Formulations of poly(vinyl alcohol) functionalized silk fibroin nanoparticles for the oral delivery of zwitterionic ciprofloxacin.

Fibroin nanoparticles (FNP) have been employed in numerous biomedical applications. However, limited research has focused on the oral delivery of FNP and in-depth molecular interactions between the encapsulated drug and FNP. Therefore, this work developed the FNP, functionalized with poly(vinyl alcohol) (PVA), to orally deliver the zwitterionic ciprofloxacin, focused on the molecular interactions. The particles were formulated using both desolvation (the drug precipitated during the particles formulation) and adsorption (the drug adsorbed on the particles surfaces) methods. The optimal formula possessed a size of ~630 nm with narrow size distribution (measured by DLS method), spherical shape (determined by SEM), and moderate drug loading (confirmed by FT-IR, XRD, and DSC techniques) of ~50% for the desolvation method and ~43% for the adsorption method. More than 80% of the drug molecules resided on the particle surfaces, mainly via electrostatic forces with fibroin. The drug was physically adsorbed onto FNP, which followed Langmuir model and pseudo second-order kinetics. In the in-vitro simulated gastric condition at pH 1.2, the ciprofloxacin bound strongly with FNP via electrostatic forces, thus hindering the drug release (< 40%). Contrastingly, in the simulated intestinal condition at pH 6.8, the particles could control the drug release rates dependent on the PVA amount, with up to ~100% drug release. Lastly, the particles possessed adequate antibacterial activities on Bacillus subtilis, Escherichia coli, and Salmonella enterica, with MIC of 128, 8, and 32 µg/mL, respectively. In summary, the FNP and PVA functionalized FNP could be a potential oral delivery system for zwitterionic drugs.

An open-label, randomized, non-inferiority trial of the efficacy and safety of ciprofloxacin versus an aminoglycoside + ciprofloxacin in the treatment of bubonic plague (IMASOY): study protocol for a randomized control trial-an update to the published protocol.

This article reports an update to the protocol of the IMASOY trial, which was prospectively registered on clinicaltrials.gov (NCT04110340) in October 2019.

Quahogging in a Marine Habitat: An Extremely Rare Source of an Organism to Cause Endocarditis.

A 66-year-old man with a history of apical variant hypertrophic cardiomyopathy, heart failure with preserved ejection fraction (HFpEF), severe pulmonary hypertension, and prior Group B streptococcal mitral valve endocarditis four months before, presented with generalized body shakes and urinary incontinence. Computed tomography angiography revealed an acute left M1 occlusion. The patient underwent mechanical thrombectomy. Within 24 hours of presentation, he developed hypotension, tachycardia, and fever. Infectious workup revealed a leukocytosis. One out of two sets of blood cultures revealed bacteremia with Shewanella algae. A transthoracic echocardiogram revealed a large mitral valve vegetation with multiple mobile components portending a high thromboembolic risk, as evidenced by his acute presentation with multiple embolic infarcts. He was diagnosed with infectious endocarditis caused by Shewanella algae, a rare marine environment pathogen. He was treated with ciprofloxacin 750 mg twice daily orally and meropenem 2 g every eight hours intravenously with an initial decrease in the mitral valve vegetation size. He was discharged on ceftriaxone 2g and ciprofloxacin 750mg every 12 hours for a total of six weeks from his first negative blood cultures. He was monitored through transthoracic echocardiography as he continued medical management with levofloxacin 750 mg daily. Six months after his discharge from the hospital he developed worsening heart failure and elected to pursue comfort measures only.

Dry powder inhalation containing muco-inert ciprofloxacin and colistin co-loaded liposomes for pulmonary P. Aeruginosa biofilm eradication.

