Ciprofloxacin

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Abstract
Ciprofloxacin is a broad spectrum fluoroquinolone antibacterial agent. Since its introduction in the 1980s, most Gram-negative bacteria have remained highly susceptible to this agent in vitro; Gram-positive bacteria are generally susceptible or moderately susceptible. Ciprofloxacin attains therapeutic concentrations in most tissues and body fluids. The results of clinical trials with Ciprofloxacin have confirmed its clinical efficacy and low potential for adverse effects. Ciprofloxacin is effective in the treatment of a wide variety of infections, particularly those caused by Gram-negative pathogens. These include complicated urinary tract infections, sexually transmitted diseases (gonorrhoea and chancroid), skin and bone infections, gastrointestinal infections caused by multiresistant organisms, lower respiratory tract infections (including those in patients with cystic fibrosis), febrile neutropenia (combined with an agent which possesses good activity against Gram-positive bacteria), intra-abdominal infections (combined with an antianaerobic agent) and malignant external Otitis. Ciprofloxacin should not be considered a first-line empirical therapy for respiratory tract infections if penicillin-susceptible Streptococcus pneumoniae is the primary pathogen; however, it is an appropriate treatment option in patients with mixed infections (where S. pneumoniae may or may not be present) or in patients with predisposing factors for Gram-negative infections. Clinically important drug interactions involving Ciprofloxacin are well documented and avoidable with conscientious prescribing. Recommended dosage adjustments in patients with impaired renal function vary between countries; major adjustments are not required until the estimated Creatinine clearance is 90% with 3- to 7-day Ciprofloxacin regimens (500 mg/day; >90% of patients were female), and were slightly lower with single-dose regimens. A3-day course of low-dose Ciprofloxacin (100mg twice daily) was as effective as cotrimoxazole (trimethoprim-sulfamethoxazole) [3- and 7-day regimens], nitrofurantoin (7 days) and Ofloxacin (3 days) in this indication. Cure rates ranged from 76 to 96% in complicated urinary tract infections, and Ciprofloxacin was as effective as cotrimoxazole, ceftazidime, aminoglycosides and other fluoroquinolones. Ciprofloxacin showed efficacy similar to that of ceftriaxone, ceftazidime and fleroxacin and greater than that of imipenem-cilastatin in patients with pneumonia (mostly nosocomial). In patients with acute exacerbation of chronic bronchitis, rates of cure/improvement were generally >90% and were similar to those achieved with rufloxacin, cotrimoxazole, amoxicillin (with and without clavulanic acid), Ceftibuten, Cefixime, cefuroxime axetil and Cefaclor. Although the use of fluoroquinolones in the treatment of lower respiratory tract infections in which S. pneumoniae is a suspected pathogen is an issue of concern, a recent review showed that the clinical and bacteriological efficacy of Ciprofloxacin are similar to that of traditional agents in these infections, including those caused by S. pneumoniae. Ciprofloxacin was as effective as cefuroxime axetil and amoxicillin-clavulanic acid, respectively, in the treatment of acute and chronic sinusitis. Clinical and bacteriological cure rates with Ciprofloxacin in patients with chronic Otitis media ranged from 58 to 70% and were higher than with amoxicillin-clavulanic acid in one study. High cure rates were observed in the treatment of malignant Otitis externa (>95%); compared with historical controls, Ciprofloxacin markedly shortened the hospital stay in this infection. Single-dose, 3- or 5-day Ciprofloxacin regimens produced cure or marked improvement in approximately 90% of patients with travellers’ and non-traveller’ diarrhoea and shigellosis (including infections caused by multiresistant strains). Ciprofloxacin was also shown to be effective in controlling institutional outbreaks of salmonellosis, but microbiological relapse rates varied between studies; prolonged faecal excretion of salmonellae is a concern. Cure rates of 100% were reported in patients with typhoid fever, including those with up to 40% multiresistant strains, in most studies. 14-day regimens may be more effective than 7-day regimens in patients with symptoms for ≥10 days duration. Ciprofloxacin produced cure rates of 100% in patients with cholera and reduced symptom duration. Ciprofloxacin treatment of skin/skin structure infections was as effective as cefotaxime, ceftazidime and other fluoroquinolones in moderate to severe infections. Increased resistance to MRSA would appear to limit its usefulness as first-line empirical therapy in these infections, most notably in institutions where MRSA predominate. Ciprofloxacin is effective in the treatment of osteomyelitis, where it has been used as sequential therapy to facilitate early discharge from hospital. Ciprofloxacin monotherapy is probably not appropriate in patients with febrile neutropenia. The ideal regimen in this infection remains to be defined, but ciprofloxacin-containing combination regimens appear to be at least as effective as standard regimens. Ciprofloxacin has demonstrated usefulness as prophylaxis in patients with neutropenia; however, this practice potentially limits its future usefulness as empirical treatment and increases the potential for development of resistance. In a limited number of comparative trials, Ciprofloxacin, in combination with an antianaerobic agent, has demonstrated efficacy similar to that of amoxicillin/clavulanic acid plus metronidazole and that of imipenem-cilastatin in intra-abdominal infection. In patients undergoing CAPD, Ciprofloxacin (25 to 50 mg/L per dialysate bag) appeared to be more effective than oral Ciprofloxacin in the treatment of peritonitis. Its clinical activity against Gram-positive pathogens in this setting has not been encouraging and further clarification is needed. Ciprofloxacin monotherapy showed similar efficacy to standard combination regimens in the treatment of pelvic inflammatory disease, endometritis and gallbladder infections; anaerobic pathogens accounted for the majority of treatment failures in ciprofloxacin-treated patients with gynaecological infections, indicating that