Efficacy and Safety of Antofloxacin-Based Triple Therapy for Helicobacter pylori Eradication Failure in China.

AIMS: Quinolone-containing triple therapy has been considered as the second-line therapy for eradication of Helicobacter pylori (H. pylori). At present, there are no data to show the efficacy and safety of antofloxacin-based rescue therapy for the eradication of H. pylori, and this pilot clinical trial was designed. METHODS: A total of 196 patients who failed H. pylori eradication using the clarithromycin-based or metronidazole-based triple or bismuth quadruple therapy were randomly allocated to one of the following rescue eradication therapy groups: AEA group (antofloxacin 200 mg once daily, esomeprazole 20 mg + amoxicillin 1000 mg twice daily) for 14 days, or LEA group (levofloxacin 500 mg once daily, esomeprazole 20 mg + amoxicillin 1000 mg twice daily) for 14 days. The minimal inhibitory concentrations were tested by the E-test method. The gyrA mutation was analyzed by sequencing. Follow-up 13/14C-urea breath test was examined at 1 month after discontinuation. RESULTS: A total of 178 eligible patients were included in this study. The eradication rate was significantly higher in AEA group than in LEA group according to both ITT (87.6% vs. 68.5%; P = 0.002) and PP analyses (90.7% vs. 70.1%; P = 0.001). ITT analyses indicated that the eradication rate was significantly higher in AEA group than in LEA group with Asn87 mutation (78.9% vs. 31.3%; P = 0.005) and levofloxacin-resistant strains (76.9% vs. 44.2%; P = 0.003). Two groups exhibited similar adverse event rates (AEA 14.6% vs. LEA 20.2%, P = 0.323). CONCLUSIONS: The findings showed that antofloxacin may be a promising candidate in rescue therapy for H. pylori eradication failure in China.

The necessity and effect of prophylactic quinolone ear drops after ventilation tube insertion for otitis media with effusion.

BACKGROUND: Otitis media with effusion (OME) is a condition where non-infective fluid builds up in the middle ear. Long-term OME can cause damage to the middle ear and hearing impairment. Ventilation tube insertion (VTI) is an efficient procedure to drain persistent OME. However, the effect of prophylactic ear drops after VTI remains controversial because no infection is present. This study investigated the need for and effect of quinolone ear drops in patients with OME after VTI. METHODS: Between July 2018 and July 2021, 272 patients (436 ears with OME) who underwent VTI were enrolled. Prophylactic quinolone ear drops (ofloxacin) were used in 271 OME ears and not used in 165. The clinical findings and effect of the ear drops were assessed. RESULTS: The group with postoperative ofloxacin had less postoperative otorrhea (p < 0.001). In univariate analysis, age ≥ 13 years (odds ratio [OR] = 1.499, 95% confidence interval [CI]: 1.003-2.238, p = 0.046) was significantly associated with recovery to normal middle ear functioning (type A on postoperative tympanometry). No adenoid hypertrophy (OR = 1.692, 95% CI: 1.108-2.585, p = 0.014) and no postoperative otorrhea (OR = 2.816, 95% CI: 1.869-4.237, p < 0.001) were significant independent factors associated with middle ear recovery in both univariate and multivariate analysis. After VTI, 65% of tympanic membranes in the group with postoperative ofloxacin recovered to normal, while in 67% of tympanic membranes in the group without ofloxacin scarring remained. CONCLUSIONS: Patients who received prophylactic postoperative ofloxacin had less postoperative otorrhea. No adenoid hypertrophy and no postoperative otorrhea were significant independent predictors of middle ear recovery to normal function in both univariate analysis and multivariate analysis. However, prophylactic ofloxacin was not an independent predictor of normal middle ear functioning after VTI. After VTI, most OME patients who had used ofloxacin postoperatively had eardrums that were in better condition than those of patients who had not used ofloxacin. In this study, we confirmed the advantages and limitations of OME after VTI with prophylactic ofloxacin, thus providing clinicians with some guidance regarding the decision to administer prophylactic ofloxacin.

