Development of a dosing-adjustment tool for fluoroquinolones in osteoarticular infections: The Fluo-pop study.

Fluoroquinolones efficacy depend on both the drug exposure and the level of drug resistance of the bacteria responsible for the infection. Specifically for the Staphylococcus species, which is the microorganism mainly involved in osteoarticular infections (OAI), in-vitro data reported that an AUC/MIC ratio above 115 h maximizes drug efficacy. However, data on OAI patients are lacking and a simple approach to access AUCs is still a clinical issue. We conducted a prospective, single-center study in 30 OAI patients hospitalized in the Rennes University Hospital to model ofloxacin pharmacokinetics and to define a limited sampling strategy (LSS) suitable for ofloxacin and levofloxacin treatments. Modeling was conducted with the Monolix software. The final model was externally validated using levofloxacin data. Monte-Carlo simulations were used to evaluate the probability of target attainment (PTA) of different dosing regimens. Two hundred and ninety-seven (297) ofloxacin concentrations were available for the pharmacokinetic modeling. Ofloxacin pharmacokinetics was best described using a bicompartmental model with a first order elimination, and a transit compartment model absorption. CKD-EPI and sex explained half of ofloxacin pharmacokinetic variability. For LSS, the 0, 1 h and 3 h sampling scheme resulted in the best approach both for BID and TID dosages (R2 adjusted = 91.1% and 95.0%, outliers = 4.8% and 5.0%, respectively). PTA allows choosing the best drug and dosage according to various hypotheses. A simple 3-sample protocol (pre-dose, 1 h after intake and 3 h after intake) to estimate ofloxacin and levofloxacin AUC allows optimal drug dosage for the treatment of osteoarticular infections.

In Vivo Bioluminescent Monitoring of Therapeutic Efficacy and Pharmacodynamic Target Assessment of Antofloxacin against Escherichia coli in a Neutropenic Murine Thigh Infection Model.

Antimicrobial resistance among uropathogens has increased the rates of infection-related morbidity and mortality. Antofloxacin is a novel fluoroquinolone with broad-spectrum antibacterial activity against urinary Gram-negative bacilli, such as Escherichia coli This study monitored the in vivo efficacy of antofloxacin using bioluminescent imaging and determined pharmacokinetic (PK)/pharmacodynamic (PD) targets against E. coli isolates in a neutropenic murine thigh infection model. The PK properties were determined after subcutaneous administration of antofloxacin at 2.5, 10, 40, and 160 mg/kg of body weight. Following thigh infection, the mice were treated with 2-fold-increasing doses of antofloxacin from 2.5 to 80 mg/kg administered every 12 h. Efficacy was assessed by quantitative determination of the bacterial burdens in thigh homogenates and was compared with the bioluminescent density. Antofloxacin demonstrated both static and killing endpoints in relation to the initial burden against all study strains. The PK/PD index area under the concentration-time curve (AUC)/MIC correlated well with efficacy (R2 = 0.92), and the dose-response relationship was relatively steep, as observed with escalating doses of antofloxacin. The mean free drug AUC/MIC targets necessary to produce net bacterial stasis and 1-log10 and 2-log10 kill for each isolate were 38.7, 66.1, and 147.0 h, respectively. In vivo bioluminescent imaging showed a rapid decrease in the bioluminescent density at free drug AUC/MIC exposures that exceeded the stasis targets. The integration of these PD targets combined with the results of PK studies with humans will be useful in setting optimal dosing regimens for the treatment of urinary tract infections due to E. coli.

Preclinical assessment of scleral lens as a reservoir-based ocular therapeutic system.

