Aims: Typhoid fever is a life-threatening disease in the developing world that claims >600,000 deaths per year. Its causative agent Salmonella Typhimurium (S. Typhi) can be treated with ciprofloxacin, an effective broad-spectrum antibiotic that enhances the natural host defenses. However, the emergence of resistant bacterial strains may be a warning alarm against the clinical use of this antibiotic. This study was aimed to investigate the efficiency of ciprofloxacin treatment (250 mg/mL) against S. Typhi by altering the production of serum cytokines IL-10, 1L-6 and TNF-α in acute typhoid fever patients in Diwanyah Hospitals. Methodology and results: ELISA and Western Blot methods were used to investigate cytokine levels in patients and healthy controls sera. Our results showed that all cytokines’ levels before treatment with ciprofloxacin were significantly higher than the control (healthy group). However, treated patients with ciprofloxacin revealed a significantly reduced concentration of IL-10 and TNF-α compared to untreated control samples. However, the level of IL-6 was higher even with ciprofloxacin treatment. Conclusion, significance and impact of study The study concluded that ciprofloxacin (250 mg/mL) might significantly alter serum cytokines IL-6, IL-10 and TNF-α levels in acute typhoid fever patients. Therefore, further molecular studies are essential to understand the effect of ciprofloxacin on the production of cytokines.
Typhoid Fever ; Ciprofloxacin ; Salmonella typhimurium ; Cytokines

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*

Objective: To investigate the molecular characteristics of ciprofloxacin-cefotaxime-azithromycin co-resistant Salmonella enterica serovar Thompson (S. Thompson) isolates from sporadic cases of foodborne diseases and aquatic foods in Hunan province. Methods: Ciprofloxacin-cefotaxime-azithromycin co-resistant S. Thompson isolates were selected from samples, and broth microdilution method was used to determine the resistance to 11 antibiotics of these isolates in vitro. Whole genome sequencing was used for investigating antimicrobial resistance gene patterns and phylogenetic relationships of strains. Results: Nine ciprofloxacin-cefotaxime-azithromycin co-resistant isolates were recovered from 19 S. Thompson isolates. Among nine ciprofloxacin-cefotaxime-azithromycin co-resistant isolates, eight of them harbored IncC plasmids, simultaneously carrying plasmid-mediated quinolone resistance (PMQR) genes qepA and qnrS1, β-lactamase resistance gene bla_CMY-2, azithromycin resistance gene mph(A), and one isolate harbored IncR plasmid, and carried PMQR genes qnrB4 and aac(6')-Ib-cr, bla_OXA-10 and mph(A). Genetic environment analysis showed that qnrS1, qepA, mph(A) and bla_CMY-2 genes might be integrated on genomes of strains by ISKra4, IS91, IS6100 and ISEcp1, respectively. Phylogenetic core genome comparisons demonstrated that ciprofloxacin-cefotaxime-azithromycin co-resistant isolates from patients and aquatic foods were genetically similar and clustered together. Conclusion: Ciprofloxacin-cefotaxime-azithromycin co-resistant S. Thompson isolates have been isolated from both human and aquatic food samples, suggesting that the spread of multidrug resistant Salmonella between human and aquatic animals.
Animals ; Humans ; Ciprofloxacin ; Cefotaxime ; Azithromycin ; Serogroup ; Phylogeny ; Drug Resistance, Multiple, Bacterial/genetics* ; Anti-Bacterial Agents/pharmacology* ; Salmonella ; Quinolones ; Foodborne Diseases ; Plasmids ; Salmonella enterica ; Microbial Sensitivity Tests

