Principen (Ampicillin)

Ampicillin Sodium and Sulbactam Sodium

Ampicillin sodium and sulbactam sodium is a fixed combination of the sodium salts of ampicillin (an aminopenicillin antibiotic) and sulbactam (a b-lactamase inhibitor); sulbactam synergistically expands ampicillin’s spectrum of activity against many strains of b-lactamase-producing bacteria.

Uses

Ampicillin sodium and sulbactam sodium is used parenterally for the treatment of skin and skin structure, intra-abdominal, and gynecologic infections caused by susceptible bacteria. The drug also has been used parenterally for the treatment of other infections, including respiratory tract infections caused by susceptible bacteria.

Ampicillin sodium and sulbactam sodium is used principally for the treatment of infections caused by, or suspected of being caused by, susceptible β-lactamase-producing strains of staphylococci, Enterobacteriaceae, and/or Bacteroides. Although ampicillin sodium and sulbactam sodium may also be effective in the treatment of infections caused by non-β-lactamase-producing bacteria susceptible to ampicillin alone, most clinicians prefer an aminopenicillin alone for these infections. Ampicillin sodium and sulbactam sodium is generally reserved for infections caused by β-lactamase-producing bacteria when an aminopenicillin alone would be ineffective.

Ampicillin sodium and sulbactam sodium may be particularly useful for the empiric treatment of intra-abdominal or gynecologic infections likely to involve anaerobes (e.g., mixed aerobic-anaerobic infections) or for infections suspected of being caused by both ampicillin-resistant and ampicillin-susceptible bacteria. For most other infections caused by susceptible organisms—including Staphylococcus aureus, S. epidermidis, Bacteroides, Klebsiella pneumoniae, Escherichia coli, indole-positive Proteeae (e.g., Proteus vulgaris, Providencia rettgeri, Morganella morganii), Eikenella corrodens, or Pasteurella multocida—ampicillin sodium and sulbactam sodium is generally considered an alternative to other anti-infectives.

When treating infections caused by Enterobacteriaceae in severely ill patients, some clinicians recommend combined therapy with ampicillin sodium and sulbactam sodium and an aminoglycoside. Because ampicillin sodium and sulbactam sodium is not active against Pseudomonas, it should not be used alone in infections known or suspected to be caused by Pseudomonas aeruginosa.

The relative efficacy of ampicillin sodium and sulbactam sodium compared with other anti-infective combinations that include a β-lactamase inhibitor (e.g., amoxicillin and clavulanate potassium, ticarcillin disodium and clavulanate potassium) remains to be established.

Prior to initiating therapy with ampicillin sodium and sulbactam sodium, appropriate specimens should be obtained to identify the causative organism(s) and perform in vitro susceptibility tests. Ampicillin sodium and sulbactam sodium may be started before susceptibility results are available if the infection is believed to be caused by β-lactamase-producing bacteria susceptible to the drug. However, therapy should be discontinued and replaced with appropriate anti-infective therapy if the organism is found to be resistant.

If the infection is caused by non-β-lactamase-producing organisms susceptible to ampicillin, some clinicians suggest switching to an aminopenicillin alone, unless this is impractical.

Skin and Skin Structure Infections

Parenteral ampicillin sodium and sulbactam sodium is used in adults and children 1 year of age or older for the treatment of a variety of skin and skin structure infections, including wound infections, cellulitis, ulcers, abscesses, and furunculosis, caused by susceptible b-lactamase-producing strains of Staphylococcus aureus, Escherichia coli, Klebsiella (including K. pneumoniae), Proteus mirabilis, Bacteroides (including B. fragilis), or Acinetobacter.

The drug also has been effective when used in adults for the treatment of skin and skin structure infections caused by other susceptible gram-positive bacteria, including S. epidermidis, S. warneri, or Enterococcus faecalis (formerly Streptococcus faecalis), or other susceptible gram-negative bacteria, including susceptible strains of Citrobacter, Enterobacter, or Morganella morganii. In controlled studies in adults with serious skin and skin structure infections, parenteral ampicillin sodium and sulbactam sodium was at least as effective as a regimen of clindamycin with or without an aminoglycoside. Parenteral ampicillin sodium and sulbactam sodium therapy generally results in clinical and bacteriologic cure rates of 86-100% in adults with skin and skin structure infections caused by susceptible bacteria.

Although parenteral ampicillin sodium and sulbactam sodium appears to be an effective regimen for the treatment of serious skin and skin structure infections, concomitant use of an anti-infective agent that is active against Pseudomonas (e.g., an aminoglycoside) may be necessary in some of these infections. In addition, less severe skin and skin structure infections (e.g., cellulitis, impetigo, erysipelas) usually can be treated with other more cost-effective therapies that have a narrower spectrum of activity (e.g., penicillinase-resistant penicillins, erythromycin, cephalosporins).

Intra-abdominal and Gynecologic Infections

Parenteral ampicillin sodium and sulbactam sodium is used effectively in adults for the treatment of a variety of intra-abdominal and gynecologic infections caused by susceptible E. coli, Klebsiella (including K. pneumoniae), Bacteroides (including B. fragilis), or Enterobacter. Most intra-abdominal and gynecologic infections are mixed aerobic-anaerobic infections, and efficacy of ampicillin sodium and sulbactam sodium in these polymicrobial infections is based on the drug’s broad spectrum of activity against both gram-positive and gram-negative aerobic and anaerobic bacteria and on its distribution into most tissues and fluids.Depending on suspected organisms and severity of the infection, addition of an aminoglycoside may be considered.

Intra-abdominal Infections

Parenteral ampicillin sodium and sulbactam sodium has been effective when used in adults as an adjunct to surgical measures (e.g., drainage) in the treatment of appendicitis, peritonitis, perforated appendix, diverticulitis, postoperative bowel infections, small bowel infarct, intra-abdominal or retroperitoneal abscess, cholecystitis, and secondary liver infections caused by susceptible bacteria.

Use of parenteral ampicillin sodium and sulbactam sodium therapy in adults with intra-abdominal infections has been associated with clinical and bacteriologic cure rates of 78-96%. In a few studies in adults, parenteral ampicillin sodium and sulbactam sodium appeared to be at least as effective as other regimens used in the adjunctive treatment of intra-abdominal infections (e.g., clindamycin or metronidazole and an aminoglycoside, cefoxitin with or without an aminoglycoside, imipenem and cilastatin sodium) and generally was associated with fewer adverse effects than these other regimens.

However, in at least one study, parenteral ampicillin sodium and sulbactam sodium was less effective than a regimen of clindamycin and gentamicin in the treatment of patients with perforated or gangrenous appendicitis; most treatment failures in patients receiving ampicillin sodium and sulbactam sodium were the result of overgrowth with Pseudomonas.

Some clinicians suggest that, although parenteral ampicillin sodium and sulbactam sodium alone may be as effective as multiple-drug regimens for the treatment of less severe intra-abdominal infections, an aminoglycoside probably should be used concomitantly with the drug for empiric therapy in more serious intra-abdominal infections, including hospital-acquired infections, pending results of in vitro susceptibility tests. In addition, some clinicians suggest that other anti-infective agents (e.g., ticarcillin disodium and clavulanate potassium) may be preferred for empiric therapy in serious intra-abdominal infections.

Gynecologic Infections

Parenteral ampicillin sodium and sulbactam sodium is used effectively in adults for the treatment of gynecologic infections including endometritis (after abortion or curettage), postpartum endomyometritis, posthysterectomy pelvic cellulitis, vaginal cuff abscess, salpingitis, tubo-ovarian abscess, pelvic peritonitis or abscess, surgical wound sepsis, uncomplicated acute pelvic inflammatory disease (PID), or complicated PID that may include pelvic peritonitis, tubo-ovarian abscesses, endometritis, or posthysterectomy pelvic cellulitis.

The clinical and bacteriologic cure rates of parenteral ampicillin sodium and sulbactam in the treatment of these gynecologic infections have been 83-100%. In several studies in patients with mixed aerobic-anaerobic gynecologic infections, parenteral ampicillin sodium and sulbactam sodium was as effective as cefoxitin or cefotetan or multiple-drug regimens such as clindamycin or metronidazole and an aminoglycoside in the treatment of these infections and generally was associated with fewer adverse effects.

The fact that ampicillin sodium and sulbactam sodium generally is considered to be inactive against Mycoplasma and to have incomplete inhibitory activity against Chlamydia should be considered if the drug is used in the treatment of gynecologic infections, and concomitant tetracycline (e.g., doxycycline) or, alternatively, macrolide therapy probably should be included if there is a possibility that these organisms are involved in the gynecologic infection being treated. Parenteral ampicillin sodium and sulbactam sodium is effective for the treatment of both gonococcal and nongonococcal PID and appears to be at least as effective in the treatment of these infections as cefoxitin or a regimen of metronidazole or clindamycin given with gentamicin. In the treatment of PID, ampicillin sodium and sulbactam sodium generally has good coverage against Chlamydia trachomatis, N. gonorrhoeae, and anaerobes and appears to be effective for patients who have tuboovarian abscess.

When a parenteral regimen is indicated for the treatment of patients with PID, the US Centers for Disease Control and Prevention (CDC) and other clinicians generally recommend a regimen of cefotetan or cefoxitin given in conjunction with doxycycline or a regimen of clindamycin given in conjunction with gentamicin; however, a regimen of IV ampicillin sodium and sulbactam sodium given in conjunction with doxycycline is one of several alternative parenteral regimens recommended for the treatment of PID. For further information on treatment of PID, see Uses: Pelvic Inflammatory Disease in Cefotetan 8:12.07.12.

Gonorrhea and Associated Infections

Parenteral ampicillin sodium and sulbactam sodium has been used effectively in the treatment of uncomplicated gonorrhea caused by penicillinase-producing strains of Neisseria gonorrhoeae (PPNG) and nonpenicillinase-producing strains of the organism. An oral preparation of ampicillin and sulbactam (sultamicillin; not commercially available in the US) also has been effective when used for the treatment of uncomplicated gonorrhea.