PURPOSE: Bacterial keratitis is a sight threatening infection of the cornea which remains one of the most important potential complications of contact lens use. If the corneal ulcer is small, peripheral with no impending perforation present, intensive monotherapy with fluoroquinolones could be used. Therefore, a study was conducted with the objective to provide pharmacological data of the intra-ocular diffusion after administration of Ofloxacin using a scleral lens reservoir, as well as an evaluation of surface tolerability in rabbits. MATERIALS AND METHODS: Samples of corneas, aqueous humor and vitreous were collected to measure the drug levels of Ofloxacin using High Performance Liquid Chromatography. The corneas were examined by electron microscopy scanning and the eyeballs by light polarizing microscopy in order to evaluate surface tolerability. RESULTS: Ofloxacin levels found in the aqueous humor and cornea were higher than those previously reported. The mean Ofloxacin corneal levels exceeded the MIC (Minimum Inhibitory Concentration) for which 90% of isolates are indicated for all bacteria implicated in keratitis. CONCLUSION: To our knowledge, this is the first preclinical study assessing local tolerance and intra-ocular diffusion of Ofloxacin after administration using a scleral lens reservoir.

Risk of bleeding and antibiotic use in patients receiving continuous phenprocoumon therapy. A case-control study nested in a large insurance- and population-based German cohort.

There is major concern about coumarins interacting with various drug classes and increasing the risk of overanticoagulation. The aim of the study was to assess bleeding risk in patients with concurrent use of antibiotics and phenprocoumon, the most widely prescribed coumarin in many European countries. We conducted a nested-case-control study within a cohort of 513,338 incident and continuous phenprocoumon users ≥ 18 years of age using claims data of the statutory health insurance company AOK, covering 30% of the German population. Bleeding risk associated with current use of antibiotics for systemic use (antibacterials/antimycotics) was calculated using conditional logistic regression in 13,785 cases with a bleeding event and 55,140 risk-set sampling-matched controls. Bleeding risk associated with any antibacterial use in phenprocoumon users was significantly increased [odds ratio (OR) 2.37, 95% confidence interval (CI) 2.20-2.56]. The association was stronger for gastrointestinal than for cerebral bleeding (OR 2.09, 95% CI 1.84-2.38 and OR 1.34, 95% CI 1.03-1.74, respectively) and highest for other/unspecified bleeding (OR 2.92, 95% CI 2.62-3.26). Specific antibiotic classes were strongly associated with bleeding risk, e.g. cotrimoxazole (OR 3.86, 95% CI 3.08-4.84) and fluorquinolones (OR 3.13, 95% CI 2.74-3.59), among those highest for ofloxacin (OR 5.00, 95% CI 3.01-8.32). Combined use of phenprocoumon and antimycotics was not significantly associated with bleeding risk. Risk was not significantly modified by age (pint=0.25) or sex (pint=0.96). The association was stronger the closer the antibiotic exposure was to the bleeding event. Among continuous phenprocoumon users, antibiotics - particularly quinolones and cotrimoxazole - should be prescribed after careful consideration due to an increased bleeding risk. Close monitoring of international normalised ratio levels after prescription is recommended.

Single daily dose of moxifloxacin versus ofloxacin plus metronidazole as a new treatment approach to uncomplicated pelvic inflammatory disease: a multicentre prospective randomized trial.

OBJECTIVES: To evaluate the efficacy and safety of moxifloxacin versus ofloxacin plus metronidazole in patients with uncomplicated pelvic inflammatory disease (uPID; defined as PID symptoms and signs, but no complications such as septicemia, perihepatitis, and tubo-ovarian abscess) in Turkey. STUDY DESIGN: This was a multicenter, prospective, randomized, parallel-group study conducted between June 2010 and March 2013 in four hospitals in Turkey. Women received a 14-day course of either oral moxifloxacin at 400mg once daily (n = 560) or oral ofloxacin at 400mg twice daily plus oral metronidazole at 500 mg twice daily (n = 543). RESULTS: A total of 1156 women were randomized to the study. Total compliance was achieved in 1103 patients. For the primary measure of efficacy (clinical cure), moxifloxacin showed no difference compared with ofloxacin plus metronidazole (445/560 [79.5%] vs. 449/543 [82.7%]; p = 0.172). Bacteriological cure rates were high and comparable between treatment arms (99/119 [83.2%] vs. 93/110 [84.5%]; p = 0.781). Drug-related adverse events occurred less frequently with moxifloxacin than with ofloxacin plus metronidazole (210/560 [37.5%] vs. 252/543 [46.4%]; p = 0.003). Furthermore, moxifloxacin treatment was lower in cost and achieved higher patient compliance compared with ofloxacin plus metronidazole (31.4 Euros vs. 23.4 Euros and 7/578 (1.2%) vs. 22/578 (3.8%), respectively; p = 0.005). CONCLUSIONS: In patients with uPID, once-daily moxifloxacin monotherapy was clinically and microbiologically as efficacious as twice-daily ofloxacin plus metronidazole therapy and was associated with fewer drug-related adverse events, lower patient non-compliance, and a lower treatment cost.

