Pharmacology Update

Sparfloxacin: A New Antibacterial Agent

By William T. Elliott MD, FACP, and James Chan PharmD, PhD

The fda has recently approved the second of two extended-spectrum fluoroquinolone antibacterial agents primarily for the treatment of community-acquired pneumonia and chronic bronchitis. Rhone- Poulenc Rorer’s sparfloxacin (Zagam) and Ortho’s levofloxacin (see Intern Med Alert 1997;19:85-86) both represent well-tolerated, broad spectrum antibiotics for this important indication.

Sparfloxacin was developed in Japan and is a chemically unique quinolone, with an amino substituent in the five-position and a fluorine substituent in the eight-position of the quinolone nucleus. The amino substituent enhances gram-positive activity,1 while the fluorine substituent increases plasma half-life2 but also appears to increase the risk of phototoxicity (e.g., lomefloxacin).

Like levofloxacin, sparfloxacin is dosed once a day and provides a wide range of coverage including activity against common gram-positive and gram-negative respiratory pathogens as well as the atypical pathogens Chlamydia pneumonia and Mycoplasma pneumonia. Importantly, these drugs seem to be active against penicillin-resistant pneumococcus and multidrug-resistant H. influenza and M. catarrhalis.

Indications

Sparfloxacin is indicated for the treatment of adults (18 years old) with the following infections caused by susceptible strains of the designated microorganisms: Community-acquired pneumonia caused by Chlamydia pneumoniae, Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella catarrhalis, Mycoplasma pneumoniae, or Streptococcus pneumoniae, acute bacterial exacerbation of chronic bronchitis caused by Chlamydia pneumoniae, Enterobacter cloacae, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Moraxella catarrhalis, Staphylococcus aureus, or Streptococcus pneumoniae.2

Potential Advantages

Sparfloxacin has a serum elimination half-life of 20 hours and is dosed once daily. It has a large volume of distribution as it penetrates well into body tissues, especially respiratory tissue.1,2

Sparfloxacin is active against a broad range of gram-positive and gram-negative microorganisms including atypical respiratory pathogens and penicillin- and erythromycin-resistant Streptococcus pneumoniae.1,3 In comparative trials, sparfloxacin was as effective as amoxicillin/clauvulanate, cefaclor, erythromycin, amoxicillin, ofloxacin, or amoxicillin plus ofloxacin for clearing community-acquired pneumonia.1,2,5-7

Sparfloxacin is more active than ciprofloxacin against Mycobacterium tuberculosis.1

Potential Disadvantages

Sparfloxacin is less active against P. aeruginosa than ciprofloxacin with a median MIC90 two- to four-fold higher.1 Photosensitivity is the most common adverse reaction, with an overall rate of nearly 8% in clinical trials (126 of 1585). Moderate to severe phototoxic reactions occurred in 3.9% of patients. Patients must be instructed to avoid exposure to the sun, bright natural light, and UV rays throughout the entire duration of treatment and for five days after treatment is stopped. Phototoxic reactions have occurred even with the use of sun screens and can occur following a single dose.2

A moderate prolongation of the QTc interval (approximate 2% incidence) occurs with sparfloxacin. The mean prolongation is about 10 msec. A small percent of patients (0.7%) had a clinically significant QTc interval prolongation of more than 500 msec. Torsades de pointes has been reported in patients receiving sparfloxacin with disopyramide and amiodarone. The drug is contraindicated in patients who are taking agents known to prolong the QTc interval and in individuals with a known QTc prolongation.2 Other side effects include diarrhea (4.6%), nausea (4.3%), and headache (4.2%).2

Dosage

Sparfloxacin is supplied in 200 mg tablets. The initial dose is 400 mg (2 ´ 200 mg) on the first day as a loading dose, then 200 mg every 24 hours for a total of 10 days. In patients with renal impairment (creatinine clearance < 50 mL/min), the 400 mg loading dose is used, but the maintenance dose should be reduced to 200 mg every 48 hours for a total of 10 days.2 Sparfloxacin can be taken with food but not with sulcrafate or antacids.

Comments

Sparfloxacin along with levofloxacin are recently introduced fluoroquinolone antimicrobials with activity against common respiratory pathogens. The drug is as efficacious as other oral antibacterials for the same indication. Both sparfloxacin and levofloxacin may be considered for the treatment of respiratory infections caused by penicillin-resistant Streptococcus pneumoniae.8 Sparfloxacin has greater in vitro activity against this organism as well as more favorable pharmacodynamics (i.e., plasma levels relative to minimum inhibitory concentrations) than levofloxacin,9 but the potential for phototoxicity and prolongation of QTc may be problematic. Prudent use of these new agents are essential.

Sparfloxacin is priced in the same range as levofloxacin, clarithromycin, and cefuroxime axetil and somewhat more than azithromycin.

Clinical Implications

Sparfloxacin is another extended-spectrum antibacterial with activity against common gram-positive, gram-negative, and atypical pathogens of the respiratory tract. It offers the ease of once-a-day dosing, but adverse reactions may be of concern compared with other drugs for the same indication. With the emergence of drug-resistant Streptococcus pneumoniae, the rational use of antibiotics is paramount in limiting the spread of this organism. These new fluoroquinolones, if used appropriately, can provide us with a useful alternative to older agents against this organism.

References

1. Goa KL, et al. Drugs 1997;53:700-725.

2. Zagam Product Information. Rhone-Poulenc Rorer. January 1997.

3. Cohen MA, et al. Diagn Microbiol Infect Dis 1996; 25:53-64.

4. Barrett MS, et al. Diagn Microbiol Infect Dis 1996; 24:113-116.

5. Portier H, et al. J Antimicrob Chemother 1996;37 (Suppl. A):83-91.

6. Lode H, et al. Eur Respir J 1995;8:1999-2007.

7. Allegra L, et al. J Antimicrob Chemother 1996;37 (Suppl. A):93-104.

8. Medical Letter 1997;39:41-43.

9. Stein GE. CID 1996;23 (Suppl. 1):19-24.