Development of a dosing-adjustment tool for fluoroquinolones in osteoarticular infections: The Fluo-pop study.

Fluoroquinolones efficacy depend on both the drug exposure and the level of drug resistance of the bacteria responsible for the infection. Specifically for the Staphylococcus species, which is the microorganism mainly involved in osteoarticular infections (OAI), in-vitro data reported that an AUC/MIC ratio above 115 h maximizes drug efficacy. However, data on OAI patients are lacking and a simple approach to access AUCs is still a clinical issue. We conducted a prospective, single-center study in 30 OAI patients hospitalized in the Rennes University Hospital to model ofloxacin pharmacokinetics and to define a limited sampling strategy (LSS) suitable for ofloxacin and levofloxacin treatments. Modeling was conducted with the Monolix software. The final model was externally validated using levofloxacin data. Monte-Carlo simulations were used to evaluate the probability of target attainment (PTA) of different dosing regimens. Two hundred and ninety-seven (297) ofloxacin concentrations were available for the pharmacokinetic modeling. Ofloxacin pharmacokinetics was best described using a bicompartmental model with a first order elimination, and a transit compartment model absorption. CKD-EPI and sex explained half of ofloxacin pharmacokinetic variability. For LSS, the 0, 1 h and 3 h sampling scheme resulted in the best approach both for BID and TID dosages (R2 adjusted = 91.1% and 95.0%, outliers = 4.8% and 5.0%, respectively). PTA allows choosing the best drug and dosage according to various hypotheses. A simple 3-sample protocol (pre-dose, 1 h after intake and 3 h after intake) to estimate ofloxacin and levofloxacin AUC allows optimal drug dosage for the treatment of osteoarticular infections.

Accuracy and patient perceived difficulty of utilizing ototopical antibiotic therapy.

PURPOSE: To examine how patients self-administer ear drops, ascertain their perceived difficulty in performing the task and determine if they are able to deliver the correct dosage. MATERIALS AND METHODS: This is a prospective cohort study performed in an otology outpatient clinic with twenty-one subjects with a condition requiring ototopical antibiotics. The number of ear drops applied as well as skills performed during ear drop application was measured. Patient reported difficulty and confidence in application of ear drops data was also obtained. RESULTS: The mean number of drops applied was 2.91 ± 2.1 (target = 3 drops) with a large variance in drop application, range of 0.6 to 9.2 drops. If "correct dosage" is considered 85-115% of the intended dose, then almost half of patients, 47.6%, underdosed with 23.8% that over dosed. Patients reported that the average difficulty in applying drops to themselves was 3.6 (1 being easy and 10 being difficult). Patients reported a high confidence level in applying the correct dose of ear drops of 6.7 (1 being not confident and 10 being very confident). CONCLUSIONS: In our study of 21 patients self-administering ear drops, only 28.6% of patients were able to correctly apply the appropriate treatment dose, with almost half of patients underdosing. Questionnaire data indicated that most patients were unaware they were administering an incorrect dose. Inaccurate administration of ear drops could be problematic and lead to longer durations of symptoms, false treatment failures, and increased costs.

A VigiBase descriptive study of fluoroquinolone induced disabling and potentially permanent musculoskeletal and connective tissue disorders.

Recent drug safety concerns described fluoroquinolone (FQ)-induced serious musculoskeletal reactions. The objective of this study was to characterize reports with FQ-associated disabling musculoskeletal disorders, from VigiBase. The analysis included all FQ-induced musculoskeletal and connective tissue disorders adverse drug reaction (ADR) reports (up to July-2019), (disabling/incapacitating, or recovered/resolved with sequelae or fatal). We described aspects like reporter, suspected FQs, ADRs, associated corticosteroid therapy. We also looked into the disproportionality data in terms of proportional reporting ratio (PRR) and information component (IC) values. A total of 5355 reports with 13,563 ADRs and 5558 FQs were reported. The majority of reports were for patients aged 18-64 (62.67%), and the female gender prevailed (61.76%). Consumers reported almost half (45.99%), with a peak in reporting rates in 2017. Top reported ADRs were arthralgia (16.34%), tendonitis (11.04%), pain in extremity (9.98%), tendon pain (7.63%), and myalgia (7.17%). Top suspected FQs were levofloxacin (50.04%), ciprofloxacin (38.41%), moxifloxacin (5.16%), ofloxacin (3.17%) and norfloxacin (1.01%). For these, FQs-ADR association was supported by the disproportionality analysis. Corticosteroids were associated with about 7% of tendon related reports. The results augment the existing data on FQs safety concerns, specifically their potential effect on the musculoskeletal system.

