Vedolizumab for the Treatment of Chronic Pouchitis.

BACKGROUND: Approximately half the patients with ulcerative colitis who undergo restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) will subsequently have pouchitis, and among those patients, one fifth will have chronic pouchitis. METHODS: We conducted a phase 4, double-blind, randomized trial to evaluate vedolizumab in adult patients in whom chronic pouchitis had developed after undergoing IPAA for ulcerative colitis. Patients were assigned (in a 1:1 ratio) to receive vedolizumab intravenously at a dose of 300 mg or placebo on day 1 and at weeks 2, 6, 14, 22, and 30. All the patients received concomitant ciprofloxacin from weeks 1 to 4. The primary end point was modified Pouchitis Disease Activity Index (mPDAI)-defined remission (an mPDAI score of ≤4 and a reduction from baseline of ≥2 points in the mPDAI total score; scores range from 0 to 12, with higher scores indicating more severe pouchitis) at week 14. The mPDAI is based on clinical symptoms and endoscopic findings. Other efficacy end points included mPDAI-defined remission at week 34, mPDAI-defined response (a reduction from baseline of ≥2 points in the mPDAI score) at weeks 14 and 34, and PDAI-defined remission (a PDAI score of ≤6 and a reduction from baseline of ≥3 points; scores range from 0 to 18, with higher scores indicating more severe pouchitis) at weeks 14 and 34. The PDAI is based on clinical symptoms, endoscopic findings, and histologic findings. RESULTS: Among the 102 patients who underwent randomization, the incidence of mPDAI-defined remission at week 14 was 31% (16 of 51 patients) with vedolizumab and 10% (5 of 51 patients) with placebo (difference, 21 percentage points; 95% confidence interval [CI], 5 to 38; P = 0.01). Differences in favor of vedolizumab over placebo were also seen with respect to mPDAI-defined remission at week 34 (difference, 17 percentage points; 95% CI, 0 to 35), mPDAI-defined response at week 14 (difference, 30 percentage points; 95% CI, 8 to 48) and at week 34 (difference, 22 percentage points; 95% CI, 2 to 40), and PDAI-defined remission at week 14 (difference, 25 percentage points; 95% CI, 8 to 41) and at week 34 (difference, 19 percentage points; 95% CI, 2 to 37). Serious adverse events occurred in 3 of 51 patients (6%) in the vedolizumab group and in 4 of 51 patients (8%) in the placebo group. CONCLUSIONS: Treatment with vedolizumab was more effective than placebo in inducing remission in patients who had chronic pouchitis after undergoing IPAA for ulcerative colitis. (Funded by Takeda; EARNEST ClinicalTrials.gov number, NCT02790138; EudraCT number, 2015-003472-78.).

Ciprofloxacin and pegylated G-CSF combined therapy mitigates brain hemorrhage and mortality induced by ionizing irradiation.

Introduction: Brain hemorrhage was found between 13 and 16 days after acute whole-body 9.5 Gy 60Co-γ irradiation (IR). This study tested countermeasures mitigating brain hemorrhage and increasing survival from IR. Previously, we found that pegylated G-CSF therapy (PEG) (i.e., Neulasta®, an FDA-approved drug) improved survival post-IR by 20-40%. This study investigated whether Ciprofloxacin (CIP) could enhance PEG-induced survival and whether IR-induced brain hemorrhage could be mitigated by PEG alone or combined with CIP. Methods: B6D2F1 female mice were exposed to 60Co-γ-radiation. CIP was fed to mice for 21 days. PEG was injected on days 1, 8, and 15. 30-day survival and weight loss were studied in mice treated with vehicles, CIP, PEG, or PEG + CIP. For the early time point study, blood and sternums on days 2, 4, 9, and 15 and brains on day 15 post-IR were collected. Platelet numbers, brain hemorrhage, and histopathology were analyzed. The cerebellum/pons/medulla oblongata were detected with glial fibrillary acidic protein (GFAP), p53, p16, interleukin-18 (IL-18), ICAM1, Claudin 2, ZO-1, and complement protein 3 (C3). Results: CIP + PEG enhanced survival after IR by 85% vs. the 30% improvement by PEG alone. IR depleted platelets, which was mitigated by PEG or CIP + PEG. Brain hemorrhage, both surface and intracranial, was observed, whereas the sham mice displayed no hemorrhage. CIP or CIP + PEG significantly mitigated brain hemorrhage. IR reduced GFAP levels that were recovered by CIP or CIP + PEG, but not by PEG alone. IR increased IL-18 levels on day 4 only, which was inhibited by CIP alone, PEG alone, or PEG + CIP. IR increased C3 on day 4 and day 15 and that coincided with the occurrence of brain hemorrhage on day 15. IR increased phosphorylated p53 and p53 levels, which was mitigated by CIP, PEG or PEG + CIP. P16, Claudin 2, and ZO-1 were not altered; ICAM1 was increased. Discussion: CIP + PEG enhanced survival post-IR more than PEG alone. The Concurrence of brain hemorrhage, C3 increases and p53 activation post-IR suggests their involvement in the IR-induced brain impairment. CIP + PEG effectively mitigated the brain lesions, suggesting effectiveness of CIP + PEG therapy for treating the IR-induced brain hemorrhage by recovering GFAP and platelets and reducing C3 and p53.

