PHASE II SINGLE-CENTER, RANDOMIZED, OPEN-LABEL, PROSPECTIVE, STUDY TO DETERMINE THE IMPACT OF SERIAL PROCALCITONIN

This phase II trial studies the effect of imipenem-relebactam in treating patients with cancer who have a fever due to low white blood cell counts (febrile neutropenia). In this study, imipenem-relebactam will be compared to the standard-of-care treatment (cefepime, meropenem, or piperacillin/tazobactam) for the treatment of febrile neutropenia. Imipenem-relebactam is used to treat infections. Giving imipenem-relebactam may help to control febrile neutropenia in patients with cancer.

PRIMARY OBJECTIVES:

I. To evaluate the safety and tolerability of imipenem-relebactam plus vancomycin, daptomycin, or linezolid compared with SOC plus vancomycin, daptomycin or linezolid as empiric therapy in febrile neutropenic adults with cancer.

OUTLINE: Patients are randomized to 1 of 2 groups.

GROUP I (TREATMENT): Patients receive imipenem/cilastatin/relebactam IV over 30-60 minutes once every 6 hours (q6h) for 2 days for a minimum of 8 doses. Patients may also receive gram-positive therapy at the discretion of the primary team or emergency center physician consisting of vancomycin IV q12h or linezolid IV or orally (PO) q12h. Patients may continue to receive imipenem/cilastatin/relebactam IV over 30-60 minutes for up to 14 days if clinically indicated by the assessment of the treating physician.

GROUP II (STANDARD OF CARE): Patients receive cefepime IV q8h for a minimum of 6 doses, meropenem IV q8h for a minimum of 6 doses, or piperacillin/tazobactam IV q6h for a minimum of 8 doses. Patients may also receive gram-positive therapy at the discretion of the primary team or emergency center physician consisting of vancomycin IV q12h or linezolid IV or PO q12h.

Patients in both groups may receive other additional therapy (double-gram negative therapy) consisting of tobramycin IV q24h, amikacin IV q24h, ciprofloxacin IV q8h, minocycline q12h, tigecycline on days 1-2 q12h, doxycycline q12h, and/or bactrim. After at least 48 hours of gram-negative antimicrobial therapy, patients may be allowed to switch to PO or IV therapy such as linezolid PO, ampicillin, amoxicillin, amoxicillin/clavulanate PO, minocycline PO, ciprofloxacin PO, levofloxacin PO, cefpodoxime PO, trimethoprim/sulfamethoxazole PO, ceftriaxone IV, ertapenem IV, daptomycin IV and/or vancomycin IV for outpatient or home administration as clinically indicated. While in the hospital, patients undergo the collection of blood samples daily for 2 weeks, and urine samples every 2 days for up to 2 weeks.

After completion of study treatment, patients are followed up at 2, 21-28, and 35-42 days.

Eligibility Criteria:
Inclusion Criteria:

* Has provided written informed consent, and has the willingness and ability to comply with all study procedures
* \>= 18 years old
* 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:

  * Absolute neutrophil count (ANC) \< 500 cells/mm3 or has an ANC that is expected to decrease to \< 500 cells/mm\^3 within 48 hours of trial entry and fever defined as:
* Single oral temperature measurement of \> 100.4 degree F (38.0 degree C).
* Requires hospitalization for IV empiric antibiotic therapy
* 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 or urine pregnancy test within 5 days
  * 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 up 28 days post treatment

Exclusion Criteria:

* History of any hypersensitivity or allergic reaction to any carbapenem
* Fever suspected to be caused by a noninfectious cause (eg, fever related to drug or blood product administration)
* Confirmed fungal infection (eg, Pneumocystis jirovecii etiology in patients with pneumonia) that justifies adding additional empiric antimicrobial therapy (eg, antifungals)
* Confirmed viral infection that justifies adding additional empiric antiviral therapy (eg, ganciclovir, foscarnet)
* Evidence of significant hepatic impairment (any of the following):

  * Known acute viral hepatitis
  * Alanine aminotransferase (ALT) level \> 5 times the upper limit of normal (x upper limit of normal \[ULN\]). Total bilirubin \> 3 x 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
* Known to be human immunodeficiency virus positive
* Severely impaired renal function, defined as creatinine clearance (CrCl) =\< 30 mL/min estimated by the Cockcroft-Gault formula
* Expected requirement for hemodialysis while on study therapy
* Received \> 36 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
* Past or current history of epilepsy or seizure disorder; exception: well-documented febrile seizure of childhood
* 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)
* Unable or unwilling to adhere to the study-specified procedures and restrictions
* 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
* Participation in any other ongoing imipenem-relebactam trial