Activity of new macrolides againstBordetella pertussis andBordetella parapertussis

MICs and MBCs of four new macrolides (azithromycin, clarithromycin, dirithromycin and roxithromycin) and two older macrolides (erythromycin and josamycin) forBordetella pertussis andBordetella parapertussis were determined. The activity of the new macrolides was as good as that of erythromycin, while josamycin was slightly less active.Bordetella parapertussis was more resistant thanBordetella pertussis.     

Neutrophil defensins stimulate the release of cytokines by airway epithelial cells: modulation by dexamethasone

OBJECTIVE AND DESIGN: Neutrophils may contribute to recruiting other cells to sites of inflammation by generating chemotactic signals themselves, or by stimulating other cell types to release chemoattractants such as interleukin-8 (IL-8). Recently, we demonstrated that neutrophil-derived alpha-defensins are able to increase IL-8 expression in airway epithelial cells. In addition, it has previously been reported that neutrophil elastase-induced IL-8 synthesis was insensitive to inhibition by the glucocorticoid dexamethasone. The aim of the present study was to investigate the effect of defensins on the expression of various cytokines in cultured airway epithelial cells and to examine the effect of dexamethasone on defensin-induced cytokine synthesis in these cells. METHODS: Cultures of A549 cells and primary bronchial epithelial cells (PBEC) were stimulated with defensins either alone or in the presence of dexamethasone. Supernatants were analyzed for IL-8, ENA-78, IL-6, MCP-1 and GM-CSF by ELISA. In addition, IL-8 and ENA-78 mRNA was detected by Northern blot analysis. RESULTS: Defensins increased IL-8 expression, ENA-78, MCP-1 and GM-CSF release from A549 cells, whereas in PBEC only IL-8 and IL-6 were increased. Pre-treatment with dexamethasone significantly reduced defensin-induced IL-6, IL-8 and ENA-78 synthesis in airway epithelial cells. In addition, dexamethasone also reduced the neutrophil chemotactic activity in supernatants of these cells. CONCLUSIONS: The results from the present study indicate that defensins differentially induce cytokine secretion by A549 cells and PBEC. Glucocorticoids may interfere with the defensin-induced inflammatory process by reducing defensin-induced cytokine secretion in lung epithelial cells.     

Airway epithelial cells release eosinophil survival-promoting factors (GM-CSF) after stimulation of proteinase-activated receptor 2

BACKGROUND: Epithelium is considered an active participant in allergic inflammation. Proteinase-activated receptor (PAR) 2 is expressed in a variety of cell types, including epithelial cells, and has been implicated in inflammation. OBJECTIVE: PAR-2-mediated activation of airway epithelial cells induces the release of mediators that could promote eosinophil survival and mediate eosinophil recruitment. METHODS: PAR-2-activating peptides were used to activate the human airway epithelial cell line A549, as well as primary cultures of small airway epithelial cells (SAECs). Human peripheral blood eosinophils were cultured in the presence or absence of epithelial cell supernatants. Survival was assessed by using an Annexin V apoptosis detection kit. GM-CSF and eotaxin were measured by using ELISA. RESULTS: Eosinophils undergo apoptosis in the absence of growth factors. Supernatants from PAR-2-activated A549 epithelial cells increased eosinophil survival. Supernatants from resting SAECs also increased eosinophil survival, but supernatants from PAR-2-activated SAECs showed a greater effect. The effect of PAR-2-activated epithelial cell supernatants on eosinophil survival was completely inhibited by a neutralizing anti-GM-CSF antibody but not an anti-IL-5 antibody. Resting A549 cells did not release any detectable GM-CSF, whereas PAR-2-activated cells released 35 pg/10(6) cells. Resting SAECs released 754.3 pg/10(6) cells of GM-CSF, which was further increased to 1360.5 pg/10(6) cells after PAR-2-mediated activation. Budesonide inhibited this PAR-2 effect. PAR-2-activated epithelial cells also released eotaxin. CONCLUSION: PAR-2-mediated activation of airway epithelial cells induced release of GM-CSF, which promoted eosinophil survival and activation. It also induced release of eotaxin, which could mediate eosinophil recruitment to the airways.     

