To reduce the development of drug-resistant bacteria and maintain the
effectiveness of ceftriaxone for injection, and other antibacterial drugs,
ceftriaxone for injection should be used only to treat or prevent infections
that are proven or strongly suspected to be caused by bacteria.
DESCRIPTION:
Ceftriaxone for injection, USP is a sterile, semisynthetic, broad-spec-
trum cephalosporin antibiotic for intravenous or intramuscular adminis-
tration. Ceftriaxone sodium is (6R, 7R)-7-[2-(2-Amino-4-thiazolyl) gly-
oxylamido]-8-oxo-3-[[(1,2,5,6-tetrahydro-2-methyl-5,6-dioxo-as-triazin-3-y
l)thio]methyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid, 72-
(Z)-(O-methyloxime), disodium salt, sesquaterhydrate.
The chemical formula of ceftriaxone sodium is C18H16N8Na2O7S3•3.5H2O.
It has a calculated molecular weight of 661.60 and the following structural
formula:
Ceftriaxone sodium is a white to yellowish crystalline powder which is
readily soluble in water, sparingly soluble in methanol and very slightly
soluble in ethanol. The pH of a 1% aqueous solution is approximately 6.7.
The color of ceftriaxone sodium solutions ranges from light yellow to
amber, depending on the length of storage, concentration and diluent used.
Each vial contains ceftriaxone sodium equivalent to 250 mg, 500 mg, 1
gram or 2 grams of ceftriaxone activity. Ceftriaxone sodium contains
approximately 83 mg (3.6 mEq) of sodium per gram of ceftriaxone
activity.
CLINICAL PHARMACOLOGY:
Average plasma concentrations of ceftriaxone following a single 30-
minute intravenous (IV) infusion of a 0.5, 1 or 2 gm dose and intramus-
cular (IM) administration of a single 0.5 (250mg/mL or 350 mg/mL con-
centrations) or 1 gm dose in healthy subjects are presented in Table 1.
Table 1. Ceftriaxone Plasma Concentrations After Single Dose
Administration
*IV doses were infused at a constant rate over 30 minutes.
Ceftriaxone was completely absorbed following IM administration with
mean maximum plasma concentrations occurring between 2 and 3hours
post-dose. Multiple IV or IM doses ranging from 0.5 to 2 gm at 12- to 24-
hour intervals resulted in 15% to 36% accumulation of ceftriaxone above
single dose values.
Ceftriaxone concentrations in urine are shown in Table 2.
Table 2. Urinary Concentrations of Ceftriaxone After Single Dose
Administration
Thirty-three percent to 67% of a ceftriaxone dose was excreted in the
urine as unchanged drug and the remainder was secreted in the bile and
ultimately found in the feces as microbiologically inactive compounds. After
a 1 gm IV dose, average concentrations of ceftriaxone, determined from
1 to 3 hours after dosing, were 581 mcg/mL in the gallbladder bile,
788 mcg/mL in the common duct bile, 898mcg/mL in the cystic duct bile,
78.2 mcg/gm in the gallbladder wall and 62.1 mcg/mL in the concurrent
plasma.
Over a 0.15 to 3 gm dose range in healthy adult subjects, the values
of elimination half-life ranged from 5.8 to 8.7 hours; apparent volume of
distribution from 5.78 to 13.5 L; plasma clearance from 0.58 to 1.45 L/hour;
and renal clearance from 0.32 to 0.73 L/hour. Ceftriaxone is reversibly
bound to human plasma proteins, and the binding decreased from a
value of 95% bound at plasma concentrations of < 25mcg/mL to a value
of 85% bound at 300 mcg/mL. Ceftriaxone crosses the blood placenta
barrier.
The average values of maximum plasma concentration, elimination half-
life, plasma clearance and volume of distribution after a 50mg/kg IV dose
and after a 75 mg/kg IV dose in pediatric patients suffering from bacte-
rial meningitis are shown in Table 3. Ceftriaxone penetrated the inflamed
meninges of infants and pediatric patients; CSF concentrations after a
50 mg/kg IV dose and after a 75mg/kg IV dose are also shown in Table3.