However, penicillins, including ampicillin sodium and sulbactam sodium, are not included in current CDC recommendations for the treatment of gonorrhea. A single 1.5- or 3-g IM dose of ampicillin sodium and sulbactam sodium (1 or 2 g of ampicillin and 0.5 or 1 g of sulbactam) given alone or in conjunction with oral probenecid (1 g) has been effective in men and women for the treatment of uncomplicated urethral and endocervical gonorrhea caused by PPNG or nonpenicillinase-producing N. gonorrhoeae.

This regimen has been associated with a bacteriologic cure rate of 82-100% in adults with uncomplicated PPNG infections. In one study, more treatment failures were reported in patients with PPNG infections who received IM ampicillin sodium and sulbactam sodium without concomitant oral probenecid; however, in another study, regimens of the drug with or without concomitant oral probenecid appeared to be equally effective.

A single 3-g dose of ampicillin sodium and sulbactam sodium (2 g of ampicillin and 1 g of sulbactam) given in conjunction with oral probenecid (1 g) has been effective in the treatment of anorectal gonococcal infections in both men and women and also has been effective for the treatment of pharyngeal gonococcal infections in a few men. Single-dose ampicillin sodium and sulbactam sodium therapy for gonorrhea is ineffective in the treatment of coexisting chlamydial or mycoplasmal infections and generally does not prevent postgonococcal urethritis.

Respiratory Tract Infections

In uncontrolled studies, parenteral ampicillin sodium and sulbactam sodium has been used with some success in adults and children for the treatment of lower respiratory tract infections, including pneumonia, bronchitis, acute exacerbations of chronic bronchitis, and bronchiectasis caused by susceptible staphylococci, streptococci, Haemophilus influenzae, H. parainfluenzae, Moraxella catarrhalis (formerly Branhamella catarrhalis), E. coli, Klebsiella, or Proteus mirabilis. In most reported cases, parenteral ampicillin sodium and sulbactam sodium therapy resulted in clinical and bacteriologic cure rates of 75-96% in adults with lower respiratory tract infections.

Some clinicians suggest that parenteral ampicillin sodium and sulbactam sodium is an effective alternative for the treatment of lower respiratory tract infections known or suspected of being caused by ampicillin-resistant organisms, including community-acquired or nosocomial pneumonia, chronic obstructive pulmonary disease, and exacerbation of severe chronic bronchitis in hospitalized patients. However, long-term efficacy and rate of relapse associated with use of parenteral ampicillin sodium and sulbactam sodium in the treatment of lower respiratory tract infections remain to be established.

In addition, overgrowth with Ps. aeruginosa has been reported in some patients receiving parenteral ampicillin sodium and sulbactam sodium alone for the treatment of respiratory infections. Parenteral ampicillin sodium and sulbactam sodium has been effective in a few patients for the treatment of respiratory tract infections (e.g., pneumonia, tracheobronchitis) or bacteremia caused by strains of Acinetobacter baumannii (A. calcoaceticus subsp. anitratus) that were resistant to imipenem and cilastatin sodium as well as most other anti-infective agents tested.

However, other anti-infectives (e.g., imipenem and cilastatin sodium or meropenem with or without an aminoglycoside) currently are preferred in the treatment of infections caused by susceptible Acinetobacter. Parenteral ampicillin sodium and sulbactam sodium also has been used in a limited number of adults and children for the treatment of various ear, nose, and throat infections including tonsillitis, sinusitis, rhinitis, pharyngitis, acute epiglottitis, and acute and chronic otitis media caused by susceptible staphylococci, streptococci, Klebsiella, Proteus, M. catarrhalis, or H. influenzae. Although the drug generally was effective in the treatment of these infections and had a clinical cure rate of 98%, other anti-infective agents are considered drugs of choice for these infections.

Bone and Joint Infections

Parenteral ampicillin sodium and sulbactam sodium has been effective when used in a limited number of adults or children for the treatment of bone and joint infections including osteomyelitis and/or septic arthritis caused by susceptible b-lactamase-producing organisms. In one pediatric study, an initial phase of parenteral ampicillin sodium and sulbactam sodium therapy (50 mg/kg of ampicillin and 12. mg/kg of sulbactam IV every 6 hours) was followed by therapy with an oral formulation of ampicillin and sulbactam (sultamicillin; not commercially available in the US). Although parenteral ampicillin sodium and sulbactam sodium appeared to be effective in the treatment of acute bone and joint infections, further studies are needed to evaluate the long-term efficacy of the drug in these infections.

Perioperative Prophylaxis

Parenteral ampicillin sodium and sulbactam sodium has been used effectively in adults and children 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). However, less costly anti-infectives, often with narrower spectra of activity (e.g., cephalosporins), generally have been preferred when prophylaxis was indicated in such procedures. In adults undergoing biliary tract surgery, a single 3-g dose of ampicillin and sulbactam (2 g of ampicillin and 1 g of sulbactam) was as effective as a single dose of cefazolin (1 g) or cefoxitin (2 g) in preventing postoperative wound infection.

A single 1.5-g dose of ampicillin and sulbactam (1 g of ampicillin and 0.5 g of sulbactam) has been used effectively for prophylaxis in various gynecologic procedures, including abdominal or vaginal hysterectomy and first-trimester vacuum aspiration abortions.

When given immediately prior to the procedure in patients undergoing first-trimester abortions, the drug reduced the incidence of early postoperative infections (e.g., endometritis) but not the incidence of late infections. In addition, because the drug generally is considered inactive against chlamydia, it cannot prevent postoperative infections with this organism. In a study in adults, parenteral ampicillin sodium and sulbactam sodium was as effective as cefoxitin for prevention of postoperative infections in patients undergoing colorectal or transurethral surgery. In a study in children 5-13 years of age undergoing appendectomy, a single dose of ampicillin and sulbactam (15 mg/kg of ampicillin and 7.5 mg/kg of sulbactam) given IV at the time of anesthesia was as effective as a single dose of metronidazole (7.5 mg/kg) and cefotaxime (25 mg/kg) in the prevention of postoperative sepsis; therapy with the drug was continued for 72 hours after surgery in patients with gangrenous or perforated appendixes at the time of surgery.

Some clinicians suggest that parenteral ampicillin sodium and sulbactam sodium is an effective alternative to other anti-infective regimens used for perioperative prophylaxis in patients undergoing GI or gynecologic surgery. However, further study is needed to evaluate more fully such use of parenteral ampicillin sodium and sulbactam sodium. Parenteral ampicillin sodium and sulbactam sodium also has been used with some success for perioperative prophylaxis in patients with head and neck cancer undergoing surgery. Although in one study ampicillin sodium and sulbactam sodium appeared to be as effective as a regimen of clindamycin and amikacin in such patients, patients who received ampicillin and sulbactam had a higher incidence of postoperative infection with anaerobes than patients who received the other regimen.

Meningitis

Parenteral ampicillin sodium and sulbactam sodium has been used effectively in a few adults for the treatment of meningitis caused by N. meningitidis or S. pneumoniae. In addition, an IV formulation of the drug containing an 8:1 ratio of ampicillin to sulbactam (not commercially available in the US) has been used effectively in children 1 month to 14 years of age for the treatment of meningitis caused by H. influenzae, S. pneumoniae, N. meningitidis, K. pneumoniae, or Listeria. In one study in infants and children, ampicillin sodium (400 mg/kg daily) and sulbactam sodium (50 mg/kg daily) was as effective as a regimen of IV chloramphenicol (100 mg/kg daily) and IV ampicillin (400 mg/kg daily) for the treatment of meningitis caused by H. influenzae, S. pneumoniae, or N. meningitidis.

Although a few clinicians suggest that parenteral ampicillin sodium and sulbactam sodium therapy may be an effective alternative to therapy with ampicillin and chloramphenicol in infants and children for the treatment of meningitis caused by H. influenzae, S. pneumoniae, or N. meningitidis and might be especially useful in areas where ampicillin- and chloramphenicol-resistant strains have been reported, other drugs are preferred for the treatment of CNS infections and some clinicians strongly discourage use of ampicillin sodium and sulbactam sodium in these infections. Results of at least one study using animal models suggest that ampicillin sodium and sulbactam sodium may be of limited value for the treatment of meningitis caused by organisms less susceptible to the drug (e.g., Escherichia coli), and treatment failures have been reported when the drug was used in patients with meningitis caused by K. pneumoniae.

Urinary Tract Infections

Parenteral ampicillin sodium and sulbactam sodium has been used in a limited number of adults or children for the treatment of uncomplicated urinary tract infections caused by susceptible bacteria, including S. epidermidis, E. coli, K. pneumoniae, or P. mirabilis. Although the drug was effective in up to 90% of these infections, treatment failures have been reported and further study is needed to evaluate more fully use of ampicillin sodium and sulbactam sodium in the treatment of complicated urinary tract infections.

Dosage and Administration

Reconstitution and Administration

Ampicillin sodium and sulbactam sodium is administered by IM or slow IV injection or by IV infusion. Ampicillin and sulbactam also have been administered orally as a preparation containing the drugs covalently linked as a double ester in a single molecule (sultamicillin; CP-49,), but an oral dosage form currently is not commercially available in the US. IM or IV solutions of ampicillin sodium and sulbactam sodium should be allowed to stand after dissolution to allow any foaming to dissipate in order to permit visual inspection for complete solubilization.

IM Injection

For IM injection, vials labeled as containing 1.5 or 3 g of combined ampicillin and sulbactam should be reconstituted 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). Reconstituting ampicillin sodium and sulbactam sodium with lidocaine hydrochloride can minimize the local pain associated with IM injection of the drug. IM injections should be made deeply into a large muscle mass within 1 hour after reconstitution.

IV Injection or Infusion

For IV administration, bottles labeled as containing 1.5 or 3 g of combined ampicillin and sulbactam may be reconstituted directly to the desired concentration with a compatible IV solution (See Chemistry and Stability: Stability.). Vials labeled as containing 1.5 or 3 g of the drug initially should be reconstituted with sterile water for injection to yield solutions containing 375 mg of the drug per mL (250 mg of ampicillin and 125 mg of sulbactam per mL).

An appropriate volume of reconstituted drug then should be diluted immediately with a compatible IV solution to yield solutions containing 3-45 mg of the drug per mL (2-30 mg of ampicillin and 1-15 mg of sulbactam per mL). ADD-Vantage® vials labeled as containing 1.5 or 3 g of combined ampicillin and sulbactam should be reconstituted with the 0.9% sodium chloride injection diluent provided according to the manufacturer’s directions. IV injections of ampicillin sodium and sulbactam sodium should be given slowly over at least 10-15 minutes to avoid the possibility of seizures. IV infusions of the drug also should be infused slowly over 15-30 minutes.