Pseudomonas aeruginosa (PA), a predominant pathogen in lung infections, poses significant challenges due to its biofilm formation, which is the primary cause of chronic and recalcitrant pulmonary infections. Bacteria within these biofilms exhibit heightened resistance to antibiotics compared to their planktonic counterparts, and their secreted toxins exacerbate lung infections. Diverging from traditional antibacterial therapy for biofilm eradication, this study introduces a novel dry powder inhalation containing muco-inert ciprofloxacin and colistin co-encapsulated liposomes (Cipro-Col-Lips) prepared using ultrasonic spray freeze drying (USFD) technique. This USFD dry powder is designed to efficiently deliver muco-inert Cipro-Col-Lips to the lungs. Once deposited, the liposomes rapidly diffuse into the airway mucus, reaching the biofilm sites. The muco-inert Cipro-Col-Lips neutralize the biofilm-secreted toxins and simultaneously trigger the release of their therapeutic payload, exerting a synergistic antibiofilm effect. Our results demonstrated that the optimal USFD liposomal dry powder formulation exhibited satisfactory in vitro aerosol performance in terms of fine particle fraction (FPF) of 44.44 ± 0.78 %, mass median aerodynamic diameter (MMAD) of 4.27 ± 0.21 µm, and emitted dose (ED) of 99.31 ± 3.31 %. The muco-inert Cipro-Col-Lips effectively penetrate the airway mucus and accumulate at the biofilm site, neutralizing toxins and safeguarding lung cells. The triggered release of ciprofloxacin and colistin works synergistically to reduce the biofilm's antibiotic resistance, impede the development of antibiotic resistance, and eliminate 99.99 % of biofilm-embedded bacteria, including persister bacteria. Using a PA-beads induced biofilm-associated lung infection mouse model, the in vivo efficacy of this liposomal dry powder aerosol was tested, and the results demonstrated that this liposomal dry powder aerosol achieved a 99.7 % reduction in bacterial colonization, and significantly mitigated inflammation and pulmonary fibrosis. The USFD dry powder inhalation containing muco-inert Cipro-Col-Lips emerges as a promising therapeutic strategy for treating PA biofilm-associated lung infections.

Efficacy of empirical Ciprofloxacin or Cefixime plus Metronidazole therapy for the treatment of liver abscess: a randomized control clinical trial.

Liver abscess is a potentially life-threatening medical emergency. Prompt empirical antimicrobial with or without percutaneous aspiration or drainage is therapeutic. The rational for using empirical intravenous broad-spectrum antimicrobials upfront instead of oral Fluoroquinolone or Cephalosporin is contentious. In this double blind randomized control clinical trial 69 participants received Ciprofloxacin (500 mg q 12 hourly) and 71 participants received Cefixime (200 mg q 12 hourly) orally for 2 weeks. Both the group received oral Metronidazole (800 mg q 8 hourly) for 2 weeks and percutaneous drainage or aspiration of the abscess was done as per indication and followed-up for 8 weeks. Out of 140 participants, 89.3% (N = 125) achieved clinical cure, 59 (85.5%) in Ciprofloxacin group and 66 (93%) in Cefixime group (p = 0.154). Mean duration of antimicrobial therapy was 16.2 ± 4.3 days, 15.1 ± 4.5 days in Ciprofloxacin group and 16.0 ± 4.2 days in Cefixime group (p = 0.223). Total 15 (10.7%) participants had treatment failure, 10 (14.5%) in Ciprofloxacin group and 5 (7.0%) in Cefixime group (p = 0.154). The most common reason for treatment failure was need of prolong (> 4 weeks) antimicrobial therapy due to persistent hepatic collection requiring drainage, which was significantly (p = 0.036) higher in Ciprofloxacin (14.5%, N = 10) group, compared to the Cefixime (4.2%, N = 3) group. In conclusion, both, the Ciprofloxacin or Cefixime plus Metronidazole for duration of 2-3 weeks were efficacious as empirical oral antimicrobial regimen along with prompt percutaneous drainage or aspiration for the treatment of uncomplicated liver abscess with similar efficacy. Oral Cefixime was better than Ciprofloxacin in term of lesser chance of treatment failure due to persistent collection which is required to be investigated further in larger clinical trial.Trial registration: clinicaltrials.gov PRS ID: NCT03969758, 31/05/2019.

Comparison of ciprofloxacin versus fosfomycin versus fosfomycin plus trimethoprim/sulfamethoxazole for preventing infections after transrectal prostate biopsy.

