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Information on Ceftriaxone Injection, including its dosage, contraindications, warnings, and pharmacokinetics. It discusses the incidence of postoperative infections reduced by preoperative administration, the symptoms and treatment of overdosage, and the availability of dosage forms. It also includes tables on beta-lactamase hydrolysis, pharmacokinetic parameters, and urinary and fecal excretion profile.
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Including Patient Medication Information
Ceftriaxone (as Ceftriaxone Sodium USP) 1000 mg / 50 mL and 2000 mg / 50 mL in single dose GALAXY containers
Ready-to-Use
Sterile Solution (frozen)
Antibiotic
Baxter Corporation 7125 Mississauga Road Mississauga, Ontario L5N 0C
Control #: 215096 Date of Revision: May 28, 2020
Uncomplicated Gonorrhea (cervical/urethral, pharyngeal and rectal) caused by N. gonorrhoeæ (penicillinase and nonpenicillinase producing strains).
Susceptibility Testing: Specimens for bacteriologic culture should be obtained prior to therapy in order to identify the causative organisms and to determine their susceptibilities to ceftriaxone. Therapy may be instituted before results of susceptibility testing are known. However, modification of the treatment may be required once these results become available.
Prophylaxis: The preoperative administration of a single 1 g dose of Ceftriaxone Injection, USP (ceftriaxone sodium) may reduce the incidence of postoperative infections in patients undergoing vaginal or abdominal hysterectomy, coronary artery bypass surgery, or in patients at risk of infection undergoing biliary tract surgery. If signs of post-surgical infection should appear, specimens for culture should be obtained for identification of the causative organism(s) so that the appropriate therapy may be instituted.
To reduce the development of drug-resistant bacteria and maintain the effectiveness of Ceftriaxone Injection, USP and other antibacterial drugs, Ceftriaxone Injection, USP should be used only to treat 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.
CONTRAINDICATIONS
Ceftriaxone Injection, USP is contraindicated in patients with known hypersensitivity to ceftriaxone sodium or any component of the container, other cephalosporins, or penicillins (see WARNINGS).
Hyperbilirubinemic neonates and preterm neonates should not be treated with ceftriaxone. In vitro studies have shown that ceftriaxone can displace bilirubin from its binding to serum albumin, leading to a possible risk of bilirubin encephalopathy in these patients (see PRECAUTIONS).
Ceftriaxone Injection, USP is contraindicated in neonates (≤28 days old) if they require (or are expected to require) treatment with calcium-containing intravenous solutions including continuous calcium-containing infusions such as parenteral nutrition because of the risk of precipitation of ceftriaxone-calcium (see WARNINGS, ADVERSE REACTIONS, DOSAGE AND ADMINISTRATION, PHARMACEUTICAL INFORMATION and PHARMACOLOGY ).
Hypersensitivity Before therapy with Ceftriaxone Injection, USP (ceftriaxone sodium) is instituted, careful inquiry should be made concerning previous hypersensitivity reactions to ceftriaxone, other cephalosporins, penicillins or other allergens Ceftriaxone Injection, USP should only be administered with caution to any patient who has demonstrated any form of allergy
particularly to drugs. As with other cephalosporins, anaphylactic reactions with fatal outcome have been reported, even if a patient is not known to be allergic or previously exposed. Ceftriaxone Injection, USP should be administered with caution to patients with type I hypersensitivity reaction to penicillin. Cross-hypersensitivity among β-lactam antibiotics have been clearly documented and may occur in up to 10% of patients with a history of penicillin allergy. If an allergic reaction occurs, the administration of Ceftriaxone Injection, USP should be discontinued and appropriate therapy instituted (see CONTRAINDICATIONS and ADVERSE REACTIONS).
Solutions containing dextrose should be use with caution, if at all, in patients with known allergy to corn or corn products.
Hemolytic Anemia CEFTRIAXONE INJECTION, USP SHOULD NOT BE USED IN PATIENTS WITH A HISTORY OF CEPHALOSPORIN-ASSOCIATED HEMOLYTIC ANEMIA SINCE THE RECURRENCE OF HEMOLYSIS IS MUCH MORE SEVERE.
An immune mediated hemolytic anemia has been observed in patients receiving cephalosporin class antibacterials, including ceftriaxone sodium. Severe cases of hemolytic anemia, including fatalities, have been reported in both adults and children. If a patient develops anemia anytime during, or within 2-3 weeks subsequent to the administration of ceftriaxone sodium, the diagnosis of a cephalosporin-associated anemia should be considered and the drug discontinued until the etiology is determine d.