Synergistic Effect of Co-Delivering Ciprofloxacin and Tetracycline Hydrochloride for Promoted Wound Healing by Utilizing Coaxial PCL/Gelatin Nanofiber Membrane.

Combining multiple drugs or biologically active substances for wound healing could not only resist the formation of multidrug resistant pathogens, but also achieve better therapeutic effects. Herein, the hydrophobic fluoroquinolone antibiotic ciprofloxacin (CIP) and the hydrophilic broad-spectrum antibiotic tetracycline hydrochloride (TH) were introduced into the coaxial polycaprolactone/gelatin (PCL/GEL) nanofiber mat with CIP loaded into the PCL (core layer) and TH loaded into the GEL (shell layer), developing antibacterial wound dressing with the co-delivering of the two antibiotics (PCL-CIP/GEL-TH). The nanostructure, physical properties, drug release, antibacterial property, and in vitro cytotoxicity were investigated accordingly. The results revealed that the CIP shows a long-lasting release of five days, reaching the releasing rate of 80.71%, while the cumulative drug release of TH reached 83.51% with a rapid release behavior of 12 h. The in vitro antibacterial activity demonstrated that the coaxial nanofiber mesh possesses strong antibacterial activity against E. coli and S. aureus. In addition, the coaxial mats showed superior biocompatibility toward human skin fibroblast cells (hSFCs). This study indicates that the developed PCL-CIP/GEL-TH nanofiber membranes hold enormous potential as wound dressing materials.

Effect of antibiotic pretreatment on bacterial engraftment after Fecal Microbiota Transplant (FMT) in IBS-D.

Fecal microbiota transplantation (FMT) is an attractive strategy to correct microbial dysbiosis in diarrhea-predominant irritable bowel syndrome (IBS-D). Although the mechanism of FMT is thought to be bacterial engraftment, the best approach to achieve engraftment after FMT in IBS-D (and other diseases) is not clear. We evaluated the effect of FMT (with or without pretreatment with antibiotics) on gut microbiome and symptoms in patients with IBS-D. In this randomized, placebo-controlled, single-center study, 44 patients with IBS-D with a least moderate severity (IBS severity scoring system, i.e., IBS-SSS, ≥175) were randomly assigned to one of four groups: single-dose oral FMT alone, single-dose oral FMT following a 7-day pretreatment course of Ciprofloxacin and Metronidazole (CM-FMT) or Rifaximin (R-FMT), or Placebo FMT. Primary endpoint was engraftment post-FMT and secondary endpoints were changes in IBS-SSS, and IBS-quality of life (IBS-QOL) at week 10. Median engraftment was significantly different among the three FMT groups (P = .013). Engraftment post-FMT was significantly higher in the FMT alone arm (15.5%) compared to that in R-FMT group (5%, P = .04) and CM-FMT group (2.4%, P = .002). The mean change in IBS-SSS and IBS-QOL from baseline were not significantly different among the four groups or between the three FMT groups combined vs. placebo at week 10. In summary, antibiotic pretreatment significantly reduced bacterial engraftment after FMT in patients with IBS-D.

