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CBRNE - Plague: Treatment & Medication
Updated: Sep 22, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Prehospital Care
- Provide supportive care.
- Crystalloid infusion to maintain normal vital signs and clinical hydration state may be necessary.
- Administer oxygen via nasal cannula, nonrebreather mask, or intubation as determined by the respiratory distress of the patient. Use pulse oximetry to monitor the degree of respiratory compromise.
- Assume universal precautions, including goggles, gloves, and gown, when dealing with any patient with an infectious disease presentation. Masks should be worn if respiratory involvement is possible.
Emergency Department Care
- Depending on the stage of presentation, supportive care varies. Early presentation may require only crystalloid administration with monitoring of vital signs, clinical state, and urine output.2
- Septic shock requires invasive hemodynamic monitoring with crystalloid and vasopressor agents. Airway management may require intubation and mechanical ventilation with positive end-expiratory pressure (PEEP).
- Empiric antibiotic coverage is discussed in Medication.
- Use strict isolation precautions.
- If respiratory symptoms are present, institute universal precautions with strict respiratory isolation for the first 96 hours of therapy.14
- If no respiratory symptoms are present, only 48 hours of isolation or isolation until purulent drainage from the bubo ceases is required.
- Incinerate or autoclave all contaminated material.
- Inform the laboratory of the possibility of handling plague infected material. Cases of laboratory-acquired plague have occurred.
Consultations
- Consult an infectious disease specialist.
- Early notification of the CDC allows samples to be sent to the headquarters in Colorado for diagnosis by fluorescent antibody testing. The CDC, in conjunction with the Department of Health, will attempt to identify the source of the plague and implement early epidemiologic measures to control a potential epidemic.
- Consult a medical intensivist as indicated.
Medication
Medical management of plague can involve a myriad of supportive medications, including crystalloids, colloids, medications used for intubation, vasopressor agents, and antiulcer and antipyretic agents. This section only describes antibiotic management of plague. Early administration of antibiotics is essential after samples for diagnostic purposes have been obtained.
Antibiotics
Drugs that cover Y pestis should be empirically given to any patient with predisposing risk factors and signs and symptoms of the plague. Antibiotic treatment duration should be 10 days. In severe cases, a 2-drug regimen should be used. Antibiotic regimens for postexposure prophylaxis should be considered for close contacts of infected patients. Dosages and antibiotics are covered below.
Gentamicin (Garamycin, Jenamicin)
Aminoglycoside antibiotic for gram-negative coverage. Drug of choice (DOC) with consideration of use as secondary agent.
Adult
5 mg/kg IV/IM qd or 2 mg/kg loading dose followed by 1.7 mg/kg IV/IM tid
Pediatric
2.5 mg/kg IV/IM tid (neonates and premature infants require varying dosages)
Coadministration with other aminoglycosides, cephalosporins, penicillins, and amphotericin B may increase nephrotoxicity; because aminoglycosides enhance effects of neuromuscular blocking agents, prolonged respiratory depression may occur; coadministration with loop diuretics may increase auditory toxicity of aminoglycosides; possible irreversible hearing loss of varying degrees may occur (monitor regularly)
Documented hypersensitivity to aminoglycosides; non–dialysis-dependent renal insufficiency; use of concomitant live bacterial vaccines
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Narrow therapeutic index (not intended for long-term therapy); caution in renal failure (not on dialysis), myasthenia gravis, hypocalcemia, and conditions that depress neuromuscular transmission; adjust dose in renal impairment; caution in neutropenic or ICU patients; may cause vestibular, renal, and auditory damage
Streptomycin sulfate
Alternative DOC in combination with consideration of use with a secondary agent. Drug often not commercially available. Treatment usually limited to 5 d due to toxicity concerns. Continuation of secondary agent for full 10 d recommended.
