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PubMed2002

Decrease in acetylcholine-induced current by neomycin in PC12 cells.

The effects of neomycin, one of the aminoglycoside antibiotics, on the acetylcholine (ACh)-induced current (I(ACh)) were studied in pheochromocytoma cells by using the whole-cell clamp technique. The I(ACh) proved to be generated through neuronal nicotinic receptor. ACh (30 microM) induced an inward current at a holding potential of -80 mV. When cells were treated with neomycin (0.01-1 mM) and ACh (30 microM) simultaneously, an inhibitory effect of neomycin on the peak of I(ACh) was found. This effect was fast, reversible, and concentration dependent. Pretreatment with neomycin for 3-8 min had no effect on the inhibition of I(ACh) induced by neomycin. External application of 0.1 mM neomycin neither shifted the dose-response curve of the peak I(ACh) to the right (dissociation constant (K(d)) = 16.5 microM) nor affected its coefficient (1.8) but inhibited the curve amplitudes by approximately 33%. Stimulated protein kinase C activation by using an exogenous activator produced inhibition of I(ACh), while using protein kinase C inhibitor (PKCI 19-31) had no effect on the inhibition of I(ACh) induced by neomycin. These results suggest that neomycin has an inhibitory effect on I(ACh) without the involvement of phospholipase C. It indicates that neomycin binds to a specific site on the cell membrane, probably on the neuronal nicotinic receptor-coupled channel, and inhibits the I(ACh) in a noncompetitive manner, thus controlling the immediate catecholamine release from the sympathetic cells.

Acetylcholine↗
PubMed1986

Derivatization of primary amines by 2-naphthalenesulfonyl chloride for high-performance liquid chromatographic assay of neomycin sulfate.

A normal phase high-performance liquid chromatographic (HPLC) method has been developed for the assay of neomycin sulfate. The method involves pre-column derivatization with 2-naphthalenesulfonyl chloride (NSCl) followed by extraction in chloroform and chromatography using a normal phase silica column with detection at 254 nm. The standard curve for the HPLC assay of neomycin sulfate is linear with a correlation coefficient of 0.9996 over the range of 0.02 to 0.4 mg/ml. Neomycins B, and C, and neamine can be separated and quantified isocratically with relative standard deviations of 0.92% and 1.4% for neomycin (B + 1/2C) and neamine, respectively. Prednisolone is used as an internal standard to aid in quantification. Mass spectrometric data confirms that neomycin is derivatized at all the six primary amines on the neomycin molecule. Eight lots of neomycin sulfate were used to compare the HPLC [NSCl and 1-fluoro-2,4-dinitrobenzene (DNFB)], gas-liquid chromatographic and microbiological assay methods. The average results of the NSCl-HPLC method fell between those of the microbiological and DNFB-HPLC methods. Also, good correlation of the neomycin C contents in neomycin were obtained between the NSCl-HPLC and DNFB-HPLC methods.

Amines↗
PubMed1995

Prospective evaluation of neomycin serum concentrations after direct corpora cavernosa irrigation during penile prosthesis placement.

OBJECTIVES: To determine if toxic serum levels of neomycin are generated after direct corpora cavernosa irrigation during penile prosthesis placement. METHODS: We have used an infection prophylaxis technique that involves directly irrigating the corpora cavernosa tissue (through the corporotomy) with 0.5% neomycin solution. Serum neomycin concentrations were measured at 1 hour and 4 hours after irrigation in 13 patients undergoing penile prosthesis placement. A subset of patients who had preimplant and postimplant serum creatinine concentrations was evaluated for changes in renal function. RESULTS: The mean 1-hour postirrigation serum neomycin level was 1.2 micrograms/mL and the mean 4-hour postirrigation level was 1.2 micrograms/mL. These serum neomycin concentrations are lower than those thought to be necessary to produce nephrotoxicity or ototoxicity. Renal function was not significantly affected by the neomycin irrigation. CONCLUSIONS: Although aminoglycosides are ototoxic and neomycin has the highest nephrotoxic potential of the aminoglycosides, we conclude that direct irrigation of the corpora cavernosa with 0.5% neomycin solution does not produce significant systemic exposure to result in nephrotoxicity or ototoxicity. One-time prophylactic neomycin irrigation remains an effective, safe, and economic adjunct to penile prosthesis placement.

