Levofloxacin: an updated review of its use in the treatment of bacterial infections

Levofloxacin is the L-form of the fluoroquinolone antibacterial agent, ofloxacin. In in vitro studies, levofloxacin demonstrated a broad range of activity against Gram-positive and -negative organisms and anaerobes. The drug is more active against Gram-positive organisms than ciprofloxacin, but less active than newer fluoroquinolones such as gatifloxacin. Its activity against Streptococcus pneumoniae is unaffected by the presence of penicillin resistance. In several randomised controlled trails, 5 to 14 days' treatment with intravenous and/or oral levofloxacin proved an effective therapy for upper and lower respiratory tract infections. In patients with mild to severe community-acquired pneumonia (CAP), intravenous and/or oral levofloxacin 500mg once or twice daily was as effective as intravenous and/or oral gatifloxacin, clarithromycin, azithromycin or amoxicillin/clavulanic acid. Overall, clinical response rates with levofloxacin ranged from 86 to 95% versus 88 to 96% with comparator agents; bacteriological response rates were 88 to 95% and 86 to 98%, respectively. Sequential (intravenous +/- oral switch) therapy with levofloxacin 750mg once daily was as effective as intravenous imipenem/cilastatin (+/- oral switch to ciprofloxacin) in patients with severe nosocomial pneumonia. Generally, oral levofloxacin 250 or 500mg once daily was at least as effective as oral cefaclor, cefuroxime axetil, clarithromycin or moxifloxacin in patients with acute exacerbations of chronic bronchitis as assessed by either clinical or bacteriological response rates. This approach also provided similar efficacy to amoxicillin/ clavulanic acid or clarithromycin in patients with acute sinusitis. Sequential therapy with levofloxacin 500mg twice daily for 7 to 14 days' was as effective as intravenous imipenem/cilastatin in patients with suspected bacteraemia. Oral levofloxacin 500mg once daily for 7 to 10 days was also an effective treatment in patients with uncomplicated skin and skin structure infections, and in those with complicated urinary tract infections. A higher dosage of sequential levofloxacin 750mg once daily proved as effective as intravenous ticarcillin/clavulanic acid (+/- oral switch to amoxicillin/clavulanic acid) in the treatment of complicated skin and skin structure infections. Pharmacoeconomic studies suggest that levofloxacin may be cost-saving in comparison to conventional therapies. CONCLUSIONS: Levofloxacin continues to demonstrate good clinical efficacy in the treatment of a range of infections, including those in which S. pneumoniae is a potential pathogen. Importantly, it has efficacy in CAP similar to that of gatifloxacin and at least as good as that of the third generation cephalosporins. Extensive clinical data confirm the good tolerability profile of this agent without the phototoxicity, hepatic and cardiac events evident with some of the other newer fluoroquinolone agents. Levofloxacin therefore offers a unique combination of documented efficacy and tolerability, and provides an important option for the treatment of bacterial infections.     

Pharmacodynamic target attainment analysis against Streptococcus pneumoniae using levofloxacin 500 mg, 750 mg and 1000 mg once daily in plasma (P) and epithelial lining fluid (ELF) of hospitalized patients with community acquired pneumonia (CAP)

The pharmacokinetics and pharmacodynamics of levofloxacin in patients with respiratory infections such as community-acquired pneumonia (CAP) are poorly documented. This work aimed at assessing the pharmacodynamic target attainment against Streptococcus pneumoniae using levofloxacin 500 mg, 750 mg and 1000 mg administered once daily in plasma (P) and epithelial lining fluid (ELF) of hospitalized patients with community acquired pneumonia. The pharmacokinetics of levofloxacin in elderly (>/=65 years) compared with younger patients (<65 years) hospitalized with CAP were simulated. Susceptibility data with S. pneumoniae from our ongoing national surveillance study (Canadian Respiratory Organism Susceptibility Study-CROSS) were then used to produce pharmacodynamic indices of AUC(0-24)/MIC(all.) Monte Carlo simulations were then used to analyse target attainment of levofloxacin using doses of 500 mg, 750 mg and 1000 mg once daily to achieve free drug AUC(0-24)/MIC(all) >/= 30-100 versus S. pneumoniae in patients with CAP. Pharmacokinetics of levofloxacin simulated after 500 mg, 750 mg and 1000 mg once daily dosing resulted in levofloxacin volume of distribution: elderly patients = younger patients, while levofloxacin clearance was: elderly patients < younger patients. Levofloxacin t(1/2) values were longer in elderly patients (9.8 +/- 2.5h) than younger patients with CAP (7.4 +/- 2.5h). Free levofloxacin AUC(0-24) as well as AUC(0-24)/MIC(all) for S. pneumoniae were higher in elderly patients than younger patients. Monte Carlo simulation using levofloxacin 500 mg yielded probabilities of achieving free-drug AUC(0-24)/MIC(all) of 30 in P and ELF (95.7% and 98.1%) in elderly and younger patients (72.7% and 80.6%) respectively. Levofloxacin 750 mg and 1000 mg once daily had probability of achieving free-drug AUC(0-24)/MIC(all) of 30 in P/ELF of 98.1%/98.6% and 99.2%/99.0%, respectively, in elderly patients compared with 89.9%/94.1% and 95.2%/96.5%, respectively, for younger patients. Probability of achieving of AUC(0-24)/MIC(all) of 100 in P or ELF was very low in both patient populations at different doses except in the case of elderly patients receiving levofloxacin in a dose of 1000 mg once daily P/ELF of 78.5%/87.0%. We conclude that levofloxacin pharmacokinetics in elderly patients with CAP are markedly different from those of younger patients. Levofloxacin 750 mg OD provides high probabilities of achieving free-drug AUC(0-24)/MIC(all) of 30 in both plasma and epithelial lining fluid in patients with CAP including younger patients. Levofloxacin 500 mg OD provides high probabilities of achieving free-drug AUC(0-24)/MIC(all) of 30 in elderly patients with CAP, although we favour the 750 mg dosing in these patients as well. Levofloxacin 750 mg OD results in high probability of pharmacodynamic target attainment and improved bacteriological outcome against S. pneumoniae in patients with CAP.     

