Ampicillin


Article Author:
Basil Peechakara
Hajira Basit


Article Editor:
Mohit Gupta


Editors In Chief:
Yvonne Carter
Jason Wallen


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Avais Raja
Orawan Chaigasame
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Hussain Sajjad
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James Hughes
Beata Beatty
Daniyal Ameen
Altif Muneeb
Beenish Sohail
Nazia Sadiq
Hajira Basit
Phillip Hynes
Komal Shaheen
Sandeep Sekhon


Updated:
10/22/2019 12:43:05 PM

Indications

Indications

Penicillins had been very effective against S. aureus; however, in the past, 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 = 0.03-0.06mg/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 (Listeria monocytogens, Neisseria meningitidis), Escherichia coli, and Group B Streptococci. Adding aminoglycosides increases its effectiveness against gram-negative bacteria

Septicemia and Endocarditis[3]

Caused by: Gram-positive bacteria, including penicillin-susceptible Staphylococci, Streptococcus spp., and enterococci.

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 antibiotic 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

  • Endocarditis prophylaxis (Off Label):

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 (Off label)

Endocarditis caused by Listeria: IV/IM 200 mg/kg/day every 6 hours for 4 to 6 weeks 

  • GI tract infections

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

  • GU tract infections:

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

  • Respiratory tract infection

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

  • Bacterial meningitis/ septicemia:

IV 150 to 200 mg/kg/day every every 6 to 8 hours

  • Gonorrhea

IV 3.5 g administered once with 1 g probenecid

  • Urinary tract infection caused by ampicillin susceptible enterococcus

IV/IM 1 to 2 g every 4 to 6 hrs

  • Listeria

IV 2 g every 4 hours

  • S. agalactiae (off-label)

Maternal prophylaxis to prevent newborn infection:

IV first dose 2 g followed by 1 g every 4 hours till delivery

Mechanism of Action

The mode of action of beta-lactam antibiotics 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. Inactivation of PBPs by bound antibiotic 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]

Administration

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.

Adverse Effects

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

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

Hypersensitivity reactions

  • Skin rashes and urticaria occur frequently. Reports also exist of some cases of erythema multiforme and exfoliative dermatitis. Anaphylaxis is the most severe 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 elevations are possible with repeated intramuscular administration in individuals receiving larger than usual doses. Evidence indicates that SGOT gets released in the intramuscular injection site, and the increased quantities seen in the blood may not necessarily be from the liver as a source.

Hemato-lymphatic systems

  • Reports exist of anemia, thrombocytopenic purpura, thrombocytopenia, eosinophilia, agranulocytosis, and leukopenia during ampicillin 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. Such cases warrant discontinuation of therapy and substitution of appropriate treatment.

Contraindications

Infection by penicillinase-producing organisms

Ampicillin is contraindicated in the treatment of infections caused by penicillinase-producing organisms.

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.

Clostridium difficile infection [9]

Antibacterial treatment alters the natural flora of the intestine leading to overgrowth of C. difficile. Clostridium 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 antibiotic use not directed against the organism might require cessation of therapy. Adequate fluid and electrolyte management and protein supplementation along with the antibiotic 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 to 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.

Monitoring

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

Toxicity

In cases of overdose, discontinuation of the medication, symptomatic treatment, and supportive care institution is necessary. In patients with decreased renal function, the antibiotic is removable via hemodialysis but not peritoneal dialysis. Whole bowel irrigation has been proven to be effective in severe cases.[13]

Enhancing Healthcare Team Outcomes

Ampicillin is often prescribed by many healthcare workers, 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 compliance and therapeutic effectiveness, reporting any concerns to the prescriber. There should be an interprofessional effort to minimize and limit the use of antibiotics to only those with bacterial infections that will benefit from the course of therapy and avoid use in nonbacterial illnesses. [Level V]


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Ampicillin - Questions

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A 55-year-old man presents to the hospital with complaints of profuse, foul-smelling diarrhea for one day. The patient was in the usual state of health before that and denied eating outside or being in contact with anyone with a similar illness. However, he recalls a visit to his primary care provider 2 weeks ago for the treatment of bacterial sore throat. Also, the stool examination is positive for the Clostridium difficile toxin. Which of the following is the most likely antibiotic prescribed to the patient for the treatment of sore throat predisposing him to Clostridium difficile infection?



