Class: Extended-spectrum Penicillins
Chemical Name: 2R-(2α,3Z,5α)]-3-(2-Hydroxyethylidene)-7-oxo-4-oxa-1-azabicyclo[3.2.0] heptane-2-carboxylic acid monopotassium salt mixt. with[2S - [2α,5α,6β(S*)]] - 6 - [(carboxy - 3 - thienylacetyl)amino] - 3,3 - dimethyl - 7 - oxo - 4 - thia - 1 - azabicyclo[3.2.0] heptane-2-carboxylic acid disodium salt
Molecular Formula: C15H14N2Na2O6S2C8H9NO5•KC15H16N2O6S2•C8H9NO5
CAS Number: 4697-14-7
Brands: Timentin
Introduction
Antibacterial; β-lactam antibiotic; fixed combination of ticarcillin (an extended-spectrum penicillin) and clavulanate (a β-lactamase inhibitor).1 3 4 7 9 10 21 55 77 97
Uses for Ticarcillin Disodium and Clavulanate Potassium
Bone and Joint Infections
Treatment of bone and joint infections caused by β-lactamase-producing Staphylococcus aureus.1 78
Gynecologic Infections
Treatment of gynecologic infections (e.g., endometritis) caused by β-lactamase-producing S. aureus, S. epidermidis, Enterobacter (including E. cloacae), Escherichia coli, Klebsiella pneumoniae, or Prevotella melaninogenicus.1 98 99 100 101 102 103 104 66
Intra-abdominal Infections
Treatment of intra-abdominal infections (e.g., peritonitis) caused by β-lactamase-producing E. coli, K. pneumoniae, or Bacteroides fragilis group.1 103 104 105 106 113 114 115 116 117 127 128
Respiratory Tract Infections
Treatment of lower respiratory tract infections caused by β-lactamase-producing S. aureus, Haemophilus influenzae, or Klebsiella.1 76 77 79 106
Septicemia
Treatment of septicemia caused by β-lactamase-producing S. aureus, E. coli, Klebsiella, or Pseudomonas (including Ps. aeruginosa).1 76 77 79 106
Skin and Skin Structure Infections
Treatment of skin and skin structure infections caused by β-lactamase-producing S. aureus, E. coli, or Klebsiella.1 76 77 79
Urinary Tract Infections (UTIs)
Treatment of uncomplicated or complicated UTIs caused by β-lactamase-producing S. aureus, Citrobacter, E. cloacae, E. coli, Klebsiella, Pseudomonas (including Ps. aeruginosa), or Serratia marcescens.1 76 77 79 106
Ticarcillin Disodium and Clavulanate Potassium Dosage and Administration
Administration
Administer by IV infusion over 30 minutes.1
IV Administration
Intermittent IV infusions may be administered directly into a vein or via a Y-type administration set.1 111 134 When a Y-type administration set is used, other IV solutions flowing through a common administration tubing or site should be discontinued while ticarcillin and clavulanate is being infused.1 111 134
If an aminoglycoside or other anti-infective agent is administered concomitantly, the drugs should be administered separately.1 111 134
Reconstitution and Dilution
Reconstitute vials containing a combined potency of 3.1 g of the drugs by adding approximately 13 mL of sterile water for injection or sodium chloride injection to provide a solution containing approximately 200 mg of ticarcillin/mL and 6.7 mg of clavulanic acid/mL.1
Shake vial until the drug is dissolved.1
Reconstituted solutions should be further diluted to a concentration of 10–100 mg/mL in a compatible IV solution.1
Alternatively, ADD-Vantage vials should be reconstituted according to the manufacturer’s directions.