Preparation and characterization of 2-hydroxyethyl starch microparticles for co-delivery of multiple bioactive agents.

The present study reports the generation of 2-hydroxyethyl starch microparticles for co-delivery and controlled release of multiple agents. The obtained microparticles are characterized by using Fourier transform infrared spectroscopy, differential scanning calorimetry, X-ray diffraction analysis, energy-dispersive X-ray spectroscopy, and scanning electron microscopy. By using ofloxacin and ketoprofen as drug models, the release sustainability of the microparticles is examined at pH 1.2, 5.4, and 6.8 at 37 °C, with Fickian diffusion being found to be the major mechanism controlling the kinetics of drug release. Upon being loaded with the drug models, the microparticles show high efficiency in acting against Escherichia coli and Bacillus cereus. The results suggest that our reported microparticles warrant further development for applications in which co-administration of multiple bioactive agents is required.

Polyvinyl Alcohol/Chitosan Single-Layered and Polyvinyl Alcohol/Chitosan/Eudragit RL100 Multi-layered Electrospun Nanofibers as an Ocular Matrix for the Controlled Release of Ofloxacin: an In Vitro and In Vivo Evaluation.

A novel nanofiber insert was prepared with a modified electrospinning method to enhance the ocular residence time of ofloxacin (OFX) and to provide a sustained release pattern by covering hydrophilic polymers, chitosan/polyvinyl alcohol (CS/PVA) nanofibers, with a hydrophobic polymer, Eudragit RL100 in layers, and by glutaraldehyde (GA) cross-linking of CS-PVA nanofibers for the treatment of infectious conjunctivitis. The morphology of the prepared nanofibers was studied using scanning electron microscopy (SEM). The average fiber diameter was found to be 123 ± 23 nm for the single electrospun nanofiber with no cross-linking (OFX-O). The single nanofibers, cross-linked for 10 h with GA (OFX-OG), had an average fiber diameter of 159 ± 30 nm. The amount of OFX released from the nanofibers was measured in vitro and in vivo using UV spectroscopy and microbial assay methods against Staphylococcus aureus, respectively. The antimicrobial efficiency of OFX formulated in cross-linked and non-cross-linked nanofibers was affirmed by observing the inhibition zones of Staphylococcus aureus and Escherichia coli. In vivo studies using the OFX nanofibrous inserts on a rabbit eye confirmed a sustained release pattern for up to 96 h. It was found that the cross-linking of the nanofibers by GA vapor could reduce the burst release of OFX from OFX-loaded CS/PVA in one layer and multi-layered nanofibers. In vivo results showed that the AUC0-96 for the nanofibers was 9-20-folds higher compared to the OFX solution. This study thus demonstrates the potential of the nanofiber technology is being utilized to sustained drug release in ocular drug delivery systems.

Treatment with a neutrophil elastase inhibitor and ofloxacin reduces P. aeruginosa burden in a mouse model of chronic suppurative otitis media.

