Overview of multidrug-resistant gram-negative bacteria

Infectious Diseases Society of America (IDSA), 2023Paul, 2022

Gram-negative bacteria commonly cause biliary tract, intra-abdominal and urinary tract infections. They can also cause post-traumatic wound infections, bloodstream infections and sepsis. A range of other infections (eg pneumonia, osteomyelitis) may be caused by gram-negative bacteria, but this is less common. The incidence of infections caused by multidrug-resistant gram-negative bacteria is increasing in Australia and, even more so, overseasAustralian Commission on Safety and Quality in Health Care (ACSQHC), 2013Norgaard, 2019. Gram-negative bacteria that may develop resistance to multiple antibiotics include the Enterobacterales (eg Escherichia coli, Klebsiella species, Enterobacter cloacae complex), Acinetobacter baumannii and Pseudomonas aeruginosaNorgaard, 2019.

Antibiotic resistance can be intrinsic or acquired.

Intrinsic resistance describes predictable patterns of resistance related to cell structure or function (eg reduced permeability of cell membranes to some antibiotics, upregulation of efflux pumps). Intrinsic resistance can often guide therapy as soon as the organism is known (eg Pseudomonas species are resistant to ceftriaxone) and usually does not mandate additional infection control precautions.

Acquired resistance describes resistance mechanisms that can be transmitted from one bacterium to another (eg via a plasmid that encodes a beta-lactamase or carbapenemase enzyme). The likelihood that a bacterium has acquired resistance depends on the prevalence of transmissible resistance in the local environment (ie local epidemiology) and patient factors (eg antibiotic exposure contributing to expression of resistance genes). As such, acquired resistance may be less predictable (eg E. coli may not be suspected to be carbapenemase producing until susceptibility results are confirmed). Additionally, because acquired resistance can be transmitted to other bacteria, additional infection control precautions may be required.

This topic includes:

Predictable resistance (eg intrinsic resistance of P. aeruginosa to ceftriaxone) is beyond the scope of this topic but is addressed, when appropriate, in the relevant clinical topics.

For a general discussion of antimicrobial resistance and identification of organisms of concern, see An overview of antimicrobial resistance.

Figure 1. Risk factors for infection with a multidrug-resistant gram-negative bacterium

Australian Commission on Safety and Quality in Health Care (ACSQHC), 2013Wilson, 2016

A patient with one or more of the risk factors below is at increased risk of infection with a multidrug-resistant gram-negative bacterium (such as an ESBL- or carbapenemase-producing organism). However, a patient at increased risk will not necessarily be infected or colonised with a resistant bacterium.

Consider whether to modify empirical therapy for the individual patient, taking into account the severity of infection. Culture results are particularly important to guide ongoing therapy.

Risk factors for infection with a multidrug-resistant gram-negative bacterium include:

  • recent stay in hospital or a long-term care facility (eg within 6 months) in a country with a high prevalence of multidrug-resistant gram-negative bacteria [NB1] [NB2]
  • recent stay in an Australian or overseas hospital or a long-term care facility (eg within 6 months) with a known outbreak of multidrug-resistant gram-negative bacteria [NB2]
  • recent overseas travel (eg within 6 months) to an area with a high prevalence of multidrug-resistant gram-negative bacteria, particularly if associated with antibiotic use or medical care [NB2]
  • previous colonisation or infection with a multidrug-resistant gram-negative bacterium, particularly if recent or associated with the current episode of care
  • frequent stays, or a current prolonged stay, in a hospital with a high prevalence of multidrug-resistant gram-negative bacteria, particularly if associated with antibiotic exposure
  • residence in an aged-care facility with a high prevalence of multidrug-resistant gram-negative bacteria, particularly if the patient has had multiple courses of antibiotics.

Local policies should address the role of routine rectal screening in patients with risk factors for multidrug-resistant gram-negative bacteria.

Note:

ESBL = extended-spectrum beta-lactamase

NB1: This risk factor is associated with the highest risk of infection with a multidrug-resistant gram-negative bacterium.

NB2: This risk factor also applies in neonates born to mothers with this risk factor.