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Uses

Endocarditis

Treatment of native valve endocarditis caused by penicillin-susceptible staphylococci. Consider that the majority of staphylococci are resistant to penicillin G and must be treated with a penicillinase-resistant penicillin (e.g., nafcillin, oxacillin).

Treatment of endocarditis caused by Streptococcus pyogenes (group A β-hemolytic streptococci).

Treatment of native valve or prosthetic valve endocarditis caused by viridans streptococci (e.g., S. milleri, S. mitis, S. mutans) or S. bovis (nonenterococcal group D streptococcus). Used alone or in conjunction with gentamicin.

Treatment of enterococcal endocarditis; used in conjunction with an aminoglycoside.

Meningitis and Other CNS Infections

Treatment of meningitis caused by nonpenicillinase-producing S. aureus or S. epidermidis. Consider that the majority of staphylococci are resistant to penicillin G.

Treatment of meningitis caused by susceptible S. pneumoniae. Consider that S. pneumoniae with intermediate resistance or complete resistance to penicillin G have been reported with increasing frequency; treatment failures have occurred when penicillin G was used alone in treatment of CNS infections caused by these strains.

Treatment of meningitis caused by susceptible S. agalactiae (group B streptococci). Ampicillin usually the preferred penicillin for empiric treatment of neonatal S. agalactiae meningitis; treatment can be changed to penicillin G after in vitro susceptibility testing is completed.

Treatment of meningitis caused by L. monocytogenes; used alone or in conjunction with an aminoglycoside (e.g., gentamicin). Ampicillin in conjunction with an aminoglycoside usually is the regimen of choice for L. monocytogenes meningitis.

Treatment of meningitis caused by Neisseria meningitidis. Drug of choice.

Pharyngitis and Tonsillitis

Treatment of pharyngitis and tonsillitis caused by Streptococcus pyogenes (group A β-hemolytic streptococci).

AAP, IDSA, AHA, and others recommend oral penicillin V or IM penicillin G benzathine as treatments of choice; oral cephalosporins and oral macrolides are considered alternatives. Amoxicillin sometimes used instead of penicillin V, especially for young children.

A second episode can be retreated with the same or other treatment of choice; other regimens (amoxicillin and clavulanate, clindamycin, penicillin G benzathine with or without rifampin) recommended for symptomatic patients with multiple, recurrent episodes.

Consider that multiple, recurrent episodes of symptomatic pharyngitis within several months to years may indicate that a streptococcal carrier experiencing repeated episodes of nonstreptococcal (e.g., viral) pharyngitis; treatment not usually recommended for streptococcal pharyngeal carriers.

Respiratory Tract Infections

Treatment of respiratory tract infections caused by susceptible streptococci, including S. pneumoniae. Consider that S. pneumoniae with intermediate resistance or complete resistance to penicillin G have been reported with increasing frequency.

Septicemia

Treatment of bacteremia caused by susceptible streptococci.

Has been used for treatment of bacteremia caused by susceptible Acinetobacter faecalis, Enterobacter aerogenes, Escherichia coli, Proteus mirabilis, Salmonella, and Shigella, but other more effective anti-infectives (e.g., third generation cephalosporins, aminoglycosides, aminopenicillins, extended-spectrum penicillins) are preferred for these infections.

Skin and Skin Structure Infections

Treatment of skin and skin structure infections caused by susceptible staphylococci or streptococci.

Drug of choice for treatment of severe S. pyogenes infections, including cellulitis, erysipelas, and necrotizing fasciitis; if presence of staphylococci is suspected, a penicillinase-resistant penicillin (with or without vancomycin) usually is used.

Actinomycosis

Treatment of actinomycosis; drug of choice for all forms of actinomycosis, including thoracic, abdominal, CNS, and cervicofacial infections.

Anthrax

Treatment of clinically apparent inhalational, GI, or meningeal anthrax or anthrax septicemia caused by susceptible Bacillus anthracis that occurs as the result of natural or endemic exposures to the organism. Considered a drug of choice, but B. anthracis with naturally-occurring penicillin resistance have been reported rarely and there are published reports of strains engineered to have penicillin and tetracycline resistance as well as resistance to other anti-infectives (e.g., macrolides, chloramphenicol, rifampin).

