[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Pharmacology](https://durgical.com/en/pharmacology/) › Penicillin groups # Penicillin groups Penicillins grouped by spectrum: natural, antistaphylococcal, aminopenicillins and antipseudomonal, and why β-lactamase inhibitors are added. Updated Nov 12, 2026 On this page - The basics Key points - Shared features - Natural penicillins - Antistaphylococcal (penicillinase-resistant) penicillins - Aminopenicillins - Antipseudomonal penicillin and β-lactamase inhibitors - Penicillin allergy - Memory aid - Example drugs - Study Test yourself - Connections Connections All penicillins share the β-lactam ring fused to a thiazolidine ring and kill growing bacteria by blocking the penicillin-binding proteins (PBPs) that cross-link the cell wall. Chemical changes to the side chain created groups with different strengths: resistance to staphylococcal penicillinase, better reach into gram-negative bacteria, or activity against Pseudomonas. Knowing the group tells you what a penicillin covers and what it misses. ## Key points - Natural penicillins (benzylpenicillin, phenoxymethylpenicillin, and the depot benzathine and procaine forms) remain the drugs of choice for streptococci and syphilis. - Antistaphylococcal penicillins (oxacillin, cloxacillin, dicloxacillin, flucloxacillin, nafcillin) resist staphylococcal penicillinase but do not cover MRSA, enterococci, Listeria or gram-negative bacteria. - Aminopenicillins (ampicillin, amoxicillin) add some gram-negatives and cover Enterococcus faecalis and Listeria. - Piperacillin, the antipseudomonal penicillin, is given with tazobactam for serious hospital infections. - β-lactamase inhibitors (clavulanic acid, sulbactam, tazobactam) protect the partner penicillin from many β-lactamases and widen its spectrum, including to anaerobes such as Bacteroides fragilis. ## Shared features - Bactericidal: they acylate PBPs and stop peptidoglycan cross-linking, so dividing bacteria lyse - Time-dependent killing: what counts is the time the level stays above the MIC, which is why most are given several times a day or by extended infusion - Mostly cleared by the kidneys (nafcillin is the exception, cleared in bile) - Most reach the cerebrospinal fluid only when the meninges are inflamed ## Natural penicillins Benzylpenicillin (penicillin G) is given intravenously or intramuscularly; phenoxymethylpenicillin (penicillin V) resists stomach acid and is oral. Benzathine and procaine benzylpenicillin are intramuscular depot forms that release the drug slowly: benzathine penicillin treats syphilis, including in pregnancy, and prevents relapses of rheumatic fever. Their spectrum is narrow: streptococci, Treponema pallidum, Neisseria meningitidis and many anaerobes of the mouth. Penicillinase-producing staphylococci destroy them. ## Antistaphylococcal (penicillinase-resistant) penicillins A bulky side chain shields the β-lactam ring from staphylococcal penicillinase. Oxacillin and nafcillin are intravenous; cloxacillin, dicloxacillin and flucloxacillin are oral options in many countries. They are drugs of choice for serious methicillin-susceptible Staphylococcus aureus (MSSA) infections and for skin and soft-tissue infections. They are not a substitute for penicillin G, do not work against MRSA, and miss enterococci, Listeria and gram-negative bacteria. ## Aminopenicillins An amino group helps ampicillin and amoxicillin cross the outer membrane of some gram-negative bacteria (Haemophilus influenzae, Escherichia coli, Proteus) when these do not make β-lactamase. They are key drugs against Enterococcus faecalis and Listeria monocytogenes, and amoxicillin is a first choice for otitis media, sinusitis and community pneumonia in many guidelines. Rash is more frequent with them than with other penicillins. ## Antipseudomonal penicillin and β-lactamase inhibitors Piperacillin reaches Pseudomonas aeruginosa and more Enterobacterales; combined with tazobactam it is a broad intravenous antibiotic for hospital pneumonia, intra-abdominal and complicated urinary infections. The inhibitors clavulanic acid, sulbactam and tazobactam have little antibacterial action of their own; they inactivate many β-lactamases so that the partner is not destroyed. Amoxicillin–clavulanic acid