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A 16-year-old boy presents to the hospital with a puncture wound on his right foot. On inquiry, he states that he was walking in his backyard when he stepped on a nail about a week ago. The pain was moderate at that time but for the last two days, it has been increasingly getting worse and is now accompanied by a discharge. On examination, there is a small inflamed puncture wound with erythema around the skin. The area is warm and tender to touch with a purulent discharge. Gram staining of the discharge reveals gram-positive cocci in clusters. Which of the following is least likely to be effective in treating this infection?



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A 25-year-old male presents to the hospital with complaints of bloody diarrhea, abdominal cramps, and high-grade fever for two days. He recently came back from a trip to Mexico, where he enjoyed eating and drinking local beverages from roadside stalls. Initially, the diarrhea was mild, but now it is profuse and bloody. Blood and stool cultures are drawn, and empiric treatment with ampicillin for suspected gram-negative enterobacilli is initiated. What is the most likely reason for preferring oral ampicillin over amoxicillin in this case?



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A 10-year-old girl is brought to her primary care provider by her mother three days after a recent diagnosis of the streptococcal throat infection. The mother complains that there has been no improvement in the girl's condition, and she still has high fever and difficulty swallowing. The provider prescribed ampicillin at the time of initial presentation. What is the most likely mode of antibiotic resistance in this patient?



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A 5-year-old boy accompanied by his mother presents to his primary care provider with complaints of sore throat and high fever for three days. Today his temperature is 101 F. On examination, he has anterior cervical lymphadenopathy and white exudates over the tonsils. A rapid strep test comes out to be positive. Treatment with ampicillin is discussed upon which the mother recalls severe hives and wheezing on ingestion of the same category of the drug to which ampicillin belongs. To what category does ampicllin belong?



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A 35-year-old male patient with meningitis is found to have growth of Listeria monocytogenes from the culture of cerebrospinal fluid. The physician ordered 250 mg of ampicillin intravenously. The nurse takes an ampicillin vial and proceeds to administer the drug. What are the steps must be taken to do so?



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Ampicillin - References

References

Wilson WR,Karchmer AW,Dajani AS,Taubert KA,Bayer A,Kaye D,Bisno AL,Ferrieri P,Shulman ST,Durack DT, Antibiotic treatment of adults with infective endocarditis due to streptococci, enterococci, staphylococci, and HACEK microorganisms. American Heart Association. JAMA. 1995 Dec 6     [PubMed]
Biggs BA,Kucers A, Penicillins and related drugs. The Medical journal of Australia. 1986 Dec 1-15     [PubMed]
Tipper DJ, Mode of action of beta-lactam antibiotics. Pharmacology     [PubMed]
Kaushik D,Mohan M,Borade DM,Swami OC, Ampicillin: rise fall and resurgence. Journal of clinical and diagnostic research : JCDR. 2014 May;     [PubMed]
Heintz BH,Halilovic J,Christensen CL, Vancomycin-resistant enterococcal urinary tract infections. Pharmacotherapy. 2010 Nov;     [PubMed]
Rowe B,Ward LR,Threlfall EJ, Multidrug-resistant Salmonella typhi: a worldwide epidemic. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 1997 Jan;     [PubMed]
Bratzler DW,Dellinger EP,Olsen KM,Perl TM,Auwaerter PG,Bolon MK,Fish DN,Napolitano LM,Sawyer RG,Slain D,Steinberg JP,Weinstein RA, Clinical practice guidelines for antimicrobial prophylaxis in surgery. American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists. 2013 Feb 1;     [PubMed]
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]
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]
Massoll AF,Powers SC,Betten DP, Agranulocytosis occurrence following recent acute infectious mononucleosis. The American journal of emergency medicine. 2017 May;     [PubMed]
Thompson DF,Ramos CL, Antibiotic-Induced Rash in Patients With Infectious Mononucleosis. The Annals of pharmacotherapy. 2017 Feb;     [PubMed]
Tenenbein M,Cohen S,Sitar DS, Whole bowel irrigation as a decontamination procedure after acute drug overdose. Archives of internal medicine. 1987 May;     [PubMed]
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]

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