Infection (2018) 46:431–434
Ceftolozane‑tazobactam therapy for multidrug‑resistant Pseudomonas
aeruginosa infections in patients with hematologic malignancies
and hematopoietic‑cell transplant recipients
· James S. Lewis II.
Received: 8 December 2017 / Accepted: 14 February 2018 / Published online: 19 February 2018
© Springer-Verlag GmbH Germany, part of Springer Nature 2018
Multidrug-resistant (MDR) Pseudomonas aeruginosa infection causes signiﬁcant mortality among patients with hematologic
malignancies and hematopoietic-cell transplant recipients. Ceftolozane-tazobactam (C-T) is a novel therapeutic option for
MDR-P. aeruginosa infections but clinical experience in these patients is limited. We report favorable clinical outcomes and
lack of limiting toxicities using C-T monotherapy to treat invasive MDR-P. aeruginosa infections in these patient populations.
Keywords Ceftolozane-tazobactam · Pseudomonas aeruginosa · Hematologic malignancy · Hematopoietic-cell transplant
Pseudomonas aeruginosa, and particularly multidrug-
resistant (MDR)-P. aeruginosa, is a signiﬁcant cause of
morbidity and mortality among patients with hematologic
malignancies and those who have undergone hematopoietic-
cell transplant (HCT) . Defects in host immunity such
as neutropenia, inappropriate empiric therapy, and use of
agents with limited therapeutic windows such as polymix-
ins or aminoglycosides contribute to MDR- P. aeruginosa
infection-attributable mortality rates of up to 40% [2–4].
Ceftolozane-tazobactam represents an attractive therapeutic
option due to its activity against MDR-P. aeruginosa strains
[5–7]. Clinical experience using ceftolozane-tazobactam
in patients with invasive MDR-P. aeruginosa infections is
accumulating but is still relatively lacking among patients
with hematologic malignancies and HCT recipients [8–12].
The purpose of this study was to report our experience using
ceftolozane-tazobactam for invasive MDR-P. aeruginosa
infections in these patient populations.
We conducted a retrospective study of adult (≥ 18 years old)
HCT recipients or those with a hematologic malignancy who
received ceftolozane-tazobactam monotherapy for MDR-P.
aeruginosa infections at Oregon Health and Science Univer-
sity (OHSU). Clinical data including age, gender, estimated
glomerular ﬁltration rate (EGFR), type of underlying hema-
tologic malignancy, receipt of HCT, absolute neutrophil
count (ANC) at time of infection onset, antibiotic therapy,
antibiotic susceptibility results, and clinical outcomes were
determined by review of electronic medical records.
Clinical success was deﬁned as resolution of signs and
symptoms of the infection during treatment with ceftolo-
zane-tazobactam, clearance of bacteremia (if present) within
72 h of initiation of ceftolozane-tazobactam, and absence
of infection recurrence, deﬁned as signs and symptoms of
infection along with culture positivity for P. aeruginosa
while receiving ceftolozane-tazobactam or within 30 days
of completion of ceftolozane-tazobactam therapy .
Antimicrobial susceptibility testing was performed by
the clinical microbiology laboratory utilizing Clinical and
Laboratory Standards Institute (CLSI) breakpoints and
results were reported as “susceptible” (S), “resistant” (R), or
“intermediate” (I). Strains were considered to be MDR when
non-susceptible (intermediate or resistant) to at least three
of the following antimicrobials: cefepime or ceftazidime,
piperacillin-tazobactam, meropenem, ciproﬂoxacin, and an
aminoglycoside (tobramycin or gentamicin) .
* Morgan Hakki
Division of Infectious Diseases, Department of Internal
Medicine, Oregon Health and Science University, 3181
SW Sam Jackson Park Road, Mail Code L457, Portland,
OR 97239, USA
Department of Pharmacy, Oregon Health and Science
University, Portland, OR, USA