CDC Guidelines for the Prevention and Treatment of Anthrax, 2023.

This report updates previous CDC guidelines and recommendations on preferred prevention and treatment regimens regarding naturally occurring anthrax. Also provided are a wide range of alternative regimens to first-line antimicrobial drugs for use if patients have contraindications or intolerances or after a wide-area aerosol release of: Bacillus anthracis spores if resources become limited or a multidrug-resistant B. anthracis strain is used (Hendricks KA, Wright ME, Shadomy SV, et al.; Workgroup on Anthrax Clinical Guidelines. Centers for Disease Control and Prevention expert panel meetings on prevention and treatment of anthrax in adults. Emerg Infect Dis 2014;20:e130687; Meaney-Delman D, Rasmussen SA, Beigi RH, et al. Prophylaxis and treatment of anthrax in pregnant women. Obstet Gynecol 2013;122:885-900; Bradley JS, Peacock G, Krug SE, et al. Pediatric anthrax clinical management. Pediatrics 2014;133:e1411-36). Specifically, this report updates antimicrobial drug and antitoxin use for both postexposure prophylaxis (PEP) and treatment from these previous guidelines best practices and is based on systematic reviews of the literature regarding 1) in vitro antimicrobial drug activity against B. anthracis; 2) in vivo antimicrobial drug efficacy for PEP and treatment; 3) in vivo and human antitoxin efficacy for PEP, treatment, or both; and 4) human survival after antimicrobial drug PEP and treatment of localized anthrax, systemic anthrax, and anthrax meningitis. Changes from previous CDC guidelines and recommendations include an expanded list of alternative antimicrobial drugs to use when first-line antimicrobial drugs are contraindicated or not tolerated or after a bioterrorism event when first-line antimicrobial drugs are depleted or ineffective against a genetically engineered resistant: B. anthracis strain. In addition, these updated guidelines include new recommendations regarding special considerations for the diagnosis and treatment of anthrax meningitis, including comorbid, social, and clinical predictors of anthrax meningitis. The previously published CDC guidelines and recommendations described potentially beneficial critical care measures and clinical assessment tools and procedures for persons with anthrax, which have not changed and are not addressed in this update. In addition, no changes were made to the Advisory Committee on Immunization Practices recommendations for use of anthrax vaccine (Bower WA, Schiffer J, Atmar RL, et al. Use of anthrax vaccine in the United States: recommendations of the Advisory Committee on Immunization Practices, 2019. MMWR Recomm Rep 2019;68[No. RR-4]:1-14). The updated guidelines in this report can be used by health care providers to prevent and treat anthrax and guide emergency preparedness officials and planners as they develop and update plans for a wide-area aerosol release of B. anthracis.

Safety of Antimicrobials for Postexposure Prophylaxis and Treatment of Anthrax: A Review.

BACKGROUND: Bacillus anthracis, the causative agent for anthrax, poses a potential bioterrorism threat and is capable of causing mass morbidity and mortality. Antimicrobials are the mainstay of postexposure prophylaxis (PEP) and treatment of anthrax. We conducted this safety review of 24 select antimicrobials to identify any new or emerging serious or severe adverse events (AEs) to help inform their risk-benefit evaluation for anthrax. METHODS: Twenty-four antimicrobials were included in this review. Tertiary data sources (e.g. Lactmed, Micromedex, REPROTOX) were reviewed for safety information and summarized to evaluate the known risks of these antimicrobials. PubMed was also searched for published safety information on serious or severe AEs with these antimicrobials; AEs that met inclusion criteria were abstracted and reviewed. RESULTS: A total of 1316 articles were reviewed. No consistent observations or patterns were observed among the abstracted AEs for a given antimicrobial; therefore, the literature review did not reveal evidence of new or emerging AEs that would add to the risk-benefit profiles already known from tertiary data sources. CONCLUSIONS: The reviewed antimicrobials have known and/or potential serious or severe risks that may influence selection when recommending an antimicrobial for PEP or treatment of anthrax. Given the high fatality rate of anthrax, the risk-benefit evaluation favors use of these antimicrobials for anthrax. The potential risks of antimicrobials should not preclude these reviewed antimicrobials from clinical consideration for anthrax but rather guide appropriate antimicrobial selection and prioritization across different patient populations with risk mitigation measures as warranted.

Safety of Antimicrobials During Pregnancy: A Systematic Review of Antimicrobials Considered for Treatment and Postexposure Prophylaxis of Plague.

