Source:http://www4.wiwiss.fu-berlin.de/dailymed/resource/drugs/2416
Predicate | Object |
---|---|
rdf:type | |
rdfs:label |
Zosyn (Injection, Solution)
|
dailymed-instance:dosage |
ZOSYN should be administered by intravenous infusion
over 30 minutes. The usual daily dose of ZOSYN
for adults is 3.375 g every six hours totaling 13.5 g (12 g piperacillin/1.5 g
tazobactam).<br/>Nosocomial Pneumonia: Initial presumptive treatment of patients with nosocomial
pneumonia should start with ZOSYN at a dosage of 4.5 g
every six hours plus an aminoglycoside, totaling 18.0 g (16.0 g piperacillin/2.0 g
tazobactam). Treatment with the aminoglycoside should be continued
in patients from whom Pseudomonas aeruginosa is isolated. If Pseudomonas aeruginosa is not isolated, the aminoglycoside may be discontinued at the discretion
of the treating physician. Due to the in vitro inactivation of the aminoglycoside
by beta-lactam antibiotics, Zosyn and the aminoglycoside are recommended
for separate administration. Zosyn and the aminoglycoside should be
reconstituted, diluted, and administered separately when concomitant
therapy with aminoglycosides is indicated. In circumstances where coadministration
via Y-site is necessary, reformulated Zosyn containing EDTA supplied
in Galaxy containers is compatible for simultaneous
coadministration via Y-site infusion only with the following aminoglycosides
under the following conditions: The following compatibility information does not
apply to the Zosyn (piperacillin/tazobactam) formulation not containing
EDTA. This information does not apply to Zosyn in vials or bulk pharmacy
containers. Refer to the package insert for Zosyn vials or bulk pharmacy
containers for instructions. Zosyn Galaxy containers are available
as 2.25 g per 50 mL, 3.375 g per 50 mL, and 4.5 g per 100 mL. Zosyn
3.375 g per 50 mL Galaxy containers are NOT compatible
with gentamicin for coadministration via a Y-site due to the higher
concentrations of piperacillin and tazobactam. Zosyn is not compatible with tobramycin
for simultaneous coadministration via Y-site infusion. Compatibility
of Zosyn with other aminoglycosides has not been established. Only
the concentration and diluents for amikacin or gentamicin with the
dosages of Zosyn listed above have been established as compatible
for coadministration via Y-site infusion. Simultaneous coadministration
via Y-site infusion in any manner other than listed above may result
in inactivation of the aminoglycoside by Zosyn.<br/>Renal Insufficiency: In patients with renal insufficiency (Creatinine
Clearance���40 mL/min), the intravenous dose of ZOSYN
should be adjusted to the degree of actual renal function impairment.
In patients with nosocomial pneumonia receiving concomitant aminoglycoside
therapy, the aminoglycoside dosage should be adjusted according to
the recommendations of the manufacturer. The recommended daily doses
of ZOSYN for patients with renal insufficiency are as follows: For patients on hemodialysis, the maximum dose
is 2.25 g every twelve hours for all indications other than nosocomial
pneumonia and 2.25 g every eight hours for nosocomial pneumonia.
Since hemodialysis removes 30% to 40% of the administered dose, an
additional dose of 0.75 g ZOSYN should be administered following
each dialysis period on hemodialysis days. No additional dosage of
ZOSYN is necessary for CAPD patients.<br/>Duration of Therapy: The usual duration of ZOSYN treatment is from seven
to ten days. However, the recommended duration of ZOSYN treatment
of nosocomial pneumonia is 7 to 14 days. In all conditions, the duration
of therapy should be guided by the severity of the infection and the
patient's clinical and bacteriological progress.<br/>Pediatric Patients: For children with appendicitis and/or peritonitis
9 months of age or older, weighing up to 40 kg, and with normal renal
function, the recommended Zosyn dosage is 100 mg piperacillin/12.5
mg tazobactam per kilogram of body weight, every 8 hours. For pediatric
patients between 2 months and 9 months of age, the recommended Zosyn
dosage based on pharmacokinetic modeling, is 80 mg piperacillin/10
mg tazobactam per kilogram of body weight, every 8 hours (see PRECAUTIONS, General, Pediatric
Use and CLINICAL PHARMACOLOGY). Pediatric
patients weighing over 40 kg and with normal renal function should
receive the adult dose. There are no dosage recommendations for Zosyn
in pediatric patients with impaired renal function. Zosyn in Galaxy containers should not be used in pediatric patients
who require less than the full adult dose of Zosyn in order to prevent
unintentional overdose. The other available formulations of Zosyn
can be used in this population.<br/>DIRECTIONS FOR USE OF ZOSYN (PIPERACILLIN AND TAZOBACTAM INJECTION)
IN GALAXY CONTAINERS (PL 2040 PLASTIC): ZOSYN Injection (PL 2040 Plastic) is to be administered
after thawing to room temperature using sterile equipment. Administer by infusion over a period of at least 30 minutes.
During the infusion it is desirable to discontinue the primary infusion
solution. ZOSYN should not be mixed with other
drugs in a syringe or infusion bottle since compatibility has not
been established. ZOSYN is not chemically stable
in solutions that contain only sodium bicarbonate and solutions that
significantly alter the pH. ZOSYN should not
be added to blood products or albumin hydrolysates.
|
dailymed-instance:descripti... |
ZOSYN (piperacillin and tazobactam
injection) in Galaxy Containers (PL 2040 Plastic)
is a sterile injectable antibacterial combination product consisting
of the semisynthetic antibiotic piperacillin sodium and the��-lactamase
inhibitor tazobactam sodium for intravenous administration. Piperacillin sodium is derived from D(-)-��-aminobenzyl-penicillin.
The chemical name of piperacillin sodium is sodium (2S,5R,6R)-6-[(R)-2-(4-ethyl-2,3-dioxo-1-piperazine-carboxamido)-2-phenylacetamido]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate.
The chemical formula is CHNNaOS and the molecular weight is 539.5. The chemical structure
of piperacillin sodium is: Tazobactam sodium,
a derivative of the penicillin nucleus, is a penicillanic acid sulfone.
Its chemical name is sodium (2S,3S,5R)-3-methyl-7-oxo-3-(1H-1,2,3-triazol-1-ylmethyl)-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate-4,4-dioxide.
