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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.
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Aminoglicósidos , Antibacterianos , Gentamicinas , Gonorrea , Pruebas de Sensibilidad Microbiana , Neisseria gonorrhoeae , Neisseria gonorrhoeae/efectos de los fármacos , Gentamicinas/farmacología , Antibacterianos/farmacología , Humanos , Aminoglicósidos/farmacología , Gonorrea/tratamiento farmacológico , Gonorrea/microbiología , Netilmicina/farmacologíaRESUMEN
Wound infection is one of the most important causes of morbidity and mortality worldwide. The aim of this study was to identify the organisms and their sensitivity pattern from wound infection patients attending in a tertiary care hospital in Dhaka city. This cross-sectional study was carried out in a total of 240 aseptically collected wound swab samples from wound infection suspected patients visiting Bangladesh Medical College Hospital, Dhaka, Bangladesh were analyzed from July 2017 to June 2019. Bacteriological culture of the samples, colony morphology, Gram's staining, and biochemical tests were done following standard microbiological techniques. The antimicrobial susceptibility testing was performed by modified Kirby-Bauer disc diffusion technique following clinical and laboratory standards institute guidelines. Out of 240 wound swab samples from suspected patients of wound infection, 126(52.5%) showed bacterial growth whereas 114(47.5%) were culture negative. No sample yielded more than one organism. Among 126 culture positive cases 75(59.52%) were male and 51(40.48%) were female. The higher rate of bacterial infections 26.19% was noted in the age group of 21-30 years, followed by the age group of 31-40 years, 41-50 years, 51-60 years. Among 126 culture positive cases, 74.6% were Gram negative and 25.4% were Gram positive bacteria. Out of total 126 isolates, E. coli was the most prevalent pathogen 31(24.60%) followed by Staphylococcus aureus 29(23.01%); Pseudomonas 27(21.43%); Klebsiella 18(14.29%); Enterobacter 12(9.52%); Acinetobacter 4(3.17%), while Coagulase negative Staphylococcus 3(2.38%) and Proteus 2(1.59%) were least detected isolates in wound swab. Highly effective antibiotics against Staph aureus were vancomycin 100.0%; imipenem 100.0%; linezolid 100.0% and meropenem 89.65%. Amikacin; gentamicin; netilmicin; imipenem and meropenem showed higher sensitivity in E coli, Klebsiella and Enterobacter species. Colistin was 88.88% effective against Pseudominas spp. followed by imipenem 81.48%, piperacillin-tazobactam 77.78%, meropenem 70.37% and amikacin 51.85%. Acinetobacter spp. showed 75.0% and 50.0% sensitivity to netilmicin and colistin respectively. Injectable and reserve drugs were sensitive to bacterial populations among patients of wound infections in our hospital. It is a wake-up call for clinician to treat wound infections. To prevent the increase resistance to antibiotics, it is necessary to avoid the administration of uncontrolled and unnecessary antibiotics available.
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Colistina , Infección de Heridas , Humanos , Masculino , Femenino , Adulto Joven , Adulto , Colistina/farmacología , Escherichia coli , Netilmicina/farmacología , Meropenem/farmacología , Amicacina/farmacología , Centros de Atención Terciaria , Estudios Transversales , Bangladesh/epidemiología , Antibacterianos/uso terapéutico , Antibacterianos/farmacología , Staphylococcus aureus , Pruebas de Sensibilidad Microbiana , Imipenem/farmacologíaRESUMEN
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 IS26-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.
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Acinetobacter baumannii , Amicacina , Amicacina/farmacología , Netilmicina , Tobramicina/farmacología , Acinetobacter baumannii/genética , Proteína 1 Similar al Receptor de Interleucina-1 , Australia , Antibacterianos/farmacología , Aminoglicósidos/farmacología , Gentamicinas , Células Clonales , Farmacorresistencia Bacteriana/genética , Pruebas de Sensibilidad MicrobianaRESUMEN
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 λemis=483 nm/λexcit=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 λemis=482.2 nm/λexcit=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.
