Clevidipine in acute heart failure: Results of the A Study of Blood Pressure Control in Acute Heart Failure-A Pilot Study (PRONTO).

BACKGROUND: Rapid blood pressure (BP) control improves dyspnea in hypertensive acute heart failure (AHF). Although effective antihypertensives, calcium-channel blockers are poorly studied in AHF. Clevidipine is a rapidly acting, arterial selective intravenous calcium-channel blocker. Our purpose was to determine the efficacy and safety of clevidipine vs standard-of-care intravenous antihypertensive therapy (SOC) in hypertensive AHF. METHODS: This is a randomized, open-label, active control study of clevidipine vs SOC in emergency department patients with AHF having systolic BP ≥160 mm Hg and dyspnea ≥50 on a 100-mm visual analog scale (VAS). Coprimary end points were median time to, and percent attaining, a systolic BP within a prespecified target BP range (TBPR) at 30 minutes. Dyspnea reduction was the main secondary end point. RESULTS: Of 104 patients (mean [SD] age 61 [14.9] years, 52% female, 80% African American), 51 received clevidipine and 53 received SOC. Baseline mean (SD) systolic BP and VAS dyspnea were 186.5 (23.4) mm Hg and 64.8 (19.6) mm. More clevidipine patients (71%) reached TBPR than did those receiving SOC (37%; P = .002), and clevidipine was faster to TBPR (P = .0006). At 45 minutes, clevidipine patients had greater mean (SD) VAS dyspnea improvement than did SOC patients (-37 [20.9] vs -28 mm [21.7], P = .02), a difference that remained significant up to 3 hours. Serious adverse events (24% vs 19%) and 30-day mortality (3 vs 2) were similar between clevedipine and SOC, respectively, and there were no deaths during study drug administration. CONCLUSIONS: In hypertensive AHF, clevidipine safely and rapidly reduces BP and improves dyspnea more effectively than SOC.

Efficacy of telavancin in patients with specific types of complicated skin and skin structure infections.

BACKGROUND: Telavancin is approved in the USA and Canada for the treatment of Gram-positive complicated skin and skin structure infections (cSSSIs) based on the results of the Phase 3 Assessment of TeLAvancin in complicated Skin and skin structure infections (ATLAS) trials, which demonstrated non-inferiority of telavancin to vancomycin. METHODS: We conducted a post hoc analysis of the ATLAS studies (ClinicalTrials.gov identifiers NCT00091819 and NCT00107978) to explore the efficacy of telavancin in patients with various types of cSSSIs. RESULTS: A total of 1794 patients were included in this analysis; 1434 patients were clinically evaluable (CE) and 563 of these had methicillin-resistant Staphylococcus aureus (MRSA). Among CE patients with major abscesses (n = 619), cure rates were 91% for telavancin and 90% for vancomycin (95% CI for the difference -3.6 to 5.7). In patients with infective cellulitis (n = 519), cure was achieved in 87% and 88% of telavancin- and vancomycin-treated patients, respectively (95% CI for the difference -6.2 to 5.2). Cure rates in patients with wound infections were 85% in the telavancin group and 86% in the vancomycin group (95% CI for the difference -10.5 to 9.0). Cure rates for each type of cSSSI in patients infected with MRSA were also similar between the two treatment arms. Among CE patients infected with Panton-Valentine leucocidin (PVL)-positive MRSA (n = 447), cure rates were 93% for telavancin and 90% for vancomycin (95% CI for the difference -2.2 to 8.2). CONCLUSIONS: Cure rates were similar for telavancin and vancomycin in patients with different types of cSSSIs, including infections caused by MRSA and PVL-positive strains of MRSA.

Comparison of the efficacy and safety of oritavancin front-loaded dosing regimens to daily dosing: an analysis of the SIMPLIFI trial.