and ampicillin–sulbactam gain activity against β-lactamase-producing H. influenzae, MSSA and B. fragilis. None of these inhibitors stops carbapenemases. ## Penicillin allergy About one in ten patients in the United States reports a penicillin allergy, but when evaluated fewer than one in a hundred are truly allergic. The label often comes from a childhood viral rash, a family history or a side effect such as diarrhoea, and it pushes clinicians to broader, less suitable antibiotics. True reactions are immediate (IgE-mediated, up to anaphylaxis) or delayed (severe rashes, organ or blood injury). A careful history, risk stratification, skin testing and supervised oral challenge can remove a wrong label; people with severe delayed reactions such as Stevens–Johnson syndrome are not challenged. ## Memory aid «Natural, Nafcillin, Amino, Pip»: narrow (strep, syphilis) → staph-proof → gram-negative door opener (plus enterococcus and Listeria) → Pseudomonas; add an inhibitor to beat β-lactamases. ## Test yourself Think of the answer, then tap the question to see it. ## Which penicillin group is the drug of choice for serious MSSA infections? The antistaphylococcal (penicillinase-resistant) penicillins, such as oxacillin, nafcillin or cloxacillin. ## Which penicillins cover Enterococcus faecalis and Listeria? The aminopenicillins, ampicillin and amoxicillin. ## Why is clavulanic acid added to amoxicillin? It inactivates many β-lactamases, so amoxicillin is not destroyed and covers producers such as some H. influenzae, MSSA and B. fragilis. ## Which penicillin is combined with tazobactam to cover Pseudomonas aeruginosa? Piperacillin. ## Of patients who report a penicillin allergy, how many are truly allergic when evaluated? Fewer than one in a hundred; most labels can be removed after careful evaluation. [Add to my cards (5)](https://durgical.app/estudiar/?add=/en/pharmacology/topics/penicillin-groups/) [More Pharmacology questions →](https://durgical.com/en/practice/?f=pharmacology) ## Example drugs - [Benzylpenicillin (penicillin G)](https://durgical.com/en/pharmacology/benzylpenicillin/) - [Phenoxymethylpenicillin (penicillin V)](https://durgical.com/en/pharmacology/phenoxymethylpenicillin/) - [Benzathine benzylpenicillin](https://durgical.com/en/pharmacology/benzathine-benzylpenicillin/) - [Procaine benzylpenicillin](https://durgical.com/en/pharmacology/procaine-benzylpenicillin/) - [Oxacillin](https://durgical.com/en/pharmacology/oxacillin/) - [Nafcillin](https://durgical.com/en/pharmacology/nafcillin/) - [Cloxacillin](https://durgical.com/en/pharmacology/cloxacillin/) - [Dicloxacillin](https://durgical.com/en/pharmacology/dicloxacillin/) - [Flucloxacillin](https://durgical.com/en/pharmacology/flucloxacillin/) - [Ampicillin](https://durgical.com/en/pharmacology/ampicillin/) - [Amoxicillin](https://durgical.com/en/pharmacology/amoxicillin/) - [Amoxicillin + clavulanic acid](https://durgical.com/en/pharmacology/amoxicillin-clavulanic-acid/) - [Ampicillin + sulbactam](https://durgical.com/en/pharmacology/ampicillin-sulbactam/) - [Piperacillin + tazobactam](https://durgical.com/en/pharmacology/piperacillin-tazobactam/) ## Connections ## Related classes 1 - [Beta-lactams](https://durgical.com/en/pharmacology/classes/beta-lactams/) [← All of pharmacology](https://durgical.com/en/pharmacology/) Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given. Sources: [DailyMed - PENICILLIN G POTASSIUM injection, powder, for solution](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1442486a-05d6-4dce-8b95-857a30f478c2) (DailyMed (U.S. National Library of Medicine), 2026); [Nafcillin Injection: MedlinePlus Drug Information](https://medlineplus.gov/druginfo/meds/a685019.html) (MedlinePlus (U.S. National Library of Medicine), 2026); [Piperacillin and Tazobactam Injection: MedlinePlus Drug Information](https://medlineplus.gov/druginfo/meds/a694003.html) (MedlinePlus (U.S. National Library of Medicine), 2026); [Clinical Features of Penicillin Allergy](https://www.cdc.gov/antibiotic-use/hcp/clinical-signs/index.html) (Centers for Disease Control and Prevention (CDC), 2026). ## **Spotted a mistake?** We are always improving for the community. Tell us what is wrong and our team will review it. 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