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.

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.

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.

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.

Therapeutic concentration of ciprofloxacin and transfer across the human term placenta.

BACKGROUND: Pregnant women have an increased risk of infections, and early and decisive treatment is preferred to prevent complications. Although ciprofloxacin is very commonly used, safety aspects of maternal treatment during pregnancy are limited, and avoidance of its use during late pregnancy is recommended. OBJECTIVE: The aim is to estimate maternal-to-fetal transfer clearance of ciprofloxacin at a therapeutic concentration and to determine fetal exposure to maternally administered ciprofloxacin. STUDY DESIGN: Transplacental pharmacokinetics were determined with an ex vivo placental model, which is a reliable experimental model for estimating fetal drug exposure. Human placentas from uncomplicated term pregnancies were collected after delivery and a suitable cotyledon was cannulated. Ciprofloxacin was added at a therapeutic concentration (1.6 µg/mL) to the maternal compartment, and antipyrine was included as a reference drug (10.0 µg/mL). Samples were collected from the maternal and fetal compartment at 12 time points (-2 to 180 minutes), and the integrity and metabolic parameters were measured consecutively. Drug concentrations were determined using ultra-performance liquid chromatography-tandem mass spectrometry. RESULTS: A total of 5 human placentas from healthy term pregnancies were collected after delivery and cannulated with success. Ciprofloxacin crossed the placenta; its mean concentration in the fetal compartment was 0.3 µg/mL, accounting for 22% (0.29/1.30; range, 15%-31%) of the maternal concentration after 3 hours. The fetal/maternal ciprofloxacin concentration ratio increased gradually over time and reached 0.53. The transfer clearance for ciprofloxacin was 0.28 mL/min (range, 0.21-0.41 mL/min) during the first hour and 0.21 mL/min (range, 0.14-0.26 mL/min) during the following 2 hours. After end perfusion, the mean tissue concentration and proportion of ciprofloxacin were 0.7 µg/g and 11% (14/130; range, 7%-14%), respectively. CONCLUSION: Ciprofloxacin crossed the placenta at a slow, constant rate, indicating moderate fetal exposure. This study verifies an accumulation of ciprofloxacin in the placenta that may lengthen the duration of fetal exposure. These results are an essential element of fetal risk assessment, but further studies are needed to estimate fetal safety.

Development of Inhalable Nanostructured Lipid Carriers for Ciprofloxacin for Noncystic Fibrosis Bronchiectasis Treatment.

PURPOSE: Ciprofloxacin (CIP) has poor lung targeting after oral inhalation. This study developed optimized inhalable nanostructured lipid carriers (NLCs) for CIP to enhance deposition and accumulation in deeper parts of the lungs for treatment of noncystic fibrosis bronchiectasis (NCFB). METHODS: NLC formulations based on stearic acid and oleic acid were successfully prepared by hot homogenization and in vitro-characterized. CIP-NLCs were formulated into nanocomposite micro particles (NCMPs) for administration in dry powder inhalation (DPI) formulations by spray-drying (SD) using different ratios of chitosan (CH) as a carrier. DPI formulations were evaluated for drug content and in vitro deposition, and their mass median aerodynamic diameter (MMAD), fine particle fraction (FPF), fine particle dose (FPD), and emitted dose (ED) were determined. RESULTS: The CIP-NLCs were in the nanometric size range (102.3 ± 4.6 nm), had a low polydispersity index (0.267 ± 0.12), and efficient CIP encapsulation (98.75% ± 0.048%), in addition to a spherical and smooth shape with superior antibacterial activity. The in vitro drug release profile of CIP from CIP-NLCs showed 80% release in 10 h. SD of CIP-NLCs with different ratios of CH generated NCMPs with good yield (>65%). The NCMPs had a corrugated surface, but with increasing lipid:CH ratios, more spherical, smooth, and homogenous NCMPs were obtained. In addition, there was a significant change in the FPF with increasing lipid:CH ratios (P ˂ 0.05). NCMP-1 (lipid:CH = 1:0.5) had the highest FPD (45.0 µg) and FPF (49.2%), while NCMP-3 (lipid:CH = 1:1.5) had the lowest FPF (37.4%). All NCMP powders had an MMAD in the optimum size range of 3.9-5.1 µm. CONCLUSION: Novel inhalable CIP NCMP powders are a potential new approach to improved target ability and delivery of CIP for NCFB treatment.

