Antibiotics and Bacterial Structures

• Antimicrobial drugs are also known as antibiotics
• NURS1059 is the course number for the 2024-2025 academic year

Method for Studying Antimicrobials

• Understand the organism's structure related to bacteria and viruses
• Understand the basic way to kill the microorganism
• General MOA refers to the general mechanism of action
• Relate the drug's name to its general mechanism of action
• Relate the drug to its intended purpose
• Relate the drug to its adverse effects

Bacteria Structure

• Understanding bacterial structure is the key to the MOA of antibacterial drugs

Cell Walls

• Nearly all prokaryotes (bacteria) have a cell wall
• Cell walls provide physical protection
• Cell walls prevent the cell from bursting in a hypotonic environment
• Gram stain is used to differentiate cell walls of bacteria
• Gram-positive bacteria have simpler cell walls with peptidoglycan
• Gram-negative bacteria have less peptidoglycan and are more complex
• Gram-negative bacteria are more likely to cause disease

Capsule

• The cell wall of many bacteria is covered by a capsule, a sticky layer of polysaccharides or protein
• Capsules enable bacteria to adhere to their substrate and other individuals in a colony
• Capsules shield pathogenic bacteria from attacks by a host's immune system

Anti-Bacterial Agents

• Anti-microbial agents produce a “cidal" or "stasis" effect
• Cidal agents kill, and are bactericidal or germicides
• Stasis agents inhibit growth, and are bacteriostatic meaning it limits or stops growth
• Sepsis is bacterial contamination
• Asepsis is the absence of significant contamination
• Aseptic technique used in surgery helps minimize contamination

Sources of Antibiotics

• Natural antibiotics are derived from fungal sources
• Natural antibiotics are often more toxic than synthetic antibiotics
• Organisms develop resistance faster to natural antimicrobials due to pre-exposure in nature
• Semi-synthetic drugs were developed to decrease toxicity and increase effectiveness
• Synthetic drugs have an advantage in that the bacteria are not exposed to them in their natural environment
• Synthetic drugs are designed to have greater effectiveness and less toxicity
• The sources of antibacterial agents can be natural, semi-synthetic, and synthetic
• Natural antibacterial agents mainly come from fungal sources
• Semi-synthetic agents are chemically-altered natural compounds
• Synthetic agents are chemically designed in the lab
• Toxicity decreases from Natural -> Semi-synthetic -> Synthetic
• Effectiveness increases from Natural -> Semi-synthetic -> Synthetic

Structure & Function (MOA)

• Antibiotics are usually classified based on their structure and/or function
• Structure is defined as molecular structure which can include B-Lactams or Aminoglycosides
• B-Lactams includes a Beta-Lactam ring
• Aminoglycosides vary only by side chains attached to the basic structure
• Function is how the drug works
• Function constitutes the Mode Of Action
• There are typically 5 function groups
• These are all components or functions necessary for bacterial growth
• Target indicates the “Target” of action for antibiotics in a bacteria

Antibiotics Category Classification

• Antibiotics are classified into broad categories based on their chemical structures and MOA
• Penicillins
• Sulphonamides
• Cephalosporins
• Carbapenems
• Macrolides
• Quinolones
• Aminoglycosides
• Tetracyclines
• Other miscellaneous categories

Function Classification

• Five functional groups cover most antibiotics
• Functional groups refers to the way we kill the organism
• General MOA applies
• Classifications include:
  • Inhibitors of cell wall synthesis
  • Inhibitors of protein synthesis
  • Inhibitors of membrane function
  • Anti-metabolites
  • Inhibitors of nucleic acid synthesis
• Outside action leads to alteration of membranes and cell walls
• Outside action interferes with growth and causes death via membrane leakage
• Inside action causes damage to proteins or nucleic acids
• Inside action leads to proteins denaturing to change shape and lose function
• Inside action means DNA and RNA cannot make proteins which is incompatible with life

Inhibitors of Cell Wall Synthesis

• Beta-lactams
• Glycopeptides
• Fosfomycins

Beta-Lactams

• Characterized by a Beta-lactam ring in its molecular structure
• MOA is to inhibit cell wall synthesis by the bacteria
• The most widely used group of antibiotics, around 50 currently on the market
• Humans have no cell wall (no peptidoglycan), making this a selective medication
• Beta-lactams are all bactericidal
• Beta-lactams are nontoxic
• Beta-lactams are relatively inexpensive
• Beta-lactams are organic acids, and most are soluble in water