BACKGROUND: The safety profile of antimicrobials used during pregnancy is one important consideration in the decision on how to treat and provide postexposure prophylaxis (PEP) for plague during pregnancy. METHODS: We searched 5 scientific literature databases for primary sources on the safety of 9 antimicrobials considered for plague during pregnancy (amikacin, gentamicin, plazomicin, streptomycin, tobramycin, chloramphenicol, doxycycline, sulfadiazine, and trimethoprim-sulfamethoxazole [TMP-SMX]) and abstracted data on maternal, pregnancy, and fetal/neonatal outcomes. RESULTS: Of 13 052 articles identified, 66 studies (case-control, case series, cohort, and randomized studies) and 96 case reports were included, totaling 27 751 prenatal exposures to amikacin (n = 9), gentamicin (n = 345), plazomicin (n = 0), streptomycin (n = 285), tobramycin (n = 43), chloramphenicol (n = 246), doxycycline (n = 2351), sulfadiazine (n = 870), and TMP-SMX (n = 23 602). Hearing or vestibular deficits were reported in 18/121 (15%) children and 17/109 (16%) pregnant women following prenatal streptomycin exposure. First trimester chloramphenicol exposure was associated with an elevated risk of an undescended testis (odds ratio [OR] 5.9, 95% confidence interval [CI] 1.2-28.7). Doxycycline was associated with cardiovascular malformations (OR 2.4, 95% CI 1.2-4.7) in 1 study and spontaneous abortion (OR 2.8, 95% CI 1.9-4.1) in a separate study. First trimester exposure to TMP-SMX was associated with increased risk of neural tube defects (pooled OR 2.5, 95% CI 1.4-4.3), spontaneous abortion (OR 3.5, 95% CI 2.3-5.6), preterm birth (OR 1.5, 95% CI 1.1-2.1), and small for gestational age (OR 1.6, 95% CI 1.2-2.2). No other statistically significant associations were reported. CONCLUSIONS: For most antimicrobials reviewed, adverse maternal/fetal/neonatal outcomes were not observed consistently. Prenatal exposure to streptomycin and TMP-SMX was associated with select birth defects in some studies. Based on limited data, chloramphenicol and doxycycline may be associated with adverse pregnancy or neonatal outcomes; however, more data are needed to confirm these associations. Antimicrobials should be used for treatment and PEP of plague during pregnancy; the choice of antimicrobials may be influenced by these data as well as information about the risks of plague during pregnancy.

Food selection and effect of home preparation procedure for antibiotic food mixtures on homogeneity, stability, and dissolution.

Amoxicillin, doxycycline, and clindamycin are among the commonly used antibiotics to treat bacterial infections. However, dosage forms of antibiotics for pediatric patients may not be as readily available as the formulations for adult patients. As such, it is anticipated that during a public health emergency, special instruction may need to be provided on home preparation and administration procedures to dose pediatric patients using available stockpiles of oral tablet and capsule dosage forms. Mixing crushed tablets or capsule contents with soft- or liquid- foods is one of the most common home preparation procedures. To gain knowledge for safe and effective use of prepared drug product instead of the intended intact dosage form, the impact of manipulation of the dosage form was studied. Capsule opening, capsule content assay and uniformity, dissolution, homogeneity, and stability studies of drug mixed with various liquid and soft foods were carried out using intact capsules of amoxicillin, doxycycline, and clindamycin. Higher recovery of capsule contents was achieved when using hands or knives to open capsules compared to using scissors. The capsules of all three antibiotic products contained the labeled amount of active pharmaceutical ingredients (API). The peanut butter-drug mixtures failed both United States Pharmacopeia (USP) assay and dissolution criteria because the peanut butter significantly affected the solubility of the drugs, and hence it was omitted from further study. All drug-food mixtures of the three antibiotic products and 15 selected foods exhibited fast dissolution (e.g., >80 % in 60 min) in the tested medium, except for the amoxicillin-chocolate pudding mixture. Three household containers (cups, plates, and bowls) and four mixing times (0.5 min, 1 min, 2 min, and 5 min) were found to be suitable for preparation of homogeneous mixtures of the antibiotics and foods. For practical purposes, 1 to 2 min mixing time is sufficient to produce homogeneous mixtures. The results of this study provided product quality data on the interactions between the antibiotics and the foods and can potentially support future development of home preparation instructions of antibiotics for pediatric patients or patients with swallowing difficulties.