Ciprofloxacin; Uses, Dosage, Side Effects, Interactions, Pregnancy

Ciprofloxacin is a synthetic broad spectrum fluoroquinolone antibiotic. The chemical classification of ciprofloxacin is Quinolones. Ciprofloxacin binds to and inhibits bacterial DNA gyrase, an enzyme essential for DNA replication. This agent is more active against Gram-negative bacteria than Gram-positive bacteria.

Ciprofloxacin is a broad-spectrum antimicrobial carboxyfluoroquinoline.The bactericidal action of ciprofloxacin results from inhibition of the enzymes topoisomerase II (DNA gyrase) and topoisomerase IV, which are required for bacterial DNA replication, transcription, repair, strand supercoiling repair, and recombination. It is a second-generation fluoroquinolone with a broad spectrum of activity that usually results in the death of the bacteria.

Mechanism of Action of Ciprofloxacin 

Ciprofloxacin usually is bactericidal in action. Like other fluoroquinolone anti-infectives, ciprofloxacininhibits DNA synthesis in susceptible organisms via inhibition of the enzymatic activities of 2 members of the DNA topoisomerase class of enzymes, DNA gyrase and topoisomerase IV. DNA gyrase and topoisomerase IV have distinct essential roles in bacterial DNA replication. DNA gyrase, a type II DNA topoisomerase, was the first identified quinolone target; DNA gyrase is a tetramer composed of 2 GyrA and 2 GyrB subunits. DNA gyrase introduces negative superhelical twists in DNA, an activity important for initiation of DNA replication. DNA gyrase also facilitates DNA replication by removing positive super helical twists. Topoisomerase IV, another type II DNA topoisomerase, is composed of 2 ParC and 2 ParE subunits. DNA gyrase and topoisomerase IV are structurally related; ParC is homologous to GyrA and ParE is homologous to GyrB. Topoisomerase IV acts at the terminal states of DNA replication by allowing for separation of interlinked daughter chromosomes so that segregation into daughter cells can occur. Fluoroquinolones inhibit these topoisomerase enzymes by stabilizing either the DNA-DNA gyrase complex or the DNA-topoismerase IV complex; these stabilized complexes block movement of the DNA replication fork and thereby inhibit DNA replication resulting in cell death.

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The mechanism by which ciprofloxacin’s inhibition of DNA gyrase or topoisomerase IV results in death in susceptible organisms has not been fully determined. Unlike beta-lactam anti-infectives, which are most active against susceptible bacteria when they are in the logarithmic phase of growth, studies using Escherichia coli and Pseudomonas aeruginosa indicate that ciprofloxacin can be bactericidal during both logarithmic and stationary phases of growth; this effect does not appear to occur with gram-positive bacteria (e.g., Staphylococcus aureus). In vitro studies indicate that ciprofloxacin concentrations that approximate the minimum inhibitory concentration (MIC) of the drug induce filamentation in susceptible organisms; high concentrations of the drug result in enlarged or elongated cells that may not be extensively filamented. Although the bactericidal effect of some fluoroquinolones (e.g., norfloxacin) evidently requires competent RNA and protein synthesis in the bacterial cell, and concurrent use of anti-infectives that affect protein synthesis (e.g., chloramphenicol, tetracyclines) or RNA synthesis (e.g., rifampin) inhibit the in vitro bactericidal activity of these drugs, the bactericidal effect of ciprofloxacin is only partially reduced in the presence of these anti-infectives. This suggests that ciprofloxacin has an additional mechanism of action that is independent of RNA and protein synthesis.

