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We evaluated markers of alternative and classical macrophage activation in the lungs of patients with CF and evaluated these characteristics in the context of Pseudomonas aeruginosa (PA) infection, immunomodulatory drug therapy and pulmonary function.
Azithromycin was more effective than doxycycline in treating patients infected with M genitalium. The extended course of azithromycin was highly effective but was given after the initial treatment with doxycycline. Randomised clinical trials are needed to compare the different dosages of azithromycin.
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Observational data strongly suggest an association between Chlamydia pneumoniae and atherosclerotic cardiovascular disease. However, few studies have mechanistically linked C. pneumoniae to vascular remodeling. The purpose of the present study was to examine the mechanistic relationship between C. pneumoniae and human vascular smooth muscle cell (VSMC) physiology. We sought to determine the influence of human VSMC infection by C. pneumoniae on (1) VSMC proliferation and (2) activation of the proinflammatory and proliferative transcription factors nuclear factor kappaB (NF-kappaB) and activator protein 1 (AP-1).
The effect of macrolides on the superoxide (O2 (-)) production by neutrophils was studied. Resting neutrophils become primed by lipopolysaccharide (LPS) or N-formyl-methionyl-leucyl-phenylalanine (fMLP), and primed neutrophils generate O2 (-) in response to fMLP or adhesion, respectively. Both LPS-primed fMLP-stimulated O2 (-) generation by macrolide-treated neutrophils and adhesion-stimulated O2 (-) generation by macrolide-treated fMLP-primed neutrophils were inhibited. Macrolide inhibition of O2 (-) generation was dependent on serum or pH. Serum could be substituted by NaHCO3. The intensity of inhibition was azithromycin = roxithromycin > clarithromycin > erythromycin, in that order. Non-antimicrobial derivatives of erythromycin, that is, EM703 and EM900, inhibited O2 (-) generation at pH 7.4. NH4Cl abolished the activity of azithromycin (AZ) only when added to neutrophils with AZ but not after incubation with AZ, suggesting that NH4Cl prevented the influx of AZ. AZ did not affect the expression of alkaline phosphatase, CD11b, and cytochrome b558 in both resting and LPS-primed neutrophils. These results suggested that macrolides did not affect granule mobilization but inhibited O2 (-) generation selectively.
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Of a total of 275 S. pyogenes isolates recovered, 105 (38%) were erythromycin-resistant (MIC > or = 1 microgram/ml) [corrected], with 54, 45 and 1% of them carrying mef(A), erm(A) [subclass erm(TR)] and erm(B) gene, respectively. The prevalence of erythromycin-resistant strains was 29 and 42% during the time periods December, 1998, to December, 1999, and January, 2000, to December, 2000, respectively. All erythromycin-resistant isolates were also resistant to clarithromycin and azithromycin. The isolates carrying the erm(A) gene were inducibly resistant to clindamycin. The 275 S. pyogenes isolates had ceprozil MICs < or = 0.032 microgram/ml.
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A multicentre, collaborative study was performed in Asia and Europe during the winter of 1997-1998 to determine the in vitro activity of selected antimicrobial agents against common respiratory pathogens. Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis isolates were collected from 48 sites in China, France, Germany, Italy, Japan, Spain and the UK and tested in a central laboratory in the USA. Broth microdilution MICs were determined for beta-lactams (penicillin, amoxycillin/clavulanate, cefuroxime, ceftriaxone), macrolides (azithromycin, clarithromycin), sulphonamides (co-trimoxazole), glycopeptides (vancomycin) and fluoroquinolones (levofloxacin). The percentage of isolates susceptible to each antimicrobial class varied substantially by country. Penicillin susceptibility amongst pneumococci ranged from 34% in France and Spain to 92% in Germany, and macrolide susceptibility varied between 26% in China and 91% in the UK. In most countries beta-lactam, macrolide and cotrimoxazole resistance was more prevalent amongst penicillin-intermediate and -resistant S. pneumoniae isolates. However, little or no resistance was detected to levofloxacin (0.3% intermediate and resistant) or vancomycin (0% intermediate and resistant). For H. influenzae the prevalence of beta-lactamase production varied from 6% in China and Germany to 32% in Spain, and for M. catarrhalis, from 79% in Germany to 98% in Japan. With the exception of ampicillin, beta-lactamase production had a minimal effect on beta-lactam activity against H. influenzae or M. catarrhalis. Our findings demonstrate that antimicrobial resistance profiles of common respiratory isolates differ dramatically between countries in Asia and Europe.
