Craniodental ecomorphology of the large Jurassic ichthyosaurian Temnodontosaurus.

Marine amniotes have played many crucial roles in ocean ecosystems since the Triassic, including predation at the highest trophic levels. One genus often placed into this guild is the large Early Jurassic neoichthyosaurian Temnodontosaurus, the only post-Triassic ichthyosaurian known with teeth which bear a distinct cutting edge or carina. This taxonomically problematic genus is currently composed of seven species which show a wide variety of skull and tooth morphologies. Here we assess the craniodental disparity in Temnodontosaurus using a series of functionally informative traits. We describe the range of tooth morphologies in the genus in detail, including the first examples of serrated carinae in ichthyosaurians. These consist of false denticles created by the interaction of enamel ridgelets with the carinal keel, as well as possible cryptic true denticles only visible using scanning electron microscopy. We also find evidence for heterodonty in the species T. platyodon, with unicarinate mesial teeth likely playing a role in prey capture and labiolingually compressed, bicarinate distal teeth likely involved in prey processing. This type of heterodonty appears to be convergent with a series of other marine amniotes including early cetaceans. Overall, the species currently referred to as the genus Temnodontosaurus show a range of craniodental configurations allowing prey to be captured and processed in different ways - for example, T. eurycephalus has a deep snout and relatively small bicarinate teeth likely specialised for increased wound infliction and grip-and-tear feeding, whereas T. platyodon has a more elongate yet robust snout and larger teeth and may be more adapted for grip-and-shear feeding. These results suggest the existence of niche partitioning at higher trophic levels in Early Jurassic ichthyosaurians and have implications for future work on the taxonomy of this wastebasket genus, as well as for research into the ecology of other extinct megapredatory marine tetrapods.

Rothia spp. infective endocarditis: A systematic literature review.

OBJECTIVE: To describe the epidemiological, clinical, microbiological, and therapeutic features and outcomes of Rothia infective endocarditis (RIE) and extracardiac infections (ECRI). METHODS: We performed a systematic literature review of published cases of RIE and ECRI. RESULTS: After inclusion of a personal case report, 51 cases of RIE and 215 cases of ECRI were reported. Compared with ECRI patients, RIE patients were significantly more often males (80% versus 59%), intravenous drug users (IVDU) (20% versus 3%), immunocompetent (76% versus 31%), and infected with R. dentocariosa (55% versus 13%) but lacked significant differences with regard to median age (45 years [6-79]), rate of orodental abnormalities (33%), and six-month mortality (14%). Following microbiological documentation, RIE was most often treated with a beta-lactam antibiotic alone (39%) for a median duration of six weeks and required surgery in 39% of cases. CONCLUSION: RIE is rare and likely secondary to a dental portal of entry or cutaneous inoculation in IVDU. Its prognosis seems to be favorable.

Aetiology and pathogenesis of hidradenitis suppurativa.

Hidradenitis suppurativa (HS) is a chronic inflammatory disorder. Patients develop inflamed nodules and abscesses and, at later stages of disease, epithelialized tunnels and scars in skinfolds of axillary, inguinal, gluteal and perianal areas. Quality of life is affected due to severe pain, purulent secretion, restricted mobility and systemic involvement. Genetics and lifestyle factors including smoking and obesity contribute to the development of HS. These factors lead to microbiome alteration, subclinical inflammation around the terminal hair follicles, and infundibular hyperkeratosis, resulting in plugging and rupture of the follicles. Cell-damage-associated molecules and propagating bacteria trigger inflammation and lead to massive immune cell infiltration that clinically manifests as inflamed nodules and abscesses. The immune system plays a key role also in the progression and chronification of skin alterations. Innate proinflammatory cytokines (e.g. interleukin-1ß and tumour necrosis factor-α), mediators of activated T helper (Th)1 and Th17 cells (e.g. interleukin-17 and interferon-γ), and effector mechanisms of neutrophilic granulocytes, macrophages and plasma cells are involved. Simultaneously, skin lesions contain anti-inflammatory mediators (e.g. interleukin-10) and show limited activity of Th22 and regulatory T cells. The inflammatory vicious circle finally results in pain, purulence, tissue destruction and scarring. Chronic inflammation in patients with HS is also frequently detected in organs other than the skin, as indicated by their comorbidities. All these aspects represent a challenge for the development of therapeutic approaches, which are urgently needed for this debilitating disease. This scholarly review focuses on the causes and pathogenetic mechanisms of HS and the potential therapeutic value of this knowledge.