Indications of Ciprofloxacin 

• Urinary tract infections (UTI) caused by certain bacteria such as E. coli.
• Infectious diarrheas caused by E. coli, Campylobacter jejuni, and Shigella bacteria.
• Skin infections
• Lung or airway Infections, for example, TB (tuberculosis), pneumonic and septicemic plague due to Yersinia pestis (Y. pestis), lower respiratory tract infections, and chronic bronchitis)
• Bone and Joint Infections
• Anthrax patients with fever and low white blood cell counts, and intra-abdominal infections.
• Typhoid fever
• Cervical and urethral gonorrhea due to Neisseria gonorrhoeae
• Chronic bacterial prostatitis
• Acute uncomplicated cystitis
• Escherichia urinary tract infection
• Infectious diarrhea
• Neutropenia, Febrile
• Otitis Media (OM)
• Plague caused by Yersinia pestis
• Sinusitis, Acute
• Typhoid fever caused by Salmonella typhi
• Hospital-acquired bacterial pneumonia
• Inhaled anthrax caused by Bacillus anthracis
• Skin-structure infections
• Kidney infections in children
• Uncomplicated Gonorrhea caused by Neisseria gonorrhoeae
• Acute exacerbation of chronic bronchitis caused by Moraxella catarrhalis
• Complicated Intra-Abdominal Infections
• Conjunctivitis caused by Haemophilus influenzae
• Conjunctivitis caused by Staphylococcus epidermidis
• Corneal Ulcers caused by Serratia marcescens
• Corneal Ulcers caused by Staphylococcus aureus
• Corneal Ulcers caused by Staphylococcus epidermidis
• Corneal Ulcers caused by Streptococcus Pneumoniae
• Corneal Ulcers caused by Streptococcus Viridans Group
• Corneal Ulcers caused by pseudomonas aeruginosa
• Lower respiratory tract infection caused by Enterobacter cloacae
• Lower respiratory tract infection caused by Escherichia coli
• Lower respiratory tract infection caused by Haemophilus influenzae
• Lower respiratory tract infection caused by Haemophilus parainfluenzae
• Lower respiratory tract infection caused by Klebsiella pneumoniae
• Lower respiratory tract infection caused by Proteus mirabilis
• Lower respiratory tract infection caused by penicillin-susceptible Streptococcus pneumoniae
• UTI caused by Citrobacter diversus
• UTI caused by Citrobacter frendii
• UTI caused by Entercococcus faecalis
• UTI caused by Enterobacter cloacae
• UTI caused by Klebsiella pneumoniae
• UTI caused by Morganella morganii
• UTI caused by Proteus mirabilis
• UTI caused by Providencia rettgeri
• UTI caused by Pseudomonas aeruginosa
• UTI caused by Serratia marcescens
• UTI caused by methicillin-susceptible Staphylococcus epidermidis
• Acute otitis externa caused by Staphylococcus aureus
• Acute otittis externa caused by Pseudomonas aeruginosa
• Acute, uncomplicated Cystitis caused by Escherichia coli
• Acute, uncomplicated Cystitis caused by Staphylococcus saprophyticus
• Chronic Prostatitis caused by Escherichia coli
• Chronic Prostatitis caused by Proteus mirabilis
• Complicated Pyelonephritis caused by Escherichia coli
• Complicated UTI caused by Escherichia coli

For the treatment of the following infections caused by susceptible organisms: urinary tract infections, acute uncomplicated cystitis, chronic bacterial prostatitis, lower respiratory tract infections, acute sinusitis, skin and skin structure infections, bone and joint infections, complicated intra-abdominal infections (used in combination with metronidazole), infectious diarrhea, typhoid fever (enteric fever), uncomplicated cervical and urethral gonorrhea, and inhalational anthrax (post-exposure).

