Bacterial Infections and Classification

• Infectious ailments arise from pathogenic organisms, like bacteria, fungi, parasites, and viruses.
• Bacteria are single-celled microorganisms present ubiquitously, posing both harmless and dangerous potentials.
• Antibiotics combat bacterial infections in humans by disrupting the bacteria's growth and function.

Bacteria Classification

• Bacteria are categorized as either Gram-positive or Gram-negative, based on their response to the Gram stain procedure.
• Gram-positive bacteria stain purple
• Gram-negative bacteria stain pink.
• Gram stain results dictate appropriate antibiotic therapy due to cell membrane composition differences affecting drug penetration.
• Gram-negative bacterial infections are more challenging to treat due to their complex cell wall structure.
• Bacteria are also classified based on their need for oxygen as either:
  • Aerobes: requiring oxygen.
  • Anaerobes: not requiring oxygen, they are commonly found in the GI tract.
• Bacteria can cause multiple disorders depending on how they accumulate in the body
  • streptococcus pyogenes can cause strep throat from airborne droplets.
  • The same bacteria can cause skin infections if transferred via contaminated surfaces with an open sore.
• Healthcare-associated infections are infections acquired during treatment for other conditions and are often antibiotic-resistant.

Common Gram-Positive Bacteria & Infections:

• Staphylococcus aureus often causes skin infections.
• Streptococcus pyogenes is linked to strep throat.
• Enterococcus faecalis can lead to urinary tract infections (UTIs).

Common Gram-Negative Bacteria & Infections:

• Pseudomonas aeruginosa often causes meningitis and pneumonia.
• Klebsiella Pneumoniae is linked to UTIs and pneumonia.
• Escherichia Coli is a common cause of pneumonia, UTIs and diarrhea.
• Enterobacter species is linked to urinary and respiratory tract infections.

Antibiotic Terminology:

• Antibiotic spectrum refers to the range of bacteria susceptible to a specific antibiotic.
• Broad Spectrum Antibiotic is effective against both Gram-positive and Gram-negative bacteria.
• Bacteria Resistance signifies some bacteria's capacity to withstand antibiotic effects.
• MRSA (Methicillin-resistant Staphylococcus aureus) is a drug-resistant strain, with Vancomycin being one of the few effective antibiotics.

Antibiotic Classifications:

• Antibiotics are grouped into classes based on chemical structure, antibacterial spectrum, mechanism of action, potency, toxicity, and pharmacokinetic properties.
• Antibiotics target foreign bacteria.

Antibiotic Mechanisms of Action:

• Interference with bacterial cell wall synthesis results in unstable cell walls, leading to rupture and cell death.
• Interference with protein synthesis leads to malfunction.
• Interference with DNA and RNA replication prevents bacterial multiplication and infection survival.
• Antimetabolite action disrupts metabolic reactions, impairing bacterial growth and function.

Antibiotic Types:

• Bactericidal antibiotics kill bacteria directly.
• Bacteriostatic antibiotics inhibit bacterial growth.

Antibiotic Classes:

• Classes covered include Sulfonamides, Penicillins, Cephalosporins, Macrolides, Tetracyclines, Aminoglycosides, and Fluoroquinolones.

Sulfonamides

• Sulfonamides were among the first antibiotics used.
• Mechanism: bacteriostatic, preventing bacteria from making folic acid, essential for DNA and RNA synthesis.
• Spectrum: broad, effective against both Gram-positive and Gram-negative bacteria.
• Adverse Effects: include nausea, vomiting, diarrhea, and potential kidney damage with dehydration.
• Drug Interactions with warfarin increase bleeding risk; with sulfonylureas, increase hypoglycemia risk.
• Example: Sulfamethoxazole-trimethoprim (SMZ-TMP or Bactrim), which is a combination drug which functions similarly, but one component is not a sulfonamide

Beta Lactam Antibiotics

• Beta Lactam antibiotics include penicillins and cephalosporins, named for their beta-lactam ring structure, sharing a common action.

