Source:http://www4.wiwiss.fu-berlin.de/dailymed/resource/drugs/1200
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Tobramycin (Injection, Solution)
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Tobramycin Injection may be given intramuscularly or intravenously.
Recommended dosages are the same for both routes. This insert is for a Pharmacy
Bulk Package and is intended for preparing I.V. admixtures only. Dosage recommendations
for intramuscular use are for informational purposes only. The patient's
pretreatment body weight should be obtained for calculation of correct dosage.
It is desirable to measure both peak and trough serum concentrations (see WARNINGS box and PRECAUTIONS). Administration
for Patients with Normal Renal Function���Adults with Serious Infections: 3 mg/kg/day in 3 equal doses
every 8 hours (see Table 1). Adults
with Life-Threatening Infections: Up to 5 mg/kg/day may be administered
in 3 or 4 equal doses (see Table 1). The dosage should be reduced to
3 mg/kg/day as soon as clinically indicated. To prevent increased toxicity
due to excessive blood levels, dosage should not exceed 5 mg/kg/day unless
serum levels are monitored (see WARNINGS box and PRECAUTIONS). *Applicable to all product forms except Tobramycin Injection,
10 mg/mL (Pediatric). Pediatric
Patients (Greater Than 1 Week of Age) : 6 to 7.5 mg/kg/day in 3
or 4 equally divided doses (2 to 2.5 mg/kg every 8 hours or 1.5 to 1.89 mg/kg
every 6 hours). Premature
or Full-Term Neonates 1 Week of Age or Less : Up to 4 mg/kg/day
may be administered in 2 equal doses every 12 hours. It
is desirable to limit treatment to a short term. The usual duration of treatment
is 7 to 10 days. A longer course of therapy may be necessary in difficult
and complicated infections. In such cases, monitoring of renal, auditory,
and vestibular functions is advised, because neurotoxicity is more likely
to occur when treatment is extended longer than 10 days. Dosage in Patients with Cystic Fibrosis���In patients with cystic fibrosis,
altered pharmacokinetics may result in reduced serum concentrations of aminoglycosides.
Measurement of tobramycin serum concentration during treatment is especially
important as a basis for determining appropriate dose. In patients with severe
cystic fibrosis, an initial dosing regimen of 10 mg/kg/day in 4 equally divided
doses is recommended. This dosing regimen is suggested only as a guide. The
serum levels of tobramycin should be measured directly during treatment due
to wide interpatient variability. Administration
for Patients With Impaired Renal Function���Whenever possible, serum tobramycin concentrations should be monitored
during therapy. Following a loading dose of 1 mg/kg,
subsequent dosage in these patients must be adjusted, either with reduced
doses administered at 8-hour intervals or with normal doses given at prolonged
intervals. Both of these methods are suggested as guides to be used when serum
levels of tobramycin cannot be measured directly. They are based on either
the creatinine clearance or the serum creatinine of the patient, because these
values correlate with the half-life of tobramycin. The dosage schedules derived
from either method should be used in conjunction with careful clinical and
laboratory observations of the patient and should be modified as necessary.
Neither method should be used when dialysis is being performed. Reduced
dosage at 8-hour intervals: When the creatinine clearance rate is 70 mL or
less per minute or when the serum creatinine value is known, the amount of
the reduced dose can be determined by multiplying the normal dose from Table
1 by the percent of normal dose from the accompanying nomogram. An
alternate rough guide for determining reduced dosage at 8-hour intervals (for
patients whose steady-state serum creatinine values are known) is to divide
the normally recommended dose by the patient's serum creatinine. Normal
dosage at prolonged intervals: If the creatinine clearance rate is not available
and the patient's condition is stable, a dosage frequency in hours for the dosage given in Table 1 can
be determined by multiplying the patient's serum creatinine by 6. Dosage in Obese Patients���The appropriate
dose may be calculated by using the patient's estimated lean body weight
plus 40% of the excess as the basic weight on which to figure mg/kg. Intravenous Administration���For intravenous administration, the usual volume of diluent (0.9%
Sodium Chloride Injection or 5% Dextrose Injection) is 50 to 100 mL for adult
doses. For pediatric patients, the volume of diluent should be proportionately
less than for adults. The diluted solution usually should be infused over
a period of 20 to 60 minutes. Infusion periods of less than 20 minutes
are not recommended because peak serum levels may exceed 12 mcg/mL (see WARNINGS box). Tobramycin
Injection should not be physically premixed with other drugs but should be
administered separately according to the recommended dose and route. Parenteral
drug products should be inspected visually for particulate matter and discoloration
prior to administration, whenever solution and container permit. Directions for Proper Use of Pharmacy Bulk Package Use Aseptic Technique���Not for Direct Infusion The
pharmacy bulk package is for use in a Pharmacy Admixture Service only. Parenteral drug products should be inspected visually for
particulate matter and discoloration prior to administration, whenever solution
and container permit.