Therapeutic Indications of Ciprofloxacin 

• Ciprofloxacin (IV, conventional tablets, oral suspension) is used in adults for the treatment of bone and joint infections, including osteomyelitis, caused by susceptible E. cloacae,  Ps. aeruginosa, or S. marcescens.
• Ciprofloxacin (IV, conventional tablets, oral suspension) is used in adults for the treatment of bone and joint infections, including osteomyelitis, caused by susceptible E. aerogenes, E. coli, K. pneumoniae, M. morganii, P. mirabilis. The drug also has been used in adults for the treatment of bone and joint infections caused by susceptible S. aureus, S. epidermidis, other coagulase-negative staphylococci, or Enterococcus faecalis (formerly S. faecalis), but other anti-infectives generally are preferred for these infections. Although resistance to ciprofloxacin has been reported in some strains of oxacillin-resistant S. aureus, oral ciprofloxacin may be a useful alternative to parenteral anti-infectives for the treatment of infections caused by susceptible oxacillin-resistant staphylococci.
• Although only limited experience is available to date, ciprofloxacin is recommended by the American Heart Association (AHA) and Infectious Diseases Society of America (IDSA) as an alternative agent for the treatment of native or prosthetic valve endocarditis caused by fastidious gram-negative bacilli known as the HACEK group (Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, Haemophilus aphrophilus, H. influenzae, H. parainfluenzae, H. paraphrophilus, Kingella denitrificans, K. kingae).
• Ciprofloxacin is used in adults or children for inhalational anthrax (postexposure) to reduce the incidence or progression of disease following suspected or confirmed exposure to aerosolized B. anthracis spores.
• Natural penicillins (e.g., oral penicillin V, IM penicillin G benzathine, IM penicillin G procaine) generally have been considered drugs of choice for the treatment of mild, uncomplicated cutaneous anthrax caused by susceptible strains of B. anthracis that occurs as the result of naturally occurring or endemic exposure to anthrax, although some clinicians suggest use of oral fluoroquinolones (ciprofloxacin, ofloxacin, levofloxacin), oral amoxicillin, or oral doxycycline if in vitro tests indicate susceptibility.
• A 60-day anti-infective regimen is recommended for postexposure prophylaxis in laboratory workers exposed to confirmed B. anthracis cultures; anti-infective prophylaxis is not necessary for unvaccinated workers employed in biosafety level 3 laboratories that maintain recommended conditions. Following a bioterrorism-related event, use of anti-infective prophylaxis in asymptomatic individuals in the general population is not indicated unless appropriate public health or law-enforcement agencies have ascertained that a risk of exposure to B. anthracis spores exists.699 In addition, the CDC states that postexposure prophylaxis is not indicated for the prevention of cutaneous anthrax, for autopsy personnel examining bodies infected with anthrax when appropriate isolation precautions and procedures are followed, for hospital personnel caring for patients with anthrax, or for individuals who routinely open or handle mail in the absence of a suspicious letter or credible threat.
• The possible benefits of postexposure prophylaxis against anthrax should be weighed against the possible risks to the fetus when choosing an anti-infective for postexposure prophylaxis in pregnant women. The CDC and other experts state that ciprofloxacin should be considered the drug of choice for initial postexposure prophylaxis in pregnant women exposed to B. anthracis spores and that, if in vitro studies indicate that the organism is susceptible to penicillin, then consideration can be given to changing the postexposure regimen to amoxicillin. Women who become pregnant while receiving anti-infective prophylaxis should continue the existing regimen and consult with a healthcare provider or public health official to discuss whether an alternative regimen might be more appropriate.
• Although ciprofloxacin generally is not recommended for use in infants and children, the benefits of ciprofloxacin prophylaxis outweigh the risks for inhalational anthrax (postexposure) and the drug may be used in children to reduce the incidence or progression of disease following exposure to aerosolized B. anthracis spores.
• Ciprofloxacin (IV, conventional tablets, oral suspension) is used for the treatment of clinically apparent inhalational anthrax, cutaneous anthrax, or GI and oropharyngeal anthrax, and for prophylaxis following ingestion of B. anthracis spores in contaminated meat.
• Ciprofloxacin (conventional tablets, oral suspension) is used in adults and children for inhalational anthrax (postexposure) to reduce the incidence or progression of disease following suspected or confirmed exposure to aerosolized Bacillus anthracis spores.
• Ciprofloxacin (IV, conventional tablets, oral suspension) is used in men for the treatment of recurrent urinary tract infections and chronic prostatitis caused by E. coli or P. mirabilis.
• Ciprofloxacin extended-release tablets containing ciprofloxacin hydrochloride are used only for the treatment of uncomplicated urinary tract infections (acute cystitis) caused by susceptible E. coli or K. pneumoniae in adults.
