associated with increased rate of lung function decline and rate of intravenous antibiotics compared with patients with either pathogen alone., (Copyright © 2015 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

Background: Clinical and demographical knowledge on Spanish cystic fibrosis (CF) patients is incomplete as no national registry exists. CF-microbiology has not been studied at national level. The results of the first Spanish multicenter study on CF microbiology are presented., Methods: 24 CF-Units for adult (n=12) and pediatric (n=12) patients from 17 hospitals provided sputa and clinical data from 15 consecutive patients. Cultures and susceptibility testing were performed. Colonization impact on pulmonary function was assessed., Results: 341 patients [mean (SD) age 21 (11) years, 180≥18years, mean (SD) FEV1=68 (25)%] were included. Pseudomonas aeruginosa was reported as chronic, intermittent or absent in 46%, 22% and 32% of patients, respectively. The annual prevalence was 62%. Positive P. aeruginosa and methicillin-resistant Staphylococcus aureus cultures were significantly associated with lower FEV1 (p<0.001 and p=0.003, respectively)., Conclusions: The representative subset of the Spanish CF-population which has been clinically, demographically and microbiologically characterized will serve as a reference for future CF studies in Spain., (Copyright © 2015 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

With intensified antibiotic therapy and longer survival, patients with cystic fibrosis (CF) are colonized with a more complex pattern of bacteria and fungi. However, the clinical relevance of these emerging pathogens for lung function remains poorly defined. The aim of this study was to assess the association of bacterial and fungal colonization patterns with lung function in adolescent patients with CF. Microbial colonization patterns and lung function parameters were assessed in 770 adolescent European (German/Austrian) CF patients in a retrospective study (median follow-up time: 10years). Colonization with Pseudomonas aeruginosa and MRSA were most strongly associated with loss of lung function, while mainly colonization with Haemophilus influenzae was associated with preserved lung function. Aspergillus fumigatus was the only species that was associated with an increased risk for infection with P. aeruginosa. Microbial interaction analysis revealed three distinct microbial clusters within the longitudinal course of CF lung disease. Collectively, this study identified potentially protective and harmful microbial colonization patterns in adolescent CF patients. Further studies in different patient cohorts are required to evaluate these microbial patterns and to assess their clinical relevance., (Copyright © 2016 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

Pyodermas are a common group of infectious dermatological conditions on which few studies have been conducted. This study aimed to characterise the clinical and bacteriological profile of pyodermas, and to determine the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) infection in primary pyodermas in a dermatology outpatient department in Kashmir. Methods We conducted a hospital based cross-sectional study in the outpatient Department of Dermatology, Sexually Transmitted Diseases and Leprosy of Shri Maharaja Hari Singh Hospital, Srinagar, Jammu and Kashmir, India. Patients presenting with primary pyodermas were included in the study. A detailed history and complete physical and cutaneous examination was carried out along with microbiological testing to find aetiological microorganisms and their respectiveantimicrobial susceptibility patterns. Antimicrobial susceptibility testing, including that for methicillin resistance, was carried out by standard methods as outlined in the current Clinical and Laboratory Standards Institute guidelines. Results In total, 110 patients were included; the age of the study population ranged from 3 to 65 years (mean age 28 years); 62% were male. Poor personal hygiene was noted in 76 (69%). Furunculosis (56; 51%) was the most common clinical presentation. Staphylococcus aureus was isolated in 89 (81%) of cases, and MRSA formed 54/89 (61%) of Staphylococcus aureus isolates. All MRSA strains were sensitive to vancomycin. Conclusion The prevalence of MRSA was high in this sample of communityacquired primary pyodermas. It is therefore important to monitor the changing trends in bacterial infection and their antimicrobial susceptibility patterns and to formulate a definite antibiotic policy which may be helpful in decreasing the incidence of MRSA infection.