[Infectious exacerbation of chronic obstructive pulmonary disease: prospects for high-dose levofloxacin therapy].

This open comparative randomized study of efficacy, safety, and pharmacoeconomic characteristics of hilifox-750 (750 mg daily for 5 days) and amoxiclav 2X (875/125 mg twice daily for 10 days) included 60 patients with chronic obstructive pulmonary disease (COPD). Duration of the study was 6 months. Medians of age and smoking index in the group treated with hilifox-750 were 63.5 yr (59, 67) and 30 packs/yr (15, 60) respectively. The treatment reduced cough, apnea, sputum volume and pyoptysis with comparative rates of normalization of body temperature and peripheral leukocyte counts in both groups. Helifox-750 promoted decrease in coughing and apnea within the first three days of therapy. 28 (93%) and 26 (87%) patients recovered by day 4 of helifox and amoxiclav therapy (F-test p = 0.67). Both drugs showed comparable bacteriological efficacy. They were not different in terms of side effect frequency that were mild, resolved spontaneously and did not require withdrawal of therapy. Helifox had advantages over amoxiclav in that it reduced duration of antibacterial therapy to 5 days and of temporary incapacity to 12 days (vs 14); moreover, it needs to be taken only once daily.

Assessment of the combination of doripenem plus a fluoroquinolone against non-susceptible Acinetobacter baumannii isolates from nosocomial pneumonia patients.

Carbapenem- and fluoroquinolone-non-susceptible Acinetobacter baumannii were obtained from four nosocomial pneumonia patients who were clinically cured following combination therapy with doripenem/levofloxacin or ciprofloxacin. In vitro synergy of doripenem/levofloxacin or ciprofloxacin was evaluated using time-kill analysis. In vivo synergy was tested using a mouse lethal infection model. In time-kill studies, doripenem and levofloxacin were both bactericidal when tested at Cmax; at ½Cmax, the combination showed synergy up to 8 hours. Ciprofloxacin, alone or combined with doripenem, was not bactericidal. For mouse septicemia, doripenem (100 mg/kg) was ≥90% effective in preventing death in all four isolates. Levofloxacin (200 mg/kg) was 73% effective, and ciprofloxacin (35 mg/kg) was ineffective in preventing death. At lower drug concentrations, increased efficacy was observed for doripenem/levofloxacin, but not for doripenem/ciprofloxacin. Overall, the results suggest that a doripenem/levofloxacin combination may have clinical utility in treating some non-susceptible A. baumannii infections.

Evaluation of efficacy and tolerability of fixed dose combination of ofloxacin with ornidazole infusion (infusion O2) in the management of diarrhoea and dysentery.

