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For infectious and inflammatory eye lesions, the main methods of controlling pathogens include antibacterial agents of various classes and antiseptics. However, the use of these agents has a number of limitations: they are able to act primarily on the surface of the eye tissue, and in accordance with clinical recommendations, they should be used as an addition to antibacterial therapy.Antibacterial therapy remains the main recommendation for the treatment of bacterial eye infections, both in the anterior segment and in deeper lesions. In most countries, drugs from the group of fluoroquinolones and aminoglycosides are more often prescribed empirically, to which an acceptable level of sensitivity of microorganisms remains. Among aminoglycosides, the greatest sensitivity of eye infection pathogens is currently determined to netilmicin.The review examines the prospects and effectiveness of using netilmicin as monotherapy, as well as in combination with fluoroquinolones for topical treatment of bacterial infections in ophthalmology, and provides examples of the successful use of netilmicin.

Purpose: Single doses of gentamicin have demonstrated clinical efficacy in the treatment of urogenital gonorrhea, but lower cure rates for oropharyngeal and anorectal gonorrhea. Formulations selectively enriched in specific gentamicin C congeners have been proposed as a less toxic alternative to gentamicin, potentially permitting higher dosing to result in increased plasma exposures at the extragenital sites of infection. The purpose of the present study was to compare the antibacterial activity of individual gentamicin C congeners against Neisseria gonorrhoeae to that of other aminoglycoside antibiotics. Methods: Antimicrobial susceptibility of three N. gonorrhoeae reference strains and 152 clinical isolates was assessed using standard disk diffusion, agar dilution, and epsilometer tests. Results: Gentamicin C1, C2, C1a, and C2a demonstrated similar activity against N. gonorrhoeae. Interestingly, susceptibility to the 1-N-ethylated aminoglycosides etimicin and netilmicin was significantly higher than the susceptibility to their parent compounds gentamicin C1a and sisomicin, and to any other of the 25 aminoglycosides assessed in this study. Propylamycin, a 4'-propylated paromomycin analogue, was significantly more active against N. gonorrhoeae than its parent compound, too. Conclusion: Selectively enriched gentamicin formulations hold promise for a less toxic but equally efficacious alternative to gentamicin. Our study warrants additional consideration of the clinically established netilmicin and etimicin for treatment of genital and perhaps extragenital gonorrhea. Additional studies are required to elucidate the mechanism behind the advantage of alkylated aminoglycosides. [ABSTRACT FROM AUTHOR]

Purpose: to evaluate the netilmicin efficacy and safety in chronic blepharitis treatment. Methods: 30 posterior or mixed chronic blepharitis (CB), meibomian gland dysfunctions (MGD) and dry eye (DE) patients were examined. All patients received 0.3 % netilmicin (Nettacin; instillations, 3 times a day) and 0.3 % netilmicin (Nettavisk; applications, at night) for 14 days. Evaluated: integral indicator of СB subjective symptoms (II-SS, scores); integral indicator of CB objective signs (II-OS, scores); OSDI (scores); tear film brake up time (TBUT, s); lower tear meniscus height (LTMH, µm; OptoVue); Bijsterveld`s xerosis index (XI, scores); Korb`s MGD severity (MGD-S, scores). Control points: 1 — when included in the study, 2 — 15 days of observation. The criteria for the therapy effectiveness included the II-OS and II-SS positive dynamics, and the safety criteria included the absence of significant negative dynamics of OSDI, TBUT, LTMH, XI, MGD-S. Statistics: M ± s calculation, Wilcoxon t-test (differences were considered significant at p < 0.05). Results. At the 2nd control point, there was a statistically significant decrease in II-SS (from 3.62 ± 0.49 to 2.47 ± 0.50) and II-OS (from 3.58 ± 0.50 to 2.45 ± 0,50). Also, at the 2nd control point, a significant decrease in OSDI was recorded (from 35.40 ± 3.59 to 26.40 ± 3.06) and insignificant trend towards a decrease in LTMH (from 325.10 ± 21.26 to 319.80 ± 41 26), an increase in XI (from 5.10 ± 0.40 to 5.23 ± 0.50), an increase in TBUT (from 5.47 ± 0.57 to 5.63 ± 0.56) and a decrease in MGD-S (from 2.16 ± 0.38 to 1.97 ± 0.18). Conclusion. As a result of the use of 0.3 % netilmicin, a significant decrease in the severity of CB symptoms and signs was noted, which indicates a good clinical effectiveness of the therapeutic effect. At the same time, the absence of significant negative dynamics of indicators characterizing the state of the ocular surface (OSDI, TBUT, LTMH, XI, MGD-S) during therapy indicates the safety of using 0.3 % netilmicin for the CB treatment in conditions of comorbidity, including MGD and DE.

