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Table 1.  

Population Category Antimicrobial*,†
Class
Dosage§
Adults
aged ≥18 yrs
First-line Ciprofloxacin
Fluoroquinolone
400 mg every 8 hrs IV or
750 mg every 12 hrs PO
Levofloxacin
Fluoroquinolone
750 mg every 24 hrs IV or PO
Moxifloxacin
Fluoroquinolone
400 mg every 24 hrs IV or PO
Gentamicin
Aminoglycoside
5 mg/kg every 24 hrs IV or IM
Streptomycin**
Aminoglycoside
1 g every 12 hrs IV†† or IM
Alternatives Doxycycline
Tetracycline
200 mg loading dose, then 100 mg every 12 hrs IV or PO
Chloramphenicol¶,**
Amphenicol
12.5–25 mg/kg every 6 hrs IV§§
(maximum 1 g/dose)
Ofloxacin¶,¶¶
Fluoroquinolone
400 mg every 12 hrs PO***
Gemifloxacin
Fluoroquinolone
320 mg every 24 hrs PO
Amikacin
Aminoglycoside
15–20 mg/kg every 24 hrs IV or IM
Tobramycin
Aminoglycoside
5–7 mg/kg every 24 hrs IV or IM
Plazomicin¶,**
Aminoglycoside
15 mg/kg every 24 hrs IV
Trimethoprim-sulfamethoxazole
Sulfonamide
5 mg/kg (trimethoprim component) every 8 hrs
IV or PO
Children
aged ≥1 mos to ≤17 yrs (unless otherwise noted)
First-line Ciprofloxacin
Fluoroquinolone †††
10 mg/kg every 8 or 12 hrs IV or
15 mg/kg every 8 or 12 hrs PO
(maximum 400 mg/dose IV, 500 mg/dose every 8 hrs PO, or 750 mg/dose every 12 hrs PO)
Levofloxacin
Fluoroquinolone †††
Body weight <50 kg: 8 mg/kg every 12 hrs IV or PO
(maximum 250 mg/dose)
Body weight ≥50 kg:
500–750 mg every 24 hrs IV or PO
Gentamicin
Aminoglycoside
4.5–7.5 mg/kg every 24 hrs IV or IM
Streptomycin**
Aminoglycoside
15 mg/kg every 12 hrs IV†† or IM
(maximum 1 g/dose)
Alternatives Doxycycline
Tetracycline †††
Body weight <45 kg: 4.4 mg/kg loading dose, then 2.2 mg/kg every 12 hrs IV or PO
Body weight ≥45 kg: 200 mg loading dose, then 100 mg every 12 hrs IV or PO
Chloramphenicol¶,**
Amphenicol
12.5–25 mg/kg every 6 hrs IV§§
(maximum 1 g/dose)
Moxifloxacin§§§
Fluoroquinolone †††
Infants and children aged ≥3 mos to ≤23 mos:
6 mg/kg every 12 hrs IV or PO¶¶¶
Children aged 2–5 yrs: 5 mg/kg every 12 hrs IV or PO¶¶¶
Children aged 6–11 yrs: 4 mg/kg every 12 hrs IV or PO¶¶¶
Children and adolescents aged 12 to 17 yrs:
Body weight <45 kg: 4 mg/kg every 12 hrs IV or PO¶¶¶
Maximum dose for all children <45 kg: 200 mg/dose
Body weight ≥45 kg: 400 mg every 24 hrs IV or PO¶¶¶
Ofloxacin¶,¶¶
Fluoroquinolone †††
7.5 mg/kg every 12 hrs PO***
(maximum 400 mg/dose)
Amikacin
Aminoglycoside
15–20 mg/kg every 24 hrs IV or IM
Tobramycin
Aminoglycoside
4.5–7.5 mg/kg every 24 hrs IV or IM
Trimethoprim-sulfamethoxazole
Sulfonamide
Infants and children aged ≥2 mos to ≤17 yrs:
5 mg/kg (trimethoprim component) every 8 hrs IV or PO

Table 1. Treatment of adults and children with pneumonic or septicemic plague

Abbreviations: IM = intramuscular; IV = intravenous; PO = per os.

Note: All oral antimicrobials recommended in these guidelines can be administered via alternative enteral routes (e.g., nasogastric tube and gastric tube) except for ciprofloxacin.

* Dual therapy with two distinct classes of antimicrobials should be used for initial treatment of patients with severe pneumonic or septicemic plague and patients infected after intentional release of Yersinia pestis.

Antimicrobials are not listed in order of preference within each category.

§ Recommended treatment duration is 10–14 days.

Not approved by the Food and Drug Administration (FDA) for treatment of plague. In some instances, these antimicrobials have been used off label for the treatment of naturally occurring plague[17,19,88]. Large-scale distribution and use of these antimicrobials during a bioterrorism response might be under FDA-issued Emergency Use Authorization.

** At the time of publication, these antimicrobials might not be readily and consistently available in the United States because of limited production.

†† The IV formulation of streptomycin is not approved by FDA; however, the IM formulation of streptomycin has been given intravenously as an off-label use (Sources: Morris JT, Cooper RH. Intravenous streptomycin: a useful route of administration. Clin Infect Dis 1994;19:1150–1. Pérez Tanoira R, Sánchez-Patán F, Jiménez Girón A. et al. Tolerance and safety of intravenous streptomycin therapy in patients with tuberculosis. Infection 2014;42:597–8).

§§ The lower end of the chloramphenicol dosing range (12.5 mg/kg every 6 hours) is sufficient for treatment of plague in most cases. Severe infections might require increased dosing, but these doses should be decreased as soon as feasible (Sources: Chloramphenicol sodium succinate [Package insert]. Lake Zurich, IL: Fresenius Kabl, LLC; 2019. Chloromycetin sodium succinate [Package insert]. Bristol, TN: Monarch Pharmaceuticals, LLC; 2004). Serum concentration monitoring should be performed when available, especially in children.