Beta-Lactams Subgroups

• Penicillin for narrow spectrum of bacterial control includes Pen G and Pen V
• Penicillin for narrow spectrum of bacterial control includes Cloxacillin and Oxacillin
• Penicillin for extended spectrum of bacterial control includes Amoxicillin and Ampicillin
• Penicillin for extended spectrum of bacterial control includes Carboxypenicillins and Ureidopenicillins
• Carbapenems includes Imipenem and Ertapenem
• Cephalosporins includes Cefazolin, Cefaclor, Cefixime, Cefuroxime, and Ceftriaxone
• Monobactams inclues Aztreonam
• B-lactamase Inhibitors includes Tazobactam and Clavulanica acid
• Combinations includes Amoxicillin/clavulanic acid, Imipenem/cilastatin and Piperacillin/tazobactam

Penicillin Subclass

• MOA is Bactericidal
• Penicillin interferes with the synthesis of bacterial cell walls
• Penicillin doesn't hinder growth of human cells
• Penicillin weakens bacteria cell walls to destroy bacteria by osmotic lysis
• Penicillin is most effective against bacteria that rapidly multiply
• Treats otitis media, pneumonia, meningitis, UTIs, syphilis, gonorrhoea
• Used as prophylaxis for surgical or dental procedures
• Contraindications include drug allergies
• Adverse effects include diarrhea and GI upset
• Adverse effects include Thrombophlebitis
• Electrolyte imbalance is also an adverse effect
• Hyperkalemia and hypernatremia is an adverse effect due to having larger amounts of it in the formulation
• Interactions with NSAIDs increases free active med
• With Methotrexate, there is decreased kidney elimination
• Warfarin use increases its effects, by reducing levels of vitamin K in the GIT
• With oral contraceptive use potentially reduces efficacy

Cephalosporin Subclass

• MOA is bactericidal
• Cephalosporin is broad-spectrum
• Cephalosporin interferes with bacterial cell wall synthesis
• Cephalosporin binds to penicillin-binding proteins (PBP) in the bacterial cell wall
• There are four generations of cephalosporins, each producing various actions
• Cephalosporins are a semi-synthetic antibiotic
• They are produced by fungus but synthetically modified to produce an antibiotic
• Cephalosporins are structurally and pharmacologically related to penicillin
• Indicated (used) when treating Penicillin allergies
• Indicated (used) for Urinary and Respiratory Tract Infections (UTI, RTI)
• Indicated (used) for Abdominal infections and Septicemia
• Indicated (used) for Meningitis and Ear Infections
• Adverse effects include diarrhea and secondary infection, such as oral thrush or yeast infections
• Thrombophlebitis and electrolyte imbalances, such as hyperkalemia/natremia, are adverse events
• Renal (potentially nephrotoxic) and liver issues are adverse events
• Absorption may be inhibited by antacids, H2 antagonists and FE supplements with drug interactions
• Alcohol usage can cause reactions

Cephalosporin Generations (Approved for use in Canada)

• Gen I includes Cefazolin (IV), Cephalexin (Keflex®, po) and Cefadroxil
  • Gen I treats Gram (+) Staphylococcus and Streptococcus
• Gen 2 includes Cefuroxime, Cefaclor, Cefoxitin and Cefprozil
  • Gen 2 is effective against Gram (-) and slightly less so with Gram (+)
• Gen 3 includes Ceftriaxone (Rocephin®, IV), Ceftazidime, Cefotaxime and Cefixime
  • Gen 3 has coverage against Gram (-) and may be effective against Pneumonia
• Gen 4: Cefepime has a very broad spectrum on Gram (-) and (+)
• Gen 5: Ceftobiprole and Ceftolozane-tazobactam has similar coverage to Gen 3 and 4, MRSA and enterococci coverage

Carbapenum Subclass

• MOA is bactericidal
• Binds to penicillin-binding proteins
• Inhibits bacterial cell wall synthesis
• Acts against gram-positive and gram-negative aerobic and anaerobic organisms
• Broadest antibacterial spectra of any antibiotic to date
• Treats body cavity and connective tissue infections
• Examples: Meropenem, Ertapenem and Imipenem
• May cause drug-induced seizure activity in a small percentage of clients

