Antibiotics Classification: Gram Positive vs Gram Negative

Antibiotics Classification

• Gram Positive vs Gram Negative: Key difference lies in the composition of bacterial cell walls.

Beta-Lactams

• Penicillins: Inhibit cross-linking of peptidoglycan in cell walls, leading to autolysis and cell death.
  • Penicillin G: Parenteral administration, 4-6 hour half-life.
  • Penicillin V: Oral administration, 6-8 hour half-life.
  • Benzathine Penicillin G: Intramuscular administration.
  • Indications: Streptococcal pharyngitis, scarlet fever, poststreptococcal reactive arthritis, syphilis, leptospirosis.
• Antistaphylococcal Penicillins:
  • Methicillin (MSSA): Indications - skin infections, sepsis, endocarditis, osteoarthritis.
  • Oxacillin (MSSA): Indications - skin infections, sepsis, endocarditis, osteoarthritis.
  • Cloxacillin (MSSA): Indications - skin infections, sepsis, endocarditis, osteoarthritis.
  • Dicloxacillin (MSSA): Indications - skin infections, sepsis, endocarditis, osteoarthritis.
• Aminopenicillins:
  • Ampicillin: Indications - pneumonia, L. monocytogenes infection, dental infections, infectious endocarditis.
  • Amoxicillin: Indications - pneumonia, L. monocytogenes infection, dental infections, infectious endocarditis.

Beta-Lactamase Inhibitor Combinations

• Mechanism of Action: Beta-lactamase inhibitors structurally resemble beta-lactams and bind to many beta-lactamases, rendering them unable to inactivate the co-administered beta-lactam.

Cephalosporins

• Generations:
  1. First-Generation Cephalosporins: Active against Gram-positive cocci, some Gram-negative bacilli.
  2. Second-Generation Cephalosporins: Active against anaerobic GNB, more resistant to beta-lactamases.
  3. Third-Generation Cephalosporins: Active especially on GNB, including non-fermentatives.
  4. Fourth-Generation Cephalosporins: Superior activity against streptococci, Ps. aeruginosa.
  5. Fifth-Generation Cephalosporins: Active against MRSA.
• Adverse Effects: Allergic reactions, hematological reactions, neurological toxicity, Clostridium difficile colitis.

Carbapenems

• No activity against MRSA.
• Active against: Gram-positive cocci, Gram-positive bacilli, Gram-negative cocci, Gram-negative bacilli, anaerobic bacteria.
• Indications: Severe localized or generalized infections with multidrug-resistant germs, nosocomial infections.
• Adverse Effects: Allergic reactions, neurological toxicity, digestive disorders, hematological disorders.

Monobactams

• Active against: Gram-negative aerobic cocci and bacilli.
• Indications: Severe aerobic GNB infections, especially in patients with beta-lactam allergy.
• Aztreonam: Inhalational administration in patients with cystic fibrosis, secondary prophylaxis of Ps. aeruginosa infections.

Glycopeptides

• Mechanism of Action: Inhibition of cell wall synthesis.
• Time-dependent antimicrobials.
• Active against: Gram-positive bacteria, including MRSA.
• Indications: Severe infections due to streptococci, enterococci, pneumococci, MRSA/MSSA in patients allergic to beta-lactams.
• Adverse Effects: Red man syndrome, nephrotoxicity, ototoxicity, cytopenias, hypersensitivity reactions.

Oxazolidinones

• Mechanism of Action: Inhibition of protein synthesis.
• Active against: Gram-positive bacteria, including MRSA, VRE.
• Indications: Systemic infections with vanco-R, methi-R, or vanco-S staphylococci/enterococci.
• Adverse Effects: Digestive disorders, myelosuppression, peripheral neuropathy, lactic acidosis.

Macrolides

• Mechanism of Action: Inhibition of bacterial protein synthesis.
• Active against: Gram-positive cocci, some Gram-negative bacilli, atypical bacteria, mycobacteria.
• Indications: Mild to moderate URT and LRT infections, Legionnaire's disease, diphtheria, pertussis, atypical mycobacteriosis.
• Adverse Effects: Digestive disorders, allergic reactions, hepatotoxicity, reversible ototoxicity.

Tetracyclines

• Mechanism of Action: Inhibition of bacterial protein synthesis.
• Active against: Gram-positive and Gram-negative bacteria, some anaerobic bacteria, rickettsiae, chlamydiae, mycoplasma.
• Indications: Community-acquired pneumonia, M. catarrhalis infections, brucellosis, Legionnaire's disease.### Brucellosis
• Brucellosis is caused by bacteria of the genus Brucella.
• The treatment of brucellosis involves the use of tetracyclines, such as doxycycline, and rifampicin.

