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Setting: The shorter treatment regimen (STR) for multidrug- or rifampicin-resistant tuberculosis (MDR/RR-TB) has achieved successful outcomes in many countries. However, there are few studies on high-dose gatifloxacin-based STR with adverse drug reactions (ADRs) and management. Design: A prospective observational study was conducted with MDR/RR-TB patients who were treated with a standardized 9 or 12 - month regimen: including gatifloxacin (Gfx), clofazimine (Cfz), ethambutol (EMB), and pyrazinamide (PZA), and supplemented by amikacin (Am), isoniazid (INH), and prothionamide (Pto) during an intensive phase of 4 or 6 - month. Monitored ADRs monthly until treatment completion and then followed up every three months for one year. Results: Among the 42 eligible patients, 35 (83.3%) completed treatment successfully, 1 (2.4%) lost to follow-up (LTFU), and 6 (14.3%) failed due to ADRs, with no death. The most important ADR was drug-induced liver damage, which occurred in 24 out of 42 (57.1%) patients and resulted in 4 (9.5%) failed treatments and 4 (9.5%) adjusted treatments. QT interval prolongation occurred in 17 out of 42 (40.5%) patients, 9 (21.4%) of them with the corrected QT interval according to Fridericia (QTcF) > 500 ms resulting in 7 (16.7%) adjusted treatments. Conclusions: This study confirmed the effectiveness of the high-dose gatifloxacin-based STR but severe ADRs, especially hepatotoxicity and QT interval prolongation should never be ignored.

PURPOSE The objective of this study was to compare the clinical and microbiological profiles of culture-proven pure Corynebacterium keratitis with mixed infection and their antibiotic susceptibility patterns over a 2-year period. METHODS A retrospective analysis of culture-proven cases of Corynebacterium keratitis over a 2-year period was performed in 3 different tertiary eye care centers. All isolates were tested for antibiotic susceptibility in vitro using the disc-diffusion method for 7 antibiotics. RESULTS Altogether 108 cases were identified as culture-positive Corynebacterium keratitis in 3 tertiary eye care centers. Of these, 60.2% (n = 65) and 39.8% (n = 43) of cases were due to pure Corynebacterium and mixed infection, respectively. The mean duration of symptoms was 23.2 ± 29.6 days. In the mixed-infection group, fungus was identified as the coexistent pathogen in 22 cases (51.1%). Ocular surface disorder was the most common risk factor (33.9%) in Corynebacterium keratitis. The most frequently isolated species was Corynebacterium amycolatum (22.2%) in both groups. Therapeutic keratoplasty was performed in 8.3% of cases. There was no significant difference in the outcome between the 2 groups. Cefazolin resistance was seen in 13.9% of patients, and all isolates were susceptible to vancomycin. The resistance pattern showed emerging resistance toward fluoroquinolone because the isolates were resistant to gatifloxacin (58.3%), moxifloxacin (47.2%), ciprofloxacin (54.6%), and ofloxacin (45.4%). CONCLUSIONS Ocular surface disorder is the most common risk factor in Corynebacterium keratitis. Although fluoroquinolones are commonly used as first-line therapy in microbial keratitis, the in vitro resistance pattern indicates that these are less likely to be effective in infection with Corynebacterium species.

Ophthalmic infections can cause damage to the structure of the eye which can lead to vision loss and blindness if left untreated. Ophthalmic infection or eye infections are caused by exposure to bacterial, fungal viral and protozoan are common with frequently reported in Asian countries. In the present study, the external ocular infected samples collected from Thanjavur Medical College Hospital, Thanjavur. Seven strains were isolated from the external ocular infected samples and identified a standard manual of Determinative Bacteriology by Bergy’s manual 12th edition. The commercial antibiotics and eye drops tested against Bacillus cereus, B. subtilis, Escherichia coli, Klebsiella sp. Pseudomonas sp. Streptococcus sp. and Staphylococcus aureus. The majority of the isolates were sensitive to tobramycin followed by moxifloxacin, gatifloxacin and ofloxacin. The resistant antibiotics are ciprofloxin and sensitive antibiotic was ampicillin was recorded with respective bacteria.

Introduction The US Food and Drug Administration issued safety warnings about neuropathy in 2013 and dysglycemia in 2018 caused by fluoroquinolone use, mainly based on case reports and case series. We conducted this systematic review to evaluate the safety of fluoroquinolones in diabetic patients by investigating their dysglycemic and neuropathic effects. Methods PubMed, Scopus, and Google Scholar were searched for randomized controlled trials and observational studies published from inception till September 2019 evaluating the safety of fluoroquinolones. Efficacy studies of fluoroquinolones reporting these adverse effects were also included. Primary outcomes were hypoglycemia, hyperglycemia, and neuropathy among patients with or without diabetes and treated with fluoroquinolones compared with placebo or other antibiotics. The Cochrane Collaboration tool for randomized controlled trials and modified Newcastle-Ottawa quality-assessment scale were used for assessment of the included studies. Results and discussion A total of 725 studies were identified in the initial search. After screening of titles and abstracts and full-text review, 16 articles fulfilled the inclusion criteria. The sampled patients were aged 30-78 years. Hyperglycemia was reported in 1,588 patients that received fluoroquinolone among eight studies with 4,663 patients, and hypoglycemia was reported in 2,179 patients that received fluoroquinolones among eleven studies with 6,208 patients. Dysglycemia was not generally associated with diabetes mellitus per se. Nevertheless, patients with more comorbidities, especially those with chronic kidney disease, receiving antidiabetics and/or steroids had more glycemic events when treated with fluoroquinolones. Conclusion Moxifloxacin was found to be associated the most and ciprofloxacin the least with dysglycemia. fluoroquinolones must be used with great caution among diabetic patients who have comorbidities and are receiving antidiabetics and/or steroids. Further evidence is required from studies on neuropathy caused by fluoroquinolones.

Актуальность. Проблема гнойно-воспалительных осложнений при травмах вспомогательного аппарата глаза остается актуальной для клинической офтальмохирургии, поскольку данные состояния нередко обусловливают тяжелое протекание пред- и послеоперационного периода, которое проявляется нарушением общих и местных механизмов регулирования, генерализацией процесса и задержкой заживления ран. Цель исследования заключалась в изучении видового состава микрофлоры ран вспомогательного аппарата глаза, определении чувствительности выделенных микроорганизмов к наиболее часто используемым антибиотикам и их способность образовывать биопленки. Материалы и методы. В работе исследовали видовой состав микрофлоры ран 53 пациентов с травматическими повреждениями вспомогательного аппарата глаза за 2018–2019 годы. Осуществлено исследование мазков с ран с последующим определением видового состава и идентификацией микроорганизмов, которые проводили с использованием классических бактериологических методик. Результаты. Идентифицировали 67 штаммов микроорганизмов. Доминирующим оказался Staphylococcus aureus, второе место занял Acinetobacter spp., третье — Micrococcus spp. Частота выявления микроорганизмов в монокультуре с ран составила 33 (66 %), в 17 (34 %) случаях — в ассоциациях. Исследовали чувствительность выделенных штаммов к наиболее часто используемым антибиотикам, среди которых наиболее активным оказался гатифлоксацин. Провели оценку формирования биопленок штаммами S. aureus, поскольку он является комменсалом и превалирует в этиологии раневой инфекции (31 %). Выводы. Установлено, что у штаммов S. aureus (n = 21), которые выделили из ран пациентов, в 15 случаях (71 %) наблюдалась высокая способность к формированию биопленок, в 6 случаях (29 %) отмечалось умеренное биопленкообразование.

Highlights • Shorter treatment regimen for multidrug-resistant tuberculosis. • Effect of companion drug resistance on adverse outcomes. • Gatifloxacin and isoniazid minimum inhibitory concentration. • Whole-genome sequencing. • Non-eligibility for the regimen not associated with adverse outcome. • Exclusions justified only in the case of fluoroquinolone or kanamycin resistance., Objectives We investigated whether companion drug resistance was associated with adverse outcomes of the shorter multidrug-resistant tuberculosis (MDR-TB) treatment regimen in Bangladesh after adjustment for fluoroquinolone resistance. Methods MDR-TB/rifampicin-resistant tuberculosis patients registered for treatment with a standardized gatifloxacin-based shorter MDR-TB treatment regimen were selected for the study. Drug resistance was determined by the proportion method, gatifloxacin and isoniazid minimum inhibitory concentration testing for selected isolates, and whole-genome sequencing. Results Low-level fluoroquinolone resistance and high-level fluoroquinolone resistance were the most important predictors of adverse outcomes, with pyrazinamide resistance having a significant yet lower impact. In patients with fluoroquinolone-/second-line-injectable-susceptible tuberculosis, non-eligibility for the shorter MDR-TB treatment regimen (initial resistance to pyrazinamide, ethionamide, or ethambutol) was not associated with adverse outcome (adjusted odds ratio 1.01; 95% confidence interval 0.4–2.8). Kanamycin resistance was uncommon (1.3%). Increasing levels of resistance to isoniazid predicted treatment failure, also in a subgroup of patients with high-level fluoroquinolone-resistant tuberculosis. Conclusions Our results suggest that resistance to companion drugs in the shorter MDR-TB treatment regimen, except kanamycin resistance, is of no clinical importance as long as fluoroquinolone susceptibility is preserved. Hence, contrary to current WHO guidelines, exclusions to the standard regimen are justified only in the case of fluoroquinolone resistance. and possibly kanamycin resistance.

