Drug class: Chloramphenicol
VA class: AM150
Molecular formula: C₁₅H₁₅Cl₂N₂NaO₈
CAS number: 982-57-0

Medically reviewed by Drugs.com on Jun 14, 2024. Written by ASHP.

Introduction

Antibacterial; broad-spectrum anti-infective.^{104 110 112}

Uses for Chloramphenicol

Meningitis

Alternative for treatment of meningitis caused by susceptible bacteria, including Haemophilus influenzae,^{110 112 418} Neisseria meningitidis,^{110 418} or Streptococcus pneumoniae.^{110 418} Generally used only when penicillins and cephalosporins are contraindicated or ineffective.^{101 102 104 105 110 197 418}

Despite evidence of in vitro activity against Listeria monocytogenes, has been ineffective for treatment of systemic infections caused by this organism.⁴⁷⁵

Do not use for treatment of meningitis caused by gram-negative bacilli.⁴⁷⁵

Rickettsial Infections

Possible alternative to tetracyclines for treatment of rickettsial infections.^{104 110 112 197 292 500 525 526 529 530} CDC and other experts state that doxycycline is the drug of choice for treatment of all rickettsial infections in all age groups (including children <8 years of age).^{292 500 525} Some of these infections can be rapidly progressive and may be fatal or lead to long-term sequelae; do not delay empiric treatment while waiting for confirmatory testing.^{292 500 525} If considering an alternative to doxycycline, consultation with an expert recommended.⁵²⁵

Possible alternative to doxycycline for treatment of certain tickborne rickettsial diseases, including Rocky Mountain spotted fever (RMSF) caused by Rickettsia rickettsii.^{292 500 525} Doxycycline is drug of choice for treatment of RMSF, regardless of patient age.^{292 500 525} Consider chloramphenicol only in certain patients when doxycycline cannot be used (e.g., those with history of potentially life-threatening allergic reactions to doxycycline, pregnant women).^{292 500 525 530} There is some epidemiologic evidence that risk of death in patients with RMSF is higher in those treated with chloramphenicol than in those treated with a tetracycline;^{292 500 527} close monitoring required if chloramphenicol used.^{292 500 527}

Possible alternative to doxycycline for treatment of endemic typhus (murine typhus; fleaborne typhus) caused by R. typhi or R. felis and for treatment of epidemic typhus (louseborne typhus; sylvatic typhus) caused by R. prowazekii.^{197 292 529 530} Doxycycline is drug of choice for treatment of endemic typhus and epidemic typhus, regardless of patient age.²⁹²

Has been used for treatment of scrub typhus caused by Orientia tsutsugamushi;^{110 178 197 526} recommended as possible alternative to doxycycline.^{197 526 529} Consider that chloramphenicol resistance and persistence or relapse reported.^{110 178}

Do not use for treatment of anaplasmosis caused by Anaplasma phagocytophilum (also known as human granulocytic anaplasmosis; HGA) or ehrlichiosis caused by Ehrlichia chaffeensis (also known as human monocytic ehrlichiosis; HME).^{159 500} Doxycycline is drug of choice for treatment of human ehrlichiosis and anaplasmosis, regardless of patient age.^{159 292 500} Chloramphenicol considered ineffective; use not supported by results of in vitro susceptibility testing.^{159 500}

Typhoid Fever and Other Severe Salmonella Infections

Has been used for treatment of typhoid fever (enteric fever) caused by susceptible Salmonella enterica serovar Typhi^{104 110 112 134 136 139 140 173 174 175 183 197} and treatment of paratyphoid fever caused by S. enterica serovar Paratyphi.^{110 140 174}

Although chloramphenicol was a drug of choice for treatment of infections caused by typhoidal Salmonella in the past,^{104 173 175 183} multidrug-resistant strains of S. enterica serovar Typhi (i.e., strains resistant to ampicillin, chloramphenicol, and/or co-trimoxazole) are reported worldwide and common in many regions of the world.^{173 175 183 292} Whenever possible, select anti-infectives for treatment of typhoid fever based on results of in vitro susceptibility testing.^{175 292}

Do not use to treat typhoid carrier state.^{104 110 112} Depending on susceptibility of the strain, a fluoroquinolone (e.g., ciprofloxacin), ampicillin, amoxicillin, or co-trimoxazole usually recommended to treat typhoid carrier state.^{173 175 197 292}

Do not use for treatment of uncomplicated Salmonella gastroenteritis.^{104 110}

Anthrax

Alternative for treatment of anthrax^{† [off-label]}.^{104 668 670 671 672 673 680 683}

Has in vitro activity against Bacillus anthracis,^{161 668} but limited clinical data exist regarding use in the treatment of anthrax.^{668 680}

