- [Narrator] Just in time training for plague response,
part two, plague treatment and prophylaxis division
of vector borne diseases, national center
for emerging and zoonotic infectious diseases
centers for disease control and prevention.
- Welcome to part two of CDCs training
on plague response for healthcare providers
- [Narrator] Christina Nelson, MD, MPH
medical officer division of vector borne diseases
centers for disease control and prevention.
- This video provides an overview
of treatment recommendations
for the different clinical forms of plague guidance
for pre and post exposure prophylaxis and considerations
following a known or suspected bioterrorism attack
for a review of the epidemiology
and different clinical forms of plague.
Please see part one of this series.
Treatment of plague depends on several factors
including clinical form, patient age, severity of illness
consideration such as pregnancy status
and whether the illness originates
from a suspected bioterrorism attack
or a naturally occurring source.
The list shown here provides an overview
of the recommended first line antimicrobials for treatment
of plague in patients 18 years of age or older
as well as alternative treatments.
If the first line therapies are contraindicated
or unavailable, the first line agents for all clinical forms
of plague are the Fluroquinolones, Ciprofloxin, moxifloxacin
and Levofloxacin.
The aminoglycoside, streptomycin
and gentamycin are also acceptable.
First line agents
for all clinical forms except plague meningitis.
Doxycycline is a first line therapy for bubonic
and pharyngeal plague only.
alternative antimicrobials for bubonic and pharyngeal
plague include the Fluroquinolones, Aminoglycoside
Amphenicols, Sulfonamides
and additional tetracycline shown here
for pneumonic and septicemic plague.
Doxycycline is not first line
but is an appropriate alternative treatment.
If first line antimicrobials are not available
additional tetracycline are not recommended
as alternative treatments for pneumonic, septicemic
or meningitic plague, as mentioned earlier, patient
age is a factor when making treatment decisions
recommendations differ slightly when treating children
between the ages of one month and 18 years.
The major differences between treatment recommendations
for children versus adults are as follows.
Number one, moxifloxacin is not a first line agent
for children since it is not FDA approved
for this age group.
Number two gemifloxacin and Plazomicin are not recommended
as alternative agents in children
for children as with adults, doxycycline is recommended
as a first line option for the treatment of bubonic
and pharyngeal plague only doxycycline
may be safely administered
to children under the age of eight
as there is no evidence of two staining.
When given in short courses of two weeks
or less and prompt treatment of plague is life saving.
A loading dose
of doxycycline should be administered for both children
and adults.
For pneumonic or septicemic plague.
First line antimicrobials are the Fluroquinolones
and aminoglycoside shown here,
for detailed information on weight based dosing
including maximum doses for children
please consult the full treatment guidelines published
in CDCs MMWR.
- [Narrator] For more detailed information,
please consult the full
treatment guidelines published in CDCs morbidity
and mortality weekly report that can be found
at bit.ly/MMWRPlague
- Plague meningitis has some specific
treatment considerations.
If plague meningitis is suspected the first line therapy
for both adults and children is chloramphenicol
plus either Levofloxacin or Moxifloxacin.
Although chloramphenicol has a long history
of successful use in plague meningitis
it is not readily available in the United States.
If chloramphenicol is not available
a suggested alternative is a first line fluroquinolone
plus streptomycin or gentamycin, severity of
illness can also be a consideration when treating patients
with plague, consider using oral antimicrobials, if possible
for patients with mild to moderate disease
in patients with severe disease
or for patients unable to tolerate oral medications
intravenous antimicrobials are appropriate
both Fluroquinolones
and tetracycline have good oral bioavailability
additional advantages of oral antimicrobials include ease
of administration, preservation of IV medical supplies
in the event of a bioterrorism attack
decreased risk of hospital acquired infections
in patients and reduced risk to healthcare workers.
For example, by needles, stick injury.
Next let's touch briefly
on preexposure prophylaxis of plague.
Preexposure prophylaxis of plague
in the clinical setting is not necessary as long
as standard and droplet precautions can be maintained.
However, in the event
of personal protective equipment shortages
poor ventilation or hospital overcrowding
preexposure prophylaxis can be considered
for frontline healthcare workers, caring for patients
with pneumonic plague, pneumonic plague is
the only clinical form that can be transmitted
from person to person, therefore healthcare workers
caring for patients with other clinical forms
of plague do not require preexposure prophylaxis.
