Central Nervous System Antimicrobial Exposure and Proposed Dosing for Anthrax Meningitis.

BACKGROUND: The high mortality of systemic anthrax is likely a consequence of the severe central nervous system (CNS) inflammation that occurs in anthrax meningitis. Effective treatment of such infections requires, at a minimum, adequate cerebrospinal fluid (CSF) antimicrobial concentrations. METHODS: We reviewed English medical literature and regulatory documents to extract information on serum and CSF exposures for antimicrobials with in vitro activity against Bacillus anthracis. Using CSF pharmacokinetic exposures and in vitro B. anthracis susceptibility data, we employed population pharmacokinetic modeling and Monte Carlo simulations to predict whether a specific antimicrobial dosage would likely achieve effective CSF antimicrobial activity in patients with normal to inflamed meninges (i.e., an intact to markedly disrupted blood brain barrier). RESULTS: Probability of microbiologic success at achievable antimicrobial dosages was high (≥95%) for ciprofloxacin, levofloxacin (500 mg q12 h), meropenem, imipenem/cilastatin, penicillin G, ampicillin, ampicillin/sulbactam, doxycycline, and minocycline; acceptable (90-95%) for piperacillin/tazobactam and levofloxacin (750 mg q24 h); and low (<90%) for vancomycin, amikacin, clindamycin, and linezolid. CONCLUSION: Prompt empiric antimicrobial therapy of patients with suspected or confirmed anthrax meningitis may reduce the high morbidity and mortality. Our data support using several ß-lactam-, fluoroquinolone-, and tetracycline-class antimicrobials as first-line and alternative agents for treatment of patients with anthrax meningitis; all should achieve effective microbiologic exposures. Our data also suggest antimicrobials that should not be relied upon to treat suspected or documented anthrax meningitis. Furthermore, the protein synthesis inhibitors clindamycin and linezolid can decrease toxin production and may be useful components of combination therapy.

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.

Epidemiologic Features of the Monkeypox Outbreak and the Public Health Response - United States, May 17-October 6, 2022.

On May 17, 2022, the Massachusetts Department of Health announced the first suspected case of monkeypox associated with the global outbreak in a U.S. resident. On May 23, 2022, CDC launched an emergency response (1,2). CDC's emergency response focused on surveillance, laboratory testing, medical countermeasures, and education. Medical countermeasures included rollout of a national JYNNEOS vaccination strategy, Food and Drug Administration (FDA) issuance of an emergency use authorization to allow for intradermal administration of JYNNEOS, and use of tecovirimat for patients with, or at risk for, severe monkeypox. During May 17-October 6, 2022, a total of 26,384 probable and confirmed* U.S. monkeypox cases were reported to CDC. Daily case counts peaked during mid-to-late August. Among 25,001 of 25,569 (98%) cases in adults with information on gender identity,† 23,683 (95%) occurred in cisgender men. Among 13,997 cisgender men with information on recent sexual or close intimate contact,§ 10,440 (75%) reported male-to-male sexual contact (MMSC) ≤21 days preceding symptom onset. Among 21,211 (80%) cases in persons with information on race and ethnicity,¶ 6,879 (32%), 6,628 (31%), and 6,330 (30%) occurred in non-Hispanic Black or African American (Black), Hispanic or Latino (Hispanic), and non-Hispanic White (White) persons, respectively. Among 5,017 (20%) cases in adults with information on HIV infection status, 2,876 (57%) had HIV infection. Prevention efforts, including vaccination, should be prioritized among persons at highest risk within groups most affected by the monkeypox outbreak, including gay, bisexual, and other men who have sex with men (MSM); transgender, nonbinary, and gender-diverse persons; racial and ethnic minority groups; and persons who are immunocompromised, including persons with advanced HIV infection or newly diagnosed HIV infection.

Postexposure Prophylaxis and Treatment of Bacillus anthracis Infections: A Systematic Review and Meta-analyses of Animal Models, 1947-2019.

