Trovafloxacin: New Fluoro- quinolone Antibacterial
By William T. Elliott, MD, and James Chan, PharmD, PhD
Pfizer has received approval to market trova-floxacin (Trovan), a new fluoroquinolone antibacterial. The drug was approved by the FDA for 14 indications, the largest number of indications ever given a new drug. Although similar to its cousin quinolones levofloxacin, sparfloxacin, and grepafloxacin, trova-floxacin is unique among this group for its activity against anerobes. This accounts for its approval not only for respiratory infections, but also intra-abdominal, post-surgical, gynecologic, and pelvic infections.
Trovafloxacin is a broad spectrum naphthyridone fluoroquinolone with activity against gram-positive organisms, such as Streptococcus pneumoniae, and anaerobic organisms, such as Bacteroides fragilis. Its activity against gram-negative organisms is similar to that of ciprofloxacin except for poorer coverage against Pseudomonas aeruginosa. An intravenous form of trovafloxacin is marketed as alatrofloxacin, an L-alanine-L-alanine form of trovafloxacin.
Table: Dosages for trovafloxacin
| Infection | Daily Dose | Total Duration |
| Nosocomial Pneumonia* | 300 mg IV followed by 200 mg oral | 10-14 days |
| Community acquired pneumonia | 200 mg oral or IV followed by 200 mg oral | 7-14 days |
| Acute bacterial exacerbation of chronic bronchitis | 100 mg qd | 7-10 days |
| Acute sinusitis | 200 mg qd | 10 days |
| Complicated intra-abdominal infections, including post-surgical infections | 300 mg IV followed by 200 mg oral | 7-14 days |
| Gynecologic and pelvic infections | 300 mg IV followed by 200 mg oral | 7-14 days |
| Prophylaxis of infections associated with elective colorectal surgery, vaginal and abdominal hysterectomy | 200 mg IV or oral | single dose within 30 min to 4 hrs before surgery |
| Uncomplicated skin and skin structure infections | 100 mg qd | 7-10 days |
| Complicated skin and skin structure infections, including diabetic foot infections | 200 mg IV or po followed by 200 mg qd oral | 10-14 days |
| Uncomplicated urinary tract infection | 100 mg qd | 3 days |
| Chronic bacterial prostatitis | 200 mg qd | 28 days |
| Uncomplicated urethral gonorrhea in males and endocervical and rectal gonorrhea in females | 100 mg qd | single dose |
| Cervicitis | 200 mg qd | 5 days |
| Pelvic inflammatory disease (mild-to-moderate) | 200 mg qd | 14 days |
* When P. aeruginosa is a documented or presumptive pathogen, combination with an aminoglycoside or aztreonam is indicated.8
Indications
Trovafloxacin is indicated for a wide range of infections including the following: Noscominal pneumonia caused by E. coli, P. aeruginosa, H. influenazae, or S. aureus; community acquired pneumonia caused by S. pneumonia, H. influenzae, K. pneumoniae, S. aureus, M. pneumoniae, M. catarrhalis, L. pneumophila, or C. pneumoniae; acute bacterial exacerbation of chronic bronchitis caused by H. influenzae, M. catarrhalis, S. pneumoniae, S. aureus, or H. parainfluenzae; and acute sinusitis caused by H. influenzae, M. catarrhalis, or S. pneumoniae.
It is also approved for complicated intra-abdominal infections, including post-surgical infections caused by E. coli, B. fragilis, viridan group streptococci, P. aeruginosa, K. pneumoniae, Peptostreptococcus species, or Prevotella species; gynecological and pelvic infections, including endomyometritis, parametritis, septic abortion; and post-partum infections caused by E. coli, B. fragilis, viridan group streptococci, E. faecalis, Streptococcus agalactiae, Peptostreptococcus species, P. revotilla species, or G. vaginalis.
Trovafloxacin is also indicated for uncomplicated skin and skin structure infections caused by S. aureus, S. pyogenes, or S. agalactiae; complicated skin and skin structure infections, including diabetic foot infections caused by S. aureus, S. agalactiae, P. aeruginosa, E. faecalis, E. coli, or P. mirabilis; and uncomplicated urinary tract infection caused by E. coli.
In the genitourinary system, the drug is indicated for chronic bacterial prostatitis caused by E. coli, E. facaelis, or S. epidermidis. It also covers uncomplicated urethral gonorrhea in males and endocervical and rectal gonorrhea in females caused by N. gonorrheae and cervicitis causes by C. trachomatis or pelvic inflammatory disease (mild-to-moderate) caused by N. gonorrheae or C. trachomatis.