The chemical formula is CHNNaOS and the molecular weight is 322.3. The chemical structure
of tazobactam sodium is: ZOSYN in the
Galaxy Container (PL 2040 Plastic) is a frozen iso-osmotic sterile
non-pyrogenic premixed solution. The components and dosage formulations
are given in the table below: The pH has been adjusted between 5.5 to 6.8 with
sodium bicarbonate and hydrochloric acid. The
solution is intended for intravenous use only. The plastic container is fabricated from a specially designed multilayer
plastic, PL 2040. Solutions are in contact with the polyethylene layer
of this container and can leach out certain chemical components of
the plastic in very small amounts within the expiration period. The
suitability of the plastic has been confirmed in tests in animals
according to the USP biological tests for plastic containers, as well
as by tissue culture toxicity studies. The
approximate total sodium content for ZOSYN in Galaxy Containers is
5.58 mEq (128 mg) per 50 mL in the 2.25 g dose, 8.38
mEq (192 mg) per 50 mL in the 3.375 g dose, and 11.17 mEq
(256 mg) per 100 mL in the 4.5 g dose.
|
dailymed-instance:clinicalP... |
Adults: Peak plasma concentrations
of piperacillin and tazobactam are attained immediately after completion
of an intravenous infusion of ZOSYN. Piperacillin plasma concentrations,
following a 30-minute infusion of ZOSYN, were similar to those attained
when equivalent doses of piperacillin were administered alone, with
mean peak plasma concentrations of approximately 134��g/mL,
242��g/mL, and 298��g/mL for the 2.25 g,
3.375 g, and 4.5 g ZOSYN (piperacillin/tazobactam) doses,
respectively. The corresponding mean peak plasma concentrations of
tazobactam were 15��g/mL, 24��g/mL, and 34��g/mL,
respectively. Following a 30-minute I.V. infusion
of 3.375 g ZOSYN every 6 hours, steady-state plasma concentrations
of piperacillin and tazobactam were similar to those attained after
the first dose. In like manner, steady-state plasma concentrations
were not different from those attained after the first dose when 2.25 g
or 4.5 g doses of ZOSYN were administered via 30-minute infusions
every 6 hours. Steady-state plasma concentrations after 30-minute
infusions every 6 hours are provided in Table
2. Following single or multiple
ZOSYN doses to healthy subjects, the plasma half-life of piperacillin
and of tazobactam ranged from 0.7 to 1.2 hours and was unaffected
by dose or duration of infusion. Piperacillin
is metabolized to a minor microbiologically active desethyl metabolite.
Tazobactam is metabolized to a single metabolite that lacks pharmacological
and antibacterial activities. Both piperacillin and tazobactam are
eliminated via the kidney by glomerular filtration and tubular secretion.
Piperacillin is excreted rapidly as unchanged drug with 68% of the
administered dose excreted in the urine. Tazobactam and its metabolite
areeliminated primarily by renal excretion with 80% of the administered
dose excreted as unchanged drug and the remainder as the single metabolite.
Piperacillin, tazobactam, and desethyl piperacillin are also secreted
into the bile. Both piperacillin and tazobactam
are approximately 30% bound to plasma proteins. The protein binding
of either piperacillin or tazobactam is unaffected by the presence
of the other compound. Protein binding of the tazobactam metabolite
is negligible. Piperacillin and tazobactam
are widely distributed into tissues and body fluids including intestinal
mucosa, gallbladder, lung, female reproductive tissues (uterus, ovary
and fallopian tube), interstitial fluid, and bile. Mean tissue concentrations
are generally 50% to 100% of those in plasma. Distribution of piperacillin
and tazobactam into cerebrospinal fluid is low in subjects with non-inflamed
meninges, as with other penicillins. After
the administration of single doses of piperacillin/tazobactam to subjects
with renal impairment, the half-life of piperacillin and of tazobactam
increases with decreasing creatinine clearance. At creatinine clearance
below 20 mL/min, the increase in half-life is twofold for piperacillin
and fourfold for tazobactam compared to subjects with normal renal
function. Dosage adjustments for ZOSYN are recommended when creatinine
clearance is below 40 mL/min in patients receiving the usual
recommended daily dose of ZOSYN. (See DOSAGE AND ADMINISTRATION section for specific recommendations for the treatment of patients
with renal insufficiency.) Hemodialysis removes
30 to 40% of a piperacillin/tazobactam dose with an additional 5%
of the tazobactam dose removed as the tazobactam metabolite. Peritoneal
dialysis removes approximately 6% and 21% of the piperacillin and
tazobactam doses, respectively, with up to 16% of the tazobactam dose
removed as the tazobactam metabolite. For dosage recommendations for
patients undergoing hemodialysis, see DOSAGE AND ADMINISTRATION section. The half-life of piperacillin and of tazobactam increases
by approximately 25% and 18%, respectively, in patients with hepatic
cirrhosis compared to healthy subjects. However, this difference does
not warrant dosage adjustment of ZOSYN due to hepatic cirrhosis.<br/>Pediatrics: Piperacillin and tazobactam pharmacokinetics were
studied in pediatric patients 2 months of age and older. The clearance
of both compounds is slower in the younger patients compared to older
children and adults. In a population PK analysis,
estimated clearance for 9 month-old to 12 year-old patients was comparable
to adults, with a population mean (SE) value of 5.64 (0.34) mL/min/kg.
The piperacillin clearance estimate is 80% of this value for pediatric
patients 2 - 9 months old. In patients younger than 2 months of
age, clearance of piperacillin is slower compared to older children;
however, it is not adequately characterized for dosing recommendations.
The population mean (SE) for piperacillin distribution volume is 0.243
(0.011) L/kg and is independent of age.<br/>Microbiology: Piperacillin sodium exerts bactericidal activity
by inhibiting septum formation and cell wall synthesis of susceptible
bacteria. In vitro, piperacillin is active against a variety of gram-positive
and gram-negative aerobic and anaerobic bacteria. Tazobactam sodium
has little clinically relevant in vitro activity against bacteria
due to its reduced affinity to penicillin-binding proteins. It is,
however, a��-lactamase inhibitor of the Richmond-Sykes class
III (Bush class 2b&2b') penicillinases and cephalosporinases.
It varies in its ability to inhibit class II and IV (2a&4) penicillinases.
