Ciprofloxacin Group Research Articles

Highly selective electrochemical detection of ciprofloxacin using reduced graphene oxide/poly(phenol red) modified glassy carbon electrode

In this study, a novel sensor for highly selective and rapid detection of ciprofloxacin is fabricated. A facile strategy was employed to fabricate the electrode by electro-polymerization of phenol red (PPR) followed by drop-casting of reduced graphene oxide (rGO). Under optimized experimental conditions, the developed electrode shows, two linear ranges 0.002–0.05 μM and 0.05–400 μM, and the sensitivities equal to 516.41 μA μM−1 cm−2 and 0.239 μA μM−1 cm−2, respectively for ciprofloxacin detection. The rGO/PPR/GCE electrode enhanced sensitivity and low detection limit (LOD) (2 nM) of ciprofloxacin due to selective adsorption, which is accomplished by a combination of electrostatic attraction at SO3¯ sites in the PPR film, and the formation of charge assisted hydrogen bonding between ciprofloxacin and rGO surface functional groups. The novel nanocomposite was characterized by Fourier transform infrared spectroscopy (FTIR), field emission scanning electron microscopy (FE-SEM), cyclic voltammetry (CV) and electrical impedance spectroscopy (EIS). Differential pulse voltammetry (DPV) was used to study the response of ciprofloxacin towards the modified electrode. The composite modified electrode displayed good electro-catalytic activity towards the oxidation of ciprofloxacin at pH 5.5 and exhibited high sensitivity and specificity towards ciprofloxacin. The practical applicability was tested in the spiked animal serum sample. The recovery of analytes in spiked samples was 97 ± 6% over the range 0.002–400 μML−1. It shows that the developed electrode can be used as a potential tool for a rapid, simple, and sensitive detection of ciprofloxacin in the serum sample.

A Comprehensive Study of a New 1.75 Hydrate of Ciprofloxacin Salicylate: SCXRD Structure Determination, Solid Characterization, Water Stability, Solubility, and Dissolution Study

One problem that often arises during the formulation of a dosage form is the solubility and dissolution of the active ingredients. This problem arises in ciprofloxacin, which is a BCS class IV fluoroquinolone antibiotic. A pseudopolymorph is a kind of polymorph in which the number of hydrates is different. In this study, a new pseudopolymorph comprised of ciprofloxacin and salicylic acid was found, namely the salt ciprofloxacin salicylate 1.75 hydrate form. This new solid phase was analyzed by Fourier-transform infrared spectroscope (FTIR), Raman spectroscopy, and thermal analysis and proven by Powder X-ray Diffractometry (PXRD) analysis. The crystal structure was successfully determined by Single Crystal X-ray Diffractometry (SCXRD) analysis. It was found that the piperazinyl group of ciprofloxacin is protonated by H+ from the carboxylic group of salicylic acid. In the unit cell, two ciprofloxacin and two salicylic acid molecules were independent with four water molecules, in which one water molecule had 0.5 occupancy due to inversion symmetry. Interestingly, this hydrate crystal dehydrated by grinding for 105 minutes forms an anhydrous crystalline phase, which was analyzed with FTIR, Raman spectroscopy, thermal analysis, and PXRD. The solubility and dissolution tests were carried out using UV-Visible spectrophotometry and a multiple linear regression method. This new hydrate solid phase has a better profile than the original ciprofloxacin crystal, according to the solubility and dissolution tests.

Assessment of oral ciprofloxacin impaired gut barrier integrity on gut bacteria in mice

Gut bacteria and gut barrier plays important roles in body homeostasis. Ciprofloxacin (CPFX) is widely used to treat bacterial infections. However, whether high dosage of CPFX has side effects on gut barrier integrity is still unclear. Our results indicated that the High CPFX treatment (1 mg/ml) caused weight loss, nervousness, anorexia, and increased apoptosis cells in gut, but less influence was observed in the Low CPFX group (0.2 mg/ml). Meanwhile, the High CPFX treatment impaired tight junction molecules Ocln/ZO-1 level and down-regulated antibacterial genes expression (reg3γ, pla2g2α and defb1). Further, the High CPFX treatment increased pro-inflammatory cytokine IL-1β in intestinal tract, decreased IL-17A of duodenum but increased IL-17A of colon at day 37. In addition, the gut bacterial diversity and richness behaved significantly loss regarding CPFX treatment, especially in the High CPFX group during the experiment. Indole exhibited sharply decline in both Low and High CPFX groups at day 7, and the High CPFX mice needed longer time on restoring indole level. Meanwhile, CPFX treatment strongly decreased the concentrations of butyric acid and valeric acid at day 1. Correlation analysis indicated that the linked patterns between the key bacteria (families Bacteroidales_S247, Ruminococcaceae and Desulfovibrionaceae) and metabolites (indole and butyric acid) were disturbed via the CPFX treatment. In conclusion, the High CPFX treatment impaired the gut barrier with the evidence of reduced expression of tight junction proteins, increased apoptosis cells and inflammatory cells, decreased the bacterial diversity and composition, which suggesting a proper antibiotic-dosage use should be carefully considered in disease treatment.