Influence of macrolides on mucoid alginate biosynthetic enzyme from Pseudomonas aeruginosa

Objective: The long-term administration of erythromycin (EM), clarithromycin (CAM) or azithromycin (AZM) has generally resulted in a favorable outcome for patients with diffuse panbronchiolitis (DPB) infected with mucoid Pseudomonas aeruginosa. To elucidate the mechanism involved, the influence of macrolides on mucoid alginate production by P. aeruginosa was investigated in vitro.
Methods: The macrolides used in this study were EM with a 14-membered ring, AZM with a 15-membered ring, midecamycin (MDM) with a 16-membered ring, and CP-4305, which has had mycarose removed from MDM, The effects of macrolides on mucoid P. aeruginosa were investigated by quantitative assay of alginate production and inhibition of guanosine diphospho-D-mannose dehydrogenase activity.
Results: After incubation with EM, AZM and CP-4305, the structural material of P. aeruginosa biofilm was distorted, and the enzymatic activity of GDP-D-mannose dehydrogenase, the most important enzyme in mucoid alginate biosynthesis, was inhibited. However, these effects were not observed with the 16-membered macrolide MDM.
Conclusions: The basic mechanism of clinical efficacy seen characteristically in 14- or 15-membered macrolides for patients with airway biofilm disease depends on the ability of such macrolides to inhibit alginate production by P. aeruginosa. Furthermore, this suggests that the inhibitory effect observed with 14-, 15- and 16-membered macrolides may depend on the sugar chain connected with the macrolide ring.     

Bronchial epithelial cell-derived cytokines (G-CSF and GM-CSF) promote the survival of peripheral blood neutrophils in vitro.

Neutrophil accumulation in the respiratory tract occurs in a variety of inflammatory disorders, particularly those associated with cigarette smoking. We examined whether bronchial epithelial cells could contribute to this accumulation through the production of factors that increased the survival of neutrophils. Pure primary cultures of human bronchial epithelial cells (HBEC) were used to generate conditioned medium (CM), and the effect of this CM on the survival of neutrophils in vitro was examined. When neutrophils were cultured in control medium, survival was 8.7 +/- 1.7% at 72 h. In contrast, culture of neutrophils in CM resulted in a dose-dependent increase in survival: 22.6 +/- 5.5, 43.6 +/- 4.2, and 64 +/- 3.8% in 1, 10, and 50% CM respectively (mean +/- SEM; P < 0.05). As evidenced by the examination of neutrophil DNA, this prolongation of survival was associated with suppression of apoptosis. Cytokines with known actions on neutrophil biology identified in the CM included granulocyte colony-stimulating factor (G-CSF), granulocyte/macrophage colony-stimulating factor (GM-CSF), and interleukin-8. Through the use of specific neutralizing antibodies, G-CSF and GM-CSF were identified as promoting neutrophil survival. Neutrophil survival was prolonged in the presence of either recombinant human (rh) G-CSF or rhGM-CSF alone in a dose-dependent fashion. In contrast to the response of eosinophils to HBEC-CM, steroid treatment did not prevent the increase in neutrophil survival induced by HBEC-CM. In summary, we show that bronchial epithelial cells markedly increase the survival of human neutrophils in vitro via the release of G-CSF and GM-CSF.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of pH variation on the susceptibility ofHelicobacter pylori to three macrolide antimicrobial agents and temafloxacin

The in vitro susceptibility of 27 clinical isolates ofHelicobacter pylori to erythromycin, clarithromycin, azithromycin and temafloxacin under various pH conditions was evaluated. Clarithromycin (MIC90 0.03 µg/ml) was found to be significantly more active than either erythromycin (MIC90 0.125 µg/ml) or azithromycin (MIC90 0.25 µg/ml) at a neutral pH. Lowering the pH to 5.75 resulted in a loss in efficacy from 8- to 32-fold for all three macrolides studied. The MIC90 of clarithromycin (0.5 µg/ml) remained lower than those of azithromycin (2 µg/ml) and erythromycin (4 µg/ml). No synergism or antagonism was observed with combinations of clarithromycin and temafloxacin at either the neutral or lower pH values.     

