Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The emergence of drug-resistant pathogens such as staphylococci and enterococci in the hospital setting has long being recognized as a serious clinical problem. Staphylococcus aureus is the causative agent of many nosocomial infections from minor skin abscesses to serious, potentially life threatening diseases such as bone and soft tissue intra-surgical infections, sepsis and invasive endocarditis, while enterococci are responsible for nosocomial bacteraemia, surgical wound infections and endocarditis. The most infamous drug-resistant forms of these include MRSA (methicillin resistant S. aureus), VISA (vancomycin insensitive S. aureus), hVISA (heterogenous vancomycin insensitive S. aureus) and VRE (vancomycin resistant S. aureus). While enhanced hygiene awareness is essential to any solution, the identification of effective novel antimicrobial compounds remains a major goal in eradicating these and other infections caused by multi-drug resistant pathogens. In recent years a class of antimicrobial peptides, the Lantibiotics, have been the focus of an ever increasing level of attention. This interest has been prompted by an enhanced appreciation of the mode of action of these peptides (including, in many cases, the ability to bind lipid II) and their frequently high levels of antimicrobial activity. Here we review lantibiotic-related issues in drug discovery, outline the strategies that have been employed to identify these peptides and summarize the use of bioengineering to generate enhanced forms of these peptides as well as the application of the associated biological machinery to generate novel forms of existing pharmaceutical compounds. In so doing we highlight how some, or all, of these approaches have the potential to result in the development of clinically important drugs.
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PMID:Discovery of medically significant lantibiotics. 1927 38

Molecular epidemiology studies have allowed the identification of the methicillin (meticillin)-resistant (MRSA) and methicillin-susceptible (MSSA) clonal complexes (CCs) and clones of Staphylococcus aureus circulating in a Spanish hospital recently. Of 81 isolates tested, 32.1% were MRSA. Most of them carried staphylococcal cassette chromosome mec (SCCmec) IVc (88.5%) and belonged to CC5 (88.5%; multilocus sequence typing types ST125 [mainly associated with spa type t067], ST5, and ST228). A higher diversity was found among MSSA isolates (67.9%). Eighty percent shared the genetic background of major MRSA lineages (CC5 [38.2%; ST125 and ST5], CC30 [25.5%; ST30], CC45 [14.5%; ST45 and ST47], and CC8 [1.8%; ST8]), but CC12, CC15, CC51, and CC59 were also detected. Many exotoxin genes were present in each of the 81 isolates, independent of whether they were involved in sepsis (11 to 22) or other types of infections (13 to 21), and they appeared in 73 combinations. The relevant data are that (i) all isolates were positive for hemolysin and leukotoxin genes (98.8% for lukED and 25.9% for lukPV); (ii) all contained an enterotoxin gene cluster (egc with or without seu), frequently with one or more genes encoding classical enterotoxins; (iii) about half were positive for tst and 95% were positive for exfoliatin-encoding genes (eta, etb, and/or etd); and (iv) the four agr groups were detected, with agrII (55.6%) and agrIII (23.5%) being the most frequent. Taken together, results of the present study suggest a frequent acquisition and/or loss of exotoxin genes, which may be mediated by efficient intralineage transfer of mobile genetic elements and exotoxin genes therein and by eventual breakage of interlineage barriers.
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PMID:Clonal complexes and diversity of exotoxin gene profiles in methicillin-resistant and methicillin-susceptible Staphylococcus aureus isolates from patients in a Spanish hospital. 1945 76

LBM415 is an antibacterial agent belonging to the peptide deformylase inhibitor class of compounds. It has previously been shown to demonstrate good activity in vitro against a range of pathogens. In this study, the in vivo efficacy of LBM415 was evaluated in various mouse infection models. We investigated activity against a systemic infection model caused by intraperitoneal inoculation of Staphylococcus aureus (methicillin [meticillin] susceptible [MSSA] and methicillin resistant [MRSA]) and Streptococcus pneumoniae (penicillin susceptible [PSSP] and multidrug resistant [MDRSP]), a thigh infection model caused by intramuscular injection of MRSA, and a lung infection produced by intranasal inoculation of PSSP. In the systemic MSSA and MRSA infections, LBM415 was equivalent to linezolid and vancomycin. In the systemic PSSP infection, LBM415 was equivalent to linezolid, whereas against systemic MDRSP infection, the LBM415 50% effective dose (ED50) was 4.8 mg/kg (dosed subcutaneously) and 36.6 mg/kg (dosed orally), compared to 13.2 mg/kg for telithromycin and >60 mg/kg for penicillin V and clarithromycin. In the MRSA thigh infection, LBM415 significantly reduced thigh bacterial levels compared to those of untreated mice, with levels similar to those after treatment with linezolid at the same dose levels. In the pneumonia model, the ED50 to reduce the bacterial lung burden by >4 log10 in 50% of treated animals was 23.3 mg/kg for LBM415, whereas moxifloxacin showed an ED50 of 14.3 mg/kg. In summary, LBM415 showed in vivo efficacy in sepsis and specific organ infection models irrespective of resistance to other antibiotics. Results suggest the potential of peptide deformylase inhibitors as a novel class of therapeutic agents against antibiotic-resistant pathogens.
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PMID:In vivo characterization of the peptide deformylase inhibitor LBM415 in murine infection models. 1959 76