OBJECTIVE: To assess positive culture rate and antimicrobial susceptibilities of Mycoplasma hominis (MH) and Ureaplasma urealyticum (UU) in symptomatic general population and pregnant women admitted with preterm labor and premature rupture of membranes. METHODS: We retrospectively reviewed medical records of patients who have undergone culture test and antimicrobial susceptibilities at our center from January 2017 to April 2018. Patients with positive culture for MH, UU, or both were included in this study. RESULTS: There were 200 patients who were eligible for enrollment. Of these patients, 34 (17%) were pregnant women and 166 (83%) were non-pregnant women. Of these 200 patients, positive culture results were as follows: MH only, n=10 (5%); UU only, n=58 (29%); and both MH and UU, n=36 (18%). Susceptibilities of MH only to doxycycline, erythromycin, ciprofloxacin, and azithromycin were 100%, 10%, 40%, and 0%, respectively. Susceptibilities of UU only to doxycycline, erythromycin, ciprofloxacin, and azithromycin were 94.8%, 87.9%, 5.2%, and 81%, respectively. Susceptibilities of both MH and UU to doxycycline, erythromycin, ciprofloxacin, and azithromycin were 97.2%, 5.6%, 11.1%, and 11.1%, respectively. CONCLUSION: UU only was the leading causative pathogen for genitourinary infection in our study. MH only accounted for about one sixth of UU only infections. Doxycycline was still the best antibiotics as most patients with MH only, UU only, or both MH and UU positive culture showed susceptibility. For ciprofloxacin, less than 12% of those with UU only and both MH and UU culture positive results showed susceptibility.
Anti-Bacterial Agents ; Azithromycin ; Ciprofloxacin ; Doxycycline ; Erythromycin ; Female ; Humans ; Medical Records ; Membranes ; Mycoplasma hominis ; Mycoplasma ; Obstetric Labor, Premature ; Pregnancy ; Pregnant Women ; Retrospective Studies ; Rupture ; Ureaplasma urealyticum ; Ureaplasma

Anthrax, caused by Bacillus anthracis, is a non-contagious infectious disease that affects a wide range of animal species (primarily ruminants) including humans. Due to the often-fatal outcome in humans, quick administration of definitely effective antimicrobials is crucial either as prophylaxis or as a clinical case therapy. In this study, 110 B. anthracis strains, temporally, geographically, and genetically different, isolated during anthrax outbreaks in Italy from 1984 to 2017, were screened using a broth microdilution method to determine their susceptibility to 16 clinically relevant antimicrobial agents. The strains were isolated from various matrices (human, animal, and environmental samples) and were representative of thirty distinct genotypes previously identified by 15-loci multiple-locus variable-number of tandem repeats analysis. The antimicrobials tested were gentamicin, ceftriaxone, streptomycin, penicillin G, clindamycin, chloramphenicol, vancomycin, linezolid, cefotaxime, tetracycline, erythromycin, rifampin, amoxicillin, ciprofloxacin, doxycycline, and trimethoprim. All isolates were susceptible to most of the tested antimicrobials, with the exception of trimethoprim for which all of them showed high minimal inhibitory concentration values. An intermediate level of susceptibility was recorded for ceftriaxone and cefotaxime. Although the Centers for Disease Control and Prevention recommend the use of doxycycline, ciprofloxacin, penicillin G, and amoxicillin for treatment of human cases and for post-exposure prophylaxis to anthrax spores, this study shows a high degree of in vitro susceptibility of B. anthracis to many other antimicrobials, suggesting the possibility of an alternative choice for prophylaxis and therapy.
Amoxicillin ; Animals ; Anthrax ; Anti-Infective Agents ; Bacillus anthracis ; Bacillus ; Cefotaxime ; Ceftriaxone ; Centers for Disease Control and Prevention (U.S.) ; Chloramphenicol ; Ciprofloxacin ; Clindamycin ; Communicable Diseases ; Disease Outbreaks ; Doxycycline ; Erythromycin ; Genotype ; Gentamicins ; Humans ; In Vitro Techniques ; Italy ; Linezolid ; Methods ; Microbial Sensitivity Tests ; Penicillin G ; Post-Exposure Prophylaxis ; Rifampin ; Spores ; Streptomycin ; Tandem Repeat Sequences ; Tetracycline ; Trimethoprim ; Vancomycin

Isolates of 24 enterococci, 5 Enterococcus casseliflavus and 19 Enterococcus gallinarum, possessing vanC genes and showing low-level resistance to vancomycin were obtained from mice from commercial mouse breeding companies. Since some of these isolates showed resistance to other antibiotics, the purpose of this study was to clarify the resistant profiles of these isolates. One E. casseliflavus isolate showed resistance to erythromycin with a minimal inhibitory concentration (MIC) of 8 μg/mL and also showed apparent resistance to fluoroquinolones with an MIC of 32 μg/mL for ciprofloxacin. The MICs of 2 other fluoroquinolone-resistant E. casseliflavus and E. gallinarum isolates were 3 and 6 μg/mL, respectively. These 3 resistant isolates showed an absence of macrolide- and fluoroquinolone-resistant genes, including amino acid substitutions in the quinolone resistance determining regions of DNA gyrase and topoisomerase IV. Resistance to tetracycline was detected in 2 E. gallinarum isolates that were highly resistant, exhibiting MICs of 48 and 64 μg/mL and possessing tet(O) genes. The results indicate that antibiotic-resistant enterococci are being maintained in some laboratory mouse strains that have never been treated with an antibiotic.
Amino Acid Substitution ; Animals ; Anti-Bacterial Agents ; Breeding ; Ciprofloxacin ; DNA Gyrase ; DNA Topoisomerase IV ; Drug Resistance, Microbial ; Enterococcus ; Erythromycin ; Fluoroquinolones ; Mice ; Tetracycline ; Vancomycin

