A trait of the bacterial Genus/species. ALL members in the Genus/species are resistant. ^[1]

Why does intrinsic resistance exist? The organism may lack the target, exclude the drug, pump it out or constitutively inactivate it. It is a predictable species phenotype rather than a resistance event newly acquired by that isolate.

Expanded intrinsic resistance examples (from a 2001 table reproduced in the deck): ^[1]

Some intrinsic resistance can be difficult to detect and may require special laboratory techniques. ^[1]

Clinical implication: The lab should never report susceptibility for intrinsically resistant combinations. If such a result appears, it is edited to "resistant." This is called interpretive reading of susceptibility data. ^[1]

EUCAST expert rules assist clinical microbiologists by recommending: suppression of inappropriate results, editing susceptible to intermediate or resistant based on inferred resistance mechanisms, and listing intrinsic and exceptional resistance phenotypes. The key teaching point: intrinsic resistance — do not test, and edit a false-susceptible result to resistant. ^[1]

Certain antibiotic/organism combinations are prone to rapid mutational resistance developing DURING treatment. ^[1]

Why does this happen? When a large bacterial population is exposed to a single drug, spontaneous mutants with altered drug targets or upregulated efflux pumps have a survival advantage. The drug kills susceptible bacteria, selecting for the resistant mutant (selective pressure).

Lecture-era implication: avoid an agent when resistance is likely to emerge rapidly, and use a validated combination when the disease specifically requires it. The slide's “never use monotherapy” is not a universal rule.

Transposable elements are "jumping genes" with an ability to change their genomic or plasmid positions. ^[1]

This is the most clinically threatening mechanism because:

• Plasmids can carry multiple resistance genes simultaneously → a single transfer event can make a bacterium resistant to many drug classes at once
• Integrons can capture and express multiple resistance gene cassettes
• Transposons ("jumping genes") can insert into chromosomes or plasmids, spreading resistance within and between species
• Transfer occurs via conjugation (plasmid transfer via pilus), transformation (uptake of free DNA), or transduction (bacteriophage-mediated)

This is why ESBL-producing E. coli often show co-resistance to cotrimoxazole, fluoroquinolones, and aminoglycosides—the resistance genes travel together on the same mobile genetic element. ^[1]

How to read the gene-transfer figures

• The integron cartoon shows an integrase (intI), an attachment site and a promoter that captures and expresses resistance-gene cassettes.
• A transposon can move a resistance determinant between chromosome and plasmid.
• Slide 11's long IncA/C plasmid is not a decorative genome strip: the arrows identify several resistance loci packaged beside transfer machinery. Conjugation moves the whole plasmid, so one encounter may transmit a multidrug phenotype rather than one isolated resistance gene.

Detection of inducible clindamycin resistance in Streptococcus and Staphylococcus aureus – the D-test. ^[1]

The mechanism: Some staphylococci and streptococci carry the erm gene, which encodes methylation of the 23S ribosomal RNA. This methylation confers resistance to MLS_B antibiotics (Macrolides, Lincosamides, Streptogramin B). In some strains, this gene is inducible—it is only "switched on" when a macrolide (e.g., erythromycin) is present. Such strains appear erythromycin-resistant but clindamycin-susceptible on standard disc testing.

The D-test: Place an erythromycin disc adjacent to a clindamycin disc. If the clindamycin zone is flattened on the side facing erythromycin (forming a "D" shape), the erm gene is inducible → clindamycin will fail clinically → report as erythromycin-R, clindamycin-R, D-test positive. ^{[1] [2]}

If no flattening occurs → true clindamycin susceptibility → report as erythromycin-R, clindamycin-S, D-test negative. ^[1]

The lecture presents a concentric model of AMR ecosystems with increasing selection pressure: ^[1]

The lecture illustrates how AMR organisms overlap across hospitals, community, and food-producing animals, with horizontal transfer of resistance genes spanning all three: ^[1]

• Hospital-predominant: P. aeruginosa, A. baumannii
• Shared across hospital + community + food animals: E. coli, VRE, C. difficile, MRSA, Salmonella, Campylobacter
• Community-predominant: S. pneumoniae, H. influenzae

This overlap explains why interventions in only one sector are insufficient — resistance genes flow bidirectionally between reservoirs.

