Treatment of Carbapenem-Resistant Enterobacteriaceae Infections with Ceftazidime-Avibactam

Abstract

BackgroundCRE 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.MethodsFrom 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.ResultsThe 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 blaKPC-2 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. 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.ConclusionIn 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.

Ceftazidime-Avibactam for the Treatment of Serious Gram-Negative Infections with Limited Treatment Options: A Systematic Literature Review

“…Recurrence occurred in two patients (18%). Decreased sensitivity to ceftazidime-avibactam was noted in one patient (9%), and three patients (27%) had CRE isolated after C 7 days of treatment [39]. In the cohort of six patients, five achieved clinical cure; however, two relapsed with the same KPC-3producing K. pneumoniae strain within 3 weeks of completing ceftazidime-avibactam treatment [38].…”

“…Data for 1155 patients treated with ceftazidimeavibactam from 16 retrospective non-comparative cohort/chart review studies were identified (Table 3) [32][33][34][35][36][37][38][39][40][41][42][43][44][45][46], the majority of which involved CRE/CPE infections (981 patients); six publications included data for P. aeruginosa infections (124 patients). Emergence of resistance and/or reduced susceptibility to ceftazidime-avibactam was reported in seven of these publications, including one OXA-48-producing K. pneumoniae in a single patient [35]; in the remaining cases, the resistant strains were either K. pneumoniae carbapenemase (KPC)-producing K. pneumoniae or carbapenem-resistant K. pneumoniae (CRKP) with unreported resistance mechanisms [32-35, 46, 47].…”

“…Emergence of resistance and/or reduced susceptibility to ceftazidime-avibactam was reported in seven of these publications, including one OXA-48-producing K. pneumoniae in a single patient [35]; in the remaining cases, the resistant strains were either K. pneumoniae carbapenemase (KPC)-producing K. pneumoniae or carbapenem-resistant K. pneumoniae (CRKP) with unreported resistance mechanisms [32-35, 46, 47]. Decreased sensitivity to ceftazidime-avibactam was reported in one patient with KPC-producing K. pneumoniae [39].…”

“…Five patients (21%) with documented microbiological cure died versus ten patients (71%) with no documented microbiological cure (P = 0.01). Rahmati et al (2017) and Krapp et al (2017) reported outcomes for 11 and 6 patients, respectively, with KPC-producing K. pneumoniae infections treated with ceftazidime-avibactam in the US [38,39]. In the cohort of 11 patients, the clinical success rate was 73%, 30-day survival was 82%, 90-day survival was 73%, and in-hospital mortality was 27% [39].…”

“…Rahmati et al (2017) and Krapp et al (2017) reported outcomes for 11 and 6 patients, respectively, with KPC-producing K. pneumoniae infections treated with ceftazidime-avibactam in the US [38,39]. In the cohort of 11 patients, the clinical success rate was 73%, 30-day survival was 82%, 90-day survival was 73%, and in-hospital mortality was 27% [39]. Mortality was 75% among four patients receiving CRRT or haemodialysis (P = 0.02); however, as noted above, approved ceftazidime-avibactam dosing recommendations are not currently available for patients on CRRT (moreover, ceftazidimeavibactam dosages were not reported in this congress abstract).…”