Objective: To determine bacteria obtained from eye infections, both resistance and minimal inhibitory concentration (MIC) to gatifloxacin, moxifloxacin, tigecycline, linezolid and imipenem, in vitro. Methods: A cross-sectional descriptive study was undergone with 50 samples from 50 eyes of patients diagnosed with keratitis or endophthalmitis, who came to a consultation at the Fundacion Oftalmologica de Santander (Floridablanca, Colombia) from August to November 2014. The MICs of the isolated microorganisms were established through Etest® strips (BioMerieux SA, Marcy-l'Etoile - France). Results: Of the 50 samples in total, 17 different bacteria species or groups were isolated. The main isolate for gram-positives was Methicillin Resistant Coagulase-Negative Staphylococcus (17 samples), and for gram-negatives was Pseudomonas aeruginosa (6 samples). The susceptibility percentages sorted from highest to lowest for gram-positive isolates (n=38) were: imipenem 90.3%, linezolid 87.9%, tigecycline 78.1%, gatifloxacin 68.8% and moxifloxacin 68.8%. For gram-negative isolates (n=12), they were: imipenem 72.7%, gatifloxacin 70%, moxifloxacin 66.7% (no reference cut-off points were found for Pseudomonas aeruginosa), tigecycline 22.2%, and linezolid 0% (as expected according to its inhibition spectrum). Conclusions: Although fourth generation fluoroquinolones are currently the preferred initial empirical monotherapy in our practice, given the increasing bacterial resistance, in cases in which gram-positive bacteria were isolated in the initial staining imipenem, linezolid or tigecycline could be used as an alternative. On the other hand, for cases of gram-negative bacteria, no antimicrobial susceptibility exceeded 80%, so using two antimicrobials looking for a synergy between them could be a better option. Abbreviations: S = Susceptibility, IS = Intermediate susceptibility, R = Resistance.

Purpose. to evaluate the efficacy of perioperative antibacterial prophylaxis using eye drops with fluoroquinolones with the evaluation of conjunctival microflora structure with its antibiotic resistance.Patients and Methods. The study was carried out using the results of one preoperative and four times postoperative swabs taken from the conjunctival cavity in 50 patients (52 eyes) aged 49 to 91 undergoing phacoemulsification. All the strains were undergoing the 16 antibacterial drugs-panel susceptibility testing including the most common ophthalmic dosage form in the Russian Federation. The antibacterial drugs instillations were used during the postoperative period: levofloxacin in group 1 (30 eyes) and moxifloxacin in group 2 (22 eyes).Results. The structure of conjunctival microflora in the two groups was similar prior to phacoemulsification. In 32 cases (61.5 %) bacterial growth was obtained preoperatively. Among them S. epidermidis strains were detected in 68.8 %, S. aureus strains were detected in 31.2 %. During the use of postoperative antibiotic prophylaxis, the number of positive swabs was constantly decreasing. In 1 hour a qualitative change in the microflora structure was observed. The number of S. aureus strains reduced. The number of S. epidermidis strains increased to 80 %. And previously undetected Corynebacterium spp. strains were found. In 1 day the conjunctival microflora was represented only by S. epidermidis. In 1 week all the swabs were sterile. In 1 month after phacoemulsification, positive swabs were obtained in 7.7 % (mainly S. epidermidis) only in group 1, where levofloxacin instillations were used as the postoperative antibiotic prophylaxis (р < 0,05). Moxifloxacin, gatifloxacin and antiseptic drugs showed the highest in vitro activity against selected strains.Conclusion. The strains of coagulase-negative staphylococcus S. epidermidis prevailed in conjunctival microflora structure. During the use of postoperative antibiotic prophylaxis, the number of positive swabs is progressively reduced to zero by the 7th day in both groups. A more persistent permanent effect of moxifloxacin, maintaining for 1 month after the operation was found in comparing two patients’ groups received fluoroquinolone eye drops to prevent infection after phacoemulsification.

Purpose The purpose of this study was to explore the C-X-C chemokines CXCL2 and CXCL10 as potential anti-inflammatory targets for Bacillus endophthalmitis. Methods Bacillus endophthalmitis was induced in C57BL/6J, CXCL2-/-, and CXCL10-/- mice. At specific times postinfection, eyes were analyzed for Bacillus, retinal function, and inflammation. The efficacies of intravitreal anti-CXCL2 and anti-CXCL10 with or without gatifloxacin in B. cereus endophthalmitis were also assessed using the same techniques. Results Despite similar Bacillus growth in eyes of C57BL/6J, CXCL2-/-, and CXCL10-/- mice, retinal function retention was greater in eyes of CXCL2-/- and CXCL10-/- mice compared to that of C57BL/6J mice. Neutrophil migration into eyes of CXCL2-/- and CXCL10-/- mice was reduced to a greater degree compared to that of eyes of C57BL/6J mice. Infected CXCL2-/- and CXCL10-/- mouse eyes had significantly less inflammation compared to that of C57BL/6J eyes. Retinal structures in infected eyes of CXCL2-/- mice were preserved for a longer time than in CXCL10-/- eyes. Compared to untreated eyes, there was less inflammation and significant retention of retinal function in eyes treated with anti-CXCL2 and anti-CXCL10 with or without gatifloxacin. Conclusions For Bacillus endophthalmitis, the absence of CXCL2 or CXCL10 in mice resulted in retained retinal function and less inflammation. The absence of CXCL2 led to a better clinical outcome than the absence of CXCL10. The use of anti-CXCL2 and anti-CXCL10 limited inflammation during B. cereus endophthalmitis. These results highlight the utility of CXCL2 and CXCL10 as potential targets for anti-inflammatory therapy that can be tested in conjunction with antibiotics for improving treating Bacillus endophthalmitis.

Introduction: Fluoroquinolone eye drops are prescribing by Ophthalmologist in many ocular diseases as conjunctivitis, keratitis, bacterial corneal ulcers etc in more and more amount. There are many brands of fluoroquinolones drugs available in Indian market. Costly drugs can lead to economic burden on patients. Modifications in pharmaceutical policy are required, and prices of the drug should be controlled in effective way for all the drugs. Hence this study was done to assess the cost variation of fluoroquinolones ophthalmic solutions available in Indian market. Materials and Method: The maximum and minimum price of each brand of the drug in INR was noted by using CIMS January to April 2018 edition Drug Today April to June 2018 Vol-1. The cost ratio and the percentage cost variation for individual drug brands was calculated. The cost of each eye drop was calculated. At last the cost ratio and percentage cost variation of various brands was compared. Result:Percentage variation in cost for fluoroquinolones eye preparations marketed in India was found to be Eye drop Ciprofloxacin (0.3%) of 5ml:210.39, Eye drop Ciprofloxacin (0.3%) of 10 ml:162, Eye drop Gatifloxacin (0.3%) of 5ml:156, Eye drop Moxifloxacin (0.5%) of 5ml:196.95, Eye drop Ofloxacin (0.3%) of 5ml:245.16,Eye drop Ofloxacin(0.3%) of 10ml:62.5,Eye drop Norfloxacin(0.3%) of 5ml:120.68, Eye drop Sparfloxacin (0.3%):8.31,Eye drop Lomefloxacin (0.3%):16.17 Conclusion:There is a wide difference in the cost of different brands of fluoroquinolones eye preparations available in India. The clinicians prescribing these drugs should be aware of these variations in cost to reduce the cost of drug therapy. Keywords: Fluoroquinolones, Percentage cost variation, Keratitis, Bacterial corneal ulcer, Conjunctivitis

Fluoroquinolones are available only with a physician's prescription and are sold in tablet and injectable forms. Examples of these medicines are moxifloxacin ciprofloxacin, levofloxacin, lomefloxacin, norfloxacin, enoxacin, gatifloxacin, and sparfloxacin. In the wake of the anthrax terrorist attacks in the United States in 2001, ciprofloxacin received extensive media attention because it was the only drug labeled as approved by the Food and Drug Administration (FDA) for both prophylaxis and treatment of inhalation anthrax (the most serious form of the disease). However, in late October 2001, the FDA issued a notice clarifying that the antibiotic doxycycline is also approved for anthrax prophylaxis and that doxycycline and amoxicillin are also approved for treatment for all forms of anthrax. This study is intended to understand the side effects of using these drugs especially when it comes to the calf pain, tendonitis and rupture.

