Disease relevance of MK 0787

• A concomitant 68.7% increase in the incidence of imipenem-resistant Pseudomonas aeruginosa occurred throughout the medical center (P<.01) [1].
• A nosocomial outbreak of infections due to imipenem-resistant Acinetobacter baumannii occurred in a New York hospital after increased use of imipenem for cephalosporin-resistant klebsiella infections [2].
• Imipenem-resistant Escherichia coli [3].
• Increased use of imipenem against cephalosporin-resistant klebsiella may lead to imipenem resistance among other species, particularly acinetobacter [2].
• Simultaneous resistance to metronidazole, co-amoxiclav, and imipenem in clinical isolate of Bacteroides fragilis [4].

Psychiatry related information on MK 0787

• The data indicate that exposure of E. coli and S. aureus to a sub-MIC of imipenem enhances the susceptibility of these potential pathogens to cellular and humoral host defense mechanisms [5].
• One death in the comprehensive broad-spectrum empirical antimicrobial therapy group was associated with peritonitis from Clostridium perfringens that was sensitive to imipenem plus cilastin sodium, and the other was associated with peritonitis from Pseudomonas aeruginosa that was resistant to imipenem plus cilastin sodium [6].
• It could be a factor of imipenem resistance if the antibiotic influx into the bacteria was decreased or if the beta-lactamase Id was synthesized at a high level [7].
• We describe the case of an 84-year-old woman who developed a confusional state and suffered from a generalized tonic-clonic seizure while she was treated with imipenem, a beta-lactam antibiotic [8].

High impact information on MK 0787

• Controlled clinical trial of pefloxacin versus imipenem in severe acute pancreatitis [9].
• METHODS: In a multicenter study, 60 patients with severe acute pancreatitis with necrosis affecting at least 50% of the pancreas were randomly allocated to receive intravenous treatment for 2 weeks with pefloxacin, 400 mg twice daily (30 patients), or imipenem, 500 mg three times daily (30 patients), within 120 hours of onset of symptoms [9].
• After treatment with imipenem, pus drained from the pleural cavity yielded an identical isolate that had become highly resistant to imipenem and co-amoxiclav [4].
• Enterococcal superinfection in paediatric oncology patients treated with imipenem [10].
• Efficacy of imipenem in experimental Legionnaires' disease [11].

Chemical compound and disease context of MK 0787

• CONCLUSIONS: Despite its theoretical potential, pefloxacin is inferior to imipenem in the prevention of infections associated with severe pancreatitis [9].
• Monotherapy for fever and neutropenia in cancer patients: a randomized comparison of ceftazidime versus imipenem [12].
• Guidelines are presented for appropriate dosing of imipenem/cilastatin in relation to renal function, body weight, and infecting pathogen [13].
• Ciprofloxacin alone or regimens combining ciprofloxacin with rifampin or rifampin plus imipenem reduced the number of E. coli in polymicrobic subcutaneous abscesses but had little effect on P. aeruginosa in polymicrobic abscesses [14].
• The efficacy and safety of ceftazidime in the treatment of hospital-acquired pneumonias were comparable to results previously demonstrated for amikacin, cefotaxime, and imipenem in studies conducted at our institution [15].

Biological context of MK 0787

• Because IMP-1 has been found in several clinically important carbapenem-resistant pathogens, there is a need for inhibitors of this enzyme that could protect broad spectrum antibiotics such as imipenem from hydrolysis and thus extend their utility [16].
• We have characterized the binding site in the protein D2 channel by studying the competitive inhibition, by various solutes, of imipenem diffusion into the periplasm [17].
• Imipenem is highly stable against attack by beta-lactamases of both plasmid and chromosomal origin, and is more stable by several thousand-fold than earlier beta-lactamase stable compounds [18].
• Several isolates were reported by the clinical microbiology laboratories as being susceptible to imipenem [19].
• The amino acid sequence of OprE had some clusters of sequence homologous with that of OprD of P. aeruginosa, which might be responsible for the outer membrane permeability of imipenem and basic amino acids [20].