Development of interpretive criteria and quality control limits for macrolide and clindamycin susceptibility testing of Streptococcus pneumoniae.

A six-laboratory collaborative study was conducted to develop MIC and zone diameter quality control limits and interpretive criteria for antimicrobial susceptibility testing of Streptococcus pneumoniae with azithromycin, clarithromycin, dirithromycin, and clindamycin. The MICs of all of the agents plus erythromycin for 302 clinical isolates of pneumococci that had been selected with an emphasis on resistant strains were determined by use of the National Committee for Clinical Laboratory Standards (NCCLS)-recommended broth microdilution procedure. The zone diameters of the isolates were also determined for the same agents except erythromycin by the NCCLS disk diffusion test procedure. Repeated testing of S. pneumoniae ATCC 49619 with different sources and lots of media and disks allowed development of MIC and zone diameter quality control ranges for these agents. Interpretive criteria for the MIC of azithromycin were established and were as follows: susceptible, < or = 0.5 microgram/ml; intermediate, 1 microgram/ml; and resistant, > or = 2 micrograms/ml. The interpretive criteria advocated for the MICs of clarithromycin and clindamycin were as follows: susceptible, < or = 0.25 microgram/ml; intermediate, 0.5 microgram/ml; and resistant, > or = 1 microgram/ml. Comparison of MICs and disk diffusion zone diameters led to the development of interpretive criteria for the zone diameters for azithromycin, clarithromycin, and clindamycin that correlated well with these MIC breakpoints. Testing of this organism collection also led to the reestablishment of the erythromycin MIC breakpoints as being identical to those of clarithromycin, which resulted in equivalent cross-susceptibility and cross-resistance for the three macrolides that are currently marketed in the United States. Thus, the susceptibility of pneumococci to azithromycin and clarithromycin can be predicted accurately by testing only erythromycin in clinical laboratories. This recommendation, as well as the interpretive and quality control criteria that are described, have been accepted by NCCLS and are included in the latest NCCLS susceptibility testing guidelines.     

Antiangiogenic and antitumor effects of 14-membered ring macrolides on mouse B16 melanoma cells

We examined the effects of macrolide antibiotics on tumor angiogenesis, tumor growth and metastasis in the B16BL6 mouse melanoma and C57BL mouse system. Two 14-membered ring macrolide antibiotics, roxithromycin and clarithromycin, significantly reduced the dense capillary network area in a mouse dorsal air sac angiogenesis model, whereas a 15-membered ring macrolide, azithromycin, and a 16-membered ring macrolide, josamycin, did not show any inhibitory effect on angiogenesis at the same dose. Intraperitoneal administration of roxithromycin and clarithromycin at 50 mg/kg/day reduced the tumor size of B16BL6 melanoma to about 41% and 56%, respectively, of that of the control, and significantly suppressed pulmonary metastasis of B16BL6 cells in a spontaneous system. Azithromycin and josamycin, on the other hand, did not inhibit tumor growth or pulmonary metastasis of B16BL6 cells. Immunohistochemistry revealed that roxithromycin and clarithromycin reduced the tumor vascularity and increased apoptosis of the tumor cells in vivo. These results suggest that 14-membered ring macrolides have antiangiogenic and antitumor effects and might have possible therapeutic applications.     

Comparative in vitro activity of azithromycin,clarithromycin, erythromycin and lomefloxacin againstMycoplasma pneumoniae,Mycoplasma hominis andUreaplasma urealyticum

The in vitro activity of three macrolides, azithromycin, clarithromycin and erythromycin and a new fluoroquinolone, lomefloxacin, against pathogenic mycoplasma (16 to 18 strains ofMycoplasma pneumoniae, 41 to 77 strains ofMycoplasma hominis, 65 to 104 strains ofUreaplasma urealyticum) was compared. The three macrolides were highly active againstMycoplasma pneumoniae. Clarithromycin was the most active macrolide againstUreaplasma urealyticum whereas azithromycin was somewhat more active than erythromycin againstMycoplasma hominis. Lomefloxacin was moderately active against all three mycoplasma species.     

