CRE is an
urgent threats to public health with a high mortality estimated at >30-50%. Until
recently, polymyxin-based antibiotics were the only
available options. However, a new therapeutic option has become available:
ceftazidime-avibactam. We sought to describe outcomes from these infections
treated with ceftazidime-avibactam.
Methods: From 9/2015 to 12/ 2016,
we reviewed charts of 11 patients infected with CRE who received
ceftazidime-avibactam at USC (Los Angeles, CA). Sixteen isolates analyzed. All
isolates were resistant to meropenem (MIC ≥ 16).Carbapenemase
production confirmed by detection of blaKPC. Clinical success
defined as clinical improvement, lack of recurrence, and survival in 90 days.
Recurrence defined as clinical signs of infection and recovery of CRE after ≥ 7 days of treatment.
Results: The median age was 49
(35-89); 73% (7/11) female; and 27% (3/11) solid organ transplants. All CRE
infections caused by Klebsiella pneumoniae. All sequence type 258, 7/11
and 4/11 blaKPC-3.
Nine capsular type wzi-154 and 2 wzi-29. qSOFA
score was 0 (0-2) predicting mortality of 3%. Seven had intraabdominal
infections; 2 pyelonephritis, 1 skin and soft tissue infection, and 1 primary
bacteremia. There were five episodes of secondary bacteremia. The patients were
treated for a median duration of 15 (3-43) days. All received other antibiotics
prior to ceftazidime-avibactam. 87% (9/11) treated with monotherapy and 13%
(2/11) in conjunction with colistemethate sodium. 27%
(3/11) were receiving CRRT or hemodialysis during treatment. No incidents of renal
toxicity observed using RIFLE criteria. Clinical success was 73% (8/11); 30 day
survival rate 82% (9/11); 90 day survival rate 73% (8/11); and in hospital mortality
27% (3/11). Patients receiving CRRT or hemodialysis had 75% (3/4) mortality (P=0.02).
Recurrence occurred in 18% (2/11). Decreased sensitivity to
ceftazidime-avibactam noted in one patient. 27% (3/11) had CRE isolated after ≥ 7 days treatment.
CRE-infected patient treated with
overall mortality rate was 27% with the
highest mortality among those receiving renal replacement therapy which was
comparable to a prior studies. Additional research is needed to optimize use of
ceftazidime-avibactam to treat CRE infections.
Elham Rahmati, M.D.1, Emily Blodget, M.D.1, Rosemary C. She, M.D.2, Jennifer Cupo Abbott, PharmD3, Robert A. Bonomo, MD4 and Brad Spellberg, M.D.1, (1)Infectious Diseases, USC+LAC Medical Center, Los Angeles, CA, (2)Pathology, Keck School of Medicine of USC, Los Angeles, CA, (3)Pharmacy, USC+LAC, Los Angeles, CA, (4)Department of Molecular Biology and Microbiology, Case Western Reserve University School of Medicine, Cleveland, OH
None R. C. She,
None J. Cupo Abbott,
None R. A. Bonomo,
None B. Spellberg,