Levofloxacin : a review of its use as a high-dose, short-course treatment for bacterial infection

Levofloxacin (Levaquin) is a fluoroquinolone antibacterial that is the L-isomer of ofloxacin. A high-dose (750 mg) short-course (5 days) of once-daily levofloxacin is approved for use in the US in the treatment of community-acquired pneumonia (CAP), acute bacterial sinusitis (ABS), complicated urinary tract infections (UTI) and acute pyelonephritis (AP).The broad spectrum antibacterial profile of levofloxacin means that monotherapy is often a possibility in patients with CAP at times when other agents may require combination therapy, although levofloxacin can be used in combination therapy when necessary. The high-dose, short-course levofloxacin regimen maximizes its concentration-dependent bactericidal activity and may reduce the potential for resistance to emerge. In addition, this regimen lends itself to better compliance because of the shorter duration of treatment and the convenient once-daily administration schedule. Oral levofloxacin is rapidly absorbed and is bioequivalent to the intravenous formulation; importantly, patients can transition between the formulations, which results in more options in regards to the treatment regimen and the potential for patients with varying degrees of illness to be treated. Levofloxacin has good tissue penetration and an adequate concentration can be maintained in the urinary tract to treat uropathogens. Levofloxacin is generally well tolerated and has good efficacy in the treatment of patients with CAP, ABS, complicated UTI and AP. The efficacy and tolerability of levofloxacin 500 mg once daily for 10 days in patients with CAP, ABS and UTIs is well established, and the high-dose, short-course levofloxacin regimen has been shown to be noninferior to the 10-day regimen in CAP and ABS, and to have a similar tolerability profile. Similarly, the high-dose, short-course levofloxacin regimen is noninferior to ciprofloxacin in patients with complicated UTI or AP. Thus, levofloxacin is a valuable antimicrobial agent that has activity against a wide range of bacterial pathogens; however, its use should be considered carefully so that the potential for resistance selection can be minimized and its usefulness in severe infections and against a range of penicillin- and macrolide-resistant pathogens can be maintained.     

Cefuroxime axetil: an updated review of its use in the management of bacterial infections

Cefuroxime axetil, a prodrug of the cephalosporin cefuroxime, has proven in vitro antibacterial activity against several gram-positive and gram-negative organisms, including those most frequently associated with various common community-acquired infections. In numerous randomised, controlled trials, 5 to 10 days' treatment with oral cefuroxime axetil (250 or 500 mg twice daily) was an effective treatment in patients with upper (URTI) and lower respiratory tract infections (LRTI) as assessed by clinical and bacteriological criteria. The drug was as effective as several other cephalosporins, quinolones, macrolides and amoxicillin/clavulanic acid. Shorter courses (5 to 10 days') of cefuroxime axetil were at least as effective as a 10 day course. Furthermore, sequential therapy with intravenous cefuroxime (750 mg 2 or 3 times daily for 2 to 5 days) followed by oral cefuroxime axetil (500 mg twice daily for 3 to 8 days) proved an effective treatment in adult patients with community-acquired pneumonia (CAP). This approach provided similar efficacy to intravenous ampicillin/sulbactam followed by oral amoxicillin/clavulanic acid, a full parenteral course of cefuroxime, or intravenous then oral azithromycin or clarithromycin. Additionally, cefuroxime axetil was an effective treatment in patients with genitourinary, skin and soft-tissue infections, and erythema migrans associated with early stage Lyme disease. The drug is well tolerated by adult and paediatric patients, with adverse effects that are consistent with those of other cephalosporins. The majority of adverse events (primarily gastrointestinal disturbances) were mild to moderate in intensity and reversible upon discontinuation of treatment, with very few serious adverse events reported. Conclusions: Cefuroxime axetil is a broad spectrum antibacterial agent with a pharmacokinetic profile that permits convenient twice-daily administration. The drug is an effective and well tolerated treatment in patients with various infections, including otitis media, pharyngitis, sinusitis, CAP and acute exacerbations of chronic bronchitis. Cefuroxime axetil proved effective as a component of intravenous/oral sequential therapy in the treatment of CAP, although there are currently no dosage recommendations available for this regimen in some countries. Cefuroxime axetil may be considered as an empirical therapy for a range of community-acquired infections, including those in which beta-lactamase-producing strains of common respiratory pathogens are identified as the causative organisms. In an era of rapidly emerging bacterial resistance, empirical treatment with bacterial agents, potentially preventing the emergence of bacterial resistance to agents such as cefuroxime axetil may ensure the appropriate use of newer antibacterial agents, potentially preventing the emergence of bacterial resistance to these newer drugs.     