Tumor-derived granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor prolong the survival of neutrophils infiltrating bronchoalveolar subtype pulmonary adenocarcinoma

We evaluated the role of the tumor environment in the regulation of apoptosis of tumor-infiltrating neutrophils, the number of which correlates negatively with outcome, in patients with adenocarcinoma of the bronchioloalveolar (BAC) subtype. We examined three different parameters of apoptosis, namely morphological aspect, annexin-V expression, and DNA fragmentation. Bronchoalveolar lavage fluid (BALF) supernatants from patients with BAC significantly inhibited the 24-hour spontaneous apoptosis of normal peripheral blood neutrophils in vitro compared to BALF supernatants from control patients (64 +/- 4% versus 90 +/- 2% measured by annexin-V flow cytometry, P = 0.04). The alveolar neutrophil count correlated positively with the granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) concentrations in the patient's BALF. Furthermore, neutralizing antibodies (Abs) against GM-CSF and G-CSF significantly inhibited BALF anti-apoptotic activity (15 to 40% and 34 to 63% inhibition, respectively), whereas neutralizing Abs against interleukin (IL)-8, IL-6, IL-1beta and tumor necrosis factor-alpha had no significant effect. In an attempt to identify the cell origin of anti-apoptotic cytokines, we tested in vitro the effect of BAC cells (A549 cell line and primary culture derived from a patient's BAC tumor) on the apoptosis of peripheral blood neutrophils. Cell-free supernatants from tumor cells did not inhibit neutrophil apoptosis. In contrast, cell-free supernatants from tumor cells previously exposed to conditioned media from peripheral blood mononuclear cells and alveolar macrophages significantly inhibited spontaneous neutrophil apoptosis. This inhibition was partially lifted when conditioned media from mononuclear cells were previously treated with Abs against IL-1beta and tumor necrosis factor-alpha. As in vivo, neutralizing Abs against GM-CSF significantly inhibited the anti-apoptotic activity of cell culture supernatants, and combination with Abs against G-CSF had an additive effect. In vivo, GM-CSF and G-CSF were strongly expressed by tumor cells and moderately or not expressed by the normal epithelium, as assessed by immunohistochemical studies. These findings demonstrate that the tumor environment generates local conditions that prolong alveolar neutrophil survival through the production of soluble factors, thereby contributing to the persistence of the neutrophil alveolitis observed in BAC.     

327例输卵管性不孕患者生殖道衣原体、支原体检测及药物敏感分析

目的 探讨输卵管性不孕症患者生殖道衣原体和支原体感染的状况及药物敏感性,指导临床合理用药.方法 随机选取327例输卵管性不孕症患者作为不孕组和286名健康孕妇作为对照组,采集宫颈分泌物,检测沙眼衣原体(CT)、解脲支原体(UU)和人型支原体(MH),以及UU和MH耐药性.结果 不孕组CT感染率(14.99%)、UU感染率(23.24%)、UU+MH感染率(29.05%)、CT+UU+MH感染率(9.17%)及总感染率(88.99%)均高于对照组(依次为:2.80%、6.99%、8.39%、4.55%、29.02%),两组比较,差异有统计学意义(P＜0.05);UU对罗红霉素(敏感性为96.05%)、交沙霉素(敏感性为96.05%)、四环素(敏感性为82.89%)强力霉素(敏感性为92.11%)、克拉霉素(敏感性为96.05%)敏感率较高,对环丙沙星和乙酰螺旋霉素相对耐药;MH对交沙霉素(敏感性为95.83%)、强力霉素(敏感性为91.67%)、美满霉素(敏感性为83.33%)、壮观霉素(敏感性为75.00%)较敏感,对红霉素、罗红霉素、阿奇霉素、克拉霉素不敏感,耐药性较高;UU+MH仅仅对交沙霉素(敏感性为90.52%)较敏感,对红霉素、罗红霉素、乙酰螺旋霉素、环丙沙星、氧氟沙星、阿奇霉素、克拉霉素的耐药性极高(77.89%-91.58%).结论 CT、UU、MH感染与输卵管性不孕有一定相关性,输卵管性不孕患者CT、UU和MH感染率较高于能生育者;UU和MH及UU+MH对多种常见抗菌药物具有较强的耐药性,临床治疗应重视病原学检测,合理使用抗生素.