BACKGROUND: Anthrax is endemic to many countries, including the United States. The causative agent, Bacillus anthracis, poses a global bioterrorism threat. Without effective antimicrobial postexposure prophylaxis (PEPAbx) and treatment, the mortality of systemic anthrax is high. To inform clinical guidelines for PEPAbx and treatment of B. anthracis infections in humans, we systematically evaluated animal anthrax treatment model studies. METHODS: We searched for survival outcome data in 9 scientific search engines for articles describing antimicrobial PEPAbx or treatment of anthrax in animals in any language through February 2019. We performed meta-analyses of efficacy of antimicrobial PEPAbx and treatment for each drug or drug combination using random-effects models. Pharmacokinetic/pharmacodynamic relationships were developed for 5 antimicrobials with available pharmacokinetic data. Monte Carlo simulations were used to predict unbound drug exposures in humans. RESULTS: We synthesized data from 34 peer-reviewed studies with 3262 animals. For PEPAbx and treatment of infection by susceptible B. anthracis, effective monotherapy can be accomplished with fluoroquinolones, tetracyclines, ß-lactams (including penicillin, amoxicillin-clavulanate, and imipenem-cilastatin), and lipopeptides or glycopeptides. For naturally occurring strains, unbound drug exposures in humans were predicted to adequately cover the minimal inhibitory concentrations (MICs; those required to inhibit the growth of 50% or 90% of organisms [MIC50 or MIC90]) for ciprofloxacin, levofloxacin, and doxycycline for both the PEPAbx and treatment targets. Dalbavancin covered its MIC50 for PEPAbx. CONCLUSIONS: These animal studies show many reviewed antimicrobials are good choices for PEPAbx or treatment of susceptible B. anthracis strains, and some are also promising options for combating resistant strains. Monte Carlo simulations suggest that oral ciprofloxacin, levofloxacin, and doxycycline are particularly robust choices for PEPAbx or treatment.

Mental Illness in Adults With HIV and HCV Infection: Indian Health Service, 2001-2020.

INTRODUCTION: Mental health disorders (MHDs) and substance use disorders (SUDs) in people living with HIV, hepatitis C virus (HCV) infection, and HIV/HCV coinfection are common and result in significant morbidity. However, there are no national prevalence estimates of these comorbidities in American Indian and Alaska Native (AI/AN) adults with HIV, HCV infection, or HIV/HCV coinfection. This study estimates the prevalence of MHD and SUD diagnoses in AI/AN adults diagnosed with HIV, HCV infection, or HIV/HCV coinfection within the Indian Health Service (IHS). METHODS: In 2021, a cross-sectional study using data from the National Patient Information Reporting System was completed to identify MHD or SUD diagnoses in AI/AN adults with HIV, HCV infection, or HIV/HCV coinfection within the IHS during fiscal years 2001‒2020. Logistic regression was used to compare the odds of MHD or SUD diagnoses, adjusting for age and sex. RESULTS: Of AI/AN adults diagnosed with HIV, hepatitis C virus infection, or HIV/HCV coinfection, the period prevalence of MHD or SUD diagnoses ranged from 57.2% to 81.1%. Adjusting for age and sex, individuals with HCV infection had higher odds of receiving a MHD diagnosis (AOR=1.57; 95% CI=1.47, 1.68) or SUD diagnosis (AOR=3.40; 95% CI=3.18, 3.65) than those with HIV, and individuals with HIV/HCV coinfection had higher odds of receiving a MHD diagnosis (AOR=1.60; 95% CI=1.35, 1.89) or SUD diagnosis (AOR=2.81; 95% CI=2.32, 3.41) than those with HIV. CONCLUSIONS: MHD and SUD diagnoses were common in AI/AN adults diagnosed with HIV, HCV infection, or HIV/HCV coinfection, highlighting the need for culturally appropriate screening and treatment programs sensitive to the diverse strengths of AI/AN populations and structural challenges they endure.