BACKGROUND: To evaluate antibiotic prophylaxis in transrectal prostate biopsies due to the recommendation of the European Medicines Agency (EMA): We describe our single center experience switching from ciprofloxacin to fosfomycin trometamol (FMT) alone and to an augmented prophylaxis combining fosfomycin and trimethoprim/sulfamethoxazole (TMP/SMX). METHODS: Between 01/2019 and 12/2020 we compared three different regimes. The primary endpoint was the clinical diagnosis of an infection within 4 weeks after biopsy. We enrolled 822 men, 398 (48%) of whom received ciprofloxacin (group-C), 136 (16.5%) received FMT (group-F) and 288 (35%) received the combination of TMP/SMX and FMT (group-BF). RESULTS: Baseline characteristics were similar between groups. In total 37/398 (5%) postinterventional infections were detected, of which 13/398 (3%) vs 18/136 (13.2%) vs 6/288 (2.1%) were detected in group-C, group-F and group-BF respectively. The relative risk of infectious complication was 1.3 (CI 0.7-2.6) for group-C vs. group-BF and 2.8 (CI 1.4-5.7) for group-F vs. group-BF respectively. CONCLUSION: The replacement of ciprofloxacin by fosfomycin alone resulted in a significant increase of postinterventional infections, while the combination of FMT and TMP/SMX had a comparable infection rate to FQ without apparent adverse events. Therefore, this combined regimen of FMT and TMP/SMX is recommended.

Ceftazidime Poloxamer Gel: Expanding the Therapeutic Armamentarium for Ciprofloxacin-Resistant Pseudomonas Mastoid Cavity Otorrhea.

OBJECTIVE: To present and evaluate the treatment of ciprofloxacin-resistant Pseudomonas mastoid cavity otorrhea with a ceftazidime thermosensitive poloxamer gel. STUDY DESIGN: A retrospective clinical capsule report. PATIENTS: Three patients diagnosed with ciprofloxacin-resistant Pseudomonas otorrhea in the setting of a previous canal-wall-down mastoidectomy between March 2019 and June 2023 visiting our tertiary care institution were retrospectively reviewed. INTERVENTION: Application of a 2% ceftazidime thermosensitive poloxamer gel to mastoid cavity. MAIN OUTCOME MEASURES: No evidence of disease during microscopic inspection of the ear within a month of initial treatment or bacterial eradication on subsequent culture. RESULTS: Two patients had complete resolution of symptoms and achieved a safe and dry ear after topical application of the hydrogel. The second patient had pseudomonal eradication on culture, but persistent otorrhea due to other multidrug-resistant bacteria and an anatomically unfavorable mastoid cavity, which ultimately resolved after revision surgery. CONCLUSIONS: This small case series suggests that topical treatment of mastoid cavity otorrhea with a 2% ceftazidime poloxomer gel is a potential therapeutic avenue in patients with ciprofloxacin-resistant Pseudomonas .

Holistic Study Design Following Quality by Design Approach for Fabrication of Hybrid Polymeric Nanoparticulate Based Dry Powders as Carriers for Ciprofloxacin.

Resistance to antibiotics such as Ciprofloxacin (CIP) is becoming a critical issue and needs to be addressed globally. CIP is widely used because of manifold uses; however, the long-term therapy poses serious health risks including FDA black box warnings such as tendinitis and peripheral neuropathy. Therefore, nanotechnology-based products can be an effective measure to improve therapeutic outcomes by maintaining the dose at the target site while reducing the dose-dependent toxicity. Biodegradable and biocompatible polymers, Chitosan (CS) and Hyaluronic acid (HA) were used in this work due to their diverse biological characteristics. A simple yet economical ionic gelation method was employed to synthesize nanoparticles with a plexus-like network; nanoplexes, followed by spray-drying to obtain the dry powders to improve stability. Quality by Design (QbD) approach was utilized during the study for robustness and standardization followed by Design of Experiment (DoE) for optimization in a holistic way. The mean particle size of the optimized powder sample was found to be 301.1 nm with a percentage encapsulation efficiency (% EE) of 78.8%. In-vitro dissolution studies corroborated the controlled release of CIP over 48 h. Also, mathematical kinetic modeling was applied to obtain thorough insight into the mechanism of drug release. Moreover, minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were presented to be lower in the case of prepared dry powder as compared to CIP, stating that nanotechnology can improve antimicrobial activity.

