Necrotizing Soft-Tissue Infections Stevens, Dennis L; Bryant, Amy E
The New England journal of medicine,
12/2017, Volume:
377, Issue:
23
Journal Article
Peer reviewed
The hallmarks of necrotizing fasciitis are friable superficial fascia, gray exudate without pus, and widespread tissue destruction. The infection is either polymicrobial or monomicrobial. Early ...surgical débridement and appropriate antibiotics are crucial for recovery.
Patterns of connectivity between breeding and wintering grounds can have important implications for individual fitness and population dynamics. Using light-level geolocators and stable hydrogen ...isotopes (δ²H) in feathers, we evaluated differential migration of Savannah sparrows (Passerculus sandwichensis) breeding on Kent Island in the Bay of Fundy, New Brunswick, Canada in relation to sex, age, and body size. Based on geolocators recovered from 38 individuals between 2012 and 2014, the winter distribution was centered in North Carolina (median latitude 34°, range 26°–41°), with males overwintering, on average, approximately 275 km further north than females. Based on analyses of tail feather samples collected from 106 individuals from the same population between 2008 and 2012, males and adults had more negative δ²H values than females and juveniles, respectively, providing additional evidence that males wintered north of females and that adults wintered north of juveniles. Winter latitude and δ²H values within each sex were not found to be related to body size. From geolocator data, males returned to the breeding grounds, on average, 14 days earlier than females. For males, there was some evidence that arrival date on the breeding grounds was negatively correlated with winter latitude and that individuals which arrived earlier tended to breed earlier. Thus, benefits for males of early arrival on the breeding grounds may have contributed to their wintering farther north than females. Social dominance may also have contributed to age and sex differences in winter latitude, whereby dominant males and adults forced subordinate females and juveniles further south.
Abstract
Background
Apart from their antimicrobial activities, some antibiotics have immunomodulatory effects on host cells, particularly monocytes. Because hyperactivation of the pro-inflammatory ...cytokine response contributes to acute lung injury in patients with bacterial pneumonia and other lung diseases, antimicrobial agents with immunomodulatory activity can reduce cytokine-mediated tissue injury and improve outcomes.
Objectives
Omadacycline has been recently FDA-approved for community-acquired bacterial pneumonia and acute bacterial skin and skin-structure infections. The present study investigated omadacycline’s ability to modulate LPS-induced production of pro-inflammatory cytokines (TNF-α, IL-1β), acute-phase reactants (IL-6) and anti-inflammatory cytokines (IL-4, IL-10) by human monocytes in vitro.
Methods
Isolated human monocytes from healthy consenting adults were cultured in RPMI with 1% pooled human serum. Cells were pre-exposed to omadacycline (0.5–64 μg/mL), minocycline (25, 50 or 25 μg/mL) or azithromycin (20, 40 or 80 μg/mL) for 2 h, followed by stimulation with Escherichia coli LPS for 24 h. Cytokines elaborated in the culture supernatant were quantitated by multiplex immunoassay.
Results
Omadacycline dose-dependently suppressed LPS-induced production of all cytokines tested. Only high-dose minocycline (100 μg/mL) modestly suppressed TNF-α whereas minocycline significantly increased LPS-induced IL-1β production. Lower concentrations of minocycline were also stimulatory for IFN-γ, IL-6 and IL-4. Except for suppression of IL-6, azithromycin was largely without effect.
Conclusions
Omadacycline has unique and broad immunomodulatory properties. Such activity supports its use in settings where hyperactivation of the immune response contributes to tissue injury and poor outcomes, especially at sites where pro-inflammatory M-type 1 macrophages dominate the cellular immune response.
Extracellular protein toxins contribute to the pathogenesis of a wide variety of Staphylococcus aureus infections. The present study investigated the effects that cell-wall active antibiotics and ...protein-synthesis inhibitors have on transcription and translation of genes for Panton-Valentine leukocidin, alpha-hemolysin, and toxic-shock syndrome toxin 1, in both methicillin-sensitive and methicillin-resistant S. aureus Subinhibitory concentrations of nafcillin induced and prolonged mRNA for Panton-Valentine leukocidin, alpha-toxin, and toxic-shock syndrome toxin 1 and increased toxin production. In contrast, clindamycin and linezolid markedly suppressed translation, but not transcription, of toxin genes. These results suggest (1) that protein-synthesis inhibition is an important consideration in the selection of antimicrobial agents to treat serious infections caused by toxin-producing gram-positive pathogens and (2) that, by inducing and enhancing toxin production, inadvertent use of beta-lactam antibiotics to treat methicillin-resistant S. aureus infections may contribute to worse outcomes
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This review summarizes the general concepts of innate and acquired immunity, including vaccine use and hesitancy, as they relate to reduction of the global burden of highly communicable infectious ...diseases.
Vaccination to increase herd immunity remains the cornerstone of disease prevention worldwide yet global vaccination goals are not being met. Modern obstacles to vaccine acceptance include hesitancy, reduced altruistic intentions, impact of COVID-19, distrust of science and governmental agencies as well as recent geopolitical and environmental disasters. Together, such barriers have negatively impacted immunization rates worldwide, resulting in epidemics and pandemics of serious life-threatening infections from vaccine-preventable diseases, especially those affecting children. In addition, pathogens thought to be controlled or eradicated are reemerging with new genetic traits, making them more able to evade natural and acquired immunity, including that induced by available vaccines. Lastly, many serious and widespread infectious diseases await development and utilization of efficacious vaccines.