¶¶ Additional fluoroquinolone alternatives, such as delafloxacin, also can be considered depending on drug availability.

*** Ofloxacin suspension for oral liquid administration is not available in the United States.

††† Data on use of fluoroquinolones and doxycycline in infants and young children are limited.

§§§ Moxifloxacin is not FDA approved for use in children aged ≤17 years but has been used off label[79]. Data on use in neonates and children aged ≤2 months are extremely limited; however, successful use in neonates has been reported (Source: Watt KM, Massaro MM, Smith B, Cohen-Wolkowiez M, Benjamin DK Jr, Laughon MM. Pharmacokinetics of moxifloxacin in an infant with Mycoplasma hominis meningitis. Pediatr Infect Dis J 2012;31:197–9). For children aged 12–17 years weighing ≥45 kg with risk factors for cardiac events, consider 200 mg twice daily to reduce risk for QT prolongation.

¶¶¶ Although no commercial liquid formulation is available for moxifloxacin, hospitals and compounding retail pharmacies can use a published recipe to make liquid suspension.

Table 2.  

Population Category Antimicrobial*,†
Class
Dosage§
Adults aged ≥18 yrs First-line Ciprofloxacin
Fluoroquinolone
400 mg every 8 hrs IV or
750 mg every 12 hrs PO
Levofloxacin
Fluoroquinolone
750 mg every 24 hrs IV or PO
Moxifloxacin
Fluoroquinolone
400 mg every 24 hrs IV or PO
Doxycycline
Tetracycline
200 mg loading dose, then 100 mg every 12 hrs IV or PO
Gentamicin
Aminoglycoside
5 mg/kg every 24 hrs IV or IM
Streptomycin**
Aminoglycoside
1 g every 12 hrs IV†† or IM
Alternatives Chloramphenicol¶,**
Amphenicol
12.5–25 mg/kg every 6 hrs IV§§
(maximum 1 g/dose)
Ofloxacin¶,¶¶
Fluoroquinolone
400 mg every 12 hrs PO***
Gemifloxacin
Fluoroquinolone
320 mg every 24 hrs PO
Amikacin
Aminoglycoside
15–20 mg/kg every 24 hrs IV or IM
Tobramycin
Aminoglycoside
5–7 mg/kg every 24 hrs IV or IM
Plazomicin¶,**
Aminoglycoside
15 mg/kg every 24 hrs IV
Tetracycline
Tetracycline
500 mg every 6 hrs PO
Omadacycline
Tetracycline
200 mg loading dose on day 1,
then 100 mg every 24 hrs IV or
450 mg loading dose every 24 hrs on days 1 and 2, then 300 mg every 24 hrs PO
Minocycline
Tetracycline
200 mg loading dose, then 100 mg every 12 hrs IV or PO
Eravacycline
Tetracycline
1 mg/kg every 12 hrs IV
Trimethoprim-sulfamethoxazole
Sulfonamide
5 mg/kg (trimethoprim component) every 8 hrs IV or PO
Children aged ≥1 mos to ≤17 yrs (unless otherwise noted) First-line Ciprofloxacin
Fluoroquinolone †††
10 mg/kg every 8 or 12 hrs IV
15 mg/kg every 8 or 12 hrs PO
(maximum 400 mg/dose IV, 500 mg/dose every 8 hrs PO or 750 mg/dose every 12 hrs PO)
Levofloxacin
Fluoroquinolone †††
Body weight <50 kg: 8 mg/kg every 12 hrs IV or PO
(maximum 250 mg/dose)
Body weight 50 kg:
500–750 mg every 24 hrs IV or PO
Doxycycline
Tetracycline †††
Body weight <45 kg:
4.4 mg/kg loading dose, then 2.2 mg/kg every 12 hrs IV or PO
Body weight ≥45 kg:
200 mg loading dose, then 100 mg every 12 hrs IV or PO
Gentamicin
Aminoglycoside
4.5–7.5 mg/kg every 24 hrs IV or IM
Streptomycin**
Aminoglycoside
15 mg/kg every 12 hrs IV†† or IM
(maximum 1 g/dose)
Alternatives Chloramphenicol¶,**
Amphenicol
12.5–25 mg/kg every 6 hrs IV§§
(maximum 1 g/dose)
Moxifloxacin§§§
Fluoroquinolone †††
Infants and children aged ≥3 mos to ≤23 mos:
6 mg/kg every 12 hrs IV or PO¶¶¶
Children aged 2–5 yrs: 5 mg/kg every 12 hrs IV or PO¶¶¶
Children aged 6–11 yrs: 4 mg/kg every 12 hrs IV or PO¶¶¶
Children and adolescents aged 12 to ≤17 yrs:
Body weight <45 kg: 4 mg/kg every 12 hrs IV or PO¶¶¶
Maximum dose for all children <45 kg: 200 mg/dose
Body weight ≥45 kg: 400 mg every 24 hrs IV or PO¶¶¶
Ofloxacin¶,¶¶
Fluoroquinolone †††
7.5 mg/kg every 12 hrs PO***
(maximum 400 mg/dose)
Amikacin
Aminoglycoside
15–20 mg/kg every 24 hrs IV or IM
Tobramycin
Aminoglycoside
4.5–7.5 mg/kg every 24 hrs IV or IM
Tetracycline
Tetracycline †††
10 mg/kg every 6 hrs PO
(maximum 500 mg/dose)
Minocycline
Tetracycline †††
4 mg/kg loading dose (maximum dose 200 mg), then 2 mg/kg every 12 hrs IV or PO (maximum 100 mg/dose)
Trimethoprim-sulfamethoxazole
Sulfonamide
Infants and children aged ≥2 mos to ≤17 yrs: 5 mg/kg (trimethoprim component) every 8 hrs IV or PO

Table 2. Treatment of adults and children with bubonic or pharyngeal plague

Abbreviations: IM = intramuscular; IV = intravenous; PO = per os.

Note: All oral antimicrobials recommended in these guidelines can be administered via alternative enteral routes (e.g., nasogastric tube and gastric tube) except for ciprofloxacin.

