L.C. Parish, MD1, J. A. Witkowski, MD2 and H.B. Routh, MB, BSM3
1Departments of Dermatology and Cutaneous Biology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
2Departments of Dermatology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
3Paddington Testing Company, Inc., Philadelphia, Pennsylvania, USA
Moxifloxacin (Avelox®, Bayer), which is available for oral administration, is a broad-spectrum synthetic antimicrobial agent with excellent Gram-positive activity and good Gram-negative activity. The US FDA recently approved this drug for the treatment of bacterial skin infections.
bacterial skin infections, Gram-positive, Gram-negative, fluoroquinolones, moxifloxacin
Moxifloxacin, also known as Bay12-8039, is a new oral 8- methoxyfluoroquinolone that has significant use in the treatment of bacterial infections of the skin. It differs from the other quinolones by having a methoxy radical at the 8-position, with an S, S-configured diazabicyclonoyl ring moiety at the 7-position, and by having improved anti-bacterial activity over other similar quinolones.1, 2, 3
Mechanism of Action
Moxifloxacin is bactericidal against a range of Gram-positive and Gram-negative organisms. Such activity arises through the inhibition of DNA gyrase (topoisomerase II) and topoisomerase IV, which bacteria require for DNA replication, transcription, repair, and recombination. Moxifloxacin contains the C8- methoxy moiety that augments its antibacterial activity and reduces the possibility of Gram-positive mutations. Because the 8-fluoroquinolones use a different mechanism of action than do the aminoglycosides, beta-lactams, macrolides, or tetracyclines, there has been no known cross-resistance between the quinolones and these antimicrobial agents. While crossresistance does occur between moxifloxacin and other quinolones with Gram-negative bacteria, moxifloxacin continues to have more activity against most Gram-positive bacteria, particularly those now resistant to other fluoroquinolones.4-7 This agent also shows significant activity against Mycobacterium leprae.8 (See Table 1)
Moxifloxacin has a rapid rate of absorption with the majority of the administered dose available systemically within two hours. It is 50% bound to serum proteins, so that tissue levels will often exceed plasma concentrations in the skin, in subcutaneous tissue, and in blister formations. The skin blister concentration/plasma concentration ratio of 1.5 at 24 hours demonstrates that moxifloxacin penetrates well into inflammatory lesions.9 There is excellent bioavailability (>85%) and a half-life of 11-14 hours.
This 8-methoxyfluoroquinolone is not affected by, nor does it affect, the cytochrome P450 system. About 45% of the drug is excreted unmetabolized. Thirty-eight percent of the agent is eliminated in the feces with sulfate conjugation, while 14% is converted to a glucuronide conjugate and is excreted in the urine.
Renal and hepatic insufficiency does not affect the pharmacokinetics. Although photosensitivity is a potential unwanted effect with 8-fluoroquinolones, moxifloxacin has not produced UVA or UVB sensitivity. The photosensitivity of lomefloxacin, sparfloxacin, and pefloxacin has limited their usefulness.9
Iron and antacids can reduce the bioavailability of all agents in this group, but there are no drug-drug interactions with digoxin, glyburide, probenicid, ranitidine, theophylline, or warfarin. When moxifloxacin was given with a 500-calorie fat meal, there was no decrease in absorption.
|Aerobic Gram-positive bacteria||Staphylococcus aureus (methicillin-suspectible), Staphylococcus epidermidis (methicillin-susceptible), Streptococcus pneumoniae (including penicillin-susceptible/resistant|
strains), Streptococcus pyogenes
|Aerobic Gram-negative bacteria||Escherichia coli, Haemophilus influenzae, Hemophilus parainfluenzae, Klebsiella oxytoca, Klebsiella pneumoniae, Moraxella catarrhalis, Proteus mirabilis|
|Anaerobic bacteria||Fusobacterium species, Peptostrptococcus species, Prevotella species|
|Other microorganisms||Chylamydia pneumoniae, Legionella pneumophila, Mycobacterium leprae, Mycoplasma pneumoniae|
Table 1: Selected bacteria susceptible to moxifloxacin.
Moxifloxacin, given once daily as a 400mg tablet, is useful in treating uncomplicated skin infections of bacterial origin. In a study of 351 patients with such infections,7 moxifloxacin (400mg, daily) administered orally for 7 days was compared with cephalexin (500mg, tid).10 Moxifloxacin was 90% successful clinically, compared to 91% for the cephalosporin. Both eradicated Staphylococcus aureus (moxifloxacin 92%, cephalexin 93%), with moxifloxacin eradicating more of the Streptococcus species (90% to 82%).
