PURPOSE: The combined use of antibiotics and anti-inflammatory medicine to manage bacterial endotoxin-induced inflammation following injuries or diseases is increasing. The cytokine level produced by macrophages plays an important role in this treatment course. Ciprofloxacin and indomethacin, two typical representatives of antibiotics and anti-inflammatory medicine, are cost-effective and has been reported to show satisfactory effect. The current study aims to investigate the effect of ciprofloxacin along with indomethacin on the secretion of inflammatory cytokines by macrophages in vitro. METHODS: Primary murine peritoneal macrophages and RAW 264.7 cells were administrated with lipopolysaccharide (LPS) for 24 h. The related optimal dose and time point of ciprofloxacin or indomethacin in response to macrophage inflammatory response inflammation were determined via macrophage secretion induced by LPS. Then, the effects of ciprofloxacin and indomethacin on the secretory functions and viability of various macrophages were determined by enzyme-linked immunosorbent assay and flow cytometry analysis, especially for the levels of interleukin (IL)-1β, IL-6, IL-10, and tumor necrosis factor (TNF)-α. The optimal dose and time course of ciprofloxacin affecting macrophage inflammatory response were determined by testing the maximum inhibitory effect of the drugs on pro-inflammatory factors at each concentration or time point. RESULTS: According to the levels of cytokines secreted by various macrophages (1.2 × 10⁶ cells/well) after administration of 1 μg/mL LPS, the optimal dose and usage timing for ciprofloxacin alone were 80 μg/mL and 24 h, respectively, and the optimal dose for indomethacin alone was 10 μg/mL. Compared with the LPS-stimulated group, the combination of ciprofloxacin and indomethacin reduced the levels of IL-1β (p < 0.05), IL-6 (p < 0.05), IL-10 (p < 0.01)), and TNF-α (p < 0.01). Furthermore, there was greater stability in the reduction of inflammatory factor levels in the combination group compared with those in which only ciprofloxacin or indomethacin was used. CONCLUSION The combination of ciprofloxacin and indomethacin suppressed the levels of inflammatory cytokines secreted by macrophages in vitro. This study illustrates the regulatory mechanism of drug combinations on innate immune cells that cause inflammatory reactions. In addition, it provides a new potential antibacterial and anti-inflammatory treatment pattern to prevent and cure various complications in the future.
Humans ; Mice ; Animals ; Cytokines ; Lipopolysaccharides/pharmacology* ; Interleukin-10 ; Indomethacin/therapeutic use* ; Interleukin-6/therapeutic use* ; Ciprofloxacin/therapeutic use* ; Macrophages ; Tumor Necrosis Factor-alpha ; Inflammation/drug therapy* ; Anti-Inflammatory Agents/therapeutic use* ; Anti-Bacterial Agents/therapeutic use*

No abstract available.
Aged ; Anti-Bacterial Agents/pharmacology/therapeutic use ; Cefotaxime/therapeutic use ; China ; Ciprofloxacin/therapeutic use ; Citrobacter freundii/drug effects/*enzymology/isolation & purification ; Drug Resistance, Multiple, Bacterial ; Humans ; Imipenem/pharmacology ; Male ; Microbial Sensitivity Tests ; Respiratory Tract Infections/*diagnosis/drug therapy/microbiology ; Thienamycins/pharmacology ; beta-Lactamases/*metabolism