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Netilmicina , Ninhidrina , Indicadores y Reactivos , Espectrometría de Fluorescencia/métodos , FormaldehídoRESUMEN
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.
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Antiinfecciosos Locales , Endoftalmitis , Masculino , Femenino , Humanos , Persona de Mediana Edad , Anciano , Adolescente , Povidona Yodada , Profilaxis Antibiótica , Antibacterianos/uso terapéutico , Inyecciones Intravítreas , Proyectos Piloto , Netilmicina , Endoftalmitis/microbiología , Cloranfenicol , ConjuntivaRESUMEN
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.
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Blefaritis , Infecciones Estafilocócicas , Humanos , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Vancomicina/farmacología , Vancomicina/uso terapéutico , Netilmicina , Pruebas de Sensibilidad Microbiana , Infecciones Estafilocócicas/tratamiento farmacológico , Staphylococcus , Staphylococcus aureus , Blefaritis/tratamiento farmacológico , Blefaritis/microbiologíaRESUMEN
BACKGROUND: Eye examinations for ROP screening in preterm newborns are characterized by two main problems: infection control and poor tear secretion. Therefore, in order to reduce the risk of ocular infection and to protect the ocular surface, netilmicin eye drops are usually used after the exams. The purpose of our study was to evaluate the safety and tolerability of ozonated-oils eyedrops during the eye examination of preterm babies in the screening for ROP, sparing the use of antibiotics eyedrops. METHODS: All newborn infants that needed to be screened for ROP were divided into two groups: in group A we used topical netilmicin eye drops and in group B ozonated-oils eyedrops. We looked for any sign of conjunctival injection and chemosis, infectious conjunctivitis, blepharoconjunctivitis, erythema, and edema of the eyelids. RESULTS: A total of 162 adverse effects out of 3546 examinations (4,5%) were reported acutely: in group A (1778 examinations), they consisted of 47 reactive conjunctivitis, 3 cases of blepharoconjunctivitis, 30 of eyelids swelling, and 3 infectious conjunctivitis, compared to 39 cases of conjunctival injection, 3 blepharoconjunctivitis, 33 eyelids swelling and 4 infectious conjunctivitis in group B (1768 examinations). No significant differences were found in the comparison of the two groups. CONCLUSIONS: Ozonated-oils eyedrops should be considered a valid and safe alternative for the lubrification of the ocular surface and an adjuvant strategy to further minimize the risk of microbial contamination during screening for ROP.
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Conjuntivitis , Liposomas , Lactante , Humanos , Recién Nacido , Soluciones Oftálmicas/efectos adversos , Netilmicina , Conjuntivitis/inducido químicamente , AceitesRESUMEN
The current study was carried out to investigate metabolic activities and main probiotic characteristics of two Latilactobacillus sakei strains (8.P1 and 28.P2) isolated from pastirma, a highly seasoned, air-dried cured beef. Both strains showed antimicrobial activity against important foodborne pathogens like Listeria monocytogenes, Staphylococcus aureus, Pseudomonas aeruginosa and so forth. For the characterization of antimicrobial activity, the effect of various enzymes, temperature and pH were tested. The results of the tests demonstrated that the antimicrobial activity of strains was based on the production of protein-structured compounds such as bacteriocin or bacteriocin like peptides. In metabolic activity studies, amounts of the lactic acid, proteolytic activity and hydrogen peroxide produced by the 8.P1 and 28.P2 were found to range between 16.09 and 17.32 mg/mL, 0.24 and 0.04 mg/mL and 0.98 and 0.04 µg/mL, respectively. It was also observed that neither strain could produce exopolysaccharide. Both strains were found susceptible to vancomycin, chloramphenicol, gentamicin, tetracycline, and netilmicin sulfate. When the strains are evaluated with respect to their probiotic potential, 28.P2 could tolerate acidic conditions, but 8.P1 showed sensitivity. The survival rate of the strains in the simulated gastric juice and their adhesion abilities were found suitable to stay alive in the gastrointestinal tract and to proliferate in the intestine. The evaluation of all the features of both strains demonstrated that both strains had the potential to be used as a protective culture. In addition, it was observed that 8.P1 and 28.P2 were more suitable as a starter culture and a probiotic candidate respectively.
