Ampicillin is a penicillinase-sensitive penicillin having the same mechanism of action as penicillin. It is a D-Ala-D-Ala structural analog binding penicillin-binding proteins (transpeptidases).

It blocks transpeptidase cross-linking of peptidoglycan in cell wall and activates autolytic enzymes. Having a wider spectrum and can also be combined with clavulanic acid to protect against destruction by beta-lactamase. It is used in the treatment of the following conditions:

• Genitourinary tract infections:

  • Treatment of genitourinary tract infections caused by:

    • Escherichia coli,

    • Proteus mirabilis,

    • enterococci,

    • Shigella,

    • Salmonella typhosa and other Salmonella, and

    • nonpenicillinase-producing N. gonorrhoeae.

Not advised for use as a first-line gonorrhoea therapy.

• Treatment of GI tract infections caused by

  • Shigella,

  • S. typhosa and other Salmonella,

  • E. coli,

  • P. mirabilis, and

  • enterococci.

Due to the emergence of resistance, it is not suggested as a first-line treatment for Salmonellosis (nontyphoid), Shigellosis, or typhoid fever (Salmonella enterica) species

• Respiratory tract infections:

  • RTIs caused by nonpenicillinase-producing H. influenzae, staphylococci, and streptococci, including Streptococcus pneumoniae.

Ampicillin Injections:

• Gastrointestinal infections:

  • Treatment of Shigella, various Salmonella, and S. typhi (typhoid fever)-related gastrointestinal illnesses (dysentery).

Note: Due to the emergence of resistance, ampicillin is not advised as a first-line treatment for Shigellosis, Salmonellosis (nontyphoid), or typhoid fever (S. enterica species).

• Bacterial Meningitis:

  • treatment for bacterial meningitis brought on by gram-negative bacteria such N. meningitidis, E. coli, and group B streptococci.

• Respiratory tract infections:

  • Treatment of respiratory tract infections brought on by group A beta-hemolytic streptococci, H. influenzae, S. pneumoniae, and Staphylococcus aureus (penicillinase and nonpenicillinase generating).

• Septicemia and endocarditis:

  • Treatment of gram-negative sepsis brought on by E. coli, P. mirabilis, and Salmonella species, as well as septicemia and endocarditis brought on by susceptible gram-positive organisms such Streptococcus species, penicillin-resistant staphylococci, and enterococci.

• Urinary tract infections:

  • Treatment of urinary tract infections caused by E. coli and P. mirabilis.

• Off Label Use of Ampicillin in Adults:

  • Endocarditis, prophylaxis;

  • Endocarditis, treatment (HACEK organisms) (adults);

  • Osteomyelitis, native vertebral;

  • Prophylaxis in patients with prosthetic joint implants undergoing dental procedures which produce bacteremia;

  • Prosthetic joint infection;

  • Surgical prophylaxis;

  • Group B streptococcus (maternal dose for neonatal prophylaxis);

  • Urinary tract infection due to ampicillin-susceptible Enterococcus spp.

Ampicillin Dose in Adults

Usual Dose:

• 250 to 500 mg taken orally each six hours
• Intramuscular and Intravenous:
  • 1 to 2 g every four to six hours, or split dosages of 50 to 250 mg/kg per day
  • Maximum: 12 g/day

Dose in the treatment of Endocarditis (off-label):

