Carbapenemase-producing Enterobacteriaceae (CPE) are an important and increasing threat to global health. Both clonal spread and plasmid-mediated transmission contribute to the ongoing rise in incidence of these bacteria. Among the 4 classes of β-lactamases defined by the Ambler classification system, the carbapenemases that confer carbapenem resistance in Enterobacteriaceae belong to 3 of them: Class A (K. pneumoniae carbapenemases, KPC), Class B (metallo-β-lactamases, MBL including New Delhi metallo-β-lactamases, NDM) and Class D (OXA-48-like carbapenemases). KPC-producing CPE are the most commonly occurring CPE in the United States. MBL-producing CPE have been most commonly associated with the Indian Subcontinent as well as with specific countries in Europe, including Romania, Denmark, Spain, and Hungary. The epicenter of OXA-48-like-producing is in Turkey and surrounding countries. Detailed knowledge of the epidemiology and molecular characteristics of CPE is essential to stem the spread of these pathogens.

The efficacy of ceftazidime-avibactam—a cephalosporin–β-lactamase inhibitor combination with in vitro activity against Klebsiella pneumoniae carbapenemase–producing carbapenem-resistant Enterobacteriaceae (CRE)—compared with colistin remains unknown. Patients initially treated with either ceftazidime-avibactam or colistin for CRE infections were selected from the Consortium on Resistance Against Carbapenems in Klebsiella and other Enterobacteriaceae (CRACKLE), a prospective, multicenter, observational study. Efficacy, safety, and benefit-risk analyses were performed using intent-to-treat analyses with partial credit and the desirability of outcome ranking approaches. The ordinal efficacy outcome was based on disposition at day 30 after starting treatment (home vs not home but not observed to die in the hospital vs hospital death). All analyses were adjusted for confounding using inverse probability of treatment weighting (IPTW). Thirty-eight patients were treated first with ceftazidime-avibactam and 99 with colistin. Most patients received additional anti-CRE agents as part of their treatment. Bloodstream (n = 63; 46%) and respiratory (n = 30; 22%) infections were most common. In patients treated with ceftazidime-avibactam versus colistin, IPTW-adjusted all-cause hospital mortality 30 days after starting treatment was 9% versus 32%, respectively (difference, 23%; 95% bootstrap confidence interval, 9%–35%; P = .001). In an analysis of disposition at 30 days, patients treated with ceftazidime-avibactam, compared with those treated within colistin, had an IPTW-adjusted probability of a better outcome of 64% (95% confidence interval, 57%-71%). Partial credit analyses indicated uniform superiority of ceftazidime-avibactam to colistin. Ceftazidime-avibactam may be a reasonable alternative to colistin in the treatment of K. pneumoniae carbapenemase–producing CRE infections. These findings require confirmation in a randomized controlled trial.

Methylation of 16S ribosomal RNA (rRNA) has recently emerged as a new mechanism of resistance against aminoglycosides among gram-negative pathogens b

Klebsiella pneumoniae producing Klebsiella pneumoniae carbapenemase (KPC) has been associated with serious infections and high mortality. The optimal antimicrobial therapy for infection due to KPC-producing K. pneumoniae is not well established. We conducted a retrospective cohort study to evaluate the clinical outcome of patients with bacteremia caused by KPC-producing K. pneumoniae . A total of 41 unique patients with blood cultures growing KPC-producing K. pneumoniae were identified at two medical centers in the United States. Most of the infections were hospital acquired (32; 78%), while the rest of the cases were health care associated (9; 22%). The overall 28-day crude mortality rate was 39.0% (16/41). In the multivariate analysis, definitive therapy with a combination regimen was independently associated with survival (odds ratio, 0.07 [95% confidence interval, 0.009 to 0.71], P = 0.02). The 28-day mortality was 13.3% in the combination therapy group compared with 57.8% in the monotherapy group ( P = 0.01). The most commonly used combinations were colistin-polymyxin B or tigecycline combined with a carbapenem. The mortality in this group was 12.5% (1/8). Despite in vitro susceptibility, patients who received monotherapy with colistin-polymyxin B or tigecycline had a higher mortality of 66.7% (8/12). The use of combination therapy for definitive therapy appears to be associated with improved survival in bacteremia due to KPC-producing K. pneumoniae .

There are no data comparing outcomes of patients treated with ceftazidime-avibactam versus comparators for carbapenem-resistant Enterobacteriaceae infections. At our center, ceftazidime-avibactam treatment of carbapenem-resistant Klebsiella pneumoniae bacteremia was associated with higher rates of clinical success ( P = 0.006) and survival ( P = 0.01) than other regimens. Across treatment groups, there were no differences in underlying diseases, severity of illness, source of bacteremia, or strain characteristics (97% produced K. pneumoniae carbapenemase). Aminoglycoside- and colistin-containing regimens were associated with increased rates of nephrotoxicity ( P = 0.002).