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Bacteriocinas , Latilactobacillus sakei , Probióticos , Animales , Antibacterianos/farmacología , Bacteriocinas/química , Bovinos , Cloranfenicol , Peróxido de Hidrógeno/farmacología , Ácido Láctico , Netilmicina , Tetraciclinas , VancomicinaRESUMEN
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.
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Catarata , Netilmicina , Humanos , Netilmicina/uso terapéutico , Implantación de Lentes Intraoculares/efectos adversos , Dexametasona/efectos adversos , Hidrogeles/efectos adversos , Calidad de Vida , Inflamación/tratamiento farmacológico , Inflamación/etiología , Soluciones Oftálmicas/uso terapéutico , Método Doble Ciego , Catarata/complicaciones , Complicaciones Posoperatorias/tratamiento farmacológico , Complicaciones Posoperatorias/prevención & control , Resultado del TratamientoRESUMEN
Netilmicin (NET) is an antibiotic widely used in healthcare and agriculture, but it can accumulate in the environment to threat human health. Netilmicin (NET) is an antibiotic used for veterinary purposes, for human therapy and for agricultural purposes. Therefore, there is a need to develop high-sensitive measuring methods to detect NET. Aptamer-based detecting methods are highly sensitive, inexpensive, and portable. In this study, we developed an aptamer-based fluorescence method to detect and quantify NET. NET was first conjugated to magnetic beads by amidation reaction and then NET-coated beads were used as the stationary phase to isolate aptamers by systematic evolution of ligands by exponential enrichment (SELEX) screening method. After ten rounds of SELEX screening, 32 aptamers with NET-binding affinity were obtained and the candidate aptamer APT-21 was finally chosen by comprehensively comparing their secondary structure characters and NET-binding affinity. APT-21 bound to NET with high affinity (Kd = 194.1 nmol/L) and high specificity that it displayed low cross-binding activities on 7 different structural analogs. We also developed a fluorometric assay using SYBR Green I (SG-I) and the APT-21. Key experimental parameters were optimized, including buffer system, SG-I and APT-21 reaction time, SG-I concentration, and aptamer concentration, to improve the detecting sensitivity. Our results suggest that the low limit of detection (LOD) of this method reached a low level of 1.95 nM and it also exhibited a good linear range up to 200 nM. Moreover, we successfully applied our method to detect the NET spiked in tap water and river water with good recoveries in the range from 97% to 111%. In conclusion, our current study isolated a NET-specific aptamer and developed an aptamer-based quantification method, which is promising to apply to detect NET in environmental samples.
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Aptámeros de Nucleótidos , Antibacterianos/análisis , Aptámeros de Nucleótidos/química , Dimaprit/análogos & derivados , Humanos , Netilmicina , Técnica SELEX de Producción de Aptámeros/métodos , AguaRESUMEN
Plazomicin is currently the only next-generation aminoglycoside approved for clinical use that has the potential of evading the effects of widespread enzymatic resistance factors. However, plazomicin is still susceptible to the action of the resistance enzyme AAC(2')-Ia from Providencia stuartii. As the clinical use of plazomicin begins to increase, the spread of resistance factors will undoubtedly accelerate, rendering this aminoglycoside increasingly obsolete. Understanding resistance to plazomicin is an important step to ensure this aminoglycoside remains a viable treatment option for the foreseeable future. Here, we present three crystal structures of AAC(2')-Ia from P. stuartii, two in complex with acetylated aminoglycosides tobramycin and netilmicin, and one in complex with a non-substrate aminoglycoside, amikacin. Together, with our previously reported AAC(2')-Ia-acetylated plazomicin complex, these structures outline AAC(2')-Ia's specificity for a wide range of aminoglycosides. Additionally, our survey of AAC(2')-I homologues highlights the conservation of residues predicted to be involved in aminoglycoside binding, and identifies the presence of plasmid-encoded enzymes in environmental strains that confer resistance to the latest next-generation aminoglycoside. These results forecast the likely spread of plazomicin resistance and highlight the urgency for advancements in next-generation aminoglycoside design.
