Bugs and Drugs of Importance

Classification of clinically important bacteria: Gram-positive cocci (STAPHS AND STREPS )

Staphylococcus aureus two types: MSSA (meticillin susceptible) and MRSA (meticillin resistant)

-Streptococcus pyogenes (sore throat causing)

-Streptococcus Pneumoniae (cause of pneumonia)

-Strep. epidermis (contaminant)

-Enterococci (in the gut)(class of bacteria)

Classification of clinically important bacteria :Gram-negative cocci

-Neisseria two types: Neisseria gonorrhoeae and N. meningitidis

-Moraxella (class of bacteria)

Classification of clinically important bacteria: Gram-positive rods

-Listeria (in soft cheeses) (class of bacteria)

-Corynebacteria (class of bacteria)

-Bacillus cereus

Clostridioides Difficile

-Clostridiodies botulinum

-Clostridium tetani

-Clostridium perfringens

Classification of clinically important bacteria: Gram-negative rods (everything else)

E.coli

H.pylori

P.aeruginosa

Klebsiella pneumoniae

Proteus mirabilis

Salmonella

How do we tell the difference between gram positive and negative in vitro?

gram staining

Why do gram negative not hold on to the stain

gram negative have the outer cell wall

Gram negative cell wall structure

Why are gram negatives harder to treat

-Lipopolysaccharide chains on outside

-Outer and inner membrane = hard for antibiotics to penetrate

Whats the difference between aerobic vs anaerobic gram negative bacteria?

Aerobic:

-Require oxygen for growth (Obligate aerobes) OR can survive with & without oxygen (Facultative anaerobes)

-Use oxidative phosphorylation (aerobic respiration)

Anaerobic:

-Grow in low/no oxygen environments (Obligate anaerobes)

-Use fermentation or anaerobic respiration

what is the difference between rapid and fastidious aerobic gram negative bacteria?

-rapid grow quickly and easily - some of these ferment sugars

-Fastidious grow slower in special enriched conditions e.g. haemophilus

give an example of a non-fermenting gram-negative rapid bacteria?

Pseudomonas aeurinosa - hard to treat due to resistance mechanisms being developed

what are Pseudomonas' ( non-fermenting gram-negative rapid bacteria) resistance mechanisms?

-Produce enzymes that can activate beta lactams

-efflux pumps to pump drugs out

-Drug modifying enzymes within its cytoplasm

-often multi-drug resistant

give an example of a fermenting gram negative rapid bacteria?

Enterobacteriaceae

What is the difference between colonisation, infection and contamination

-Colonisation: organism is part of our microbiome

-Contamination: microorganism present thats not supposed to be there

-Infection: microorganism is causing a clinical problem signs and symptoms

Give examples for non-fermenting gram negative rods?

-Haemophilus influenzae (food poisoning)

-Helicobacter pylori (gastric ulcers and cancer)

Other bacteria

M. tuberculosis

C. pneumoniae

M. pneumoniae

Classification of clinically important antibacterials: Beta-lactams

1) Penicillins e.g. amoxicillin

2) Cephalosporins e.g. cefalexin

3) Carbapenems d.g. meropenem

note: cause hypersensitivity reactions and don't work against MRSA

What are the main examples of penicillin to be aware of ?

not that important but good for your own info

Natural penicillins:

Benzylpenicillin

Phenoxymethylpenicillin

Aminopenicillins:

Amoxicillin

Ampicillin

Anti-staphylococcal penicillin's

flucloxacillin

Penicillins with beta-lactamase inhibitors:

Co-amoxiclav, piperacillin & tazobactam

Antipseudomonal penicillin :

Piperacillin

Penicillin / beta-lactamase inhibitor combinations (BLIs):

-Amoxicillin with clavulanic acid (co-amoxiclav)

• Piperacillin with tazobactam

Classification of clinically important antibacterials: Tetracyclines

Doxicycline

MOA: Bind to 30S subunit of bacterial ribosome, preventing protein chain elongation

example of clinically important antibacterials: aminoglycosides

-Gentamycin'