BACKGROUND/AIMS: This study was performed to compare the prevalence rates of primary antibiotic resistance in Helicobacter pylori (H. pylori) isolates among different regions of Korea. METHODS: H. pylori were isolated from gastric mucosal biopsy specimens of 99 Koreans who lived in Gyeonggi (n=40), Kangwon province (n=40) and Busan (n=19) from April to August in 2008. All the patients had no history of H. pylori eradication therapy. The susceptibilities of the H. pylori isolates to amoxicillin, clarithromycin, metronidazole, tetracycline, azithromycin, ciprofloxacin, levofloxacin, and moxifloxacin were tested according to the agar dilution method. RESULTS: There was a difference in resistance to clarithromycin in three institutes located among Gyeonggi (32.5%), Kangwon province (12.5%) and Busan (42.1%) by One way ANOVA test (p=0.027) and nonparametric Kruskal Wallis test (p=0.027). However, by post-hoc analysis, there was no statistically significant difference among three regions. Similarly, the other 7 antibiotics (amoxicillin, metronidazole, tetracycline, azithromycin, ciprofloxacin, levofloxacin and moxifloxacin) did not show any significant difference. CONCLUSIONS: There was no significant regional difference of the primary antibiotic resistance of H. pylori. However, the included patient number might not be enough for this conclusion demanding further evaluations.
Amoxicillin/pharmacology ; Anti-Bacterial Agents/pharmacology/therapeutic use ; Aza Compounds/pharmacology ; Azithromycin/pharmacology ; Ciprofloxacin/pharmacology ; Clarithromycin/pharmacology ; *Drug Resistance, Bacterial ; Female ; Helicobacter Infections/*epidemiology/microbiology ; Helicobacter pylori/*drug effects/isolation & purification ; Humans ; Male ; Metronidazole/pharmacology ; Microbial Sensitivity Tests ; Middle Aged ; Ofloxacin/pharmacology ; Quinolines/pharmacology ; Republic of Korea/epidemiology ; Tetracycline/pharmacology

BACKGROUND/AIMS: This study was performed to compare the prevalence rates of primary antibiotic resistance in Helicobacter pylori (H. pylori) isolates among different regions of Korea. METHODS: H. pylori were isolated from gastric mucosal biopsy specimens of 99 Koreans who lived in Gyeonggi (n=40), Kangwon province (n=40) and Busan (n=19) from April to August in 2008. All the patients had no history of H. pylori eradication therapy. The susceptibilities of the H. pylori isolates to amoxicillin, clarithromycin, metronidazole, tetracycline, azithromycin, ciprofloxacin, levofloxacin, and moxifloxacin were tested according to the agar dilution method. RESULTS: There was a difference in resistance to clarithromycin in three institutes located among Gyeonggi (32.5%), Kangwon province (12.5%) and Busan (42.1%) by One way ANOVA test (p=0.027) and nonparametric Kruskal Wallis test (p=0.027). However, by post-hoc analysis, there was no statistically significant difference among three regions. Similarly, the other 7 antibiotics (amoxicillin, metronidazole, tetracycline, azithromycin, ciprofloxacin, levofloxacin and moxifloxacin) did not show any significant difference. CONCLUSIONS: There was no significant regional difference of the primary antibiotic resistance of H. pylori. However, the included patient number might not be enough for this conclusion demanding further evaluations.
Amoxicillin/pharmacology ; Anti-Bacterial Agents/pharmacology/therapeutic use ; Aza Compounds/pharmacology ; Azithromycin/pharmacology ; Ciprofloxacin/pharmacology ; Clarithromycin/pharmacology ; *Drug Resistance, Bacterial ; Female ; Helicobacter Infections/*epidemiology/microbiology ; Helicobacter pylori/*drug effects/isolation & purification ; Humans ; Male ; Metronidazole/pharmacology ; Microbial Sensitivity Tests ; Middle Aged ; Ofloxacin/pharmacology ; Quinolines/pharmacology ; Republic of Korea/epidemiology ; Tetracycline/pharmacology

AIMTo find new antibacterial agents of quinolone with high activity and low toxicity.

METHODSTo design and synthesize 7-(7-aminomethyl-5-azaspiro [2,4] hept-5-yl)-1-cyclopropyl-6-fluoro-8-methoxy-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid and its analogues, and to study their antibacterial activity in vitro and in vivo.

