Antibacterial Activity of Imipenem: The First Thienamycin Antibiotic

Kropp, Helmut; Gerckens, Lynn S.; Sundelof, Jon G.; Kahan, Frederick M.

doi:10.1093/clinids/7.supplement_3.s389

Cited by 115 publications

(52 citation statements)

References 135 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…29 In general, Imipenem has an unusually broad spectrum, a high potency, a stability to ß-lactamase, and no cross-resistance with other ß-lactam agents. [34][35][36] It is interesting that the activity of test penicillins and cefazolin against ß-lactamase-producing Prevotella was decreased remarkably in the present study, while these antibiotics inhibited the growth of the ß-lactamase-nonproducing…”

Section: Discussionmentioning

confidence: 45%

Past administration of β-lactam antibiotics and increase in the emergence of β-lactamase–producing bacteria in patients with orofacial odontogenic infections

Kuriyama¹,

Nakagawa²,

Karasawa³

et al. 2000

Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, an

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 45%

Past administration of β-lactam antibiotics and increase in the emergence of β-lactamase–producing bacteria in patients with orofacial odontogenic infections

Kuriyama¹,

Nakagawa²,

Karasawa³

et al. 2000

Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, an

View full text Add to dashboard Cite

“…The stability of thienamycins to ␤-lactamase hydrolysis was noted in early studies of imipenem, including low k cat values for the class A ␤-lactamase of B. cereus and a class C P. aeruginosa ␤-lactamase (150,208,270,366). Charnas and Knowles observed biphasic kinetics when RTEM was acylated by carbapenem compounds; an initial burst was followed by a slower steady-state reaction, strongly suggestive of a branched reaction pathway (80,114).…”

Section: Inhibitory Activity Of Carbapenemsmentioning

confidence: 92%

Three Decades of β-Lactamase Inhibitors

Drawz¹,

2010

View full text Add to dashboard Cite

SUMMARYSince the introduction of penicillin, β-lactam antibiotics have been the antimicrobial agents of choice. Unfortunately, the efficacy of these life-saving antibiotics is significantly threatened by bacterial β-lactamases. β-Lactamases are now responsible for resistance to penicillins, extended-spectrum cephalosporins, monobactams, and carbapenems. In order to overcome β-lactamase-mediated resistance, β-lactamase inhibitors (clavulanate, sulbactam, and tazobactam) were introduced into clinical practice. These inhibitors greatly enhance the efficacy of their partner β-lactams (amoxicillin, ampicillin, piperacillin, and ticarcillin) in the treatment of seriousEnterobacteriaceaeand penicillin-resistant staphylococcal infections. However, selective pressure from excess antibiotic use accelerated the emergence of resistance to β-lactam-β-lactamase inhibitor combinations. Furthermore, the prevalence of clinically relevant β-lactamases from other classes that are resistant to inhibition is rapidly increasing. There is an urgent need for effective inhibitors that can restore the activity of β-lactams. Here, we review the catalytic mechanisms of each β-lactamase class. We then discuss approaches for circumventing β-lactamase-mediated resistance, including properties and characteristics of mechanism-based inactivators. We next highlight the mechanisms of action and salient clinical and microbiological features of β-lactamase inhibitors. We also emphasize their therapeutic applications. We close by focusing on novel compounds and the chemical features of these agents that may contribute to a “second generation” of inhibitors. The goal for the next 3 decades will be to design inhibitors that will be effective for more than a single class of β-lactamases.

show abstract

“…hnipenem is a carbapenem antibiotic with the broadest antibacterial spectrum of any of the currently available beta-lactam drugs (10,11). It is active against most clinically significant Gram-positive species including the enterococci, most Gram-negative species and anaerobes (10,11).…”

Section: Methodsmentioning

confidence: 99%

“…It is active against most clinically significant Gram-positive species including the enterococci, most Gram-negative species and anaerobes (10,11). Irnipenem is always administered jointly with cilastatin, which inhibits inactivation of irnipenem by a renal brush border enzyme dehydropeptidase 1, and eliminates any renal tubular toxicity of imipenem (12).…”

Section: Methodsmentioning

confidence: 99%

A Prospective Randomized Trial of Imipenem‐Cilastatin Versus Clindamycin/Tobramycin in the Treatmentof Intra‐Abdominal and Pelvic Infections

Mandell

Turgeon

Ronalds

1992

Canadian Journal of Infectious Diseases and Medical Microbiolog

View full text Add to dashboard Cite

THE CANADIAN C LINICAL TRIALS G ROUPLAOBJECTIVE: A Canadian multicentre clinical trial in the treatment of intra-abdominal and pelvic infections to compare the efficacy and safety of monotherapy using imipen em-cllastatin (imipenem) (500 mg intravenously every 6 h) versus combination therapy with clindamycin/ tobramycin (clindamycin 600 mg intravenously every 6 h and tobramycin l. 7 mg/kg intraven ously every 8 h). METHoDs: Two hundred and fifty patients were entered (88 definite and 162 possible infections) and all were evalu able for analysis of adverse events and intention to treat analysis of efficacy. Dichotomous outcomes u sed were: cured versus noncured (improved, failed, relapsed). REsULTS: No statistically significant differen ces were found with the intention to treat analysis (P=0.88) or with definite infections (P=0.81). For overall bacteriological response, no significant differen ces were noted (P=0.1). Eleven and 15 patients on imipenem and clindamycin/ tobramycin, respectively, were colonized with bacteria. Enterococci colonized four of 11 imipenem cases and five of 15 clindamycin/ tobramycin cases while fungi colonized six patients on imipenem and four on clindamycin/tobramycin. Five patients on imipenem and seven on clindamycin/tobramycin developed superinfection. In the imipenem group. one case had a bacterial superinfection while four cases were du e to Candida albicans. Seven of seven superinfections on clindamycin/tobramycin were bacterial. Three bacteria initially sen sitive to the assigned study drug developed resistance. In two patients on imipenem, Enterococcus faeca lis and Pseudomonas aeruginosa became resistant after 14 and 10 days of therapy, respectively. On clindamycin/tobramycin, one instance of Bacteroidesjragilis resistance after eight days of therapy was seen. Eigh ty-three adverse events occurred; 4 7 in the imipen em group and 36 in the clindamycin/tobramycin group. This resulted in discontinuation of antibacterial therapy in 13 patients, seven of wh om were on imipenem and six on clindamycin/tobramycin. Comparison of adverse effects showed statistically significant differences for nausea (P=0.02) and hepatotoxicity (P=0.05) occurring with greater frequ en cy in the imipenem and clindamycin/ tobramycin groups, respectively. CoNCLUSIONS: These data support the conclusion that monotherapy with imipenem (500 mg intravenou sly every 6 h) is as efficacious as clindamycin/tobramycin for treatment of intra-abdominal and pelvic infections. Both regimens are well tolerated. (Pour resume, voir page 280)

show abstract

Antibacterial Activity of Imipenem: The First Thienamycin Antibiotic

Cited by 115 publications

References 135 publications

Past administration of β-lactam antibiotics and increase in the emergence of β-lactamase–producing bacteria in patients with orofacial odontogenic infections

Past administration of β-lactam antibiotics and increase in the emergence of β-lactamase–producing bacteria in patients with orofacial odontogenic infections

Three Decades of β-Lactamase Inhibitors

A Prospective Randomized Trial of Imipenem‐Cilastatin Versus Clindamycin/Tobramycin in the Treatmentof Intra‐Abdominal and Pelvic Infections

Contact Info

Product

Resources

About