Ampicillin : Therapeutic uses, Dosage & Side Effects
Ampicillin is a semisynthetic extended spectrum aminopenicillin antibiotic. It is not resistant to penicillinase or to other β-lactamases. It is used for treating infections caused by certain types of bacteria.
Dose : 0 .5-2 g oral/ i.m. /i.v. depending on severity of infection, every 6 hours; children 25-50 mg/kg/day
Route : Oral, IV, IM
Onset of action : ?
Plasma Half-life : 1 hours
Duration of action : ?
Bioavailability : 40% (oral)
Plasma protein binding : 15-25%
Metabolism : 12-50%
Pregnancy risk category : B
Chemical formula : C16H19N3O4S
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
Trade name : Principen, Ampilin, Roscillin, Biocilin
Antibacterial spectrum : Ampicillin is active against gram-positive bacteria and many gram-negative bacilli, e.g. H. influenzae, E. coli, Proteus, Salmonella and Shigella. It is active against all organisms sensitive to Penicillin-G(PnG). However, due to widespread use, many of these have developed resistance; usefulness of this antibiotic has decreased considerably.
- Ampicillin is more active than PnG for Strep. viridans and enterococci; equally active for pneumococci, gonococci and meningococci (penicillinase resistant strains are resistant to ampicillin as well); but less active against other gram-positive cocci.
- Penicillinase producing Staph. are not affected, as are other gram-negative bacilli, such as Pseudomonas, Klebsiella, indole positive Proteus and anaerobes like Bacteroides fragilis.
Therapeutic uses : Ampicillin is used for following purposes :
- Urinary tract infections Ampicillin has been the drug of choice for most acute infections, but resistance has increased and fluoroquinolones cotrimoxazole are now more commonly used for empirical therapy.
- Respiratory tract infections including bronchitis, sinusitis, otitis media, etc. are usually teated with ampicillin, but higher doses (50-80 mg /kg/ day) are generally required now.
- Meningitis Ampicillin has been a first line drug, but a significant number of meningococci, rneumococci and H. influenzae are now resistant. It is usually combined with a third generation cephalosporin/ chloramphenicol for empiricial therapy.
- Gonorrhoea It is one of the first line drugs for oral treatment of nonpenicillinase producing gonococcal infections. A single dose of 3.5 g ampicillin + 1 g probenecid (ROSCIND, DYNACIL-PRB cap) is adequate and convenient for urethritis.
- Typhoid fever Due to emergence of resistance it is now rarely used when other first line drugs cannot be given. It is less efficacious than ciprofloxacin in eradicating carrier state. Salmonella diarrhoeas should usually not be treated with antimicrobials, including ampicillins.
- Bacillary dysentery due to Shigella often responds to ampicillin, but many strains are now resistant; quinolones are preferred.
- Cholecystitis Ampicillin is a good drug because high concentrations are attained in bile.
- Subacute bacterial endocarditis Ampicillin 2 g i.v. 6 hourly is used in place of PnG. Concurrent gentamicin is advocated.
- Septicaemias and mixed infections Injected ampicillin may be combined with gentamicin or one of the third generation cephalosporins.
Mechanism of action : Penicillins interfere with the synthesis of bacterial cell wall.
- The penicillins interfere with the last step of bacterial cell wall synthesis (transpeptidation or cross-linkage), resulting in exposure of the osmotically less stable membrane.
- Cell lysis can then occur, either through osmotic pressure or through the activation of autolysins. These drugs are bactericidal and work in a time-dependent fashion.
Penicillins are only effective against rapidly growing organisms that synthesize a peptidoglycan cell wall. Consequently, they are inactive against organisms devoid of this structure, such as mycobacteria, protozoa, fungi, and viruses.
Side effects : Ampicillin may cause following adverse reactions :
- Diarrhoea is frequent after oral administration. It is incompletely absorbed- the unabsorbed drug irritates the lower intestines as well as causes marked alteration of bacterial flora. Nausea, vomiting, anorexia, gastritis, generalized abdominal cramps, oral candidiasis, black hairy tongue, mouth or tongue soreness, glossitis, stomatitis, enterocolitis, and pseudomembranous colitis may also occur in few patients.
- It produces a high incidence (up to 10%) of rashes, especially in patients with AIDS, EB virus infections or lymphatic leukaemia. Concurrent administration of allopurinol also increases the incidence of rashes. Sometimes the rashes may not be allergic, but toxic in nature. Patients with a history of immediate type of hypersensitivity to PnG should not be given ampicillin as well.
- Some may develop black ‘furry’ tongue’.
Drug Interactions :
- Hydrocortisone inactivates ampicillin if mixed in the i.v. solution.
- By inhibiting colonic flora, it may interfere with deconjugation and enterohepatic cycling of oral contraceptives resulting in failure of oral contraception.
- Probenecid retards renal excretion of ampicillin.
- Contraindicated in patients with history of a previous hypersensitivity reaction to any of the penicillins.
For detailed query or in case of uncertainty, Always consult your doctor or pharmacist.