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Saturday, August 9, 2025

Glycylcyclines


Generic and Brand Names

  • Tigecycline — Tygacil

Class

  • Glycylcyclines — semisynthetic derivatives of tetracyclines

  • Designed to overcome common tetracycline resistance mechanisms (efflux pumps, ribosomal protection)

Mechanism of Action

  • Binds reversibly to the 30S ribosomal subunit of bacteria

  • Blocks entry of amino-acyl tRNA into the A site of the ribosome

  • Inhibits protein synthesis, leading to bacteriostatic effect (bactericidal against some organisms)

  • Not affected by most tetracycline-specific efflux pumps or ribosomal protection proteins

Spectrum of Activity

  • Gram-positive: MRSA, MSSA, Streptococcus spp., Enterococcus spp. (including VRE)

  • Gram-negative: Broad activity including multidrug-resistant Acinetobacter spp., but no activity against Pseudomonas aeruginosa, Proteus spp., Providencia spp.

  • Anaerobes: Bacteroides spp., Clostridium spp. (except C. difficile)

  • Atypicals: Legionella, Mycoplasma, Chlamydophila

Indications

  • Complicated skin and skin structure infections (cSSSI)

  • Complicated intra-abdominal infections (cIAI)

  • Use only when alternative treatments are not suitable, due to increased mortality risk observed in some studies

  • Not indicated for diabetic foot infection without osteomyelitis, hospital-acquired pneumonia, or ventilator-associated pneumonia

Dosage and Administration

  • Adults:

    • Initial: 100 mg IV once

    • Maintenance: 50 mg IV every 12 hours

  • Administer via IV infusion over 30–60 minutes

  • Duration depends on infection site and clinical response (typically 5–14 days)

  • No adjustment in renal impairment

  • Adjust in severe hepatic impairment (Child-Pugh C): Maintenance 25 mg IV every 12 hours

Monitoring

  • Clinical improvement and resolution of infection

  • Liver function tests in prolonged therapy

  • Signs of superinfection (including C. difficile-associated diarrhoea)

  • Coagulation parameters if at risk of bleeding (tigecycline may prolong PT/INR)

Contraindications

  • Known hypersensitivity to tigecycline, tetracyclines, or any formulation components

  • Use in pregnancy unless clearly needed (can affect fetal tooth and bone development)

  • Avoid in children under 8 years (tooth discoloration, enamel hypoplasia, bone growth inhibition)

Precautions

  • Increased mortality risk compared to other antibiotics in pooled analyses — use only when benefits outweigh risks

  • Hepatic impairment — adjust dose in severe cases

  • Possible tooth discoloration and inhibition of bone growth in children and foetuses

  • Risk of pancreatitis (rare) — discontinue if suspected

  • Potential for photosensitivity (class effect)

Adverse Effects

  • Common: Nausea, vomiting, diarrhoea, headache

  • Less common: Abdominal pain, anorexia, dizziness, injection site reactions

  • Serious: Hepatic dysfunction, pancreatitis, anaphylaxis, C. difficile-associated diarrhoea, coagulopathy, increased mortality in certain infections

Drug Interactions

  • Anticoagulants (warfarin): Tigecycline may increase INR — monitor coagulation parameters

  • Oral contraceptives: May reduce effectiveness — advise additional contraception

  • P-gp substrates/inhibitors: Monitor for altered effects of co-administered drugs

  • Minimal CYP450 interaction

Overdose

  • No specific antidote

  • Symptoms: Exacerbation of adverse effects (e.g., nausea, vomiting, hepatic enzyme elevations)

  • Management: Supportive care, monitor vitals and organ function

Patient Counselling

  • Explain purpose and IV route of administration

  • Possible nausea/vomiting; report persistent or severe GI symptoms

  • Advise women using oral contraceptives to use backup contraception

  • Report symptoms of jaundice, severe abdominal pain, or allergic reaction

  • Complete the full course even if feeling better

  • Avoid unnecessary sunlight exposure; use protective clothing/sunscreen


Comparison Table

FeatureGlycylcyclines (Tigecycline)Tetracyclines (e.g., Doxycycline)Newer Tetracycline Derivatives (e.g., Omadacycline, Eravacycline)
Resistance profileRetains activity against many tetracycline-resistant strains (efflux & ribosomal protection)Often ineffective against resistant strainsOvercomes many resistance mechanisms, similar to tigecycline
Gram-positive coverageMRSA, VRE, StreptococcusMRSA (variable), no VREMRSA, some VRE
Gram-negative coverageBroad, excludes Pseudomonas, Proteus, Providencia, MorganellaNarrower, limited activity vs. MDR strainsBroader than tetracyclines, eravacycline active against some carbapenem-resistant strains
Anaerobe coverageStrongLimitedEravacycline strong, omadacycline limited
AtypicalsYesYesYes
IndicationscSSSI, cIAI (when no alternatives)Respiratory infections, acne, STIs, zoonosesCAP, ABSSSI (omadacycline), cIAI (eravacycline)
Mortality signalYes — increased all-cause mortality in pooled trialsNoNo
Oral availabilityNo (IV only)YesOmadacycline — oral & IV; Eravacycline — IV only
Safety issuesGI effects, hepatotoxicity, pancreatitis, photosensitivity, tooth/bone effectsGI effects, photosensitivity, tooth/bone effectsSimilar to tetracyclines; eravacycline generally better tolerated than tigecycline
Best avoided inBacteremia, pneumonia, when safer options existPregnancy, children under 8Pregnancy, children under 8




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