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PubMed1981

Comparison of an immunoassay and a microbiological assay for tobramycin serum concentrations.

An enzyme multiplied immunoassay technique (EMIT) and a microbiological assay were compared as methods for determining the concentration of tobramycin in human serum. Tobramycin sulfate in various concentrations (0.4-20.0 microgram/ml) was dissolved in lyophilized human serum. Tobramycin concentration was determined by EMIT assay and a microbiological agar diffusion assay using Bacillus subtilis ATCC 6633 as the test organism. Serum samples of 162 patients who received tobramycin 60 mg i.m. were also assayed by the two methods. The effect of six antibiotics on the determination of tobramycin concentration by EMIT assay was measured. To test whether freezing affects tobramycin concentration measured by EMIT assay, tobramycin in five concentrations in lyophilized human serum were frozen and analyzed at weekly intervals for seven weeks. The concentration of tobramycin determined by EMIT assay and microbiological assay in both lyophilized human serum and patient samples were highly correlated (r = 0.994 and 0.949) respectively). Dibekacin, an aminoglycoside structurally similar to tobramycin, interfered with the determination of tobramycin concentration. No effect of freezing was observed. The results of this study show that EMIT assay is an acceptable method for routine laboratory analysis of tobramycin serum concentration. It is as accurate as the microbiological assay tested.

Anti-Bacterial Agents↗
PubMed1995

Tobramycin Serum Concentrations After Aerosol and Oral Administration in Cystic Fibrosis.

We sought to describe tobramycin absorption after aerosol administration to cystic fibrosis (CF) subjects. Serum tobramycin concentrations were determined by modification of the radioimmuno-assay (RIA) technique, lowering the limit of detection from 1.0 &mgr;g ml(minus sign1) to 0.05 &mgr;g ml(minus sign1). In 37 studies, after aerosol delivery of 666 plus minus 195 mg to the airway of 24 patients, in which 222 samples were assayed, only 1 serum sample contained tobramycin at a concentration greater than 1.0 &mgr;g ml(minus sign1). Twenty-six of the 37 studies permitted estimation of pharmacokinetic parameters of tobramycin. The serum clearance of tobramycin following aerosol adminstration is 39.13 plus minus 0.393 L h(minus sign1) (mean plus minus standard error of the mean), with an elimination half-life of 3.072 plus minus 0.194 h. The half-life was significantly longer than that found after intravenous adminstration. The elimination rate constant (K(e)) was calculated to be 0.234 plus minus 0.002 h(minus sign1). Estimated total-body clearance in which systemic absorption was determined from sputum and urinary recovery of tobramycin was 0.094 plus minus 0.002 1 hr(minus sign1) kg(minus sign1). We also studied tobramycin absorption in six CF subjects after ingestion of a 80-mg m(minus sign2) dose, to gain insight into the tobramycin levels observed after swallowing an aerosol. Four out of the six subjects had measurable serum tobramycin concentration after ingestion. The serum concentration-time curve mirrored what was seen after aerosol administration. We concluded that tobramycin has poor systemic absorption in CF subjects after aerosol administration. Tobramycin in serum after aerosol administration is in part due to the gastrointestinal absorption of swallowed drug, as well as absorption from lower respiratory tract.

Journal Article↗
PubMed1988

Moxalactam vs tobramycin-clindamycin. A randomized trial in secondary peritonitis.

One hundred five patients with peritonitis were randomized to receive either tobramycin sulfate plus clindamycin phosphate or moxalactam alone before surgical intervention. Fifty-nine patients were evaluable. A mean of 3.1 (moxalactam) and 3.5 (tobramycin-clindamycin) pathogens per patient were identified. Overall success rate was 85% (tobramycin-clindamycin, 24/30; moxalactam, 26/29). When patients with appendicitis were excluded, there was an observed but not statistically significant advantage of moxalactam over tobramycin-clindamycin (85% vs 67%). There were five deaths (tobramycin-clindamycin, four; moxalactam, one). Other complications included hypoprothrombinemia (tobramycin-clindamycin, five; moxalactam, five), renal dysfunction (tobramycin-clindamycin, three; moxalactam, one), and superinfection (tobramycin-clindamycin, nine; moxalactam, six). More wound infections were noted in the group given tobramycin-clindamycin. These data suggest that moxalactam is as safe and efficacious as tobramycin plus clindamycin. The observed benefits of this agent warrant study in a larger sample to verify advantages of moxalactam over combination therapy.

