For which adverse effect with the nurse be alert in a patient who is taking tobramycin as an antibiotic therapy?

Tobramycin

Tobrex, TOBI, TOBI Podhaler, Bethkis, Kitabis Pak, and generics; previously available as Nebcin

Antibiotic, aminoglycoside

Injection: 10 mg/mL (2 mL), 40 mg/mL (2, 30, 50 mL); may contain phenol and bisulfites

Powder for injection: 1.2 g; preservative free

Ophthalmic ointment (Tobrex): 0.3% (3.5 g)

In combination with dexamethasone (TobraDex): 0.3% tobramycin with 0.1% dexamethasone (3.5 g); contains 0.5% chlorobutanol

Ophthalmic solution (Tobrex and generics): 0.3% (5 mL)

In combination with dexamethasone as an ophthalmic suspension (both products contain 0.01% benzalkonium chloride and EDTA):

TobraDex and generics: 0.3% tobramycin with 0.1% dexamethasone (2.5, 5, 10 mL)

TobraDex ST: 0.3% tobramycin with 0.05% dexamethasone (5 mL)

Nebulizer solution:

Bethkis: 300 mg/4 mL (56s); preservative free

TOBI, Kitabis Pak, and generics: 300 mg/5 mL (56s); preservative free

170 mg/3.4 mL (mixed in 0.45% NS, preservative free, use with eFlow/Trio nebulizer)

Powder for inhalation:

TOBI Podhaler: 28 mg capsules (224 capsules in 4 weekly packs with 2 Podhaler inhalation devices)

General information

Tobramycin closely resembles gentamicin in its microbiological and toxicological properties. The two drugs have similar half-lives, peak serum concentrations, lack of protein binding, volumes of distribution, and predominantly renal excretion by glomerular filtration. The main advantage of tobramycin may be its greater intrinsic activity against Pseudomonas aeruginosa. Not all bacterial strains resistant to gentamicin are invariably also resistant to tobramycin. Because of its inherent potential for ototoxicity and nephrotoxicity, renal function and eighth nerve function should be closely monitored [1,2].

The efficacy and safety of tobramycin solution for inhalation in patients with cystic fibrosis have been reviewed [3]. Cyclical treatment with inhaled tobramycin seems to improve pulmonary function and reduce hospitalization rates and the use of systemic antibiotics.

Tobramycin:

3 mg/kg of body weight/24 hr equally divided into 3 doses and given every 8 hours (1 mg/kg every 8 hours). Up to 5 mg/kg equally divided into 3 or 4 doses may be given in life-threatening infections (1.25 mg/kg every 6 hours or 1.67 mg/kg every 8 hours). Reduce to usual dose as soon as feasible. For obese patients, the dosing weight used to calculate the mg/kg dose is achieved by adding the ideal or lean body weight (IBW) to 40% of the excess over IBW.

Dosing weight = IBW + 0.4 (Total body weight − IBW)

Do not exceed 5 mg/kg/day unless serum levels are monitored.

Studies suggest that in certain populations a single daily dose of 5 to 7 mg/kg (instead of divided into 2 to 3 doses) may provide higher peak levels and enhance drug effectiveness while actually reducing or having no adverse effects on risk of toxicity. Various procedures for monitoring blood levels are in use. Some health facilities are monitoring with trough levels; others may draw levels at predetermined times and plot the concentration on nomograms. Depending on the protocol in place, doses or intervals may be adjusted. SeeDose Adjustments andPrecautions.

Pre-Clinical Research

The antibacterial activity of tobramycin is similar to that of gentamicin. Tobramycin is active against all the Enterobacteriaceae including Escherichia coli, the Enterobacter, Klebsiella,, Proteus, Salmonella, Shigella, Providencia, Serratia, etc. Tobramycin is some 2 to 4 times more active than gentamicin against Pseudomonas aeruginosa and some strains of pseudomonas that are resistant to gentamicin retain sensitivity to tobramycin. Tobramycin has no activity against Mycobacterium tuberculosis or other mycobacteria Kucers et al (1997), Scholar and Pratt (2000), Edson and Terrell (1999).

Inhalation

Tobramycin has been used extensively in cystic fibrosis because of its effect onPseudomonas organisms. Used as an adjunct to intravenous antibiotics in acute infections, it can lower sputum colony counts. Aerosolized antibiotics over prolonged periods can improve lung function and reduce hospital admissions, but they carry the potential risk of drug toxicity and resistance. In a review of clinical studies it was concluded that there was no evidence of nephrotoxicity or ototoxicity [79], although long-term toxicity studies at higher dosages are awaited.