In this study, netilmicin (NTM) was selectively assessed in its dosage forms after a facile derivatization reaction. The proposed approach was based on the interaction between NTM and o‐phthalaldehyde/2‐mercaptoethanol (Roth's reagent). The reaction product was fluorometrically measured at λemission of 434 nm after λexcitation of 338 nm. All reaction conditions for achieving the optimum fluorescence switch‐on activity were visualized and monitored. Moreover, the method was validated under ICH guidelines, and was linear over the range 30–210 ng/ml after plotting netilmicin concentrations against the corresponding fluorescence intensity values. In addition, the selectivity of the developed method was investigated against either the co‐formulated drug (dexamethasone) or a common ophthalmic drop excipient (benzalkonium chloride) without interference from either of them. Furthermore, the developed method was applied to assay netilmicin in various samples of pharmaceutical eye drops with good recovery. Finally, multicriteria greenness and whiteness metrics were used to evaluate the sustainability, greenness, and whiteness of the approach. The applied tools were the AGREE algorithm, the RGB 12 algorithm, and HEXAGON. [ABSTRACT FROM AUTHOR]

Introduction: To demonstrate efficacy and safety of an ophthalmic hydrogel formulation of netilmicin/dexamethasone, containing xanthan gum twice a day (b.i.d.) versus netilmicin/dexamethasone eye drops four times a day (q.i.d) to treat inflammation and prevention of infection after cataract surgery. Methods: Patients undergoing phacoemulsification with intraocular lens implantation (IOL) were randomised in two groups: group 1, twice daily (b.i.d.) dexamethasone 0.1%/netilmicin 0.3% (Netildex) ophthalmic gel; group 2, four times daily (q.i.d.) dexamethasone 0.1%/netilmicin 0.3% (Netildex) eye drops. Both treatments were administered for 14 days after surgery. Patients were evaluated before surgery, on the day of surgery and at 1, 7, 15 and 60 postoperative days. The primary efficacy endpoint was evaluation of cellularity and flare in the anterior chamber through slit-lamp biomicroscopy 7 days after surgery. Secondary endpoints included: presence of signs/symptoms of postoperative ocular inflammation and incidence of infection. Results: One hundred seventy-three patients were randomised and 168 were evaluable. Flare and cellularity were resolved at day 7 in 92.5% of patients and almost completely by day 15. In both intent to treat (ITT) and per-protocol (PP) populations, the efficacy analysis demonstrated that the gel formulation administered twice a day was non-inferior to the eye drops administered four times a day. For ITT analysis, the lower limit of the 97.5% confidence interval (− 0.0535) was greater than the non-inferiority limit of -0.10. For the PP analysis, the lower limit of the 97.5% confidence interval (− 0.0526) was greater than the non-inferiority limit of − 0.10. The patient's global tolerability and reported symptoms were similar between treatment groups. No microbial load and no safety events were observed. Conclusions: Efficacy of the gel reduced posology (twice a day) is not inferior to four times a day eye drops. Both treatments were well tolerated and efficacious. The new reduced posology hydrogel formulation may improve patient compliance and quality of life. Trial Registration: Eudract: 2016-0021138-63; ClinicalTrial.gov: NCT029738880. [ABSTRACT FROM AUTHOR]

Netilmicin (NET) is a typical veterinary antibiotic used in aquaculture and animal husbandry, but its excessive accumulation poses a serious threat to the ecological environment and human health. Therefore, a novel and highly sensitive Crispr-Cas12a-mediated colorimetric aptasensor was developed by combining the enzyme-assisted signal amplification strategy and magnetic NMOF-Pt nanozyme composite material (NPSM) for the visual detection of veterinary antibiotic residues in real samples. A high-affinity truncated aptamer (N-20) targeting NET was evolved from a parental aptamer sequence with the help of comprehensive recognition mechanism studies. Subsequently, N-20 was elaborately designed into the isothermal enzyme-assisted strand displacement amplification reaction. The amplified products (Act-DNAs) activated the trans-cleavage activity in the Crispr Cas12a system. The NMOF-Pt nanozyme was released from NPSM after cleaving the single chain of DNA (ssDNA). The quantity of released nanozyme was positively correlated with the amount of NET to quantitatively achieve the detection with the linear range and limits of detection (LOD) of about 0.003–30 ng/mL and 1.15 pg/mL, respectively. This method was successfully applied to detect NET in Lake water, milk and pork samples with satisfactory recoveries ranging from 89.9 % to 104.3 %. The constructed aptasensor demonstrated superior analytical performance and exhibited enormous application prospects in food supervision, environment monitoring, and medical laboratory science. • A truncated aptamer against Netilmicin was evolved from a parental aptamer. • The recognition mechanism was studied by molecular computational simulation • A high-sensitivity colorimetric aptasensor was constructed to detect Netilmicin. • The delicate design strategy greatly improved the sensitivity in sample detection. [ABSTRACT FROM AUTHOR]