Dosage

Dosage of ampicillin sodium and sulbactam sodium generally is expressed in terms of the total of the ampicillin and sulbactam content of the fixed combination. Potency of both ampicillin sodium and sulbactam sodium are expressed in terms of the bases of the drugs. Ampicillin sodium and sulbactam sodium is commercially available for parenteral administration as a sterile powder containing a 2:1 ratio of ampicillin to sulbactam. The manufacturer’s dosage recommendations for adults are the same for IM and IV administration; however, higher serum concentrations usually are attained with IV administration of the drug, and this route generally is preferred, especially for severe infections.

Adult Dosage

The usual adult IM or IV dosage of ampicillin and sulbactam for the treatment of skin and skin structure, intra-abdominal, or gynecologic infections caused by susceptible organisms ranges from 1.5 g (1 of ampicillin and 0.5 g of sulbactam) to 3 g (2 g of ampicillin and 1 g of sulbactam) every 6 hours. The maximum adult dosage of sulbactam recommended by the manufacturer is 4 g (i.e., 8 g of ampicillin and 4 g of sulbactam in fixed combination) daily.

While comparative efficacy of various dosages in the usual range have not been established, most patients in clinical studies of these infections received the maximum 3-g (2 g of ampicillin and 1 g of sulbactam) recommended dosage. For the treatment of acute pelvic inflammatory disease (PID) in adults and adolescents when a parenteral regimen is indicated, IV ampicillin and sulbactam may be given in a dosage of 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). The parenteral regimen may be discontinued 24 hours after clinical improvement; however, oral doxycycline (100 mg twice daily) should be continued to complete 14 days of therapy.

Pediatric Dosage

Pediatric patients who weigh 40 kg or more may receive the usual adult dosage of ampicillin sodium and sulbactam sodium. For the treatment of skin and skin structure infections in pediatric patients 1 year of age or older, the usual dosage of ampicillin and sulbactam is 300 mg/kg daily (200 mg of ampicillin and 100 mg of sulbactam) given by IV infusion in equally divided doses every 6 hours.

The manufacturer recommends that the duration of IV ampicillin sodium and sulbactam sodium therapy in pediatric patients not exceed 14 days; in clinical studies, most children received an oral anti-infective after an initial regimen of IV ampicillin sodium and sulbactam sodium. The American Academy of Pediatrics (AAP) suggests that pediatric patients 1 month of age or older receive ampicillin sodium and sulbactam sodium in a dosage of 100-150 mg/kg of ampicillin daily in 4 divided doses for the treatment of mild to moderate infections or a dosage of 200-300 mg/kg of ampicillin daily in 4 divided doses for the treatment of severe infections.

Dosage in Renal Impairment

In patients with impaired renal function, doses and/or frequency of administration of ampicillin sodium and sulbactam sodium should be modified in response to the degree of renal impairment, severity of infection, and susceptibility of the causative organism.

Because the pharmacokinetics of both ampicillin and sulbactam are affected to the same degree in patients with renal impairment, the recommended 2:1 ratio of the drugs remains the same regardless of the degree of renal impairment. The manufacturer recommends that patients with renal impairment receive the usually recommended doses of ampicillin and sulbactam but that these doses be given less frequently than usual and that dosing intervals be based on the patient’s creatinine clearance.

The manufacturer recommends that patients with creatinine clearances of 30 mL/minute per 1.73 m or greater 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) of the drug every 6-8 hours and that patients with creatinine clearances of 15-29 or 5-14 mL/minute per 1.73 m receive these doses every 12 or 24 hours, respectively. Because ampicillin and sulbactam are removed by hemodialysis, 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 preferably should be given immediately after dialysis.

Cautions

Ampicillin sodium and sulbactam sodium generally is well tolerated. The frequency and severity of adverse effects reported with the commercially available fixed-combination preparation for parenteral administration generally are similar to those reported with parenteral ampicillin alone. With the exception of local reactions at the IM injection site, adverse effects generally have been reported in 10% or less of patients receiving parenteral ampicillin sodium and sulbactam sodium, and have been severe enough to require discontinuance of the drug in less than 1% of patients.

The most frequent adverse effects of parenteral ampicillin sodium and sulbactam sodium are pain at the IM or IV injection site, diarrhea, and rash. Parenteral sulbactam sodium alone is associated with few adverse effects, principally pain at the injection site and diarrhea. For information on adverse effects reported with ampicillin and other aminopenicillins as well as the usual precautions and contraindications associated with these drugs, see Cautions in the Aminopenicillins General Statement 8:12.16.08.

GI Effects

Diarrhea, nausea, and vomiting have been reported in up to 4% of patients receiving parenteral ampicillin sodium and sulbactam sodium. Flatulence, abdominal discomfort or distension, rectal bleeding, and glossitis have been reported in less than 1% of patients receiving the drug parenterally.

Gastritis, stomatitis, and black or hairy tongue have been reported in patients receiving aminopenicillins, and these reactions may occur with ampicillin sodium and sulbactam sodium. In one study, parenteral ampicillin sodium and sulbactam sodium therapy decreased total counts of normal anaerobic fecal flora but did not substantially affect total counts of normal aerobic fecal flora. This may have occurred because only low concentrations of ampicillin and sulbactam are excreted in feces.

Clostridium difficile-associated diarrhea and colitis (also known as antibiotic-associated pseudomembranous colitis) caused by toxin-producing clostridia has been reported with parenteral ampicillin sodium and sulbactam sodium and has also been reported with use of an oral preparation containing ampicillin and sulbactam (sultamicillin; not currently available in the US). Colitis may occur during or following discontinuance of the drug and may range in severity from mild to life-threatening.

Mild cases of colitis may respond to discontinuance of ampicillin sodium and sulbactam sodium alone, but diagnosis and management of moderate to severe cases should include appropriate bacteriologic studies and treatment with fluid, electrolyte, and protein supplementation as indicated. If colitis is moderate to severe or is not relieved by discontinuance of the drug, appropriate anti-infective therapy (e.g., oral metronidazole or vancomycin) should be administered.

Dermatologic and Sensitivity Reactions

Rash has been reported in less than 2% of patients receiving parenteral ampicillin sodium and sulbactam sodium. Urticaria, pruritus, dry skin, and erythema also have been reported with the drug. Erythema multiforme and an occasional case of exfoliative dermatitis have been reported in patients receiving aminopenicillins and these dermatologic reactions may occur with ampicillin sodium and sulbactam sodium. The manufacturer states that such reactions may be controlled with antihistamines and, if necessary, systemic corticosteroids.

Whenever such hypersensitivity reactions occur during therapy with ampicillin sodium and sulbactam sodium, the drug should be discontinued, unless the opinion of the physician dictates otherwise. Serious and occasionally fatal hypersensitivity reactions, including anaphylaxis, can occur during penicillin therapy. (See Cautions: Precautions and Contraindications.)

Several patients have developed systemic allergic reactions during parenteral ampicillin sodium and sulbactam sodium therapy that required discontinuance of the drug. In one patient, the reaction consisted of neck tightness, difficulty and pain when breathing, generalized weakness, and hypertension. If a severe hypersensitivity reaction occurs during ampicillin sodium and sulbactam sodium therapy, the drug should be discontinued and the patient given appropriate treatment (e.g., epinephrine, corticosteroids, maintenance of an adequate airway, oxygen) as indicated.

Local Reactions

The most frequent adverse effect of parenteral ampicillin sodium and sulbactam sodium is pain at the injection site. Pain at the injection site has been reported in 3-16% of patients receiving the drug IM and in up to 3% of patients receiving the drug IV. Pain following IM administration of ampicillin sodium and sulbactam sodium may last for 5-60 minutes and may be minimized or avoided if 0.5 or 2% lidocaine hydrochloride is used as the diluent when preparing IM injections of the drug. Phlebitis, thrombophlebitis, and inflammation at the injection site also have been reported in up to 3% of patients receiving the drug IV.

Other Adverse Effects

Although a definite causal relationship to the drug has not been established, transient increases in serum concentrations of AST (SGOT) and/or ALT (SGPT), alkaline phosphatase, LDH, creatine kinase (CK, creatine phosphokinase, CPK), bilirubin, and Gamma-glutamyltransferase (Gamma-glutamyl transpeptidase, GT, GGTP) have been reported in up to 11% of patients receiving parenteral ampicillin sodium and sulbactam sodium.

Decreased concentrations of serum albumin and total protein also have been reported. Increased BUN and serum creatinine concentrations, presence of red blood cells and hyaline casts in urine, urine retention, dysuria, and hematuria have been reported in less than 1% of patients receiving the drug.

Decreased hemoglobin concentration, hematocrit, and erythrocyte, leukocyte, neutrophil, lymphocyte, and platelet counts and increased lymphocyte, monocyte, basophil, eosinophil, and platelet counts have been reported in patients receiving parenteral ampicillin sodium and sulbactam sodium. Although some of these hematologic changes may represent hypersensitivity reactions, many have not been attributed directly to the drug.

Other adverse effects that have been reported in less than 1% of patients receiving parenteral ampicillin sodium and sulbactam sodium include headache, fatigue, malaise, confusion, dizziness, changes in smell or taste perception, chest pain or tightness, edema, facial swelling, chills, throat tightness, substernal pain, epistaxis, and mucosal bleeding. In at least one patient, acute hyperpyrexia (oral temperatures up to 40°C) occurred approximately 30 minutes after initiation of parenteral ampicillin sodium and sulbactam sodium therapy. Rapid defervescence occurred within 1 hour after completion of the infusion, but the reaction recurred with each subsequent dose.

This reaction did not appear to be a hypersensitivity reaction to either drug nor a reaction to some contaminant. Instead, it presumably was caused by the sulbactam sodium component since the patient previously had received ampicillin alone without a similar reaction and the reaction recurred with different lot numbers of the combination but did not occur in other patients.

