Ampicillin

J01C - Beta-lactam antibacterials, penicillins ATC J01CF02+J01CA04 Small molecule approved 1965 Oral Parenteral Natural product

🧬 Cross-allergy: Penicillins

JFDA label: Ultracloxam

Mechanism of Action

Inhibitor of Bacterial penicillin-binding protein — Bacterial penicillin-binding protein inhibitor

Target	Action	Gene / class
Bacterial penicillin-binding protein efficacy	INHIBITOR

Indications

Approved

Bacterial meningitis
GI tract infections
Gastrointestinal infections
Genitourinary tract infections
Injection
Oral
Respiratory tract infections
Septicemia and endocarditis
Urinary tract infections

Off-label

Community-acquired pneumonia (children)
Endocarditis, prophylaxis
Endocarditis, treatment (HACEK organisms) (adults)
Group B streptococcus (maternal dose for neonatal prophylaxis)
Osteomyelitis, native vertebral
Prophylaxis in patients with prosthetic joint implants undergoing dental procedures which produce bacteremia
Prosthetic joint infection
Surgical prophylaxis (liver transplantation)
Urinary tract infection due to ampicillin-susceptible Enterococcus spp

Antimicrobial Spectrum

Expected / intrinsic spectrum (EUCAST breakpoints & labels) — not local resistance. Source: EUCAST v16 · curated · openfda-label.

Bacteria

Organism	Activity	MIC
Acinetobacter calcoaceticus	Active	—
Anaerobes	Susceptible	21.0 mg/L
Bacteroides fragilis	Active	—
Enterobacterales	Susceptible	8.0 mg/L
Enterococcus faecalis	Susceptible	4.0 mg/L
Enterococcus spp.	Susceptible	4.0 mg/L
Escherichia coli	Susceptible	8.0 mg/L
Haemophilus influenzae	Susceptible	2.0 mg/L
Haemophilus influenzae	Susceptible	14.0 mg/L
Listeria monocytogenes	Susceptible	1.0 mg/L
Listeria monocytogenes	Susceptible	1.0 mg/L
Moraxella catarrhalis	Susceptible	-1.0 mg/L
Morganella morganii	Active	—
Neisseria gonorrhoeae	Active	—
Pasteurella multocida	Susceptible	1.0 mg/L
Proteus mirabilis	Active	—
Proteus vulgaris	Active	—
Providencia rettgeri	Active	—
Providencia stuartii	Active	—
Staphylococcus aureus	Active	—
Staphylococcus epidermidis	Active	—
Staphylococcus saprophyticus	Active	—
Streptococcus pneumoniae	Susceptible	0.5 mg/L
Streptococcus pneumoniae	Susceptible	0.06 mg/L
Streptococcus pyogenes	Active	—
Streptococcus viridans	Active	—
Viridans group streptococci	Susceptible	0.5 mg/L
Haemophilus influenzae	Resistant	2.0 mg/L

Class profile

gramStatus	Both
spectrumBreadth	Moderate
atypicalCoverage	No
isBactericidal	1
moaCategory	Cell wall synthesis inhibitor (beta-lactam, PBP binding)
pdIndex	Time-dependent
postAntibioticEffect	None
mrsaCoverage	0
resistanceMechanisms	Beta-lactamase production,PBP mutations,Reduced permeability

Contraindications

Source: Lexicomp

Hypersensitivity (eg, anaphylaxis) to ampicillin, any component of the formulation, or other penicillins Absolute
infections caused by penicillinase-producing organisms Absolute

Adverse Reactions

Very Common >10%Common 1–10%Uncommon 0.1–1% Rare 0.01–0.1%Very Rare <0.01%Not Known

Nervous system disorders (4)

Not Known Brain disease (penicillin-induced) · glossalgia · seizure · sore mouth

Hepatobiliary disorders (1)

Not Known Increased serum AST

Renal and urinary disorders (1)

Not Known Interstitial nephritis (rare)

Blood and lymphatic system disorders (6)

Not Known Agranulocytosis · anemia · eosinophilia · hemolytic anemia · immune thrombocytopenia · leukopenia

Immune system disorders (2)

Not Known Anaphylaxis · Serum sickness-like reaction

Gastrointestinal disorders (9)

Not Known Diarrhea · enterocolitis · glossitis · melanoglossia · nausea · oral candidiasis · pseudomembranous colitis · stomatitis · vomiting