*Monotherapy is recommended for patients with naturally occurring plague, although dual therapy can be considered for patients with large buboes. Dual therapy with two distinct classes of antimicrobials should be used for initial treatment of patients infected after intentional release of Yersinia pestis.

Antimicrobials are not listed in order of preference within each category.

§ Recommended treatment duration is 10–14 days.

Not approved by the Food and Drug Administration (FDA) for treatment of plague. In some instances, these antimicrobials have been used off label for the treatment of naturally occurring plague[17,19,88]. Large-scale distribution and use of these antimicrobials during a bioterrorism response might be under FDA-issued Emergency Use Authorization.

** At the time of publication, these antimicrobials might not be readily and consistently available in the United States because of limited production.

†† The IV formulation of streptomycin is not approved by FDA; however, the IM formulation of streptomycin has been given intravenously as an off-label use (Sources: Morris JT, Cooper RH. Intravenous streptomycin: a useful route of administration. Clin Infect Dis 1994;19:1150–1. Pérez Tanoira R, Sánchez-Patán F, Jiménez Girón A. et al. Tolerance and safety of intravenous streptomycin therapy in patients with tuberculosis. Infection 2014;42:597–8).

§§ The lower end of the chloramphenicol dosing range (12.5 mg/kg every 6 hours) is sufficient for treatment of plague in most cases. Severe infections might require increased dosing, but these doses should be decreased as soon as feasible. (Sources: Chloramphenicol sodium succinate [Package insert]. Lake Zurich, IL: Fresenius Kabl, LLC; 2019. Chloromycetin sodium succinate [Package insert]. Bristol, TN: Monarch Pharmaceuticals, LLC; 2004). Serum concentration monitoring should be performed when available, especially in children.

¶¶ Additional fluoroquinolone alternatives, such as delafloxacin, also can be considered depending on drug availability.

*** Ofloxacin suspension for oral liquid administration is not available in the United States.

††† Data on use of fluoroquinolones and tetracyclines in infants and young children are limited. Because of the risk for permanent tooth discoloration and tooth enamel hypoplasia, tetracycline and minocycline should only be used for children aged <8 years when other treatment options have been exhausted.

§§§ Moxifloxacin is not FDA approved for use in children aged ≤17years but has been used off label[79]. Data on use in neonates and children aged ≤2 months are extremely limited; however, successful use in neonates has been reported (Source: Watt KM, Massaro MM, Smith B, Cohen-Wolkowiez M, Benjamin DK Jr, Laughon MM. Pharmacokinetics of moxifloxacin in an infant with Mycoplasma hominis meningitis. Pediatr Infect Dis J 2012;31:197–9). For children aged 12–17 years weighing ≥45 kg with risk factors for cardiac events, consider 200 mg twice daily to reduce risk for QT prolongation.

¶¶¶ Although no commercial liquid formulation is available for moxifloxacin, hospitals and compounding retail pharmacies can use a published recipe to make liquid suspension.

Table 3.  

Population Category Antimicrobial*
Class
Dosage
Adults
aged ≥18 yrs
First-line†,§ Chloramphenicol¶,**
Amphenicol
25 mg/kg every 6 hrs IV††
(maximum 1 g/dose)
Levofloxacin
Fluoroquinolone
750 mg every 24 hrs IV or PO
Moxifloxacin
Fluoroquinolone
400 mg every 24 hrs IV or PO
Neonates, infants, and children aged ≤17 yrs (unless otherwise noted) First-line†,§ Chloramphenicol¶,**
Amphenicol
Neonates aged ≤7 days:
25 mg/kg/dose every 24 hrs IV††
Neonates aged 8–28 days:
25 mg/kg/dose every 12 hrs IV††
Infants and children aged ≥29 days
to ≤17 yrs:
25 mg/kg every 6 hrs IV††
(maximum 1 g/dose)
Levofloxacin
Fluoroquinolone §§
Neonates aged ≤28 days:
10 mg/kg/dose every 12 hrs IV
Infants and children aged ≥29 days to ≤17 yrs:
Body weight <50 kg: 8 mg/kg every 12 hrs IV or PO
(maximum 250 mg/dose)
Body weight ≥50 kg: 500–750 mg every 24 hrs IV or PO
Moxifloxacin¶¶
Fluoroquinolone §§
Infants and children aged ≥3 mos to ≤23 mos:
6 mg/kg every 12 hrs IV or PO***
Children aged 2–5 yrs:
5 mg/kg every 12 hrs IV or PO***
Children aged 6–11 yrs:
4 mg/kg every 12 hrs IV or PO***
Children and adolescents aged 12 to ≤17 yrs:
Body weight <45 kg:
4 mg/kg every 12 hrs IV or PO***
Maximum dose for all children <45 kg: 200 mg/dose
Body weight ≥45 kg:
400 mg every 24 hrs IV or PO***

Table 3. Treatment of patients of all ages and pregnant women with plague meningitis

Abbreviations: IV = intravenous; PO = per os.

Note: All oral antimicrobials recommended in these guidelines can be administered via alternative enteral routes (e.g., nasogastric tube and gastric tube) except for ciprofloxacin.

*Antimicrobials are not listed in order of preference within each category.

Dual therapy with chloramphenicol plus moxifloxacin or levofloxacin should be used for initial treatment of patients with plague who present with symptoms of meningitis. If chloramphenicol is not available, a nonfluoroquinolone first-line or alternative antimicrobial for treatment of septicemic plague can be substituted Table 1. Recommended treatment duration is 10–14 days.

§ For patients with secondary plague meningitis, chloramphenicol should be added to the patient’s existing antimicrobial treatment regimen for plague. If chloramphenicol is not available, or clinicians would prefer to avoid using this drug in young children because of potential adverse effects, moxifloxacin or levofloxacin can be added to the patient’s existing treatment regimen instead. After chloramphenicol, moxifloxacin, or levofloxacin have been added, the entire regimen of antimicrobials the patient is receiving for plague should be continued for an additional 10 days.

