Tetracyclines et Glycylcyclines

Tetracyclines & Glycylcyclines

• Tetracyclines and Glycylcyclines are a group of antibiotics
• Types of Tetracyclines: Doxycycline, Minocycline, Tetracycline, Oxytetracycline, Demeclocycline, Eravacycline, Omadacycline, Sarecycline
• Types of Glycylcyclines: Tigecycline

Mechanism of Action - Bacteriostatic

• Binds with 30S ribosome subunit
• Inhibits protein synthesis

Mechanism of Resistance

• Efflux pump
• Plasmid mediated
• Inactivating enzymes

Antimicrobial Spectrum - Gram-positive Bacteria

• Staphylococcus aureus
• Methicillin-resistant Staphylococcus aureus
• Streptococcus pneumoniae (Pneumococcus)
• Bacillus anthracis
• Erysipelothrix rhusiopathiae

Antimicrobial Spectrum - Gram-negative Bacteria - Aerobes

• Moraxella catarrhalis
• Neisseria gonorrhoeae (Gonococcus)
• Escherichia coli
• Klebsiella pneumoniae
• Acinetobacter
• Haemophilus influenzae
• Haemophilus ducreyi

Antimicrobial Spectrum - Gram-negative Bacteria - Anaerobes

• Brucella
• Yersinia pestis
• Yersinia enterocolitica
• Francisella tularensis
• Vibrio cholerae
• Pasteurella multocida
• Klebsiella granulomatis
• Streptobacillus moniliformis
• Legionella pneumophila
• Burkholderia pseudomallei
• Campylobacter jejuni

Antimicrobial Spectrum - Gram-positive Bacteria - Anaerobes

• Peptostreptococcus anaerobius
• Peptostreptococcus magnus
• Clostridium tetani
• Clostridium perfringens
• Clostridium septicum
• Clostridium novyi
• Clostridium histolyticum
• Propionibacterium acnes

Antimicrobial Spectrum - Gram-negative Bacteria - Anaerobes

• Helicobacter pylori

Antimicrobial Spectrum - Spirochetes

• Leptospira icterohaemorrhagiae
• Treponema pallidum
• Borrelia burgdorferi
• Borrelia recurrentis

Antimicrobial Spectrum - Rickettsiae

• Rickettsia (rickettsi, conorii, akari, typhi)
• Coxiella burnetti

Antimicrobial Spectrum - Actinomycetes

• Nocardia asteroids
• Actinomyces israelli

Antimicrobial Spectrum - Mycobacteria

• Mycobacterium leprae
• Mycobacterium fortuitum, abscessus, chelonae, marinum, ulcerans

Antimicrobial Spectrum - Chlamydiae

• Chlamydia trachomatis, psittaci, pneumoniae

Antimicrobial Spectrum - Parasite - Protozoa

• Plasmodium falciparum
• Entamoeba histolytica
• Dientamoeba fragilis
• Balantidium coli

Antimicrobial Spectrum - Parasite - Filarial Worm-Nematode

• Wuchereria bancrofti

Route of Administration

• Doxycycline: Oral, Intravenous/Infusion, Topical-subgingival gel
• Minocycline: Oral, Intravenous/Infusion, Topical-subgingival gel, microspheres, Intrapleural
• Tetracycline: Oral, Intravenous/Infusion, Topical-subgingival fibres, eye/ear-ointment, drops, Intrapleural
• Demeclocycline: Oral
• Oxytetracycline: Oral, Intravenous/Infusion, Topical-eye/ear ointment, drops
• Tigecycline: Intravenous infusion

Therapeutic Uses - Chronic Periodontitis

• Subgingival gel and microspheres are inserted into periodontal pockets during scaling and root planning.
• Doxycycline - Subantimicrobial, low dose 20mg twice daily; Minocycline

Therapeutic Uses - Bacterial Infections

• Cholera, Brucellosis, plague, Leptospirosis, Tularemia, Bartonellosis
• Non gonococcal urethritis, cervicitis, epididymitis, Gonorrhea, MRSA, Acne
• SDD- 40mg twice daily

Therapeutic Uses - Peptic Ulcer Disease due to H.pylori

• Tetracycline

Therapeutic Uses - Sexually Transmitted Infections

• Lymphogranuloma venereum, nonspecific urethritis, cervicitis, epididymitis
• Pelvic inflammatory disease, Inclusion conjunctivitis, trachoma, Pneumonia, Psittacosis

Therapeutic Uses - Mycobacterium Infections

• Leprosy - Minocycline
• Nontuberculous or atypical Mycobacterium marinum & fortuitum infections
• Doxycycline; Minocycline

Therapeutic Uses - Rickettsial Infections

• Rocky mountain spotted fever, murine typhus, Q fever, rickettsialpox, african tick bite fever.