Chronic suppurative otitis media (CSOM) is a widespread, debilitating problem with poorly understood immunology. Here, we assess the host response to middle ear infection over the course of a month post-infection in a mouse model of CSOM and in human subjects with the disease. Using multiparameter flow cytometry and a binomial generalized linear machine learning model, we identified Ly6G, a surface marker of mature neutrophils, as the most informative factor of host response driving disease in the CSOM mouse model. Consistent with this, neutrophils were the most abundant cell type in infected mice and Ly6G expression tracked with the course of infection. Moreover, neutrophil-specific immunomodulatory treatment using the neutrophil elastase inhibitor GW 311616A significantly reduces bacterial burden relative to ofloxacin-only treated animals in this model. The levels of dsDNA in middle ear effusion samples are elevated in both humans and mice with CSOM and decreased during treatment, suggesting that dsDNA may serve as a molecular biomarker of treatment response. Together these data strongly implicate neutrophils in the ineffective immune response to P. aeruginosa infection in CSOM and suggest that immunomodulatory strategies may benefit drug-tolerant infections for chronic biofilm-mediated disease.

Topical versus systemic antibiotics for chronic suppurative otitis media.

BACKGROUND: Chronic suppurative otitis media (CSOM), sometimes referred to as chronic otitis media (COM), is a chronic inflammation and often polymicrobial infection (involving more than one micro-organism) of the middle ear and mastoid cavity, characterised by ear discharge (otorrhoea) through a perforated tympanic membrane. The predominant symptoms of CSOM are ear discharge and hearing loss. Antibiotics are the most common treatment for CSOM, which act to kill or inhibit the growth of micro-organisms that may be responsible for the infection. Antibiotics can be administered both topically and systemically, and can be used alone or in addition to other treatments for CSOM such as ear cleaning (aural toileting). OBJECTIVES: To assess the effects of topical versus systemic antibiotics for people with CSOM. SEARCH METHODS: The Cochrane ENT Information Specialist searched the Cochrane ENT Register; Central Register of Controlled Trials (CENTRAL via the Cochrane Register of Studies); Ovid MEDLINE; Ovid Embase; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 16 March 2020. SELECTION CRITERIA: We included randomised controlled trials (RCTs) with at least a one-week follow-up involving patients (adults and children) who had chronic ear discharge of unknown cause or CSOM, where the ear discharge had continued for more than two weeks. The studies compared topical antibiotics against systemic (oral, injection) antibiotics. We separated studies according to whether they compared the same type of antibiotic in both treatment groups, or different types of antibiotics. For each comparison we considered whether there was background treatment for both treatment groups, for example aural toileting (ear cleaning). DATA COLLECTION AND ANALYSIS: We used the standard Cochrane methodological procedures. We used GRADE to assess the certainty of the evidence for each outcome. Our primary outcomes were: resolution of ear discharge or 'dry ear' (whether otoscopically confirmed or not, measured at between one week and up to two weeks, two weeks up to four weeks, and after four weeks), health-related quality of life using a validated instrument, ear pain (otalgia) or discomfort or local irritation. Secondary outcomes included hearing, serious complications and ototoxicity measured in several ways. MAIN RESULTS: Six studies (445 participants), all with high risk of bias, were included. All but two studies included patients with confirmed CSOM, where perforation of the ear drum was clearly documented. None of the studies reported results for resolution of ear discharge after four weeks or health-related quality of life. 1. Topical versus systemic administration of the same type of antibiotics (quinolones) Four studies (325 participants) compared topical versus systemic (oral) administration of ciprofloxacin. Three studies reported resolution of ear discharge at one to two weeks and found that the topical administration may slightly increase resolution (risk ratio (RR) 1.48, 95% confidence interval (CI) 1.24 to 1.76; 285 participants; 3 studies; I2 = 0%; low-certainty evidence). In these studies, aural toileting was either not mentioned, or limited to the first visit. Three studies (265 participants) reported that they did not suspect ototoxicity in any participants, but it is unclear how this was measured (very low-certainty evidence). No studies reported the outcomes of ear pain or serious complications. No studies reported results for hearing, despite it being measured in three studies. 2. Topical versus systemic administration of different types of antibiotics (quinolones versus aminoglycosides) One study (60 participants) compared topical ciprofloxacin versus gentamicin injected intramuscularly. No aural toileting was reported. Resolution of ear discharge was not measured at one to two weeks. The study did not report any 'side effects' from which we assumed that no ear pain, suspected ototoxicity or serious complications occurred (very low-certainty evidence). The study stated that "no worsening of the audiometric function related to local or parenteral therapy was observed". 3. Topical versus systemic administration of different types of antibiotics (quinolones versus amoxicillin-clavulanic acid) One study compared topical ofloxacin with amoxicillin-clavulanic acid with all participants receiving suction ear cleaning at the first visit. It is uncertain if there is a difference between the two groups in resolution of ear discharge at one to two weeks due to study limitations and the very small sample size (RR 2.93, 95% CI 1.50 to 5.72; 56 participants; very low-certainty evidence). It is unclear if there is a difference between topical quinolone compared with oral amoxicillin-clavulanic acid with regards to ear pain, hearing or suspected ototoxicity (very low-certainty evidence). No studies reported the outcome of serious complications. AUTHORS' CONCLUSIONS: There was a limited amount of low-quality evidence available, from studies completed over 15 years ago, to examine whether topical or systemic antibiotics are more effective in achieving resolution of ear discharge for people with CSOM. However, amongst this uncertainty there is some evidence to suggest that the topical administration of antibiotics may be more effective than systemic administration of antibiotics in achieving resolution of ear discharge (dry ear). There is limited evidence available regarding different types of antibiotics. It is not possible to determine with any certainty whether or not topical quinolones are better or worse than systemic aminoglycosides. These two groups of compounds have different adverse effect profiles, but there is insufficient evidence from the included studies to make any comment about these. In general, adverse effects were poorly reported.