The global burden of communicable diseases remains high, necessitating continued pathogen surveillance as well as vaccine development, deployment and continued efficacy testing. Equally important is the need to educate aggressively the people and their leaders on the benefits of vaccination to the individual, local community and the human population as a whole.
Necrotizing Soft-Tissue Infections Yildiz, Halil; Yombi, J. Cyr; Stevens, Dennis L ...
The New England journal of medicine,
03/2018, Volume:
378, Issue:
10
Journal Article
Peer reviewed
To the Editor:
In their review article, Stevens and Bryant (Dec. 7 issue)
1
discuss necrotizing soft-tissue infections. Early diagnosis is missed in 85 to 100% of cases.
2
In Figure 2 of the article ...(available at NEJM.org), the authors propose an algorithm that is based on the Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score. However, Borschitz et al.
3
found that serum sodium and glucose levels are of less value than the erythrocyte count and fibrinogen levels, which is why they proposed a modified LRINEC scoring system. They exchange the sodium and glucose levels for the erythrocyte count (1 point for . . .
Life-threatening soft tissue infections caused by Clostridium species have been described in the medical literature for hundreds of years largely because of their fulminant nature, distinctive ...clinical presentations and complex management issues. The Clostridium species perfringens, septicum and histolyticum are the principal causes of trauma-associated gas gangrene and their incidence increases dramatically in times of war, hurricanes, earthquakes and other mass casualty conditions. Recently, there has also been an increased incidence of spontaneous gas gangrene caused by Clostridium septicum in association with gastrointestinal abnormalities and neutropenia. Similarly, over the last 15 years there has been increased recognition of a toxic shock-like syndrome associated with Clostridium sordellii in individuals skin-popping black tar heroin, in women undergoing childbirth or other gynecologic procedures including medically-induced abortion. Like their cousins Clostridium tetanus and Clostridium botulinum, the pathogenesis of these clostridial infections is largely the consequence of potent exotoxin production. Strategies to inhibit toxin production, neutralize circulating toxins and prevent their interaction with cells of the innate immune response are sorely needed. Recent studies have elucidated novel targets that may hold promise for newer therapeutic modalities.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Puerperal sepsis caused by group A Streptococcus (GAS) remains an important cause of maternal and infant mortality worldwide, including countries with modern antibiotic regimens, intensive care ...measures and infection control practices. To provide insights into the genesis of modern GAS puerperal sepsis, we reviewed the published cases and case series from 1974 to 2009, specifically seeking relationships between the likely source of pathogen acquisition, clinical signs, and symptoms at infection onset and patient outcomes that could provide clues for early diagnosis. Results suggest that the pathogenesis of pregnancy-related GAS infections in modern times is complex and not simply the result of exposure to GAS in the hospital setting. Additional research is needed to further explore the source of GAS, the specific M types involved, and the pathogenesis of these pregnancy-related infections to generate novel preventative and therapeutic strategies.
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As the infectious disease paradigm undergoes a subtle shift, unusual infections associated with malignancy and immunosuppression are being increasingly reported. Spontaneous or non-traumatic ...Clostridium septicum infection is one such unusual infection which has gained prominence. This article aims to understand the pathophysiology, clinical manifestations and current trends in diagnosing and treating this rare but deadly infection. To understand the multifactorial causation of this infection a review of published cases of spontaneous C. septicum gas gangrene was performed and a total of 94 such cases were identified. Several factors were analyzed for each case: age, infection location and underlying illness, presenting signs and symptoms, neutropenia, gross pathology of the colon, antibiotic use, surgical intervention, and survival. A known or occult malignancy was present in 71% patients and an overall mortality of 67% was observed.
•This article summarizes the pathophysiology, clinical spectrum, diagnosis and management of spontaneous C. septicum infections.•A systematic review and analysis is performed for published spontaneous C. septicum gas gangrene cases since 1956 to 2016.•Reviewed data suggests that a known or occult malignancy was present in 71% cases.•Pathophysiology of spontaneous C. septicum infection is discussed and gaps in the current understanding are identified
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Purpose: Spoken discourse analysis is commonly employed in the assessment and treatment of people living with aphasia, yet there is no standardization in assessment, analysis, or reporting ...procedures, thereby precluding comparison/meta-analyses of data and hindering replication of findings. An important first step is to identify current practices in collecting and analyzing spoken discourse in aphasia. Thus, this study surveyed current practices, with the goal of working toward standardizing spoken discourse assessment first in research settings with subsequent implementation into clinical settings. Method: A mixed-methods (quantitative and qualitative) survey was publicized to researchers and clinicians around the globe who have collected and/or analyzed spoken discourse data in aphasia. The survey data were collected between September and November 2019. Results: Of the 201 individuals who consented to participate, 189 completed all mandatory questions in the survey (with fewer completing nonmandatory response questions). The majority of respondents reported barriers to utilizing discourse including transcription, coding, and analysis. The most common barrier was time (e.g., lack of time). Respondents also indicated that there was a lack of, and a need for, psychometric properties and normative data for spoken discourse use in the assessment and treatment of persons with aphasia. Quantitative and qualitative results are described in detail. Conclusions: The current survey study evaluated spoken discourse methods in aphasia across research and clinical settings. Findings from this study will be used to guide development of process standardization in spoken discourse and for the creation of a psychometric and normative property database.
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DOBA, IZUM, KILJ, NUK, ODKLJ, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
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