The effect of antibiotics on the gut microbiome: a metagenomics analysis of microbial shift and gut antibiotic resistance in antibiotic treated mice

BackgroundEmergence of antibiotic resistance is a global public health concern. The relationships between antibiotic use, the gut community composition, normal physiology and metabolism, and individual and public health are still being defined. Shifts in composition of bacteria, antibiotic resistance genes (ARGs) and mobile genetic elements (MGEs) after antibiotic treatment are not well-understood.MethodsThis project used next-generation sequencing, custom-built metagenomics pipeline and differential abundance analysis to study the effect of antibiotic monotherapy on resistome and taxonomic composition in the gut of Balb/c mice infected with E. coli via transurethral catheterization to investigate the evolution and emergence of antibiotic resistance.ResultsThere is a longitudinal decrease of gut microbiota diversity after antibiotic treatment. Various ARGs are enriched within the gut microbiota despite an overall reduction of the diversity and total amount of bacteria after antibiotic treatment. Sometimes treatment with a specific class of antibiotics selected for ARGs that resist antibiotics of a completely different class (e.g. treatment of ciprofloxacin or fosfomycin selected for cepA that resists ampicillin). Relative abundance of some MGEs increased substantially after antibiotic treatment (e.g. transposases in the ciprofloxacin group).ConclusionsAntibiotic treatment caused a remarkable reduction in diversity of gut bacterial microbiota but enrichment of certain types of ARGs and MGEs. These results demonstrate an emergence of cross-resistance as well as a profound change in the gut resistome following oral treatment of antibiotics.

Antibacterial effectiveness of calcium hydroxide alone or in combination with Ibuprofen and Ciprofloxacin in teeth with asymptomatic apical periodontitis: a randomized controlled clinical study.

To evaluate the antimicrobial effectiveness of Ca(OH)2 paste combined with Ibuprofen or Ciprofloxacin in infected root canals of teeth with asymptomatic apical periodontitis. Forty-five patients were randomly divided into three groups using a web programme according to the medication selected: Ca(OH)2 : 1g Ca(OH)2 powder with 1mL propylene glycol, Ca(OH)2 +Ibuprofen: 50mg of Ibuprofen was added into 950mg Ca(OH)2 powder and mixed with 1mL propylene glycol, Ca(OH)2 +Ciprofloxacin: 50mg of Ciprofloxacin was added into 950mg Ca(OH)2 powder and mixed with 1mL propylene glycol. Root canal bacteriological samples were collected before root canal treatment (S1) and after chemo-mechanical procedures (S2). After root canal preparation, the intracanal medicaments were placed into the root canals to a level approximately 1mm short of the working length using K-files and access cavities were filled temporarily. The participants were scheduled for a second visit 7days later when the medication was removed mechanically, and after irrigation of the root canals, the final samples (S3) were collected. Samples were subjected to quantitative real-time polymerase chain reaction to evaluate the numbers of total bacteria, Enterococcus faecalis and Streptococcus species. For intragroup analysis, a Friedman test was used to compare reduction of counts of total bacteria, Streptococci and E.faecalis amongst the three samples (S1, S2 and S3). The chi-square test was used to compare the number of root canals positive for bacteria in S1, S2 and S3 amongst the groups. Intragroup analysis revealed a significant reduction in the number of intracanal bacterial cells from S1 to S2 and from S2 to S3 in all medication groups (P<0.01). Although there was no significant difference amongst the groups when comparing quantitative S1 or S2 data, there were significantly lower bacterial counts in the Ca(OH)2 +Ciprofloxacin group (0.49×102 ) than the pure Ca(OH)2 (1.25×102 ) and Ca(OH)2 +Ibuprofen groups (0.76×102 ) at S3. The percentage reduction from S1 to S3 and from S2 to S3 was significantly greater in the Ca(OH)2+Ciprofloxacin than the pure Ca(OH)2 and Ca(OH)2+Ibuprofen groups (P<0.05). In the Ca(OH)2 +Ciprofloxacin group, there were significantly fewer positive cases (8/15) than the pure Ca(OH)2 (13/15) and Ca(OH)2 +Ibuprofen (13/15) groups (P<0.05). The addition of Ciprofloxacin to Ca(OH)2 provided further antibacterial effectiveness when used as an intracanal medicament in vivo during root canal treatment.

Can antibiotic preference affect bleeding in percutaneous nephrolithotomy? Retrospective comparative study of two commonly used antibiotics.

