Factors associated with mortality in Infections caused by Carbapenem-resistant Enterobacteriaceae.

INTRODUCTION: There is little information about weigh of factors possibly associated with mortality, in infections caused by Carbapenem-resistant Enterobacteriaceae (CRE) in Latin America. METHODOLOGY: A case-controls study nested in a historical cohort was performed including all patients with CRE infections diagnosed between June 2013 and December 2018 at Hospital Universitario San Ignacio in Bogotá, Colombia. Univariate and multivariate analysis were performed to compare cases of mortality within the first month after the infection diagnosis with surviving patients. RESULTS: A total of 131 patients were included. The overall 30-day mortality rate was 38.17%. In the multivariate analysis, a direct association was found between mortality and septic shock (OR 26.7 CI6.6-107.3 p < 0.01), post-chemotherapy febrile neutropenia (OR 3.3 CI1.06-10.8 p = 0.04) and Charlson Index ≥ 3 (OR 5.5 CI 1.5-20.06 p < 0.01). An inverse association was found with interventions to control the infectious focus (OR 0.3 CI0.1-0.7 p < 0.01). The MIC of different antibiotics and the use of combined antibiotic therapy (triple therapy vs. double therapy or monotherapy) were not associated with mortality. CONCLUSIONS: In patients with CRE infections, septic shock, a Charlson comorbidity index ≥ 3, and post-chemotherapy febrile neutropenia are independently related to an increase in mortality. The control of the infectious focus is a protective factor. A rapid identification of these patients, and the implementation of measures to control infectious focus and to detect CRE colonization in patients who are going to be taken to myelosuppressive chemotherapy could impact positively the prognosis of these patients.

Pneumonia and Renal Replacement Therapy Are Risk Factors for Ceftazidime-Avibactam Treatment Failures and Resistance among Patients with Carbapenem-Resistant Enterobacteriaceae Infections.

Ceftazidime-avibactam was used to treat 77 patients with carbapenem-resistant Enterobacteriaceae (CRE) infections at our center. Thirty- and 90-day survival rates were 81% and 69%, respectively; these rates were higher than those predicted by SAPS II and SOFA scores at the onset of infection. Clinical success was achieved for 55% of patients but differed by the site of infection. Success rates were lowest for pneumonia (36%) and higher for bacteremia (75%) and urinary tract infections (88%). By multivariate analysis, pneumonia (P = 0.045) and receipt of renal replacement therapy (RRT) (P = 0.046) were associated with clinical failure. Microbiologic failures occurred in 32% of patients and occurred more commonly among patients infected with KPC-3-producing CRE than among those infected with KPC-2-producing CRE (P = 0.002). Pneumonia was an independent predictor of microbiologic failure (P = 0.007). Ceftazidime-avibactam resistance emerged in 10% of patients, including 14% of those infected with Klebsiella pneumoniae and 32% of those with microbiologic failure. RRT was an independent predictor of the development of resistance (P = 0.009). Resistance was identified exclusively among K. pneumoniae bacteria harboring variant KPC-3 enzymes. Upon phylogenetic analysis of whole-genome sequences, resistant isolates from 87.5% (7/8) of patients clustered within a previously defined sequence type 258 (ST258) clade II sublineage; resistant isolates from one patient clustered independently from other ST258 clade II isolates. In conclusion, our report offers new insights into the utility and limitations of ceftazidime-avibactam across CRE infection types. Immediate priorities are to identify ceftazidime-avibactam dosing and therapeutic regimens that improve on the poor outcomes among patients with pneumonia and those receiving RRT.

Multicenter Study of Outcomes with Ceftazidime-Avibactam in Patients with Carbapenem-Resistant Enterobacteriaceae Infections.

Ceftazidime-avibactam is a novel cephalosporin-beta-lactamase inhibitor combination that is active against many carbapenem-resistant Enterobacteriaceae (CRE). We describe a retrospective chart review for 60 patients who received ceftazidime-avibactam for a CRE infection. In-hospital mortality was 32%, 53% of patients had microbiological cure, and 65% had clinical success. In this severely ill population with CRE infections, ceftazidime-avibactam was an appropriate option.

Identification of an NDM-5-producing Escherichia coli Sequence Type 167 in a Neonatal Patient in China.

Emergence of New Delhi metallo-ß-lactamase-producing Enterobacteriaceae has become a challenging threat to public health. Two carbapenem-resistant Escherichia coli, strain QD28 and QD29, were recovered from the aspirating sputum of a neonate and the urine of an adult in a Chinese hospital in 2013. Molecular typing revealed that both isolates belonged to the sequence type 167, but they were clonally diverse. Both isolates exhibited resistance to carbapenems, cephalosporins, ciprofloxacin, gentamicin, piperacillin-tazobactam and trimethoprim-sulfamethoxazole. In addition, strain QD28 was also resistant to aztreonam, and strain QD29 was resistant to amikacin, fosfomycin and minocycline. Antimicrobial resistance gene screening revealed that strain QD28 harbored aac(6')-Ib, blaCTX-M-14, blaNDM-5, blaTEM-1 and sul1 genes, and strain QD29 harbored aac(6')-Ib, blaCTX-M-3, blaNDM-5, blaTEM-1, rmtB, sul1 and sul2 genes. The blaNDM-5 gene was found to be located on a 46-kb plasmid in two isolates, and further sequence analysis showed that this plasmid was highly similar to the previously reported IncX3 plasmid pNDM-MGR194 in India. This is the first identification of blaNDM-5-carrying E. coli in the neonatal infection.