Not approved by the Food and Drug Administration (FDA) for treatment of plague. Chloramphenicol has been used off label for the treatment of naturally occurring plague[17,19,88]. Large-scale distribution and use of these antimicrobials during a bioterrorism response might be under FDA-issued Emergency Use Authorization.

** At the time of publication, these antimicrobials might not be readily and consistently available in the United States because of limited production.

†† After clinical improvement, chloramphenicol can be reduced to a lower dose of 12.5 mg/kg every 6 hours in adults and given orally. Serum concentration monitoring should be performed when available, especially in children (Source: Tunkel AR, Hartman BJ, Kaplan SL, et al. Practice guidelines for bacterial meningitis. Clin Infect Dis 2004;39:1267–84).

§§ Data on use of fluoroquinolones in infants and young children are limited.

¶¶ Moxifloxacin is not FDA approved for use in children aged ≤17 years but has been used off label[79]. Data on use in neonates and children aged ≤2 months are extremely limited; however, successful use in neonates has been reported (Source: Watt KM, Massaro MM, Smith B, Cohen-Wolkowiez M, Benjamin DK Jr, Laughon MM. Pharmacokinetics of moxifloxacin in an infant with Mycoplasma hominis meningitis. Pediatr Infect Dis J 2012;31:197–9). For children aged 12–17 years weighing ≥45 kg with risk factors for cardiac events, consider 200 mg twice daily to reduce risk for QT prolongation.

*** Although no commercial liquid formulation is available for moxifloxacin, hospitals and compounding retail pharmacies can use a published recipe to make a liquid suspension.

Table 4.  

Population Category Antimicrobial*,†
Class
Dosage§
Adults
aged ≥18 yrs
First-line Ciprofloxacin
Fluoroquinolone
500–750 mg every 12 hrs PO
Levofloxacin
Fluoroquinolone
500–750 mg every 24 hrs PO
Moxifloxacin
Fluoroquinolone
400 mg every 24 hrs PO
Doxycycline
Tetracycline
100 mg every 12 hrs PO
Alternatives Ofloxacin¶,**,††
Fluoroquinolone
400 mg every 12 hrs PO
Gemifloxacin
Fluoroquinolone
320 mg every 24 hrs PO
Tetracycline
Tetracycline
500 mg every 6 hrs PO
Omadacycline
Tetracycline
300 mg every 24 hrs PO
Minocycline
Tetracycline
100 mg every 12 hrs PO
Trimethoprim-
sulfamethoxazole
Sulfonamide
5 mg/kg (trimethoprim component) every 12 hrs PO
Children
aged ≥1 mos to ≤17 yrs (unless otherwise noted)
First-line Ciprofloxacin
Fluoroquinolone §§
15 mg/kg every 12 hrs PO
(maximum 750 mg/dose)
Levofloxacin
Fluoroquinolone §§
Body weight <50 kg: 8 mg/kg every 12 hrs PO
(maximum 250 mg/dose)
Body weight ≥50 kg:
500–750 mg every 24 hrs PO
Doxycycline
Tetracycline §§
Body weight <45 kg:
2.2 mg/kg every 12 hrs PO
Body weight ≥45 kg:
100 mg every 12 hrs PO
Alternatives Moxifloxacin¶¶
Fluoroquinolone §§
Infants and children aged ≥3 mos to ≤23 mos:
6 mg/kg every 12 hrs PO***
Children aged 2–5 yrs:
5 mg/kg every 12 hrs PO***
Children aged 6–11 yrs:
4 mg/kg every 12 hrs PO***
Children and adolescents aged 12 to ≤17 yrs:
Body weight <45 kg: 4 mg/kg every 12 hrs PO***
Maximum dose for all children <45 kg:
200 mg/dose
Body weight ≥45 kg: 400 mg every 24 hrs PO***
Ofloxacin¶,**,††
Fluoroquinolone §§
7.5 mg/kg every 12 hrs PO
(maximum 400 mg/dose)
Tetracycline
Tetracycline §§
10 mg/kg every 6 hrs PO
(maximum 500 mg/dose)
Minocycline
Tetracycline §§
2 mg/kg every 12 hrs PO (maximum 100 mg/dose)
Trimethoprim-sulfamethoxazole
Sulfonamide
Infants and children aged ≥2 mos to ≤17 yrs:
5 mg/kg (trimethoprim component) every 12 hrs PO

Table 4. Pre- and postexposure prophylaxis for adults and children potentially exposed to Yersinia pestis

Abbreviations: PO = per os.

Note: All oral antimicrobials recommended in these guidelines can be administered via alternative enteral routes (e.g., nasogastric tube and gastric tube) except for ciprofloxacin.

* Prophylaxis with a single antimicrobial class is recommended for potentially exposed persons following a case of naturally acquired infection or intentional release of Yersinia pestis, with targeting of drug choice if engineered resistance is detected in the aftermath of a bioterrorism attack.

Antimicrobials are not listed in order of preference within each category.

§ Pre-exposure prophylaxis can be discontinued 48 hours after the last perceived exposure. Recommended duration for postexposure prophylaxis is 7 days.

Not approved by the Food and Drug Administration (FDA) for treatment of plague. In some instances, these antimicrobials have been used off label for the treatment of naturally occurring plague[17,19,88]. Large-scale distribution and use of these antimicrobials during a bioterrorism response might be under FDA-issued Emergency Use Authorization.

** Additional fluoroquinolone alternatives, such as delafloxacin, also can be considered depending on drug availability.

†† Ofloxacin suspension for oral liquid administration is not available in the United States.

§§ Data on use of fluoroquinolones and tetracyclines in infants and young children are limited. Because of the risk for permanent tooth discoloration and tooth enamel hypoplasia, tetracycline and minocycline should only be used for children aged <8 years when other prophylaxis options have been exhausted.