Treatment of mild-to-moderate pelvic inflammatory disease with a short-course azithromycin-based regimen versus ofloxacin plus metronidazole: results of a multicentre, randomised controlled trial.

OBJECTIVE: A multicentre, randomised non-inferiority trial compared the efficacy and safety of 14 days of ofloxacin and metronidazole (standard-of-care (SoC)) versus a single dose of intramuscular ceftriaxone followed by 5 days of azithromycin and metronidazole (intervention arm (IA)) in women with mild-to-moderate pelvic inflammatory disease (PID). METHODS: Women with a clinical diagnosis of PID presenting at sexual health services were randomised to the SoC or IA arms. Treating clinicians and participants were not blinded to treatment allocation but the clinician performing the assessment of primary outcome was blinded. The primary outcome was clinical cure defined as ≥70% reduction in the modified McCormack pain score at day 14-21 after starting treatment. Secondary outcomes included adherence, tolerability and microbiological cure. RESULTS: Of the randomised population 72/153 (47.1%) reached the primary end point in the SoC arm, compared with 68/160 (42.5%) in the IA (difference in cure 4.6% (95% CI -15.6% to 6.5%). Following exclusion of 86 women who were lost to follow-up, attended outside the day 14-21 follow-up period, or withdrew consent, 72/107 (67.3%) had clinical cure in the SoC arm compared with 68/120 (56.7%) in the IA, giving a difference in cure rate of 10.6% (95% CI -23.2% to 1.9%). We were unable to demonstrate non-inferiority of the IA compared with SoC arm. Women in the IA took more treatment doses compared with the SoC group (113/124 (91%) vs 75/117 (64%), p=0.0001), but were more likely to experience diarrhoea (61% vs 24%, p<0.0001). Of 288 samples available for analysis, Mycoplasma genitalium was identified in 10% (28/288), 58% (11/19) of which had baseline antimicrobial resistance-associated mutations. CONCLUSION: A short-course azithromycin-based regimen is likely to be less effective than the standard treatment with ofloxacin plus metronidazole. The high rate of baseline antimicrobial resistance supports resistance testing in those with M. genitalium infection to guide appropriate therapy. TRIAL REGISTRATION NUMBER: 2010-023254-36.

Chronic suppurative otitis media due to Streptomyces cacaoi, the second case report in human infection.