Anatomical context of MK 0787

• Overall, the excellent activity of imipenem is the result of (1) the lack of a permeability barrier; (2) high affinity for PBP-2, a critical protein in cell wall synthesis in gram-negative bacteria, and for critical penicillin-binding proteins of gram-positive species; and, above all, (3) its great beta-lactamase stability [18].
• Less than 1 percent of a radiolabeled dose of either compound can be recovered in the feces, making clinically significant alterations of the fecal flora unlikely with the imipenem/cilastatin combination [21].
• Against penicillin-resistant strains, the best killing activity at cerebrospinal fluid concentrations was obtained with imipenem and ceftriaxone-vancomycin [22].
• These data suggest that infants should receive an imipenem dose of 20 mg/kg administered every 12 h for the treatment of bacterial infections outside the central nervous system [23].
• The title enzyme deactivates the potent carbapenem antibiotic imipenem in the kidney, producing low antibiotic levels in the urinary tract [24].

Associations of MK 0787 with other chemical compounds

• RESULTS: The incidences of infected necrosis and extrapancreatic infections were 34% and 44%, respectively, in the pefloxacin group and 10% and 20% in the imipenem group [9].
• Carbohydrate analyses of the purified human dipeptidase demonstrated that it was not a glycoprotein, a characteristic that distinguishes it from porcine and rat renal dipeptidase. beta-Lactamase activity of the purified human enzyme was demonstrated by measuring its activity against the two beta-lactam antibiotics, imipenem and SCH 29482 [25].
• Factors predisposing to seizures in seriously ill infected patients receiving antibiotics: experience with imipenem/cilastatin [13].
• METHODS--A prospective clinical trial was conducted in which eligible neutropenic patients with cancer were randomized to one of four treatment arms: ceftazidime alone; imipenem alone; ceftazidime plus amikacin; and imipenem plus amikacin [26].
• METHODS: Patients were randomized to either ciprofloxacin plus metronidazole intravenously (CIP/MTZ IV) or imipenem intravenously (IMI IV) throughout their treatment course, or ciprofloxacin plus metronidazole intravenously and treatment with oral ciprofloxacin plus metronidazole when oral feeding was resumed (CIP/MTZ IV/PO) [27].

Gene context of MK 0787

• Resistance to beta-lactam and FQ was correlated with ampC and mexC gene expression levels, respectively, whereas imipenem resistance was attributable to decreased oprD expression [28].
• However, measurement of beta-lactamase activities (including measurements under conditions where TEM-1 beta-lactamase was inhibited) indicated that the imipenem-intermediate isolate expressed six- to eightfold less beta-lactamase than did the other isolates [29].
• These results demonstrate that in clinical practice, gyrA mutations are the major mechanism of resistance to fluoroquinolones even in the strains of P. aeruginosa resistant to imipenem and lacking OprD, concomitant resistance to these drugs being the result of the addition of at least two independent mechanisms [30].
• In mice with IL-6 levels >14,000 pg/ml, 25% survived if imipenem was started at 6 h, whereas none survived if antibiotics were started later (P < 0.05) [31].
• The results showed that oprD was relatively stable against carbapenem antibiotics. oprM was induced significantly by imipenem in only one strain and oprN was induced by imipenem in most of the strains [32].

Analytical, diagnostic and therapeutic context of MK 0787

• BACKGROUND & AIMS: Antibiotic prophylaxis in severe pancreatitis has recently yielded promising clinical results, with imipenem significantly reducing the incidence of infected necrosis compared with an untreated control group [9].
• Western blot analysis revealed reduced expression of the basic amino acid and carbapenem-specific OprD porin in all imipenem-resistant mutants [33].
• Forty-seven patients were treated with imipenem (test group), and 46 patients were treated with the combination therapy (control group) [34].
• Multiple doses of imipenem/cilastatin were administered to patients with end-stage renal disease undergoing long-term hemodialysis [35].
• Because the infection originates mostly from a certain tissue, we assessed tissue concentrations of imipenem using microdialysis in patients in intensive care with serious infections compared with healthy volunteers [36].

References