By Stan Deresinski, MD, FACP, FIDSA

Clinical Professor of Medicine, Stanford University

Dr. Deresinski reports no financial relationships relevant to this field of study.

SYNOPSIS: CDC efforts, implemented at the local level, have been associated with a modest reduction in the incidences of Escherichia coli and Klebsiella pneumoniae with an ESBL phenotype and a more dramatic reduction in carbapenem-resistant Enterobacteriaceae.

SOURCE: Woodworth KR, Walters MS, Weiner LM, et al. Vital Signs: Containment of novel multidrug-resistant organisms and resistance mechanisms — United States, 2006-2017. MMWR Morb Mortal Wkly Rep 2018;67:396-401.

Woodworth and colleagues examined the trend in incidence of isolation of Enterobacteriaceae (focusing on Escherichia coli and Klebsiella pneumoniae) with an ESBL phenotype as evidenced by resistance to an extended spectrum (“third generation”) cephalosporin, or of Enterobacteriaceae resistant to an anti-pseudomonal carbapenem (CRE). They used data from the National Healthcare Safety Network from 2006-2015.

During that time, the proportion of Enterobacteriaceae with an ESBL phenotype decreased by approximately 2% each year, although in short-term acute care hospitals, the proportion remained stable among E. coli and K. pneumoniae, starting at 16.7% in 2006 and ending at 18.9% in 2015. (See Figure 1.) In contrast, the proportion of those with a CRE phenotype decreased by 15% annually during the same period. (See Figure 2.)

Testing for the presence of five carbapenemases was performed on 4,442 CRE isolates from January 2017 to September 2017 as well as 1,334 carbapenem-resistant Pseudomonas aeruginosa (CRPA). A carbapenemase was detected in 32% of CRE (65% of CRE K. pneumoniae) and in 1.9% of CRPA. KPC accounted for 88% of carbapenemases in CRE, while among the 25 CRPA, VIM was present in 72%.

A study of a median of 10.5 contacts in the healthcare setting of patients with CRE found that 11% of the contacts were colonized with a CRE carrying one of five carbapenemases; this proportion was higher in post-acute care facility contacts (14%) than in short-stay acute care hospitals (5.8%).

COMMENTARY

These results provide clear evidence of a decreased incidence of CRE from 2006-2015 but a much lesser improvement in incidence of ESBL phenotype Enterobacteriaceae. Woodworth and colleagues suggested that these differing results are the consequence of the more extensive control efforts directed at CRE than ESBL-producing organisms. Thus, the CDC developed CRE-specific guidance in 2009 (and subsequently updated them twice and also published an extensive report on the subject) for healthcare facilities that identified the presence of CRE with recommendations that included laboratory surveillance and targeted screening for asymptomatic colonization. Finally, in 2017, the CDC outlined a rapid reaction approach to the detection of even a single isolate of an emerging antibiotic-resistant pathogen. This approach, as summarized by Woodworth et al, rests upon the following:

  • Rapid detection of targeted organisms and determination of their resistance mechanisms;
  • On-site assessment to identify gaps in infection prevention;
  • Identification of asymptomatic colonization by contact screening;
  • Coordination of response among relevant facilities;
  • Continuation with these interventions until any transmission is controlled.

These efforts are now also CDC-supported by establishment of the Antibiotic Resistance Laboratory Network, which provides testing for carbapenemases in CRE and CRPA at 56 state and local public health laboratories as well as screening for colonization at seven regional laboratories.

Of the carbapenemase-positive isolates, 65% of which were K. pneumoniae, 221 expressed a carbapenemase other than KPC, and these included the metallo-β-lactamases NDM, VIM, and IMP. The presence of even small numbers of metallo-β-lactamases (VIM, NDM) is of concern, given their resistance to the currently commercially available β-lactamase inhibitors, including avibactam.

Despite this, the report reviewed here provides evidence that directed attention to an emerging problem of antibiotic resistance can provide significant improvement. Now we need even more of such efforts.

 

Figure 1: Percentage of ESBL-phenotype Escherichia coli and Klebsiella pneumoniae Causing Central Line-associated Bloodstream and Catheter-associated Urinary Tract Infections

Figure 1

Source: Centers for Disease Control and Prevention

 

Figure 2: Percentage of CRE Escherichia coli and Klebsiella pneumoniae Causing Central Line-associated Bloodstream and Catheter-associated Urinary Tract Infections

Figure 2

Source: Centers for Disease Control and Prevention