A randomised clinical trial of single or extended dosing ciprofloxacin versus no intervention for prevention of ventilation tube otorrhoea and obstruction (PreVenTO2).

OBJECTIVES: To determine the effectiveness of ciprofloxacin .3% antibiotic eardrops in preventing clinically significant postoperative otorrhoea and tube obstruction following grommet insertion in children. DESIGN: Three-arm parallel assessor-blinded randomised controlled trial. Randomisation in 1: 1: 1 ratio to single intraoperative application of ciprofloxacin drops, extended 5 day postoperative application and no drops. Patients were assessed by blinded assessors at 6 weeks postoperatively. SETTING: The study was conducted in a large tertiary health network in Melbourne, Australia. PARTICIPANTS: All children, 17 years and under, undergoing bilateral middle ear ventilation tube surgery with or without concurrent upper airway surgery for recurrent acute otitis media and chronic otitis media with effusion were approached. MAIN OUTCOME MEASURES: Presence of postoperative otorrhoea and ventilation tube obstruction at 6 weeks postoperatively. RESULTS: Two-hundred and fifty-six paediatric patients completed the study with a median age of 4.02 years. One-hundred and fifty-three participants were male. Ear analysis (n = 512) showed intraoperative antibiotics were more effective than no drops in preventing otorrhoea (RR = .341, 95% CI .158-.738, NNT =11.25, p = .006). Postoperative antibiotics were more effective than no drops in preventing ventilation tube obstruction (RR = .424, 95% CI .193 to .930, NNT =14.7, p = .032). CONCLUSION: Intraoperative topical ciprofloxacin was effective at preventing early postoperative otorrhoea, and a prolonged course was effective at preventing ventilation tube obstruction. Future studies on this topic should seek to clarify whether particular subgroups of patients benefit more from prophylactic topical antibiotics and model for cost-effectiveness.

Transrectal povidone-iodine efficiency in reducing infections occurring after transrectal ultrasound guided biopsy of the prostate.

ABSTRACT: The present study aimed to compare infectious complications in men undergoing transrectal ultrasound-guided prostate biopsy (TRUS-Bx) with and without povidone-iodine transrectal injection using a gavage syringe.The records of 112 patients, who underwent TRUS-Bx between January 2016 and December 2019, were retrospectively reviewed. The biopsy indication was considered high prostate-specific antigen (PSA) level and/or suspicious digital rectal prostate examination findings. Patients' ages, underlying diseases, PSA levels, prostate volumes, pathologic results, and infectious complications after the biopsy were investigated. All the patients received 1500 mg of ciprofloxacin (750 mg twice a day) for 5 days, starting from the day before the procedure. Forty-seven (41.96%) patients received ciprofloxacin prophylaxis with povidone-iodine transrectal injection, while 65 (58.03%) only received ciprofloxacin prophylaxis. All the patients, who were readmitted to the hospital after the procedure, especially with a temperature of higher than 37.8°C, were detected. For the purposes of the study, the priority was placed on the emergence of the rate of febrile infectious complications. Differences in febrile infectious complications in patients, who received ciprofloxacin prophylaxis with transrectal povidone-iodine, and those, who received ciprofloxacin prophylaxis alone before TRUS-Bx, were studied.Febrile infectious complications developed in 10 cases (15.38%) in patients, who received ciprofloxacin antibiotics prophylaxis alone. In the povidone-iodine rectal disinfection group, there was only 1 case of febrile infectious complication (2%). There was no significant difference by clinicopathologic features, age, PSA level, and cancer detection rate between both groups (P > .05). Multivariate logistic regression analysis did not identify any patient subgroups at a significantly higher risk of infection after prostate biopsy. There was no significant side effect associated with povidone iodine.In addition to the use of prophylactic antibiotics, transrectal povidone-iodine was useful in reducing the febrile infection complications following TRUS-Bx.

Dynamics of the QTc interval over a 24-h dose interval after start of intravenous ciprofloxacin or low-dose erythromycin administration in ICU patients.