Aldo Caporossi,1 Giovanni Alessio,2 Francesco Fasce,3 Giorgio Marchini,4 Antonio Rapisarda,5 Vincenzo Papa6 1Department of Ophthalmology, Policlinico Universitario A. Gemelli IRCSS Università Cattolica del Sacro Cuore, Roma, Italy; 2Ophthalmology Unit, Dipartimento di Scienze mediche di base, Neuroscienze e Organi di Senso Università di Bari, Azienda Ospedaliera Policlinico Consorziale, Bari, Italy; 3Ophthalmology Unit, IRCSS San Raffaele, Milano, Italy; 4Ophthalmology Unit, Ospedale Policlinico G.B. Rossi, Università di Verona, Verona, Italy; 5Ophthalmology Unit, Azienda Ospedaliera Garibaldi, Catania, Italy; 6Medical Affairs SIFI SpA, Catania, ItalyCorrespondence: Vincenzo PapaMedical Affairs SIFI SpA, Via E. Patti 36, Aci S. Antonio, Catania, ItalyEmail vincenzo.papa@sifigroup.comPurpose: To evaluate the short-term anti-inflammatory effect of dexamethasone/netilmicin fixed combination in the management of ocular inflammation after cataract surgery.Patients and Methods: Open-label, randomized, active-controlled, clinical study conducted in 6 sites in Italy; 238 patients were randomized 2:1 to dexamethasone/netilmicin (dexa/net, n=158) or betamethasone/chloramphenicol (beta/chl, n=80). Treatment started the day of surgery and continued 4 times daily for 7 days. The primary efficacy parameter was the anterior chamber (AC) flare. The percentage of patients displaying none or mild (ie, only barely detectable) AC flare was defined as “efficacy rate”, whereas the percentage of patients showing a decrease of AC flare score from baseline was defined as “percentage of responders”. Additional parameters evaluated were AC cells, conjunctival hyperaemia, corneal and lid oedema, symptoms of ocular discomfort, visual acuity, and intraocular pressure. Dexa/net was considered effective if the efficacy rate was not inferior (by means of 97.5% confidence interval) to that of beta/chl.Results: After 7 days of treatment, no AC flare was observed in 92.8% (dexa/net) and 92.3% (beta/chl) of patients, whereas no AC cells were observed in 91.5% (dexa/net) and 93.6% (beta/chl) of patients, respectively. The “efficacy rate” was 100% in both groups, whereas the “percentage of responders” was 94.1% in the dexa/net and 93.6% in the beta/chl group. The p-value to reject the null hypothesis of inferiority was < 0.001. Other efficacy parameters confirmed both treatments as highly effective, despite their difference in steroid content (2 mg/mL for beta/chl vs 1 mg/mL for dexa/net). IOP and visual acuity at the end of the study were comparable. Two cases of allergic conjunctivitis were considered adverse events and were both related to dexa/net.Conclusion: Short-term use of dexa/net fixed combination is safe and effective in the control of post-operative inflammation following uncomplicated cataract surgery.Keywords: cataract surgery, fixed combination, netilmicin, chloramphenicol

Antonio Rapisarda,1 Paolo Arpa,2 Paolo Maria Fantaguzzi,3 Francesco Faraldi,4 Roberto Ratiglia,5 Stanislao Rizzo,6 Paola Vaona,4 Claudio Iannacone,7 Vincenzo Papa8 1Department of Ophthalmology, Azienda Ospedaliera Garibaldi, Catania, Italy; 2Department of Ophthalmology, Ospedale San Gerardo, Monza, Italy; 3Department of Ophthalmology, Ospedale Morgagni Pierantoni, Forlì, Italy; 4Department of Ophthalmology, Presidio Ospedaliero Oftalmico, Torino, Italy; 5Department of Ophthalmology, Policlinico Mangiagalli Regina Elena, Milano, Italy; 6Department of Ophthalmology, Azienda Ospedaliera Pisana, Pisa, Italy; 7Sparc Consulting, Milano, Italy; 8Medical Affairs, SIFI SpA, Catania, ItalyCorrespondence: Vincenzo PapaMedical Affairs SIFI SpA, Via E. Patti 36, Aci S. Antonio, Catania, ItalyEmail vincenzo.papa@sifigroup.comPurpose: To evaluate the effect of dexamethasone/netilmicin (dexa/net) fixed combination in the treatment of ocular inflammation after sutureless micro-incisional vitreoretinal surgery (MIVS).Patients and Methods: This multicenter, open, randomized, active-controlled, parallel-group, clinical trial was run in 6 sites in Italy. Treatment started the day of surgery and continued 4 times daily for 14 days. Patients were 1:1 randomized to dexa/net (eyedrops solution and eye gel) or dexamethasone/tobramycin (dexa/tobra) eyedrops suspension and ointment. Viscous formulations (gel or ointment) were used alone during the early post-operative phase; afterwards, a combination of eye drops during daytime and viscous formulations at bedtime was adopted. The primary efficacy parameter evaluated was bulbar conjunctival hyperemia. Additional efficacy and safety parameters (palpebral conjunctival hyperemia, anterior chamber flare and cells, symptoms of ocular discomfort and ocular tolerance, adverse events and intraocular pressure) were also evaluated. Control visits were performed at day 1, day 4 and day 14 after surgery; the endpoint of the study was set at 14± 2 days after surgery.Results: A complete resolution of bulbar conjunctiva hyperaemia at the study end point was reached in 92.9% of patients treated with dexa/net and 75.0% of those treated with dexa/tobra (p=0.02, Fisher’s exact test). No differences were observed between treatments for other efficacy parameters. Statistically significant differences in favour of dexa/net (p< 0.0001, ANOVA) were observed for most of subjective tolerance variables examined (blurred vision, foreign body sensation, stickiness, burning) starting day 1 after surgery when only the viscous formulations were used. No increase in intraocular pressure or adverse events was observed during the study.Conclusion: The combination dexa/net is safe and effective in the treatment of post-operative inflammation following sutureless MIVS. In particular, the use of eye gel formulation is characterized by a great tolerability.Keywords: vitreoretinal surgery, fixed combination, xanthan gum, tolerability