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Acetiltransferasas/química , Antibacterianos/química , Proteínas Bacterianas/química , Farmacorresistencia Bacteriana/genética , Providencia/enzimología , Sisomicina/análogos & derivados , Acetiltransferasas/genética , Acetiltransferasas/metabolismo , Amicacina/química , Amicacina/metabolismo , Amicacina/farmacología , Antibacterianos/metabolismo , Antibacterianos/farmacología , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Sitios de Unión , Clonación Molecular , Cristalografía por Rayos X , Escherichia coli/genética , Escherichia coli/metabolismo , Expresión Génica , Vectores Genéticos/química , Vectores Genéticos/metabolismo , Humanos , Cinética , Modelos Moleculares , Netilmicina/química , Netilmicina/metabolismo , Netilmicina/farmacología , Unión Proteica , Conformación Proteica en Hélice alfa , Conformación Proteica en Lámina beta , Dominios y Motivos de Interacción de Proteínas , Providencia/química , Providencia/efectos de los fármacos , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Sisomicina/química , Sisomicina/metabolismo , Sisomicina/farmacología , Especificidad por Sustrato , Tobramicina/química , Tobramicina/metabolismo , Tobramicina/farmacologíaRESUMEN
CONTEXT: Isepamicin is a new semisynthetic aminoglycoside derived from gentamicin B and it is effective against Gram negative bacteria. Antibiotic resistance is an emerging problem and new options need for the treatment of infections caused by Gram negative bacteria. AIMS: In this study we aimed to investigate the in vitro efficiency in carbapenem susceptible and nonsusceptible Enterobacterales and Pseudomonas aeruginosa. METHODS AND MATERIAL: A total of 214 isolates of Gram-negative bacteria (Enterobacterales nâ¯=â¯129 and P. aeruginosa nâ¯=â¯85). Identification of the bacteria was tested in Vitek MS (Biomeriux, France). Susceptibility of isepamicin, amikacin, gentamicin, tobramycin and netilmicin was determined by Kirby Bauer disc diffusion method. The breakpoints for susceptibility to isepamicin, amikacin, gentamicin, streptomycin, tobramycin and netilmicin were evaluated according to the Comité de l'Antibiogramme dela Société Française de Microbiologie (CA-SFM) and EUCAST, respectively. Aminoglycoside modifying enzyme (AME) genes were investigated by multiplex PCR method. RESULTS: Isepamicin susceptibility was determined as 92.3% for Enterobacterales and 67% for P. aeruginosa and 94.4% for carbapenem resistant Enterobacterales. The most common AME gene was aac (6')-Ib in both Enterobacterales (76%) and P. aeruginosa (14.1%). Seven of the isepamicin intermediate or resistant isolates were positive aac (6')-Ib in Enterobacterales and P. aeruginosa. CONCLUSIONS: In this study, isepamicin showed good efficiency against both susceptible and carbapenem nonsusceptible Enterobacterales. But amikacin was prior to isepamicin P. aeruginosa isolates. Isepamicin could be a therapeutic option for the infections caused by Enterobacterales.
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Antibacterianos , Bacterias Gramnegativas/efectos de los fármacos , Amicacina , Aminoglicósidos/farmacología , Antibacterianos/farmacología , Carbapenémicos , Gentamicinas/farmacología , Pruebas de Sensibilidad Microbiana , Netilmicina , Pseudomonas aeruginosa/efectos de los fármacos , TobramicinaRESUMEN
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.
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Colistina , Netilmicina , Antibacterianos/farmacología , Farmacorresistencia Bacteriana Múltiple , Humanos , Pruebas de Sensibilidad Microbiana , Nigeria , Prevalencia , TigeciclinaRESUMEN
We studied possible otoprotective effect of drugs widely used for the correction of perinatal hypoxic brain damage in premature infants. The experiments were carried out on immature rabbits with an immature hearing organ. The auditory function was assessed by DPOAE and ABR methods in intact animals and rabbits treated with therapeutic doses of netromycin alone or in combination with the drugs that normalize metabolic processes in the brain (Cortexin, Cogitum, Elkar, vitamin B2, ATP, and cocarboxylase). It was found that the administered drugs produced an otoprotective effect and reduced the severity, but did not eliminate the ototoxic effect.
