Antimicrobial Treatment for Systemic Anthrax: Analysis of Cases from 1945 to 2014 Identified Through a Systematic Literature Review

Abstract

Background Systemic anthrax is associated with high mortality. Current national guidelines, developed for the individualized treatment of systemic anthrax, outline the use of combination intravenous antimicrobials for a minimum of two weeks; bactericidal and protein synthesis inhibitor antimicrobials for all cases of systemic anthrax; and at least 3 antimicrobials with good blood-brain barrier penetration for anthrax meningitis. However, in an anthrax mass casualty incident, large numbers of anthrax cases may create challenges in meeting antimicrobial needs. Methods To further inform our understanding of the role of antimicrobials in treating systemic anthrax, a systematic review of the English language literature was conducted to identify cases of systemic anthrax treated with antimicrobials for which a clinical outcome was recorded. Results A total of 149 cases of systemic anthrax were identified (cutaneous [n=59], gastrointestinal [n=28], inhalation [n=26], primary anthrax meningitis [n=19], multiple routes [n=9], and injection [n=8]). Among the identified 59 cases of cutaneous anthrax, 33 were complicated by meningitis (76% mortality), while 26 simply had evidence of the systemic inflammatory response syndrome (4% mortality); 21 of 26 (81%) of this latter group received monotherapy. Subsequent analysis regarding combination antimicrobial therapy was restricted to the remaining 123 cases of more severe anthrax (overall 67% mortality). Recipients of combination bactericidal and protein synthesis inhibitor therapy had a 45% survival versus 28% in the absence of combination therapy (p = 0.07). For meningitis cases (n=77), survival was greater for those receiving a total of ≥3 antimicrobials over the course of treatment (3 of 4; 75%), compared to receipt of 1 or 2 antimicrobials (12 of 73; 16%) (p = 0.02). Median parenteral antimicrobial duration was 14 days. Conclusion Combination bactericidal and protein synthesis inhibitor therapy may be appropriate in severe anthrax disease, particularly anthrax meningitis, in a mass casualty incident.

Pathology of wild-type and toxin-independent Bacillus anthracis meningitis in rabbits

“…One of the treatment challenges at the acute stage is the onset of meningitis in more than 50% of the cases in humans and NHP, which manifests as massive hemorrhages in the brain cortex (cardinal's cap) [ 12 , 13 ]. Patient data reported between 1945 to 2014 [ 14 ] demonstrates that antibiotic treatment of patients that were negative for meningitis was effective in 71% of the cases while the treatment of meningitis-positive patients was effective in less than 20%. In the rabbit model, careful analysis of brain bacterial loads in correlation with different bacteremia levels revealed that specific accumulation of bacteria in the brain starts at bacteremia levels higher than 10 4 CFU/ml [ 15 ], a finding that correlates well with the reduction in the efficacy of the antibiotic treatment and the development of meningitis in humans.…”

Optical Screening for Rapid Antimicrobial Susceptibility Testing and for Observation of Phenotypic Diversity among Strains of the Genetically Clonal Species Bacillus anthracis

“…The consideration of antimicrobial resistance phenotypes is an essential part of the ongoing effort to prepare for and respond to an intentional release or an outbreak of anthrax because without timely, effective therapy, this disease is associated with high rates of mortality (10). B. anthracis is usually susceptible to the antimicrobial agents approved for treatment and postexposure prophylaxis, although naturally occurring resistance to penicillin (PEN) has been documented, and a single isolate with resistance to erythromycin has been reported (11)(12)(13)(14)(15).…”

Evaluation of Combination Drug Therapy for Treatment of Antibiotic-Resistant Inhalation Anthrax in a Murine Model

“…Although data are limited, regimens comprising multiple antimicrobials appear to offer survival advantages in both animals and humans (9,10). Therefore, there is a demonstrated need to develop effective multidrug treatment strategies for early empirical treatment of anthrax or antibiotic-resistant anthrax.…”