Purpose: To study the effectiveness and safety of co-administration of moxifloxacin with netilmicin in drug-resistant tuberculosis (TB) patients, and its impact on levels of inflammatory factors and immune function. Methods: We enrolled 100 patients with drug-resistant TB admitted to People’s Hospital of Rizhao between May 2017 and October 2019. The patients were randomly allocated to control group and study group, with 50 patients per group. The control group received moxifloxacin at a dose of 0.2 g t.i.d. for 6 months and the study group received netilmicin at a dose of 0.1 g t.i.d. plus. The response, incidence of adverse reactions, expression levels of inflammatory factors, immune function, and sputum-negative status after 2, 4 and 6 months of TB treatment were compared. Results: The study group showed markedly higher response than the control group (p < 0.05). Moreover, there were lower incidence of adverse effects in the study group than in the control group (p < 0.05). The expression levels of inflammatory factors were significantly lower in the study group, while the concentrations of CD3+, CD4+, and CD8+ were markedly higher (p < 0.05). After 2, 4 and 6 months of TB treatment, cases of sputum-negative conversion were significantly higher in the study group than in the control group (p < 0.05). Conclusion: Co-administration of moxifloxacin with netilmicin produces much higher effectiveness and safety than moxifloxacin monotherapy, decreases inflammatory factor levels and improves immune function in patients with drug-resistant TB. [ABSTRACT FROM AUTHOR]

Background: Colistin is currently used as a last line antibiotic for the treatment of extensively drug-resistant Gram-negative bacteria. The widespread dissemination of ESBL-producing and carbapenem-resistant Gram-negative bacteria necessitated the re-introduction of colistin which was initially abandoned as a result of high toxicities. This study aimed at determining the epidemiology of Enterobacteriaceae isolates that are resistant to colistin, tigecycline, and netilmicin and the risk factors that may contribute to the resistance observed within Southeastern Nigeria. Methods: A total of 400 participants who came to the hospitals for various reasons and suspected to have bacterial infections were enrolled in this study. Phenotypic resistance to colistin was detected using broth microdilution technique on cation - adjusted Mueller-Hinton broth while resistance to colistin and netilmicin was detected using the Kirby-Bauer disk diffusion method using tigecycline disk (10 µg) and netilmicin disk (30 µg). Risk factors were determined by the administration of questionnaires to the participants. Results: Our study found an overall high prevalence of colistin - resistant Enterobacteriaceae (45.8%) and a high prevalence for colistin and tigecycline (22.2%) and colistin and netilmicin (31.7%) resistant isolates. Among the risk factors that contribute to colistin, non-completion of antibiotics was found to be more significant (p = 0.039 and an odds ratio of 0.324 - 0.972 at 95% confidence interval). Conclusions: Our finding is significant in that colistin resistance was determined to be present among populations that have not been exposed to colistin therapy. [ABSTRACT FROM AUTHOR]

Abstract Objective The rapid emergence of drug resistant Leishmanial strains makes it imperative to continue the development of cheap and effective drugs against the parasite. Due to the absence of effective vaccines against leishmaniasis, current therapeutic measures exclusively rely on chemotherapy. Here we attempt, to identify novel antileishmanial from a list of known drugs determined from a previous bioinformatics study. Synergism between various drug combinations (involving netilmicin, suramin, paromomycin and curcumin) have been estimated to identify potent multidrug therapies to combat the disease. Results The drugs were screened against Leishmania promastigotes by utilizing the MTT assay and against intracellular amastigotes using murine Macrophage like tumor cell, RAW 264.7 as a host. In vitro drug interactions were tested for several drug combinations with a modified fixed ratio isobologram method against both Leishmania major and Leishmania donovani. This work reports the in vitro antileishmanial activity for the aminoglycoside netilmicin (for some Leishmania parasites) and the anti-trypanosomatid suramin. Synergism was also observed between paromomycin–suramin and netilmicin–curcumin.