Creatinine↗
PubMed1972

Bacteria of porcine skin, xenografts, and treatment with neomycin sulfate.

Homogenized 4-mm punch biopsies were taken from pigs and bacteriologically evaluated to determine the efficacy of surgical scrub procedures and the subsequent treatment of tissue with 0.5% neomycin sulfate-sodium bisulfite (neomycin-bisulfite) as a decontaminating agent. The majority of the lots of porcine skin taken directly from animals for xenografts in the treatment of burns contained viable bacteria at the time of grafting although scrubbing procedures substantially reduced the skin bacteria. The porcine bacteria consisted primarily of coagulase-negative staphylococci with most strains exhibiting caseinolytic and elastase activity. Staphylococci were the only abundant bacteria found in postscrub biopsies and in saline solutions used to wash the dermatome during its use. After an overnight exposure of grafting tissue soaked in neomycin-bisulfite, the spent neomycin-bisulfite solutions were tested for bacteriostatic and bactericidal activity by comparison to unused neomycin. All solutions tested were equal in bacteriostatic strength, but the bactericidal action of some spent solutions was decreased. Neomycin alone exerted a more lethal effect on sensitive bacteria than the neomycin-bisulfite solution. The desirability of having viable porcine skin for a xenograft necessitated using or discarding the tissue after storage in neomycin-bisulfite at 4 C for a maximum of 72 hr. Certain contaminating microorganisms were unaffected by antibiotic treatment, and the prolonged use of neomycin without bisulfite would have primarily eradicated only the porcine coagulase-negative staphylococci. Neither the presence of this group in grafting tissue nor their proteolytic activity had any observed adverse effect on xenografting success.

Animals↗
PubMed1988

Absorption of neomycin from the equine uterus: effect of bacterial and chemical endometritis.

Plasma concentrations of neomycin were measured after intrauterine infusion of 3.3 mg/kg neomycin sulphate. Mares infected two hours previously with an intra-uterine infusion of beta-haemolytic streptococci absorbed approximately 12 per cent of the neomycin in both the oestrous and the luteal phases of the cycle. Normal mares in oestrus absorbed 6 per cent of the neomycin infused and luteal mares absorbed 56 per cent. In infected mares the peak plasma concentrations occurred two hours after neomycin infusion, earlier than in healthy mares. Cervical flushings after neomycin infusion in infected luteal mares revealed an increased reflux of neomycin when compared with healthy mares. Prior infusion of 30 ml of 10 per cent Lugol's iodine into the uterus resulted in 31 per cent of neomycin being absorbed by oestrous mares and 64 per cent by mares in the luteal phase. Peak plasma concentrations occurred 30 minutes after infusion in both phases. In the luteal phase the mares' absorption of neomycin may have been maximal.

Absorption↗
PubMed1991

Neomycin mimics the effects of high extracellular calcium concentrations on parathyroid function in dispersed bovine parathyroid cells.

We examined the effects of the polycationic antibiotic, neomycin, on the function of dispersed bovine parathyroid cells. Neomycin caused a reversible, dose-dependent inhibition of low calcium (Ca++)-stimulated PTH release, with half-maximal inhibition at 30 microM. Maximal inhibition (with 200 microM neomycin) was not additive with the suppressive effects of high (2 mM) Ca++. Neomycin also inhibited dopamine-stimulated cAMP accumulation by 90-98% at 100-200 microM, with a half-maximal effect at 40-50 microM. This action was reversible and was blocked by preincubating the cells overnight with 0.5 microgram/ml pertussis toxin. In addition to its suppressive effects on cAMP metabolism and PTH release, neomycin stimulated the accumulation of inositol phosphates and produced a transient increase in the cytosolic Ca++ concentration (Cai) in fura-2-loaded parathyroid cells. The neomycin-evoked spike in Cai persisted despite removal of extracellular Ca++, indicating that it arises from intracellular Ca++ stores. Exposure of cells to elevated magnesium (Mg++) concentrations elicited a similar spike in Cai but blocked the spike in Cai in response to subsequent addition of neomycin and vice versa. Thus, Mg++ and neomycin mobilize Ca++ from the same intracellular store(s). These results indicate that a polycation, neomycin, closely mimics the effects of polyvalent cations on parathyroid function, suggesting that both agents regulate parathyroid function via similar biochemical pathways.