Efficacy of Honey-based Ophthalmic Formulation in Patients with Corneal Ulcer: A Randomized Clinical Trial.

AIM: The aim of this study was to evaluate the efficacy of honey-based ophthalmic drop in patients with foreign body induced corneal ulcer. BACKGROUND: Honey is traditionally used for skin, mucosal and corneal ulcers. Its use is well studied in human skin and mucosal ulcers and animal model of corneal ulcer with promising effects. METHODS: In this randomized clinical trial, 50 patients with foreign body induced corneal ulcer were allocated to receive 70% sterile honey-based ophthalmic formulation or 0.3% ophthalmic ciprofloxacin, as the standard treatment every 6 hours. All the patients were examined for the size of corneal epithelial defect, corneal infiltration and depth and followed on a daily basis until complete healing. Duration for complete healing was considered as the outcome measure. Smear, culture, antibiogram and minimum inhibition concentration (MIC) tests were performed for honey and ciprofloxacin in all patients. RESULTS: The average durations of complete healing of corneal epithelial defect in the honey and ciprofloxacin groups were 3.88 ± 3.44 vs. 6.32 ± 3.69days, respectively (p=0.020). No significant difference was observed between two groups regarding an average duration of healing of corneal infiltration (8.12 ±1.94 days vs. 8.64±2.15 days, p=0.375). MIC of honey for pseudomonas aeruginosa was 60%w/w, for E.Coli 40% w/w, and for staphylococcus aureus 30% w/w. CONCLUSION: Honey based ophthalmic drop can acceleratethe corneal epithelial defect healing in patients with foreign body induced corneal ulcer, compared to ophthalmic ciprofloxacin as a standard treatment. The study was registered in Iranian registry of clinical trial center (IRCT) with registration number IRCT2015020120892N1.

Randomized Trial of Ciprofloxacin Doxycycline and Hydroxychloroquine Versus Budesonide in Active Crohn's Disease.

BACKGROUND: Increased mucosa-associated E. coli are present in Crohn's disease, but their role in pathogenesis is uncertain. AIMS: To assess efficacy and safety of an antibiotic/hydroxychloroquine combination effective against E. coli inside macrophages. METHODS: Adults with moderately active disease (CDAI > 220-450 plus C reactive protein ≥ 5 mg/l and/or fecal calprotectin > 250 µg/g) were randomized to receive (open-label) oral budesonide (Entocort CR 9 mg/day 8 weeks, 6 mg/day 2 weeks, 3 mg/day 2 weeks) or oral ciprofloxacin 500 mg bd, doxycycline 100 mg bd, hydroxychloroquine 200 mg tds for 4 weeks, followed by doxycycline 100 mg bd and hydroxychloroquine 200 mg tds for 20 weeks. Primary endpoints were remission (CDAI ≤ 150) at 10 weeks, remission maintained to 24 weeks, and remission maintained to 52 weeks. Patients not responding (CDAI fall by > 70) by 10 weeks were invited to crossover onto the alternative therapy. RESULTS: Fifty-nine patients were recruited across 8 sites. Including crossover, 39 patients received antibiotics/hydroxychloroquine and 39 received budesonide. At 10 weeks, 24 weeks, and 52 weeks on initial therapy, only 2/27, 2/27, and 1/27 were in remission on antibiotics/hydroxychloroquine compared with 8/32, 1/32, and 1/32 on budesonide (P = 0.092 at 10 weeks). Withdrawals by 10 weeks due to adverse events were seen in 15 receiving antibiotics/hydroxychloroquine and 6 budesonide. Results including crossover were more promising with 9/24 patients receiving antibiotics/hydroxychloroquine per protocol in remission by 24 weeks. No correlation was seen between response to antibiotics/hydroxychloroquine and ASCA/OmpC antibody status or disease location. CONCLUSION: Overall results with this antibiotic/hydroxychloroquine combination were unimpressive, but long-term remission is seen in some patients and justifies further study.

Kidney stone formation and the gut microbiome are altered by antibiotics in genetic hypercalciuric stone-forming rats.