Objective:Bleeding is one of the most common and alarming complication of percutaneous nephrolithotomy (PCNL). In this study, we aimed to compare the effects of ciprofloxacin and cefuroxime on the bleeding in PCNL procedures.Methods:The study was a retrospective analysis of 97 patients who underwent PCNL between February 2011 and June 2017. We just included the patients who had single tract lower pole PCNL for more objective evaluation of bleeding in the study. The patients were divided into two groups as ciprofloxacin group (Group-I, n:40) and cefuroxime group (Group-II, n:56) according to the type of antibiotic used in the operation. Patient age, gender, body mass index, stone size, preoperative INR, preoperative and postoperative platelet counts and difference, operative time, need for blood transfusion, postoperative fever, hospital stay, postoperative hemoglobin and hematocrit drop were analyzed.Results:There was no statistically significant difference in patients’ gender distribution, body mass index, preoperative INR, preoperative and postoperative platelet counts, preoperative and postoperative platelet difference, duration of operation, hospital stay, postoperative fever and need for postoperative blood transfusion between two antibiotic groups (p > 0.05). Mean patient age was 42,75±16,97 in Group-I and 35,54±14,71 in Group-II (p < 0.05). The mean stone size of Group-I and Group-II were 27,23±7,05 mm and 30,59±8,20, respectively (p < 0.05). The mean postoperative hemoglobin and hematocrit drop were significantly higher in Group-I than in Group-II. The mean hemoglobin drop was 1,73±0,95 for Group-I and 1,28±0,67 for Group-II (p < 0.05). The mean hematocrit drop was 5,17±2,76 for Group-I and 3,80±1,99 for Group-II (p < 0.05).Conclusion:On the basis of the results of the initial study, the antibiotic preference in patients undergoing surgery may be one of the bleeding factors during and after PCNL.

Treatment responses to Azithromycin and Ciprofloxacin in uncomplicated Salmonella Typhi infection: A comparison of Clinical and Microbiological Data from a Controlled Human Infection Model.

BackgroundThe treatment of enteric fever is complicated by the emergence of antimicrobial resistant Salmonella Typhi. Azithromycin is commonly used for first-line treatment of uncomplicated enteric fever, but the response to treatment may be sub-optimal in some patient groups when compared with fluoroquinolones.MethodsWe performed an analysis of responses to treatment with azithromycin (500mg once-daily, 14 days) or ciprofloxacin (500mg twice-daily, 14 days) in healthy UK volunteers (18–60 years) enrolled into two Salmonella controlled human infection studies. Study A was a single-centre, open-label, randomised trial. Participants were randomised 1:1 to receive open-label oral ciprofloxacin or azithromycin, stratified by vaccine group (Vi-polysaccharide, Vi-conjugate or control Men-ACWY vaccine). Study B was an observational challenge/re-challenge study, where participants were randomised to challenge with Salmonella Typhi or Salmonella Paratyphi A. Outcome measures included fever clearance time, blood-culture clearance time and a composite measure of prolonged treatment response (persistent fever ≥38.0°C for ≥72 hours, persistently positive S. Typhi blood cultures for ≥72 hours, or change in antibiotic treatment). Both trials are registered with ClinicalTrials.gov (NCT02324751 and NCT02192008).FindingsIn 81 participants diagnosed with S. Typhi in two studies, treatment with azithromycin was associated with prolonged bacteraemia (median 90.8 hours [95% CI: 65.9–93.8] vs. 20.1 hours [95% CI: 7.8–24.3], p<0.001) and prolonged fever clearance times <37.5°C (hazard ratio 2.4 [95%CI: 1.2–5.0]; p = 0.02). Results were consistent when studies were analysed independently and in a sub-group of participants with no history of vaccination or previous challenge. A prolonged treatment response was observed significantly more frequently in the azithromycin group (28/52 [54.9%]) compared with the ciprofloxacin group (1/29 [3.5%]; p<0.001). In participants treated with azithromycin, observed systemic plasma concentrations of azithromycin did not exceed the minimum inhibitory concentration (MIC), whilst predicted intracellular concentrations did exceed the MIC. In participants treated with ciprofloxacin, the observed systemic plasma concentrations and predicted intracellular concentrations of ciprofloxacin exceeded the MIC.InterpretationAzithromycin at a dose of 500mg daily is an effective treatment for fully sensitive strains of S. Typhi but is associated with delayed treatment response and prolonged bacteraemia when compared with ciprofloxacin within the context of a human challenge model. Whilst the cellular accumulation of azithromycin is predicted to be sufficient to treat intracellular S. Typhi, systemic exposure may be sub-optimal for the elimination of extracellular circulating S. Typhi. In an era of increasing antimicrobial resistance, further studies are required to define appropriate azithromycin dosing regimens for enteric fever and to assess novel treatment strategies, including combination therapies.Trial registrationClinicalTrials.gov (NCT02324751 and NCT02192008).

