Data obtained as part of our routine drug monitoring of teicoplanin therapy (therapeutic drug monitoring, TDM) in adult critically ill patients being treated for suspected or documented Grampositive multiresistant infections were assessed, retrospectively. Data were available for 202 patients (146 male, 56 female; age 58 ± 16 years) with a total number of 829 teicoplanin trough plasma levels (C min) assessed. The percentage of patients with adequate teicoplanin concentrations (C min ≥ 10 mg/L) during the treatment period substantially increased from 3.2% on day 2, to 35%, 70%, 90% and ∼95% on days 4, 7, 11 and 15, respectively. The findings suggest that optimal teicoplanin therapy was achieved only after at least 4, and probably 7, days of therapy in most cases, mainly because of a failure to use an appropriate loading dose. Among the possible causes for the reluctance to use a loading dose, concern over the potential nephrotoxicity of teicoplanin was a major factor. We conclude that loading doses of teicoplanin (6 mg/kg every 12 h for at least three doses) must be considered mandatory in all patients, regardless of their renal function, to enable optimal drug concentrations to be achieved early in the treatment period. Subsequently, TDM is important to ensure that dose regimens are optimized to the individual requirements of the patients.

SUMMARY BackgroundIntravenous administration of a third-generation cephalosporin is optimal antibiotic treatment for spontaneous bacterial peritonitis.

The findings support the suitability of intravenous levofloxacin 500mg twice daily in the treatment of early-onset VAP in ICU patients with normal renal function. Levofloxacin may represent a valid alternative to non-pseudomonal beta-lactams or aminoglycosides in the empirical treatment of early-onset VAP. However, further larger studies are warranted to investigate its efficacy.

Levofloxacin is considered an effective antibiotic in the treatment of community-acquired lower respiratory tract infections (LRTIs). A study was carried out on 17 in-patients to assess the pharmacokinetics of a 500 mg once-daily switch intravenous (i.v.)/oral regimen of levofloxacin in the treatment of LRTI patients. Blood samples were collected under steady-state conditions at appropriate intervals. Levofloxacin plasma concentrations were analysed by means of HPLC and pharmacokinetic parameters were estimated using the WinNonlin pharmacokinetic software package. A lower clearance of levofloxacin (<2 mL/min/kg), conditioning both a longer elimination half-life (approximately 9 h) and a larger AUC(0-tau) (approximately 80 mg/L x h), was observed for both routes in our patients than in healthy volunteers. These differences may be explained considering that levofloxacin is excreted mainly as unchanged drug by the renal route, and most of our patients (71%) were very elderly subjects whose renal function physiologically declines with age. The almost complete (> or =99%) absolute oral bioavailability suggests that a comparable exposure to the iv regimen may be achieved after oral administration. The overall clinical success rate was 94.1%.

This study assessed the urinary pharmacokinetics and theoretical pharmacodynamics of levofloxacin in ICU patients treated with 500 mg b.i.d. i.v. for ventilator associated pneumonia to evaluate if this high dosage regimen might ensure appropriate exposure in the treatment of severe UTIs in ICU patients. Nineteen patients (11M, 8F; age, 52 +/- 21 years; weight, 75 +/- 16 kg) presenting with normal renal function (estimated creatinine clearance, 1.83 +/- 0.61 ml/min/kg; diuresis, 1709 +/- 643ml / 24h) were assessed. In steady-state conditions, urine samples were collected at 0-2h, 2-4h, 4-8h and 8-12h during a dosing interval, and urinary concentrations of levofloxacin were assayed by HPLC. Mean (+/- SD) levofloxacin urinary concentrations were 329.1 +/- 159.9, 388.6 +/- 143.5, 266.0 +/- 102.8 and 168.1 +/- 93.3mg/L at 0-2h, 2-4h, 4-8h and 8-12h, respectively, with urinary AUC0-tau of 3171.4 +/- 1192.1mg/L x h. Mean (+/- SD) levofloxacin excretion rates were 44.1 +/- 20.7, 42.8 +/- 8.2, 31.7 +/- 5.8 and 19.8 +/- 4.2 mg/h during the 0-2h, 2-4, 4-8h and 8-12h interval, respectively. Our findings suggest that, consistently with levofloxacin showing high renal excretion as unmodified drug, 500mg b.i.d. i.v. of levofloxacin ensure and maintain urinary concentrations at least 50-fold higher than the MIC90 of most sensitive uropathogens during the overall dosing interval in ICU patients with normal renal function. Considering the major pharmacodynamic determinants for the concentration-dependent bactericidal activity of levofloxacin as applicable at the urinary level (CU/MIC of >12.2 and/or AUC24h U /MIC of >125h), this high dosage regimen may ensure optimal exposure for the treatment of catheter-related and severe lower UTIs not only against sensitive microorganisms, but probably also whenever microorganisms usually considered as intermediate susceptible or resistant to levofloxacin may be involved.