Lenampicillin is a prodrug of ampicillin that inhibits bacterial penicillin binding proteins (transpeptidase) and thus is effective against a wide range of bacterial infections. The drug was developed and marketed in Japan (Takacillin, Varacillin), however its current marketing status is unknown and supposed to be discontinued.

Flucloxacillin is an isoxazolyl penicillin of the β-lactam group of antibiotics, which exerts a bactericidal effect upon many Gram-positive organisms including β-lactamase-producing staphylococci and streptococci. While no longer used in the United States, Flucloxacillin is supplied under a variety of trade names in other countries, including Floxapen, Flopen, Staphylex. Floxapen is indicated for the treatment of infections due to sensitive Gram-positive organisms, including β-lactamase-producing staphylococci and streptococci. Typical indications including, skin and soft tissue infections; respiratory tract infections; other infections caused by floxapen-sensitive organisms, like example, osteomyelitis, urinary tract infection, septicaemia, endocarditis. Floxapen is also indicated for use as a prophylactic agent during major surgical procedures when appropriate; for example cardiothoracic and orthopaedic surgery. Flucloxacillin, by its action on the synthesis of the bacterial wall, exerts a bactericidal effect on streptococci except those of group D (Enterococcus faecalis) staphylococci. It is not active against methicillin-resistant staphylococci. There is evidence that the risk of flucloxacillin induced liver injury is increased in subjects carrying the HLA-B*5701 allele. Despite this strong association, only 1 in 500-1000 carriers will develop liver injury. Consequently, the positive predictive value of testing the HLA-B*5701 allele for liver injury is very low (0.12%) and routine screening for this allele is not recommended. Flucloxacillin diffuses well into most tissue. Specifically, active concentrations of flucloxacillin have been recovered in bones: 11.6 mg/L (compact bone) and 15.6 mg/L (spongy bone), with a mean serum level of 8.9 mg/L. Flucloxacillin diffuses in only small proportion into the cerebrospinal fluid of subjects whose meninges are not inflamed. It is also excreted in small quantities in mother's milk. In normal subjects approximately 10% of the flucloxacillin administered is metabolised to penicilloic acid. The elimination half-life of flucloxacillin is in the order of 53 minutes.

Bacmecillinam is the orally active 1’-ethoxycarbonyloxyethyl ester of macillinam. It is rapidly absorbed and hydrolyzed, liberating the antibacterially active drug mecillinam. Protective effects of bacmecillinam was tested in experimental mouse intraperitoneal infection model. Drug demonstrated the potent protective effects against E. coli GN 2411-5, E. coli 2848, K. pneumoniae 8045, E. cloacae F-1510 and P. mirabilis F-783 infection.

Temocillin was marketed by Beecham Pharmaceuticals in the UK in the 1980s but achieved little commercial success and was withdrawn, though it remained available via the manufacturer’s medical department. Presently licensed to Eumedica, temocillin is being re-launched in the UK and Belgium for treating UTI, sepsis, and respiratory infections by ESBL (Extended-spectrum beta-lactamases) and AmpC-producing Enterobacteriaceae. It acts by inhibiting the synthesis of the peptidoglycan layer of bacterial cell walls. It irreversibly binds to the active site of specific transpeptidases and carboxypeptidases known as Penicillin Binding Proteins (PBP), preventing peptidoglycan production.

Metampicillin is the approved name for the penicillin resulting from the reaction of ampicillin with formaldehyde. Metampicillin is hydrolysed in aqueous solution with the formation of ampicillin. Metampicillin has broad spectrum of activity coupled with a marked degree of stability to bacterial penicillinase. Furthermore, metampicillin is reported to be absorbed to a greater extent than ampicillin, resulting in superior blood levels in human subjects, and also giving high levels of antibiotic in bile following parenteral administration. Metampicillin showed a spectrum and level of activity similar to that of ampicillin in vitro, and both compounds were inactive against penicillinase-producing strains of bacteria. The activity of metampicillin was markedly reduced by human serum, and the compound was less active than ampicillin in the presence of human serum. Following the oral administration of metampicillin to man, metampicillin was not detected in the blood stream nor in urine, and ampicillin alone was demonstrated in these subjects. The serum concentrations of ampicillin that were produced following the oral administration of metampicillin were somewhat lower than those obtained with equivalent doses of ampicillin. Adminstration of metampicillin by the intramuscular (i.m.) route to volunteers resulted in the appearance of both ampicillin and metampicillin in the blood, and of ampicillin alone in the urine of these subjects. When parenteraly administered, metampicillin appeared to be a particularly suitable penicillin for the treatment of biliary tract infections. Metampicillin is a cell wall biosynthesis inhibitor.

Clometocillin, one of the forms of penicillin, was active against pen-I or pen-R pneumococci and was used in children. The modern information about its application is not available.

Apalcillin is a naphthydridine derivative of ampicillin. Apalcillin has a broad spectrum of antibacterial activity that is very similar to that of piperacillin, except that apalcillin is significantly more active against Pseudomonas aeruginosa and Acinetobacter spp. Against Acinetobacter spp., apalcillin is uniquely active, compared to the other penicillins and comparison drugs. Strains producing high amounts of β-lactamases do become resistant to apalcillin. PAH (p-aminohippurate) clearance was significantly decreased during apalcillin infusion. Apalcillin appeared to compete with PAH for proximal tubular secretion but induced no further renal dysfunction.

The phthalidyl thiazolidine carboxylic ester of ampicillin, talampicillin (Talpen, Beecham), has been introduced recently to improve absorption and to reduce these side effects. After oral administration talampicillin is rapidly absorbed and hydrolysed by tissue esterases in the intestinal wall to release into the circulation ampicillin and the ester moiety, mainly 2-hydroxymethyl-benzoic acid. No unchanged talampicillin is detectable in the peripheral blood. It is not approved by the FDA for use in the United States

Propicillin (Baycillin Mega) is this semisynthetic penicillin, analogous to penicillin V, was introduced in the early 1960s. Although it is better absorbed from the gastrointestinal tract, overall it is inferior to phenoxymethylpenicillin and phenoxyethylpenicillin because of its lower antibacterial activity. Propicillin is used by propicillin-susceptible pathogens in adults and adolescents from 14 years to treat mild to moderate bacterial infections. These include skin infections, ear, nose and throat infections (such as otitis media, sinusitis, tonsillitis, pharyngitis) and infections of the bronchi andlung inflammation. Moreover propicillin can for prevention and treatment of scarlet fever or against rheumatic fever are used (bacterial infection of the nose and throat). Even with tooth or jaw surgery the drug is used to treat an endocarditis endocarditis prevent. Its mechanism of action could be due to binding to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, thus propicillin may inhibit the third and last stage of bacterial cell wall synthesis

Tobicillin (TBPC) is an ester derivative of penicillin G. It is a beta-Lactam antibiotic, peptidoglycan biosynthesis inhibitor. TBPC was shown to be the effective antibiotic for the treatment of enterococcicosis in yellowtail.