a 61-year - old man with a history of impaired glucose tolerance , hypertension , and chemical pneumonitis without chronic lung disease sought care at a community hospital in northwestern minnesota after experiencing 2 days of fever , productive cough , and exertional dyspnea . during recent travel through parks in the western united states , he had been exposed to animal antlers and hides , wild bison , and donkeys . on hospital admission ,
the patient s temperature was 37.3c , blood pressure 148/72 , pulse 100 , respiratory rate 20 , and room air oxygen saturation 89% ( median 95% , range 65%100% ) .
laboratory tests ( table 1 ) and chest imaging ( figure 1 ) were performed .
blood samples for culture were obtained , and ceftriaxone ( 2 g ) and azithromycin ( 500 mg ) ( table 2 ) were administered intravenously ( iv ) for presumed community - acquired pneumonia ( cap ) .
initial admission was to a community hospital ; on day 4 , the patient was transferred to a tertiary referral center . 
chest x - ray and computed tomographic scan images for a patient with inhalation anthrax , minnesota , usa .
a ) on hospital day 1 , the x - ray image revealed a right upper lobe infiltrate and widening of the mediastinum .
b ) on hospital day 2 , computed tomographic scan of the chest with intravenous contrast showed dense consolidation of the right upper lobe , mediastinal adenopathy ( small arrow ) , and bilateral pleural effusions ( large arrows ) .
c ) by hospital day 4 , progressive infiltrates in the right lung were present .
* iv , intravenous ; hospital day , number of days in hospital including day of admission ; ph , post - hospitalization days . 
iv medication was discontinued and oral medication was started on day of discharge ( hospital day 26 ) and continued for 35 additional days to complete 60 days of therapy . on hospital day 2 , the patient had increasing tachycardia and higher oxygen requirements .
a bacillus species was isolated from blood cultures and sent to the minnesota department of health public health laboratory ( mdhphl ) for identification , and iv ciprofloxacin was initiated . on hospital day 3 , the patient s condition continued to decline ( table 1 ) .
mdhphl identified b. anthracis in the blood cultures , and meropenem and vancomycin were added to the treatment regimen .
the isolate was sent to the centers for disease control and prevention ( cdc , atlanta , ga , usa ) . on hospital day 4 , the patient was transferred to a referral center with progressive respiratory failure requiring endotracheal intubation .
iv ciprofloxacin was continued , and iv rifampin and clindamycin were administered ( table 2 ) .
a chest tube was placed in the right pleural space , and 550 ml of serosanguineous fluid was drained during the initial 24 hours .
pleural fluid analysis showed a leukocyte count of 3,389 cells / ml ( neutrophils 38% , lymphocytes 56% , monocytes 6% ) , a lactate dehydrogenase level of 352 , and negative gram stain results . on day 5 ,
anthrax immune globulin ( aig ) was requested from cdc on day 4 and administered on day 5 without adverse reaction .
the patient s disease course was complicated by nonoliguric renal failure ; serum creatinine peaked at 1.5 mg / dl . on day 8 ,
rifampin was discontinued ; meropenem , which had been discontinued on day 5 , was resumed for prophylaxis against nosocomial infection and improved central nervous system coverage of b. anthracis infection .
after stabilization , the patient was maintained on volume control ventilation : tidal volume 500 ml , positive end 
the patient was extubated on day 11 , and the chest tube was removed on day 13 ; left - sided pleural effusion did not recur .
he completed a 10-day course of clindamycin and a 14-day course of meropenem . upon discharge on day 26 ,
cdc performed susceptibility testing using broth microdilution ( technical appendix ) . in compliance with the investigational new drug protocol for aig administration
, we obtained serial serum samples to assess levels of lethal factor ( lf ) and anti  protective antigen ( pa ) igg .
we used an elisa to determine serum anti - pa igg levels before and after aig administration ( 4 ) .
the lower limit of quantification ( lloq ) for this assay is 3.7 g / ml .