The slide's provocative line—“multi means one critically important class”—describes an operational MDRO label, not the formal MDR phenotype. ^[1]

For healthcare epidemiology, CDC defines an MDRO as a microorganism resistant to one or more antimicrobial classes; therefore named organisms such as MRSA or VRE can qualify. By contrast, the widely used acquired-resistance terminology defines MDR as non-susceptibility to at least one agent in at least three relevant antimicrobial categories. Always state which definition and organism-specific panel you are using. ^[11]

Historical communication statistic (2013–2016): “1 superbug every 17 minutes; 1 blood infection every 3 hours.” The numerator includes all clinical isolates and therefore is not equivalent to symptomatic infection. ^[1]

Extended HA snapshot (2013–2016) — additional MDROs tracked: ^[1]

A group of enzymes produced by some Enterobacteriaceae: E. coli, Klebsiella pneumoniae, Proteus, Enterobacter, Shigella, Salmonella. ^[1]

What do ESBLs do? They hydrolyze the β-lactam ring of cephalosporins (including 3GC like ceftriaxone) and monobactams (aztreonam), rendering them ineffective. ESBLs are typically plasmid-mediated (TEM, SHV, CTX-M types), meaning they spread horizontally.

Why is ESBL a problem beyond cephalosporin resistance?

ESBL organisms are often multidrug-resistant – co-resistant to cotrimoxazole (Septrin), fluoroquinolones (levofloxacin, ciprofloxacin), and aminoglycosides (gentamicin). ^[1]

This is because the same plasmid carrying the ESBL gene often carries resistance genes for other drug classes.

For invasive ESBL-E infection outside the urinary tract, current IDSA guidance generally prefers meropenem, imipenem-cilastatin or ertapenem; critical illness/hypoalbuminaemia favours meropenem or imipenem-cilastatin. Uncomplicated cystitis and selected urinary infections have different active options, so “all ESBL = carbapenem” is too broad. ^[8]

Epidemiology:

Half of the in-patient ESBL burden occurs in aged ≥75 years. There has been a 3× increase in ESBL-EC from 2003 to 2016 in the HKW cluster, with seasonal surges. ^[1]

The slide calls A. baumannii “less virulent,” but this is too dismissive: CRAB causes severe ventilator-associated pneumonia, bloodstream, wound and other healthcare-associated infections in vulnerable hosts. Colonisation must still be distinguished from infection.

Key features:

• Acquired resistance occurs readily DURING treatment (a consequence of the organism's ability to rapidly incorporate resistance genes)
• Carbapenem WAS the treatment of choice before widespread resistance emerged
• Some isolates are resistant to polymyxins, but the therapeutic landscape is no longer simply “colistin or nothing.” ^[1]

Surveillance definitions:

• CRAB = Carbapenem-resistant A. baumannii
• MRAB = Multidrug-resistant A. baumannii (definition not standardized)

MDR/XDR/PDR classification (proposed but not standardized):

For current CRAB treatment, IDSA 2024 prefers sulbactam-durlobactam plus imipenem-cilastatin or meropenem where available; high-dose ampicillin-sulbactam plus another active agent is an alternative when it is unavailable. CRE therapy should be selected by carbapenemase mechanism and susceptibility, not reflexive colistin. ^[8]

Visual disease burden in the slides

• The MRSA montage links colonisation to invasive syndromes: wound/prosthetic-joint infection, vertebral osteomyelitis, septic arthritis, line infection and endocarditis (vegetation on echocardiography).
• The influenza A/H1N1 case shows bilateral air-space disease and, histologically, diffuse alveolar damage plus bacterial suppuration—recognise post-influenza necrotising S. aureus pneumonia as a rapidly progressive emergency.
• The CA-MRSA bar chart rises from 173 cases in 2007 to a peak around 2017–2019, then falls during COVID-era ascertainment. It is historical surveillance; the drop does not prove organism disappearance.