Although chloramphenicol has been suggested as an alternative for treatment of naturally occurring anthrax in patients hypersensitive to penicillins or as one of several options for use in multiple-drug regimens for treatment of anthrax,⁶⁷⁰ WHO states chloramphenicol is no longer recommended for such infections because evidence of in vivo efficacy in treatment of severe anthrax is lacking and the drug is associated with serious adverse effects.⁶⁸⁰

For treatment of inhalational anthrax that occurs as the result of exposure to B. anthracis spores in the context of biologic warfare or bioterrorism, CDC, AAP, and the US Working Group on Civilian Biodefense recommend initial treatment with a multiple-drug parenteral regimen that includes a fluoroquinolone (preferably ciprofloxacin) or doxycycline and 1 or 2 additional anti-infectives predicted to be effective (e.g., clindamycin, rifampin, a carbapenem [doripenem, imipenem, meropenem], chloramphenicol, vancomycin, penicillin, ampicillin, linezolid, gentamicin, clarithromycin).^{668 671 672 673 683}

For treatment of systemic anthrax with possible or confirmed meningitis, CDC and AAP recommend a regimen of IV ciprofloxacin with an IV bactericidal anti-infective (preferably meropenem) and an IV protein synthesis inhibitor (preferably linezolid).^{671 672 673} These experts recommend IV chloramphenicol as a possible alternative to linezolid, but use only if clindamycin and rifampin not available.^{671 672 673}

Burkholderia Infections

Has been used in patients with cystic fibrosis¹¹² and has been recommended as an alternative for treatment of infections caused by Burkholderia cepacia^{† [off-label]}.¹⁹⁷ However, B. cepacia usually resistant to chloramphenicol in vitro.^{104 110} Optimum treatment regimens for chronic B. cepacia complex infections not identified; select treatment regimen based on in vitro susceptibility data and previous clinical responses.¹⁷⁷ Anti-infectives that have been recommended include meropenem, imipenem, co-trimoxazole, ceftazidime, doxycycline, and chloramphenicol;²⁹² some experts recommend use of multiple-drug regimens.²⁹²

Has been used in conjunction with doxycycline and co-trimoxazole for treatment of melioidosis^{† [off-label]} caused by B. pseudomallei.^{154 176 197} Ceftazidime or a carbapenem (either meropenem or imipenem) usually drugs of choice for initial treatment,^{104 110 152 153 154 156 180 197 292} followed by long-term treatment (≥3 months) with an oral anti-infective (e.g., co-trimoxazole, amoxicillin and clavulanate potassium, doxycycline).^{104 180 292} B. pseudomallei may be difficult to eradicate and relapse of melioidosis may occur, especially if there is poor compliance with the follow-up regimen.^{104 152 153 154 156 180}

Plague

Alternative for treatment of plague^{† [off-label]} caused by Yersinia pestis, including naturally occurring or endemic plague or pneumonic plague that occurs following exposure to Y. pestis in the context of biologic warfare or bioterrorism.^{133 197 292 683 689}

Streptomycin (or gentamicin) historically considered drug of choice for treatment of plague.^{104 197 292 683 688} Alternatives include fluoroquinolones (ciprofloxacin, levofloxacin, moxifloxacin), doxycycline (or tetracycline), chloramphenicol, or co-trimoxazole (may be less effective than other alternatives).^{104 292 683 688}

Chloramphenicol considered a drug of choice for treatment of plague meningitis.^{104 292 683}

Tularemia

Alternative for treatment of tularemia^{† [off-label]} caused by Francisella tularensis,^{133 197 683 689} including naturally occurring or endemic tularemia or tularemia that occurs following exposure to F. tularensis in the context of biologic warfare or bioterrorism.^{683 689}

Streptomycin (or gentamicin) generally considered drug of choice for treatment of tularemia.^{104 197 292 683 689} Alternatives include tetracyclines (doxycycline), chloramphenicol, or ciprofloxacin.^{197 292 683 689}

Some clinicians state reserve chloramphenicol for treatment of tularemic meningitis (usually in conjunction with streptomycin)^{104 683} and do not use for other forms of tularemia.¹⁰⁴

Chloramphenicol Dosage and Administration

General

• Because differences between therapeutic and toxic plasma concentrations of chloramphenicol are narrow and because of interindividual differences in metabolism and elimination of the drug, most clinicians recommend that plasma concentrations of chloramphenicol be monitored in all patients receiving the drug and dosage adjusted accordingly.^{101 102 104 105 107 108 109 110 112 114 115 179 184 301}

• Blood samples to measure peak plasma concentrations of chloramphenicol usually obtained 0.5–1.5 hours after an IV dose.^{179 184 301}