• Ciprofloxacin (IV, conventional tablets, oral suspension) is used in adults for the treatment of skin and skin structure infections caused by susceptible C. freundii, E. cloacae, E. coli, K. oxytoca, K. pneumoniae, M. morganii, P. mirabilis, P. vulgaris, P. stuartii, P. aeruginosa,  S. aureus (oxacillin-susceptible strains), S. epidermidis (oxacillin-susceptible strains), or S. pyogenes (group A beta-hemolytic streptococci). The drug has been effective in the treatment of cellulitis, abscesses, folliculitis, furunculosis, pyoderma, postoperative wound infections, and infected ulcers, burns, or wounds.
• Clinical improvement has occurred when oral ciprofloxacin was used alone for the treatment of acute exacerbations of bronchopulmonary Ps. aeruginosa infections in adults with cystic fibrosis.
• Ciprofloxacin is used for the treatment of nosocomial pneumonia, including hospital-acquired, ventilator-associated, and healthcare-associated pneumonia.
• IV ciprofloxacin is used for the treatment of nosocomial pneumonia caused by susceptible H. influenzae or K. pneumoniae and for the treatment of acute bacterial sinusitis caused by H. influenzae, S. pneumoniae (penicillin-susceptible strains), or M. catarrhalis. Ciprofloxacin (IV, conventional tablets, oral suspension) is used in adults for the treatment of respiratory tract infections, including bronchiectasis, bronchitis, lung abscess, and pneumonia, caused by susceptible  E. cloacae, E. coli, Haemophilus influenzae, H. parainfluenzae K. pneumoniae, P. mirabilis, Ps. aeruginosa, or S. pneumoniae (penicillin-susceptible strains).
• Oral or IV ciprofloxacin is used in the treatment of malignant otitis externa caused by Ps. aeruginosa.
• IV ciprofloxacin has been used with some success for the treatment of meningitis caused by gram-negative bacteria.
• Ciprofloxacin (IV initially followed by oral therapy with conventional tablets or oral suspension) is used in conjunction with oral metronidazole for the treatment of complicated intra-abdominal infections caused by E. coli, Ps. aeruginosa, P. mirabilis, K. pneumoniae, or Bacteroides fragilis.
• Ciprofloxacin (conventional tablets, oral suspension) has been used for the short-term treatment of travelers’ diarrhea or for the prevention of travelers’ diarrhea in adults traveling for relatively short periods of time to high-risk areas. The most common cause of travelers’ diarrhea worldwide is noninvasive enterotoxigenic strains of E. coli (ETEC), but travelers’ diarrhea also can be caused by various other bacteria including enteroaggregative E. coli (EAEC), Campylobacter jejuni, Shigella, Salmonella, A. hydrophila, Plesiomonas shigelloides, Yersinia enterocolitica, or V. parahaemolyticus or non-O-group V. cholerae. In some cases, travelers’ diarrhea is caused by a parasitic enteric pathogen (e.g., Giardia duodenalis (also known as G. lamblia or G. intestinalis), Cryptosporidium parvum, Cyclospora cayetanensis, Entamoeba histolytica, Dientamoeba fragilis) or a viral enteric pathogen (e.g., rotavirus, norovirus).
• Although GI infections caused by Yersinia enterocolitica or Y. pseudotuberculosis usually are self-limited and anti-infective therapy unnecessary, the American Academy of Pediatrics (AAP), US Centers for Disease Control and Prevention (CDC), IDSA, and others recommend use of anti-infectives in immunocompromised individuals or for the treatment of severe infections or when septicemia or other invasive disease occurs.
• Ciprofloxacin (conventional tablets, oral suspension) is used for the treatment of shigellosis caused by susceptible Shigella.
• Although co-trimoxazole generally is the drug of choice for GI infections caused by Cyclospora or Isospora, ciprofloxacin is recommended as an alternative. Ciprofloxacin may not be as effective, but may be useful for the treatment of these infections in patients who cannot tolerate co-trimoxazole.
• Ciprofloxacin (conventional tablets, oral suspension) is used in adults for the treatment of infectious diarrhea caused by susceptible strains of enterotoxigenic E. coli, Campylobacter fetus subsp. jejuni, Salmonella, Shigella (S. flexneri, S. boydii, S. sonnei, S. dysenteriae), or Vibrio.
• Ciprofloxacin is recommended for use in a multiple-drug regimen for the empiric treatment of culture-negative endocarditis.
• A single oral dose of ciprofloxacin (conventional tablets, oral suspension) has been used for the treatment of uncomplicated urethral, endocervical, rectal, or pharyngeal gonorrhea caused by susceptible Neisseria gonorrhoeae.
• Oral ciprofloxacin (administered with or without metronidazole) has been used for induction of remission of mildly to moderately active Crohns disease.
• Oral ciprofloxacin was used with some success in a limited number of women for the treatment of urethral and cervical infections caused by C. trachomatis or Mycoplasma hominis. The drug generally has been ineffective in both men and women for the treatment of urogenital infections caused by Ureaplasma urealyticum.
• Ciprofloxacin (conventional tablets, oral suspension) has been effective in men for the treatment of chancroid, genital ulcers caused by Haemophilus ducreyi.
• Ciprofloxacin is recommended as an alternative to penicillin G for the treatment of infections caused by Capnocytophaga canimorsus.
• Ciprofloxacin has been used in the treatment of brucellosis caused by Brucella melitensis, and some clinicians suggest that a regimen of ciprofloxacin and rifampin can be used as an alternative regimen for the treatment of the disease.