Antibiotics can alter the gut microbiome (GMB), which may be associated with stone disease. We sought to determine the effect that antibiotics have on the GMB, urine ion excretion and stone formation in genetic hypercalciuric stone-forming (GHS) rats. 116th generation GHS rats were fed a fixed amount of a normal calcium (1.2%) and phosphate (0.65%) diet, and divided into three groups (n = 10): control (CTL) diet, or supplemented with ciprofloxacin (Cipro, 5 mg/day) or Bactrim (250 mg/day). Urine and fecal pellets were collected over 6, 12 and 18 weeks. Fecal DNA was amplified across the 16S rRNA V4 region. At 18 weeks, kidney stone formation was visualized by Faxitron and blindly assessed by three investigators. After 18 weeks, urine calcium and oxalate decreased with Bactrim compared to CTL and Cipro. Urine pH increased with Bactrim compared to CTL and Cipro. Urine citrate increased with Cipro compared to CTL and decreased by half with Bactrim. Calcification increased with Bactrim compared to CTL and Cipro. Increased microbial diversity correlated with decreased urinary oxalate in all animals (R = - 0.46, p = 0.006). A potential microbial network emerged as significantly associated with shifts in urinary pH. Bactrim and Cipro differentially altered the GMB of GHS rats. The Bactrim group experienced a decrease in urine calcium, increased CaP supersaturation and increased calcification. The GMB is likely a contributing factor to changes in urine chemistry, supersaturation and stone risk. Further investigation is required to fully understand the association between antibiotics, the GMB and kidney stone formation.

Influenza virus infection augments susceptibility to respiratory Yersinia pestis exposure and impacts the efficacy of antiplague antibiotic treatments.

Various respiratory viral infections in general and seasonal influenza in particular may increase the susceptibility to bacterial infections. Plague caused by Yersinia pestis endangers large populations during outbreaks or bioterrorism attacks. Recommended antibiotic countermeasures include well-established protocols based on animal studies and corroborated by effective treatment of human cases. Until now, prior exposure to viral respiratory infections was not taken into consideration when selecting the appropriate treatment for plague. Here, we show that as late as 25 days after exposure to influenza virus, convalescent mice still exhibited an increased susceptibility to sublethal doses of Y. pestis, presented with aberrant cytokine expression, and impaired neutrophil infiltration in the lungs. Increased levels of M2 alveolar macrophages and type II epithelial cells, as well as induction in metalloproteases expression and collagen and laminin degradation, suggested that the previous viral infection was under resolution, correlating with enhanced susceptibility to plague. Surprisingly, postexposure prophylaxis treatment with the recommended drugs revealed that ciprofloxacin was superior to doxycycline in mice recovering from influenza infection. These results suggest that after an influenza infection, the consequences, such as impaired immunity and lung tissue remodeling and damage, should be considered when treating subsequent Y. pestis exposure.

Synthesis and characterization of novel tamarind gum and rice bran oil-based emulgels for the ocular delivery of antibiotics.

In this study, we developed tamarind gum (TG) and rice bran oil (RBO)-based emulgels. The control formulation (TR0), did not contain RBO. The emulgels were named as TR1, TR2, TR3, and TR4, which contained 5% (w/w), 10% (w/w), 15% (w/w), and 20% (w/w/) of RBO, respectively. The microscopic studies showed that the emulgels were biphasic in nature. FTIR spectroscopy revealed the reduction in the hydrogen bonding with an increase in the RBO content. Impedance profiles suggested that the resistive component of the emulgels was increased as the RBO content was increased. The thermal analysis suggested that the addition of RBO reduced the water holding capacity of the emulgels. Stress relaxation studies revealed that the fluidic component was considerably higher in TG/RBO-based emulgels as compared to TR0. In vitro release study of the model drug (ciprofloxacin HCl; a hydrochloride salt of ciprofloxacin) suggested a significantly lower release from the emulgel matrices (TR1-TR4) in comparison to TR0. However, ex vivo corneal permeation of the drug increased with an increase in the RBO content. Since the emulgels were able to improve the corneal permeation of the model drug, the emulgels can be explored to deliver drugs to the internal structures of the eye.