Oritavancin is a novel lipoglycopeptide with demonstrated effectiveness against complicated skin and skin structure infections (cSSSI) caused by Gram-positive pathogens, including those caused by methicillin-resistant Staphylococcus aureus (MRSA). The pharmacokinetic and pharmacodynamic profile of oritavancin is favorable for single or infrequent dosing. A phase 2, multicenter, randomized, double-blind, parallel, active-comparator study (ClinicalTrials.gov identifier, NCT00514527) of single and infrequent dosing of intravenous (i.v.) oritavancin for the treatment of cSSSI caused by Gram-positive pathogens (wound infections, major abscess, and cellulitis) was undertaken to evaluate the noninferiority of front-loaded dosing regimens compared to a daily-dosing regimen. A total of 302 patients ≥ 18 years of age were randomized equally to one of three oritavancin treatment groups, receiving either a daily dose (200 mg) administered for 3 to 7 days, a single dose (1,200 mg), or an infrequent dose (800-mg dose, with the option for an additional 400 mg on day 5). The primary efficacy was defined as a clinical response in clinically evaluable (CE) patients assessed at days 21 to 29 (test of cure [TOC]). The cure rates in the CE population were 72.4% (55/76) in the daily-dose group, 81.5% (66/81) in the 1,200-mg-single-dose group, and 77.5% (55/71) in the infrequent-dose group. In patients with MRSA at baseline, the cure rates were 78.3% (18/23), 73.0% (27/37), and 87.0% (20/23) in the daily-, 1,200-mg-single-, and infrequent-dose groups, respectively; however, the study was not powered to assess outcomes in the MRSA subpopulation, and given the heterogeneity of the types of infection and the small sample size, these do not suggest any true differences in efficacy rates for these pathogens. The frequencies of adverse events were similar among treatment groups. The results of this study show that single- and infrequent-dosing schedules of oritavancin were as efficacious as daily administration and had a similar safety profile in treating cSSSI caused by Gram-positive pathogens, including MRSA.

Clevidipine for severe hypertension in patients with renal dysfunction: a VELOCITY trial analysis.

INTRODUCTION: Acute and severe hypertension is common, especially in patients with renal dysfunction (RD). Clevidipine is a rapidly acting (t½âˆ¼1 min) intravenous (IV) dihydropyridine calcium-channel blocker metabolized by blood and tissue esterases and may be useful in patients with RD. The purpose of this analysis was to assess the safety and efficacy of clevidipine in patients with RD. METHODS: VELOCITY, a multicenter open-label study of severe hypertension, enrolled 126 patients with persistent systolic blood pressure (SBP) >180 mmHg. Investigators pre-specified a SBP initial target range (ITR) for each patient to be achieved within 30 min. Blood pressure monitoring was by cuff. Clevidipine was infused via peripheral IV at 2 mg/h for at least 3 min, then doubled every 3 min as needed to a maximum of 32 mg/h (non-weight-based treat-to-target protocol). Per protocol, clevidipine was continued for at least 18 h (96 h maximum). RD was diagnosed and reported as an end-organ injury by the investigator and was defined as requiring dialysis or an initial creatinine >2.0 mg/dl. Primary endpoints were the percentage of patients within the ITR by 30 min and the percentage below the ITR after 3 min of clevidipine infusion. RESULTS: Of the 24 patients with moderate to severe RD, most (13/24) were dialysis dependent. Forty-six percent were male, with mean age 51 ± 14 years; 63% were black and 96% had a hypertension history. Median time to achieve the ITR was 8.5 min. Almost 90% of patients reached the ITR in 30 min without evidence of overshoot and were maintained on clevidipine through 18 h. Most patients (88%) transitioned to oral antihypertensive therapy within 6 h of clevidipine termination. CONCLUSIONS: This report is the first demonstrating that clevidipine is safe and effective in RD complicated by severe hypertension. Prolonged infusion maintained blood pressure within a target range and allowed successful transition to oral therapy.

Clevidipine for severe hypertension in acute heart failure: a VELOCITY trial analysis.