Untargeted next-generation sequencing-based first-line diagnosis of infection in immunocompromised adults: a multicentre, blinded, prospective study.

OBJECTIVE: Infections are the major cause of morbidity and mortality in immunocompromised patients. Improving microbiological diagnosis in these patients is of paramount clinical importance. METHODS: We performed this multicentre, blinded, prospective, proof-of-concept study, to compare untargeted next-generation sequencing with conventional microbiological methods for first-line diagnosis of infection in 101 immunocompromised adults. Patients were followed for 30 days and their blood samples, and in some cases nasopharyngeal swabs and/or biological fluids, were analysed. At the end of the study, expert clinicians evaluated the results of both methods. The primary outcome measure was the detection rate of clinically relevant viruses and bacteria at inclusion. RESULTS: Clinically relevant viruses and bacteria identified by untargeted next-generation sequencing and conventional methods were concordant for 72 of 101 patients in samples taken at inclusion (κ test=0.2, 95% CI 0.03-0.48). However, clinically relevant viruses and bacteria were detected in a significantly higher proportion of patients with untargeted next-generation sequencing than conventional methods at inclusion (36/101 (36%) vs. 11/101 (11%), respectively, p <0.001), and even when the latter were continued over 30 days (19/101 (19%), p 0.003). Untargeted next-generation sequencing had a high negative predictive value compared with conventional methods (64/65, 95% CI 0.95-1). CONCLUSIONS: Untargeted next-generation sequencing has a high negative predictive value and detects more clinically relevant viruses and bacteria than conventional microbiological methods. Untargeted next-generation sequencing is therefore a promising method for microbiological diagnosis in immunocompromised adults.

Pharmacological study of cefoxitin as an alternative antibiotic therapy to carbapenems in treatment of urinary tract infections due to extended-spectrum-ß-lactamase-producing Escherichia coli.

Cefoxitin could be an alternative to carbapenems in extended-spectrum-beta-lactamase-producing Escherichia coli (ESBL-EC) infections. However, pharmacological and clinical data regarding cefoxitin are limited. Using a recent pharmacological model and the MICs of ESBL-EC collected from pyelonephritis, we determined the probabilities to reach four pharmacological targets: free cefoxitin concentrations above the MIC during 50% and 100% of the administration interval (T>MIC = 50% and T>MIC = 100%, respectively) and free cefoxitin concentrations above 4× MIC during 50% and 100% of the administration interval (T>4MIC = 50% and T>4MIC = 100%, respectively). Cefoxitin could be used to treat ESBL-EC pyelonephritis, but administration modalities should be optimized according to MICs in order to reach pharmacological targets.

Accuracy of postcontrast 3D turbo spin-echo MR sequence for the detection of enhanced inflammatory lesions in patients with multiple sclerosis.

BACKGROUND AND PURPOSE: Therapeutic strategies for patients with MS partly rely on contrast-enhanced MR imaging. Our aim was to assess the diagnostic performance of 3D turbo spin-echo MR imaging with variable refocusing flip angles at 3T for the detection of enhanced inflammatory lesions in patients with multiple sclerosis. MATERIALS AND METHODS: Fifty-six patients with MS were prospectively investigated by using postcontrast T1-weighted axial 2D spin-echo and 3D TSE MR images. The order in which both sequences were performed was randomized. Axial reformats from 3D T1 TSE were generated to match the 2D spin-echo images. The reference standard was defined by using clinical data and all MR images available. Three separate sets of MR images (2D spin-echo images, axial reformats, and multiplanar images from 3D TSE sequences) were examined in a blinded fashion by 2 neuroradiologists separately for the detection of enhanced MS lesions. Image artifacts and contrast were evaluated. RESULTS: No artifacts related to vascular pulsation were observed on 3D TSE images, whereas image artifacts were demonstrated on 2D spin-echo images in 41 patients. One hundred twelve enhanced MS lesions were identified in 19 patients. Sixty-four lesions were correctly diagnosed by using 2D spin-echo images; 90, by using 3D TSE axial reformatted views; and 106, by using multiplanar analysis of the 3D TSE sequence. Multiplanar analysis was 94.7% sensitive and 100% specific for the diagnosis of patients with at least 1 enhanced lesion. Contrast of enhanced MS lesions was significantly improved by using the 3D TSE sequence (P < .011). CONCLUSIONS: The 3D TSE sequence with multiplanar analysis is a useful tool for the detection of enhanced MS lesions.