Comparison of gatifloxacin and levofloxacin administered at various dosing regimens to hospitalised patients with community-acquired pneumonia: pharmacodynamic target attainment study using North American surveillance data for Streptococcus pneumoniae

This work aimed at determining the target attainment potential of gatifloxacin and levofloxacin in specific age-related patient populations such as elderly (> or =65 years) versus younger (<65 years) hospitalised patients with community-acquired pneumonia (CAP). Previously described population pharmacokinetic models of gatifloxacin and levofloxacin administration in patients with serious CAP were utilised to simulate gatifloxacin and levofloxacin pharmacokinetics. Pharmacokinetic simulations and susceptibility data for Streptococcus pneumoniae from the ongoing national surveillance study, Canadian Respiratory Organism Susceptibility Study (CROSS), were then used to produce pharmacodynamic indices of free-drug area under the curve over 24h relative to the minimum inhibitory concentration (free-drug AUC(0-24)/MIC(all)). Monte Carlo simulations were then used to analyse target attainment both of gatifloxacin and levofloxacin to achieve free-drug AUC(0-24)/MIC(all)> or =30 against S. pneumoniae in patients with CAP. Dosing regimens for gatifloxacin were 400 mg once daily (qd) administered to younger patients (<65 years) and gatifloxacin 200 mg qd to elderly patients (> or =65 years). Dosing regimens for levofloxacin were simulated as 500 mg, 750 mg and 1000 mg qd administered to elderly patients as well as younger patients. Monte Carlo simulations using gatifloxacin 400mg against S. pneumoniae yielded probabilities of achieving free-drug AUC(0-24)/MIC(all) of 30 of 96.6% for all patients, 92.3% for younger patients and 97.7% for elderly patients. When administered to elderly patients, a reduced dose of gatifloxacin 200mg qd could achieve a target attainment potential of 91.4%. Monte Carlo simulation using levofloxacin 500 mg qd yielded probabilities of achieving free-drug AUC(0-24)/MIC(all) of 30 of 92.3% for all patients, 95.7% for elderly patients compared with 72.7% for younger patients. Using levofloxacin 750 mg and 1000 mg qd had probabilities of achieving free-drug AUC(0-24)/MIC(all) of 30 of 97.0% and 98.3%, 98.1% and 99.2%, and 90.1% and 95.2% for all patients, elderly patients and younger patients, respectively. The probability of achieving free-drug AUC(0-24)/MIC(all) of 100 was low both with gatifloxacin and levofloxacin, except in the case of elderly patients receiving levofloxacin in a dose of 1000 mg qd (78.5%). We conclude that gatifloxacin and levofloxacin pharmacokinetics in elderly patients with CAP are markedly different from those of younger patients. Higher gatifloxacin/levofloxacin AUC and longer half-life (t(1/2)) values in elderly patients with CAP compared with younger patients provide better pharmacodynamic parameters (free-drug AUC(0-24)/MIC) leading to a higher probability of pharmacodynamic target attainment and improved bacteriological outcome against S. pneumoniae. Gatifloxacin 400mg qd results in a high probability of target attainment and improved bacteriological outcome against S. pneumoniae both in young and elderly CAP patients. However, gatifloxacin administered at a lowered dose of 200 mg qd in elderly patients could still be successful in producing a favourable antibacterial effect. Levofloxacin administered at a dose of 750 mg qd results in a high probability of target attainment and improved bacteriological outcome against S. pneumoniae in all patients with CAP.     

Gatifloxacin: a review of its use in the management of bacterial infections.