Acute severe hypertension occurs in approximately 50% of patients with acute heart failure (AHF). Clevidipine, the latest-generation dihydropyridine calcium channel blocker, may be useful in the treatment of this patient population. The Evaluation of the Effect of Ultra-Short-Acting Clevidipine in the Treatment of Patients With Severe Hypertension (VELOCITY) trial enrolled 126 patients with systolic blood pressure (SBP) >180 mm Hg for treatment with clevidipine to a patient-specific prespecified initial target range (ITR) of SBP to be achieved within 30 minutes. Of the enrolled patients, 19 had AHF on presentation. Primary end points were the percentage in whom ITR was achieved within 30 minutes and the number whose SBP was below the ITR after 3 minutes of clevidipine infusion. Among the 19 AHF patients in VELOCITY, median time to ITR was 11.3 minutes (95% confidence interval, 7-19). ITR was reached in most patients (94%) within 30 minutes. No patient had hypotension below the ITR, and heart rate remained stable. At 18 hours, 16 of 19 patients had received continuous clevidipine infusion, and their SBP was reduced by mean of 50 mm Hg (25%) from baseline. There were no treatment-related adverse events or adverse events that led to clevidipine discontinuation. Clevidipine safely decreases SBP in AHF and does not cause unexpected hypotension. The results of this post hoc subgroup analysis suggest that clevidipine is safe, well tolerated, and efficacious in AHF patients with hypertension.

Clevidipine, an intravenous dihydropyridine calcium channel blocker, is safe and effective for the treatment of patients with acute severe hypertension.

STUDY OBJECTIVE: We assess the safety and efficacy of intravenous clevidipine for treating patients with acute severe increase in blood pressure by using prespecified, non-weight-based titration dosing, with continuous maintenance infusion for 18 hours or longer. METHODS: Prospective, open-label, single-arm evaluation of patients aged 18 years or older and presenting in the emergency department or ICU with severe hypertension (systolic blood pressure >180 mm Hg and/or diastolic blood pressure >115 mm Hg) and treated with clevidipine to achieve a predetermined, patient-specific systolic blood pressure target range. Clevidipine was initiated at 2 mg per hour and titrated as needed in doubling increments every 3 minutes to a maximum of 32 mg per hour, during 30 minutes, and then continued for a total duration of 18 to 96 hours. RESULTS: Study patients commonly presented with both acute hypertension and end-organ injury; 81% (102/126) had demonstrable end-organ injury at baseline. Within 30 minutes of starting clevidipine, 88.9% (104/117) of patients achieved target range. Median time to target range was 10.9 minutes. No concomitant intravenous antihypertensives were needed in 92.3% (108/117) of patients receiving 18 hours or more of clevidipine infusion. Clevidipine was well tolerated with successful transition to oral antihypertensive therapy after infusion to a defined blood pressure target in 91.3% (115/126) of patients. CONCLUSION: Clevidipine, dosed in a non-weight-based manner, was safe and effective in a cohort of patients with severe hypertension at a starting dose of 2 mg per hour, followed by simple titration during 18 hours or more of continuous infusion. Patients were effectively managed via simple blood pressure cuff monitoring throughout.

A review of telavancin in the treatment of complicated skin and skin structure infections (cSSSI).

Telavancin is a novel antibiotic being investigated for the treatment of serious infections caused by Gram-positive bacteria, including complicated skin and skin structure infections (cSSSI) and pneumonia. This once-daily intravenous lipoglycopeptide exerts rapid bactericidal activity via a dual mechanism of action. It is intended for use to combat infections caused by Staphylococcus aureus and other Gram-positive bacteria, including methicillin-resistant and vancomycin-intermediate strains of S. aureus (MRSA and VISA, respectively). Vancomycin is the current gold standard in treating serious infections caused by Gram-positive bacteria, especially MRSA. In recent clinical trials, telavancin has shown excellent efficacy in phase II and III multinational, randomized, double-blinded studies of cSSSI. In the phase II FAST 2 study, which compared telavancin 10 mg/kg intravenously q 24 h vs standard therapy (an antistaphylococcal penicillin at 2 g IV q 6 h or vancomycin 1 gm IV q 12 h), the clinical success rate in the telavancin-treated group was 96% vs 94% in the standard therapy group. In two identical phase III trials comparing telavancin versus vancomycin at the doses of the FAST 2 study for cSSSI, the clinical cure rates were 88.3% and 87.1%, respectively. Two additional phase III clinical trials investigating telavancin for use in hospital-acquired pneumonia, caused by Gram-positive bacteria are currently ongoing. Telavancin is currently under regulatory review in both the United States and Europe for the indication of treatment of cSSSI.