Table 3. Average Pharmacokinetic P arameters of Ceftriaxone in
Pediatric Patients With Meningitis
Compared to that in healthy adult subjects, the pharmacokinetics of cef-
triaxone were only minimally altered in elderly subjects and in patients with
renal impairment or hepatic dysfunction (Table 4); therefore, dosage
adjustments are not necessary for these patients with ceftriaxone dosages
up to 2 gm per day. Ceftriaxone was not removed to any significant
extent from the plasma by hemodialysis. In 6 of 26 dialysis patients, the
elimination rate of ceftriaxone was markedly reduced.
Table 4. Average Pharmacokinetic Parameters of Ceftriaxone in
Humans
* Creatinine clearance.
The elimination of ceftriaxone is not altered when ceftriaxone is co-
administered with probenecid.
Pharmacokinetics in the Middle Ear Fluid:
In one study, total ceftriaxone concentrations (bound and unbound) were
measured in middle ear fluid obtained during the insertion of tympanos-
tomy tubes in 42 pediatric patients with otitis media. Sampling times were
from 1 to 50 hours after a single intramuscular injection of 50 mg/kg of
ceftriaxone. Mean (±SD) ceftriaxone levels in the middle ear reached a peak
of 35 (±12) mcg/mL at 24 hours, and remained at 19 (±7) mcg/mL at
48 hours. Based on middle ear fluid ceftriaxone concentrations in the 23
to 25 hour and the 46 to 50 hour sampling time inter vals, a half-life of
25 hours was calculated. Ceftriaxone is highly bound to plasma proteins.
The extent of binding to proteins in the middle ear fluid is unknown.
Interaction with Calcium:
Two in vitro studies, one using adult plasma and the other neonatal
plasma from umbilical cord blood have been carried out to assess inter-
action of ceftriaxone and calcium. Ceftriaxone concentrations up to 1mM
(in excess of concentrations achieved in vivofollowing administration of
2 grams ceftriaxone infused over 30 minutes) were used in combination
with calcium concentrations up to 12 mM (48 mg/dL). Recovery of cef-
triaxone from plasma was reduced with calcium concentrations of 6mM
(24 mg/dL) or higher in adult plasma or 4 mM (16 mg/dL) or higher in
neonatal plasma. This may be reflective of ceftriaxone-calcium precipitation.
Microbiology:
Mechanism of Action:
Ceftriaxone is a bactericidal agent that acts by inhibition of bacterial cell
wall synthesis. Ceftriaxone has activity in the presence of some beta-lac-
tamases, both penicillinases and cephalosporinases, of Gram-negative and
Gram-positive bacteria.
Mechanism of Resistance:
Resistance to ceftriaxone is primarily through hydrolysis by beta-lac-
tamase, alteration of penicillin-binding proteins (PBPs), and decreased
permeability.
Interaction with Other Antimicrobials In an in vitrostudy antagonistic
effects have been observed with the combination of chloramphenicol and
ceftriaxone.
Ceftriaxone has been shown to be active against most isolates of the
following bacteria, both in vitro and in clinical infections as described in
the INDICATIONS AND USAGE section:
•Gram-negative bacteria
Acinetobacter calcoaceticus
Enterobacter aerogenes
Enterobacter cloacae
Escherichia coli
Haemophilus influenzae
Haemophilus parainfluenzae
Klebsiella oxytoca
Klebsiella pneumoniae
Moraxella catarrhalis
Morganella morganii
Neisseria gonorrhoeae
Neisseria meningitidis
Proteus mirabilis
Proteus vulgaris
Pseudomonas aeruginosa
Serratia marcescens
•Gram-positive bacteria
Staphylococcus aureus
Staphylococcus epidermidis
Streptococcus pneumoniae
Streptococcus pyogenes
Viridans group streptococci
•Anaerobic bacteria
Bacteroides fragilis
Clostridium species
Peptostreptococcus species
The following in vitro data are available, but their clinical signifi-
cance is unknown. At least 90 percent of the following microorganisms
exhibit an in vitro minimum inhibitory concentration (MIC) less than or
equal to the susceptible breakpoint for ceftriaxone. However, the efficacy
of ceftriaxone in treating clinical infections due to these microorgan-
isms has not beenestablished in adequate and well-controlled clinical trials.