Acute diarrhoea in adults is one of the most commonly encountered medical emergency in general practice and is responsible for considerable morbidity around the world. To evaluate the efficacy and tolerability of fixed dose combination of ofloxacin with ornidazole infusion (infusion O2) in the management of diarrhoea and dysentery, a study was carried out among 290 patients, age group from 18 to 65 years suffering from diarrhoea, dysentery, gastro-enteritis. Study drug infusion O2, (Medley Pharmaceutical, Mumbai) containing ofloxacin 200 mg + ornidazole 500 mg was administrated twice daily for a duration of 5 days. Number of soft or watery stool, body temperature, nausea, abdominal pain, gas and flatulence were recorded at baseline and at the end of the study. Tolerability and efficacy was evaluated based on the global assessment by the investigator based on a 3-point scale marked as excellent/good/poor. Two hundred and fifty-six-patients (160 male and 96 female) were included for final analysis, 34 patients lost to follow-up. Mean number of watery stool per day was reduced from 9.273 +/- 0.4537 to 1.375 +/- 0.07001 (p < 0.0001) by infusion O2. Body temperature was significantly reduced from 38.055 +/- 0.045 degrees C to 36.778 +/- 0.016 degrees C (p < 0.0001) at the end of the study. Pretreatment symptom nausea was significantly reduced in 90.34% of patients. Improvement in vomiting symptoms was reported in 72.35% of patients after administration of anti-emetic drug; 96.84% and 77.25% of patients reported improvement in abdominal pain and gas/flatulence respectively at the end of the trial by infusion O2. As per investigators' assessment about efficacy of trial drug, 98.43% of patients reported good to excellent and 1.56% reported poor efficacy. As per investigators' assessment about tolerability 98.43% of patients reported good to excellent and 1.17% reported poor tolerability. Minor incidences of nausea, gastritis, metallic taste were reported in 7.42%, 7.14%, and 5.85% of patients respectively. No serious adverse events were reported which led to withdrawal of patient from the study. Result of this study shows that, combination of ofloxacin with ornidazole infusion (infusion O2) significantly reduces number of watery stool and associated symptoms like nausea, abdominal pain, flatulence/gas with excellent tolerability.

Clinical and economic impact of a pharmacist-managed i.v.-to-p.o. conversion service for levofloxacin in Taiwan.

OBJECTIVE: A pharmacist-managed antibiotic intravenous to oral (i.v.-top. o.) conversion program has been incorporated to minimize unnecessary i.v. antibiotic usage. This study evaluated the clinical and economical impacts of a pharmacist-directed i.v.-to-p.o. conversion program for levofloxacin in Taiwan. METHODS: Data was retrospectively collected by chart review during the pre-intervention period (PIP). During the intervention proactive conversion period (PCP), pharmacists reviewed and intervened on all levofloxacin orders. The detailed reimbursements for medications and inpatient expenses from the Bureau of National Health Insurance (NHI), Taiwan were calculated. The clinical impacts during the PIP and PCP were compared with the duration of the i.v. levofloxacin therapy, total used i.v./p.o. ratio levofloxacin, and total length of hospital stay. The financial impact was compared with medication costs and total inpatient expenditures. RESULTS: The mean length of hospital stay was significantly decreased from 27.2 days to 16.1 days (p = 0.001) after the conversion program was implemented. The i.v. over p.o. ratio for DDD was 3.0 ± 0.6 vs. 2.1 ± 0.6 for PIP vs. PCP group (p = 0.032). The cost of the levofloxacin was significantly decreased ($ 568.9 ± 262.9 vs. $ 449.0 ± 266.4, PIP vs. PCP, p = 0.044). The total inpatient expenditures were also significantly reduced ($ 6,096 ± 5,164.0 vs. $ 3,649.6 ± 3, 740.4, PIP vs. PCP, p = 0.017). CONCLUSIONS: The pharmacist-managed i.v.-to-p.o. conversion service not only decreased the length of hospital stays, but also produced significant cost savings, both on medication costs and the total inpatient expenditures. This represents strong evidence for implementing the i.v.-to-p.o. conversion service in Taiwan.

Evaluation by Monte Carlo simulation of levofloxacin dosing for complicated urinary tract infections caused by Escherichia coli or Pseudomonas aeruginosa.