Reversible glycogenosis has been reported in animals receiving sulbactam. Diffuse hepatocellular glycogen deposits associated with increases in liver enzymes and hepatomegaly have occurred in rats and dogs that received high doses of sulbactam for prolonged periods of time. These adverse effects in animals were dose and time dependent and are not expected to occur in humans with the usually recommended ampicillin sodium and sulbactam sodium dosages and corresponding plasma concentrations of the drug attained during the relatively short periods of therapy.

To date, similar glycogen deposits have not been reported in humans receiving ampicillin sodium and sulbactam sodium, although patients with preexisting liver dysfunction, diabetes mellitus, hypoglycemia, or glycogen storage disease were excluded from most early clinical studies of the drug. In subsequent studies in patients with type I or II diabetes mellitus, sulbactam given at the usually recommended dosages did not appear to affect glucose mobilization or regulation.

Precautions and Contraindications

Ampicillin sodium and sulbactam sodium shares the toxic potentials of the penicillins, including the risk of hypersensitivity reactions, and the usual precautions of penicillin therapy should be observed. (See Cautions in the Aminopenicillins General Statement 8:12.16.08.) Prior to initiation of therapy with ampicillin sodium and sulbactam sodium, careful inquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins, or other drugs.

There is clinical and laboratory evidence of partial cross-allergenicity among penicillins and other b-lactam antibiotics including cephalosporins and cephamycins.(See Cautions: Hypersensitivity Reactions, in the Natural Penicillins General Statement 8:12.16.04.) Ampicillin sodium and sulbactam sodium is contraindicated in patients who are hypersensitive to any penicillin. Because C. difficile-associated diarrhea and colitis has been reported with the use of anti-infective agents, including ampicillin sodium and sulbactam sodium, it should be considered in the differential diagnosis of patients who develop diarrhea during ampicillin sodium and sulbactam sodium therapy.

Because a high percentage of patients with infectious mononucleosis have developed rash during therapy with aminopenicillins (see Cautions: Ampicillin Rash, in the Aminopenicillins General Statement 8:12.16.08), the manufacturer recommends that ampicillin sodium and sulbactam sodium not be used in patients with the disease. As with use of other anti-infective agents, use of ampicillin sodium and sulbactam sodium may result in overgrowth of nonsusceptible organisms, especially Pseudomonas or Candida. Careful monitoring of the patient and periodic in vitro susceptibility tests are essential. If superinfection occurs, the drug should be discontinued and appropriate therapy initiated. For a more complete discussion of these and other precautions associated with the use of ampicillin, see Cautions: Precautions and Contraindications, in the Aminopenicillins General Statement 8:12.16.08.

Pediatric Precautions

Safety and efficacy of IV ampicillin sodium and sulbactam sodium in children 1 year of age or older have been established for the treatment of skin and skin structure infections. Safety and efficacy of IV ampicillin sodium and sulbactam sodium for the treatment of other infections (e.g., intra-abdominal infections) in pediatric patients have not been established. In addition, safety and efficacy of IM administration of the drug in pediatric patients have not been established. Various combinations of ampicillin and sulbactam (e.g., 1.3:1, 2:1, 3:1, 4:1, 7:1, and 8:1 ratios of ampicillin to sulbactam) have been administered IM or IV to neonates and children 1 month to 17 years of age without unusual adverse effects.

The most frequent adverse effects of parenteral ampicillin sodium and sulbactam sodium in children are transient increases in serum liver enzyme concentrations, diarrhea, and rash. An oral preparation containing ampicillin and sulbactam (sultamicillin; not commercially available in the US) also has been used in children 5 months to 17 years of age. Although the oral preparation generally was well tolerated in children, diarrhea occurred in 42% of children receiving the formulation in one study and was severe enough to require discontinuance of the drug in 14%.

Geriatric Precautions

Although serum half-lives of ampicillin and sulbactam are slightly longer in geriatric adults than in younger adults, dosage of ampicillin sodium and sulbactam sodium does not need to be modified in geriatric patients with renal function normal for their age. In geriatric adults with renal impairment, doses and/or frequency of administration of ampicillin sodium and sulbactam sodium should be modified in response to the degree of renal impairment, severity of infection, and susceptibility of the causative organism. (See Dosage and Administration: Dosage in Renal Impairment.)

Mutagenicity and Carcinogenicity

Studies have not been performed to date to evaluate the mutagenic or carcinogenic potential of ampicillin sodium and sulbactam sodium.

Pregnancy, Fertitlity and Lactation

Safe use of ampicillin sodium and sulbactam sodium during pregnancy has not been definitely established. Reproduction studies in mice, rats, and rabbits using ampicillin and sulbactam doses up to 10 times the usual human dose have not revealed evidence of impaired fertility or harm to the fetus. Ampicillin alone has been administered to pregnant women, especially in the treatment of urinary tract infections, without evidence of adverse effects to the fetus, and the drug has been recommended by various authorities for the treatment of susceptible infections during pregnancy.

However, there are no adequate or controlled studies using ampicillin sodium and sulbactam sodium in pregnant women, and the drug should be used during pregnancy only when clearly needed. Although the clinical importance is unclear, administration of ampicillin alone to pregnant women has resulted in a transient decrease in plasma concentrations of total conjugated estriol, estriol glucuronide, conjugated estrone, and estradiol; this effect also may occur following administration of ampicillin sodium and sulbactam sodium.

IV administration of ampicillin to guinea pigs has resulted in decreased uterine tone and decreased frequency, height, and duration of uterine contractions. While it is not known whether use of ampicillin sodium and sulbactam sodium in humans during labor or delivery could have any immediate or delayed adverse effects on the fetus, prolong the duration of labor, or increase the likelihood of forceps delivery, other obstetrical intervention, or resuscitation of the neonate, ampicillin alone is considered the drug of choice for administration during labor (intrapartum) in the prevention of neonatal group B streptococcal (GBS) infections. Because ampicillin and sulbactam are distributed into milk in low concentrations, ampicillin sodium and sulbactam sodium should be used with caution in nursing women.

Drug Interactions

For further information on these and other drug interactions reported with aminopenicillins, see Drug Interactions in the Aminopenicillins General Statement 8:12.16.08. In addition, while not all drug interactions reported with other penicillins have been reported with aminopenicillins, the possibility that they could occur with these drugs should be considered.

Aminoglycosides

Both ampicillin and sulbactam are potentially physically and/or chemically incompatible with aminoglycosides and can inactivate the drugs in vitro. In one in vitro study, sulbactam concentrations of 25 mcg/mL had no appreciable affect on aminoglycosides in serum at 37°C. However, at concentrations of 75 mcg/mL, sulbactam inactivated tobramycin (but not other aminoglycosides tested) and, at concentrations of 200 mcg/mL or greater (with or without ampicillin), sulbactam inactivated amikacin, gentamicin, netilmicin (no longer commercially available in the US), and tobramycin.

Some clinicians suggest that in vivo inactivation of aminoglycosides by sulbactam is unlikely to occur since sulbactam concentrations of 25 mcg/mL usually are not achieved clinically. Although in vivo inactivation of aminoglycosides has not been reported to date with aminopenicillins, including ampicillin, in vivo inactivation of aminoglycosides has been reported in patients receiving concomitant therapy with an extended-spectrum penicillin. (See Drug Interactions: Aminoglycosides, in the Extended-Spectrum Penicillins General Statement 8:12.16.08.) For information on antibacterial synergism between ampicillin and aminoglycosides, see Drug Interactions: Aminoglycosides, in the Aminopenicillins General Statement 8:12.16.08.

Probenecid

Oral probenecid administered shortly before or concomitantly with ampicillin sodium and sulbactam sodium competitively inhibits renal tubular secretion of both ampicillin and sulbactam and produces higher and prolonged serum concentrations of the drugs. The serum half-life of sulbactam may be increased by 18-45% by concomitant probenecid. The effect of probenecid on the pharmacokinetics of the drugs occasionally may be used to therapeutic advantage (e.g., for the treatment of gonorrhea).

Allopurinol

An increased incidence of rash reportedly occurs in patients with hyperuricemia who are receiving allopurinol and concomitant ampicillin compared with those receiving either drug alone. It is unclear whether this increased incidence of rash is caused by concomitant use of the drug or the hyperuricemia present in these patients. The manufacturer states that there are no data to date on concomitant use of allopurinol with ampicillin sodium and sulbactam sodium.

Laboratory Test Interferences

For more complete information on these and other laboratory test interferences reported with penicillins, see Laboratory Test Interferences in the Natural Penicillins General Statement 8:12.16.04.

Although there is limited information on laboratory test interferences with aminopenicillins and although not all laboratory test interferences reported with other penicillins have been reported with ampicillin, the possibility that these interferences could occur with any of the aminopenicillins should be considered. Ampicillin reportedly interferes with urinary glucose determinations using cupric sulfate (e.g., Benedict’s solution, Clinitest®) but does not affect glucose oxidase methods (e.g., Clinistix®, Tes-Tape®).

Acute Toxcicity

Limited information is available on the acute toxicity of ampicillin sodium and sulbactam sodium in humans. Overdosage of the drug would be expected to produce manifestations that principally are extensions of the adverse reactions reported with the drug. The fact that high CSF concentrations of b-lactam antibiotics may cause neurologic effects, including seizures, should be considered.

Because ampicillin and sulbactam are both removed from the circulation by hemodialysis, these procedures may enhance elimination of the drug from the body if overdosage occurs in patients with impaired renal function; these procedures probably are unnecessary in patients with normal renal function.

Mechanism of Action

Ampicillin sodium and sulbactam sodium usually is bactericidal in action. Concurrent administration of sulbactam does not alter the mechanism of action of ampicillin. However, because sulbactam has a high affinity for and binds to certain b-lactamases that generally inactivate ampicillin by hydrolyzing the b-lactam ring, concurrent administration of the drug with ampicillin results in a synergistic bactericidal effect which expands the spectrum of activity of ampicillin against many strains of b-lactamase-producing bacteria that are resistant to ampicillin alone.

For information on the mechanism of action of ampicillin, see Mechanism of Action in the Natural Penicillins General Statement 8:12.16.04 and in the Aminopenicillins General Statement 8:12.16.08. Sulbactam generally acts as an irreversible inhibitor and is active against a wide range of bacterial b-lactamases.

