Tissue penetration and antimicrobial activity of standard- and high-dose trimethoprim/sulfamethoxazole and linezolid in patients with diabetic foot infection

Gary E. Stein, John K. Throckmorton, Amy E. Scharmen, William J. Weiss, Laszlo Prokai, Curtis L. Smith, Daniel H. Havlichek

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Objectives: The purpose of this study was to conduct a pharmacokinetic and pharmacodynamic evaluation of high (320/1600 mg) and standard (160/800 mg) doses of trimethoprim/sulfamethoxazole and linezolid in outpatients with mild diabetic foot infections (DFIs). Methods: Both viable skin/soft tissue from the infection site and serum were obtained at various times after antibiotic administration from 18 patients (6 per study group) being treated with linezolid, standard doses of trimethoprim/sulfamethoxazole or high doses of trimethoprim/sulfamethoxazole during a follow-up clinic visit. These samples were assayed for drug concentrations by liquid chromatography in tandem with mass spectrometry. Patient sera were also utilized in time-kill assays against two strains of Staphylococcus aureus and three strains of b-haemolytic streptococci. Results: The mean tissue/serum ratio for linezolid was 0.46 (range, 0.18-0.71). The mean tissue/serum ratio for trimethoprim was 1.2 (range, 0.3-4.5) for both standard and high doses, and 0.23 (range, 0.1-0.46) and 0.36 (range, 0.14-1.28) for standard and high doses of sulfamethoxazole, respectively. Linezolid exhibited inhibitory activity in time-kill assays against strains of S. aureus (0.45(0.5 log10 cfu/mL) and b-haemolytic streptococci (2.2(0.6 log10 cfu/mL), while trimethoprim/sulfamethoxazole exhibited bactericidal (.3 log kill) activity against all of these isolates. These findings were consistent foreach sampling time and for high aswell as standard doses of trimethoprim/sulfamethoxazole. Conclusions: This pharmacokinetic/pharmacodynamic study found that trimethoprim/sulfamethoxazole exhibits good skin/soft tissue penetration in patients with DFIs as well as bactericidal activity in serum against strains of S. aureus and b-haemolytic streptococci.

Original languageEnglish
Article numberdkt267
Pages (from-to)2852-2858
Number of pages7
JournalJournal of Antimicrobial Chemotherapy
Volume68
Issue number12
DOIs
StatePublished - 1 Dec 2013

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Linezolid
Diabetic Foot
Sulfamethoxazole Drug Combination Trimethoprim
Infection
Streptococcus
Staphylococcus aureus
Serum
Pharmacokinetics
Sulfamethoxazole
Skin
Soft Tissue Infections
Trimethoprim
Ambulatory Care
Tandem Mass Spectrometry
Liquid Chromatography
Outpatients

Keywords

  • Diabetes
  • Pharmacokinetics
  • Time-kill

Cite this

@article{8f3f259eaa8c4b31bf915cd20e3c3719,
title = "Tissue penetration and antimicrobial activity of standard- and high-dose trimethoprim/sulfamethoxazole and linezolid in patients with diabetic foot infection",
abstract = "Objectives: The purpose of this study was to conduct a pharmacokinetic and pharmacodynamic evaluation of high (320/1600 mg) and standard (160/800 mg) doses of trimethoprim/sulfamethoxazole and linezolid in outpatients with mild diabetic foot infections (DFIs). Methods: Both viable skin/soft tissue from the infection site and serum were obtained at various times after antibiotic administration from 18 patients (6 per study group) being treated with linezolid, standard doses of trimethoprim/sulfamethoxazole or high doses of trimethoprim/sulfamethoxazole during a follow-up clinic visit. These samples were assayed for drug concentrations by liquid chromatography in tandem with mass spectrometry. Patient sera were also utilized in time-kill assays against two strains of Staphylococcus aureus and three strains of b-haemolytic streptococci. Results: The mean tissue/serum ratio for linezolid was 0.46 (range, 0.18-0.71). The mean tissue/serum ratio for trimethoprim was 1.2 (range, 0.3-4.5) for both standard and high doses, and 0.23 (range, 0.1-0.46) and 0.36 (range, 0.14-1.28) for standard and high doses of sulfamethoxazole, respectively. Linezolid exhibited inhibitory activity in time-kill assays against strains of S. aureus (0.45(0.5 log10 cfu/mL) and b-haemolytic streptococci (2.2(0.6 log10 cfu/mL), while trimethoprim/sulfamethoxazole exhibited bactericidal (.3 log kill) activity against all of these isolates. These findings were consistent foreach sampling time and for high aswell as standard doses of trimethoprim/sulfamethoxazole. Conclusions: This pharmacokinetic/pharmacodynamic study found that trimethoprim/sulfamethoxazole exhibits good skin/soft tissue penetration in patients with DFIs as well as bactericidal activity in serum against strains of S. aureus and b-haemolytic streptococci.",
keywords = "Diabetes, Pharmacokinetics, Time-kill",
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Tissue penetration and antimicrobial activity of standard- and high-dose trimethoprim/sulfamethoxazole and linezolid in patients with diabetic foot infection. / Stein, Gary E.; Throckmorton, John K.; Scharmen, Amy E.; Weiss, William J.; Prokai, Laszlo; Smith, Curtis L.; Havlichek, Daniel H.

