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)

Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) continues to make headlines because of large outbreaks in daycare centers and among members of athletic teams. CA-MRSA infections in children commonly lead to hospitalization. Life-threatening infections, such as necrotizing pneumonitis and brain abscess, can occur. The organism has crossed into hospitals and is now a common cause of hospital-acquired sepsis. Multidrug-resistant strains of MRSA are emerging in Asia, with the resistance based on either a novel gene cassette or a transmissible plasmid. The routine use of antibiotics in livestock seems to be contributing to the emergence of resistant organisms, and some of these have already produced human infection. Fortunately, most cutaneous CA-MRSA infections present as abscesses or furunculosis, and these manifestations generally respond to drainage. The recurrence and attack rates of close contacts are high and relate to persistent colonization.
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PMID:How to handle a CA-MRSA outbreak. 1898 67

The presence of multiresistant pathogens in a hospital leads very often to a severe sepsis that threatens the patients' life. For this reason, in the interests of the patients in the Intensive Care Unite (ICU) of the Lodz Medical University Hospital No.1, a wide monitoring of the epidemiological situation and the rational antibiotic therapy, taking the resistance mechanisms of pathogens into account, have been started since 2002. Restrictive procedures of the insertion of central venous and dialysis catheters were elaborated as well as the permanent monitoring of the MRSA carrier state among the medical staff was undertaken. A procedure of the primary bacteriological examination for all new patients in the ICU was also introduced. All these actions resulted in a considerable, statistically significant (p=0.043), decrease in bloodstream infections from 14.2 infections per 100 patients in 2002 to 2.0 infections per 100 patients in 2006. A drop in the number of infections of central venous catheters was also observed: from 4.3 infections per 100 patients in 2002 to 1.9 infections per 100 patients in 2006 (p=0.025). Administration of ceftazidime and clavulanic acid, which are MRSA inductors, only in the events of guided therapy when other therapeutic options were failed as well as the reduction of the MRSA carrier state among the medical staff brought about a radical elimination of MRSA from the bloodstream infections. The obtained results show that the severe infections caused by multiresistant pathogens in hospitals can be effectively reduced due to cooperation between clinicians and microbiology laboratories.
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PMID:[Sepsis--a new life-threat or better defined old disease entity]. 1914 75

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

Meticillin-resistant Staphylococcus aureus (MRSA) is an important cause of infection, particularly in hospitalized patients and those with significant healthcare exposure. In recent years, epidemic community-associated MRSA (CA-MRSA) infections occurring in patients without healthcare risk factors have become more frequent. The most common manifestation of CA-MRSA infection is skin and soft tissue infection, although necrotizing pneumonia, sepsis and osteoarticular infections can occur. CA-MRSA strains have become endemic in many communities and are genetically distinct from previously identified MRSA strains. CA-MRSA may be more capable colonizers of humans and more virulent than other S. aureus strains. Specific mechanisms of pathogenicity have not been elucidated, but several factors have been proposed as responsible for the virulence of CA-MRSA, including the Panton-Valentine leukocidin, phenol-soluble modulins and type I arginine catabolic mobile element. The movement of CA-MRSA strains into the nosocomial setting limits the utility of using clinical risk factors alone to designate community- or healthcare-associated status. Identification of unique genetic characteristics and genotyping are valuable tools for MRSA epidemiological studies. Although the optimum pharmacological therapy for CA-MRSA infections has not been determined, many CA-MRSA strains remain broadly susceptible to several non-beta-lactam antibacterial agents. Empirical antibacterial therapy should include an MRSA-active agent, particularly in areas where CA-MRSA is endemic.
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PMID:Community-associated meticillin-resistant Staphylococcus aureus infections: epidemiology, recognition and management. 1940 50

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


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