Teicoplanin compared to flucloxacillin for antibiotic treatment of neutropenic patients

Smith, C L; Milliken, Sam; Powles, R; Costa, Francesco; Gore, M.; Benjamin, Suzanne; Talbot, D C; Ellis, Lawrence D.; Large, J; Jameson, Beryl

doi:10.1111/j.1365-2141.1990.tb07927.x

Cited by 5 publications

(1 citation statement)

References 13 publications

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“…Piperacillin, an acylureido penicillin, in combination with the β‐lactamase inhibitor tazobactam, is a frequently used intravenous antibiotic, especially in the empirical treatment of hospital‐acquired infections. Other combination therapy with piperacillin involves β‐lactams such as flucloxacillin [1–5] or aminoglycosides [6–8]. The combination of piperacillin and flucloxacillin together with an aminoglycoside has been used successfully for the treatment of infections in children with cancer [2, 3].…”

Section: Introductionmentioning

confidence: 99%

Inhibition of flucloxacillin tubular renal secretion by piperacillin

Landersdorfer

Kirkpatrick

Kinzig

et al. 2008

Brit J Clinical Pharma

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WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Most β‐lactams are excreted by filtration and to a greater extent by tubular secretion, which is a capacity‐limited saturable pathway. • Pharmacokinetic interactions between co‐administered β‐lactams have been frequently reported; however, their mechanism and possible clinical benefits are not well defined. • We are not aware of the interaction between piperacillin and flucloxacillin being reported in the literature. WHAT THIS STUDY ADDS • Piperacillin inhibits the renal and nonrenal elimination of flucloxacillin to a clinically significant extent, but not vice versa. • Modelling suggests that the mechanism for the decrease of renal clearance of flucloxacillin is probably competitive inhibition of renal tubular secretion by piperacillin. • Piperacillin has a 15‐times higher affinity for the renal transporter than flucloxacillin based on the molar ratio. AIMS To explore the extent, time course, site(s), mechanism and possible clinical relevance of the pharmacokinetic (PK) interaction between piperacillin and flucloxacillin. METHODS A single‐dose, randomized, six‐way crossover study in 10 healthy volunteers where all subjects received all of the following as 5‐min intravenous infusions: (i) 1.5 g piperacillin, (ii) 0.5 g flucloxacillin, (iii) 1.5 g piperacillin + 0.5 g flucloxacillin, (iv) 3 g piperacillin, (v) 1 g flucloxacillin, and (vi) 3 g piperacillin + 1 g flucloxacillin. Drug concentrations in plasma and urine were determined by high‐performance liquid chromatography. WinNonlin® was used for PK modelling and statistics. RESULTS Piperacillin significantly decreased the renal clearance of flucloxacillin from 5.44 to 2.29 l h−1 (medians, P < 0.01) and the nonrenal clearance of flucloxacillin from 2.67 to 1.80 l h−1 (P < 0.01). The renal clearance of flucloxacillin was reduced to 45% (point estimate, 90% confidence interval 40 to 50%) and the nonrenal clearance to 66% (59, 73). The extent of interaction was larger at the higher doses. Competitive inhibition of tubular secretion by piperacillin was identified as the most likely mechanism for the decreased renal clearance of flucloxacillin. Piperacillin had a 15‐times higher affinity for the renal transporter than flucloxacillin based on the molar ratio. Piperacillin PK was only slightly affected by flucloxacillin. CONCLUSIONS Piperacillin inhibits renal and nonrenal elimination of flucloxacillin. This interaction seems clinically significant, as total clearance was reduced by a factor of 1.5 for the lower and 2.1 for the higher doses. PK interactions, especially with piperacillin, are likely to occur also with other β‐lactam combinations and might be useful to improve the effectiveness of antibacterial treatment.

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Section: Introductionmentioning

confidence: 99%

Inhibition of flucloxacillin tubular renal secretion by piperacillin

Landersdorfer

Kirkpatrick

Kinzig

et al. 2008

Brit J Clinical Pharma

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A survey of the use of teicoplanin in patients with haematological malignancies and solid tumours

Davies

1998

Infection

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A significant number of open and comparative studies have now addressed the use of teicoplanin in the treatment of documented or presumed infection in patients with haematological and non-haematological malignancy. Available evidence suggests that teicoplanin is an effective agent against such infections, with an excellent safety profile. The use of teicoplanin and vancomycin may be justified as part of the initial management of clinically infected right atrial catheters in patients with malignancy. The first-line use of glycopeptides may also be appropriate in units where streptococcal and methicillin resistant staphylococcal infections are prevalent. However, such a policy should be reviewed regularly. Except in the above situations, a delay in the introduction of either teicoplanin or vancomycin in cancer patients does not appear to produce any excess mortality, but there may be some additional morbidity in terms of fever and malaise. The introduction of glycopeptides as second-line agents is indicated for sensitive, microbiologically documented infections and for patients who have not responded to empirical, first-line therapy. Non-inpatient treatment with teicoplanin is an area of ongoing interest and may be justified on both humanitarian and pharmacoeconomic grounds. The use of glycopeptides in the prophylactic setting remains controversial and should be avoided while the emergence of resistance, particularly in enterococci, should be monitored closely.

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