Dual inhibitors of bacterial gyrB and parE based on a 5-(2-pyrimidinyl)-imidazo[1,2-a]pyridine template exhibited MICs (microg/mL) of 0.06-64 (Sau), 0.25-64 (MRSA), 0.06-64 (Spy), 0.06-64 (Spn), and 0.03-64 (FQR Spn). Selected examples were efficacious in mouse sepsis and lung infection models at <50mg/kg (PO dosing).
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PMID:5-(2-Pyrimidinyl)-imidazo[1,2-a]pyridines are antibacterial agents targeting the ATPase domains of DNA gyrase and topoisomerase IV. 1968 22

Fosfomycin (FOM) is an antibiotic which has varying application indications across the globe. European, Japanese, South African and Brazilian usage practices are much broader, involving multiple formulations of FOM than the currently limited application of FOM in the United States, where uncomplicated urinary tract infection represents the only indication for FOM-tromethamine. Based on early difficulty in determining FOMs genuine in vitro activity, there was initial skepticism about its efficacy and application range. However, in the mid 1970s, correctly executed experiments coupled with an improved understanding of microbiological concepts opened the door for broader use of FOM. During the following 40 years FOM was evaluated in pre-clinical and clinical trials in a wide range of applications and in a multitude of settings. The gathering of pharmacokinetic and pharmacodynamic data was incorporated into large scale studies in which FOM efficacy was further explored and proven. Among European nations, intravenous FOM-disodium for patients presenting with soft tissue infections, sepsis or deep seated infectious processes has become well accepted over the last two decades. The recent emergence of bacterial strains, which impede and encumber pharmacotherapy, namely, MRSA, ESBL and MSSA, lends itself to the idea of reviving long-standing, sensibly used antimicrobial agents like FOM. This review provides a comprehensive conspectus on FOM's history, mode of action, tissue penetration characteristics, resistance, antibacterial activity, combination partners and clinical uses among other facets of interest.
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PMID:Fosfomycin: an old, new friend? 1991 79

Community acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infection has become a major pathogen causing significant infection in children in Saudi Arabia. It has emerged as a frequent cause of skin and soft tissue infections and can be associated with life-threatening complications such as necrotizing pneumonia and sepsis. Between January 2005 and March 2008, 5 (6%) previously healthy children with invasive CA-MRSA infections were identified from 80 children with community-onset MRSA infections. Three children had osteomyelitis, with one patient presenting a fulminant and extensive soft tissue and bone destruction complicated by deep vein thrombosis and pathological fracture. One child had deep-seated infection, and one infant had severe orbital cellulitis and bilateral orbital abscess complicated by subdural empyema. The median age was 4-years (range 3 months to 17 years). Only one patient had a risk factor. Two patients were initially treated with ineffective antimicrobial therapy (beta-lactam). One isolate showed inducible clindamycin resistance. The recovery was uneventful in all patients. This report should increase the awareness of clinicians regarding severe CA-MRSA infections and highlight the challenges encountered in the choice of therapy of serious infections caused by this organism.
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PMID:Severe community-acquired infection caused by methicillin-resistant Staphylococcus aureus in Saudi Arabian children. 2038 32

