Timentin

Generic Name: 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

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 Timentin

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

Slideshow: 10 Things to Know About Antibiotic Resistance

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

Timentin 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 Timentin

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 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 Timentin

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

Timentin 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 Spectrum

  • 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

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions July 1, 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 pathogenic bacteria and its comparison with other antibiotics. Chemotherapy. 1983; 29:111-5. [IDIS 169054] [PubMed 6839863]

54. Adam D, Visser ID, Koeppe P. Pharmacokinetics of amoxicillin and clavulanic acid administered alone and in combination. Antimicrob Agents Chemother. 1982; 22:353-7. [IDIS 157283] [PubMed 7137979]

55. Neu HC, Fu KP. Clavulanic acid, a novel inhibitor of β-lactamases. Antimicrob Agents Chemother. 1978; 14:650-5. [IDIS 176038] [PubMed 310279]

56. Stein GE, Gurwith MJ. Amoxicillin-potassium clavulanate, a β-lactamase-resistant antibiotic combination. Clin Pharm. 1984; 3:591-9. [IDIS 193403] [PubMed 6391783]

57. Al Roomi LG, Sutton AM, Cockburn F et al. Amoxycillin and clavulanic acid in the treatment of urinary infection. Arch Dis Child. 1984; 59:256-9. [IDIS 184059] [PubMed 6712275]

58. Reading C, Farmer T, Cole M. The β-lactamase stability of amoxycillin with the β-lactamase inhibitor, clavulanic acid. J Antimicrob Chemother. 1983; 11:27-32. [PubMed 6600741]

59. Staniforth DH, Jackson D, Clarke HL et al. Amoxycillin/clavulanic acid: the effect of probenecid. J Antimicrob Chemother. 1983; 12:272-5.

60. Jackson D, Cooper DL, Horton R et al. Absorption, pharmacokinetic and metabolic studies with Augmentin. In: Croydon EA, Michel MF, eds. Augmentin: Proceedings of the European symposium Scheveningen, The Netherlands 28–29 June, 1982. Amsterdam: Elsevier; 1983:83-101.

61. Dalet F, Cabrera E, Donate T et al. Pharmacokinetics of the association amoxycillin and clavulanic acid in renal insufficiency and during haemodialysis. In: Croydon EA, Michel MF, eds. Augmentin: Proceedings of the European symposium Scheveningen, The Netherlands 28–29 June, 1982. Amsterdam: Elsevier; 1983:109-20.

62. Ronald AR. Amoxicillin and potassium clavulanate: an antibiotic combination. Mechanism of action, pharmacokinetics, antimicrobial spectrum, clinical efficacy and adverse effects. Commentary 3. Pharmacotherapy. 1984; 4:135.

63. Hardwick MJ (Beecham Laboratories, Bristol, TN): Personal communication; 1985 Mar 19.

64. Williams ME, Thomas D, Harman CP. Positive direct antiglobulin tests due to clavulanic acid. Antimicrob Agents Chemother. 1985; 27:125-7. [IDIS 195276] [PubMed 3872623]

65. Munich R, Luthy R, Blaser J et al. Human pharmacokinetics and CSF penetration of clavulanic acid. J Antimicrob Chemother. 1981; 8:29-37. [PubMed 7251537]

66. Faro S, Martens M, Philips LE et al. Ticarcillin disodium/clavulanate potassium versus clindamycin/gentamicin in the treatment of postpartum endometritis. J Reprod Med. 1988; 33(Suppl):603-6. [PubMed 3294407]

67. Bennett S, Wise R, Weston D et al. Pharmacokinetics and tissue penetration of ticarcillin combined with clavulanic acid. Antimicrob Agents Chemother. 1983; 23:831-4. [IDIS 172590] [PubMed 6614890]

68. Fuchs PC, Jones RN, Barry AL et al. Disk diffusion susceptibility testing of ticarcillin plus clavulanic acid. J Clin Microbiol. 1984; 19:555-7. [PubMed 6715524]

69. Barry AL, Ayers LW, Gavan TL et al. In vitro activity of ticarcillin plus clavulanic acid against bacteria isolated in three centers. Eur J Clin Microbiol. 1984; 3:203-6. [PubMed 6147246]

70. Chattopadhyay B, Hall I. In vitro activity of ticarcillin plus clavulanic acid (BRL 28500, Timentin) against ticarcillin-resistant gram-negative rods. Curr Med Res Opin. 1984; 9:157-60. [PubMed 6568146]

71. Clarke AM, Zemcov SJV. Clavulanic acid in combination with ticarcillin: an in-vitro comparison with other β-lactams. J Antimicrob Chemother. 1984; 13:121-8.

