Kinetics of kill of bacterial conjunctivitis isolates with moxifloxacin, a fluoroquinolone, compared with the aminoglycosides tobramycin and gentamicin.

PURPOSE: To compare the kinetics and speed of kill of Streptococcus pneumoniae and Haemophilus influenzae on exposure to three topical ophthalmic antibiotic solutions. MATERIALS AND METHODS: Bacterial conjunctivitis isolates of S. pneumoniae and H. influenzae were exposed to 1:1000 dilutions of moxifloxacin 0.5%, tobramycin 0.3%, gentamicin 0.3%, and water (control). At 15, 30, 60, 120, and 180 minutes after exposure, aliquots were collected, cells were cultured, and viable cell counts were determined using standard microbiological methods. RESULTS: Moxifloxacin achieved 99.9% kill (3-log reduction) at approximately 2 hours for S. pneumoniae and at 15 minutes for H. influenzae. Tobramycin and gentamicin did not achieve 3-log reduction of S. pneumoniae during the 180-minute study period. An increase in bacterial growth was noted for these isolates. Gentamicin took more than 120 minutes to achieve the 3-log reduction of H. influenzae and tobramycin did not reach the 3-log reduction of this pathogen during the 180-minute study period. CONCLUSION: Moxifloxacin killed S. pneumoniae and H. influenzae in vitro faster than tobramycin and gentamicin, suggesting its potential clinical benefit as a first-line treatment for bacterial conjunctivitis to minimize patient symptoms and to limit the contagiousness of the disease.

Comparison of fluoroquinolone kinetics of kill in susceptible and resistant gram-positive conjunctival pathogens.

INTRODUCTION: The purpose of this study was to compare moxifloxacin's rate of kill of susceptible and resistant Gram-positive organisms with that of ciprofloxacin and ofloxacin, using concentrations found in human conjunctiva after instillation of one drop. METHODS: Staphylococcus aureus (S. aureus) and Streptococcus pneumoniae (S. pneumoniae) isolates were exposed to moxifloxacin, ciprofloxacin, or ofloxacin diluted to human conjunctival concentrations achieved after instillation of one drop. These treated isolates were cultured on blood agar plates at 0, 15, 30, and 60 minutes after exposure, and incubated to observe the number of surviving colony-forming units/mL. RESULTS: In susceptible S. pneumoniae, moxifloxacin showed the most rapid reduction of colonies at 15 and 30 minutes, with the fewest colonies at 60 minutes compared with ciprofloxacin and ofloxacin. In S. pneumoniae resistant to ciprofloxacin and ofloxacin, moxifloxacin had rapid reduction in colonies at each time point and near-eradication at 60 minutes, while ciprofloxacin and ofloxacin had an increase in colonies at 60 minutes. In susceptible S. aureus, moxifloxacin had a rapid decrease in colonies at 15 and 30 minutes, compared with a slight reduction in colonies at these intervals for the other antibiotics. In methicillin-resistant S. aureus with cross-resistance to fluoroquinolones and other antibiotics, moxifloxacin had a decrease in colonies at each time point compared with an increase at each time point for ciprofloxacin and ofloxacin. CONCLUSION: Moxifloxacin showed an increased speed of kill against both of the common susceptible Gram-positive conjunctival pathogens, compared with the inconsistency of killing activity of two other fluoroquinolones tested. In addition, at the concentration level achieved in the conjunctiva after the instillation of one drop, moxifloxacin effectively and rapidly killed resistant Gram-positive conjunctival pathogens, while ciprofloxacin and ofloxacin had no effect against these organisms.

The pharmacodynamic properties of azithromycin in a kinetics-of-kill model and implications for bacterial conjunctivitis treatment.

