Amoxil beecham

“Cure” was defined as resolution of pretreatment clinical signs and symptoms and no further requirement for antimicrobial therapy for CAP.

“Improvement” was defined as clinical findings that subsided significantly, albeit with incomplete resolution of clinical evidence of infection in a subject who required no further antimicrobial therapy for CAP.

“Failure” (i.e., presumptive microbiological failure [final culture not obtained]) was defined as no apparent response to therapy or as an incomplete response requiring additional antimicrobial therapy for CAP.

The secondary efficacy variables included the microbiological response, according to pathogen, at the test-of-cure visit; transition in signs and symptoms during therapy; and clinical response at the visit that occurred 1 month after therapy for patients considered to have clinical success at the test-of-cure visit. A total enrollment of 212 patients was expected to yield 79 clinically evaluable patients in each treatment group.

With 79 patients per treatment group, there was an

80%

A patient was considered to be clinically evaluable unless he or she (1) had an unconfirmed diagnosis; (2) was lost to follow-up; (3) did not take?1 dose of study drug; (4) had an insufficient

course

Patients were considered to be microbiologically evaluable if they were clinically evaluable, if their infection was bacteriologically proven, and if they had an appropriate bacteriologic culture. For purposes of efficacy analysis, 2-sided 95% CIs around the difference in clinical success rates were generated. To establish that levofloxacin was at least as effective as the comparator, the upperbound of the confidence interval must have been?15 percentage points. A safety analysis, which included all enrolled patients who took study drug, was done for adverse event

data

Ninety-five of 132 patients who received levofloxacin were clinically evaluable, compared with 89 of 137 patients who were treated with

the

Disposition of patients in levofloxacin and comparator treatment arms in a study of the safety and efficacy of levofloxacin for the treatment of community-acquired pneumonia.

a Two patients who were randomized to receive levofloxacin received treatment with the comparator

and

b Reasons for premature discontinuation of therapy are shown in table 1.

Disposition of patients in levofloxacin and comparator treatment arms in a study of the safety and efficacy of levofloxacin for the treatment of community-acquired pneumonia. a Two patients who were randomized to receive levofloxacin received treatment with the comparator and were analyzed with the comparator group. b Reasons for premature discontinuation of therapy are shown in table 1.

Reasons for premature discontinuation of therapy ina study of the safety and efficacy of levofloxacin for the treatment of community-acquired pneumonia.

Reasons for premature discontinuation of therapy ina study of the safety and efficacy of levofloxacin for the treatment of community-acquired pneumonia. The demographic characteristics of the 2 treatment groups were comparable and are presented in table 2.

In general, the demographic and baseline characteristics of the clinically evaluable and intent-to-treat populations were comparable. Demographic characteristics of participants (intent-to-treat population) in a study of the safety and efficacy of levofloxacin for the treatment of community-acquired pneumonia. Demographic characteristics of participants (intent-to-treat population) in a study of the safety and efficacy of levofloxacin for the treatment of community-acquired pneumonia. Mean APACHE IIscores were comparable for both treatment groups (they were 15.9 for patients in the levofloxacin arm and 16.0 for patients in the comparator arm). These scores confirmed that patients who were entered into the study

were

APACHE II scores and components of the APACHE II score (for the intent-to-treat population) in a study of the safety and efficacy of levofloxacin for the treatment of community-acquired pneumonia. APACHE II scores and components of the APACHE II score (for the intent-to-treat population) in a study of the safety and efficacy of levofloxacin for the treatment of community-acquired pneumonia.

The duration of therapy (oral or iv) in the safety-evaluable population (which is the same as an “intent-to-treat” population) was a mean (±SD) of 10.74± 4.29 days for

patients

with

Clinical success was achieved in 89.5% of clinically evaluable patients (85 of 95 patients) treated with levofloxacin and in 83.1% of clinically evaluable comparator-treated patients (74 of 89 patients) (95% CI, ?16.8 to 4.2).