The purpose of this study was to examine the prognostic impact of corticosteroids in hemodynamically stabile Staphylococcus aureus bacteremia (SAB). There were 361 hemodynamically stabile methicillin-sensitive SAB patients with prospective follow-up and grouping according to time-point, dose and indication for corticosteroid therapy. To enable analyses without external interfering corticosteroid therapy all patients with corticosteroid therapy equivalent to prednisone >10 mg/day for ≥1 month prior to positive blood culture results were excluded. Twenty-five percent (92) of patients received corticosteroid therapy of which 11 % (40) had therapy initiated within 1 week (early initiation) and 9 % (31) had therapy initiated 2-4 weeks after (delayed initiation) positive blood culture. Twenty-one patients (6 %) had corticosteroid initiated after 4 weeks and were not included in the analyses. A total of 55 % (51/92) received a weekly prednisone dose >100 mg. Patients with early initiated corticosteroid therapy had higher mortality compared to patients treated without corticosteroid therapy at 28 days (20 % vs. 7 %) (OR, 3.11; 95%CI, 1.27-7.65; p < 0.05) and at 90 days (30 % vs. 10 %) (OR, 4.01; 95%CI, 1.82-8.81; p < 0.001). Considering all prognostic markers, early initiated corticosteroid therapy predicted 28-day (HR, 3.75; 95%CI, 1.60-8.79; p = 0.002) and 90-day (HR, 3.10; 95%CI, 1.50-6.39; p = 0.002) mortality in Cox proportional hazards regression analysis. When including only patients receiving early initiated corticosteroid therapy with prednisone ≥100 mg/week the negative prognostic impact on 28-day mortality was accentuated (HR 4.8, p = 0.001). Corticosteroid therapy initiation after 1 week of positive blood cultures had no independent prognostic impact. Early initiation of corticosteroid therapy may be associate to increased mortality in hemodynamically stabile SAB.

Background: A porcine model of haematogenous Staphylococcus aureus sepsis has previously been established in our research group. In these studies, pigs developed severe sepsis including liver dysfunction during a 48 h study period. As pigs were awake during the study, animal welfare was challenged by the severity of induced disease, which in some cases necessitated humane euthanasia. A pilot study was therefore performed in order to establish the sufficient inoculum concentration and application protocol needed to produce signs of liver dysfunction within limits of our pre-defined humane endpoints., Methods: Four pigs received 1 × 10(8) cfu/kg BW of S. aureus, and two controls were sham inoculated with saline. A fixed infusion rate of 3 mL/min was used, while the inoculum concentration, i.e., the dose volume, was changed between the pigs. The following dose volumes were used: 10 mL (n = 1), 20 mL (n = 2), and 30 mL (n = 1), corresponding to infusion durations of 3.33, 6.66, and 10 min at dose rates of 3 × 10(7), 1.5 × 10(7), and 1 × 10(7) cfu/min/kg BW, respectively. Blood samples were drawn for complete blood count, clinical chemistry, and inflammatory markers before and every 6 h after inoculation. Prior to euthanasia, a galactose elimination capacity test was performed to assess liver function. Pigs were euthanised 48 h post inoculation for necropsy and histopathological evaluation., Results: While infusion times of 6.66 min, and higher, did not induce liver dysfunction (n = 3), the infusion time of 3.33 min (n = 1) caused alterations in parameters similar to what had been seen in our previous studies, i.e., increasing bilirubin and aspartate aminotransferase, as well as histopathological occurrence of intravascular fibrin split products in the liver. This pig was however euthanised after 30 h, according to humane endpoints., Conclusions: A usable balance between scientific purpose and animal welfare could not be achieved, and we therefore find it hard to justify further use of this conscious porcine sepsis model. In order to make a model of translational relevance for human sepsis, we suggest that future model versions should use long-term anaesthesia.

