(soft music)
- Welcome to part two of CDC's training
on plague response for health care providers.
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, considerations
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 fluoroquinolones,
ciprofloxacin, moxifloxacin, and levofloxacin.
The aminoglycosides, streptomycin and gentamicin,
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 fluoroquinolones,
aminoglycosides, amphenicols, sulfonamides,
and additional tetracyclines 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 tetracyclines 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 1, Moxifloxacin is not a first line agent
for children since it is not FDA approved
for this age group.
Number 2: 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 8,
as there is no evidence of tooth staining
when given in short courses of 2 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 fluoroquinolones and aminoglycosides shown here.
For detailed information on weight-based dosing,
including maximum doses for children,
please consult the full treatment guidelines published
in CDC's MMWR.
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 fluoroquinolone plus streptomycin
or gentamicin.
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 fluoroquinolones and tetracyclines
have good oral bioavailability.
Additional advantages of oral antimicrobials
include ease of administration, preservation
of I.V. medical supplies in the event
of a bioterrorism attack, decreased risk
of hospital acquired infections in patients,
and reduced risk to health care workers,
for example, by needle stick injury.
Next, let's touch briefly
on pre-exposure prophylaxis of plague.
Pre-exposure 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,
pre-exposure prophylaxis can be considered
for frontline health care workers caring
for patients with pneumonic plague.
Pneumonic plague is the only clinical form
that can be transmitted from person to person.
Therefore, health care workers caring for patients
with other clinical forms of plague
do not require pre-exposure prophylaxis.
The optimal duration for pre-exposure 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 pre-exposure 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 health care 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 considerations specific
to bioterrorism attacks will be discussed
in a later section.
Fever watch may be considered as an alternative
to pet 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.
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.
The recommended duration
for post-exposure prophylaxis is seven days.
For prophylaxis, antimicrobials
should be administered orally.
Note that aminoglycosides 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 bioweapon.
An outbreak of plague following the release of Y pestis
as a bioweapon 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 likely result in bubonic plague,
and contamination of food and/or water supplies
would likely lead to exposed 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 fluoroquinolone and doxycycline,
a recommended fluoroquinolone
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 engineering 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,
gentamicin is preferred over streptomycin
for pregnant patients due to lower risk of ototoxicity.
Plague in neonates has been rarely described.
Generally, antimicrobials
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 breastmilk.
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, aminoglycosides
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 drug levels is helpful
in ensuring effective therapeutic levels
and avoiding toxicity.
Note that chloramphenicol should always be dosed based
on total body weight regardless of body mass index.
Serum concentration monitoring
should be performed when available.
For obese adults, ciprofloxacin 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 8 mg/kg per day.
Finally, although immunocompromised patients
and patients aged 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 aged 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 aged 65 and over,
clinicians should consider using doxycycline
over fluoroquinolones due to the risks for QTc prolongation,
neuro-psychiatric 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.