Enterococcus spp. are opportunistic pathogens that cause lameness in broiler chickens, resulting in serious economic losses worldwide. Virulence of Enterococcus spp. is associated with several putative virulence genes including fsr, efm, esp, cylA, cad1, ace, gelE, and asa1. In this study, multiplex polymerase chain reaction (PCR) for the simultaneous detection of these virulence genes in Enterococcus spp. was developed, and detection limits for E. faecium, E. faecalis, and E. hirae were 64.0 pg/µL, 320.0 pg/µL, and 1.6 ng/µL DNA, respectively. Among 80 Enterococcus isolates tested, efm and cad1 were detected in all 26 E. faecium samples, and only cad1 was observed in E. hirae. Additionally, the presence of virulence genes in 25 E. faecalis isolates were 100% for cad1, 88.0% for gelE, 64.0% for fsr, 44.0% for asa1, 16.0% for cylA, and 4.0% for esp. No virulence genes were found in E. gallinarum isolates. A total of 49 isolates were resistant to tigecycline and to at least 2 different classes of antibiotics. The most prevalent resistance was to ciprofloxacin (73.5%), quinupristin/dalfopristin (55.1%), and tetracycline (49.0%). No strains were resistant to vancomycin or linezolid. This is the first multiplex PCR assay to simultaneously detect eight virulence genes in Enterococcus spp., and the method provides diagnostic value for accurate, rapid, and convenient detection of virulence genes. Additionally, we report the prevalence of virulence genes and antimicrobial resistance in Enterococcus isolates from commercial broiler chickens suffering lameness.
Anti-Bacterial Agents ; Chickens ; Ciprofloxacin ; DNA ; Drug Resistance, Microbial ; Enterococcus ; Limit of Detection ; Linezolid ; Methods ; Multiplex Polymerase Chain Reaction ; Prevalence ; Tetracycline ; Vancomycin ; Virulence

ciprofloxacin (56.4%, 86.3%), piperacillin/tazobactam (99.0%, 84.8%), amikacin (97.4%, 98.3%), and imipenem (99.8%, 98.8%). The susceptibility rates of Enterococcus spp. to ampicillin were 61.0%, amoxicillin/clavulanate, 63.6%; ciprofloxacin, 49.7%; imipenem, 65.2%; and vancomycin, 78.2%. The susceptibility rates of Pseudomonas aeruginosa and Acinetobacter spp. to imipenem were 77.4% and 36.7%, respectively.CONCLUSION: Enterococcus spp. with susceptibility to limited antibiotics was one of the main pathogens in Korean IAIs, along with E. coli and Klebsiella spp., which were highly susceptible to imipenem, amikacin, and piperacillin/tazobactam. Meanwhile, the low susceptibilities of E. coli or Klebsiella spp. to amoxicillin/clavulanate, advanced-generation cephalosporins, and ciprofloxacin should be considered when determining empirical antibiotic therapy in clinical practice.]]>
Acinetobacter ; Amikacin ; Ampicillin ; Anti-Bacterial Agents ; Cefotaxime ; Ceftazidime ; Cephalosporins ; Ciprofloxacin ; Cross Infection ; Enterococcus ; Epidemiology ; Escherichia coli ; Humans ; Imipenem ; Intraabdominal Infections ; Klebsiella ; Korea ; Peritoneal Dialysis, Continuous Ambulatory ; Peritonitis ; Pseudomonas aeruginosa ; Retrospective Studies ; Vancomycin