Gatifloxacin is an 8-methoxy fluoroquinolone antibacterial agent. The drug has a broader spectrum of antibacterial activity than the older fluoroquinolones (e.g. ciprofloxacin) and shows good activity against many Gram-positive and Gram-negative pathogens, atypical organisms and some anaerobes. Notably, gatifloxacin is highly active against both penicillin-susceptible and -resistant strains of Streptococcus pneumoniae, a common causative pathogen in community-acquired pneumonia (CAP), acute sinusitis and acute bacterial exacerbations of bronchitis. Gatifloxacin is absorbed well from the gastrointestinal tract (oral bioavailability is almost 100%). Therefore, patients can be switched from intravenous to oral therapy without an adjustment in dosage. High concentrations of gatifloxacin are achieved in plasma and target tissues/fluids. Gatifloxacin has a long plasma elimination half-life, thus allowing once-daily administration. Few clinically significant interactions between gatifloxacin and other drugs have been reported. In patients with CAP, clinical response rates in recipients of intravenous/oral gatifloxacin 400 mg/day ranged from 86.8 to 98.0% and rates of bacterial eradication ranged from 83.1 to 100% (up to 28 days post-treatment). Gatifloxacin showed efficacy similar to that of amoxicillin/clavulanic acid, ceftriaxone (with or without erythromycin) with or without stepdown to clarithromycin, levofloxacin or clarithromycin. Gatifloxacin was as effective as clarithromycin or amoxicillin/clavulanic acid, and was significantly more effective (in terms of clinical response; p < 0.035) than 7 to 10 days' treatment with cefuroxime axetil in the treatment of acute exacerbations of chronic bronchitis. In acute sinusitis, gatifloxacin showed clinical efficacy similar to that of clarithromycin, trovafloxacin or amoxicillin/clavulanic acid. Genitourinary infections were also successfully treated with gatifloxacin. Gatifloxacin is generally well tolerated. Its tolerability profile was broadly similar to those of comparator agents in comparative trials. The most common adverse events are gastrointestinal symptoms (oral formulation) and injection site reactions. CONCLUSIONS: Gatifloxacin has an extended spectrum of antibacterial activity and provides better coverage of Gram-positive organisms (e.g. S. pneumoniae) than some older fluoroquinolones. The drug has favourable pharmacokinetic properties, is administered once daily and is at least as well tolerated as other fluoroquinolones. Gatifloxacin is a useful addition to the fluoroquinolones currently available for use in the clinical setting and has an important role in the management of adult patients with various bacterial infections. As with other fluoroquinolones, careful control of gatifloxacin usage in the community is important in order to prevent the emergence of bacterial resistance and thus preserve the clinical value of this agent.     

Concentrations in plasma, urinary excretion and bactericidal activity of levofloxacin (500 mg) versus ciprofloxacin (500 mg) in healthy volunteers receiving a single oral dose

In a randomised crossover study, 14 volunteers received a single oral dose of 500 mg levofloxacin or 500 mg ciprofloxacin in order to assess plasma concentrations by high-pressure liquid chromatography (up to 24 h), urinary excretion and urinary bactericidal titres (UBTs) at intervals up to 120 h. The median maximum concentration of levofloxacin in plasma was 6.1 mg/L and that of ciprofloxacin was 2.3 mg/L. The median cumulative level of renal excretion of the administered dose of the parent drug was 81.2% for levofloxacin and 36.2% for ciprofloxacin. UBTs were determined for a reference strain and nine clinical uropathogens. The median UBTs of both quinolones measured within the first 12 h were between 0 and 1:≥1024, correlating with the minimum inhibitory concentrations (MICs) of the strains. For Gram-negative strains, the UBTs of both quinolones were comparable despite the lower MICs of ciprofloxacin. During further time courses, however, the UBTs of levofloxacin were significantly higher than those of ciprofloxacin. For Gram-positive strains, for which the MICs of levofloxacin were equal to or lower than those of ciprofloxacin, the UBTs of levofloxacin were already significantly higher from the beginning. It can be concluded that overall the doses of the two tested fluoroquinolones may be considered equivalent with regard to treatment of complicated urinary tract infections, although the recommended dosing is twice daily for ciprofloxacin and once daily for levofloxacin.     

Pharmacokinetics/pharmacodynamics of levofloxacin 750 mg once daily in young women with acute uncomplicated pyelonephritis

