Comparative Study To Determine The Efficacy, Safety, And Tolerability Of Ceftolozane-Tazobactam

Study Groups and Study Drug Administration:

If participant is found to be eligible to take part in this study and participant agrees,
participant will be randomly assigned (as in the flip of a coin) to either receive either the
study drug (Group 1) or a standard treatment antibiotic (Group 2). This is done because no
one knows if one study group is better, the same, or worse than the other group. Both
participant and the study doctor will know what participant is receiving.

- If participant is in Group 1, participant will receive ceftolozane-tazobactam by vein
over 1 hour every 8 hours.

- If participant is in Group 2, participant will receive a standard treatment antibiotic.
This may include one of the following 3 options:

- cefepime by vein over about 30 minutes every 8 hours.

- meropenem by vein over about 30 minutes every 8 hours.

- piperacillin/tazobactam by vein over about 1 hour every 6 hours.

Participant will receive the study drugs by vein for at least 3 days. After 3 days, if the
study doctor thinks it is in participant's best interest and participant is eligible,
participant may switch to receiving a different antibiotic either by mouth or by vein. The
study doctor will tell participant more about what antibiotic participant may begin to
receive, how it is administered, and its possible risks. If participant begins taking the
study drugs by mouth, the study doctor or study staff will tell participant how and when to
take each drug.

If the doctor thinks it is needed, participant will be given additional standard drugs to
help control the infection. Participant may ask the study staff for information about how the
drugs are given and their risks.

Length of Study:

Participant may receive the study drugs for up to 14 days. Participant will no longer be able
to receive the study drugs if the disease gets worse, if intolerable side effects occur, if
participant needs treatment that is not allowed on this study, or if participant is unable to
follow study directions.

Participation on this study will be over after the late follow-up visit.

Study Visits:

Participant will have the following tests/procedures while participant is in the hospital. If
participant begins to take the study drugs by mouth, participant will no longer have these
study visits.

Each day for up to 2 weeks, if the doctor thinks it is needed, blood (about 1 tablespoon) or
urine will be collected for routine tests.

Every 2 days for up to 2 weeks, blood (about 1 tablespoon) will be drawn to check for
infection. Participant will stop having these blood draws when there is no longer a sign of
infection and participant does not have a fever.

Twice each week for up to 2 weeks, participant will have a physical exam.

Follow-Up:

Within 72 hours (3 days) after participant's last dose of participant's assigned study
treatment and before starting the second antibiotic therapy (if applicable):

- Participant will have a physical exam.

- Blood (about 1 tablespoon) and urine will be collected for routine tests.

- If participant tested positive for infection at the beginning of the study, blood (about
1 tablespoon) will be drawn to check for infection. The study doctor will tell
participant if participant will have this blood draw.

About 21-28 days (3-4 weeks) after participant's first dose of study drug, participant will
return to MD Anderson for the following tests/procedures:

- Participant will have a physical exam.

- If participant tested positive for infection at the beginning of the study, blood (about
1 tablespoon) will be drawn to check for infection. The study doctor will tell
participant if participant will have this blood draw.

- If participant can become pregnant, blood (about 1 teaspoon) will be drawn for a
pregnancy test.

About 35-42 days (5-6 weeks) after participant's first dose of study drug, a member of the
study staff will call participant to ask about any new drugs participant may have started and
if participant is having any side effects. If participant is called, it should last about 10
minutes. If the doctor or study staff thinks it is needed, participant will be asked to come
back to the clinic for the following tests/procedures:

- Participant will have a physical exam.

- If the doctor thinks it is needed, blood (about 1 tablespoon) will be drawn to check for
infection.

At any of these follow-up visits, if participant's doctor thinks it is needed, participant
will have a chest x-ray or CT scan to check participant's lungs.

Inclusion Criteria:

1. Has provided written informed consent, and has the willingness and ability to comply
with all study procedures

2. Male or female >/=18 years old

3. Patients with neutropenic fever who have existing malignancy or have undergone
hematopoietic stem cell transplantation. Neutropenic fever is defined as the presence
of neutropenia defined by: 1) Absolute neutrophil count (ANC) < 500 cells/mm3 or has
an ANC that is expected to decrease to < 500 cells/mm3 within 48 hours of trial entry
and fever defined as: 2) Single oral temperature measurement of > 101°F (38.3°C) or a
temperature of > 100.4°F (38.0°C) sustained over a 1-hour period

4. Requires hospitalization for IV empiric antibiotic therapy

5. If female: Not breastfeeding; Agrees to not attempt to become pregnant during the
study; Is surgically sterile or at least 2-years postmenopausal, or if of childbearing
potential, has negative screening serum pregnancy test (if serum pregnancy test
results are not available at the time of enrollment, a negative urine pregnancy test
is required within 24 hours.); If of childbearing potential (including being < 2 years
postmenopausal), is willing to practice sexual abstinence or use an effective dual
form of contraception with her partner (eg, 2 barrier methods, barrier method plus
hormonal method) during treatment and for >/= 28 days after the last dose of any study
therapy (IV or oral)

Exclusion Criteria:

1. History of any hypersensitivity or allergic reaction to any cephalosporin antibiotic
or tazobactam.

2. Fever suspected to be caused by a noninfectious cause (eg, fever related to drug or
blood product administration)

3. Confirmed fungal infection (eg, Pneumocystis jirovecii etiology in patients with
pneumonia) that justifies adding additional empiric antimicrobial therapy (eg,
antifungals)

4. Confirmed viral infection that justifies adding additional empiric antiviral therapy
(eg, ganciclovir, foscarnet)

5. Evidence of significant hepatic impairment (any of the following): Known acute viral
hepatitis; Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level >
5 times the upper limit of normal (× ULN). Patients with values > 3 × ULN and < 5 ×
ULN are eligible if the value is acute and directly related to the infectious process
being treated. Total bilirubin > 3 × ULN unless isolated hyperbilirubinemia is
directly related to the acute infection or due to known Gilbert disease;
Manifestations of end-stage liver disease, such as ascites or hepatic encephalopathy

6. Known to be human immunodeficiency virus positive

7. Severely impaired renal function, defined as creatinine clearance (CrCl) estimated by the Cockcroft-Gault formula.

8. Expected requirement for hemodialysis while on study therapy

9. Received > 24 hours of IV antibacterial therapy (with study drugs) within 72 hours of
the initiation of inpatient IV study drug for treatment of suspected infection.
Antibiotic prophylaxis and oral antibiotics is allowed. Prophylactic use of antiviral
or antifungal medication is permitted.

10. Requirement for any non-study potentially effective concomitant systemic antibacterial
therapy

11. Past or current history of epilepsy or seizure disorder; exception: well-documented
febrile seizure of childhood

12. Evidence of immediately life-threatening disease, progressively fatal disease, or life
expectancy of 3 months or less (eg, moribund or with shock unresponsive to fluid
replacement)

13. Unable or unwilling to adhere to the study-specified procedures and restrictions

14. Any condition that would make the patient, in the opinion of the Investigator,
unsuitable for the study (eg, would place a patient at risk or compromise the quality
of the data

15. Participation in any other ongoing ceftolozane/tazobactam trial.