Penicillins

• Penicillins come from mold.
• There are four subgroups: natural, penicillinase resistant, aminopenicillins, and extended spectrum.
• Mechanism: bactericidal, inhibiting synthesis of the bacterial peptidoglycan cell wall.
• Bacteria can resist antibiotics. Some produce beta-lactamase, an enzyme that destroys penicillin.
• Beta-lactamase inhibitors can be added to overcome this.
• Spectrum: activity varies by subgroup:
  • Natural penicillins are effective against Gram-positive infections.
  • Penicillinase-resistant penicillins target resistant Staphylococcal infections.
  • Aminopenicillins are effective against Gram-positive and some Gram-negative infections.
  • Extended spectrum penicillins target serious Gram-negative infections.
• Adverse Events: generally nontoxic; common effects include nausea and rashes. Some patients develop allergies, with anaphylaxis being a possible life-threatening reaction.
• Drug Interactions: can increase bleeding risk with warfarin, decrease oral contraceptive effectiveness, and increase antibacterial effect with aminoglycosides.
• Examples:
  • Natural penicillins - Penicillin
  • Penicillinase resistant penicillins - Cloxacillin
  • Aminopenicillins - Amoxicillin
  • Extended spectrum penicillins - Piperacillin/tazobactam (Zosyn)

Common Uses

• Natural penicillins treat strep throat.
• Penicillinase-resistant penicillins treat resistant staph infections (*not MRSA).
• Aminopenicillins are effective against ear infections, sinusitis, respiratory and skin infections, urinary tract infections.
• Extended spectrum penicillins treat resistant Gram-negative infections like pneumonia, intraabdominal infections & sepsis.

Cephalosporins

• Cephalosporins are structurally and pharmacologically similar to penicillins within the beta lactam family.
• Mechanism: bactericidal, interfering with bacterial cell wall synthesis.
• Spectrum: Cephalosporins can destroy bacteria related to their generation.
• Adverse Events: include diarrhea, abdominal cramps, rash, itching, redness, and edema. Cross-sensitivity to penicillins may occur in 1-4% of patients.
• Drug Interactions increasing the risk of bleeding when taken with warfarin, decreasing the effectiveness of oral contraceptives, and increasing the antibacterial effect when used in combination with aminoglycosides.

Cephalosporin Generations:

• Five generations exist, with Gram-negative coverage increasing with each.
  • First-generation: mostly Gram-positive coverage.
  • Last generation: Gram-negative coverage.
  • Second generation has some anaerobic coverage.
  • Fifth generation: covers Gram-positive (including MRSA) and Gram-negative bacteria.

Macrolides

• Macrolides became available in the 1950s, including erythromycin, azithromycin, & clarithromycin.
• Mechanism: commonly bacteriostatic, and can be bactericidal at high concentrations.
• They inhibit protein synthesis within the bacterial cell.
• Spectrum: primarily Gram-positive.
• Adverse Events: include nausea, vomiting, diarrhea, and minor skin rashes.
• Drug Interactions: possible competition with other drugs for metabolic enzymes in the liver.
• Examples: Erythromycin, Azithromycin, Clarithromycin.
• Uses: Upper and lower respiratory tract infections and penicillin allergies.

Tetracyclines:

• Tetracyclines inhibit protein synthesis in susceptible bacteria.
• Spectrum: Tetracyclines have activity against a variety of gram-negative and gram-positive bacteria.
• Are pregnancy category D due to slow fetal skeletal development.
• Drug Interactions: absorption is reduced when taken with antacids, dairy products, and calcium.
• Examples: Doxycycline, minocycline, and tigecycline.
• Are used to treat acne, skin infections respiratory, and Gl tract infections.

Aminoglycosides:

• Aminoglycosides exhibit poor absorption from the GI tract, which necessitates their administration via IM or IV for systemic effects.
• Mechanism: bactericidal, inhibiting protein synthesis.
• Spectrum: effective against Gram-negative bacteria, primarily used in hospitalized patients with serious infections.
• Adverse Events: cause kidney and ear damage, and are pregnancy category D and have been shown to cause hearing loss and deafness in the fetus.
• Drug Interactions: the increased risk of respiratory issues and ototoxic and nephrotoxic effects if mixed with particular drugs like anesthetics, furosemide, and cephalosporins
• Example: Amikacin commonly used for serious gram-negative infections

Fluoroquinolones

• Advantageous for broad-spectrum activity and good oral absorption.
• Mechanism: inhibiting bacterial enzymes.
• Spectrum: broad-spectrum activity against Gram-negative bacteria, and some Gram-positive bacteria.
• Adverse Events: commonly include headache, dizziness, GI issues, and rash and are not recommended in women and children.
• Drug Interactions: Avoid antacids several hours before and after dosing because they can decrease the absorption.
• Examples: Ciprofloxacin, levofloxacin, and moxifloxacin
• Common Uses: Urinary tract infections, respiratory, abdominal, bone, and soft tissue infections.

Antibiotic Selection:

• Empiric therapy involves prescribing antibiotics based on the likely pathogens causing an infection before lab results are available.
• Sensitivity analysis is used to test the cultures for susceptibilities.
• Minimize the use of broad-spectrum antibiotics to limit antibiotic resistance.