Purpose: To assess trends in antibiotic sensitivity of pseudomonas and compare multidrug resistance (MDR) between Pseudomonas endophthalmitis cases presenting in two consecutive 6-year time frames in a tertiary center in South India. Methods: This is a retrospective comparative series of all Pseudomonas endophthalmitis cases treated from June 2004 to May 2016. Microbiological culture results in all endophthalmitis patients were screened for pseudomonas. Positive cases in the initial 6 and final 6 years were compared for sensitivity to antibiotics and the proportion of MDR. MDR was defined as resistance to at least two different classes of antibiotics. Results: Pseudomonas accounted for 74 of 389 endophthalmitis cases (19%), 42 in initial 6 and 32 in final 6 years. Sensitivity to ciprofloxacin, ofloxacin, gatifloxacin, moxifloxacin, and ceftazidime was 85.7%, 82.9%, 76.5%, 76.9%, 88.1% up to 2010 which reduced to 75%, 59.4%, 68.8%, 56.3%, 56.3%, respectively, after 2010, being significant for ofloxacin (P = 0.0349) and ceftazidime (P = 0.0028). Susceptibility to amikacin, gentamicin, and tobramycin changed non-significantly from 83.3%, 43.9%, 47.6% to 71.9%, 61.3%, 61.3%, respectively. Twenty of 74 cases (27%) were MDR with 16.7% in first 6 years versus 40.6% in final 6 years. Postoperative MDR cases rose from 10.3% to 50% (P = 0.0048). Conclusion: This study shows rising resistance of Pseudomonas to fluoroquinolones, amikacin, and ceftazidime in endophthalmitis. MDR also showed an upward trend, particularly in postsurgical cases.

AIM: To provide statistical evidence for the use of antibiotics in ophthalmology by assessing the distribution and antibiotic sensitivity of bacterial isolates from ocular specimens with suspected microbial infections. METHODS: This study applied a retrospective analysis of 3690 bacterial isolates from ocular specimens, which were obtained from the conjunctiva, cornea, aqueous humor, vitreous body, and other ocular sites of the patients at Shandong Eye Institute in northern China from January 2013 to December 2017. The parameters assessed mainly included the distribution of isolated bacteria and the results of susceptibility tests for antibiotics. In the analysis of antibiotic sensitivities, the bacteria were divided into four groups according to gram staining, and statistical methods were used to compare their antibiotic sensitivities. RESULTS: Among the 3690 isolated bacterial strains, Staphylococcus epidermidis (2007, 54.39%) accounted for the highest proportion. As for the total isolates, their sensitivity rate to gatifloxacin was up to 90.01%, with four types of gram-stained bacteria being all highly sensitive to it, but their sensitivity rate to levofloxacin was only 51.91%. The sensitivity rate of gram-negative bacilli (G-B) to levofloxacin was 83.66%, significantly higher than the other three types of gram-stained bacteria (P

Aim To evaluate the relative efficacy and safety of besifloxacin for treatment of acute bacterial conjunctivitis. Methods A comprehensive search in PubMed, EMBASE Web of Science, Cochrane Central Database and CNKI was undertaken for randomized controlled trials (RCTs) comparing besifloxacin with other treatments or placebo. The primary outcome measures were clinical resolution, rates of bacterial eradication, individual clinical outcomes, cure rates, and bacterial eradication rates of different kinds of pathogens. Safety outcomes were the number of adverse effects (AEs). The final search was performed on August 2018. Results Six RCTs were included. Four studies compared the efficacy and safety of besifloxacin with placebo, 1 study compared besifloxacin with moxifloxacin, and 1 study compared besifloxacin with gatifloxacin. A total of 2780 patients met the inclusion criteria. Besifloxacin presented higher efficacy and safety than did placebo in clinical resolution, rates of bacterial eradication, individual clinical outcomes, cure rates, bacterial eradication rates of different kinds of pathogens and the number of AEs. There was no significant difference between besifloxacin and moxifloxacin or gatifloxacin in the comparison items mentioned above. Conclusion Besifloxacin is highly effective and safe for treatment of acute bacterial conjunctivitis. Further comparative trials regarding the effect of besifloxacin for treatment of acute bacterial conjunctivitis will aid in treatment decisions.

Numerous clinical studies have evaluated the performance of Sanjin tablets (SJTs) in the treatment of acute lower urinary tract infections (ALUTIs) in China. The present meta-analysis aimed to determine the efficacy and safety of SJT combined with antibiotics for the treatment of patients with ALUTIs and to evaluate the quality of evidence. The Cochrane Library, PubMed, EMBASE, Web of Science, Chinese BioMedical Database, China National Knowledge Infrastructure, WanFang and VIP databases were searched for entries added between inception and December 2018 to identify relevant randomized controlled trials (RCTs). The Cochrane risk-of-bias tool and Consolidated Standards of Reporting Trials for Traditional Chinese Medicine were used for assessing the methodological quality and reporting quality of eligible studies, respectively. Meta-analysis and quality of evidence assessment were performed with RevMan 5.3 and Grading of Recommendations, Assessment, Development and Evaluations (GRADE), respectively. A total of 8 RCTs comprising 790 patients with ALUTIs were included in the present meta-analysis. The cure rate of SJTs combined with gatifloxacin tablets (GTs) was higher than that of GTs alone [relative ratio (RR)=1.30, 95% CI=1.07-1.57, P=0.009]. The cure rate of SJTs combined with levofloxacin tablets (LTs) was higher than that of LTs alone (RR=1.13, 95% CI=1.04-1.24, P=0.006). SJTs combined with LTs was better in improving the total effective rate than LTs alone (RR=1.11, 95% CI=1.03-1.19, P=0.005). The recurrence rate for SJTs combined with antibiotics was lower than that associated with antibiotics alone (RR=0.35, 95% CI=0.13-0.97, P=0.04). The bacterial clearance rate achieved with SJTs combined with antibiotics was higher than that obtained with antibiotics alone (RR=1.41, 95% CI=1.09-1.84, P=0.009). The present meta-analysis demonstrated that, compared with the effects of antibiotics treatment, SJTs combined with antibiotics improved the cure rate, total effective rate and bacterial clearance rate, and decreased the recurrence rate. In addition, no serious adverse reactions were observed in patients with ALUTIs. However, the GRADE quality of evidence was low. Thus, further large-scale and rigorously designed clinical trials are required to improve the quality of evidence.

To evaluate the in vitro efficacy of three commercial ophthalmic solutions (gatifloxacin, levofloxacin and gentamicin) against cysts of Acanthamoeba species.Experimental study METHODS: Acanthamoeba cysts belonging to genotypes T3, T4 and T5 were incubated with three ophthalmic solutions for different periods of time; 1, 24, 48 and 72 h at 37 °C. After incubation, treated cysts were stained with trypan blue and counted to express the percent of growth inhibition. Additionally, the viability of treated cysts was assessed by culturing them in PYG medium at 30 °C for 72 h as well as on non-nutrient agar plates at 30 °C for 1 month.Acanthamoeba cysts of all genotypes were susceptible to gentamicin and gatifloxacin after exposure for 1 h and 24 h, respectively, and for levofloxacin, cysts of all genotypes were resistant to levofloxacin even after 72 h of incubation. Gentamicin and gatifloxacin showed statistically highly significant difference (P 0.001), and levofloxacin showed statistically significant difference (P 0.05) in comparison to non-treated control.Gentamicin and gatifloxacin were highly effective against Acanthamoeba cysts. Although our results should be confirmed in animal models, this result will guide the choice of the appropriate ophthalmic drugs for early treatment of eye infection caused by Acanthamoeba spp.

