Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Efficacy and safety of imipenem/cilastatin in neonatal Klebsiella pneumonia sepsis was investigated in 45 infants compared to 39 control infants on conventional antibiotic regimen. Sensitivity to imipenem was 94% followed by cephoxitin (88%), quinolons (80%), and amikacin (52%) according to susceptibility results in the study group. Treatment duration of surviving infants was 16.5 +/- 4.6 and 20.3 +/- 6.4 days in the study and control groups respectively (p < 0.05). Five infants (11%) vs 27 (69%) were unresponsive (septic deaths) to treatment in the study and control groups respectively (p < 0.001). The cure rates were 73% and 28% respectively (p < 0.001). Sequelae free discharge rates were 67% and 23% respectively (p < 0.001). The most frequent adverse effects of imipenem/cilastatin were Candida albicans superinfection (20%); Candida albicans colonisation (10%); impairment of liver and renal functions (19% and 10% respectively); seizures (5%); thrombocytosis (3%); thrombophlebitis (3%); urine discoloration (3%); and Staphylococcus epidermidis colonisation (2%). Imipenem is considered a good alternative for neonatal Klebsiella pneumonia sepsis with these results, however, one must be aware of the increased risk of Candida albicans superinfection.
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PMID:Neonatal Klebsiella pneumonia sepsis and imipenem/cilastatin. 1077 55

The activity of cefpirome, cefepime and piperacillin/tazobactam previously unused in the hospital was evaluated in parallel with five broad-spectrum antibiotics (ceftazidime, ceftriaxone, imipenem, ciprofloxacin and amikacin) currently being used to treat serious infections in the National University Hospital, Singapore. Two hundred and two clinically significant, organisms consecutively isolated during 1998 were included in the study. In vitro efficacy of cefepime, cefpirome and piperacillin/tazobactam was not superior to imipenem, ciprofloxacin and amikacin which are currently used. More than 40% of Enterbacteriaceae were found to be ESBL producers. The incidence of nosocomial organisms resistant to drugs used in serious infections had increased since 1995. Imipenem-resistance occurred in 34.4% of Acinetobacter spp. and 19.2% Pseudomonas aeruginosa. No single agent appeared to be suitable for empirical monotherapy of serious sepsis.
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PMID:Widespread resistance to new antimicrobials in a university hospital before clinical use. 1169 75

The ability of cefoxitin, clindamycin, imipenem, meropenem, metronidazole and piperacillin-tazobactam to cause gram-negative anaerobic bacteria to release endotoxin and the influence of such liberated endotoxin on antibiotic efficacy were investigated in in-vivo experiments in animal models. Experimental infections in various animal models (mice, hamster and infant rats) with cultures of wild and reference strains of Bacteroides fragilis group and Fusobacterium spp. were carried out by injecting these animals with different inocula (10(6), 10(7) and 10(8) cfu/ml) of the bacterial suspension, Appropriate doses of the test antibiotics were then injected and the plasma lipopolysaccharide (endotoxin) release measured by the Limulus Amoebocyte Lysate (LAL) Assay. Evidence of worsening of the outcome of the infections post-therapy was assessed, including histopathological changes in the internal organs. Infection with generalized septicemia was established with F. nucleatum in the mice and hamster models while with the B. fragilis group, infections only led to intra-abdominal abscess formation. Plasma endotoxin release was higher in animals infected with F. nucleatum than B. fragilis and was unrelated to the bacterial inoculum. Imipenem, meropenem and cefoxitin, in that order, induced the highest levels of endotoxin activities in the animal model, particularly following F. nucleatum infection. Histological examination of the internal organs of various animals showed variation in the pattern of histopathological changes; grades 3-4 inflammatory changes in the liver were observed in the Fusobacterium-infected animals that were treated with the carbapenems and cefoxitin. Therapy with the other antibiotics did not exacerbate anaerobic sepsis. In this study, bacteremia did not lead to massive endotoxin release and antibiotic therapy appeared not to have negatively influenced the outcome of most of the gram-negative anaerobic infections, except for infections caused by Fusobacterium spp. However, it is conceivable that if the gastrointestinal tract is the source of the endotoxin in patients with systemic inflammatory response syndrome, then the obligate anaerobes like Bacteroides and Fusobacterium species, which are members of the gut flora, may play a major role in the unfavorable outcome of antibiotic therapy in some of these infections.
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PMID:Influence of in-vivo endotoxin liberation on anti-anaerobic antimicrobial efficacy. 1176 Feb 15

