These are gram-negative bacteria that are resistant to at least one antimicrobial in three or more antimicrobial classes (antipseudomonal penicillins, third-generation cephalosporins, fluoroquinolones, carbapenems, and aminoglycosides).

Carbapenem-resistant Enterobacteriaceae (CRE)

Extended-spectrum beta-lactamases (ESBL)

Multidrug-resistant gram-negative bacilli (MDR-GNB)

Multidrug-resistant organisms (MDRO)

New Delhi metallo-beta-lactamase-1 (NDM-1)

All these resistant bacteria have the capability of causing diverse infections, including:

• Pneumonia
• Bacteremia
• Urinary tract sepsis
• Central line-associated infections
• Ventilator-associated pneumonia (VAP)
• Surgical site infections
• VAP from A. baumannii now accounts for 8.4% of GNR pneumonias in the ICU

• Several different classes of MDR-GNRs exist based on their resistance mechanism.
  1. ESBL: These bacteria contain enzymes that break open the beta-lactam ring of penicillins, cephalosporins, and aztreonam and thus inactivate antibiotics from those classes. Enzymes conferring resistance include:
     1. TEM beta-lactamases
     2. SHV beta-lactamases
     3. CTX-M beta-lactamases
     4. OXA beta-lactamases
     5. These enzymes are plasmid-mediated and thus can spread from one gram-negative bacteria to another, causing outbreaks in a single institution
  2. CRE: Enzymes conferring resistance include:
     1. Class A beta-lactamases: Encoded on chromosomes or plasmids (e.g., Klebsiella pneumoniae carbapenemase [KPC], which has caused outbreaks in hospitals around the world)
     2. Class B: Metallo-beta-lactamases (e.g., NDM-1). Encoded on a mobile plasmid that can spread to other gram-negative bacteria
     3. Class C and class D beta-lactamases
  3. MCR-1 gene: In May 2016, the MCR-1 gene was reported for the first time in E. coli from a patient (urine culture) in the U.S. This gene makes bacteria resistant to the antibiotic colistin, which is used to treat other MDR-GNR organisms. This raises the concern that this plasma-encoded gene could be spread to CRE bacteria.
• Stenotrophomonas maltophilia: MDR-GNR that acts as an opportunistic pathogen among mostly hospitalized patients with high morbidity and mortality. It has intrinsic or acquired resistance mechanisms to multiple antibiotic classes and has the ability to adhere to foreign materials and form a biofilm, which escapes host defenses.
• Acinetobacter sp. (e.g., Acinetobacter baumannii): Strains have emerged that are resistant to all commercially available antibiotics. These bacteria have the capability to acquire diverse mechanisms of resistance including:
  1. AmpC beta-lactamases
  2. Beta-lactamases: Serine and metallo-beta-lactamases

Other gram-negative rods such as:

• Pseudomonas aeruginosa
• Klebsiella pneumoniae that are not ESBL or CRE by resistance pattern
• Morganella morganii
• Providencia, Proteus sp., Serratia

• Detection of ESBL and CRE bacteria can pose problems for the clinical microbiology laboratory:
  1. To detect ESBL bacteria: Automated systems such as Vitek 2 disk diffusion or broth dilution techniques, or double disk test or E-test strip with clavulanate.
  2. To detect CRE: Modified Hodge test to detect carbapenemase-producing bacteria. Polymerase chain reaction testing, pulsed-field gel electrophoresis, and whole genome sequencing are useful for detecting CRE.
  3. In 2010, testing guidelines with respect to susceptibility involving several beta-lactam antibiotics were changed to better identify these bacteria via automated systems.

Clinical testing is the same in infections from these resistant organisms as with nonresistant organisms:

• Cultures of any wounds, blood, sputum, urine, catheter tips
• CBC, liver function tests, urinalysis

• Morbidity and mortality can be quite high with infections from these MDR bacteria.
  1. Nosocomial Acinetobacter pneumonia carries a mortality rate of 35% to 70%.
  2. Stenotrophomonas infections carry a mortality rate of 21% to 69%.
  3. ESBL infections carry a mortality rate of 3.7% despite therapy with carbapenem antibiotics.