• Generally adjust chloramphenicol dosage to maintain plasma concentrations of 5–20 mcg/mL (usually 10–20 mcg/mL).^{101 102 104 105 107 108 110 179} In pediatric patients beyond the neonatal period, AAP suggests adjusting dosage to maintain target plasma concentrations of 15–25 mcg/mL.²⁹² Some clinicians suggest adjusting dosage in pediatric patients to maintain peak plasma concentrations of 15–25 mcg/mL for treatment of meningitis or 10–20 mcg/mL for treatment of other infections.¹⁸⁴

• Chloramphenicol plasma concentrations >25 mcg/mL have been associated with toxicity.^{104 179}

• Use no longer than necessary to eradicate the infection with little or no risk of relapse;¹¹² switch IV chloramphenicol to an appropriate oral anti-infective as soon as feasible.¹¹²

• Avoid repeated courses of chloramphenicol if possible.¹¹²

Administration

Administer IV.¹¹²

Has been administered IM^†,^{104 108 110 113} but plasma concentrations unpredictable following IM injection.¹⁰⁴ Manufacturer states do not give IM since this route may be ineffective.¹¹²

Has been administered orally as the base or palmitate;^{104 110} oral preparations no longer commercially available in US.

IV Administration

Reconstitution

Reconstitute vial containing 1 g of chloramphenicol (as the sodium succinate) by adding 10 mL of aqueous diluent (e.g., sterile water for injection, 5% dextrose injection) to provide a solution containing 100 mg/mL.¹¹²

Rate of Administration

Inject appropriate dose of reconstituted solution IV over ≥1 minute.¹¹²

Has been given by intermittent IV infusion^† over 15–60 minutes.^{55 104 110 301}

Dosage

Available as chloramphenicol sodium succinate; dosage expressed in terms of chloramphenicol.¹¹²

Pediatric Patients

General Dosage for Neonates

IV

Manufacturer states 25 mg/kg daily given in 4 equally divided doses every 6 hours usually provides and maintains blood and tissue concentrations adequate for most indications.¹¹² After first 2 weeks of life, manufacturer states full-term neonates may receive up to 50 mg/kg daily given in 4 equally divided doses every 6 hours.¹¹² If higher dosage required for treatment of severe infections, use such dosage only to maintain blood concentrations within a therapeutically effective range.¹¹²

Some clinicians recommend loading dose of 20 mg/kg followed 12 hours later by maintenance dosage based on age and weight.¹⁸⁴ These clinicians recommend maintenance dosage of 25 mg/kg once every 24 hour in neonates ≤7 days of age.¹⁸⁴ In neonates >7 days of age, these clinicians recommend maintenance dosage of 25 mg/kg once every 24 hours in those weighing ≤2 kg and 25 mg/kg once every 12 hours in those weighing >2 kg.¹⁸⁴

Other clinicians recommend loading dose of 20 mg/kg followed 12 hours later by a different maintenance dosage based on age and weight.³⁰¹ In premature neonates, these clinicians recommend maintenance dosage of 22 mg/kg once every 24 hours in those weighing ≤1.2 kg and 25 mg/kg once every 24 hours in those ≤1 week of age weighing ≤2 kg.³⁰¹ In full-term neonates, these clinicians recommend maintenance dosage of 25 mg/kg daily in divided doses every 12 hours in those <2 weeks of age and 25–50 mg/kg daily in divided doses every 12 hours in those 2–4 weeks of age.³⁰¹

Use with caution in neonates because immature metabolic processes in this age group may result in excessive plasma concentrations of chloramphenicol.¹¹² (See Pediatric Use under Cautions.)

General Dosage for Pediatric Patients Beyond the Neonatal Period

IV

Manufacturer states 50 mg/kg daily given in 4 divided doses every 6 hours provides blood concentrations adequate for most indications in pediatric patients.¹¹² Manufacturer states up to 100 mg/kg daily may be required for severe infections (e.g., bacteremia, meningitis), especially when adequate CSF concentrations desired;¹¹² reduce dosage to 50 mg/kg daily as soon as possible.¹¹²

AAP recommends 50–100 mg/kg daily given in 4 divided doses for severe infections.²⁹²

General Dosage for Pediatric Patients with Immature Metabolic Processes

IV

Manufacturer states 25 mg/kg daily usually produces therapeutic blood concentrations in young infants and other pediatric patients in whom immature metabolic functions are suspected.¹¹²

Carefully monitor chloramphenicol concentrations because high concentrations may occur and tend to increase with succeeding doses.¹¹² (See Pediatric Use under Cautions.)

