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 can be taken orally. 
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. 
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 
Caused by: Gram-negative bacteria (Listeria monocytogens, Neisseria meningitidis), Eschrichia coli and Group B Streptococci. Adding aminoglycosides increases its effectiveness against gram-negative bacteria
Septicemia and Endocarditis 
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 
Caused by sensitive strains of Escherichia coli and Proteus mirabilis.
Gastrointestinal infections 
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 prior to the results.
Prophylaxis in surgery 
Ampicillin is routinely used in orthopedic surgeries especially in prosthetic implants  and dental surgeries
Neonatal Group B Stretococcal infection prophylaxis 
Can be administered as an alternative to intramuscular penicillin
In the respiratory tract, oral or dental procedure: Iv or im 50 mg/kg per 30-60 mins
In gastrointestinal or genitourinary procedure:
Only for patients at risk for endocarditis:
High risk: iv/im 2g 30 mins before the procedure, followed by 1g 6 hrs later with an aminoglycoside
Endocarditis caused by Listeria: iv/im 200mg/kg/day every 6 hrs for 4-6 weeks
Body weight less than 40 kg: iv/im 50mg/kg/day q 6-8 hrs
Body weight more than 40 kg: iv/im 500mg q6hr
Body weight less than 40 kg: iv/im 50mg/kg/day q 6-8 hrs
Body weight more than 40 kg: iv/im 500mg q6hr
Body weight less than 40 kg: iv/im 250-500 mg/kg/day q 6-8 hrs
Body weight more than 40 kg: iv/im 25-50mg/kg/day q6hr
Iv 150-200mg/kg/day every q 6-8 hrs
Iv 3.5g administered once with 1 g probenecid
iv/im 1-2g q 4-6 hrs
Iv 2g q 4 hrs
Maternal prophylaxis to prevent new born infection:
Iv first dose 2g followed by 1g q 4 hrs till delivery
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 (PBP's). These proteins perform vital roles in cell cycle related, morphogenetic formation of cell wall peptidoglycan. Inactivation of PBP's by bound antibiotic has immediate arresting actions on their function. The second stage comprises of the physiological effects caused by this receptor-ligand interaction. PBP's 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. 
Ampicillin may be administered orally, intramuscularly, or intravenously.
Parenteral administration is preferred for severe or moderately severe infections. Oral route should not be the initial therapy in life threatening conditions and it should always be followed after parenteral therapy.
When it is administered orally, it is administered on an empty stomach with 1 or 2 full glasses of water to increase absorption.
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.
If ampicillin is administered intramuscularly, it should be injected 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 a period of 3-5 minutes by intravenous injection.
Formulations reconstituted from 1 or 2 g vials must be given over a period of over 10 - 15 minutes by intravenous injection.
Half-life of ampicillin is 0.7 - 1.5 hours in adults with normal kidney function.
The primary adverse effects for ampicillin include seizure, diarrhea, enterocolitis, pseudomembranous colitis, vomiting, agranulocytosis, hemolytic anemia, eosinophilia, and immune thrombocytopenia.
Common adverse effects are described in detail:
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.
A moderate elevation of serum glutamic oxaloacetic transaminase (SGOT) is reported, commonly in infants, its significance is unknown. Mild transient elevations 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 therapy. These reactions are reversible on discontinuation of therapy, the etiology being a hypersensitive phenomenon.
Central nervous system
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.
Infection by penicillinase-producing organisms
Ampicillin is contraindicated in the treatment of infections caused by penicillinase-producing organisms.
Serious and life threatening anaphylactoid reactions have been reported with penicillin therapy. Although anaphylaxis is more common following parenteral therapy, it has also been demonstrated after oral administration. It is more apt in a patient with 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 with it 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 over growth of C. difficile. Clostridium 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. CDAD may be considered with 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 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 (43%) of patients with infectious mononucleosis started on ampicillin 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 the drug is discontinued. In majority of the cases, the rash is maculopapular, generalized and pruritic. Therefore, ampicillin administration is not recommended 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 a strongly suspected or proven bacterial infection or a prophylactic indication is not likely to result in a benefit to the patient and rather 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 required. In patients with decreased renal function, the antibiotic can be removed via hemodialysis but not peritoneal dialysis. Whole bowel irrigation has been proven to be effective in severe cases .
Ampicillin is often prescribed by many healthcare workers including the nurse practitioner. However, we have entered an era of drug resistance and it is important for all healthcare workers to not empirically prescribe ampicillin for every type of infection. 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 illness. [Level V]
|||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]|
|||Biggs BA,Kucers A, Penicillins and related drugs. The Medical journal of Australia. 1986 Dec 1-15 [PubMed PMID: 3540540]|
|||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 PMID: 7474277]|
|||Heintz BH,Halilovic J,Christensen CL, Vancomycin-resistant enterococcal urinary tract infections. Pharmacotherapy. 2010 Nov; [PubMed PMID: 20973687]|
|||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 PMID: 8994789]|
|||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 PMID: 23327981]|
|||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]|
|||Tipper DJ, Mode of action of beta-lactam antibiotics. Pharmacology [PubMed PMID: 3889939]|
|||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]|
|||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]|
|||Massoll AF,Powers SC,Betten DP, Agranulocytosis occurrence following recent acute infectious mononucleosis. The American journal of emergency medicine. 2017 May; [PubMed PMID: 27912922]|
|||Thompson DF,Ramos CL, Antibiotic-Induced Rash in Patients With Infectious Mononucleosis. The Annals of pharmacotherapy. 2017 Feb; [PubMed PMID: 27620494]|
|||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]|