Glycopeptides Subclass

• MOA is bactericidal
• Glycopeptides have a complex chemical structure
• Inhibit cell wall synthesis at a site different than the beta-lactams
• Resistance is largely restricted to nosocomial enterococcus faecium
• Used for: MRSA, endocarditis (gram + infections)
• Example: Vancomycin

Vancomycin

• Inhibits bacterial cell wall by binding to a cell wall precursor, causes cell lysis and may also inhibit RNA synthesis
• Used primarily to treat serious infections that cannot be treated with less toxic agents like penicillin
• Useful in treating Clostridium difficile, MRSA
• Only comes in IV formulations
• Diarrhea (bloody), nausea, tinnitus and irritation at IV site are adverse effects
• Hearing loss, kidney damage and hypokalemia are adverse events from vancomycin use
• Red man syndrome and anaphylaxis are adverse events from vancomycin use
• Red man syndrome is an infusion-related reaction and includes pruritis and erythematous rash that involves the face and neck
• With red man syndrome, infusion is stopped while Benadryl is given and then restarted slowly

Beta-Lactam Resistant Bacteria

• There are mechanisms that bacteria will use to adapt to Beta-Lactams
• The mechanisms include reducing access to protein receptors on bacteria
• The mechanisms include reducing binding affinity of the protein receptors on a bacteria
• Production of beta lactamase is a mechanisms, an enzyme that destroys the B-Lactam
• Natural or acquired resistance is a mechanism
• This is a huge problem, started when penicillin was discovered and overprescribed
• An example is Staphylococcus Aureus (MRSA)

Anti-Metabolites

• Used primarily as a Bacteriostatic
• Called folate pathway inhibitors or anti-metabolites
• Folic acid is essential for the synthesis of DNA and chromosomes in bacteria
• These drugs compete for folate binding sites and block metabolism of DNA
• Humans do not synthesize folic acid, making this a good selective medication

Sulfonamides

• Bacteriostatic in low doses
• Bactericidal in higher doses
• Introduced in the 1930's
• Sulfanilamide and single drug/combinations constitute the treatment
• Urinary tract infection (UTI), ear infections, and respiratory tract infections (RTI) are indications for use
• Sulfasalazine is another sulfonamide, used in the treatment of RA and ulcerative colitis-but not for infections
• Commonly prescribed agents include sulfadiazine, sulfamethoxazole and sulfisoxazole
• Trimethoprim/sulfamethoxazole (Cotrimoxaxole, Septra®) is bactericidal
• They achieve high concentration levels in the kidneys when eliminated, which produces bactericidal effects
• Adverse Effects include nausea, vomiting, anorexia, diarrhea, rash, photosensitivity, tinnitus, headache, dizziness, drowsiness and confusion
• Drug Interactions (Cautions) include hypoglycaemia, enhanced warfarin effect and enhanced Methotrexate toxicity
• Contraindications include known allergies to sulfonamides and pregnancy

Inhibitors of Protein Synthesis

• Subclasses include Aminoglycosides and Tetracyclines

Aminoglycosides

• MOA is bactericidal
• Acts by binding to ribosomes and prevent protein synthesis in bacterial cells
• Usually used in coombination with other antibiotics
• Effective primarily against Gram (-) bacteria that can cause UTI, Wound infections, Septicaemia
• Mainstay treatment of nosocomial infections
• Reserved mainly for use in life-threatening infections
• Monitoring of drug levels is required

Anti-Protein Antibiotics

• Gentamicin, Kanamycin, Neomycin, Streptomycin, Tobramycin are natural antibiotics
• Amikacin and Netilmicin are semi-synthetic antibiotics
• Poorly absorbed when administered orally
• Dizziness, headache, skin rash and fever are some advertse effects
• Not Favourable for long-term use due to possible renal failure (5-25%)
• Nephrotoxicity can be reversable in some instances
• Ototoxic (hearing and balance), headaches, vertigo are adverse events
• Any drug that can increase risk of nephrotoxicity interacts with the drug
• Reduce amount of Vit K so will enhance effects of anticoagulants
• Contraindicated in pregnancy

