Penicillins are beta-lactam antibiotics that are bactericidal by unknown mechanisms but perhaps by activating autolytic enzymes that destroy the cell wall in some bacteria.
(See also Overview of Antibacterial Medications.)
Penicillins
Penicillin | Route |
|---|---|
Natural penicillins | |
Parenteral | |
Parenteral (IM only) | |
Parenteral | |
Oral | |
Aminopenicillins | |
Oral or parenteral | |
Parenteral | |
Oral | |
Oral | |
Penicillinase-resistant (antistaphylococcal) penicillins | |
Oral | |
Oral or parenteral | |
Oral or parenteral | |
Broad-spectrum (antipseudomonal) penicillin | |
Parenteral | |
Resistance
Some bacteria produce beta-lactamases, which inactivate beta-lactam antibiotics; this effect can be blocked by adding a beta-lactamase inhibitor.
However, traditional beta-lactamase inhibitors (eg, sulbactam, tazobactam) do not reliably inhibit the following:
AmpC beta-lactamases, commonly produced by Enterobacter, Serratia, Citrobacter, Providencia, and Morganella species or by Pseudomonas aeruginosa
Extended-spectrum beta-lactamases (ESBLs) produced by some Klebsiella pneumoniae, Escherichia coli, and other Enterobacterales (formerly Enterobacteriaceae)
Carbapenemases
Novel, non–beta-lactam beta-lactamase inhibitors, such as avibactam, relebactam, and vaborbactam, do have activity against AmpC, ESBLs, and even some carbapenemases such as the Klebsiella pneumoniae carbapenemases (KPCs), which have become increasingly common in Klebsiella species and other Enterobacterales. However, there are no currently available beta-lactamase inhibitors active against metallo-beta-lactamases (MBLs), such as NDM-1 (New Delhi MBL-1), VIMs (Verona integron–encoded MBLs), and IMP (imipenem)-types, which can inactivate all beta-lactam antibiotics except for . However, many strains that produce MBLs also produce other beta-lactamases that can hydrolyze aztreonam.
Pharmacokinetics of Penicillins
Amoxicillinamoxicillin is absorbed better, has fewer gastrointestinal effects, and can be given less frequently.
Penicillins are distributed rapidly in the extracellular fluid of most tissues, particularly when inflammation is present.
1).
Pharmacokinetics reference
1. Centers for Disease Control and Prevention (CDC): Inadvertent use of Bicillin C-R to treat syphilis infection—Los Angeles, California, 1999-2004. MMWR Morb Mortal Wkly Rep 54(9):217–219, 2005.
Indications for Penicillins
Penicillin G–like antibiotics
Gram-positive bacteria
Some gram-negative cocci (eg, meningococci)
A minority of gram-negative bacilli are also susceptible to large parenteral doses of penicillin G. Most staphylococci, most Neisseria gonorrhoeae, many anaerobic gram-negative bacilli, and about 30% of Haemophilus influenzae are resistant.
Penicillin G is the medication of choice for syphilis, for certain clostridial infectionsendocarditis due to susceptible enterococci. Penicillin G
Pure benzathine penicillin
A mixture of equal amounts of benzathine and procaine penicillin G
A 3:1 mixture of 0.9 million units benzathine and 0.3 million units procaine penicillin G
Of the 3 products, only pure benzathine penicillin is recommended for treating syphilis and preventing rheumatic fever. Pure benzathine penicillin and the mixture of equal amounts are indicated for treating upper respiratory infections and skin and soft-tissue infections caused by susceptible streptococci.
Amoxicillin and ampicillin
Certain gram-negative bacilli, such as non-beta-lactamase–producing H. influenzae, E. coli, and Proteus mirabilis; Salmonella species; and Shigella species
The addition of a beta-lactamase inhibitor (clavulanate or sulbactam) allows use against methicillin-sensitive staphylococci, H. influenzae, Moraxella catarrhalis, Bacteroides species, E. coli, and K. pneumoniae.
Penicillinase-resistant (antistaphylococcal) penicillins
Penicillinase-producing methicillin-sensitive Staphylococcus aureus
These antibiotics are also used to treat some Streptococcus pneumoniae, group A streptococcal, and methicillin-sensitive coagulase-negative staphylococcal infections.
Broad-spectrum (antipseudomonal) penicillin
Some strains of Enterobacter and Serratia species
Many strains of P. aeruginosa
The addition of a beta-lactamase inhibitor enhances activity against beta-lactamase–producing methicillin-sensitive S. aureus, E. coli, K. pneumoniae, H. influenzae, and gram-negative anaerobic bacilli but not against gram-negative bacilli that produce AmpC beta-lactamase or KPC and may only partially inhibit ESBL produced by some K. pneumoniae, E. coli, and other Enterobacterales. Broad-spectrum penicillins exhibit synergy with aminoglycosides and are usually used with this class to treat P. aeruginosa infections.
Contraindications to Penicillins
Penicillins are contraindicated in patients who have had serious allergic reactions to them.
Use of Penicillins During Pregnancy and Breastfeeding
Penicillins enter breast milk in small amounts. Their use is usually considered compatible with breastfeeding.
Adverse Effects of Penicillins
Adverse effects of penicillins include
Hypersensitivity reactions, including rashes (most common)
Gastrointestinal discomfort including nausea, vomiting, and diarrhea
Other adverse effects occur less commonly.
Oral penicillin may cause black hairy tongue, which occurs because of irritation of the glossal surface and keratinization of the superficial layers. This is a rare and harmless condition that resolves after the antibiotic is stopped.
Hypersensitivity
Most adverse effects are hypersensitivity reactions:
Immediate reactions: Anaphylaxis (which can cause death within minutes), urticaria and angioneurotic edema (in 1 to 5/10,000 injections), and death (in about 0.3/10,000 injections)
Delayed reactions: Serum sickness, rashes (eg, macular, papular, morbilliform), and exfoliative dermatitis (which usually appears after 7 to 10 days of therapy)
Most patients who report an allergic reaction to penicillin do not react to subsequent exposure to penicillin. Although small, risk of an allergic reaction is about 10 times higher for patients who have had a previous allergic reaction. Many patients report adverse reactions to penicillin that are not truly allergic (eg, gastrointestinal adverse effects, nonspecific symptoms).
If patients have a vague or inconsistent history of penicillin allergy and taking alternative antibiotics is not effective or convenient, skin testing may be done. Desensitization may be attempted in patients with a positive skin test if there is no alternative to a penicillin-type antibiotic. However, patients with a history of anaphylaxis to penicillin should not be given other penicillins or any beta-lactam with similar side chains (including for skin testing), except in very rare circumstances when no substitute can be found and the antibiotic can be given under supervision in a controlled environment. In such cases, special precautions and desensitization regimens are required.
Rashes
Other adverse effects
Penicillins can also cause
Central nervous system toxicity (eg, seizures) if doses are high, especially in patients with renal insufficiency
Nephritis
Clostridioides (formerly Clostridium) difficile–induced diarrhea (pseudomembranous colitis)
Coombs-positive hemolytic anemia
Leukopenia
Thrombocytopenia
Other adverse effects include pain at the IM injection site, thrombophlebitis when the same site is used repeatedly for IV injection, and, with oral formulations, gastrointestinal disturbances.
