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Imipenem/cilastatin is the first of a new class of beta-lactam antibiotics called carbapenems. The antibacterial spectrum of imipenem exceeds any antibiotic investigated to date and includes gram-positive, gram-negative, and anaerobic organisms. Only methicillin-resistant organisms, Strep. faecium, Pseudomonas cepacia, and Pseudomonas maltophilia have been shown to be resistant. Imipenem is administered in a 1:1 ratio with cilastatin, which inhibits a renal enzyme (dehydropeptidase) and improves urinary recovery of imipenem. The elimination half-life of both compounds is 1.0 hours and recommended doses are 0.25-0.5 g iv q6h. Adverse events are similar in nature and incidence to beta-lactam antibiotics, with phlebitis/thrombophlebitis, diarrhea, nausea, skin rash, and elevations of hepatic enzymes most common. Clinical studies in phase II and III trials have shown imipenem/cilastatin to be effective in soft tissue infections, endocarditis, obstetrics and gynecology, complicated urinary tract infections, mixed anaerobic-aerobic infections, osteomyelitis, bacteremias, and pneumonias. Several comparative clinical trials have shown imipenem/cilastatin to be equal in efficacy to combination therapy. Imipenem/cilastatin may prove to be an alternative to combination antibiotic therapy because of its extremely broad spectrum of activity.
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PMID:Imipenem/cilastatin: the first carbapenem antibiotic. 391 Mar 85

Imipenem is the first of a new class of beta-lactam antimicrobial agents with remarkable and extremely potent in vitro activity against most commonly isolated bacterial pathogens, including Staphylococcus aureus, enterococcus, members of the family Enterobacteriaceae, Pseudomonas aeruginosa, Bacteroides fragilis, and Hemophilus influenzae. The clinical efficacy and toxicity of imipenem were evaluated in 35 patients with 38 different infections. The overall clinical response was favorable (infections cured or improved) in 89% of the infections (34 of 38). Of the 17 infections with P. aeruginosa, 15 were cured or improved. However, P. aeruginosa isolates resistant to imipenem emerged during the therapy of six infections, and two cases of P. aeruginosa septicemia later relapsed after imipenem therapy. Gastrointestinal toxicity (nausea with or without emesis) occurred in 17% of the patients (6 of 35) but was ameliorated by slowing the rate of intravenous infusion or lowering the dose of imipenem. Except for certain severe P. aeruginosa infections, imipenem is effective and relatively safe therapy for infections caused by susceptible organisms.
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PMID:Imipenem therapy of Pseudomonas aeruginosa and other serious bacterial infections. 659 61

A retrospective, open, 3-year trend analysis of imipenem use in bone marrow transplant (BMT) patients was conducted at a 1000-bed tertiary care hospital. Broad-spectrum antibacterial drugs are routinely used to treat infections in the febrile neutropenic host. The antibacterial activity and acceptable tolerance profile of imipenem makes this agent a potentially useful addition to the traditional armamentarium which includes aminoglycosides, cephalosporins, and glycopeptides. Some authorities recommend imipenem as monotherapy in the treatment of fever of unknown origin in this select patient population. Eighty-three treatment courses (one treatment course per patient) were evaluated. The major indications for initiating therapy were fever of neutropenia (28%), suspected infection in the absence of fever (55%), and documented infection (17%). Imipenem was used as a first-line agent in 42% of patients, although imipenem monotherapy was not common. Concurrent antibacterials were usually vancomycin and tobramycin. Seventeen patients required modification of the initial regimen with vancomycin and/or tobramycin for additional coverage after an average of 8 days of imipenem therapy. Forty-eight bacterial isolates were obtained in cultures from 35 patients during the study, with gram-positive organisms predominating (in particular, staphylococci and streptococci). Pretherapy and superinfecting organisms were primarily gram-positive. Overall clinical success or improvement occurred in 42% of patients. Microbiologic outcome was indeterminate in 89% of patients, microbiologic eradication occurred in 1%, and superinfection occurred in 6%. Imipenem was relatively well tolerated. Rash and nausea/vomiting were reported most often; 29% of those patients who had adverse reactions discontinued therapy.
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PMID:A retrospective evaluation of imipenem use in bone marrow transplant patients. 785 35

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

Toxic Shock Syndrome (TSS) secondary to mastitis is seldom described. We present a case of TSS due to postpartum mastitis caused by Methicillin-resistant Staphylococcus aureus (MRSA). Five weeks after giving birth to a healthy boy, a 23-year-old secundipara was readmitted to the hospital with a fever, systemic erythema, nausea, vomiting, diarrhea, diffuse myalgia, generalized itching, orthostatic syncopes, photophobia, oligurea and pain in the left breast. Laboratory data on admission revealed deteriorated renal and coagulation function. Administration of Vancomycin, Imipenem, dopamin and nafamostat mesilate was started immediately after admission, that was effective. The patient recuperated steadily over the next week with apparent desquamation of the skin on her face, breast and extremities especially palms and soles. MRSA isolated from her milk was coagulase type II producing toxic shock syndrome toxin-1 (TSST-1) and enterotoxin C. Also immunoglobulin G against TSST-1 was not detected from her sera both on admission and on discharge, which suggested that the patient belongs to the high risk group of TSS recurrence.
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PMID:[A case of toxic shock syndrome secondary to mastitis caused by methicillin-resistant Staphylococcus aureus]. 1171 66

Imipenem-relebactam (I-R) is a novel beta-lactam/beta-lactamase inhibitor combination given with cilastatin. It is indicated for the treatment of complicated urinary tract infections, complicated intra-abdominal infections, and hospital-acquired or ventilator-associated bacterial pneumonia. A literature search was completed to evaluate the evidence to date of I-R. I-R has in vitro activity against multidrug-resistant organisms including carbapenem-resistant Pseudomonas aeruginosa and extended-spectrum beta-lactamase and carbapenem-resistant Enterobacterales. It was granted FDA approval following the promising results of two phase II clinical trials in patients with complicated urinary tract infections and complicated intra-abdominal infections. The most common adverse drug events associated with I-R were nausea (6%), diarrhea (6%), and headache (4%). I-R is a new beta-lactam/beta-lactamase inhibitor combination that will be most likely used for patients with multidrug-resistant gram-negative infections in which there are limited or no available alternative treatment options.
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PMID:A Clinical Review and Critical Evaluation of Imipenem-Relebactam: Evidence to Date. 3326 97


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