MLSK

• MLSK = Macrolides, lincosamides, streptogramins, ketolides
• Bacteriostatic
• Can be bactericidal in high enough doses
• There are Four different antibiotic classes unrelated in terms of structure, but have similar MOA and spectrum of activity

Macrolides

• MOA: Bacteriostatic, and can be bactericidal in high doses
• Inhibits protein synthesis in susceptible bacteria (RNA)
• Can fight bacteria that get into host cells as opposed to just bloodstream
• Examples: Erythromycin, Azithromycin and Clarithromycin
• GIT infections, respiratory infections and STDs or those with beta lactam contraindications are indications for use of the drugs
• Adverse effects- Gl upset, Vertigo, Rash, Headache
• Cardiac arrest, hepatoxicity and tinnitus are possible adverse events
• Contraindications involve death with comination drug therapy is used

Lincosamides

• MOA: bacteriostatic
• MOA may be bactericidal
• Inhibits protein synthesis by binding to bacterial ribosomes and preventing peptide bond formation
• Does not interfere with human cells
• Examples: Lincomycin and Clindamycin, a semi-synthetic derivative of lincomycin

Tetracyclines

• MOA: bacteriostatic
• Inhibits protein synthesis in susceptible bacteria
• Binds to portion of ribosome to inhibit bacterial growth
• Demeclocycline, oxytetracycline and tetracycline are natural
• Doxycycline and minocycline are semisynthetic
• Used for gram -ve and +ve bacteria and acne in adolescents
• Used for lyme disease, syphilis, Chlamydia, mycoplasma, and some protozoa
• Adverse effects: Superinfection (esp. candida), GI upset and photosensitivity
• Drug interactions can have enhancing effect
• Should not be administered with milk, antacids, iron
• Children under 8 years (inhibits skeletal growth) are negatively affected by the drug
• Contraindicated during pregnancy

Inhibitors of Nucleic Acid Synthesis

• Quinolones are bactericidal
• MOA = interfere with the synthesis of DNA
• This MOA is a shared process with human cells
• There are 2 generations of this category of drugs
• The first Generation of Quinolones had a very narrow spectrum
• Gen 1 is not used very much and is more susceptible to bacterial resistance
• Gen 2 of these drugs are widely used
• Fluorquinolones are a subclass of Quinolones

Fluoroquinolones

• MOA: Bactericidal
• MOA: Inhibit and impair the replication of bacterial DNA
• MOA: Metabolised by liver and excreted by urine (except for moxifloxacin
• Treatment for many types of bacterial infections, UTI's, soft/respiratory tract infections through oral or injection means
• Adverse effects: Gl upset, headaches, dizziness, fever, tinnitus
• Adverse Events: Tendonitis/Tendinopathy (Achilles tendon rupture), Peripheral Neuropathy, CNS disorders Cardiac arrythmias
• Decreases absorption when used with antacids or calcium/magnesium supplement
• Has previous allergic reaction to the medications like cardiac disorders that predispose to arrhythmias or bradycardia
• Use of medications known to prolong the QT interval or to cause bradycardia
• 5 common examples include Ciprofloxacin (Cipro), Norfloxacin, Ofloxacin, and Levofloxacin,

Fluoroquinolones by Version (Used in Canada)

• Gen 2 can inhibit against some Gram negative bacteria.
  • Nalidixic and Cinoxacin
• Gen 3 effective against some Gram negative and positive bacteria
  • Levofloxacin
• Gen 4 effective against both strains of bacteria
  • Moxifloxacin

General Nursing Considerations for Antibiotics

• Take microbiology specimens before antibiotics are started
• Blood, Urine C/S (culture and sensitivity)
• Tissue swabs C/S (throat, wounds)
• Ensure MD or NP is alerted to new C&S results
• Always check allergies and be aware of cross-allergies
• Be aware of factors that contribute to resistance- pt teaching?
• Ensure pre-op antibiotics are given as per protocol
• Screen for history of resistant infections (MRSA, VRE, CPE)
• Follow instructions on mixing IV drugs
• Monitor IV site
• Food and drug interactions

This quiz covers tetracyclines, quinolones, and bacterial cell structures. It explores mechanisms of action, contraindications, and structural differences. Key topics include antibiotic interactions and bacterial virulence factors.