BACKGROUND: Streptomyces cacaoi, Gram-positive, branched, filamentous bacillus forms without fragmentation, are saprophytic soil organisms rarely known to cause invasive infections other than mycetoma. Here we describe a case of chronic suppurative otitis media caused by Streptomyces cacaoi in a patient with hyperlipidemia in China. CASE PRESENTATION: A 62-year-old female patient with hyperlipidemia suffered chronic suppurative otitis media caused by Streptomyces cacaoi. She had a favorable outcome with a 4-week course of ofloxacin ear drops. CONCLUSIONS: Streptomyces cacaoi is rarely reported to cause human infection. The introduction of molecular techniques improves the ability to identify rare species such as Streptomyces considerably. We report the case improve our ability to identify this pathogen and expand the range of known bacterial causes of human infection.

Prospective 3-arm study on pain and epithelial healing after corneal crosslinking.

PURPOSE: To investigate the effect of 3 regimes on pain and wound healing after corneal crosslinking (CXL). SETTING: Tertiary academic referral center, Utrecht, the Netherlands. DESIGN: Prospective cohort study. METHODS: Consecutive progressive keratoconus patients who underwent 9 mW/cm epithelium-off CXL were included. Patients received a bandage contact lens (n = 20), occlusive patch (n = 20), or antibiotic ointment (n = 20) after treatment. Pain scores and quality of life, measured by the McGill Pain Questionnaire and Visual Analogue Scale (VAS), were analyzed. Epithelial healing after 2 days, correlations between pain and psychological factors that influence pain perception (depression anxiety stress score and pain catastrophizing score), and oral pain medication were evaluated. RESULTS: Sixty eyes of 52 patients were analyzed. On average, patients experienced considerable pain after CXL (median VAS score 6.2, range 0 to 10). The postoperative regimen did not significantly affect pain scores, although the antibiotic ointment group reported a higher VAS score (median VAS score 7.2 vs 6.7 and 6.0; P = .57). Occlusive patching showed a trend to quicker resolution of epithelial defects (85% completely healed vs 65% with lenses and 70% with antibiotic ointment; P = .43). Correlations with pain-modulating psychological factors were weak (R < 0.3) and not significant. The use of pain medication corresponded poorly to the prescribed use. CONCLUSION: This study demonstrated clinical equivalence of 3 regimes in combating postoperative pain after routine CXL. Wound healing appeared quicker in the occlusive patch group and therefore might be the best standard of care after CXL. The clinical tradition of using bandage contact lenses should be reevaluated.

Biliary antibiotics irrigation for E. coli-induced chronic proliferative cholangitis and hepatolithiasis: A pathophysiological study in rabbits.

BACKGROUND: The gram-negative bacteria secreted endotoxin, Lipopolysaccharide (LPS), plays important roles in the formation and recurrence of hepatolithiasis and chronic biliary inflammation in patients of Southeast Asia. We aimed to elucidate the anti-inflammatory effect and mechanism of local antibiotics irrigation on chronic proliferative cholangitis (CPC) and hepatolithiasis. METHODS: Escherichia coli was injected into rabbit bile ducts to induce CPC. Rabbits were divided into sham operation (SO), povidone-iodine, Metronidazole plus chlorhexidine, ofloxacin, furacillin, Neosporin® G.U., and CPC groups. Local irrigation was performed for 28 days after CPC was established. Residual E. coli and LPS, and the expression of MCP-1, CD14, COX-2, VEGF, IL-6, NF-κB, TNF-α, Fas, TGF-ß1, α-SMA, Collagen-I, ß-glucuronidase, PKC, C-myc, and Mucin 5AC were assessed in bile duct tissues. RESULTS: The residual E. coli and LPS, and expression of MCP-1, CD14, COX-2, IL-6, NF-κB, TNF-α, Fas, TGF-ß1, α-SMA, ß-glucuronidase, PKC, C-myc, and Mucin 5AC in the SO, povidone-iodine, Metronidazole plus chlorhexidine, ofloxacin, and Neosporin® G.U. groups were significantly lower than those in the furacillin and CPC groups (P<0.05). VEGF and Collagen-I levels in the SO, povidone-iodine, metronidazole plus chlorhexidine, and ofloxacin groups were significantly lower than those in the furacillin, Neosporin® G.U., and CPC groups (P<0.05). CONCLUSIONS: LPS affects the pathophysiology of E. coli caused chronic proliferative cholangitis and hepatolithiasis recurrence. Local antibiotics irrigation could prevent chronic proliferative cholangitis and stones formation by decreasing LPS-induced proinflammatory and profibrotic cytokines release. Povidone iodine, metronidazole plus chlorhexidine, and ofloxacin were more effective than Neosporin® G.U. and furacillin.