The optimal duration
for preexposure prophylaxis is not known
and has not been studied in clinical trials.
However, based on animal models
and our knowledge of Yersinia pestis,
it is reasonable to discontinue preexposure prophylaxis
48 hours after the last perceived exposure
to a person or animal with pneumonic plague.
Now let's move on to post exposure prophylaxis or PEP
which is warranted in four major scenarios.
In the first scenario, people who have sustained close
contact with a person who had known or suspected pneumonic
plague and were not wearing appropriate personal
protective equipment should receive post exposure
prophylaxis.
This situation can apply to any close contact
of a person with pneumonic plague,
including healthcare personnel.
The second scenario involves laboratory personnel
exposed to infectious materials or potentially
infectious clinical specimens while not wearing
appropriate personal protective equipment.
The third scenario applies to a person not
wearing appropriate personal protective equipment who
had direct contact with infected animals, including animals
who died of plague or any carcass in a mass die off scenario
in a plague endemic area.
The fourth scenario in which post exposure prophylaxis is
warranted would be following a bioterrorism attack
in which people may have been exposed to intentionally
released, Y pestis or may have had close sustained exposure
to people who are sick with pneumonic plague
and coughing, additional treatment consideration specific
to bioterrorism attacks will be discussed
in a later section.
Fever watch may be considered as an alternative to PEP
for people who had low risk exposure.
However, there are no set criteria for determining who
should be managed by fever watch versus immediate PEP
- [Narrator] Fever watch, take temperature daily for seven
days following last perceived exposure
- Factors to consider when deciding between PEP or fever
watch include the nature of the exposure
the incubation period of Y. pestis
and the person's level of concern,
for laboratory personnel working with the organism
on the bench is lower risk than sniffing a plate
or accidentally coming into contact with the bacteria.
People who recall an exposure that occurred more
than seven days ago may be
outside of the incubation period for Y. pestis.
The recommended antimicrobials and appropriate dosing
for pre or post exposure prophylaxis are shown here.
- [Narrator] First line pre and post exposure prophylaxis
of plague Ciprofloxin in adults, 500 to 750 milligrams
Q12H PO in children, 15 milligrams per kilogram,
Q12H PO maximum 750 milligrams
per dose Levofloxacin in adults, 500 to 750 milligrams
Q24H PO in children with a body weight
less than 50 kilograms, eight milligrams per kilogram,
Q12H PO maximum 250 milligrams
per dose in children with a body weight
more than 50 kilograms, 500 to 750 milligrams
Q24H PO, Moxifloxacin in adults, 400 milligrams,
Q24H PO in children as an alternative only
it is not FDA approved
for use in children aged 17 years or less, but has been used
off label, doxycycline in adults, 100 milligrams,
Q12H PO in children with a body weight
less than 45 kilograms, 2.2 milligrams per kilogram,
Q12H PO in children with a body weight more
than 45 kilograms, 100 milligrams, Q12H PO.
- The recommended duration
for post exposure prophylaxis is seven days.
For prophylaxis, antimicrobials should be
administered orally,
note that aminoglycoside are not recommended
as they are not available in an oral formulation.
Now we will discuss considerations
for the treatment and prophylaxis of plague
in the event of a bioterrorism attack
as discussed in part one of this training
Y.pestis has long been used or considered as a bio weapon
an outbreak of plague following the release
of Y.pestis as a bio weapon could look quite different
from naturally occurring plague.
Additionally, the release mechanism would
influence the clinical manifestations that develop.
For example, an attack
with aerosolized Y. pestis would likely result
in people developing pneumonic plague
a release of infected fleas would result
in bubonic plague and contamination
of food or water supplies would likely lead to
expose people developing pharyngeal or septicemic plague.
However, it is important to note
that any method of release could result
in multiple clinical forms of plague.
Clinicians would need to maintain a high index
of suspicion in the wake
of an intentional release, following a bioterrorism attack.
Two different classes
of antimicrobials should be administered
to patients with suspected plague.
The rationale for using two different classes is
that Y. pestis strains used in a bioterrorism attack
may have been engineered to be resistant to antimicrobials.
Some possible treatment combinations include a
recommended fluroquinolone and doxycycline
a recommended fluroquinolone
and a recommended aminoglycoside
or a recommended aminoglycoside and doxycycline
note that both antimicrobials used do not necessarily
need to be first line, but ideally at least one should be
due to the risk of engineered resistance.