Injectable Modified Sodium Alginate Microspheres for Enhanced Operative Efficiency and Safety in Endoscopic Submucosal Dissection.

Endoscopic submucosal dissection (ESD) is an effective method for resecting early-stage tumors in the digestive system. To achieve a low injection pressure of the injected fluid and continuous elevation of the mucosa following injection during the ESD technique, we introduced an innovative injectable sodium-alginate-based drug-loaded microsphere (Cipro-ThSA) for ESD surgery, which was generated through an emulsion reaction involving cysteine-modified sodium alginate (ThSA) and ciprofloxacin. Cipro-ThSA microspheres exhibited notable adhesiveness, antioxidant activity, and antimicrobial properties, providing a certain level of postoperative wound protection. In vitro cell assays confirmed the decent biocompatibility of the material. Lastly, according to animal experiments involving submucosal elevation of porcine colons, Cipro-ThSA microspheres ensure surgically removable lift height while maintaining the mucosa for approximately 246% longer than saline, which could effectively reduce surgical risks while providing sufficient time for operation. Consequently, the Cipro-ThSA microsphere holds great promise as a novel submucosal injection material, in terms of enhancing the operational safety and effectiveness of ESD surgery.

Perceived benefit of antibiotics irrigation before pharyngeal repair of severe cut-throat injuries.

INTRODUCTION: Wound irrigation has been employed as an important surgical step to remove bacteria, devitalized tissues, and foreign bodies from surgical sites to prevent infection and confer to the wound maximum potential of healing. METHOD: A prospective study was conducted at Federal Medical Centre, Gusau, between January 2019- August 2023 to assess the benefit of antibiotics as additives in irrigation of dirty wounds. Seven (7) patients in total were presented with severe cut-throat injuries that require laryngopharyngoplasty. A combination of injection ciprofloxacin and metronidazole were used as additives into 1 L of normal saline, low pressure irrigation was done using 20mls syringe fitted to a broken needle or canular. Dysphagia Outcome and Severity Scale (DOSS) was used to assess return of pharyngeal function. RESULT: The mean time of presentation of the patients was 34 ± 29 h (µ ± standard deviation) and a range of 6-72 h. The mean repair time was 58.3 ± 38.4 h with a range of 24-120 h. Most of the patients (85.7 %) had dysphagia outcome and severity scale of level 5 when per oral feeding was started with steady progress until discharge day. CONCLUSION: Wound irrigation is one of the most crucial steps in treating severe cut-throat injuries. Based on our experience, adding antibiotics to the irrigant has shown potential in the control of local infection, particularly where patients present late.

Synthesis and characterization of pH-sensitive nanocarrier based chitosan-g-poly(itaconic acid) for ciprofloxacin delivery for anti-bacterial application.

This study aims to develop pH-sensitive and controlled release of ciprofloxacin from ciprofloxacin-loaded grafted chitosan-coated zinc oxide nanoparticles (Cip@Gchit/Zn-NPs) for the treatment of bacterial infections in the human colon. For this aim, first, the chitosan-g-poly(itaconic acid) [Chit-g-poly (Itac)] was synthesized via grafting of itaconic acid onto chitosan in the presence of cerium ammonium nitrate (CAN) under an inert atmosphere using conventional methods, while zinc oxide nanoparticles (Zn-NPs) were prepared via sol-gel technique. Characterization of the synthesized Cip@Gchit/Zn-NPs was analyzed using XRD, FT-IR, SEM, TGA, and zeta potential analysis. The antibacterial efficacy of Cip@Gchit/Zn-NPs against three pathogenic bacteria, namely Pseudomonas aeruginosa, Escherichia coli, and Staphylococcus aureus, was superior to that of tetracycline reference drugs, as evidenced by larger inhibition zones. Cytotoxicity assessment of Cip@Gchit/Zn-NPs on the human chondrocyte cell line C28/I2 via MTT assay revealed 100 % cell viability at a concentration of 500 µg/mL. The loading efficiency of ciprofloxacin into Gchit/Zn-NPs was evaluated at various ratios, demonstrating lower loading efficiency; however, sustained release of ciprofloxacin from Cip@Gchit/Zn-NPs was excellent, with 98.13 % release observed at pH 7.2 over 10 h. Kinetic analysis of ciprofloxacin release followed the first-order kinetic models.