• Enterococcus, native or prosthetic valve (penicillin/gentamicin-susceptible strains):
  • For native valves and symptoms that have appeared for less than three months, administer 2 g intravenously every four hours while also taking ceftriaxone for six weeks, or administer 2 g intravenously every four hours while also taking gentamicin for four to six weeks.
• Enterococcus, native or prosthetic valve (penicillin-susceptible/aminoglycoside resistant strains):
  • 2 g intravenously every four hours when taking ceftriaxone concurrently for six weeks.
• Enterococcus, native or prosthetic valve (penicillin-susceptible/gentamicinresistant/ streptomycin-susceptible strains):
  • For 4 to 6 weeks, provide 2 g intravenously every 4 hours while also taking streptomycin (4 weeks for a native valve and symptoms that have been present for less than 3 months; 6 weeks for a native valve or prosthetic valve).
• HACEK organisms, native or prosthetic valve (off-label use):
  • 2 g intravenously every 4 hours for either 6 or 4 weeks (native valve) (prosthetic valve).
• Listeria monocytogenes:
  • 2 g intravenously every four hours
• Viridans group streptococcus (VGS) and S. bovis:
  • Native valve:
    • Highly susceptible to penicillin (2 g intravenously every 4 hours for 4 weeks (monotherapy) or for 2 weeks with concurrent gentamicin): MIC 0.12 mcg/mL
  • Native valve:
    • MIC >0.12 to 0.5 mcg/mL; relatively resistant to penicillin: 2 g intravenously every 4 hours for 4 weeks with concurrent gentamicin for the first 2 weeks
  • Prosthetic valve:
    • Highly susceptible to penicillin (2 g intravenously every 4 hours for 6 weeks; MIC 0.12 mcg/mL) (with or without concomitant gentamicin for the first 2 weeks)
  • Prosthetic valve:
    • MIC >0.12 mcg/mL; penicillin-resistant to some extent or completely: 2 g every 4 hours with concurrent gentamicin for 6 weeks

Dose in the prophylaxis of Endocarditis (off-label):

• Dental, oral, or respiratory tract procedures:
  • Patients who are not allergic to penicillin and who are unable to take oral amoxicillin should receive 2 g intramuscularly or intravenously within 30 to 60 minutes after the surgery.
  • When administering intramuscular injections to patients who are on anticoagulant therapy, caution should be exercised.
  • When possible, oral regimens should be delivered in these conditions.
  • Patients unable to accept or absorb oral drugs should be treated with intravenously given antibiotics.

Note: According to American Heart Association (AHA) recommendations, prophylaxis is currently only advised for patients undergoing invasive procedures and those whose underlying heart problems may put them at a higher risk of negative consequences in the event that an infection occurs.

• Genitourinary and gastrointestinal tract procedures:

Note:

• Regular prophylaxis is not advised.
• Consider only in high-risk patients who have an established GI or GU enterococcal infection or for those who are already receiving antibiotic therapy to prevent a wound infection or sepsis associated with a GI or GU procedure in which enterococcal coverage is desired (e.g., prosthetic heart valve, previous endocarditis, some categories of congenital heart disease, cardiac valvulopathy in cardiac transplant patients).

• High-risk patients:

  • 2 g within 30 minutes of the surgery, then 1 g of ampicillin (or amoxicillin) taken orally 6 hours later; ampicillin and gentamicin must be taken together.

• Moderate-risk patients:

  • 30 minutes before the procedure, consume 2 g.

Dose in the treatment of Genitourinary or gastrointestinal infections:

• Oral, Intramuscular, Intravenous: 500 mg every 6 hours

Dose in the treatment of Group B streptococcus (maternal dose for neonatal prophylaxis) (off-label):

• Initial intravenous injection of 2 g, followed by 1 g every 4 hours until delivery.

Dose in the treatment of bacterial Meningitis:

• Pathogen specific therapy eg,
  • Enterococcus spp [ampicillin susceptible],
  • Haemophilus influenzae [beta-lactamase negative],
  • Listeria monocytogenes,
  • Neisseria meningitidis [penicillin MIC <0.1 mcg/mL],
  • Streptococcus agalactiae,
  • Streptococcus pneumoniae [penicillin MIC ≤0.06 mcg/mL]):
    • 2 g Intravenous every 4 hours.
    • Use in combination with gentamicin for susceptible Enterococcus spp;
    • addition of an aminoglycoside may be considered for L. monocytogenes or S. agalactiae.
  • Mild to moderate infections:
    • 250 - 500 mg orally 6 hourly.

Dose in the treatment of native vertebral Osteomyelitis as off-label use:

• Enterococcus spp (penicillin-susceptible):
  • Patients with infective endocarditis are advised to have a continuous intravenous infusion of 12 g every 24 hours or 2 g every 4 hours for 6 weeks, along with an aminoglycoside for 4 to 6 weeks.

Dose in the treatment of Prosthetic joint infection, Enterococcus spp (penicillin-susceptible) (off-label):

• Consider adding an aminoglycoside to the intravenous continuous infusion of 12 g every 24 hours or 2 g every 4 hours for 4 to 6 weeks.