Reconstitute pharmacy bulk packages containing a combined potency of 31 g by adding 76 mL of sterile water for injection or sodium chloride injection to provide a solution containing approximately 300 and 10 mg/mL of ticarcillin and clavulanic acid, respectively; the diluent may be added in 2 portions.134
Pharmacy bulk packages of the drug are not intended for direct IV infusion; prior to administration, solutions reconstituted in the pharmacy bulk package must be further diluted with a compatible IV infusion solution to a concentration of 10–100 mg/mL of ticarcillin.134
Thaw the commercially available injection (frozen) at room temperature (22°C) or in a refrigerator (4°C); do not force thaw by immersion in a water bath or by exposure to microwave radiation.111
A precipitate may have formed in the frozen injection, but should dissolve with little or no agitation after reaching room temperature.111 Discard thawed injection if an insoluble precipitate is present or if container seals or outlet ports are not intact.111
Additives should not be introduced into the thawed injection.111 The thawed injections should not be used in series connections with other plastic containers, since such use could result in air embolism from residual air being drawn from the primary container before administration of fluid from the secondary container is complete.111
Rate of Administration
Administer by IV infusion over 30 minutes.1 111 134
Dosage
Available as a fixed-combination of ticarcillin disodium and clavulanate potassium; dosage expressed in terms of g of ticarcillin plus g of clavulanic acid (i.e., g of “Timentin”) or in terms of the ticarcillin content of the fixed-ratio combination.1 Potency of both ticarcillin disodium and clavulanate potassium are expressed in terms of the bases.1
Duration of therapy depends on severity of infection; generally should be continued for ≥48 hours after manifestations of infection (e.g., fever, elevated leukocyte count) have subsided.1 113 129 Usual duration is 10–14 days; more prolonged therapy may be necessary in difficult and complicated infections.1
Pediatric Patients
Mild to Moderate Infections
IV
Children 3 months to 16 years of age weighing <60 kg: 200 mg/kg (of ticarcillin) daily given in divided doses every 6 hours.1
Children 3 months to 16 years of age weighing ≥60 kg: 3.1 g of the fixed-combination (3 g of ticarcillin and 100 mg of clavulanic acid) every 6 hours.1
Children ≥1 month of age: AAP recommends 100–200 mg/kg (of ticarcillin) daily given in 4 divided doses.118
Severe Infections
IV
Children 3 months to 16 years of age weighing <60 kg: 300 mg/kg (of ticarcillin) daily given in divided doses every 4 hours.1
Children 3 months to 16 years of age weighing ≥60 kg: 3.1 g of the fixed-combination (3 g of ticarcillin and 100 mg of clavulanic acid) every 4 hours.1
Children ≥1 month of age: AAP recommends 200–300 mg/kg (of ticarcillin) daily given in 4 divided doses.118
Adults
General Adult Dosage in Those Weighing <60 kg
IV
200–300 mg/kg (of ticarcillin) daily given in divided doses every 4–6 hours.1
Bone and Joint Infections in Adults Weighing ≥60 kg
IV
3.1 g of the fixed-combination (3 g of ticarcillin and 100 mg of clavulanic acid) every 4–6 hours.1
Gynecologic Infections in Adults Weighing ≥60 kg
Moderate Infections
IV
200 mg/kg (of ticarcillin) daily given in divided doses every 4–6 hours.1
Severe Infections
IV
300 mg/kg (of ticarcillin) daily given in divided doses every 4 hours.1
Intra-abdominal Infections in Adults Weighing ≥60 kg
IV
3.1 g of the fixed-combination (3 g of ticarcillin and 100 mg of clavulanic acid) every 4–6 hours.1
Duration of treatment is ≥5–7 days;113 129 usually 10–14 days for peritonitis.1 104 129 More prolonged therapy may be needed in some cases.1 129 If clinical improvement is not evident within 4 days or if fever or leukocytosis persists for >5 days, the possibility of undrained intra-abdominal infection or inadequately treated extra-abdominal infection should be considered.113 Shorter courses (e.g., 2–5 days) may be appropriate for acute bacterial contamination following penetrating trauma if therapy is initiated soon after injury and surgical measures are instituted promptly.82 129