Rickettsial Infections

IV

Children: 12.5–25 mg/kg every 6 hours for 5–10 days recommended by some clinicians.^{526 530}

Known or suspected RMSF: Initiate anti-infective treatment promptly and continue for ≥3 days after fever subsides and until there is evidence of clinical improvement.^{292 500} Minimum duration of treatment is 5–7 days;^{292 500} longer duration may be required for severe or complicated disease.⁵⁰⁰

If considering chloramphenicol for treatment of rickettsial infection, expert consultation recommended.⁵²⁵ (See Rickettsial Infections under Uses.)

Typhoid Fever and Other Severe Salmonella Infections

IV

Children ≥2 years of age: 60 mg/kg daily in 4 divided doses has been given until defervescence, followed by 40 mg/kg daily in 4 divided doses to complete 14 days of treatment.¹³⁴

Children ≥14 years of age: 50 mg/kg daily in 4 divided doses (up to 3 g daily) has been given for 14 days.¹⁴⁰

To lessen possibility of relapse, some clinicians recommend adjusting dosage to provide therapeutic plasma concentrations and continuing treatment for 8–10 days after patient becomes afebrile.¹¹²

Anthrax†

Treatment of Systemic Anthrax (Naturally Occurring or Endemic Exposure)†

IV

Children: 50–75 mg/kg daily given in divided doses every 6 hours has been recommended.⁶⁷⁰ Usual duration is ≥14 days after symptoms abate.⁶⁷⁰

Treatment of Systemic Anthrax (Biologic Warfare or Bioterrorism)†

IV

Full-term or preterm neonates: AAP recommends 25 mg/kg daily given as a single daily dose in those ≤7 days of age and 50 mg/kg daily given in divided doses every 12 hours in those 1–4 weeks of age.⁶⁷¹

Children ≥1 month of age: AAP recommends 100 mg/kg daily given in divided doses every 6 hours.⁶⁷¹

Used as part of a multiple-drug regimen;⁶⁷¹ continue parenteral regimen for ≥2–3 weeks until patient is clinically stable and can be switched to appropriate oral anti-infectives.⁶⁷¹

Plague†

Treatment of Plague (Biologic Warfare or Bioterrorism)†

IV

Children ≥2 years of age: 25 mg/kg 4 times daily (adjust dosage to maintain plasma concentrations of 5–20 mcg/mL) recommended by some experts (e.g., the US Working Group on Civilian Biodefense).⁶⁸⁸ Other experts (e.g., US Army Medical Research Institute of Infectious Diseases [USAMRIID]) recommend loading dose of 25 mg/kg followed by 15 mg/kg every 6 hours (adjust dosage based on plasma concentrations).⁶⁸³

Can be switched to an oral anti-infective when clinically indicated; total duration of treatment usually 10–14 days.^{683 688}

Tularemia†

Treatment of Tularemia (Biologic Warfare or Bioterrorism)†

IV

Children: 15 mg/kg 4 times daily recommended by some experts (e.g., the US Working Group on Civilian Biodefense).⁶⁸⁹

Can be switched to an oral anti-infective when clinically indicated; total duration of treatment usually 14–21 days.⁶⁸⁹

Treatment of Tularemic Meningitis†

IV

Children: 15 mg/kg every 6 hours (up to 4 g daily) given for 14–21 days in conjunction with streptomycin (or gentamicin).¹⁰⁴

Adults

General Dosage for Adults

IV

Manufacturer recommends 50 mg/kg daily given in divided doses every 6 hours.¹¹²

Infections caused by less susceptible organisms: Manufacturer states up to 100 mg/kg daily may be required.¹¹² However, because of concern that toxic plasma chloramphenicol concentrations may occur with this high dosage, some clinicians suggest that 75 mg/kg daily be used initially for treatment of these infections.^{102 105} Reduce dosage to 50 mg/kg daily as soon as possible.¹¹²

Rickettsial Infections

IV

60–75 mg/kg daily in 4 divided doses for 5–10 days recommended by some clinicians.^{526 530}

Scrub typhus caused by O. tsutsugamushi: 50–100 mg/kg daily (up to 3 g daily) in divided doses every 6 hours has been recommended.⁵²⁶

Known or suspected RMSF: Initiate anti-infective treatment promptly and continue for ≥3 days after fever subsides and until there is evidence of clinical improvement.⁵⁰⁰ Minimum duration of treatment is 5–7 days;⁵⁰⁰ longer duration may be required for severe or complicated disease.⁵⁰⁰

If considering chloramphenicol for treatment of rickettsial infection, expert consultation recommended.⁵²⁵ (See Rickettsial Infections under Uses.)

