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

The concentration and accessibility of endotoxin can increase following antibiotic killing of gram-negative bacteria. There are indications that antibiotics may differ in this respect. We measured endotoxin levels in RPMI 1640 and tumor necrosis factor alpha (TNF-alpha) and interleukin-6 production in whole blood ex vivo after exposure of log-phase Escherichia coli to antibiotics belonging to different classes, in a final concentration of 0.5, 5, or 50 times the MIC. After 4 h of incubation at 50 times the MIC, ceftazidime and ciprofloxacin treatment resulted in levels of endotoxin, TNF-alpha, and interleukin-6 significantly higher than those of imipenem and gentamicin (P < 0.001). Similar differences in cytokine induction were measured after 8 h of incubation. At 0.5 times the MIC, the differences between the antibiotics in measured endotoxin and cytokine levels were small, with levels comparable to the levels in untreated cultures. Polymyxin B and, to a lesser degree, recombinant bactericidal/permeability-increasing protein 21 (rBPI-21) were found to be potent inhibitors of TNF-alpha release, supporting the concept that the differences between the antibiotics in cytokine production were indeed due to differences in amounts of biologically active endotoxin. The presence of serum from patients suffering from untreated sepsis decreased TNF-alpha production significantly, in a concentration-dependent manner.
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PMID:Release of tumor necrosis factor alpha and interleukin 6 during antibiotic killing of Escherichia coli in whole blood: influence of antibiotic class, antibiotic concentration, and presence of septic serum. 776 3

A mouse model of bacteremia was used to compare the efficacies of 1.5- and 3.0-g intravenous doses of ampicillin-sulbactam. Seven strains of Escherichia coli producing various levels of TEM-1 beta-lactamase were used as the challenge isolates. These strains included six clinical isolates (MICs from 2/1 micrograms/ml [with 2 and 1 microgram/ml being the respective concentrations of ampicillin and sulbactam] to 32/16 micrograms/ml) with similar degrees of virulence in mice and a laboratory genetic transformant (E. coli AFE) which hyperproduces TEM-1 (MIC = 128/64 micrograms/ml). Human pharmacokinetics were simulated by injecting mice subcutaneously twice (1 h apart) with ampicillin-sulbactam at concentrations of 40 mg/kg of body weight (1.5 g) and 80 mg/kg (3.0 g). Against two clinical isolates for which ampicillin-sulbactam MICs were < or = 8/4 micrograms/ml, no difference was observed in either the rate or level of killing between the two doses, and both doses were 100% protective against lethal infection. Against the four clinical isolates for which ampicillin-sulbactam MICs were between 16/8 and 32/16 micrograms/ml, a slight delay in killing was noted with three of the strains. This delay was followed by a rapid 2- to 3-log drop in the level of bacteremia, and both doses of ampicillin-sulbactam were 100% protective against lethal septicemia. With strain AFE, no killing was observed with the 40-mg/kg dose compared with a 2-log killing with the 80-mg/kg dose. This difference in killing correlated with a decreased protective efficacy of the 40-mg/kg dose. These data suggest that the 1.5-g preparation of ampicillin-sulbactam is as effective as the 3.0-g dose in the treatment of experimentally induced E. coli bacteremia, as long as ampicillin-sulbactam MICs are 32/16 micrograms/ml or less.
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PMID:Comparison of ampicillin-sulbactam regimens simulating 1.5- and 3.0-gram doses to humans in treatment of Escherichia coli bacteremia in mice. 778 98

The aim of this study was to investigate beta-lactam resistance in Escherichia coli and Klebsiella spp. blood culture isolates in Finland. Special attention was given to extended-spectrum beta-lactamases. A total of 566 Escherichia coli and 108 Klebsiella spp. blood culture isolates were collected from hospitals throughout Finland and their susceptibility to beta-lactam antibiotics studied. Twenty percent of Escherichia coli and 69% of Klebsiella spp. strains were resistant to ampicillin. The mechanisms of resistance were studied by hybridization, isoelectric focusing and the clavulanate double-disk potentiation test. Of the ampicillin-resistant Escherichia coli strains, 83% produced TEM-1. Of the ampicillin-resistant Klebsiella spp. strains, 43% produced SHV-1. Only nine Escherichia coli and three Klebsiella spp. isolates were resistant to cefuroxime (MIC > or = 32 micrograms/ml), and none were resistant to third-generation cephalosporins. These data were compared with cefuroxime and third-generation cephalosporin consumption levels in Finnish hospitals. Although the use of cephalosporins is far more extensive in Finland than in other Scandinavian countries, none of the isolates produced extended-spectrum beta-lactamases. In conclusion, resistance to cefuroxime has remained rare in Finland, and cefuroxime is still an alternative to third-generation cephalosporins in the treatment of septicemia.
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PMID:Beta-lactam resistance among Escherichia coli and Klebsiella species blood culture isolates in Finnish hospitals. Finnish Study Group for Antimicrobial Resistance. 795 66

