Surveillance and GP Resistance Mechanisms

Question 1

Q: What factors make antibiotic resistance complex?

Answer 1

Single drugs can be inactivated by multiple resistance mechanisms.

Organisms may use various mechanisms to resist a single drug and different drug classes.

Resistance genes are often on mobile genetic elements like plasmids or phages.

Resistance can spread between bacterial species, genera, and families

Question 2

What are the goals of WHO’s Global Action Plan on AMR (May 2015)?

Answer 2

Improve awareness and understanding of AMR through education, communication, and training.

Strengthen the evidence base via surveillance and research.

Reduce infections with effective sanitation, hygiene, and IPC measures.

Optimize antimicrobial use in humans and animals.

Increase sustainable investment in new medicines, diagnostics, and vaccines.

Question 3

What approaches and systems support the fight against AMR?

Answer 3

One Health approach integrating human, animal, and environmental health.

Global Antimicrobial Resistance and Use Surveillance System (GLASS).

Question 4

Key AMR Organisms (“The Naughty List”)

Answer 4

Methicillin-Resistant Staphylococcus aureus (MRSA)

Vancomycin-Resistant Enterococci (VRE)

Extended-Spectrum Beta-Lactamase (ESBL)-producing Gram-negative bacteria

Carbapenemase-Producing Enterobacterales (CPE)

Carbapenemase-Producing Organisms (e.g., Pseudomonas, Acinetobacter)

Question 5

What trends in healthcare-associated infections (HCAIs) are notable?

Answer 5

Increasing resistance in S. pneumoniae, N. gonorrhoeae, Shigella, and TB (e.g., XDR TB).

Resistance crossing from healthcare to community settings (e.g., MRSA, CPE)

Question 6

What are some of the main surveillance systems?

Answer 6

EARS-NET
iNAP2

Question 7

What is EARS-Net, and what does it monitor?

Answer 7

European Antimicrobial Resistance Surveillance System, renamed in 2010.

Tracks AMR trends in eight pathogens (e.g., E. coli, S. aureus, S. pneumoniae).

Initially focused on S. aureus and S. pneumoniae, now includes 30 EU/EEA countries.

Question 8

What is iNAP2?

Answer 8

Ireland’s Second National Action Plan on AMR (2021-2025).

Focus areas: stewardship, surveillance, and funding (2.2 million euros).

New AMRIC division for enhanced surveillance.

Question 9

How does surveillance data support AMR control?

Answer 9

Tracks emergence and spread of AMR phenotypes.

Informs policymakers and evaluates intervention effects.

Collected locally via WHONET, BacLink, or LIMS systems.

Question 10

Q: What are key strategies to address AMR?

Answer 10

Education and awareness.

Infection prevention and control (IPC).

Judicious use of antibiotics.

Increased investment in research.

Implementation of One Health approaches.

Question 11

Q: Outline the evolution and spread of MRSA.

Answer 11

Emerged in the 1960s and peaked at 42% prevalence in Ireland by 2006.

Community-Associated MRSA (CA-MRSA) emerged in the 1990s, showing high virulence and less antibiotic cross-resistance compared to healthcare-associated strains.

Livestock-Associated MRSA (LA-MRSA) identified as a rising threat.

Ireland’s MRSA prevalence declined to 9.7% in 2023, with the EU/EEA weighted mean at 16.7%.

CA-MRSA outbreaks reported in schools, sports teams, and community groups.

Question 12

What did MRSA peak at at when in ireland

Answer 12

42% in 2006

Question 13

What is MRSA at in 2023 in ireland, how does this compare to eu average

Answer 13

9.7%

Below eu average of 16.7%

Question 14

How does MRSA develop resistance to methicillin?

Answer 14

mecA/mecC genes produce PBP2a, reducing beta-lactam affinity.

Heterogeneous resistance: mecA expression in only a subset of cells.

Resistance genes are located on the staphylococcal chromosomal cassette mec (SCCmec), a mobile genetic element.

