Ampicillin
[CAS# 7177-48-2]

Identification

• Classification: API >> Antibiotics >> Penicillin
• Name: Ampicillin
• Synonyms: Ampicillin trihydrate; D-(-)-6-(2-Amino-2-phenylacetamido)-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid trihydrate
• Molecular Formula: C₁₆H₁₉N₃O₄S^.3(H₂O)
• Molecular Weight: 403.45
• CAS Registry Number: 7177-48-2
• EC Number: 615-347-9
• SMILES: CC1([C@@H](N2[C@H](S1)[C@@H](C2=O)NC(=O)[C@@H](C3=CC=CC=C3)N)C(=O)O)C.O.O.O

Properties

• Melting point: 198 - 200 ºC (Decomposes) (Expl.)
• Water solubility: 0.1-1 g/100 mL at 21 ºC

Safety Data

• Hazard Symbols: GHS07;GHS08 Danger
• Hazard Statements: H315-H317-H319-H334-H335
• Precautionary Statements: P233-P260-P261-P264-P264+P265-P271-P272-P280-P284-P302+P352-P304+P340-P305+P351+P338-P319-P321-P332+P317-P333+P317-P337+P317-P342+P316-P362+P364-P403-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Respiratory sensitization	Resp. Sens.	1	H334
Skin sensitization	Skin Sens.	1	H317
Skin irritation	Skin Irrit.	2	H315
Eye irritation	Eye Irrit.	2	H319
Specific target organ toxicity - single exposure	STOT SE	3	H335
Carcinogenicity	Carc.	2	H351
Reproductive toxicity	Lact.	-	H362

Discovory and Applicatios

Ampicillin is a well-established β-lactam antibiotic belonging to the penicillin class, developed to combat a broader range of bacterial infections than its predecessors. It was introduced in the early 1960s as a semi-synthetic derivative of penicillin and represented a significant advance in antimicrobial therapy at the time. Ampicillin was developed through structural modifications of the natural penicillin molecule, notably by introducing an amino group to the α-carbon of the acyl side chain. This modification allowed the molecule to better penetrate the outer membrane of certain Gram-negative bacteria, expanding its antibacterial spectrum.

The discovery of ampicillin followed the success of earlier penicillins, such as penicillin G and penicillin V, which were primarily effective against Gram-positive organisms. These earlier compounds faced limitations in treating infections caused by Gram-negative bacteria due to the permeability barrier of the bacterial outer membrane. Scientists working on penicillin derivatives aimed to enhance the spectrum of activity, leading to the development of ampicillin as one of the first broad-spectrum penicillins. It was first marketed by Beecham (now part of GlaxoSmithKline) in the early 1960s and quickly became a cornerstone in clinical antibacterial therapy.

Ampicillin works by inhibiting bacterial cell wall synthesis. It binds to penicillin-binding proteins (PBPs) involved in the final stages of peptidoglycan cross-linking, an essential process for bacterial cell wall structural integrity. This inhibition leads to the weakening of the bacterial cell wall, resulting in cell lysis and death, especially in actively dividing bacterial cells. Ampicillin is bactericidal and, like other penicillins, exhibits time-dependent killing, meaning its efficacy is related to the duration for which its concentration exceeds the minimum inhibitory concentration (MIC) of the pathogen.

The clinical applications of ampicillin are broad. It has been used effectively to treat a variety of infections, including respiratory tract infections, urinary tract infections, meningitis, gastrointestinal infections, and septicemia. It is particularly useful against organisms such as *Streptococcus pneumoniae*, *Enterococcus faecalis*, *Haemophilus influenzae*, *Escherichia coli*, *Salmonella* spp., and *Listeria monocytogenes*. Ampicillin’s efficacy against *Listeria monocytogenes* and *Enterococcus faecalis* makes it a key agent in treating meningitis and endocarditis caused by these organisms. It is frequently used in combination with other antibiotics such as gentamicin for synergistic effects in severe infections.

In addition to systemic use, ampicillin has been employed in combination with sulbactam, a β-lactamase inhibitor, to overcome resistance mediated by β-lactamase enzymes produced by certain bacteria. The sulbactam-ampicillin combination restores the antibacterial activity of ampicillin against β-lactamase-producing strains of *Haemophilus influenzae*, *Moraxella catarrhalis*, and *Staphylococcus aureus*. This combination is used in both hospital and outpatient settings for a wider spectrum of infections.

Ampicillin is available in various formulations, including oral capsules, oral suspensions, and injectable forms. Oral administration is typically used for mild to moderate infections, while the intravenous or intramuscular routes are preferred for more severe or systemic infections. However, its oral bioavailability is somewhat limited, and the absorption can be affected by food intake. As with other penicillins, hypersensitivity reactions, ranging from mild skin rashes to severe anaphylaxis, are known adverse effects associated with ampicillin.

With the rise of antimicrobial resistance, the use of ampicillin has declined in certain contexts where resistant organisms are prevalent. Nonetheless, it remains an important and effective agent, especially where susceptibility is confirmed or in pathogens for which it is still a first-line option. In microbiological research, ampicillin is also used as a selective agent in bacterial cloning to maintain plasmids carrying the ampicillin resistance gene.

In conclusion, ampicillin is a historically significant and clinically valuable antibiotic, with a well-characterized mechanism of action and a broad range of applications in infectious disease management. Its development marked a milestone in the expansion of the penicillin family and continues to contribute to antibacterial therapy and research.

References

1969. Kinetics and Mechanism of Degradation of Ampicillin in Solution. Journal of Pharmaceutical Sciences, 58(4).
DOI: 10.1002/jps.2600580412

1979. A modified quantitative determination of ampicillin in biological fluids. Clinical Chemistry, 25(9).
DOI: 10.1093/clinchem/25.9.1674a

1979. Treatment of Bacterial Meningitis with Intravenous Amoxicillin. Antimicrobial Agents and Chemotherapy, 16(2).
DOI: 10.1128/aac.16.2.171