This pilot study was undertaken to characterise the pharmacokinetics, pharmacodynamics and potential clinical efficacy of levofloxacin 750 mg once daily for 5 days for treatment of women with acute uncomplicated pyelonephritis. Four women diagnosed with acute pyelonephritis were enrolled. Following pre-therapy specimen collection, an initial oral dose of 750 mg levofloxacin was administered. The mean pharmacokinetic parameters for the first dose were: maximum serum concentration (C(max)) 12.5+/-4.7 mg/L (range 5.6-16.0mg/L) (fC(max) 8.8+/-3.3, where f indicates the levofloxacin free or non-protein-bound fraction), area under the serum concentration-time curve (AUC) 85.4+/-14.1 mgh/L (range 66.2-96.8 mgh/L) (fAUC 59.8+/-9.9) and serum half-life (t(1/2)) 6.7+/-0.5h. Mean urine concentrations were 88.0+/-100mg/L at the 0-3 h collection, 307+/-143 mg/L at 3-6 h, 170+/-107 mg/L at 6-12 h and 85+/-8 mg/L at 12-24 h. Mean levofloxacin serum pharmacodynamics for infecting Escherichia coli were: C(max)/minimum inhibitory concentration (MIC) 323+/-185(fC(max)/MIC 226+/-129); and AUC/MIC 2339+/-830(fAUC/MIC 1647+/-579). Mean urine levofloxacin concentration/MIC ratios were: 900+/-1389 for 0-3 h, 12100+/-4950 for 3-6 h, 5922+/-3912 for 6-12 h and 2233+/-1037 for 12-24 h. Levofloxacin eradicated E. coli from the urine by 3-6 h after the first dose. Levofloxacin 750 mg once daily for 5 days has pharmacodynamics that support further evaluation of this regimen for treatment of women with acute uncomplicated pyelonephritis.     

Which fluoroquinolones are suitable for the treatment of urinary tract infections?

A number of fluoroquinolone agents are now available for clinical use and even more under development. Whether these compounds are equally effective and thus interchangeable in the treatment of urinary tract infection (UTI) has to be answered by comparing their antimicrobial activity against uropathogens, the pharmacokinetic and pharmacodynamic parameters and outcome of statistically meaningful clinical studies. Whereas almost all fluoroquinolones give equivalent results with short term therapy of acute uncomplicated cystitis in women, for patients with complicated UTI, only those compounds at the appropriate dosage regimen should be chosen for empiric therapy, which would exhibit sufficiently high urinary bactericidal activity against Gram-negative as well as Gram-positive uropathogens. When considering antibacterial activity, pharmacokinetic and pharmacodynamic properties as well as the results of the published clinical studies, a dosage of 500 mg ciprofloxacin twice daily, 500 mg levofloxacin once daily, or 400 mg gatifloxacin once daily may be comparable dosage regimens in the treatment of severe complicated UTI. In the case of ciprofloxacin (750 mg twice daily) and levofloxacin (500 mg twice daily), the dose could even be increased in UTI caused by less susceptible uropathogens, such as Pseudomonas aeruginosa.     

Telithromycin

Telithromycin, the first member of the ketolide antibacterials, has good activity against community-acquired respiratory pathogens, including multiple-drug-resistant strains of Streptococcus pneumoniae. Telithromycin 800 mg once daily has been US FDA approved for the treatment of acute bacterial sinusitis (ABS; treatment duration 5 days), acute bacterial exacerbations of chronic bronchitis (AECB; 5 days) and mild-to-moderate community-acquired pneumonia (CAP; 7-10 days). In patients with CAP, telithromycin was as effective as amoxicillin 1000 mg three times daily for 10 days, clarithromycin 500 mg twice daily for 10 days or trovafloxacin 200 mg once daily for 7-10 days. In patients with AECB, telithromycin was as effective as a 10-day regimen of amoxicillin/clavulanic acid 500/125 mg three times daily, cefuroxime axetil 500 mg twice daily or clarithromycin 500 mg twice daily. In patients with ABS, telithromycin was as effective as a 10-day course of amoxicillin/clavulanic acid 500/125 mg three times daily or cefuroxime axetil 250 mg twice daily. Telithromycin was generally well tolerated and most adverse events were of mild-to-moderate severity and transitory. The most common adverse events with telithromycin were diarrhoea and nausea (10.8% and 7.9% of 2702 patients in clinical trials); these events occurred in 8.6% and 4.6% of 2139 comparator-treated patients.     

短疗程高剂量左氧氟沙星治疗慢性阻塞性肺疾病急性加重期的临床疗效和安全性

目的：观察静脉应用左氧氟沙星高剂量750 mg,qd,共5天,与常规剂量500 mg,qd,共10天,治疗慢性阻塞性肺疾病急性加重期（AECOPD）的临床疗效和安全性。方法：对60例急性下呼吸道感染患者双盲、随机分为治疗组静脉应用左氧氟沙星高剂量750 mg,qd,共5天（30例）和左氧氟沙星组常规剂量500 mg,qd,共10天（30例）进行治疗。结果：左氧氟沙星高剂量组痊愈20例,显效7例,进步3例,治愈率为66.6%,有效率为90.0%。左氧氟沙星常规剂量组痊愈18例,显效8例,进步3例,无效1例,治愈率为60.0%,总有效率为86.7%。两组总有效率比较差异有统计学意义（P〈0.05）。治疗组细菌总清除率为81.9%,对照组为77.8%,不良反应发生率分别为3.33%和6.66%。结论：短疗程大剂量的左氧氟沙星治疗慢性阻塞性肺疾病急性加重期（AECOPD）疗效好,安全性高。     