Finally, the drug is the first oral drug ever approved for prophylaxis of infections associated with elective colorectal surgery and vaginal and abdominal hysterectomy.
Potential Advantages
Trovafloxain has shown excellent in vitro activity against S. pneumoniae, including multiply resistant strains.1-3 Resistance to other antibiotics did not appear to affect the susceptiblity to trovafloxacin.1,4 It is generally more active than levofloxacin and sparfloxacin.1,2 Trovafloxacin is also active against anaerobic organisms, including Bacteroides species, Prevotella species, Peptostreptococcus species, and Clostridium perfringens and difficile.4-6 Some strains of E. facaelis are susceptible to trovafloxacin. About 30% of vancomycin-resistant enterococci were susceptible to the drug.1,7
Potential Disadvantages
Trovafloxacin is about two-fold less active than ciprofloxacin against Pseudomonas aeruginosa.1,7
The most common side effect of trovafloxacin is lightheadedness and/or dizziness (up to 11%), which was reported significantly more frequently in females under 45 years of age. Patients should know how they react to the drug before operating an automobile or machinery. The incidence of dizziness may be reduced substantially if trovafloxacin is taken at bedtime or with food.8 Nausea is reported with a frequency of 4-8%. Concomitant administration of intravenous morphine and oral trovafloxain resulted in a significant reduction in bioavailability of trovafloxacin. Morphine should be administered at least two hours after oral trovafloxacin taken on an empty stomach or at least four hours after oral trovafloxacin is taken with food.8 Trovafloxacin can cause elevation of liver enzymes during or soon after prolonged therapy (21 days or more). Periodic assessment is advised.8
Dosing Information
Trovafloxacin is supplied in 100 mg and 200 mg tablets. Parenteral: equivalent to 5 mg/mL (200 mg, 300 mg).
Dosage
The dosages for various indications are shown in the table.
Trovafloxacin may be taken without regard to meals. Vitamins or minerals containing iron, aluminum, or magnesium-based antacids, antacids containing citric acid buffered with sodium citrate, or sucralfate should be taken at least two hours before or after trovafloxacin.8 No adjustment is required in patients with impaired renal function, as the drug is eliminated primarily in the feces. Dosage adjustment is recommended in patients with chronic hepatic disease.8
Comments
Trofloxacin is a broad spectrum fluoroquinolone with activity against the gram-negative, gram-positive, anaerobic, and atypical microrganism (e.g., M. pneumoniae, C. pneumoniae). It has the broadest FDA-approved indication of any currently marketed antibiotic. Trovafloxacin is not readily water soluble and is not suitable for intravenous administration. Alatrofloxacin, an L-alanyl-L-alamine derivative, is rapidly converted to trovafloxacin and is similar pharmacokinetically to oral administration of similar doses.9 No adjustment is needed when switching from IV or oral for comparable dosages.8 Comparative clinical trials have only been reported by Pfizer and have not been published. These trials suggest that trovafloxacin (100 mg daily) is at least comparable to clarithromycin (500 mg bid) for the treatment of acute bacterial exacerbation of chronic bronchitis. Sequential therapy with alatrofloxacin and trovafloxacin appeared comparable to sequential IV ciprofloxacin/ampicillin and oral ciprofloxacin/amoxicillin or IV ceftriaxone and cefpodoxime (with or without erythromycin) in hospitalized community-acquired pneumonia. Sequential therapy with alatrofloxacin and trovafoxacin also appeared comparable to sequential IV imipenem and amoxicillin/clavulante in complicated intra-abdominal infections.8
Clinical Implications
Trovafloxacin's activity against S. pneumoniae and anaerobes provides clinicians with another option for the treatment of respiratory tract and intraabdominal infections. Agents such as trovafloxacin need to be used judiciously, as the potential for the development of resistance following widespread use remains a concern. The daily cost of trovafloxacin is about $5.00 for 100 mg daily and about $6.00 for 200 mg daily.
References
1. Hoogkamp-Korstanje JAA. J Antimicrob Chemother 1997;40:427-431.
2. Barry AL, et al. Antimicrob Agents Chemother 1996;40:2431-2433.
3. Visalli MA, et al. J Antimicrob Chemother 1996;37: 77-84.
4. Spangler SK, et al. Antimicrob Agents Chemother 1994;38:2471-2476.
5. Child J, et al. J Antimicrob Chemother 1995;35: 869-876.
6. Brighty KE, et al. J Antimicrob Chemother 1997;39 (Suppl B):1-14.
7. Haria M, et al. Drugs 1997;54:435-445.
8. Trovan Product Information. Pfizer. December 1997.
9. Vincent J, et al. J Antimicrob Chemother 1997;39 (Suppl. B):75-80.
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