Lipase and pH-responsive diblock copolymers featuring fluorocarbon and carboxyl betaine for methicillin-resistant staphylococcus aureus infections.

The emergence of multidrug-resistant bacteria along with their resilient biofilms necessitates the development of creative antimicrobial remedies. We designed versatile fluorinated polymer micelles with surface-charge-switchable properties, demonstrating enhanced efficacy against Methicillin-Resistant Staphylococcus Aureus (MRSA) in planktonic and biofilm states. Polymethacrylate diblock copolymers with pendant fluorocarbon chains and carboxyl betaine groups were prepared using reversible addition-fragmentation chain transfer polymerization. Amphiphilic fluorinated copolymers self-assembled into micelles, encapsulating ciprofloxacin in their cores (CIP@FCBMs) for antibacterial and antibiofilm applications. As a control, fluorine-free copolymer micelles loaded with ciprofloxacin (CIP@BCBMs) were prepared. Although both CIP@FCBMs and CIP@BCBMs exhibited pH-responsive surface charges and lipase-triggered drug release, CIP@FCBMs exhibited powerful antimicrobial and antibiofilm activities in vitro and in vivo, attributed to superior serum stability, higher drug loading, enhanced fluorination-facilitated cellular uptake, and lipase-triggered drug release. Collectively, reversing surface charge, on-demand antibiotic release, and fluorination-mediated nanoparticles hold promise for treating bacterial infections and biofilms.

GO/AgNW aided sustained release of ciprofloxacin loaded in Starch/PVA nanocomposite mats for wound dressings application.

Compared to conventional bandages, which do not meet all wound care requirements, nanofiber wound dressings could provide a potentially excellent environment for healing. In the present research, nanocomposite membrane based on starch (St) - polyvinyl alcohol (PVA) nanofibers containing ciprofloxacin antibiotic drug loaded on graphene oxide­silver nanowire (GO-AgNWs) hybrid nanoparticles is produced by electrospinning process. Morphological studies showed that the length and diameter of silver nanowires are 21 ± 9.17 µm and 82 ± 10.52 nm, respectively. The contact angle of 57.1° due to the hydrophilic nature of nanofibers, also the swelling degree of 679.51 % and, the water vapor permeability of 2627 ± 56 (g/m2.day) can be expressed as a confirmation of the ability of this wound dressing to manage secretions around the wound. In evaluating the antibacterial activity of these nanocomposite membranes against Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus bacteria, the most potent antibacterial effect is in the case of nanofibers containing a high percentage of starch and nanoparticles carrying ciprofloxacin; with non-growth halos of 47.58 mm and 22.06 mm was recorded. The release of ciprofloxacin drug in vitro was reported to be 61.69 % during 24 h, and the final release rate was 82.17 %. Despite the biocompatibility and cell viability of 97.74 % and the biodegradability rate of 28.51 %, the StP-GOAgNWCip nanocomposite membrane can be introduced as a suitable candidate for wound dressing.

Safety of Nebulized Ciprodex for Postoperative Management of Tracheal Resection.