Fever is defined as a rectal temperature greater than 38.0 degrees C (>100.4 degrees F). A recently documented fever at home should be considered the same as a fever in the ED and should be managed similarly. All febrile infants younger than 28 days should receive a "full sepsis workup" and be admitted for parenteral antibiotic therapy. Clinical and laboratory criteria can be used to identify a low-risk population of febrile infants aged 1 to 4 months who have not received 2 doses of conjugate vaccines for bacterial meningitis. Children with sickle cell disease are at high risk and require special evaluation. MRSA infections are now common and should be considered in all patients with pyoderma, severe pneumonia, and catheter-related sepsis. HSV infection of the CNS should be considered whenever a patient has altered mental status and CSF findings are not diagnostic of bacterial meningitis. Fever rarely represents life-threatening pathology; however, a handful of less common serious causes of pediatric fever exist with the potential for morbidity and mortality.
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PMID:Pediatric emergencies associated with fever. 1994 99

This case study is a collage of case studies regarding CA-MRSA in the athletic setting and is based on CA-MRSA cases observed by one of the authors while working as a school nurse in the high school setting. It is also based on multiple case studies of high school and college athletic teams documented in the literature. While CA-MRSA has been long been associated with superficial skin infections, the pathogenic capacity of CA-MRSA is now being well documented in the literature. Since 1994, there have been several cases documented where otherwise healthy children have contracted CA-MRSA infections that quickly progressed to bacteremia, sepsis, and death. Athletes, including those on high school teams, have been the subject of an increasing number of reported CA-MRSA cases (Patel, Fischer, Calfee, Plante, & Fadale, 2007). The purpose of this article is to show the importance of prevention and early treatment for suspected CA-MRSA infections. The ethical principle of justice supports nursing and public attention to prevention rather than tertiary care. In this situation, school and professional attention to hygiene would have prompted different behaviors, and this outcome might have been avoided. The cost of good hygiene practices in the locker room would have cost the school $41.45 and a little time for education. The combined estimated cost of secondary, tertiary, and rehabilitative care is $208,079 (see Table 7). The cost for permanent disability in a young person cannot be fully captured fiscally, nor should it be.
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PMID:Financial analysis of methicillin-resistant Staphylococcus aureus in a high school wrestler. 1947 78

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) strains have emerged as serious health threats in the last 15 years. They are associated with large numbers of atopic dermatitis skin and soft tissue infections, but when they originate from skin and mucous membranes, have the capacity to produce sepsis and highly fatal pulmonary infections characterized as necrotizing pneumonia, purpura fulminans, and postviral toxic shock syndrome. This review is a discussion of the emergence of 3 major CA-MRSA organisms, designated CA-MRSA USA400, followed by USA300, and most recently USA200. CA-MRSA USA300 and USA400 isolates and their methicillin-sensitive counterparts (community-associated methicillin-sensitive S aureus) typically produce highly inflammatory cytolysins alpha-toxin, gamma-toxin, delta-toxin (as representative of the phenol soluble modulin family of cytolysins), and Panton Valentine leukocidin. USA300 isolates produce the superantigens enterotoxin-like Q and a highly pyrogenic deletion variant of toxic shock syndrome toxin 1 (TSST-1), whereas USA400 isolates produce the superantigens staphylococcal enterotoxin B or staphylococcal enterotoxin C. USA200 CA-MRSA isolates produce small amounts of cytolysins but produce high levels of TSST-1. In contrast, their methicillin-sensitive S aureus counterparts produce various cytolysins, apparently in part dependent on the niche occupied in the host and levels of TSST-1 expressed. Significant differences seen in production of secreted virulence factors by CA-MRSA versus hospital-associated methicillin-resistant S aureus and community-associated methicillin-sensitive S aureus strains appear to be a result of the need to specialize as the result of energy drains from both virulence factor production and methicillin resistance.
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PMID:Secreted virulence factor comparison between methicillin-resistant and methicillin-sensitive Staphylococcus aureus, and its relevance to atopic dermatitis. 2010 35

The physiologic process of wound healing is impaired and prolonged in paediatic patients receiving chemotherapy. Due to profound immunosuppression, wound infection can easily spread and act as the source of sepsis. Referring to in vitro studies, which confirmed the antibacterial potency of special honey preparations against typical isolates of nosocomially acquired wound infections (including MRSA and VRE) and considering the encouraging reports from other groups, Medihoney has now been used in wound care at the Department of Pediatric Oncology, Children's Hospital, University of Bonn for three years. Supplemented with exemplary clinical data from pediatric oncology patients, this presentation reviews the scientific background and our promising experience with Medihoney in wound care issues at our institution.
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PMID:Antibacterial honey (Medihoney) for wound care of immunocompromised pediatric oncology patients. 2020 81


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