Aim To reveal the cytotoxicity and related mechanisms of gatifloxacin (GFX) to stromal fibroblasts (SFs) in vitro. Methods SFs were treated with GFX at different concentrations (0.009375%-0.3%), and their viability was detected by MTT method. The cell morphology was observed using light/transmission electron microscope. The plasma membrane permeability was measured by AO/EB double-staining. Then cell cycle, phosphatidylserine (PS) externalization, and mitochondrial transmembrane potential (MTP) were analyzed by flow cytometry. DNA damage was analyzed by electrophoresis and immunostaining. ELISA was used to evaluate the caspase-3/-8/-9 activation. Finally, Western blotting was applied for detecting the expressions of apoptosis-related proteins. Results Morphological changes and reduced viability of GFX-treated SFs demonstrated that GFX above 0.009375% had cytotoxicity to SFs with dependence of concentration and time. GFX-treating cells also showed G1 phase arrest, increased membrane permeability, PS externalization and DNA damage, which indicated that GFX induced apoptosis of SFs. Additionally, GFX could activate the caspase-8, caspase-9, and caspase-3, induce MTP disruption, downregulate B-cell leukemia-2 (Bcl-2) and B-cell leukemia-XL (Bcl-XL), and upregulate Bcl-2 assaciated X protein (Bax), Bcl-2-associated death promoter (Bad), Bcl-2 interacting domain (Bid) and cytoplasmic cytochrome C in SFs, suggesting that caspase-dependent extrinsic and intrinsic pathways were related to GFX-contributed apoptosis of SFs. Conclusion The cytotoxicity of GFX induces apoptosis of SFs through triggering the caspase-dependent extrinsic and intrinsic pathways.

AIM: To evaluate the quantitatively changes in lipid layer thickness (LLT) when 3% diquafosol eye drop is used for dry eye patients using the tear film interferometer. METHODS: A total 124 participants (32 males, 92 females; mean age, 28.9y) diagnosed with dry eye disease (DED) received topical instillation of 4 ophthalmic solutions in one eye: diquafosol, normal saline, 0.1% sodium hyaluronate and 0.3% gatifloxacin, in a masked manner. LLT was measured using an interferometer at baseline and 20min after the instillation of each ophthalmic solutions. RESULTS: Changes of LLT after instillation (nm, mean± standard error) were as follows: 12.6±2.0 for diquafosol (P

Purpose: To compare equal concentrations (0.5%) of moxifloxacin and gatifloxacin ophthalmic solutions with regard to conjunctival bacterial reduction as well as anterior chamber penetratio...

Endophthalmitis, an intraocular infection, may lead to irreversible loss of vision. Antimicrobial chemotherapy is prescribed prior to ocular surgical procedures to avoid endophthalmitis. Fluoroquinolones are the most commonly prescribed and used antibiotics during such procedures. However, the selection of a single entity and proper regimen is not specified in medical guidelines. The objective of this study is to develop a rapid and selective simultaneous high-performance liquid chromatography-tandem mass spectroscopic method to explore the bioavailability of 4 fluoroquinolones, including 0.5% moxifloxacin hydrochloride, 0.3% gatifloxacin, 0.3% ciprofloxacin hydrochloride, and 0.3% ofloxacin, in human aqueous humor after antibiotic topical administration using gemifloxacin as Internal Standard according to the European Medicines Agency (EMA) and US Food and Drug Administration (FDA) guidelines. The newly validated method was capable of accurately and precisely quantifying each antibiotic at the lowest reported lower limit of quantification of 10 ng/mL and operating on a very low pipetting volume of 15 μL, indicating a reliable quantitation of all analytes simultaneously using a very small quantity of aqueous humor with total chromatographic run time of 2.5 min. Sixty-seven patients were divided into 4 groups for each antibiotic. Before the cataract surgery, each group received 4 drops of one of the antibiotics over 1 h, separated by 15 min time interval. After 15–20 min from the last drop, approximately 50–100 μL of aqueous humor was collected during surgery for analysis. The average concentrations of moxifloxacin, gatifloxacin, ofloxacin and ciprofloxacin in aqueous humor samples were 891.8, 271.7, 191.4 and 69.5 ng/mL, respectively. Only moxifloxacin average concentration was higher than the minimum inhibitory concentration for the common endophthalmitis pathogens.

Importance Off-label treatment was common for ophthalmia neonatorum because only erythromycin ointment had been approved by the US Food and Drug Administration (FDA) for this indication. Ophthalmia neonatorum was previously considered a different indication from bacterial conjunctivitis in older children and adults because of uncertain similarities in the cause of disease and the treatment course between the 2 populations. Prospective therapeutic clinical studies were required to demonstrate the effectiveness of treatment for ophthalmia neonatorum. Objective To review the therapeutic clinical trials for patients with bacterial conjunctivitis to evaluate the similarity in the cause of disease and the treatment response between neonates and older children and adults. Design, setting, and participants In this comparative effectiveness research review of pooled data from the most recent 30 bacterial conjunctivitis trials (N = 2018) submitted to the FDA to support the approval of topical ophthalmic solutions for older children and adults, 95% CIs were constructed from clinical cure rates. Cure rates in 3 neonatal randomized clinical trials (N = 392) of patients treated with ophthalmic anti-infective solutions of ciprofloxacin, gatifloxacin, and moxifloxacin were constructed and compared. The baseline ocular swab cultures were analyzed. Main outcomes and measures Cure rates of neonatal trials were compared with the 95% CIs among older children and adults. The bacterial organisms isolated from these 2 populations were compared. Results The 3 neonatal trials enrolled a total of 392 patients, and the 30 trials of older children and adults enrolled a total of 2018 patients. Neonatal clinical cure rates for moxifloxacin (day 4, 48%), ciprofloxacin (day 4, 49%; day 5, 61%), and gatifloxacin (day 7, 79%) were within the 95% CI for products approved to treat older children and adults with bacterial conjunctivitis. Bacterial organisms were consistent between these 2 populations. Conclusions and relevance Comparison of the pooled analysis of these historical trial data suggests similarity in the cause of disease and the treatment response between neonates and older children and adults with bacterial conjunctivitis. Therefore, it was appropriate to extrapolate the effectiveness from older children and adults to neonates to support the approval of therapies for ophthalmia neonatorum. Based on this analysis, ophthalmic solutions of ciprofloxacin, gatifloxacin, and moxifloxacin are now approved for all age groups. This analysis presents an approach of using pooled data from previously underpowered individual trials to establish the similarities in the cause of disease and in treatment response between children and adults, which are the fundamental elements used to evaluate whether extrapolation of effectiveness can be used to support drug approval.

Resistance to anti-tuberculosis (anti-TB) antibiotics is a major public health concern for many high-TB burden countries in Asia, including Bangladesh. Therefore, to represent the overall drug-resistance pattern against TB in Bangladesh, a systematic review and meta-analysis was conducted. Databases such as PubMed, Scopus, and Google Scholar were searched to identify studies related to antibiotic-resistant TB. A total of 24 studies covering 13,336 patients with TB were secured and included. The random-effects model was used to calculate the summary estimates. The pooled prevalence of any, mono, multi, poly, and extensive anti-TB antibiotic-resistances were 45.3% [95% CI: 33.5&ndash, 57.1], 14.3% [95% CI: 11.4&ndash, 17.2], 22.2% [95% CI: 18.8&ndash, 25.7], 7.7% [95% CI: 5.6&ndash, 9.7], and 0.3% [95% CI: 0.0&ndash, 1.0], respectively. Among any first and second-line anti-TB drugs, isoniazid (35.0%) and cycloserine (44.6%) resistances were the highest, followed by ethambutol (16.2%) and gatifloxacin (0.2%). Any, multi, and poly drug-resistances were higher in retreatment cases compared to the newly diagnosed cases, although mono drug-resistance tended to be higher in newly diagnosed cases (15.7%) than that in retreatment cases (12.5%). The majority (82.6%) of the included studies were of high quality, with most not exhibiting publication bias. Sensitivity analyses confirmed that all outcomes are robust and reliable. It is concluded that resistance to anti-TB drugs in Bangladesh is rampant and fast growing. Therefore, the implementation of a nationwide surveillance system to detect suspected and drug-resistant TB cases, as well as to ensure a more encompassing treatment management by national TB control program, is highly recommended.

Coagulase-negative staphylococci (CoNS) are frequently isolated from wound infections. There are limited data examining the prevalence of methicillin-resistant CoNS (MRCoNS) among Egyptian patients after surgery. Thus, we studied 208 hospitalised patients, who had skin and soft tissue infections (SSTIs) due to various causes. Samples were cultured for isolation and identification of CoNS and isolates were screened for susceptibility against 23 different antimicrobials. Out of 241 Staphylococcal isolates, 114 (47.3%) were CoNS. The prevalence of MRCoNS among surgical site infection, diabetic foot, abscess, and burn patients was 13.4%, 11.5%, 15.6%, and 10.3%, respectively. The lowest resistance of the 27 identified MRCoNS isolates was to vancomycin, amikacin and gatifloxacin (7% each). We conclude that CoNS isolates are major pathogens associated with wound infections at our institution and MRCoNS probably poses a substantial threat for patients in Egypt, though most MRCoNS isolates demonstrated susceptibility to vancomycin.