Infection with Burkholderia mallei (formerly Pseudomonas mallei) can cause a subcutaneous infection known as "farcy" or can disseminate to condition known as Glanders. It is primarily a disease affecting horses, donkeys and mules. In humans, Glanders can produce four types of disease: localized form, pulmonary form, septicemia, and chronic form. Necrosis of the tracheobronchial tree and pustular skin lesions characterize acute infection with B. mallei. Other symptoms include febrile pneumonia, if the organism was inhaled, or signs of sepsis and multiple abscesses, if the skin was the port of entry. Glanders is endemic in Africa, Asia, the Middle East, and Central and South America. Glanders has low contiguous potential, but because of the efficacy of aerosolized dissemination and the lethal nature of the disease, B. mallei was considered a candidate for biological warfare. During World War I, Glanders was believed to have been spread to infect large numbers of Russian horses and mules on the Eastern front. The Japanese infected horses, civilians and prisoners of war during World War II. The USA and the Soviet Union have shown interest in B. mallei in their biological warfare program. The treatment is empiric and includes mono or poly-therapy with Ceftazidime, Sulfadiazine, Trimethoprim + Sulfamethoxazol, Gentamicin, Imipenem etc. Aggressive control measures essentially eliminated Glanders from the west. However, with the resurgent concern about biological warfare, B. mallei is now being studied in a few laboratories worldwide. This review provides an overview of the disease and presents the only case reported in the western world since 1949.
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PMID:[Glanders--a potential disease for biological warfare in humans and animals]. 1217 May 62

Complicated urinary infections tend to eventuate in severe pyoseptic complications--bacteriuria, sepsis. The search for methods of fighting agents of urinary infections goes in the direction of perfection of already existing methods and in the direction of design of novel antibacterial drugs. In the middle 1980s the first carbapenem drug-imipenem--was proposed for urological clinical practice. Mechanism of its action as that of the other beta-lactam antibiotics consists in impairment of synthesis of bacterial cell wall as a result of the drug penetration through the surface membrane and irreversible binding with penicillin-binding proteins. Imipenem is active against most gram-positive and gram-negative aerobic and anaerobic microorganisms which cause severe urological infections. The article presents the results of treatment of 45 patients with severe urological infections with multiple resistance of the causing agent and failure of previous treatment. Imipenem was given in a daily dose 1.5-2.0 g. Sometimes a stepwise regimen was used: 500 mg 4 times a day intravenously for the first 3-4 days, then 500 mg twice a day intramuscularly for the following 3-4 days. In detection of highly sensitive bacteria (E. coli, Proteus mirabilis) daily doses were reduced to 1 g. In long standing infection caused by Pseudomonas aeruginosa imipenem was combined with amicacin. In high surgical risk of postoperative period imipenem was given prior to surgery and continued after it for 5 to 14 days. Good therapeutic results were achieved: clinical effect reached 95.5%, antibacterial efficiency was 87.8%. Thus, imipenem is antibiotic of the first line in empirical therapy of severe bacterial infections in urology as it has a wide spectrum of antibacterial action. We believe that this drug should not be left as a reserve but used for a starting empirical therapy of severe infections in urological hospital.
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PMID:[Effectiveness of imipenem/cilastatin (Tienam, MSD) in treating complicated infections in urology]. 1218 53

Coagulation and complement proteinases are activated in sepsis, and one approach to therapy is to develop proteinase inhibitors that will specifically inhibit these proteinases without inhibiting activated protein C, a proteinase that is beneficial to survival. In this study, we made mutants of the serpin alpha(1)-PI, designed to mimic the specificity of C1-inhibitor. The P3-P2-P1 residues of alpha1-PI were changed from IPM to LGR and PFR, sequences preferred by C1s and kallikrein, respectively. Inhibition of C1s, kallikrein, factor XIIa, and activated protein C was assessed by SDS-PAGE, and by determination of the k(app) and SI. alpha(1)-PI-LGR inhibited C1s with a rate of 7790 M(-1)s(-1), but only minimal inhibition of C1 in a hemolytic assay was observed. Kallikrein, factor XIIa, and activated protein C were inhibited with rates of 382,180 M(-1)s(-1), 10,400 M(-1)s(-1), and 3500 M(-1)s(-1), respectively. alpha(1)-PI-PFR was a poor inhibitor of C1s, factor XIIa, and activated protein C, but had enhanced reactivity with kallikrein. Changing the P4' residue of alpha(1)-PI-LGR Pro to Glu reduced the activity with C1s, consistent with the idea that C1s requires hydrophobic residues in this region of the serpin for optimal interaction. The data provide insight into the requirements for kallikrein and C1s inhibition necessary for designing inhibitors with appropriate properties for further investigation as therapeutic agents.
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PMID:alpha(1)-Proteinase inhibitor mutants with specificity for plasma kallikrein and C1s but not C1. 1219 78

We describe our therapeutic principles in connection with the treatment of 43 patients (30 male and 13 female) with acute necrotizing pancreatitis. The etiology of the disease was alcohol in 72.1%, gallstones in 23.3%, trauma, hyperlipidemia, ERCP and unknown in 4.7%. In all patients, the necrosis was proved by CT and histological examination. The patients were treated in intensive care unit. It involved prophylactic antibiotics (Imipenem) and early nasojejunal feeding. In each case, we endeavoured to delay surgery, which was a wide necrosectomy extending to the retroperitoneum. In 13 patients (30.2%) CT-guided percutaneous drainage was performed because of extensive peripancreatic fluid. Ten such patients were operated on at a later time. In 81.4% (35 patients) an average of 1.8 operations were performed. The first indications were acute abdomen, septic necrosis and multi-organ failure (MOF) unreactive to conservative therapy. Five patients (11.6%) were cured with conservative treatment and 3 patients (7%) were cured by treatment which included percutaneous drainage. Twenty-seven reoperations were performed in 12 patients because of sepsis, suspected peritonitis, abscess, bleeding and gastro-intestinal perforation. The average hospital stay was 44.5 days (3-120 days) long, and mortality was 16.2%. In our opinion in addition to intensive therapy, prophylactic antibiotics, early nasojejunal feeding and late, delayed surgery are important in the treatment of acute necrotizing pancreatitis. Percutaneous peripancreatic drainage is a useful way to delay operation. These therapeutic possibilities improve the survival rate of patients with pancreatic necrosis.
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PMID:[Therapeutic strategy in acute necrotizing pancreatitis]. 1223 83