Tazobactam does not induce chromosomally-mediated��-lactamases
at tazobactam concentrations achieved with the recommended dosage
regimen. Piperacillin/tazobactam has been shown
to be active against most strains of the following microorganisms
both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section.<br/>Aerobic and facultative Gram-positive microorganisms:: Staphylococcus aureus (excluding methicillin and oxacillin-resistant isolates)<br/>Aerobic and facultative Gram-negative microorganisms:: Acinetobacter baumaniiEscherichia coliHaemophilus influenzae (excluding��-lactamase
negative, ampicillin-resistant isolates)Klebsiella pneumoniaePseudomonas aeruginosa (given in combination with
an aminoglycoside to which the isolate is susceptible)<br/>Gram-negative anaerobes:: Bacteroides fragilis group (B. fragilis, B. ovatus, B. thetaiotaomicron, and B.
vulgatus) The following in vitro
data are available, but their
clinical significance is unknown. At least 90% of the following microorganisms exhibit in vitro minimum
inhibitory concentration (MIC) less than or equal to the susceptible
breakpoint for piperacillin/tazobactam. However, the safety and effectiveness
of piperacillin/tazobactam in treating clinical infections due to
these bacteria have not been established in adequate and well-controlled
clinical trials.<br/>Aerobic and facultative Gram-positive microorganisms:: Enterococcus faecalis (ampicillin or penicillin-susceptible isolates only)Staphylococcus epidermidis (excluding
methicillin and oxacillin-resistant isolates)Streptococcus agalactiaeStreptococcus pneumoniae(penicillin-susceptible isolates only)Streptococcus pyogenesViridans group streptococci<br/>Aerobic and facultative Gram-negative microorganisms::<br/>Gram-positive anaerobes::<br/>Gram-negative anaerobes:: These
are not��-lactamase producing bacteria and, therefore, are susceptible
to piperacillin alone.<br/>Susceptibility Testing Methods: As is recommended with all antimicrobials, the results
of in vitro susceptibility tests, when available, should be provided
to the physician as periodic reports, which describe the susceptibility
profile of nosocomial and community acquired pathogens. These reports
should aid the physician in selecting the most effective antimicrobial.<br/>Dilution Techniques:: Quantitative methods are used to determine antimicrobial
minimum inhibitory concentrations (MICs). These MICs provide estimates
of the susceptibility of bacteria to antimicrobial compounds. The
MICs should be determined using a standardized procedure. Standardized
procedures are based on a dilution method (broth or agar) or equivalent
with standardized inoculum concentrations and standardized concentrations
of piperacillin and tazobactam powders.1,2 MIC values should be determined using serial dilutions
of piperacillin combined with a fixed concentration of 4��g/mL
tazobactam. The MIC values obtained should be interpreted according
to criteria provided in Table 3.<br/>Diffusion Technique:: Quantitative methods that require measurement of
zone diameters also provide reproducible estimates of the susceptibility
of bacteria to antimicrobial compounds. One such standardized procedure1,3 requires the use of standardized inoculum
concentrations. This procedure uses paper disks impregnated with 100��g
of piperacillin and 10��g of tazobactam to test the susceptibility
of microorganisms to piperacillin/tazobactam. The disk diffusion interpreted
criteria are provided in Table 3.<br/>Anaerobic Techniques: For anaerobic bacteria, the susceptibility to piperacillin/tazobactam
can be determined by the reference agar dilution method.4 A report of S (���Susceptible���) indicates
that the pathogen is likely to be inhibited if the antimicrobial compound
in the blood reaches the concentrations usually achievable. A report
of I (���Intermediate���) indicates that the results
should be considered equivocal, and, if the microorganism is not fully
susceptible to alternative, clinically feasible drugs, the test should
be repeated. This category implies possible clinical applicability
in body sites where the drug is physiologically concentrated orin
situations where high dosage of drug can be used. This category also
provides a buffer zone, which prevents small, uncontrolled technical
factors from causing major discrepancies in interpretation. A report
of R (���Resistant���) indicates that the pathogen is not
likely to be inhibited if the antimicrobial compound in the blood
reaches the concentrations usually achievable; other therapy should
be considered.<br/>Quality Control: Standardized susceptibility test procedures require
the use of laboratory control microorganisms to control the technical
aspects of the procedures.1,2,3,4 Standard piperacillin/tazobactam powder should provide the following
ranges of values noted in Table 4.
Quality control microorganisms are specific strains of microorganisms
with intrinsic biological properties relating to resistance mechanisms
and their genetic expression within the microorganism; the specific
strains used for microbiological quality control are not clinically
significant.
|
dailymed-instance:activeIng... | |
dailymed-instance:contraind... |
ZOSYN is contraindicated in patients with a history
of allergic reactions to any of the penicillins, cephalosporins, or��-lactamase inhibitors.
