Carbapenem-resistant

enterobacteriaceae: An Urgent Threat

Amber Miller, Pharm.D.

PGY1 Pharmacy Resident, Sentara Healthcare

 

 

Carbapenem-resistant enterobacteriaceae (CRE) refers to a family of bacteria that has conferred resistance to multiple antimicrobials, including most beta-lactams and carbapenems. Since the first documented case in the United States in 2001, there has been a rapid increase in CRE prevalence.  It is estimated that around 9,000 health-care associated infections per year are a result of CRE with a mortality rate of up to 50% in patients with CRE bacteremia. ¹ The Centers for Disease Control and Prevention (CDC) has classified CRE as an "urgent threat", indicating that these multi-drug resistant infections are of high-consequence and are associated with significant risk and mortality. The CDC has made the identification and reduction of transmission of CRE an urgent public health priority. ²

 

CRE can be categorized based on two major types of resistance mechanisms: carbapenemase-producing (CP-CRE) and non-carbapenemase-producing (NCP-CRE). CP-CRE develops as a result of enzymes that are able to hydrolyze the beta-lactam ring portion of the carbapenem structure, therefore inactivating its antimicrobial properties. Examples of carbapanemases include the klebsiella pneumoniae carbapenemase (KPC), New Delhi Metallo-beta-lactamase (NDM), oxacillin-hydrolyzing beta-lactamase (OXA), and Verona integrin-encoded metallo-beta-lactamase (VIM). KPC is significantly more common than the other carbapenemases in the United States and is unquestionably the enzyme of most concern due to its rapid transmission and increase in prevalence in recent years. ³ CP-CRE are considered to have plasmid-mediated resistance, which occurs when the resistance genes located on bacterial plasmids are transferred from one bacterial cell to another. This type of resistance is easily transferable between strains, species, patients and facilities, resulting in difficulty slowing and preventing the spread of CRE. ^{4, 5} The NCP-CRE is much less common and develops through other mechanisms, typically beta-lactamases (e.g., AmpC, ESBL) in combination with alterations in bacterial cell membrane (e.g., porin mutations). ³

 

Risk factors for developing CRE infections include residence at a long-term care facility, long-standing invasive lines and devices, extensive wound care, colonization with concurrent bacteria, recent use of a beta-lactam or fluoroquinolone, non-responding infections or signs of sepsis while on antimicrobial therapy, and immunocompromised individuals. ⁶ Patients can be solely colonized, indicating that CRE is present in the body and will grow on a culture but that the patient has no signs or symptoms of systemic involvement. Colonized CRE can progress to infection and transmission can still occur even if there is no active infection. Colonization, however, does not require antibiotic treatment. CRE infection refers to the presence of signs and symptoms of systemic or site-specific involvement. Patients with CRE infection should be treated appropriately based on available antimicrobial options and culture and sensitivity data. ⁷

 

Treatment options for CRE infections are limited due to the extent of antibiotics affected. It is important to note that available literature supporting the optimal treatment of CRE infections is largely collected from small, single-center case reports, case series, or retrospective cohorts. Large, randomized trials are needed to identify optimal antimicrobial regimen and dosing for these infections. Because of this reason, there may be minor differences in dosing recommendations in the primary literature. However, multiple meta-analyses and review articles agree on dosing regimens which are reviewed in articles by Petrosillo et al. and Morrill et al. ^{1, 8} A summary of the recommended dosing regimens can be found in Table 1.

VSHP Leadership Profile

What is your current leadership position in VSHP? President

 

 

What benefits do you see in being active in a professional association such as VSHP?  Ever since I was a student, I have seen the value of professional Pharmacy organizations. In addition to serving as the voice of the profession for legislative and regulatory issues, I have seen the value they provide to individual members with what is important to them, such as: networking, education, development, and job placement.

 

What initially motivated you to get involved in VSHP? I've been involved with VSHP since I was a student at VCU/MCV. When I moved back to Virginia in 2011, VSHP was in the midst of dramatic change. The organization demonstrated a commitment to representing me and my professional interests. Further, the networking and programming available through the Spring and Fall Seminars was extremely valuable to me. It made me feel like I had a professional home.

 

Where did you go to pharmacy school? VCU/MCV School of Pharmacy

 

Where have you trained or worked?  PGY1/PGY2 Combined Health System Pharmacy Administration/Master's Degree Residency Program at the University of Wisconsin Hospital and Clinics; Clinical and Operations Manager, University of Pittsburgh Medical Center (UPMC); Director, Pharmacy Services UPMC International and Commercial Services Division (Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione (ISMETT) in Palermo, Italy and UPMC Beacon Hospital in Dublin, Ireland); Assistant Professor, University of Pittsburgh School of Pharmacy; Assistant Dean, VCU School of Pharmacy-UVA Division; Administrator, Pharmacy Services, UVA Health System

 

Describe your current area of practice and practice setting: Academic Medical Center focusing on pharmacy practice administration

 

What advice would you give to student pharmacists? Take advantage of as many opportunities to learn and grow outside of classes as possible. Extracurricular professional organization involvement is a wonderful way for you to get the most out of the profession and your education.

 

What pharmacy related issues keep you up at night? Reimbursement issues and the rising costs of medications keep me up at night. These issues, coupled with the seemingly constant barrage of value proposition questioning regarding pharmacy services, have resulted in many sleepless nights.

 

Do you have any special interests or hobbies outside of work? My hobbies include: motorcycling, working with my hands, playing with my 5 year old son and my 2 year old daughter.

 

What is your favorite place to vacation? I prefer to vacation anywhere cellular service is not available.

 

What 3 adjectives would people use to best describe you?

I would say, handsome, smart and funny, but the student on rotation with me says: Accountable. Communicative. Approachable. She's probably more accurate.