Randomized Controlled Trial of Balloon Dilation in Treatment of Subglottic Stenosis With a Rabbit Model.

OBJECTIVES: Identify the effects of balloon dilation duration and topical ciprofloxacin-dexamethasone application in treatment of subglottic stenosis. STUDY DESIGN: Randomized controlled trial. SETTING: Animal research facility. SUBJECTS AND METHODS: Forty-four rabbits underwent subglottic injury in an Institutional Animal Care and Use Committee-approved study. One week after injury, the subglottis of each rabbit was measured and treated with endoscopic balloon dilation for 2 rounds of short duration (SBD; 3 seconds), long duration (LBD; 30 seconds), or LBD with topical ciprofloxacin-dexamethasone application (LBD+C). The subglottis of each rabbit was remeasured at the study endpoint: 1 month postdilation or following development of life-threatening respiratory distress. RESULTS: Of 44 rabbits, 35 (80%) survived to endoscopic balloon dilation, with 21 rabbits developing a grade III Cotton-Myer stenosis. Prior to dilation, there was no difference in stenosis rates among groups (all subjects, P = .99; grade III stenosis only, P = .52). Among grade III subjects, improvement in stenosis after dilation was -1% (SD, 21%) for SBD, 27% (SD, 38%) for LBD, and 58% (SD, 29%) for LBD+C (P = .01). Early euthanasia/death rates among grade III subjects were 85% for SBD, 63% for LBD, and 17% for LBD+C (P = .03). Time to early euthanasia/death was 5.0 days for the SBD group and 8.4 days for the LBD group (P = .04). CONCLUSION: SBD was inferior to LBD or LBD+C in multiple metrics. LBD+C offered significant improvements in stenosis size and mortality over the SBD group and had the lowest rate of early mortality. Further research is needed to identify optimal balloon dilation treatment duration.

Carbapenems versus ciprofloxacin/metronidazole for decreasing complications and hospital stay following complicated acute appendicitis surgery: A prospective cohort in an Ecuadorian population.

BACKGROUND: After appendectomy due to complicated acute appendicitis (CAA), there are some alternatives as antibiotic scheme: ciprofloxacin/metronidazole; as well as monoscheme based on carbapenems: ertapenem, meropenem, and imipenem. AIM: This study aims to prove the efficacy of carbapenems versus ciprofloxacin/metronidazole in CAA post-operative management in terms of preventing complications during post-operative period and decreasing hospital stay. MATERIALS AND METHODS: This was an observational, analytical, longitudinal, and prospective cohort study (March 2014-November 2016). Patients were classified into two groups, according to the prescribed antibiotic scheme: some carbapenems or ciprofloxacin/metronidazole. RESULTS: Ninety-eight patients were enrolled. There was an requirement for antibiotic therapy rotation only in the ciprofloxacin/metronidazole (7/49, 14.3%; p = 0.004). Carbapenems reached a mean hospital stay of 4.45 days, in contrast with ciprofloxacin/metronidazole, 8.29 days (p = 0.020). In post-surgical follow-up, there were more cases of curative resolution in the group in the carbapenems group (35/49 vs. 15/49 p < 0.001) as well as a greater number of cases with some late infection in the ciprofloxacin/metronidazole group (1/49 vs. 10/49, p = 0.010). CONCLUSION: In the post-operative management of CAA, carbapenems represent an important indication to be considered as first-line antibiotic therapy.

ANTECEDENTES: Tras la cirugía por apendicitis aguda complicada existen varias alternativas de esquema antibiótico, entre las que destacan ciprofloxacino/metronidazol, o bien monoterapia con algún carbapenémico, como ertapenem, meropenem e imipenem. OBJETIVO: Determinar la eficacia de los carbapenémicos en comparación con ciprofloxacino/metronidazol en el manejo posquirúrgico de la apendicitis aguda complicada, en términos de prevención de complicaciones durante el ­posoperatorio y de reducción de la estancia hospitalaria. MÉTODO: Estudio observacional, analítico, longitudinal, prospectivo y de cohorte, de marzo de 2014 a noviembre de 2016. Los pacientes fueron clasificados en dos grupos según el esquema antibiótico prescrito: un carbapenémico o ciprofloxacino/metronidazol. RESULTADOS: Se seleccionaron 98 pacientes. Solo hubo necesidad de rotación de antibiótico en el grupo de ciprofloxacino/metronidazol (7 de 49, 14.3%; p = 0.004). En el grupo de carbapenémico, la media de estancia hospitalaria fue de 4.45 días, y en el grupo de ciprofloxacino/metronidazol fue de 8.29 días (p = 0.020). En el seguimiento posquirúrgico hubo más casos de resolución curativa en el grupo de carbapenémico (35 de 49 vs. 15 de 49; p < 0.001), así como un mayor número de casos con alguna infección tardía en el grupo de ciprofloxacino/metronidazol (1 de 49 vs. 10 de 49; p < 0.001). CONCLUSIÓN: En el manejo posquirúrgico de la apendicitis aguda complicada, los carbapenémicos representan una importante indicación que debe considerarse como antibioticoterapia de primera línea.