Tetracyclines

• Tetracyclines are a class of antibiotics that inhibit protein synthesis by binding to the 30S ribosomal subunit.
• Side effects of tetracyclines include:
  • Skin manifestations: photosensitization, morbilliform eruptions, urticaria
  • Digestive disorders: nausea, vomiting, abdominal pain
  • Dental and bone abnormalities: yellow-brown deposits and staining of the teeth, tooth enamel hypoplasia
  • Contraindications: pregnancy, breast-feeding, children under 8 years old
  • Nephrotoxicity, neurotoxicity, hepatotoxicity, hematological disorders

Fluoroquinolones

• Fluoroquinolones are a class of antibiotics that inhibit bacterial DNA synthesis by acting on DNA gyrase and topoisomerase IV enzymes.
• They have good oral bioavailability and tissue diffusion in the respiratory tract, kidney, liver, bile, muscle, prostate, skin, and bone.
• Representatives of fluoroquinolones include:
  • "Old" FQ (urinary): norfloxacin, ciprofloxacin
  • "New" FQ (respiratory): levofloxacin, moxifloxacin
• Spectrum of fluoroquinolones:
  • Respiratory FQ: S. pneumoniae, Neisseria spp., M. catharralis, M. tuberculosis, Legionella spp.
  • Others: Enterobacteriaceae, Pseudomonas aeruginosa, Mycobacterium spp., Atypical bacteria (Mycoplasma spp., Chlamydia spp., Coxiella spp.)
• Side effects of fluoroquinolones:
  • C. difficile infection, digestive disorders, osteo-muscular disorders, hepatic disorders, cardiac disorders, cutaneous disorders, neurological disorders, renal disorders, hematological disorders

Lincosamides

• Clindamycin is a lincosamide that has excellent bone diffusion and an extended spectrum compared to macrolides.
• Indications of clindamycin:
  • Osteoarticular infections
  • Skin and soft tissue infections
  • Aspiration pneumonia
  • Infections with anaerobes (except Bacteroides)
  • Cerebral toxoplasmosis
  • Can replace penicillin in allergic patients

Fosfomycin

• Fosfomycin is a antibiotic that inhibits the synthesis of the bacterial wall.
• Forms of fosfomycin: fosfomycin trometamol (PO), fosfomycin sodium (IV)
• Activity spectrum: GPC, GNB (no activity against Acinetobacter, anaerobes)
• Indications:
  • Acute cystitis
  • Asymptomatic bacteriuria in pregnant women
• Side effects:
  • None mentioned

Nitrofurantoin

• Nitrofurantoin is an antibiotic that alters proteins, nucleic acids, and bacterial lipids.
• Spectrum: GPC, Proteus spp., E. coli
• Indications:
  • Treatment of asymptomatic bacteriuria
  • Uncomplicated/complicated low UTIs
  • Chemoprophylaxis before transurethral interventions

Metronidazole

• Metronidazole is an antibiotic that inhibits bacterial DNA synthesis.
• Spectrum: anaerobic bacteria, protozoa (Trichomonas vaginalis, Giardia lamblia, Entamoeba histolytica)
• Adverse effects:
  • Digestive disorders, metallic taste
  • Neurological disorders: reversible peripheral neuropathy
  • Mutagenic and carcinogenic potential
  • Turns urine red
  • Interactions: disulfiram (+alcohol) effect, anti-vitamin K effect

Tigecycline

• Tigecycline is a antibiotic that inhibits bacterial protein synthesis by binding to the 30S ribosomal subunit.
• Good tissue diffusion in alveolar macrophages, bone, muscle, fatty tissue, etc.
• Spectrum:
  • Streptococci, pneumococci PS,PR
  • Staphylococci MS, MR
  • Resistant enterococci
  • C. difficile
  • Enterobacteriaceae, MDR/XDR
• Indications:
  • Intra-abdominal infections of unspecified etiology
  • Severe soft tissue infections
  • "Salvage" treatment in complicated C. difficile infections
• Side effects:
  • Digestive: nausea, vomiting, acute pancreatitis
  • Photosensitivity
  • Hepatic cytolysis syndrome

Aminoglycosides

• Aminoglycosides are a class of antibiotics that inhibit bacterial protein synthesis.
• Representatives of aminoglycosides:
  • First generation: streptomycin
  • Second generation: gentamicin, tobramycin
  • Third generation: amikacin
• Spectrum of aminoglycosides:
  • GPC, GNC, GPB
  • M. tuberculosis, Brucella spp., Yersinia spp., Francisella tularensis
• Indications:
  • Infective endocarditis
  • Localized/generalized staphylococcal infections
  • High urinary tract infections
  • Severe listeria infections
  • Tuberculosis with MDR strains
• Side effects:
  • Nephrotoxicity, ototoxicity, vestibular toxicity
  • Rapidly reversible neuromuscular blockage after iv administration of calcium gluconate
  • Allergic reactions
  • Drug interactions

Colistin (Polymyxins)

• Colistin is a antibiotic that binds to the negatively charged lipopolysaccharide molecules in the bacterial outer membrane and disrupts the normally tightly packed lipopolysaccharide molecules, leading to increased permeability and lysis of bacteria.
• Spectrum: aerobic Gram-negative bacteria (including P. aeruginosa)
• Indications:
  • Severe localized or generalized infections with multidrug-resistant germs
  • Especially nosocomial infections
• Side effects:
  • Nephrotoxicity
  • Neurotoxicity
  • Remember to monitor the creatinine and urea levels!