Typhoid Fever and Other Salmonella Infections

IV

50 mg/kg daily in 4 divided doses given for 14 days has been used.¹⁴⁰ Alternatively, 60 mg/kg daily in 4 divided doses has been given until defervescence, followed by 40 mg/kg daily in 4 divided doses to complete 14 days of treatment.¹³⁴

To lessen possibility of relapse, some clinicians recommend adjusting dosage to provide therapeutic plasma concentrations and continuing treatment for 8–10 days after patient becomes afebrile.¹¹²

Anthrax†

Treatment of Systemic Anthrax (Naturally Occurring or Endemic Exposure)†

IV

50–100 mg/kg daily in divided doses every 6 hours has been recommended.⁶⁷⁰ Usual duration is ≥14 days after symptoms abate.⁶⁷⁰

Treatment of Systemic Anthrax (Biologic Warfare or Bioterrorism)†

IV

1 g every 6–8 hours recommended by CDC.^{672 673} Used as part of a multiple-drug parenteral regimen;^{672 673} continue for ≥2–3 weeks until patient is clinically stable and can be switched to appropriate oral anti-infectives.^{672 673}

Plague†

Treatment of Plague (Biologic Warfare or Bioterrorism)†

IV

25 mg/kg 4 times daily (adjust dosage to maintain plasma concentrations of 5–20 mcg/mL) recommended by some experts (e.g., the US Working Group on Civilian Biodefense).⁶⁸⁸ Other experts (e.g., USAMRIID) recommend loading dose of 25 mg/kg followed by 15 mg/kg every 6 hours (adjust dosage based on plasma concentrations).⁶⁸³

Can be switched to an oral anti-infective when clinically indicated; total duration of treatment usually 10–14 days.^{683 688}

Tularemia†

Treatment of Tularemia (Biologic Warfare or Bioterrorism)†

IV

15 mg/kg 4 times daily recommended by some experts (e.g., the US Working Group on Civilian Biodefense).⁶⁸⁹ Other experts (e.g., USAMRIID) recommend 15–25 mg/kg every 6 hours.⁶⁸³

Can be switched to an appropriate oral anti-infective when clinically indicated;⁶⁸⁹ total duration of treatment usually 14–21 days.⁶⁸⁹

Treatment of Tularemic Meningitis†

IV

15–25 mg/kg every 6 hours (up to 4 g daily) given for 14–21 days in conjunction with streptomycin (or gentamicin).¹⁰⁴

Special Populations

Hepatic Impairment

Base dosage on plasma chloramphenicol concentrations, especially in pediatric patients, and adjust accordingly.^{110 112 301}

Renal Impairment

Base dosage on plasma chloramphenicol concentrations, especially in pediatric patients, and adjust accordingly.^{110 112 301}

Geriatric Patients

Select dosage with caution, usually starting at low end of dosage range.¹¹² Consider greater frequency of decreased renal, hepatic, and/or cardiac function in geriatric patients;¹¹² consider monitoring renal function.¹¹² (See Geriatric Use under Cautions.)

Cautions for Chloramphenicol

Contraindications

• Hypersensitivity to chloramphenicol.¹¹²

• Previous toxic reaction to chloramphenicol.¹¹²

• Trivial infections or when not indicated (e.g., colds, influenza, throat infections, prophylaxis).¹¹²

Warnings/Precautions

Warnings

Hematologic Effects

Serious and fatal blood dyscrasias (aplastic anemia, hypoplastic anemia, thrombocytopenia, granulocytopenia) reported with both short-term and prolonged use.¹¹² Aplastic anemia attributed to chloramphenicol, which later terminated in leukemia, has occurred.¹¹²

Two forms of hematologic toxicity may occur with chloramphenicol.^{104 110 112}

Most common type is a dose-related, reversible bone marrow depression.^{104 110 112} Characterized by anemia, leukopenia, reticulocytopenia, thrombocytopenia, increased concentrations of serum iron, increased serum iron-binding capacity, and vacuolization of erythroid and myeloid precursors.^{104 112} More likely to occur in patients receiving chloramphenicol dosage ≥4 g daily and in those with plasma chloramphenicol concentrations >25 mcg/mL.¹⁰⁴ Usually reversible after discontinuance of chloramphenicol.^{104 110 112}

Second type is a rare, but often fatal, irreversible aplastic anemia that does not appear to be dose related.^{104 110 112} Has been associated with a mortality rate >50%.^{104 110} Bone marrow aplasia or hypoplasia may occur weeks or months after the drug was discontinued.¹¹² Pancytopenia frequently observed peripherally, but in some cases only 1 or 2 major cell types (erythrocytes, leukocytes, platelets) may be depressed.¹¹²

Paroxysmal nocturnal hemoglobinuria reported.¹¹² Hemolytic anemia reported when chloramphenicol used in patients with glucose-6-phosphate dehydrogenase deficiency.^{104 110}