Antimicrobial susceptibility testing should be obtained
if a bioterrorism attack is suspected, however
do not wait for confirmation of the diagnosis
or results of susceptibility testing to begin treatment
following a bioterrorism attack, people who are exposed
but have not yet developed illness should be
provided post exposure prophylaxis
PEP with one antimicrobial class is recommended
using the antimicrobials listed previously and referenced
in the plague clinical treatment guidelines
use of one antimicrobial is recommended to reduce the risk
of adverse reactions.
If testing indicates that the intentionally released strain
of Y. pestis is resistant to the initial PEP antimicrobial
the PEP antimicrobial should be changed.
If a person develops symptoms of plague while taking PEP
they should begin receiving antimicrobial treatment
with two different antimicrobial classes.
Finally, we will discuss considerations
for antimicrobial therapy in certain populations.
This discussion will focus only on key differences
in recommended treatment consult the full CDC
guidelines published in MMWR for complete details.
If a pregnant patient develops plague concerns
about fetal safety should not preclude treatment
or prophylaxis, pregnant patients who contract
plague have worse outcomes than the general population.
Even with appropriate treatment
there is a high rate of fetal loss or preterm birth.
If an aminoglycoside is prescribed, gentamycin is preferred
over streptomycin for pregnant patients due
to lower risk of ototoxicity.
Plague in neonates has been rarely described.
Generally antimicrobial should be administered
intravenously whenever possible.
Oral formulations are not recommended
due to the immature intestinal system of neonates.
Despite the risk of gray baby syndrome
chloramphenicol should be considered for neonates
with plague meningitis due to the severity of this disease.
Although it has not been studied in detail.
There are no reports of Y. Pestis
transmission by breast milk
therefore mothers with bubonic or septicemic plague
and mothers taking antimicrobial prophylaxis after exposure
to Y. pestis can continue to breastfeed their infants.
If able, lactating mothers
with pneumonic plague should avoid direct breastfeeding
until they have received antimicrobial treatment
for at least 48 hours
and have demonstrated clinical improvement
unless the breastfeeding infant is also
receiving antimicrobial treatment or prophylaxis.
In which case breastfeeding may continue.
The majority of antimicrobials recommended
for Y. pestis treatment
or prophylaxis produce low concentrations in breast milk
and have an acceptable safety profile,
note that because chloramphenicol has the potential
for serious adverse reactions in infants
including gray baby syndrome
other drugs should be used preferentially
for lactating mothers.
When possible, people who are underweight
or obese may require special dosing considerations.
Differing volumes of distribution for medications can result
in either decreased efficacy or increased risk of toxicity.
In particular
aminoglycoside have a narrow therapeutic window
and require careful dose adjustments
in underweight patients.
The aminoglycoside dose should be based
on total body weight.
The aminoglycoside dose
for obese patients should be based on adjusted body weight.
Measuring serum aminoglycoside levels is helpful
in ensuring effective therapeutic levels
and avoiding toxicity.
Note that chloramphenicol should always be dose based
on total body weight, regardless of body mass index serum
concentration monitoring should be performed when available
for obese adults Ciprofloxin should be dosed
at the upper end of the dose range.
Also for obese adults.
Trimethoprim sulfamethoxazole should be dosed according
to adjusted body weight when prescribing doses more
than eight milligrams per kilogram per day.
Finally, although immunocompromised patients
and patients age 65
and over may develop more severe manifestations of plague.
There are no differences
in the recommended antimicrobials or dosing.
However, treatment duration may need to be extended
if an appropriate clinical response is not seen
after 10 to 14 days
clinicians should also be aware of the risks of polypharmacy
in immunocompromised patients or patients age 65 and over
for example there is an increased possibility
of severe injury and hyperkalemia.
If Trimethoprim sulfamethoxazole is administered
with an ACE inhibitor, angiotensin receptor blocker
or potassium sparing diuretic
for post exposure prophylaxis of patients age 65
and over clinicians should consider using doxycycline
over Fluroquinolones due to the risks
for QTC prolongation, neuropsychiatric disturbances
including dizziness and imbalance and damage
to connective tissues.
In an emergency the CDC emergency operation
center can be reached 24 hours a day,
seven days a week at 800-232-4636.
Thank you for watching part two in this series
- [Narrator] Just in time training for plague response.
Thank you for watching division of vector borne diseases
national center for emerging
and zoonotic infectious diseases centers
for disease control and prevention.