The emergence of infections caused by bacterial pathogens that are resistant to current antibiotic therapy is a critical healthcare challenge. Aminoglycosides are natural antibiotics with broad spectrum of activity; however, their clinical use is limited due to considerable nephrotoxicity. Moreover, drug-resistant bacteria that cause infections in human as well as livestock are less responsive to conventional antibiotics. Herein, we report the in vitro antibacterial evaluation of five different aminoglycosides, including ribostamycin, against a panel of Gram-positive and Gram-negative pathogens. Eight of the tested bacterial strains are linked to gastrointestinal (GI) infections. The minimum inhibitory concentration (MIC) of ribostamycin against three different Escherichia coli strains is in the range of 0.9–7.2 μM and against a strain of Haemophilus influenzae is 0.5 μM. We also found that the MIC of ribostamycin was considerably enhanced from 57.2 to 7.2 μM, an 8-fold improvement, when bacteria were treated with a combination of ribostamycin and ethylenediaminetetraacetic acid (EDTA). These findings demonstrate a promising approach to enhance the clinical potential of ribostamycin and provide a rational for its antibiotic reclassification from special level to non-restricted level. [ABSTRACT FROM AUTHOR]

Aminoglycosides are important treatment options for serious lung infections, but modeling analyses to quantify their human lung epithelial lining fluid (ELF) penetration are lacking. We estimated the extent and rate of penetration for five aminoglycosides via population pharmacokinetics from eight published studies. The area under the curve in ELF vs plasma ranged from 50% to 100% and equilibration half-lives from 0.61 to 5.80 h, indicating extensive system hysteresis. Aminoglycoside ELF peak concentrations were blunted, but overall exposures were moderately high., Competing Interests: The authors declare no conflict of interest.

In this study, netilmicin (NTM) was selectively assessed in its dosage forms after a facile derivatization reaction. The proposed approach was based on the interaction between NTM and o-phthalaldehyde/2-mercaptoethanol (Roth's reagent). The reaction product was fluorometrically measured at λ emission of 434 nm after λ excitation of 338 nm. All reaction conditions for achieving the optimum fluorescence switch-on activity were visualized and monitored. Moreover, the method was validated under ICH guidelines, and was linear over the range 30-210 ng/ml after plotting netilmicin concentrations against the corresponding fluorescence intensity values. In addition, the selectivity of the developed method was investigated against either the co-formulated drug (dexamethasone) or a common ophthalmic drop excipient (benzalkonium chloride) without interference from either of them. Furthermore, the developed method was applied to assay netilmicin in various samples of pharmaceutical eye drops with good recovery. Finally, multicriteria greenness and whiteness metrics were used to evaluate the sustainability, greenness, and whiteness of the approach. The applied tools were the AGREE algorithm, the RGB 12 algorithm, and HEXAGON., (© 2023 John Wiley & Sons Ltd.)

Abstract Acanthamoeba keratitis (AK) is a sight-threatening corneal infection. The early symptoms include redness, pain, photophobia and intense tearing. Chronic infection usually progresses to stromal inflammation, ring ulcers, corneal opacification and hypopyon. Here we document an AK case in a high myopic 38-year-old woman from Mexico City, with a history of wearing contact lenses while swimming. Corneal scrapes cultures were positive only for amoebae, consequently a treatment including netilmicin 0.3% and oral itraconazole 100 mg/12 h was prescribed. The infection was resolved after 8 months, leaving a slight leucoma outside the visual axis, with a visual acuity of 20/150. In the laboratory, the amoebic isolate was axenized in PYG medium, with an optimal growth at 30 °C, and was identified morphologically as Acanthamoeba polyphaga according to the taxonomic criteria of Page (1988) and placed in the T4 group by genotyping. The virulence of this strain (40%) was determined by intranasal inoculation of 1 × 106/20 μl trophozoites in BALB/c mice recovering from brain, proving their invasion ability and by the interaction with monolayers of epithelial cells of the established MDCK line of canine kidney origin (1:2 ratio of interaction), at 1, 3, 6, 8 and 24 h; trophozoites migrated to cell junctions inducing few lytic zones. In addition to the biological characterization, in vitro drug sensitivity tests were performed using chlorhexidine, itraconazole, netilmicin and voriconazole. Results revealed that voriconazole was the most effective compound. A. polyphaga remains as one of the most frequently isolated species producing AK. The treatment of AK case using netilmicin and oral itraconazole solved the disease, but the healing process was wide-ranging (8 months). The use of voriconazole and chlorhexidine may be an alternative treatment of future AK cases in Mexico. Graphical abstract Image 1 Highlights • Description of a case of amoebic keratitis in Mexico. • Importance of the evaluation of drug sensitivity to ensure a good prognosis in the pathologies caused by Amphizoic amoebae. • Amoebae of the T4 group are the most frequent etiological agents of AK cases in Mexico and around the world. [ABSTRACT FROM AUTHOR]