•Gram-negative bacteria
Citrobacter diversus
Citrobacter freundii
Providencia species (including Providencia rettgeri )
Salmonella species (including Salmonella typhi )
Shigella species
•Gram-positive bacteria
Streptococcus agalactiae
•Anaerobic bacteria
Porphyromonas (Bacteroides) melaninogenicus
Prevotella (Bacteroides) bivius
Susceptibility Test Methods:
When available, the clinical microbiology laboratory should provide the
results of in vitro susceptibility test results for antimicrobial drug prod-
ucts used in resident hospitals to the physician as periodic reports that
describe the susceptibility profile of nosocomial and community-acquired
pathogens. These reports should aid the physician in selecting an anti-
bacterial drug product for treatment.
Dilution techniques: Quantitative methods are used to determine
antimicrobial minimal inhibitory concentrations (MICs). These MICs pro-
vide estimates of the susceptibility of bacteria to antimicrobial com-
pounds. The MICs should be determined using a standardized test
method 1,3. The MIC values should be interpreted according to criteria
provided in Table 5.
Diffusion techniques: Quantitative methods that require measurement
of zone diameters also provide reproducible estimates of the susceptibility
of bacteria to antimicrobial compounds. The zone size provides an esti-
mate of the susceptibility of bacteria to antimicrobial compounds. The zone
size should be determined using a standardized test method.2,3 .This pro-
cedure uses paper disks impregnated with 30 mcg ceftriaxone to test the
susceptibility of microorganisms to ceftriaxone. The disk diffusion inter-
pretive criteria are provided in Table 5.
Anaerobic techniques: For anaerobic bacteria, the susceptibility to
ceftriaxone as MICs can be determined by a standardized agar test
method 3,4 . The MIC values obtained should be interpreted according to
the criteria provided in Table 5.
Dose/Route
Average Plasma Concentrations (mcg/mL)
0.5 hr 1 hr 2 hr 4 hr 6 hr 8 hr 12 hr 16 hr 24 hr
0.5 gm IV* 82 59 48 37 29 23 15 10 5
0.5 gm IM
250 mg/mL 22 33 38 35 30 26 16 ND 5
0.5 gm IM
350 mg/mL 20 32 38 34 31 24 16 ND 5
1 gm IV* 151 111 88 67 53 43 28 18 9
1 gm IM 40 68 76 68 56 44 29 ND ND
2 gm lV* 257 192 154 117 89 74 46 31 15
ND = Not determined.
Dose/Route
Average Urinary Concentrations (mcg/mL)
0 to 2 hr 2 to 4 hr 4 to 8 hr 8 to 12 hr
12 to
24 hr
24 to
48 hr
0.5 gm IV 526 366 142 87 70 15
0.5 gm IM 115 425 308 127 96 28
1 gm IV 995 855 293 147 132 32
1 gm IM 504 628 418 237 ND ND
2 gm IV 2692 1976 757 274 198 40
ND = Not determined.
50 mg/kg IV 75 mg/kg IV
Maximum Plasma
Concentrations (mcg/mL) 216 275
Elimination Half-life (hr) 4.6 4.3
Plasma Clearance (mL/hr/kg) 49 60
Volume of Distribution (mL/kg) 338 373
CSF Concentration –
inflamed meninges (mcg/mL) 5.6 6.4
Range (mcg/mL) 1.3 to 18.5 1.3 to 44
Time after dose (hr) 3.7 (± 1.6) 3.3 (± 1.4)
Subject Group
Elimination
Half-Life
(hr)
Plasma
Clearance
(L/hr)
Volume of
Distribution
(L)
Healthy Subjects 5.8 to 8.7 0.58 to 1.45 5.8 to 13.5
Elderly Subjects
(mean age, 70.5 yr) 8.9 0.83 10.7
Patients With
Renal Impairment
Hemodialysis Patients
(0 to 5 mL/min)* 14.7 0.65 13.7
Severe (5 to 15 mL/min) 15.7 0.56 12.5
Moderate (16 to 30 mL/min) 11.4 0.72 11.8
Mild (31 to 60 mL/min) 12.4 0.70 13.3
Patients With
Liver Disease 8.8 1.1 13.6
Table 5. Susceptibility Test Interpretive Criteria for Ceftriaxone.