Respiratory Tract Infections in Adults Weighing ≥60 kg
IV
3.1 g of the fixed-combination (3 g of ticarcillin and 100 mg of clavulanic acid) every 4–6 hours.1
Septicemia in Adults Weighing ≥60 kg
IV
3.1 g of the fixed-combination (3 g of ticarcillin and 100 mg of clavulanic acid) every 4–6 hours.1
Skin and Skin Structure Infections in Adults Weighing ≥60 kg
IV
3.1 g of the fixed-combination (3 g of ticarcillin and 100 mg of clavulanic acid) every 4–6 hours.1
Urinary Tract Infections (UTIs) in Adults Weighing ≥60 kg
IV
3.1 g of the fixed-combination (3 g of ticarcillin and 100 mg of clavulanic acid) every 4–6 hours.1
Some clinicians suggest that 3.1 g of the fixed-combination every 6–8 hours may be adequate.82
Special Populations
Hepatic Impairment
Modification of usual dosage not necessary in patients with hepatic impairment alone.82 83 Dosage adjustment recommended in patients with both hepatic and renal impairment.1
Adults with hepatic impairment and with Clcr<10 mL/minute should receive an initial loading dose of 3.1 g of the fixed-combination followed by a maintenance dosage of 2 g of the fixed-combination once every 24 hours.1
Renal Impairment
Dosage adjustment is recommended in patients with renal impairment.1
Adults with renal impairment should receive an initial loading dose of 3.1 g of the fixed-combination followed by maintenance dosage based on Clcr (see Table).1
Maintenance Dosage for Adults with Renal Impairment1
Clcr (mL/min)
|
Maintenance Dosage (in terms of g of fixed-combination)
|
|---|
>60
|
3.1 g every 4 hours
|
30–60
|
2 g every 4 hours
|
10–30
|
2 g every 8 hours
|
<10
|
2 g every 12 hours
|
<10 with Hepatic Dysfunction
|
2 g every 24 hours
|
Hemodialysis Patients
|
2 g every 12 hours; additional 3.1 g given following each hemodialysis session
|
Peritoneal Dialysis Patients
|
3.1 g every 12 hours
|
Cautions for Ticarcillin Disodium and Clavulanate Potassium
Contraindications
Warnings/Precautions
Warnings
Superinfection/Clostridium difficile-associated Colitis
Possible emergence and overgrowth of nonsusceptible organism.1 Institute appropriate therapy if superinfection occurs.1
Treatment with anti-infectives may permit overgrowth of clostridia.1 Consider Clostridium difficile-associated diarrhea and colitis (antibiotic-associated pseudomembranous colitis) if diarrhea develops and manage accordingly.1
Some mild cases of C. difficile-asssociated diarrhea and colitis may respond to discontinuance alone.1 Manage moderate to severe cases with fluid, electrolyte, and protein supplementation; appropriate anti-infective therapy (e.g., oral metronidazole or vancomycin) recommended if colitis is severe.1
Nervous System Effects
Seizures reported with high dosage (especially in patients with renal failure).1
Sensitivity Reactions
Hypersensitivity Reactions
Serious and occasionally fatal hypersensitivity reactions, including anaphylaxis, reported with penicillins.1
Prior to initiation of therapy, make careful inquiry regarding previous hypersensitivity reactions to penicillins, cephalosporins, or other drugs.1 Partial cross-allergenicity occurs among penicillins and other β-lactam antibiotics including cephalosporins and cephamycins.1
If a severe hypersensitivity reaction occurs, discontinue immediately and institute appropriate therapy as indicated (e.g., epinephrine, corticosteroids, maintenance of an adequate airway and oxygen).1
General Precautions
Selection and Use of Anti-infectives
To reduce development of drug-resistant bacteria and maintain effectiveness of ticarcillin and clavulanate and other antibacterials, use only for treatment or prevention of infections proven or strongly suspected to be caused by susceptible bacteria.b
When selecting or modifying anti-infective therapy, use results of culture and in vitro susceptibility testingb In the absence of such data, consider local epidemiology and susceptibility patterns when selecting anti-infectives for empiric therapy.b
