Levofloxacin is a broad-spectrum antibacterial agent with activity against a range of Gram-positive, Gram-negative, atypicals and anaerobes. It provides clinical and bacteriological efficacy in a range of infections, including those caused by both penicillin-susceptible and resistant strains of Streptococcus pneumoniae .

The pharmacokinetic profile of Levofloxacin is compatible with once-daily administration and 100% bioavailability allows for sequential intravenous to oral therapy.

The recent approvals in the US for the use in the treatment of Nosocomial pneumonia and chronic bacterial prostatitis and introduction of a short-course, high-dose regimen for use in community acquired pneumonia further extend the role of levofloxacin in treating bacterial infections. 1

Levofloxacin today is approved for 10 vital indications which are discussed in this issue.

Respiratory Tract Infections

The effectiveness of levofloxacin in the treatment of community-acquired pneumonia (CAP), acute exacerbations of chronic bronchitis (AECB) and acute sinusitis is well established. Levofloxacin is also approved for nosocomial pneumonia.

Nosocomial pneumonia

Therapy of nosocomial pneumonia is usually empiric and includes broad-spectrum antimicrobial agent. Levofloxacin has been found to be efficacious and beneficial in nosocomial pneumonia. Use of Levofloxacin 750 mg has further enhanced the clinical cure rates in nosocomial pneumonia.2

In patients with severe nosocomial pneumonia the bacteriological response rates with sequential levofloxacin 750 mg once daily was similar to that seen in intravenous Imipenem-Cilastatin (± switch to oral Ciprofloxacin) in a randomized non-blind trial (438 patients). The microbiological eradication rate with levofloxacin was 67% and with Imipenem-Cilastatin was 61%.3

Levofloxacin monotherapy was as safe and effective as the comparator regimen against most Gram-negative and Gram-positive pathogens, including a number of Pseudomonas aeruginosa.3

Community acquired pneumonia

In this multicentre, double blind investigation, subjects (528 patients) with mild to severe CAP (community-acquired pneumonia) were randomized to treatment with levofloxacin dosage of 750 mg per day for 5 days. Another group was given Levofloxacin 500 mg per day for 10 days. Clinical success rates were 92.4% in 750 mg group and 91.1% in the 500 mg group.

A 5 days course of levofloxacin 750 mg is as effective as levofloxacin 500 mg for 10 days.1

Acute exacerbations of chronic bronchitis

In randomized, double-blind, double-dummy, three-arm parallel design, multicentre study evaluating 832 patients received levofloxacin 250 mg OD, Levofloxacin 500 mg OD and Cefuroxime axetil 250 mg b.i.d. for 7-10 days. Clinical response rate was 70%, 70% and 61% respectively.

Levofloxacin (250 mg and 500 mg) OD is effective and well tolerated in treatment of AECB in adult patients. Both doses of levofloxacin were at least as effective as cefuroxime axetil and were active against pathogens like Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis 4

Acute maxillary sinusitis

In a comparative trial patients with acute sinusitis randomly received Levofloxacin 500 mg orally OD and amoxicillin-clavulanate 500/125 mg orally 3 times daily for 10 to 14 days. Clinical success rate was 88% and 87% respectively.

The results of this study show that once-daily administration of levofloxacin is as effective and better tolerated than amoxicillin-clavulanate administered 3 times daily for treating acute sinusitis in adult outdoor patients.5

Genitourinary Tract infections

Chronic bacterial prostatitis

Prostatitis has remained a pathological entity that is sometimes difficult to treat. Part of the difficulty revolves about the putative offending pathogens. For acute prostatitis, members of the Enterobacteriaceae, particularly Escherichia coli, play a central role, while intracellular pathogens such as Chlamydia are more frequently seen in chronic prostatitis. Consequently, a drug needs to be able to penetrate to this specialized site in both the acute and chronic infection forms of the disease and also have potent activity against the most common causative pathogens, both intracellular and extracellular. Levofloxacin has such an activity profile. 7

In randomized double-blind multicentric trial 377 patients with chronic bacterial prostatitis were evaluated. The clinical response rate was 75% and 73% for the patients received Levofloxacin 500 mg OD and Ciprofloxacin500 mg b.i.d. for 28 days.