Perform adequate hematologic studies prior to and approximately every 2 days during chloramphenicol therapy.¹¹² Patients should be hospitalized during treatment to facilitate appropriate laboratory studies and clinical observation.¹¹² Consider that peripheral blood studies may detect leukopenia, reticulocytopenia, or granulocytopenia before these become irreversible, but cannot be relied on to detect bone marrow depression prior to development of aplastic anemia.¹¹²

Discontinue chloramphenicol if reticulocytopenia, leukopenia, thrombocytopenia, anemia, or any other hematologic abnormalities attributable to the drug occur.¹¹²

Sensitivity Reactions

Hypersensitivity Reactions

Hypersensitivity reactions, including anaphylaxis,¹¹² rash (macular and vesicular),¹¹² angioedema,¹¹² urticaria,¹¹² and fever,¹¹² reported in patients receiving chloramphenicol.

Herxheimer-like reactions reported in patients receiving the drug for treatment of typhoid fever.¹¹²

Other Warnings and Precautions

Gray Syndrome

A type of circulatory collapse, referred to as the gray syndrome, has occurred in neonates and premature infants receiving chloramphenicol.^{104 110 112} Most cases have occurred when the drug was initiated within first 48 hours of life; also reported in older infants and in infants born to mothers who received chloramphenicol during late pregnancy or during labor.^{110 112} (See Pediatric Use under Cautions.)

Similar syndrome has been reported in older children and adults following chloramphenicol overdosage.^{104 110}

May occur because chloramphenicol impairs myocardial contractility by directly interfering with myocardial tissue respiration and oxidative phosphorylation.^{104 110} Has been attributed to high plasma concentrations of the drug.^{104 110 112}

Selection and Use of Anti-infectives

Use only when other potentially less toxic anti-infectives cannot be used or would be ineffective.¹¹² Do not use for trivial infections or when not indicated (e.g., for colds, influenza, throat infections, prophylaxis).¹¹²

When selecting or modifying anti-infective therapy, use results of culture and in vitro susceptibility testing.¹¹² In the absence of such data, consider local epidemiology and susceptibility patterns when selecting anti-infectives for empiric therapy.¹¹²

May be initiated pending results of in vitro susceptibility testing, but discontinue if causative organism found to be susceptible to potentially less toxic anti-infectives.¹¹² Base decision to continue chloramphenicol rather than switching to a less toxic anti-infective on severity of infection, comparative in vitro susceptibility, expected efficacy in the specific infection, and comparative safety profiles of the drugs.¹¹²

Continue chloramphenicol no longer than required to eradicate the infection with little or no risk or relapse.¹¹² Avoid repeated courses of the drug if possible.¹¹²

Nervous System Effects

Optic neuritis,^{104 110 112} rarely resulting in optic atrophy and blindness,^{104 110} reported, usually following long-term therapy.^{104 110 112} Symptoms tend to be reversible, but permanent vision loss may occur.^{104 110} Promptly discontinue chloramphenicol if optic neuritis occurs.¹¹²

Peripheral neuritis reported, usually following long-term therapy.^{104 110 112} Promptly discontinue chloramphenicol if peripheral neuritis occurs.¹¹²

Headache,^{104 110 112} ophthalmoplegia,^{104 110} depression,^{104 110 112} confusion,^{104 110 112} and delirium^{110 112} reported.

Sodium Content

Each 1 g of chloramphenicol in the reconstituted solution contains approximately 52 mg (2.25 mEq) of sodium.¹¹²

Superinfection

As with other anti-infectives, overgrowth of nonsusceptible organisms, including fungi, may occur.¹¹²

Discontinue chloramphenicol and institute appropriate therapy if infection caused by nonsusceptible organisms occurs.¹¹²

Specific Populations

Pregnancy

No adequate and well-controlled studies evaluating chloramphenicol in pregnant women;¹¹² no animal reproduction studies.¹¹²

Studies using oral chloramphenicol (no longer available in US) indicate the drug crosses the placenta.^{110 112}

Use during late pregnancy and during labor has been associated with the gray syndrome and other adverse effects in the fetus or infant.^{110 112} (See Gray Syndrome under Cautions.)

Because of potential toxic effects on the fetus, manufacturer states use chloramphenicol during pregnancy only if potential benefits justify potentials risks to the fetus.¹¹²

Lactation

Studies using oral chloramphenicol (no longer available in US) indicate the drug is distributed into human milk.¹¹²

Potentially could cause serious adverse effects in breast-fed infants.¹¹² (See Gray Syndrome under Cautions.)