QTc interval prolongation is an adverse effect associated with the use of fluoroquinolones and macrolides. Ciprofloxacin and erythromycin are both frequently prescribed QTc-prolonging drugs in critically ill patients. Critically ill patients may be more vulnerable to developing QTc prolongation, as several risk factors can be present at the same time. Therefore, it is important to know the QTc-prolonging potential of these drugs in the intensive care unit (ICU) population. The aim of this study was to assess the dynamics of the QTc interval over a 24-hour dose interval during intravenous ciprofloxacin and low-dose erythromycin treatment. Therefore, an observational study was performed in ICU patients (≥18 years) receiving ciprofloxacin 400 mg t.i.d. or erythromycin 100 mg b.i.d. intravenously. Continuous ECG data were collected from 2 h before to 24 h after the first administration. QT-analyses were performed using high-end holter software. The effect was determined with a two-sample t-test for clustered data on all QTc values. A linear mixed model by maximum likelihood was applied, for which QTc values were assessed for the available time intervals and therapy. No evident effect over time on therapy with ciprofloxacin and erythromycin was observed on QTc time. There was no significant difference (p = 0.22) in QTc values between the ciprofloxacin group (mean 393 ms) and ciprofloxacin control group (mean 386 ms). The erythromycin group (mean 405 ms) and erythromycin control group (mean 404 ms) neither showed a significant difference (p = 0.80). In 0.6% of the registrations (1.138 out of 198.270 samples) the duration of the QTc interval was longer than 500 ms. The index groups showed slightly more recorded QTc intervals over 500 ms. To conclude, this study could not identify differences in the QTc interval between the treatments analyzed.

Effectiveness and antimicrobial susceptibility profiles during primary antimicrobial prophylaxis for pediatric acute myeloid leukemia.

Limited data are available on antimicrobials exposure and microbiology evolution in pediatric acute myeloid leukemia (AML) patients underwent antimicrobials prophylaxis. To assess the effectiveness of antimicrobials prophylaxis, antibiotic susceptibilities of bacteria, and exposure of antimicrobials during intensive chemotherapy for AML patients, 90 consecutive de novo AML patients aged 0-18 years between January 1, 1997 and March 31, 2018 were enrolled. Vancomycin, ciprofloxacin and voriconazole prophylaxis was administered from January 1, 2010. During the preprophylaxis period, January 1997 to December 2009, 62 patients experienced a total of 87 episodes of bloodstream infection (BSI) and 17 episodes of invasive fungal infection (IFI) among 502 courses of chemotherapy. In contrast, 16 episodes of BSI occurred and no IFIs were reported to occur in 28 patients who received 247 courses of chemotherapy in the prophylaxis period. Patients who received antimicrobial prophylaxis had a significant reduction of BSI, IFI, and febrile neutropenia in comparison with patients without prophylaxis. Exposure to amikacin, carbapenem, amphotericin B was reduced in the prophylaxis period. Imipenem susceptibility of Enterobacter cloacae as well as vancomycin susceptibility of Enterococcus species were reduced in the prophylaxis period. At the time of the last follow up, patients with prophylaxis had a better subsequent 5-year overall survival rate than those without prophylaxis. Prophylactic antimicrobials administration in children with AML who undergo chemotherapy can significantly reduce the rates of life-threatening infection, exposure to antimicrobials, and might result in a better outcome.

Relay oral therapy in febrile urinary tract infections caused by extended spectrum beta-lactamase-producing Enterobacteriaceae in children: A French multicenter study.