Effect of Calcium Hydroxide Alone or in Combination with Ibuprofen and Ciprofloxacin on Nuclear Factor Kappa B Ligand and Osteoprotegerin Level in Periapical Lesions: A Randomized Controlled Clinical Study

IntroductionThe aim of the present study was to evaluate the effects of calcium hydroxide (Ca[OH]2), Ca(OH)2 + ibuprofen, and Ca(OH)2 + ciprofloxacin in terms of receptor activator of nuclear factor kappa B ligand (RANKL) and osteoprotegerin (OPG) levels in asymptomatic periapical lesions. MethodsSixty-six patients were randomly divided into 3 groups using a Web program according to the medication selected: Ca(OH)2, Ca(OH)2 + ibuprofen, and Ca(OH)2 + ciprofloxacin. After removing gutta-percha from the root canals, the RANKL and OPG samples were taken from the interstitial fluid of the apical tissues using 3 paper points. At the second appointment, medicaments were removed, and second sampling was performed using the same method. The RANKL and OPG levels were measured by the enzyme-linked immunosorbent assay, and the RANKL/OPG ratio was calculated. ResultsAccording to the intragroup analysis, there were no statistically significant differences between the preoperative and postoperative levels of the RANKL/OPG ratio in any of the groups. Intergroup analyses showed that there were no statistically significant differences among the Ca(OH)2, Ca(OH)2 + ibuprofen, Ca(OH)2 + ciprofloxacin groups in terms of the percentage change in RANKL/OPG levels before and after treatment. ConclusionsWithin the limitations of the present study, it can be concluded that addition of ibuprofen or ciprofloxacin to Ca(OH)2 paste does not provide any extra benefit in terms of lowering RANKL and OPG levels.

Outcomes of Third-Generation Cephalosporin Plus Ciprofloxacin or Doxycycline Therapy in Patients with Vibrio vulnificus Septicemia: A Propensity Score-Matched Analysis.

BackgroundCombination therapy with a third-generation cephalosporin (TGC) and a tetracycline analogue is recommended for Vibrio vulnificus infection. The combination of a TGC and ciprofloxacin has synergistic in vitro bactericidal activity against V. vulnificus. No clinical study has compared the standard regimen with TGC plus ciprofloxacin therapy for V. vulnificus infection.MethodsPatients with a confirmed V. vulnificus infection at two medical centers in Korea from 1991 to 2016 were enrolled in this study. The patients were grouped according to the type of antibiotic administered. A retrospective propensity-score-matched case-control study of patients treated with TGC plus doxycycline or TGC plus ciprofloxacin was performed. The clinical characteristics and outcomes of the patients were analyzed.ResultsA total of 218 patients were confirmed to have V. vulnificus septicemia during the study, and the 30-day survival rate was 39% (85/218). The patients were classified into the following six treatment groups: TGC monotherapy (n = 82), TGC plus doxycycline therapy (n = 42), TGC plus ciprofloxacin therapy (n = 39), ciprofloxacin monotherapy (n = 14), other β-lactam monotherapy (n = 10), and other (n = 31). The survival rates of these groups were as follows: TGC monotherapy (35%), TGC plus doxycycline (38%), TGC plus ciprofloxacin (54%), ciprofloxacin monotherapy (29%), other β-lactam (20%), and other (39%). The 30-day survival rate showed no significant difference between the TGC plus doxycycline and TGC plus ciprofloxacin groups (log-rank test, P = 0.18). Among the 81 patients treated with TGC plus doxycycline or TGC plus ciprofloxacin, 12 per treatment group were selected by propensity-score matching. There was no significant difference in the baseline characteristics or the frequency of fasciotomy between the two groups. The 30-day survival rate showed no significant difference between the TGC plus doxycycline (50%) and TGC plus ciprofloxacin (67%) groups (log-rank test, P = 0.46).ConclusionOur data suggest that the outcome of TGC plus ciprofloxacin therapy was comparable to that of TGC plus doxycycline therapy in patients with V. vulnificus septicemia.

Ciprofloxacin for BK viremia prophylaxis in kidney transplant recipients: Results of a prospective, double-blind, randomized, placebo-controlled trial.

In kidney transplantation, BK virus infection has historically resulted in high rates of graft dysfunction and graft loss. Unlike other opportunistic infections, no therapies have been shown to prevent BK. The purpose of the current study was to evaluate the safety and efficacy of ciprofloxacin for the prevention of BK viremia in kidney transplant recipients. Two hundred kidney transplant recipients were enrolled in a prospective, randomized, double-blind, placebo-controlled trial comparing a 3-month course of ciprofloxacin (n=133) vs placebo (n=67) for the prevention of BK viremia. The primary endpoint of BK viremia at month 6 posttransplant occurred in 25 (18.8%) patients in the ciprofloxacin group and 5 (7.5%) in the placebo group (P=.03). Higher rates of BK viremia (23.3% vs 11.9%; P=.06) and BK nephropathy (5.8% vs 1.5%; P=.26) remained at 12months in the ciprofloxacin group. Ciprofloxacin use was associated with a significantly higher rate of fluoroquinolone-resistant gram-negative infections (83.3% vs 50%; P=.04). A 3-month course of ciprofloxacin was ineffective at preventing BK viremia in kidney transplant recipients and was associated with an increased risk of fluoroquinolone-resistant infections. Clinical trial registration number: NCT01789203.