Susceptibility of staphylococci to ceftriaxone may be deduced from test-
ing only penicillin and either cefoxitin or oxacillin.
* The current absence of data on resistant isolates precludes defining any
category other than ‘Susceptible’. If isolates yield MIC results other than
susceptible, they should be submitted to a reference laboratory for addi-
tional testing.
† Disc diffusion interpretive criteria for ceftriaxone discs against
Streptococcus pneumoniae are not available, however, isolates of
pneumococci with oxacillin zone diameters of >20 mm are suscepti-
ble (MIC ≤ 0.06 mcg/mL) to penicillin and can be considered suscep-
tible to ceftriaxone. Streptococcus pneumoniae isolates should not be
reported as penicillin (ceftriaxone) resistant or intermediate based
solely on an oxacillin zone diameter of ≤ 19 mm. The ceftriaxone MIC
should be determined for those isolates with oxacillin zone diameters
≤ 19 mm.
A report of Susceptible indicates that the antimicrobial is likely to
inhibit growth of the pathogen if the antimicrobial compound reaches the
concentration at the infection site necessary to inhibit growth of the
pathogen. A report of Intermediateindicates that the result should be con-
sidered equivocal, and if the microorganism is not fully susceptible to alter-
native, clinically feasible drugs, the test should be repeated. This category
implies possible clinical applicability in body sites where the drug is
physiologically concentrated or in situations where a high dosage of
drug can be used. This category also provides a buffer zone that prevents
small uncontrolled technical factors from causing major discrepancies in
interpretation. A report of Resistantindicates that the antimicrobial is not
likely to inhibit growth of the pathogen if the antimicrobial compound
reaches the concentrations usually achievable at the infection site; other
therapy should be selected.
Quality Control: Standardized susceptibility test procedures require the
use of laboratory controls to monitor and ensure the accuracy and pre-
cision of supplies and reagents used in the assay, and the techniques of
the individual performing the test1,2,3,4. Standard ceftriaxone powder
should provide the following range of MIC values noted in Table 6. For
the diffusion technique using the 30 mcg disk, the criteria in Table 6 should
be achieved.
Table 6. Acceptable Quality Control Ranges for Ceftriaxone
INDICATIONS AND USAGE:
Before instituting treatment with ceftriaxone, appropriate specimens
should be obtained for isolation of the causative organism and for deter-
mination of its susceptibility to the drug. Therapy may be instituted prior
to obtaining results of susceptibility testing.
To reduce the development of drug-resistant bacteria and maintain the
effectiveness of ceftriaxone for injection, USP and other antibacterial
drugs, ceftriaxone for injection, USP should be used only to treat or pre-
vent infections that are proven or strongly suspected to be caused by sus-
ceptible bacteria. When culture and susceptibility information are avail-
able, 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. Ceftriaxone
for injection, USP is indicated for the treatment of the following infections
when caused by susceptible organisms:
Lower Respiratory Tract Infections:
caused by Streptococcus pneumoniae, Staphylococcus aureus,
Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneu-
moniae, Escherichia coli, Enterobacter aerogenes, Proteus mirabilis or
Serratia marcescens.
Acute Bacterial Otitis Media:
caused by Streptococcus pneumoniae, Haemophilus influenzae(includ-
ing beta-lactamase producing strains) or Moraxella catarrhalis(including
beta-lactamase producing strains).