Skin and subcutaneous tissue disorders (4)

Not Known Erythema multiforme · exfoliative dermatitis · skin rash · urticaria

General disorders and administration site conditions (1)

Not Known Fever

Other (4)

Not Known Appearance of a rash should be carefully evaluated to differentiate (if possible) nonallergic ampicillin rash from hypersensitivity reaction. Incidence is higher in patients with viral infection · lymphocytic leukemia · or patients that have hyperuricemia · Salmonella infection

Respiratory, thoracic and mediastinal disorders (1)

Not Known Stridor

Dosing

Source: Lexicomp

Usual dosage range: Oral: 250 to 500 mg every 6 hours IM, IV: 1 to 2 g every 4 to 6 hours or 50 to 250 mg/kg/day in divided doses (maximum: 12 g/day) Endocarditis, treatment (off-label dose; AHA [Baddour 2015]): IV: Enterococcus, native or prosthetic valve (penicillin/gentamicin-susceptible strains): 2 g every 4 hours with concomitant ceftriaxone for 6 weeks or 2 g every 4 hours with concomitant gentamicin for 4 to 6 weeks (4 weeks for native valve and symptoms present and symptoms present ≥3 months or for prosthetic valve) Enterococcus, native or prosthetic valve (penicillin-susceptible/aminoglycoside-resistant strains): 2 g every 4 hours with concomitant ceftriaxone for 6 weeks Enterococcus, native or prosthetic valve (penicillin-susceptible/gentamicin-resistant/streptomycin-susceptible strains): 2 g every 4 hours with concomitant streptomycin for 4 to 6 weeks (4 weeks for native valve and symptoms present and symptoms present ≥3 months or prosthetic valve). HACEK organisms, native or prosthetic valve (off-label use): 2 g every 4 hours for 4 weeks (native valve) or 6 weeks (prosthetic valve). Viridans group streptococcus (VGS) and S. bovis: Native valve: Highly penicillin-susceptible (MIC ≤0.12 mcg/mL): 2 g every 4 hours for 4 weeks (monotherapy) or for 2 weeks with concomitant gentamicin Native valve: Relatively penicillin-resistant (MIC >0.12 to Prosthetic valve: Highly penicillin-susceptible (MIC ≤0.12 mcg/mL): 2 g every 4 hours for 6 weeks (with or without concomitant gentamicin for the first 2 weeks) Prosthetic valve: Relatively or fully penicillin-resistant (MIC >0.12 mcg/mL): 2 g every 4 hours with concomitant gentamicin for 6 weeks Endocarditis, prophylaxis (off-label use): Dental, oral, or respiratory tract procedures: IM, IV: 2 g within 30 to 60 minutes prior to procedure in patients not allergic to penicillin and unable to take oral amoxicillin. IM injections should be avoided in patients who are receiving anticoagulant therapy. In these circumstances, orally administered regimens should be given whenever possible. Intravenously administered antibiotics should be used for patients who are unable to tolerate or absorb oral medications. Note: American Heart Association (AHA) guidelines now recommend prophylaxis only in patients undergoing invasive procedures and in whom underlying cardiac conditions may predispose to a higher risk of adverse outcomes should infection occur (Wilson 2007). Genitourinary and gastrointestinal tract procedures: IM, IV: Note: Routine prophylaxis for GI/GU procedures is no longer recommended by the AHA. Consider only in patients with the highest risk of adverse outcome from endocarditis (eg, prosthetic heart valve, previous endocarditis, some categories of congenital heart disease, cardiac valvulopathy in cardiac transplant patients) who have an established GI or GU enterococcal infection or for those already receiving antibiotic therapy to prevent a wound infection or sepsis associated with a GI or GU proced