Alternative for use in multiple-drug regimens for treatment of anthrax that occurs as the result of exposure to B. anthracis spores in the context of biologic warfare or bioterrorism. Initiate treatment with IV ciprofloxacin or doxycycline and 1 or 2 anti-infectives predicted to be effective (e.g., chloramphenicol, clindamycin, rifampin, vancomycin, clarithromycin, imipenem, penicillin, ampicillin); if meningitis is established or suspected, use IV ciprofloxacin (rather than doxycycline) and chloramphenicol, rifampin, or penicillin. Because of concerns regarding possible penicillin resistance or induction of penicillin resistance during treatment, use of a penicillin alone is not recommended for treatment of inhalational anthrax that occurs as the result of biologic warfare or bioterrorism when high concentrations of the organism are likely to be present, although penicillin can be included in appropriate combination regimens.

Treatment of mild, uncomplicated cutaneous anthrax caused by susceptible B. anthracis that occurs as the result of naturally occurring or endemic exposure to anthrax. If cutaneous anthrax occurs in the context of biologic warfare or bioterrorism, initial drugs of choice are ciprofloxacin or doxycycline. If penicillin susceptibility is confirmed, consideration can be given to changing to a penicillin in infants and children or in pregnant or lactating women; amoxicillin usually is recommended.

Alternative for postexposure prophylaxis of anthrax following exposure to B. anthracis spores (inhalational anthrax). Ciprofloxacin and doxycycline are initial drugs of choice following suspected or confirmed bioterrorism-related anthrax exposure. If penicillin susceptibility is confirmed, consideration can be given to changing prophylaxis to a penicillin (e.g., amoxicillin, penicillin V, penicillin G procaine) in infants and children and in pregnant or lactating women; amoxicillin usually is recommended.

Clostridium Infections

Treatment of infections caused by Clostridium perfringens, including empyema and gas gangrene. The drug of choice. In treatment of gas gangrene, used as an adjunct to debridement and excision of the infected area; hyperbaric oxygen therapy also may be useful in the management of spreading, necrotic types of infections.

Adjunct to tetanus immune globulin (TIG), tetanus toxoid adsorbed, sedatives, and muscle relaxants in the treatment of active tetanus infection. Although C. tetani is susceptible to penicillin G, the nature of the infected wound generally makes the organism inaccessible to anti-infectives. Anti-infective agents cannot neutralize toxin already formed and cannot eradicate C. tetani spores which may revert to toxin-producing vegetative forms. Treatment of a tetanus wound consists of surgical debridement and prevention of associated infections that could create an anaerobic environment and help proliferation of C. tetani.

Adjunct to active immunization with tetanus toxoid or, preferably, tetanus toxoid adsorbed and passive immunization with TIG in the prophylactic treatment of individuals with tetanus-prone wounds (e.g., a severe deep puncture wound). ACIP states that chemoprophylaxis against tetanus is neither practical nor useful in managing wounds and proper immunization is the most important measure.

Adjunct in the treatment of wound botulism caused by germination of C. botulinum spores in a contaminated wound with in vivo toxin production. Anti-infective agents have no known direct effects on botulinum toxin and therefore are not usually indicated in the management of most forms of botulism (foodborne botulism, infant botulism, adult or child infectious botulism), except for the treatment of secondary infection (e.g., respiratory or urinary tract infections). If anti-infective therapy is needed for the treatment of secondary infection in a patient with botulism, aminoglycosides, tetracyclines, and clindamycin should not be used since these anti-infective agents may exacerbate neuromuscular blockade.

Treatment strategies for most forms of botulism include intensive supportive care (including aggressive use of respiratory care) and prompt administration of botulinum antitoxin when appropriate. Botulinum antitoxin also may be indicated for botulism that occurs in the context of biologic warfare or bioterrorism. Timely administration of botulinum antitoxin is important since it can minimize subsequent nerve damage but will not reverse existent paralysis. Botulinum antitoxin is not commercially available in the US but is available from the CDC.