In the intent-to-treat population, clinical success was achieved in 72.7% of levofloxacin-treated patients (96 of 132 patients) and in 64.2% of the comparator-treated patients (88 of 137 patients) (95% CI, ?19.9 to 2.9)( table 4).

Overall clinical response forintent-to-treat and clinically evaluable patients in a study of the safety andefficacy of levofloxacin in the treatment of community-acquired pneumonia.

Overall clinical response forintent-to-treat and clinically evaluable patients in a study of the safety andefficacy of levofloxacin in the treatment of community-acquired pneumonia.

Among patients with cultures of respiratory samples that yielded positive results for S.

pneumoniae , 86.7% of patients treated with levofloxacin (13 of 15 patients) and 85.0% of patients in the comparator group (17 of 20 patients) demonstrated clinical success. For patients with Haemophilus influenzae , 100% of patients treated with levofloxacin (4 of 4 patients) and 87.5% of patients treated with the comparator (7 of 8 patients) demonstrated clinical success. pneumoniae , clinical success was demonstrated in 100% of patients in the levofloxacin group (5 of 5 patients) and in 80.0% of patients in the comparator group (8 of 10 patients). For patients with results of serological testing that were positive for any of the 3 a typical pathogens, 96.0% of patients in the levofloxacin group (24 of 25 patients) and 91.2% of patients in the comparator group (31 of 34 patients) demonstrated clinical success ( table 5).

Clinical response rates, after therapy, for clinically evaluable patients with pathogens of primary interest in a study of the safety and efficacy of levofloxacin for the treatment of community-acquired pneumonia, summarized by source.

Clinical response rates, after therapy, for clinically evaluable patients with pathogens of primary interest in a study of the safety and efficacy of levofloxacin for the treatment of community-acquired pneumonia, summarized by source.

Among patients with pneumococcal bacteremia at study entry, clinical success was demonstrated in 77.8% of the levofloxacin-treated clinically evaluable patients (7 of 9 patients) and in 77.8% of the comparator-treated clinically evaluable patients (7 of 9 patients).

There were no cases confirmed by follow-up culture of persistent pneumococcal bacteremia in either group of patients.

Thirty-eight patients in the clinically evaluable population required mechanical ventilation at study admission because of the severity of their illness. For this group of patients, clinical success was achieved in 84.2% of patients treated with levofloxacin (16 of 19 patients) and in 63.2% of patients treated with the comparator (12 of 19 patients) ( table 6).

Clinical response rates among clinically evaluable patients requiring mechanical ventilation at study entry in astudy of the safety and efficacy of levofloxacin for the treatment of community-acquired pneumonia.

Clinical response rates among clinically evaluable patients requiring

mechanical

study

Thirty patients required vasopressor therapy during the study because of the severity of their illness.

For this group of patients, clinical success was demonstrated in 68.8% of patients treated with levofloxacin (11 of 16 patients) and in 50% of patients treated with the comparator (7 of 14 patients) ( table 7).

Clinical response rates among clinically evaluable patients requiring vasopressor therapy in a study of the safety and efficacy of levofloxacin for the treatment of community-acquired pneumonia.

Clinical response rates among clinically evaluable patients requiring vasopressor therapy in a study of the safety and efficacy of levofloxacin for the treatment of community-acquired pneumonia. A secondary efficacy variable was microbiological eradication.

Among patients evaluable for microbiological efficacy, the overall post therapy eradication rates for pathogens were 87.7% (64 of 73 patients) and 81.8% (81 of 99 patients) for the levofloxacin and comparator arms, respectively (95% CI, ?17.3 to 5.5).

Rates of eradication of infection were 84.9% (45 of 53 patients) for the levofloxacin group and 75.0% (48 of 64 patients) for the comparator group (95% CI, ?25.2 to 5.4)( table 8).

