Penetration of levofloxacin into skin tissue after oral administration of multiple 750 mg once-daily doses

Chow, Andrew; Chen, A; Lattime, H; Morgan, Nancy; Wong, F; Fowler, Cynthia; Williams, R R

doi:10.1046/j.1365-2710.2002.00396.x

Cited by 14 publications

(9 citation statements)

References 31 publications

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“…He found the highest concentration of levofloxacin 6 h after administration of the dose, with a mean concentration of 11.87 ± 2.58 mg/kg. Our results for wound tissue in diabetic patients treated with 500 mg of levofloxacin, at 10.78 ± 6.48 mg/kg, were similar to the figures reported by Chow et al 9 However, unlike Chow and colleagues, at steady state, after at least 6 days of oral therapy with levofloxacin, we did not find a correlation between tissue concentration of levofloxacin and time from last dose to sampling (Table 1). In this study, a variety of pathogens were isolated, including multi-resistant and non-fermenting bacteria.…”

Section: Discussionsupporting

confidence: 90%

“…These tissue concentrations were similar to those reported for ofloxacin in necrotic foot lesions of diabetic and non-diabetic patients with peripheral arterial occlusive disease. 7,8 Chow et al 9 examined skin tissue of healthy volunteers with a dose of 750 mg levofloxacin once daily for 3 days. He found the highest concentration of levofloxacin 6 h after administration of the dose, with a mean concentration of 11.87 ± 2.58 mg/kg.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Tissue and serum levofloxacin concentrations in diabetic foot infection patients

Oberdorfer¹,

Swoboda²,

Hamann³

et al. 2004

Journal of Antimicrobial Chemotherapy

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Tissue and serum levofloxacin concentrations in diabetic foot infection patients

Oberdorfer¹,

Swoboda²,

Hamann³

et al. 2004

Journal of Antimicrobial Chemotherapy

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“…No significant effect of local infection on tissue penetration was detected for these two drugs [21, 22]. Other methods such as skin biopsy have reported tissue to plasma ratios of around 2 [23, 24]. In lung resections ciprofloxacin concentrations exceeded corresponding plasma concentrations by more than sevenfold [25].…”

Section: Discussionmentioning

confidence: 99%

Tissue pharmacokinetics of levofloxacin in human soft tissue infections

Bellmann

Kuchling²,

Dehghanyar

et al. 2004

Brit J Clinical Pharma

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Aims The present study addressed the ability of levofloxacin to penetrate into subcutaneous adipose tissues in patients with soft tissue infection. Methods Tissue concentrations of levofloxacin in inflamed and healthy subcutaneous adipose tissue were measured in six patients by microdialysis after administration of a single intravenous dose of 500 mg. Levofloxacin was assayed by high‐performance liquid chromatography. Results The mean concentration vs time profile of free levofloxacin in plasma was identical to that in inflamed and healthy tissues. The ratios of the mean area under the free levofloxacin concentration vs time curve from 0 to 10 h (AUC(0,10 h)) in tissue to that in plasma were 1.2 ± 1.0 for inflamed and 1.1 ± 0.6 for healthy subcutaneous adipose tissue (mean ± SD). The mean difference in the ratio of the AUCtissue : AUCplasma for inflamed and healthy tissue was 0.09 (95% confidence interval −0.58, 0.759, P > 0.05). Interindividual variability in tissue penetration was high, as indicated by a coefficient of variation of approximately 82% for AUCtissue : AUCplasma ratios. Conclusions The penetration of levofloxacin into tissue appears to be unaffected by local inflammation. Our plasma and tissue data suggest that an intravenous dose of 500 mg levofloxacin provides effective antibacterial concentrations at the target site. However, in treatment resistant patients, tissue concentrations may be sub‐therapeutic.

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“…It may be hypothesized that the higher 750-mg/day dose of levofloxacin would be more desirable in patients with severe burn injury due to the high incidence of severe infections caused by less-susceptible organisms and possibly poor perfusion of infected tissue, which may limit drug penetration (5,6,14).…”

mentioning

confidence: 99%

Levofloxacin Pharmacokinetics and Pharmacodynamics in Patients with Severe Burn Injury

Kiser

Hoody

Obritsch

et al. 2006

Antimicrob Agents Chemother

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Levofloxacin pharmacokinetics were studied in 11 patients with severe burn injuries. Patients (values are means ؎ standard deviations; age, 41 ؎ 17 years; weight, 81 ؎ 12 kg; creatinine clearance, 114 ؎ 40 ml/min) received intravenous levofloxacin at 750 mg (n ‫؍‬ 10 patients) or 500 mg (n ‫؍‬ one patient) once daily. Blood samples were collected on day 1 of levofloxacin therapy; eight patients were studied again on days 4 to 6. The pharmacodynamic probability of target attainment (PTA) was evaluated by Monte Carlo simulation. Mean systemic clearance, half-life, and area under the concentration-time curve over 24 h after levofloxacin at 750 mg were 9.0 ؎ 3.2 liters/h, 7.8 ؎ 1.6 h, and 93 ؎ 31 mg · h/liter, respectively. There were no differences in pharmacokinetic parameters between day 1 and day 4; however, large intrapatient and interpatient variability was observed. Levofloxacin pharmacokinetics in burned patients were similar to those reported in other critically ill populations. Levofloxacin at 750 mg achieved >90% PTA for gram-negative and gram-positive pathogens with MICs of <0.5 g/ml and MICs of <1 g/ml, respectively. However, satisfactory PTA was not obtained with less-susceptible gram-negative organisms with MICs of 1 g/ml or any organism with a MIC of >2 g/ml. The results of this study indicate that levofloxacin should be administered at 750 mg/day for treatment of systemic infections in severely burned patients. However, even 750 mg/day may be inadequate for gram-negative organisms with MICs of 1 to 2 g/ml even though they are defined as susceptible. Alternative antibiotics or treatment strategies should be considered for infections due to these pathogens.

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Penetration of levofloxacin into skin tissue after oral administration of multiple 750 mg once-daily doses

Abstract: The results support the clinical usage of levofloxacin 750 mg once-daily for complicated SSSIs.

Cited by 14 publications

References 31 publications

Tissue and serum levofloxacin concentrations in diabetic foot infection patients

Tissue and serum levofloxacin concentrations in diabetic foot infection patients

Tissue pharmacokinetics of levofloxacin in human soft tissue infections

Levofloxacin Pharmacokinetics and Pharmacodynamics in Patients with Severe Burn Injury

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