Abstract：

Objective To explore the effects of mycoplasma and chlamydia infections on tubal infertilityand to assess the antibiotic susceptibility and resistance of female urogenital, and consequently to guide clinical rational drug use. Methods 327 tubal infertility women as infertility group and 286 healthy pregnant women as control group were randomly selected, detected chlamydia trachomatis ( CT) , ureaplasma urealyticum ( UU) and mycoplasma hominis ( MH) in cervical secretions and drug resistance of UU and MH. Results CT infection rates ( 14. 99% ), UU infection rates (23. 24% ) , UU + MH infection rates (29.05% ) ,CT + UU + MH infection rates(9. 17% )and total infection rates(88.99% )in infertility group is higher than those (order: 2. 80% ,6. 99% , 8. 39% ,4. 55% ,29.02% ) in the control group, comparisons of two groups are statistically significant differences (P ＜ 0.05 ), the susceptibility of UU to roxithromycin (sensitivity is 96. 05% ), josamycin ( sensitivity is 96.05% ), tetracycline ( sensitivity is 82.89%), vibramycin( sensitivity is 92. 11% ) and clarithromycin( sensitivity is 96.05% ) were relatively high and low to ciprofloxacin and acetyl spiramycin. The susceptibility of MH to josamycin ( sensitivity is 95. 83% ) , vibramycin ( sensitivity is 91. 67% ), minocin ( sensitivity is 83.33%) and actinospectacin ( sensitivity is 75. 00% ) were relatively high and low to erythromycin, azithromycin, roxithromycin and clarithromycin. UU + MH was only sensitive to josamycin ( sensitivity is 90. 52% ), high resistance ( 77. 89% -91. 58% ) to erythromycin, azithromycin, acetyl spiramycin, ciprofloxacin, ofloxacin, azithromycin and clarithromycin.Conclusion Infection of CT, UU, MH and tubal infertility have certain relevance, the rates of CT, UU and MH infection in tubal infertility patients higher than fertile people. For many commonantibacterial drugs, UU, MH and UU + MH has strong resistance, the etiology detection and using adapted antibios should be taken seriously in clinical treatment.     

Comparative antimicrobial activity of the new macrolides againstBorrelia burgdorferi

The in vitro and in vivo activity of the new macrolides azithromycin, clarithromycin and roxythromycin was compared with that of erythromycin againstBorrelia burgdorferi. In in vitro tests using ten clinical isolates all macrolides were highly active againstBorrelia burgdorferi (MIC90 0.015–0.06 µg/ml). Azithromycin was more potent than the other macrolides in experimental animal infection, eradicating the organism in all animals tested at a dosage of 8 mg/kg.     

327例输卵管性不孕患者生殖道衣原体、支原体检测及药物敏感分析

目的 探讨输卵管性不孕症患者生殖道衣原体和支原体感染的状况及药物敏感性,指导临床合理用药.方法 随机选取327例输卵管性不孕症患者作为不孕组和286名健康孕妇作为对照组,采集宫颈分泌物,检测沙眼衣原体（CT）、解脲支原体（UU）和人型支原体（MH）,以及UU和MH耐药性.结果 不孕组CT感染率（14.99%）、UU感染率（23.24%）、UU＋MH感染率（29.05%）、CT＋UU＋MH感染率（9.17%）及总感染率（88.99%）均高于对照组（依次为：2.80%、6.99%、8.39%、4.55%、29.02%）,两组比较,差异有统计学意义（P＜0.05）;UU对罗红霉素（敏感性为96.05%）、交沙霉素（敏感性为96.05%）、四环素（敏感性为82.89%）强力霉素（敏感性为92.11%）、克拉霉素（敏感性为96.05%）敏感率较高,对环丙沙星和乙酰螺旋霉素相对耐药;MH对交沙霉素（敏感性为95.83%）、强力霉素（敏感性为91.67%）、美满霉素（敏感性为83.33%）、壮观霉素（敏感性为75.00%）较敏感,对红霉素、罗红霉素、阿奇霉素、克拉霉素不敏感,耐药性较高;UU＋MH仅仅对交沙霉素（敏感性为90.52%）较敏感,对红霉素、罗红霉素、乙酰螺旋霉素、环丙沙星、氧氟沙星、阿奇霉素、克拉霉素的耐药性极高（77.89%-91.58%）.结论 CT、UU、MH感染与输卵管性不孕有一定相关性,输卵管性不孕患者CT、UU和MH感染率较高于能生育者;UU和MH及UU＋MH对多种常见抗菌药物具有较强的耐药性,临床治疗应重视病原学检测,合理使用抗生素.     