72. Casey P, Glauser M. Susceptibility of gram-negative bacteria and Staphylococcus aureus to combinations of ticarcillin and clavulanic acid. Eur J Microbiol. 1983; 2:541-7.

73. Fuchs PC, Barry AL, Thornsberry C et al. In vitro activity of ticarcillin plus clavulanic acid against 632 clinical isolates. Antimicrob Agents Chemother. 1984; 25:392-4. [PubMed 6721472]

74. Wheat PF, Spencer RC. The effect of varying ratios of ticarcillin to clavulanic acid against gentamicin-resistant and gentamicin-sensitive Enterobacteriaceae. J Antimicrob Chemother. 1984; 14:195-6. [PubMed 6568225]

75. Paisley JW, Washington JA. The combined activity of clavulanic acid and ticarcillin against ticarcillin-resistant, gram-negative bacilli. Antimicrob Agents Chemother. 1978; 14:224-7. [IDIS 93449] [PubMed 308792]

76. File TM, Tan JS, Salstrom SJ et al. Timentin versus piperacillin or moxalactam in the therapy of acute bacterial infections. Antimicrob Agents Chemother. 1984; 26:310-3. [IDIS 190359] [PubMed 6508263]

77. Roselle GA, Bode R, Hamilton B et al. Clinical trial of the efficacy and safety of ticarcillin and clavulanic acid. Antimicrob Agents Chemother. 1985; 27:291-6. [IDIS 197541] [PubMed 3888101]

78. Macko V, Lind R, Zeluff B et al. Timentin therapy for osteomyelitis. Program and abstracts of the twenty-third Interscience Conference on Antimicrobial Agents and Chemotherapy; Las Vegas, NV: Oct 1983. Abstract no 846.

79. Marier RL, Alderidge KE, Derks FW et al. Ticarcillin/clavulanic acid (TIC-CA) (BRL 28500) in the therapy of serious infections. Program and abstracts of the twenty-third Interscience Conference on Antimicrobial Agents and Chemotherapy. Las Vegas, NV: Oct 1983. Abstract no 848.

80. Jacobs RF, Trang JM, Kearns GL et al. Ticarcillin/clavulanic acid pharmacokinetics in children and young adults with cystic fibrosis. J Pediatr. 1985; 106:1001-7. [IDIS 200969] [PubMed 3998937]

81. Bourgault AM, Lamothe F, Parent M. Inoculum effects on the bactericidal activities of seven antimicrobial agents against Bacteroides fragilis. Program and abstracts of the twenty-fourth Interscience Conference on Antimicrobial Agents and Chemotherapy. Washington, DC: Oct 1984. Abstract no 1264.

82. Reviewers’ comments (personal observations).

83. Yancey R. (Beecham Laboratories, Bristol, TN): Personal communication; 1985 Jul 18.

84. Rolinson GN. Clavulanic acid/antibiotic ratios. J Antimicrob Chemother. 1985; 15:256-7. [PubMed 3980316]

85. BRL 28500—1.2 g by bolus intravenous injection over 30 seconds, with and without orally administered probenecid. Paper presented at the 21st Interscience Conference on Antimicrobial Agents and Chemotherapy. Chicago, IL: Oct 1981.

90. Baxter Healthcare Corporation. Descriptive information on premixed Galaxy and Viaflex Plus container frozen products. Deerfield, IL; 1990 Aug.

91. Doern GV. Branhamella catarrhalis—an emerging human pathogen. Diagn Microbiol Infect Dis. 1986; 4:191-201. [PubMed 3514103]

92. Gutman L, Williamson R, Kitzis MD et al. Synergism and antagonism in double beta-lactam antibiotic combinations. Am J Med. 1986; 80(Suppl 5C):21-9. [IDIS 217461] [PubMed 3487247]

93. Moosdeen F, Keeble J, Williams JD. Induction/inhibition of chromosomal β-lactamases by β-lactamase inhibitors. Rev Infect Dis. 1986; 8(Suppl 5):S562-8.

94. Neu HC. Contribution of beta-lactamases to bacterial resistance and mechanisms to inhibit beta-lactamases. Am J Med. 1985; 79(Suppl 5B):2-12.

95. Sanders CC, Sanders WE Jr. Type I β-lactamases of gram-negative bacteria: interactions with β-lactam antibiotics. J Infect Dis. 1986; 154:792-800. [IDIS 226042] [PubMed 3490520]

96. Tausk F, Stratton CW. Effect of clavulanic acid on the activity of ticarcillin against Pseudomonas aeruginosa. Antimicrob Agents Chemother. 1986; 30:584-9. [IDIS 224476] [PubMed 3098162]

97. The United States pharmacopoeia, 26th rev, and The national formulary, 21st ed. Rockville, MD: The United States Pharmacopeial Convention, Inc; 2003:1834-6.