Approximately 10% of infective endocarditis (IE) involves the right side of the heart with the majority of these cases occurring in intravenous drug users. Patients are less likely to present with classical IE signs of a new murmur and peripheral stigmata, are more frequently immunocompromised and often have significant social difficulties. These factors result in both diagnostic and therapeutic challenges in this patient group that are not often seen in other patient populations with IE., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Objective: Report of an uncommon complication of acupuncture and wet cupping., Methods: A 54-year-old man presented with neck pain and fever. Magnetic resonance imaging of the cervical spine revealed an epidural abscess at C4 to T2., Results: The symptoms related to epidural abscess resolved partially after treatment with antibiotics., Conclusion: Acupuncture and wet-cupping therapy should be taken into consideration as a cause of spinal epidural abscesses in patients who present with neck pain and fever. Furthermore, acupuncture and wet-cupping practitioners should pay attention to hygienic measures., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Although infective endocarditis (IE) is relatively uncommon, it remains an important clinical entity with a high in-hospital and 1-year mortality. It is most commonly caused by viridans streptococci. Staphylococcus aureus is responsible for a malignant course of IE and often requires early surgery to eradicate. Other rarer causes are various bacilli, including the HACEK (Haemophilus, Actinobacillus,Cardiobacterium, Eikenella and Kingella spp.) group of organisms and fungi. The clinical presentation varies. Patients may present with a nonspecific illness, valve dysfunction, heart failure (HF) and symptoms due to peripheral embolisation. The diagnosis is traditionally based on the modified Duke criteria and rests mainly on clinical features and to a lesser extent on certain laboratory findings,microbiological assessment and cardiovascular imaging. Identification of the offending micro-organism is not only important from a diagnostic point of view, but also makes targeted antibiotic treatment possible and provides useful prognostic information. A significant proportion of microbiological cultures are negative, frequently owing to the administration of antibiotics prior to appropriate culture.Blood-culture-negative IE poses significant diagnostic and treatment challenges. The course of the disease is frequently complicated, and sequelae include HF, local intracardiac extension of infection (abscess, fistula, pseudoaneurysm), stroke and intracranial haemorrhage due to septic emboli or mycotic aneurysm formation as well as renal injury. Management includes prolonged intravenous antibiotics and consideration for early surgery with removal of infective tissue and valve replacement in patients who have poor prognostic features or complications. Antibiotic administration for at-risk patients to prevent bacteraemia during specific procedures (particularly dental) is recommended to prevent IE. The patient population who would benefit from antibiotic prophylaxis has become increasingly restricted,and guidelines recommend prophylaxis only for patients with cyanotic congenital heart disease, prosthetic heart valves and a previous episode of IE. The management of a patient with IE is challenging and often requires multidisciplinary input from an IE heart team,which includes cardiologists

Central line-associated bloodstream infections (CLABSIs) are not easily treated, and many catheters (e.g., hemodialysis catheters) are not easily replaced. Biofilms (the source of infection) on catheter surfaces are notoriously difficult to eradicate. We have recently demonstrated that modest elevations of temperature lead to increased staphylococcal susceptibility to vancomycin and significantly soften the biofilm matrix. In this study, using a combination of microbiological, computational, and experimental studies, we demonstrate the efficacy, feasibility, and safety of using heat as an adjuvant treatment for infected hemodialysis catheters. Specifically, we show that treating with heat in the presence of antibiotics led to additive killing of Staphylococcus epidermidis with similar trends seen for Staphylococcus aureus and Klebsiella pneumoniae. The magnitude of temperature elevation required is relatively modest (45-50°C) and similar to that used as an adjuvant to traditional cancer therapy. Using a custom-designed benchtop model of a hemodialysis catheter, positioned with tip in the human vena cava as well as computational fluid dynamic simulations, we demonstrate that these temperature elevations are likely achievable in situ with minimal increased in overall blood temperature.

Cross-linked polyvinyl alcohol (PVA) and polyvinyl pyrrolidone (PVP) composite nanofibrous membranes have been prepared by electrospinning. Mechanical properties of the membranes improved significantly with PVP addition. PVP improved hydrophilicity and sustainable degradation of the membranes. Biocompatibility of the membranes was assessed by in vitro culture of native skin cells (L929 fibroblast and HaCaT keratinocytes). Tests showed sustained release of the antibiotic ciprofloxacin hydrochloride monohydrate by the membranes. Further, zone of inhibition study against Staphylococcus aureus growth demonstrated protective action against external pathogenic microbes. These studies show these simple PVA-PVP nanofibrous membranes are promising interactive antibiotic-eluting wound dressing materials.