Fosfomycin trometamol vs ciprofloxacin for antibiotic prophylaxis before transrectal ultrasonography-guided prostate biopsy: A meta-analysis of clinical studies

ABSTRACTObjectives: To perform a systematic review and meta-analysis of clinical studies to assess the comparative prophylactic effectiveness of fosfomycin trometamol (FMT) vs ciprofloxacin (CIP) in men who underwent transrectal ultrasonography-guided prostate needle biopsy (TRUS-PNB), as infectious complications are a major concern after TRUS-PNB and although fluoroquinolones are currently the first choice, an increase in resistance has raised the question about its recommendation and FMT is a broad-spectrum oral antibiotic with low bacterial resistance.Methods: A systematic review was performed between January 1970 and June 2017 using the Web of Science, Scopus and PubMed databases to identify relevant studies. Preferred Reporting Items for Systematic Reviews and Meta-analysis criteria were used for article selection. Outcomes of interest were febrile and afebrile urinary tract infections (UTIs) and the presence of fluoroquinolone-resisitant (FQR)- or extended-spectrum β-lactamase (ESBL)-producing uropathogens in urinary cultures.Results: Four studies including 2331 men were analysed; 1088 had FMT and 1243 CIP as antibiotic prophylaxis before TRUS-PNB. FMT prophylaxis resulted in significantly less afebrile (odds ratio [OR] 0.21, 95% confidence interval [CI] 0.12–0.38; P < 0.001) and febrile (OR 0.15, 95% CI 0.07–0.31; P < 0.001) UTIs than CIP. Amongst all urine cultures, patients in the FMT arm also had a significantly lower prevalence of FQR and ESBL (E. coli or K. pneumoniae) microorganisms when compared to the CIP group (OR 0.25, 95% CI 0.12–0.21, P = 0.001; and OR 0.24, 95% CI 0.10–0.58, P = 0.001, respectively).Conclusions: Antibiotic prophylaxis with FMT before TRUS-PNB was associated with lower rates of infectious complications when compared to CIP.Abbreviations: CIP: ciprofloxacin; ESBL: extended-spectrum β-lactamase; FMT: fosfomycin trometamol; FQR: fluoroquinolone-resisitant; OR: odds ratio; PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses; TRUS-PNB: TRUS-guided prostate needle biopsy

Sniffing out resistance – Rapid identification of urinary tract infection-causing bacteria and their antibiotic susceptibility using volatile metabolite profiles

Antibiotic resistance is set to be an unprecedented threat to modern medicine. ‘Sniffing’ bacteria potentially offers a rapid way to determine susceptibility. A successful proof-of-principle study is described, using thermal desorption-gas chromatography-mass spectrometry (TDGCMS) to ‘smell’ cephalexin and ciprofloxacin resistant and sensitive Urinary Tract Infection (UTI)-causing bacteria. 578 peaks at unique retention times were detected from 86 chromatograms of 18 bacterial isolates (E. coli, K. pneumoniae and P. aeruginosa). The isolates were grown with and without the presence of antibiotic. Chi-square analysis found 9 compounds that differed significantly between cephalexin sensitive and resistant isolates, and 22 compounds that differed significantly between ciprofloxacin sensitive and resistant isolates, at p ≤ 0.05. When antibiotic was added to the media, more differences were found in the cephalexin group, attributed to lysis, but not in the ciprofloxacin group. Further work with large sample sizes will potentially enable the development of diagnostic algorithms using presence/absence of particular compounds of interest.

β-Glucan of Candida albicans Cell Wall Extract Inhibits Salmonella Typhimurium Colonization by Potentiating Cellular Immunity (CD8 + and CD4 + T Cells).

Antimicrobial resistance has been reported in the drugs used for the treatment of typhoid fever. The immunomodulatory substance β-glucan can be used as an alternative therapy as it potentiates host immunity. The aims of this study are to observe the effect of Candida albicans cell wall (CCW) extract towards host immunity (TCD8+ and TCD4+ cells in spleen, intestinal sIgA) and its capacity to kill Salmonella in the intestine and liver of typhoid fever mice models. Typhoid fever mice models were created by infecting mice with S. Typhimurium orally. Mice were divided into four groups: the Non-Infected, Infected, CCW (infected mice treated with 300 µg CCW extract/mouse once a day), and Ciprofloxacin groups (infected mice treated with 15 mg/kg BW ciprofloxacin twice a day). Secretory IgA (sIgA) concentrations of mice in the CCW group remained unchanged. However, their TCD4+ and TCD8+ cells increased substantially compared to those in the Non-Infected group. In the Ciprofloxacin group, sIgA concentrations increased markedly compared to those in the Non-Infected and CCW groups; TCD4+ and TCD8+ cells also increased significantly compared to those in the Infected Group, but not significant compared to those in the CCW group. Colonization of S. Typhimurium in the intestine and liver decreased significantly in the CCW and Ciprofloxacin groups compared to that in the Infected group, with the lowest reduction being found in the Ciprofloxacin group. The inhibition of S. Typhimurium colonization by CCW is associated with the increase in TCD4+ and TCD8+ cells.