RESULTSTwenty new compounds (2 - 11, 17 - 26) were obtained including five targeted compounds (22 - 26). The structures of the compounds were confirmed by 1HNMR, MS and HRMS. Compounds 22 - 26 showed broad spectrum of antibacterial activity against Gram-positive and Gram-negative organisms. Especially for compound 24, the relevant MIC values for 13 strains of Gram-positive organisms were < 0.001 - 0.03 mg(-1), including 4 strains of S. pneumoniae, 2 strains of S. pyogenes, 3 strains of S. aureus and 2 strains of Enterococci which exhibited more potent activity than contrast agents (clinafloxacin and gatifloxacin). The MIC values of 24 for 6 strains Gram-positive organisms were 0.01 - 1 mg x L(-1), which exhibited equal or lower activity than contrast agents. They were more effective than ciprofloxacin and gatifloxacin against intraperitoneal infections caused by S. pneumoniae and S. aureus in mice.

CONCLUSIONCompounds (23, 24 and 26) showed excellent antibacterial activity in vitro and in vivo and should be worth further investigation.

Animals ; Anti-Bacterial Agents ; chemical synthesis ; pharmacology ; Ciprofloxacin ; pharmacology ; Female ; Fluoroquinolones ; pharmacology ; Male ; Mice ; Mice, Inbred ICR ; Molecular Conformation ; Molecular Structure ; Quinolines ; chemical synthesis ; chemistry ; pharmacology ; therapeutic use ; Spiro Compounds ; chemical synthesis ; chemistry ; pharmacology ; therapeutic use ; Staphylococcus aureus ; drug effects ; Streptococcus pneumoniae ; drug effects

No abstract available.
Anti-Bacterial Agents/pharmacology ; Bacterial Proteins/genetics ; Ceftriaxone/pharmacology/therapeutic use ; Ciprofloxacin/pharmacology/therapeutic use ; DNA, Bacterial/analysis/metabolism ; Disk Diffusion Antimicrobial Tests ; *Drug Resistance, Bacterial ; Female ; Humans ; Neisseria meningitidis/drug effects/genetics/*isolation & purification ; Polymerase Chain Reaction ; Sepsis/*diagnosis/drug therapy/microbiology ; Transcription Factors/genetics ; Young Adult

To clarify the characteristics of the virulence factors (VFs) of ciprofloxacin resistant Escherichia coli (CFRE) with acute uncomplicated cystitis (AUC), we determined the VFs and the phylogenetic background of all 54 CFRE strains and the 55 randomly selected ciprofloxacin sensitive E. coli strains (CFSE) from patients with AUC in 22 Korean hospitals. The prevalence of the VFs was as follows: fimA, papEF, papGIII, sfaI, dafaBC, cnf1, and hlyA were presented in 96%, 54%, 68%, 91%, 49%, 72%, and 29% of the samples, respectively. The expressions of papEF, cnf1, and hlyA were significantly more prevalent in the CFSE. Moreover, the expressions of cnf, and papEF significantly reduced the risk of ciprofloxacin resistance. The CFSE was also marginally associated with the group B2 (P=0.05). Although the presence of pyuria and a previous cystitis history were not related with the phylotyping and the expressions of VFs, group B2, and fimA and papEF were more expressed in the younger age patients (P<0.05). In conclusion, the CFRE exhibits a selective loss of VFs and the non-B2 phylotype in Korean AUC patients. The group B2 and the presence of fimA and papEF are associated with a younger age of AUC patients.
Adolescent ; Adult ; Aged ; Asian Continental Ancestry Group/genetics ; Bacterial Typing Techniques ; *Ciprofloxacin/pharmacology/therapeutic use ; *Cystitis/drug therapy/microbiology/urine ; Drug Resistance, Bacterial/drug effects/*genetics ; *Escherichia coli/classification/genetics/pathogenicity ; Escherichia coli Infections/*drug therapy ; Female ; Genotype ; Humans ; Microbial Sensitivity Tests ; Middle Aged ; Phylogeny ; Prospective Studies ; Urine/*microbiology ; Young Adult