Patients who receive prolonged or frequent courses of ceftriaxone sodium may benefit from periodic monitoring for signs and symptoms of hemolytic anemia, including measurement of haematological parameters or drug-induced antibody testing, where appropriate (see ADVERSE REACTIONS).
Clostridium Difficile-Associated Disease Clostridium difficile -associated disease (CDAD) has been reported with use of many antibacterial agents, including ceftriaxone sodium. CDAD may range in severity from mild diarrhea to fatal colitis. It is important to consider this diagnosis in patients who present with diarrhea, or symptoms of colitis, pseudomembranous colitis, toxic megacolon, or perforation of colon subsequent to the administration of any antibacterial agent. CDAD has been reported to occur over 2 months after the administration of antibacterial agents.
Treatment with antibacterial agents may alter the normal flora of the colon and may permit overgrowth of Clostridium difficile. Clostridium difficile produces toxins A and B, which contribute to the development of CDAD. CDAD may cause significant morbidity and mortality. CDAD can be refractory to antimicrobial therapy.
If the diagnosis of CDAD is suspected or confirmed, appropriate therapeutic measures should be initiated. Mild cases of CDAD usually respond to discontinuation of antibacterial agents not directed against Clostridium difficile. In moderate to severe cases, consideration should be given to management with fluids and electrolytes, protein supplementation and treatment with an antibacterial agent clinically effective against Clostridium difficile. Surgical evaluation should be
signs and symptoms to resolve.
Susceptibility/Resistance
Development of Drug Resistant Bacteria Prescribing CEFTRIAXONE INJECTION, USP in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to the patient and risks the development of drug- resistant bacteria.
PRECAUTIONS
General Alterations in prothrombin time (see ADVERSE REACTIONS) and hypoprothrombinemia have occurred rarely in patients treated with ceftriaxone sodium. Patients with impaired vitamin K synthesis or low vitamin K stores (e.g. chronic hepatic disease and malnutrition) may require monitoring of hematology and coagulation parameters during Ceftriaxone Injection, USP treatment. Vitamin K administration (10 mg weekly) may be necessary if the prothrombin time is prolonged before or during treatment.
Prolonged treatment with ceftriaxone sodium may result in overgrowth of non-susceptible organisms and organisms initially sensitive to the drug. Development of resistant organisms during the administration of ceftriaxone sodium in clinical trials has been observed in 6% of the 94 patients infected with P. æruginosa , in 33% of 3 patients infected with Citrobacter species and in 10% of the 10 patients infected with Enterobacter species. If superinfection occurs, appropriate measures should be taken.
Ceftriaxone Injection, USP should be administered with caution to individuals with a history of gastrointestinal disease, particularly colitis.
As with other dextrose-containing solutions, Ceftriaxone Injection, USP should be prescribed with caution in patients with overt or known subclinical diabetes mellitus or carbohydrate intolerance for any reason.
Renal and Hepatic Impairment Although transient elevations of BUN and serum creatinine have been observed in clinical studies, there is no other evidence that ceftriaxone sodium, when administered alone, is nephrotoxic.
In severe renal impairment (creatinine clearance of less than 10 mL/min), periodic monitoring of serum ceftriaxone concentrations is recommended. The maximum daily dose should not exceed 2 g. In severe renal impairment associated with clinically significant hepatic impairment, close monitoring of serum ceftriaxone concentrations, at regular intervals, is recommended. If there is evidence of accumulation, dosage should be decreased accordingly.
Interactions Interactions between ceftriaxone sodium and other drugs have not been fully evaluated.
Pregnancy The safety of Ceftriaxone Injection, USP in the treatment of infections during pregnancy has not been established. Ceftriaxone Injection, USP should only be used during pregnancy if the likely benefit outweighs the potential risk to the fetus and/ or the mother. Ceftriaxone has been detected in the umbilical cord blood, amniotic fluid and placenta. At parturition, 1 hour after a 2 g IV dose of ceftriaxone sodium, average ceftriaxone concentrations in maternal serum, umbilical cord serum, amniotic fluid, and placenta were 106 ± 40 mcg/mL, 19.5 ± 11.5 mcg/mL, 3.8 ± 3.2 mcg/mL and 20.9 ± 4.4 mcg/g.
Nursing Mothers Ceftriaxone is excreted in human milk at low concentrations, (e.g. the peak concentration of total drug in milk ranged between 0.45 to 0.65 mcg/mL, approximately five hours after the administration of 1 g IV or IM). The clinical significance of this is unknown, therefore, caution should be exercised when ceftriaxone sodium is administered to a nursing mother.