• Some clinicians suggest that fluoroquinolones (e.g., ciprofloxacin) may be an alternative to tetracyclines for the treatment of other Vibrio infections, including gastroenteritis or wound infections caused by V. parahaemolyticus or V. vulnificus.
• Ciprofloxacin is used for perioperative prophylaxis in high risk patients undergoing genitourinary surgery.
• Ciprofloxacin has been used for the treatment of cholera caused by Vibrio cholerae 01 or 0139 in adults or children.
• Ciprofloxacin (conventional tablets, oral suspension) is used in adults for the treatment of typhoid fever (enteric fever) caused by susceptible strains of Salmonella typhi, including chloramphenicol-resistant strains.
• Ciprofloxacin (IV, conventional tablets, oral suspension) is recommended as an alternative to aminoglycosides (streptomycin or gentamicin) for the treatment of tularemia caused by Francisella tularensis.
• Oral ciprofloxacin has been used effectively for selective decontamination of the GI tract in granulocytopenic patients or other debilitated patients (e.g., those with cirrhosis).
• Ciprofloxacin has been used with some success in a limited number of patients for the treatment of various rickettsial infections.
• Ciprofloxacin (IV, conventional tablets, oral suspension) is recommended as an alternative agent for the treatment of plague caused by Yersinia pestis and also is recommended for postexposure prophylaxis following a high-risk exposure to Y. pestis, including exposure in the context of biologic warfare or bioterrorism.
• Ciprofloxacin (conventional tablets, oral suspension) is used in adults to eliminate nasopharyngeal carriage of Neisseria meningitidis.
• Although resistance to ciprofloxacin has been reported in strains of oxacillin-resistant S. aureus, oral ciprofloxacin (750 mg every 12 hours for 7-28 days) has been used to temporarily eliminate oxacillin-resistant S. aureus colonization in patients with serious diseases who were at risk for infection.
• Oral ciprofloxacin (conventional tablets, oral suspension) has been used in the treatment of mycobacterial infections, including those caused by Mycobacterium tuberculosis, M. fortuitum, or M. avium complex (MAC).
• Although ciprofloxacin reportedly has some activity in vitro against Plasmodium falciparum, oral ciprofloxacin has been ineffective when used alone in the treatment of uncomplicated malaria caused by chloroquine-resistant P. falciparum.
• Ciprofloxacin has been effective for the treatment of Legionnaires’ Disease caused by Legionella pneumophila, and some clinicians suggest that ciprofloxacin may be considered a drug of choice for this infection, especially in immunocompromised patients (e.g., transplant recipients).
• Oral ciprofloxacin is considered an alternative agent for the treatment of granuloma inguinale (donovanosis) caused by Klebsiella granulomatis (formerly Calymmatobacterium granulomatis).
• Ciprofloxacin (IV, conventional tablets, oral suspension) has been used as an alternative agent for the treatment of disseminated gonococcal infections caused by susceptible N. gonorrhoeae.
• Ciprofloxacin has been used in the treatment of cat scratch disease caused by Bartonella henselae (formerly Rochalimaea henselae).
• Ciprofloxacin hydrochloride and dexamethasone otic suspension is applied to the ear canal and middle ear for the treatment of acute otitis media caused by susceptible strains of S. aureus, S. pneumoniae, H. influenzae, Moraxella catarrhalis, or Ps. aeruginosa in pediatric patients’ tympanostomy tubes.
• Ciprofloxacin hydrochloride and hydrocortisone otic suspension is applied to the ear canal for the treatment of acute bacterial otitis externa caused by susceptible strains of S. aureus, Ps. aeruginosa, or Proteus mirabilis.
• Ciprofloxacin ophthalmic solution is used in the treatment of conjunctivitis caused by susceptible Staphylococcus aureus , S. epidermidis, Streptococcus pneumoniae, or Haemophilus influenzae.
• Ciprofloxacin ophthalmic solution is used in the treatment of keratitis (corneal ulcer) caused by susceptible Pseudomonas aeruginosa, Serratia marcescens, Staphylococcus aureus, S. epidermidis, Streptococcus pneumoniae, or viridans streptococci,.

Contra Indications of Ciprofloxacin 

• History of severe hypersensitivity (e.g. anaphylactic reaction) to any other type of betalactam antibacterial agent (penicillins, monobactams, and carbapenems).
• Hemolytic anemia
• Liver problems
• Interstitial nephritis
• Subacute cutaneous lupus erythematosus
• Systemic lupus erythematosus
• use should be avoided in pregnant or lactating women, and in children with developing teeth because they may result in permanent staining (dark yellow-gray teeth with a darker horizontal band that goes across the top and bottom rows of teeth), and possibly affect the growth of teeth and bones.
• Allergy
• Avoid taking this medicine if you have a known allergy to it or any other fluoroquinolones.
• Avoid if you have a past history of tendinitis or tendon rupture after using this medicine.
• Myasthenia Gravis
• Use by those who are hypersensitive to any member of the quinolone class of antimicrobial agents
• Ciprofloxacin is also considered to be contraindicated in children (except for the indications outlined above), in pregnancy, to nursing mothers, and in people with epilepsy or other seizure disorders.

FDA pregnancy  risk category C

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