OBJECTIVE: Anastomotic complications after tracheal resection/cricotracheal resection (TR/CTR), such as granulation tissue formation, can lead to severe morbidity. The off-label use of nebulized ciprofloxacin-dexamethasone (Ciprodex) for granulation tissue prophylaxis has anecdotally been used after TR/CTR, especially in pediatric patients. However, its use in the adult population, and its safety and side effect profile post-TR/CTR has not been reported. This study aims to characterize the incidence of adverse side effects associated with nebulized Ciprodex in post-TR/CTR patients. METHODS: A retrospective review of all patients who underwent TR/CTR from June 2015 to July 2023 was performed. The use of nebulized Ciprodex (1 mL ciprofloxacin-dexamethasone 0.3%-0.1% otic suspension in 4 mL normal saline) while inpatient was evaluated. Potential side effects were defined as oral thrush, ageusia, arthralgia, and allergic reaction, and were recorded for all patients. RESULTS: Seventy-three patients underwent TR/CTR from June 2015 to July 2023. Of these, 53 (72.6%) had documented Ciprodex administration during their postoperative course. One (1.9%) patient reported at least one side effect, including one instance of skin rash (1.9%) and one instance of allergic reaction (1.9%). There were no other side effects attributed to Ciprodex use. CONCLUSIONS: The incidence of side effects related to the use of nebulized Ciprodex is felt to be minimal in post-TR/CTR. Although Ciprodex may have the potential to treat granulation tissue in the airway, further studies are needed to verify its efficacy and safety. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:3695-3697, 2024.

Antimicrobial prophylaxis protocol based on rectal swab culture before prostate biopsy to prevent infectious complications: a prospective randomized comparative study.

PURPOSE: To evaluate the benefit of targeted antibiotic prophylaxis (TAP) based on rectal swab culture in comparison with standard empiric antimicrobial prophylaxis in patients undergoing transrectal ultrasound-guided needle biopsy of the prostate (TRUS-BP), as well as to assess rate of fecal carriage of Fluoroquinolone-resistant Enterobacterales FQRE. PATIENTS AND METHODS: We prospectively analyzed data that randomized 157 patients within two groups: (G1) TAP according to rectal swab performed 10 days before PB; (G2): empirical antibiotic prophylaxis with ciprofloxacin. Prevalence of FQRE digestive carriage and risk factors were investigated. Incidence of infectious complications after (TRUS-BP) in each group was compared. RESULTS: G2 included 80 patients versus 77 in G1. There was no difference between the two groups regarding age, diabetes, prostate volume, PSA, number of biopsy cores, and risk factors for FQRE. In G2, the prevalence of FQRE digestive carriage was 56.3% all related to E. coli species. In the case of digestive carriage of FQRE, TAP according to the rectal swab culture with third-generation cephalosporins was performed in 73.3%. Patients with FQRE had history of FQ use within the last 6 months in 17.8% (p = 0.03). Rate of febrile urinary tract infection after PB was 13% in G1 and 3.8% in G2 (p = 0.02). CONCLUSIONS: Incidence of FQ resistance in the intestinal flora of our local population was prevalent. Risk factor for resistance was the use of FQ within the last 6 months. TAP adapted to rectal swab, mainly with third-generation cephalosporins, significantly reduced the rate of infectious complications after (TRUS-BP).

Enrofloxacin pharmacokinetics in yellow catfish (Pelteobagrus fulvidraco): A comparative analysis of oral, intramuscular, and bath administration.

Enrofloxacin (ENR) residues in yellow catfish (Pelteobagrus fulvidraco) often exceed the standard due to excessive use. This study explored the pharmacokinetics of ENR and its metabolite ciprofloxacin (CIP) in yellow catfish following a single dose of 10 mg/kg body weight via intramuscular injection (IM), oral gavage (PO), or a 5-h drug bath at 10 mg/L and 25°C. High-performance liquid chromatography-mass spectrometry was used to determine the ENR and CIP concentrations in various tissues. The highest ENR concentration occurred with IM administration, peaking at 4.124 mg/L in the plasma, 8.359 mg/kg in the kidney, 6.272 mg/kg in the liver, and 5.192 mg/kg in the muscle. However, PO administration resulted in the longest metabolic time, with elimination half-lives of 56.47 h in plasma, 86.43 h in the kidney, 76.25 h in the liver, and 64.75 h in muscle. Additionally, the area under the concentration-time curve values for IM, PO, and bath administration in yellow catfish plasma were 108.36, 88.96, and 22.08 mg·h/L, respectively. These results indicate the effectiveness of all three administration methods in treating bacterial diseases in yellow catfish. The selection of an appropriate administration method depends on the minimal inhibitory concentration of ENR against pathogenic bacteria. Yellow catfish subjected to PO and IM administration require longer resting periods before they can be marketed than those receiving drug bath administration.