|
dailymed-instance:supply |
ZOSYN (piperacillin and tazobactam
injection) in Galaxy Container (PL 2040 Plastic)
is supplied as a frozen, iso-osmotic, sterile, nonpyrogenic solution
in single-dose plastic containers as follows: 2.25 g (piperacillin sodium equivalent to 2 g piperacillin/tazobactam
sodium equivalent to 0.25 g tazobactam) in 50 mL. Each container
has 5.58 mEq (128 mg) of sodium. Supplied 24/box���NDC 0206-8860-02 3.375 g (piperacillin sodium equivalent to 3 g
piperacillin/tazobactam sodium equivalent to 0.375 g tazobactam)
in 50 mL. Each container has 8.38 mEq (192 mg) of sodium. Supplied
24/box���NDC 0206-8861-02 4.5 g (piperacillin
sodium equivalent to 4 g piperacillin/tazobactam sodium equivalent
to 0.5 g tazobactam) in 100 mL. Each container has 11.17
mEq (256 mg) of sodium. Supplied 12/box���NDC 0206-8862-02 Store at or below -20��C (-4��F). [See DOSAGE AND ADMINISTRATION,
DIRECTIONS FOR USE OF ZOSYN (PIPERACILLIN AND TAZOBACTAM INJECTION)
IN GALAXY' CONTAINERS (PL 2040 PLASTIC).]<br/>Also Available: ZOSYN (piperacillin and tazobactam for injection)
is also supplied as follows: 2.25 g single-dose
vial containing piperacillin sodium equivalent to 2 g of piperacillin
and tazobactam sodium equivalent to 0.25 g of tazobactam. Each
vial contains 5.58 mEq (128 mg) of sodium. Supplied 10/box���NDC
0206-8852-16 3.375 g single-dose vial
containing piperacillin sodium equivalent to 3 g of piperacillin
and tazobactam sodium equivalent to 0.375 g of tazobactam. Each
vial contains 8.38 mEq (192 mg) of sodium. Supplied 10/box���NDC
0206-8854-16 4.5 g single-dose vial containing
piperacillin sodium equivalent to 4 g of piperacillin and tazobactam
sodium equivalent to 0.5 g of tazobactam. Each vial contains
11.17 mEq (256 mg) of sodium. Supplied 10/box���NDC 0206-8855-16 ZOSYN (piperacillin and tazobactam for injection) is also
supplied in the ADD-Vantage Vial as follows: 2.25 g ADD-Vantage vial (piperacillin
sodium equivalent to 2 g piperacillin and tazobactam sodium equivalent
to 0.25 g of tazobactam). Each ADD-Vantage vial
contains 5.58 mEq (128 mg) of sodium. Supplied 10/box���NDC
0206-8852-18 3.375 g ADD-Vantage vial (piperacillin sodium equivalent to 3 g piperacillin and
tazobactam sodium equivalent to 0.375 g of tazobactam). Each
ADD-Vantage vial contains 8.38 mEq (192 mg)
of sodium. Supplied 10/box���NDC 0206-8854-18 4.5 g ADD-Vantage vial (piperacillin sodium
equivalent to 4 g piperacillin and tazobactam sodium equivalent
to 0.5 g of tazobactam). Each ADD-Vantage vial
contains 11.17 mEq (256 mg) of sodium. Supplied 10/box���NDC
0206-8855-18<br/>Also Available: ZOSYN (piperacillin and tazobactam for injection)
is also supplied as a powder in the pharmacy bulk vial as follows: 40.5 g pharmacy-bulk vial containing piperacillin
sodium equivalent to 36 grams of piperacillin and tazobactam
sodium equivalent to 4.5 grams of tazobactam. Each pharmacy-bulk
vial contains 100.4 mEq (2,304 mg) of sodium. NDC 0206-8859-10 ZOSYN (piperacillin and tazobactam for injection) vials
should be stored at controlled room temperature 20��C to 25��C
(68��F to 77��F) prior to reconstitution.
|
dailymed-instance:activeMoi... | |
dailymed-instance:inactiveI... | |
dailymed-instance:precautio... |
General: Bleeding manifestations have occurred in some patients
receiving��-lactam antibiotics, including piperacillin. These
reactions have sometimes been associated with abnormalities of coagulation
tests such as clotting time, platelet aggregation, and prothrombin
time, and are more likely to occur in patients with renal failure.
If bleeding manifestations occur, ZOSYN should be discontinued and
appropriate therapy instituted. The possibility
of the emergence of resistant organisms that might cause superinfections
should be kept in mind. If this occurs, appropriate measures should
be taken. As with other penicillins, patients
may experience neuromuscular excitability or convulsions if higher
than recommended doses are given intravenously (particularly in the
presence of renal failure). ZOSYN in Galaxy
Containers contains a monosodium salt of piperacillin, a monosodium
salt of tazobactam, and sodium from other formulation components.
The approximate total sodium content for ZOSYN in Galaxy Containers
is 5.58 mEq (128 mg) per 50 mL in the 2.25 g dose, 8.38
mEq (192 mg) per 50 mL in the 3.375 g dose, and 11.17 mEq
(256 mg) per 100 mL in the 4.5 g dose. This should be considered
when treating patients requiring restricted salt intake. Periodic
electrolyte determinations should be performed in patients with low
potassium reserves, and the possibility of hypokalemia should be kept
in mind with patients who have potentially low potassium reserves
and who are receiving cytotoxic therapy or diuretics. As with other
semisynthetic penicillins, piperacillin therapy has been associated
with an increased incidence of fever and rash in cystic fibrosis patients. In patients with creatinine clearance���40 mL/min
and dialysis patients (hemodialysis and CAPD), the intravenous dose
should be adjusted to the degree of renal function impairment. Prescribing Zosyn (piperacillin
and tazobactam) 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 development of drug-resistant
bacteria.<br/>Information for Patients: Patients should be counseled that antibacterial drugs
including Zosyn should only be used to treat bacterial infections.
They do not treat viral infections (e.g., the common cold). When Zosyn
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
Zosyn or other antibacterial drugs in the future. Diarrhea is a common problem caused by antibiotics which usually
ends when the antibiotic is discontinued. Sometimes after starting
treatment with antibiotics, patients can develop watery and bloody
stools (with or without stomach cramps and fever) even as late as
two or more months after having taken the last dose of the antibiotic.
If this occurs, patients should contact their physician as soon as
possible.<br/>Laboratory Tests: Periodic assessment of hematopoietic function should
be performed, especially with prolonged therapy, ie,���21 days.
(See ADVERSE REACTIONS,
Adverse Laboratory Events.)<br/>Drug Interactions:<br/>Aminoglycosides: The mixing of beta-lactam antibiotics with aminoglycosides in vitro can result in substantial inactivation
of the aminoglycoside. However, amikacin and gentamicin have been
shown to be compatible in vitro with reformulated Zosyn containing EDTA supplied in vials or bulk
pharmacy containers in certain diluents at specific concentrations
for a simultaneous Y-site infusion. Reformulated Zosyn containing EDTA is not compatible with tobramycin
for simultaneous coadministration via Y-site infusion. The inactivation of aminoglycosides in the presence of
penicillin-class drugs has been recognized. It has been postulated
that penicillin-aminoglycoside complexes form; these complexes are
microbiologically inactive and of unknown toxicity. Sequential administration
of Zosyn with tobramycin to patients with normal renal function and
mild to moderate renal impairment has been shown to modestly decrease
serum concentrations of tobramycin but does not significantly affect
tobramycin pharmacokinetics. When aminoglycosides are administered
in combination with piperacillin to patients with end-stage renal
disease requiring hemodialysis, the concentrations of the aminoglycosides
(especially tobramycin) may be significantly altered and should be
monitored. Since aminoglycosides are not equally susceptible to inactivation
by piperacillin, consideration should be given to the choice of the
aminoglycoside when administered in combination with piperacillin
to these patients.<br/>Probenecid: Probenecid administered concomitantly with ZOSYN
prolongs the half-life of piperacillin by 21% and of tazobactam by
71%.<br/>Vancomycin: No pharmacokinetic interactions have been noted between
ZOSYN and vancomycin.<br/>Heparin: Coagulation parameters should be tested more frequently
and monitored regularly during simultaneous administration of high
doses of heparin, oral anticoagulants, or other drugs that may affect
the blood coagulation system or the thrombocyte function.<br/>Vecuronium: Piperacillin when used concomitantly with vecuronium
has been implicated in the prolongation of the neuromuscular blockade
of vecuronium. ZOSYN could produce the same phenomenon if given along
with vecuronium. Due to their similar mechanism of action, it is expected
that the neuromuscular blockade produced by any of the non-depolarizing
muscle relaxants could be prolonged in the presence of piperacillin.