Dose in the treatment of Prophylaxis in total joint replacement patients undergoing dental procedures which produce bacteremia (off-label):

Note: Patients with prosthetic joint implants typically don't need to take prophylactic antibiotics before dental work. Planning an invasive oral operation may benefit from dental consultation with the patient's orthopaedic surgeon to discuss infection risks.

• Intramuscular, Intravenous: 2 g 1 hour prior to the procedure.

Dose in the treatment of Respiratory tract infections:

• Ingest 250 mg four times per day
• 250 to 500 mg intramuscularly or intravenously every six hours

Dose in the treatment of Sepsis:

Note: Every 3 to 4 hours, 150–200 mg/kg/day (corresponding to 6–12 g/day) should be administered.

• Intramuscular, Intravenous: 60 minutes before making a surgical incision, take 2 g with cefotaxime.
  In longer procedures, the dose may be given again in two hours.

Dose in the Surgical (perioperative) prophylaxis in liver transplantation (off-label):

• IV: Every 4 to 6 hours, administer 1 to 2 g intravenously, with or without an aminoglycoside.

Dose in the treatment of Urinary tract infections (ampicillin-susceptible Enterococcus; off-label):

• 4 times a day, or 50 to 100 mg/kg, up to a daily dose cap of 2,000 mg.

Ampicillin Dose in Children

General dosing for susceptible infection :

• Infants, Children, and Adolescents:

  • Mild to moderate infection:

    • Maximum daily dose: 8 g/day; intramuscular, intravenous: 50 to 200 mg/kg/day split every 6 hours.

  • Severe infection (eg, meningitis, endocarditis):

    • Maximum daily dose: 12 g/day; intramuscular, intravenous: 300–400 mg/kg/day split every 4–6 hours.

Dose in the treatment of Community-acquired pneumonia (CAP):

• Infants >3 months, Children, and Adolescents:

Note: If community-acquired MRSA is suspected, add vancomycin or clindamycin to the empiric course of treatment. If atypical pneumonia cannot be ruled out in children under the age of five, a macrolide antibiotic should be added. 

• Empiric treatment or S. pneumoniae (MICs for penicillin ≤2 mcg/mL) or H. influenzae (betalactamase negative) in fully immunized patients:

  • Every six hours, 150 to 200 mg/kg/day intravenously split.

• Group A Streptococcus:

  • daily 200 mg/kg split intravenously every 6 hours.

• Pneumoniae (MICs for penicillin ≥4 mcg/mL):

  • Every six hours, 300 to 400 mg/kg/day intravenously split.

Dose in the Endocarditis:

Treatment:

• Children and Adolescents:
  • 200 - 300 mg/kg/day Intravenous divided every 4 - 6 hours
  • The maximum dose is 12 gms/day.
  • Use for at least 4 weeks while also taking other antibiotics.
  • Some species can need a longer timeframe.

• Dental/oral procedures or respiratory tract procedures (eg, tonsillectomy, adenoidectomy):

  • Infants, Children, and Adolescents:
    • Intravenous, Intramuscular:
      • 30 to 60 minutes prior to the surgery, 50 mg/kg.
      • 2,000 mg maximum per dosage.
    • Patients who are taking anticoagulant therapy should refrain from having intramuscular (IM) injections.
    • Orally given regimens should be used whenever possible in these conditions.
    • Patients who are unable to tolerate or absorb oral drugs should be treated with intravenously (IV) given antibiotics.

Dose in the treatment of complicated Intra-abdominal infection:

• Infants, Children, and Adolescents:
  • 200 mg/kg/day Intravenous divided every 6 hours; maximum single dose: 2,000 mg; maximize doses if undrained abdominal abscesses.

Dose in the treatment of Meningitis (including health care-associated meningitis and ventriculitis):

• Infants, Children, and Adolescents:
  • 300–400 mg/kg per day Intravenous split every four to six hours; the daily maximum dose is twelve gm

Dose in the treatment of Peritonitis (CAPD) Limited data available:

• Infants, Children, and Adolescents:
  • Intraperitoneal: 125 mg/liter of dialysate for 2 weeks.