antimicrobial susceptibility testing ( technical appendix ) performed on the b. anthracis isolate showed a mic of penicillin of < 0.015 g / ml and mic of ciprofloxacin of 0.12 g / ml . the patient s initial plasma lf level was 58.0 ng / ml , which declined to 1.5 ng / ml before aig administration : pleural fluid lf was 16.2 ng / ml at initial drainage and declined steadily ( figure 2 ) . before aig administration , no anti - pa igg was discernable because these quantifications were below the lloq ( figure 2 ) . immediately after aig administration ,
anti - pa igg reached maximal value of 160.5 g / ml and maintained a plateau thereafter .
plasma and pleural fluid lethal factor levels and anti - protective antigen igg ( aig ) levels for a patient from the time of examination in the community hospital emergency department to discharge from the tertiary referral center .
asterisks indicate that anti - protective aig levels obtained before anthrax immune globulin administration were below the lower limit of quantification .
the patient s initial plasma lethal factor level was 58.0 ng / ml and declined to 1.5 ng / ml before aig administration .
we describe the second us case of naturally acquired inhalation anthrax since the bioterrorism - related infections of 2001 and the third known case worldwide in which the patient received aig ( 2,6 ) . before this case
, the most recent case in the united states had occurred in pennsylvania during 2006 ( 2 ) .
that patient had a 3-day prodromal illness , and initial plasma lf ( 294.3 ng / ml ) and pleural fluid lf ( 543.2 ng / ml ) levels substantially higher than those reported here .
seroconversion to anti - pa igg occurred before aig administration in the 2006 case , possibly because of a longer interval between symptom onset and aig infusion ( 10 vs. 6 days ) .
the patient , who appears to have been in the fulminant phase of illness when tailored antimicrobial drug therapy was initiated on hospital day 4 , died on day 7 despite aig treatment ( 6 ) .
( 7 ) proposed a scoring system derived from multivariate analysis to distinguish inhalation anthrax from cap on the basis of clinical features at disease onset . in the case - patient described here ,
3 of 5 identifying variables were present : elevated alanine aminotransferase / aspartate aminotransferase , normal leukocyte count , and tachycardia .
the 2 remaining possible variables , low serum sodium level and nausea / vomiting were not present .
this correlated with a sensitivity of 82% and specificity of 81% for diagnosing anthrax rather than cap .
mediastinal widening , exhibited in the patient in this report , has also been proposed as a characteristic that can distinguish anthrax from cap . when anthrax patients were compared with an age- , sex- , and race - matched control population , mediastinal widening occurred in 82% of anthrax patients and 8% of cap patients ( 8) . a systematic review of inhalation anthrax cases showed improved survival if antimicrobial drugs were initiated during the prodromal rather than fulminant phase of illness : 75% of patients who survived and 10% of those who died were administered antimicrobial drugs in the prodromal phase ( 9 ) .
a new staging system for inhalation anthrax was proposed that divides the prodromal period into early and intermediate progressive stages ( 10 ) .
early diagnosis facilitated implementation of multi  antimicrobial drug therapy during the intermediate progressive stage , which is associated with increased the survival rate ( 67% vs. 21% ) ( 9 ) . for the case discussed here , systems to facilitate cooperation between a community hospital and state health agency enabled definitive identification of b. anthracis within 24 hours of culture becoming positive , leading to specific interventions including combination antimicrobial therapy , pleural drainage , and aig administration .  
drainage of pleural fluid has also been associated with increased survival ( 83% vs. 9% ) ( 9 ) ; it was performed shortly after the current patient s illness reached the late fulminant stage .
besides elevated lf levels in pleural fluid of recent us case - patients , patients with bioterrorism - related cases had large quantities of b. anthracis cell wall antigens , which further supports use of drainage procedures ( 11 ) .  
although no clinical studies have reported on efficacy of passive immunization of humans against anthrax as treatment , mortality rates have been reduced in studies of inhalation anthrax in which animals were given polyclonal antibodies against pa ( 12 ) .
aig administration in the current case was associated with a reduction in toxemia , although the role of passive immunization in anthrax treatment needs further evaluation .
 bacillus anthracis was identified in a 61-year - old man hospitalized in minnesota , usa . 
 cooperation between the hospital and the state health agency enhanced prompt identification of the pathogen . 
 treatment comprising antimicrobial drugs , anthrax immune globulin , and pleural drainage led to full recovery ; however , the role of passive immunization in anthrax treatment requires further evaluation . 