Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: KEGG:D00206 (IPM)
 1,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Imipenem/cilastatin was used for the treatment of 594 bacterial infections in 545 patients at a dosage of 1.5 g/day (n = 283), 2.0 g/day (n = 129), 3.0 g/day (n = 102), or 4 g/day (n = 11). The most common indications for therapy were nosocomial pneumonias followed by intraabdominal postoperative infections, and skin and soft tissue infections. Out of 1171 bacterial strains isolated from 932 patients, seven showed primary resistance to imipenem. The causative agent was eliminated in 87% of the patients. Treatment failed in 24 of the 594 patients. In 35 patients therapy was stopped because of side effects. The most frequent side effect was local irritation at the site of intravenous application.
Infection 1986
PMID:[Dosage of imipenem/cilastatin]. 375 49

Imipenem/cilastatin in a doses of 1.5/day was used to treat 31 moderate to severe infections, predominantly soft tissue infections with bone involvement, in 30 surgical patients. A clinical success was achieved in 93% of the patients. In one patient with diabetic gangrene of the foot, imipenem/cilastatin treatment performed as a last resort was not able to prevent amputation. One patient died from his underlying disease while on therapy. All isolates except one Pseudomonas diminuta strain regarded as contaminant were initially sensitive to imipenem. Two Pseudomonas aeruginosa strains developed resistance by the end of therapy. Staphylococcus aureus and coagulase-negative staphylococci were the most common aetiologic agents. Only few clinical and biochemical side-effects were observed: in two cases an allergic rash appeared following several days' treatment. Four patients developed thrombocytopenia, which, however, was completely reversible after the end of therapy.
Infection 1986
PMID:[Efficacy and tolerance of imipenem/cilastatin in the treatment of surgical infections with and without bone involvement]. 375 50

In an open prospective study the efficacy and tolerance of imipenem/cilastatin was investigated in 24 critically ill patients on mechanical ventilation with nosocomial respiratory tract infection. Nine patients had previously received antibiotic therapy, eight of them with various other beta-lactam antibiotics which had failed. Imipenem was given in a dose of 1-3 g/24 h over 5-37 (mean 11) days. Seven patients were additionally treated with aminoglycosides, one patient with erythromycin. Pseudomonas aeruginosa (n = 14), Staphylococcus aureus (n = 4), Haemophilus influenzae (n = 4) and Escherichia coli (n = 3) were the potential pathogens most frequently isolated from tracheo-bronchial secretions. All of the isolates were susceptible to imipenem. 91% of the infections without and 77% with involvement of P. aeruginosa were successfully treated. Two patients who had not responded to previous treatment succumbed to the consequences of progressive respiratory distress syndrome. All of the gram-positive and 85% of the gram-negative pathogens (Pseudomonas not included) were eliminated in the course of therapy. By contrast, 64% of the isolates of P. aeruginosa persisted; half of these became imipenem-resistant. Nine patients showed adverse reactions including one case of pseudomembranous colitis or laboratory abnormalities which were all reversible. Imipenem/cilastatin proved highly effective and was relatively well tolerated; it is suitable as a single agent for the initial treatment of nosocomial respiratory tract infections in ventilated patients, although only with limitations in cases of infection due to P. aeruginosa.
Infection 1986
PMID:[Treatment of respiratory tract infections with imipenem/cilastatin in critical patients with respiratory insufficiency]. 375 53