OBJECTIVES: We need studies assessing therapeutic options for oral relay in febrile urinary tract infection (FUTI) due to ESBL-producing Enterobacteriaceae (ESBL-E) in children. Amoxicillin-clavulanate/cefixime (AC-cefixime) combination seems to be a suitable option. We sought to describe the risk of recurrence at 1 month after the end of treatment for FUTI due to ESBL-E according to the oral relay therapy used. MATERIALS AND METHODS: We retrospectively identified children <18 years who were included in a previous prospective observational multicentric study on managing FUTI due to ESBL-E between 2014 and 2017 in France. We collected whether children who received cotrimoxazole, ciprofloxacin or the AC-cefixime combination as the oral relay therapy reported a recurrence within the first month after the end of treatment. Then, we analyzed the susceptibility drug-testing of the strains involved. RESULTS: We included 199 children who received an oral relay therapy with cotrimoxazole (n = 72, 36.2%), ciprofloxacin (n = 38, 19.1%) or the AC-cefixime combination (n = 89, 44.7%). Nine (4.5%) patients had a recurrence within the first month after the end of treatment, with no difference between the 3 groups of oral relay (p = 0.8): 4 (5.6%) cotrimoxazole, 2 (5.3%) ciprofloxacin and 3 (3.4%) AC-cefixime combination. Phenotype characterization of 249 strains responsible for FUTI due to ESBL-E showed that 97.6% were susceptible to the AC-cefixime combination. CONCLUSIONS: The AC-cefixime combination represents an interesting therapeutic option for oral relay treatment of FUTI due to ESBL-E as the recurrence rate at 1 month after the end of treatment was the same when compared to cotrimoxazole and ciprofloxacin.

Validity of caregivers' reports on prior use of antibacterials in children under five years presenting to health facilities in Gulu, northern Uganda.

INTRODUCTION: Given the frequent initiation of antibacterial treatment at home by caregivers of children under five years in low-income countries, there is a need to find out whether caregivers' reports of prior antibacterial intake by their children before being brought to the healthcare facility are accurate. The aim of this study was to describe and validate caregivers' reported use of antibacterials by their children prior to seeking care at the healthcare facility. METHODS: A cross sectional study was conducted among children under five years seeking care at healthcare facilities in Gulu district, northern Uganda. Using a researcher administered questionnaire, data were obtained from caregivers regarding reported prior antibacterial intake in their children. These reports were validated by comparing them to common antibacterial agents detected in blood and urine samples from the children using liquid chromatography with tandem mass spectrometry (LC-MS/MS) methods. RESULTS: A total of 355 study participants had a complete set of data on prior antibacterial use collected using both self-report and LC-MS/MS. Of the caregivers, 14.4% (51/355, CI: 10.9-18.5%) reported giving children antibacterials prior to visiting the healthcare facility. However, LC-MS/MS detected antibacterials in blood and urine samples in 63.7% (226/355, CI: 58.4-68.7%) of the children. The most common antibacterials detected from the laboratory analysis were cotrimoxazole (29%, 103/355), ciprofloxacin (13%, 46/355), and metronidazole (9.9%, 35/355). The sensitivity, specificity, positive predictive value (PPV), negative predictive value and agreement of self-reported antibacterial intake prior to healthcare facility visit were 17.3% (12.6-22.8), 90.7% (84.3-95.1), 76.5% (62.5-87.2), 38.5% (33.0-44.2) and 43.9% (k 0.06) respectively. CONCLUSION: There is low validity of caregivers' reports on prior intake of antibacterials by these children. There is need for further research to understand the factors associated with under reporting of prior antibacterial use.

Dry powder formulation for pulmonary infections: Ciprofloxacin loaded in chitosan sub-micron particles generated by electrospray.

Electrospray was used as a one-step technique to generate inhalable ciprofloxacin-loaded chitosan sub-micron particles with potential use in the treatment of pulmonary infections. The effect of operating parameters was studied and the preparation method optimized. The final sizes of ciprofloxacin-loaded particles were 386.1 ± 248.5 nm and 501.1 ± 276.3 nm for high and low molecular weight chitosan, respectively. The high surface charge of the particles formed, around +45 mV, enhances their mucoadhesive properties. The particles were biocompatible with alveolar cell line (A549), and showed a high antimicrobial activity against two of the most common respiratory pathogens Staphylococcus aureus and Pseudomonas aeruginosa.

Identification of pathogens isolated in acute external otitis cases and evaluation of aminoglycoside and quinolone sensitivity.