Risk factors for developing ESBL E. coli: can clinicians predict infection in patients with prior colonization?

BACKGROUND: Extended-spectrum ß-lactamase-producing Escherichia coli (ESBLEC) is an increasing cause of hospital-acquired infection. Risk factors for ESBLEC colonization and infection have been reported, but information is lacking about the risk factors for acquiring ESBLEC infection in patients with prior colonization. AIM: To identify risk factors for development of infection in patients colonized with ESBLEC. METHODS: A retrospective study was performed at Hôpital Necker-Enfants Malades, Paris from 2007 to 2010. A multi-variable model was created to compare a group of patients with nosocomial ESBLEC infection following documented ESBLEC colonization with a control group of patients colonized with ESBLEC (case-control design). FINDINGS: In total, 118 patients were included: 40 (26 adults, 14 children) with colonization and infection and 78 (51 adults, 27 children) with colonization alone. The median time from colonization to infection was 12.5 days [25-75% confidence interval (CI) 5-40]. ESBLEC infections included urinary tract infection (85%), bacteraemia (7.5%) and lower respiratory tract infection (7.5%). On multi-variate analysis, use of ß-lactam/ß-lactamase inhibitor prior to infection [odds ratio (OR) 3.2, 95% CI 1.073-9.864); P = 0.037] and urinary catheterization were reported as risk factors for ESBLEC infection in colonized patients (OR 5.2, 95% CI 1.984-13.569; P = 0.0008). CONCLUSION: Identification of these risk factors will be helpful to identify patients colonized with ESBLEC who will require antibiotics for ESBLEC in the case of nosocomial infection. Limiting the use of specific antibiotics and controlling the duration of urinary catheterization will be helpful for prevention of ESBLEC infection.

Evaluation of the Andromas matrix-assisted laser desorption ionization-time of flight mass spectrometry system for identification of aerobically growing Gram-positive bacilli.

Matrix-associated laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) is a rapid and simple microbial identification method. Previous reports using the Biotyper system suggested that this technique requires a preliminary extraction step to identify Gram-positive rods (GPRs), a technical issue that may limit the routine use of this technique to identify pathogenic GPRs in the clinical setting. We tested the accuracy of the MALDI-TOF MS Andromas strategy to identify a set of 659 GPR isolates representing 16 bacterial genera and 72 species by the direct colony method. This bacterial collection included 40 C. diphtheriae, 13 C. pseudotuberculosis, 19 C. ulcerans, and 270 other Corynebacterium isolates, 32 L. monocytogenes and 24 other Listeria isolates, 46 Nocardia, 75 Actinomyces, 18 Actinobaculum, 11 Propionibacterium acnes, 18 Propionibacterium avidum, 30 Lactobacillus, 21 Bacillus, 2 Rhodococcus equi, 2 Erysipelothrix rhusiopathiae, and 38 other GPR isolates, all identified by reference techniques. Totals of 98.5% and 1.2% of non-Listeria GPR isolates were identified to the species or genus level, respectively. Except for L. grayi isolates that were identified to the species level, all other Listeria isolates were identified to the genus level because of highly similar spectra. These data demonstrate that rapid identification of pathogenic GPRs can be obtained without an extraction step by MALDI-TOF mass spectrometry.

MALDI-TOF MS Andromas strategy for the routine identification of bacteria, mycobacteria, yeasts, Aspergillus spp. and positive blood cultures.

All organisms usually isolated in our laboratory are now routinely identified by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) using the Andromas software. The aim of this study was to describe the use of this strategy in a routine clinical microbiology laboratory. The microorganisms identified included bacteria, mycobacteria, yeasts and Aspergillus spp. isolated on solid media or extracted directly from blood cultures. MALDI-TOF MS was performed on 2665 bacteria isolated on solid media, corresponding to all bacteria isolated during this period except Escherichia coli grown on chromogenic media. All acquisitions were performed without extraction. After a single acquisition, 93.1% of bacteria grown on solid media were correctly identified. When the first acquisition was not contributory, a second acquisition was performed either the same day or the next day. After two acquisitions, the rate of bacteria identified increased to 99.2%. The failures reported on 21 strains were due to an unknown profile attributed to new species (9) or an insufficient quality of the spectrum (12). MALDI-TOF MS has been applied to 162 positive blood cultures. The identification rate was 91.4%. All mycobacteria isolated during this period (22) were correctly identified by MALDI-TOF MS without any extraction. For 96.3% and 92.2% of yeasts and Aspergillus spp., respectively, the identification was obtained with a single acquisition. After a second acquisition, the overall identification rate was 98.8% for yeasts (160/162) and 98.4% (63/64) for Aspergillus spp. In conclusion, the MALDI-TOF MS strategy used in this work allows a rapid and efficient identification of all microorganisms isolated routinely.