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dailymed-instance:descripti... |
Tobramycin sulfate, a water-soluble antibiotic of the aminoglycoside
group, is derived from the actinomycete Streptomyces
tenebrarius. Tobramycin Injection is a clear and colorless sterile
aqueous solution for parenteral administration. Each
mL contains tobramycin sulfate equivalent to 40 mg tobramycin; sodium metabisulfite
added as an antioxidant, 3 mg; and edetate disodium added as a stabilizer,
0.1 mg. Contains sulfuric acid and may contain sodium hydroxide for pH adjustment.
pH 4.0 (3.0 to 6.5). Tobramycin sulfate is, O-3-amino-3-deoxy-��-D-glucopyranosyl-(1���4)-O-[2,6-diamino-2,3,6-trideoxy-��-D-ribo-hexopyranosyl-(1���6)]-2-deoxy-L-streptamine
(2:5)(salt) and has the chemical formula (CHNO)���5HSO. The molecular weight is 1,425.39. The structural
formula for tobramycin is as follows: A
pharmacy bulk package is a container of a sterile preparation for parenteral
use that contains many single doses. The contents are intended for use in
a pharmacy admixture service and are restricted to the preparation of admixtures
for intravenous infusion (see DOSAGE AND
ADMINISTRATION, Directions for proper
use of Pharmacy Bulk Package).
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Tobramycin is rapidly absorbed following intramuscular administration.
Peak serum concentrations of tobramycin occur between 30 and 90 minutes after
intramuscular administration. Following an intramuscular
dose of 1 mg/kg of body weight, maximum serum concentrations reach about 4��g/mL, and measurable levels persist for as long as 8 hours. Therapeutic
serum levels are generally considered to range from 4 to 6��g/mL. When
tobramycin sulfate is administered by intravenous infusion over a 1-hour period,
the serum concentrations are similar to those obtained by intramuscular administration.
Tobramycin is poorly absorbed from the gastrointestinal tract. In
patients with normal renal function, except neonates, tobramycin administered
every 8 hours does not accumulate in the serum. However, in those patients
with reduced renal function and in neonates, the serum concentration of the
antibiotic is usually higher and can be measured for longer periods of time
than in normal adults. Dosage for such patients must, therefore, be adjusted
accordingly (see DOSAGE AND ADMINISTRATION). Following parenteral administration, little,
if any, metabolic transformation occurs, and tobramycin is eliminated almost
exclusively by glomerular filtration. Renal clearance is similar to that of
endogenous creatinine. Ultrafiltration studies demonstrate that practically
no serum protein binding occurs. In patients with normal renal function, up
to 84% of the dose is recoverable from the urine in 8 hours and up to 93%
in 24 hours. Peak urine concentrations ranging from
75 to 100��g/mL have been observed following the intramuscular injection
of a single dose of 1 mg/kg. After several days of treatment, the amount of
tobramycin excreted in the urine approaches the daily dose administered. When
renal function is impaired, excretion of tobramycin sulfate is slowed, and
accumulation of the drug may cause toxic blood levels. The
serum half-life in normal individuals is 2 hours. An inverse relationship
exists between serum half-life and creatinine clearance, and the dosage schedule
should be adjusted according to the degree of renal impairment (see DOSAGE AND ADMINISTRATION). In patients
undergoing dialysis, 25% to 70% of the administered dose may be removed, depending
on the duration and type of dialysis. Tobramycin can
be detected in tissues and body fluids after parenteral administration. Concentrations
in bile and stools ordinarily have been low, which suggests minimum biliary
excretion. Tobramycin has appeared in low concentration in the cerebrospinal
fluid following parenteral administration, and concentrations are dependent
on dose, rate of penetration, and degree of meningeal inflammation. It has
also been found in sputum, peritoneal fluid, synovial fluid, and abscess fluids,
and it crosses the placental membranes. Concentrations in the renal cortex
are several times higher than the usual serum levels. Probenecid
does not affect the renal tubular transport of tobramycin. Microbiology���Tobramycin acts by inhibiting synthesis of protein in bacterial
cells. In vitro tests demonstrate that
tobramycin is bactericidal. Tobramycin has been shown