OBJECTIVE: This study aimed to identify pathogens isolated in acute external otitis cases and determine their distribution according to ages and seasons as well as investigate the susceptibility or resistance to the aminoglycoside and quinolone group antibiotics of which topical forms are available. METHOD: A total of 168 patients diagnosed with acute external otitis were evaluated retrospectively. Growing bacteria were identified according to the species by conventional methods. Antibiotic susceptibility status was determined for the growing bacteria. RESULTS: The most common bacteria detected were pseudomonas group bacteria (38.7 per cent). Resistance to the amikacin group of antibiotics was found to be the lowest and resistance to the ciprofloxacin group of antibiotics was the highest. CONCLUSION: External auditory canal cultures should be taken simultaneously with empirical treatment. Seasonal effect and age group should be taken into consideration in the choice of treatment and after questioning about chronic exposure to water. Empirical treatment should then be started.

Effect of 7 vs 14 Days of Antibiotic Therapy on Resolution of Symptoms Among Afebrile Men With Urinary Tract Infection: A Randomized Clinical Trial.

Importance: Determination of optimal treatment durations for common infectious diseases is an important strategy to preserve antibiotic effectiveness. Objective: To determine whether 7 days of treatment is noninferior to 14 days when using ciprofloxacin or trimethoprim/sulfamethoxazole to treat urinary tract infection (UTI) in afebrile men. Design, Setting, and Participants: Randomized, double-blind, placebo-controlled noninferiority trial of afebrile men with presumed symptomatic UTI treated with ciprofloxacin or trimethoprim/sulfamethoxazole at 2 US Veterans Affairs medical centers (enrollment, April 2014 through December 2019; final follow-up, January 28, 2020). Of 1058 eligible men, 272 were randomized. Interventions: Participants continued the antibiotic prescribed by their treating clinician for 7 days of treatment and were randomized to receive continued antibiotic therapy (n = 136) or placebo (n = 136) for days 8 to 14 of treatment. Main Outcomes and Measures: The prespecified primary outcome was resolution of UTI symptoms by 14 days after completion of active antibiotic treatment. A noninferiority margin of 10% was selected. The as-treated population (participants who took ≥26 of 28 doses and missed no more than 2 consecutive doses) was used for the primary analysis, and a secondary analysis included all patients as randomized, regardless of treatment adherence. Secondary outcomes included recurrence of UTI symptoms and/or adverse events within 28 days of stopping study medication. Results: Among 272 patients (median [interquartile range] age, 69 [62-73] years) who were randomized, 100% completed the trial and 254 (93.4%) were included in the primary as-treated analysis. Symptom resolution occurred in 122/131 (93.1%) participants in the 7-day group vs 111/123 (90.2%) in the 14-day group (difference, 2.9% [1-sided 97.5% CI, -5.2% to ∞]), meeting the noninferiority criterion. In the secondary as-randomized analysis, symptom resolution occurred in 125/136 (91.9%) participants in the 7-day group vs 123/136 (90.4%) in the 14-day group (difference, 1.5% [1-sided 97.5% CI, -5.8% to ∞]) Recurrence of UTI symptoms occurred in 13/131 (9.9%) participants in the 7-day group vs 15/123 (12.9%) in the 14-day group (difference, -3.0% [95% CI, -10.8% to 6.2%]; P = .70). Adverse events occurred in 28/136 (20.6%) participants in the 7-day group vs 33/136 (24.3%) in the 14-day group. Conclusions and Relevance: Among afebrile men with suspected UTI, treatment with ciprofloxacin or trimethoprim/sulfamethoxazole for 7 days was noninferior to 14 days of treatment with regard to resolution of UTI symptoms by 14 days after antibiotic therapy. The findings support the use of a 7-day course of ciprofloxacin or trimethoprim/sulfamethoxazole as an alternative to a 14-day course for treatment of afebrile men with UTI. Trial Registration: ClinicalTrials.gov identifier: NCT01994538.

[Achilles tendinopathy in a hemodialysis patient complicated by rupture of the Achilles tendon due to self-medication with ciprofloxacin: about a case]. / Tendinopathie achilléenne compliquée d´une rupture du tendon d´Achille consécutives à une automédication par la ciprofloxacine chez une hémodialysée: à propos d´un cas.