The mainstay of treatment of foodborne botulism, infant botulism, and adult and child infectious botulism is use of botulinum antitoxin and supportive care. Anti-infectives are not indicated for the treatment of these forms of botulism since lysis of intraluminal C. botulinum may increase the amount of toxin in the body, but anti-infectives may be used for the treatment of secondary infections if necessary.

Diphtheria

Adjunct to diphtheria antitoxin for treatment of diphtheria caused by Corynebacterium diphtheriae. Diphtheria antitoxin is the most important aspect of treatment of respiratory diphtheria. Anti-infectives may eliminate C. diphtheriae from infected sites, prevent spread of the organism and further toxin production, and prevent or terminate the diphtheria carrier state, but appear to be of no value in neutralizing diphtheria toxin and should not be considered a substitute for antitoxin therapy.

Because diphtheria infection often does not confer immunity, active immunization with a diphtheria toxoid preparation should be initiated or completed during convalescence.

Prevention of diphtheria in close contacts of patients with respiratory or cutaneous diphtheria. Prophylaxis is indicated in all household or other close contacts of individuals with suspected or proven diphtheria, regardless of vaccination status; prophylaxis should be initiated promptly and should not be delayed pending culture results. An age-appropriate diphtheria toxoid preparation also may be indicated.

Elimination of diphtheria carrier state in individuals known to carry toxigenic strains of C. diphtheriae.

Erysipelothrix rhusiopathiae Infections

Treatment of infections caused by Erysipelothrix rhusiopathiae, including erysipeloid or endocarditis. A drug of choice.

Leptospirosis

Treatment of leptospirosis†. A drug of choice. Many leptospiral infections are self-limited, and the effectiveness of anti-infective therapy in the treatment of the disease has been questioned. Anti-infective therapy initiated after the fifth day of illness probably will not alter the course of the disease.

Listeria Infections

Treatment of infections caused by L. monocytogenes (e.g., infections during pregnancy, granulomatosis infantiseptica, sepsis, meningitis, endocarditis, foodborne infections). Ampicillin used alone or in conjunction with gentamicin or streptomycin generally is considered the treatment of choice for these infections.

For treatment of foodborne Listeria infections, the CDC recommends use of ampicillin, penicillin G, or co-trimoxazole when there is invasive disease.

Lyme Disease

Treatment of early or late Lyme disease† when a parenteral regimen is indicated.

Treatment of late Lyme disease when neurologic manifestations affecting the CNS or peripheral nervous system are present.

Alternative to IV ceftriaxone or IV cefotaxime for patients with late neurologic disease affecting the CNS or peripheral nervous system (e.g., encephalopathy, neuropathy). Treatment of neurologic (e.g., radicular pain, motor deficits) abnormalities in patients with Lyme meningitis† or arthritis associated with Lyme disease†. Ceftriaxone may be preferable to penicillin G for serious manifestations of early disseminated or late Lyme disease (i.e., those involving major organs) based on ceftriaxone’s greater in vitro and in vivo activity against B. burgdorferi, excellent CSF penetration, and prolonged serum concentrations achievable with once-daily administration.

Necrotizing Ulcerative Gingivitis

Treatment of acute necrotizing ulcerative gingivitis (Vincent’s infection, trench mouth, Fusobacterium gingivitis or pharyngitis, Leptotrichia buccalis infection).

Neisseria Infections

Treatment of upper respiratory tract infections, bacteremia, and meningitis caused by N. meningitidis. (See Meningitis and Other CNS Infections under Uses.) The drug of choice for most meningococcal infections.

Does not eliminate the meningococcus carrier state and should not be used for chemoprophylaxis in asymptomatic N. meningitidis carriers. Ceftriaxone, ciprofloxacin, or rifampin usually used to eliminate nasopharyngeal carriage of N. meningitidis.

Should not be used for treatment of gonorrhea. Previously used for treatment of uncomplicated gonorrhea and disseminated gonococcal infections caused by susceptible nonpenicillinase-producing N. gonorrhoeae. No longer recommended by CDC or other experts (high incidence of penicillinase-producing strains).

