How should imipenem-cilastatin be Used in the treatment of fever and infection in neutropenic cancer patients?

Raad, Issam; Abi-Said, Dima; Rolston, Kenneth V. I.; Karl, L R N Cynthia; Bodey, Gerald P.

doi:10.1002/(sici)1097-0142(19980615)82:12<2449::aid-cncr20>3.0.co;2-o

Cited by 22 publications

(7 citation statements)

References 25 publications

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“…Monotherapy with imipenem, a potent beta-lactam antibiotic, or with ceftazidime, a third-generation cephalosporin, has been successfully tested in a number of trials in febrile neutropenic adults [4,6,7,20,[27][28][29][30] and pediatric cancer patients [8,31] and is also approved by the Infectious Diseases Society of America (IDSA) [32]. A retrospective analysis of several prospective open and randomized trials evaluating imipenem in neutropenic cancer patients did not show the emergence of drug resistance [33]. Because of the increasing frequency of infections caused by gram-positive organisms, especially those susceptible only to vancomycin, there is an ongoing debate on whether glycopeptides should be included in the initial antimicrobial regimen for febrile neutropenic patients [26].…”

Section: Discussionmentioning

confidence: 99%

Short Courses of Intravenous Empirical Antibiotic Treatment in Selected Febrile Neutropenic Children with Cancer

2002

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Section: Discussionmentioning

confidence: 99%

Short Courses of Intravenous Empirical Antibiotic Treatment in Selected Febrile Neutropenic Children with Cancer

2002

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“…The safety of therapy was evaluated by monitoring laboratory values. Nephrotoxicity and hepatotoxicity are defined as an increase in serum creatinine, transaminases, bilirubin or alkaline phosphatase by at least twice the upper normal limit [ 14 , 22 ]. Hypokalemia was defined as an increase in serum potassium level > 10 mmol below the lower limit of the normal range [ 23 ].…”

Section: Methodsmentioning

confidence: 99%

A Comparative Study of Piperacillin-Tazobactam With and Without Vancomycin as Empirical Therapy for Febrile Neutropenic Patients With Solid Tumor Malignancies

Sirkhazi

Sarriff

Aziz³

et al. 2015

World J Oncol

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BackgroundThe objective of this study was to evaluate the outcomes, mortality and toxicity associated with piperacillin-tazobactam (PT) and the addition of vancomycin (VM) to the empirical treatment of febrile neutropenic cancer patients.MethodA retrospective study on adult febrile neutropenic patients who were admitted between September 2008 and May 2013 with solid tumor malignancies was conducted at King Fahad Specialist Hospital Dammam, Saudi Arabia.ResultsOut of 86 febrile neutropenic patients, 60 patients were treated with PT group and 26 patients were with PT + VM group. The two groups were comparable in terms of outcome, mortality, nephrotoxicities and hepatotoxicities. The median duration of neutropenia in PT treatment group was 4 days (range 1 - 10) in the female and 7 days (range 1 - 13) in males while in PT + VM 6 days (range 1 - 5) in female and 7.5 days (range 1 - 6) in male with significance P = 0.007. There was no significant difference in terms of duration of fever and length of stay between the two treatment groups. There were no deaths reported during treatment in both groups. In PT, the microbial eradication was 27/40 (67.5%) patients (14/27 (51.9%) of female and 13/27 (48.1%) of male)), whereas it was 13/40 (32.5%) patients (9/13 (69.2%) of female and 4/13 (30.8%) of male)) in PT + VM group. Overall, there was no significant difference in terms of microbiological eradication between the two groups (OR: 1.22; 95% CI: 0.486 - 3.072; X2 stat: 0.182; P = 0.67). Response to therapy in clinically defined infections was higher 16/23 (69.56%) in PT treatment group than 7/23 (30.44%) in PT + VM group. But there was no significant difference between the two treatment groups in terms of clinically defined infections (OR: 1.013; 95% CI: 0.359 - 2.862; X2 stat: 0.001; P = 0.98). There was no significant difference in renal and liver functions between the two groups in terms of serum creatinine level and clearance, alkaline phosphate and alanine tranferase and gama glutamyl tranferase. The most commonly isolated organisms were Escherichais coli (eighteen isolates), Staphylococcus aureus (seven isolates), Streptococcus spp (six isolates) and Klebsiella pneumonia (four isolates). The overall success rate was similar in both treatment arms and treatment was well tolerated, with no severe adverse reactions reported.ConclusionAlthough the addition of VM might provide an additional value for coverage of gram-positive pathogens. This study demonstrates that there was no significant difference in terms of response rate in both treatment groups, which could be due to the low local methicillin-resistant Staphylococcus aureus (MRSA) rates and other resistant gram-positive organisms at our institution, stressing the importance of local antibiograms in developing empirical neutropenic fever protocols.

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“…Imipenem is a beta-lactam antibiotic, a N-formimidoyl derivative of thienamycin, which is usually administered in a mixture with cilastatin to prevent the renal degradation of imipenem. [1][2][3][4] Cilastatin is a competitive inhibitor of the renal hydrolytic enzyme, dehydropeptidase I; it has no intrinsic antimicrobial activity, but retards the renal metabolism of imipenem. Imipenem has a broad antimicrobial activity against Gram-negative, Gram-positive and anaerobic pathogens, 1) which allows it to be used as a monotherapy, e.g., in the management of febrile neutropenia.…”

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confidence: 99%

“…Imipenem has a broad antimicrobial activity against Gram-negative, Gram-positive and anaerobic pathogens, 1) which allows it to be used as a monotherapy, e.g., in the management of febrile neutropenia. 1,2,[4][5][6][7][8] Sodium bisulfite (SBS), used as a stabilizer in injectable preparations, is known to degrade various drugs including thiamine, 9) epinephrine, 10) gabexate mesilate, 11) nafamostat mesilate, 12) urokinase, 13) morphine 14) and fluorouracil. 15) However, there are no reports of detailed kinetic studies on the degradation of imipenem in the presence of SBS.…”

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Prediction of the Stability of Imipenem in Intravenous Mixtures

Yoshida

Takasu

Shimizu

et al. 2013

CHEMICAL & PHARMACEUTICAL BULLETIN

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The purpose of this study was to predict the stability of imipenem in a mixed infusion. The hydrolysis of imipenem in aqueous solution was found to be accelerated by pH, and by increasing concentrations of sodium bisulfite (SBS) and L-cysteine. Equations were derived for the degradation rate constants (k(obs)) of pH, SBS and L-cysteine and fractional rate constants were estimated by nonlinear least-squares method (quasi-Newton method using the solver in Microsoft Excel) at 25°C. The activation energy (Ea) and frequency factor (A) were calculated using the Arrhenius equation. The pH of the mixed infusion was estimated using the pH characteristic (PHC) curve. From these results, an equation was derived giving the residual ratio (%) of imipenem at any time after mixing an infusion containing SBS and/or L-cysteine at any temperature and at pH 4.0-10.0. A high correlation was shown to exist between the estimated and determined residual ratios (%).

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How should imipenem-cilastatin be Used in the treatment of fever and infection in neutropenic cancer patients?

Cited by 22 publications

References 25 publications

Short Courses of Intravenous Empirical Antibiotic Treatment in Selected Febrile Neutropenic Children with Cancer

Short Courses of Intravenous Empirical Antibiotic Treatment in Selected Febrile Neutropenic Children with Cancer

A Comparative Study of Piperacillin-Tazobactam With and Without Vancomycin as Empirical Therapy for Febrile Neutropenic Patients With Solid Tumor Malignancies

Prediction of the Stability of Imipenem in Intravenous Mixtures

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