Hematologic Effects
Bleeding manifestations reported with some β-lactam antibiotics.1 These reactions have sometimes been associated with abnormal coagulation tests (e.g., clotting time, platelet aggregation, PT) and are most likely to occur in patients with renal failure.1
Periodically evaluate hematologic function.1
If bleeding manifestations occur, discontinue ticarcillin and clavulanate and institute appropriate measures.1
Sodium Content and Electrolyte Imbalance
Fixed-combination of ticarcillin and clavulanate contains a theoretical sodium content of 4.51 mEq (103.6 mg) per g of ticarcillin.1
Consider sodium content when used in patients requiring restricted salt intake.1
Hypokalemia reported rarely; consider the possibility of hypokalemia in patients with fluid and electrolyte imbalance.1 Periodically monitor serum potassium in patents receiving prolonged treatment.1
Laboratory Monitoring
Periodically assess organ system functions, including renal, hepatic, and hematopoietic, during prolonged therapy.1 (See Hematologic Effects under Cautions and see Sodium Content and Electrolyte Imbalance under Cautions).1
Specific Populations
Pregnancy
Category B.1
Lactation
Penicillins52 and clavulanic acid63 are distributed into milk. Use with caution.1
Pediatric Use
Safety and efficacy not established in children <3 months of age for any indication.1
Safety and efficacy not established for treatment of septicemia and/or infections suspected or known to be caused by H. influenzae type b (Hib) in children ≤16 years of age.1 Other anti-infectives should be used in pediatric patients with meningeal infection originating from a distant infection site, those with suspected or documented meningitis, or those requiring prophylaxis against CNS infections.1
Adverse effects profile in pediatric patients similar to that in adults.1
Hepatic Impairment
No dosage adjustments required in patients with hepatic impairment alone;82 83 dosage adjustment recommended in those with both hepatic and renal impairment.1 (See Hepatic Impairment under Dosage and Administration.)
Renal Impairment
Dosage adjustments recommended in patients with renal impairment and in those undergoing hemodialysis or peritoneal dialysis.1 (See Renal Impairment under Dosage and Administration.)
Common Adverse Effects
GI effects (diarrhea, nausea, epigastric pain); hypersensitivity reactions; local reactions (pain, induration, thrombophlebitis).1
Interactions for Ticarcillin Disodium and Clavulanate Potassium
Specific Drugs
Drug
|
Interaction
|
|---|
Aminoglycosides
|
In vitro evidence of additive or synergistic antibacterial effects against Enterobacteriaceae and Ps. aeruginosa1 8 11 15 16 17 18 46
|
Probenecid
|
Increased ticarcillin serum concentrations and prolonged half-life;1 pharmacokinetics of clavulanate not affected1
|
Ticarcillin Disodium and Clavulanate Potassium Pharmacokinetics
Absorption
Bioavailability
Ticarcillin not appreciably absorbed from GI tract2 4 7 and must be administered parenterally.1
Concomitant administration of clavulanate potassium does not affect the pharmacokinetics of ticarcillin;1 not known whether ticarcillin affects the pharmacokinetics of clavulanate potassium.67
Distribution
Extent
Both ticarcillin and clavulanate are distributed into blister fluid, peritoneal fluid,3 and bone.3
Only low ticarcillin concentrations attained in CSF.3 4 7 26 29
Like other penicillins, ticarcillin probably crosses the placenta and is distributed into milk in low concentrations.7 Clavulanic acid readily crosses the placenta138 and is distributed into milk in low concentrations.63
Plasma Protein Binding
Ticarcillin is 45–65% bound to serum proteins.1 2 4 7 27 1 Clavulanate is 22–30% bound to serum proteins.19 56 83
Elimination
Metabolism
Metabolic fate of clavulanate has not been fully elucidated; the drug appears to be extensively metabolized.139 60
Elimination Route
Clavulanic acid is eliminated in urine principally by glomerular filtration.56 59 60 1
