Patients who are considered suitable by their physicians, to take part in this research, will
have a physical examination (including an ECG), blood and urine samples taken, as well as a
sample of the secretions or tissue around their infection site. In addition, the site of the
infection will be photographed. The patients will be randomly assigned one of the treatments:
IV/PO moxifloxacin (drug under evaluation) or IV piperacillin/tazobactam followed by PO
amoxicillin/clavulanic acid (i. e., one of the reference treatments for this kind of
infection). The maximum treatment duration will be 21 days, and the minimum will be 7 days.
During the hospitalization, the patients will have a physical examination every day. On Day
3-5 during therapy as well as at the end of treatment, the patients will have repeated
examinations. These tests and evaluations will be repeated 14 to 28 days after the end of
treatment. During this visit, blood and urine samples will be taken only if judged necessary
by the physicians.
Subgroup 1B: Moxifloxacin, 400 mg administered IV once daily and piperacillin/tazobactam
placebo administered IV three times daily followed by moxifloxacin 400 mg administered PO
once daily and amoxicillin/clavulanic acid oral placebo tablets twice daily. IV
administration sequence: piperacillin/tazobactam placebo followed by moxifloxacin.
Treatment group 2 (Piperacillin/tazobactam IV/amoxicillin/clavulanic acid tablets):
Subgroup 2A: Piperacillin/tazobactam, 4. 0/0. 5 g administered IV three times daily and
moxifloxacin placebo administered IV od followed by amoxicillin/clavulanic acid oral tablets,
875/125 mg twice daily and moxifloxacin placebo PO od. IV administration sequence:
piperacillin/tazobactam followed by moxifloxacin placebo. Subgroup 2B:
Piperacillin/tazobactam, 4. 0/0. 5 g administered IV three times daily and moxifloxacin placebo
administered IV od followed by amoxicillin/clavulanic acid oral tablets, 875/125 mg twice
daily and moxifloxacin placebo PO od. IV administration sequence: moxifloxacin placebo
followed by piperacillin/tazobactam. Subjects will be treated for a minimum of 7 days and a
maximum of 21 days at the discretion of the investigator.)
Inclusion Criteria:
Subjects must meet all of the following inclusion criteria:
1. Written informed consent
2. Men or women of 18 years and above with a diagnosis of bacterial skin and skin
structure infection that requires
1. Hospitalization and
2. Initial parenteral therapy for at least 48 hours and
3. Meets at least one of the following criteria:
- Involvement of deep soft tissue (e. g. fascial, muscle layers)
- Requirement for a significant surgical intervention including surgical
drainage, drainage procedure guided by imaging and/or debridement
- Association with a significant underlying disease that may complicate
response to treatment. An underlying disease is considered significant if it
includes any of the following conditions that are present at the time of
presentation: cancer (except basal- or squamous-cell cancer of the skin),
cardiac (i. e., congestive heart disease), diabetes mellitus, hepatic (i. e.,
cirrhosis or another form of chronic liver disease), immunologic, renal
disease, respiratory, transplantation or vascular disease
3. Duration of infection < 21 days
4. Diagnosis of one of the following skin and skin structure infections that requires
hospitalization and initial parenteral antibiotic therapy for at least 48 hours:
1. Major abscess (es) associated with extensive cellulitis, which requires
antibiotic therapy in addition to surgical incision and drainage
2. Diabetic foot infection of mild to severe intensity (PEDIS grade 2-4) in the
presence or absence of osteomyelitis. Subjects with osteomyelitis may only be
enrolled if the infected bone is completely removed by surgery and if residual
infection requiring antibiotics is still present following surgery
3. Wound infection including: post surgical (surgical incision), post-traumatic,
human bite/clenched fist and animal bite wound and wound associated with
injection drug abuse:
- Infections must have occurred within 30 days of a surgical procedure,
trauma, animal bite, or human bite, and involve the skin and skin structures
at the site of the incision, trauma, or bite
- In addition, post-surgical/trauma wound infections must meet the following
criteria:
- Involvement of deep soft tissues (e. g. fascial and muscle layers) of the
incision/trauma
- At least one of the following criteria:
- Purulent drainage from the deep incision/trauma
- Identification of an infecting organism from an aseptically obtained culture
of fluid or tissue from incision/trauma
- At least one of the following signs and symptoms:
1. Localized pain or tenderness
2. Fever (see below) AND The incision (in case of post-surgical wound infections) is
deliberately opened by a surgeon, unless the culture is negative
- Abscess or other evidence of infection involving the deep incision/trauma,
found on direct examination, during reoperation/operation (in case of
trauma), or by histologic or radiologic examination
- Diagnosis of a deep incisional/post-trauma SSI by a surgeon or attending
physician
- Bite wounds/clenched fist infections and wounds associated with injection
drug abuse must meet the criteria defining a cSSSI
d. Infected ischemic ulcers with at least one of the following conditions:
- Peripheral vascular disease
- Conditions pre-disposing to pressure sores such as paraplegia, peripheral
neuropathy
5. Presence of at least 3 of the following signs or symptoms:
1. Purulent drainage or discharge
2. Erythema extending > 1 cm from the wound edge
3. Fluctuance
4. Pain or tenderness to palpation
5. Swelling or induration
6. Fever, defined as body temperature
- > 37. 5°C (axillary)
- > 38°C (orally)
- > 38. 5°C (tympanically) or
- > 39°C (rectally) OR Elevated total peripheral white blood cell (WBC) count
> 12,000/mm3 OR > 15 % immature neutrophils (bands) regardless of total
peripheral WBC count
7. C reactive protein (CRP) > 20 mg/L
6. Specimen obtained for culture from infected area by needle aspiration of obviously
purulent material or by tissue biopsy or by curettage of the surface of ulcer within
48 hours prior to the initiation of study drug therapy
7. Duration of treatment of the skin/skin structure infection is anticipated to be at
least 7 days.