Efficacy of inhaled ciprofloxacin agents for the treatment of bronchiectasis: a systematic review and meta-analysis of randomized controlled trials

Background:The efficacy of inhaled ciprofloxacin agents in the treatment of patients with bronchiectasis is controversial. The objective of the study was to review systematically the efficacy of inhaled ciprofloxacin agents in patients with bronchiectasis.Methods:We searched PubMed, EMBASE, and Cochrane Library databases for randomized controlled trials (RCTs) evaluating inhaled ciprofloxacin agents among patients with bronchiectasis. Data were pooled using a meta-analysis technique.Results:Two phase II and four phase III RCTs were included with a total of 1685 patients. Treatment durations of phase III studies were 48 weeks, while those of phase II studies were shorter. Pooled analysis of overall studies exhibited a statistically significant benefit of inhaled ciprofloxacin agents in three exacerbation outcome measures, including time to first exacerbation (hazard ratio 0.74, 95% confidence interval [CI] 0.63–0.86, I2 23%), exacerbation frequency (risk ratio [RR] 0.73, 95% CI 0.61–0.86, I2 42%), and exacerbation proportion (RR 0.85, 95% CI 0.76–0.96, I2 25%) without significant heterogeneity. Outcomes evaluating pulmonary function, quality of life, and adverse events were not significantly different between the two groups. Although eradication of respiratory pathogens was more frequently observed, the emergence of ciprofloxacin resistance was also significantly higher in the ciprofloxacin group.Conclusions:A meta-analysis of RCTs of inhaled ciprofloxacin agents showed clinical benefit in terms of pulmonary exacerbations in patients with bronchiectasis. Since a significant increase of resistance was also noticed, clinical trials with a longer study period are required for a conclusive assessment.The reviews of this paper are available via the supplemental material section.

Infectious Complications after High-Dose Chemotherapy and Autologous Stem Cell Transplantation for Hematologic Malignancies in a 12-Year Period in Hospital Britanico, Uruguay

Introduction: Autologous stem cell transplant (ASCT) plays a central role in the treatment of diverse diseases. Infection is one of the major causes of morbidity and costs of the procedure, representing the 2ndcause of death (24%) after primary disease (69%). Thus, preventing infections is a major goal.1There are no publications concerning infections in ASCT in our country.Patients and Methods: Retrospective single center study.Objectives: to compare the incidence of febrile neutropenia (FN) and characteristics of infections between 2 different antibacterial approaches. From January 2006 - December 2017, 279 ASCT have been done in our center. We included 266 patients with complete data: 249 received 1 ASCT and 17 received two. Anti-bacterial prophylaxis from 2006-2013 (Group 1) was ciprofloxacin from day 0 to neutrophil recovery. From 2013 to present (Group 2), levofloxacin was used. First febrile episode empirical treatment was Ceftazidime-Amikacin in Group 1 and Meropenem in Group 2.Results: Median age was 56 years (18-72). MM and NHL (79,7%), 40% in complete remission, were the prevailing diseases. Median CD34+ cells transplanted was 4,87 x 106/kg (0,88-37). Median duration of neutropenia was 11 days (9-32). (Table 1)Group 1: 28% had no FN episodes. Catheter-related and gastrointestinal were the most prevalent sites of infection. Positive cultures were 17,4%, 66,6% Gram+. 91% received Ceftazidime+Amikacine. A 2ndantibiotic was added in 52 patients (60%). Six patients required intensive care unit (ICU) admission (4.9%), due to pneumonia (3), sepsis (2) and viral encephalitis (1). Median days at discharge after ASCT was 17 (10-56); 20,6 for those who had FN episodes and 16,5 for those who did not (p= 0,004).Group 2: 13,8 % had no FN episodes. Pneumonia and catheter-related infections were the most prevalent sites of infection. Positive cultures: 20 %; 69% Gram +. 70 patients received an additional agent (56%).Six patients required ICU admission (4,1%), 1 due to pneumonia, 1 sepsis, 1 alitiasic cholecystitis, 1 catheter-related infection and pneumonia, 1 bradyarrhythmia and 1 atrial fibrillation. Median days at discharge after ASCT was +16 (12-62), 19,8 for those who experienced FN and 17 for those who did not (p=0,184).Incidence of FN was 72% in Group 1 and 86,2% in Group 2 (p=0,004). Culture-negativity was 82,6% in Group 1 and 80% in Group 2. In blood + cultures, Gram + agents represented 66.6% in Group 1 and 69% in Group 2 (p=0.68).Discussion: FN is common in ASCT (63-94%)2,3, implying longer hospitalization, more diagnostic procedures and increase in morbidity and mortality. Significant differences in FN incidence between groups, in favor of Ciprofloxacin prophylaxis (72% vs 86,2% (p=0,004) were found. The incidence of positive cultures was similar in both groups. Gram+ agents were the most common isolation. Prophylaxis with quinolones leaded to a low Gram negative bacteria isolation, as reported by others.4Most infectious episodes were associated with fever of unknown origin: 53 % in Group 1 and 56.8 % in Group 2, with differences in sites of infection's frequency: catheter-related infection prevailed in Group 1 and pneumonia in Group 2. (Table 2)We hypothesized that a better Gram+ coverage with Levofloxacin might have help to reduce the incidence of clinical catheter infections. A 2nd antibiotic was needed in 60% from Group 1 and 56% in Group 2 (p=0,47). Median to neutrophil recovery was shorter in Group 1 (+8 vs +10), (p=0,0001). ICU admission was mostly due to sepsis, similar in both groups (p=0,74). During hospitalization, 2 patients died of sepsis in Group 1 and 0 in Group 2. Mortality rate was 1,87 %, similar to international reports.5 Patients in Group 2 were older, with more advanced diseases and hypogammaglobulinemia, which may contribute to difference in favor of Ciprofloxacin group in terms of FN and days to hematopoiesis recovery. (Table 3)Levofloxacin prophylaxis was not associated with an increase in resistant bacteria nor Clostridium difficile infection.Conclusions: The incidence of FN in ASCT was high. Levofloxacin prophylaxis was associated with more FN episodes and later discharge. Epidemiology and severity of infections and 2nd antibiotic requirement were comparable in both groups. Patients admitted for ASCT in the last 7 years had additional risk features that may contribute to explain the differences found. Mortality rate was low in both groups. DisclosuresNo relevant conflicts of interest to declare.