Telavancin versus standard therapy for treatment of complicated skin and skin structure infections caused by gram-positive bacteria: FAST 2 study.

Telavancin is a bactericidal lipoglycopeptide with a multifunctional mechanism of action. We conducted a randomized, double blind, active-control phase II trial. Patients > or = 18 years of age with complicated skin and skin structure infections caused by suspected or confirmed gram-positive organisms were randomized to receive either telavancin at 10 mg/kg intravenously every 24 h (q24h) or standard therapy (antistaphylococcal penicillin at 2 g q6h or vancomycin at 1 g q12h). A total of 195 patients were randomized and received at least one dose of study medication. Clinical success rates were similar in all analysis populations at test of cure. In microbiologically evaluable patients with Staphylococcus aureus at baseline (n = 91), 96% of the telavancin group and 90% of the standard-therapy group were cured. Among patients with methicillin-resistant S. aureus (MRSA) at baseline (n = 45), clinical cure rates were also 96% for telavancin and 90% for standard therapy. Microbiologic eradication in patients with S. aureus infection was better with telavancin compared to standard therapy (92% versus 78%, P = 0.07) and significantly better in patients with MRSA (92% versus 68%; P = 0.04). Therapy was discontinued for an adverse event (AE) in 6% and 3% of the patients receiving telavancin and standard therapy, respectively. Except for two cases of rash in the telavancin group, these AEs were similar in type and severity in the two groups. The overall incidences and severities of AEs and laboratory abnormalities were similar between the two groups. These data support the ongoing studies assessing the efficacy and safety of telavancin in the treatment of serious gram-positive infections, particularly involving MRSA.

Efficacy and safety of telithromycin 800 mg once daily for 7 days in community-acquired pneumonia: an open-label, multicenter study.

BACKGROUND: Community-acquired pneumonia (CAP) remains a major cause of morbidity and mortality throughout the world. Telithromycin (a new ketolide) has shown good in vitro activity against the key causative pathogens of CAP, including S pneumoniae resistant to penicillin and/or macrolides. METHODS: The efficacy and safety of telithromycin 800 mg orally once daily for 7 days in the treatment of CAP were assessed in an open-label, multicenter study of 442 adults. RESULTS: Of 149 microbiologically evaluable patients, 57 (9 bacteremic) had Streptococcus pneumoniae. Of the 57 S pneumoniae pathogens isolated in these patients, 9 (2 bacteremic) were penicillin- or erythromycin-resistant; all 57 were susceptible to telithromycin and were eradicated. Other pathogens and their eradication rates were: Haemophilus influenzae (96%), Moraxella catarrhalis (100%), Staphylococcus aureus (80%), and Legionella spp. (100%). The overall bacteriologic eradication rate was 91.9%. Of the 357 clinically evaluable patients, clinical cure was achieved in 332 (93%). In the 430 patients evaluable for safety, the most common drug-related adverse events were diarrhea (8.1%) and nausea (5.8%). CONCLUSION: Telithromycin 800 mg once daily for 7 days is an effective and well-tolerated oral monotherapy and offers a new treatment option for CAP patients, including those with resistant S pneumoniae.

Telavancin versus standard therapy for treatment of complicated skin and soft-tissue infections due to gram-positive bacteria.