International audience; We report a case of acquired fluoroquinolone (FQ) resistance under short-course multidrug-resistant tuberculosis (MDR-TB) treatment. The patient was managed at Kabutare hospital, one of the two specialized MDR-TB clinics in Rwanda. A low dose of moxifloxacin was used in the first three critical months. Acquired resistance was identified at the ninth month of treatment, 3 months after stopping kanamycin in a strain initially susceptible only to FQs, kanamycin, and clofazimine. Fluoroquinolone resistance was detected in the same month by deep sequencing as routinely used second-line line probe assay and phenotypic drug susceptibility testing. High-dose FQ, preferably gatifloxacin, should be used to maximize effectiveness.

BackgroundSince a meta-analysis showed little or no effect of second-line injectables on treatment success, and using injectables may induce ototoxicity, injectable-free rifampicin-resistant tuberculosis (RR-TB) treatment regimens are recommended. However, acquired resistance preventing activity was overlooked. No previous study assessed the effect of shortening the duration of kanamycin administration to 2 months during the intensive phase of the RR-TB shorter treatment regimen (STR).MethodsRetrospective cohort study of the effect of using 2 months of kanamycin instead of the standard 4(+) months (extension if lack of smear conversion at 4 months) on recurrence (either treatment failure or relapse) and fluoroquinolone acquired drug resistance, in patients treated with a gatifloxacin-based STR in Damien Foundation supported clinics in Bangladesh. Logistic regression was used to estimate associations.ResultsFive of 52 (9.6%) treated with a STR containing two months of kanamycin had recurrence, compared to 21 of 738 (2.8%) patients treated with the standard STR containing 4(+) months of kanamycin (OR 3.7; 95%CI:1.5-10.3). In those with initially fluoroquinolone-susceptible TB, acquired resistance to fluoroquinolone was detected in none of 639 patients treated with 4(+) months of kanamycin and two (4.5%) of 44 treated with two months of kanamycin (OR 75.2; 95%CI:3.6-1592.1).ConclusionTwo months of kanamycin was insufficient to prevent recurrence with acquired resistance to gatifloxacin, the core drug of the most effective RR-TB STR. Injectable mediated resistance prevention is important to reach high effectiveness, to safeguard all treatment options after recurrence, and to prevent the spread of resistant TB. Studies on all-oral regimens should also assess the effect of regimen composition on resistance acquisition. Until evidence shows that other drugs can assure at least the same strong resistance preventing activity of the injectables, it seems wise to continue using this group of drugs, and adapt the regimen if any ototoxicity is detected.

Background Empirical antibiotic treatment is a common practice to manage chronic dacryocystitis in many healthcare settings in spite of the probability for changing in the types of microbial isolates. The aims of this study were to find out the current clinicomicrobiological profile of adult cases with chronic dacryocystitis and to determine the antibiogram of the isolated organisms to the commonly prescribed antibiotics. Results Of the 25 samples obtained, 15 (60%) yielded a positive culture, 12 (48%) showed single bacterial isolate while 3 (12%) had mixed (two types) bacterial isolates. A total of 18 different strains of microorganisms were obtained from 25 cases, with 12/18 (66.7%) Gram-positive, 5/18 (27.7%) Gram-negative isolates, and 1/18 (5.5%) was fungal isolate. Coagulase-negative staphylococci were the most frequently found Gram-positive bacteria (22.2%), while Klebsiella species was the predominant of Gram-negative bacteria (16.6%). The majority of the isolated bacterial strains were sensitive to gatifloxacin (88%) and amikacin (88%) while the main resistance of the bacterial isolates, recovered from chronic dacryocystitis, was to cephalexin (59%). Conclusion There is a continuous possibility of changing the type of pathogens responsible for dacryocystitis as well as their susceptibility to antibiotics. Microbiological study with microbial culture and antibiotic sensitivity test has to be done to all cases of chronic dacryocystitis for a better choice of antibiotic prophylaxis and treatment options, and to guard against the emergence of more drug-resistant strains.

Background Clostridium difficile infection (CDI) has an increasing pediatric prevalence worldwide. However, molecular characteristics of C. difficile in Chinese children with acute gastroenteritis have not been reported. Methods A five-year cross-sectional study was conducted in a tertiary children’s hospital in Zhejiang. Consecutive stool specimens from outpatient children with acute gastroenteritis were cultured for C. difficile, and isolates then were analyzed for toxin genes, multi-locus sequence type and antimicrobial resistance. Diarrhea-related viruses were detected, and demographic data were collected. Results A total of 115 CDI cases (14.3%), and 69 co-infected cases with both viruses and toxigenic C. difficile, were found in the 804 stool samples. The 186 C. difficile isolates included 6 of toxin A-positive/toxin B-positive/binary toxin-positive (A+B+CDT+), 139 of A+B+CDT−, 3 of A−B+CDT+, 36 of A−B+CDT− and 2 of A−B−CDT−. Sequence types 26 (17.7%), 35 (11.3%), 39 (12.4%), 54 (16.7%), and 152 (11.3%) were major genotypes with significant differences among different antimicrobial resistances (Fisher's exact test, P −B+ isolates had significantly higher resistance, compared to erythromycin, rifampin, moxifloxacin, and gatifloxacin, than that of the A+B+ (χ2 = 7.78 to 29.26, P χ2 = 4.39, P = 0.036). Conclusions CDI has been revealed as a major cause of acute gastroenteritis in children with various genotypes. The role of toxigenic C. difficile and risk factors of CDI should be emphatically considered in subsequent diarrhea surveillance in children from China.

The inability to use powerful antituberculosis drugs in an increasing number of patients seems to be the biggest threat towards global tuberculosis (TB) elimination. Simplified, shorter and preferably less toxic drug regimens are being investigated for pulmonary TB to counteract emergence of drug resistance. Intensified regimens with high-dose anti-TB drugs during the first weeks of treatment are being investigated for TB meningitis to increase the survival rate among these patients. Moxifloxacin, gatifloxacin and levofloxacin are seen as core agents in case of resistance or intolerance against first-line anti-TB drugs. However, based on their pharmacokinetics (PK) and pharmacodynamics (PD), these drugs are also promising for TB meningitis and might perhaps have the potential to shorten pulmonary TB treatment if dosing could be optimized. We prepared a comprehensive summary of clinical trials investigating the outcome of TB regimens based on moxifloxacin, gatifloxacin and levofloxacin in recent years. In the majority of clinical trials, treatment success was not in favour of these drugs compared to standard regimens. By discussing these results, we propose that incorporation of extended PK/PD analysis into the armamentarium of drug-development tools is needed to clarify the role of moxifloxacin, gatifloxacin and levofloxacin for TB, using the right dose. In addition, to prevent failure of treatment or emergence of drug-resistance, PK and PD variability advocates for concentration-guided dosing in patients at risk for too low a drug-exposure.

BackgroundIn the experimental arm of the OFLOTUB trial, gatifloxacin replaced ethambutol in the standard 4-month regimen for drug-susceptible pulmonary tuberculosis. The study included a nested pharmacokinetic (PK) study. We sought to determine if PK variability played a role in patient outcomes.MethodsPatients recruited in the trial were followed for 24 months, and relapse ascertained using spoligotyping. Blood was drawn for drug concentrations on 2 separate days during the first 2 months of therapy, and compartmental PK analyses was performed. Failure to attain sustained sputum culture conversion at the end of treatment, relapse, or death during follow-up defined therapy failure. In addition to standard statistical analyses, we utilized an ensemble of machine-learning methods to identify patterns and predictors of therapy failure from among 27 clinical and laboratory features.ResultsOf 126 patients, 95 (75%) had favorable outcomes and 19 (15%) failed therapy, relapsed, or died. Pyrazinamide and rifampicin peak concentrations and area under the concentration-time curves (AUCs) were ranked higher (more important) than gatifloxacin AUCs. The distribution of individual drug concentrations and their ranking varied significantly between South African and West African trial sites; however, drug concentrations still accounted for 31% and 75% of variance of outcomes, respectively. We identified a 3-way antagonistic interaction of pyrazinamide, gatifloxacin, and rifampicin concentrations. These negative interactions disappeared if rifampicin peak concentration was above 7 mg/L.ConclusionsConcentration-dependent antagonism contributed to death, relapse, and therapy failure but was abrogated by high rifampicin concentrations. Therefore, increasing both rifampin and gatifloxacin doses could improve outcomes.Clinical Trials RegistrationNCT002216385.

