Fluoroquinolones 

1. Classification of Fluoroquinolones

Fluoroquinolones are concentration-dependent bactericidal antibiotics that inhibit bacterial DNA replication.

Generations & Spectrum

Generation

Drugs

Key Coverage

ICU Relevance

2nd

Ciprofloxacin, Ofloxacin

Strong Gram-negative incl. Pseudomonas

Sepsis, UTI

3rd

Levofloxacin

Gram-negative + better Streptococci

CAP

4th

Moxifloxacin

Gram-negative + Gram-positive + Anaerobes

CAP, intra-abdominal

Newer

Delafloxacin

MRSA + Pseudomonas

Resistant infections

Feature

Ciprofloxacin

Levofloxacin

Moxifloxacin

Pseudomonas

Strong

Moderate

No 

Pneumococcus

Weak

Strong

Strong

Anaerobes

No

No

Yes 

UTI

Yes 

Yes 

No 

QT risk

Low

Moderate

High


2. Mechanism of Action

Fluoroquinolones inhibit:

  • DNA gyrase (Topoisomerase II) → Gram-negative organisms
  • Topoisomerase IV → Gram-positive organisms

Concentration-dependent killing

  • Efficacy linked to Cmax/MIC and AUC/MIC
  • Post-antibiotic effect present

 Pharmacokinetics

Parameter

Feature

Oral bioavailability

Very high (~100%)

Tissue penetration

Excellent (lung, prostate)

CSF penetration

Moderate

Renal elimination

Most except moxi

Dose adjustment

Required in renal failure (except moxi)

 Avoid giving with:

  • Antacids
  • Iron
  • Calcium
    → Chelation ↓ absorption


3. Spectrum of Activity 

Gram-Negative Coverage

  • Enterobacteriaceae
  • H. influenzae
  • Neisseria
  • Moraxella
  • Pseudomonas (Ciprofloxacin > Levofloxacin)

Gram-Positive

  • Streptococcus pneumoniae (Levo/Moxi)
  • MSSA
  • MRSA (Delafloxacin only)

Atypicals 

  • Legionella
  • Mycoplasma
  • Chlamydophila

Anaerobes

  • Moxifloxacin only (moderate)

 Poor activity:

  • Enterococci
  • Most anaerobes (except moxi)
  • ESBL organisms (variable)


4. Individual Drugs in Detail

A. Ciprofloxacin

Best for:

  • Pseudomonas
  • Complicated UTI
  • Intra-abdominal infections (with metronidazole)


B. Levofloxacin

Best for:

  • Community-acquired pneumonia (CAP)-Respiratory fluoroquinolone
  • Atypical pneumonia
  • UTI


C. Moxifloxacin

Unique Feature:

  • Has anaerobic coverage
  • No reliable Pseudomonas coverage

 Not used in UTI (poor urinary excretion)


D. Delafloxacin

Newer FQ

  • Covers MRSA
  • Covers Pseudomonas

Used in:

  • Skin & soft tissue infections
  • Resistant organisms


5. ICU Indications 

1. Severe CAP

According to IDSA:

  • Beta-lactam + macrolide
    OR
  • Respiratory FQ monotherapy (Levo/Moxi)

2. Urosepsis

  • Ciprofloxacin (if susceptible)

3. Intra-abdominal infection

  • Ciprofloxacin + Metronidazole
  • Moxifloxacin monotherapy (selected cases)

4. Atypical Pneumonia

  • Legionella → Levofloxacin preferred

5. Post-exposure Anthrax

  • Ciprofloxacin drug of choice



6. Adverse Effects 

 Tendinopathy & Tendon Rupture

  • Achilles tendon
  • Higher risk in elderly & steroids

 CNS Effects

  • Delirium
  • Seizures
  • Psychosis

 QT Prolongation

  • Moxifloxacin > Levo > Cipro

 Dysglycemia

  • Hypo or hyperglycemia

 Aortic Aneurysm Risk

  • Increased collagen degradation


 Contraindicated:

  • Pregnancy
  • Children (cartilage toxicity)


7. Resistance Mechanisms

  1. Mutation in DNA gyrase gene
  2. Efflux pumps
  3. Reduced porin entry

Cross-resistance common within class.