Drug related adverse events caused discontinuation in 3% of the moxifloxacin patients, while 4% of the cephalexin treated patients stopped treatment. The unwanted reactions most commonly found included nausea (8%), diarrhea (6%), headache (2%), abdominal pain (2%), vomiting (2%), taste perversion (1%), and dyspepsia (1%). Abnormal liver function studies (elevated bilirubin levels) occurred in 1% of the study group.
When compared to other available fluoroquinolones, moxifloxacin receives a high rating. There is no interference with the QTc interval. It has a favorable safety profile. The dosage is not dependent upon creatinine levels, as is the case with ofloxacin and levofloxacin. Headaches and dizziness are uncommon, contrary to the experience with trovafloxacin.
Many clinicians may select a macrolide or a cephalosporin as their first choice for treating bacterial skin infections. However, the excellent penetration of the quinolones and their broader antibacterial spectrum make them an integral part of the dermatologic armamentarium.11 The safety profile of moxifloxacin, its bactericidal activity, and its once daily dosage highlight its attributes. (See Table 2.)
Moxifloxacin has an excellent safety and efficacy profile and can be used in dermatologic practice as part of the antimicrobial armamentarium to treat bacterial skin and skin structure infections.12
- Siefert HM, Domdey-Bette A, Henninger K, Hucke F, Kohlsdorfer C, Stass HH. Pharmacokinetics of the 8-methoxyquinolone, moxifloxacin: a comparison in humans and other mammalian species. J Antimicrob Chemother 43(suppl B):69-76 (1999 May).
- Stass HH, Dalhoff A, Kubitza D, Schuhly U. Pharmacokinetics, safety, and tolerability of ascending single doses of moxifloxacin, a new 8- methoxyquinolone administered to healthy subjects. Antimicrob Agents Chemother 42(8):2060-5 (1998 Aug).
- Malathum K, Singh KV, Murray BE. In vitro activity of moxifloxacin, a new 8-methoxyquinolone against Gram-positive bacteria. Diagn Microbiol Infect Dis 35(2):127-133 (1999 Oct).
- Goldstein EJ, Citron DM, Merriam CV, Warren Y, Tyrrell K. Comparative in vitro activities of GAR-936 against aerobic and anaerobic animal and human bite wound pathogens. Antimicrob Agents Chemother 44(10):2747-51 (2000 Oct).
- Jones ME, Visser MR, Klootwijk M, Heisig P, Verhoef J, Schmitz FJ. Comparative activities of clinafloxacin, grepafloxacin, levofloxacin, moxifloxacin, ofloxacin, sparfloxacin, and trovafloxacin and nonquinolones linezolid, quinupristin-dalfopristin, gentamicin, and vancomycin against clinical isolates of ciprofloxacin resistant and susceptible Staphylococcus aureus strains. Antimicrob Agents Chemother 43(2):421-3 (1999 Feb).
- Esposito S, Noviello S, Ianniello F, Novelli A. In vitro activity of moxifloxacin compared to other fluoroquinolones against different erythromycin-resistant phenotypes of Group A beta-haemolytic Streptococcus. Chemotherapy 46(1):23-7 (2000 Jan-Feb).
- Goldstein EJ, Citron DM, Hudspeth M, Hun Gerardo S, Merriam CV. In vitro activity of Bay 12-8039, a new 8-methoxyquinolone, compared to the activities of 11 other oral antimicrobial agents against 390 aerobic and anaerobic bacteria isolated from human and animal bite wound skin and soft tissue infections in humans. Antimicrob Agents Chemother 41(7):1552-7 (1997 Jul).
- Consigny S, Bentoucha A, Bonnafous P, Grosset J, Ji B. Bactericidal activities of HMR 3647, moxifloxacin, and rifapentine against Mycobacterium leprae in mice. Antimicrob Agents Chemother 44(10):2919- 21 (2000 Oct).
- Traynor NJ, Barratt MD, Lovell WW, Ferguson J, Gibbs NK. Comparison of an in vitro cellular phototoxicity model against controlled clinical trials of fluoroquinolone skin phototoxicity. Toxicol In Vitro 14(3):275-83 (2000 Jun).
- Parish LC, Routh HB, Miskin B, et al. Moxifloxacin versus cephalexin in the tretment of uncomplicated skin infections. Int J Clin Pract 54(8):497-503 (2000 Oct).
- Sadick NA. Systemic antibacterial agents. In: Wolverton SE. Comprehensive Dermatologic Drug Therapy. Philadelphia: WB Saunders p28-54 (2001).
- MacGowan A. Moxifloxacin (Bay 12-8039) a new methoxy quinolone antibacterial. Expert Opin Investig Drugs 8:181-199 (1999).