¶¶ Moxifloxacin is not FDA approved for use in children aged ≤17 years but has been used off label (79). Data on use in neonates and children aged ≤2 months are extremely limited; however, successful use in neonates has been reported (Source: Watt KM, Massaro MM, Smith B, Cohen-Wolkowiez M, Benjamin DK Jr, Laughon MM. Pharmacokinetics of moxifloxacin in an infant with Mycoplasma hominis meningitis. Pediatr Infect Dis J 2012;31:197–9). For children aged 12–17 years weighing ≥45 kg with risk factors for cardiac events, consider 200 mg twice daily to reduce risk for QT prolongation.

*** Although no commercial liquid formulation is available for moxifloxacin, hospitals and compounding retail pharmacies can use a published recipe to make liquid suspension.

Table 5.  

Category Antimicrobial*,†
Class
Dosage§,¶
First-line: Gentamicin plus either ciprofloxacin or levofloxacin Ciprofloxacin
Fluoroquinolone
400 mg every 8 hrs IV or
500 mg every 8 hrs PO
Levofloxacin
Fluoroquinolone
750 mg every 24 hrs IV or PO
Gentamicin**
Aminoglycoside
5 mg/kg every 24 hrs IV or IM
Alternatives Moxifloxacin
Fluoroquinolone
400 mg every 24 hrs IV or PO
Ofloxacin**,††
Fluoroquinolone
400 mg every 12 hrs PO
Streptomycin§§
Aminoglycoside
1 g every 12 hrs IV or IM
Amikacin**
Aminoglycoside
15–20 mg/kg every 24 hrs IV or IM
Tobramycin**
Aminoglycoside
5–7 mg/kg every 24 hrs IV or IM
Plazomicin**,§§
Aminoglycoside
15 mg/kg every 24 hrs IV
Doxycycline
Tetracycline
200 mg loading dose IV, then
100 mg every 12 hrs IV or PO or
200 mg every 24 hrs IV
Chloramphenicol**,§§
Amphenicol
12.5–25 mg/kg every 6 hrs IV¶¶
(maximum 1 g/dose)
Trimethoprim-sulfamethoxazole**
Sulfonamide
5 mg/kg (trimethoprim component) every 8 hrs IV or PO

Table 5. Treatment of pregnant women with pneumonic, septicemic, bubonic, or pharyngeal plague

Abbreviations: IM = intramuscular; IV = intravenous; PO = per os.

Note: All oral antimicrobials recommended in these guidelines can be administered via alternative enteral routes (e.g., nasogastric tube and gastric tube) except for ciprofloxacin.

* Dual therapy with distinct classes of antimicrobials is recommended for treatment of plague in pregnant women caused by naturally acquired infection or intentional release of Yersinia pestis.

Antimicrobials are not listed in order of preference within each category.

§ Recommended treatment duration is 10–14 days.

Parenteral administration is preferred route for all antimicrobials initially, when applicable.

** Not approved by the Food and Drug Administration (FDA) for treatment of plague. In some instances, these antimicrobials have been used off label for the treatment of naturally occurring plague[17,19,88]. Large-scale distribution and use of these antimicrobials during a bioterrorism response might be under FDA-issued Emergency Use Authorization.

†† Additional fluoroquinolone alternatives, such as gemifloxacin and delafloxacin, also can be considered depending on drug availability.

§§ At the time of publication, these antimicrobials might not be readily and consistently available in the United States because of limited production.

¶¶ The lower end of the chloramphenicol dosing range (12.5 mg/kg every 6 hours) is sufficient for treatment of plague in most cases. Severe infections might require increased dosing, but these doses should be decreased as soon as feasible (Sources: Chloramphenicol sodium succinate [Package insert]. Lake Zurich, IL: Fresenius Kabl, LLC; 2019. Chloromycetin sodium succinate [Package insert]. Bristol, TN: Monarch Pharmaceuticals, LLC; 2004). Serum concentration monitoring should be performed when available.

Table 6.  

Category Antimicrobial*,†
Class
Dosage§
First-line Ciprofloxacin
Fluoroquinolone
500 mg every 8 hrs PO or
750 mg every 12 hrs PO
Levofloxacin
Fluoroquinolone
750 mg every 24 hrs PO
Alternatives Moxifloxacin
Fluoroquinolone
400 mg every 24 hrs PO
Ofloxacin¶,**
Fluoroquinolone
400 mg every 12 hrs PO
Tetracycline¶, ††
Tetracycline
500 mg every 6 hrs PO
Doxycycline
Tetracycline
100 mg every 12 hrs PO
Minocycline¶, ††
Tetracycline
200 mg loading dose, then 100 mg every 12 hrs PO
Trimethoprim-sulfamethoxazole
Sulfonamide
5 mg/kg (trimethoprim component) every 12 hrs PO

Table 6. Pre- and postexposure prophylaxis for pregnant women potentially exposed to Yersinia pestis

Abbreviations: PO = per os.

Note: All oral antimicrobials recommended in these guidelines can be administered via alternative enteral routes (e.g., nasogastric tube and gastric tube) except for ciprofloxacin.

* Prophylaxis with a single antimicrobial class is recommended for potentially exposed pregnant women following a case of naturally acquired infection or intentional release of Yersinia pestis, with targeting of drug choice if engineered resistance is detected in the aftermath of a bioterrorism attack.

Antimicrobials are not listed in order of preference within each category.

§ Pre-exposure prophylaxis can be discontinued 48 hours after the last perceived exposure. Recommended duration for postexposure prophylaxis is 7 days.

Not approved by the Food and Drug Administration (FDA) for treatment of plague. In some instances, these antimicrobials have been used off label for the treatment of naturally occurring plague[17,19,88]. Large-scale distribution and use of these antimicrobials during a bioterrorism response might be under FDA-issued Emergency Use Authorization.

** Additional fluoroquinolone alternatives, such as gemifloxacin and delafloxacin, also can be considered depending on drug availability.

†† In utero exposure can lead to permanent discoloration of developing teeth in the fetus. This is more likely to occur following repeated or long-term exposure.