The drug is considered a “suicide inhibitor” because the interaction between sulbactam and target b-lactamases causes both the drug and the enzyme to be incapable of further action. Sulbactam has a much greater affinity for b-lactamases than does ampicillin or other b-lactam antibiotics, and the drug quickly forms an enzyme-inhibitor complex with target b-lactamases; this complex evolves into one or more irreversibly inactivated proteins. Sulbactam inhibition of b-lactamases is concentration and time dependent. At low sulbactam concentrations, a first-order reaction occurs and at high concentrations a zero-order reaction occurs.

Results of in vitro studies indicate that ampicillin to sulbactam ratios of 2:1, 1:1, or 1:2 result in optimal b-lactamase inhibition and antibacterial activity. Sulbactam inactivates both plasmid- and chromosome-mediated b-lactamases. In vitro studies indicate that sulbactam generally inhibits staphylococcal b-lactamases and b-lactamases classified as Richmond-Sykes types II, III (TEM type, HSV-1), IV, V (PSE and OXA types), and VI .

The drug generally does not inhibit inducible, chromosomally mediated cephalosporinases classified as Richmond-Sykes type I, which may be produced by Pseudomonas aeruginosa, Citrobacter, Enterobacter, and Serratia. In addition to its affinity for bacterial b-lactamases, sulbactam has an affinity for and binds to some bacterial penicillin-binding proteins (PBPs). PBPs are the target enzymes of b-lactam antibiotics and this binding may be the mechanism of sulbactam’s intrinsic antibacterial activity against some organisms. (see Spectrum.) It also may contribute to the synergistic bactericidal effect that occurs between sulbactam and ampicillin or other b-lactam anti-infective agents.

Sulbactam has a strong affinity for PBP 1a of Proteus mirabilis and Escherichia coli and PBP 2 of Acinetobacter. The drug has a lesser affinity for PBPs of Staphylococcus aureus, PBP 1a of E. coli, and PBP 2 of E. coli or P. mirabilis.

The minimum bactericidal concentration (MBC) of ampicillin sodium and sulbactam sodium for ampicillin-resistant strains of S. aureus, Haemophilus influenzae, and Bacteroides fragilis generally is only 1-2 times higher than the minimum inhibitory concentration (MIC); however, the MBC may be 8 times higher than the MIC for some strains. Unlike clavulanic acid, sulbactam generally does not induce production of type I chromosomally mediated cephalosporinases in Pseudomonas or Enterobacteriaceae, including Citrobacter, Enterobacter, Morganella, and Serratia marcescens.

Spectrum Ampicillin sodium and sulbactam sodium has a wide spectrum of activity and is active in vitro against many gram-positive and -negative aerobic and anaerobic bacteria. Ampicillin sodium and sulbactam sodium is active in vitro against organisms susceptible to ampicillin alone. In addition, because sulbactam can inhibit certain b-lactamases that generally inactivate ampicillin, ampicillin sodium and sulbactam sodium is active in vitro against many b-lactamase-producing organisms that are resistant to ampicillin alone, including ampicillin-resistant strains of staphylococci, Haemophilus, Neisseria, and Bacteroides.

Sulbactam alone has some intrinsic antibacterial activity against certain organisms. In vitro, sulbactam concentrations of 0.1-4 mcg/mL inhibit many strains of Neisseria meningitidis, nonpenicillinase- and penicillinase-producing N. gonorrhoeae, non-b-lactamase-producing Moraxella catarrhalis (formerly Branhamella catarrhalis), and some strains of Acinetobacter. In addition, sulbactam concentrations of 8-16 mcg/mL inhibit some strains of Bacteroides and Legionella in vitro. However, sulbactam concentrations of 25 mcg/mL or greater generally are required for in vitro inhibition of other gram-positive or -negative bacteria, and the drug is not therapeutically useful alone.

In Vitro Susceptibility Testing

The National Committee for Clinical Laboratory Standards (NCCLS) states that, for streptococci and non-b-lactamase-producing enterococci, results of in vitro susceptibility tests using ampicillin can be used to predict susceptibility to ampicillin sodium and sulbactam sodium. However, to determine susceptibility of staphylococci and gram-negative enteric bacteria to ampicillin sodium and sulbactam sodium, NCCLS recommends that disk-diffusion and dilution susceptibility tests be performed using appropriate combinations of ampicillin sodium and sulbactam sodium. For information on interpretive criteria specified for ampicillin, see Spectrum: In Vitro Susceptibility Testing in the Aminopenicillins General Statement 8:12.16.08.

To test in vitro susceptibility to ampicillin sodium and sulbactam sodium, a 1:1 ratio of ampicillin to sulbactam generally is used for disk-diffusion procedures and a 2:1 ratio of the drugs is used for agar or broth dilution procedures. Results of in vitro susceptibility tests with ampicillin sodium and sulbactam sodium may be affected by inoculum size.

For many ampicillin-resistant bacteria (e.g., Escherichia coli, Klebsiella, Proteus, Haemophilus influenzae, Bacteroides), MICs of ampicillin sodium and sulbactam sodium may be 2-32 times greater when the size of the inoculum is increased from 104 or 105 to 107 or 108 colony-forming units (CFU) per mL. Results of in vitro susceptibility tests generally are unaffected by changes in pH between 6-7.5. NCCLS states that, if results of in vitro susceptibility testing indicate that a clinical isolate is susceptible to ampicillin sodium and sulbactam sodium, then an infection caused by this strain may be appropriately treated with the dosage of the drug recommended for that type of infection and infecting species, unless otherwise contraindicated.

If results indicate that a clinical isolate has intermediate susceptibility to ampicillin sodium and sulbactam sodium, then the strain has a minimum inhibitory concentration (MIC) that approaches usually attainable blood and tissue concentrations and response rates may be lower than for strains identified as susceptible. Therefore, the intermediate category implies clinical applicability in body sites where the drugs are physiologically concentrated (e.g., urine) or when a high dosage of the drug can be used.

This intermediate category also includes a buffer zone which should prevent small, uncontrolled technical factors from causing major discrepancies in interpretation, especially for drugs with narrow pharmacotoxicity margins. If results of in vitro susceptibility testing indicate that a clinical isolate is resistant to ampicillin sodium and sulbactam sodium, the strain is not inhibited by systemic concentrations of the drug achievable with usual dosage schedules and/or MICs fall in the range where specific microbial resistance mechanisms are likely and efficacy has not been reliably demonstrated in clinical studies.

Strains of staphylococci resistant to penicillinase-resistant penicillins also be considered resistant to ampicillin sodium and sulbactam sodium, although results of in vitro susceptibility tests may indicate that the organisms are susceptible to the drug. In addition, NCCLS currently recommends that non-b-lactamase-producing strains of H. influenzae that are resistant to ampicillin (BLNAR H. influenzae) be considered resistant to ampicillin sodium and sulbactam sodium despite the fact that results of in vitro susceptibility tests may indicate that the organisms are susceptible to the drug.

Disk Susceptibility Tests

When the disk-diffusion procedure is used to test susceptibility to ampicillin sodium and sulbactam sodium, a disk containing 20 mcg of the drug (10 mcg of ampicillin and 10 mcg of sulbactam) is used. When disk-diffusion susceptibility testing is performed according to NCCLS standardized procedures using NCCLS interpretive criteria, Staphylococcus, Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter with growth inhibition zones of 15 mm or greater are susceptible to ampicillin sodium and sulbactam sodium, those with zones of 12-14 mm have intermediate susceptibility, and those with zones of 11 mm or less are resistant to the drug.

When disk-diffusion susceptibility testing is performed according to NCCLS standardized procedures using Haemophilus test medium (HTM), Haemophilus with growth inhibition zones of 20 mm or greater are considered susceptible to ampicillin sodium and sulbactam sodium and those with zones of 19 mm or less are considered resistant to the drug.

Dilution Susceptibility Tests When dilution susceptibility testing (agar or broth dilution) is performed according to NCCLS standardized procedures using NCCLS interpretive criteria, Staphylococcus, Enterobacteriaceae, and Ps. aeruginosa and other non-Enterobacteriaceae gram-negative bacilli (e.g., other Pseudomonas spp., Acinetobacter, Stenotrophomona maltophilia) with MICs of 8 mcg/mL or less of ampicillin in the presence of sulbactam at a constant 2:1 ratio are susceptible to ampicillin sodium and sulbactam sodium, those with MICs of 16 mcg/mL of ampicillin have intermediate susceptibility, and those with MICs of 32 mcg/mL or greater of ampicillin are resistant to the drug.

When susceptibility of Haemophilus is tested according to NCCLS standardized procedures using HTM, Haemophilus with MICs of 2 mcg/mL or less of ampicillin in the presence of sulbactam at a constant 2:1 ratio are susceptible to ampicillin sodium and sulbactam sodium and those with MICs of 4 mcg/mL or greater of ampicillin in the presence of sulbactam at a constant 2:1 ratio are resistant to the drug.

Gram-positive Aerobic Bacteria

Gram-positive Aerobic Cocci

Ampicillin sodium and sulbactam sodium is active in vitro against most gram-positive aerobic cocci including Streptococcus pneumoniae, S. pyogenes (group A b-hemolytic streptococci), S. agalactiae (group B streptococci), viridans streptococci, and penicillinase-producing and nonpenicillinase-producing strains of Staphylococcus aureus, S. epidermidis, S. saprophyticus, and S. warneri.

The drug is active in vitro against many strains of Enterococcus faecalis (formerly S. faecalis) and some strains of E. faecium (formerly S. faecium). Ampicillin sodium and sulbactam sodium is active in vitro against most strains of penicillinase-producing staphylococci that are resistant to ampicillin alone. Ampicillin sodium and sulbactam sodium also is active in vitro against some strains of staphylococci resistant to penicillinase-resistant penicillins including methicillin-resistant S. aureus (MRSA) and methicillin-resistant S. epidermidis.

However, because it is unclear whether in vitro activity against these organisms will correlate with in vivo activity, the manufacturer, NCCLS, and most clinicians currently state that strains of staphylococci resistant to penicillinase-resistant penicillins (e.g., nafcillin, oxacillin) should be considered resistant to ampicillin sodium and sulbactam sodium. In in vitro studies using dilutions containing a 2:1 ratio of ampicillin to sulbactam, the MIC90 (minimum inhibitory concentration of the drug at which 90% of strains tested are inhibited) of ampicillin sodium and sulbactam sodium for penicillinase-producing and nonpenicillinase-producing strains of S. aureus and S. epidermidis is 0.12-8 mcg/mL of ampicillin in the presence of sulbactam at a constant 2:1 ratio of the drugs.