Adult
30 mg/kg/d IM divided bid/qid; not to exceed 2 g/d
Pediatric
20-30 mg/kg/d IM divided bid/qid
Newborn infants with transplacental infection by plague should receive gentamicin instead
Nephrotoxicity may be increased with aminoglycosides, cephalosporins, penicillins, amphotericin B, and loop diuretics
Documented hypersensitivity; those with non–dialysis-dependent renal insufficiency
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Because of narrow therapeutic index and toxic hazards associated with extended administration, not intended for long-term therapy; adjust dose in patients with renal impairment; caution in myasthenia gravis, renal failure (not on dialysis), hypocalcemia, and conditions that depress neuromuscular transmission
Chloramphenicol (Chloromycetin)
DOC to be used as secondary agent in plague meningitis (better CNS penetration), profound hypotension, and pleural and/or pericardial involvement. May be considered as secondary agent. DOC for pregnant patients. Binds to 50S bacterial ribosomal subunits and inhibits bacterial growth. Effective against gram-negative and gram-positive bacteria.
Adult
50-100 mg/kg/d IV divided q6h
30 mg/kg/d PO divided q6h may be substituted for IV in last 5 d of therapy
Pediatric
<7 days: 25 mg/kg PO/IV qd
>7 days: 50 mg/kg/d PO/IV divided q12h
Concurrently with barbiturates, chloramphenicol serum levels may decrease while barbiturate levels may increase, causing toxicity; manifestations of hypoglycemia may occur with sulfonylureas; rifampin may reduce serum chloramphenicol levels, presumably through hepatic enzyme induction; may increase effects of anticoagulants; may increase serum hydantoin levels, possibly resulting in toxicity; chloramphenicol levels may be increased or decreased
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Use only for indicated infections or as prophylaxis for bacterial infections; serious and fatal blood dyscrasias (aplastic anemia, hypoplastic anemia, thrombocytopenia, granulocytopenia) can occur; evaluate baseline and perform periodic blood studies approximately every 2 d while in therapy; discontinue upon appearance of reticulocytopenia, leukopenia, thrombocytopenia, anemia, or findings attributable to chloramphenicol; adjust dose in liver or kidney dysfunction; caution in pregnancy at term or during labor because of potential toxic effects on fetus (gray syndrome)
Doxycycline (Doryx, Vibramycin, Bio-Tab)
Inhibits protein synthesis and thus bacterial growth by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria.
May be considered as secondary agent or for postexposure prophylaxis.
Adult
Loading dose 200 mg IV; thereafter, 100 mg IV bid for 10 d
Pediatric
<45 kg: 2.2 mg/kg IV bid (maximum daily dose of 200 mg)
>45 kg: Administer as in adults
Bioavailability decreases with antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate; tetracyclines can increase hypoprothrombinemic effects of anticoagulants; tetracyclines can decrease effects of oral contraceptives, causing breakthrough bleeding and increased risk of pregnancy
Documented hypersensitivity; severe hepatic dysfunction; breastfeeding; children <8 y; live bacterial vaccines
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Photosensitivity may occur with prolonged exposure to sunlight or tanning equipment; reduce dose in renal impairment; consider drug serum level determinations in prolonged therapy; tetracycline use during tooth development (last one half of pregnancy through age 8 y) can cause permanent discoloration of teeth; Fanconilike syndrome may occur with outdated tetracyclines
Ciprofloxacin (Cipro)
Fluoroquinolone that inhibits bacterial DNA synthesis and, consequently, growth, by inhibiting DNA gyrase and topoisomerases, which are required for replication, transcription, and translation of genetic material. Quinolones have broad activity against gram-positive and gram-negative aerobic organisms. Has no activity against anaerobes.
Animal studies have shown effectiveness against the plague. Can be considered as a secondary agent or as an agent for postexposure prophylaxis.
Adult
400 mg IV bid or 500 mg PO bid
Pediatric
15 mg/kg IV bid or 20 mg/kg PO bid
Antacids, iron salts, and zinc salts may reduce serum levels; administer antacids 2-4 h before or after taking fluoroquinolones; cimetidine may interfere with metabolism of fluoroquinolones; ciprofloxacin reduces therapeutic effects of phenytoin; probenecid may increase ciprofloxacin serum concentrations; may increase toxicity of theophylline, caffeine, cyclosporine, and digoxin (monitor digoxin levels); may increase effects of anticoagulants (monitor PT)
Documented hypersensitivity; use of live vaccines
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Dosage adjustments (adult adjustments)
CrCl (mL/min) <10: 50% of PO or IV dose q12h
HD: 0.25-0.5 g PO or 0.2-0.4 g IV q12h
During peritoneal dialysis: 0.25-0.5 g PO or 0.2-0.4 g IV q8h
In prolonged therapy, perform periodic evaluations of organ system functions (eg, renal, hepatic, hematopoietic); adjust dose in renal function impairment; superinfections may occur with prolonged or repeated antibiotic therapy
Not drug of first choice in pediatric patients because of increased incidence of adverse events compared with controls, including arthropathy; no data exist for dose for pediatric patients with renal impairment (ie, CrCl <50 mL/min)
Tetracycline (Sumycin, Tetracyn IV)
Treats susceptible bacterial infections of both gram-positive and gram-negative organisms as well as mycoplasmal, chlamydial, and rickettsial infections; inhibits bacterial protein synthesis by binding with 30S and possibly 50S ribosomal subunits of susceptible bacteria; use with either streptomycin or gentamicin. Consider as a secondary agent or for postexposure prophylaxis.
