Maximising Moxifloxacin

Fluoroquinolone antibiotics have been a mainstay of the antibiotic arsenal since the introduction of nalidixic acid in the 1960s. Due to the worldwide increase of antimicrobial resistance, fluoroquinolones are generally reserved for proven or suspected infections where alternative agents are ineffective or contraindicated.

Moxifloxacin is the only fourth generation broad-spectrum fluoroquinolone antibiotic currently marketed in Australia, listed under the brand name Avelox^®. Its bactericidal action is exhibited through the inhibition of DNA gyrase (a type II topoisomerase) and topoisomerase IV, which are required for replication, transcription, repair, and recombination of bacterial DNA.

The main difference when compared to other fluoroquinolones, such as ofloxacin and ciprofloxacin, is its selectivity to topoisomerase IV, thus leading to an enhanced Gram-positive coverage. Similar to all other fluoroquinolines, the rate and extent of the bactericidal properties of moxifloxacin are dependent on the antibiotic concentration, therefore the best predictive outcome for such antibiotics are those with minimum inhibitory concentration and peak plasma concentration.

The adverse effects from fluoroquinolones may include rash, itch, dizziness, dyspepsia, restlessness, arthralgia, arthritis, raised liver enzymes, hypersensitivity reactions, as well as blood dyscrasias. Notably, the FDA introduced a black box label warning for patients using fluoroquinolones due to the raised risk of tendon damage, especially the Achilles tendon, in patients over 60 years of age. Moxifloxacin presents an extra risk factor by prolonging the QT interval, which increases the risk of potentially fatal cardiac arrhythmias.

In Australia, moxifloxacin is generally treated as one of the last-line antibiotics, only used when conditions are severe, or when other treatments have failed or are contraindicated. Table 1 shows the dosage and administration for approved indications, although it should be remembered that moxifloxacin does not reliably show activity against Pseudomonas aeruginosa, unlike its other counterparts such as ciprofloxacin.

Table 1: Dosage and administration guide for moxifloxacin

Moxifloxacin is only available in doses of 400mg, as two different presentations: an intravenous infusion, and oral tablets. These forms provide clinicians an option for route of administration, although it is highly recommended to swap from intravenous to oral therapy as soon as clinically appropriate, in part due to the high cost of each moxifloxacin 400mg/250mL IV bag, which is equivalent to five of the 400mg tablets.

Intravenous moxifloxacin is generally used to initiate therapy, or when the oral route is unavailable. The bactericidal activity is concentration dependant, and both routes of administration demonstrate similar distribution profiles, with the C_max and AUC almost matching. As the absolute oral bioavailability is around 90%, some hospitals in the United States have moved towards using oral tablets wherever possible, even if it is to be crushed and administered via a gastric/nasogastric feeding tube, primarily to reduce medication costs.

Pharmacists and nurses can assist in encouraging intravenous to oral conversions. In such cases, cost savings may be significant for the hospital, especially throughout winter, when an increased number of patients are admitted to hospital for treatment of community acquired pneumonia, some whom will have immediate penicillin hypersensitivity and will require moxifloxacin.

This further signifies the important role of all healthcare professionals in antimicrobial stewardship, promoting quality use of medications, as well as a commitment to strive towards seeking the best outcome for both the hospital and the patient.

Needing ideas for swapping IV to oral therapy? You may like to read: IV to Oral Switch Therapy