to be active against most strains of the following organisms both in vitro and in clinical infections: (see INDICATIONS AND USAGE.) Gram-positive aerobes Staphylococcus aureus Gram-negative aerobes Citrobacter sp Enterobacter sp Escherichia coli Klebsiella sp Morganella morganii Pseudomonas aeruginosa Proteus mirabilis Proteus vulgaris Providencia sp Serratia sp Aminoglycosides
have a low order of activity against most gram-positive organisms, including Streptococcus pyogenes, Streptococcus pneumoniae,
and enterococci. Although most strains of enterococci
demonstrate in vitro resistance, some
strains in this group are susceptible. In vitro studies have shown that an aminoglycoside combined with an antibiotic
that interferes with cell-wall synthesis affects some enterococcal strains
synergistically. The combination of penicillin G and tobramycin results in
a synergistic bactericidal effect in vitro against
certain strains of Enterococcus faecalis.
However, this combination is not synergistic against other closely related
organisms, e.g., Enterococcus faecium.
Speciation of enterococci alone cannot be used to predict susceptibility.
Susceptibility testing and tests for antibiotic synergism are emphasized. Cross-resistance
between aminoglycosides may occur. Susceptibility
Tests: Diffusion Techniques: Quantitative
methods that require measurement of zone diameters give the most precise estimate
of the susceptibility of bacteria to antimicrobial agents. One such procedure
is the National Committee for Clinical Laboratory Standards (NCCLS) approved
procedure. This method has been recommended for use with disks
to test susceptibility to tobramycin. Interpretation involves correlation
of the diameters obtained in the disk test with the minimum inhibitory concentration
(MIC) for tobramycin. Reports from the laboratory giving
results of the standard single-disk susceptibility test with a 10-��g
tobramycin disk should be interpreted according to the following criteria: A report of���Susceptible���indicates that
the pathogen is likely to be inhibited by generally achievable blood levels.
A report of���Intermediate���suggests that the organism would
be susceptible if high dosage is used or if the infection is confined to tissues
and fluids in which high antimicrobial levels are attained. A report of���Resistant���indicates that achievable concentrations are unlikely to be inhibitory, and
other therapy should be selected. Standardized procedures
require the use of laboratory control organisms. The 10-��g tobramycin
disk should give the following zone diameters: Dilution Techniques: Broth
and agar dilution methods, such as those recommended by the NCCLS,
may be used to determine the minimum inhibitory concentration (MIC) of tobramycin.
MIC tests results should be interpreted according to the following criteria: As with standard diffusion methods, dilution procedures
require the use of laboratory control organisms. Standard tobramycin powder
should give the following MIC values:
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A hypersensitivity to any aminoglycoside is a contraindication
to the use of tobramycin. A history of hypersensitivity or serious toxic reactions
to aminoglycosides may also contraindicate the use of any other aminoglycoside
because of the known cross-sensitivity of patients to drugs in this class.
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Tobramycin Injection, USP is available as: Store at 20 to 25��C (68 to 77��F). [See USP Controlled
Room Temperature.]
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Pharmacy Bulk Package��� Not for Direct
Infusion
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Serum and urine specimens for examination should be collected
during therapy, as recommended in the WARNINGS box. Serum calcium, magnesium, and sodium should be monitored. Peak
and trough serum levels should be measured periodically during therapy. Prolonged
concentrations above 12��g/mL should be avoided. Rising trough levels
(above 2��g/mL) may indicate tissue accumulation. Such accumulation,
advanced age, and cumulative dosage may contribute to ototoxicity and nephrotoxicity.
It is particularly important to monitor serum levels closely in patients with
known renal impairment. A useful guideline would be
to perform serum level assays after 2 or 3 doses, so that the dosage could
be adjusted if necessary, and also at 3-to 4-day intervals during therapy.