We evaluated, by Monte Carlo simulation, 500-mg once-daily, 100-mg thrice-daily, 200-mg twice-daily, and 200-mg thrice-daily dose regimens of levofloxacin (LVFX), for the ratio of area under the concentration-time curve for 24 h (AUC(0-24)) to minimum inhibitory concentration (MIC) (AUC(0-24)/MIC) and the ratio of maximum plasma concentration (C(max)) to MIC (C(max)/MIC), which predict microbiological outcomes, and the C(max)/MIC, which inhibits fluoroquinolone resistance selection, in complicated urinary tract infections (UTIs) with Escherichia coli or Pseudomonas aeruginosa. Monte Carlo simulation was performed for 10000 cases using the pharmacokinetic data of patients with complicated UTIs and the LVFX MIC distributions for E. coli or P. aeruginosa clinical strains. The probabilities of achieving the AUC(0-24)/MIC target (66.2-67.9%) and the C(max)/MIC target (64.5-67.5%) to eradicate E. coli were similar among the 4 regimens. In eradication of P. aeruginosa, the 200-mg thrice-daily and the once-daily dose regimens produced higher probabilities of achieving the AUC(0-24)/MIC target (57.5%) and C(max)/MIC target (55.1%), respectively. For the probabilities of achieving the C(max)/MIC targets that prevent the emergence of fluoroquinolone resistance, the once-daily dose regimen (66.8%) did not differ from the other multiple-dose regimens (62.3-66.2%) in E. coli, whereas the former regimen (44.2%) was superior to the latter regimens (10.8-31.7%) in P. aeruginosa. The 500-mg once-daily dose regimen of LVFX, which produced the larger AUC(0-24) and higher C(max), could ensure the efficacy of eradication of uropathogens and reduce the risk of fluoroquinolone resistance selection in complicated UTIs.

Assessment of Helicobacter pylori eradication rate of triple combination therapy containing levofloxacin.

BACKGROUND/AIMS: Owing to its high efficacy, ease of use, perfect adaptation and low complication profile, it is suggested that the triple therapy combination consisting of levofloxacin, amoxicillin and proton pump inhibitor may be an alternative for the first-line and second-line treatment of Helicobacter pylori. The aim of this study is to evaluate the efficacy of the triple therapy regimen containing two different doses of levofloxacin in the first-line eradication treatment. MATERIAL AND METHODS: 110 naïve patients with anti Helicobacter pylori treatment indications according to Maastricht III Consensus Report were included to the study. Patients were randomized into two groups as the patients treated with a levofloxacin (500 mg o.i.d), amoxicillin (1 g b.i.d) and proton pump inhibitor (b.i.d) combination for 10 days (Group 1, n=60) and patients treated with a levofloxacin (500 mg b.i.d), amoxicillin (1 g b.i.d) and proton pump inhibitor (b.i.d) combination for 10 days (Group 2, n=50). Eradication rate was assessed at the 6th week of therapy just subsequent to termination of treatment. RESULTS: 110 treatment-naïve patients (60 female, mean age: 44.1±14.7 years) were randomized and all patients completed the study. Helicobacter pylori eradication of the Group 1 was 60% and in Group 2 was 72.7%. The difference between the two groups was not statistically significant (p=0.427). None of patients experienced severe complication that would lead to discontinuation of therapy. CONCLUSION: It is observed that the efficacy of the triple therapy combination containing levofloxacin is not within acceptable limits for the first-line Helicobacter pylori eradication.

Sensitivity and proportionality assessment of metabolites from microdose to high dose in rats using LC-MS/MS.

BACKGROUND: The objective of this study was to evaluate the sensitivity requirement for LC-MS/MS as an analytical tool to characterize metabolites in plasma and urine at microdoses in rats and to investigate proportionality of metabolite exposure from a microdose of 1.67 µg/kg to a high dose of 5000 µg/kg for atorvastatin, ofloxacin, omeprazole and tamoxifen. RESULTS: Only the glucuronide metabolite of ofloxacin, the hydroxylation metabolite of omeprazole and the hydration metabolite of tamoxifen were characterized in rat plasma at microdose by LC-MS/MS. The exposure of detected metabolites of omeprazole and tamoxifen appeared to increase in a nonproportional manner with increasing doses. Exposure of ortho- and para-hydroxyatorvastatin, but not atorvastatin and lactone, increased proportionally with increasing doses. CONCLUSION: LC-MS/MS has demonstrated its usefulness for detecting and characterizing the major metabolites in plasma and urine at microdosing levels in rats. The exposure of metabolites at microdose could not simply be used to predict their exposure at higher doses.

