Ampicillin Sodium and Sulbactam Sodium

Name: Ampicillin Sodium and Sulbactam Sodium

Uses for Ampicillin Sodium and Sulbactam Sodium

Bone and Joint Infections

Treatment of bone and joint infections† (including osteomyelitis and/or septic arthritis) caused by susceptible β-lactamase-producing bacteria.30 58 62 64 90

Intra-abdominal Infections

Treatment of intra-abdominal infections caused by susceptible β-lactamase-producing Escherichia coli, Klebsiella (including K. pneumoniae), Bacteroides (including B. fragilis), or Enterobacter.1 4 29 30 47 53 64 82 85

May be as effective as multiple-drug regimens for treatment of less severe intra-abdominal infections, but an aminoglycoside probably should be used concomitantly for empiric therapy in more serious intra-abdominal infections, including hospital-acquired infections, pending results of in vitro susceptibility tests.64 101 102

Gynecologic Infections

Treatment of serious gynecologic infections (e.g., endometritis, postpartum endomyometritis, posthysterectomy pelvic cellulitis, vaginal cuff abscess, salpingitis, tubo-ovarian abscess, pelvic peritonitis or abscess, surgical wound sepsis) caused by susceptible β-lactamase-producing E. coli or Bacteroides (including B. fragilis).1 49 50 52 54 55 56 74 75 76 83 91

Treatment of pelvic inflammatory disease (PID).6 7 When a parenteral regimen is indicated for PID, CDC and others recommend a regimen of IV ampicillin and sulbactam and IV doxycycline as an alternative6 7 since it provides good coverage against C. trachomatis, N. gonorrhoeae, and anaerobes and is effective for tubo-ovarian abscess.6

Respiratory Tract Infections

Treatment of lower respiratory tract infections† (including pneumonia,57 77 84 87 89 bronchitis,29 57 61 84 87 89 acute exacerbations of chronic bronchitis,84 87 bronchiectasis)84 87 caused by susceptible Staphylococcus, Streptococcus, Haemophilus influenzae, H. parainfluenzae, Moraxella catarrhalis, E. coli, Klebsiella, or Proteus mirabilis.77 81 84 87 89

Has been used for treatment of respiratory tract infections (e.g., pneumonia, tracheobronchitis) or bacteremia caused by Acinetobacter† resistant to imipenem and other anti-infectives.93 Imipenem or meropenem with or without an aminoglycoside usually are recommended for treatment of infections caused by susceptible Acinetobacter.4 101

Skin and Skin Structure Infections

Treatment of skin and skin structure infections (e.g., wound infections, cellulitis, ulcers, abscesses, furunculosis) caused by susceptible β-lactamase-producing S. aureus,1 58 71 87 90 Enterobacter,1 E. coli,1 58 71 87 90 Klebsiella (including K. pneumoniae),1 71 P. mirabilis,1 58 71 90 Bacteroides (including B. fragilis),1 or Acinetobacter.1 29 30 48 58 61 64 86 87 90

Also has been used for treatment of skin and skin structure infections caused by susceptible S. epidermidis†,58 71 87 90 S. warneri†,58 90 Enterococcus faecalis†,58 71 90 Citrobacter†,71 or Morganella morganii†.58 90

Bite Wounds

Empiric treatment of animal or human bites†.4 5 Active against most likely bite pathogens, including anaerobes, Staphylococcus, Eikenella corrodens, Pasteurella multocida.5

Alternative for treatment of infections caused by P. multocida† or E. corrodens†.4 5

Gonorrhea and Associated Infections

Has been used for treatment of uncomplicated gonorrhea† caused by susceptible Neisseria gonorrhoeae.29 30 47 79 80 94 95 However, penicillins, including ampicillin sodium and sulbactam sodium, are not included in current CDC recommendations for treatment of gonorrhea.6

Meningitis

Alternative for treatment of meningitis† caused by susceptible N. meningitidis, H. influenzae, or S. pneumoniae.78 59 87 Other drugs generally preferred and some clinicians strongly discourage use of ampicillin and sulbactam in CNS infections.101 Treatment failures reported when used for treatment of meningitis caused by K. pneumoniae.35

