Penicillins had been very effective against S. aureus; in the past, however, S. aureus has become capable of exhibiting resistance against them by producing a penicillin hydrolyzing enzyme – penicillinase. After that, subsequent efforts to overcome this issue and extend the antimicrobial coverage of penicillins, ampicillin was developed. It is also resistant to acid so that it can be administered orally.[1]
Ampicillin has effective minimum inhibitory concentration for most of medically important organisms in infectious disease like E. coli: MIC = 4 mg/L, S. aureus: MIC = 0.6-1 mg/L, Streptococcus pneumoniae: MIC = 0.03-0.06 mg/L, H. influenzae: MIC = 0.25 mg/L.[1]
Ampicillin is FDA approved for the treatment of the infections caused by specific bacteria listed as follows:
Respiratory tract infection
Caused by: Streptococcus pneumoniae, penicillinase, and non-penicillinase producing Staphylococcus aureus, group A beta-hemolytic Streptococci, Hemophilus influenzae.
Bacterial meningitis[2]
Caused by: Gram-negative bacteria: Neisseria meningitidis, Escherichia coli, and, Gram-positive bacteria: Listeria monocytogenes, Group B Streptococci. Adding aminoglycosides increases its effectiveness against gram-negative bacteria
Septicemia and Endocarditis[3]
Caused by: Gram-positive bacteria, including penicillin-susceptible Staphylococcus spp., Streptococcus spp., and Enterococcus spp.
Gram-negative bacteria including Escherichia coli, Salmonella spp., Proteus mirabilis.
Endocarditis caused by enterococci usually responds to intravenous ampicillin. Adding aminoglycosides with ampicillin may increase its effectiveness when treating endocarditis caused by streptococci.
Genitourinary infections[4]
Caused by sensitive strains of Escherichia coli and Proteus mirabilis.
Gastrointestinal infections[5]
Caused by Salmonella typhi, Shigella spp., and other Salmonella spp., and usually improve with oral or intravenous therapy. Culture must be obtained for susceptibility, and antimicrobial sensitivity; however, empiric therapy may be started before receiving the results.
Prophylaxis in surgery[6]
Ampicillin is a routinely selected agent in orthopedic surgeries, especially in prosthetic implants and dental surgeries.[7]
Neonatal Group B Streptococcal infection prophylaxis[6]
Can be administered as an alternative to intramuscular penicillin
Dosing
In the respiratory tract, oral or dental procedure: IV or IV 50 mg/kg per 30 to 60 minutes
In gastrointestinal or genitourinary procedure:
Only for patients at risk for endocarditis:
High risk: IV/IM 2g 30 minutes before the procedure, followed by 1 g, 6 hours later with an aminoglycoside
Endocarditis caused by Listeria sp.: IV/IM 200 mg/kg/day every 6 hours for 4 to 6 weeks
Bodyweight less than 40 kg: IV/IM 50 mg/kg/day every 6 to 8 hours
Bodyweight more than 40 kg: IV/IM 500 mg every 6 hours
Bodyweight less than 40 kg: IV/IM 50 mg/kg/day every 6 to 8 hours
Bodyweight more than 40 kg: IV/IM 500 mg every 6 hours
Bodyweight less than 40 kg: IV/IM 250 to 500 mg/kg/day every 6 to 8 hours
Bodyweight more than 40 kg: IV/IM 25 to 50 mg/kg/day every 6 hours
IV 150 to 200 mg/kg/day every every 6 to 8 hours
IV 3.5 g administered once with 1 g probenecid
IV/IM 1 to 2 g every 4 to 6 hrs
IV 2 g every 4 hours
Maternal prophylaxis to prevent newborn infection:
IV first dose 2 g followed by 1 g every 4 hours till delivery
The mode of action of beta-lactam antimicrobials on sensitive organisms can be considered to be a two-step process: In the first step, the drug binds to primary receptors called membrane-bound penicillin-binding proteins (PBPs). These proteins perform vital roles in cell cycle-related, morphogenetic formation of cell wall peptidoglycan structure. Inactivation of PBPs by bound antimicrobial has immediate arresting actions on their function. The second stage comprises the physiological effects caused by this receptor-ligand interaction. PBPs 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.[8]
Ampicillin administration can be oral, intramuscular, or intravenous.
Parenteral administration is preferable for severe or moderately severe infections. The oral route should not be the initial therapy in life-threatening conditions but can follow after parenteral therapy.
Oral administration
When administered orally, it should be on an empty stomach with 1 or 2 full glasses of water to increase absorption.
Intravenous administration
For intravenous administration, ampicillin may be administered as an IV bolus. Reconstitution of vials containing 125, 250, or 500 mg of the drug with 5 ml bacteriostatic or sterile water is recommended. Vials containing 1 or 2 g should be reconstituted 7.4 or 14.8 ml, respectively, of bacteriostatic or sterile water.
Intramuscular administration
If administering ampicillin intramuscularly, the injection should be into a large muscle mass. Reconstitute with bacteriostatic or sterile water to create solutions containing 125 or 250 mg/ml
Rate of administration
Formulations reconstituted from 125, 250, or 500 mg vials must be given over 3 to 5 minutes by intravenous injection.
Formulations reconstituted from 1 or 2 g vials must be given over 10 to 15 minutes by intravenous injection.
Half-life
The half-life of ampicillin is 0.7 to 1.5 hours in adults with normal kidney function.
