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Volunteers received 1 drop of 0.5% levofloxacin in each eye and were assigned sequentially to 1 of 5 groups for tear sampling. Tear samples were collected on Schirmer test strips at 9 predetermined time points ranging from 5 minutes to 24 hours after administration. Six tear samples were collected at each time point (1 eye each from 6 volunteers), except the 24-hour time point, at which 12 samples were collected (both eyes of 6 volunteers). No eye had > 1 tear sample taken during the study. Levofloxacin concentrations were measured using reverse-phase high-performance liquid chromatography.
Sinusitis remains 1 of the most common reasons for antimicrobial prescriptions in the United States, with health care costs approaching $4 billion annually. We utilized the serial sinus aspirate sampling (SSAS) technique to obtain daily specimens to evaluate the time course of drug effect in patients with acute maxillary sinusitis. Eighteen patients with a radiologically confirmed acute maxillary sinusitis were enrolled into a study evaluating the relationship between levofloxacin exposure and the time course of antimicrobial effect using SSAS. SSAS was performed daily during therapy for bacteriologic evaluation. Six steady-state levofloxacin concentrations were obtained. Levofloxacin plasma and sinus aspirate concentrations were modeled using Monte Carlo Parametric Expectation Maximization algorithm implemented in S-ADAPT 1.53. Endpoints evaluated included time to resolution of signs and symptoms and time to sinus sterilization. Among the 18 enrolled patients, 15 were clinically evaluable. From these, 1 Streptococcus pneumoniae, 3 Haemophilus influenzae, 1 Moraxella catarrhalis, 1 Corynebacterium spp., and 1 coagulase-negative Staphylococcus organisms were isolated, with the latter 2 organisms being likely contaminants. For the pathogens, levofloxacin MIC values ranged from 0.03 to 2 mg/L. All pathogens were eradicated by the 4th day of therapy. The median and mean time to sinus sterilization (pathogens only) was 1 and 1.4 days, respectively. The median time to resolution of each sign and symptom ranged from 1.5 to 12-19 days, with the 83% of total signs and symptoms resolved by the end of therapy (day 5). The mean plasma area under the concentration-time curve (AUC) (mg x h/L) was 100.1 (n = 14, %CV = 27). Plasma AUC/MIC ratios ranged from 33.9 to 1696 for isolated pathogens. In this pilot SSAS study, levofloxacin rapidly eradicated isolated pathogens from the maxillary sinus.
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Review of the existing preclinical and clinical data on MP-376, with a focus on the efficacy and safety of the compound on chronic airways infections due to PA.
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The phototoxic effects of quinolone antimicrobial agents on mouse auricular skin and retina were examined histologically. Sparfloxacin at 50 or 100 mg/kg, which alone causes no histologic change, was orally administered to albino Balb/c mice, which were irradiated with ultraviolet A for 4 hr immediately after administration. In the auricle, degeneration of basal epidermal cells was sporadically observed at 2 hr (during the irradiation). Foci of slight edema with degenerated fibroblasts were seen in the dermis at 4 hr. Edema and neutrophil infiltration in the dermis became severe up to 96 hr. Initial changes in the retina were observed at 2 hr. Vacuolation of the photoreceptor segments (particularly the inner segment) was occasionally associated with swelling of retinal pigment epithelial cells. The segments became disorganized with time, and the outer nuclear layer showed reduced cellularity. The segments and layer were partially thinned and lost 96 hr later. Enoxacin at 400 and 800 mg/kg induced similar lesions to those of sparfloxacin. Levofloxacin caused similar lesions in the auricle but no change in the retina. The combination of oral administration of quinolone and ultraviolet A irradiation, which never caused apparent morphological changes alone, was shown to be able to induce phototoxic lesions in albino mice. Therefore, this method is thought to be useful to examine morphological changes caused by quinolone phototoxicity.
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Antibiotic resistance and poor compliance are the main causes of Helicobacter pylori (H. pylori) eradication failure. This study evaluated the eradication rate, tolerability, and compliance of levofloxacin- azithromycin combined triple therapy for H. pylori eradication.