In the event of changing renal function, more frequent serum levels should
be obtained and the dosage or dosage interval adjusted according to the guidelines
provided in the DOSAGE AND ADMINISTRATION section. In order to measure the peak level,
a serum sample should be drawn about 30 minutes following intravenous infusion
or 1 hour after an intramuscular injection. Trough levels are measured by
obtaining serum samples at 8 hours or just prior to the next dose of tobramycin.
These suggested time intervals are intended only as guidelines and may vary
according to institutional practices. It is important, however, that there
be consistency within the individual patient program unless computerized pharmacokinetic
dosing programs are available in the institution. These serum-level assays
may be especially useful for monitoring the treatment of severely ill patients
with changing renal function or of those infected with less sensitive organisms
or those receiving maximum dosage. Neuromuscular blockade
and respiratory paralysis have been reported in cats receiving very high doses
of tobramycin (40 mg/kg). The possibility of prolonged or secondary apnea
should be considered if tobramycin is administered to anesthetized patients
who are also receiving neuromuscular blocking agents, such as succinylcholine,
tubocurarine, or decamethonium, or to patients receiving massive transfusions
of citrated blood. If neuromuscular blockade occurs, it may be reversed by
the administration of calcium salts. Cross-allergenicity
among aminoglycosides has been demonstrated. In patients
with extensive burns, altered pharmacokinetics may result in reduced serum
concentrations of aminoglycosides. In such patients treated with tobramycin,
measurement of serum concentration is especially important as a basis for
determination of appropriate dosage. Elderly patients
may have reduced renal function that may not be evident in the results of
routine screening tests, such as BUN or serum creatinine. A creatinine clearance
determination may be more useful. Monitoring of renal function during treatment
with aminoglycosides is particularly important in such patients. An
increased incidence of nephrotoxicity has been reported following concomitant
administration of aminoglycoside antibiotics and cephalosporins. Aminoglycosides
should be used with caution in patients with muscular disorders, such as myasthenia
gravis or parkinsonism, since these drugs may aggravate muscle weakness because
of their potential curare-like effect on neuromuscular function. Aminoglycosides
may be absorbed in significant quantities from body surfaces after local irrigation
or application and may cause neurotoxicity and nephrotoxicity. Aminoglycosides
have not been approved for intraocular and/or subconjunctival use. Physicians
are advised that macular necrosis has been reported following administration
of aminoglycosides, including tobramycin, by these routes. See WARNINGS box regarding concurrent use of
potent diuretics and concurrent and sequential use of other neurotoxic or
nephrotoxic drugs. The inactivation of tobramycin and
other aminoglycosides by��-lactam-type antibiotics (penicillins or cephalosporins)
has been demonstrated in vitro and
in patients with severe renal impairment. Such inactivation has not been found
in patients with normal renal function who have been given the drugs by separate
routes of administration. Therapy with tobramycin may
result in overgrowth of nonsusceptible organisms. If overgrowth of nonsusceptible
organisms occurs, appropriate therapy should be initiated.<br/>Pregnancy Category D: Aminoglycosides can cause fetal harm when administered to
a pregnant woman. Aminoglycoside antibiotics cross the placenta, and there
have been several reports of total irreversible bilateral congenital deafness
in children whose mothers received streptomycin during pregnancy. Serious
side effects to mother, fetus, or newborn have not been reported in the treatment
of pregnant women with other aminoglycosides. If tobramycin is used during
pregnancy or if the patient becomes pregnant while taking tobramycin, she
should be apprised of the potential hazard to the fetus.<br/>Pediatric Use: See INDICATIONS AND USAGE and DOSAGE AND ADMINISTRATION.<br/>Geriatric Use: Elderly patients may be at a higher risk of developing nephrotoxicity
and ototoxicity while receiving tobramycin (see WARNINGS, PRECAUTIONS, AND
OVERDOSAGE ). Other factors that may contribute to nephrotoxicity
and ototoxicity are rising trough levels, excessive peak concentrations, dehydration,
concomitant use of other neurotoxic or nephrotoxic drugs, and cumulative dose.
