Comparative effect of ciprofloxacin and moxifloxacin on the modulation of bile acid profiles and gut microbiota in rats

Abstract Fluoroquinolones are an important class of antimicrobial agents to manage infectious diseases. However, knowledge about how host bile acids are modified by fluoroquinolones is limited. We investigated and compared the impact of fluoroquinolones on circulating bile acid profiles and gut microbiota from in vivo studies. We administered ciprofloxacin (100 mg/kg/day) or moxifloxacin (40 mg/kg/day) orally to male Wistar rats for seven days. Fifteen bile acids (BAs) from the serum and large intestine were quantified by HPLC-MS/MS. The diversity of gut microbiota after ciprofloxacin and moxifloxacin treatment was analyzed using high-throughput, next-generation sequencing technology. The two fluoroquinolone-treated groups had different BA profiles. Ciprofloxacin significantly reduced the hydrophobicity index of the BA pool, reduced secondary BAs, and increased taurine-conjugated primary BAs in both the serum and large intestine as compared with moxifloxacin. Besides, ciprofloxacin treatment altered intestinal microbiota with a remarkable increase in Firmicutes to Bacteroidetes ratio, while moxifloxacin exerted no effect. What we found suggests that different fluoroquinolones have a distinct effect on the host BAs metabolism and intestinal bacteria, and therefore provide guidance on the selection of fluoroquinolones to treat infectious diseases.

Molecular basis of high-level ciprofloxacin resistance in Neisseria gonorrhoeae strains from Shandong Province, China

In the study, the ciprofloxacin resistance rate was 100%. High-level ciprofloxacin resistance rate was 63.55%. Sixteen different mutation patterns involved in the formation of ciprofloxacin resistance were identified. The most prevalent were patterns P7 (25.2%), P8 (15.0%), P9 (11.2%), P1 (10.3%), and P5 (10.3%). All of the 107 NG isolates analyzed for mutations in the study have demonstrated a change of Ser-91 → Phe in the gyrA gene, and all except one have demonstrated a change in position 95 of the amino acid sequence. All of the 68 high-level QRNG isolates had double mutations in gyrA gene combined with a single or two mutations in parC gene. It is most important that a new mutation site of Ile-97 → Met in gyrA and a new mutation of Leu-106 → Ile in parC were found in the study, both leading to high-level ciprofloxacin resistance (MIC values, 8 µg/mL, 32 µg/mL, respectively). Therefore, we confim that gyrA mutations are necessary for the fluoroquinolone resistance phenotype and parC mutations are correlated intimately with high-level fluoroquinolone resistance. In China fluoroquinolone resistance in Neisseria gonorrhoeae strains is very serious and the new mutation sites in the fluoroquinolone resistance-determining regions emerge more and more quickly. Hence, in China fluoroquinolones, which are used to treat gonorrhoea presently, should be substituted by a new antibiotics.

Efficacy evaluation of some antibiotics against syrian brucella spp isolates, in vitro

Brucellosis is an endemic zoonosis in Syria, affecting large numbers of animals and there are an increasing number of cases in humans. The aim of this study is to investigate the in vitro efficacy of various traditional and new antibiotics against89 Brucella isolates (isolated from domestic animals) collected from different Syrian regions. Minimum inhibitory concentrations (MICs) of seventeen antibiotics were determined. Ciprofloxacin and ofloxacin were the most effective antibiotics, whereas sparfloxacin, levofloxacin, doxycycline and tetracycline had a moderate activity. In contrast, moxifloxacin and rifampicin had a low activity, while streptomycin, spiramycin and cephalosporines were ineffective. As a result, we come to the conclusion that a combination between one effective quinolone and doxycycline has a good efficacy against Brucella. Further in vivo studies are necessary to support this suggestion.

Ciprofloxacin susceptibility reduction of salmonella strains isolated from outbreaks

The antimicrobial susceptibility of 212 Salmonella strains isolated from patients and foods was evaluated and 45 percent were found to be resistant to nalidixic acid. Nalidixic acid resistant strains showed a higher minimal inhibitory concentration for ciprofloxacin than sensitive strains. During the study an increase of strains with reduced susceptibility to ciprofloxacin was also observed.