Approximately 60–70% of a ticarcillin dose and 35–45% of a clavulanate dose is eliminated unchanged in urine within 6 hours.1
Half-life
In adults with normal renal function, ticarcillin has a distribution half-life of 0.27 hours67 and an elimination half-life of 1.1–1.2 hours1 67 and clavulanic acid has a distribution half-life of 0.42 hours67 and an elimination half-life of 1.1–1.5 hours.1 67
Special Populations
Serum concentrations of ticarcillin and of clavulanic acid are higher and the serum half-lives prolonged in patients with renal impairment.1 In patients with impaired renal function, the elimination half-life of ticarcillin and of clavulanic acid averaged 4.9 and 2.3 hours, respectively, in those with Clcr 11–37 mL/minute and averaged 8.5 and 2.9 hours, respectively, in those with Clcr <8 mL/minute.a
Stability
Storage
Parenteral
Powder for Injection
≤24°C.1 If sterile powder or solutions of the drug darken, this indicates degradation of clavulanate potassium and a loss of potency.83
Reconstituted vials or pharmacy bulk packages containing approximately 200 or 300 mg of ticarcillin/mL and 6.7 or 10 mg of clavulanic acid/mL prepared with sterile water for injection or sodium chloride injection are stable for 6 hours at 21–24°C or 72 hours when refrigerated at 4°C.1
Reconstituted solutions that have been further diluted in sodium chloride injection or lactated Ringer’s injection to a ticarcillin concentration of 10–100 mg/mL are stable for 24 hours at 21–24°C or for up to 30 days frozen at -18°C; at 4°C, these solutions are stable for 4 days when prepared from pharmacy bulk packages and for 7 days when prepared from vials.1
Reconstituted solutions of the drug that have been further diluted in 5% dextrose injection to a ticarcillin concentration of 10–100 mg/mL are stable for 24 hours at 21–24°C, for 3 days at 4°C, or for up to 7 days frozen at -18°C.1 Frozen solutions that have been thawed should be used within 8 hours or discarded; once thawed, these solutions should not be refrozen.1
When prepared from the pharmacy bulk package, reconstituted solutions that have been further diluted in sterile water for injection to a ticarcillin concentration of 10–100 mg/mL are stable for 24 hours at 21–24°C or 4 days at 4°C.1
Injection (Frozen)
≤ -20° C.90 112 Thawed solutions of the commercial frozen injection stable for 24 hours at room temperature (22°C) or 7 days at 4°C.111 112 121
Do not refreeze after thawing.90 111
Compatibility
For information on systemic interactions resulting from concomitant use, see Interactions.
Drug Compatibility
Y-Site CompatibilityHID
Compatible
|
|---|
Allopurinol sodium
|
Amifostine
|
Aztreonam
|
Bivalirudin
|
Cefepime HCl
|
Clarithromycin
|
Cyclophosphamide
|
Dexmedetomidine HCl
|
Diltiazem HCl
|
Docetaxel
|
Doxorubicin HCl liposome injection
|
Etoposide phosphate
|
Famotidine
|
Fenoldopam mesylate
|
Filgrastim
|
Fluconazole
|
Fludarabine phosphate
|
Foscarnet sodium
|
Gallium nitrate
|
Gemcitabine HCl
|
Granisetron HCl
|
Heparin sodium
|
Hetastarch in lactated electrolyte injection (Hextend)
|
Melphalan HCl
|
Meperidine HCl
|
Milrinone lactate
|
Morphine sulfate
|
Ondansetron HCl
|
Pemetrexed disodium
|
Perphenazine
|
Propofol
|
Remifentanil HCl
|
Sargramostim
|
Teniposide
|
Theophylline
|
Thiotepa
|
Vinorelbine tartrate
|
Incompatible
|
|---|
Amphotericin B cholesteryl sulfate complex
|
Azithromycin
|
Drotrecogin alfa (activated)
|
Lansoprazole
|
Variable
|
|---|
Topotecan HCl
|
Vancomycin HCl
|
Actions and SpectrumActions
Fixed combination of ticarcillin disodium (an extended-spectrum penicillin) and clavulanate potassium (a β-lactamase inhibitor).1 3 4 7 9 10 21 55 77 97
Clavulanate potassium synergistically expands ticarcillin’s spectrum of activity against β-lactamase-producing bacteria by irreversibly and completely inhibiting β-lactamase.1 9 19 20 21 55 69 70 73 74 75 77
Usually bactericidal.1
Like other β-lactam antibiotics, antibacterial activity results from inhibition of bacterial cell wall synthesis.1