Switch on the fluorescence activity of netilmicin through its reaction with each acetylacetone/formaldehyde and ninhydrin/phenylacetaldehyde. [Display omitted] • Two spectrofluorimetric methods were developed and validated to determine netilmicin. • Hantzsch reaction was applied to turn on the fluorescence activity of netilmicin. • Ninhydrin and phenylacetaldehyde were reacted with netilmicin to form a fluorescence product. • The methods were applied for determining netilmicin in its pharmaceutical samples. Netilmicin is an aminoglycoside antibiotic used to treat infections caused by a broad spectrum of Gram-negative and Gram-positive bacteria and is pharmaceutically formulated in ophthalmic dosage forms. In this study, two spectrofluorimetric approaches were designed and developed to switch-on the fluorescence activity of NTC. The first method, or Hantzsch (HNZ) method, was relied on measuring the generated fluorescence intensity upon the condensation of NTC with acetylacetone and formaldehyde (Hantzsch reaction) at λ emis = 483 nm/ λ excit = 425.5 nm. While the second fluorometric method (NHD method) was relied on measuring the generated fluorescence intensity upon the condensation of NTC with ninhydrin/phenylacetaldehyde at λ emis = 482.2 nm/ λ excit = 385.8 nm. The reaction conditions for the two approaches were well investigated and optimized. The selectivity study for the methods was investigated by determining NTC in the presence of the co-formulated drug (dexamethasone) and pharmaceutical excipients. The validation for two approaches was performed based on ICH guidelines, and ranges of linearity were 0.1 - 1.2 and 1.5 - 6.0 µg/mL, while LOD values were 0.039 and 0.207 µg/mL for the HNZ method and the NHD method, respectively. Finally, NTC has been determined in different ophthalmic preparations by the proposed approaches with adequate recovery values. [ABSTRACT FROM AUTHOR]

Objective. Aim. To evaluate current susceptibility patterns of the potential ocular bacterial pathogens to netilmicin in comparison with other antimicrobials in Russia. Materials and Methods. Overall in the study were included 200 S. aureus strains (100 — MRSA), 50 — coagulase-negative staphylococci, 50 — P. aeruginosa, 50 — Acinetobacter spp., and 50 — Enterobacteriaceae strains, isolated from outpatients and inpatients located in 17 cities of different regions of Russia during 2010–2014. All strains were identified to the species level using MALDI-TOF mass-spectrometry. Minimal inhibitory concentrations (MICs) of netilmicin and other antimicrobials were determined by serial dilution method and interpreted according EUCAST criteria (v.4.1). Results. Activity of netilmicin against methicillin-susceptible S. aureus strains (98% of isolates were susceptible to netilmicin) according to MIC50/90 values was superior compare to other aminoglycosides (gentamicin, tobramycin) and lower only if compared with respiratory quinolones and fusidic acid. In spite the fact that all MRSA isolates were formally resistant to netilmicin (as well as to gentamicin and tobramycin), according to MIC50/90 values and MIC distributions netilmicin was superior to majority of antimicrobials tested with exception of tigecycline, fusidic acid and co-trimoxazole. Against coagulase-negative staphylococci netilmicin (96% isolates susceptible) was the most in vitro active among all antimicrobials tested. According to MIC50/90 values, in vitro activity of netilmicin (46% isolates susceptible) against Enterobacteriaceae was comparable with the activity of other aminoglycosides, quinolones, cephalosporins, co-trimoxazole, and inhibitor-protected aminopenicillins. In vitro activity of netilmicin against P. aeruginosa and Acinetobacter spp. (50% and 76% susceptible isolates, respectively) was higher compare with other aminoglycosides (amikacin, gentamicin, tobramycin), and with other antimicrobials tested except colistin. Conclusions. Netilmicin might be considered as an option for the topical treatment of bacterial eye infections, especially nosocomial, as well as for topical prophylaxis in eye surgery.

Purpose: To explore whether topical antibiotic prophylaxis in patients scheduled for intravitreal injections achieves surface sterility in a greater proportion of subjects as compared to povidone-iodine alone., Material and Methods: A randomized, triple-blind clinical trial., Population: patients scheduled for intravitreal injections for maculopathy., Inclusion Criteria: any sex and race, age 18 years and above. Subjects were randomized into 4 groups: the first group applied chloramphenicol (CHLORAM), the second netilmicin (NETILM), the third a commercial ozonized antiseptic solution (OZONE), and the fourth applied no drops (CONTROL)., Outcome Variable: percentage of non-sterile conjunctival swabs. Specimens were collected before and after the application of 5% povidone-iodine moments before the injection., Results: Ninety-eight subjects (33.7% females, 64.3% males), mean age: 70.2 ± 9.3 years (54-91). Before povidone-iodine, both the CHLORAM and NETILM group showed a lower percentage of non-sterile swabs (61.1% and 31.3% respectively), as compared to the OZONE (83.3%) and CONTROL (86.5%) groups (p < .04). However, this statistical difference was lost after the application of povidone-iodine for 3 min. Percentage of non-sterile swabs in each group after applying 5% povidone-iodine: CHLORAM 11.1%, NETILM 12.5%, CONTROL 15.4%, OZONE 25.0%. This was not statistically significant (p > .05)., Conclusions: Topical antibiotic prophylaxis with chloramphenicol or netilmicin drops decreases the bacterial load on the conjunctiva. However, after the application of povidone-iodine, all groups showed a significant reduction in the percentage of non-sterile swabs, and this value was comparable among all groups. For this reason, authors conclude that povidone-iodine alone is sufficient and prior topical antibiotic prophylaxis is not indicated., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The amikacin plus gentamicin-containing SuperAminoglycoside medium was developed for screening multiple-aminoglycoside resistance in Gram-negative bacteria (Enterobacteriaceae, Pseudomonas aeruginosa , and Acinetobacter baumannii ). It was evaluated using aminoglycoside-susceptible ( n =12) and aminoglycoside-resistant ( n =59) Gram-negative isolates, including 16S rRNA methylase producers ( n =20). Its sensitivity and specificity of detection were, respectively, of 95% and 96% for detecting multiple aminoglycoside-resistant methylase producers. [ABSTRACT FROM AUTHOR]