盐酸左氧氟沙星治疗呼吸系统细菌感染的临床比较研究

目的观察盐酸左氧氟沙星对呼吸系统细菌感染效果。方法选取呼吸系统细菌感染患者150例,分为左氧氟沙星组和环丙沙星组,分别静点左氧氟沙星和环丙沙星,比较两组患者的症状缓解时间和细菌清除率。结果左氧氟沙星组的细菌清除率为90.27%,症状缓解时间为(3.5±1.2)d,环丙沙星组的细菌清除率为73.97%,症状缓解时间为(6.8±1.4)d,统计学分析,P<0.05,有统计学意义。结论盐酸左氧氟沙星治疗呼吸系统细菌感染起效快、细菌清除率高。     

高剂量左氧氟沙星治疗老年下呼吸道感染的疗效分析

目的:评价高剂量左氧氟沙星注射液治疗老年下呼吸道感染的临床疗效及安全性。方法:60例老年下呼吸道细菌感染患者,分为试验组(左氧氟沙星500mg静脉滴注,1次.d-1)与对照组(莫西沙星400mg静脉滴注,1次.d-1),疗程7~14d。结果:试验组与对照组对咳嗽、咳痰、发热、外周血白细胞恢复的有效率均在80.00%以上,临床总有效率分别为90.00%、86.67%,细菌清除率分别为76.92%、81.25%,2组疗效比较差异无统计学意义;药品不良反应发生率分别为16.67%、13.33%,2组间差异无统计学意义。结论:高剂量左氧氟沙星治疗老年下呼吸道感染安全、有效。     

Clinical implications of 750 mg, 5-day levofloxacin for the treatment of community-acquired pneumonia

OBJECTIVE: To evaluate the time to symptom resolution and i.v.-to-p.o. transition in community-acquired pneumonia (CAP) patients treated with 750 mg or 500 mg levofloxacin. RESEARCH DESIGN: A retrospective, subset analysis of a multicenter, randomized, double-blind, controlled trial comparing 750 mg levofloxacin for 5 days to 500 mg levofloxacin for 10 days for the treatment of CAP. PATIENTS AND METHODS: A total of 528 CAP patients were included. Baseline symptoms were re-evaluated on Day 3 of therapy, and time to i.v.-to-p.o. transition was recorded for inpatients. RESULTS: For the overall population, 67.4% of patients receiving 750 mg levofloxacin had resolution of fever by Day 3 of therapy, compared to 54.6% of 500 mg treated patients (P = 0.006). Patients who started on 750 mg levofloxacin i.v. (N = 108) transitioned to p.o. in an average of 2.68 days while those starting on 500 mg i.v. (N = 124) transitioned in 2.95 days (P = 0.144). The median time for i.v.-to-p.o. switch was 2.35 days and 2.75 days for patients receiving 750 mg and 500 mg levofloxacin, respectively (P = 0.098, log rank test). By Day 3 of therapy, 68% of patients receiving the 750 mg dose had transitioned from i.v. to p.o. levofloxacin, compared with 61% of the 500 mg group (P = 0.280). The safety profiles were comparable for the two regimens. CONCLUSIONS: The 750 mg levofloxacin dose resulted in a greater proportion of patients with resolution of CAP symptoms by Day 3 when compared with 500 mg therapy. Consequently, the 750 mg regimen trended toward more rapid transition to p.o., potentially resulting in lower overall drug costs. Time to switch from i.v. to p.o. was determined by the investigators' discretion rather than a set protocol. Additionally, length of stay data was not collected in this study, which can significantly impact overall healthcare costs. Further research is required to fully understand the economic impact of the 750 mg, 5-day levofloxacin regimen.     

High-dose levofloxacin in community-acquired pneumonia: a randomized, open-label study