Perioperative Prophylaxis

Perioperative prophylaxis† to reduce the incidence of infections in patients undergoing contaminated or potentially contaminated surgery (e.g., GI or biliary tract surgery, vaginal or abdominal hysterectomy, transurethral prostatectomy).29 30 51 60 98 99 100 Other anti-infectives with narrower spectra of activity (e.g., cephalosporins) generally preferred when prophylaxis is indicated in such procedures.96 97

Ampicillin Sodium and Sulbactam Sodium Dosage and Administration

Administration

Administer by slow IV injection or IV infusion or by IM injection.1

Dosage is the same for IM and IV administration;1 higher serum concentrations usually are attained with IV administration1 30 33 46 63 67 and IV route generally preferred, especially for severe infections.101 102

For solution and drug compatibility information, see Compatibility under Stability.

IV Administration

Reconstitution and Dilution

IV solutions are prepared by reconstituting vials containing 1.5 or 3 g of combined ampicillin and sulbactam with sterile water for injection to provide solutions containing 375 mg/mL (250 mg of ampicillin and 125 mg of sulbactam per mL).1 An appropriate volume of the reconstituted solution should then be immediately diluted with a compatible IV solution to yield solutions containing 3–45 mg/mL (2–30 mg of ampicillin and 1–15 mg of sulbactam per mL).1

ADD-Vantage vials containing 1.5 or 3 g of combined ampicillin and sulbactam should be reconstituted according to the manufacturer’s directions with the 0.9% sodium chloride injection diluent provided.1

Infusion bottles containing 1.5 or 3 g of combined ampicillin and sulbactam may be reconstituted to the desired concentration with a compatible IV solution (see Solution Compatibility under Stability.)1

IV solutions should be allowed to stand after dissolution to allow any foaming to dissipate in order to permit visual inspection for complete solubilization.1

Rate of Administration

For IV injection, given slowly over a period of ≥10–15 minutes.1

IV infusions should be infused slowly over 15–30 minutes.1

IM Administration

IM injections should be made deeply into a large muscle mass.1

Reconstitution

IM solutions are prepared by reconstituting vials containing 1.5 or 3 g of combined ampicillin and sulbactam with 3.2 or 6.4 mL, respectively, of sterile water for injection or 0.5 or 2% lidocaine hydrochloride injection to provide a solution containing 375 mg of the drug per mL (250 mg of ampicillin and 125 mg of sulbactam per mL).1 Use of lidocaine hydrochloride can minimize local pain associated with IM injection of the drug.47 64 92

IM solutions should be allowed to stand after dissolution to allow any foaming to dissipate in order to permit visual inspection for complete solubilization.1 IM solutions should be used within 1 hour after reconstitution.1

Dosage

Available as fixed combination containing ampicillin sodium and sulbactam sodium; dosage generally expressed in terms of the total of the ampicillin and sulbactam content of the fixed combination.1 Potency of both ampicillin sodium and sulbactam sodium are expressed in terms of the bases.1

Pediatric Patients

General Pediatric Dosage IV

Children ≥1 month of age†: AAP recommends 100–150 mg/kg of ampicillin daily in 4 divided doses for treatment of mild to moderate infections or 200–400 mg/kg of ampicillin daily in 4 divided doses for treatment of severe infections.5

Skin and Skin Structure Infections IV

Children ≥1 year of age: 300 mg/kg daily (200 mg of ampicillin and 100 mg of sulbactam) in equally divided doses every 6 hours.1

Manufacturer recommends that IV treatment in pediatric patients not exceed 14 days; in clinical studies, most children received an appropriate oral anti-infective after an initial IV regimen of ampicillin and sulbactam.1

Acute Pelvic Inflammatory Disease IV

Adolescents: 3 g (2 g of ampicillin and 1 g of sulbactam) every 6 hours in conjunction with doxycycline (100 mg orally or IV every 12 hours).6 Parenteral regimen may be discontinued 24 hours after clinical improvement; oral doxycycline (100 mg twice daily) should be continued to complete 14 days of therapy.6

Adults

General Adult Dosage Intra-abdominal, Gynecologic, or Skin and Skin Structure Infections IV or IM