The MIC90 of ampicillin sodium and sulbactam sodium for group A β-hemolysis streptococci, group B streptococci, S. pneumoniae, and E. faecalis is 0.03-1 mcg/mL of ampicillin in the presence of sulbactam at a constant 2:1 ratio of the drugs. Although some strains of E. faecium are inhibited in vitro by 0.5-8 mcg/mL of ampicillin in the presence of sulbactam at a constant 2:1 ratio of the drugs, many strains of the organism require concentrations of 16 mcg/mL or greater for in vitro inhibition and are considered resistant to the drug. (See Resistance.)

Gram-positive Aerobic Bacilli

Ampicillin sodium and sulbactam sodium is active in vitro against Listeria monocytogenes. The drug reportedly is inactive against Nocardia asteroides.

Gram-negative Aerobic Bacteria

Neisseria

Ampicillin sodium and sulbactam sodium is active in vitro against most strains of Neisseria meningitidis and penicillinase-producing and nonpenicillinase-producing N. gonorrhoeae. Although penicillinase-producing N. gonorrhoeae (PPNG) usually is resistant to ampicillin alone, most strains of the organism are susceptible in vitro to ampicillin sodium and sulbactam sodium. In in vitro studies using dilutions containing a 2:1 ratio of ampicillin to sulbactam, the MIC90 of ampicillin sodium and sulbactam sodium for N. meningitidis is 0.12-2 mcg/mL or less of ampicillin in the presence of sulbactam at a constant 2:1 ratio of the drugs. The MIC90 of the drug for PPNG is 4 mcg/mL of ampicillin in the presence of 2 mcg/mL of sulbactam.

Haemophilus

Ampicillin sodium and sulbactam sodium is active in vitro against most b-lactamase-producing and non-b-lactamase-producing strains of Haemophilus influenzae and H. ducreyi. Although some strains of non-b-lactamase-producing H. influenzae that are resistant to ampicillin (BLNAR H. influenzae) may be susceptible to ampicillin sodium and sulbactam sodium in vitro, NCCLS currently recommends that these strains be considered resistant to the drug. The MIC90 of ampicillin sodium and sulbactam sodium reported for non-b-lactamase-producing strains of H. influenzae is 0.25-0.5 mcg/mL and the MIC90 of the drug for b-lactamase producing strains is 0.78-2 mcg/mL of ampicillin in the presence of sulbactam at a constant 2:1 ratio of the drugs.

Moraxella catarrhalis

Ampicillin sodium and sulbactam sodium is active in vitro against both b-lactamase-producing and non-b-lactamase-producing strains of Moraxella catarrhalis (formerly Branhamella catarrhalis). The MIC90 of the drug reported for these organisms is 0.015-0.8 mcg/mL of ampicillin in the presence of sulbactam at a constant 2:1 ratio of the drugs.

Enterobacteriaceae

Ampicillin sodium and sulbactam sodium is active in vitro against Enterobacteriaceae that are susceptible to ampicillin alone (e.g., some strains of Escherichia coli, Proteus mirabilis, Salmonella, Shigella). In addition, ampicillin sodium and sulbactam sodium is active in vitro against many b-lactamase-producing Enterobacteriaceae that are resistant to ampicillin alone, including many strains of b-lactamase-producing Citrobacter, Klebsiella, Morganella morganii, Proteus, Providencia, and Yersinia enterocolitica and some strains of b-lactamase-producing E. coli.

Although ampicillin sodium and sulbactam sodium is active in vitro against some strains of Enterobacter cloacae, E. aerogenes, and E. agglomerans, many strains of Enterobacter as well as most strains of Serratia are resistant to the drug. (See Resistance.) In in vitro studies using dilutions containing a 2:1 ratio of ampicillin to sulbactam, the MIC90 of ampicillin sodium and sulbactam sodium for E. coli, including multiple-drug resistant strains, generally is 4-16 mcg/mL of ampicillin in the presence of sulbactam at a constant 2:1 ratio of the drugs.

However, the MIC90 for E. coli occasionally has been reported as 16-32 mcg/mL. The MIC90 of the drug forKlebsiella, including K. pneumoniae and K. oxytoca, and for Citrobacter and Proteus is 1-16 mcg/mL of ampicillin in the presence of sulbactam at a constant 2:1 ratio of the drugs. Serratia marcescens usually has an MIC90 of 16-32 mcg/mL or greater of ampicillin in the presence of sulbactam at a constant 2:1 ratio and generally is considered resistant to the drug. In one study, the MIC90 of ampicillin sodium and sulbactam sodium for Shigella, including S. boydii, S. dysenteriae, S. flexneri, and S. sonnei, was 8 mcg/mL of ampicillin in the presence of 4 mcg/mL of sulbactam.

Other Gram-negative Aerobic Bacteria

Ampicillin sodium and sulbactam sodium is active in vitro against Acinetobacter. The MIC90 of the drug reported for Acinetobacter baumannii (A. calcoaceticus subsp. anitratus), A. lwoffi (A. calcoaceticus subsp. lwoffi), and A. haemolyticus is 1-8 mcg/mL of ampicillin in the presence of sulbactam at a constant 2:1 ratio of the drugs. Ampicillin sodium and sulbactam sodium generally is inactive against Pseudomonas, including Ps. aeruginosa.

Some strains of Burkholderia pseudomallei (formerly Ps. pseudomallei) and B. cepacia (formerly Ps. cepacia) may be inhibited in vitro by the drug. In one study, the MIC90 of ampicillin sodium and sulbactam sodium reported for Legionella, including L. pneumophila, was 2 mcg/mL of ampicillin in the presence of 1 mcg/mL of sulbactam. Ampicillin sodium and sulbactam sodium has some in vitro activity against Campylobacter fetus subsp. jejuni.

Anaerobic Bacteria

Ampicillin sodium and sulbactam sodium is active in vitro against both gram-positive and -negative anaerobic bacteria and is active against some anaerobes that are resistant to many other anti-infective agents, including other b-lactam antibiotics, metronidazole, and clindamycin. Ampicillin sodium and sulbactam sodium is active in vitro against gram-positive anaerobic bacteria including Actinomyces, Bifidobacterium, Clostridium, Eubacterium, Lactobacillus, Peptococcus, Peptostreptococcus, and Propionibacterium. The MIC90 of ampicillin sodium and sulbactam sodium reported forClostridium, including C. clostridioforme (C. clostridiiforme), C. difficile, C. innocuum, C. perfringens, C. ramosum, C. subterminale, and C. tertium is 0.5-8 mcg/mL of ampicillin in the presence of sulbactam in a constant 2:1 ratio of the drugs.

Most other susceptible gram-positive anaerobes are inhibited in vitro by ampicillin sodium and sulbactam concentrations of 0.25-2 mcg/mL of ampicillin in the presence of sulbactam at a constant 2:1 ratio of the drugs. Ampicillin sodium and sulbactam sodium is active in vitro against gram-negative anaerobic bacteria including most strains of Bacteroides, Porphyromonas, Prevotella, and Fusobacterium.

The MIC90 of the drug reported for most Bacteroides in the B. fragilis group (e.g., B. fragilis, B. caccae, B. distasonis, B. ovatus, B. thetaiotamicron, B. uniformis, B. vulgatus) is 1.6-16 mcg/mL of ampicillin in the presence of sulbactam at a constant 2:1 ratio of the drugs. The MIC90 of the drug reported for B. capillosus and B. ureolyticus is 0.25-4 mcg/mL of ampicillin in the presence of sulbactam at a constant 2:1 ratio of the drugs. Ampicillin sodium and sulbactam sodium concentrations of 32 mcg/mL of ampicillin in the presence of 16 mcg/mL of sulbactam may be required for in vitro inhibition of B. gracilis, and this organism generally is considered resistant to the drug.

The MIC90 of ampicillin sodium and sulbactam sodium for Porphyromonas asaccharolyticus (B. asaccharolytica), Prevotella bivius (B. bivia), P. disiens (B. disiens), P. intermedius (B. intermedia), P. loescheii (B. loescheii), P. melaninogenicus (B. melaninogenica), and P. oralis (B. oralis) is 0.25-4 mcg/mL of ampicillin in the presence of sulbactam at a constant 2:1 ratio of the drugs. Fusobacterium, including F. nucleatum, generally is inhibited in vitro by concentrations of 0.1-8 mcg/mL of ampicillin in the presence of sulbactam at a constant 2:1 ratio of the drugs; however, some strains of F. necrophorum may be resistant to ampicillin sodium and sulbactam sodium.

Chlamydia and Mycoplasma

Ampicillin sodium and sulbactam sodium generally is considered inactive against Mycoplasma and Chlamydia, including C. trachomatis. Like most other penicillins (e.g., amoxicillin, carbenicillin, mezlocillin, penicillin G, piperacillin, ticarcillin), ampicillin reportedly has an incomplete inhibitory effect against Chlamydia and may be bacteriostatic but not bactericidal against these organism.

Resistance Gram-negative aerobic bacilli that produce Richmond-Sykes type I chromosomally mediated b-lactamases (e.g., Pseudomonas aeruginosa, Citrobacter, Enterobacter, Serratia) generally are resistant to ampicillin sodium and sulbactam sodium because sulbactam does not inhibit most type I b-lactamases. Some strains of Klebsiella, Escherichia coli, and Acinetobacter and rare strains of Neisseria gonorrhoeae are resistant to ampicillin sodium and sulbactam sodium. Rarely, strains of Bacteroides fragilis resistant to ampicillin sodium and sulbactam sodium have been reported.

A few strains of B. fragilis resistant to the drug also were resistant to cefoxitin, extended-spectrum penicillins, clindamycin, and/or imipenem and cilastatin sodium. Results of in vitro studies using ampicillin-resistant strains of Staphylococcus aureus, Haemophilus influenzae, and B. fragilis indicate that serial passage of these strains in the presence of ampicillin sodium and sulbactam sodium or continuous culture in the presence of subinhibitory concentrations of the drug does not result in resistance to ampicillin sodium and sulbactam sodium. Enterococcus faecium (formerly Streptococcus faecium) generally is resistant to ampicillin sodium and sulbactam sodium.