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To evaluate the prevalence of and associated factors for recurrent Chlamydia trachomatis infection in pregnant women, a retrospective cohort study was conducted in an urban prenatal clinic in an underserved area. Women with chlamydial carriage in pregnancy between 1992 and 1996 were identified by a direct DNA assay. Entrance criteria limited the population to those who were positive for chlamydia, were treated, had proof of cure and had at least one subsequent test for chlamydia, all in the same pregnancy. Of the 149 women who met entrance criteria, 25 (17%) had recurrent chlamydial carriage. The only identified risk factor was maternal age <20 years (21 of 98 vs. 4 of 51, odds ratio = 3.21). Infection with gonorrhea or other sexually transmitted diseases during the same pregnancy were not predictive of reinfection. Initial therapy with azithromycin, when compared to erythromycin, did not appear protective for recurrent infection. Pregnant adolescents are more likely to have recurrent chlamydial infection. Prenatal care programs should consider this when counseling and treating these patients.
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Chronic inflammation of the airways is a central component in lung diseases and is frequently associated with bacterial infections. Monitoring the pro-inflammatory capability of bacterial virulence factors in vivo is challenging and usually requires invasive methods.
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The incidence of syphilis has been increasing in the United States since reaching a nadir in 2000. Several clinical trials have demonstrated that treatment with oral azithromycin may be useful for syphilis control. After reports of azithromycin treatment failures in San Francisco, we investigated the clinical and epidemiologic characteristics of patients with syphilis due to azithromycin-resistant Treponema pallidum infection.
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Comparison of the sunitinib C(max) for the sunitinib + clarithromycin group with that of the sunitinib group gave a ratio of 94.4% [90% confidence interval (CI) (76.1, 117.1)]; for the sunitinib + azithromycin group, the ratio was 106.2% (90% CI 85.5, 131.7). Comparison of the sunitinib AUC(0-t) of the sunitinib + clarithromycin and sunitinib + azithromycin groups with that of the sunitinib group showed ratios of 86.86% (90% CI 69.7, 108.3) and 99.8% (90% CI 80.1, 124.5), respectively.
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A 35-year-old woman complaining of fever and cough consulted a local clinic. She did not recover despite treatment with oral azithromycin, and a chest X-ray demonstrated infiltrates in both lungs. She was then admitted to our hospital and treated with intravenous pazufloxacin and oral clarithromycin. However, she did not respond to the treatment and her respiratory condition deteriorated. Thereafter, she was treated with high doses of corticosteroids, and her condition rapidly improved radiologically and clinically. The diagnosis was confirmed to be Mycoplasma pneumoniae pneumonia by the increased antibody-titer and positive M. pneumoniae PCR of bronchoalveolar lavage. In summary, we encountered a case of severe M. pneumoniae pneumonia, which induced acute respiratory failure even though the patient was receiving appropriate antibiotic treatment. The patient was recovered with steroid pulse therapy.
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The oral cavity is the ecological niche for Actinobacillus actinomycetemcomitans and Haemophilus aphrophilus, but occasionally they cause severe nonoral infections. In this study we present 20 systemic or nonoral infections due to A. actinomycetemcomitans and H. aphrophilus, comprising all isolates of these species forwarded to and stored in Finnish reference laboratories during the years 1988-2000. The time from specimen collection to correct species identification was 9.3 days for A. actinomycetemcomitans and 10.7 days for H. aphrophilus. A. actinomycetemcomitans strains represented serotypes a, b, c, and d. Arbitrarily primed PCR distinguished four A. actinomycetemcomitans and six H. aphrophilus genotypes. Antimicrobial susceptibility testing with benzylpenicillin, amoxicillin, tetracycline, metronidazole, azithromycin, and trovafloxacin showed generally good activities against the present strains, and the susceptibility patterns closely resembled those of oral strains. The prolonged time to recover and identify A. actinomycetemcomitans and H. aphrophilus from systemic and nonoral infections may delay the correct diagnosis of the patient, but the good antimicrobial efficacies of antimicrobial agents against these pathogens give a good prognosis for the patients and advance the treatment of severe infections caused by these fastidious organisms of oral origin.