(For additional information see "Ampicillin: Pediatric drug information") Usual dosage range: Infants, Children, and Adolescents: Oral: 50 to 100 mg/kg/day divided every 6 hours (maximum: 2 to 4 g/day) IM, IV: 25 to 200 mg/kg/day divided every 3 to 4 hours (maximum: 12 g/day) Community-acquired pneumonia (CAP) (IDSA/PIDS 2011): Infants >3 months, Children, and Adolescents: IV: Note: May consider addition of vancomycin or clindamycin to empiric therapy if community-acquired MRSA suspected. In children ≥5 years, a macrolide antibiotic should be added if atypical pneumonia cannot be ruled out. Maximum daily dose of ampicillin: 12 g/day (Red Book [AAP 2012]). Empiric treatment or S. pneumoniae (moderate to severe; MICs to penicillin ≤2.0 mcg/mL) or H. influenzae (beta-lactamase negative) (preferred): 150 to 200 mg/kg/day divided every 6 hours Group A Streptococcus (moderate to severe) (preferred): 200 mg/kg/day divided every 6 hours S. pneumoniae (moderate to severe; MICs to penicillin ≥4.0 mcg/mL) (alternative to ceftriaxone): 300 to 400 mg/kg/day divided every 6 hours Endocarditis, prophylaxis (off-label use): Note: AHA guidelines (Baltimore 2015) limit the use of prophylactic antibiotics to patients at the highest risk for infective endocarditis (IE) or adverse outcomes (eg, prosthetic heart valves, patients with previous IE, unrepaired cyanotic congenital heart disease, repaired congenital heart disease with prosthetic material or device during first 6 months after procedure, repaired congenital heart disease with residual defects at the site or adjacent to site of prosthetic patch or device, and heart transplant recipients with cardiac valvulopathy): Dental, oral, or respiratory tract procedures (eg, tonsillectomy, adenoidectomy): Infants, Children, and Adolescents: IM, IV: 50 mg/kg within 30 to 60 minutes before procedure; maximum dose: 2,000 mg/dose. IM injections should be avoided in patients who are receiving anticoagulant therapy. In these circumstances, orally administered regimens should be given whenever possible. Intravenously administered antibiotics should be used for patients who are unable to tolerate or absorb oral medications (Wilson 2007). Endocarditis treatment (off-label): Children and Adolescents: IV: 200 to 300 mg/kg/day divided every 4 to 6 hours; maximum daily dose: 12 g/day; use in combination with other antibiotics for at least 4 weeks; some organisms may require longer duration (AHA [Baltimore 2015]) Genitourinary or gastrointestinal infections: Oral: Infants and Children ≤20 kg: 100 mg/kg/day in divided doses 4 times daily Children and Adolescents >20 kg: 500 mg 4 times daily IM, IV: Infants and Children Children and Adolescents ≥40 kg: 500 mg every 6 hours Mild to moderate infections: Infants, Children, and Adolescents: Oral: 50 to 100 mg/kg/day divided every 6 hours (maximum: 2 to 4 g/day) (Red Book [AAP 2012]) IM, IV: 100 to 150 mg/kg/day divided every 6 hours (maximum: 2 to 4 g/day) (Red Book [AAP 2012]) Respiratory

Refer to adult dosing.

There are no dosage adjustments provided in the manufacturer’s labeling; however, the following adjustments have been recommended (Aronoff 2007): CrCl >50 mL/minute: Administer every 6 hours CrCl 10 to 50 mL/minute: Administer every 6 to 12 hours CrCl End-stage renal disease (ESRD) on intermittent hemodialysis (IHD) (administer after hemodialysis on dialysis days): Dialyzable (20% to 50%): IV: 1 to 2 g every 12 to 24 hours (administer after hemodialysis on dialysis days) (Heintz 2009). Note: Dosing dependent on the assumption of 3 times/week, complete IHD sessions. Peritoneal dialysis (PD): IV: 250 mg every 12 hours (Aronoff, 2007) Continuous renal replacement therapy (CRRT) (Heintz, 2009): Drug clearance is highly dependent on the method of renal replacement, filter type, and flow rate. Appropriate dosing requires close monitoring of pharmacologic response, signs of adverse reactions due to drug accumulation, as well as drug concentrations in relation to target trough (if appropriate). The following are general recommendations only (based on dialysate flow/ultrafiltration rates of 1 to 2 L/hour and minimal residual renal function) and should not supersede clinical judgment: IV: CVVH: Loading dose of 2 g followed by 1 to 2 g every 8 to 12 hours CVVHD: Loading dose of 2 g followed by 1 to 2 g every 8 hours CVVHDF: Loading dose of 2 g followed by 1 to 2 g every 6 to 8 hours

There are no dosage adjustments provided in the manufacturer’s labeling.

Warnings & Precautions

Source: Lexicomp

Hypersensitivity/anaphylactoid reactions

Serious and occasionally severe or fatal hypersensitivity (anaphylactoid) reactions have been reported in patients on penicillin therapy, especially with a history of beta-lactam hypersensitivity or a history of sensitivity to multiple allergens. Serious anaphylactoid reactions require emergency treatment and airway management. Appropriate treatments must be readily available.