Pasteurella Infections

Treatment of infections caused by Pasteurella multocida; a drug of choice for local infections, septicemia, osteomyelitis, endocarditis, or other serious infections.

Rat-bite Fever

Treatment of rat-bite fever caused by Streptobacillus moniliformis (erythema arthriticum epidemicum, Haverhill fever) or Spirillum minus (sodoku). Drug of choice.

Relapsing Fever

Alternative to tetracyclines for treatment of tick-borne (endemic) or louse-borne (epidemic) relapsing fever† caused by Borrelia.

Syphilis

Treatment of syphilis. Penicillin G is drug of choice for all stages and forms of syphilis, including primary infection (i.e., ulcer or chancre at the infection site), secondary infection (i.e., manifestations that include rash, mucocutaneous lesions, and adenopathy), tertiary infection (i.e., cardiac, ophthalmic, auditory, or gummatous lesions), early latent syphilis (latent syphilis acquired within the preceding year), late latent syphilis or latent syphilis of unknown duration, neurosyphilis, and congenital syphilis.

Penicillin G benzathine is drug of choice for treatment of primary syphilis, secondary syphilis, latent syphilis, and tertiary syphilis in adults, adolescents, and children.

Penicillin G potassium or penicillin G sodium is drug of choice for treatment of neurosyphilis in adults and adolescents; alternatively, penicillin G procaine (with oral probenecid) may be used if compliance can be ensured.

Penicillin G potassium or sodium or penicillin G procaine recommended for congenital syphilis (proven or highly probable). Penicillin G benzathine is not recommended for the treatment of known congenital syphilis, but may be used in infants at lower risk of congenital syphilis.

Fixed combination of penicillin G benzathine and penicillin G procaine (Bicillin^® C-R, Bicillin^® C-R 900/300) should not be used for treatment of any form of syphilis since it may not result in the sustained serum concentrations required for syphilis treatment and could increase the risk for treatment failure and neurosyphilis, especially among HIV-infected patients.

Efficacy of currently recommended syphilis treatment regimens may be reduced in HIV-infected patients; higher doses and/or more prolonged duration of therapy may be necessary in these patients. Careful follow-up is recommended in all patients coinfected with syphilis and HIV to assure adequacy of treatment.

There are no proven alternatives to penicillin G for treatment of congenital syphilis or syphilis during pregnancy in patients with penicillin hypersensitivity. These patients should be desensitized, if necessary, and treated with penicillin G.

Whipple's Disease

Treatment of Whipple’s disease† caused by Tropheryma whippelii.

Yaws, Pinta, and Bejel

Treatment of yaws (T. pertenue), pinta (T. carateum), and bejel (T. pallidum var. endemic syphilis). Drug of choice.

Prevention of Perinatal Group B Streptococcal Disease

Prevention of early-onset neonatal group B streptococcal (GBS) disease†.

Intrapartum anti-infective prophylaxis to prevent early-onset neonatal GBS disease is administered to women identified as GBS carriers during routine prenatal GBS screening performed at 35–37 weeks during the current pregnancy and to women who have GBS bacteriuria during the current pregnancy, a previous infant with invasive GBS disease, unknown GBS status with delivery at <37 weeks gestation, amniotic membrane rupture for ≥18 hours, or intrapartum temperature of ≥38°C.

When intrapartum GBS prophylaxis is indicated, IV penicillin G is the drug of choice. Although IV ampicillin can be used, CDC and AAP state that penicillin G is preferred since it has a narrower spectrum of activity and is less likely to select for antibiotic-resistant organisms.

Prevention of Rheumatic Fever Recurrence

Prevention of recurrence of rheumatic fever (secondary prophylaxis). Continuous prophylaxis recommended following treatment of documented rheumatic fever (even if manifested solely by Sydenham chorea) and in those with evidence of rheumatic heart disease.

AHA recommends IM penicillin G benzathine, oral penicillin V, or oral sulfadiazine for such prophylaxis.