(See package insert for vecuronium bromide.)<br/>Methotrexate: Limited data suggests that coadministration of methotrexate
and piperacillin may reduce the clearance of methotrexate due to competition
for renal secretion. The impact of tazobactam on the elimination of
methotrexate has not been evaluated. If concurrent therapy is necessary,
serum concentrations of methotrexate as well as the signs and symptoms
of methotrexate toxicity should be frequently monitored.<br/>Drug/Laboratory Test Interactions: As with other penicillins, the administration of
ZOSYN may result in a false-positive reaction for glucose in the urine
using a copper-reduction method (CLINITEST). It is
recommended that glucose tests based on enzymatic glucose oxidase
reactions (such as DIASTIX or TES-TAPE) be used. There have been reports of positive
test results using the Bio-Rad Laboratories Platelia Aspergillus EIA test in patients receiving
piperacillin/tazobactam injection who were subsequently found to be
free of Aspergillus infection.
Cross-reactions with non-Aspergillus
polysaccharides and polyfuranoses with the Bio-Rad Laboratories
Platelia Aspergillus EIA
test have been reported. Therefore, positive
test results in patients receiving piperacillin/tazobactam should
be interpreted cautiously and confirmed by other diagnostic methods.<br/>Carcinogenesis, Mutagenesis, Impairment of Fertility: Long-term carcinogenicity studies in animals have
not been conducted with piperacillin/tazobactam, piperacillin, or
tazobactam.<br/>Piperacillin/Tazobactam: Piperacillin/tazobactam was negative in microbial
mutagenicity assays at concentrations up to 14.84/1.86��g/plate.
Piperacillin/tazobactam was negative in the unscheduled DNA synthesis
(UDS) test at concentrations up to 5689/711��g/mL. Piperacillin/tazobactam
was negative in a mammalian point mutation (Chinese hamster ovary
cell HPRT) assay at concentrations up to 8000/1000��g/mL.
Piperacillin/tazobactam was negative in a mammalian cell (BALB/c-3T3)
transformation assay at concentrations up to 8/1��g/mL.
In vivo, piperacillin/tazobactam did not induce chromosomal aberrations
in rats dosed I.V. with 1500/187.5 mg/kg; this dose is similar
to the maximum recommended human daily dose on a body-surface-area
basis (mg/m).<br/>Piperacillin: Piperacillin was negative in microbial mutagenicity
assays at concentrations up to 50��g/plate. There was no
DNA damage in bacteria (Rec assay) exposed to piperacillin at concentrations
up to 200��g/disk. Piperacillin was negative in the UDS
test at concentrations up to 10,000��g/mL. In a mammalian
point mutation (mouse lymphoma cells) assay, piperacillin was positive
at concentrations���2500��g/mL. Piperacillin was
negative in a cell (BALB/c-3T3) transformation assay at concentrations
up to 3000��g/mL. In vivo, piperacillin did not induce
chromosomal aberrations in mice at I.V. doses up to 2000 mg/kg/day
or rats at I.V. doses up to 1500 mg/kg/day. These doses are half
(mice) or similar (rats) to the maximum recommended human daily dose
based on body-surface area (mg/m). In another in vivo
test, there was no dominant lethal effect when piperacillin was administered
to rats at I.V. doses up to 2000 mg/kg/day, which is similar
to the maximum recommended human daily dose based on body-surface
area (mg/m). When mice were administered piperacillin
at I.V. doses up to 2000 mg/kg/day, which is half the maximum
recommended human daily dose based on body-surface area (mg/m), urine from these animals was not mutagenic when tested
in a microbial mutagenicity assay. Bacteria injected into the peritoneal
cavity of mice administered piperacillin at I.V. doses up to 2000 mg/kg/day
did not show increased mutation frequencies.<br/>Tazobactam: Tazobactam was negative in microbial mutagenicity
assays at concentrations up to 333��g/plate. Tazobactam
was negative in the UDS test at concentrations up to 2000��g/mL.
Tazobactam was negative in a mammalian point mutation (Chinese hamster
ovary cell HPRT) assay at concentrations up to 5000��g/mL.
In another mammalian point mutation (mouse lymphoma cells) assay,
tazobactam was positive at concentrations���3000��g/mL.