Manufacturer states discontinue nursing or the drug, taking into account importance of the drug to the woman.¹¹²

Pediatric Use

Use with caution in premature and full-term neonates and infants because of potential toxicity.¹¹²

Gray syndrome has occurred in neonates and premature infants receiving chloramphenicol.^{104 110 112} Symptoms of gray syndrome in infants usually develop 2–9 days after initiation of chloramphenicol and include abdominal distension (with or without emesis), progressive pallid cyanosis, flaccidity, and vasomotor collapse (frequently accompanied by irregular respiration).^{104 110 112} Can be fatal within a few hours after onset of symptoms;¹¹² may be reversible with complete recovery if chloramphenicol discontinued at early evidence of symptoms.¹¹²

Immature metabolic processes in neonates and infants or other pediatric patients may result in excessive chloramphenicol concentrations.^{104 110 112} Determine plasma concentrations of the drug at appropriate intervals and adjust dosage accordingly.^{110 112} (See General under Dosage and Administration.)

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric adults respond differently than younger patients.¹¹² Other reported clinical experience has not identified differences in responses between geriatric and younger adults.¹¹²

Substantially eliminated by kidneys; increased risk of adverse effects in those with impaired renal function.¹¹² Select dosage with caution because of age-related decreases in renal, hepatic, and/or cardiac function and potential for concomitant disease and drug therapy.¹¹² (See Geriatric Patients under Dosage and Administration.)

Hepatic Impairment

Excessive chloramphenicol concentration may occur in patients with impaired hepatic function.¹¹² Determine chloramphenicol concentrations at appropriate intervals and adjust dosage accordingly.¹¹²

Renal Impairment

Excessive chloramphenicol concentrations may occur in patients with impaired renal function.¹¹² Determine chloramphenicol concentrations at appropriate intervals and adjust dosage accordingly.¹¹²

Common Adverse Effects

Hematologic effects (blood dyscrasias, bone marrow depression), GI effects (nausea, vomiting, diarrhea, glossitis, stomatitis, enterocolitis).¹¹²

Drug Interactions

Inhibits CYP isoenzymes 2C9 and 3A4.^{104 110}

Specific Drugs

Chloramphenicol Pharmacokinetics

Absorption

Bioavailability

Chloramphenicol sodium succinate is a prodrug; inactive until hydrolyzed in vivo to active chloramphenicol.^{102 107 110}

Bioavailability following IV administration varies; considerable interindividual variation in plasma chloramphenicol concentrations.^{101 102 107 109 110 114}

Distribution

Extent

Widely distributed into body tissues and fluids, including ascitic fluid, pleural fluid, synovial fluid, saliva, and aqueous and vitreous humor.^{104 107 110 112} Highest concentrations attained in liver and kidneys.¹¹²

Distributed into CSF, even in absence of meningeal inflammation.^{55 104 110 112} CSF concentrations reported to be ≥50% of concurrent plasma concentrations in patients with uninflamed meninges.^{104 110 112} In 3 neonates 2–6 weeks of age, CSF concentrations were 45–89% of concurrent plasma concentrations.⁵⁵

Crosses the placenta.^{104 107 110 112}

Distributed into human milk.^{104 107 110 112}

Plasma Protein Binding

Approximately 60%.¹⁰⁷

Elimination

Metabolism

Chloramphenicol sodium succinate is hydrolyzed to active chloramphenicol, presumably by esterases in liver, kidneys, and lungs.^{102 107 110} Rate and extent of hydrolysis highly variable.^{101 102 107 109 110 114}

Chloramphenicol is then metabolized principally in the liver to chloramphenicol glucuronide, an inactive metabolite.^{104 110}

Elimination Route

Approximately 30% of an IV dose excreted unchanged in urine,^{102 107} but fraction excreted in urine varies considerably and may range from 6–80%.^{102 107 109 110}

Small amounts of the dose (2–3%) eliminated in bile;^{104 110} about 1% eliminated in feces.^{104 110}

Half-life

Adults with normal renal and hepatic function: 1.2–4.1 hours.^{101 104 107 110}

Neonates and infants: Plasma half-life inversely related to age.¹¹⁰ In one study, plasma half-life was 10–36 hours in neonates 1–8 days of age and 5.5–15.7 hours in infants 11 days to 8 weeks of age.¹¹⁰ Premature infants and neonates have immature mechanisms for glucuronide conjugation and excretion which results in higher and more prolonged chloramphenicol concentrations.^{107 110 112}

Special Populations

Impaired hepatic function: Elimination half-life prolonged and clearance decreased.^{107 110}

Impaired renal function: Elimination half-life not substantially prolonged, but accumulation of inactive conjugated metabolite may occur.¹¹⁰