Empirical levofloxacin-containing versus clarithromycin-containing sequential therapy for Helicobacter pylori eradication: a randomised trial.

BACKGROUND AND AIMS: Antimicrobial drug resistance is a major cause of the failure of Helicobacter pylori eradication and is largely responsible for the decline in eradication rate. Quadruple therapy has been suggested as a first-line regimen in areas with clarithromycin resistance rate >15%. This randomised trial aimed at evaluating the efficacy of a levofloxacin-containing sequential regimen in the eradication of H pylori-infected patients in a geographical area with >15% prevalence of clarithromycin resistance versus a clarithromycin containing sequential therapy. METHODS: 375 patients who were infected with H pylori and naïve to treatment were randomly assigned to one of the following treatments: (1) 5 days omeprazole 20 mg twice daily + amoxicillin 1 g twice daily followed by 5 days omeprazole 20 mg twice daily +clarithromycin 500 mg twice daily + tinidazole 500 mg twice daily; or (2) omeprazole 20 mg twice daily +amoxicillin 1 g twice daily followed by omeprazole 20 mg twice daily + levofloxacin 250 mg twice daily +tinidazole 500 mg twice daily; or (3) omeprazole 20 mg twice daily + amoxicillin 1 g twice daily followed by omeprazole 20 mg twice daily + levofloxacin 500 mg twice daily + tinidazole 500 mg twice daily. Antimicrobial resistance was assessed by the E-test. Efficacy, adverse events and costs were determined for each group. RESULTS: Eradication rates in the intention-to-treat analyses were 80.8% (95% CI, 72.8% to 87.3%) with clarithromycin sequential therapy, 96.0% (95% CI, 90.9%to 98.7%) with levofloxacin-250 sequential therapy, and 96.8% (95% CI, 92.0% to 99.1%) with levofloxacin-500 sequential therapy. No differences in prevalence of antimicrobial resistance or incidence of adverse events were observed between groups. Levofloxacin-250 therapy was cost-saving compared with clarithromycin sequential therapy. CONCLUSION: In an area with >15% prevalence of clarithromycin resistant H pylori strains, a levofloxacin containing sequential therapy is more effective, equally safe and cost-saving compared to a clarithromycin containing sequential therapy.

Comparative analysis of length of stay, total costs, and treatment success between intravenous moxifloxacin 400 mg and levofloxacin 750 mg among hospitalized patients with community-acquired pneumonia.

OBJECTIVE: This study aimed to evaluate the length of stay (LOS), costs, and treatment consistency among patients hospitalized with community-acquired pneumonia (CAP) initially treated with intravenous (IV) moxifloxacin 400 mg or IV levofloxacin 750 mg. METHODS: Adults with CAP receiving IV moxifloxacin or IV levofloxacin for > or =3 days were identified in the Premier Perspective comparative database. Primary outcomes were LOS and costs. Secondary outcomes included treatment consistency, which was defined as 1) no additional IV moxifloxacin or levofloxacin after > or =1 day off study drug; 2) no switch to another IV antibiotic; and 3) no addition of another IV antibiotic. RESULTS: A total of 7720 patients met inclusion criteria (6040 receiving moxifloxacin; 1680 receiving levofloxacin). Propensity matching created two cohorts (1300 patients each) well matched for demographic, clinical, hospital, and payor characteristics. Before the patients were matched, mean LOS (5.87 vs. 5.46 days; P = 0.0004) and total costs per patient ($7302 vs. $6362; P < 0.0001) were significantly greater with moxifloxacin. After the patients were matched, mean LOS (5.63 vs. 5.51 days; P = 0.462) and total costs ($6624 vs. $6473; P = 0.476) were comparable in both cohorts. Treatment consistency was higher for moxifloxacin before (81.0% vs. 78.9%; P = 0.048) and after matching (82.8% vs. 78.0%; P = 0.002). CONCLUSIONS: In-hospital treatment of CAP with IV moxifloxacin 400 mg or IV levofloxacin 750 mg was associated with similar hospital LOS and costs in propensity-matched cohorts.