Animals↗
PubMed1992

Neomycin induces stimulatory and inhibitory effects on leukotriene generation, guanine triphosphatase activity, and actin polymerization within human neutrophils.

The effects of neomycin on human neutrophils (PMN) were studied with respect to the generation of leukotrienes, the involvement of guanine triphosphate binding proteins (G proteins) and the polymerization of actin. Incubation of neutrophils with neomycin induced the generation of low amounts of leukotrienes. Co-incubation of neutrophils with neomycin and the direct G-protein activator sodium fluoride (NaF) resulted in an enhanced leukotriene formation at 0.5 mM neomycin and an inhibition at a concentration of 10 mM. Simultaneous incubation with neomycin and formyl-methionyl-leucyl-phenylalanine (FLMP) did not affect the FMLP-induced leukotriene formation. However, pretreatment of neutrophils with 10 mM neomycin followed by the addition of NaF or FMLP resulted in an enhanced generation of leukotrienes. Crude membrane fractions of PMN incubated with neomycin at different concentrations showed an enhanced (0.5 mM) as well as a reduced (10 mM) guanine triphosphatase activity. Furthermore, incubation of neutrophils with neomycin above a concentration of 0.5 mM led to the depolymerization of actin. The presented results show inhibitory and stimulatory effects of neomycin on various cell functions, which may reflect differences in transmembrane signalling.

Actins↗
PubMed1976

Inhibition of digoxin absorption by neomycin.

The effect of the administration of the antibiotic neomycin sulfate on the absorption of digoxin was assessed in crossover studies in normal human volunteers. Doses of neomycin (1 and 3 g) markedly depressed serum digoxin concentrations, the areas under the serum concentration-time curves, and cumulative 6-day urinary digoxin excretion after the oral ingestion of 0.5 mg of the cardiac glycoside in tablet form. Neomycin also prolonged the mean time at which peak serum digoxin levels were attained by 1.7 to 3 hr. The inhibition of digoxin absorption was also seen: (1) when the antibiotic was given 3 or 6 hr before the cardiac glycoside, (2) with digoxin tablets of varying dissolution rate, (3) when digoxin or neomycin solutions were used instead of tablets, and (4) in a patient who had had a total gastrectomy. When neomycin was administered with maintenance doses of digoxin, steady state serum digoxin concentrations were significantly reduced. When neomycin was given after a 9-day period of digitalization, the terminal serum digoxin half-life was not significantly shortened. Single doses of neomycin did not interfere with the extent of absorption of d-xylose. In vitro, neomycin did not affect the movement of digoxin across dialysis membranes, nor did it precipitate digoxin out of human bile or intestinal fluid. Neomycin thus clearly depresses the rate and extent of digoxin absorption in man. The mechanism of this effect remains to be established.

Adult↗
PubMed1979

Interactions of neomycin with monomolecular films of polyphosphoinositides and other lipids.

The interactions of calcium and the aminoglycosidic antibiotic, neomycin, with various lipids were investigated in monomolecular films. Lipids were spread over a subphase of 0.05 M N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid, pH 7.0, and NaCl to give an ionic strength of 0.2. Measurements of surface pressure (pi) were taken with a Wilhelmy balance. In the absence of Ca2+, 1 muM--1 mM neomycin in the subphase decreased pi (i.e. condensed films) of all acidic lipids tested. In the presence of 1 mM Ca2+, neomycin did not change pi of films of phosphatidylserine, phosphatidylinositol and phosphatidic acid while it lowered pi of cardiolipin and cerebroside sulfate films. A unique pattern of interaction was observed with polyphosphoinositide monolayers. In the absence of Ca2+, 1 muM neomycin decreased pi followed by an increase of pi at higher neomycin concentrations. Ca2+ (1 mM) condensed the film significantly more than did neomycin. However, as little as 1 muM neomycin induced expansion of the calcium/lipid film which at 1 mM neomycin reached the same pi as in the absence of Ca2+. Such expansion was observed at all pressures of the film including the collapse pressure indicating a strong 'complex' between the drug and polyphosphoinositide not antagonized by Ca2+. In the absence of possible hydrophobic interactions, both the condensation and the expansion of the film should be mediated by ionic forces. Combined in vivo and in vitro evidence is discussed to suggest the polyphosphoinositides as the physiological receptors for aminoglycosides in the mammalian cell membrane.