Question 15

What mechanisms lead to glycopeptide resistance in MRSA?

Answer 15

VISA:
- Thickened, poorly cross-linked cell wall traps vancomycin.
- Overproduction of D-Ala-D-Ala precursors reduces binding efficacy.
- Mutations in regulatory systems like WalKR contribute to structural changes.

Question 16

What mechanisms lead to glycopeptide resistance in MRSA?
(VRSA)

Answer 16

Horizontal transfer of vanA gene alters peptidoglycan precursors from D-Ala-D-Ala to D-Ala-D-Lac.

Rare but significant clinical concern due to high-level resistance

Question 17

How is MRSA detected in labs?

Answer 17

Screening:
- Chromagar for nasal, groin, or axillary samples.

Phenotypic tests:
- Cefoxitin MIC >4 mg/L or zone <22 mm (disk diffusion).
- Latex agglutination for PBP2a detection.

Genotypic methods:
- PCR for mecA/mecC genes.

Question 18

Q: What are the resistance mechanisms in VRE?

Answer 18

Intrinsic resistance via altered PBPs.

Acquired resistance:
- vanA: High resistance to vancomycin and teicoplanin.
- vanB: Resistance to vancomycin but susceptibility to teicoplanin

Question 19

What clinical and epidemiological trends are notable for VRE?

Answer 19

VRE emerged in 1990 and remains a major nosocomial pathogen.

Resistance to fluoroquinolones, aminoglycosides, macrolides, and linezolid.

High prevalence of multidrug-resistant (MDR) strains, with 58.8% of invasive isolates resistant to two or more antimicrobial groups.

Decline in Irish VRE prevalence from 38.6% (2019) to 21.4% (2023), lowest since 2008.

EU/EEA average VREfm prevalence at 16.8%, with rising trends in Eastern Europe.

Question 20

When did VRE emerge?

Answer 20

1990

Question 21

What is VRE resistant against

Answer 21

fluoroquinolones
Aminoglycosides
Macrolides
Linezolid

Question 22

Comment on MDR in VREfm

Answer 22

58.8% of invasive VRE isolates are MDR i.e. are resistant to two or more antimicrobial classes

Question 23

When was VREfm at its highest in ireland

Answer 23

Irish VRE prevalence was 38.6% (2019)

Question 24

How does Ireland VREfm compare to eu average

Answer 24

in 2023 VRE stands at 21.4%
This is the lowest since 2008

Question 25

What VRE in particular are we most concerned with in europe

Answer 25

VREfm ->E. faecium
Prevalence of 16.8% with trends rising in eastern europe in particular

Question 26

Q: How is VRE detected?

Answer 26

Screening:
- Chromagar for rectal swabs.

Confirmation:
- Real-time PCR for vanA/vanB genes.

EUCAST methods:
- MIC determination: VanA MIC >64 mg/L indicates high-level resistance.
- Disk diffusion: Vancomycin 5 µg zone <12 mm indicates resistance.

Question 27

How does S. pneumoniae develop resistance to penicillin?

Answer 27

Altered PBPs (e.g., PBP2x, PBP2b, PBP1a) from mutations or horizontal gene transfer reduce beta-lactam binding.

Question 28

Q: What are lab methods for detecting penicillin non-susceptible S. pneumoniae (PNSP)?

Answer 28

Oxacillin disk diffusion: Susceptible strains reported as penicillin susceptible.

MIC testing for penicillin and cefotaxime confirms non-susceptibility.

Question 29

Q: What trends are notable in S. pneumoniae resistance?

Answer 29

AMR to multiple drug classes is common, often linked to mobile genetic elements like transposons.

Incidence of invasive isolates increased in 2023 compared to 2021, reflecting a return to pre-COVID infection rates.

In Ireland, Penicillin Non-Wild Type (PenNWT) strains decreased to 17.5% in 2023 from 23.6% in 2022.