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Ácido Aspártico/análogos & derivados , Carnitina/farmacología , Péptidos y Proteínas de Señalización Intercelular/farmacología , Netilmicina/efectos adversos , Ototoxicidad/prevención & control , Sustancias Protectoras/farmacología , Adenosina Trifosfato/farmacología , Animales , Animales Recién Nacidos , Ácido Aspártico/farmacología , Carnitina/análogos & derivados , Potenciales Evocados Auditivos del Tronco Encefálico/efectos de los fármacos , Potenciales Evocados Auditivos del Tronco Encefálico/fisiología , Netilmicina/antagonistas & inhibidores , Emisiones Otoacústicas Espontáneas/efectos de los fármacos , Emisiones Otoacústicas Espontáneas/fisiología , Ototoxicidad/fisiopatología , Conejos , Riboflavina/farmacología , Tiamina Pirofosfato/farmacologíaRESUMEN
Orofacial infections are considered as one of most common infections and need rapid and adequate treatment as they affect a very delicate region and are associated with serious life-threatening complications. Orofacial infections can be either odontogenic that is with an origin in teeth and associated structures or non-odontogenic, not associated with teeth, can affect facial spaces and spread from one space to another, so a good knowledge about diagnosis and treating these infections is of utmost importance, and can include both non-surgical and surgical treatment. The aim of our study was to determine the most common cause of orofacial infections, the most common bacterial microorganisms and their antibiotic susceptibility. Materials and Methods: A descriptive study was undertaken in the Department of Oral and Maxillofacial Surgery, Al-Shaheed Ghazi Al-Hariry Hospital, Baghdad, Iraq from 1st January to 30th September 2015. This study included 45 patients with different forms of orofacial infections; data regarding age, gender, underlying cause, facial space involvement, presenting signs were collected through history, clinical examination and radiographs, incision and drainage with swab sample for culture and sensitivity test was performed. Results: Patients with orofacial infections showed a female to male ratio of 1.25:1. The mean age was 32.8 years. Most of the patients were in their 4th decade of life (27%). Most infections were odontogenic in origin (62%), the most common facial space involved was submandibular (65%), the most common isolated microorganism was Streptococcus pyogenes (59%), and most patients were treated using an extra-oral surgical approach (78%). Antibiotics to which bacterial isolated showed the most sensitivity were netilmicin, cefoperazone and rifampicin (91%). Pain and limitation of mouth opening gradually decreased in most of patients during the two weeks follow up period. Conclusion: Orofacial infections were more common in females, in the third and fourth decade of life, were odontogenic in origin, were mostly caused by Streptococcus pyogenes, and most isolates were susceptible to netilmicin, cefoperazone and rifampicin. Pain and trismus decreased over two weeks post-treatment.
