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)

A multicentre, non-comparative study was performed to evaluate the clinical efficacy and safety of imipenem/cilastatin given iv to 53 seriously ill patients with severe bacterial infections, including 16 episodes of UTI, 12 pleuropulmonary, eight intra-abdominal, seven osteoarticular, and two soft tissue infections, three episodes of catheter related sepsis, two primary bacteraemias, one case of endocarditis, one of endophthalmitis, and one of disseminated gonococcal infection. Twenty-five patients were bacteraemic. The overall rate of clinical response was 94% of treated episodes; three cases failed to respond. Adverse reactions were mild and comparable with those reported with other beta-lactams. No patient had clinical superinfection; colonization occurred in seven patients. Imipenem is effective and safe as a single drug therapy for a wide range of infections in seriously ill patients.
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PMID:Imipenem in the treatment of severe bacterial infections in seriously ill patients. 346 85

Imipenem (N-formimidoyl thienamycin) is a new carbapenem beta-lactam antibiotic with a broad antibacterial spectrum. Forty-five patients were treated with either 500 or 1,000 mg of imipenem/cilastatin four times daily, the duration varying according to clinical response. The diagnoses were urinary tract infection, 10 patients; septicemia, six; intraabdominal sepsis, six; pneumonia, six (two cases of Legionnaires' disease); skin and soft tissue infection, four; and other diagnoses, 13. Of the 32 clinically assessable patients, 17 were cured, nine improved, three died, and three were withdrawn from the trial. Of 21 patients who were microbiologically assessable, 13 were cured. In six cases of complicated urinary tract infection, the organism--which had been eradicated from the urine during treatment--reappeared after completion of antibiotic therapy. Two patients developed adverse clinical reactions that were thought to be drug-related (drug-induced fever and nausea plus vomiting, respectively). Both patients had mildly abnormal results in liver function tests, and one developed a positive direct Coombs' test. Fifty-seven percent of the patients developed some degree of phlebitis, which was moderate to severe in 19%. In this study imipenem/cilastatin proved to be a highly effective agent for the treatment of a variety of serious bacterial infections.
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PMID:Imipenem/cilastatin in the treatment of serious bacterial infections. 390 Dec 12

The protective effect of volume support, imipenem, and the anti-endotoxin antibody E5 given as mono- or combination therapy was studied in fulminant intraabdominal sepsis in rats. Mortality, blood levels of bacteria, endotoxin, tumor necrosis factor (TNF), and lactate, and packed cell volume were measured. All monotherapy regimens improved survival, and protection decreased with delayed intervention. Volume support prevented dehydration and lactate accumulation but had no effect on levels of bacteria, endotoxin, or TNF. Imipenem killed bacteria and released endotoxin, and lactacidosis was reduced. E5 reduced endotoxin, TNF, and lactate but not bacteremia. The imipenem-induced increase in plasma endotoxin was abolished by E5. When E5 was added to a regimen of volume support plus imipenem 6 h after induction, it gave an extra improvement of survival, but this synergism disappeared when intervention was delayed 4 h more. The primary effect of E5 was a reduction in plasma endotoxin level.
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PMID:Synergistic effect of E5, imipenem, and volume support during fulminant intraabdominal sepsis in rats. 779 5

The in-vitro susceptibility pattern to newer beta lactams namely Ticer/Clav, Azlocillin, Piperacillin and Imipenem was determined with 50 clinical strains isolated from neutropenic patients with strains isolated from neutropenic patients with sepsis, with an objective of evolving a strategy for empirical antibiotic therapy for febrile neutropenic patients. The MIC90 value for Imipenem for the Gram negative bacilli tested, other than Pseudomonas was < 0.25 mcg/ml therapy revealing a high degree of susceptibility, while for Ps. aeruginosa and related species MIC50 and MIV90 values were 2.0 and 64.0 micrograms/ml respectively. A comparatively lower degree of susceptibility was found among Gram negative bacilli included in the study to ticar/clavu, azlocillin and piperacillin indicating a moderate degree of resistance to these antibiotics. The data from this study suggests that (i) Ureidopenicillins with an aminoglycoside should be effective therapy for proven Pseudomonas and other Gram negative sepsis in febrile neutropenic patients. (ii) Imipenem would be the antibiotic of choice in Gram negative bacterial sepsis in febrile neutropenic patients where the organism is resistant to cephalosporins and ureidopenicillins.
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PMID:In vitro evaluation of newer beta-lactam antibiotics against gram negative bacilli isolated from neutropenic patients. 806 32