1.5 g (1 g of ampicillin and 0.5 g of sulbactam) to 3 g (2 g of ampicillin and 1 g of sulbactam) every 6 hours.1

Acute Pelvic Inflammatory Disease IV

3 g (2 g of ampicillin and 1 g of sulbactam) every 6 hours in conjunction with doxycycline (100 mg orally or IV every 12 hours).6 7 Parenteral regimen may be discontinued 24 hours after clinical improvement; oral doxycycline (100 mg twice daily) should be continued to complete 14 days of therapy.6 7

Prescribing Limits

Pediatric Patients

IV

Maximum sulbactam dosage is 4 g (i.e., 8 g of ampicillin and 4 g of sulbactam in fixed combination) daily.1

Duration of therapy should be ≤14 days.1

Adults

IV or IM

Maximum sulbactam dosage is 4 g (i.e., 8 g of ampicillin and 4 g of sulbactam in fixed combination) daily.1

Special Populations

Renal Impairment

Dosage adjustments necessary in patients with renal impairment.1 3

Patients with renal impairment should receive the usually recommended dose but these doses should be given less frequently than usual; dosing intervals are based on the patient’s Clcr.1 The manufacturer recommends that patients with Clcr ≥30 mL/minute per 1.73 m2 should receive 1.5 g (1 g of ampicillin and 0.5 g of sulbactam) to 3 g (2 g of ampicillin and 1 g of sulbactam) every 6–8 hours and patients with Clcr 15–29 or 5–14 mL/minute per 1.73 m2 receive these doses every 12 or 24 hours, respectively.1

Some clinicians suggest that patients undergoing hemodialysis receive 1.5 g (1 g of ampicillin and 0.5 g of sulbactam) to 3 g (2 g of ampicillin and 1 g of sulbactam) once every 24 hours and that the dose should preferably be given immediately after dialysis.34 72

Geriatric Patients

No dosage adjustments except those related to renal impairment. (See Renal Impairment under Dosage and Administration.)

Ampicillin Sodium and Sulbactam Sodium Pharmacokinetics

Absorption

Bioavailability

Peak ampicillin serum concentrations attained with ampicillin and sulbactam are similar to those attained with ampicillin alone.1

Peak serum concentrations of ampicillin and sulbactam attained immediately following completion of a 15-minute IV infusion of ampicillin and sulbactam.1 63

Following IM injection, both drugs are rapidly and almost completely absorbed;30 33 46 67 peak serum concentrations of ampicillin and sulbactam generally attained within 30–40 and 30–52 minutes, respectively.30 67

Peak serum concentrations and AUCs of ampicillin and sulbactam are slightly higher in geriatric patients than in younger adults, presumably because of reduced renal clearance in the elderly.3 31

Distribution

Extent

Both ampicillin and sulbactam widely distributed into fluids and tissues,1 3 29 30 33 including peritoneal fluid,1 3 29 30 43 44 60 65 blister fluid,1 3 29 30 36 65 68 tissue fluid,1 sputum,3 30 middle ear effusion,3 65 intestinal mucosa,1 30 45 65 bronchial wall,42 alveolar lining fluid,42 sternum,41 pericardium,41 myocardium,41 endocardium,41 prostate,29 30 65 gallbladder,29 30 39 65 bile,30 39 65 myometrium,30 65 73 salpinges,30 65 73 ovaries,30 65 73 and appendix.1 60 65 Concentrations of the drugs in most of these tissues and fluids are 53–100% of concurrent serum concentrations.33 42 43 65

Both ampicillin and sulbactam distributed into CSF in low concentrations following IV or IM administration.1 3 29 30 35 37 38 59 65 CSF concentrations generally higher in patients with inflamed meninges than in those with uninflamed meninges.35 37 38 59 65

Ampicillin and sulbactam both readily cross the placenta3 30 65 and concentrations in umbilical cord blood may be similar to serum concentrations.65 Ampicillin and sulbactam both distributed into milk in low concentrations.1 30 65 108

Plasma Protein Binding

Ampicillin approximately 15–28% and sulbactam approximately 38% bound to serum proteins.1 3 29 33 65