Las infecciones orofaciales se consideran una de las infecciones más comunes y necesitan un tratamiento rápido y adecuado, ya que afectan una región muy delicada y se asocian con complicaciones graves que amenazan la vida. Las infecciones orofaciales pueden ser odontogénicas que se originan en los dientes y las estructuras asociadas, o no odontogénicas, no asociadas con los dientes, pueden afectar los espacios faciales y propagarse de un espacio a otro, por lo que un buen conocimiento sobre el diagnóstico y el tratamiento de estas infecciones es de suma importancia, y puede incluir tratamiento no quirúrgico y quirúrgico. El objetivo de nuestro estudio fue determinar la causa más común de infecciones orofaciales, los microorganismos bacterianos más comunes y su susceptibilidad a los antibióticos. Material y Métodos: se realizó un estudio descriptivo en el Departamento de Cirugía Oral y Maxilofacial, Hospital Al-Shaheed Ghazi Al-Hariry, Bagdad, Iraq del 1 de enero al 30 de septiembre de 2015. Este estudio incluyó a 45 pacientes con diferentes formas de infecciones orofaciales; Se recopilaron datos sobre edad, sexo, causa subyacente, afectación del espacio facial, signos de presentación a través de la historia, examen clínico y radiografías, incisión y drenaje con muestra de hisopo para cultivo y prueba de sensibilidad. Resultado: Los pacientes con infecciones orofaciales mostraron una relación mujer/hombre de 1.25: 1. La edad media fue de 32,8 años. La mayoría de los pacientes estaban en su cuarta década de vida (27%). La mayoría de las infecciones fueron de origen odontogénico (62%), el espacio facial más común involucrado fue submandibular (65%), el microorganismo aislado más común fue Streptococcus pyogenes (59%), y la mayoría de los pacientes fueron tratados con un abordaje quirúrgico extraoral (78%). Los antibióticos a los que las bacterias aisladas mostraron mayor sensibilidad fueron netilmicina, cefoperazona y rifampicina (91%). El dolor y la limitación de la apertura de la boca disminuyeron gradualmente en la mayoría de los pacientes durante el período de seguimiento de dos semanas. Conclusión:Las infecciones orofaciales fueron más comunes en las mujeres, en la tercera y cuarta década de la vida, fueron de origen odontogénico, fueron causadas principalmente por Streptococcus pyogenes y la mayoría de los aislamientos fueron susceptibles a la netilmicina, cefoperazona y rifampicina. El dolor y el trismo disminuyeron durante las dos semanas posteriores al tratamiento.
Asunto(s)
Humanos , Masculino , Femenino , Preescolar , Niño , Adolescente , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Adulto Joven , Enfermedades Periodontales/terapia , Enfermedades Maxilomandibulares/etiología , Control de Infección Dental , Streptococcus pyogenes , Infecciones Bacterianas , Farmacorresistencia Microbiana , Netilmicina/uso terapéutico , Enfermedades Maxilomandibulares/cirugía , Epidemiología Descriptiva , Irak , Angina de Ludwig/terapia , Antibacterianos , Antibacterianos/uso terapéuticoRESUMEN
PURPOSE: To compare the immunosuppressive and cytotoxic effects of three anti-inflammatory eye drops formulations containing betamethasone plus chloramphenicol (B+C), dexamethasone plus netilmicin (D+N) or dexamethasone plus tobramycin (D+T).Methods: The eye drops formulations have been tested at different dilutions on cytokine synthesis by mouse or human cultured macrophages, as well as proliferation and viability of cultured human corneal cells (HCE).Results: B+C reduced IL6 and TNFα production by cultured mouse or human macrophages more potently than D+N and D+T, with the tree formulations having the same impact on IL-10 expression. We also found that the eye drops preparations reduced proliferation of HCE cells, with D+T showing the higher anti-proliferative potency and B+C showing the lower cytotoxic potential.Conclusion: Our study points out that it may be erroneous to consider routinely-used anti-inflammatory eye drops preparations with analogous formulations as readily interchangeable and of similar potency and tolerability.
Asunto(s)
Antibacterianos/toxicidad , Epitelio Corneal/efectos de los fármacos , Glucocorticoides/toxicidad , Macrófagos/efectos de los fármacos , Administración Oftálmica , Animales , Betametasona/toxicidad , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Cloranfenicol/toxicidad , Citocinas/metabolismo , Dexametasona/toxicidad , Combinación de Medicamentos , Epitelio Corneal/metabolismo , Células HeLa , Humanos , Macrófagos/metabolismo , Ratones , Netilmicina/toxicidad , Soluciones Oftálmicas , Tobramicina/toxicidadRESUMEN
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/12â¯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 1â¯×â¯106/20⯵l 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 24â¯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.