Abscess↗
PubMed1982

Tobramycin nephrotoxicity: failure of cefotaxime to potentiate renal toxicity.

The aim of our prospective clinical study was to determine whether the combination of tobramycin plus cefotaxime is more nephrotoxic than tobramycin alone. The studies were carried out in 30 patients with serious infections and normal renal function. Groups of ten patients each received either 2 g cefotaxime or 1 mg/kg body weight tobramycin or cefotaxime and tobramycin in the same dosage every eight hours intravenously for at least seven days. Serum creatinine, creatinine clearance and alanine aminopeptidase (AAP) excretion in 24-hour urine were determined before, during and five days after the antibiotics had been discontinued. These were used as parameters for glomerulotubular injury. The plasma levels of tobramycin and cefotaxime (assayed by agar diffusion) did not differ when the drugs were given alone or in combination. None of the patients treated with cefotaxime alone showed any signs of renal damage. In contrast, tobramycin alone or in combination with cefotaxime caused an increase in urinary enzymes in all patients. This activity was a mean five to six times greater than the initial values prior to antibiotic therapy. There were no significant differences between the AAP increase during treatment with tobramycin and tobramycin plus cefotaxime. Four to five days after discontinuing antibiotic therapy, AAP activity decreased to values similar to those measured prior to therapy. In some of the patients receiving tobramycin alone or in combination with cefotaxime, increased creatinine levels, a reduction in creatinine clearance to 60 ml/min and an increase in renal enzyme excretion could be observed. Thus, treatment with high doses of cefotaxime does not seem to increase tobramycin nephrotoxicity in patients with normal renal function. The nephrotoxicity of this drug combination is obviously due to the aminoglycoside.

Adolescent↗
PubMed1999

Tobramycin penetration into epithelial lining fluid of patients with pneumonia.

OBJECTIVE: To study the penetration of tobramycin in lung tissue evaluated as the concentration in epithelial lining fluid and to characterize the time course of the drug in the treatment of patients with pneumonia. METHODS: The subjects were 16 patients with pneumonia and taking tobramycin who had clinical indications for bronchoscopy. Bronchoscopy with bronchoalveolar lavage of the pneumonic area was performed once on each patient 1/2%, 2, 4, or 8 hours after the previous tobramycin dose. Urea was used as an endogenous marker for quantification of epithelial lining fluid obtained at bronchoalveolar lavage. Tobramycin concentrations in serum were measured for all patients at the aforementioned 4 time points. Tobramycin concentration was determined by means of fluorescent polarization immunoassay modified for bronchoalveolar samples. RESULTS: Levels of tobramycin in the fluid of the epithelial lining were 2.33+/-0.5 at 1/2 hour, 1.67+/-0.6 at 2 hours, 1.62+/-1.19 at 4 hours, and 0.77+/-0.38 microg/mL at 8 hours. The ratio of epithelial lining fluid to serum concentration of tobramycin was 0.30+/-0.03 at 1/2 hour, 0.42+/-0.16 at 2 hours, 0.64+/-0.37 at 4 hours, and 1.53+/-0.76 at 8 hours. The ratio at peak serum time was similar to that reported for tobramycin and netilmicin. CONCLUSIONS: High peak serum concentrations of tobramycin are necessary to obtain microbiologically active concentrations at the alveolar level. The fluid of the epithelial lining constitutes a deep compartment for aminoglycosides. The disappearance of tobramycin was slower than at the serum level.

Adult↗
PubMedDate not supplied

The in vitro elution characteristics of vancomycin and tobramycin from calcium sulfate beads.

The purpose of this study was to determine the elution characteristics of vancomycin and tobramycin when mixed with calcium sulfate to form antibiotic beads. Calcium sulfate was combined with vancomycin and tobramycin separately to form 2 types of antibiotic beads, which were packaged and labeled separately. The packaged calcium sulfate beads with vancomycin and tobramycin were then gas sterilized. The beads were placed in phosphate-buffered saline and kept at 36 degrees C for 6 weeks. Two separate series of assays were run simultaneously for both types of beads. In one assay, a bead containing vancomycin was placed in a fresh vial of phosphate buffered saline after each assay. The same was done with beads containing tobramycin. In the second series of assays, 9 vials of phosphate buffered saline each containing 1 vancomycin bead and 9 vials of phosphate buffered saline each containing 1 tobramycin bead was arranged. The phosphate-buffered saline was then assayed at predetermined times for both the vancomycin bead series and the tobramycin bead series. The amount of vancomycin and tobramycin assayed nearly equaled the calculated amount of antibiotic per bead measured before bead construction. Also, the elution of antibiotic from the calcium sulfate was complete within 72 hours. In conclusion, the construction and gas sterilization of calcium sulfate beads containing vancomycin and tobramycin does not destroy vancomycin and tobramycin. Also, the complete elution of available vancomycin and tobramycin in calcium sulfate beads occurs within 72 hours.

