Piperacillin/Tazobactam versus Imipenem: A Double-Blind, Randomized Formulary Feasibility Study at a Major Teaching Hospital

Marra, Fawziah; Reynolds, Robert P.; Stiver, Grant; Bryce, Elizabeth; Sleigh, Kenna; Frighetto, Luciana; MacDougall, Cathy; Jewesson, Peter J.

doi:10.1016/s0732-8893(97)00239-3

Cited by 26 publications

(36 citation statements)

References 26 publications

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“…The efficacy rates reported for these therapy regimens ranged from 52% to 84% [4,9,11,13,15,16,20]. In our study the response rate to the initial therapy was similar to that reported for those regimens and for other combination therapies comprising piperacillin/tazobactam plus amikacin or tobramycin [3,14].…”

Section: Discussionsupporting

confidence: 85%

Piperacillin, beta-lactam inhibitor plus gentamicin as empirical therapy of a sequential regimen in febrile neutropenia of pediatric cancer patients

Fleischhack

Schmidt-Niemann

Wulff

et al. 2001

Supportive Care in Cancer

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The beta-lactam/beta-lactamase inhibitor combinations are a good choice for empirical antimicrobial therapy in febrile neutropenic patients, because their antibacterial spectra include both gram-negative and gram-positive pathogens. This trial was initiated to assess the efficacy and safety of piperacillin with the beta-lactam inhibitors sulbactam (PSG group) or tazobactam (PTG group) and gentamicin as initial therapy in febrile neutropenia of pediatric patients. In a prospective study, 239 episodes of fever and neutropenia were analyzed for the clinical and microbiological response dependent on infection etiology and treatment group: 66.5% of episodes were classified as fever of unknown origin (FUO) and 33.5%, as microbiologically or clinically documented infections; 19.2% of all episodes were due to bacteremia, predominantly caused by gram-positive organisms (69.6%). The response to the initial therapy was 55.2% overall and 65.4% in episodes of FUO with a significant higher success rate in the PSG group than in the PTG group (70.1% vs. 52.4%, P=0.039), and 35.0% in documented infections. In episodes with documented infection longer duration of fever and antimicrobial therapy was recorded than for FUO episodes. Four patients died of causes related to infection. Fever relapse occurred in 26 episodes (11.1%), predominantly in patients who were still neutropenic. Toxic side effects were minimal. The initial therapy of piperacillin with sulbactam or tazobactam in combination with gentamicin is well tolerated, and its efficacy is comparable to that of other combination therapies or of monotherapy with beta-lactam antibiotics in pediatric neutropenic cancer patients.

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Section: Discussionsupporting

confidence: 85%

Piperacillin, beta-lactam inhibitor plus gentamicin as empirical therapy of a sequential regimen in febrile neutropenia of pediatric cancer patients

Fleischhack

Schmidt-Niemann

Wulff

et al. 2001

Supportive Care in Cancer

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“…Comparator drug subcategories included a β-lactam arm in 16 studies [39-46,48-51,53,54,56,58], fluoroquinolone in 5 studies [44,46,47,55,57], aminoglycoside in 2 studies [53,56], and vancomycin in 1 study [52]; 6 employed double coverage [44,45,52-54,56]. The primary outcome for 17 of these 20 studies was clinical success [39-52,54,57,58] and 16 of 20 included a microbiological response assessment for underlying pathogens [39-43,45-48,50,52-54,56-58] (Table 1). Ten of 20 studies provided information about the minimum number of imipenem and comparator doses required for inclusion in analysis, 7 of which included patients if they received at least 1 dose of either imipenem or the comparator [39,41,42,46,47,50,57], and 1 study each excluding patients receiving fewer than 5 [49], 6 [40], and 15 [55] doses (Table 2).…”