Tazobactam was negative in a cell (BALB/c-3T3) transformation assay
at concentrations up to 900��g/mL. In an in vitro cytogenetics
(Chinese hamster lung cells) assay, tazobactam was negative at concentrations
up to 3000��g/mL. In vivo, tazobactam did not induce chromosomal
aberrations in rats at I.V. doses up to 5000 mg/kg, which is
23 times the maximum recommended human daily dose based on body-surface
area (mg/m).<br/>Pregnancy:<br/>Teratogenic effects���Pregnancy Category B:<br/>Nursing Mothers: Piperacillin is excreted in low concentrations in
human milk; tazobactam concentrations in human milk have not been
studied. Caution should be exercised when ZOSYN is administered to
a nursing woman.<br/>Pediatric Use: Use of Zosyn in pediatric patients 2 months of age
or older with appendicitis and/or peritonitis is supported by evidence
from well-controlled studies and pharmacokinetic studies in adults
and in pediatric patients. This includes a prospective, randomized,
comparative, open-label clinical trial with 542 pediatric patients
2-12 years of age with complicated intra-abdominal infections, in
which 273 pediatric patients received piperacillin/tazobactam. Safety
and efficacy in pediatric patients less than 2 months of age have
not been established . There are no dosage recommendations for
Zosyn in pediatric patients with impaired renal function.<br/>Geriatric Use: Patients over 65 years are not at an increased
risk of developing adverse effects solely because of age. However,
dosage should be adjusted in the presence of renal insufficiency. In general, dose selection for
an elderly patient should be cautious, usually starting at the low
end of the dosing range, reflecting the greater frequency of decreased
hepatic, renal, or cardiac function, and of concomitant disease or
other drug therapy. The approximate total sodium
content for ZOSYN in Galaxy Containers is 5.58 mEq (128 mg) per 50 mL
in the 2.25 g dose, 8.38 mEq (192 mg) per 50 mL in the 3.375 g
dose, and 11.17 mEq (256 mg) per 100 mL in the 4.5 g
dose. At the usual recommended doses, patients would receive approximately
790 to 1050 mg/day (33.5 to 44.6 mEq) of sodium. The geriatric population
may respond with a blunted natriuresis to salt loading. This may be
clinically important with regard to such diseases as congestive heart
failure. This drug 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. Because elderly
patients are more likely to have decreased renal function, care should
be taken in dose selection, and it may be useful to monitor renal
function.
|
dailymed-instance:overdosag... |
There have been post-marketing reports of overdose
with piperacillin/tazobactam. The majority of those events experienced,
including nausea, vomiting, and diarrhea, have also been reported
with the usual recommended dosages. Patients may experience neuromuscular
excitability or convulsions if higher than recommended doses are given
intravenously (particularly in the presence of renal failure). Treatment should be supportive and symptomatic according
to the patient's clinical presentation. Excessive serum concentrations
of either piperacillin or tazobactam may be reduced by hemodialysis.
Following a single 3.375 g dose of piperacillin/tazobactam, the
percentage of piperacillin and tazobactam dose removed by hemodialysis
was approximately 31% and 39%, respectively.
|
dailymed-instance:genericMe... |
Piperacillin sodium and Tazobactam sodium
|
dailymed-instance:fullName |
Zosyn (Injection, Solution)
|
dailymed-instance:adverseRe... |
Adverse Events From Clinical Trials: During the initial clinical investigations, 2621
patients worldwide were treated with ZOSYN in phase 3 trials. In the
key North American clinical trials (n=830 patients), 90% of the adverse
events reported were mild to moderate in severity and transient in
nature. However, in 3.2% of the patients treated worldwide, ZOSYN
was discontinued because of adverse events primarily involving the
skin (1.3%), including rash and pruritus; the gastrointestinal system
(0.9%), including diarrhea, nausea, and vomiting; and allergic reactions
(0.5%). Adverse local reactions that were reported,
irrespective of relationship to therapy with ZOSYN, were phlebitis
(1.3%), injection site reaction (0.5%), pain (0.2%), inflammation
(0.2%), thrombophlebitis (0.2%), and edema (0.1%). Based on patients from the North American trials (n=1063), the events
with the highest incidence in patients, irrespective of relationship
to ZOSYN therapy, were diarrhea (11.3%); headache (7.7%); constipation
(7.7%); nausea (6.9%); insomnia (6.6%); rash (4.2%), including maculopapular,
bullous, urticarial, and eczematoid; vomiting (3.3%); dyspepsia (3.3%);
pruritus (3.1%); stool changes (2.4%); fever (2.4%); agitation (2.1%);
pain (1.7%); moniliasis (1.6%); hypertension (1.6%); dizziness (1.4%);
abdominal pain (1.3%); chest pain (1.3%); edema (1.2%); anxiety (1.2%);
rhinitis (1.2%); and dyspnea (1.1%). Additional
adverse systemic clinical events reported in 1.0% or less of the patients
in the initial North American trials are listed below within each
body system. Autonomic
nervous system���hypotension, ileus, syncope Body as a whole���rigors, back pain, malaise Cardiovascular���tachycardia, including
supraventricular and ventricular; bradycardia; arrhythmia, including
atrial fibrillation, ventricular fibrillation, cardiac arrest, cardiac
failure, circulatory failure, myocardial infarction Central nervous system���tremor,
convulsions, vertigo Gastrointestinal���melena, flatulence, hemorrhage,
gastritis, hiccough, ulcerative stomatitis Pseudomembranous colitis was reported in one patient during the clinical
trials. The onset of pseudomembranous colitis symptoms may occur during
or after antibacterial treatment. Hearing and Vestibular System���tinnitus Hypersensitivity���anaphylaxis Metabolic and Nutritional���symptomatic
hypoglycemia, thirst Musculoskeletal���myalgia, arthralgia Platelets, Bleeding, Clotting���mesenteric embolism, purpura, epistaxis, pulmonary embolism
(See PRECAUTIONS,
General.) Psychiatric���confusion, hallucination,
depression Reproductive,
Female���leukorrhea, vaginitis Respiratory���pharyngitis,
pulmonary edema, bronchospasm, coughing Skin and Appendages���genital pruritus,
diaphoresis Special
senses���taste perversion Urinary���retention, dysuria, oliguria,
hematuria, incontinence Vision���photophobia Vascular (extracardiac)���flushing<br/>Nosocomial Pneumonia Trials: In a completed study of nosocomial lower respiratory
tract infections, 222 patients were treated with ZOSYN in a dosing
regimen of 4.5 g every 6 hours in combination with an aminoglycoside
and 215 patients were treated with imipenem/cilastatin (500 mg/500 mg
q6h) in combination with an aminoglycoside. In this trial, treatment-emergent
adverse events were reported by 402 patients, 204 (91.9%)
in the piperacillin/tazobactam group and 198 (92.1%) in the imipenem/cilastatin
group. Twenty-five (11.0%) patients in the piperacillin/tazobactam
