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Antimicrobial Susceptibility of Bacillus anthracis
This is an official CDC Health Advisory
Distributed via the Health Alert Network
October 22, 2001, 21:12 EDT (9:12 PM EDT)
Antimicrobial Susceptibility of Bacillus anthracis: Isolates Associated with
Intentional Distribution in Florida, New Jersey, New York, Pennsylvania,
Virginia, and Washington, D.C., September - October, 2001
The antimicrobial susceptibility patterns of eleven Bacillus anthracis
isolates associated with intentional exposures on the east coast have been
determined. The susceptibility patterns of all the isolates were similar and are
described below. CDC will be issuing updated treatment recommendations for
anthrax and will disseminate them as soon as they are completed.
Ciprofloxacin <0.06 ug/ml (susceptible)
Tetracycline = 0.06 ug/ml (susceptible)
Doxycycline <0.03 ug/ml (susceptible)
Penicillin <0.06 ug/ml - 0.12ug/ml ("susceptible" but see below)
Amoxicillin < 0.03 ug/ml ("susceptible" but see below)
Erythromycin = 1 ug/ml (intermediate)
Azithromycin =2 ug/ml (borderline susceptible)
Clarithromycin =0.25 ug/ml (susceptible)
Rifampin = 0.5 ug/ml (susceptible)
Clindamycin <0.5 ug/ml (susceptible)
Vancomycin = 1-2 ug/ml (susceptible)
Chloramphenicol = 4 ug/ml (susceptible)
Ceftriaxone = 16 -32 ug/ml (intermediate or resistant)
The penicillin MICs were <0.06 to 0.12 ug/ml, which, using the NCCLS
staphylococcal breakpoint for penicillin, would be considered susceptible
(resistance is defined as >0.25 ug/ml).
All of the B. anthracis isolates were also susceptible to ciprofloxacin
(MIC< 0.06 ug/ml), chloramphenicol (MIC = 4 ug/ml), tetracycline (MIC=0.06
ug/ml), doxycycline (MIC=0.06 ug/ml), rifampin (MIC<0.5 ug/ml), and
vancomycin (MIC 1-2 ug/ml).
Although there are no amoxicillin breakpoints defined for staphylococci by
NCCLS, the amoxicillin results (MIC <0.03 ug/ml) were considered susceptible
for B. anthracis. However, the erythromycin MICs of all eleven strains of B.
anthracis would be categorized as intermediate (MIC= 1 ug/ml ). The MICs to
clarithromycin (MIC=0.25 ug/ml) and azithromycin (MIC=2 ug/ml) are susceptible
(but azithromycin MICs are at the susceptible breakpoint). Using the NCCLS
ceftriaxone breakpoints designated for gram-negative organisms (since there are
no breakpoints specifically for ceftriaxone for staphylococci) all isolates
would be considered as intermediate (MIC =16 ug/ml) or resistant (MIC=32 ug/ml).
These MICs suggest the presence of a cephalosporinase in the isolates.
Additional studies are in progress to define the beta-lactamases of B.
anthracis.
Conclusions
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The current B. anthracis strains
associated with the intentional exposures are susceptible to ciprofloxacin
and doxycycline, the two drugs approved for post-exposure prophylaxis to B.
anthracis and recommended as part of initial therapy of inhalational or
cutaneous anthrax.
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The current strains also are
susceptible to chloramphenicol, clindamycin, rifampin, vancomycin, and
clarithromycin, but limited or no data exists regarding the use of these
agents in the treatment or prophylaxis of B. anthracis infections.
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Cephalosporins should not be used
for post-exposure prophylaxis or treatment of B. anthracis infections.
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The likelihood of a
beta-lactamase induction event that would increase penicillin MICs is
significantly higher in infections where high concentrations of organisms
are present. Thus, treatment of known B. anthracis infections with a
penicillin type drug alone (i.e., penicillin G, ampicillin, etc.) in the
setting where high concentrations of organisms are present is a concern.
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The likelihood of a
beta-lactamase induction event that would increase penicillin MICs is lower
when only small numbers of vegetative cells are present, such as during post
exposure prophylaxis. Thus, amoxicillin or penicillin VK may be an option
for post-exposure prophylaxis where ciprofloxacin or doxycycline are
contraindicated.
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Additional studies are in
progress to assess the susceptibility of the penicillinase activity observed
in these strains to beta-lactamase inhibitors.
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Clinical experience is limited,
but combination therapy with two or more antimicrobials may be appropriate
in patients with severe infection.
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