Efficacy and Therapeutic Drug Monitoring of Continuous Beta-Lactam Infusion for Osteoarticular Infections Caused by Fluoroquinolone-Resistant Pseudomonas aeruginosa: A Prospective Cohort Study.

BACKGROUND AND OBJECTIVES: Osteoarticular infections (OIs) caused by fluoroquinolone-resistant Pseudomonas aeruginosa, including multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains, have poor outcomes. We evaluated the outcomes of an optimized strategy of continuous beta-lactam infusion (BL-CI) guided by therapeutic drug monitoring (TDM) for OIs caused by fluoroquinolone-resistant P. aeruginosa. METHODS: A prospective observational study of patients with P. aeruginosa OIs in a hospital-based BL-CI program (2016-2018) was carried out. TDM targeting free BL concentrations in plasma (fCss) of at least 3-4 × MIC was performed. We compared failure rates between patients with OIs caused by fluoroquinolone-resistant strains who were treated with BL-CI, with or without colistin, and patients with OIs caused by fluoroquinolone-susceptible strains who were treated with ciprofloxacin. RESULTS: Fifty-two patients were included in the study, 19 (36.5%) of whom had OIs caused by fluoroquinolone-resistant P. aeruginosa (13 (68.4%) MDR/XDR strains; 11 (57.9%) device-related infections). The median duration of BL-CI was 36 days; ten patients (52.6%) received BL-colistin combinations. Eighty-two samples were utilized in the TDM, and most patients were found to have a median fCss of 3-10 × MIC; 17 dose adjustments were performed and eight patients needed dose decreases, five of which were due to chronic kidney disease or acute kidney injury (AKI). BL-CI was well tolerated, with the most frequent adverse event being AKI. Failure occurred to 4 patients (21.1%), which was similar to the failure rate of patients with OIs caused by fluoroquinolone-susceptible P. aeruginosa treated with ciprofloxacin (5/30 [16.7%]) (p = 0.699). TDM was also used in the initial BL treatment of patients with OIs caused by susceptible strains before those patients were switched to treatment with ciprofloxacin alone (33 patients, 110 samples, 19 dose adjustments). CONCLUSIONS: BL-CI used with/without colistin and supported by TDM may be an alternative and effective treatment option for OIs caused by fluoroquinolone-resistant P. aeruginosa, where limited available therapeutic options exist, especially in the setting of multidrug resistance. Future research should elucidate whether this strategy can produce outcomes similar to those of patients treated for OIs caused by fluoroquinolone-susceptible strains.

Current routines for antibiotic prophylaxis prior to transrectal prostate biopsy: a national survey to all urology clinics in Sweden.