INTRODUCTION: Antibiotics have traditionally been classified as bactericidal or bacteriostatic. Azithromycin belongs to the parent class of macrolides that are characteristically bacteriostatic. Some evidence suggests that this molecule demonstrates bactericidal kill and has concentration-dependent effects. This study tests the hypothesis that azithromycin demonstrates a bactericidal, concentration-dependent antibiotic effect at concentrations corresponding to and exceeding published tear and conjunctival levels. METHODS: The antibacterial activity of different concentrations of azithromycin 1% in DuraSite(R) (AzaSite(R); Inspire Pharmaceuticals Inc, Durham, NC, USA) was evaluated using a kinetics-of-kill model. Recent conjunctivitis isolates of Staphylococcus aureus, Streptococcus pneumoniae or Haemophilus influenzae were exposed to four concentrations of azithromycin (100, 250, 500 and 750 microg/ml). Starting concentrations were similar to the maximum concentrations (Cmax) that have been demonstrated in conjunctiva (83 microg/g) and tears (288 microg/ml) following topical ocular administration. The percentage of surviving bacteria at 30 and 60 minutes following exposure to each concentration were determined. RESULTS: Azithromycin failed to demonstrate bactericidal activity (i.e. a 3-log reduction in surviving bacteria) against S. aureus, S. pneumoniae or H. influenzae. Furthermore, the rate and extent of antibacterial activity with azithromycin did not change with higher concentrations, even at the highest tested concentration of 750 microg/ml. CONCLUSION: Similar to the parent macrolide class, azithromycin demonstrates bacteriostatic activity against common conjunctival pathogens up to the maximum tested concentration of 750 microg/ml (i.e. 2.6-times and 9-times published Cmax tear and conjunctival concentration, respectively). Azithromycin's bacteriostatic effects and prolonged elimination half-life will likely lead to a corresponding increase in the emergence of macrolide-resistant isolates.

Ocular distribution, bactericidal activity and settling characteristics of TobraDex ST ophthalmic suspension compared with TobraDex ophthalmic suspension.

INTRODUCTION: TobraDex ophthalmic suspension (tobramycin 0.3%, dexamethasone 0.1%; Alcon Laboratories Inc, Fort Worth, Tex) is frequently used for inflammatory ocular conditions where a risk of bacterial ocular infection exists. A new formulation, TobraDex ST ophthalmic suspension (tobramycin 0.3%, dexamethasone 0.05%, Alcon), utilises a novel suspension technology to reduce viscosity and help prevent settling in the container. METHODS: A rabbit model that closely mimics the human eye and a clinical study with cataract patients was used to compare the pharmacokinetics and tissue permeability of TobraDex ST and TobraDex. An in-vitro model was used to assess the bactericidal activity using the rabbit tear concentrations of tobramycin 10 minutes after a single topical dose. RESULTS: Concentrations of both tobramycin and dexamethasone were greater in the tear film and ocular tissues of rabbits treated with TobraDex ST. There was an 8.3-fold increase in tobramycin concentration in the rabbit tear film 10 minutes after dosing with TobraDex ST compared with TobraDex. Concentrations of tobramycin and dexamethasone in ocular tissues from rabbits exposed to TobraDex ST were up to 12.5-fold greater relative to TobraDex. The in-vitro bactericidal activity (>99.9% kill, 3-log reduction) of TobraDex ST toward tobramycin-resistant and methicillin-resistant Staphylococcus aureus occurred in 90 minutes. TobraDex ST killed Streptococcus pneumoniae 3-log in 5 minutes. TobraDex had no activity toward tobramycin-resistant, methicillin-resistant S. aureus and required approximately 120 minutes for 3-log reduction of S. pneumoniae. In humans, the mean ratio of dexamethasone levels in the aqueous humour at 1 hour was 1.17 in favour of TobraDex ST. CONCLUSION: TobraDex ST demonstrated improved suspension formulation characteristics, enhanced pharmacokinetic distribution and improved bactericidal characteristics, and may provide a useful alternative as compared to TobraDex.

Speed of bacterial kill with a fluoroquinolone compared with nonfluoroquinolones: clinical implications and a review of kinetics of kill studies.

It is important to rapidly eradicate bacteria in patients with bacterial conjunctivitis in order to decrease disease transmission, shorten symptom duration, and minimize the emergence of resistant bacteria. This paper presents the results of kinetics of kill studies on 3 commonly isolated pathogens in bacterial conjunctivitis. A more rapid speed of kill with moxifloxacin compared with other nonfluoroquinolone antibiotics (tobramycin, gentamicin, polymyxin B/trimethoprim, or azithromycin) was observed in Staphylococcus aureus, Streptococcus pneumoniae, and Haemophilus influenzae infections. Moxifloxacin achieved a 99.9% kill at approximately 1 h for S aureus, 2 h for S pneumoniae, and 30 min for H influenzae. In comparison, other nonfluoroquinolone therapies took longer to achieve a bactericidal (3-log) kill and some demonstrated no change or an increase in bacterial growth. Based on these findings, it is concluded that moxifloxacin kills bacteria more rapidly than nonfluoroquinolone topical ocular antibiotics.