Imipenem/cilastatin sodium (IPM/CS) which is a broad-spectrum agent against both Gram-positive and -negative bacteria was used in combination with fosfomycin (FOM) as a second-line chemotherapy for severe infections associated with hematologic disorders. FOM was partnered with IPM because FOM may enhance the bacteriocidal effects of IPM when given as pretreatment to IPM/CS therapy. Fifty two patients were treated with IPM/CS plus FOM. Of them, 41 were evaluated for effectiveness. Eleven patients were not evaluated: 4 were treated with a combination of other regimens such as cefixime, gamma-globulin, G-CSF and a large dose of methyl prednisolone; 2 were given IPM/CS plus FOM as a first choice; 3 were observed to have gastrointestinal side effects such as nausea which led to the discontinuation of the combination therapy; and 2 were thought to be suffering from not infectious but tumor fever. An excellent response was observed in 15 (36.6%) patients and a good response in 10 (24.4%), for a overall efficacy rate of 61.0%. Efficacies was 71.4% (5/7) in patients with sepsis, and 60.0% (9/15) in patients whose peripheral granulocyte count was below 100/microliters before chemotherapy. The elimination rates of Gram-positive and -negative bacteria were 57.1% (4/7) and 75.0% (6/8), respectively. In particular, 75.0% (3/4) of Pseudomonas aeruginosa identified were eliminated. Two patients who suffered from tumor fever, 2 who did not receive chemotherapy before the combination chemotherapy and 3 who did not receive a full course of the combination chemotherapy because of side effects, were included in the final evaluation of safety. Side effects were observed in 18 of 48 patients (37.5%). In 1 patient, skin eruption occurred 3 days after the initiation of the combination chemotherapy. In 17 patients, gastrointestinal symptoms such as nausea and vomiting were identified after a few days of IPM/CS plus FOM administration. Degree's of the symptoms were mild, however. Therefore, the treatment was not withdrawn. No abnormal laboratory results such as eosinophilia, liver disfunction or renal disfunction were observed. These results show that IPM/CS plus FOM is effective as a second-line combination chemotherapy for the treatment of severe infections in patients with hematologic disorders.
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PMID:[Clinical evaluation of imipenem/cilastatin sodium and fosfomycin as second-line combination chemotherapy in severe infections associated with hematologic disorders]. 833 78

Cilastatin, an inhibitor of the tubular brush border enzyme dehydropeptidase-I, is added in a fixed combination to imipenem. Cilastatin has been demonstrated in different animal models and in one clinical trial, to reduce the nephrotoxicity associated with cyclosporin A. To evaluate a possible nephroprotective effect of cilastatin following allogeneic BMT we conducted a retrospective analysis of 104 patients transplanted in our BMT Unit from January 1991 to January 1995. Imipenem/cilastatin (I/C) was used in a non-randomized manner in 64 patients during this period. Acute renal failure (ARF) was diagnosed in 32 patients (30%). ARF was not associated with gender, sepsis, conditioning regimen, underlying disease, bilirubin, or age. VOD occurred in 12/32 (37.5%) of patients with ARF whereas it occurred in only 7/72 (9.7%) of patients without ARF (P < 0.0007). ARF was not correlated with use of aminoglycosides, vancomycin, ciprofloxacine, ceftazidime or amphotericin-B. However, 13 patients of 64 exposed to I/C (20.3%) developed ARF vs 19 of 40 patients (47.5%) who were not exposed to I/C (P < 0.003; OR 0.28). Stratified analysis and multiple logistic regression confirmed the I/C nephroprotective action. The mean cyclosporin A levels in the I/C group were significantly decreased (208.6 +/- 64.9) vs the non-I/C group (265 +/- 118). We conclude that these results suggest I/C may counteract acute cyclosporin A nephrotoxicity following BMT and further prospective clinical trials are needed to confirm if routine administration of cilastatine confers benefit in the BMT setting.
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PMID:Nephroprotective effect of cilastatin in allogeneic bone marrow transplantation. Results from a retrospective analysis. 889 92

Carbapenems are active beta-lactam antibiotics versus most of the gram positive and gram negative microorganisms and anaerobes although their activity is lacking in the case of Staphylococcus sp. resistant to methicillin, Enterococcus faecium and Streptococcus pneumoniae with high resistance to penicillin and some gram negative bacilli which naturally produce an methaloenzyme able to hydrolyze them such as Stenotrophomonas maltophilia. Imipenem, the first synthetized carbapenem requires administration with cilastatin to avoid inactivation by renal dehydropeptidase 1. Meropenem does not require being taken with the renal enzyme inhibitor, with its activity being similar to that of imipenem. In abdominal infection the carbapenems have shown to be the authentic monotherapy in this type of infections being as effective as the different schedules of antibiotic associations normally used. Treatment with carbapenems in bacterial meningitis should be currently limited to the cases produced by gram negative bacilli producers of wide spectrum beta-lactamases (WSBL), cases of meningitis by Pseudomonas aeruginosa or gram negative bacilli producers of inducible cephalosporinase. Meropenem is the carbapenem of choice probably in these cases because the carbapenems are often the only active antibiotics and meropenem, specifically, does not have the risk of convulsions observed with imipenem-cilastatin. The carbapenems have shown to be useful in skin and soft tissue infections as well as in obstetric and gynecologic infections as monotherapy similar to the schedules of the currently used antibiotic associations. In the case of nosocomial pneumonias, all the studies have evaluated the carbapenems in monotherapy as useful and effective, specially in the case of pneumonia by gram negative bacilli. Finally, in non filiated nosocomial sepsis and specially in the case of neutropenic patients, the use of carbapenems is particularly attractive in gram negative sepsis in intensive care units. The appearance in the last few years of strains of gram negative bacilli, producers of wide spectrum beta-lactamase or stable repressed hyperproducers of class I chromosomic cephalosporinase, as well as other multiresistant gram negative bacilli, such as Acinetobacter baumanii make the carbapenems, in many cases, the only effective antibiotic in this type of infections.
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PMID:[The role of carbapenems in the treatment of nosocomial infection]. 941 75

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


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