In vitro evaluation of local antibiotic delivery via fibrin hydrogel

Background/purposeFibrin hydrogel is commonly used as hemostatic agent and scaffold but it is questionable for carrying antibiotics. Thus, this study aimed to investigate whether the fibrin hydrogel can be used to deliver the optimal concentration of ciprofloxacin against oral pathogen. Materials and methodsThe optimal concentration of ciprofloxacin was investigated from broth microdilution technique against three common oral bacteria. Ten times the bactericidal concentration of ciprofloxacin loaded to 0.4% fibrin hydrogel was observed by using a confocal laser scanning microscope and then was left in tris-buffer saline solution (TBS) for 0, 1, 12, 24, 72 and 168 h in parallel with the control group of ciprofloxacin loaded to 0.5% alginate hydrogel and ciprofloxacin solution. Spectrophotometer was used to analyze the accumulated drug release from the collected TBS, of which the measurement method was calibrated. The efficacy of the released ciprofloxacin was tested using an agar well diffusion assay. The inhibition zone of the released ciprofloxacin from fibrin hydrogel was statistically compared with 150 and 1500 μg/ml ciprofloxacin solution, while non-loaded fibrin hydrogel served as the control. ResultsThe results revealed that minimum inhibitory concentration was 1–2 μg/ml and minimum bactericidal concentration was 4–15 μg/ml. The fibrin hydrogel gradually released ciprofloxacin until 168 h while the alginate hydrogel immediately liberated all the loaded ciprofloxacin within an hour. The agar well diffusion significantly showed greater clear zone in fibrin hydrogel loaded ciprofloxacin compared to non-loaded fibrin hydrogel but not with ciprofloxacin in TBS. ConclusionThe results suggested that fibrin hydrogel can be used for local ciprofloxacin delivery without interfering the efficacy of ciprofloxacin.

Synthesis of Amphiphilic Copolymers Containing Ciprofloxacin and Amine Groups and Their Antimicrobial Performances As Revealed by Confocal Laser-Scanning Microscopy and Atomic-Force Microscopy.

Two series of amphiphilic antimicrobial copolymers containing ciprofloxacin (CPF) and amine functional groups have been synthesized via free-radical copolymerization. The chemical structures of the different amine groups and the copolymer compositions have been systematically varied to study how the structure of the copolymer exerts an influence on the antibacterial activity. The viability of Escherichia coli in the presence of antimicrobial copolymers was observed by confocal laser-scanning microscopy (CLSM). CLSM as well as atomic-force microscopy (AFM) were applied to visualize changes in morphology of bacteria treated with antimicrobial copolymers and elucidate the antimicrobial mechanism of the antimicrobial copolymers. Morphological changes of bacteria observed via AFM and CLSM demonstrated that the antibacterial mechanism was due to the disruption of the bacterial membrane. The destruction of the cell membrane was also confirmed by the leakage of intracellular components, which had a strong absorbance at 260 nm. The inhibitory process was monitored by UV absorption dynamically.