Cytosolic PLA2 (cPLA2) and Ca(2+)-independent PLA2 (iPLA2) play a significant role in insulin β-cells secretion. Bacterial infections may be responsible of the onset of diabetes. The mechanism by which Staphylococcus aureus infection of INS-1 cells alters glucose-induced insulin secretion has been examined. After acute infection, insulin secretion and PLA2 activities significantly increased. Moreover, increased expressions of phospho-cPLA2, phospho-PKCα and phospho-ERK 1/2 were observed. Chronic infection causes a decrease in insulin release and a significant increase of iPLA2 and COX-2 protein expression. Moreover, insulin secretion in infected cells could be restored using specific siRNAs against iPLA2 isoform and specific COX-2 inhibitor., (Copyright © 2015. Published by Elsevier B.V.)

Measures of ventilation distribution are promising for monitoring early lung disease in cystic fibrosis (CF). This study describes the cross-sectional and longitudinal impacts of pulmonary inflammation and infection on ventilation homogeneity in infants with CF.Infants diagnosed with CF underwent multiple breath washout (MBW) testing and bronchoalveolar lavage at three time points during the first 2 years of life.Measures were obtained for 108 infants on 156 occasions. Infants with a significant pulmonary infection at the time of MBW showed increases in lung clearance index (LCI) of 0.400 units (95% CI 0.150-0.648; p=0.002). The impact was long lasting, with previous pulmonary infection leading to increased ventilation inhomogeneity over time compared to those who remained free of infection (p<0.05). Infection with Haemophilus influenzae was particularly detrimental to the longitudinal lung function in young children with CF where LCI was increased by 1.069 units for each year of life (95% CI 0.484-1.612; p<0.001).Pulmonary infection during the first year of life is detrimental to later lung function. Therefore, strategies aimed at prevention, surveillance and eradication of pulmonary pathogens are paramount to preserve lung function in infants with CF., (Copyright ©ERS 2015.)

Background: Chronic rhinosinusitis is a common, heterogeneous condition. An effective means of mitigating disease in chronic rhinosinusitis patients remains elusive. A variety of causes have been implicated, with the biofilm theory gaining increasing prominence., Objective: This article reviews the literature on the role of biofilms in chronic rhinosinusitis, in terms of pathophysiology and with regard to avenues for future treatment., Methods: A systematic review of case series was performed using databases with independently developed search strategies, including Medline, Embase, Cumulative Index to Nursing and Allied Health Literature, Cochrane library, and Zetoc, in addition to conference proceedings and a manual search of literature, with the last search conducted on 18 January 2014. The search terms included the following, used in various combinations to maximise the yield of articles identified: 'biofilms', 'chronic rhinosinusitis', 'DNase', 'extracellular DNA' and 'biofilm dispersal'., Results: The existing evidence lends further support for the role of biofilms (particularly the Staphylococcus aureus phenotype) in more severe, recalcitrant disease and poorer surgical outcomes., Conclusion: Multimodality treatment, with a shift in paradigm to incorporate anti-biofilm strategies, is likely to form the mainstay of future recalcitrant chronic rhinosinusitis management.

Background: Staphylococcus aureus left-sided native valve infective endocarditis (LNVIE) has higher complication and mortality rates compared with endocarditis from other pathogens. Whether echocardiographic variables can predict prognosis in S aureus LNVIE is unknown., Methods and Results: Consecutive patients with LNVIE, enrolled between January 2000 and September 2006, in the International Collaboration on Endocarditis were identified. Subjects without S aureus IE were matched to those with S aureus IE by the propensity of having S aureus. Survival differences were determined using log-rank significance tests. Independent echocardiographic predictors of mortality were identified using Cox-proportional hazards models that included inverse probability of treatment weighting and surgery as a time-dependent covariate. Of 727 subjects with LNVIE and 1-year follow-up, 202 had S aureus IE. One-year survival rates were significantly lower for patients with S aureus IE overall (57% S aureus IE versus 80% non-S aureus IE; P<0.001) and in the propensity-matched cohort (59% S aureus IE versus 68% non-S aureus IE; P<0.05). Intracardiac abscess (hazard ratio, 2.93; 95% confidence interval, 1.52-5.40; P<0.001) and left ventricular ejection fraction <40% (odds ratio, 3.01; 95% confidence interval, 1.35-6.04; P=0.004) were the only independent echocardiographic predictors of in-hospital mortality in S aureus LNVIE. Valve perforation (hazard ratio, 2.16; 95% confidence interval, 1.21-3.68; P=0.006) and intracardiac abscess (hazard ratio, 2.25; 95% confidence interval, 1.26-3.78; P=0.004) were the only independent predictors of 1-year mortality., Conclusions: S aureus is an independent predictor of 1-year mortality in subjects with LNVIE. In S aureus LNVIE, intracardiac abscess and left ventricular ejection fraction <40% independently predicted in-hospital mortality and intracardiac abscess and valve perforation independently predicted 1-year mortality., (© 2015 American Heart Association, Inc.)