Who is to blame? Perspectives of caregivers on barriers to accessing healthcare for the under-fives in Butere District, Western Kenya.

BACKGROUND: Kenya, like many developing nations, continues to experience high childhood mortality in spite of the many efforts put in place by governments and international bodies to curb it. This study sought to investigate the barriers to accessing healthcare services for children aged less than five years in Butere District, a rural district experiencing high rates of mortality and morbidity despite having relatively better conditions for child survival. METHODS: Exit interviews were conducted among caregivers seeking healthcare for their children in mid 2007 in all the 6 public health facilities. Additionally, views from caregivers in the community, health workers and district health managers were sought through focus group discussions (FGDs) and key informant interviews (KIs). RESULTS: Three hundred and ninety-seven respondents were surveyed in exit interviews while 45 respondents participated in FGDs and KIs. Some practices by caregivers including early onset of child bearing, early supplementation, and utilization of traditional healers were thought to increase the risk of mortality and morbidity, although reported rates of mosquito net utilization and immunization coverage were high. The healthcare system posed barriers to access of healthcare for the under fives, through long waiting time, lack of drugs and poor services, incompetence and perceived poor attitudes of the health workers. FGDs also revealed wide-spread concerns and misconceptions about health care among the caregivers. CONCLUSION: Caregivers' actions were thought to influence children's progression to illness or health while the healthcare delivery system posed recurrent barriers to the accessing of healthcare for the under-fives. Actions on both fronts are necessary to reduce childhood mortality.

Comparison of the in vitro efficacies of moxifloxacin and amoxicillin against Listeria monocytogenes.

Listeria monocytogenes is a facultative intracellular bacterium that causes severe infections associated with a high mortality rate. Moxifloxacin presents extended activity against gram-positive bacteria and has recently been suggested to be a potential alternative in the treatment of listeriosis. We evaluated the in vitro efficacy of moxifloxacin against L. monocytogenes using a combination of epidemiological and experimental approaches. The median MIC of moxifloxacin for a large collection of L. monocytogenes strains of various origins (human, food, and environment) was 0.5 microg/ml (MIC range, 0.064 to 1 microg/ml). No differences were observed, irrespective of the origin of the strains. Moreover, no cross-resistance with fluoroquinolones was detected in strains that have been reported to be resistant to ciprofloxacin. The in vitro activities of moxifloxacin and amoxicillin were compared by time-kill curve and inhibition of intracellular growth experiments by using a model of bone marrow-derived mouse macrophages infected by L. monocytogenes EGDe. Both moxifloxacin and amoxicillin were bactericidal in broth against extracellular forms of L. monocytogenes. However, moxifloxacin acted much more rapidly, beginning to exert its effects in the first 3 h and achieving complete broth sterilization within 24 h of incubation. Moxifloxacin has a rapid bactericidal effect against intracellular reservoirs of bacteria, whereas amoxicillin is only bacteriostatic and appears to prevent cellular lysis and the subsequent bacterial spreading to adjacent cells. No resistant bacteria were selected during the in vitro experiments. Taken together, our results suggest that moxifloxacin is an interesting alternative to the reference treatment, combining rapid and bactericidal activity, even against intracellular bacteria.

Evaluation of moxalactam with the BD phoenix system for detection of methicillin resistance in coagulase-negative staphylococci.

The performance of moxalactam with the BD Phoenix system for the detection of methicillin resistance in coagulase-negative staphylococci was evaluated by use of a collection of 186 strains. Moxalactam was a better drug as an indicator of methicillin resistance for mecA-positive strains than oxacillin and cefoxitin were. For strains other than Staphylococcus saprophyticus, a moxalactam MIC >16 microg/ml was indicative of methicillin resistance.