Retrospective assessment of potential interaction between levofloxacin and warfarin.

OBJECTIVE: There is currently a controversy regarding interactions between levofloxacin and warfarin. The aim of this study was to determine the clinical relevance of this interaction in our setting. SETTING: A university hospital in Barcelona, Spain. METHODS: We carried out a retrospective evaluation of all patients hospitalized in our hospital during the period 2000-2005, selecting all those concomitantly treated with levofloxacin and warfarin for the study. The following data were compiled: demographic information, concomitant medication, comorbid conditions, and relevant analytical parameters, particularly the international normalized ratio (INR), including values taken before, during, and after concomitant administration of the two study drugs. Patients for whom INR values during concomitant administration were not available were excluded. Differences in INR before and during the potential interaction, and before and after the interaction were analyzed with the Wilcoxon t test using SPSS (V12.0). In addition, patients were stratified according to presence or not of toxic habits (smoking/alcohol consumption) to investigate the possible impact of these factors on the interaction under study. RESULTS: Among the 30 patients identified, 9 were excluded because INR data during concomitant administration of warfarin and levofloxacin were not available. Statistical analysis demonstrated significant increase in INR (P = 0.001) following addition of levofloxacin to warfarin therapy. CONCLUSIONS: The results of this study reaffirm the hypothesis that concomitant administration of levofloxacin and warfarin leads to INR increase; hence close monitoring of INR is advisable when patients are prescribed this combination of drugs.

A comparison of levofloxacin and moxifloxacin use in hospitalized community-acquired pneumonia (CAP) patients in the US: focus on length of stay.

OBJECTIVE: Length of stay (LOS) and hospitalization costs were compared among patients admitted for community-acquired pneumonia (CAP) and initially treated with either levofloxacin 750 mg intravenous (IV) or with moxifloxacin 400 mg IV. Hospital-related complications and relationship of LOS and comorbidities were descriptively examined. METHODS: A retrospective database study was conducted of adult patients admitted for CAP and given levofloxacin 750 mg IV or moxifloxacin 400 mg IV through the first 3 days of hospitalization, using the Premier Perspective comparative database. Cohorts were matched 1:1 by hospital geographic location, by coarse caliper propensity scores using all baseline covariates, and by Mahalanobis metric matching based on age and severity (All Patient Refined-Diagnosis-related Groups Severity of Illness (APR-DRG SOI) index). Comparisons between groups were further adjusted for characteristics that remained imbalanced after matching using generalized estimating equation methodology. RESULTS: The initial sample of 3868 patients (levofloxacin = 827; moxifloxacin = 3041) was reduced to 1594 (797 patients per treatment group) after matching. Analyses of matched cohorts showed that the mean hospital LOS was significantly shorter for patients treated with levofloxacin 750 mg IV than for those patients treated with moxifloxacin 400 mg IV (5.8 vs. 6.4 days, respectively; least squares mean difference = 0.54 days; p = 0.020). Hospitalization costs were also lower for the levofloxacin 750 mg IV-treated patients (least squares mean difference = US$129; p = 0.753). There were no significant differences in the percentage of patients experiencing complications. LIMITATIONS: Although claims databases provide large sample sizes and reflect routine care, they do have several inherent limitations. Since randomization of subjects is not possible, adequate statistical techniques must be used to ensure treatment groups are balanced with respect to patient and clinical characteristics. In addition, data may be missing or miscoded. CONCLUSIONS: This retrospective study suggests that among patients hospitalized with CAP, initial treatment with levofloxacin 750 mg IV is associated with a significantly shorter mean hospital LOS compared with treatment with moxifloxacin 400 mg IV. The clinical implications of a shorter hospital LOS include improved patient and economic outcomes.