98. Apuzzio JJ, Kaminski Z, Gamesh V et al. Comparative clinical evaluation of ticarcillin plus clavulanic acid versus clindamycin plus gentamicin in treatment of post-cesarean endomyometritis. Am J Med. 1985; 79(Suppl 5B):164-7. [IDIS 208960] [PubMed 4073085]

99. Pastorek JG, Aldridge KE, Cunningham GL et al. Comparison of ticarcillin plus clavulanic acid with cefoxitin in the treatment of female pelvic infection. Am J Med. 1985; 70(Suppl 5B):161-3.

100. Yonekura ML. The treatment of endomyometritis. J Reprod Med. 1988; 33(Suppl):579-83. [PubMed 3260948]

101. Sanders CV, Pastorek JG, Miller JM et al. Ticarcillin disodium and clavulanate potassium in the treatment of post-cesarean-section endomyometritis. J Reprod Med. 1988; 33(Suppl):584-7. [PubMed 3260949]

102. McGregor JA, Christiansen FB. Treatment of obstetric and gynecologic infections, with an emphasis on beta-lactamase-producing organisms. J Reprod Med. 1988; 33(Suppl):591-4. [PubMed 3294404]

103. Holloway WJ. Infection in women: clinical experience with beta-lactamase inhibitors. J Reprod Med. 1988; 33(Suppl):595-7. [PubMed 3294405]

104. Levine DP, Wilson RF. Treatment of penetrating abdominal trauma and gynecologic infections. J Reprod Med. 1988; 33(Suppl):598-602. [PubMed 3294406]

105. Itokazu GS, Danziger LH. Ampicillin-sulbactam and ticarcillin-clavulanic acid: a comparison of their in vitro activity and review of their clinical efficacy. Pharmacotherapy. 1991; 11:382-414. [IDIS 387558] [PubMed 1745624]

106. Anon. The choice of antibacterial drugs. Med Lett Drugs Ther. 2001; 43:69-78. [PubMed 11518876]

107. Apuzzio JJ, Ganesh V, Kaminski Z et al. Comparison of ticarcillin plus clavulanic acid with clindamycin and gentamicin in the treatment of postcesarean endometritis. Surg Gynecol Obstet. 1988; 166:413-7. [IDIS 313767] [PubMed 3259017]

108. Cuchural GJ Jr, Tally FP, Jacobus NV et al. Susceptibility of Bacteroides fragilis group in the United States: analysis by site of isolation. Antimicrob Agents Chemother. 1988; 32:717-22. [PubMed 3395102]

109. Fuchs PC, Jones RN, Barry AL et al. Effect of clavulanic acid on the susceptibility of clinical anaerobic bacteria to ticarcillin: a multicenter study. Diagn Microbiol Infect Dis. 1988; 9:47-50. [PubMed 3370931]

110. Food and Drug Administration. Antibiotic drugs; nafcillin sodium injection (Docket No. 89N-0494). Fed Regist. 1990; 55:277-8.

111. GlaxoSmithKline. Timentin (ticarcillin disodium and clavulanate potassium) injection (Galaxy [PL 2040] plastic container) prescribing information. In: Physicians’ desk reference. 57th ed. Montvale, NJ: Medical Economics Company Inc; 2003:1659-61.

112. Baxter Healthcare Corporation. Descriptive information on premixed frozen products. Deerfield, IL; 1992 Sep.

113. Bohnen JMA, Solomkin JS, Dellinger EP et al. Guidelines for clinical care: anti-infective agents for intra-abdominal infection. A Surgical Infection Society policy statement. Arch Surg. 1992; 127:83-9. [PubMed 1734854]

114. Dellinger EP. Design and evaluation of clinical trials of antimicrobial agents in surgery. Surg Gynecol Obstet. 1991; 172(Suppl):65-72. [PubMed 2024229]

115. Levin S, Goodman LJ. Selected overview of nongynecologic surgical intra-abdominal infections: prophylaxis and therapy. Am J Med. 1985; 79(Suppl 5B):146-56. [IDIS 208957] [PubMed 3934966]

116. Fink MP, Helsmoortel CM, Arous EJ. Comparison of the safety and efficacy of parenteral ticarcillin/clavulanate and clindamycin/gentamicin in serious intra-abdominal infections. J Antimicrob Chemother. 1989; 24(Suppl B):147-56. [PubMed 2691476]

117. Sirinek KR, Levine BA. A randomized trial of ticarcillin and clavulanate versus gentamicin and clindamycin in patients with complicated appendicitis. Surg Gynecol Obstet. 1991; 172(Suppl):30-5. [IDIS 281374] [PubMed 2024224]

118. Committee on Infectious Diseases, American Academy of Pediatrics. 2000 Red book: report of the Committee on Infectious Disease. 25th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2000:659.