Neonates The safety of ceftriaxone sodium in neonates (birth to 28 days of age) has not been established (see HUMAN PHARMACOLOGY). In vitro studies have shown that ceftriaxone can displace bilirubin from serum albumin. Ceftriaxone Injection, USP should not be used in neonates (especially prematures), at risk of developing bilirubin encephalopathy (see CONTRAINDICATIONS).
Elderly Patients
The elimination of ceftriaxone may be reduced in elderly patients possibly due to impairment of both renal and hepatic function (see HUMAN PHARMACOLOGY).
Drug-Laboratory Test Interactions Ceftriaxone may interfere with urine glucose determinations utilizing the copper -reduction test (Clinitest), but not utilizing the glucose-oxidase test (Diastix or Tes Tape). In patients treated with ceftriaxone sodium the Coombs' test may rarely become false-positive; and ceftriaxone sodium, like other antibiotics, may result in false-positive tests for galactosemia.
ADVERSE REACTIONS
During clinical trials and post-marketing experience with ceftriaxone sodium the following adverse reactions have been observed:
Clinical Adverse Experiences Dermatological: Rash (1.3%); exanthema, allergic dermatitis and pruritis (0.1-1.0%); urticaria (post-marketing reports). Isolated cases of severe cutaneous adverse reactions (erythema multiforme, Stevens Johnson Syndrome, or Lyell's Syndrome/toxic epidermal necrolysis) have also been reported.
Hematological: Anemia (0.1-1.0%); auto-immune hemolytic anemia and serum sickness (<0.1%); immune hemolytic anemia (post-marketing reports - see WARNINGS for more information on hemolytic anemia); granulocytopenia (post-marketing reports). Isolated cases of agranulocytosis (<500/mm^3 ) have been reported, most of them after 10 days of treatment and
Ultrasonographic shadows suggesting precipitations in the kidneys accompanied by calcium ceftriaxone precipitate in the urine was observed in one patient dosed with ceftriaxone sodium at 10 g/day (2.5 times the maximum recommended dose). No other case of overdosage has been reported to date with ceftriaxone sodium. No specific information on symptoms or treatment is available. Excessive serum concentration of ceftriaxone cannot be reduced by hemodialysi s or peritoneal dialysis. Treatment should be symptomatic.
Ceftriaxone Injection, USP is administered intravenously.
Dosage and route of administration should be determined by the severity of infection, susceptibility of the causative organisms, and condition of the patient. The intravenous route is preferable for patients with septicemia or other severe or life-threatening infections.
DOSAGE
Adults
Type of Infection Route Dose Frequency
Total Daily Dose Moderate and Severe Infections
IV 1 or 2 g q24h 1 or 2 g 0.5 or 1 g q12h 1 or 2 g
There is limited experience with daily doses of 3-4 g administered as a single dose or two equally divided doses. The total daily dose should not exceed 4 g.
Infants and Children (One Month to 12 Years of Age)
Type of Infection Route Dose Frequency
Total Daily Dose Serious Miscellaneous Infections
IV 25 or 37.5 mg/kg
q12h 50 or 75 mg/kg
The total daily dose should not exceed 2 g. If body weight is 50 kg or more the adult dose should be used. Meningitis IV 50 mg/kg* q12h (^100) mg/kg
With the exception of gonorrhea, which is treated with a single dose, the administration of Ceftriaxone Injection, USP should be continued for a minimum of 48 to 72 hours after the
For management of a suspected drug overdose, contact your regional Poison Control Centre.
patient defervesces or after evidence of bacterial eradication has been obtained, usually 4 to 14 days. In bone and joint infections, the average duration of treatment during clinical trials was 6 weeks, with a range of 1 to 13 weeks, depending on the severity of the infection.
When treating infections caused by beta hemolytic streptococcus , it is recommended that therapy be continued for at least 10 days. The average duration of therapy for infections associated with beta hemolytic streptococcus during clinical trials was 2 weeks, with a range of 1 to 5 weeks, depending on the site and severity of the infection.
Prophylaxis (Vaginal or Abdominal Hysterectomy, Coronary Artery Bypass Surgery, Biliary Tract Surgery): For preoperative use as prophylaxis before vaginal or abdominal hysterectomy, coronary artery bypass surgery, or biliary tract surgery in patients at risk of infection, a single dose of 1 g administered 1/2 to 2 hours before surgery is recommended.