We described three septicemia cases in which blood cultures yielded gram-positive cocci identified as Leuconostoc spp. and Pediococcus spp. Patients were three male adults aged 63 to 71 years with severe underlying diseases, pancreatic cancer, esophageal cancer and diabetes mellitus with chronic renal failure. They had fever and chills at the onsets of septicemia with acute obstructive suppurative cholangitis, acute pneumonia, and infection complicated with invasion sites of esophageal cancer contagious to bronchus and subcutaneous tissue. Blood cultures yielded catalase and oxidase negative highly vancomycin-resistant (MIC: 1024 micrograms/ml <) gram-positive cocci showing alpha or gamma hemolysis on blood agar plates. Two cases were polymicrobial infections. In one case with esophageal cancer, clinical symptoms persisted after the start of antimicrobial chemotherapy and the patient died 10 days later associated with complications of esophageal cancer. Leuconostoc lactis, Leuconostoc mesenteroides subsp. dextranicum, and Pediococcus acidilactici wee identified by physiological reactions. These strains were also highly resistant to teicoplanin and fosfomycin, and tolerant to all rested beta-lactams such as benzylpenicillin. This is the first report in Japan to our knowledge on the identification of Leuconostoc spp. and Pediococcus spp. isolated from human infectious diseases.
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PMID:[Microbiological and clinical studies of vancomycin resistant Leuconostoc spp. and Pediococcus spp. isolated from septicemia patients]. 796 99

The efficiencies of two dosage schedules of amikacin (2 x 10 mg/kg of body weight per 24 h and 1 x 20 mg/kg/24 h intramuscularly for 5 days) against Pseudomonas aeruginosa sepsis in rabbits were compared. Blood samples were drawn at various times after the first application, and amikacin concentrations in serum were assayed microbiologically. The dynamics of the bactericidal effect of amikacin was simulated in vitro with the same strain of P. aeruginosa. No regrowth was found with the 20-mg/kg dose when the bacterial inoculum was in contact with experimental and theoretically predicted serum amikacin concentrations. The killing effect was present even when the drug levels decreased considerably below the MIC. The interrelationship between simulated amikacin concentrations in serum and the corresponding average killing rates was described appropriately by the standard Emax model. The higher amikacin dose performed its bacterial effect faster and the drug persisted longer in the blood. The two amikacin regimens were therapeutically equivalent, but the once-daily schedule had some advantages over the twice-daily drug administration which became evident when both the pharmacokinetic and the pharmacodynamic parameters of the drug were considered.
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PMID:Pharmacokinetic and pharmacodynamic approach for comparing two therapeutic regimens using amikacin. 806 80

Arbekacin (ABK) was administered to 17 patients with MRSA infections that complicated underlying hematopoietic disorders, and the efficacy and safety were evaluated. The underlying diseases included acute myelocytic leukemia (8 cases), acute lymphocytic leukemia (1) myelodysplastic syndrome (3), chronic myelocytic leukemia (1), non-Hodgkin's lymphoma (2), Hodgkin's disease (1) and adult T cell leukemia (1). The infections consisted of septicemia (5 cases), pneumonia (4), upper respiratory tract infections (6) and urinary tract infections (2). ABK was administered by i.v. drip infusion in daily doses of 150-200 mg, given in two divided dosages. The therapeutic efficacies were: excellent in 2 (2 septicemias), good in 7 (1 septicemia, 4 upper respiratory infections, 2 urinary tract infections), fair in 2 (septicemia and pneumonia) and poor in 6 (1 septicemia, 3 pneumonias, 2 upper respiratory infections). As a side effect, reversible renal dysfunction was detected in four cases. Causative bacteria were isolated from six cases. They were all coagulase type II and MIC's of ABK were from 0.25 microgram/ml to 4.0 micrograms/ml. Arbekacin therapy was found to be effective even in patients with hematopoietic disorders accompanied by MRSA infections.
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PMID:[Clinical efficacy of arbekacin on MRSA infections with hematopoietic disorders. The Hanshin Study Group of Hematopoietic Disorders and Infections]. 807 85

The serum bactericidal test (SBT) is used to monitor antibiotic treatment during therapy. Compared to other methods of sensitivity testing, such as MIC (minimum inhibitory concentration) determination, the SBT also takes into consideration the pharmacokinetic qualities of the drug tested. Serum bactericidal titers are measured during therapy of different infectious diseases to estimate therapeutic outcome. Until now serum bactericidal titers of 1:8 in non-granulocytopenic patients, and titers > or = 1:16 in granulocytopenic patients have been shown to correlate with a successful treatment outcome in patients with gram-negative sepsis. In patients with endocarditis a peak serum bactericidal titer of at least 1:32 should be achieved. Another way to apply the serum bactericidal test is to compare the activity of different antibiotics in volunteers. The present study as well as data from the literature indicate that ciprofloxacin has markedly higher serum bactericidal activity than ofloxacin. Of the so called "basic cephalosporins" cefotiam achieved the highest serum bactericidal activity against the Enterobacteriaceae tested. Since 3rd generation cephalosporins are in general highly active against gram-negative rods, we were interested in using the SBT to compare different dosage regimens. In several studies serum bactericidal titers of > or = 1:8 were achieved with the 1 g dosis of cefotaxime, cefmenoxime and especially ceftazidime against the gram-negative rods tested.
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PMID:[Evaluation of the serum bactericidal test]. 814 31