Spectrum of activity includes many gram-positive and -negative aerobes and some anaerobes.1 Inactive against mycobacteria, Mycoplasma, Rickettsia, fungi, and viruses.a
Gram-positive aerobes: active in vitro and in clinical infections against S. aureus and S. epidermidis.1 Also active in vitro against Streptococcus pneumoniae (penicillin-susceptible strains only), S. agalactiae (group B streptococci), S. pyogenes (group A β-hemolytic streptococci), S. bovis, and viridans streptococci.1 Oxacillin-resistant (methicillin-resistant) staphylococci are resistant.1
Gram-negative aerobes: active in vitro and in clinical infections against Citrobacter, Enterobacter (including E. cloacae), Escherichia coli, Haemophilus influenzae (except β-lactamase-negative, ampicillin-resistant strains; BLNAR), Klebsiella (including K. pneumoniae), Pseudomonas (including Ps. aeruginosa), and Serratia marcescens.1 Also active in vitro against Acinetobacter, Moraxella catarrhalis, Morganella morganii, Neisseria gonorrhoeae, Pasteurella multocida, Proteus mirabilis, P. penneri, P. vulgaris, Providencia, and Stenotrophomonas maltophilia.1 Pseudomonas resistant to ticarcillin generally also are resistant to ticarcillin and clavulanate.69 70
Anaerobes: active in vitro and in clinical infections against Bacteroides fragilis group and Prevotella melaninogenicus.1 Also active in vitro against Clostridium, Eubacterium, Fusobacterium, Peptostreptococcus, and Veillonella.1
Advice to Patients
Advise patients that antibacterials (including ticarcillin and clavulanate) should only be used to treat bacterial infections and not used to treat viral infections (e.g., the common cold).b
Importance of completing full course of therapy, even if feeling better after a few days.b
Advise patients that skipping doses or not completing the full course of therapy may decrease effectiveness and increase the likelihood that bacteria will develop resistance and will not be treatable with ticarcillin and clavulanate or other antibacterials in the future.b
Importance of discontinuing therapy and informing clinician if an allergic reaction occurs.a
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.1
Importance of women informing clinician if they are or plan to become pregnant or plan to breast-feed.1
Importance of informing patients of other important precautionary information. (See Cautions.)
Preparations
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Ticarcillin Disodium and Clavulanate Potassium
Routes
|
Dosage Forms
|
Strengths
|
Brand Names
|
Manufacturer
|
|---|
Parenteral
|
For injection
|
3 g (of ticarcillin) and 100 mg (of clavulanic acid) (labeled as a combined total potency of 3.1 g)
|
Timentin
|
GlaxoSmithKline
|
|
|
30 g (of ticarcillin) and 1 g (of clavulanic acid) (labeled as a combined total potency of 31 g) pharmacy bulk package
|
Timentin
|
GlaxoSmithKline
|
|
For injection, for IV infusion
|
3 g (of ticarcillin) and 100 mg (of clavulanic acid) (labeled as a combined total potency of 3.1 g)
|
Timentin ADD-Vantage
|
GlaxoSmithKline
|
Ticarcillin Disodium and Clavulanate Potassium in Water
Routes
|
Dosage Forms
|
Strengths
|
Brand Names
|
Manufacturer
|
|---|
Parenteral
|
Injection (frozen) for IV infusion
|
30 mg (of ticarcillin) per mL (3 g) and 1 mg (of clavulanic acid) per mL (100 mg) (labeled as a combined total potency of 3.1 g)
|
Timentin Iso-osmotic in Sterile Water Injection (Galaxy [Baxter])
|
GlaxoSmithKline
|
Disclaimer
This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.
The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.
AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions July 2007. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.
References
1. GlaxoSmithKline. Timentin (sterile ticarcillin disodium and clavulanate potassium for intravenous administration) prescribing information. Research Triangle Park, NC; 2001 Apr.
2. GlaxoSmithKline. Ticar (sterile ticarcillin disodium for intramuscular or intravenous administration) prescribing information. Research Triangle Park, NC; 2002 Sept.