A 88-year-old woman, who had lived in a nursing home, was admitted to our hospital because of the suspicion of pulmonary tuberculosis. She had a cough, fever and diarrhea on admission. She suffered from sepsis because Listeria monocytogenes was isolated from only the blood culture twice. We immediately administered imipenem/cilastatin to her on admission. She simultaneously had pulmonary non-tuberculous mycobacterial infection because the chest roentgenogram showed a cavity in the right upper lung field and Mycobacterium intracellulare was isolated from the sputum many times. She was treated with isoniazid, rifampicin and clarithromycin for the pulmonary non-tuberculous mycobacterial infection. Her condition improved soon after the administration of IPM/CS but a low grade fever and cough persisted. L. monocytogenes and M. intracellulare are important pathogens in the elderly because cell-mediated immunity mainly works as host defenses against both organisms.
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PMID:[An elderly case with Listeria monocytogenes sepsis and pulmonary non-tuberculous mycobacterial infection]. 1260 49

We report a patient with bacterial translocation-associated sepsis who was healthy and did not have any related-background. The 57-year-old male had been well until 16 hours before admission, when nausea and vomiting gradually developed and increased in intensity. In the morning of May 22, 2002, he had shaking chills, temperature of 38.6 degrees C and watery diarrhea, and was admitted to Kawasaki Municipal Hospital. On admission, temperature was 40.7 degrees C but otherwise physical examination revealed no particular abnormality. Laboratory data showed total white blood cells of 28,400/microliter, platelet count of 130,000/microliter, creatinine of 2.0 mg/dl and C-reactive protein of 7.5 mg/dl. 1 g of cefmetazole was administered every eight hours. In the early morning of May 23, he suddenly went into shock. At that time, laboratory findings revealed total white blood cells of 33,700/microliter, platelet count of 65,000/microliter, C-reactive protein of 24.9 mg/dl, creatinine of 5.6 mg/dl and serum potassium concentration of 5.7 mEq/l. Gram positive cocci and gram negative rods were isolated from blood culture obtained on admission. Cefmetazole was changed to 1.5 g/day of imipenem/cilastatin sodium and 600 mg/day of clindamycin. In addition, hemodialysis and endotoxin removal with an adsorbent column using polymyxin B were performed. Bacteria detected in the blood on admission were identified as Klebsiela oxytoca and Enterococcus faecium. Imipenem/cilastatin sodium and clindamycin were continued for 13 days. The patient recovered fully and was discharged on June 11. This case suggests that bacterial translocation-associated sepsis might occur even in a hitherto healthy adult.
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PMID:[A case of probable bacterial translocation-associated sepsis in healthy adult]. 1510 13

The purpose of this study was to extend the use of microdialysis to the investigation of antibiotic distribution into the intraperitoneal fluid of rats with or without peritonitis. Microdialysis probes were inserted into the jugular vein and peritoneal cavity of control rats or rats with intra-abdominal sepsis (n = 8 in each group) induced by cecal ligation and punctures. Imipenem (IPM) probe recoveries were determined in each rat by retrodialysis by drug. IPM was infused intravenously at a dose of 30 mg . kg(-1) over 30 min, microdialysis samples were collected for 120 min, and IPM concentrations were determined by high-performance liquid chromatography. Intraperitoneal infection had no statistically significant effect on IPM clearance (11.9 +/- 2.3 ml.min(-1).kg(-1) in control rats versus 10.9 +/- 2.1 ml.min(-1).kg(-1) in rats with peritonitis) or the volume of distribution (296 +/- 47 ml.kg(-1) in control rats versus 310 +/- 49 ml.kg(-1) in rats with peritonitis). IPM concentration profiles in intraperitoneal fluid and blood were virtually superimposed in control rats, whereas in infected animals, the mean intraperitoneal IPM concentrations were apparently slightly lower than corresponding blood levels. However, the areas under the concentration-versus-time curve estimated in intraperitoneal fluid and blood were not significantly different in both groups, with the corresponding ratios close to unity (1.01 +/- 0.19 and 0.89 +/- 0.28 in control rats and rats with peritonitis, respectively). In conclusion, IPM distribution in intraperitoneal fluid is rapid and complete both in control rats and in rats with peritonitis.
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PMID:Microdialysis study of imipenem distribution in the intraperitoneal fluid of rats with or without experimental peritonitis. 1637 63


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