Two broadly cross-reactive anti-lipopolysaccharide core monoclonal antibodies WN1 222.5 and SZ27/150.3 were used in an ELISA system to detect the accessibility of core epitopes in Escherichia coli (four clinical isolates and NCTC 10418) grown to early stationary phase in the absence and presence of a half, a quarter and an eighth the MIC of temocillin, ampicillin, chloramphenicol, gentamicin and ciprofloxacin. The bacteria were coated on to ELISA microtitre plates. By comparing ELISA-titre ratios, temocillin induced a significantly large increase in binding of WN1 222.5 to all strains except NCTC 10418. Ampicillin and chloramphenicol induced a small increase in the binding of WN1 222.5 in some instances. Ciprofloxacin and gentamicin caused no increase in binding. Lipopolysaccharide SZ27/150.3 was only tested against temocillin-grown bacteria, but binding was not increased significantly compared with WN1 222.5. The results obtained demonstrate the potential use of temocillin to improve the clinical efficacy of immunotherapeutic monoclonal antibodies in Gram-negative sepsis.
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PMID:The accessibility of cross-reactive anti-lipopolysaccharide-core monoclonal antibodies to Escherichia coli grown in sub-MICs of temocillin and other antibiotics. 833 96

The purpose of selective decontamination of the digestive tract (SDD) is to eradicate potentially disease-producing micro-organisms from the oropharynx and gastro-intestinal tract of intensive care unit (ICU) patients, thereby reducing the incidence of nosocomial sepsis, particularly pneumonia. Microbial biofilms form on endotracheal (ET) tubes even when SDD is being administered and may represent a persistent focus for infection. The aim of this investigation was to determine the susceptibilities of organisms adherent to ET tubes to SDD antibiotics (amphotericin B, tobramycin and polymyxin) and to measure the concentrations of these agents in the tracheal aspirates of 11 patients who were being mechanically ventilated. Following extubation, a section was cut from the tip of each ET tube and any adherent microorganisms subsequently isolated were identified and their MICs determined. Samples of tracheal aspirate were obtained three hours after administration of the SDD regimen and the concentrations of the constituent antimicrobials were measured. Enterobacteriaceae were not recovered from any of the tubes but six strains of Staphylococcus aureus, three Pseudomonas spp., three enterococci and four yeasts were isolated. Wide variations in the concentrations of all antibiotics were observed and in many cases they were below the MICs for the organisms isolated. In particular, tobramycin concentrations were uniformly less than the median MIC for the S. aureus isolates and this may account for the predominance of Gram-positive bacteria adherent to the ET tubes. Microbial biofilms attached to these tubes may have a role in the pathogenesis of nosocomial pneumonia in ICU patients.
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PMID:Selective decontamination of the digestive tract (SDD) does not prevent the formation of microbial biofilms on endotracheal tubes. 833 97

We examined the impact of dose fractionation and altered MICs on survivorship in a neutropenic rat model of Pseudomonas aeruginosa sepsis employing the new fluoroquinolone antibiotic lomefloxacin. Once-daily administration of a drug dose which produced a high peak concentration/MIC (peak/MIC) ratio (ca. 20/1) produced significantly better survivorship compared with regimens employing the same daily dose but on a more fractionated schedule. The use of a smaller dose, producing lower (< 10/1) peak/MIC ratios, did not show this effect, as once-daily and twice-daily regimens produced equivalent results (the area under the concentration-time curve/MIC ratio was linked to survivorship). Challenge with resistant mutants selected for altered MICs of fluoroquinolones (two and four times the MIC for the parent strain, respectively) resulted in markedly diminished survivorship. Challenge with the parent strain and use of a drug dose which produced a peak/MIC ratio identical to that for animals challenged with the mutant for which the MIC was four times that for the parent strain and treated with the larger drug dose produced survivorship curves which were not different. For this animal model, peak/MIC ratio was linked to survivorship, particularly when high ratios (10/1 to 20/1) were obtained. At lower doses, producing peak/MIC ratios < 10/1, the area under the concentration-time curve relative to the MIC appeared to be most closely linked to outcome. The time that levels in plasma exceeded the MIC did not influence survivorship. The hypothesis most likely to explain these findings is that higher peak/MIC ratios can suppress the parent strain and mutant organisms (gyrA and transport mutants) for which the MIC is higher but limited (no more than eight times that for the parent strain).
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PMID:Pharmacodynamics of a fluoroquinolone antimicrobial agent in a neutropenic rat model of Pseudomonas sepsis. 838 15


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