Calcium↗
PubMed1993

Neomycin blocks dihydropyridine-insensitive Ca2+ influx in bovine adrenal chromaffin cells.

There is evidence that bovine adrenal chromaffin cells are provided with both dihydropyridine-sensitive and -resistant voltage-sensitive Ca2+ influx pathways. Although recent electrophysiological work indicates that the dihydropyridine-resistant pathway is partially mediated by omega-conotoxin-sensitive and -insensitive Ca2+ channels, the pharmacological sensitivity of the latter channels remains elusive. We have now found that combined incubations with nitrendipine (1 microM) and neomycin (0.5 mM) reduced high K+ (50 mM)-evoked intracellular Ca2+ concentration ([Ca2+]i) transients to a larger extent than each drug separately. [Ca2+]i was measured using the fluorescent intracellular Ca2+ indicator fura-2. Neomycin (0.05-2 mM) reduced high K(+)-evoked 45Ca2+ uptake in a dose-dependent manner (IC50 = 0.09 mM). In the presence of nitrendipine (1 microM), the minimal neomycin concentration necessary for total blockade of 45Ca2+ uptake was reduced to 0.3 mM. Moreover, in the absence of nitrendipine the 45Ca2+ uptake remaining in 0.3 mM neomycin (26% of maximum) was similar to the fractional inhibition by nitrendipine alone (29%). Neomycin (0.05-2 mM) inhibited the [Ca2+]i transient induced by the L-type Ca2+ channel agonist Bay K 8644 (1 microM) much more extensively at 2 mM than at 0.3 mM (percent inhibition = 59% and 15%, respectively). Neomycin (0.05-2 mM) blocked high K(+)-evoked noradrenaline and adrenaline release in a dose-dependent fashion (IC50 = 0.8-1.1 mM), the blockade efficiency being enhanced in the presence of 1 microM nitrendipine (IC50 = 0.17-0.19 mM). It is concluded that neomycin (< or = 0.3 mM) blocks preferentially the dihydropyridine-insensitive Ca2+ influx pathway of the chromaffin cell. Moreover, both the dihydropyridine-sensitive and the dihydropyridine-resistant, neomycin-sensitive Ca2+ influx pathways contribute strongly to depolarization-evoked catecholamine secretion.

Adrenal Medulla↗
PubMed2001

Effects of neomycin on the development of tolerance to morphine antinociception.

The effects of neomycin on the development of tolerance to morphine antinociception were examined in mice. Because neomycin did not readly cross blood brain barrier, we examined the effects of neomycin following systemic, intracerebroventricular (i.c.v.) and intrathecal (i.t.) injections on the morphine tolerance. Daily subcutaneous (s.c.), i.c.v. and i.t. injections of morphine produced tolerance regardless of route of administration. Both i.c.v. and i.t. neomycin, which alone produced no changes in the basal tail flick latencies, significantly attenuated the development of tolerance to antinociception produced by repeated systemic morphine, while intraperitoneal (i.p.) administration of neomycin did not affect morphine tolerance. Further, i.c.v. and i.t. neomycin attenuated the development of tolerance to antinociception produced by repeated i.c.v. and i.t. morphine, respectively, which were not attenuated by systemic neomycin. This results indicate a potential role for neomycin-sensitive Ca2+ channels on the development of tolerance to the morphine antinoception.

Analgesics↗
PubMed1998

Binding of neomycin to the TAR element of HIV-1 RNA induces dissociation of Tat protein by an allosteric mechanism.