Impairment of Renal and/or Hepatic Function : In patients with mild to moderate renal impairment, changes in the dosage regimen are not required, provided liver function is not impaired. In cases of preterminal renal failure (creatinine clearance less than 10 mL/min), periodic monitoring of serum ceftriaxone concentrations is recommended. The daily dosage should be limited to 2 g or less. In patients with liver damage, there is no need for the dosage to be reduced provided renal function is not impaired. In cases of coexistent renal and clinically significant hepatic insufficiency, close monitoring of serum ceftriaxone concentrations, at regular intervals, is recommended. If there is evidence of accumulation, dosage should be decreased accordingly.
ADMINISTRATION
Ceftriaxone Injection, USP is for intravenous administration using sterile equipment. It should be administered intravenously by infusion over a period of 30 minutes.
Do not add supplementary medication.
NOTE: Ceftriaxone Injection, USP solution should not be physically mixed with aminoglycoside antibiotics nor administered at the same site because of possible chemical incompatibility. There have also been literature reports of physical incompatibilities between ceftriaxone and vancomycin, amsacrine, or fluconazole.
Precipitation of ceftriaxone-calcium can occur when ceftriaxone sodium is mixed with calcium-containing solutions in the same IV administration line Ceftriaxone for Injection USP must not be administered simultaneously with calcium-containing IV solutions, including continuous calcium-containing infusions such as parenteral nutrition via a Y-site. However, in patients other than neonates, Ceftriaxone Injection, USP and calcium-containing solutions may be administered sequentially of one another if the infusion lines are thoroughly flushed between infusions with a compatible fluid (see CONTRAINDICATIONS and WARNINGS).
Proper Name: ceftriaxone sodium
Chemical Name : − 6 R -[6α, 7 β( Z )]]-7-[[(2-Amino-4-thiazolyl)(methoxyimino)acetyl]amino]-8-oxo-3- [[(1,2,5,6-tetrahydro-2-methyl-5,6-dioxo-1,2,4-traizin-3-yl)thio]methyl]-5-thia-1- azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid, disodium salt hemiheptahydrate − (6 R , 7 R )-7-[[(2 Z )-(2-Amino-4-thiazolyl)(methoxyimino)acetyl]amino]-8-oxo-3- [[(1,2,5,6-tetrahydro-2-methyl-5,6-dioxo-1,2,4-traizin-3-yl)thio]methyl]-5-thia-1- azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid, disodium salt hemiheptahydrate − Disodium ( Z )-(6 R , 7 R )-7-[2-(2-Amino-1,3-thiazol-4-yl)-2-(methoxy- imino)acetamido]-8-oxo-3-[(2,5-dihydro-2-methyl-6-oxido-5-oxo-1,2,4-triazin-3- yl)thiomethyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate, hemiheptahydrate − (6 R , 7 R )-7-[2-(2-Amino-4-thiazolyl)glyoxylamido]-3-[[2,5-dihydro-6-hydroxy-2- methyl-5-oxo- as -traizin-3-yl)thio]methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2- ene-2-carboxylic acid 7^2 -( Z )-( O -methyloxime), disodium salt hemiheptahydrate
Structural Formula:
Molecular Formula : Ceftriaxone Sodium C 18 H 16 N 8 Na 2 O 7 S 3 · 3½ H2O
Molecular Mass : Ceftriaxone Sodium 661.6 0 Anhydrous 598.5 6
Description: White or yellowish, crystalline, slightly hygroscopic powder. Freely soluble in water, sparingly soluble in methanol, very slightly soluble in ethanol.
Composition: Ceftriaxone Injection, USP is supplied as a frozen, iso-osmotic, sterile, nonpyrogenic solution premixed in a dextrose diluent. Dextrose, USP has been added to adjust the osmolality (approximately 1.9 g and 1.2 g as dextrose hydrous to the 1 g and 2 g dosages, respectively). The pH may be adjusted with sodium hydroxide and/or hydrochloric acid. Solutions of premixed Ceftriaxone Injection, USP may range from light yellow to amber in color. After thawing, the solution is intended for intravenous use only. The pH of thawed solutions may range from 6. to 8.0.
Ceftriaxone Injection, USP contains approximately 83 mg (3.6 mEq) of sodium per gram of ceftriaxone activity.
Stability and Storage Recommendations Store in a freezer capable of maintaining a temperature at -20°C to -25°C.