3. Kucers A, Crowe S, Grayson ML et al, eds. The use of antibiotics. A clinical review of antibacterial, antifungal, and antiviral drugs. 5th ed. Jordan Hill, Oxford: Butterworth-Heinemann; 1997:145-62,192-203.
4. Brogden RN, Heel RC, Speight TM et al. Ticarcillin: a review of its pharmacological properties and therapeutic efficacy. Drugs. 1980; 20:325-52. [IDIS 128876] [PubMed 7002527]
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7. Neu HC. Carbenicillin and ticarcillin. Med Clin North Am. 1982; 66:61-77. [PubMed 7038341]
8. Lorian V, ed. Antibiotics in laboratory medicine. Baltimore: Williams & Wilkins; 1980:298-341, 418-73, 607-722.
9. Wise R. β-Lactamase inhibitors. J Antimicrob Chemother. 1982; 9(Suppl B):31-40. [PubMed 6977527]
10. Basker MJ, Edmondson RA, Sutherland R. Comparative antibacterial activity of azlocillin, mezlocillin, carbenicillin and ticarcillin and relative stability to beta-lactamases of Pseudomonas aeruginosa and Klebsiella aerogenes. Infection. 1979; 7:67-72. [PubMed 108220]
11. Fass RJ. Comparative in vitro activities of β-lactam-tobramycin combinations against Pseudomonas aeruginosa and multidrug-resistant gram-negative enteric bacilli. Antimicrob Agents Chemother. 1982; 21:1003-6. [IDIS 151726] [PubMed 6810755]
12. Pickering LK, Rutherford I. Effect of concentration and time upon inactivation of tobramycin, gentamicin, netilmicin and amikacin by azlocillin, carbenicillin, mecillinam, mezlocillin and piperacillin. J Pharmacol Exp Ther. 1981; 214:345-9.
13. Pickering LK, Gearhart P. Effect of time and concentration upon interaction between gentamicin, tobramycin, netilmicin, or amikacin and carbenicillin or ticarcillin. Antimicrob Agents Chemother. 1979; 15:592-6. [PubMed 464591]
14. Hale DC, Jenkins R, Matsen JM. In-vitro inactivation of aminoglycoside antibiotics by piperacillin and carbenicillin. Am J Clin Pathol. 1980; 74:316-9. [IDIS 123587] [PubMed 6447998]
15. Yoshikawa TT, Shibata SA. In vitro antibacterial activity of amikacin and ticarcillin, alone and in combination, against Pseudomonas aeruginosa. Antimicrob Agents Chemother. 1978; 13:997-9. [PubMed 98109]
16. Scribner RI, Marks MI, Weber AH et al. Activities of various β-lactams and aminoglycosides, alone and in combination, against isolates of Pseudomonas aeruginosa from patients with cystic fibrosis. Antimicrob Agents Chemother. 1982; 21:939-43. [IDIS 151719] [PubMed 6810757]
17. White GW, Malow JB, Zimelis VM et al. Comparative in vitro activity of azlocillin, ampicillin, mezlocillin, piperacillin, and ticarcillin, alone and in combination with an aminoglycoside. Antimicrob Agents Chemother. 1979; 15:540-3. [IDIS 123117] [PubMed 111616]
18. Chanbusarakum P, Murray PR. Analysis of the interactions between piperacillin, ticarcillin, or carbenicillin and aminoglycoside antibiotics. Antimicrob Agents Chemother. 1978; 14:505-6. [PubMed 101133]
19. Hunter PA, Coleman K, Fisher J et al. In vitro synergistic properties of clavulanic acid, with ampicillin, amoxycillin and ticarcillin. J Antimicrob Chemother. 1980; 6:455-70. [PubMed 6968746]
20. Spratt BG, Jobanputra V, Zimmermann W. Binding of thienamycin and clavulanic acid to the penicillin-binding proteins of Escherichia coli K-12. Antimicrob Agents Chemother. 1977; 12:406-9. [PubMed 334066]
21. Reading C, Cole M. Clavulanic acid: a beta-lactamase-inhibiting beta lactam from Streptomyces clavuligerus. Antimicrob Agents Chemother. 1977; 11:852-7. [PubMed 879738]
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