Resistance to aminopenicillins in some enterococci (e.g., E. faecalis, E. faecium) can result from b-lactamase production or from decreased binding to and/or increased production of penicillin-binding proteins with a low affinity for the drugs (e.g., PBP 5 or 6). Enterococci that exhibit ampicillin resistance secondary to b-lactamase production may be susceptible in vitro when the aminopenicillin is combined with a b-lactamase inhibitor (e.g., clavulanic acid, sulbactam); however, addition of the b-lactamase inhibitor does not necessarily result in susceptibility to the aminopenicillin in such strains. Some strains of enterococci with relatively high aminopenicillin resistance secondary to b-lactamase production may remain resistant or be only moderately more susceptible to the aminopenicillin combined with a b-lactamase inhibitor.

Strains that exhibit ampicillin resistance secondary to alterations in PBPs remain resistant when the drug is combined with a b-lactamase inhibitor such as sulbactam or clavulanic acid, and some evidence suggests that such strains occasionally may emerge secondary to high-dose drug exposure. In addition, enterococci resistant to multiple drugs (e.g., vancomycin, teicoplanin, aminoglycosides, ampicillin, penicillin G, imipenem, tetracyclines, synergistic combinations of b-lactam anti-infectives) have been reported with increasing frequency.

Pharmacokinetics

Cross-over studies using fixed combinations of ampicillin sodium and sulbactam sodium, ampicillin sodium alone, and sulbactam sodium alone indicate that concomitant administration of sulbactam sodium does not appreciably affect the pharmacokinetics of either drug. Dosage of ampicillin sodium and sulbactam sodium generally is expressed in terms of the total of the ampicillin and sulbactam content of the fixed combination. The pharmacokinetics of ampicillin and sulbactam following parenteral administration are similar and reportedly are best described by an open, 2-compartment model. For additional information on absorption, distribution, and elimination of ampicillin, see Pharmacokinetics in the Aminopenicillins General Statement 8:12.16.08 and in Ampicillin 8:12.16.08.

Absorption

Sulbactam sodium is not absorbed appreciably from the GI tract and must be given parenterally. Although sulbactam is orally bioavailable following administration of an oral formulation containing ampicillin and sulbactam covalently linked as a double ester in a single molecule (sultamicillin; CP-49,), this formulation currently is not commercially available in the US. Peak serum concentrations of ampicillin and sulbactam are attained immediately following completion of a 15-minute IV infusion of ampicillin sodium and sulbactam sodium. In adults with normal renal function, peak serum concentrations of ampicillin are 40-71 mcg/mL following administration of a 1.5-g dose of ampicillin and sulbactam (1 g of ampicillin and 0.5 g of sulbactam) or 109-150 mcg/mL following a 3-g dose of the drug (2 g of ampicillin and 1 g of sulbactam); peak serum concentrations of sulbactam following these doses are 21-40 or 48-88 mcg/mL, respectively. Following IM injection of ampicillin sodium and sulbactam sodium, both drugs are rapidly and almost completely absorbed. Peak serum concentrations of ampicillin and sulbactam generally are attained within 30-40 and 30-52 minutes, respectively. In healthy adults with normal renal function, IM injection of 1.5 g of ampicillin sodium and sulbactam sodium (1 g of ampicillin and 0.5 g of sulbactam) results in peak serum concentrations of ampicillin of 8-37 mcg/mL and of sulbactam of 6-24 mcg/mL. Peak serum concentrations and areas under the concentration-time curve (AUCs) of ampicillin and sulbactam are slightly higher in geriatric patients than in younger adults; this presumably occurs because of reduced renal clearance in the elderly. In a study in healthy geriatric adults 65-85 years of age, a single 3-g dose of ampicillin and sulbactam (2 g of ampicillin and 1 g of sulbactam) given IV over 30 minutes resulted in peak serum concentrations of ampicillin and sulbactam that averaged 112. and 59. mcg/mL, respectively; the same dose administered to healthy adults 20-64 years of age resulted in peak serum concentrations of 82.4-99.8 and 42.5-52.2 mcg/mL, respectively. In a study in neonates who received ampicillin sodium and sulbactam sodium in a 1:1 ratio (50 mg/kg of each drug) given by rapid IV injection every 12 hours, plasma concentrations of ampicillin at 3, 8, and 12 hours after a dose averaged 86.., and 56. mcg/mL, respectively, and those of sulbactam at the same intervals averaged 110.., and 38. mcg/mL, respectively. There is no evidence that sulbactam accumulates in serum following IM or IV administration of 0.5-g doses every 6 hours for 3 days in adults with normal renal function. In a few patients with chronic renal failure undergoing continuous ambulatory peritoneal dialysis, intraperitoneal administration of a single 3-g dose of ampicillin and sulbactam (2 g of ampicillin and 1 g of sulbactam) instilled over 6 hours resulted in peak plasma concentrations of ampicillin and sulbactam of 87.5 and 27.8 mcg/mL, respectively.

Distribution

Following IM or IV administration of ampicillin sodium and sulbactam sodium, both ampicillin and sulbactam are well distributed into fluids and tissues. Although sulbactam reportedly distributes into certain tissues and fluids (e.g., blister fluid, peritoneal fluid, intestinal mucosa) to a greater extent than ampicillin, sulbactam distribution may vary and appears to depend on the degree of local inflammation. Ampicillin and sulbactam distribute into peritoneal fluid, blister fluid, tissue fluid, sputum, middle ear effusion, intestinal mucosa, bronchial wall, alveolar lining fluid, sternum, pericardium, myocardium, endocardium, prostate, gallbladder, bile, myometrium, salpinges, ovaries, and appendix. Concentrations of the drugs in most of these tissues and fluids generally are 53-100% of concurrent serum concentrations. In adults with normal renal function, the apparent volume of distribution at steady state of ampicillin is 0.28-0.33 L/kg and that of sulbactam is 0.24-0.4 L/kg. The apparent volume of distribution of sulbactam at steady state in infants and children is 0.31-0.38 L/kg. Both ampicillin and sulbactam are distributed into CSF in low concentrations following IV or IM administration in adults and children. CSF concentrations of the drugs generally are higher in patients with inflamed meninges than in those with uninflamed meninges. In a study in adults receiving 0.8- to 2-g doses of ampicillin IV every 4 hours and 1-g doses of sulbactam IV every 6 hours, ampicillin concentrations in CSF ranged from less than 0.3 to 9.6 mcg/mL in those with mild meningeal inflammation and 1.4-23. mcg/mL in those with marked inflammation; sulbactam CSF concentrations in these patients ranged from less than 0.5 to 4.7 mcg/mL and from 1-10. mcg/mL, respectively. In patients undergoing cholecystectomy who received a single 1.5-g IV dose of ampicillin and sulbactam (1 g of ampicillin and 0.5 g of sulbactam), concentrations of ampicillin 0.25-1.5 hours after the dose averaged 15.9 mcg/mL in gallbladder bile, 7.7 mcg/g in gallbladder, and 20.2 mcg/mL in serum; concentrations of sulbactam in these samples averaged 4.3 mcg/mL, 6.3 mcg/g, and 19. mcg/mL, respectively. Ampicillin is approximately 15-28% bound to serum proteins and sulbactam is approximately 38% bound to serum proteins. Ampicillin and sulbactam both readily cross the placenta and concentrations in umbilical cord blood may be similar to serum concentrations. Ampicillin and sulbactam are distributed into milk in low concentrations. In lactating women who received 500-mg or 1-g doses of sulbactam by IV infusion over 20 minutes every 6 hours, concentrations of the drug in milk averaged 0.52 mcg/mL in samples obtained at random intervals between the first and thirteenth doses.

Elimination

Serum concentrations of ampicillin and sulbactam both decline in a biphasic manner and half-lives of the drugs are similar. In healthy adults with normal renal function, both ampicillin and sulbactam have a distribution half-life (t1/2a) of about 15 minutes and an elimination half-life (t1/2b) of about 1 hour. In some studies, the t1/2b of ampicillin ranged from 0.8-1.3 hours and that of sulbactam ranged from 0.97-1.4 hours. The t1/2b of ampicillin and sulbactam are slightly longer in geriatric adults than in younger adults. In a study in healthy geriatric adults 65-85 years of age with renal function normal for their age, the elimination half-life of ampicillin averaged 1.4 hours and that of sulbactam averaged 1.6 hours.

In other studies in geriatric patients, the t1/2b of sulbactam and ampicillin were 2.2 hours compared with 0.8-1.2 hours in young adults. In infants and children younger than 12 years of age, sulbactam has a t1/2? of 0.92-1.9 hours. In neonates, the half-lives of ampicillin and sulbactam vary inversely with age; as renal tubular function matures, the drugs are cleared more rapidly. In a study in premature neonates 6 days of age or younger, the half-life of ampicillin averaged 9.4 hours and the half-life of sulbactam averaged 7.9 hours. The major route of elimination of both sulbactam and ampicillin is glomerular filtration and tubular secretion.

Only small amounts of the drugs are eliminated in feces and bile. Following IM or IV administration of ampicillin sodium and sulbactam sodium in adults with normal renal function, approximately 75-92% of the dose of ampicillin and the dose of sulbactam is excreted unchanged in urine within 8 hours. Serum concentrations of both ampicillin and sulbactam are higher and the half-lives of the drugs prolonged in patients with renal impairment.

The elimination kinetics of both drugs appear to be affected to the same degree by impaired renal function. In one study, the half-lives of ampicillin and sulbactam averaged 1.6 and 1.6 hours, respectively, in adults with creatinine clearances of 30-60 mL/minute and 3.4 and 3.7 hours, respectively, in those with clearances of 7-30 mL/minute. In adults with creatinine clearances less than 7 mL/minute, the t1/2b of ampicillin and sulbactam averaged 17.4 and 13.4 hours, respectively.