Influence of azithromycin and clarithromycin on macrolide susceptibility of viridans streptococci from the oral cavity of healthy volunteers

Oral viridans streptococci are a reservoir of resistance genes for pathogens. Through prolonged exposure, long-acting macrolides (e.g., azithromycin) may induce the resistance of the commensals to macrolides more frequently than macrolides with a shorter half-life (e.g., clarithromycin). In a prospective, randomized, evaluator-blinded trial in healthy volunteers receiving standard courses of either azithromycin (n = 20) or clarithromycin (n = 20), we compared the susceptibility of oral viridans streptococci to macrolides over a period of 12 weeks. There was a significant temporal increase in the numbers of resistant isolates in both groups (p < 0.0005 at week 1). The proportion of macrolide-resistant isolates over time was significantly higher following azithromycin treatment (p = 0.0005), but returned to baseline values until week 12 in both groups. Temporal differential effects of azithromycin and clarithromycin on the induction of resistance were observed and need to be investigated regarding their effect on co-colonizing pathogens.     

Topical Azithromycin and Clarithromycin Inhibit Acute and Chronic Skin Inflammation in Sensitized Mice, with Apparent Selectivity for Th2-Mediated Processes in Delayed-Type Hypersensitivity

Macrolide antibiotics inhibit the secretion of Th1 cytokines while their effects on the release of Th2 cytokines are variable. We investigated molecular and cellular markers of Th1- and Th2-mediated inflammatory mechanisms and the anti-inflammatory activity of azithromycin and clarithromycin in phorbol 12-myristate 13-acetate (PMA) and oxazolone (OXA)-induced skin inflammation. Dexamethasone (50 μg/ear), azithromycin, and clarithromycin (500 μg/ear) reduced TNF-α and interleukin (IL)-1β concentration in ear tissue by inhibiting inflammatory cell accumulation in PMA-induced inflammation. In OXA-induced early delayed-type hypersensitivity (DTH), the macrolides (2 mg/ear) and dexamethasone (25 μg/ear) reduced ear tissue inflammatory cell infiltration and secretion of IL-4 while clarithromycin also decreased IFN-γ concentration. Macrolides showed better activity when administered after the challenge. In OXA-induced chronic DTH, azithromycin (1 mg/ear) reduced the number of ear tissue mast cells and decreased the concentration of IL-4 in ear tissue and of immunoglobulin (Ig)E in serum. Clarithromycin (1 mg/ear) reduced serum IgE concentration, possibly by a mechanism independent of IL-4, while both macrolides attenuated mast cell degranulation. In conclusion, azithromycin and clarithromycin attenuate pro-inflammatory cytokine production and leukocyte infiltration during innate immune reactions, while selectively affecting Th2 rather than Th1 immunity in DTH reactions.     

Activity of telithromycin and seven other agents against 1034 pediatric Streptococcus pneumoniae isolates from ten central and eastern European centers

