Ampicillin/Sulbactam

Article Author:
Basil Peechakara
Article Editor:
Mohit Gupta
Updated:
10/27/2018 12:32:08 PM
PubMed Link:
Ampicillin/Sulbactam

Indications

Ampicillin/sulbactam combination shows synergy to cover strains of bacteria resistant to ampicillin, thus providing a broader coverage.[1]

Lower Respiratory Tract Infections

Ampicillin/sulbactam, when compared with various third-generation cephalosporins (cefuroxime[2] and cefotaxime[3]), second-generation cephalosporin (cefoxitin), mezlocillin, ticarcillin/clavulanate,[4] and imipenem/cilastatin[5] had higher efficacy although not clinically significant in the treatment of lower respiratory tract infections.

Aspiration Pneumonia

In a study by Kadowaki et al.,[6] the efficacy of ampicillin/sulbactam, clindamycin, and imipenem/cilastatin was compared. Cure rates for ampicillin/sulbactam were comparable to imipenem/cilastatin being the highest, although clindamycin was found to be the least expensive.

Gynecological Infections

Pelvic inflammatory disease is caused by sexually transmitted organisms (Neisseria gonorrhoeae or Chlamydia trachomatis) or anaerobic vaginal flora. First-line treatment includes cefoxitin or cefotetan with doxycycline or clindamycin with gentamycin plus doxycycline. Ampicillin/sulbactam is comparable in efficacy and is an important alternate regimen for gynecological infections.[4]

Intra-abdominal Infections

Ampicillin/sulbactam should be used in mild to moderate community-acquired intra-abdominal infections; however, more serious infections require a broader coverage against facultative and gram-negative aerobic bacteria where the combination of antimicrobials may be required (carbapenem in combination with vancomycin).[7]

Diabetic Foot Infections

Ampicillin/sulbactam when compared to imipenem/cilastatin[8] and piperacillin/tazobactam are comparably effective. However, piperacillin/tazobactam has a broader coverage, and the most common gram-negative bacterium isolated was Pseudomonas aeruginosa.

Pediatric Infections

In the pediatric population, it is used in epiglottitis, periorbital infections, acute fulminant meningococcemia, and sepsis management.[9]

Skin Infections

Ampicillin/sulbactam has an efficacy comparable to third-generation cephalosporins in the treatment of skin infections in patients with or without a history of intravenous drug abuse.[10]

Infection in the Intensive Care Unit (ICU) with Acinetobacter baumannii

It is effective and safe to use ampicillin/sulbactam in multidrug-resistant A. baumannii infections.[11]

Mechanism of Action

Ampicillin is a beta-lactam antibiotic, and sulbactam is a beta-lactamase inhibitor.

Ampicillin

The mode of action of ampicillin, like any other beta-lactam antibiotics, on sensitive organisms, can be considered to be a 2-step process. In the first step, the drug binds to primary receptors called membrane-bound penicillin-binding proteins. These proteins perform vital roles in cell cycle related, the morphogenetic formation of cell wall peptidoglycan. Inactivation of penicillin-binding proteins by bound antibiotic has immediate arresting actions on their function. The second stage comprises the physiological effects caused by this receptor-ligand interaction. Penicillin-binding proteins are involved in the late stages of peptidoglycan synthesis in the cell wall. Because peptidoglycan maintains the integrity of the cell wall, which resides in a hypotonic environment, its disruption causes lysis and cell death.[12]

Sulbactam

It is a beta-lactamase inhibitor and inhibits the action of any bacteria producing the enzyme after binding to it and thereby not allowing its action on the antibiotic.

Administration

Ampicillin/sulbactam is not absorbed adequately after oral absorption. In intravenous formulations, penetration into tissue/fluids includes intraperitoneal fluid (60%), myometrium (64%), sputum (12% to 14%), cerebrospinal fluid (CSF) (11% to 14%). As ampicillin/sulbactam is primarily excreted renally, its half-life increases in patients with impaired renal function.[13] Pharmacokinetics of ampicillin/sulbactam does not change in the pediatric population as compared to adults.[14] Caution must be observed in the administration to neonates with age less than 1 week and premature infants due to an underdeveloped urinary system.