Oral probenecid administered shortly before or with ampicillin sodium and sulbactam sodium competitively inhibits renal tubular secretion of both ampicillin and sulbactam and produces higher and prolonged serum concentrations of the drugs. (See Drug Interactions: Probenecid.) Cystic fibrosis patients may eliminate sulbactam at faster rates than healthy individuals. In a study in children with cystic fibrosis, plasma clearance and apparent volume of distribution of sulbactam were about 1.5-2 times higher, peak plasma sulbactam concentrations were about 50% lower, and t1/2b of the drug slightly shorter in these children than in children without cystic fibrosis. Further study is needed to determine if this effect is clinically important since use of usual dosages of the drug in patients with cystic fibrosis may result in lower serum concentrations than expected. In healthy adults with normal renal function, renal clearance of ampicillin is 203-319 mL/minute and that of sulbactam is 169-204 mL/minute. Ampicillin and sulbactam are both removed by hemodialysis.

The amount of the drugs removed during hemodialysis depends on several factors (e.g., type of coil used, dialysis flow rate). In a few patients undergoing chronic dialysis, a 4-hour period of hemodialysis removed into the dialysate about 35% of the ampicillin dose and 45% of the sulbactam dose when a single 3-g dose of ampicillin and sulbactam (2 g of ampicillin and 1 g of sulbactam) was given 2 hours prior to dialysis.

Chemistry and Stability

Chemistry

Ampicillin sodium and sulbactam sodium is a fixed combination of the sodium salts of ampicillin and sulbactam. Ampicillin is an aminopenicillin. (See Ampicillin 8:12.16.08.) Sulbactam, a b-lactamase inhibitor, is a synthetic penicillinate sulfone containing a b-lactam ring and derived from 6-aminopenicillanic acid. Although sulbactam has minimal antibacterial activity when used alone, the combined use of sulbactam sodium and certain penicillins or cephalosporins (e.g., amoxicillin, ampicillin, cefazolin, cefoperazone, ceftizoxime, ceftriaxone, penicillin G) results in a synergistic effect that expands the spectrum of activity of the penicillin or cephalosporin against many strains of b-lactamase-producing bacteria. Ampicillin sodium and sulbactam sodium is commercially available as a sterile powder for parenteral use containing a 2:1 ratio of ampicillin to sulbactam.

Potency of the combination drug is expressed in terms of the total ampicillin content plus the total sulbactam content; each labeled mg of the combination provides not less than 563 mcg of ampicillin and 280 mcg of sulbactam, calculated on the anhydrous basis. Although not currently commercially available in the US, an oral preparation containing ampicillin and sulbactam covalently linked as a double ester in a single molecule (sultamicillin; CP-49,) has been studied. Ampicillin sodium and sulbactam sodium for parenteral use occurs as a white to off-white powder that is freely soluble in aqueous diluents.

Each 1.5 g of ampicillin and sulbactam (1 g of ampicillin and 0.5 g of sulbactam) contains approximately 5 mEq (115 mg) of sodium; 3 g of the drug (2 g of ampicillin and 1 g of sulbactam) contains approximately 10 mEq (230 mg) of sodium. Following reconstitution, ampicillin sodium and sulbactam sodium solutions containing 375 mg/mL (250 mg of ampicillin and 125 mg of sulbactam per mL) occur as pale yellow to yellow solutions and have a pH of 8-10. Dilute solutions of the drug containing up to 30 mg of ampicillin and 15 mg of sulbactam are essentially colorless to pale yellow and have a pH of 8-10.

Stability

Commercially available ampicillin sodium and sulbactam sodium sterile powder should be stored at 30°C or colder. The stability of ampicillin sodium in solution is concentration dependent, decreasing as the concentration of the drug increases. Ampicillin sodium appears to be especially susceptible to inactivation in solutions containing dextrose, which appears to have a catalytic effect on hydrolysis of the drug.

Sulbactam sodium is much more stable in aqueous solution than ampicillin sodium, but when combined with ampicillin sodium, sulbactam sodium does not substantially improve nor adversely affect the stability of the aminopenicillin. Therefore, the stability of ampicillin sodium and sulbactam sodium solutions is similar to that of ampicillin sodium solutions.

Following reconstitution with sterile water for injection or 0.5 or 2% lidocaine hydrochloride injection, ampicillin sodium and sulbactam sodium solutions for IM injection containing 375 mg/mL (250 mg of ampicillin and 125 mg of sulbactam per mL) are stable for at least 1 hour, and the manufacturer recommends that such solutions be used within this time period. Following reconstitution with sterile water for injection or 0.9% sodium chloride injection, ampicillin sodium and sulbactam sodium solutions for IV administration containing 45 mg/mL (30 mg of ampicillin and 15 mg of sulbactam per mL) are stable for 8 hours at 25°C or 48 hours at 4°C, and solutions containing 30 mg/mL (20 mg of ampicillin and 10 mg of sulbactam per mL) are stable for 72 hours at 4°C.

The manufacturer states that solutions for IV administration containing 45 mg/mL (30 mg of ampicillin and 15 mg of sulbactam per mL) in lactated Ringer’s injection or 1/6 M sodium lactate injection are stable for 24 or 8 hours, respectively, when refrigerated at 4°C and for 8 hours at 25°C, although some investigators have reported more prolonged stability. Likewise, the manufacturer states that solutions in 5% dextrose injection containing 30 mg/mL (20 mg of ampicillin and 10 mg of sulbactam per mL) are stable for 2 hours at 25°C or 4 hours when refrigerated at 4°C and those containing 3 mg/mL (2 mg of ampicillin and 1 mg of sulbactam per mL) are stable for 4 hours at 25°C, despite some data suggesting more prolonged stability.

The manufacturer also states that solutions of the combination in 5% dextrose with 0.45% sodium chloride injection containing 3 mg/mL are stable for 4 hours at 25°C and those containing 15 mg/mL (10 mg of ampicillin and 5 mg of sulbactam per mL) are stable for 4 hours at 4°C, although some investigators also have reported more prolonged stability with such solutions. Similarly, while some data indicate more prolonged stability than that recommended by the manufacturer, the manufacturer states that solutions diluted in 10% invert sugar and containing 3 mg/mL (2 mg of ampicillin and 1 mg of sulbactam per mL) are stable for 4 hours at 25°C and those containing 30 mg/mL (20 mg of ampicillin and 10 mg of sulbactam per mL) are stable for 3 hours when refrigerated.

The manufacturer states that commercially available ampicillin sodium and sulbactam sodium in ADD-Vantage® containers that has been reconstituted with 0.9% sodium chloride injection to a maximum concentration of 30 mg/mL (20 mg of ampicillin and 10 mg of sulbactam per mL) is stable for 8 hours at 25°C.

Therefore, it is recommended that such solutions be completely administered within 8 hours to ensure proper potency. Ampicillin sodium and sulbactam sodium is potentially physically and/or chemically incompatible with some drugs, including aminoglycosides, idarubicin hydrochloride, or ondansetron hydrochloride, but the compatibility depends on several factors (e.g., concentrations of the drugs, specific diluents used, resulting pH, temperature).

Specialized references should be consulted for specific compatibility information. Because of the potential for incompatibility, ampicillin sodium and sulbactam sodium and aminoglycosides should not be admixed. For information on the in vitro and in vivo incompatibility of penicillins and aminoglycosides, see Drug Interactions: Aminoglycosides, in the Aminopenicillins General Statement 8:12.16.08. For further information on chemistry and stability, mechanism of action, spectrum, resistance, pharmacokinetics, uses, cautions, drug interactions, and laboratory test interferences of ampicillin, see the Aminopenicillins General Statement 8:12.16.08 and see Ampicillin 8:12.16.08.

Preparations

Formulation	Dosage	Product Name	Manufacturer
Parenteral For Injection	1 g (of ampicillin) and 0.5 g (of sulbactam), combined total potency of 1.5 g	Unasyn®	Pfizer
Parenteral For Injection	2 g (of ampicillin) and 1 g (of sulbactam), combined total potency of 3 g	Unasyn®	Pfizer
Parenteral For Injection	10 g (of ampicillin) and 5 g (of sulbactam), combined total potency of 15 g	Unasyn®	Pfizer
Pharmacy Bulk Package for Injection, for IV Infusion	1 g (of ampicillin) and 0.5 g (of sulbactam), combined total potency of 1.5 g	Unasyn®	Pfizer
Pharmacy Bulk Package for Injection, for IV Infusion	2 g (of ampicillin) and 1 g (of sulbactam), combined total potency of 3 g	Unasyn®	Pfizer
ADD-Vantage® System	1 g (of ampicillin) and 0.5 g (of sulbactam), combined total potency of 1.5 g	Unasyn® ADD-Vantage®	Pfizer
ADD-Vantage® System	2 g (of ampicillin) and 1 g (of sulbactam), combined total potency of 3 g	Unasyn® ADD-Vantage®	Pfizer
Piggyback System	1 g (of ampicillin) and 0.5 g (of sulbactam), combined total potency of 1.5 g	Unasyn® Piggyback	Pfizer
Piggyback System	2 g (of ampicillin) and 1 g (of sulbactam), combined total potency of 3 g	Unasyn® Piggyback	Pfizer

Synonyms of Ampicillin:

Aminobenzylpenicillin, Ampicilina [INN-Spanish], Ampicillin Acid, Ampicillin Anhydrate, Ampicillin Anhydrous, Ampicillin Base, Ampicillin Sodium, Ampicillin Trihydrate, Ampicillin [Usan:Ban:Inn:Jan], Ampicillina [Dcit], Ampicilline, Ampicilline [INN-French], Ampicillinum [INN-Latin], Anhydrous Ampicillin, Bayer 5427, D-Ampicillin

Dosage forms of Ampicillin:
Ampicillin Sodium 250 mg/vial	Ampicillin Sodium 500 mg/vial	Ampicillin tr 250 mg capsule	Ampicillin Sodium 1 g/vial
Ampicillin Sodium 2 g/vial	Principen 250 mg/5ml Suspension 100ml Bottle	Ampicillin 1 gm vial	Principen 250 mg/5ml Suspension 200ml Bottle
Ampicillin 2 gm vial	Ampicillin 10 gm vial	Ampicillin 250 mg capsule	Ampicillin 500 mg capsule
Ampicillin tr 500 mg capsule

How can i get Ampicillin online over the counter?

You can buy Ampicillin OTC in online drugstore with low cost.

Therapeutic classes of Ampicillin:

Anti-Bacterial Agents, Penicillins

Delivery

Australia, Canada, Mexico, New Zealand, USA, Europe [Belgium, France, Norway, Holland, Ireland, Spain, Switzerland, Great Britain (UK), Italy] and etc.