Levofloxacin 500 mg OD for 28 days is as effective as Ciprofloxacin 500 mg b.i.d. for 28 days for the treatment of chronic bacterial prostatitis.8

Uncomplicated UTI

Uncomplicated UTI responds equally well to a 3-day course of oral levofloxacin 250 mg once daily or oral ofloxacin 200 mg twice daily.9

In acute pyelonephritis, oral levofloxacin 250 mg once daily for 7-10 days was as effective as oral ciprofloxacin 500 mg twice daily for 10 days.

Complicated UTI

In a non blind (n=461) trial clinical response rate was 93% in Levofloxacin group and 89% in Lomefloxacin group. 1

Oral Levofloxacin 250 mg once daily for 7-10 days was as effective as Lomefloxacin 400 OD for 14 days.1

Complicated skin & skin structure infections

In a randomized, non-blind multicentre trial evaluating 399 patients in complicated skin and skin structure infections levofloxacin 750 mg o.d. was compared with ticarcillin-clavulanate 3.1 g (4 times daily). The clinical success rates were 84% with levofloxacin and 80% with ticarcillin-clavulanate combination and bacteriological cure rates were 84% and 71% respectively.3

Uncomplicated skin and skin structure infections

In a randomized, multicentric, non-blind trial evaluating 469 patients in uncomplicated skin and skin structure infections levofloxacin 500 mg o.d. was compared with ciprofloxacin 500 mg b.i.d. The clinical success rates were 98% with levofloxacin and 94% with ciprofloxacin and bacteriological cure rates were 98% and 89% respectively.

It can be concluded that levofloxacin is a broad-spectrum antibacterial agent with activity against a range of Gram-positive and Gram-negative bacteria and atypical organisms. It provides clinical and bacteriological efficacy in a range of infections, including caused by both penicillin-susceptible and resistant strains of S. pneumoniae. Levofloxacin also has a pharmacokinetic profile that is compatible with once daily administration and allows for sequential intravenous to oral therapy. The recent approvals in the US for use in the treatment of nosocomial pneumonia and chronic bacterial prostatitis, and the introduction of a short-course, high dose regimen for use in CAP, further extend the role of levofloxacin in treating bacterial infections.1

Levofloxacin is approved by US FDA for the treatment of 10 indications1

No.	Indication	Dosage	Duration
1	Acute Exacerbations of Chronic Bronchitis	500 mg OD	7 days
2	Acute maxillary sinusitis	500 mg OD	10-14 days
3	Community Acquired Pneumonia	500 mg OD 750 mg OD	7-14 days 5 days
4	Nosocomial pneumonia	750 mg OD	7-14 days
5	Complicated UTI	250 mg OD	10 days
6	Uncomplicated UTI	250 mg OD	3 days
7	Chronic bacterial prostatitis	500 mg OD	28 days
8	Acute pyelonephritis	250 mg OD	10 days
9	Uncomplicated skin and skin structure infections	500 mg OD	7-10 days
10	Complicated skin and skin structure infections	750 mg OD	7-14 days

References
1. Drugs 2003, 63(24):2769-2802. 2. Clinical Therapeutics 2003, 25(2):485-514. 3. Drugs 2002, 62(14):2127-2167. 4. Journal of Antimicrobial Chemotherapy 1999, 43(4):529-39. 5. Otolaryngol Head Neck Surg 1999, 120(3):320-7. 6. Pharmacotherapy 1998, 18(6):1255-63. 7. Antimicrob Agents Chemother 2000, 44(8):2046-51. 8. Urology 2003, 62(3): 537-41. 9. Infect Dis Clin Pract 2000, 9:329-9. 10. Urology 1998, 51(4): 610-5. 11. Urology 1998, 52(1):51-5.