Neomycin inhibits the binding of Tat-derived peptides to the trans-activating region (TAR) of HIV-1 RNA. Kinetic studies reveal that neomycin acts as a noncompetitive inhibitor that can bind to the Tat-TAR complex and increase the rate constant (koff) for dissociation of the peptide from the RNA. Neomycin effects a conformational change in the structure of TAR that can be detected by circular dichroism spectroscopy. The increase in ellipticity measured at 265 nm upon binding of the aminoglycoside is opposite to the decrease seen when Tat peptides bind to the RNA. Thus, the structural transition induced by neomycin is apparently incompatible with the binding of Tat and underlies the inhibitory action of the antibiotic. The binding site for neomycin on TAR was identified in ribonuclease protection experiments and is located in the stem immediately below the three-nucleotide bulge that serves as the primary identity element for Tat. Apparent protection of residues in the bulge by neomycin may represent additional contacts to the aminoglycoside, but more likely result from changes in the structure of this region when the ligand binds to the RNA. Binding assays using variants of TAR in which inosine residues were substituted for guanosine residues support the results from the ribonuclease protection experiments. Inosine substitutions in the lower stem, but not the upper stem, decrease the binding constant for neomycin by approximately 100-fold. Neither of these variants affected the binding affinity of Tat peptide. In addition, these latter experiments suggest that the aminoglycoside may be located in the minor groove of the stem. This mode of association may be a critical aspect of neomycin's ability to bind to the Tat-TAR complex and could serve as a guide for the design of other drugs that bind to specific RNA targets as noncompetitive inhibitors.

Allosteric Regulation↗
PubMed2001

Aminoglycoside-nucleic acid interactions: remarkable stabilization of DNA and RNA triple helices by neomycin.

The stabilization of poly(dA).2poly(dT) triplex, a 22-base DNA triplex, and poly(rA).2poly(rU) triple helix by neomycin is reported. The melting temperatures, the association and dissociation kinetic parameters, and activation energies (E(on) and E(off)) for the poly(dA).2poly(dT) triplex in the presence of aminoglycosides and other triplex binding ligands were determined by UV thermal analysis. Our results indicate that: (i) neomycin stabilizes DNA triple helices, and the double helical structures composed of poly(dA).poly(dT) are virtually unaffected. (ii) Neomycin is the most active and triplex-selective stabilization agent among all aminoglycosides, previously studied minor groove binders, and polycations. Its selectivity (DeltaT(m3-->2) vs DeltaT(m2)(-->)(1)) exceeds most intercalating drugs that bind to triple helices. (iii) Neomycin selectively stabilizes DeltaT(m3)(-->)(2) for a mixed 22-base DNA triplex containing C and T bases in the pyrimidine strand. (iv) The rate constants of formation of triplex (k(on)) are significantly enhanced upon increasing molar ratios of neomycin, making triplex association rates closer to duplex association rates. (v) E(on) values become more negative upon increasing concentration of aminoglycosides (paromomycin and neomycin). E(off) values do not show any change for most aminoglycosides except neomycin. (vi) Aminoglycosides can effectively stabilize RNA [poly(rA).2poly(rU)] triplex, with neomycin[being one of the most active ligands discovered to date (second only to ellipticine). (vii) The stabilization effect of aminoglycosides on triple helices is parallel to their toxic behavior, suggesting a possible role of intramolecular triple helix (H-DNA) stabilization by the aminoglycosides.

Aminoglycosides↗
PubMed2004

On the mechanism for neomycin reversal of wortmannin inhibition of insulin stimulation of glucose uptake.

