Clinical trial NCT00253955 (phase 3, status: completed)
Conditions: pneumonia
ICD codes: A01.03, A02.22, A54.84, B01.2, B06.81, B77.81, J12.0
Drugs: levofloxacin, piperacillin/tazobactam
SMILES: [H][C@]12SC(C)(C)[C@@H](N1C(=O)[C@H]2NC(=O)[C@H](N)C1=CC=C(O)C=C1)C(O)=O, [H][C@]12SC(C)(C)[C@@H](N1C(=O)[C@H]2NC(=O)[C@H](NC(=O)N1CCN(CC)C(=O)C1=O)C1=CC=CC=C1)C(O)=O
Eligibility criteria:

        Inclusion Criteria:

        Subjects meeting all of the following criteria will be considered for enrollment into the
        study:

          -  General ward or ICU hospitalized subject.

          -  Subject with diagnosis of hospital-acquired pneumonia of presumed bacterial origin
             based upon:

               -  Infection developing after at least 72 hours following hospital admission and

               -  At least three of the four following signs:

                    -  Fever, defined as body temperature (oral or tympanic temperature ≥ 38°C or
                       rectal temperature ≥ 38.5°C)

                    -  Purulent tracheal sputum production/secretion or change in sputum character

                    -  Total peripheral white blood cell (WBC) count > 12 G/L or < 4.5 G/L or 15%
                       immature neutrophils (bands), regardless of total peripheral WBC count

                    -  Increased plasma or serum C reactive protein (CRP) level as shown by a level
                       of at least twice the upper boundary of the hospital normal range and

                    -  Chest X-ray findings (anterior posterior [AP] or posterior anterior [PA], if
                       possible lateral view) in agreement with the clinical diagnosis of bacterial
                       pneumonia, i.e. appearance of new, progressive pulmonary infiltrate(s)
                       attributable to infectious etiology.

          -  Subjects are required to have specimens collected for microbiological documentation
             within 24 hours prior to enrolment. Specimens should include at least one invasive or
             noninvasive lower respiratory tract specimen for Gram stain, culture and
             susceptibility testing, and at least 2 venous blood samples for culture and
             susceptibility testing.

        Exclusion Criteria:

        Subjects presenting with any of the following will not be included in the study:

        Related to the hospital-acquired pneumonia (HAP):

          -  Suspected viral or fungal pneumonia, or HAP strongly suspected to be caused by MRSA
             (methicillin-resistant Staphylococcus aureus) or organisms responsible for atypical
             pneumonia, such as Chlamydia pneumoniae, Legionella pneumophila or Mycoplasma
             pneumoniae

          -  Patients with severe HAP, defined as presence of at least one of the following:

               -  In previously non-ventilated patients: need for mechanical ventilation
                  consequently to HAP

               -  In previously ventilated patients: oxygenation rate defined by partial pressure
                  of oxygen in arterial blood (PaO2)/fraction of inspired oxygen (FiO2) < 200

          -  Radiographic findings compatible with severe HAP, i.e. showing either:

               -  Rapid progression (e.g. increase in the size of the opacity by ≥ 50% within 48
                  hours of the current evaluation)

               -  OR multilobar pneumonia (> 2 lobes) or involvement of both lungs

               -  OR cavitation of a lung infiltrate

          -  Evidence of severe sepsis with hypotension and/or end-organ dysfunction, i.e.:

               -  Shock commonly evidenced by: systolic blood pressure < 90 mmHg or diastolic blood
                  pressure < 60 mmHg

               -  In absence of previous vasopressors use, vasopressors use (except for fluid
                  replacement) for more than 4 hours

               -  In presence of vasopressors use, increase in vasopressors use (except for fluid
                  replacement) for more than 4 hours

               -  OR marked reduction in urine output (unless another explanation is available),
                  i.e. in 1 hour: < 20 mL or in 4 hours: < 80 mL

               -  OR acute renal failure requiring dialysis

               -  OR profound alteration of mental status, i.e. marked lethargy/stupor/coma

        Related to medical history/concomitant conditions:

          -  Patients with any concomitant pulmonary diseases, conditions or complications that
             could confound the interpretation or evaluation of drug efficacy or safety, including
             severe bronchiectases, cystic fibrosis, active pulmonary tuberculosis or acute
             pulmonary embolism, empyema, lung abscess or extra pulmonary extension of the LRTI
             (lower respiratory tract infection), such as meningitis, septic arthritis,
             endocarditis, known bronchial obstruction due to tumor or foreign body or with a
             history of post-obstructive pneumonia (this does not exclude patients with COPD
             [chronic obstructive pulmonary disease]), primary lung cancer or another malignancy
             metastatic to the lungs, and/or requiring chemotherapeutic treatment (for this or
             other reasons)

          -  Patients with any known or suspected bacterial infection other than the disease under
             investigation which will require concomitant use of a systemic antimicrobial agent
             other than the study drug allocated

          -  Patients who have received previous systemic antibiotics longer than 24 hours within
             72 hours prior to the enrolment for the same episode of HAP

          -  Body weight > 95 kg

          -  Patients with impaired renal function, as shown by creatinine clearance < 20 mL/min

          -  Hepatic cirrhosis with Child-Pugh score > or = B

          -  Immuno-compromised patients, such as those presenting with either:

               -  Known HIV infection with a CD4 + T-lymphocyte count < 0.2 G/L (i.e. < 200
                  cells/mm3)

               -  Neutropenia - neutrophil count < 1.0 G/I (i.e. < 1000/mm3)

               -  Patients on maintenance (≥ 3 months) corticosteroid therapy (> 20 mg/day
                  equivalent prednisolone)

        Related to study drugs:

          -  Patients with a microbiologically documented infection with a pathogen known prior to
             inclusion to be resistant to at least one of the study medications

          -  Patients with known or suspected hypersensitivity to, or known or suspected serious
             adverse reaction to levofloxacin and/or piperacillin/tazobactam and/or any other
             quinolones, beta-lactamase inhibitors, penicillins and/or to cephalosporins

          -  Patients with epilepsy or a history of epilepsy or with predisposition to seizures
             (e.g. patients with pre-existing central nervous system lesions)

          -  Patients with known or suspected history of tendon disorders unless a potential
             relationship to fluoroquinolone administration has been excluded.

          -  Patients with latent or actual known defects in glucose-6-phosphate dehydrogenase
             activity

        General:

          -  Women who are breast-feeding, or are failing to use adequate contraception; for
             example, systemic hormones (birth control pills, implant), intrauterine device or
             barrier method (diaphragm with intravaginal spermicide, cervical cap, male or female
             condom), or are pregnant, as demonstrated by urine or serum pregnancy tests carried
             out before exposure to study medication or the start of any study procedure that could
             pose a risk to the foetus

          -  Patients with a recent (within three months prior to study entry) history of drug or
             alcohol abuse

          -  Patients who have received any investigational drug within one month prior to study
             entry.

        The above information is not intended to contain all considerations relevant to a patient's
        potential participation in a clinical trial.