Section: Resultsmentioning

confidence: 99%

Imipenem resistance of Pseudomonas in pneumonia: a systematic literature review

et al. 2010

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BackgroundPneumonia, and particularly nosocomial (NP) and ventilator-associated pneumonias (VAP), results in high morbidity and costs. NPs in particular are likely to be caused by Pseudomonas aeruginosa (PA), ~20% of which in observational studies are resistant to imipenem. We sought to identify the burden of PA imipenem resistance in pneumonia.MethodsWe conducted a systematic literature review of randomized controlled trials (RCT) of imipenem treatment for pneumonia published in English between 1993 and 2008. We extracted study, population and treatment characteristics, and proportions caused by PA. Endpoints of interest were: PA resistance to initial antimicrobial treatment, clinical success, microbiologic eradication and on-treatment emergence of resistance of PA.ResultsOf the 46 studies identified, 20 (N = 4,310) included patients with pneumonia (imipenem 1,667, PA 251; comparator 1,661, PA 270). Seven were double blind, and 7 included US data. Comparator arms included a β-lactam (17, [penicillin 6, carbapenem 4, cephalosporin 7, monobactam 1]), aminoglycoside 2, vancomycin 1, and a fluoroquinolone 5; 5 employed double coverage. Thirteen focused exclusively on pneumonia and 7 included pneumonia and other diagnoses. Initial resistance was present in 14.6% (range 4.2-24.0%) of PA isolates in imipenem and 2.5% (range 0.0-7.4%) in comparator groups. Pooled clinical success rates for PA were 45.2% (range 0.0-72.0%) for imipenem and 74.9% (range 0.0-100.0%) for comparator regimens. Microbiologic eradication was achieved in 47.6% (range 0.0%-100.0%) of isolates in the imipenem and 52.8% (range 0.0%-100.0%) in the comparator groups. Resistance emerged in 38.7% (range 5.6-77.8%) PA isolates in imipenem and 21.9% (range 4.8-56.5%) in comparator groups.ConclusionsIn the 15 years of RCTs of imipenem for pneumonia, PA imipenem resistance rates are high, and PA clinical success and microbiologic eradication rates are directionally lower for imipenem than for comparators. Conversely, initial and treatment-emergent resistance is more likely with the imipenem than the comparator regimens.

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“…152 A formulary feasibility study found that imipenem and piperacillin/ tazobactam were both effective and suitable for intra-abdominal infection, pneumonia, febrile neutropenia, and skin and soft tissue infection, but that imipenem should be retained due to the prevalence of multidrug-resistant Gram-negative pathogens. 75 A more recent study of febrile neutropenic patients reported that overall treatment costs were 189.55 euros less with imipenem than piperacillin/tazobactam (P < 0.001). 155 Imipenem monotherapy has been recommended in polymicrobial infections where combination therapy would be more costly, although imipenem combination therapy was recommended if Pseudomonas was present.…”

Section: De-escalation Therapymentioning

confidence: 96%

Two decades of imipenem therapy

Rodloff¹,

Goldstein²,

Torres³

2006

Journal of Antimicrobial Chemotherapy

146

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Imipenem, the first carbapenem discovered, was developed more than two decades ago in response to an unmet need for a highly potent, broad-spectrum antimicrobial agent with a strong safety profile. It has since been used to treat more than 26 million patients. In an era where antibiotic use has driven antibiotic resistance, choosing appropriate initial therapy for serious infection is critical. Appropriate antibiotic regimens must cover all likely pathogens, be administered promptly at the correct dosage and dosing interval, be well tolerated and prevent the emergence of resistance. While imipenem was initially reserved for use in intractable, serious infections, the benefits of early aggressive therapy are now known, making imipenem a core agent in de-escalation therapy due to proven efficacy and safety for indications such as nosocomial pneumonia, intra-abdominal infection, sepsis and febrile neutropenia. De-escalation therapy with an agent such as imipenem minimizes resistance development by initiating aggressive initial treatment and then tailoring therapy based on patient response and culture results, switching to a less expensive, narrower spectrum antibiotic regimen or shortening the duration of therapy. Imipenem has maintained sustained clinical efficacy, tolerability and in vitro activity against important bacterial pathogens for two decades. We review the factors that continue to make imipenem as appropriate an agent for de-escalation therapy now as it was 20 years ago.

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Piperacillin/Tazobactam versus Imipenem: A Double-Blind, Randomized Formulary Feasibility Study at a Major Teaching Hospital

Cited by 26 publications

References 26 publications

Piperacillin, beta-lactam inhibitor plus gentamicin as empirical therapy of a sequential regimen in febrile neutropenia of pediatric cancer patients

Piperacillin, beta-lactam inhibitor plus gentamicin as empirical therapy of a sequential regimen in febrile neutropenia of pediatric cancer patients

Imipenem resistance of Pseudomonas in pneumonia: a systematic literature review

Two decades of imipenem therapy

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