group and 14 (6.5%) in the imipenem/cilastatin group (p>0.05) discontinued
treatment due to an adverse event. In this
study of ZOSYN in combination with an aminoglycoside, adverse events
that occurred in more than 1% of patients and were considered by the
investigator to be drug-related were: diarrhea (17.6%), fever (2.7%),
vomiting (2.7%), urinary tract infection (2.7%), rash (2.3%), abdominal
pain (1.8%), generalized edema (1.8%), moniliasis (1.8%), nausea (1.8%),
oral moniliasis (1.8%), BUN increased (1.8%), creatinine increased
(1.8%), peripheral edema (1.8%), abdomen enlarged (1.4%), headache(1.4%), constipation (1.4%), liver function tests abnormal (1.4%),
thrombocythemia (1.4%), excoriations (1.4%), and sweating (1.4%). Drug-related adverse events reported in 1% or less of
patients in the nosocomial pneumonia study of ZOSYN with an aminoglycoside
were: acidosis, acute kidney failure, agitation, alkaline phosphatase
increased, anemia, asthenia, atrial fibrillation, chest pain, CNS
depression, colitis, confusion, convulsion, cough increased, thrombocytopenia,
dehydration, depression, diplopia, drug level decreased, dry mouth,
dyspepsia, dysphagia, dyspnea, dysuria, eosinophilia,fungal dermatitis,
gastritis, glossitis, grand mal convulsion, hematuria, hyperglycemia,
hypernatremia, hypertension, hypertonia, hyperventilation, hypochromic
anemia, hypoglycemia, hypokalemia, hyponatremia, hypophosphatemia,
hypoxia, ileus, injection site edema, injection site pain, injection
site reaction, kidney function abnormal, leukocytosis, leukopenia,
local reaction to procedure, melena, pain, prothrombin decreased,
pruritus, respiratory disorder, SGOT increased, SGPT increased, sinus
bradycardia,somnolence, stomatitis, stupor, tremor, tachycardia,
ventricular extrasystoles, and ventricular tachycardia. In a previous nosocomial pneumonia study conducted with
a dosing regimen of 3.375 g given every 4 hours with an aminoglycoside,
the following adverse events, irrespective of drug relationship, were
observed: diarrhea (20%); constipation (8.4%); agitation (7.1%); nausea
(5.8%); headache (4.5%); insomnia (4.5%); oral thrush (3.9%); erythematous
rash (3.9%); anxiety (3.2%); fever(3.2%); pain (3.2%); pruritus (3.2%);
hiccough (2.6%); vomiting (2.6%); dyspepsia (1.9%); edema (1.9%);
fluid overload (1.9%); stool changes (1.9%); anorexia (1.3%); cardiac
arrest (1.3%); confusion (1.3%); diaphoresis (1.3%); duodenal ulcer
(1.3%); flatulence (1.3%); hypertension (1.3%); hypotension (1.3%);
inflammation at injection site (1.3%); pleural effusion (1.3%); pneumothorax
(1.3%); rash, not otherwise specified (1.3%); supraventricular tachycardia
(1.3%); thrombophlebitis (1.3%); and urinary incontinence (1.3%). Adverse events irrespective of drug relationship observed
in 1% or less of patients in the above study with ZOSYN and an aminoglycoside
included: aggressive reaction (combative), angina, asthenia, atelectasis,
balanoposthitis, cerebrovascular accident, chest pain, conjunctivitis,
deafness, dyspnea, earache, ecchymosis, fecal incontinence, gastric
ulcer, gout, hemoptysis, hypoxia, pancreatitis, perineal irritation/pain,
urinary tract infection with trichomonas, vitaminBdeficiency anemia, xerosis, and yeast in urine.<br/>Pediatrics: Studies of Zosyn in pediatric patients suggest a
similar safety profile to that seen in adults. In a prospective, randomized,
comparative, open-label clinical trial of pediatric patients with
severe intra-abdominal infections (including appendicitis and/or peritonitis),
273 patients were treated with Zosyn (112.5 mg/kg every 8 hours) and
269 patients were treated with cefotaxime (50 mg/kg) plus metronidazole
(7.5 mg/kg) every 8 hours. In this trial, treatment-emergent adverse
events were reported by 146 patients, 73 (26.7%) in the Zosyn group
and 73 (27.1%) in the cefotaxime/metronidazole group. Six patients
(2.2%) in the Zosyn group and 5 patients (1.9%) inthe cefotaxime/metronidazole
group discontinued due to an adverse event. In this study, adverse events that were reported in more than 1%
of patients, irrespective of relationship to therapy with ZOSYN were:
diarrhea (7.0%), fever (4.8%), vomiting (3.7%), local reaction (3.3%),
abscess (2.2%), sepsis (2.2%), abdominal pain (1.8%), infection (1.8%),
bloody diarrhea (1.1%), pharyngitis (1.5%), constipation (1.1%) and
SGOT increase (1.1%). Adverse events reported
in 1% or less of pediatric patients receiving Zosyn are consistent
with adverse events reported in adults. Additional
controlled studies in pediatric patients showed a similar safety profile
as that described above.<br/>Post-Marketing Experience: Additional adverse events reported from worldwide
marketing experience with ZOSYN, occurring under circumstances where
causal relationship to ZOSYN is uncertain: Gastrointestinal���hepatitis, cholestatic jaundice Hematologic���hemolytic anemia, anemia, thrombocytosis,
agranulocytosis, pancytopenia Immune������hypersensitivity
reactions, anaphylactic/anaphylactoid reactions (including shock) Infections������candidal superinfections Renal���interstitial nephritis, renal failure Skin and Appendages���erythema multiforme, Stevens-Johnson
syndrome, toxic epidermal necrolysis Post-marketing
experience with Zosyn in pediatric patients suggests a similar safety
profile to that seen in adults.<br/>Adverse Laboratory Events (Seen During Clinical Trials): Of the studies reported, including that of nosocomial
lower respiratory tract infections in which a higher dose of ZOSYN
was used in combination with an aminoglycoside, changes in laboratory
parameters, without regard to drug relationship, include: Hematologic���decreases
in hemoglobin and hematocrit, thrombocytopenia, increases in platelet
count, eosinophilia, leukopenia, neutropenia. The leukopenia/neutropenia
associated with ZOSYN administration appears to be reversible and
most frequently associated with prolonged administration, ie,���21 days of therapy. These patients were withdrawn from therapy; some
had accompanying systemic symptoms (eg, fever, rigors, chills). Coagulation���positive
direct Coombs' test, prolonged prothrombin time, prolonged partial
thromboplastin time Hepatic���transient elevations of AST (SGOT), ALT
(SGPT), alkaline phosphatase, bilirubin Renal���increases in serum creatinine,
blood urea nitrogen Urinalysis���proteinuria, hematuria, pyuria Additional laboratory events include abnormalities in
electrolytes (ie, increases and decreases in sodium, potassium and
calcium), hyperglycemia, decreases in total protein or albumin, blood
glucose decreased, gamma-glutamyltransferase increased, hypokalemia,
and bleeding time prolonged. The following
adverse reaction has also been reported for PIPRACIL (piperacillin for injection): Skeletal���prolonged muscle relaxation
(See PRECAUTIONS,
Drug Interactions.) Piperacillin
therapy has been associated with an increased incidence of fever and
rash in cystic fibrosis patients.