This study aims to remind clinicians of fluoroquinolone-related tendinopathies. They are rare side effects, but which can result in functional disability. We report the case of a 79-year-old woman with a 11-year history of haemodialysis who had sudden left ankle pain and functional impairment in the ipsilateral member on day 5th after self-medication with ciprofloxacin. Comorbidities included chronic gonarthrosis, secondary hyperparathyroidism and ischemic heart disease. The diagnosis of bilateral Achilles tendinopathy and rupture of the left Achilles tendon was retained due to clinical features and confirmed by ultrasound of ankles. Ciprofloxacin-associated tendon rupture was evaluated using the French method of accountability for drug unexpected side effects or toxicity. Tendon rupture management was based on surgery followed by functional rehabilitation program with satisfactory outcome. The frequency of fluoroquinolone-related tendinopathies ranges from 15 to 20 accidents per 100,000 subjects treated, a third of whom are complicated by tendon rupture. Incidence is related to age, affecting mainly people > 60 years and involving tissular aging. Pefloxacin and ciprofloxacin are the most offending molecules. In our study, the delay in the onset of symptoms on day 5 after self-medication was consistent with literature. We detected some common contributing factors including chronic renal failure, hemodialysis and the assumption of statins and corticosteroids. Fluoroquinolone-related tendinopathies are characterized by common clinical features which allow diagnosis. They mostly affect Achilles tendon. They are bilateral in 40-66% of cases. Tendon rupture is the main complication. Management is based on surgery. It allows to restore anatomy and to prevent detrimental functional disability. We here report a rare but potentially serious fluoroquinolones-related side effect, exposing the patient to the risk of functional disability. Advanced age, chronic renal failure, chronic haemodialysis, concomitant use of statins and corticosteroids are common contributing factors confirmed in this study. Hemodialysis patients constitute a population at risk; hence the importance of remote monitoring after treatment with these molecules.

Enhanced corrosion resistance and reduced cytotoxicity of the AZ91 Mg alloy by plasma nitriding and a hierarchical structure composed of ciprofloxacin-loaded polymeric multilayers and calcium phosphate coating.

Much effort has made to lessen the cytotoxicity and enhance the corrosion resistance of biodegradable magnesium alloys, for example, by depositing multilayered polymeric coatings containing hydroxyapatite. In this work, a hierarchical structure composed of ciprofloxacin (Cip)-loaded on polyacrylic acid (PAA) and poly (ethyleneimine) (PEI) as biocompatible polymeric multilayers and calcium phosphate coating as the top layer is formed by the sol-gel method on the AZ91 Mg alloy with an intermediate layer formed by nitrogen plasma immersion ion implantation. The thicknesses of the multilayered coating and nitrided layer (Mg3 N2 ) are 10 µm and 140 nm, respectively. The corrosion current density decreases by 95.6% and the corrosion potential in the polarization curve shifts to the positive direction by 23%. The passivation process which occurs at defects by deposition of corrosion products mitigates both galvanic and localized corrosion. Slight increase in the contact angle and surface free energy, enhanced corrosion resistance, and reduced cytotoxicity are observed from the multilayered structure. The better corrosion resistance enables better control of release of Cip. Biological assessment indicates that the antibacterial activity against Escherichia coli is improved by 100% after culturing for 24 hr and the cell viability and noncytotoxic behavior of the coated AZ91 are enhanced as well. The corrosion behavior and biological results suggest that the strategy of using a hierarchical structure composed of Cip-loaded polymeric multilayers in conjunction with an intermediate plasma nitrided layer has large potential in the development of biodegradable orthopedic implants made of Mg alloys.

Population pharmacokinetics of intravenous and oral ciprofloxacin in children to optimize dosing regimens.