Anti-Bacterial Agents↗
PubMed1993

Efficacy of aerosolized tobramycin in patients with cystic fibrosis.

BACKGROUND: Direct aerosol delivery of aminoglycosides such as tobramycin to the lower airways of patients with cystic fibrosis may control infection with Pseudomonas aeruginosa and improve pulmonary function, with low systemic toxicity. We conducted a randomized crossover study to evaluate the safety and efficacy of aerosolized tobramycin in patients with cystic fibrosis and P. aeruginosa infections. METHODS: Seventy-one patients with stable pulmonary status were recruited from seven U.S. centers for the treatment of cystic fibrosis and randomly assigned to one of two crossover regimens. Group 1 received 600 mg of aerosolized tobramycin for 28 days, followed by half-strength physiologic saline (placebo) for two 28-day period. Group 2 received placebo for 28 days, followed by tobramycin for two 28-day periods. Pulmonary function, the density of P. aeruginosa in sputum, ototoxicity, nephrotoxicity, and the emergence of tobramycin-resistant P. aeruginosa were monitored. RESULTS: In the first 28-day period, treatment with tobramycin was associated with an increase in the percentage of the value predicted for forced expiratory volume in one second (9.7 percentage points higher than the value for placebo; P < 0.001), forced vital capacity (6.2 percentage points higher than the value for placebo; P = 0.014), and forced expiratory flow at the midportion of the vital capacity (13.0 percentage points higher than the value for placebo; P < 0.001). A decrease in the density of P. aeruginosa in sputum by a factor of 100 (P < 0.001) was found during all periods of tobramycin administration. Neither ototoxicity nor nephrotoxicity was detected. The frequency of the emergence of tobramycin-resistant bacteria was similar during both tobramycin and placebo administration. CONCLUSIONS: The short-term aerosol administration of a high dose of tobramycin in patients with clinically stable cystic fibrosis is an efficacious and safe treatment for endobronchial infection with P. aeruginosa.

Adolescent↗
PubMed1999

Operator error: a critical determinant of false amikacin and tobramycin concentrations using fluorescence polarization immunoassay kits and TDX analyzer.

Amikacin and tobramycin are aminoglycosides used to treat severe Gram-negative infections. Therapeutic monitoring of both drugs is essential to avoid drug toxicity. Fluorescence polarization immunoassay kits for both amikacin and tobramycin are available from Abbott Laboratories, and assays can be run using the TDx analyzer. The test code for amikacin is 3, whereas the test code for tobramycin is 2. Here the authors report that when the operator mistakenly programmed test code 3 (amikacin code) while using the tobramycin kit, the tobramycin values were falsely elevated. The instrument software does not have any mechanism to detect this error. Similarly, when the amikacin kit was used and the operator mistakenly programmed test code 2 (tobramycin code), the amikacin values were falsely lowered. For example, in a serum sample taken from a patient the true amikacin concentration was 20.9 microg/mL. When the amikacin kit was used correctly but test code 2 was programmed, the observed concentration was falsely lowered to 6.1 microg/mL. Similarly, in another specimen the true tobramycin concentration was 3.1 microg/mL. However, when the tobramycin kit was used correctly but test code 3 was used, the observed concentration was falsely elevated to 14.3 microg/mL. The authors also observed a similar effect with controls and spiked specimens containing either amikacin or tobramycin. They conclude that correct programming of the test code is vital to obtaining useful results in amikacin and tobramycin analysis using the TDx analyzer.

Amikacin↗
PubMed2006

Pharmacokinetic profile of once daily intravenous tobramycin in children with cystic fibrosis.