Daily Norfloxacin vs. Weekly Ciprofloxacin to Prevent Spontaneous Bacterial Peritonitis: A Randomized Controlled Trial.

For the prevention of spontaneous bacterial peritonitis (SBP) in cirrhotic patients with ascites, norfloxacin 400 mg per day is recommended as a standard regimen. This study aims to investigate whether ciprofloxacin once weekly administration is not inferior to norfloxacin once daily administration for the prevention of SBP. This is an investigator-initiated open-label randomized controlled trial conducted at seven tertiary hospitals in South Korea. Liver cirrhosis patients with ascites were screened, and enrolled in this randomized controlled trial if ascitic protein ≤1.5 g/dL or the presence of history of SBP. Ascitic polymorphonucleated cell count needed to be <250/mm3. Patients were randomly assigned into norfloxacin daily or ciprofloxacin weekly group, and followed-up for 12 months. Primary endpoint was the prevention of SBP. One hundred twenty-four patients met enrollment criteria and were assigned into each group by 1:1 ratio (62:62). Seven patients in the norfloxacin group and five patients in the ciprofloxacin group were lost to follow-up. SBP developed in four patients (4/55) and in three patients (3/57) in each group, respectively (7.3% vs. 5.3%, P = 0.712). The transplant-free survival rates at 1 year were comparable between the groups (72.7% vs. 73.7%, P = 0.970). Incidence of infectious complication, hepatorenal syndrome, hepatic encephalopathy, and variceal bleeding rates were not significantly different (all P = ns). The factors related to survival were models representing underlying liver function. Once weekly ciprofloxacin was as effective as daily norfloxacin for the prevention of SBP in cirrhotic patients with ascites.

Metabolomics reveals immunomodulation as a possible mechanism for the antibiotic effect of Persicaria capitata (Buch.-Ham. ex D. Don) H.Gross

IntroductionIn spite of advances in antibiotics, urinary tract infection (UTI) is still among the most common reasons for antibiotic medication worldwide. Persicaria capitata (Buch.-Ham. ex D. Don) H.Gross (P. capitata) is a herbal medicine used by the Miao people in China to treat UTI. However studies of its mechanism are challenging, owing to the complexity of P. capitata with multiple constituents acting on multiple metabolic pathways.ObjectiveThe objective of this study was to explore the working mechanism of P. capitata on urinary tract infection.MethodsRelinqing® granule, which is solely made from aqueous extracts of the whole P. capitata plant, was used in this study. Urine metabolomics based on gas chromatography-mass spectroscopy was employed to assess the metabolic changes caused by administration of Relinqing® granule in a UTI mouse model. Female specific-pathogen-free Kunming mice were divided into control group (mock infection, saline treatment), model group (E.coli infection, saline treatment), Relinqing® group (E.coli infection, Relinqing® granule treatment), ciprofloxacin group (E.coli infection, ciprofloxacin treatment), and sham-Relinqing® group (no surgery, Relinqing® granule treatment).ResultsThe results showed that after the treatments, urine levels of itaconic acid in Relinqing® group increased by 4.9 fold and 11.3 fold compared with model and ciprofloxacin groups respectively. Itaconic acid is an endogenous antibacterial metabolite produced by macrophages, which also functions as a checkpoint for metabolic reprogramming of macrophage.ConclusionOur findings suggest that this herbal medicine can cure urinary tract infection through modulation of immune system.

Clinical Efficacy Of Ceftriaxone Versus Ciprofloxacin In Paediatric Enteric Fever

Objective: Determination of the clinical effectiveness of ciprofloxacin versus ceftriaxone in children with enteric fever on the basis of defervescence within 72 hours of commencement of treatment. Duration and Place of Study: This randomized controlled trial was carried out from 15th May to 15th November 2017 in pediatrics units of Benazir Bhutto Shaheed Teaching Hospital Abbottabad and Jinnah International Hospital Abbottabad. Methodology: 90 children with uncomplicated enteric fever were admitted and divided randomly into two groups, Group A was administered I/V Ceftriaxone 75mg/kg OD and Group B was given I/V Ciprofloxacin 10mg/kg BD for seven days. Response to drug was taken as defervescence within 72 hours while continued fever after 72 hours was taken as no response. The data was analyzed by using SPSS Version 21.00. Results: In our research study 53(58.9%) children were male and 37(41.1%) patients were female. The mean age was 8.43±3.17 years encompassing 4 to 14 years, mean weight of the patients in kg was 29.54±10.8 kg. Efficacy of ceftriaxone group was 93.3% while in ciprofloxacin group 62.2% patients became afebrile in 72 hours. The proportion of achieving defervescence within 72 hours was higher with ceftriaxone than with ciprofloxacin Conclusion: Ceftriaxone is more efficacious in terms of achieving defervescence than ciprofloxacin in children having enteric fever.