Adverse Effects

The primary adverse effects for ampicillin-sulbactam include seizure, diarrhea, enterocolitis, pseudomembranous colitis, vomiting, agranulocytosis, hemolytic anemia, eosinophilia, and immune thrombocytopenia.

Common Adverse Effects

Gastrointestinal

Stomatitis, glossitis, black "hairy" tongue, nausea, vomiting, pseudomembranous colitis, enterocolitis, and diarrhea. Mainly seen with oral dose administration.

Hypersensitivity Reactions

Skin rashes and urticaria are reported frequently. Some cases of erythema multiforme and exfoliative dermatitis have also been reported. Anaphylaxis is the most serious complication experienced and is usually associated with the parenteral form.

Liver

A moderate elevation of serum glutamic oxaloacetic transaminase (SGOT) is reported, commonly in infants; its significance is unknown. Mild transient elevation is noted with repeated intramuscular administration in individuals receiving larger than usual doses. Evidence indicates that SGOT is released in the intramuscular injection site and the increased quantities seen in blood may not necessarily be from the liver as a source.

Hemato-Lymphatic Systems

Anemia, thrombocytopenic purpura, thrombocytopenia, eosinophilia, agranulocytosis, and leukopenia are reported during ampicillin-sulbactam therapy. These reactions are reversible on discontinuation of therapy, the etiology being a hypersensitive phenomenon.

Central Nervous System

Seizures

Opportunistic Infections

During therapy, there is a possibility of superinfection with some bacteria or mycotic organisms. In such cases, discontinuation of therapy and substitution of appropriate treatment is warranted.

Contraindications

Hypersensitivity

Serious and life-threatening anaphylactoid reactions have been reported with ampicillin-sulbactam therapy. Although anaphylaxis is more common following parenteral therapy, it has also been demonstrated after oral administration. Anaphylaxis is more likely in a patient with a previous history of penicillin hypersensitivity and/or reaction to multiple allergens. Before initiating therapy, a careful inquiry should be made relating to hypersensitivity reactions to cephalosporins, allergens, or penicillin. If a hypersensitivity reaction occurs, the therapy should be discontinued, and alternative therapy should be initiated. Anaphylactoid reactions require immediate emergency treatment with oxygen, epinephrine, steroids, and airway management including intubation if indicated.

Clostridium difficile Infection

Antibacterial treatment alters the natural flora of the intestine leading to overgrowth of C. difficile. C. difficile-associated diarrhea (CDAD) is reported with nearly all antibacterial agent use, especially ampicillin. The resulting severity may range from mild diarrhea to fulminant colitis. Hypertoxin producing C. difficile strains cause increased morbidity and mortality, as these strains are refractory to the recommended antimicrobial therapy and may require colectomy. C. difficile-associated diarrhea may be considered with all patients after antibacterial use who present with diarrhea. Since it is reported to occur over 2 months after the administration of antibacterial agents, a careful medical history is necessary in these cases.

If CDAD is confirmed, ongoing antibiotic use not directed against the organism might need to be discontinued. Adequate fluid and electrolyte management and protein supplementation along with the antibiotic regimen of C. difficile, and surgical evaluation should be considered if indicated.

Concomitant Infectious Mononucleosis Infection

A high proportion of patients with infectious mononucleosis started on ampicillin-sulbactam develop a rash. Ideally, the rash appears 7 to 10 days following the initiation of ampicillin-sulbactam therapy and remains for a few days to 1 week after the drug is discontinued. In the majority of cases, the rash is maculopapular, generalized, and pruritic. Therefore, ampicillin-sulbactam administration is not recommended in these patients. Whether these patients are truly allergic to penicillin remains unknown.

Monitoring

When administering a prolonged therapy, monitor renal, hepatic, and hematologic functions periodically. Monitor also for signs of anaphylaxis during the first dose.

Toxicity

In cases of overdose, discontinuation of the medication, symptomatic treatment, and supportive care institution is required. In patients with decreased renal function, the antibiotic can be removed via hemodialysis but not peritoneal dialysis.