AIM: Once-daily tobramycin in patients with cystic fibrosis (CF) is a more convenient dosing regimen than thrice daily dosing. There are limited data on the pharmacokinetic (PK) profile for once-daily tobramycin in patients with CF. The aim of this study was to define the PK parameters for once-daily tobramycin in children with CF and develop an algorithm for therapeutic drug monitoring dosing. METHODS: CF patients admitted to hospital were commenced on once-daily intravenous tobramycin (12 mg/kg/day) and ticarcillin/clavulinic acid. Serum tobramycin levels were taken at 30 min, 2-4 h and 12 h post dose. Data points for the PK model included: age, sex, weight, tobramycin dose, time of tobramycin doses and levels, tobramycin levels. WinNonMix was used to obtain the PK parameters. RESULTS: Forty-four children with 86 admissions who were aged 9 months-20 years were included. A one-compartment intravenous infusion model with first order elimination kinetics produced the best model. Population parameters were: volume of distribution (V(d)) = 0.267 L/kg (95% confidence interval (CL) 0.260-0.272), clearance (CL) 0.103 L/kg/h (95% CI 0.098-0.107) and half-life (t(1/2)) 1.82 (95% CI 1.77-1.88) h. Once the population model was established post hoc analysis was used to calculate individual subject predictions. Plots of individual prediction curves agreed well with observed values. CONCLUSION: This study has established an algorithm for routine monitoring of once-daily tobramycin in children with CF. Satisfactory serum levels of tobramycin were obtained with a dose of 12 mg/kg/day and a regimen algorithm that uses only one measurement to monitor the plasma concentration is suggested.

Adolescent↗
PubMed1984

Hydroxylamine technique for in vitro prevention of penicillin inactivation of tobramycin.

Hydroxylamine was evaluated and found to be a highly effective agent for the in vitro prevention of penicillin inactivation of tobramycin. This inactivation reaction resulted in an underestimation of tobramycin concentrations and was dependent on time, temperature, amount and type of penicillin, and amount of tobramycin. Plasma samples containing tobramycin and three clinically relevant concentrations of ticarcillin, carbenicillin, azlocillin, or piperacillin were incubated with and without hydroxylamine, and tobramycin concentrations were monitored at 0, 12, 24, 48, and 72 h. The inactivation reaction was found to be completely inhibited by hydroxylamine (1 mg/ml) compared with a 27 to 50% loss of measured tobramycin concentration in the unprotected tobramycin-penicillin samples. Hydroxylamine did not interfere with the Emit enzyme immunoassay (Syva Co.) at either high or low tobramycin concentrations. Hydroxylamine was effective in inhibiting the tobramycin inactivation at both room and refrigerator temperatures and was 100% effective in protecting tobramycin on a 1:1 molar basis.

Azlocillin↗
PubMed1994

Pulmonary retention of free and liposome-encapsulated tobramycin after intratracheal administration in uninfected rats and rats infected with Pseudomonas aeruginosa.

The pulmonary residence time of free and liposome-encapsulated tobramycin was studied with uninfected rats and rats infected with Pseudomonas aeruginosa. Chronic infection in lungs was established by intratracheal administration of 10(8) CFU of P. aeruginosa PA 508 prepared in agar beads. After 3 days, a single dose (300 micrograms) of free or liposome-encapsulated tobramycin was given intratracheally to both infected and uninfected rats. At various time intervals (0.25 to 16 h) after drug instillations, the remaining tobramycin was evaluated in blood, lungs, and kidneys by a microbiological assay. Intratracheal instillation of liposome-encapsulated tobramycin resulted in high and sustained levels of tobramycin in lungs of uninfected and infected rats over the 16-h period studied; however, the tobramycin levels were two times higher in uninfected rats. There was no tobramycin detected in the blood or kidneys from these animals. In contrast, the intratracheally instilled free tobramycin was cleared within 3 and 1 h from the lungs of uninfected and infected animals, respectively. These data suggest that the encapsulation of tobramycin in liposomes can result in a significant increase of its residence time within lungs. This study also shows that pulmonary infection was associated with a lowering of tobramycin levels in lungs.

Animals↗
PubMed1992

Lack of in vitro inactivation of tobramycin by imipenem/cilastatin.

