Penicillins

1. 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. PMID: 15758893

• Gram-positive bacteria

• Some gram-negative cocci (eg, meningococci)

Neisseria gonorrhoeae, many anaerobic gram-negative bacilli, and about 30% of Haemophilus influenzae are resistant.

syphilis, for certain clostridial infectionsendocarditis due to susceptible enterococci.

• Pure benzathine penicillin

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.

These drugs are more active against

• Enterococci

• 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.

• Urinary tract infections

• Meningococcal meningitis

• Biliary sepsis

• Respiratory infections

• Listeriameningitis

• Enterococcal infections

• Some typhoid fever and typhoid carriers

• Penicillinase-producing methicillin-sensitive Staphylococcus aureus

These drugs are also used to treat some Streptococcus pneumoniae, group A streptococcal, and methicillin-sensitive coagulase-negative staphylococcal infections.

• 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.

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 drug. 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 drug can be given under supervision in a controlled environment. In such cases, special precautions and desensitization regimens are required.

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.

Ticarcillin and carbenicillin in high doses may cause sodium overload, especially in patients with heart or kidney failure, because both are disodium salts. Ticarcillin and carbenicillin can also cause hypokalemic metabolic alkalosis because the large amount of nonabsorbable anion presented to the distal tubules alters H+ ion excretion and secondarily results in potassium loss.