Objective  To test the activity of telithromycin against 1034 Streptococcus pneumoniae isolates from pediatric patients in ten centers from ten central and eastern European countries during 2000–2001, and to compare it with the activities of erythromycin A, azithromycin, clarithromycin, clindamycin, and quinupristin–dalfopristin.
Methods  The minimum inhibitory concentrations (MICs) of telithromycin, erythromycin A, azithromycin, clarithromycin, clindamycin, levofloxacin, quinupristin–dalfopristin and penicillin G were tested by the agar dilution method with incubation in air, and mechanisms of resistance to macrolides and quinolones were investigated.
Results  Strains were isolated from sputum, tracheal aspirates, ear, eye, blood, and cerebrospinal fluid. Among S. pneumoniae strains tested, 36% had raised penicillin G MICs (≥ 0.12 mg/L). Susceptibilities were as follows: telithromycin, quinupristin–dalfopristin and levofloxacin, ≥ 99%; clindamycin, 83%; and erythromycin A, azithromycin and clarithromycin, 78%. Of 230 (22.3%) erythromycin A-resistant S. pneumoniae strains, 176 (79.6%) had erm(B) , 38 (16.1%) had mef(A) , and 10 (4.3%) had mutations in 23S ribosomal RNA or in ribosomal protein L4. The rates of drug-resistant S. pneumoniae are high in all centers except Kaunas, Riga, and Prague.
Conclusion  Telithromycin had low MICs against all strains, irrespective of macrolide, azalide or clindamycin resistance. Ribosomal methylation was the most prevalent resistance mechanism among all resistant strains, except in Sofia, where the prevalence of the efflux mechanism was higher.     

Serotyping and susceptibility to macrolides and other antimicrobial drugs ofStreptococcus pyogenes isolated from patients with invasive diseases in Southern Israel

Fifty-seven strains ofStreptococcus pyogenes isolated from septic patients and 52 isolates from nonbacteremic patients in southern israel were investigated for their susceptibility to new macrolides and other antimicrobial drugs. In addition, typing of the isolates by M protein and T antigen was performed. All organisms were susceptible to penicillin and chloramphenicol, 59% to tetracycline, and 7% to trimethoprim-sulfamethoxazole. All isolates but one (99%) were susceptible to clarithromycin, azithromycin, erythromycin, and clindamycin. The MIC90 of clarithromycin, erythromycin, and clindamycin was 0.064, 0.125, and 0.094 g/ml, respectively. Overall, 96% of the isolates could be typed by T antigen, but only 43% were M-protein typeable. No predominance of any particular M-protein type was observed. No significant differences between blood isolates and organisms derived from other sources were observed in the antibiotic susceptibility patterns or the distribution of serotypes. It is concluded that invasiveStreptococcus pyogenes infections in southern israel are caused by multiple unrelated strains. The organism remains susceptible to macrolides and clindamycin.     

Human alveolar epithelial cells engulf apoptotic eosinophils by means of integrin- and phosphatidylserine receptor-dependent mechanisms: A process upregulated by dexamethasone

BACKGROUND: We previously demonstrated receptor-mediated apoptotic-eosinophil engulfment by human small airway epithelial cells, which may represent a potentially important mechanism in the resolution of allergic and asthmatic inflammation. OBJECTIVE: A549 cells were selected as being representative of alveolar epithelial cells, and their ability to ingest human apoptotic eosinophils was examined in terms of the effects of dexamethasone treatment and the receptor-mediated recognition mechanisms important in this process. METHODS: A549 epithelial-cell expression of alpha(v)beta3, alpha(v)beta5, CD36, and the phosphatidylserine receptor was established by using immunostaining and flow cytometry, and inhibition assays were examined by using the role of these receptors in apoptotic-eosinophil recognition by resting and dexamethasone-treated A549 epithelial cells. Electron microscopy confirmed engulfment of apoptotic eosinophils, and receptor clustering around apoptotic eosinophils was examined by using immunofluorescent labeling. RESULTS: A549 epithelial cells recognized and engulfed apoptotic eosinophils but not freshly isolated cells. Dexamethasone enhanced the number of A549 cells ingesting apoptotic eosinophils and dose dependently increased their capacity for ingestion. The tetrapeptide RGDS significantly inhibited apoptotic-eosinophil uptake by A549 cells, indicating a role for integrins in the recognition process. A549 cells expressed alpha(v)beta3, alpha(v)beta5, beta5, CD36, and the phosphatidylserine receptor, and expression of these receptors was not significantly increased after dexamethasone treatment. Engulfment of apoptotic eosinophils by A549 cells involved alpha(v)beta3-, CD36-, alpha(v)beta5-, and phosphatidylserine receptor-mediated recognition mechanisms and was associated with the formation of integrin focal adhesion complexes around apoptotic eosinophils. CONCLUSIONS: These data further suggest a nonpassive role for airway epithelium in the resolution of eosinophilic inflammation in asthma.