Rash

Appearance of a rash should be carefully evaluated to differentiate a nonallergic ampicillin rash from a hypersensitivity reaction; rash occurs in 5% to 10% of children and is a generalized dull red, maculopapular rash, generally appearing 3 to 14 days after the start of therapy. It normally begins on the trunk and spreads over most of the body. It may be most intense at pressure areas, elbows, and knees.

Superinfection

Prolonged use may result in fungal or bacterial superinfection, including Clostridium difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment. Disease-related concerns:

Infectious mononucleosis

A high percentage of patients with infectious mononucleosis have developed rash during therapy; ampicillin-class antibiotics not recommended in these patients. Rash (generalized maculopapular and pruritic) usually appears 7 to 10 days after initiation and usually resolves within a week of discontinuation. It is not known whether these patients are truly allergic to ampicillin

Renal impairment

Use with caution in patients with renal impairment; dosage adjustment recommended.

Pregnancy & Lactation

Pregnancy

FDA category B

Adverse events have not been observed in animal reproduction studies. Ampicillin crosses the placenta, providing detectable concentrations in the cord serum and amniotic fluid (Bolognese 1968; Fisher 1967; MacAulay 1966). Maternal use of ampicillin has generally not resulted in an increased risk of birth defects (Aselton 1985; Czeizel 2001b; Heinonen 1977; Jick 1981; Puhó 2007). Ampicillin is recommended for use in pregnant women for the management of preterm prelabor rupture of membranes (PROM) and for the prevention of early-onset group B streptococcal (GBS) disease in newborns. Ampicillin may also be used in certain situations prior to vaginal delivery in women at high risk for endocarditis (ACOG 120 2011; ACOG 188 2018; ACOG 485 2011; CDC [RR-10] 2010). The volume of distribution of ampicillin is increased during pregnancy and the half-life is decreased. As a result, serum concentrations in pregnant patients are approximately 50% of those in nonpregnant patients receiving the sam

Lactation

Ampicillin is present in breast milk. The manufacturer recommends that caution be exercised when administering ampicillin to breastfeeding women. Due to the low concentrations in human milk, minimal toxicity would be expected in the breastfed infant. Nondose-related effects could include modification of bowel flora and allergic sensitization.

Monitoring

Efficacy	Culture and susceptibility testing; clinical resolution (temperature, WBC, CRP, procalcitonin)
Toxicity	Renal function (dose adjustment in renal impairment); hepatic function for hepatically cleared agents; signs of C. difficile infection (diarrhoea)
Clinical pearl	Culture results guide de-escalation to narrower-spectrum therapy. Review antibiotic appropriateness at 48–72 h (antimicrobial stewardship).
Counseling	Complete the full course. Report persistent diarrhoea, rash, or lack of improvement after 48–72 h.

Chemistry & Properties

Formula	C16H19N3O4S
Molecular weight	349.41 g/mol
IUPAC name	(2S,5R,6R)-6-[[(2R)-2-amino-2-phenylacetyl]amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid
CAS	69-53-4
PubChem CID	6249
InChIKey	`AVKUERGKIZMTKX-NJBDSQKTSA-N`
logP	0.32 (XLogP -1.1)
Polar surface area	112.73 Å²
H-bond acceptors / donors	5 / 3
Drug-likeness (QED)	0.67
Lipinski violations	0

SMILES

CC1(C)S[C@@H]2[C@H](NC(=O)[C@H](N)c3ccccc3)C(=O)N2[C@H]1C(=O)O

Biology & Pharmacokinetics

Pharmacokinetics

BBB penetrant	No

Enzyme interactions

Enzyme	Role	Detail
CYP2C19	Substrate	—

Transporters

BCRP (Inhibitor)BSEP (Inhibitor)MRP1 (Inhibitor)NTCP (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)OATP1B3 (Inhibitor)OCT1 (Inhibitor)OCTN2 (Inhibitor)P-gp (Inhibitor)PEPT1 (Inhibitor)PEPT2 (Inhibitor)MRP2 (Substrate)P-gp (Substrate)

Drug–drug interactions (27, DDInter)

