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The activities of ampicillin, meropenem, azithromycin, gentamicin, ciprofloxacin, and moxifloxacin against intracellular hemolysin-positive Listeria monocytogenes were measured in human THP-1 macrophages and were compared with the extracellular activities observed in broth. All extracellular concentrations were adjusted to explore ranges that are clinically achievable in human serum upon conventional therapy. In broth, ampicillin, meropenem, and azithromycin were only bacteriostatic, whereas gentamicin, ciprofloxacin, and moxifloxacin were strongly bactericidal in a concentration-dependent manner. In cells, ampicillin, meropenem, azithromycin, and ciprofloxacin were slightly bactericidal (0.3- to 0.8-log CFU reductions), moxifloxacin was strongly bactericidal (2.1-log CFU reduction), and gentamicin was virtually inactive. The difference in the efficacies of moxifloxacin and ciprofloxacin in cells did not result from a difference in levels of accumulation in cells (6.96 +/- 1.05 versus 7.75 +/- 1.03) and was only partially explainable by the difference in the MICs (0.58 +/- 0.04 versus 1.40 +/- 0.17 mg/liter). Further analysis showed that intracellular moxifloxacin expressed only approximately 1/7 of the activity demonstrated against extracellular bacteria and ciprofloxacin expressed only 1/15 of the activity demonstrated against extracellular bacteria. Gentamicin did not increase the intracellular activities of the other antibiotics tested. The data suggest (i) that moxifloxacin could be of potential interest for eradication of the intracellular forms of L. monocytogenes, (ii) that the cellular accumulation of an antibiotic is not the only determinant of its intracellular activity (for fluoroquinolones, it is actually a self-defeating process as far as activity is concerned), and (iii) that pharmacodynamics (activity-to-concentration relationships) need to be considered for the establishment of efficacy against intracellular bacteria, just as they are for the establishment of efficacy against extracellular infections.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12069960&dopt=Abstract
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Antimicrob Agents Chemother. 2002 Jul;46(7):2194-9.
Experimental acute otitis media due to nontypeable Haemophilus influenzae: comparison of high and low azithromycin doses with placebo.
Babl FE, Pelton SI, Li Z.
Maxwell Finland Laboratory for Infectious Diseases, Boston Medical Center, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
Treatment of acute otitis media (AOM) with azithromycin results in apparent clinical success, but tympanocentesis performed 4 to 6 days after initiation of therapy in children with nontypeable Haemophilus influenzae (NTHI) recovered from initial middle ear cultures demonstrates persistence of infection in more than 50% of episodes. We sought to determine the effect of azithromycin at different doses on the density of middle ear infection due to NTHI to provide additional understanding of this dichotomy between clinical and microbiologic outcome measures in AOM. In a chinchilla model of experimental otitis media (EOM), animals treated with placebo were compared to animals receiving a single daily dose 30 or 120 mg of azithromycin per kg of body weight per day for 5 days. Microbiologic outcome was assessed by obtaining quantitative cultures from the middle ear during a 5-day course and for 1 week following therapy. Azithromycin concentrations were measured to ascertain whether a concentration-dependent effect was present. Azithromycin at 30 and 120 mg/kg/day demonstrated a dose-dependent effect on the quantitative assessment of middle ear infection due to NTHI. A 30-mg/kg dose of azithromycin daily resulted in levels in serum and areas under the serum concentration-time curve at 24 h comparable to published data obtained with children given azithromycin at 5 to 10 mg/kg in multiday regimens. Increased doses of azithromycin (120 mg/kg) achieved 2.5- to 4-fold-higher levels in serum and 3- to 6-fold-higher total levels and levels in extracellular middle ear fluid as well as more rapid reduction in bacterial density and a greater proportion of middle ears with complete sterilization than either placebo or the 30-mg/kg/day regimen.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12069974&dopt=Abstract
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Jpn J Antibiot. 2002 Apr;55(2):196-202.
[Changes of antibody titers during antimicrobial therapy including levofloxacin for Chlamydia infections in the obstetrics and gynecology field]
[Article in Japanese]
Chimura T.
Department of Obstetrics and Gynecology, Shirataka Hospital.
During the 6 years from May 1995, Chlamydia antibody titers were measured in nonpregnant and pregnant women. In positive patients, changes of the antibody titer during treatment as well as the transplacental passage of antibodies into cord blood were investigated. 1) Chlamydia antibody-positive patients (n = 45) received the following therapy and changes of the IgA and IgG antibody titers during treatment were investigated: Levofloxacin alone at 300 mg/day for 14 days (n = 29), additional clarithromycin at 400 mg/day for 14 days (n = 10), additional azithromycin at 500 mg/day for 3 days (n = 3), clarithromycin alone at 400 mg/day for 14 days (n = 3). These patients were classified into four groups depending on either they were positive for both IgA and IgG (groups A-C) or were only positive for IgA or IgG (group D). Clearance of antibodies over time tended to be faster for IgA than IgG, but 25/38 (65.8%) showed negative for both antibodies after 6 years. 2) Antibody-positive women who were about 16 weeks pregnant (n = 61) were treated with clarithromycin (400 mg/day for 14 days) and the cord blood antibody titer was measured at the term of delivery. Cord blood IgA was not detected and IgG was strongly correlated with the maternal blood level (r = 0.945).
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12071097&dopt=Abstract
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