DIRECTIONS FOR USE
Thawing of Plastic Container Thaw frozen container at room temperature (15 - 25°C) or under refrigeration (3 - 7°C). [DO NOT FORCE THAW BY IMMERSION IN WATER BATHS OR BY MICROWAVE IRRADIATION.]
The approximate thaw times are as follows: Individual Container Entire Carton Room Temperature (15 – 25°C) 60 – 80 minutes 4 – 12 hours Refrigerated (3 – 7°C) 225 – 233 minutes 13.5 – 38.5 hours
Check for minute leaks by squeezing container firmly. If leaks are detected, discard solution as sterility may be impaired.
Do not add supplementary medication.
Visually inspect the container. If the outlet port protector is damaged, detached, or not present, discard container as solution path sterility may be impaired. Components of the solution may precipitate in the frozen state and will dissolve upon reaching room temperature with little or no agitation. Potency is not affected. Agitate after solution has reached room temperature. If after visual inspection the solution remains cloudy or if an insoluble precipitate is noted, or if any seals are not intact, the container should be discarded.
The thawed solution is stable for 21 days under refrigeration (3 - 7°C) or 48 hours at room temperature (15 - 25°C). Do not refreeze thawed antibiotics.
Page 16 of 52
Ceftriaxone Injection, USP
Table 1
Cumulative Percentage of Clinical Isolates Inhibited at
≤^
Indicated Concentrations of Ceftriaxone (mg/L)*
Microorganisms (No. Of Isolates)
0.
0.
0.
0.
0.
0.
0.
1.
2.
4
8
16
32
64
128
Aerobes Gram Negative
Acinetobacter anitratum
(28)
11
39
96
100
Acinetobacter calcoaceticus
(50)
2
6
12
24
32
66
96
100
Acinetobacter
Iwoffi
(10)
10
40
50
Citrobacter freundii
(21)
5
33
62
67
71
95
Enterobacter ærogenes
(17)
24
47
71
82
88
94
100
Enterobacter cloacae
(40)
5
28
50
55
65
75
90
93
Escherichia coli
(47)
6
66
88
94
98
100
Haemophilus influenzæ
(16)
86
94
100
Klebsiella oxytoca (21)
50
90
Klebsiella species (49)
50
90
Klebsiella pneumoniae (56)
5
41
86
100
Neisseria gonorrhea (10)**
90
100
Neisseria
meningitidis (22)**
59
68
77
100
Proteus inconstans (5)
20
80
100
Proteus mirabilis (40)
60
95
100
Proteus morganii (40)
18
43
58
75
85
90
93
98
100
Proteus rettgeri (12)
42
58
75
92
100
Proteus
vulgaris (29)
3
14
31
52
72
86
90
97
100
Pseudomonas æruginosa (64)
5
28
52
73
95
97
Pseudomonas cepacia (7)
14
43
71
100
Page 17 of 52
Ceftriaxone Injection, USP
Microorganisms (No. Of Isolates)
0.
0.
0.
0.
0.
0.
0.
1.
2.
4
8
16
32
64
128
Pseudomonas fluorescens (8)
25
75
Pseudomonas maltophilia (9)
11
22
67
78
100
Pseudomonas putida (9)
11
33
78
100
Salmonella species (18)
50
Salmonella typhi (30)**
3
7
43
100
Shigella (11)**
9
55
73
82
100
Serratia marcescens (45)
4
20
38
47
58
62
64
78
96
98
Aerobes Gram Positive Staphylococcus aureus (34)
15
85
91
97
Staphylococcus epidermidis (22)
9
23
36
50
68
82
95
Streptococcus agalacticæ (25)
48
96
100
Streptococcus pneumoniae (88)
26
39
55
80
90
100
Streptococcus pyogenes (15)
100
Anaerobes Gram Negative Bacteroides SP. (56)
2
4
5
13
29
55
71
84
91
Fusobacterium SP. (8)
13
25
38
50
63
Anaerobes Gram Positive Clostridium SP. (10)
10
20
50
60
70
80
100
Peptococcus SP. (15)
33
47
53
66
73
100
Peptostreptococcus SP. (8)
13
50
88
100
*^
The inoculum size ranged from 10
3 to 10
6 cells/mL.