Microbiological eradication rates for microbiologically evaluable

patients

Microbiological eradication rates for microbiologically evaluable patients in a study of the safety and efficacy of levofloxacin for the treatment of community-acquired pneumonia. Culture results demonstrated a broad range of organisms in addition to those not typically associated with CAP.

This range of organisms included some gram-negative organisms more typically associated with nosocomial pneumonia ( table 9). For patients with the aforementioned organisms more typically associated with nosocomial pneumonia, microbiological eradication occurred in 81.8% of patients in the levofloxacinarm (9 of 11 patients) and in 80% of patients in the comparator arm (12 of 15 patients) ( table 10). Range of suspected pathogens isolated from patients in the intent-to-treat population in a study of the safety and efficacy of levofloxacin for the treatment of community-acquired pneumonia. Range of suspected pathogens isolated from patients in the intent-to-treat population in a study of the safety and efficacy of levofloxacin for the treatment of community-acquired pneumonia. Eradication of pathogens more typically associated with nosocomial pneumonia from the microbiologically evaluable population in a study of the safety and efficacy of levofloxacin for the treatment of community-acquired pneumonia.

Eradication of pathogens more typically associated with nosocomial pneumonia from the microbiologically evaluable population in a study of the safety and efficacy of levofloxacin for the treatment of community-acquired pneumonia. All 269 patients who were enrolled in the study were evaluable for safety.

Both

the

Overall, in the population evaluable for safety, 74.2% of patients in the levofloxacin treatment group (98 of 132 patients) and 70.1% of patients in the comparator treatment group (96 of 137 patients) reported ?1 treatment-emergent adverse event during the study. Gastrointestinal disorders were the most common complaints in both treatment groups; 37.1% of levofloxacin-treated patients (49 of 132 patients) and 43.1% of comparator-treated patients (59 of 137 patients) reported gastrointestinal disorders.

Application-site disorders were more common among patients treated with the comparator, occurring in 8% of comparator-treated patients (11 of 137 patients), compared with 0.8% of patients treated with levofloxacin (1 of 132 patients). Twenty-four patients died during the study or within 30 days of receipt of the last dose of study medication (11.4% of patients in the levofloxacin-treatment group [15 of 132 patients] and 6.6% of patients in the comparator-treatment group [9 of 137 patients]).

None of the deaths was considered to be related to study therapy. The average APACHE II score for patients in the levofloxacin group who died was 20.0; for patients in the comparator group who died, the average score was 18.5. There was no statistically significant difference between mortality rates in the 2 groups ( P = .20, by Fisher exact test).

The patient population included in this study was seriously ill. All patients were hospitalized for treatment

and

Many studies of CAP tend to include ambulatory or less seriously ill patients.

Results from such studies may not adequately address the treatment challenges posed by more seriously ill patients with CAP. Such patients may be more prone to adverse events because of their underlying

condition

agent

The efficacy of levofloxacin in this patient population was 89.5% (85 of 95 patients), compared with an efficacy of 83.1% (74 of 89 patients) for the combination of a ?-lactam and amacrolide.

Among clinically evaluable patients who required mechanical ventilation, clinical success was achieved in 84.2% of patients treated with levofloxacin (16 of 19 patients), compared with 63.2% of patients treated with the comparator (12 of 19 patients).

Among clinically evaluable patients who required vasopressor support during the study, 68.8% of patients treated with levofloxacin (11 of 16 patients) achieved clinical success, compared with 50% of patients treated with the comparator (7 of 14 patients). Levofloxacin therapy may offer distinct advantages over other treatment regimens.

Plasma concentration profiles after oral and iv administration are comparable; therefore, oral and iv dosage forms can be considered interchangeable. Because of the interchangeable dosage forms, initial use of or early switching to oral treatment for patients with a functional gastrointestinal tract, even severely ill hospitalized patients, may lead to a decreased incidence of adverse events related to iv administration and, also, to decreased administration costs.