Background: The risk of infection after transrectal ultrasound (TRUS)-guided prostate biopsies is increasing. The aim of the study was to assess the use of antibiotic prophylaxis for prostate biopsy in Sweden. Methods: All public and private urology clinics reporting to the National Prostate Cancer Register of Sweden received a survey on TRUS-biopsy prophylaxis. Results: Of the 84 clinics surveyed, 76 replied (90%). If no risk factors for infection were present, a single dose of ciprofloxacin 750 mg was used by 50 clinics (66%). Multiple doses of ciprofloxacin 500 or 750 mg (n=14; 18%) or a single dose of trimethoprim-sulfamethoxazole 160/800 mg (n=7; 9%) were other common prophylaxes. Most clinics gave the prophylaxes immediately before the biopsy (n=41; 54%). Urine dipstick was used by 30 clinics (39%) and rectal enema by six (8%). In patients with high risk of infection, the survey mirrors a large variety of regiments used. Conclusions: The preference to use a single dose of ciprofloxacin 750 mg is in accordance with the Swedish national guidelines for patients with a low risk of infection. Better compliance to the guideline recommendation to use a urine dipstick would probably increase the number of patients classified as having an increased risk of infection. Being classified as a high-risk patient should lead to an extended duration of antibiotic prophylaxis, however, the variety of regimens used in the high-risk group reflects an inability to treat these patients in a standardized fashion and also highlights a need for more clear-cut guidelines. Pre-biopsy identification of high-risk patients is an important issue to tackle for the urologic clinics in order to reduce the number of infections.

TLR-2 neutralization potentiates microglial M1 to M2 switching by the combinatorial treatment of ciprofloxacin and dexamethasone during S. aureus infection.

Microglial inflammation plays a pivotal role in the pathogenesis of S. aureus induced brain abscesses. The objective of this study was to regulate microglial activation by the combinatorial treatment of ciprofloxacin either with dexamethasone or celecoxib via targeting M1 and M2 polarization. The antibiotic-immunomodulator combinations were applied either by opening both TLR-2 and GR or neutralizing each of them. Our results confirmed that dexamethasone along with ciprofloxacin attenuated bacterial burden along with ROS production more efficiently than celecoxib combination during TLR-2 neutralization. FACS data indicated microglial M1 to M2 switching that was responsible for the better resolution of microglial inflammation.

[Complex treatment of patients with pyo-necrotic complications of the neuropathic form of diabetic foot syndrome]. / Kompleksnoe lechenie bol'nykh s gnoino-nekroticheskimi oslozhneniyami pri neiropaticheskoi forme sindroma diabeticheskoi stopy.

OBJECTIVE: Of study is improving the results of treatment of patients with pyo-necrotic complications of diabetic foot syndrome by including the method of negative pressure wound treatment in the complex treatment program in combination with using of the combined antibacterial drug Cifran ST and immunocorrective therapy. MATERIAL AND METHODS: The results of examination and treatment of 184 patients with pyo-necrotic complications of the neuropathic form of diabetic foot syndrome were analyzed. According to choice of treatment methods in the postoperative period all patients were divided into two groups. In 95 patients (group I), iodine-containing ointments based on polyethylene glycol were used for local treatment of purulent foot wounds and standard systemic antibacterial therapy was performed. In 89 patients (group II), negative pressure wound treatment (NPWT) was used to treat wounds in the postoperative period. In addition to standard parenteral antimicrobial therapy, these patients also received an oral combined antibacterial drug Cifran ST and immunocorrective cytokine therapy (Leukinferon). The analysis of the dynamics of the wound process was carried out based on the clinical picture and the results of cytological, bacteriological and immunological studies of the wound exudate. RESULTS: The presented strategy of complex treatment of pyo-necrotic complications of the neuropathic form of diabetic foot syndrome allowed group II patients to significantly reduce the degree of microbial contamination of wounds, to achieve a faster regression of the content of proinflammatory and inflammatory cytokines in the wound exudate, as well as to reduce the time of wound cleansing and the transition of the pyo-necrotic process to the reparative stage in comparison with group I patients. This allowed group II patients to reduce the time of plastic closure of the wound from 24.3±0.5 to 15.6±1.7 days, to avoid generalization of infection, death and high level amputation of the limb. At the same time, 11.6% of patients in group I had high level limb amputation due to generalization of infection. The mortality rate in group I was 5.3%. CONCLUSIONS: Adding of vacuum therapy of wounds, systemic antimicrobial therapy using the combined antibacterial drug Cifran ST and immunocorrective cytokine therapy in the complex treatment program for patients with neuropathic form of diabetic foot syndrome after radical surgical treatment of the pyo-necrotic lesion allows reducing the time of wound cleansing and the transition of the pyo-necrotic process to the reparative stage. On the other hand, this makes it possible for this category of patients to perform plastic closure of the wound at an earlier date, avoid generalization of infection and high level amputation of the limb.