There is increasing resistance to the oral antibiotics currently recommended for the treatment of pyelonephritis, and increased healthcare costs are associated with the reliance on alternative intravenous agents. We, therefore, performed a systematic review of randomised controlled trials to determine the clinical efficacy and safety of oral antibiotics for the treatment of pyelonephritis in adults. A search of four major medical databases (MEDLINE, Embase+ Embase classic, CENTRAL and Cochrane Database for Systematic Reviews) in addition to manual reference searching of relevant reviews was conducted. Clinical cure and adverse event rates were reported, and trial quality and bias were assessed. A total of 277 studies were reviewed; five studies matched all eligibility criteria and were included. Antibiotics included were cefaclor, ciprofloxacin, gatifloxacin, levofloxacin, lomefloxacin, loracarbef, norfloxacin, rufloxacin and trimethoprim-sulfamethoxazole. In included studies, the clinical success of the outpatient treatment of pyelonephritis by cefaclor, ciprofloxacin and norfloxacin at 4 to 6 weeks was comparable at between 83 to 95%. Relatively high rates of adverse events were noted in a trial of ciprofloxacin (24%) and trimethoprim-sulfamethoxazole (33%). Significant heterogeneity between all aspects of the trial designs was identified, with all studies having a potential for bias. This review demonstrates a need for high-quality clinical trials into the oral antibiotic treatment of pyelonephritis, with more consistent designs and reporting of outcomes. There are data to support further research into oral norfloxacin and cefaclor for the outpatient treatment of pyelonephritis in adults.

Purpose: The purpose of this study was to evaluate the clinical efficacy and safety of a novel ophthalmic solution of pazufloxacin on the ocular surface of patients with bacterial conjunct...

Drug-induced cardiac electrophysiological abnormalities accompanied by hypoglycemia or hyperglycemia increase the risk for life-threatening arrhythmia. To assess the drug-induced cardiotoxic potential associated with extraordinary blood glucose (GLU) levels, the effect of gatifloxacin (GFLX) which was frequently associated with GLU abnormality and QT/QTc prolongations in the clinic on blood GLU and electrocardiogram (ECG) parameters was investigated in cynomolgus monkeys (n=4) given GFLX orally in an ascending dose regimen (10, 30, 60 and 100 mg/kg). Simultaneous and sequential GLU and ECG monitoring with a continuous GLU monitoring system and Holter ECG, respectively, were conducted for 24 h under free-moving conditions. Consequently, GFLX at 30 and 60 mg/kg dose-dependently induced a transient decrease in GLU without any ECG abnormality 2-4 h postdose. Highest dose of 100 mg/kg caused severe hypoglycemia with a mean GLU of

Background and objectives: Fluoroquinolones (FLQs) are an essential component of multidrug resistant-tuberculosis (MDR-TB) treatment regimen but unfortunately the emergence of FLQ resistant MDR-TB cases is challenging the current MDR-TB treatment regimen. FLQ resistance is mainly caused by gyrA gene mutation and phenotypic cross-resistance may occur among the different FLQs. A limited number of data exists regarding the cross-resistance phenomenon among FLQs and it appears that resistance to the present class representative FLQ, ofloxacin (OFX), may or may not correlate with complete cross-resistance to other FLQs. So the study was designed to observe if gyrA gene mutations confer to the phenotypic cross-resistance among FLQs [OFX, Levofloxacin (LFX) and Gatifloxacin (GFX)] tested. Methodology: Sputum samples from 68 diagnosed pulmonary MDR-TB cases were collected. All samples were subjected to Multiplex Real-time PCR for the detection of gyrA gene mutations and conventional culture on Lowenstein-Jensen (L-J) media followed by drug sensitivity testing (DST) of culture isolates (MDR-TB strains) by indirect proportion method for the detection of phenotypic resistance pattern to OFX, LFX and GFX. Results: Out of the 68 MDR-TB sputum samples 13 (19.11%) had MDR-TB bacilli with mutations in the gyrA gene and 11(16.18%) of the MDR-TB culture isolates were found to have resistance to FLQs by DST. The study observed that 11 MDR-TB samples with gyrA gene mutations showed complete phenotypic cross-resistance among OFX, LFX and GFX. Conclusion: This study found that mutation in the gyrA gene of the MDR-TB bacilli results in the complete cross-resistance among the FLQs (OFX, LFX and GFX) tested. It is therefore of utmost importance to carry out the base line resistance and cross-resistance tests for the individual FLQs prior to initiating the treatment of MDR-TB cases in Bangladesh for successful clinical outcomes.

INTRODUCTION[|]The aim of this study was to compare the effectiveness and safety of an intracameral injection of gatifloxacin with cefuroxime as prophylaxis for endophthalmitis in cataract surgery.[¤]METHODS[|]In this retrospective comparative case series, 41 eyes of 33 patients were separated into 2 groups. In the first group, an intracameral injection of cefuroxime (1 mg/0.1mL) was administered to 18 eyes, and an intracameral injection of gatifloxacin (0.3 mg/0.1 mL) was administered to 23 eyes in the second group. The best corrected visual acuity (BCVA), endothelial cell density (CD), endothelial cell coefficient of variation (CV), and central macular thickness (CMT) were evaluated at baseline and 1, 3, 6, and 12 months after surgery.[¤]RESULTS[|]No instance of acute/chronic endophthalmitis, cystoid macular edema, or bullous keratopathy was seen in any patient at the end of 1 year of follow-up. At postoperative month 1, a statistically significant increase in BCVA was seen in both groups, as well as a decrease in CD, and a statistically insignificant increase in CMT. However, the 2 groups were found statistically similar in terms of BCVA, CD, CV, and CMT values obtained in subsequent follow-ups (p>0.05).[¤]DISCUSSION AND CONCLUSION[|]VA, CMT, and endothelial cell changes were similar in both the cefuroxime group and the gatifloxacin group. Intracameral administration of 0.3 mg/0.1 mL gatifloxacin or 1 mg/0.1mL cefuroxime is effective and safe as endophthalmitis prophylaxis, given the statistically and clinically insignificant increase in CMT seen in both groups at the postoperative first month.[¤]

Purpose The potential of slow-growing mycobacteria to form biofilms in human tissues contributes to the problem of establishing an effective treatment strategy. The purpose of this study was to examine new antibiotic strategies to enhance current treatment options for these infections. Methods Sensitivities of Mycobacterium fortuitum ATCC 49404 and Mycobacterium chelonae ATCC 35752 were evaluated for different antimicrobials singly and in combination using broth microdilution and FICI (Fractional Inhibitory Concentration Index) synergy screening. Anti-biofilm effects were evaluated in an 8-well chamber slide biofilm model. The efficacy of a new treatment strategy was validated using the novel neutropenic mouse keratitis model and monitored by slit-lamp microscopy, confocal microscopy, and colony forming unit measurements. Results We reported the very first evidence that these organisms develop corneal biofilms by the accumulation of extracellular DNA (eDNA) and the presence of microcolonies using a novel mycobacterial neutropenic mouse keratitis model. The combination of amikacin and gatifloxacin or besifloxacin was more effective than the current gold-standard drug, amikacin, and we developed a novel treatment strategy (amikacin + gatifloxacin + DNase), the destruction of biofilm matrix component, eDNA, which increased the efficacy of the new antibiotic combination for treating mycobacterial infection in in vitro (P = 0.002) and in vivo (P = 0.001) compared to its respective control. Conclusion Biofilms have a role in mycobacterial keratitis leading to poor treatment outcomes in clinical practice and the use of combination therapy (amikacin + gatifloxacin + DNase) could be a useful new treatment option.