NOTE: In one study lower clinical cure rates were observed with a sin-
gle dose of ceftriaxone compared to 10 days of oral therapy. In a second
study comparable cure rates were observed between single dose ceftri-
axone and the comparator. The potentially lower clinical cure rate of cef-
triaxone should be balanced against the potential advantages of par-
enteral therapy (see CLINICAL STUDIES).
Skin and Skin Structure Infections:
caused by Staphylococcus aureus, Staphylococcus epidermidis,
Streptococcus pyogenes, Viridans group streptococci, Escherichia coli,
Enterobacter cloacae, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus
mirabilis, Morganella morganii,*Pseudomonas aeruginosa, Serratia
marcescens, Acinetobacter calcoaceticus, Bacteroides fragilis* or
Peptostreptococcus species.
Urinary Tract Infections (complicated and uncomplicated):
caused by Escherichia coli, Proteus mirabilis, Proteus vulgaris,
Morganella morganii or Klebsiella pneumoniae.
Uncomplicated Gonorrhea (cervical/urethral and rectal):
caused by Neisseria gonorrhoeae, including both penicillinase- and non-
penicillinase-producing strains, and pharyngeal gonorrhea caused by
nonpenicillinase-producing strains of Neisseria gonorrhoeae.
Pelvic Inflammatory Disease:
caused by Neisseria gonorrhoeae. Ceftriaxone sodium, like other
cephalosporins, has no activity against Chlamydia trachomatis. Therefore,
when cephalosporins are used in the treatment of patients with pelvic
inflammatory disease and Chlamydia trachomatisis one of the suspected
pathogens, appropriate antichlamydial coverage should be added.
Bacterial Septicemia:
caused by Staphylococcus aureus, Streptococcus pneumoniae,
Escherichia coli, Haemophilus influenzae or Klebsiella pneumoniae.
Bone and Joint Infections:
caused by Staphylococcus aureus, Streptococcus pneumoniae,
Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae or Enterobacter
species.
Intra-abdominal Infections:
caused by Escherichia coli, Klebsiella pneumoniae, Bacteroides frag-
ilis, Clostridium species (Note: most strains of Clostridium difficile are
resistant) or Peptostreptococcus species.
Meningitis:
caused by Haemophilus influenzae, Neisseria meningitidis or
Streptococcus pneumoniae. Ceftriaxone has also been used successfully
in a limited number of cases of meningitis and shunt infection caused by
Staphylococcus epidermidis* and Escherichia coli.*
Surgical Prophylaxis:
The preoperative administration of a single 1 gm dose of ceftriaxone
may reduce the incidence of postoperative infections in patients under-
going surgical procedures classified as contaminated or potentially con-
taminated (e.g., vaginal or abdominal hysterectomy or cholecystectomy
for chronic calculous cholecystitis in high-risk patients, such as those over
70 years of age, with acute cholecystitis not requiring therapeutic antimi-
crobials, obstructive jaundice or common duct bile stones) and in sur-
gical patients for whom infection at the operative site would present
serious risk (e.g., during coronary artery bypass surgery). Although cef-
triaxone has been shown to have been as effective as cefazolin in the pre-
vention of infection following coronary artery bypass surgery, no placebo-
controlled trials have been conducted to evaluate any cephalosporin
antibiotic in the prevention of infection following coronary artery bypass
surgery. When administered prior to surgical procedures for which it is
indicated, a single 1 gm dose of ceftriaxone provides protection from most
infections due to susceptible organisms throughout the course of the
procedure.
*Efficacy for this organism in this organ system was studied in fewer
than ten infections.
CONTRAINDICATIONS:
Ceftriaxone for injection is contraindicated in patients with known
allergy to the cephalosporin class of antibiotics.
Neonates (≤28 days):
Hyperbilirubinemic neonates, especially prematures, should not be
treated with ceftriaxone for injection. In vitro studies have shown that cef-
triaxone can displace bilirubin from its binding to serum albumin, lead-
ing to a possible risk of bilirubin encephalopathy in these patients.