Background: The conventional treatment for community-acquired pneumonia (CAP) involves combination therapy consisting of a β-lactam penicillin or a cephalosporin with a macrolide. Alternatively, high-dose levofloxacin treatment has been used as single-agent therapy for treating CAP, covering atypical pathogens. Objective: This study compared the clinical efficacy and safety of high-dose levofloxacin with combined ceftriaxone and azithromycin for the treatment of CAP. Patients and Methods: This phase IV, prospective, randomized, open-label trial enrolled patients admitted to a tertiary referral hospital for CAP treatment from 2010 to 2011. Hospital admission was decided based on clinical judgement and the pneumonia severity index. Forty subjects were enrolled and assigned to two treatment arms using a random numbers table. The 20 subjects in the experimental group were given levofloxacin 750?mg intravenously once daily, followed by the same dose of oral levofloxacin at discharge when clinically improved and the 20 subjects in the control group were given ceftriaxone 2.0?g intravenously once daily plus oral azithromycin 500?mg for 3 consecutive days, followed by oral cefpodoxime 200?mg per day at discharge after clinical improvement. The primary outcome was the clinical success rate. Secondary outcomes were the microbiological success rate and adverse events during the study. Results: Of the 40 subjects enrolled, 36 completed the study: 17 in the experimental group and 19 in the control group. The groups did not differ in terms of demographic factors or clinical findings at baseline. The clinical success rate (cured?+?improved) was 94% in the experimental (levofloxacin) group and 84% in the control group (p?>?0.05). The microbiological success rate and overall adverse events were also similar in both groups. Conclusion: Single-agent, high-dose levofloxacin treatment exhibited excellent clinical and microbiological efficacy with a safety profile comparable to that of ceftriaxone plus azithromycin therapy. Large-scale clinical trials are required to verify these results. Clinical Trial Registration: WHO International Clinical Trials Registry: KCT0000374; Daiichi-Sankyo Korea study code: T11-13-V1.     

Pharmacokinetics of ciprofloxacin XR (1000 mg) versus levofloxacin (500 mg) in plasma and urine of male and female healthy volunteers receiving a single oral dose

The new extended-release formulation of ciprofloxacin (ciprofloxacin XR) was designed for once-daily administration in the treatment of urinary tract infection (UTI). The aim of this study was to compare concentrations in plasma, urinary excretion (UE) and pharmacokinetic parameters of ciprofloxacin XR (1000 mg) versus those of levofloxacin (500 mg) in healthy volunteers receiving a single oral dose. In this randomised crossover study, 12 volunteers (6 males, 6 females) received a single oral dose of 1000 mg ciprofloxacin XR or 500 mg levofloxacin to assess the concentrations (by high-pressure liquid chromatography) in plasma up to 32 h and the UE at intervals up to 36 h. The following pharmacokinetic parameters were studied: C(max), t(max), t(1/2), AUC(plasma0-->infinity), AUC(plasma0-->last), Cl(ren), maximal urinary concentration (U(max)), AUC(urine0-->last) and UE. Both fluoroquinolones were well tolerated. The plasma concentrations of levofloxacin were significantly higher than those of ciprofloxacin XR throughout the study period. The urinary concentrations of ciprofloxacin XR were significantly higher than those of levofloxacin in the first collection interval (0-4 h), whereas the concentrations of levofloxacin were significantly higher than those of ciprofloxacin XR in the five last collection intervals (12-36 h). The median proportions of cumulative renal excretion of the administered dose of the parent drug up to 36 h were 43.1% for ciprofloxacin XR (range, 13.7-50.8%; mean +/- standard deviation (S.D.), 40.5 +/- 9.9%) and 79.8% for levofloxacin (range, 74.0-88.2%; mean +/- S.D., 80.4 +/- 5.5%). C(max), AUC(plasma0-->infinity), AUC(plasma0-->last) and UE were statistically significantly higher in the levofloxacin than in the ciprofloxacin XR phase; t(max), Cl(ren) and U(max) were statistically significantly higher in the ciprofloxacin XR phase than in the levofloxacin phase; and AUC(urine0-->last) and t(1/2) were not statistically different. After an oral administration of ciprofloxacin XR 1000 mg and levofloxacin 500 mg, C(max) and AUC(plasma0-->infinity) were significantly higher in the levofloxacin phase. UE of ciprofloxacin XR 1000 mg once daily, however, was equivalent to that of levofloxacin 500 mg, and overall comparable urinary concentrations and AUC(urine) were reached by both drugs. Therefore, it can be assumed that the two doses investigated can be considered equivalent for the treatment of UTI.     

Efficacy of 750-mg, 5-day levofloxacin in the treatment of community-acquired pneumonia caused by atypical pathogens

BACKGROUND: Current recommended durations for treatment of atypical community-acquired pneumonia (CAP) range from 10 to 21 days. However, antibiotics such as the fluoroquinolones may allow for effective, short-course regimens. OBJECTIVE: This study evaluated the efficacy of 750 mg levofloxacin for 5 days compared to a 500-mg, 10-day levofloxacin regimen for the treatment of atypical CAP. METHODS: A randomized, active-controlled, double-blind, multicenter study was conducted within the United States. Of the 528 patients enrolled in the study, 149 were diagnosed with CAP due to Legionella pneumophila, Chlamydia pneumoniae, or Mycoplasma pneumoniae. Patients' baseline symptoms were re-evaluated on Day 3 of therapy. Clinical efficacy and resolution of CAP symptoms were evaluated at the posttherapy visit (7-14 days after the last dose of active drug). RESULTS: This report represents a subgroup analysis of a previous clinical study. Among the 123 clinically evaluable patients diagnosed with atypical CAP (26 patients were unevaluable), the clinical success rates were 95.5% (63 of 66 patients) for the 750-mg group and 96.5% (55 of 57 patients) for the 500-mg group (95% CI for success rate of the 500-mg group minus that of the 750-mg group, -6.8 to 8.8). At the poststudy evaluation (31-38 days after treatment began), relapse occurred in 相似文献   