PURPOSE: To evaluate the bacterial contamination associated with contact lenses and lens care solutions used by a group of soft contact lens (CL) users (daily & extended wear CL) and the susceptibility pattern of the isolated organisms to antibiotics for 12 months duration. METHODS: This prospective case controlled, non randomized study included 50 participants of contact lens (CL) wearers from Outpatient Clinics at Al-Azhar University Hospitals, International Eye Hospital New Damietta and available special clinics, (between 2013 and 2014). The sample population was divided into two groups: a Case group: 30 contact lens users (60 eyes) were suffering from symptoms and signs of conjunctivitis in one or both eyes; a Control group: 20 CL users were not suffering from conjunctivitis. Samples were takenfromsolution in contact lens storage cases; daily wear CL, extended wear CL, andconjunctiva were cultured on different media. Microbiological identification of the organisms and their antimicrobial susceptibility were done in accordance to standard protocols. RESULTS: In the case group, positive growth was found in 85% of the lens care solution, 65% of the contact lenses, and 56.7% of the conjunctiva of participants. While in the control group, it was found in 10% , 20% and 15% respectively, with a statistically significant difference between both groups (P

Purpose Moraxella atlantae is a rare pathogen. Keratitis from this organism has never been specifically reported or described. In this report we provide the first clinical description and photograph of Moraxella atlantae infectious keratitis. Observations A 41 year-old man presented with a three day history of left eye pain. He was found to have a corneal ring ulcer and infiltrate from which Moraxella atlantae was cultured. The patient was successfully treated with intensive topical gatifloxacin (0.5%) and fortified tobramycin (1.5%); oral doxycycline was added to reduce corneal thinning. The patient's infection resolved with a residual scar and final best corrected visual acuity of 20/200 OS. Conclusions and importance Moraxella atlantae can present as a ring-shaped infectious corneal infiltrate and ulcer. Ring infiltrates have been observed with other microorganisms, including several other gram negative bacteria and classically, acanthamoeba. Frequently presumed to be purely immunologic, corneal ring infiltrates can have a number of other etiologies, including infectious and toxic. There are different types of immunologic rings as well, making differentiation of corneal rings sometimes difficult for the ophthalmologic generalist and subspecialist alike. In this paper we discuss characteristics of various corneal ring infiltrates, along with their immune pathophysiology. Infectious rings are distinguished from immunologic Wessely rings.

Bacterial conjunctivitis represents the major part of infectious conjunctivitis and, although it generally shows a spontaneous resolution, antibiotics speed the elimination of bacteria from the conjunctiva thus limiting the duration of the disease. The addition of anti-inflammatory drugs may potentiate the effectiveness of antibiotics in eradicating bacterial conjunctivitis. Aim of the present study is to compare the efficacy of two different eye drops based on ofloxacin without or with dexamethasone against bacterial conjunctivitis induced by Staphylococcus aureus or Pseudomonas aeruginosa.

About ten years ago, the first results of the so-called “Bangladesh regimen”, a short regimen lasting nine months instead of 20 months, revolutionized multidrug-resistant tuberculosis (MDR-TB) treatment. Similar short regimens were studied in different settings, relying for their efficacy on a later generation fluoroquinolone, either gatifloxacin, moxifloxacin, or levofloxacin. We review the published material on short MDR-TB regimens, describe their different compositions, their results in national tuberculosis programs in middle- and low-income countries, the risk of acquiring resistance to fluoroquinolone, and the occurrence of adverse events. With over 80% success, the regimen performs much better than longer regimens (usually around 50%). Monitoring of adverse events allows adapting its composition to prevent severe adverse events such as deafness. We discuss the current applicability and usefulness of the short injectable-containing regimen given the 2019 recommendation of the World Health Organization (WHO) for a new long all-oral regimen. We conclude that the most effective fluoroquinolone is gatifloxacin, currently not listed as an essential medicine by WHO. It is a priority to restore its status as an essential medicine.

SETTING: Data were collected from patients starting one of the shorter treatment regimens (STRs) for multidrug-resistant tuberculosis (MDR-TB) in Bangladesh, Niger or Cameroon.OBJECTIVE: To estimate the effect of either a gatifloxacin (GFX), moxifloxacin (MFX) or levofloxacin (LVX) based STR on bacteriological effectiveness.DESIGN: Retrospective study of prospectively collected data.RESULTS: Among 1530 patients, bacteriological effectiveness was 96.7% overall. Stratified by treatment with a GFX-, LVX- or MFX-based regimen effectiveness was respectively 97.5%, 95.5% and 94.7%. Compared to those on a GFX-based regimen, the estimated summary odds ratio of having an adverse outcome was more than double (OR 2.05, 95% CI 1.09–3.90) in patients treated with either an LVX-based or MFX-based regimen. After adjusting for initial resistance, patients treated with an LVX-based regimen and MFX-based regimen had respectively a 4.5- and 8.4-fold times larger odds of an adverse bacteriological outcome. None among 859 patients at risk treated with a GFX-based compared to at least 4 of 228 among those on an MFX-based regimen acquired fluoroquinolone resistance.CONCLUSION: GFX-based regimens had superior bacteriological effectiveness than MFX-based or LVX-based regimens. As GFX is currently unavailable in most MDR-TB programs, its reintroduction should be prioritised.

[THIS ARTICLE HAS BEEN RETRACTED] AIM: To evaluate the relative efficacy and safety of besifloxacin for treatment of acute bacterial conjunctivitis. METHODS: A comprehensive search in PubMed, EMBASE Web of Science, Cochrane Central Database and CNKI was undertaken for randomized controlled trials (RCTs) comparing besifloxacin with other treatments or placebo. The primary outcome measures were clinical resolution, rates of bacterial eradication, individual clinical outcomes, cure rates, and bacterial eradication rates of different kinds of pathogens. Safety outcomes were the number of adverse effects (AEs). The final search was performed on August 2018. RESULTS: Eight RCTs were included. Five studies compared the efficacy and safety of besifloxacin with placebo, 2 studies compared besifloxacin with moxifloxacin, and 1 study compared besifloxacin with gatifloxacin. A total of 3105 patients met the inclusion criteria. Besifloxacin presented higher efficacy and safety than did placebo in clinical resolution, rates of bacterial eradication, individual clinical outcomes, cure rates, bacterial eradication rates of different kinds of pathogens and the number of AEs. There was no significant difference between besifloxacin and moxifloxacin or gatifloxacin in the comparison items mentioned above. CONCLUSION: Besifloxacin is highly effective and safe for treatment of acute bacterial conjunctivitis. Further comparative trials regarding the effect of besifloxacin for treatment of acute bacterial conjunctivitis will aid in treatment decisions.

Endophthalmitis is a blinding consequence of bacterial invasion of the interior of the eye. Because of increases in the numbers of ocular surgeries and intraocular injections, the incidence of endophthalmitis is steadily increasing. Staphylococcus aureus, Enterococcus faecalis, Streptococcus pneumoniae, and Bacillus cereus are leading causes of infection following ocular procedures and trauma and are increasingly more difficult to treat due to multidrug resistance. Each of these pathogens produces pore-forming toxins that contribute to the pathogenesis of endophthalmitis. Treatment of these infections with antibiotics alone is insufficient to prevent damage to the retina and vision loss. Therefore, novel therapeutics are needed that include agents that neutralize bacterial pore-forming toxins. Here, we demonstrate that biomimetic nanosponges neutralize pore-forming toxins from these ocular pathogens and aid in preserving retinal function. Nanosponges may represent a new form of adjunct antitoxin therapy for serious potentially blinding intraocular infections., Intraocular infections are prevalent after traumatic injuries or after common ocular surgeries. Infections cause inflammation that can damage the retina and architecture of the eye, often resulting in poor visual outcomes. Severe cases may result in blindness or require enucleation of the eye. Treatments for intraocular infections include intravitreal antibiotics and corticosteroids or surgical vitrectomy in serious cases. The increase in multidrug-resistant infections calls for novel treatment options. In the present study, a biomimetic erythrocyte-derived nanosponge was tested for the ability to neutralize pore-forming toxins from the most frequent Gram-positive bacterial causes of intraocular infections (Staphylococcus aureus, Enterococcus faecalis, Streptococcus pneumoniae, and Bacillus cereus). Nanosponge pretreatment of supernatants reduced hemolytic activity in vitro. In a murine sterile endophthalmitis model, nanosponge pretreatment of injected supernatants resulted in greater retinal function and less ocular pathology compared to that in eyes injected with untreated supernatants from all pathogens except methicillin-resistant S. aureus. In a murine bacterial endophthalmitis model, treatment with gatifloxacin and gatifloxacin-nanosponges reduced intraocular bacterial burdens, except in the case of methicillin-sensitive S. aureus. For all pathogens, eyes in both treatment groups showed decreased ocular pathology and inflammation. Overall, reductions in retinal function loss afforded by gatifloxacin-nanosponge treatment were significant for E. faecalis, S. pneumoniae, and methicillin-resistant S. aureus but not for B. cereus and methicillin-sensitive S. aureus. These results suggest that clinical improvements in intraocular infections following nanosponge treatment were dependent on the complexity and types of toxins produced. Nanosponges might serve as an adjunctive therapy for the treatment of ocular infections. IMPORTANCE Endophthalmitis is a blinding consequence of bacterial invasion of the interior of the eye. Because of increases in the numbers of ocular surgeries and intraocular injections, the incidence of endophthalmitis is steadily increasing. Staphylococcus aureus, Enterococcus faecalis, Streptococcus pneumoniae, and Bacillus cereus are leading causes of infection following ocular procedures and trauma and are increasingly more difficult to treat due to multidrug resistance. Each of these pathogens produces pore-forming toxins that contribute to the pathogenesis of endophthalmitis. Treatment of these infections with antibiotics alone is insufficient to prevent damage to the retina and vision loss. Therefore, novel therapeutics are needed that include agents that neutralize bacterial pore-forming toxins. Here, we demonstrate that biomimetic nanosponges neutralize pore-forming toxins from these ocular pathogens and aid in preserving retinal function. Nanosponges may represent a new form of adjunct antitoxin therapy for serious potentially blinding intraocular infections.