Ceftriaxone is contraindicated in neonates if they require (or are
expected to require) treatment with calcium-containing IV solutions,
including continuous calcium-containing infusions such as parenteral
nutrition because of the risk of precipitation of ceftriaxone-calcium (see
CLINICAL PHARMACOLOGY, WARNINGS and DOSAGE AND
ADMINISTRATION).
A small number of cases of fatal outcomes in which a crystalline
material was observed in the lungs and kidneys at autopsy have been
reported in neonates receiving ceftriaxone and calcium-containing fluids.
In some of these cases, the same intravenous infusion line was used for
both ceftriaxone and calcium-containing fluids and in some a precipitate
was observed in the intravenous infusion line. At least one fatality has been
reported in a neonate in whom ceftriaxone and calcium-containing fluids
were administered at different time points via different intravenous lines;
no crystalline material was observed at autopsy in this neonate. There have
been no similar reports in patients other than neonates.
WARNINGS:
Hypersensitivity:
BEFORE THERAPY WITH CEFTRIAXONE IS INSTITUTED, CAREFUL
INQUIRY SHOULD BE MADE TO DETERMINE WHETHER THE PATIENT
HAS HAD PREVIOUS HYPERSENSITIVITY REACTIONS TO
CEPHALOSPORINS, PENICILLINS OR OTHER DRUGS. THIS PRODUCT
SHOULD BE GIVEN CAUTIOUSLY TO PENICILLIN-SENSITIVE PATIENTS.
ANTIBIOTICS SHOULD BE ADMINISTERED WITH CAUTION TO ANY
PATIENT WHO HAS DEMONSTRATED SOME FORM OF ALLERGY, PAR-
TICULARLY TO DRUGS. SERIOUS ACUTE HYPERSENSITIVITY REAC-
TIONS MAY REQUIRE THE USE OF SUBCUTANEOUS EPINEPHRINE AND
OTHER EMERGENCY MEASURES.
As with other cephalosporins, anaphylactic reactions with fatal outcome
have been reported, even if a patient is not known to be allergic or pre-
viously exposed.
Interaction with Calcium-Containing Products:
Do not use diluents containing calcium, such as Ringer’s solution
or Hartmann’s solution, to reconstitute ceftriaxone vials or to further
dilute a reconstituted vial for IV administration because a precipitate
can form. Precipitation of ceftriaxone-calcium can also occur when cef-
triaxone is mixed with calcium-containing solutions in the same IV
administration line. Ceftriaxone must not be administered simultane-
ously with calcium-containing IV solutions, including continuous cal-
cium-containing infusions such as parenteral nutrition via a Y-site.
However, in patients other than neonates, ceftriaxone and calcium-con-
taining solutions may be administered sequentially of one another if
the infusion lines are thoroughly flushed between infusions with a
compatible fluid. In vitro studies using adult and neonatal plasma
from umbilical cord blood demonstrated that neonates have an
increased risk of precipitation of ceftriaxone-calcium (see CLINICAL
PHARMACOLOGY, CONTRAINDICATIONS and DOSAGE AND
ADMINISTRATION).
Clostridium difficile:
Clostridium difficileassociated diarrhea (CDAD) has been reported
with use of nearly all antibacterial agents, including ceftriaxone, and
may range in severity from mild diarrhea to fatal colitis. Treatment with
antibacterial agents alters the normal flora of the colon leading to over-
growth of C. difficile.
C. difficile produces toxins A and B which contribute to the develop-
ment of CDAD. Hypertoxin producing strains of C. difficilecause increased
morbidity and mortality, as these infections can be refractory to antimi-
crobial therapy and may require colectomy. CDAD must be considered in
all patients who present with diarrhea following antibiotic use. Careful med-
ical 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. difficilemay need to be discontinued. Appropriate fluid and elec-
trolyte management, protein supplementation, antibiotic treatment of C.
difficile, and surgical evaluation should be instituted as clinically indicated.
Hemolytic Anemia:
An immune mediated hemolytic anemia has been observed in patients
receiving cephalosporin class antibacterials including ceftriaxone. Severe
cases of hemolytic anemia, including fatalities, have been reported dur-
ing treatment in both adults and children. If a patient develops anemia while
on ceftriaxone, the diagnosis of a cephalosporin associated anemia
should be considered and ceftriaxone stopped until the etiology is
determined.