BACKGROUND: Ciprofloxacin is usually used in the treatment of lower respiratory tract infections (LRTIs). Recent studies abroad have shown ciprofloxacin is inadequately dosed and might lead to worse outcomes. The aim of this study was to perform pharmacokinetic and pharmacodynamic analyses of ciprofloxacin in elderly Chinese patients with severe LRTIs caused by Gram-negative bacteria. METHODS: From September 2012 to June 2014, as many as 33 patients were empirically administered beta-lactam and ciprofloxacin combination therapy. Patients were infused with 200 or 400 mg of ciprofloxacin every 12 h, which was determined empirically by the attending physician based on the severity of the LRTI and the patient's renal condition. Ciprofloxacin serum concentrations were determined by high-performance liquid chromatography. Bacterial culture was performed from sputum samples and/or endotracheal aspirates, and the minimum inhibitory concentrations (MICs) of ciprofloxacin were determined. The ratios of the area under the serum concentration-time curve to the MIC (AUC/MIC) and of the maximum serum concentration of the drug to the MIC (Cmax/MIC) were calculated. The baseline data and pharmacokinetic parameters were compared between clinical success group and clinical failure group, bacteriologic success group and bacteriologic failure group. RESULTS: Among the 33 patients enrolled in the study, 17 were infected with Pseudomonas aeruginosa, 14 were infected with Acinetobacter baumannii, and two were infected with Klebsiella pneumoniae. The mean age of the patients was 76.9 ± 6.7 years. Thirty-one patients (93.4%) did not reach the target AUC/MIC value of >125, and 29 patients (87.9%) did not reach the target Cmax/MIC value of >8. The AUC/MIC and Cmax/MIC ratios in the clinical success group were significantly higher than those in the clinical failure group (61.1 [31.7-214.9] vs. 10.4 [3.8-66.1], Z = -4.157; 9.6 [4.2-17.8] vs. 1.3 [0.4-4.7], Z = -4.018; both P < 0.001). The AUC/MIC and Cmax/MIC ratios in the patients for whom the pathogens were eradicated were significantly higher than those in the patients without the pathogens eradicated (75.3 [31.7-214.9] vs. 10.5 [3.8-66.1], Z = -3.938; 11.4 [4.2-17.8] vs. 1.4 [0.4-5.4], Z = -3.793; P < 0.001 for both). Receiver operating characteristic curve analysis showed that the AUC/MIC and Cmax/MIC values were closely associated with clinical and bacteriologic efficacies (P < 0.001 in both). CONCLUSIONS Ciprofloxacin is inadequately dosed against Gram-negative bacteria, especially for those with relatively high MIC values. Consequently, the target values, AUC/MIC > 125 and Cmax/MIC > 8, cannot be reached.
Acinetobacter baumannii ; drug effects ; pathogenicity ; Aged ; Aged, 80 and over ; Chromatography, High Pressure Liquid ; Ciprofloxacin ; pharmacokinetics ; pharmacology ; Female ; Gram-Negative Bacteria ; drug effects ; pathogenicity ; Humans ; Male ; Microbial Sensitivity Tests ; Pseudomonas aeruginosa ; drug effects ; pathogenicity ; Respiratory Tract Infections ; drug therapy ; metabolism ; microbiology

Two manganese peroxidases (MnPs), MnP1 and MnP2, and a laccase, Lac1, were purified from Trametes polyzona KU-RNW027. Both MnPs showed high stability in organic solvents which triggered their activities. Metal ions activated both MnPs at certain concentrations. The two MnPs and Lac1, played important roles in dye degradation and pharmaceutical products deactivation in a redox mediator-free system. They completely degraded Remazol brilliant blue (25 mg/L) in 10–30 min and showed high degradation activities to Remazol navy blue and Remazol brilliant yellow, while Lac1 could remove 75% of Remazol red. These three purified enzymes effectively deactivated tetracycline, doxycycline, amoxicillin, and ciprofloxacin. Optimal reaction conditions were 50 °C and pH 4.5. The two MnPs were activated by organic solvents and metal ions, indicating the efficacy of using T. polyzona KU-RNW027 for bioremediation of aromatic compounds in environments polluted with organic solvents and metal ions with no need for redox mediator supplements.
Amoxicillin ; Biodegradation, Environmental ; Ciprofloxacin ; Doxycycline ; Hydrogen-Ion Concentration ; Ions ; Laccase ; Manganese ; Oxidation-Reduction ; Peroxidases ; Pharmaceutical Preparations ; Solvents ; Tetracycline ; Trametes