Fluoroquinolones represent the pillar of multidrug-resistant tuberculosis (MDR-TB) treatment, with moxifloxacin, levofloxacin, or gatifloxacin being prescribed to MDR-TB patients. Recently, several clinical trials of “universal” drug regimens, aiming to treat drug-susceptible and drug-resistant TB, have included a fluoroquinolone., Fluoroquinolones represent the pillar of multidrug-resistant tuberculosis (MDR-TB) treatment, with moxifloxacin, levofloxacin, or gatifloxacin being prescribed to MDR-TB patients. Recently, several clinical trials of “universal” drug regimens, aiming to treat drug-susceptible and drug-resistant TB, have included a fluoroquinolone. In the absence of clinical data comparing their side-by-side efficacies in controlled MDR-TB trials, a pharmacological rationale is needed to guide the selection of the most efficacious fluoroquinolone. The present studies were designed to test the hypothesis that fluoroquinolone concentrations (pharmacokinetics) and activity (pharmacodynamics) at the site of infection are better predictors of efficacy than the plasma concentrations and potency measured in standard growth inhibition assays and are better suited to determinations of whether one of the fluoroquinolones outperforms the others in rabbits with active TB. We first measured the penetration of these fluoroquinolones in lung lesion compartments, and their potency against bacterial populations that reside in each compartment, to compute lesion-centric pharmacokinetic-pharmacodynamic (PK/PD) parameters. PK modeling methods were used to quantify drug penetration from plasma to tissues at human-equivalent doses. On the basis of these metrics, moxifloxacin emerged with a clear advantage, whereas plasma-based PK/PD favored levofloxacin (the ranges of the plasma AUC/MIC ratio [i.e., the area under the concentration-time curve over 24 h in the steady state divided by the MIC] are 46 to 86 for moxifloxacin and 74 to 258 for levofloxacin). A comparative efficacy trial in the rabbit model of active TB demonstrated the superiority of moxifloxacin in reducing bacterial burden at the lesion level and in sterilizing cellular and necrotic lesions. Collectively, these results show that PK/PD data obtained at the site of infection represent an adequate predictor of drug efficacy against TB and constitute the baseline required to explore synergies, antagonism, and drug-drug interactions in fluoroquinolone-containing regimens.

Background Antibiotic prophylaxis in cataract surgery is intended to minimize endophthalmitis. We describe pathogenic organisms, antibiotic sensitivities, and antibiotic prophylaxis in culture-proven endophthalmitis cases. Design Retrospective consecutive case series, community-based setting. Samples 215 cases of endophthalmitis after cataract surgery performed during 2007-2012 in Kaiser Permanente, California. Methods and Main Outcome Measures Descriptive analysis of isolated organisms and antibiotic sensitivities in relation to antibiotic prophylaxis in culture-proven endophthalmitis cases. Results The majority of culture-confirmed organisms (N = 83) were Gram-positive (96%), most notably coagulase-negative Staphylococci (CoNS) (N = 34, 52%), of which all that underwent testing were sensitive to vancomycin (N = 32). Among 19 cases that had received only topical antibiotic prophylaxis, 7 (37%) were resistant to the antibiotic given: 50% of cases (5 of 10 isolates) that had received ofloxacin were resistant to this antibiotic, 40% (2 of 5 isolates) that had received gatifloxacin were resistant. In contrast, 100% of cases (N = 4) that had received aminoglycosides were susceptible. Few culture-confirmed cases occurred in patients who received intracameral antibiotic (N = 4). Conclusions In cases where fluoroquinolones were administered as antibiotic prophylaxis, isolates demonstrated a degree of bacterial resistance. The majority of endophthalmitis cases isolated following topical antibiotic prophylaxis only and were attributed to Gram-positive organisms, while few occurred in association with intracameral antibiotic.

Objective To assess collagen and α-tubulin levels of mouse tympanic membrane fibroblasts treated with quinolone and aminoglycoside antibiotics at concentrations found in eardrops. Study Design Prospective controlled cell culture study. Setting Academic tertiary medical center. Subjects Mouse tympanic membrane fibroblasts. Methods In experiment 1, fibroblasts were treated with the following for 24 or 48 hours: phosphate-buffered saline (negative control), dilute hydrochloric acid (positive control), 0.5% gatifloxacin, or commercially available 0.3% ciprofloxacin, 0.3% ciprofloxacin + 0.1% dexamethasone, 0.3% ofloxacin, 0.5% moxifloxacin, 0.3% gentamicin, or 3.5 mg/mL of neomycin + polymyxin B sulfate + hydrocortisone. In experiment 2, cells were treated with the pure form of gatifloxacin, gentamicin, ofloxacin, or ciprofloxacin. Cells were observed with phase-contrast microscope until harvested. Proteins were extracted for Western blotting with antibodies against collagen α1 type I (collagen 1A1) and α-tubulin, and for densitometry to quantify levels. Results Collagen and tubulin levels in fibroblasts treated with ofloxacin, moxifloxacin, gatifloxacin, or gentamicin for 24 hours were not different from the saline control. Fibroblasts treated with neomycin + polymyxin B + hydrocortisone, ciprofloxacin + dexamethasone, or ciprofloxacin for 24 hours had lower collagen 1A1 and α-tubulin levels (all P.001) than the negative control. After 48 hours, fibroblasts treated with neomycin + polymyxin B sulfate + hydrocortisone, ciprofloxacin + dexamethasone, ciprofloxacin, or moxifloxacin had lower collagen 1A1 ( P ≤ .007) and α-tubulin ( P.0001; except ciprofloxacin, P = .033) as compared with control. In experiment 2, only cells treated with ciprofloxacin had lower collagen 1A1 and α-tubulin levels and cell viability (all P.0001) than control. Cytotoxicity assay and phase-contrast images mirrored the protein findings. Conclusion The adverse impact of topical antibiotic exposure on tympanic membrane collagen and tubulin protein levels is drug specific. This may be important for selection of ototopical therapy.

There has been an increasing awareness of the rapidly growing mycobacteria (RGM), of which numerous species and phylogenetic groups are clearly established human pathogens. It is important to appropriately distinguish RGM from other mycobacteria, as first-line antituberculous drugs are ineffective for their treatment. Variability in susceptibility of RGM is seen in relation to species, different geographical areas, and time. Therefore, we conducted a study to speciate the isolates of RGM and perform antimicrobial susceptibility testing. The study was carried out in the department of microbiology of a tertiary care hospital. This study included 40 isolates of RGM obtained from clinical specimens from suspected cases of extrapulmonary tuberculosis. Forty isolates of RGM were speciated by phenotypic methods and drug susceptibility testing was done by broth microdilution method. Of the 40 isolates of RGM, 55% belonged to Mycobacterium fortuitum group, 35% were M. smegmatis group, and 10% were M. chelonae – abscessus group. In M. fortuitum group, sensitivity was seen to amikacin (13.63%), cefoxitin (18.18%), imipenem (31.81%), ceftriaxone (22.72%), and cotrimoxazole (31.81%). Only 14.28% and 7.14% of M. smegmatis were sensitive to cotrimoxazole and amikacin, respectively. M. chelonae – abscessus group was resistant to all the antibiotics tested and showed only intermediate sensitivity to amoxicillin–clavulanic acid (50%) and gatifloxacin (25%). A variability in sensitivity to different antimicrobials exists in all groups. Hence, it is advisable to perform antimicrobial susceptibility test before commencement of therapy.

Corneal ulcers in dogs usually have a traumatic origin. They cause a break in the continuity of underlying corneal stroma and become rapidly contaminated with bacteria. Twenty eight clinical samples were obtained from corneal ulcer affected dogs for bacterial isolation and anti-microbial susceptibility. Bacterial growth was observed in 100% of the samples (n=28) and Staphylococcus spp. was isolated and characterized by culture, gram staining and various biochemical tests. Antibiogram pattern revealed that gatifloxacin and moxifloxacin antibiotics were found to be highly effective in the treatment of corneal ulcers in dogs. Corneal culture and sensitivity testing provided useful information for the diagnosis, determination of appropriate treatment and antimicrobial therapy for corneal diseases in dogs.