PRECAUTIONS:
General:
Prescribing ceftriaxone for injection 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 devel-
opment of drug-resistant bacteria.
Although transient elevations of BUN and serum creatinine have been
observed, at the recommended dosages, the nephrotoxic potential of cef-
triaxone is similar to that of other cephalosporins.
Ceftriaxone is excreted via both biliary and renal excretion (see CLIN-
ICAL PHARMACOLOGY). Therefore, patients with renal failure normally
require no adjustment in dosage when usual doses of ceftriaxone are
administered.
Dosage adjustments should not be necessary in patients with hepatic
dysfunction; however, in patients with both hepatic dysfunction and sig-
nificant renal disease, caution should be exercised and the ceftriaxone
dosage should not exceed 2 gm daily.
Alterations in prothrombin times have occurred rarely in patients
treated with ceftriaxone. Patients with impaired vitamin K synthesis or low
vitamin K stores (e.g., chronic hepatic disease and malnutrition) may
require monitoring of prothrombin time during ceftriaxone treatment.
Vitamin K administration (10 mg weekly) may be necessary if the pro-
thrombin time is prolonged before or during therapy.
Prolonged use of ceftriaxone may result in overgrowth of nonsuscep-
tible organisms. Careful observation of the patient is essential. If super-
infection occurs during therapy, appropriate measures should be taken.
Ceftriaxone for injection should be prescribed with caution in individ-
uals with a history of gastrointestinal disease, especially colitis.
There have been reports of sonographic abnormalities in the gall-
bladder of patients treated with ceftriaxone; some of these patients also
had symptoms of gallbladder disease. These abnormalities appear on
sonography as an echo without acoustical shadowing suggesting sludge
or as an echo with acoustical shadowing which may be misinterpreted as
Pathogen
Minimum Inhibitory
Concentrations
(mcg/ml)
Disk Diffusion Zone
Diameters (mm)
(S)
Sus -
cep tible
(I)
Inter -
me diate
(R)
Re -
sist ant
(S)
Sus -
cep tible
(I)
Inter -
me diate
(R)
Re -
sist ant
Enterobacteriaceae ≤ 1 2 ≥4≥ 23 20 to 22 ≤19
Haemophilus
influenzae*≤2- - ≥26 - -
Neisseria gonor-
rhoeae*≤ 0.25 - - ≥ 35 - -
Neisseria meningi-
tidis*≤ 0.12 - - ≥ 34 - -
Streptococcus
pneumoniae†
meningitis isolates ≤ 0.5 1 ≥ 2 - - -
Streptococcus
pneumoniae† non-
meningitis isolates ≤12 ≥4- - -
Streptococcus
species beta-
hemolytic group* ≤0.5 - - ≥ 24 - -
Viridans group
streptococci ≤ 1 2 ≥ 4 ≥27 25 to 26 ≤24
Anaerobic bacteria
(agar method) ≤16 32≥64 - - -
QC Strain
Minimum
Inhibitory
Concentrations
(mcg/mL)
Disk
Diffusion
Zone diam-
eters (mm)
Escherichia coli ATCC 25922 0.03 to 0.12 29 to 35
Staphylococcus aureus ATCC 25923 ---------- 22 to 28
Staphylococcus aureus ATCC 29213 1 to 8 ---------
Haemophilus influenzae ATCC 49247 0.06 to 0.25 31 to 39
Neisseria gonorrhoeae ATCC 49226 0.004 to 0.015 39 to 51
Pseudomonas aeruginosa ATCC 27853 8 to 64 17 to 23
Streptococcus pneumoniae ATCC 49619 0.03 to 0.12 30 to 35
Bacteroides fragilis ATCC 25285 (agar
method) 32 to 128 ---------
Bacteroides thetaiotaomicron ATCC
29741 (agar method) 64 to 256 ---------
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Ceftriaxone for Injection, USP
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