Elimination

Metabolism

Both ampicillin and sulbactam partially metabolized in the liver.3 Ampicillin partially metabolized by hydrolysis of the β-lactam ring to penicilloic acid which is microbiologically inactive.3

Elimination Route

Both ampicillin and sulbactam eliminated in urine principally by glomerular filtration and tubular secretion.3 29 30 33 34 46 65 Only small amounts of the drugs eliminated in feces and bile.3 33 45

Following IM or IV administration in adults with normal renal function, approximately 75–92% of the dose of both ampicillin and sulbactam excreted unchanged in urine within 8 hours.1 65 67

Ampicillin and sulbactam both removed by hemodialysis.1 34

Half-life

In healthy adults with normal renal function, both ampicillin and sulbactam have a distribution half-life of about 15 minutes and an elimination half-life of about 1 hour.1 33 65 67

In infants and children <12 years of age, sulbactam has an elimination half-life of 0.92–1.9 hours.29 32 33 In neonates, half-lives of ampicillin and sulbactam vary inversely with age; as renal tubular function matures, the drugs are cleared more rapidly.33 40 65 66 In premature neonates ≤6 days of age, half-life of ampicillin averages 9.4 hours and half-life of sulbactam averages 7.9 hours.29

Special Populations

Half-lives are slightly longer in geriatric adults than in younger adults3 29 31 (2.2 hours compared with 0.8–1.2 hours in younger adults).29

Serum concentrations of both ampicillin and sulbactam are higher and half-lives prolonged in patients with renal impairment.1 3 29 30 33 34 65 Half-lives of ampicillin and sulbactam average 1.6 and 1.6 hours, respectively, in adults with Clcr 30–60 mL/minute and average 3.4 and 3.7 hours, respectively, in those with Clcr 7–30 mL/minute.34 In adults with Clcr <7 mL/minute, elimination half-life of ampicillin and sulbactam average 17.4 and 13.4 hours, respectively.34

Cystic fibrosis patients may eliminate sulbactam at faster rates than healthy individuals.29 32 65

Actions and Spectrum

  • Fixed combination of ampicillin sodium (an aminopenicillin) and sulbactam sodium (a β-lactamase inhibitor).1 3

  • Sulbactam synergistically expands activity of ampicillin against β-lactamase-producing bacteria by irreversibly and competitively inhibiting β-lactamases.1 3 Active against bacteria susceptible to ampicillin alone and also active against many β-lactamase-producing bacteria resistant to ampicillin alone.1 3

  • Usually bactericidal.1

  • Like other β-lactam antibiotics, antibacterial activity results from inhibition of bacterial cell wall synthesis.1 3

  • Spectrum of activity includes many gram-positive and -negative aerobes and some anaerobes.1 3

  • Gram-positive aerobes: active in vitro against β-lactamase-producing and non-β-lactamase-producing strains of Staphylococcus, S. epidermidis, and S. saprophyticus.1 Also active in vitro against Streptococcus pneumoniae, S. pyogenes (group A β-hemolytic streptococci), and Enterococcus faecalis.1 Oxacillin-resistant (methicillin-resistant) staphylococci are resistant.3

  • Gram-negative aerobes: active in vitro against β-lactamase-producing and non-β-lactamase-producing strains of Haemophilus influenzae, Moraxella catarrhalis, Escherichia coli, Klebsiella, Proteus mirabilis, and Neisseria gonorrhoeae.1 Also active in vitro against P. vulgaris, Providencia rettgeri, P. stuartii, and Morganella morganii.1 Inactive against Pseudomonas aeruginosa.1

  • Anaerobes: active in vitro against Bacteroides (including B. fragilis),1 3 Clostridium, Peptococcus, and Peptostreptococcus.1

Advice to Patients

  • Advise patients that antibacterials (including ampicillin and sulbactam) should only be used to treat bacterial infections and not used to treat viral infections (e.g., the common cold).1

  • Importance of completing the entire prescribed course of treatment, even if feeling better after a few days.1

  • 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 ampicillin and sulbactam or other antibacterials in the future.1

  • Importance of discontinuing therapy and informing clinician if an allergic reaction occurs.1

  • Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs.1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of advising patients of other important precautionary information.1 (See Cautions.)

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