Treatment of Carbapenem-Resistant Enterobacteriaceae Infections with Ceftazidime-Avibactam

Abstract

Background

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 bla_KPC. 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 harboring bla_KPC-2 and 4/11 bla_KPC-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. Eighty-seven percent (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.

Conclusion

In CRE-infected patient treated with ceftazidime-avibactam, the 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 the use of ceftazidime-avibactam to treat CRE infections.

Disclosures

All authors: No reported disclosures.