Purpose/aim of the study: The purpose of this study was to measure the pre-corneal retention time of two marketed formulations (eye drops and eye gel) of a steroid-antibiotic fixed combination (FC) containing 0.1% dexamethasone and 0.3% netilmicin. Materials and methods: Pre-corneal retention time was evaluated in 16 healthy subjects using an ultrahigh-resolution anterior segment spectral domain optical coherence tomography (OCT). All subjects randomly received both formulations of the FC (Netildex, SIFI, Italy). Central tear film thickness (CTFT) was measured before instillation (time 0) and then after 1, 10, 20, 30, 40 50, 60 and 120 min. The pre-corneal retention time was calculated by plotting CTFT as a function of time. Differences between time points and groups were analyzed by Student’s t-test. Results: CTFT increased significantly after the instillation of the eye gel formulation (p < 0.001). CTFT reached its maximum value 1 min after instillation and returned to baseline after 60 min. No effect on CTFT was observed after the instillation of eye drops. The difference between the two formulations was statistically significant at time 1 min (p < 0.0001), 10 min (p < 0.001) and 20 min (p < 0.01). Conclusions: The FC formulated as eye gel was retained on the ocular surface longer than the corresponding eye drop solution. Consequently, the use of the eye gel might extend the interval between instillations and decrease the frequency of administration. [ABSTRACT FROM AUTHOR]

Previous studies have evaluated the action of gentamicin against Malassezia pachydermatis. The aim of this study was to evaluate in vitro susceptibility of M. pachydermatis to the aminoglycosides- gentamicin, tobramycin, netilmicin and framycetin. The minimum inhibitory concentration ( MIC) of gentamicin was determined following methods M27-A3 microdilution and Etest®. The Etest® was used to determine the minimum inhibitory concentration ( MIC) of the tobramycin and netilmicin. The Kirby-Bauer test was used to determine the antibiotic susceptibility to the framycetin. The MIC50 and MIC90 were 8.12 μg/mL and 32.5 μg/mL by microdilution method for gentamicin. The MIC50, determined by the Etest®, was 8 μg/mL for gentamicin and netilmicin and 64 μg/mL for tobramycin. The MIC90 was 16 and 32 μg/mL for gentamicin and netilmicin respectively. The MIC90 was outside of the detectable limits for tobramycin. To framycetin, 28 strains (40%) of the 70 M. pachydermatis isolates tested showed a diameter of 22 mm, 22 strains (31.42%) showed a diameter of 20 mm, 16 strains showed a diameter of ≤ 18 mm, and only 5.71% of the isolates showed a diameter of ≥ 22 mm. This study provides evidence of high in vitro activity of the aminoglycosides-gentamicin, tobramycin, netilmicin and framycetin against M. pachydermatis. For gentamicin Etest® showed similar values of MIC50 y MIC90 that the obtained by microdilution method. We considered Etest® method could be a good method for these calculations with aminoglycosides. [ABSTRACT FROM AUTHOR]

Orbital complications due to ethmoiditis are rare in neonates. A case of orbital abscess due to acute ethmoiditis in a 28-day-old girl is presented. A Successful outcome was achieved following antimicrobial therapy alone; spontaneous drainage of the abscess occurred from the lower lid without the need for surgery. From this case report, we intend to emphasize on eyelid retraction as a sign of neonatal orbital abscess, and to review all the available literature of similar cases.

Pellucid marginal degeneration (PMD) is an uncommon cause of inferior peripheral corneal thinning disorder, characterized by irregular astigmatism. We analyzed a case of bilateral PMD patient and treated one eye with corneal collagen cross-linking (CXL) therapy. Corneal topography was characteristic for PMD. Visual acuity, slitlamp examinations, tonometry, and corneal thickness were observed. Simulated keratometric and topographic index values were detected with corneal topography. Uncorrected, LogMAR visual acuity has improved from +0.8 to +0.55 during the 6 months and +0.3 during the 8 months follow-up after CXL. Pachymetry values and intraocular pressure showed no changes. Keratometric values and topografic indexes disclosed no progression of the disease. CXL may postpone or eliminate the need of corneal transplantation in cases with PMD.

Netilmicin (NTM) is one of the first-line drugs for lower respiratory tract infections (LRTI) therapy, but its nephrotoxicity and ototoxicity caused by intravenous injection restrict its clinical application. Dry powder inhalation (DPI) is a popular local drug delivery system that is introduced as a solution. Due to the nature of NTM hygroscopicity that hinders its direct use through DPI, in this study, L-leucine (LL) was added into NTM dry powder to reduce its moisture absorption rate and improve its aerosolization performance. NTM DPIs were prepared using spray-drying with different LL proportions. The particle size, density, morphology, crystallinity, water content, hygroscopicity, antibacterial activity, in vitro aerosolization performance, and stability of each formulation were characterized. NTM DPIs were suitable for inhalation and amorphous with a corrugated surface. The analysis indicated that the water content and hygroscopicity were decreased with the addition of LL, whilst the antibacterial activity of NTM was maintained. The optimal formulation ND2 (NTM:LL = 30:1) showed high fine particle fraction values (85.14 ± 8.97%), which was 2.78-fold those of ND0 (100% NTM). It was stable after storage at 40 ± 2 °C, 75 ± 5% relative humidity (RH). The additional LL in NTM DPI successfully reduced the hygroscopicity and improved the aerosolization performance. NTM DPIs were proved to be a feasible and desirable approach for the treatment of LRTI.