Dose in the Surgical prophylaxis:

• Infants, Children, and Adolescents:
  • 50 mg/kg Intravenous within 60 minutes of the surgical incision; if the treatment is lengthy or there is a significant blood loss, repeat in 2 hours.
  • 2,000 mg maximum per dosage.

Pregnancy Risk Factor B

• Studies on animal reproduction have not revealed any adverse effects.
• Pregnant women should use ampicillin to manage preterm prelaborrupture of membranes (PROM), and prevent early-onset group B streptococcal disease (GBS).
• During pregnancy, the distribution volume of ampicillin exceeds the half-life.
• The serum concentrations of pregnant patients are half those of non-pregnant women who received the same dose.
• During pregnancy, higher doses might be required
• Additionally, oral absorption during labor is not well absorbed.

Ampicillin Use during breastfeeding:

• Breast milk contains low levels of ampicillin.
• Therefore, it is safe to assume that infants breastfed will experience minimal toxicity.

Ampicillin Dose in Renal Disease:

• CrCl >50 mL/minute:
  • Administer every 6 hours
• CrCl 10 to 50 mL/minute:
  • Administer every 6 to 12 hours
• CrCl <10 mL/minute:
  • Administer every 12 to 24 hours

• End-stage renal disease (ESRD) on intermittent hemodialysis (IHD) (administer after hemodialysis on dialysis days):

  • 1 to 2 g intravenously every 12 to 24 hours for dialysisable (20% to 50%). (administer after hemodialysis on dialysis days).

Note: Dosing is based on the premise that IHD sessions are complete three times a week.

• Peritoneal dialysis (PD):

  • Intravenous: 250 mg every 12 hours

• Continuous renal replacement therapy (CRRT):

  • The technique of renal replacement, the type of filter, and the flow rate all have a significant impact on drug clearance.
  • Close monitoring of the pharmacologic response, warning indicators of drug accumulation, and drug concentrations in respect to the target trough are all necessary for proper dosing (if appropriate).

• The following suggestions should not replace clinical judgement and are simply general advice (based on dialysate flow/ultrafiltration rates of 1 to 2 L/hour and limited residual renal function): Intravneous:

  • 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

Ampicillin Dose in Liver Disease:

 No dose adjustment required.

Side Effects of Ampicillin Frequency not defined.

• Central nervous system:

  • Brain disease
  • Glossalgia
  • Seizure
  • Sore mouth

• Dermatologic:

  • Erythema multiforme
  • Exfoliative dermatitis
  • Skin rash
  • Urticaria

Note: The appearance of a rash should be carefully assessed to (if feasible) distinguish between a hypersensitivity reaction and a nonallergic ampicillin rash. Individuals with viral infections, Salmonella infections, lymphocytic leukaemia, or patients with hyperuricemia have a higher incidence of these conditions.

• Gastrointestinal:

  • Diarrhea
  • Enterocolitis
  • Glossitis
  • Melanoglossia
  • Nausea
  • Oral candidiasis,
  • Pseudomembranous colitis
  • Stomatitis
  • Vomiting

• Hematologic & oncologic:

  • Agranulocytosis
  • Anemia
  • Eosinophilia
  • Hemolytic anemia
  • Immune thrombocytopenia
  • Leukopenia

• Hepatic:

  • Increased serum AST

• Hypersensitivity:

  • Anaphylaxis

• Immunologic:

  • Serum sickness-like reaction

• Renal:

  • Interstitial nephritis (rare)

• Respiratory:

  • Stridor

• Miscellaneous:

  • Fever

Contraindication to Ampicillin Include:

• Allergy reactions to ampicillin or any other penicillin, including any component of the formulation
• Infections caused by penicillinase-producing organisms

