Patients with hematological malignancies receive highly myelotoxic chemotherapy regimens that cause periods of severe myelosuppression, which places them at high risk of developing bacteremia.
At a global level, a very significant increase in multidrug-resistant (MDR) Gram-negative microorganisms, particularly Enterobacteriaceae producing extended-spectrum beta-lactamases (ESBL) and MDR P.aeruginosa, have been described during the last decade. Among the strategies to reduce bacterial resistance, ceftolozane/tazobactam (C/T) as a "carbapenem-sparing" antibiotic has been proposed.
C/T has broad-spectrum activity since it has action against ESBL-producing Enterobacteriaceae and MDR P. aeruginosa. Studies carried out in the real world using this antibiotic in patients with hematological malignancies have demonstrated clinical success in reports and case series, considered a therapeutic option in patients with Enterobacteriaceae and P. aeruginosa infections, particularly in MDR pathogens.
At the National Cancer Institute (in Spanish, Instituto Nacional de Cancerologia), Gram-negative bacilli have been identified for more than 20 years as the pathogens most frequently associated with bacteremia. Escherichia coli occupies the first place in 25% (41% ESBL), followed by Klebsiella spp. in 5.6% (11.2% ESBL) and P. aeruginosa in 5.6% (11.2% MDR). The protocol for approaching and treating hematological malignancy patients with severe neutropenia and fever is to initiate an antimicrobial regimen with piperacillin/tazobactam (P/T). In patients who persist with fever after 48 to 72 hours of starting antibiotics, who present with clinical deterioration, or in whom P/T-resistant bacteria are identified, this is escalated to carbapenem.
Therefore, it is proposed to compare the clinical and microbiological response in patients with hematological malignancies who present with severe neutropenia and fever and who present clinical data of bacteremia, with empirical treatment with C/T vs. P/T, trying to reduce the use of carbapenems in this group of patients.
All patients >18 years old
Diagnosis of any hematological malignancy
Severe neutropenia (polymorphonuclear <500 cells/mm3)
Fever (≥38.3 degrees Celsius in one measure, or ≥38 degrees Celsius in at least two measures)
Known hypersensitivity to cephalosporins or anaphylaxis with beta-lactams
Clinical signs related to hemodynamic instability
Concomitant use of another antibiotic with activity against Gram-negatives (except Trimethoprim/Sulfamethoxazole (TMP/SMX) as prophylaxis for P. jirovecii
Patients with end-stage chronic renal failure (<10 ml/min by creatinine clearance-ACCr) or on renal replacement therapy.
Parallel
Ceftolozane/tazobactam
DrugCeftolozane/tazobactam 1.5 g tid IV infusion for 1 hour during 5 to 7 days
Piperacillin/tazobactam
DrugPiperacillin/tazobactam 4.5 g qid IV infusion for 30 minutes during 5 to 7 days
Mortality of all patients at day 30
To assess the number of patients who will be alive or dead in the first 30 days. On day 30, a physical visit will be made to the patient's bedside if the patient is hospitalized. If the patient is not hospitalized, the clinical record will be evaluated, and one of the investigators will make a phone call to ensure the patient's status for that date.
Microbiological response through the sterilization of repeated blood cultures take
Number of patients that will have repeated blood cultures sterilized (no growth of the same bacteria isolated in the first set of blood cultures taken in day 1).
Clinical response measured through fever resolution
The presence of fever (\>38 Celsius degree) will be evaluated according to nursing records that are carried out three times a day (morning, afternoon, and night shifts). Clinical failure will be considered when the patient persists with fever (\>38 Celsius degrees) on day four after starting the antimicrobial regimen. Clinical success will be considered when the fever resolves between day 1 and day 3 of starting antibiotics.
Clostridioides difficile infection documented through toxin/GDH C. difficile test in those patients who develop diarrhea, abdominal pain and/or distended abdomen.
Number of patients who develop diarrhea or abdominal pain or distended abdomen, with a test positive for C. difficile (toxin/GDH C. difficile test).
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