Ciprofloxacin is a 4-quinolone derivative. It is a fluorinated analogs of nalidixic acid.
Ciprofloxacin is highly active against gram-negative bacteria and moderately active against gram-positive bacteria.
Class: Fluoroquinolone antibiotic (4-quinolone derivative; fluorinated nalidixic acid analog)
Trade Names: Cipro, Cipro I.V., Cipro XR, Proquin XR
Spectrum of Activity
- Highly active: Gram-negative bacteria (e.g., E. coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Shigella, Salmonella, Neisseria gonorrhoeae )
- Moderately active: Gram-positive bacteria (e.g., Staphylococcus aureus, Streptococcus pneumoniae, Enterococcus faecalis )
Indications
- Urinary tract infections (UTIs), including complicated and uncomplicated
- Acute pyelonephritis (usually E. coli )
- Upper and lower respiratory tract infections (excluding pneumococcal infections)
- Skin, soft tissue, bone & joint infections by gram-negative organisms
- Infectious diarrhea ( Shigella, Salmonella, E. coli, Campylobacter )
- Septicemia, meningococcal contacts
- Chronic bacterial prostatitis
- Sexually transmitted infections (STIs) like chlamydia and gonorrhea
- Sinusitis caused by gram-negative bacteria
- Anthrax (inhalation post-exposure prophylaxis and treatment)
Note: Ineffective against most anaerobic infections.
Mechanism of Action
- Bactericidal: Inhibits bacterial DNA synthesis.
- Targets topoisomerase II (DNA gyrase) in gram-negative bacteria, preventing DNA supercoiling.
- In gram-positive bacteria, inhibits topoisomerase IV , disrupting chromosome separation during replication.
- Prevents resealing of cleaved DNA strands, leading to bacterial cell death.
DNA Gyrase (Topoisomerase II)
- Enzyme essential for DNA supercoiling and compaction in bacteria.
- Catalyzes opening and closing of DNA strands without the need to rotate entire DNA loops.
- Targeted by ciprofloxacin to disrupt DNA replication.
Pharmacokinetics
- Absorption: Oral bioavailability ~70-80%, affected by food, iron, calcium.
- Distribution: Widely distributed, including eyes and cerebrospinal fluid (CSF) at ~10% plasma levels when meninges not inflamed.
- Crosses placenta and into breast milk.
- Metabolism: Hepatic metabolism, biliary excretion, and fecal elimination contribute to clearance.
- Excretion: Primarily renal via glomerular filtration and tubular secretion; probenecid inhibits excretion.
- Half-life ~4 hours; prolonged in renal impairment and elderly.
- Plasma protein binding: 20-40%
- Not significantly removed by dialysis.
Dosage and Administration
| Condition | Adult Dose | Duration |
|---|---|---|
| Acute uncomplicated UTI | 250–500 mg PO every 12 hours | 3–14 days |
| Complicated UTI | 500–750 mg PO every 12 hours | 7–14 days |
| Acute sinusitis | 500 mg PO every 12 hours | 10 days |
| Bone and joint infections | 500–750 mg PO every 12 hours | 4–6 weeks |
| Skin and soft tissue infections | 500–750 mg PO every 12 hours | 7–14 days |
| Infectious diarrhea | 500 mg PO every 12 hours | 5–7 days |
| Chronic bacterial prostatitis | 500 mg PO every 12 hours | 28 days |
| Anthrax (inhalation) | Adults: 500 mg PO every 12 hours for 60 days | 60 days |
| Gonococcal infections | Single 250 mg PO dose | Single dose |
- Adjust dose in renal impairment based on creatinine clearance.
- Elderly should receive the lowest effective dose.
- Take with plenty of fluids; can be taken with or without food.
Use in Pregnancy and Pediatrics
- Category C: Not recommended due to risk of cartilage damage (inhibition of chondrogenesis).
- Contraindicated during pregnancy, lactation, and in children.
Drug Interactions
- Decreased absorption: Antacids, iron supplements, sucralfate, zinc.
- Increased plasma levels/toxicity risk: Clozapine, methotrexate, methylxanthines, olanzapine.
- Increased serum creatinine: Cyclosporine.
- Seizure risk: With high-dose ciprofloxacin plus NSAIDs.
- Enhanced anticoagulant effect: Oral anticoagulants.