OBJECTIVE: Inactivation of aminoglycosides by beta-lactam antimicrobials both in vitro and in vivo has been documented. Such an interaction has not previously been documented between carbapenems and aminoglycosides. Examination of serum concentrations of tobramycin in a patient receiving both agents suggested that this interaction might exist. The purpose of this study was to look at this question in an in vitro model. METHODS: Low concentrations of tobramycin (10 micrograms/mL) were incubated with imipenem/cilastatin (concentrations of 10, 20, and 40 micrograms/mL) in human serum at 37 degrees C. Aliquots of these solutions were withdrawn at 0, 6, 24, 72, and 120 hours and assayed for tobramycin concentrations using a fluorescence polarization immunoassay. Aliquots of tobramycin 10 micrograms/mL and carbenicillin 200 micrograms/mL were analyzed in the same manner, as a positive control. High concentrations of tobramycin (800 micrograms/mL) and imipenem (5000 micrograms/mL)/cilastatin were incubated together at 21 degrees C and sampled at 0, 6, 24, and 72 hours for tobramycin concentrations. RESULTS: The degradation rates for low-concentration tobramycin and the various concentrations of imipenem/cilastatin were not statistically different from those of the controlled incubations. In contrast, carbenicillin significantly enhanced the degradation rate of tobramycin at this concentration (half-life 72 hours and a 34 percent loss at 24 hours, p = 0.0028). Higher in vitro concentrations of imipenem (5000 micrograms/mL)/cilastatin and tobramycin (800 micrograms/mL) resulted in significant, but moderate degradation over controlled incubations (half-life 80 hours and 10 percent loss at 12 hours, p = 0.0031). CONCLUSIONS: These results suggest that inactivation of tobramycin is not a problem at common clinically achievable imipenem serum concentrations in patients.

Anti-Bacterial Agents↗
PubMed2003

Inhalation of a dry powder tobramycin PulmoSphere formulation in healthy volunteers.

STUDY OBJECTIVES: To evaluate the efficiency and reproducibility of pulmonary delivery of an investigational tobramycin PulmoSphere formulation (PStob) [Inhale Therapeutic Systems; San Carlos, CA] by a passive dry powder inhaler, and to compare serum concentrations and whole-lung deposition with a commercial nebulized tobramycin product (TOBI; Chiron Corporation; Seattle, WA). DESIGN: A five-period, open-label, nonrandomized crossover study. PARTICIPANTS: Fourteen healthy volunteers were studied, and 12 completed the study. INTERVENTIONS: PStob powder was manufactured using lipid-based PulmoSphere technology, producing highly dispersible porous particles. PStob was radiolabeled with (99m)Tc, and in vitro experiments confirmed it as a valid drug marker. To identify whole-lung distribution via scintigraphy, subjects inhaled contents of a single capsule (72 L/min) containing 25 mg of (99m)Tc-labeled PStob (13.5 mg of tobramycin free base) in periods 1 to 3. In period 4, subjects received (99m)Tc nebulized tobramycin, approximately 2.5 mL of 300 mg/5 mL. Deposition and blood samples were obtained. In period 5, six 25-mg doses of unlabeled PStob (81 mg of tobramycin base) were inhaled and blood samples were collected. MEASUREMENTS AND RESULTS: Mean whole-lung deposition of PStob was 34 +/- 6% and nebulized tobramycin was 5 +/- 2%. Peak tobramycin concentration in serum (Cmax) values were 0.6 microg/mL with PStob and 0.28 microg/mL after nebulized tobramycin. Serum area under the curve was 4.4 microg x h/mL vs 2.1 micro g x h/mL for nebulized tobramycin. Median time to Cmax for PStob was comparable to nebulized tobramycin. CONCLUSIONS: The aerosol doses of PStob (25 mg and 150 mg) were well dispersed and tolerated. Serum drug concentrations matched scintigraphy data and were roughly twice that of the comparator. Intrasubject dose variability for three equivalent periods did not exceed 18% relative SD. PStob Cmax (0.6 microg/mL) was well below the toxic threshold (2 micro g/mL).

Administration, Inhalation↗
PubMed1996

Day-night treatment difference of tobramycin serum and intrarenal drug distribution and nephrotoxicity in rats: effects of fasting.