119. National Committee for Clinical Laboratory Standards. MIC testing supplemental tables; M100-S13 (M7). Wayne, PA:NCCLS; 2003 Jan.

120. National Committee for Clinical Laboratory Standards. Disk diffusion supplemental tables; M100-S13 (M2). Wayne, PA:NCCLS; 2003 Jan.

121. Baxter Healthcare Corporation. Descriptive information on premixed products. Deerfield, IL; 1994 Feb 21.

122. Johnson S, Gerding DN. Clostridium difficile-associated diarrhea. Clin Infect Dis. 1998; 26:1027-36. [IDIS 407733] [PubMed 9597221]

123. Gerding DN, Johnson S, Peterson LR et al for the Society for Healthcare Epidemiology of American. Position paper on Clostridium difficile-associated diarrhea and colitis. Infect Control Hosp Epidemiol. 1995; 16:459-77. [PubMed 7594392]

124. Fekety R for the American College of Gastroenterology Practice Parameters Committee. Guidelines for the diagnosis and management of Clostridium difficile-associated diarrhea and colitis. Am J Gastroenterol. 1997; 92:739-50 (IDIS 386628) [IDIS 386628] [PubMed 9149180]

125. American Society of Health-System Pharmacists Commission on Therapeutics. ASHP therapeutic position statement on the preferential use of metronidazole for the treatment of Clostridium difficile-associated disease. Am J Health-Syst Pharm. 1998; 55:1407-11. [IDIS 407213] [PubMed 9659970]

126. Wilcox MH. Treatment of Clostridium difficile infection. J Antimicrob Chemother. 1998; 41(Suppl C):41-6. [IDIS 407246] [PubMed 9630373]

127. Fabian TC, Boldreghini SJ. Antibiotics in penetrating abdominal trauma: comparison of ticarcillin plus clavulanic acid with gentamicin plus clindamycin. Am J Med. 1985; 79(Suppl 5B):157-60. [IDIS 208958] [PubMed 4073083]

128. Fink MP. Antibiotic therapy of intra-abdominal sepsis in the elderly: experience with ticarcillin and clavulanic acid. Surg Gynecol Obstet. 1991; 172(Suppl):36-41. [IDIS 281375] [PubMed 2024225]

129. DiPiro JT, Mansberger JA, Davis JB Jr. Current concepts in clinical therapeutics: intra-abdominal infections. Clin Pharm. 1986; 5:34-50. [IDIS 208867] [PubMed 3512154]

133. Idsoe O, Guthe T, Willcox RR et al. Nature and extent of penicillin side-reactions, with particular reference to fatalities from anaphylactic shock. Bull World Health Organ. 1968; 38:159-88. [PubMed 5302296]

134. GlaxoSmithKline. Timentin (sterile ticarcillin disodium and ticarcillin potassium) for intravenous administration (pharmacy bulk package not for direct infusion) prescribing information. In: Physicians’ desk reference. 57th ed. Montvale, NJ: Medical Economics Company Inc; 2000:1661-4.

135. Konishi H, Goto M, Nakamoto Y et al. Tobramycin inactivation by carbenicillin, ticarcillin, and piperacillin. Antimicrob Agents Chemother. 1983; 23:653-7. [IDIS 170751] [PubMed 6223576]

137. Labia R, Barthelemy M, Le Bouguennec CB et al. Classification of β-lactamases from Branhamella catarrhalis in relation to penicillinases produced by other bacterial species. Drugs. 1986; 31(Suppl 3):40-7. [PubMed 3488196]

138. Weber DJ, Tolkoff-Rubin NE, Rubin RH. Amoxicillin and potassium clavulanate: an antibiotic combination: mechanisms of action, pharmacokinetics, antimicrobial spectrum, clinical efficacy and adverse effects. Pharmacotherapy. 1984; 4:122-36. [IDIS 393570] [PubMed 6739312]

139. Haginaka J, Nakagawa T, Hoshino T et al. Pharmacokinetic studies of the urinary excretion of clavulanic acid in man. Chem Pharm Bull. 1981; 29:3342-9. [PubMed 7337933]

140. Newton DW, Kluza RB. pKa Values of medicinal compounds in pharmacy practice. Drug Intell Clin Pharm. 1978; 12:546-54.

a. AHFS Drug Information 2004. McEvoy GK, ed. Extended-spectrum Penicillins General Statement. American Society of Health-System Pharmacists; 2004:341-9.

b. GlaxoSmithKline. Timentin (sterile ticarcillin disodium and clavulanate potassium for intravenous administration) prescribing information. Research Triangle Park, NC; 2001 Apr.

HID. Trissel LA. Handbook on injectable drugs. 14th ed. Bethesda, MD: American Society of Health-System Pharmacists; 2007:1557-61.

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