In: Journal of Antimicrobial Chemotherapy, Vol. 68, No. 12, dkt267, 01.12.2013, p. 2852-2858.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Tissue penetration and antimicrobial activity of standard- and high-dose trimethoprim/sulfamethoxazole and linezolid in patients with diabetic foot infection

AU - Stein, Gary E.

AU - Throckmorton, John K.

AU - Scharmen, Amy E.

AU - Weiss, William J.

AU - Prokai, Laszlo

AU - Smith, Curtis L.

AU - Havlichek, Daniel H.

PY - 2013/12/1

Y1 - 2013/12/1

N2 - Objectives: The purpose of this study was to conduct a pharmacokinetic and pharmacodynamic evaluation of high (320/1600 mg) and standard (160/800 mg) doses of trimethoprim/sulfamethoxazole and linezolid in outpatients with mild diabetic foot infections (DFIs). Methods: Both viable skin/soft tissue from the infection site and serum were obtained at various times after antibiotic administration from 18 patients (6 per study group) being treated with linezolid, standard doses of trimethoprim/sulfamethoxazole or high doses of trimethoprim/sulfamethoxazole during a follow-up clinic visit. These samples were assayed for drug concentrations by liquid chromatography in tandem with mass spectrometry. Patient sera were also utilized in time-kill assays against two strains of Staphylococcus aureus and three strains of b-haemolytic streptococci. Results: The mean tissue/serum ratio for linezolid was 0.46 (range, 0.18-0.71). The mean tissue/serum ratio for trimethoprim was 1.2 (range, 0.3-4.5) for both standard and high doses, and 0.23 (range, 0.1-0.46) and 0.36 (range, 0.14-1.28) for standard and high doses of sulfamethoxazole, respectively. Linezolid exhibited inhibitory activity in time-kill assays against strains of S. aureus (0.45(0.5 log10 cfu/mL) and b-haemolytic streptococci (2.2(0.6 log10 cfu/mL), while trimethoprim/sulfamethoxazole exhibited bactericidal (.3 log kill) activity against all of these isolates. These findings were consistent foreach sampling time and for high aswell as standard doses of trimethoprim/sulfamethoxazole. Conclusions: This pharmacokinetic/pharmacodynamic study found that trimethoprim/sulfamethoxazole exhibits good skin/soft tissue penetration in patients with DFIs as well as bactericidal activity in serum against strains of S. aureus and b-haemolytic streptococci.

AB - Objectives: The purpose of this study was to conduct a pharmacokinetic and pharmacodynamic evaluation of high (320/1600 mg) and standard (160/800 mg) doses of trimethoprim/sulfamethoxazole and linezolid in outpatients with mild diabetic foot infections (DFIs). Methods: Both viable skin/soft tissue from the infection site and serum were obtained at various times after antibiotic administration from 18 patients (6 per study group) being treated with linezolid, standard doses of trimethoprim/sulfamethoxazole or high doses of trimethoprim/sulfamethoxazole during a follow-up clinic visit. These samples were assayed for drug concentrations by liquid chromatography in tandem with mass spectrometry. Patient sera were also utilized in time-kill assays against two strains of Staphylococcus aureus and three strains of b-haemolytic streptococci. Results: The mean tissue/serum ratio for linezolid was 0.46 (range, 0.18-0.71). The mean tissue/serum ratio for trimethoprim was 1.2 (range, 0.3-4.5) for both standard and high doses, and 0.23 (range, 0.1-0.46) and 0.36 (range, 0.14-1.28) for standard and high doses of sulfamethoxazole, respectively. Linezolid exhibited inhibitory activity in time-kill assays against strains of S. aureus (0.45(0.5 log10 cfu/mL) and b-haemolytic streptococci (2.2(0.6 log10 cfu/mL), while trimethoprim/sulfamethoxazole exhibited bactericidal (.3 log kill) activity against all of these isolates. These findings were consistent foreach sampling time and for high aswell as standard doses of trimethoprim/sulfamethoxazole. Conclusions: This pharmacokinetic/pharmacodynamic study found that trimethoprim/sulfamethoxazole exhibits good skin/soft tissue penetration in patients with DFIs as well as bactericidal activity in serum against strains of S. aureus and b-haemolytic streptococci.

KW - Diabetes

KW - Pharmacokinetics

KW - Time-kill

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