Although a number of studies and approaches have indicated that activation of the Ser/Thr kinase called Akt/protein kinase B is critical for the insulin-stimulated increase of glucose uptake in adipocytes, other studies have indicated that this enzyme may play an ancillary role. For example, a recent study indicated that neomycin would allow insulin-stimulated Glut4 translocation and glucose transport in the presence of the phosphatidylinositol (PI) 3-kinase inhibitor, wortmannin, a known inhibitor of Akt activation (James, D. J., Salaun, C., Brandie, F. M., Connell, J. M. C., and Chamberlain, L. H. (2004) J. Biol. Chem. 279, 20567-20570). To better understand this observation, we examined a number of downstream targets of Akt. As previously reported, treatment of 3T3-L1 adipocytes with neomycin prevented the wortmannin inhibition of insulin-stimulated glucose transport. However, in the presence of neomycin, wortmannin did not inhibit the insulin-stimulated phosphorylation of several downstream targets of Akt including a proline-rich Akt substrate of 40 kDa, ribosomal protein S6, and glycogen synthase kinase-3. In addition, neomycin did not prevent the ability of a structurally unrelated PI 3-kinase inhibitor, LY294002, to inhibit the insulin-stimulated activation of glucose uptake. Moreover, neomycin reversed the inhibitory effect of wortmannin but not LY294002 on insulin stimulation of Akt kinase activity. Finally, neomycin was found to inactivate in vitro the PI 3-kinase inhibitory actions of wortmannin but not LY294002. These results indicate that the effects of neomycin in adipocytes are not mediated via its ability to sequester phosphatidylinositol 4,5-bisphosphate but are instead caused by the ability of neomycin to inactivate wortmannin.

3T3-L1 Cells↗
PubMed1992

Neomycin is an agonist at a polyamine site on the N-methyl-D-aspartate receptor.

Neomycin appears as a full agonist and spermidine as a partial agonist at the site where polyamines enhance 1-[1-(2-thienyl)cyclohexyl][3H]piperidine ([3H]TCP) binding on the N-methyl-D-aspartate (NMDA) receptor. Other aminoglycosides also enhance [3H]TCP binding with efficacies roughly proportional to the number of primary amine groups. The polyamine antagonists ifenprodil and arcaine inhibit enhancement of [3H]TCP binding by spermidine or neomycin. The inhibition of [3H]TCP binding by arcaine is apparently competitively reduced by neomycin and spermidine, supporting a common site. Diethylenetriamine (previously described as a polyamine antagonist) may be a partial agonist. Enhancement by neomycin or spermidine is not additive to that of Mg2+, consistent with competition of Mg2+ and spermidine or neomycin at the site where these compounds enhance [3H]TCP binding. Polyamines also enhance the binding of the competitive antagonist 2-(2-carboxypiperazin-4-yl)[3H]propyl-1-phosphonic acid ([3H]CPP). Neomycin, which does not enhance [3H]CPP binding, inhibits the enhancement by spermidine. That this site is distinct from the site where spermidine and neomycin increase [3H]TCP binding is supported by different pharmacology. Arcaine and diethylenetriamine do not inhibit spermidine enhancement of [3H]CPP binding. Mg2+ also does not compete with the spermidine enhancement of [3H]CPP binding. Ifenprodil inhibits the spermidine enhancement of [3H]CPP binding. The data suggest two or more polyamine sites, with arcaine selective for the site that enhances [3H]TCP binding. Neomycin is an agonist at one polyamine site and antagonist to the second.

Adrenergic alpha-Antagonists↗
PubMed1995

Neomycin blood agar as a selective medium for vancomycin resistant Enterococcus faecium.

Neomycin blood agar is commonly used as a selective medium for the isolation of vancomycin resistant enterococci from faeces; however, not all isolates are recovered using this medium, perhaps because the neomycin concentrations are too high. To test this hypothesis, the neomycin minimum inhibitory concentration (MIC) was determined for 27 vancomycin resistant Enterococcus faecium isolates, 14 from patients with leukaemia and 13 from patients on the renal unit. A further eight isolates that had been recovered from the faeces of patients on the renal unit on neomycin agar were also studied. Eleven of the 14 isolates from the patients with leukaemia showed equal recovery on neomycin agar and blood agar and had MICs > 64 mg/l. In three other isolates there was a 4log10 reduction in recovery on neomycin agar and the MIC was 8 mg/l. Two of the non-selected isolates from the renal unit were recovered equally on the two media, the other 11 isolates showed a 4-5 log10 reduction in recovery. All eight faecal isolates recovered from patients on the renal unit on neomycin agar were highly resistant to neomycin (MIC > 64 mg/l). Comparative studies of screening media are urgently needed as vancomycin resistant enterococci become more prevalent nosocomial pathogens.

Agar↗
PubMed1986

Efficacy of endonasal neomycin-tixocortol pivalate irrigation in the treatment of chronic allergic and bacterial sinusitis.

