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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Gram-negative bacilli (GNB) septicemia are among the most serious infections encountered in the hospital since they generally occur on debilitated patients and are due to the multi-drug resistant bacteria. A retrospective study relating to 195 septicemia was carried out with an aim studying epidemiologic profile, predisposing factors, entry sites for micro-organisms, responsible GNB and their antibiotic susceptibility. GNB septicemia were mainly frequent in intensive care units (34%) and surgery (31%). Previous antibiotherapy, invasive procedures and surgical acts were the principal predisposing factors. The entry sites for micro-organisms remained unknown in 1/3 of the cases. The most common source of septicemia was the urinary tract infections. E. coli was the most frequent isolated bacteria (26%) in the community acquired spticemia whereas Klebsiella-Enterobacter-Serratia (KES), Acinetobacter and Pseudomonas were mainly encountered in nosocomial infections. Imipenem remained the most active betalactamin on GNB (2% of resistance) with amikacin (16% of resistance) among aminoglycosides. The rate of mortality was 18%. Hospitalization wards (intensive care units, surgery), entry sites unknown, septic shock syndrome were the main factors of prognosis. The development of immunology and molecular biology should improve the outcome of these infections but the preventive measures remain the most effective.
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PMID:[Epidemiology of gram negative bacterial septicemias: data from a Tunisian hospital (1996-1998)]. 1253 26

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

Imipenem, the first carbapenem discovered, was developed more than two decades ago in response to an unmet need for a highly potent, broad-spectrum antimicrobial agent with a strong safety profile. It has since been used to treat more than 26 million patients. In an era where antibiotic use has driven antibiotic resistance, choosing appropriate initial therapy for serious infection is critical. Appropriate antibiotic regimens must cover all likely pathogens, be administered promptly at the correct dosage and dosing interval, be well tolerated and prevent the emergence of resistance. While imipenem was initially reserved for use in intractable, serious infections, the benefits of early aggressive therapy are now known, making imipenem a core agent in de-escalation therapy due to proven efficacy and safety for indications such as nosocomial pneumonia, intra-abdominal infection, sepsis and febrile neutropenia. De-escalation therapy with an agent such as imipenem minimizes resistance development by initiating aggressive initial treatment and then tailoring therapy based on patient response and culture results, switching to a less expensive, narrower spectrum antibiotic regimen or shortening the duration of therapy. Imipenem has maintained sustained clinical efficacy, tolerability and in vitro activity against important bacterial pathogens for two decades. We review the factors that continue to make imipenem as appropriate an agent for de-escalation therapy now as it was 20 years ago.
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PMID:Two decades of imipenem therapy. 1699 45

We report a case of infective endocarditis caused by Acinetobacter baumannii complex in a 27-year-old male patient. The patient presented with fever of five days duration, palpitation, dyspnea, cough and chest pain. He had undergone a surgical repair of ruptured aneurysm of sinus of valsalva a month before. The transthoracic echocardiogram revealed a large vegetation on the aortic valve. Three samples of blood for culture grew gram-negative pleomorphic coccobacilli within 24 hours which were identified by cultural and biochemical characteristics to be Acinetobacter baumannii complex. Antimicrobial susceptibility was performed by Kirby-Bauer method and the isolate were found to be resistant to ampicillin, Ciprofloxacin, Ceftriaxone, Gentamicin, Amikacin, Augmentin, Levofloxacin, Piperacillin-Tazobactam, Netilimicin and sensitive to Imipenem. Patient was initially treated with Ceftraixone and Gentamicin and subsequently with Ampicillin and Amikacin but did not respond to treatment and died of sepsis before therapy with Imipenem could be started.
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PMID:Infective endocarditis due to Acinetobacter baumannii complex--a case report. 1718 61

Beta-lactams are regularly administered in intermittent short-term infusions. The percentage of the dosing interval during which free drug concentrations exceed the MIC (fT(>MIC)) is the measure of drug exposure that best correlates with clinical outcome for beta-lactams. Therefore, administration by continuous infusion has gained increasing interest recently. We studied 20 critically ill patients with nosocomial pneumonia and investigated whether continuous infusion with a reduced total dose, compared to the standard regimen of intermittent short-term infusion, results in a superior probability of target attainment as assessed by the fT(>MIC) value of imipenem. In this prospective, randomized, controlled clinical study, patients received either a loading dose of 1 g/1 g imipenem and cilastatin (as a short-term infusion) at time zero, followed by 2 g/2 g imipenem-cilastatin per 24 h as a continuous infusion for 3 days (n = 10), or 1 g/1 g imipenem-cilastatin three times per day as a short-term infusion for 3 days (total daily dose, 3 g/3 g; n = 10). Imipenem concentrations in plasma were determined by using a validated liquid chromatography-tandem mass spectrometry assay. A two-compartment open model was employed for population pharmacokinetic modeling. We simulated 10,000 intensive-care-unit patients via Monte Carlo simulations for pharmacodynamic evaluation using the target 40% fT(>MIC). The probability of target attainment by MIC for intermittent infusion was robust (>90%) up to MICs of 1 to 2 mg/liter. The corresponding value for continuous infusion was 2 to 4 mg/liter. Although all 20 patients had an fT(>MIC) of 100%, 3 patients died. Patient survival was best described by employing a sepsis-related organ failure assessment score as a covariate in a logistic regression analysis. Larger clinical trials are warranted for evaluation of continuous infusions at a reduced dose of imipenem for critically ill patients.
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PMID:Population pharmacokinetics and pharmacodynamics of continuous versus short-term infusion of imipenem-cilastatin in critically ill patients in a randomized, controlled trial. 1762 Mar 71


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