Peak and trough serum levels should be measured periodically during therapy
to assure adequate levels and to avoid potentially toxic levels (see WARNINGS and PRECAUTIONS). Tobramycin is
known to be substantially excreted by the kidney, and the risk of toxic reactions
to this drug may be greater in patients with impaired renal function. Dose
reduction is required for patients with impaired renal function (see DOSAGE ANDADMINISTRATION). Elderly patients may have reduced renal function that may not
be evident in the results of routine screening tests, such as BUN or serum
creatinine. A creatinine clearance determination may be more useful. Monitoring
of renal function during treatment with aminoglycosides is particularly important
in the elderly (see PRECAUTIONS). Tobramycin
40 mg/mL in 50 mL Pharmacy Bulk Package vial contains 35.995 mg (1.565 mEq)
of sodium.<br/>General: Prescribing tobramycin in the absence of a proven or strongly
suspected bacterial infection or a prophylactic indication is unlikely to
provide benefit to the patient and increases the risk of the development of
drug-resistant bacteria.<br/>Information for Patients: Patients should be counseled that antibacterial drugs including
tobramycin should only be used to treat bacterial infections. They do not
treat viral infections (e.g., the common cold). When an antibacterial drug
product is prescribed to treat a bacterial infection, patients should be told
that although it is common to feel better early in the course of therapy,
the medication should be taken exactly as directed. Skipping doses or not
completing the full course of therapy may (1) decrease the effectiveness of
the immediate treatment and (2) increase the likelihood that
bacteria will develop resistance and will not be treatable by tobramycin or
other antibacterial drugs in the future.
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Signs and Symptoms���The severity of the signs and symptoms
following a tobramycin overdose are dependent on the dose administered, the
patient's renal function, state of hydration, and age and whether or
not other medications with similar toxicities are being administered concurrently.
Toxicity may occur in patients treated more than 10 days, in adults given
more than 5 mg/kg/day, children given more than 7.5 mg/kg/day, or patients
with reduced renal function whose dose has not been appropriately adjusted. Nephrotoxicity
following the parenteral administration of an aminoglycoside is most closely
related to the area under the curve of the serum concentration versus time
graph. Nephrotoxicity is more likely if trough blood concentrations fail to
fall below 2��g/mL and is also proportional to the average blood concentration.
Patients who are elderly, have abnormal renal function, are receiving other
nephrotoxic drugs, or are volume depleted are at greater risk for developing
acute tubular necrosis. Auditory and vestibular toxicity has been associated
with aminoglycoside overdose; these toxicities occur in patients treated longer
than 10 days, in patients with abnormal renal function, in dehydrated patients,
or in patients receiving medications with additive auditory toxicities. These
patients may not have signs or symptoms or may experience dizziness, tinnitus,
vertigo, and a loss of high-tone acuity, as ototoxicity progresses. Ototoxicity
signs and symptoms may not begin to occur until long after the drug has been
discontinued. Neuromuscular blockade or respiratory
paralysis may occur following administration of many aminoglycosides. Neuromuscularblockade, respiratory failure, and prolonged respiratory paralysis may occur
more commonly in patients with myasthenia gravis or Parkinson's disease.
Prolonged respiratory paralysis may also occur in patients receiving decamethonium,
tubocurarine, or succinylcholine. If neuromuscular blockade occurs, it may
be reversed by the administration of calcium salts but mechanical assistance
may be necessary. If tobramycin were ingested, toxicity
would be less likely because aminoglycosides are poorly absorbed from an intact
gastrointestinal tract. Treatment���In all cases of
suspected overdosage, call your Regional Poison Control Center to obtain the
most up-to-date information about the treatment of overdose. This recommendation
is made because, in general, information regarding the treatment of overdose
may change more rapidly than the package insert. In managing overdosage, consider
the possibility of multiple drug overdoses, interaction among drugs, and unusual
drug kinetics in your patient. The initial intervention
in a tobramycin overdose is to establish an airway and ensure oxygenation
and ventilation. Resuscitative measures should be initiated promptly if respiratory
paralysis occurs. Patients that have received an overdose
of tobramycin and have normal renal function should be adequately hydrated
to maintain a urine output of 3 to 5 mL/kg/hr. Fluid balance, creatinine clearance,
and tobramycin plasma levels should be carefully monitored until the serum
tobramycin level falls below 2��g/mL. Patients
in whom the elimination half-life is greater than 2 hours or whose renal function
is abnormal may require more aggressive therapy. In such patients, hemodialysis
may be beneficial.
