Beta-Lactam and Membrane Disruptor Antibiotics

Beta-Lactam Antibiotics

• Inhibit cell wall synthesis by inhibiting peptidoglycan.
• Penicillin G and V: Effective against Gram-positive bacteria, treating streptococcal infections.
• Methicillin/Oxacillin: Gram-positive, resistant to beta-lactamases.
• Ampicillin/Carbenicillin: Broad-spectrum antibiotics.
• Carbapenems: Broadest spectrum, used for severe infections.
• Vancomycin: Glycopeptide, interferes with cross-linking; narrow therapeutic index.
• Cephalosporins (generations):
  • 1st: Cephalexin/Cephalothin, Gram-positive spectrum.
  • 2nd: Cefuroxime, extended spectrum for Gram-negative.
  • 3rd: Ceftriaxone/Cefotaxime, CNS infections.
  • 4th: Cefepime, covers third-generation resistant bacteria.
  • 5th: Ceftaroline, covers MRSA.

Cell Membrane Disruptors

• Bacitracin: Gram-positive, inhibits peptidoglycan addition.
• Polymyxins: Gram-negative, disrupts outer membrane.

Protein Synthesis Inhibitors

• Aminoglycosides: Broad-spectrum, bind 30S; narrow therapeutic index.
  • Tobramycin/Gentamicin: Require careful monitoring to prevent toxicity.
• Tetracyclines: Broad-spectrum, 30S binding; dental deposits.
• Macrolides: Bind 50S, alternative for penicillin-allergic patients.
  • Erythromycin: Treats streptococcal infections.
• Chloramphenicol: 50S binding, reserved for severe infections; risk of "grey baby syndrome".

Folic Acid Inhibitors

• Trimethoprim/Sulfamethoxazole: Treats chronic UTIs, inhibits folic acid synthesis.

DNA Synthesis Inhibitors

• Nalidixic Acid: Treats UTIs, inhibits DNA synthesis.
• Fluoroquinolones: Inhibits DNA gyrase, stopping replication.
• Nitrofurantoin: UTI treatment, targets multiple cellular processes.
• Rifampin: Inhibits DNA polymerase; used for Mycobacterium.
• Metronidazole: Causes DNA breaks under anaerobic conditions; metallic taste side effect.

Antimycobacterial Agents

• Isoniazid: Inhibits mycolic acid synthesis, potential hepatitis.
• Ethambutol: Inhibits cell wall formation, possible optic neuritis.
• Pyrazinamide: Lowers pH, GI upset.

Antifungal Agents

• Amphotericin B: Drug of choice for severe fungal infections; nephrotoxicity.
• Azoles: Inhibit sterol synthesis.
• 5-Fluorocytosine: Effective against Cryptococcus, bone marrow depression.
• Caspofungin: Effective against Candida and Aspergillus; ineffective against Cryptococcus.

Antiviral Agents

• Acyclovir: Effective against Herpes.
• Ribavirin: Effective against Respiratory Syncytial.
• M2 Inhibitor: Inhibits Influenza A.
• Neuraminidase Inhibitors: Inhibit Influenza A and B.

Antimicrobial Resistance Testing

• MRSA: mecA gene produces altered PBP2a.
• VRSA: Tested with Etest.
• ESBL: Tested with and without clavulanic acid.
• Clindamycin: erm gene.
• Carbapenemase: Modified Hodge Test.
• Glycopeptides: van A PCR.
• Oxacillin: Cefoxitin Disk test.
• Penicillin: Beta-lactamase.

Anaerobes and Growth Requirements

• Anaerobes lack oxidative enzymes (superoxide dismutase/catalase).
• Intra-abdominal abscesses are common endogenous infections.
• Anaerobic Media:
  • Requires vitamin K and hemin.
  • Thioglycollate Broth: Medium for anaerobes.
  • Phenylethyl Alcohol: Selective for Gram-positive and Gram-negative anaerobes.
  • Kanamycin-Vancomycin: Selective for Gram-negative anaerobes.
  • Bile-Esculin: Selective for Bacteroides fragilis.
  • Egg Yolk: Identifies anaerobes breaking down fats.

Selective Antibiotic Disks (Species Resistance)

• Data provided in a table format.

Gram-Negative Bacilli

• Bacteroides fragilis: Commonly isolated anaerobe, GI tract, abdominal infections.
• Fusobacterium nucleatum: Pointed, spindle-shaped; biofilm infections.
• Fusobacterium necrophorum: Pleomorphic; Lemierre's syndrome, Vincent's angina.

Pigmented Gram-Negative Bacilli

• Prevotella melaninogenica: Respiratory and periodontal infections.
• Prevotella intermedia: Gingivitis and oropharyngeal infections.
• Porphyromonas asaccharolyticus: Genital infections.
• Porphyromonas gingivalis: Gingivitis and chronic periodontitis.

Spore-Forming Gram-Positive Bacilli

• Clostridium perfringens: Double zone beta-hemolysis; gas gangrene, food poisoning.
• Clostridium tetani: Drumstick-shaped spores; tetanus (muscle spasms).
• Clostridium botulinum: Botulism (nervous system).
• Clostridiodes difficile: "Horse manure" odor; antibiotic-related diarrhea, pseudomembranous colitis.
• Clostridium septicum: Gas gangrene in malignancies.