Levofloxacin pharmacokinetics in children

Levofloxacin is a broad-spectrum fluoroquinolone antibiotic with activity against many pathogens that cause bacterial infections in children, including penicillin-resistant pneumococci. To provide dosing guidance for children, 3 single-dose, multicenter pharmacokinetic studies were conducted in 85 children in 5 age groups: 6 months to <2 years, 2 to <5 years, 5 to <10 years, 10 to <12 years, and 12 to 16 years. Each child received a single 7-mg/kg dose of levofloxacin (not to exceed 500 mg) intravenously or orally. Plasma and urine samples were collected through 24 hours after dose. Pharmacokinetic parameters were estimated and compared among the 5 age groups and to previously collected adult data. Levofloxacin absorption (as indicated by C(max) and t(max)) and distribution in children are not age dependent and are comparable to those in adults. Levofloxacin elimination (reflected by t1/2 and clearance), however, is age dependent. Children younger than 5 years of age clear levofloxacin nearly twice as fast (intravenous dose, 0.32+/-0.08 L/h/kg; oral dose, 0.28+/-0.05 L/h/kg) as adults and, as a result, have the total systemic exposure (area under the plasma drug concentration-time curve) approximately one half that of adults. The levofloxacin area under the plasma drug concentration-time curve (dose normalized) in children receiving a single dose of the oral liquid formulation is comparable to that in children receiving the intravenous formulation. To provide compatible levofloxacin exposures associated with clinical effectiveness and safety in adults, children > or =5 years need a daily dose of 10 mg/kg, whereas children 6 months to <5 years should receive 10 mg/kg every 12 hours.     

A trial of levofloxacin 750 mg once daily for 5 days versus ciprofloxacin 400 mg and/or 500 mg twice daily for 10 days in the treatment of acute pyelonephritis

ABSTRACT

Objective: A double-blind, noninferiority trial was conducted to establish the safety and efficacy of a once-daily, 5-day course of levofloxacin 750?mg compared to a twice-daily, 10-day course of ciprofloxacin in complicated urinary tract infections (cUTI) and acute pyelonephritis (AP). This report focuses on subjects with AP.

Research design and methods: Adult male and female subjects with clinical signs and symptoms of AP and laboratory confirmation of their diagnosis were randomized to receive one dose of levofloxacin 750?mg once daily intravenously (IV) or orally and one dose of placebo for 5 days, followed by placebo; or ciprofloxacin 400?mg IV and/or 500?mg orally twice daily for 10 days.

Main outcome measures: The primary, prospectively defined end point was microbiologic eradication at post-therapy (study days 15–22). Secondary outcomes included clinical response and safety and tolerability.

Results: In the modified intent-to-treat (mITT) population (levofloxacin 94, ciprofloxacin 98), 83% of levofloxacin-treated and 79.6% of ciprofloxacin-treated subjects achieved microbiological eradication (difference –3.4, 95% CI –14.4%, 7.6%). In the microbiologically evaluable (ME) population (levofloxacin 80, ciprofloxacin 76), 92.5% of levofloxacin-treated vs. 93.4% of ciprofloxacin-treated subjects (difference –0.9, 95% CI –7.1%, 8.9%) achieved microbiologic eradication. Clinical success was achieved in 86.2% vs. 80.6% (mITT) and in 92.5% vs. 89.5% (ME) of levofloxacin-treated and ciprofloxacin-treated subjects, respectively. Escherichia coli was the most commonly isolated uropathogen. Few (2.1%) of the pathogens were fluoroquinolone-resistant. Adverse events (AEs) were similar to those seen previously with both agents. Potential limitations are that this analysis is based on a subset of subjects from a larger study and, because of different durations of therapy, the results may be biased against levofloxacin.

Conclusions: High-dose, short-course therapy with levofloxacin in subjects with AP is at least as effective as standard 10-day therapy with ciprofloxacin.     

国产乳酸环丙沙星注射液药效与临床研究

用国产乳酸环丙沙星注射液２００ｍｇ静滴，每１２小时１次，疗程１０天（伤寒、副伤寒７天），治疗细菌性感染１１４例，临床有效率为９２．９２％（１０５／１１３），细菌阴转率９４．２９％（９９／１０５），细菌消除率９４．３９％（１０１／１０７），总的不良反应率７．０２％（８／１１４）。同时用头孢拉定粉针剂作随机对照治疗呼吸系统继发感染和泌尿系统复杂型感染，其中治疗呼吸系统继发感染的临床有效率、细菌阴转率及