Infection remains a major cause of morbidity and mortality for the patient with cancer who experiences episodes of severe granulocytopenia. The search continues for new antimicrobial agents with improved efficacy and lower incidence of toxicity. Imipenem is a new carbapenem antibiotic which possesses a broad antibacterial spectrum with excellent activity against Pseudomonas aeruginosa and the other commonly recovered enteric gram-negative bacilli that infect the granulocytopenic patient with cancer. The combination of imipenem plus an aminoglycoside has shown in vitro synergy against P. aeruginosa and Staphylococcus aureus whereas the combination of imipenem plus piperacillin or the extended spectrum cephalosporins have frequently shown antagonism when tested against P. aeruginosa and Serratia marcescens. The use of a P. aeruginosa-infected neutropenic rat model has provided an in vivo system to evaluate the activity of new antibiotics or antibiotic combinations. Monotherapy with imipenem is as effective in this model as any of the currently available synergistic antibiotic combinations. This degree of activity has not been found with other broad-spectrum antibiotics when used alone. Imipenem provides serum bactericidal activity well above a 1:8 dilution for the four most commonly isolated pathogens: P. aeruginosa, Escherichia coli, Klebsiella species, and S. aureus. In addition, imipenem's post-antibiotic effect against P. aeruginosa may be pertinent. Imipenem is a unique antibiotic, with properties that make it well suited for study as monotherapy for fever and suspected infection in granulocytopenic patients with cancer. A prospective randomized, double-blind study comparing imipenem with a control regimen of piperacillin plus amikacin as empiric antibiotic therapy of febrile granulocytopenic patients with cancer is currently underway at the University of Maryland Cancer Center.
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PMID:Potential of imipenem as single-agent empiric antibiotic therapy of febrile neutropenic patients with cancer. 385 17

Imipenem-cilastatin was given in doses of 1 g intravenously every 6 h to 31 patients. Twenty-five patients, with 27 infections, were clinically evaluable and received 20 to 210 g of imipenem for a duration of 5 to 56 days (average 16.3 days). Infections included seven cases of osteomyelitis, seven of bacteremia, five of cellulitis, two of pneumonia, three of pelvic cellulitis, two of intraabdominal abscess, and one each of empyema, mediastinitis, and endometritis. Fifty-five percent of the infections were caused by gram-negative bacilli, 33% were due to gram-positive organisms, and 10% were caused by anaerobes. Twenty-two patients (81%) were cured, three improved, one relapsed, and one became superinfected with a resistant organism. In 5 of 11 cases with Pseudomonas aeruginosa, the imipenem MIC for organisms isolated by the end of treatment was higher than it was initially, raising concern that imipenem should not be used alone to treat Pseudomonas aeruginosa infections. Twenty-one patients had no adverse reaction; of the remaining 10 patients, 4 had nausea, 1 had urticaria, and 6 had mild abnormalities in hepatic function; three episodes of diarrhea included two with Clostridium difficile toxin in stool and one with pseudomembranous colitis, as determined by sigmoidoscopy. Levels of creatinine, hemoglobin, leukocytes, platelets, prothrombin, and urine components were unchanged. Imipenem-cilastatin is a clinically effective antibiotic with freedom from nephrotoxicity and hematological abnormalities in the large doses used in this study.
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PMID:Safety and efficacy of high-dose treatment with imipenem-cilastatin in seriously ill patients. 386 Jan 87

Imipenem is inactivated by the renal dehydropeptidase I, which can be inhibited by cilastatin. Therefore, both compounds are administered in combination. According to the manufacturers, they are not nephrotoxic in rats. 70 female Wistar rats (n = 10/test series) were treated over five days at dosage intervals of 12 hours with intraperitoneal injections (injection volume: 10 ml/200 g body weight) of isotonic 0.9% NaCl, cilastatin (1000 mg/kg/day), imipenem (500 and 1000 mg/kg/day), cilastatin + imipenem (500 or 1000 mg/kg/day each) and cefsulodin (1000 mg/kg/day). The nocturnal excretion of renal tubular cells was determined. Furthermore, three rats in each test were treated intraperitoneally with 150 mg/kg imipenem or with the combination of imipenem and cilastatin (150 mg/kg each). Imipenem concentrations were measured over four hours in the blood of the tail vein. Commencing on the second day of study, cilastatin, imipenem and the combination of both substances induced significant surplus excretion of tubular cells compared to the control group. The tubulotoxic effects of imipenem and imipenem + cilastatin in combination were dose-dependent. The toxic effects of imipenem, imipenem + cilastatin and cefsulodin did not significantly differ. Cilastatin prolonged the half-life of imipenem in the blood from 0.4 to 0.9 h and increased the AUC of imipenem from 156 to 325 mg/l/h.(ABSTRACT TRUNCATED AT 250 WORDS)
Infection 1985
PMID:Renal tolerance of imipenem/cilastatin and other beta-lactam antibiotics in rats. 386 94