Commercial Quinolone Ear Drops Cause Perforations in Intact Rat Tympanic Membranes.

HYPOTHESIS: Commercial quinolone ear drops may promote the development of perforations (TMPs) in intact tympanic membrane (TMs). BACKGROUND: Quinolone ear drops have been associated with TMPs after myringotomy +/- tube placement in a drug-specific manner and potentiation by steroids. METHODS: Rats were randomized to six groups (10/group), with one ear receiving otic instillation of dexamethasone, ofloxacin, ciprofloxacin, ofloxacin + dexamethasone, ciprofloxacin + dexamethasone, or neomycin + polymyxin + hydrocortisone-all commercial formulations and at standard clinical concentrations-and the contralateral ear receiving saline, twice daily for 10 days. TMs were assessed over 42 days. RESULTS: No TMPs were seen in ears treated with saline, dexamethasone, or neomycin. At day 10, TMPs were seen in one of 10 ofloxacin- and three of 10 ciprofloxacin + dexamethasone-treated ears (p = 0.038). At day 14, the ofloxacin TMP healed. In contrast, the three ciprofloxacin + dexamethasone TMPs remained and one new TMP developed in this group. A ciprofloxacin and an ofloxacin + dexamethasone-treated ears also had TMPs (p = 0.023). By day 21, the ofloxacin + dexamethasone TMP and two of four of the ciprofloxacin + dexamethasone TMPs healed but two new TMPs were seen in ciprofloxacin + dexamethasone ears (p = 0.0006). At day 28, 1 of 10 ciprofloxacin and 4 of 10 ciprofloxacin + dexamethasone-treated ears had TMPs (p = 0.0006). By day 35, only one ciprofloxacin + dexamethasone had TMP (p = 0.42). All TMPS were healed at day 42. CONCLUSIONS: Application of commercial quinolone ear drops can cause TMPs in intact TMs. This effect appears to be drug-specific and potentiated by steroids.

Hybrid Ofloxacin/eugenol co-loaded solid lipid nanoparticles with enhanced and targetable antimicrobial properties.

In the global context of an imminent emergence of multidrug-resistant microorganisms, the present work combined the use of nanotechnology and the therapeutic benefits of natural compounds as a strategy to potentiate antimicrobial action of the wide-spectrum antibiotic Ofloxacin (Ofx). Hybrid solid lipid nanoparticles (SLN) were synthesized by incorporation of chitosan (Chi, a cationic biopolymer with antimicrobial activity) and eugenol (Eu, a phenolic compound that interferes with bacterial quorum sensing) into a lipid matrix by hot homogenization/ultrasonication method. The developed SLN/Chi/Eu sustainably released the encapsulated Ofx for 24 h. Characterization by DLS, TEM, DSC, TGA and XRD revealed the presence of positively charged spherical nanoparticles with diameters around 300 nm and Ofx entrapped in amorphous state. The SLN exhibited an enhanced bactericidal activity against Pseudomonas aeruginosa and Staphylococcus aureus. The minimum inhibitory concentration (MIC) for free and nanoencapsulated Ofx formulations was below 1.0 µg/ml. The MIC values decreased by 6.1- to 16.1-fold when Ofx was encapsulated in SLN/Chi/Eu. Fluorescent-labeled nanoparticles had the ability to interact with the bacterial cell membrane. Selective toxicity of SLN/Chi/Eu-Ofx was tested in the range of 0.3-30.0 µg/ml and showed no toxicity up to 3.0 µg/ml Ofx in human cell models (A549 and Wi-38) at 24 h and 48 h exposure. It was proved that the administration of hybrid SLN to mice by dry powder inhalation reached therapeutic Ofx levels in lungs.