Interacting drug	Severity	Management
Methotrexate	major
Amikacin	moderate
Balsalazide	moderate
Chloramphenicol	moderate
Chloroquine	moderate
Demeclocycline	moderate
Dexlansoprazole	moderate
Dicoumarol	moderate
Doxycycline	moderate
Ethinylestradiol	moderate
Gentamicin	moderate
Iodide I-123	moderate
Iodide I-131	moderate
Kanamycin	moderate
Lansoprazole	moderate
Minocycline	moderate
Mycophenolic acid	moderate
Oxytetracycline	moderate
Pemetrexed	moderate
Picosulfuric acid	moderate
Tetracycline	moderate
Warfarin	moderate
Clarithromycin	minor
Clindamycin	minor
Erythromycin	minor
Heparin	minor
Mefloquine	minor

Registered Products (28)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
STANDACILLIN	Vial 0.5 g	1 vial pack varies	Nabulsi Drug Store	0.420
Ampicillin	Vial 500 mg	1 vial	moon light drugs store	0.440
Swisscillin	Vial 500 mg	1 vial	مستودع ادوية أرغون	0.440
STANDACILLIN	Vial 1 g	1 vial pack varies	Nabulsi Drug Store	0.570
Ampicillin	Vial 1 g	1 vial	moon light drugs store	0.590
Swisscillin	Vial 1 g	1 vial	مستودع ادوية أرغون	0.710
AMPIDAR FORTE G.F.SUSP.	Suspension 250 mg mg/5 ml	100 ml	Dar Al Dawa Development and Investment Co Ltd/Jordan	1.730
AMPIDAR FORTE CAPS.500mg	Capsule 500 mg	16 cap pack varies	Dar Al Dawa Development and Investment Co Ltd/Jordan	1.770
Ultracillin Forte Capsules	Capsule 500 mg	2x8's pack varies	The Arab Pharmaceutical Manufactruing Co.	1.770
AMPIDAR FORTE CAPS.500mg	Capsule 500 mg	20 cap pack varies	Dar Al Dawa Development and Investment Co Ltd/Jordan	2.210
Ultracillin Forte Capsules	Capsule 500 mg	2x10 pack varies	The Arab Pharmaceutical Manufactruing Co.	2.210
PENCLODAR 500 CAPS.	Capsule 250 mg, 250 mg	16 cap pack varies	Dar Al Dawa Development and Investment Co Ltd/Jordan	2.340
Ultracloxam	Tablet 250 mg, 250 mg	2x8's	The Arab Pharmaceutical Manufactruing Co.	2.600
PENCLODAR 500 CAPS.	Capsule 250 mg, 250 mg	20 cap pack varies	Dar Al Dawa Development and Investment Co Ltd/Jordan	2.810
Ampcare	Vial 500 mg	10 vial	Oasis of Hope	3.980
PAMECIL VIAL	Vial 250 mg	10	Khoury Drug Store	4.070
Penbritin Caps.	Capsule 500 mg	20 cap	Suleiman Tannous & Sons Co. Ltd	4.080
Pamecil Vial	Vial 500 mg	10 vial pack varies	Al Hilal Drug Store	7.090
PAMECIL VIAL	Vial 1 g	10 pack varies	Al Hilal Drug Store	9.620
PAMECIL CAP	Capsule 500 mg	200 cap pack varies	Khoury Drug Store	21.270
PAMECIL CAP	Capsule 500 mg	250 cap pack varies	Khoury Drug Store	26.600
AMPIDAR FORTE CAPS.500mg	Capsule 500 mg	500 cap pack varies	Dar Al Dawa Development and Investment Co Ltd/Jordan	35.700
STANDACILLIN Vial	Vial 0.5 g	100 vial pack varies	Nabulsi Drug Store	37.700
Ultracillin Forte Capsules	Capsule 500 mg	500 cap pack varies	The Arab Pharmaceutical Manufactruing Co.	46.900
STANDACILLIN Vial	Vial 1 g	100 pack varies	Nabulsi Drug Store	51.000
PENCLODAR 500 CAPS.	Capsule 250 mg, 250 mg	500 cap pack varies	Dar Al Dawa Development and Investment Co Ltd/Jordan	57.610
Pamecil Vial	Vial 500 mg	100 vial pack varies	Al Hilal Drug Store	63.750
PAMECIL VIAL	Vial 1 g	100 vial pack varies	Al Hilal Drug Store	86.590