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INDICATIONS

• Endocarditis
• Skin and soft tissue infection (erysipelas, erysipeloid)
• Rat-bite fever
• Syphilis
• Vincent's infection fusospirochetosis (Vincent's gingivitis and pharyngitis)
• PCN procaine: anthrax due to Bacillus anthracis, including inhalation anthrax (post-exposure). However, CDC does not recommend as first line agent due to beta-lactamase production (see "biodefense-anthrax").
• Actinomycosis
• Empyema
• Pasteurella infections
• Pneumonia, upper respiratory tract infection, Otitis media, venereal infections (penicillin G benzathine suspension), rheumatic fever prophylaxis, chorea prophylaxis, upper bacterial respiratory infection, syphilis and neurosyphilis, glomerulonephritis prophylaxis, prophylaxis for rheumatic fever, rheumatic heart disease, rheumatic chorea.

• Brain Abscess
• Lung Abscess
• Endocarditis (S. viridans)
• Necrotizing Fasciitis (S. pyogenes)
• Gas Gangrene
• Lyme Arthritis
• Neisseria meningitidis
• Neurosyphilis (Treponema pallidum)

FORMS

*Prices represent cost per unit specified and are representative of "Average Wholesale Price" (AWP). AWP Prices were obtained and gathered by Lakshmi Vasist Pharm D using the Red Book, manufacturer's information, and the McKesson database.

^Dosage is indicated in mg unless otherwise noted.

USUAL ADULT DOSING

• Parenteral: Aqueous PCN G:2-4 million units IV q4h.
• Infective endocarditis (IE): 4 million units IV q4h (see resistance section for duration of treatment).
• Skin and soft tissue infections, due to susceptible streptococci (rarely used): PCN benzathine/procaine (Bicillin C-R) 2.4 million units IM x 1.
• Oral: PCN VK:250-500mg PO q6h (amoxicillin generally preferred due to better bioavailability). Twice daily administration may be considered for streptococcal tonsillopharyngitis.
• Syphilis, including primary, secondary, and latent syphilis: PCN benzathine (Bicillin L-A) 2.4 million units x 1 dose. Note: notbe be confused with Bicillin C-R.
• Late (latent) syphilis: PCN benzathine (Bicillin L-A) 2.4 million units x 3 doses at 7-day intervals. Note: not be be confused with Bicillin C-R.
• Neurosyphilis or ocular syphilis: Aqueous PCN G 3-4 million units IV q4h x 14 days. Alternative: Procaine PCN 2.4 million units q24h plus probenecid 500 mg PO q6h x 14 days.
• Note: Benzathine PCN (Bicillin L-A, use for syphilis) and benzathine/procaine PCN (Bicillin C-R use for skin/soft tissue infection) are NOT interchangeable.

RENAL DOSING

ADVERSE DRUG REACTIONS

• Hypersensitivity reaction without anaphylaxis.The most common reaction is idiopathic with a maculopapular or morbilliform rash that occurs in 1-4% of penicillin recipients and 5.2-9.5% of ampicillinrecipients (Lancet 1969;2:969; JAMA 1976;235:918).
• GI intolerance (with oral administration)
• Drug fever
• Coombs' test positive without hemolytic anemia
• Phlebitis at infusion sites and sterile abscesses at IM sites
• Jarisch-Herxheimer reaction (with treatment of syphilis or other spirochetal infections)
• C. difficile-associated colitis

• Anaphylaxis: the frequency of anaphylaxis reaction is reported at 0.004 - 0.015% of PCN courses.
• Hemolytic anemia
• Thrombocytopenia
• Leukopenia
• Interstitial nephritis
• Hepatitis
• Seizure (higher doses in pts with renal failure)

DRUG INTERACTIONS

• Probenecid: increased PCN serum concentration (beneficial if high serum level needed). Avoid co-administration in renal failure.
• Tetracyclines: antagonism, avoid co-administration. Bactericidal effect of penicillins may be diminished in vivo. In two studies involving a total of 79 patients with pneumococcal meningitis treated with either penicillin plus tetracyclines or penicillin monotherapy resulted in a higher mortality rate (79-85%) in the combination therapy compared to penicillin monotherapy (30-33%) [Arch Intern Med 1951:88:489;Ann Intern Med 1961; 55:545]. However there was not a difference in mortality between penicillin monotherapy and penicillin plus tetracyclinein the treatment of pneumococcal pneumonia [Arch Intern Med 1953; 91:197].

SPECTRUM

Detailed Spectrum of Activity

RESISTANCE

• S. pneumoniae: PCN resistance rate was 10.3 % (using resistance break point MIC of 2 mcg/mL), but only 1.2 % (using an MICs of 8 mcg/mL for IV PCN for non-meningeal involvement, MMWR 2008; 57: 1353)Without meningeal involvement, S. pneumoniae with MIC of 2 mcg/mL or lower can be treated with high dose PCN or amoxicillin (3-4 gm/day; CID 2005; 41: 139-48 ).
• S. pneumoniae break points (non-meningeal, oral therapy PCN): < 0.06 mcg/mL (sensitive); 0.12-1.0 mcg/mL (intermediate); > 2 mcg/mL (resistant).
• S. pneumoniaebreak points (non-meningeal, parenteral therapy PCN): < 2 mcg/mL (sensitive); 4 mcg/mL (intermediate); > 8 mcg/mL (resistant).
• S. pneumoniaebreak points (meningeal isolates, PCN): < 0.06 mcg/mL (sensitive); > 0.12 mcg/mL (resistant).
• IE caused by Viridans Group Streptococci and S. bovis with MIC < 0.12 mcg/mL: PCN monotherapy x 4 weeks OR PCN + gentamicin x 2 weeks (short course in uncomplicated cases only).
• IE caused by Viridans Group Streptococci and S. bovis with MIC >0.12 mcg/mL to 0.5 mcg/mL: PCN x 4 weeks + gentamicin x 2 weeks.
• IE caused by Viridans Group Streptococci and S. bovis with MIC >0.5 mcg/mL: PCN + gentamicin x 4-6 weeks.

PHARMACOLOGY

Pharmacology

COMMENTS

• Penicillin skin test: This is useful only for Type I penicillin allergy. The testing requires both major determinants (commercially available as PrePen) and minor determinants (not commercially available in the US). The use of major determinants alone will detect 75-95% of potentially positive reactions; testing with both major and minor determinants will identify 99% (NEJM 1971;285:22). A previous study showed that 80-90% of persons reporting penicillin allergy will have negative tests. The patients who need beta-lactams with a history of penicillin allergy with Type I reactions should have skin testing, and negative results when using both major and minor determinants will assure tolerance without sequelae in over 98%. Frequency of allergic reactions with cephalosporin administration to patients with a positive skin test was 5.6% and for those with a history of penicillin allergy plus a negative test, it was 1.7% (Allergy Clin N Am 1991;11:611).

REFERENCES

REFERENCED WITHIN THIS GUIDE

• Amikacin
• Clindamycin
• Gentamicin
• Gingivitis/periodontitis
• Sexually Transmitted Infections (STIs)
• Sinusitis
• Syphilis