MOA: Bind to 30S bacterial ribosomal subunit - leads to incorrect protein formation & interruption of protein synthesis

example of clinically important antibacterials: Macrolides

-Clarithromycin

MOA: Bind to 50S ribosomal subunit - stops protein chain elongation

example of clinically important antibacterials: Fluoroquinolones

Ciprofloxacin

levofloxacin

Active against pseudomonas (one of the only ones)

MOA: Inhibit DNA gyrase enzyme involved in supercoiling of bacterial DNA – leads to bacterial cell death

Has many adverse effects (MHRA warning) e.g. cardiovascular - prolong QTc interval, Neurological – dizziness, confusion, hallucinations

example of clinically important antibacterials: Glycopeptides

Vancomycin

MOA: bind to terminal D-ala-D-ala chains on peptidoglycan in cell wall, preventing further elongation

example of clinically important antibacterials: Sulphonamides and related

Co-trimoxazole: sulfamethoxazole and trimethoprim

MOA:

Inhibit sequential steps in folate biosynthesis pathway - leads to inhibition of DNA synthesis

What are the different type of antibacterials modes of action?

What drugs are active vs MRSA?

• Vancomycin

• Teicoplanin

• Linezolid

• Co-trimoxazole

• Clindamycin

• Daptomycin

• Ceftaroline

• Tigecycline

• Delafloxacin

• Dalbavancin / oritavancin

What drugs are active vs Pseudomonas aeruginosa?

• Piperacillin & tazobactam

• Ceftazidime (& BLI - avibactam)

• Cefepime

• Ceftolozane & tazobactam

• Cefiderocol

• Meropenem (& BLI - vaborbactam)

• Imipenem & cilastatin (& BLI - relebactam)

• Aztreonam

• Gentamicin

• Amikacin

• Tobramycin

• Ciprofloxacin

• Levofloxacin

• Colistin

Can all antibacterials increase the risk of Clostridioides difficile infection (CDI)

yes

Which antibiotic classes are well-recognized for increasing CDI risk?

Fluoroquinolones

Clindamycin

Cephalosporins

Beta-lactam/beta-lactamase inhibitor combinations (e.g., co-amoxiclav, piperacillin & tazobactam)

Carbapenems

What is the 1st-line treatment for the first episode of CDI?

Oral vancomycin (IV vancomycin is not effective)

What is the 2nd-line treatment for a first episode of CDI if vancomycin is ineffective?

Fidaxomicin.

What is the 1st-line treatment for CDI relapse (within 12 weeks of the previous episode)?

Fidaxomicin

What are the treatment options for recurrent CDI after 12 weeks?

Vancomycin or fidaxomicin

When is metronidazole used in CDI treatment?

Only in combination with vancomycin for life-threatening CDI (given IV).

What does time-dependent killing mean?

The effectiveness of an antibiotic depends on the time its concentration stays above the Minimum Inhibitory Concentration (MIC).

Which antibiotic classes exhibit time-dependent killing?

Penicillins

Cephalosporins

Carbapenems

Monobactams

What does concentration-dependent killing mean?

The effectiveness of an antibiotic depends on its peak concentration (Cmax) relative to the MIC—higher doses lead to stronger killing effects.

Which antibiotics exhibit concentration-dependent killing?

Aminoglycosides

Fluoroquinolones

Metronidazole

What does exposure-dependent killing mean?

The effectiveness of an antibiotic depends on the total drug exposure over time (measured as Area Under the Curve (AUC) relative to MIC)

Which antibiotics exhibit exposure-dependent killing

Glycopeptides (e.g., vancomycin)

Macrolides (e.g., azithromycin, erythromycin)

Tetracyclines

Linezolid

Give examples of antibiotics with good bioavailability

• Amoxicillin • Cefalexin/Cefadroxil • Doxycycline • Fluoroquinolones • Co-trimoxazole • Trimethoprim • Clindamycin • Linezolid • Metronidazole

Give examples of antibiotics not abosrbed orally

• Benzylpenicillin • Piperacillin • Ceftriaxone/Cefotaxime/Ceftazidime • Meropenem/Ertapenem/Imipenem • Aztreonam • Aminoglycosides • Vancomycin/Teicoplanin • Daptomycin • Fidaxomicin