Assessing National Trends and Perceived Safety of Off-Label Ciprofloxacin-Dexamethasone Use by Pediatric Otolaryngologists.

OBJECTIVES: Off-label use of Ciprodex® (ciprofloxacin-dexamethasone: CPD), an antibiotic-steroid combination solution, in the airway has been reported by pediatric otolaryngologists with anecdotal success. We examined national trends regarding off-label CPD use including prevalence, common indications, prescriber patterns, adverse events, and accessibility. METHODS: 15-item cross-sectional survey was distributed to American Society of Pediatric Otolaryngology members from January-April 2022. Univariate analyses were performed to compare responses for users of off-label CPD versus non-users. Ease of access was compared across geographies and practice types using multivariate logistic regressions. RESULTS: Of the 163 complete responses (26.6% response rate), 156 (95.7%) reported using off-label CPD. Most common indications for off-label CPD were tracheal granulation (87.8%, n = 137) and choanal atresia (82.1%, n = 128). Ease of access was significantly increased in the Midwest (OR:18.79, 95%CI:3.63-1.24, p = 0.001) and West (OR:29.92, 95%CI:3.55-682.00, p = 0.006). Ease of access was significantly lower at tertiary referral centers (OR:0.11, 95%CI:0.01-0.64, p = 0.041) and private practices (OR:0.04, 95%CI:0.002-0.33, p = 0.009) compared to academic free-standing children's hospitals. Two-thirds of respondents reported feeling "Very Comfortable" with the safety profile of off-label CPD; 99.4% (n = 156) felt that the benefits outweighed the risks of off-label use. Seven respondents (4.5%) reported adverse events (e.g., local allergic reaction, cushingoid symptoms) from off-label use. CONCLUSIONS: Our findings (26.6% response rate) suggest that off-label CPD is commonly used by pediatric otolaryngologists, many of whom reported feeling that the benefits of off-label CPD outweigh the risks. Our results establish a baseline for future efforts to assess the efficacy and safety of off-label CPD and to improve its accessibility. LEVEL OF EVIDENCE: V Laryngoscope, 134:2922-2930, 2024.

Polymeric nanoparticles delivery circumvents bacterial resistance to ciprofloxacin.

OBJECTIVE: The efficient inhibition of bacteria and their by-products from infected root canals is hampered by the limitations of traditional root canal disinfection strategies, bacterial resistance to antibiotic drugs, and regenerative endodontics. Polymeric nanoparticles nanocarrier for controlling antibiotic drug delivery were used to overcome the limitations encountered in endodontics treatment. BACKGROUND: Several polymeric nanoparticles have been used for the delivery of ciprofloxacin drug. The application of poly (ethylene glycol) methyl ether-block-poly(lactide-co-glycolide) (PEG-PLGA) nanoparticles has highlighted the clean and safe delivery of ciprofloxacin (CIP) hydrophilic drug for endodontics treatment. PEG/PLGA was prepared using the solid/oil/water method and the CIP was loaded into polymeric nanoparticles via an ion pairing agent. RESULTS: The CIP-loaded PEG-PLGA nanoparticles have a spherical shape with a 120 ± 0.43 nm size, the CIP encapsulating efficiency was 63.26 ± 9.24% with a loading content of 7.75 ± 1.13%, and sustained release was achieved over 168 h which followed Higuchi model with a non-Fickian mechanism. Moreover, CIP-loaded PEG-PLGA had low cytotoxicity to the stem cells of the apical papilla. CONCLUSION: The results conclude invigorating future perspectives of polymeric nanoparticles for a wide range of drug delivery for various disease treatments. It's anticipated that these polymeric nanoparticles may divert new expectations in the future for topical antibiotic drug delivery with discrete intracellular medicament, and a safe and clean environment.

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.).