Adult
Loading dose: 15 mg/kg PO; not to exceed 1 g
Day 1: 40-50 mg/kg PO q4h
Thereafter: 30 mg/kg PO q6h for 10-14 d
Loading dose: 5 mg/kg IV
Day 1: 15 mg/kg IV q4h
Thereafter: 5 mg/kg IV q6h; may switch to PO at any time if patient can tolerate
Prophylactic dosing: 25-50 mg/kg/d PO divided qid
Pediatric
If suspicion of plague is high, some authors recommend similar dosages and regimens for all pediatric patients, even children <8 y
Prophylactic dosing >8 years: 25-50 mg/kg/d PO divided qid
Bioavailability decreases with antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate; can decrease effects of oral contraceptives, causing breakthrough bleeding and increased risk of pregnancy; can increase hypoprothrombinemic effects of anticoagulants
Documented hypersensitivity; severe hepatic dysfunction
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Photosensitivity may occur with prolonged exposure to sunlight or tanning equipment; reduce dose in renal impairment; consider drug serum level determinations in prolonged therapy; use during tooth development (last one half of pregnancy through age 8 y) can cause permanent discoloration of teeth; Fanconilike syndrome may occur with outdated tetracyclines
Co-trimoxazole (Bactrim, Septra)
DOC for prophylaxis of pregnant women and children <8 y; inhibits bacterial synthesis of dihydrofolic acid by competing with PABA, inhibiting folic acid synthesis and resulting in the inhibition of bacterial growth.
Adult
1 DS tab PO bid for 5-10 d
Pediatric
<2 months: Do not administer
>2 months: 8 mg/kg/d trimethoprim and 40 mg/kg/d sulfamethoxazole PO divided bid for 5-10 d
May increase PT when used with warfarin (perform coagulation tests and adjust dose accordingly); coadministration with dapsone may increase blood levels of both drugs; coadministration of diuretics increases incidence of thrombocytopenia purpura in elderly patients; phenytoin levels may increase with coadministration; may potentiate effects of methotrexate in bone marrow depression; hypoglycemic response to sulfonylureas may increase with coadministration; may increase levels of zidovudine
Documented hypersensitivity; megaloblastic anemia due to folate deficiency
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Discontinue at first appearance of rash or sign of adverse reaction; obtain CBCs frequently; discontinue therapy if significant hematologic changes occur; goiter, diuresis, and hypoglycemia may occur with sulfonamides; prolonged IV infusions or high doses may cause bone marrow depression (if signs occur, give 5-15 mg/d leucovorin); caution in folate deficiency (eg, chronic alcoholics, elderly patients, those receiving anticonvulsant therapy, or those with malabsorption syndrome); hemolysis may occur in individuals with G-6-PD deficiency; patients with AIDS may not tolerate or respond to TMP-SMZ; caution in renal or hepatic impairment (perform urinalyses and renal function tests during therapy); give fluids to prevent crystalluria and stone formation
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Further Reading
Keywords
plague, bubonic plague, bubo, pneumonic plague, septicemic plague, fleabite, flea bite, black death, plague bacillus, Yersinia pestis, Y pestis, rat flea, Xenopsylla cheopis, X cheopis, bacteremia, septicemia, gangrene, cyanosis, ecchymosis, petechiae, hematochezia, hematemesis, hemoptysis, septic shock, disseminated intravascular coagulation, DIC