A cost-minimisation analysis comparing moxifloxacin with levofloxacin plus ceftriaxone for the treatment of patients with community-acquired pneumonia in Germany: results from the MOTIV trial.

OBJECTIVE: This study presents a cost-minimisation analysis of moxifloxacin compared to combination treatment with levofloxacin and ceftriaxone in patients hospitalised with community-acquired pneumonia (CAP) in Germany. RESEARCH DESIGN AND METHODS: In the MOTIV study, 738 adult patients with CAP requiring hospitalisation and initial parenteral antibiotic therapy were randomised to sequential IV/oral therapy with either moxifloxacin (n = 368), or levofloxacin and ceftriaxone (n = 365). The primary effectiveness endpoint was the proportion of patients demonstrating clinical improvement 5-7 days after the completion of study treatment. Subgroup analysis considered patients with severe CAP according to pneumonia severity index (PSI) risk class IV and V, microbiologically proven infection, a history of chronic obstructive pulmonary disease, and a history of cardiovascular disease. The analysis included the cost of study medication, hospital stay, readmission and inpatient procedures and diagnostics. Event frequency in the study was multiplied by German unit costs to estimate per-patient expenditure. The analysis was conducted from a hospital perspective. Sensitivity analysis investigated the effect of costing from an insurer perspective. RESULTS: No significant difference was found in the percentage of successfully treated patients. Average per patient cost was euro 2190 for the moxifloxacin group, and euro 2619 for the levofloxacin + ceftriaxone group (difference -euro 430, 95% CI: -euro 138, -euro 740; p < 0.05). Variability in total costs was wide, with some patients accruing up to euro 18,000. Medication cost was significantly lower with moxifloxacin than levofloxacin + ceftriaxone (-euro 470, 95% CI: -euro 522, -euro 421), and accounted for between 15 and 30% of total costs. CONCLUSIONS: In this analysis of patients hospitalised with CAP in Germany, treatment with moxifloxacin was significantly less costly than treatment with levofloxacin and ceftriaxone.

Cost-effectiveness of alternative outpatient pelvic inflammatory disease treatment strategies.

OBJECTIVE: Effectiveness differences between outpatient pelvic inflammatory disease (PID) treatment regimens are uncertain, but significant differences in cost exist. GOAL: To examine the influence of antibiotic costs on PID therapy cost-effectiveness. STUDY DESIGN: The authors used a Markov decision model to estimate the cost-effectiveness of recommended antibiotic regimens for PID and performed a value of information analysis to guide future research. RESULTS: Antibiotic costs vary between USD 43 and USD188. Pairwise comparisons, assuming a hypothetical 1% relative risk reduction in PID complications with the more expensive regimen, showed economically reasonable cost-effectiveness ratios. Value of information and sample size considerations support further investigation to detect 10% PID complication rate differences between regimens with >or=USD 50 cost differences. CONCLUSIONS: Within the cost range of recommended regimens, use of more expensive antibiotics would be economically reasonable if relatively small decreases in PID complication rates exist. Further investigation of effectiveness differences between regimens is needed.

[Effectiveness of switch therapy for peritonitis].

The usefulness of switch therapy, from injection to oral medicine, for the treatment of peritonitis was evaluated. Thirty-five patients, who agreed to enroll the study, were randomly assigned to four treatment groups; one group treated with carbapenem antibacterial agent alone and three groups treated with switch therapy, in which injectable quinolone was switched to oral quinolone. For the intravenous administration group, if the patient showed the tendency of improvement by the third day, the intravenous injection was continued. However, if the patient did not show any improvement, the medication was changed to other medicine. For the switch therapy group, if the body temperature dropped to 37.5 degrees C or lower for at least 8 hours and if blood findings and clinical findings showed the tendency of improvement by the fourth day, the medication was switched to oral medicine. There was no difference in therapeutic effects among treatment groups. However, both duration of hospitalization and total medical costs were significantly reduced in the switch therapy groups comparing to those in the intravenous administration group. The results of this study showed that the switch therapy, from injection to oral medicine, was one of useful treatments in treating peritonitis.