Simultaneous determination of intact lomefloxacin and ciprofloxacin in the presence of their acid degradation products

A reversed phase HPLC method was developed for the determination of lomefloxacin and its degradation product. In addition, two other methods have been developed for the determination of lomefloxacin hydrochloride [LF.HCl] and ciprofloxacin hydrochloride [CF.HCl] in presence of their acid induced degradation products. For the reversed phase HPLC method [determination of LF.HCl], the mobile phase used was a mixture of water: acetonitrile: triethylamine [80:20:0.6, v/v/v] adjusted to pH 3.0 with o-phosphoric acid. The flow rate was 1.5 ml/min. and the detection was carried out at 328 nm. The linearity range was found to be 0.5-6 micro g / 20 micro l for LF.HCl. The limits of detection and quantification [LOD and LOQ] were 0.22 micro g / 20 micro l and 0.74 micro g / 20 microl respectively. The second method was densitometric method for the determination of both LF.HCl and CF.HCl, the developing system used was a mixture of methanol and ammonia buffer [80:20, v/v]. Detection was carried out at 288 nm and 279 nm. for intact LF.HCl and CF.HCl respectively. The linearity ranges were found to be 1-6 micro g / 10 microl and 0.25-2.5 micro g / 10 microl for intact LF.HCl and CF.HCl respectively. LOD and LOQ were 0.1, 0.34 micro g/10 microl and 0.05, 0.18 micro g /10 microl for both drugs, respectively. The third method was derivative spectrophotometric method for the determination of [LF.HCl] and [CF.HCL]. The linearity ranges were found to be 2-8 micro g/ml and 5-12 micro g/ml for LF.HCl and CF.HCl respectively. LOD and LOQ were 0.39 micro g, 1.29 micro g/ml and 1.03, 3.45 micro g/ml for LF.HCl and CF.HCl respectively. Separation and identification of the acid degradation products of lomefloxacin hydrochloride and ciprofloxacin hydrochloride were carried out. The three described methods proved to be sensitive, precise and applicable to both dosage forms and laboratory prepared mixtures of the intact drugs and their acid degradation products

Antimicrobial susceptibility of Klebsiella pneumoniae producing extended-spectrum ß-lactamase (ESBL) isolated in hospitals in Brazil

The prevalence of Klebsiella pneumoniae producing extended-spectrum ß-lactamase (ESBL) has been increasing all over the world. Infections caused by ESBL producing isolates are difficult to detect with current susceptibility test, and are difficult to treat. ESBLs confer resistence to all currently available ß-lactam, except carbapenems. In addition, ESBL, production is usually associated with resistence to other classes of antimicrobial agents such as aminoglycosides and quinolones. The objective of this study was to evaluate in vitro susceptibility patterns of ESBL producing K. pneumoniae isolated in Brazil. Seventy-two strains were tested using E test against 30 antimicrobial agents, inclusing carbapenems, second and third generation cephalosporins, aminoglycosides, quinolones, and some new compounds. The most active compounds (i.e. 100 percent susceptibility) were meropenem (MIC90,0.125µg/mL), imipenem (MIC90,0.25µg/mL), and cefotetan (MIC90,2µg/mL). Ciprofloxacin (MIC90, 1µg/mL, 94 percent susceptibility) and cefepime (MIC90, 6µg/mL, 92 percent susceptibility), were also very active against our collection of ESBL producing K. pneumoniae. None of the six aminoglycosides showed good activity against these strains (16 percent to 41 percent susceptibility) and only 39 percent of the isolates were susceptible to piperacillin/tazobactam. The results of our study indicated that the carbapenems are most active compounds against ESBL producing K.pneumoniae in Brazil, and ciprofloxaxin remains very active against these strains. Cefotetan and cefepine were also very active against ESBL producing K.pneumoniae in Brazil; however, further studies are necessary to evaluate the role of these cephalosporins in the treatment of infections due to ESBL producing strains.