The effects of short-term food deprivation on the serum and renal distribution and nephrotoxicity of tobramycin were studied in female Sprague-Dawley rats maintained on a 14-h light/10-h dark cycle (light on: 06:00). For the distribution study, a single injection of tobramycin (40 mg/kg, i.p.) was administered at 14:00 or 02:00 to normally fed animals or to animals fasted for 12 h before tobramycin injection; these treatment times correspond to the peak and trough of tobramycin nephrotoxicity as previously determined in other studies. The serum and cortical levels of tobramycin were significantly higher 60, 120, and 240 min after the injection in fasted animals treated at 02:00 compared with normally fed animals treated at the same time (p < 0.05). In animals injected at 14:00, similar levels of tobramycin were measured in both fasted and fed rats. In the nephrotoxicity study, female Sprague-Dawley rats were fasted for 12 h before and 24 h after the timed single injection of tobramycin (150 mg/kg, i.p.). The 24-h urinary excretion of beta-galactosidase was significantly higher in fasted animals treated at 02:00 than in fed rats treated at the same time of day. Seventy-two hours following tobramycin injection, serum creatinine levels and cortical levels of tobramycin were significantly higher in fasted rats treated at 14:00 than at 02:00 and in fed rats treated at 14:00. These data suggest that a short period of food deprivation modulates the temporal variations of tobramycin nephrotoxicity.

Animals↗
PubMed2002

Tobramycin for nebulisation: new formulation. A high price for a small improvement in formulation.

(1) In patients with cystic fibrosis, chronic bronchial infection with Pseudomonas aeruginosa is a major factor in the development of chronic respiratory failure and premature death. (2) Over the last two decades, such patients have commonly received long-term treatment with antibiotic aerosols (mainly tobramycin or colistin, in off-licence uses). (3) Tobramycin solution for nebulisation is the first antibiotic preparation to be licensed in the EU for this indication. (4) Comparative evaluation of antibiotic aerosol therapy for chronic bronchial infections due to P. aeruginosa includes two large trials of nebulised tobramycin. (5) A combined analysis of these two placebo-controlled trials, both lasting 20 weeks, showed that tobramycin aerosol delayed the deterioration of respiratory function and reduced the number of hospitalisations. However, an increase in P. aeruginosa resistance to tobramycin was reported. (6) The file on tobramycin includes no precise criteria for stopping treatment, and no data on the long-term impact of the observed increase in bacterial resistance. (7) The main adverse effects of tobramycin aerosol are tinnitus and voice changes. Deafness has also been reported. (8) The available assessment file does not show whether the risk-benefit ratio of tobramycin aerosol differs from that of other nebulised antibiotics used (off-licence) in this setting. However, tobramycin is the best-assessed nebulised antibiotic for this indication. (9) In practice, tobramycin solution for nebulisation may be considered the reference long-term treatment for chronic pulmonary infections due to P. aeruginosa in patients with cystic fibrosis. Assessment should continue, however, especially regarding the possible impact on mortality and the selection of resistant strains.

Administration, Inhalation↗
PubMed1995

Perioperative ofloxacin vs. tobramycin: efficacy in external ocular adnexal sterilization and anterior chamber penetration.

OBJECTIVE: To compare the efficacy of two treatment regimens, tobramycin drops-erythromycin ointment and ofloxacin drops-placebo ointment, in sterilizing the external ocular adnexa when given perioperatively. A second objective was to determine the aqueous humour concentration of ofloxacin and tobramycin. DESIGN: Randomized double-blinded clinical trial. SETTING: University-affiliated hospital. PATIENTS: Patients aged 18 years or more scheduled to undergo planned cataract surgery who were judged likely to complete the trial. NUMBERS: Of 55 patients enrolled 6 were disqualified and 49 completed the trial. INTERVENTIONS: Preoperative instillation of 10 drops of a 0.3% solution of ofloxacin (26 eyes) or tobramycin (23 eyes) in the operative eye, starting the evening before surgery. Tobramycin-treated eyes received erythromycin ointment after surgery; ofloxacin-treated eyes received petrolatum ointment. Lid and conjunctival swabs were obtained from both eyes on the day before surgery (visit 1), at surgery (visit 2) and on the first postoperative day (visit 3). Aqueous humour samples were obtained from the study eyes at surgery. MAIN OUTCOME MEASURES: Threshold growth of bacteria on culture, aqueous humour concentration of ofloxacin or tobramycin. RESULTS: At visit 1, 96% of all eyes had positive cultures; this result persisted at visits 2 and 3 for the control eyes. For the treated eyes the incidence of positive cultures decreased from visit to visit. By visit 3 lid cultures were positive for 7 (27%) of the ofloxacin-treated eyes and 7 (30%) of the tobramycin-treated eyes; conjunctival cultures were positive for 0 (0%) of the ofloxacin-treated eyes and 1 (4%) of the tobramycin-treated eyes. No significant differences were seen in culture positivity between the treatment groups at any visit. The mean aqueous humour concentration of ofloxacin was significantly higher than that of tobramycin (0.4084 vs. 0.0279 microgram/mL) (p < 0.001). CONCLUSIONS: Both ofloxacin-placebo treatment and tobramycin-erythromycin treatment were more effective than no treatment in sterilizing the external ocular adnexa. The two treatments were equally efficacious in eliminating bacteria, more successfully in the conjunctiva than the lids. Topically administered ofloxacin demonstrated significantly greater anterior chamber penetration than topically administered tobramycin.