** The inoculum size was not reported.
Table 3 Effect of pH on the In Vitro Activity of Ceftriaxone
Organism (No. of Strains)
MIC (mg/L at Indicated pH pH 8 pH 7 pH 6 S. aureus (2) 3.13 - 6.25 3.13 0. S. epidermidis (1) 1.56 3.13 1. S. pyogenes (1) 0.025 ≤0.012 ≤0. E. coli (3) ≤0.012-0.10 0.025-0.10 ≤0.012-0. K. pneumoniæ (1) 0.05 0.05 0. S. typhimurium (2) 0.025-0.100 0.05-0.20 0.05-0. S. marcescens (1) 1.56 0.78 0. E. cloacæ (1) 1.56 12.5 25. P. vulgaris (3) ≤0.012-0.025 ≤0.012 ≤0.012-0. P. rettgeri (1) 0.025 0.10 1. P. mirabilis (1) ≤0.012 0.025 ≤0. P. æruginosa (2) 3.13-12.5 3.13-12.5 6.25-12. Heart Infusion Agar Inoculum: 10^6 cells/mL
The MICs of laboratory strains of S. aureus, E. coli, P. mirabilis, P. vulgaris and S. marcescens were within one dilution of each other when measured in the following media: Nutrient agar, DST agar, antibiotic medium No. 1 and Mueller-Hinton agar. For P. æruginosa, however, ceftriaxone was 2 to 8-fold more active in Nutrient agar than in the other media.
The effect of human serum on the MICs and the MBCs of various bacteria are shown in Table 4.
Table 4 The Effect of Serum on the MIC and MBC of Ceftriaxone (mg/L)
Organism (No. of Strains)
Isosensitest Broth Isosensitest Broth +25% Human Serum
Isosensitest Broth +75% Human Serum MIC MBC MIC MBC MIC MBC E. coli (2) 0.06 0.06 0.06-0.12 0.06-0.12 0.12-0.25 0. K. pneumoniæ (2) 0.06 0.06 0.25 0.25 0.5 0. P. mirabilis (1) 0.008 0.015 0.015 0.03 0.06 0. P. vulgaris (1) 0.06 0.25 0.25 0.25 0.5 2. P. æruginosa (2) 4.0-32.0 4.0-32.0 4.0-64.0 16.0-64.0 8.0-64.0 64.0-128. S. aureus (2) 2.0 4.0 4.0-16.0 8.0-16.0 8.0-16.0 16.0-32.
The relative rates of hydrolysis of ceftriaxone by various beta-lactamases are shown in Table 5.
Table 5
Beta-Lactamase Source Type of Beta-Lactamase^1
Richmond-Sykes Classification
Relative Rate of Hydrolysis^2 Escherichia coli^3 Klebsiella pneumoniæ Enterobacter cloacae^4 Citrobacter freundii^4 Serratia marcescens Morganella morganii^4 Proteus vulgaris^4 Shigella sonnei^3 Pseudomonas æruginosa^3 Pseudomonas æruginosa Bacteroides fragilis^4 Staphylococcus aureus^4 Bacillus cereus
Pen Cepha Cepha Cepha Cepha Cepha Cepha Pen Pen Cepha Cepha Pen Both
V 111A 1A
1A 1A 1C
V 1D
6 11 21 0 10 25
0 36 128 0 16
1 - Pen, primarily penicillin substrate; Cepha, primarily cephalosporin substrate; Both, both types. 2 - Rate in relation to cephaloridine (100%), except for S. aureus and B. cereus , which are based upon hydrolysis of penicillin G (100%). 3 - Plasmid mediated. 4 - Induced with cephalothin.
Development of Resistance: The acquisition of resistance to ceftriaxone was studied in vitro in eight strains of E. coli. MIC values were determined before and after five passages through sublethal doses of ceftriaxone. As shown in Table 6 , the increases in resistance to ceftriaxone ranged from 2 to ≥ 1024-fold.
Table 6 Effect of Five Passages Through Media Containing Ceftriaxone on the Susceptibility of Beta-Lactam Sensitive and Resistant E. coli Strains
Strain MIC (mg/L) MIC Increase (Fold)
Original susceptibility to Beta-Lactams Pre-transfer Post-transfer Cefazolin Ampicillin NIHJ 0.1 0.2 (^2) S^1 S IW431 0.025 0.39 16 S S IU586 0.05 0.2 4 S R^2 (C)^3 IW432 0.1 25.0 256 S R(C) IW434 0.1 3.13 32 R R(C) IV57 0.2 25.0 128 R R(C) IV84 0.78 100.0 128 R R(C) IU581 0.2 >100.0 (^) 1024 R R(R)^4 1 - S = Sensitive 2 - R = Resistant 3 - (C) = Chromosome-mediated resistance. 4 - (R) = R-plasmid-mediated resistance.