Table 7.  

Category Antimicrobial*,†
Class
Dosage§
First-line Gentamicin
Aminoglycoside
Neonates aged ≤7 days:
4 mg/kg every 24 hrs IM or IV
Neonates aged 8–28 days:
5 mg/kg every 24 hrs IM or IV
Ciprofloxacin
Fluoroquinolone**
10 mg/kg every 8 or 12 hrs IV
Levofloxacin
Fluoroquinolone**
10 mg/kg every 12 hrs IV
Streptomycin††
Aminoglycoside
15 mg/kg every 12 hrs IV§§ or IM
Alternatives Tobramycin
Aminoglycoside
Neonates aged ≤7 days:
4 mg/kg every 24 hrs IM or IV
Neonates aged 8–28 days:
5 mg/kg every 24 hrs IM or IV
Amikacin
Aminoglycoside
Neonates aged ≤7 days:
15 mg/kg every 24 hrs IM or IV
Neonates aged 8–28 days:
17.5 mg/kg every 24 hrs IM or IV
Chloramphenicol¶,††
Amphenicol
Neonates aged ≤14 days:
6.25 mg/kg every 6 hrs IM or IV
Neonates aged 15–28 days:
12.5 mg/kg every 6 hrs IM or IV¶¶
Doxycycline
Tetracycline**
4.4 mg/kg loading dose, then 2.2 mg/kg every 12 hrs IV

Table 7. Treatment of neonates aged ≤28 days with pneumonic or septicemic plague

Abbreviations: IM = intramuscular; IV = intravenous; PO = per os.

Note: All oral antimicrobials recommended in these guidelines can be administered via alternative enteral routes (e.g., nasogastric tube and gastric tube) except for ciprofloxacin. Additional considerations for treatment and postexposure prophylaxis of neonates, depending on the clinical status of both neonate and mother, are included in Supplementary Appendix 2 (https://stacks.cdc.gov/view/cdc/107427).

* Dual therapy with two distinct classes of antimicrobials should be used for initial treatment of neonates with severe pneumonic or septicemic plague and neonates infected after intentional release of Yersinia pestis.

Antimicrobials are not listed in order of preference within each category.

§ Recommended treatment duration is 10–14 days.

Not approved by the Food and Drug Administration (FDA) for treatment of plague. In some instances, these antimicrobials have been used off label for the treatment of naturally occurring plague[17,19,88]. Large-scale distribution and use of these antimicrobials during a bioterrorism response might be under FDA-issued Emergency Use Authorization.

** Data on use of fluoroquinolones and doxycycline in neonates are extremely limited; however, successful use of these antimicrobials in neonates has been reported (Sources: Kaguelidou F, Turner MA, Choonara I, Jacqz-Aigrain E. Ciprofloxacin Use in Neonates. Pediatr Infect Dis J 2011;30:e29–e37. Newby BD, Timberlake KE, Lepp LM, Mihic T, Dersch-Mills DA. Levofloxacin use in the neonate: A case series. J Pediatr Pharmacol Ther 2017;22:304–13. Forti G, Benincori C. Doxycycline and the teeth. Lancet 1969;1:782).

†† At the time of publication, these antimicrobials might not be readily and consistently available in the United States because of limited production.

§§ The IV formulation of streptomycin is not approved by the FDA; however, the IM formulation of streptomycin has been given intravenously as an off-label use (Sources: Morris JT, Cooper RH. Intravenous streptomycin: a useful route of administration. Clin Infect Dis 1994;19:1150–1. Pérez Tanoira R, Sánchez-Patán F, Jiménez Girón A. et al. Tolerance and safety of intravenous streptomycin therapy in patients with tuberculosis. Infection 2014;42:597–8).

¶¶ Sources: Chloramphenicol sodium succinate [Package insert]. Lake Zurich, IL: Fresenius Kabl, LLC; 2019. Chloromycetin sodium succinate [Package insert]. Bristol, TN: Monarch Pharmaceuticals, LLC; 2004. Serum concentration monitoring should be performed when available.

Table 8.  

Category Antimicrobial*,†
Class
Dosage§
First-line Gentamicin
Aminoglycoside
Neonates aged ≤7 days:
4 mg/kg every 24 hrs IM or IV
Neonates aged 8–28 days:
5 mg/kg every 24 hrs IM or IV
Ciprofloxacin
Fluoroquinolone**
10 mg/kg every 8 or 12 hrs IV
Levofloxacin
Fluoroquinolone**
10 mg/kg every 12 hrs IV
Streptomycin††
Aminoglycoside
15 mg/kg every 12 hrs IV§§ or IM
Doxycycline
Tetracycline**
4.4 mg/kg loading dose, then 2.2 mg/kg every 12 hrs IV
Alternatives Tobramycin
Aminoglycoside
Neonates aged ≤7 days:
4 mg/kg every 24 hrs IM or IV
Neonates aged 8–28 days:
5 mg/kg every 24 hrs IM or IV
Amikacin
Aminoglycoside
Neonates aged ≤7 days:
15 mg/kg every 24 hrs IM or IV
Neonates aged 8–28 days:
17.5 mg/kg every 24 hrs IM or IV
Chloramphenicol¶,††
Amphenicol
Neonates aged ≤14 days:
6.25 mg/kg every 6 hrs IM or IV
Neonates aged 15–28 days:
12.5 mg/kg every 6 hrs IM or IV¶¶

Table 8. Treatment of neonates aged ≤28 days with bubonic or pharyngeal plague

Abbreviations: IM = intramuscular; IV = intravenous.

Note: All oral antimicrobials recommended in these guidelines can be administered via alternative enteral routes (e.g., nasogastric tube and gastric tube) except for ciprofloxacin. Additional considerations for treatment and postexposure prophylaxis of neonates, depending on the clinical status of both neonate and mother, are included in Supplementary Appendix 2 (https://stacks.cdc.gov/view/cdc/107427).