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We tested 165 enterococcal isolates, biased toward vancomycin resistant (VR) isolates, collected during recent years from fecal samples of healthy subjects and clinical specimens of hospitalized patients (mostly from United States and some from Europe) for susceptibility to 19 antimicrobials. Nosocomial isolates, whether VR or not, were more often highly resistant to aminoglycosides and clindamycin than fecal isolates from healthy community volunteers and more often resistant to erythromycin, chloramphenicol, trimethoprim, levofloxacin and, for E. faecium, ampicillin (93 vs. 0%). Resistance rates were similar between nosocomial and community-fecal isolates for minocycline, rifampin and quinupristin-dalfopristin (Q-D). None of the 165 enterococci tested hybridized with aph(2'')-Ic and aph(2'')-Id probes for recently described gentamicin resistance genes and 37 of the 39 isolates with high level resistance (HLR) to gentamicin hybridized with an intragenic aac(6')-aph(2'') probe. Of the two newer drugs tested, daptomycin MIC90s were 0.25 microg/mL for E. faecalis and 1 microg/mL for E. faecium, regardless of their vancomycin resistance level or source. For Q-D, none of 28 E. faecium from community based healthy subjects in the USA and 7 of 66 E. faecium from hospitalized patients in the United States were resistant. Among these 7 Q-Dr United States isolates and 7 Q-Dr isolates from Europe (MICs of Q-D of 4-8 microg/mL), none hybridized with vat(D) (formerly satA) and vat(E) (formerly satG) DNA probes, indicating the involvement of other mechanism/s of resistance in these isolates. We also demonstrated that an intragenic probe of the gene ace from E. faecalis showed specific hybridizations to all E. faecalis isolates, suggesting the usefulness of this gene for identification of this species.
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Topical levofloxacin penetrates better than ofloxacin or ciprofloxacin into the aqueous of eyes with functioning filtering blebs. The combination of topical and oral levofloxacin may be preferable in the treatment of bleb-associated infections (NCT 00392275; Clinical trials.gov).
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This is an integrated summary of the results obtained from a 3-decade multicenter study on bacteria isolated from surgical infections in Japan between July 1982 and March 2012. During the 3-decade study, 11,196 strains were isolated from 4,787 patients consisting of 2,132 patients with primary infection and 2,655 patients with surgical site infection. Almost half of the primary infection was peritonitis, which accounted for 42.3%-55.5%. In contrast, most of the surgical site infection was wound infection, which accounted for 49.3%-66.1%. The most commonly isolated bacteria throughout three decades were Escherichia coli (1,164 strains), Enterococcus faecalis (842), Staphylococcus aureus (833), Pseudomonas aeruginosa (706), Bacteroides fragilis (705), Klebsiella pneumoniae (498), Enterobacter cloacae (391) and coagulase-negative staphylococci (CNS) (325). Overall, S. aureus and CNS had sensitivity for vancomycin, whose MIC90s were 0.78 to 3.13 μg/mL; E. faecalis had sensitivity for vancomycin and imipenem, whose MIC90s were 0.78-4 μg/mL; E coli, E. cloacae, K. pneumoniae, and B. fragilis had preferable sensitivity for imipenem. No antibacterial agents had a long-term good activity (e.g. MIC90 < 2 μg/mL) for P aeruginosa and Bilophila wadsworthia. Among antibacterial agents tested, ciprofloxacin had most bactericidal activity for P. aeruginosa; its MIC90 varied from 0.5 to 8 μg/mL. The MIC90s of all antibacterial agents tested except levofloxacin and minocycline were at least 128 μg/mL for B. wadsworthia. S. aureus accounted for approximately 20% to 60% of bacteria isolated after clean operation. Overall, at least 55% of the bacteria isolated after clean operation consisted of S. aureus, CNS, E. faecalis, E. coli, E. cloacae, K. pneunoniae, P. aeruginosa, B. fragilis, and B. wadsworthia throughout three decades. However, the percentage of other Gram-positive and negative bacteria increased with the worse of sterile condition in surgical operation. E. faecalis tended to be most commonly isolated from patients having host-compromised factors including carcinoma, diabetes, anticancer agents, steroids, immunosuppressants, and radiation, while E. coli was commonly isolated from patients having no such factors. Two-drug-resistant P. aeruginosa was first isolated in 1987, thereafter was frequently isolated, and reached 69 strains for 30 years. Three-drug-resistant P. aeruginosa was isolated in 1990, 1996, and 1998 to reach 5 strains, but not isolated in remaining 13 years. Methicillin-resistant S. aureus was highly frequently isolated between 1988 and 1991. Subsequently, the isolation frequency declined, sometimes increased in 1998, 2005, and 2006, and thereafter maintained lower levels by 2011.