Atopic eczema (AE) is associated with Staphylococcus aureus (S. aureus) colonization and skin barrier dysfunction, often measured by increased transepidermal water loss (TEWL). In the present study, the primary aim was to see whether S. aureus colonization in the vestibulum nasi and/or fauces was associated with increased TEWL in infants with healthy skin and infants with eczema. Secondarily, we aimed to investigate whether TEWL measurements on non-lesional skin on the lateral upper arm is equivalent to volar forearm in infants. In 167 of 240 infants, recruited from the general population, TEWL measurements on the lateral upper arm and volar forearm, using a DermaLab USB, fulfilled our environmental requirements. The mean of three TEWL measurements from each site was used for analysis. The infants were diagnosed with no eczema (n = 110), possible AE (n = 28) or AE (n = 29). DNA samples were analysed for mutations in the filaggrin gene (FLG). Bacterial cultures were reported positive with the identification of at least one culture with S. aureus from vestibulum nasi and/or fauces. S. aureus colonization, found in 89 infants (53%), was not associated with increased TEWL (i.e. TEWL in the upper quartile), neither on the lateral upper arm or volar forearm (p = 0.08 and p = 0.98, respectively), nor with AE (p = 0.10) or FLG mutation (p = 0.17). TEWL was significantly higher on both measuring sites in infants with AE compared to infants with possible AE and no eczema. FLG mutation was significantly associated with increased TEWL, with a 47% difference in TEWL. We conclude that S. aureus in vestibulum nasi and/or fauces was not associated with TEWL, whereas TEWL measurements on the lateral upper arm and volar forearm appear equally appropriate in infants.

Staphylococcus (S.) aureus is a common causative agent of bacterial endophthalmitis, a vision threatening complication of eye surgeries. The relative contribution of S. aureus virulence factors in the pathogenesis of endophthalmitis remains unclear. Here, we comprehensively analyzed the development of intraocular inflammation, vascular permeability, and the loss of retinal function in C57BL/6 mouse eyes, challenged with live S. aureus, heat-killed S. aureus (HKSA), peptidoglycan (PGN), lipoteichoic acid (LTA), staphylococcal protein A (SPA), α-toxin, and Toxic-shock syndrome toxin 1 (TSST1). Our data showed a dose-dependent (range 0.01 μg/eye to 1.0 μg/eye) increase in the levels of inflammatory mediators by all virulence factors. The cell wall components, particularly PGN and LTA, seem to induce higher levels of TNF-α, IL-6, KC, and MIP2, whereas the toxins induced IL-1β. Similarly, among the virulence factors, PGN induced higher PMN infiltration. The vascular permeability assay revealed significant leakage in eyes challenged with live SA (12-fold) and HKSA (7.3-fold), in comparison to other virulence factors (~2-fold) and controls. These changes coincided with retinal tissue damage, as evidenced by histological analysis. The electroretinogram (ERG) analysis revealed a significant decline in retinal function in eyes inoculated with live SA, followed by HKSA, SPA, and α-toxin. Together, these findings demonstrate the differential innate responses of the retina to S. aureus virulence factors, which contribute to intraocular inflammation and retinal function loss in endophthalmitis.