Imipenem is the first of a new class of beta-lactam antimicrobial agents with potent in vitro activity against most bacterial pathogens that cause infections in children. We studied, prospectively, the clinical efficacy and toxicity of imipenem/cilastatin in 40 children with proved or suspected bacterial infection. A dose of 100 mg/kg/day of imipenem was given to children younger than 3 years of age, while children older than 3 years of age received 60 mg/kg/day. Twenty-nine organisms were isolated from 26 patients. Infections treated included cellulitis, osteomyelitis, septic arthritis, lymphadenitis, renal infections, wound infections, and pneumonia. Bacteria isolated included Staphylococcus aureus, Streptococcus pyogenes, Haemophilus influenzae, and Pseudomonas aeruginosa. All patients responded favorably to treatment, with defervescence and improvement of symptoms. All of the infecting bacteria were susceptible to imipenem. Imipenem/cilastatin was well tolerated, with no serious side effects, and appeared to be an effective and safe antimicrobial agent in the treatment of the population studied.
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PMID:Imipenem/cilastatin for the treatment of infections in hospitalized children. 390 6

An epidemiological investigation for penicillin-resistant Streptococcus pneumonia (PRSP) was performed at 18 medical institutes in Kinki area by the questionnaire from Kinki Infection Working Group 1995. This investigation was the first report that was performed for a long term (one year) and a large area. The most frequent specimen was sputum from out-patients (50.3%) and inpatients (48.8%), and especially from spinal fluid of 3 cases were detected. Polymicrobial infection with more than 3 pathogens was 15.7%, and it was more frequent than MRSA previously investigated. Simultaneous pathogens detected with PRSP were Candida species, Haemophilus influenzae and Staphylococcus aureus. In terms of chemosusceptibility, VCM (100%), FMOX (97.9%), IPM/CS (85.9%), CEZ (93.4%) and CDTR-PI were determined to be high by sensitive. However, the sensitivity of CCL, which was one of the most common antibiotics, was only 37.7%.
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PMID:[An epidemiological investigation for gram-positive coccus, especially PRSP, in Kinki area]. 933 24

Efficacy and pharmacokinetic parameters of imipenem/cilastatin (I/C) were investigated in a retrospective evaluation in 104 premature and newborn infants. Patients enrolled in this investigation constituted a particularly high risk group with extreme prematurity, perinatal asphyxia and amnion infection as well as various malformations. In 15 of the 104 infants serum concentrations were measured for drug monitoring and determination of optimal total daily dosage. A total daily dose of 50 mg/kg birth weight for premature and newborn infants divided into two doses led to imipenem peak concentrations of 17.7 mg/l +/- 9.2 mg/l (range: 1.95-38.05) and trough levels were 2.35 mg/l +/-1.02 (range 2.34-10.88) in premature infants. Imipenem peak concentrations of 20.6 +/- 10.8 (range 3.94-32.3) and trough levels of 0.43 +/- 0.17 (range 0.16-0.94) were measured in newborns. The half-life of elimination was 3.3 h and 1.86 h, respectively. Six of the 104 treated patients died, five of them of causes unrelated to infection. Seizures occurred in 8.9% of patients during therapy with I/C compared with 5.8% of a large survey of premature and newborn infants in our intensive care unit (ICU). However, the severity of illness of these two groups cannot be compared. I/C can be expected to constitute effective therapy in premature and newborn infants with serious nosocomial infections even after failure of other broad spectrum antibiotics.
Infection 1999
PMID:Pharmacokinetic and clinical evaluation of serious infections in premature and newborn infants under therapy with imipenem/cilastatin. 1088 53

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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