The historical workflow was roughly: incubation to positivity → subculture/identification → phenotypic susceptibility, sometimes taking several days. MALDI-TOF can identify an isolated colony rapidly, but rapid identification is not the same as rapid susceptibility. Direct molecular tests may detect selected genes; phenotypic AST still tells whether the complete organism–drug combination is active. ^[1]

This statistic is sobering. It means that for many patients, the definitive answer about which antibiotic to use arrives too late. This is precisely why empirical antibiotic therapy—educated guessing based on the site of infection, likely organisms, and local resistance data—is essential.

F/20y university student with progressive community-acquired pneumonia despite antibiotics. ^[1]

• Failed to respond to initial therapy (likely macrolide)
• Given doxycycline → rapid resolution
• NPA PCR positive for M. pneumoniae; serology: < 10 (D5) → 1280 (D21) (diagnostic 4-fold rise)
• Macrolide resistance marker found: A2063G mutation ^[1]

The deck reports 40% macrolide resistance in a 2013 Hong Kong inpatient cohort. Preserve the date and population; resistance varies sharply by place and time. ^[1]

The problem of limited treatment options:

The lecture-era “no safe option” conclusion is too absolute. CDC 2026 advises considering doxycycline when confirmed/suspected M. pneumoniae is not improving on a macrolide, while accounting for paediatric and pregnancy adverse effects; most infections are self-limiting. The FDA also abolished the old A/B/C/D/X pregnancy letter categories, so the slide's B/C/D table is obsolete. ^{[15] [16]}

The severe white-out case has a large left pleural collection compressing the lung, with gas/loculations on CT—recognise complicated parapneumonic effusion/empyema requiring source control. β-lactams such as amoxicillin-clavulanate and cefepime are intrinsically inactive against cell-wall-free Mycoplasma; failure does not demonstrate acquired resistance. Recovery after doxycycline plus decortication cannot be attributed to doxycycline alone. ^[15]

F/35y with a boil for 2 days, progressing despite oral cloxacillin for 5 days. ^[1]

• Cloxacillin targets MSSA → ineffective against MRSA
• CA-MRSA should be suspected when SSTI fails standard antistaphylococcal therapy
• CA-MRSA remains susceptible to cotrimoxazole and minocycline (> 95%) ^[1]
• The images progress from a tender erythematous boil to a purulent necrotic centre. This is a source-control problem: drain/culture an abscess and assess systemic severity; do not infer CA-MRSA from appearance alone.

2-year-old with fever, cough, and SOB, given azithromycin (Zithromax) by GP for 3 days without improvement. ^[1]

• HKW cluster data shows high rates of erythromycin resistance in S. pneumoniae (used as an indicator for macrolide resistance to clarithromycin and azithromycin) ^[1]
• The radiograph shows near-complete left hemithorax opacification; CT demonstrates a large, partly loculated pleural collection with compressed lung. The core lesson is complicated pneumonia/empyema after macrolide monotherapy, requiring drainage plus guideline-concordant antibacterial therapy—not merely “choose a stronger tablet.”

Macrolide resistance rates for streptococci by age group (HKW cluster, 2014–2018): ^[1]

Erythromycin was tested and used as an indicator for resistance to clarithromycin and azithromycin. S. pneumoniae macrolide resistance exceeds 70% across all age groups in HKW*, reinforcing that macrolides should not be used as monotherapy for pneumococcal infections. ^[1]

The Hong Kong Strategy and Action Plan on Antimicrobial Resistance (2017–2022) is structured around 6 key areas ("619 — 6 key areas, 19 objectives"): ^[1]

1. Strengthen knowledge through surveillance and research
2. Optimise antimicrobial use in humans and animals
3. Reduce incidence of infection through effective sanitation, hygiene, and prevention measures
4. Improve awareness and understanding of AMR through communication, education, and training
5. Promote research on AMR
6. Strengthen partnerships and foster engagement of relevant stakeholders

Selected objectives include: setting up One Health AMR surveillance, building laboratory capacities, strengthening OTC purchase controls, enhancing antimicrobial stewardship programmes (ASP) across outpatient/inpatient/dental settings, strengthening IPC training for healthcare workers, enhancing influenza and pneumococcal vaccine uptake, and including AMR in school curricula and CME. ^[1]

The slide shows the fifth edition of IMPACT and an old mobile app. Treat it as a signpost to the programme, not proof that that edition/app remains current; use the latest HA/local guideline available at the point of care. ^[1]