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Queratitis por Acanthamoeba/parasitología , Acanthamoeba/efectos de los fármacos , Antiinfecciosos/administración & dosificación , Acanthamoeba/aislamiento & purificación , Queratitis por Acanthamoeba/tratamiento farmacológico , Adulto , Animales , Antibacterianos/administración & dosificación , Antibacterianos/farmacología , Antiinfecciosos/farmacología , Antifúngicos/administración & dosificación , Antifúngicos/farmacología , Clorhexidina/farmacología , Lentes de Contacto/efectos adversos , Lentes de Contacto/parasitología , Perros , Femenino , Humanos , Concentración 50 Inhibidora , Itraconazol/administración & dosificación , Itraconazol/farmacología , Células de Riñón Canino Madin Darby , México , Ratones , Ratones Endogámicos BALB C , Midriáticos/administración & dosificación , Netilmicina/administración & dosificación , Netilmicina/farmacología , Pruebas de Sensibilidad Parasitaria , Fenilefrina/administración & dosificación , Tropicamida/administración & dosificación , Voriconazol/farmacologíaRESUMEN
INTRODUCTION: Aminoglycoside resistance (AR) is common in health care-associated methicillin-resistant Staphylococcus aureus (HA-MRSA). AR is most often associated with the production of antibiotic modifying enzymes: bidomain AAC(6')-Ie/APH(2â³)-Ia acetyltransferase and phosphotransferase, ANT(4')-Ia nucleotidyltransferase, and APH(3â³)-IIIa phosphotransferase. AIM: Determination of aminoglycoside sensitivity, presence of genes encoding enzymes, and molecular typing of HA-MRSA strains derived from patients hospitalized in surgical and transplantation wards. MATERIALS AND METHODS: Fifty-four HA-MRSA strains, isolated from various materials from patients in the surgical and transplantation wards of Warsaw's clinical hospital, hospitalized between 1991 and 2007. The MIC values of gentamicin-GEN/tobramycin-TOB/amikacin-AK/netilmicin-NET were determined by the E-test (CLSI/EUCAST). Genes mecA/aacA-aphD/aadD/aph(3â³)-IIIa were detected using PCR. SCCmec types were determined according to the Oliveira method and the sequence type (ST)/clonal complex (CC) by the MLST method. RESULTS: Of the isolates tested, 36 (66.7%) showed resistance to at least one aminoglycoside: TOB (57.4%), GEN (53.7%), AK (55.6%), NET (24.1%). The aacA-aphD gene was present in 29 MRSA-GEN-R (most often in combination with aadD, 15/29 or aph(3â³)-IIIa, 10/29); the aacA-aphD gene was the only determinant of resistance in 1 isolate. The AR variants mainly belonged to the CC8 clonal complex (ST239/247/241/254/8) and most frequently contained SCCmec type III (3A) cassettes. CONCLUSIONS: Resistance to at least one aminoglycoside was present in 66.7% of HA-MRSA and in more than 22% to all of them. The presence of the aacA-aphD gene was sufficient to express the resistance phenotype to GEN/TOB/AK/NET. Resistant isolates were closely related to each other.
Asunto(s)
Aminoglicósidos/farmacología , Antibacterianos/farmacología , Proteínas Bacterianas/efectos de los fármacos , Kanamicina Quinasa/efectos de los fármacos , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Amicacina/farmacología , Proteínas Bacterianas/aislamiento & purificación , Gentamicinas/farmacología , Unidades Hospitalarias , Hospitales , Humanos , Kanamicina Quinasa/aislamiento & purificación , Staphylococcus aureus Resistente a Meticilina/genética , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Pruebas de Sensibilidad Microbiana , Tipificación de Secuencias Multilocus , Netilmicina/farmacología , Nucleotidiltransferasas/efectos de los fármacos , Nucleotidiltransferasas/aislamiento & purificación , Proteínas de Unión a las Penicilinas/efectos de los fármacos , Proteínas de Unión a las Penicilinas/aislamiento & purificación , Estudios Retrospectivos , Infecciones Estafilocócicas , Tobramicina/farmacologíaRESUMEN
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.
Asunto(s)
Antiprotozoarios/farmacología , Evaluación Preclínica de Medicamentos/métodos , Sinergismo Farmacológico , Leishmania/efectos de los fármacos , Leishmaniasis/tratamiento farmacológico , Netilmicina/farmacología , Suramina/farmacología , Animales , Línea Celular Tumoral , RatonesRESUMEN
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.