BACKGROUND: Telavancin, a novel lipoglycopeptide, exerts concentration-dependent, rapid bactericidal activity on account of its multiple mechanisms of action. Telavancin is highly active against gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-intermediate, and vancomycin-resistant strains. METHODS: We conducted a randomized, double-blind, controlled, phase-2 clinical trial. Patients > or = 18 years of age with a diagnosis of complicated skin and soft-tissue infection caused by suspected or confirmed gram-positive organisms were randomized to receive either intravenously administered telavancin once daily or standard therapy (antistaphylococcal penicillin 4 times daily or vancomycin twice daily). RESULTS: For the study, 167 patients were randomized and received at least 1 dose of study medication. Success rates were similar in all analysis populations at the test-of-cure evaluation. Of patients with S. aureus infection at baseline (n = 102), 80% of the telavancin group were cured and 77% of the standard therapy group were cured. For patients with MRSA infection at baseline (n = 48), cure rates were 82% for the telavancin group and 69% for the standard therapy group. Microbiologic eradication in patients with MRSA infection was 84% for the telavancin group versus 74% for the standard therapy group. MIC90 values were lower for telavancin in all tested strains of S. aureus (< or = 0.25 ug/mL) compared with the MIC90 values for vancomycin and oxacillin. Similar proportions of patients discontinued therapy for adverse events in both treatment groups (approximately 5%). Fewer serious adverse events were reported in the telavancin group (4 events) than were for the standard therapy group (9). CONCLUSION: Clinical and microbiological results of this study support the further development of telavancin, especially for treatment of infection due to MRSA.

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

Efficacy and tolerability of once-daily oral telithromycin compared with clarithromycin for the treatment of community-acquired pneumonia in adults.

BACKGROUND: Telithromycin is a new antibacterial agent of the ketolide class designed to provide optimal treatment against common bacterial respiratory tract pathogens. Telithromycin was derived by structural modification of the basic macrolide molecule to allow tight binding to the bacterial ribosome that enhances potency and minimizes the risk for the development of resistant strains. OBJECTIVE: The aim of this study was to compare the efficacy and tolerability of telithromycin 800 mg once daily with those of high-dose clarithromycin (500 mg twice daily), each for 10 days, in the treatment of adult patients with community-acquired pneumonia (CAP). METHODS: This randomized, double-blind, double-dummy, parallel-group clinical trial was conducted at 54 centers in the United States, Canada, Argentina, and Chile. Patients aged >or=18 years with acute CAP were randomized to receive 10-day treatment with oral telithromycin 800 mg once daily (administered as two 400-mg encapsulated tablets in the morning) and placebo (administered as 2 encapsulated tablets identical to the telithromycin in the evening) or high-dose clarithromycin (500 mg administered as two 250-mg identical encapsulated tablets twice daily). The primary outcome measure was clinical outcome at the posttherapy, test-of-cure visit (days 17-24 after the completion of therapy) in the clinically assessable per-protocol population. Secondary efficacy variables included bacteriologic outcome at the posttherapy, test-of-cure visit, and clinical and bacteriologic outcomes at the late posttherapy visit (day 31-45). Tolerability was assessed using investigator observation, patient self-reporting, clinical laboratory data, a 12-lead electrocardiogram, and physical examination (including vital signs). RESULTS: A total of 493 patients were enrolled and 448 patients received >or=1 dose of study medication (224 patients/group). A diagnosis of CAP was confirmed in 416 patients (205 men, 211 women; median age, 43 years; telithromycin, n = 204; clarithromycin, n = 212). Clinical cure rates were 88.3% (143/162) in the telithromycin group and 88.5% ( 138/56) in the clarithromycin group. Bacterial eradication rates were comparable between treatment groups (telithromycin, (28/32) [87.5%]; clarithromycin, (29/30) [96.7%]. Both treatment were fairly well tolerated; adverse events were experienced in 57.0% of the patients treated with telithromycin and 49.1% of those treated with clarithromycin; most of these were assessed as mild. CONCLUSIONS: In this study of adult patients with CAP, telithromycin 800 mg once daily was an effective and fairly well-tolerated regimen for initial empiric treatment, with clinical and bacteriologic efficacy and tolerability equivalent to therapy with high-dose clarithromycin (500 mg twice daily).

Tetanus immunity and physician compliance with tetanus prophylaxis practices among emergency department patients presenting with wounds.