Surgical drainage or debridement of infected wounds or abscesses, if necessary, have to
have been completed <= 48 hours after the initiation of study drug therapy
Exclusion Criteria:
1. Women, who are pregnant or lactating, or in whom pregnancy can not be excluded (Note:
a urine pregnancy test has to be performed for all women of childbearing potential
before randomization to the study drug)
2. The following skin and skin structure infections:
1. Necrotizing fasciitis including Fourniers gangrene, ecthyma gangrenosum,
streptococcal necrotizing fasciitis and clostridial necrotizing fasciitis
2. Burn wound infections
3. Secondary infections of a chronic skin disease (e. g. atopic dermatitis)
4. Infection of prosthetic materials (e. g. subcutaneous tissue infection related to
a central venous catheter or permanent cardiac pacemaker battery pack). Subjects
with removal of a prosthetic device involved in an infection should not be
included
5. Infections where a surgical procedure alone is definitive therapy
6. Subjects with uncomplicated skin and skin structure infections including
folliculitis and furunculosis, carbunculosis, simple abscesses and superficial
cellulitis
3. Known hypersensitivity to quinolones and/or any type of beta-lactam antibiotic drugs
or any of the excipients
4. Previous history of cholestatic jaundice/hepatic dysfunction associated with
amoxicillin-clavulanic acid
5. Severe, life threatening disease with a life expectancy of less than 2 months
6. Immunosuppression including:
1. Known neutropenia (neutrophil count < 1000/µL)
2. Known lymphopenia with absolute CD4+ T cell count < 200/mm3
3. AIDS-defining event and/or concomitant therapy with HAART
4. Chronic treatment (>= 2 weeks) with known immunosuppressant therapy (including
treatment with > 15 mg/day of systemic prednisone or equivalent)
5. Any other congenital or acquired immune defect or immunosuppression
7. Known severe hepatic insufficiency (Child Pugh C) or transaminases increase > 5 fold
upper limit of normal (ULN)
8. Known renal impairment with a baseline measured or calculated serum creatinine
clearance < 40 mL/min
9. Known prolongation of the QT interval or concomitant use of drugs reported to increase
the QT interval (e. g. Class IA or Class III antiarrhythmics [eg., quinidine,
procainamide, amiodarone, sotalol], neuroleptics [e. g. haloperidol], tricyclic
antidepressive agents, certain antimicrobials [e. g. pentamidine, halofantrine],
certain antihistaminics [e. g. terfenadine], and other [cisapride, vincamine IV,
depridil, diphemanil])
10. Uncorrected hypokalemia
11. Clinically relevant bradycardia
12. Clinically relevant heart failure with reduced left ventricular ejection fraction
(i. e., below 40%)
13. Previous history of symptomatic arrhythmias
14. Previous history of tendon disease/disorder with quinolones
15. Known or suspected concomitant bacterial infection requiring additional systemic
antibacterial treatment, e. g. underlying septic arthritis
16. Requiring therapy with probenecid
17. Treatment with a systemic or topical antibacterial agent for > 24 hours in the
previous 7 days preceding study entry unless the subject showed no response or had
worsening of clinical signs and symptoms despite 3 or more days of prior therapy and a
culture obtained at the time of subject enrollment showed persistence of a pathogen
which is susceptible to the study drugs. The prior antimicrobial therapy must not have
been a fluoroquinolone or a beta lactam/beta lactamase combination
18. Infection known to be due to a MRSA, MRSE or VRE as the single isolated pathogen
19. Previous enrolment in this study
20. Participation in any clinical investigational drug study within 4 weeks of screening
21. Previous history of seizure disorders
Bayer Clinical Trials Contact, Email: clinical-trials-contact@bayerhealthcare.com
Bayer Clinical Research Center, ask Contact, Austria; Not yet recruiting
Bayer Clinical Research Center, ask Contact, Belgium; Recruiting
Bayer Clinical Research Center, ask Contact, Bulgaria; Recruiting
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Bayer Clinical Research Center, ask Contact, Germany; Recruiting
Bayer Clinical Research Center, ask Contact, Greece; Recruiting
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Bayer Clinical Research Center, ask Contact, Romania; Recruiting
Bayer Clinical Research Center, ask Contact, Russian Federation; Recruiting
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Bayer Clinical Research Center, ask Contact, Ukraine; Recruiting
Bayer Clinical Research Center, ask Contact, United Kingdom; Recruiting