60 patients, aged 15-51 years, with chronic allergic or bacterial maxillary sinusitis, were entered in a controlled, double-blind study comparing the efficacy of endonasal irrigations of tixocortol pivalate (Pivalone)-neomycin and neomycin. The treatment lasted 11 days and was administered once daily. A ventilometric measurement of sinus pressure was performed every two endonasal irrigations to assess treatment efficacy. The percentage of nasal deobstruction was significantly higher with tixocortol pivalate-neomycin than with neomycin alone by the fifth examination (9th day) regardless of the etiology of the sinusitis (allergic or bacterial). After 11 days of treatment, significantly better results were obtained in cases of bacterial sinusitis (94% deobstruction with tixocortol pivalate-neomycin versus 74% with neomycin) than in cases of allergic sinusitis (69% deobstruction with tixocortol pivalate-neomycin versus 36% with neomycin).

Administration, Intranasal↗
PubMed2006

Once-daily ofloxacin otic solution versus neomycin sulfate/polymyxin B sulfate/hydrocortisone otic suspension four times a day: a multicenter, randomized, evaluator-blinded trial to compare the efficacy, safety, and pain relief in pediatric patients with otitis externa.

INTRODUCTION: Otitis externa (OE) is an infection of the external auditory canal affecting children and adults and is associated with symptoms of local pain and tenderness. Twice-daily topical treatment with ofloxacin otic solution (0.3% [Floxin otic solution]) for 10 days has been reported to be as effective and well tolerated as neomycin sulfate/polymyxin B sulfate/hydrocortisone otic suspension (Cortisporin otic suspension) administered four times daily for 10 days. OBJECTIVE: This study compared the efficacy, safety, and ear-pain resolution of once-daily ofloxacin otic solution (0.3%) versus neomycin sulfate/polymyxin B sulfate/hydrocortisone otic suspension administered four times daily, in children with OE. RESEARCH DESIGN, PATIENTS, AND METHODS: This multicenter, randomized, parallel-group, evaluator-blinded study was conducted at 34 centers in 278 pediatric OE patients aged 6 months to 12 years. Patients received five drops of ofloxacin otic solution (0.3%) in the affected ears once daily or three drops of neomycin sulfate/polymyxin B sulfate/hydrocortisone otic suspension four times daily, for 7-10 days. Patient evaluations were performed at pretherapy (day 1), end of therapy (days 7-9), and test of cure (7-10 days post-treatment) visits. Data for 208 patients were clinically evaluable and those for 90 patients were microbiologically evaluable. Scores were obtained for patient assessments of pain severity. MAIN OUTCOME MEASURES: The overall clinical response was cure in the clinically evaluable patients, demonstrated by resolution of OE signs and symptoms at the test of cure visit. The overall clinical-microbiological response was cure in the microbiologically evaluable patients demonstrated by both clinical cure and microbiological eradication. RESULTS: For the clinically evaluable patients, equivalent cure rates were obtained between the once-daily ofloxacin-treated and four-times-daily neomycin sulfate/polymyxin B sulfate/hydrocortisone-treated patients (93.8% and 94.7%, respectively). For the clinically and microbiologically evaluable patients, the overall cure rates were 96.4% versus 97.1% for the ofloxacin-treated and neomycin sulfate/polymyxin B sulfate/hydrocortisone-treated patients, respectively. The eradication rates for the prevalent pathogen, Pseudomonas aeruginosa, were 98% versus 100% for ofloxacin-treated and neomycin sulfate/polymyxin B sulfate/hydrocortisone-treated patients, respectively. Decreases in pain severity were similar in both treatment groups. Statistical analyses were limited by the small numbers of patients in each treatment group. CONCLUSION: In the treatment of OE in children, once-daily ofloxacin otic solution was as effective and safe as neomycin sulfate/polymyxin B sulfate/hydrocortisone otic suspension given four times daily. The two treatments provide rapid and comparable pain relief; however, ofloxacin otic solution does not have the risk of ototoxicity associated with neomycin and provides effective pain relief without adjunctive steroids.

Administration, Topical↗