Warnings and precautions

• Hypersensitivity/anaphylactoid reactions
  • Patients receiving penicillin therapy have reported severe or fatal allergic reactions (anaphylactoid).
  • People who have a history or multiple allergies are more likely to experience allergic reactions.
  • If severe allergic reactions occur, emergency treatment may be necessary.
  • It is essential that appropriate treatments are readily available.
• Rash:
  • To distinguish between a nonallergic and hypersensitive reaction to ampicillin, it is important to carefully evaluate the appearance of a rash.
  • Between 5% and 10% of kids are affected. The rash typically emerges 3 to 14 days after the start of treatment and is maculopapular and dull-red in colour.
  • Usually starting at the trunk, it covers most of the body.
  • In regions of pressure, such the knees and elbows, it could be more acute.
• Superinfection
  • Ampicillin use for an extended period of time can result in bacterial and fungal superinfections, including pseudomembranous colitis and Clostridioides difficile-associated diarrhoea.
  • CDAD is often observed in patients who have been taking the medication for longer than two months.
• Infectious mononucleosis
  • Patients with infectious mononucleosis should not be given ampicillin-class antibiotics due to the higher risk of drug-induced rash.
  • In general, it is pruritic and maculopapular. Typically, the rash shows about 7 to 10 days after the onset. Within a week, it vanishes.

Ampicillin: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitoring Parameters:

• CBC
• LFTs
• RFTs
• Sign/symptoms of anaphylaxis during first dose.

How to take Ampicillin?

• Oral:
  • With water, empty stomach (ie- 30 mins before or 2 hrs after meals).
• Intramuscular:
  • deep intramuscular injection into a sizable muscle mass
• Intravenous:
  • Administer a direct intravenous bolus over three to five minutes (125 to 500 mg) or over ten to fifteen minutes (1 to 2 g). Seizures may be brought on by faster infusion.
• Infusion:
  • Rapid infusion may cause seizures.

Mechanism of action of Ampicillin:

• It is a D.Ala-D.Ala structural analog binding penicillin binding protein (transpeptidases). 
• It prevents the transpeptidase from cross-linking peptidoglycans in cells wall and activates autolytic enzymes. This results in cell wall lysis.

When taken orally, absorption is 50%. Distribution into the bile is what it is. Only inflamed meninges can cause penetration into CSF.

Protein binding: Neonates: 10%; Adults: 15% to 18%

Half-life elimination: Neonates: PNA: 4 hours, 2 to 7 days PNA: 2.8 hours from 8 to 14 days PNA: 1.7 hours from 15 to 30 days Adults and children: 1 to 1.8 hours

Excretion: Urine (∼90%, unchanged within 24 hours); feces

International Brands of Ampicillin:

• Acipillin
• Alphacin
• Alphapen
• Ambiopi
• Amcillin
• APO-Ampi
• NOVO-Ampicillin
• Amcopen
• Amfipen
• Amicap
• Amillin
• Amipenix
• Ampecu
• Ampi-1
• Ampibex
• Ampiblan
• Ampicelo-500
• Ampicil
• Ampicilin
• Ampicilina
• Ampicillin
• Ampicin
• Ampiclin
• Ampiclox
• Ampicyn
• Ampiger
• Ampilag
• Ampilin
• Ampillin
• Ampimedin
• Ampina
• Ampipen
• Ampipharm
• Ampitenk
• Ampitrex
• Ampivral
• Ampliblan
• Ampolin
• Amsapen
• Ancillin
• Antallpen
• Austrapen
• Axum
• Binotal
• Biocil
• Bridopen
• Brupen
• Camicil
• Dancin
• Dhacillin
• Dibacilina
• Dinpen
• Doktacillin
• Duacillin
• Epicocillin
• Eurocin
• Excillin
• Extrapen
• Farcocillin
• Ficillin
• Flamicina
• Gobemicina
• Gobemicina Retard
• Gramcil
• Ibimycin
• Intramed
• Iwacillin
• Julphapen
• Magnapen
• Marovilina
• Maxipen
• Meprizna
• Nimpicillin
• Norcipen
• Novencil
• Omnipen
• Pamecil
• Panacta
• Pelitin
• Penbrex
• Penbritin
• Penibrin
• Penodil
• Pentrexyl
• Petercillin
• Polypen
• Primapen
• Promecilina
• Pulmosterin Retard
• Radiocillina
• Reichlin
• Rimacillin
• Roscillin
• Sanpicillin
• Semicillin
• Shacillin
• Silina
• Standacillin
• Standcillin
• Synthocilin
• Syntocil
• Totapen
• Tricil
• Trifalicina
• Trilaxin
• Viccillin
• Vidopen
• Virucil
• Winpicillin
• Z Cil
• Z cil
• Z-Cil
• Zampicillin

Ampicillin Brands in Pakistan: