Once-daily versus thrice-daily dosing of netilmicin in combination with β-lactam antibiotics as empirical therapy for febrile neutropenic patients

Rozdzinski, Eva; Kern, Winfried V.; Reichle, A.; Möritz, Thomas; Schmeiser, T.; Gaus, Wilhelm; Kurrle, E.

doi:10.1093/jac/31.4.585

Cited by 66 publications

(40 citation statements)

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“…Several trials in cancer patients with febrile neutropenia have compared aminoglycosides given once daily or several times daily with a broad-spectrum b-lactam, 23,24 all concluding that giving the aminoglycoside once daily is both efficacious and safe. However, these trials cannot be directly compared with our study.…”

Section: Discussionmentioning

confidence: 99%

Tobramycin once versus three times daily, given with penicillin G, to febrile neutropenic cancer patients in Norway: a prospective, randomized, multicentre trial

Torfoss¹,

Høiby

Tangen

et al. 2007

Journal of Antimicrobial Chemotherapy

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Objectives: Penicillin G with an aminoglycoside is the standard initial empirical treatment in febrile neutropenia in Norway. It has been argued that giving the aminoglycoside once daily to neutropenic patients with Gram-negative bacteraemia may be hazardous when penicillin G is the b-lactam antibiotic. We questioned this argument and hypothesized that tobramycin once daily was as efficacious as three times daily. Methods:We conducted a randomized prospective multicentre study, comparing the efficacy of tobramycin 6 mg/kg once (arm A) versus three times (arm B) daily, plus penicillin G 5 million IU 34, in febrile neutropenic cancer patients. Primary outcome: modification of the antibiotic regimen.Results: One hundred and seventy-four patients were evaluable for intention-to-treat analyses. One hundred and fifty-five patients had lymphoma or leukaemia as the underlying cancer diagnosis. In arm A, 35 of 88 patients and in arm B, 34 of 86 patients, that is 40% in both arms had no modification of the antibiotic regimen. No patients died while participating in the study. Upon modification of the antibiotic regimen, all patients were successfully treated. The increase in serum creatinine was modest and similar in the two treatment groups.Conclusions: When administered with penicillin G, tobramycin given once daily was as efficacious and safe as tobramycin given three times daily in cancer patients with febrile neutropenia in Norway, provided the regimen was modified according to the clinical response.

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Section: Discussionmentioning

confidence: 99%

Tobramycin once versus three times daily, given with penicillin G, to febrile neutropenic cancer patients in Norway: a prospective, randomized, multicentre trial

Torfoss¹,

Høiby

Tangen

et al. 2007

Journal of Antimicrobial Chemotherapy

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“…[4][5][6][7][8] We did not observe an increased incidence of nephrotoxicity in our patient population. However, clinically significant ototoxicity occurred with greater frequency (12%) than previously reported.…”

Section: Discussionmentioning

confidence: 89%

“…Published clinical trials have suggested that SDD aminoglycosides in combination with other antimicrobials, are safe, effective, and potentially less toxic in febrile granulocytopenic cancer patients. [3][4][5][6][7][8] Based on these findings, the empiric antimicrobial regimen in the febrile neutropenic stem cell transplant (SCT) patient at MD Anderson Cancer Center was changed to include gentamicin at a dose of 5 mg/kg administered over 1 h i.v. once daily for the duration of neutropenia in marrow and peripheral blood stem cell recipients.…”

mentioning

confidence: 99%

Toxicity of single daily dose gentamicin in stem cell transplantation

Warkentin

Ippoliti

Bruton

et al. 1999

Bone Marrow Transplant

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Summary:To determine the safety of single daily dose (SDD) gentamicin in recipients of stem cell transplantation (SCT), we evaluated all adult patients at MD Anderson Cancer Center who received SDD gentamicin for treatment of febrile neutropenia. Thirty-three patients received gentamicin 5 mg/kg i.v. every 24 h. Mean duration of therapy was 7 days (range 3-32 days). All patients received vancomycin and 17 received cisplatinum. All patients had normal renal function prior to therapy. Serum gentamicin levels were monitored only when renal function deteriorated. The incidence of nephrotoxicity and clinically significant ototoxicity was 3% and 12%, respectively. All four patients who developed ototoxicity had normal renal function before and during therapy. The mean duration of gentamicin therapy was significantly longer in patients who developed ototoxicity, 20 days vs 9 days (P = 0.001). Patients treated with SDD gentamicin for Ͼ10 days were more likely to develop ototoxicity (P = 0.045). Single daily dosing of gentamicin was associated with clinically significant ototoxicity in 12% of our patients. A larger randomized EORTC trial evaluating SDD vs MDD amikacin failed to detect a difference in ototoxicity. However, the median duration of therapy was only 8 days. The increased incidence of ototoxicity in our study may be due to prolonged therapy, type of aminoglycoside used, concomitant ototoxic agents, small sample size, or a combination of the above.

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“…More recent clinical studies have confirmed the efficacy of a single daily dose of amikacin plus ceftriaxone as a safe and effective therapy in empirical therapy of febrile granulocytopenic patients 4,5 and in children with severe gram-negative infections 6 or undergoing bone marrow transplantation. 7 It also lends itself to use alone or in combination with cephalosporins in outpatient therapy of moderate infections or in brucellosis when…”

Section: -4mentioning

confidence: 95%

Efficacy and Safety of a Single Daily Dose of Aminoglycoside Therapy

1995

Annals of Saudi Medicine

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Despite the well-recognized renal toxicity and ototoxicity of aminoglycosides, they are still commonly used in the treatment of gram-negative infections, alone or in combination with beta lactam antibiotics. Various approaches have been proposed to reduce aminoglycoside toxicity. These rely on manipulating and correcting for either patient-related factors or drug-related factors. Drug-related risk factors can be corrected for by choosing the appropriate aminoglycoside, adapting the dose and duration of treatment or by co-administration of nephroprotectants.Aminoglycosides have two virtues: 1) concentration-dependent killing and 2) post-antibiotic effect. Aminoglycosides demonstrate dose-dependent killing, i.e., the higher the level, the more rapid the killing of bacteria. The other property of aminoglycosides is the so-called postantibiotic effect. This effect is defined as the delay in regrowth of antibiotic-treated organisms following antibiotic removal. In practice, the effect of postantibiotic effect is the suppression of bacterial growth after cessation of exposure to aminoglycoside concentrations above the minimal inhibitory concentrations (MIC). The duration of this effect is dependent on the aminoglycoside serum concentration achieved and the duration of exposure. It has therefore been suggested that the administration of a large dose once daily could maximize the rate of bacterial killing, and the post-antibiotic effect, preventing regrowth of bacteria during the period of low antibiotic concentration in the serum. 1A narrow therapeutic margin and low predictability of plasma concentrations are the main reasons for drug monitoring during aminoglycoside treatment. Gentamicin, tobramycin, amikacin and netilmicin can now be accurately and rapidly measured by radioenzymatic and radio and enzyme immunoassays. Routine determinations of peak (one to two hours post dose) and trough levels are recommended to ensure adequate dosage in all patients with serious gram-negative infections, especially when renal function is impaired. However, maintaining aminoglycoside concentration within a given range is frequently difficult and will reduce but not entirely eliminate the risk of toxicity. The pharmacokinetic behavior of the aminoglycosides leads to a progressive drug accumulation in the renal tissue and the inner ear, which depends on both dosage and duration of treatment. Nephrotoxicity to aminoglycosides has been estimated to occur in up to 5% to 25% of patients, while hearing loss (cochlear) is observed in about 3% to 14% and vestibular toxicity affecting about 4% to 6% of patients when multiple daily doses of the aminoglycosides are used for therapy. In vitro and animal studies suggest that a oncedaily regimen could reduce the risk of side effects with equal or even improved efficacy of the aminoglycosides in bacterial eradication. 1,2A large number of animal data have demonstrated that the single daily administration of an aminoglycoside is less toxic than administration twice, thrice or by continuous infusion ...

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Once-daily versus thrice-daily dosing of netilmicin in combination with β-lactam antibiotics as empirical therapy for febrile neutropenic patients

Cited by 66 publications

References 0 publications

Tobramycin once versus three times daily, given with penicillin G, to febrile neutropenic cancer patients in Norway: a prospective, randomized, multicentre trial

Tobramycin once versus three times daily, given with penicillin G, to febrile neutropenic cancer patients in Norway: a prospective, randomized, multicentre trial

Toxicity of single daily dose gentamicin in stem cell transplantation

Efficacy and Safety of a Single Daily Dose of Aminoglycoside Therapy

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