Non-Spore-Forming Gram-Positive Bacilli

• Actinomyces israelii: Branching rods, actinomycosis (sulfur granules).
• Cutibacterium (Propionibacterium acnes): Acne, medical device infections.
• Lactobacillus: Rarely pathogenic, endocarditis.
• Bifidobacterium: "Dog bone" shaped; probiotic.

Gram-Positive Cocci

• Finegoldia magna: Highly virulent; skin, bone, and joint infections.
• Peptostreptococcus anaerobius: Abdominal, pelvic, brain abscesses.
• Peptoniphilus asaccharolyticus: Yellow colonies, musty odor; soft tissue infections.
• Microaerophilic Streptococcus: Butterscotch odor, beta-hemolytic; endocarditis, dental, respiratory infections.

Gram-Negative Cocci

• Veillonella: Very sensitive to oxygen, glove box.

Mycobacterium Overview

• Acid-Fast Bacilli: Unique cell wall, obligate aerobes; biosafety level 3.
• Media and Stains:
  • Lowenstein-Jensen: Egg-based, malachite green, slow-growing.
  • Middlebrook Agar: Faster colony detection.
  • Ziehl-Neelsen Stain: Heating required.
  • Kinyoun Stain: High phenol, no heating.

Mycobacterium Tuberculosis Complex Species

• M. tuberculosis: Tuberculosis in humans, respiratory droplets.
• M. bovis: Primarily cattle; unpasteurized milk.
• M. africanum: West Africa.
• M. canettii: East Africa.
• M. caprae/microti: Primarily animals.

Photochromogens

• Develop pigment with light.
• M. kansasii: Chronic pulmonary infection, yellow bacillus.
• M. marinum: Skin infections from aquatic environments.
• M. simiae: Rare respiratory infection.
• M. asiaticum: Rare pulmonary infection.

Scotochromogens

• Produce pigment in both light and dark conditions.
• M. scrofulaceum: Lymphadenitis.
• M. szulgai: Pulmonary infection; pigment dependent on temperature.
• M. gordonae: "Tap water bacillus".

Non-Photochromogens

• Non-pigmented in both light and dark conditions.
• M. avium: AIDS patients, resistant to TB drugs.
• M. ulcerans: Buruli ulcers.
• M. malmoense: Chronic pulmonary infections.
• M. haemophilium: Skin and subcutaneous infections, hemin.
• M. gastri: Nonpathogenic, gastric washings.

Rapid Growers

• Non-pigmented, grows within seven days.
• M. fortuitum: Postoperative skin infections, contaminated water.
• M. chelonae: Wound infections, especially post-cosmetic procedures, lacks iron uptake.
• M. abscessus: Opportunistic, underlying lung disease.

Other Species

• M. leprae: Leprosy (Hansen's disease), cannot be cultured in vitro.
• M. chimaera: Part of M. avium complex, cardiovascular infections.

Chlamydiaceae Family

• Obligate intracellular parasites, Gram-negative-like cell wall.
• Use host ATP, binary fission.
• Elementary Body: Infectious form.
• Reticulate Body: Metabolically active, non-infectious.
• Chlamydia trachomatis: Infects epithelial cells, trachoma (blindness), Lymphogranuloma venereum (LGV)
• Chlamydia pneumoniae

Rickettsiaceae Family

• Obligate intracellular parasites, vector-borne.
• Incubation 3-14 days, multiplies in endothelial cells.
• Rickettsia rickettsii: Rocky Mountain spotted fever, tick vector.
• Rickettsia prowazekii: Epidemic typhus, human body lice.
• Rickettsia typhi: Endemic typhus, flea vector.

Anaplasmataceae Family

• Diagnosis by observing morulae in leukocytes.
• Ehrlichia chaffeensis: Human monocytic ehrlichiosis, lone star tick.
• Anaplasma phagocytophilum: Human granulocytic anaplasmosis.

Coxiella

• Immunofluorescence, biosafety level 3.
• Coxiella burnetii: Q fever, aerosols, ticks, survives outside hosts.

Mycoplasmataceae Family

• Small, lack a cell wall.
• Mycoplasma pneumoniae: Tracheobronchitis ("walking pneumonia").
• Mycoplasma hominis: Pelvic inflammatory disease (PID), postpartum fever.
• Mycoplasma genitalium/urealyticum: Nongonococcal urethritis (NGU).

Spirochetes

• Helically coiled, motile, Gram-negative-like periplasmic flagella.
• Borrelia burgdorferi: Lyme disease, deer tick.
  • Stages: Erythema migrans (bull's-eye rash), disseminated (CNS, heart), chronic (arthritis).
• Other Borrelia Species: Relapsing fever.
• Treponema pallidum: Syphilis.
  • Stages: Primary (chancre), secondary (rash), tertiary (gummas).
  • Subspecies: pertenue (yaws), bejel, carateum.
• Leptospira interrogans: Leptospirosis (animal urine, soil/water), Weil's disease.