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dailymed-instance:genericMe... |
Tobramycin sulfate
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dailymed-instance:fullName |
Tobramycin (Injection, Solution)
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dailymed-instance:adverseRe... |
Neurotoxicity���Adverse effects on both the vestibular
and auditory branches of the eighth nerve have been noted, especially in patients
receiving high doses or prolonged therapy, in those given previous courses
of therapy with an ototoxin, and in cases of dehydration. Symptoms include
dizziness, vertigo, tinnitus, roaring in the ears, and hearing loss. Hearing
loss is usually irreversible and is manifested initially by diminution of
high-tone acuity. Tobramycin and gentamicin sulfates closely parallel each
other in regard to ototoxic potential. Nephrotoxicity���Renal function
changes, as shown by rising BUN, NPN, and serum creatinine and by oliguria,
cylindruria, and increased proteinuria, have been reported, especially in
patients with a history of renal impairment who are treated for longer periods
or with higher doses than those recommended. Adverse renal effects can occur
in patients with initially normal renal function. Clinical
studies and studies in experimental animals have been conducted to compare
the nephrotoxic potential of tobramycin and gentamicin. In some of the clinical
studies and in the animal studies, tobramycin caused nephrotoxicity significantly
less frequently than gentamicin. In some other clinical studies, no significant
difference in the incidence of nephrotoxicity between tobramycin and gentamicin
was found. Other reported adverse reactions possibly
related to tobramycin sulfate include anemia, granulocytopenia, and thrombocytopenia;
and fever, rash, itching, urticaria, nausea, vomiting, diarrhea, headache,
lethargy, pain at the injection site, mental confusion, and disorientation.
Laboratory abnormalities possibly related to tobramycin include increased
serum transaminases (SGOT, SGPT); increased serum LDH and bilirubin; decreased
serum calcium, magnesium, sodium, and potassium; and leukopenia, leukocytosis,
and eosinophilia.
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Tobramycin is indicated for the treatment of serious bacterial
infections caused by susceptible strains of the designated microorganisms
in the diseases listed below: Septicemia in the neonate,
child, and adult caused by P aeruginosa, E coli, and Klebsiella sp Lower
respiratory tract infections caused by P aeruginosa,
Klebsiella sp, Enterobacter sp, Serratia sp, E
coli, and S aureus (penicillinase
and non-penicillinase-producing strains) Serious central-nervous-system
infections (meningitis) caused by susceptible organisms Intra-abdominal
infections, including peritonitis, caused by E
coli, Klebsiella sp, and Enterobacter sp Skin, bone, and skin-structure infections
caused by P aeruginosa, Proteus sp, E coli, Klebsiella sp, Enterobacter sp, and S aureus Complicated and
recurrent urinary tract infections caused by P
aeruginosa, Proteus sp (indole-positive and indole-negative), E coli, Klebsiella sp, Enterobacter sp, Serratia sp, S aureus, Providencia sp, and Citrobacter sp Aminoglycosides,
including tobramycin sulfate, are not indicated in uncomplicated initial episodes
of urinary tract infections unless the causative organisms are not susceptible
to antibiotics having less potential toxicity. Tobramycin may be considered
in serious staphylococcal infections when penicillin or other potentially
less toxic drugs are contraindicated and when bacterial susceptibility testing
and clinical judgment indicate its use. Bacterial cultures
should be obtained prior to and during treatment to isolate and identify etiologicorganisms and to test their susceptibility to tobramycin. If susceptibility
tests show that the causative organisms are resistant to tobramycin, other
appropriate therapy should be instituted. In patients in whom a serious life-threatening
gram-negative infection is suspected, including those in whom concurrent therapy
with a penicillin or cephalosporin and an aminoglycoside may be indicated,
treatment with tobramycin sulfate may be initiated before the results of susceptibility
studies areobtained. The decision to continue therapy with tobramycin should
be based on the results of susceptibility studies, the severity of the infection,
and the important additional concepts discussed in the WARNINGS box above. To reduce the development of
drug-resistant bacteria and maintain the effectiveness of tobramycin and other
antibacterial drugs, tobramycin should be used only to treat or prevent infections
that are proven or strongly suspected to be caused by susceptible bacteria.
When culture and susceptibility information are available, they should be
considered in selecting or modifying antimicrobial therapy. In the absence
of such data, local epidemiology and susceptibility patterns may contribute
to the empiric selection of therapy.
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Tobramycin
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