Stability

Storage

Parenteral

Powder for Injection

20–25°C.¹¹²

Compatibility

Parenteral

Solution CompatibilityHID

Drug Compatibility

Actions and Spectrum

• Usually bacteriostatic in action,^{104 110 112} but may be bactericidal against some organisms.^{104 110}

• Inhibits protein synthesis in susceptible organisms by reversibly binding to peptidyl transferase cavity of the 50S ribosomal subunit of bacterial 70S ribosomes.^{104 110} This prevents aminoacyl-tRNA from binding to the ribosome and terminates polypeptide chain synthesis.¹⁰⁴ Also appears to inhibit protein synthesis in rapidly proliferating mammalian cells;^{26 29 110} dose-related bone marrow depression reported during chloramphenicol therapy may be the result of inhibition of protein synthesis in mitochondria of bone marrow cells.^{29 104 110 181}

• Chloramphenicol sodium succinate is a prodrug and is inactive until hydrolyzed in vivo to active chloramphenicol.^{102 107 110}

• Broad spectrum of activity.^{104 110 112} Active in vitro against many gram-positive and gram-negative aerobic bacteria, some anaerobic bacteria, and some other organisms (e.g., Rickettsia, Chlamydia, Mycoplasma).^{104 110 112} Inactive against Mycobacterium^{104 110} and protozoa.^{104 110}

• Gram-positive aerobes: Active in vitro against S. aureus (including some methicillin-resistant S. aureus [MRSA; also known as oxacillin-resistant S. aureus or ORSA]),^{104 110} S. epidermidis,¹¹⁰ S. pneumoniae¹¹⁰ and other streptococci.¹¹⁰ Has in vitro activity against B. anthracis.^{104 110 161 167 668}

• Gram-negative aerobes: Active in vitro against some strains of H. influenzae,^{104 110 112} H. parainfluenzae,¹¹⁰ Moraxella catarrhalis,^{104 110} N. gonorrhoeae,¹⁰⁴ and N. meningitidis.¹⁰⁴ Active in vitro against some Enterobacteriaceae, including some Citrobacter, Enterobacter, Escherichia coli, Hafnia, Klebsiella, Proteus, Providencia, Salmonella, and Shigella,^{104 110} but susceptibility is variable and many strains are resistant.^{104 110} Aeromonas,¹¹⁰ Bordetella pertussis,¹¹⁰ Brucella,¹¹⁰ Burkholderia mallei,¹¹⁰ Campylobacter jejuni,¹¹⁰ F. tularensis,⁶⁹¹ Helicobacter pylori,¹¹⁰ Legionella pneumophila,¹¹⁰ Pasteurella multocida,¹¹⁰ Vibrio parahaemolyticus,¹¹⁰ and Y. pestis¹¹⁰ usually susceptible. Although V. cholerae usually susceptible, resistance reported.¹¹⁰

• Anaerobes: Active in vitro against Actinomyces,¹¹⁰ Bifidobacterium,¹¹⁰ Clostridium,^{104 110} Eubacterium,¹¹⁰ Lactobacillus,^{104 110} Peptococcus,¹¹⁰ Peptostreptococcus,¹⁰⁴ and Propionibacterium.^{104 110} Also active against Bacteroides fragilis, Fusobacterium, Prevotella, and Veillonella.^{104 110}

• Other organisms: Active against some Rickettsia, including R. rickettsii and causative agents of various typhus fevers.¹¹⁰

• Reported incidence of chloramphenicol resistance in clinical isolates varies considerably worldwide; may be reported more frequently in regions of the world where the drug is still commonly used and has not been reserved for treatment of serious infections.^{104 110}

• Resistance has been reported in staphylococci,^{104 110} S. pneumoniae,^{104 110 126 131} E. coli,¹¹⁰ Salmonella,¹¹⁰ and Shigella.¹¹⁰ Chloramphenicol-resistant H. influenzae^{104 110 125} and N. meningitidis^{110 142} reported rarely.

• Several mechanisms of chloramphenicol resistance reported.¹⁰⁴ A common mechanism is enzymatic acetylation and inactivation by chloramphenicol acetyltransferases (CATs);^{104 110} identified in many different bacteria and may be readily transmitted to other bacteria.¹¹⁰ Other mechanisms involve transmembrane efflux pumps, decreased membrane permeability, or alterations in the 50S ribosomal subunit.^{104 110}

Advice to Patients

• Advise patients that antibacterials (including chloramphenicol) should only be used to treat bacterial infections and should not be used to treat viral infections (e.g., the common cold).¹¹²

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as concomitant illnesses.¹¹²

• Importance of women informing clinician if they are or plan to become pregnant or plan to breast-feed.¹¹²

• Importance of advising patients of other important precautionary information.¹¹² (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

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