* Dual therapy with two distinct classes of antimicrobials should be used for initial treatment of neonates infected after intentional release of Yersinia pestis.

Antimicrobials are not listed in order of preference within each category.

§ Recommended treatment duration is 10–14 days.

Not approved by the Food and Drug Administration (FDA) for treatment of plague. In some instances, these antimicrobials have been used off label for the treatment of naturally occurring plague[17,19,88]. Large-scale distribution and use of these antimicrobials during a bioterrorism response might be under FDA-issued Emergency Use Authorization.

** Data on use of fluoroquinolones and doxycycline in neonates are extremely limited; however, successful use of these antimicrobials in neonates has been reported (Sources: Kaguelidou F, Turner MA, Choonara I, Jacqz-Aigrain E. Ciprofloxacin use in neonates. Pediatr Infect Dis J 2011;30:e29–e37. Newby BD, Timberlake KE, Lepp LM, Mihic T, Dersch-Mills DA. Levofloxacin Use in the Neonate: A case series. J Pediatr Pharmacol Ther 2017;22:304–13. Forti G, Benincori C. Doxycycline and the teeth. Lancet 1969;1:782).

†† At the time of publication, these antimicrobials might not be readily and consistently available in the United States because of limited production.

§§ The IV formulation of streptomycin is not approved by FDA; however, the IM formulation of streptomycin has been given intravenously as an off-label use (Sources: Morris JT, Cooper RH. Intravenous streptomycin: a useful route of administration. Clin Infect Dis 1994;19:1150–1. Pérez Tanoira R, Sánchez-Patán F, Jiménez Girón A. et al. Tolerance and safety of intravenous streptomycin therapy in patients with tuberculosis. Infection 2014;42:597–8).

¶¶ Sources: Chloramphenicol sodium succinate [Package insert]. Lake Zurich, IL: Fresenius Kabl, LLC; 2019. Chloromycetin sodium succinate [Package insert]. Bristol, TN: Monarch Pharmaceuticals, LLC; 2004. Serum concentration monitoring should be performed when available.

Table 9.  

Category Antimicrobial*,†
Class
Dosage§
First-line Ciprofloxacin
Fluoroquinolone
15 mg/kg every 12 hrs PO
Levofloxacin
Fluoroquinolone
10 mg/kg every 12 hrs PO
Doxycycline
Tetracycline
2.2 mg/kg every 12 hrs PO
Alternatives Gentamicin**
Aminoglycoside
Neonates aged ≤7 days:
4 mg/kg every 24 hrs IM or IV
Neonates aged 8–28 days:
5 mg/kg every 24 hrs IM or IV
Ofloxacin**,††
Fluoroquinolone
7.5 mg/kg every 12 hrs PO

Table 9. Postexposure prophylaxis for neonates aged ≤28 days potentially exposed to Yersinia pestis

Abbreviations: IM = intramuscular; IV = intravenous; PO = per os.

Note: All oral antimicrobials recommended in these guidelines can be administered via alternative enteral routes (e.g., nasogastric tube and gastric tube) except for ciprofloxacin. Additional considerations for treatment and postexposure prophylaxis of neonates, depending on the clinical status of both neonate and mother, are included in Supplementary Appendix 2 (https://stacks.cdc.gov/view/cdc/107427).

* Antimicrobials are not listed in order of preference within each category.

Postexposure prophylaxis with a single antimicrobial agent is recommended for potentially exposed neonates following a case of naturally acquired infection or intentional release of Yersinia Pestis, with targeting of drug of choice if engineered resistance is detected in the aftermath of a bioterrorism attack. Postexposure prophylaxis should be given to neonates orally when possible, unless the neonate is hospitalized and has existing intravenous access. For neonates with highly concerning exposure to Y. pestis who cannot take medications orally, IV or IM formulations of the drugs listed in this table can be given.

§ Recommended postexposure prophylaxis duration is 7 days.

Data on use of fluoroquinolones and doxycycline in neonates are extremely limited; however, successful use of these antimicrobials in neonates has been reported (Sources: Kaguelidou F, Turner MA, Choonara I, Jacqz-Aigrain E. Ciprofloxacin use in neonates. Pediatr Infect Dis J 2011;30:e29–e37. Newby BD, Timberlake KE, Lepp LM, Mihic T, Dersch-Mills DA. Levofloxacin Use in the Neonate: A case series. J Pediatr Pharmacol Ther 2017;22:304–13. Forti G, Benincori C. Doxycycline and the teeth. Lancet 1969;1:782).

** Not approved by the Food and Drug Administration (FDA) for prophylaxis of plague. In some instances, these antimicrobials have been used off label for the prophylaxis of naturally occurring plague[17,19,88]. Large-scale distribution and use of these antimicrobials during a bioterrorism response might be under FDA-issued Emergency Use Authorization.

†† Ofloxacin suspension for oral liquid administration is not available in the United States.

CME / ABIM MOC / CE

Antimicrobial Treatment and Prophylaxis of Plague: Recommendations for Naturally Acquired Infections and Bioterrorism Response

  • Authors: Christina A. Nelson, MD, MPH; Dana Meaney-Delman, MD, MPH; Shannon Fleck-Derderian, MPH; Katharine M. Cooley, MPH; Patricia A. Yu, MPH; Paul S. Mead, MD, MPH
  • CME / ABIM MOC / CE Released: 9/14/2021
  • THIS ACTIVITY HAS EXPIRED
  • Valid for credit through: 9/14/2022
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Target Audience and Goal Statement

This activity is intended for infectious disease clinicians, bioterrorism experts, public health officials, internists, pediatricians, intensivists, and other clinicians caring for patients with or at risk for plague.

The goal of this activity is to describe Centers for Disease Control and Prevention recommendations to US healthcare providers regarding treatment, pre-exposure prophylaxis, and postexposure prophylaxis of plague, both for naturally acquired infections and for bioterrorism response.