The aminoglycoside antibiotics amikacin, gentamicin, and tobramycin are important therapeutic options for Acinetobacter iinfections. Several genes that confer resistance to one or more of these antibiotics are prevalent in the globally distributed resistant clones of Acinetobacter baumannii, but the aac ( 6 ')- Im ( aacA16 ) gene (amikacin, netilmicin, and tobramycin resistance), first reported in isolates from South Korea, has rarely been reported since. In this study, GC2 isolates (1999 to 2002) from Brisbane, Australia, carrying aac ( 6 ')- Im and belonging to the ST2:ST423:KL6:OCL1 type were identified and sequenced. The aac ( 6 ')- Im gene and surrounds have been incorporated into one end of the IS 26 -bounded AbGRI2 antibiotic resistance island and are accompanied by a characteristic 70.3-kbp deletion of adjacent chromosome. The compete genome of the 1999 isolate F46 (RBH46) includes only two copies of ISAba1 (in AbGRI1-3 and upstream of ampC ) but later isolates, which differ from one another by <10 single nucleotide differences (SND), carry two to seven additional shared copies. Several complete GC2 genomes with aac ( 6 ')- Im in an AbGRI2 island (2004 to 2017; several countries) found in GenBank and two additional Australian A. baumannii isolates (2006) carry different gene sets, KL2, KL9, KL40, or KL52, at the capsule locus. These genomes include ISAba1 copies in a different set of shared locations. The distribution of SND between F46 and AYP-A2, a 2013 ST2:ST208:KL2:OCL1 isolate from Victoria, Australia, revealed that a 640-kbp segment that includes KL2 and the AbGRI1 resistance island replaces the corresponding region in F46. Over 1,000 A. baumannii draft genomes also include aac ( 6 ')- Im , indicating that it is currently globally disseminated and significantly underreported. IMPORTANCE Aminoglycosides are important therapeutic options for treatment of Acinetobacter infections. Here, we show that a little-known aminoglycoside resistance gene, aac(6')-Im ( aacA16 ), that confers amikacin, netilmicin, and tobramycin resistance has been circulating undetected for many years in a sublineage of A. baumannii global clone 2 (GC2), generally with a second aminoglycoside resistance gene, aacC1 , which confers resistance to gentamicin. These two genes are commonly found together in GC2 complete and draft genomes and globally distributed. One isolate appears to be ancestral, as its genome contains few ISAba1 copies, providing insight into the original source of this insertion sequence (IS), which is abundant in most GC2 isolates. Tracking ISAba1 spread can provide a simple means to track the development and ongoing evolution as well as the dissemination of specific lineages and detect the formation of many sublineages. The complete ancestral genome will provide an essential base point for tracking this process., Competing Interests: The authors declare no conflict of interest.

Objective: To evaluate the bactericidal efficacy of several compounds used in the treatment of chronic staphylococcal anterior blepharitis through an in vitro study., Materials and Methods: Standard commercial strains of Staphylococcus aureus (SAu) (ATCC 25923 Culti-Loops) and coagulase-negative Staphylococcus (CoNS) (ATCC 12228 Culti-Loops) were cultured. Susceptibility tests were performed to vancomycin 30 μg, netilmicin 30 μg, hypochlorous acid (HOCl) 0.01% (Ocudox™, Brill®), Melaleuca alternifolia leaf oil (MeAl) (Navyblef® Daily Care, NOVAX®) and 1% chlorhexidine digluconate (DGCH) (Cristalmina™, Salvat®) using the agar disk diffusion method (Rosco Neo-Sensitabs®). After 24 h, the induced halos were measured with automatic calipers. The results were analyzed using the EUCAST- and CLSI potency Neo-Sensitabs® guidelines., Results: Vancomycin induced a halo of 22.37 mm and 21.81 mm in SAu and CoNS, respectively. Netilmicin produced halos of 24.45 mm in SAu and 32.49 mm in CoNS. MeAl induced halos of 12.65 mm in SAu and 15.83 mm in CoNS. A 12.11 mm halo was found in SAu and an 18.38 mm halo in CoNS using HOCl. DGCH produced halos of 26.55 mm and 23.12 mm in SAu and CoNS, respectively., Conclusion: Netilmicin and vancomycin demonstrated antibiotic activity against both pathogens, so they can be alternative rescue therapies to treat chronic staphylococcal blepharitis. DGCH has efficacy against both comparable to antibiotics, while HOCl and MeAl show less efficacy., (Copyright © 2023 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.)