|
dailymed-instance:warning |
SERIOUS AND OCCASIONALLY FATAL HYPERSENSITIVITY (ANAPHYLACTIC/ANAPHYLACTOID)
REACTIONS (INCLUDING SHOCK) HAVE BEEN REPORTED IN PATIENTS RECEIVING
THERAPY WITH PENICILLINS INCLUDING ZOSYN. THESE REACTIONS ARE MORE
LIKELY TO OCCUR IN INDIVIDUALS WITH A HISTORY OF PENICILLIN HYPERSENSITIVITY
OR A HISTORY OF SENSITIVITY TO MULTIPLE ALLERGENS. THERE HAVE BEEN
REPORTS OF INDIVIDUALS WITH A HISTORY OF PENICILLIN HYPERSENSITIVITY
WHO HAVE EXPERIENCED SEVERE REACTIONS WHEN TREATED WITH CEPHALOSPORINS.
BEFORE INITIATING THERAPY WITH ZOSYN, CAREFUL INQUIRY SHOULDBE MADE
CONCERNING PREVIOUS HYPERSENSITIVITY REACTIONS TO PENICILLINS, CEPHALOSPORINS,
OR OTHER ALLERGENS. IF AN ALLERGIC REACTION OCCURS, ZOSYN SHOULD BE
DISCONTINUED AND APPROPRIATE THERAPY INSTITUTED. SERIOUS ANAPHYLACTIC/ANAPHYLACTOID REACTIONS (INCLUDING
SHOCK) REQUIRE IMMEDIATE EMERGENCY TREATMENT WITH EPINEPHRINE. OXYGEN,
INTRAVENOUS STEROIDS, AND AIRWAY MANAGEMENT, INCLUDING INTUBATION,
SHOULD ALSO BE ADMINISTERED AS INDICATED. Clostridium difficile associated
diarrhea (CDAD) has been reported with use of nearly all antibacterial
agents, including ZOSYN, and may range in severity from mild diarrhea
to fatal colitis. Treatment with antibacterial agents alters the normal
flora of the colon leading to overgrowth of C. difficile. C. difficile produces toxins A and B
which contribute to the development of CDAD. Hypertoxin producing
strains of C. difficile cause
increased morbidity and mortality, as these infections can be refractory
to antimicrobial therapy and may require colectomy. CDAD must be considered
in all patients who present with diarrhea following antibiotic use.
Careful medical history is necessary since CDAD has been reported
to occur over two months after the administration of antibacterial
agents. If CDAD is suspected or confirmed, ongoing
antibiotic use not directed against C.
difficile may need to be discontinued. Appropriate fluid
and electrolyte management, protein supplementation, antibiotic treatmentof C. difficile, and surgical
evaluation should be instituted as clinically indicated.
|
dailymed-instance:indicatio... |
ZOSYN is indicated for the treatment of patients
with moderate to severe infections caused by piperacillin-resistant,
piperacillin/tazobactam-susceptible,��-lactamase producing strains
of the designated microorganisms in the specified conditions listed
below: Appendicitis (complicated by rupture
or abscess) and peritonitis caused by piperacillin-resistant,��-lactamase
producing strains of Escherichia coli or the following members of the Bacteroides fragilis
group: B. fragilis, B. ovatus, B. thetaiotaomicron , or B. vulgatus. The individual members
of this group were studied in less than 10 cases. Uncomplicated and complicated skin and skin structure infections,
including cellulitis, cutaneous abscesses and ischemic/diabetic foot
infections caused by piperacillin-resistant,��-lactamase producing
strains of Staphylococcus aureus. Postpartum endometritis or pelvic inflammatory
disease caused by piperacillin-resistant,��-lactamase producing
strains of Escherichia coli. Community-acquired pneumonia (moderate severity
only) caused by piperacillin-resistant,��-lactamase producing
strains of Haemophilus influenzae. Nosocomial pneumonia (moderate to severe)
caused by piperacillin-resistant,��-lactamase producing strains
of Staphylococcus aureus and
by piperacillin/tazobactam-susceptible Acinetobacter baumanii, Haemophilus
influenzae, Klebsiella pneumoniae, and Pseudomonas aeruginosa . (Nosocomial pneumonia caused by P.
aeruginosa should be treated in combination with an aminoglycoside.) ZOSYN is indicated only for the
specified conditions listed above. Infections caused by piperacillin-susceptible
organisms, for which piperacillin has been shown to be effective,
are also amenable to ZOSYN treatment due to its piperacillin content.
The tazobactam component of this combination product does not decrease
the activity of the piperacillin component against piperacillin-susceptible
organisms. Therefore, the treatment of mixed infections caused by
piperacillin-susceptible organisms and piperacillin-resistant,��-lactamase
producing organisms susceptible to ZOSYN should not require the addition
of another antibiotic. ZOSYN is useful as presumptive therapy in the indicated
conditions prior to the identification of causative organisms because
of its broad spectrum of bactericidal activity against gram-positiveand gram-negative aerobic and anaerobic organisms. Appropriate cultures should usually be performed before initiating
antimicrobial treatment in order to isolate and identify the organisms
causing infection and to determine their susceptibility to ZOSYN.
Antimicrobial therapy should be adjusted, if appropriate, once the
results of culture(s) and antimicrobial susceptibility testing are
known. To reduce the development of drug-resistant
bacteria and maintain the effectiveness of Zosyn (piperacillin and
tazobactam) injection and other antibacterial drugs, Zosyn (piperacillin
and tazobactam) 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 antibacterial
therapy. In the absence of such data, local epidemiology and susceptibility
patterns may contribute to the empiric selection of therapy.
|
dailymed-instance:represent... | |
dailymed-instance:routeOfAd... | |
dailymed-instance:name |
Zosyn
|