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Antimicrobial resistance in nephrology

Abstract

The prevalence of antimicrobial resistance among many common bacterial pathogens is increasing. The emergence and global dissemination of these antibiotic-resistant bacteria (ARB) is fuelled by antibiotic selection pressure, inter-organism transmission of resistance determinants, suboptimal infection prevention practices and increasing ease and frequency of international travel, among other factors. Patients with chronic kidney disease, particularly those with end-stage renal disease who require dialysis and/or kidney transplantation, have some of the highest rates of colonization and infection with ARB worldwide. These ARB include methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus spp. and several multidrug-resistant Gram-negative organisms. Antimicrobial resistance limits treatment options and increases the risk of infection-related morbidity and mortality. Several new antibiotic agents with activity against some of the most common ARB have been developed, but resistance to these agents is already emerging and highlights the dire need for new treatment options as well as consistent implementation and improvement of basic infection prevention practices. Clinicians involved in the care of patients with renal disease must be familiar with the local epidemiology of ARB, remain vigilant for the emergence of novel resistance patterns and adhere strictly to practices proven to prevent transmission of ARB and other pathogens.

Key points

  • Infections caused by antibiotic-resistant bacteria (ARB) are associated with higher mortality, longer hospitalization and a greater economic burden than those caused by antibiotic-susceptible bacteria of the same species.

  • The growing global burden of antimicrobial resistance is particularly relevant to patients with chronic kidney disease who are disproportionally affected by antimicrobial resistance when compared with the general population.

  • Consistent implementation of basic infection prevention strategies is a crucial element in the effort to prevent transmission of and infection by ARB.

  • Critical infection prevention practices include hand hygiene, cleaning and disinfection of the environment and medical equipment, and use of evidence-based practices for insertion, use and maintenance of invasive devices.

  • Novel mechanisms of antimicrobial resistance continue to emerge and spread, leading to infections that are difficult to treat and highlighting the need for development of new antimicrobial agents.

  • Antimicrobial treatment of ARB infections is a complex and evolving topic. Consultation with an infectious disease specialist should be considered in order to optimize antimicrobial agent selection and patient outcomes.

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Fig. 1: Mechanisms of action of antibacterial agents and of antibacterial resistance.
Fig. 2: Global prevalence of resistance of Enterococcus faecium to vancomycin.
Fig. 3: Estimated global prevalence of ESBL-producing Escherichia coli.
Fig. 4: Geographic distribution of carbapenemases in Enterobacteriaceae.

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Acknowledgements

T.Z.W. was supported by US National Institutes of Health, National Institute of Allergy and Infectious Disease grant T32 A1007613.

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Nature Reviews Nephrology thanks P. Tambyah and the other anonymous reviewer(s) for their contribution to the peer review of this work.

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All authors researched data for the article, contributed substantially to the discussion of content and wrote the manuscript. R.P.L.K. and D.P.C. also reviewed and edited the manuscript before submission.

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Glossary

Infections

Disease states produced by a microorganism that may be symptomatic or asymptomatic.

Multidrug resistant

(MDR). Non-susceptibility to at least one agent in three or more antimicrobial categories to which an organism does not possess intrinsic resistance.

Extensively drug resistant

Non-susceptibility to at least one agent in all but two or fewer antimicrobial categories to which an organism does not possess intrinsic resistance.

Pandrug resistant

Non-susceptibility to all agents in all antimicrobial categories to which an organism does not possess intrinsic resistance.

Colonization

The asymptomatic presence of a microorganism on or within the body.

Conjugation

Direct transfer of genetic material between bacterial cells.

Transformation

Acquisition of new genetic material (DNA) via uptake from the environment.

Transduction

Transfer of bacterial DNA from one bacterium to another via a viral vector.

Invasive MRSA infections

MRSA infections within a normally sterile body site, such as the blood.

Vancomycin-intermediate S. aureus

(VISA). An isolate of Staphylococcus aureus that exhibits an elevated minimum inhibitory concentration (MIC) for vancomycin but that does not reach the MIC considered to represent full resistance to vancomycin.

Heteroresistant or heterogeneous VISA

(hVISA). Subpopulations of Staphylococcus aureus with reduced susceptibility present among a larger population of fully susceptible organisms.

Drug efflux pumps

Proteins in the bacterial cell membrane that transport a drug, such as an antibiotic, out of the cell.

Haematogenous osteomyelitis

Infection of bone that results from inoculation of the bone by microorganisms present in the bloodstream.

Vesicoureteral reflux

Abnormal retrograde flow of urine from the urinary bladder into the ureter and, possibly, the kidney.

Ureterovesical junction stenosis

Narrowing at the site where the ureter enters the urinary bladder that may obstruct the flow of urine from the kidney into the bladder.

Neurogenic bladder

Dysfunction of the urinary bladder due to neurological damage.

Therapeutic drug monitoring

Measurement of medication concentrations in blood at specified time intervals in order to optimize treatment effectiveness and/or minimize toxicity.

Arteriovenous fistulas

(AVFs). Surgically created connections between an artery and a vein used for vascular access for haemodialysis.

Contact precautions

Interventions used to reduce the risk of transmission of organisms transmitted by contact with the affected patient and their environment.

Antibiotic selection pressure

Reduction or elimination of bacteria that are susceptible to an administered antibiotic, allowing antimicrobial-resistant bacterial populations to gain a survival advantage and thus become predominant members of the microbiota.

Antimicrobial stewardship

A set of coordinated strategies to improve the use of antimicrobial medications with the goal of enhancing patient health outcomes, reducing resistance to antibiotics and decreasing unnecessary costs.

Endogenous pathogens

Organisms that are part of the normal microbiota but that in some circumstances can cause symptomatic infection.

Colonization resistance

The ability of the body’s microbiota, such as commensal gut bacteria, to prevent colonization and infection with pathogenic organisms.

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Wang, T.Z., Kodiyanplakkal, R.P.L. & Calfee, D.P. Antimicrobial resistance in nephrology. Nat Rev Nephrol 15, 463–481 (2019). https://doi.org/10.1038/s41581-019-0150-7

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