Evaluating the potential of drug eluting contact lenses for treatment of bacterial keratitis using an ex vivo corneal model.

Corneal infections are treated by multiple instillations of eye drops each day. This study aims to investigate the effectiveness of ofloxacin-loaded contact lenses as prolonged release devices for the treatment of bacterial keratitis. Two silicone hydrogel contact lenses (SHCLs) Senofilcon A (ACUVUE OASYS®) and Narafilcon A (ACUVUE TRUEYE®) were modified by incorporation of ofloxacin alone or with vitamin E (VE). The drug uptake and in vitro release kinetics were investigated and the antibacterial efficacy was assessed against Staphylococcus aureus and Pseudomonas aeruginosa in an ex vivo rabbit corneal model. The in vitro studies showed a higher uptake (p ≤ 0.05) and longer duration of release by Narafilcon A lenses compared to the Senofilcon A lenses. The addition of VE led to a significant increase in duration of release (p < 0.05) for both lenses. The ex vivo studies confirmed the effectiveness of the ofloxacin-loaded lenses in the reduction of bacterial load to clinically insignificant levels and ofloxacin-vitamin E-loaded Narafilcon A lenses in the reduction of bacteria on the corneas to undetectable levels. Antibiotic-loaded lenses are effective in the treatment of ocular infections. Incorporation of vitamin E will sustain this effect and eliminate the need for multiple instillations of eye drops.

Development, Optimization, and In Vitro/In Vivo Characterization of Enhanced Lipid Nanoparticles for Ocular Delivery of Ofloxacin: the Influence of Pegylation and Chitosan Coating.

This study aims to investigate whether modification of solid lipid nanoparticles (SLNs) with chitosan (CTS) and polyethylene glycol (PEG) coatings enhances corneal retention time and transcorneal bioavailability. Ofloxacin (OFLOX) was selected as the model drug because of its potential benefits for the treatment of local eye infections. The OFLOX-CTS-PEG-SLN was prepared by a modified emulsion/solvent evaporation technique. A central composite design was implemented to investigate the influence of total lipid/drug ratio, surfactant concentration, PEG stearate concentration in the lipid mixture, and CTS concentration on size, entrapment, transcorneal permeation, and adhesion to the corneal mucosal membrane. The optimized OFLOX-CTS-PEG-SLN was characterized for OFLOX cumulative percentage released in simulated tear fluid and permeated across the excised bovine corneal membrane. Moreover, nanoparticle morphology, eye irritation via histopathological analysis, and OFLOX concentration in the ocular fluids and tissues were determined. A total lipid/drug ratio of 19:1, Tween 80 of 2%, PEG stearate concentration in the lipid mixture (% w/w) of 2.6%, and CTS concentration (% w/v) of 0.23% produced 132.9 nm particles entrapping 74.8% of the total drug added. The particles detached from the corneal membrane at a force of 3700 dyne/cm2. The %OFLOX released from the optimized nanoparticles was 63.3, and 66% of the drug permeated after 24 h. Compared to Oflox® drops, the optimized OFLOX-CTS-PEG-SLN exhibited similar tolerability but two- to threefold higher concentrations in the eyes of rabbits. Coating of SLN with chitosan and PEG augments the ocular bioavailability of OFLOX by increasing transcorneal permeation and enhancing mucoadhesion strength.

A Rare Case Report of Toxic Epidermal Necrolysis Due to Ofloxacin.

BACKGROUND: Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN), also known as Lyell's syndrome, are rare and life-threatening conditions, for which etiopathogenesis, as well as pharmacotherapy, is yet unclear. CASE REPORT: A 45-year-old male patient by chance on re-exposure to Ofloxacin developed Severe Cutaneous Adverse Drug Reaction (SCADR), diagnosed with toxic epidermal necrolysis. His comorbid conditions and systemic complications of TEN lead him to death. In developing countries, where antibiotics especially fluoroquinolones are widely prescribed, a physician should be now vigilant for such kind of SCADRs because of increasing numbers of such kind of reports.