PURPOSE: This study aimed to characterize pharmacokinetics of intravenous and oral ciprofloxacin in children to optimize dosing scheme. METHODS: Children treated with ciprofloxacin were included. Pharmacokinetics were described using non-linear mixed-effect modelling and validated with an external dataset. Monte Carlo simulations investigated dosing regimens to achieve a target AUC0-24 h/MIC ratio ≥ 125. RESULTS: A total of 189 children (492 concentrations) were included. A two-compartment model with first-order absorption and elimination best described the data. An allometric model was used to describe bodyweight (BW) influence, and effects of estimated glomerular filtration rate (eGFR) and age were significant on ciprofloxacin clearance. CONCLUSION: The recommended IV dose of 10 mg/kg q8h, not exceeding 400 mg q8h, would achieve AUC0-24 h to successfully treat bacteria with MICs ≤ 0.25 (e.g. Salmonella, Escherichia coli, Proteus, Haemophilus, Enterobacter, and Klebsiella). A dose increase to 600 mg q8h in children > 40 kg and to 15 mg/kg q8h (max 400 mg q8h, max 600 mg q8h if augmented renal clearance, i.e., eGFR > 200 mL/min/1.73 m2) in children < 40 kg would be needed for the strains with highest MIC (16% of Pseudomonas aeruginosa and 47% of Staphylococcus aureus). The oral recommended dose of 20 mg/kg q12h (not exceeding 750 mg) would cover bacteria with MICs ≤ 0.125 but may be insufficient for bacteria with higher MIC and a dose increase according bodyweight and eGFR would be needed. These doses should be prospectively confirmed, and a therapeutic drug monitoring could be used to refine them individually.

The Influence of Ciprofloxacin-Dexamethasone Ear Drops on Perforation Closure Rates After Endoscopic Tympanoplasty.

OBJECTIVE: Topical ciprofloxacin and dexamethasone have both been shown to disrupt healing of tympanic membrane perforations in animal models. There have been no clinical studies evaluating the effect of ciprofloxacin-dexamethasone (CD) ear drops on success of tympanoplasty. We compare perforation closure rates in pediatric endoscopic tympanoplasty with and without use of postoperative CD. STUDY DESIGN: Retrospective comparative cohort study. SETTING: Tertiary referral centre. PATIENTS: One hundred sixty-two totally endoscopic tympanoplasties with porcine-derived collagen graft in children, mean age 12.0 years (range 2.3-17.9 yrs). INTERVENTION: Prescription of CD versus no ear drops in the immediate postoperative period. MAIN OUTCOME MEASURE: Perforation closure rate 2 months after totally endoscopic tympanoplasty. RESULTS: Postoperative CD was given to 65 (40%) ears and no drops given to the remainder. Overall, successful closure of tympanic membrane perforation was achieved in 140 (86%) of ears. The closure rate was not significantly different in those ears given CD postoperatively than those not given CD (54/65 [83%] vs 86/97 [89%], Fisher's p = 0.35). Multiple logistical regression revealed no confounding effect of other variables on outcome including age, revision surgery, graft position, or type of postoperative packing material. CONCLUSIONS: Our results reveal no harm or benefit with prescription of drops containing ciprofloxacin and dexamethasone on success of perforation closure after tympanoplasty. Allocation to treatment in this retrospective study was nonrandomized and was predominantly based on a change in practice. No other variables are known to have influenced this finding but a randomized prospective study could be justified for more reliable evidence.

Distinct contribution of hyperbaric oxygen therapy to human neutrophil function and antibiotic efficacy against Staphylococcus aureus.

Staphylococcus aureus (SA) causes superficial and severe endovascular infections. The present in vitro study investigates the anti-SA mechanisms of hyperbaric oxygen therapy (HBOT) on direct bacterial killing, antibiotic potentiation, and polymorphonuclear leukocyte (PMN) enhancement. SA was exposed to isolated human PMNs, tobramycin, ciprofloxacin, or benzylpenicillin. HBOT was used as one 90-min session. Bacterial survival was evaluated after 4 h by quantitative bacteriology. PMN functionality as reactive oxygen species (ROS) production was measured by means of dihydrorhodamine 123 analysis. We showed that HBOT exhibits significant direct anti-SA effects. HBOT increased the anti-SA effects of PMNs by 18% after PMA stimulation (p = 0.0004) and by 15% in response to SA (p = 0.36). HBOT showed an additive effect as growth reductions of 26% to sub-MICs of tobramycin (p = 0.0057), 44% to sub-MICs of ciprofloxacin (p = 0.0001), and 26% to sub-MICs of penicillin (p = 0.038). The present in vitro study provides evidence that HBOT has differential mechanisms mediating its anti-SA effects. Our observation supports the clinical possibility for adjunctive HBOT to augment the host immune response and optimize the efficacy of antibiotic treatments.