STUDY OBJECTIVE: We determine tetanus seroprotection rates and physician compliance with tetanus prophylaxis recommendations among patients presenting with wounds. METHODS: A prospective observational study of patients aged 18 years or older who presented to 5 university-affiliated emergency departments (EDs) because of wounds was conducted between March 1999 and August 2000. Serum antitoxin levels were measured by enzyme immunoassay with seroprotection defined as more than 0.15 IU/mL. Seroprotection rates, risk factors for lack of seroprotection, and rates of physician compliance with tetanus prophylaxis recommendations by the Advisory Committee on Immunization Practices were determined. RESULTS: The seroprotection rate among 1,988 patients was 90.2% (95% confidence interval 88.8% to 91.5%). Groups with significantly lower seroprotection rates were persons aged 70 years or older, 59.5% (risk ratio [RR] 5.2); immigrants from outside North America or Western Europe, 75.3% (RR 3.7); persons with a history of inadequate immunization, 86.3% (RR 2.9); and persons without education beyond grade school, 76.5% (RR 2.5). Despite a history of adequate immunization, 18% of immigrants lacked seroprotection. Overall, 60.9% of patients required tetanus immunization, of whom 57.6% did not receive indicated immunization. Among patients with tetanus-prone wounds, appropriate prophylaxis (ie, tetanus immunoglobulin and toxoid) was provided to none of 504 patients who gave a history of inadequate primary immunization (of whom 15.1% had nonprotective antibody titers) and to 218 (79%) of 276 patients who required only a toxoid booster. CONCLUSION: Although seroprotection rates are generally high in the United States, the risk of tetanus persists in the elderly, immigrants, and persons without education beyond grade school. There is substantial underimmunization in the ED (particularly with regard to use of tetanus immunoglobulin), leaving many patients, especially those from high-risk groups, unprotected. Better awareness of tetanus prophylaxis recommendations is necessary, and future tetanus prophylaxis recommendations may be more effective if they are also based on demographic risk factors.

Current issues in the management of bacterial respiratory tract disease: the challenge of antibacterial resistance.

The worldwide burden of respiratory tract disease is enormous. Resistance to penicillins, macrolides, and cephalosporins is now detected among the leading bacterial pathogens that cause respiratory tract infections (RTIs)-Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. The increasing role of atypical/intracellular pathogens (eg, Chlamydia pneumoniae, Mycoplasma pneumoniae, Legionella pneumophila) in RTIs, as well as their increase in antibiotic resistance prevalence, continues to be of great concern. More recently introduced treatment options for RTIs include the newer respiratory fluoroquinolones, along with the macrolides and azalides. Although these agents demonstrate good activity against common respiratory pathogens, reduced susceptibility to these agents has been reported. The ketolides are recently developed antibacterial agents with targeted-spectrum activity against common respiratory tract pathogens, including atypical/intracellular pathogens, and a low potential for inducing resistance. These promising new drugs have shown in vitro and in vivo efficacy in the treatment of community-acquired RTIs, such as community-acquired pneumonia, acute exacerbations of chronic bronchitis, and acute bacterial maxillary sinusitis.

High-dose, short-course levofloxacin for community-acquired pneumonia: a new treatment paradigm.

Levofloxacin demonstrates concentration-dependent bactericidal activity most closely related to the pharmacodynamic parameters of the ratio of area under the concentration-time curve (AUC) to minimum inhibitory concentration (MIC) and the ratio of peak plasma concentration (C(max)) to MIC. Increasing the dose of levofloxacin to 750 mg exploits these parameters by increasing peak drug concentrations, allowing for a shorter course of treatment without diminishing therapeutic benefit. This was demonstrated in a multicenter, randomized, double-blind investigation that compared levofloxacin dosages of 750 mg per day for 5 days with 500 mg per day for 10 days for the treatment of mild to severe community-acquired pneumonia (CAP). In the clinically evaluable population, the clinical success rates were 92.4% (183 of 198 persons) for the 750-mg group and 91.1% (175 of 192 persons) for the 500-mg group (95% confidence interval, -7.0 to 4.4). Microbiologic eradication rates were 93.2% and 92.4% in the 750-mg and 500-mg groups, respectively. These data demonstrate that 750 mg of levofloxacin per day for 5 days is at least as effective as 500 mg per day for 10 days for treatment of mild-to-severe CAP.