The primary adverse effects of ampicillin include seizure, diarrhea, enterocolitis, pseudomembranous colitis, vomiting, agranulocytosis, hemolytic anemia, eosinophilia, and immune thrombocytopenia.
Common adverse effects appear below, in detail[9][10][11]:
Gastrointestinal
Hypersensitivity reactions
Liver
Hemato-lymphatic systems
Central nervous system
Opportunistic infections
Infection by penicillinase-producing organisms
Ampicillin is contraindicated in the treatment of infections caused by penicillinase-producing organisms. Penicillinase (beta-lactamase) will inactivate ampicillin.
Hypersensitivity [10]
Serious and life-threatening anaphylactoid reactions can occur with penicillin therapy. Although anaphylaxis more commonly occurs following parenteral therapy, it can also present after oral administration. It 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 clinician should discontinue ampicillin therapy and initiate alternative antimicrobial therapy. Anaphylactoid reactions require immediate emergency treatment with oxygen, epinephrine, steroids, and airway management, including intubation, if indicated.
Clostridioides difficile infection [9]
Antibacterial treatment alters the natural flora of the intestine leading to overgrowth of C. difficile. Clostridioides difficile associated diarrhea (CDAD) can occur 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. CDAD is a consideration for all patients after antibacterial use who present with diarrhea. Since it is reported to occur over two months after the administration of antibacterial agents, a careful medical history is necessary in these cases.
If CDAD is confirmed, ongoing antimicrobial use not directed against the organism might require cessation of therapy. Adequate fluid and electrolyte management and protein supplementation along with the antimicrobial regimen of C. difficile and surgical evaluation should be an option if indicated.
Concomitant infectious mononucleosis infection [12]
A high proportion (43%) of patients with infectious mononucleosis started on ampicillin can develop a rash. Ideally, the rash appears 7 to 10 days following the initiation of ampicillin therapy and remains for a few days to one week after discontinuation of the drug. In the majority of the cases, the rash is maculopapular, generalized, and pruritic. Therefore, ampicillin administration is not a recommendation in these patients. Whether these patients are truly allergic to penicillin remains unknown.
Absence of a strong indication
Ampicillin administration without a strong indication of or proof of a bacterial infection or a prophylactic indication is not likely to result in a benefit to the patient and instead increases the risk of growth of drug-resistant bacteria.
When administering a prolonged therapy, monitor renal, hepatic, and hematologic functions periodically. Additionally, watch for signs of anaphylaxis during the first dose.
In cases of overdose, discontinuation of the medication, symptomatic treatment, and supportive care institution is necessary. In patients with decreased renal function, the antimicrobial is removable via hemodialysis but not peritoneal dialysis. Whole bowel irrigation has been proven to be effective in severe cases of oral overdoses.[13]
Ampicillin is often prescribed by many clinicians, including the nurse practitioner. However, we have entered an era of drug resistance, and it is crucial for all healthcare workers not empirically to prescribe ampicillin for every type of infection. The clinician will decide to treat with ampicillin but can consult with a pharmacist, particularly one with board certification in infectious disease. Pharmacists can review the antibiogram and verify dosing and duration. Nursing can counsel the patient on how to take the medication, answer any questions, and monitor patient adherence and therapeutic effectiveness, reporting any concerns to the prescriber. There should be an interprofessional effort to minimize and limit the use of antimicrobials to only those with bacterial infections that will benefit from the course of therapy and avoid use in nonbacterial illnesses. [Level 5]
[1] | Kaushik D,Mohan M,Borade DM,Swami OC, Ampicillin: rise fall and resurgence. Journal of clinical and diagnostic research : JCDR. 2014 May; [PubMed PMID: 24995206] |
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[7] | Osmon DR,Berbari EF,Berendt AR,Lew D,Zimmerli W,Steckelberg JM,Rao N,Hanssen A,Wilson WR, Diagnosis and management of prosthetic joint infection: clinical practice guidelines by the Infectious Diseases Society of America. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2013 Jan [PubMed PMID: 23223583] |
[8] | Tipper DJ, Mode of action of beta-lactam antibiotics. Pharmacology [PubMed PMID: 3889939] |
[9] | Johnson S,Clabots CR,Linn FV,Olson MM,Peterson LR,Gerding DN, Nosocomial Clostridium difficile colonisation and disease. Lancet (London, England). 1990 Jul 14; [PubMed PMID: 1975332] |
[10] | Mirakian R,Leech SC,Krishna MT,Richter AG,Huber PA,Farooque S,Khan N,Pirmohamed M,Clark AT,Nasser SM, Management of allergy to penicillins and other beta-lactams. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology. 2015 Feb; [PubMed PMID: 25623506] |
[11] | Massoll AF,Powers SC,Betten DP, Agranulocytosis occurrence following recent acute infectious mononucleosis. The American journal of emergency medicine. 2017 May; [PubMed PMID: 27912922] |
[12] | Thompson DF,Ramos CL, Antibiotic-Induced Rash in Patients With Infectious Mononucleosis. The Annals of pharmacotherapy. 2017 Feb; [PubMed PMID: 27620494] |
[13] | Tenenbein M,Cohen S,Sitar DS, Whole bowel irrigation as a decontamination procedure after acute drug overdose. Archives of internal medicine. 1987 May; [PubMed PMID: 3579442] |