Therapeutic Uses - Protozoal Infections

• Chloroquine resistant falciparum malaria - Doxycycline, Tetracycline
• Balantidiasis - Tetracycline
• Adjunct to amoebicide in severe amoebic dysentery due to Entamoeba histolytica and in Dientamoeba fragilis infections - Tetracycline

Therapeutic Uses - Filarial Worm Infection

• Lymphatic filariasis - Doxycycline

Therapeutic Uses - Non Antimicrobial Uses

• EROSING agent, given intrapleurally to control pleural effusion in metastatic tumours - Minocycline; Tetracycline
• Treatment of chronic hyponatremia associated with the syndrome of inappropriate antidiuretic hormone secretion (SIAD)- Demeclocycline

Prophylactic Uses

• Tuberculosis (TB) - Doxycycline + Rifampin; Plague - Doxycycline / Tetracycline + Aminoglycoside; Weil's disease - Doxycycline, Tetracycline; Chloroquine resistant falciparum malaria - Doxycycline

Tigecycline Therapeutic Uses

• Complicated skin and intra abdominal infections caused by Staphylococcus aureus and MRSA
• Legionella, Klebsiella & Acinetobacter infections
• Anaerobic infections caused by Bacterioides, Peptostreptococcus, Propionic bacterium & Fusobacterium species

Adverse Drug Reactions

• Bone marrow depression
• Dose related- reversible decreased iron utilisation, reticulocytosis, anaemia, leucopenia, thrombocytopenia
• Unrelated form- irreversible- severe aplastic anaemia, bleeding

Suprainfection

• Grey baby syndrome: Fatal toxic effect of chloramphenicol in neonates, liver's inability to glucuronidate the drug

Hypersensitivity Reactions

• Nausea, vomiting, diarrhoea, glossitis, stomatitis

Therapeutic Uses - Other Indications

• Enteric fever
• Bacterial meningitis
• Severe anaerobic infections
• Typhus & spotted fever
• Eye & ear infections (Anthrax, Severe gastroenteritis, Gas gangrene, Granuloma, Inguinale, Listeriosis, Plague, Psittacosis, Tularemia)

Drug & Food Interactions

• Chelating property with dairy products & Al+++, Mg++, Ca++, Fe++ & bivalent, trivalent ions
• Food inhibits absorption of all TC except Doxycycline & Minocyclines
• Anacids, iron preparations, milk and dairy products should not be coadministered with tetracyclines

Chloramphenicol

• Bacteriostatic
• Mechanism of Action: Inhibits protein synthesis by binding with 50S ribosome
• Spectrum: Gram positive and gram negative bacteria

Mechanism of Resistance - Chloramphenicol

• Oral; intravenous, Topical - eye solution, ointment, ear drops

Other adverse drug reactions

• Intracranial hypertension in infants
• Jarisch - Herxheimer reaction in relapsing fever treated with tetracyclines
• Nephrotoxicity - caused by outdated and degraded tetracyclines; symptoms include polyuria, polydipsia, proteinuria, acidosis, glycosuria & aminoaciduria

Hepatotoxicity

• Increased liver enzymes and fatty liver changes
• Occurs esp. during pregnancy and hepatic insufficiency

Gastrointestinal (GIT) Effects

• Nausea
• Vomiting
• Irritant diarrhea
• Epigastric burning
• Oesophagitis
• Pancreatitis
• Oesophageal ulcers
• Odynophagia

Vestibular Toxicity

• Dizziness
• Vertigo
• Ataxia
• Nausea
• Vomiting
• Primarily with Minocycline & Doxycycline

Phototoxicity

• Patients should avoid direct exposure to sunlight or UV light

Diabetes Insipidus

• Demeclocycline inhibits vasopressin action
• Causes reversible nephrogenic diabetes insipidus
• Symptoms include polyuria, polydipsia, and weakness

Other Tetracycline-related adverse effects

• Tooth discoloration
• Enamel hypoplasia
• Pigmentation

Dental Discoloration

• Deciduous anterior teeth affected by tetracyclines are discoloured yellow or brownish grey, which is pronounced at the time of eruption and becomes more brownish after exposure to light
• Enamel hypoplasia and caries may occur
• Permanent teeth discoloration and pigmentation may happen from 2 months to 5 years of age

Other Effects

• Bone growth interference
• Nail discoloration and onycholysis
• Suprainfections (oral candidiasis, vulvovaginitis and pruritus ani, diarrhea(Pseudomonas, Proteus), pseudomembranous enterocolitis due to clostridium difficile)

Probiotics

• Lactobacillus Species: L.acidophilus, L.sporogens, L.rhamnosus, L.salivarius, L.plantarum, L.brevis, L.fermentum,L.helveticus, L.delbruecki, L.casei
• Bifidobacterium Species: B.longum, B.bifidum, B.infantis, B.breve, B.adolescentis
• Saccharomyces boulardii
• Streptococcus thermophilus

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