The efficacy of nebulized tobramycin 300 mg bd for 4 weeks has been studied in a randomized, double-blind, placebo-controlled trial in 74 patients with bronchiectasis andPseudomonas infection, without cystic fibrosis [< Fong 81 >]. After 4 weeks there was a significant fall in the density ofPseudomonas infection in the sputum of the treated group. This correlated with an improvement in general medical condition, as assessed subjectively 2 weeks later. There was no difference in lung function. Tobramycin resistance (MIC over 16 μg/ml) developed in 4 patients in the treated group and 1 patient in the placebo group. Adverse events were reported by 31 of the 37 patients in each arm. There were significantly increased incidences of dyspnea (32%), chest pain (19%), and wheezing (16%) in the treated group compared with placebo (8%, 0%, 0% respectively). Cough increased in 15 patients (41%) in the treated group and 9 (24%) in the placebo group. The investigators felt that the majority of these respiratory adverse events had been related to the drug. They commented that these adverse events did not generally result in withdrawal of the patients from the trial. No more details were given but the apparent adverse reactions profile of nebulized tobramycin in this group is of concern.

There was no difference between recipients of tobramycin by inhalation or placebo in serum creatinine concentrations at week 0 or week 20 in clinical trials [< Cheer 2501 >].

In two studies in which nebulized tobramycin 300 mg twice/day was administered, systemic peak concentrations were below 0.2 and 3.62 μg/ml, and trough concentrations were undetectable, making toxicity from this route of administration negligible. However, high concentrations can occur.

A 19-year-old woman who received a heart transplant was given tobramycin by inhalation forAcinetobacter baumanii pneumonia; her serum trough concentrations were toxic (> 2.0 μg/ml) [80]. Her risk factors for these toxic concentrations were renal Insufficiency and administration of the drug by positive pressure ventilation.

Tobramycin (SED-15, 3437; SEDA-29, 254; SEDA-30, 297)

8.3.2 Tobramycin

Tobramycin is somewhat similar compared to gentamicin, but its advantages include a greater intrinsic activity against Pseudomonas aeruginosa and activity against some gentamicin-resistant Pseudomonas aeruginosa and Acinetobacter baumannii strains. In addition, a lower nephrotoxicity was described [24]. The recommended dose of tobramycin is 4–7 mg/kg per day, administered as a single dose or divided into two or three equal doses [24]. As for gentamicin, a Cmax/MIC ratio of >10 predicts clinical efficacy of tobramycin [24]. Trough levels should be < 1 mg/L to minimize the risk of toxicity [2].

Tobramycin [SED-15, 3437; SEDA-32, 463; SEDA-33, 513; SEDA-35, 464]

Tobramycin

Tobramycin (see Table 37–7) offers two theoretical advantages over gentamicin for therapy for neonatal infections: increased in vitro activity against P. aeruginosa and decreased nephrotoxicity [315]. The lower incidence of nephrotoxicity for tobramycin has been documented in laboratory animals and human adults but not in neonates [316]. Because of the relative resistance of neonates to aminoglycoside nephrotoxicity, the applicability of such advantages in young infants is uncertain.

After a 2 mg/kg dose of tobramycin, mean peak serum concentrations of 4 to 6 μg/mL are observed at 30 to 60 minutes [317]. When an identical dose is given to low birth weight neonates, mean peak serum values are 8 μg/mL. Predose trough concentrations are higher in smaller and more premature infants; trough concentrations are often greater than 2 μg/mL in premature neonates receiving 2.5 mg/kg doses every 12 hours [318–320]. The serum tobramycin half-life is also prolonged in smaller, younger, and more premature infants and in those infants with delayed creatinine clearance [317,318,320]. In the first week after birth, very low birth weight infants (<1500 g) have half-life values as long as 9 to 17 hours, compared with values of 3 to 4.5 hours for larger infants (>2500 g) and older infants who are 1 to 4 weeks old. Premature infants born at less than 30 weeks of gestation, often require dosage intervals of 18 to 24 hours [318,320,321]. Therapeutic drug monitoring and individualization of the dosage schedule are often needed to provide the optimal therapy for very low birth weight infants.

Tobramycin (SED-15, 3437; SEDA-29, 254; SEDA-30, 297; SEDA-31, 428)