Adult↗
PubMed2000

Treatment of chronic suppurative otitis media with topical tobramycin and dexamethasone.

OBJECTIVES: To investigate the safety and efficacy of a topical combination of tobramycin and dexamethasone in a primate model of chronic suppurative otitis media (CSOM) and to explore the contribution of the added topical steroid for the treatment of CSOM. DESIGN: Blinded, randomized, placebo-controlled trial. SUBJECTS: Sixty juvenile cynomolgus monkeys randomized into the following 6 treatment groups of 10 monkeys each: 0.3% tobramycin (group 1), combined 0.3% tobramycin-0.1% dexamethasone (group 2), combined 1.0% tobramycin-0.33% dexamethasone (group 3), 0.1% dexamethasone (group 4), vehicle (group 5), and phosphate-buffered saline solution (group 6). INTERVENTIONS: Chronic suppurative otitis media was established by inoculating the right ear with Pseudomonas aeruginosa. After 4 weeks of drainage, animals were treated according to the group assignment with 3 drops twice daily for 7 weeks. Hearing thresholds were monitored with repeated auditory brainstem response testing (ABR), and clinical response was monitored with repeated otoscopic examinations and cultures throughout the study. Cytocochleograms were evaluated for quantification of outer hair cell loss. RESULTS: Rapid resolution of otorrhea and eradication of P aeruginosa occurred in all groups receiving tobramycin. The inclusion of dexamethasone accelerated the resolution of otorrhea and negative yields of cultures compared with tobramycin alone. Otorrhea and positive culture findings persisted in the groups not treated with topical antibiotic. Results of ABRs at 4 and 8 weeks and cytocochleograms for outer cell hair loss were not affected by drug administration. Perilymph samples collected at the end of the study showed no detectable tobramycin. CONCLUSIONS: Combined tobramycin-dexamethasone ear drops were safe and effective in the monkey CSOM model. Dexamethasone enhanced the efficacy of tobramycin.

Administration, Topical↗
PubMed2000

Inhaled tobramycin and bronchial hyperactivity in cystic fibrosis.

The use of inhaled tobramycin for prophylaxis and treatment of respiratory symptoms in cystic fibrosis (CF) is now widespread. There have been concerns that inhaling the intravenous (I.V.) formulation of tobramycin causes bronchoconstriction. Previous studies using this formulation have either not specified the nebulizing equipment, or studied older, more severely affected patients. This study investigated the incidence of bronchoconstriction with tobramycin inhalation in children with mild to moderate CF. We studied 26 patients between the ages of 7 and 17 years, with mild to moderate CF (20 female). Prior to being placed on prolonged inhaled tobramycin therapy, they underwent a "tobramycin challenge." FEV(1) was measured pre and post challenge. For the test, standard I.V. solution (80 mg/2 mL) diluted with 2 mL of normal saline was nebulized, using the Hudson (Temecula, CA) RCI Updraft II nebulizer. The nebulization lasted 2 min. There was a 3-min "quiet period," following which FEV(1) was measured. A decrease in FEV(1) by at least 10% post-tobramycin inhalation was considered to be a positive test. Results were analyzed using the Pearson Chi-square test. Five of 26 (19%) had a positive reaction to tobramycin. Sixteen of 26 (61.5%) were using salbutamol on a daily basis at the time of testing but not for 48 hr before the challenge, and 16 of 26 (61.5%) had a pre-tobramycin FEV(1) of < or =80%. Neither an FEV(1) of <80% (P = 0.93) nor regular use of salbutamol (P = 0. 34) were associated with a positive tobramycin challenge. This study suggests that, while bronchoconstriction does occur, many patients do not exhibit bronchoconstriction in response to the standard I.V. preparation and, as prior work suggests, this may be reduced further by pretreatment with salbutamol.

Administration, Inhalation↗