the addition of an antianaerobic agent may be appropriate in these infections. Data, mostly from noncomparative trials, indicate that sequential intravenous and oral Ciprofloxacin is effective in the treatment of bacteraemia/sepsis in non-neutropenic patients. Oral and intravenous Ciprofloxacin has been used successfully as preoperative prophylaxis in patients undergoing urological, biliary tract, vascular or colorectal surgery. Clinical and bacteriological cure rates of 99.5% have been reported in gonococcal infections following single-dose Ciprofloxacin (100 to 2000mg; 69% received 250mg) administration. It is as effective as standard agents and other fluoroquinolones. Clinical cure rates of 92 to 100% have been reported in patients with chancroid following single-dose Ciprofloxacin (500mg). Because of its moderate activity against Chlamydia trachomatis, Ciprofloxacin is not recommended for treatment of non-gonococcal Urethritis. Although not currently approved for use in patients 90% of respiratory tract infections and demonstrated efficacy similar to that of combination intravenous regimens in paediatric patients with cystic fibrosis. Additionally, nearly 100% of children with life-threatening multiresistant typhoid fever were cured with Ciprofloxacin. Oral Ciprofloxacin treatment is effective in some infections which would other-wise require parenteral therapy and can be used as sequential therapy after parenteral antibacterial agents. Accordingly, a number of investigators have shown cost savings with oral Ciprofloxacin in hospitalised patients, based on the assumption that the more expensive parenteral regimen would have continued had oral Ciprofloxacin not been available. Treatment with oral Ciprofloxacin also allowed early discharge of some patients, thereby substantially reducing overall treatment costs. In two prospective randomised trials conducted in the US, sequential Ciprofloxacin therapy reduced antibacterial drug costs by approximately 45% compared with parenteral therapy and reduced hospitalisation costs by 20%. Retrospective cost analyses applied to recent prospective clinical trials showed that intravenous Ciprofloxacin was more cost effective than ceftazidime in patients with nosocomial pneumonia and 40% less costly than initial treatment with imipenem-cilastatin in patients hospitalised with severe pneumonia. Used appropriately, Ciprofloxacin can be less costly and/or more cost effective than traditional parenteral regimens in selected clinical settings. More well designed studies would be helpful in further defining the most cost-efficient use of this antimicrobial agent. Evidence from clinical trials and postmarketing surveillance studies confirms the good tolerability of oral Ciprofloxacin. Overall, ciprofloxacin-related adverse events were reported in approximately 9% of patients, and led to treatment withdrawal in 1.5% of patients. Gastrointestinal adverse events, mainly nausea, diarrhoea, vomiting, dyspepsia, anorexia or abdominal pain, were reported in ≈5% of Ciprofloxacin recipients. CNS (mostly dizziness, headache, restlessness or tremors) and dermatological (mostly rash or pruritus) adverse events were the next most frequently reported events (≈2 and ≈1% of patients, respectively). Most events were mild to moderate in severity; serious adverse events occurred in 65 years) and younger patients. Although the use of Ciprofloxacin is restricted in patients 1500 paediatric patients treated with Ciprofloxacin suggest a similar tolerability profile in children/adolescents and adults. Ciprofloxacin is rarely associated with clinically relevant changes in laboratory parameters. Metabolic or nutritional disorders occur in ≈4% of patients; alterations are mostly elevations in serum glutamic oxaloacetic transaminase and/or glutamic pyruvic transaminase levels (incidence of ≈1.5% each). Changes in renal function are rare, with elevated serum Creatinine and blood urea nitrogen levels occurring in 0.25% of patients. Concurrent administration of Ciprofloxacin and theophylline can increase plasma concentrations of the latter, which may increase the potential for theophylline-related adverse events. Multivalent cation-containing preparations (e.g. aluminium- or magnesium-based antacids, iron-, calcium- or zinc-containing preparations, enterai nutrition products, didanosine and sucralfate) can substantially reduce the bioavailability of Ciprofloxacin. Oral and intravenous Ciprofloxacin are normally administered in twice-daily regimens. Recommended dosages of oral Ciprofloxacin are 500 to 1500mg daily, depending on the site and severity of infection. Intravenous dosages usually range from 400 to 800mg daily and are infused over at least 60 minutes to minimise venous irritation; higher dosages (up to 1200 mg/day) have been used in patients with serious life-threatening infections. Duration of treatment depends on infection severity but is usually 7 to 14 days, or at least 2 days after disappearance of signs and symptoms of infection. Shortened regimens have been used in some infections, e.g. 3 to 7 days’ treatment in infectious diarrhoea, 3 days’ treatment (100 or 250mg twice daily) in acute uncomplicated cystitis and single-dose treatment in patients with acute uncomplicated gonococcal Urethritis. Bone and joint infections generally require longer treatment durations (e.g. 4 to 6 weeks or longer). The international dosing guidelines in renally impaired patients recommend maximum oral and intravenous Ciprofloxacin dosages of 1000 and 800 mg/day, respectively, in patients with a Creatinine clearance between 31 and 60 ml/min/1.73m (or a serum Creatinine level of between 1.4 and 1.9 mg/dl), and 500 and 400 mg/day, respectively, in patients with a Creatinine clearance ≤30 ml/min/1.73m2 (or a serum Creatinine level of ≥2 mg/dl). Ciprofloxacin is not currently approved for use in pregnant or lactating women, or in children and adolescents <18 years of age. Plasma theophylline concentrations should be monitored and dosage adjustments made as appropriate with concurrent administration of Ciprofloxacin. If concomitant administration of multivalent cation-containing preparations cannot be avoided, Ciprofloxacin should be administered at least 2 hours before or 6 hours after administration of these products.

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