Upon completion of this activity, participants will:

  1. Describe notable changes and updates in the new Centers for Disease Control and Prevention (CDC) recommendations compared with the Working Group on Civilian Biodefense guidelines published in 2000, based on new data, expert forum discussions, and other developments
  2. Determine additional considerations regarding response to Yersinia pestis release as a biological weapon, according to the new CDC recommendations
  3. Identify additional recommendations regarding treatment, pre-exposure prophylaxis, and postexposure prophylaxis of adults and children, according to the new CDC guidelines


Disclosures

As an organization accredited by the ACCME, Medscape, LLC requires everyone who is in a position to control the content of an education activity to disclose all relevant financial relationships with any commercial interest. The ACCME defines "relevant financial relationships" as financial relationships in any amount, occurring within the past 12 months, including financial relationships of a spouse or life partner, that could create a conflict of interest.

Medscape, LLC encourages Authors to identify investigational products or off-label uses of products regulated by the US Food and Drug Administration, at first mention and where appropriate in the content.


Faculty

  • Christina A. Nelson, MD, MPH

    Bacterial Diseases Branch
    Division of Vector-Borne Diseases
    National Center for Emerging and Zoonotic Infectious Diseases
    Centers for Disease Control and Prevention (CDC)
    Fort Collins, Colorado

    Disclosures

    Disclosure: Christina A. Nelson, MD, MPH, has disclosed no relevant financial relationships.

  • Dana Meaney-Delman, MD, MPH

    Infant Outcomes Monitoring, Research and Prevention Branch
    Division of Birth Defects and Infant Disorders
    National Center on Birth Defects and Developmental Disabilities
    Centers for Disease Control and Prevention (CDC)
    Atlanta, Georgia

    Disclosures

    Disclosure: Dana Meaney-Delman, MD, MPH, has disclosed no relevant financial relationships.

  • Shannon Fleck-Derderian, MPH

    Bacterial Diseases Branch
    Division of Vector-Borne Diseases
    National Center for Emerging and Zoonotic Infectious Diseases
    Centers for Disease Control and Prevention (CDC)
    Fort Collins, Colorado

    Disclosures

    Disclosure: Shannon Fleck-Derderian, MPH, has disclosed no relevant financial relationships.

  • Katharine M. Cooley, MPH

    Bacterial Diseases Branch
    Division of Vector-Borne Diseases
    National Center for Emerging and Zoonotic Infectious Diseases
    Centers for Disease Control and Prevention (CDC)
    Fort Collins, Colorado

    Disclosures

    Disclosure: Katharine M. Cooley, MPH, has disclosed no relevant financial relationships.

  • Patricia A. Yu, MPH

    Emergency Preparedness and Response Branch
    Division of Preparedness and Emerging Infections
    National Center for Emerging and Zoonotic Infectious Diseases
    Centers for Disease Control and Prevention (CDC)
    Atlanta, Georgia

    Disclosures

    Disclosure: Patricia A. Yu, MPH, has disclosed no relevant financial relationships.

  • Paul S. Mead, MD, MPH

    Bacterial Diseases Branch
    Division of Vector-Borne Diseases
    National Center for Emerging and Zoonotic Infectious Diseases
    Centers for Disease Control and Prevention (CDC)
    Fort Collins, Colorado

    Disclosures

    Disclosure: Paul S. Mead, MD, MPH, has disclosed no relevant financial relationships.

CME Author

  • Laurie Barclay, MD

    Freelance writer and reviewer
    Medscape, LLC

    Disclosures

    Disclosure: Laurie Barclay, MD, has disclosed no relevant financial relationships.

CME Reviewer/Nurse Planner

  • Stephanie Corder, ND, RN, CHCP

    Associate Director, Accreditation and Compliance
    Medscape, LLC

    Disclosures

    Disclosure: Stephanie Corder, ND, RN, CHCP, has disclosed no relevant financial relationships.

Medscape, LLC staff have disclosed that they have no relevant financial relationships.


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CME / ABIM MOC / CE

Antimicrobial Treatment and Prophylaxis of Plague: Recommendations for Naturally Acquired Infections and Bioterrorism Response

Authors: Christina A. Nelson, MD, MPH; Dana Meaney-Delman, MD, MPH; Shannon Fleck-Derderian, MPH; Katharine M. Cooley, MPH; Patricia A. Yu, MPH; Paul S. Mead, MD, MPHFaculty and Disclosures
THIS ACTIVITY HAS EXPIRED

CME / ABIM MOC / CE Released: 9/14/2021

Valid for credit through: 9/14/2022

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Summary

This report provides CDC recommendations to U.S. health care providers regarding treatment, pre-exposure prophylaxis, and postexposure prophylaxis of plague. Yersinia pestis, the bacterium that causes plague, leads to naturally occurring disease in the United States and other regions worldwide and is recognized as a potential bioterrorism weapon. A bioweapon attack with Y. pestis could potentially infect thousands, requiring rapid and informed decision making by clinicians and public health agencies. The U.S. government stockpiles a variety of medical countermeasures to mitigate the effects of a bioterrorism attack (e.g., antimicrobials, antitoxins, and vaccines) for which the 21st Century Cures Act mandates the development of evidence-based guidelines on appropriate use. Guidelines for treatment and postexposure prophylaxis of plague were published in 2000 by a nongovernmental work group; since then, new human clinical data, animal study data, and U.S. Food and Drug Administration approvals of additional countermeasures have become available. To develop a comprehensive set of updated guidelines, CDC conducted a series of systematic literature reviews on human treatment of plague and other relevant topics to collect a broad evidence base for the recommendations in this report. Evidence from CDC reviews and additional sources were presented to subject matter experts during a series of forums. CDC considered individual expert input while developing these guidelines, which provide recommended best practices for treatment and prophylaxis of human plague for both naturally occurring disease and following a bioterrorism attack. The guidelines do not include information on diagnostic testing, triage decisions, or logistics involved in dispensing medical countermeasures. Clinicians and public health officials can use these guidelines to prepare their organizations, hospitals, and communities to respond to a plague mass-casualty event and as a guide for treating patients affected by plague.