Ticarcillin Disodium and Clavulanate Potassium

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 Cl_cr<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 Cl_cr (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

• 
  

  Hypersensitivity to any penicillin.¹

  
  

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 testing^b 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 tract^{2 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 hours^{1 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 Cl_cr 11–37 mL/minute and averaged 8.5 and 2.9 hours, respectively, in those with Cl_cr <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]

5. Barza M. Antimicrobial spectrum, pharmacology and therapeutic use of antibiotics. Part 2: penicillins. Am J Hosp Pharm. 1977; 34:57-67. [PubMed 318800]

6. Trissel LA. Handbook on injectable drugs. 12th ed. Bethesda, MD: American Society of Health-System Pharmacists, Inc.; 2003:1304-10.

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]

22. Selwyn S. Applied pharmacology, adverse effects and drug interactions. In: Selwyn S, ed. The beta-lactam antibiotics: penicillins and cephalosporins in perspective. London: Hodder and Stoughton; 1980:91-126.

23. Davies M, Morgan JR, Anand C. Administration of ticarcillin to patient with severe renal failure. Chemotherapy. 1974; 20:339-41. [PubMed 4442291]

24. Wise R, Reeves DS, Parker AS. Administration of ticarcillin, a new antipseudomonal antibiotic, in patients undergoing dialysis. Antimicrob Agents Chemother. 1974; 5:119-20. [PubMed 4840427]

25. Parry MF, Neu HC. Pharmacokinetics of ticarcillin in patients with abnormal renal function. J Infect Dis. 1976; 133:46-9. [PubMed 1107435]

26. Ervin FR, Bullock WE. Clinical and pharmacological studies of ticarcillin in gram-negative infections. Antimicrob Agents Chemother. 1976; 9:94-101. [PubMed 769676]

27. Libke RD, Clarke JT, Ralph ED et al. Ticarcillin vs carbenicillin: clinical pharmacokinetics. Clin Pharmacol Ther. 1975; 17:441-6. [PubMed 1122685]

28. Kaye D. The clinical significance of tolerance of Staphylococcus aureus. Ann Intern Med. 1980; 93:924-5. [IDIS 125298] [PubMed 7004294]

29. Parry MF, Neu HC. Ticarcillin for treatment of serious infections with gram-negative bacteria. J Infect Dis. 1976; 134:476-85. [PubMed 825582]

30. Erffmeyer JE. Adverse reactions to penicillin. Ann Allergy. 1981; 47:288-300. [PubMed 6171185]

31. Brown CH, Natelson EA, Bradshaw MW et al. Study of the effects of ticarcillin on blood coagulation and platelet function. Antimicrob Agents Chemother. 1975; 7:652-7. [PubMed 1147594]

32. Isbister JP. Penicillin allergy: a review of the immunological and clinical aspects. Med J Aust. 1971; 1:1067-74. [PubMed 4398272]

33. Sullivan TJ, Wedner HJ, Shatz GS et al. Skin testing to detect penicillin allergy. J Allergy Clin Immunol. 1981; 68:171-80. [IDIS 140792] [PubMed 6267115]

34. Edwards DJ, Schentag JJ. In vitro interactions between β-lactam antibiotics and tobramycin. Clin Chem. 1981; 27:341. [IDIS 134578] [PubMed 6970094]

35. Hoigné R, Hopf B, Sonntag R. Penicillins, cephalosporins and tetracyclines. In: Dukes MNG, ed. Meyler’s side effects of drugs. 9th ed. New York: Elsevier/North Holland Inc; 1980:411-22.

36. Kunin CM. Penicillinase-resistant penicillins. JAMA. 1977; 237:1605-6. [PubMed 576661]

38. Braude AI, Davis CE, Fierer J, eds. Medical microbiology and infectious diseases. Philadelphia: WB Saunders; 1981:782-3, 813-40, 846-50, 909-24, 958-71, 1036-8, 1044-7, 1375-6, 1395-407, 1758-60, 1787-91, 1811, 1846-7.

39. Eichenwald HF, McCracken GH. Antimicrobial therapy in infants and children. Part I. Review of antimicrobial agents. J Pediatr. 1978; 93:336-56.

40. Wilson WR, Nichols DR, Thompson RL et al. Infective endocarditis: therapeutic considerations. Am Heart J. 1980; 100:689-703. [IDIS 124308] [PubMed 7004153]

41. Casey JI, Miller MH. Infective endocarditis. Part II. Current therapy. Am Heart J. 1978; 96:263-9. [PubMed 249230]

42. Henderson JL, Polk RE, Kline BJ. In vitro inactivation of gentamicin, tobramycin, and netilmicin by carbenicillin, azlocillin, or mezlocillin. Am J Hosp Pharm. 1981; 38:1167-70. [PubMed 6455916]

43. O’Bey KA, Jim LK, Gee JP et al. Temperature dependence of the stability of tobramycin mixed with penicillins in human serum. Am J Hosp Pharm. 1982; 39:1005-8. [PubMed 7102681]

44. Witkowski JA, Parish LC. Bacterial skin infections: management of common streptococcal and staphylococcal lesions. Postgrad Med. 1982; 72:167-85. [PubMed 7088741]

45. Riff LJ, Thomason JL. Comparative aminoglycoside inactivation by β-lactam antibiotics: effect of a cephalosporin and six penicillins on five aminoglycosides. J Antibiot. 1982; 35:850-7. [IDIS 156257] [PubMed 7174538]

46. Eliopoulos GM, Moellering RC. Antibiotic synergism and antimicrobial combinations in clinical infections. Rev Infect Dis. 1982; 4:282-93. [IDIS 153667] [PubMed 7051231]

47. Sheagren JN. Staphylococcus aureus—the persistent pathogen (second of two parts). N Engl J Med. 1984; 310:1437-42. [PubMed 6371536]

49. Fuchs PC, Barry AL, Thornsberry C et al. In vitro evaluation of Augmentin by broth microdilution and disk diffusion susceptibility testing: regression analysis, tentative interpretive criteria, and quality control limits. Antimicrob Agents Chemother. 1983; 24:31-8. [IDIS 173440] [PubMed 6625554]

50. Labia R, Peduzzi J. Augmentin and β-lactamases: inactivation of β-lactamase by clavulanic acid. In: Croydon EA Michel MF, eds. Augmentin. Amsterdam: Excerpta Medica; 1983: 11-20.

52. US Food and Drug Administration. Penicillinase-resistant penicillin human prescription drugs class labeling guideline for professional labeling. [Notice of availability published in: Fed Regist. 1982; 47:41636.] Available from: Professional Labeling Branch, Division of Drug Advertising and Labeling, Food and Drug Administration, Rockville, MD.

53. Perryman F, Johnson S, Hussain Qadri SM. In vitro activity of augmentin against