Factors linked to severe outcomes in multisystem inflammatory syndrome in children (MIS-C) in the USA: a retrospective surveillance study.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a newly identified and serious health condition associated with SARS-CoV-2 infection. Clinical manifestations vary widely among patients with MIS-C, and the aim of this study was to investigate factors associated with severe outcomes. METHODS: In this retrospective surveillance study, patients who met the US Centers for Disease Control and Prevention (CDC) case definition for MIS-C (younger than 21 years, fever, laboratory evidence of inflammation, admitted to hospital, multisystem [≥2] organ involvement [cardiac, renal, respiratory, haematological, gastrointestinal, dermatological, or neurological], no alternative plausible diagnosis, and either laboratory confirmation of SARS-CoV-2 infection by RT-PCR, serology, or antigen test, or known COVID-19 exposure within 4 weeks before symptom onset) were reported from state and local health departments to the CDC using standard case-report forms. Factors assessed for potential links to severe outcomes included pre-existing patient factors (sex, age, race or ethnicity, obesity, and MIS-C symptom onset date before June 1, 2020) and clinical findings (signs or symptoms and laboratory markers). Logistic regression models, adjusted for all pre-existing factors, were used to estimate odds ratios between potential explanatory factors and the following outcomes: intensive care unit (ICU) admission, shock, decreased cardiac function, myocarditis, and coronary artery abnormalities. FINDINGS: 1080 patients met the CDC case definition for MIS-C and had symptom onset between March 11 and Oct 10, 2020. ICU admission was more likely in patients aged 6-12 years (adjusted odds ratio 1·9 [95% CI 1·4-2·6) and patients aged 13-20 years (2·6 [1·8-3·8]), compared with patients aged 0-5 years, and more likely in non-Hispanic Black patients, compared with non-Hispanic White patients (1·6 [1·0-2·4]). ICU admission was more likely for patients with shortness of breath (1·9 [1·2-2·9]), abdominal pain (1·7 [1·2-2·7]), and patients with increased concentrations of C-reactive protein, troponin, ferritin, D-dimer, brain natriuretic peptide (BNP), N-terminal pro B-type BNP, or interleukin-6, or reduced platelet or lymphocyte counts. We found similar associations for decreased cardiac function, shock, and myocarditis. Coronary artery abnormalities were more common in male patients (1·5 [1·1-2·1]) than in female patients and patients with mucocutaneous lesions (2·2 [1·3-3·5]) or conjunctival injection (2·3 [1·4-3·7]). INTERPRETATION: Identification of important demographic and clinical characteristics could aid in early recognition and prompt management of severe outcomes for patients with MIS-C. FUNDING: None.

Kawasaki Disease and Kawasaki Disease Shock Syndrome Hospitalization Rates in the United States, 2006-2018.

BACKGROUND: Kawasaki disease (KD) is a febrile illness of unknown etiology. Patients with Kawasaki disease shock syndrome (KDSS) may present with clinical signs of poor perfusion and systolic hypotension in addition to typical KD features. The United States Centers for Disease Control and Prevention analyzes and interprets large hospitalization databases as a mechanism for conducting national KD surveillance. METHODS: The Kids' Inpatient Database (KID), the National (Nationwide) Inpatient Sample (NIS), and the IBM MarketScan Commercial (MSC) and MarketScan Medicaid (MSM) databases were analyzed to determine KD-associated hospitalization rates and trends from 2006 to the most recent year of available data. KD and potential KDSS hospitalizations were defined using International Classification of Disease-Clinical Modification codes. RESULTS: For the most recent year, the KD-associated hospitalization rates for children <5 years of age were 19.8 (95% CI: 17.2-22.3, KID: 2016), 19.6 (95% CI: 16.8-22.4, NIS: 2017), 19.3 (MSC: 2018), and 18.4 (MSM: 2018) per 100,000. There was no indication of an increase in KD rates over the time period. Rates of potential KDSS among children <18 years of age, ranging from 0.0 to 0.7 per 100,000, increased; coding indicated potential KDSS for approximately 2.8%-5.3% of KD hospitalizations. CONCLUSIONS: Analyses of these large, national databases produced consistent KD-associated hospitalization rates, with no increase over time detected; however, the percentage of KD hospitalizations with potential KDSS increased. Given reports of increasing incidence elsewhere and the recent identification of a novel virus-associated syndrome with possible Kawasaki-like features, continued national surveillance is important to detect changes in disease epidemiology.

Congenital CMV-Coded Diagnosis Among American Indian and Alaska Native Infants in the United States, 2000-2017.

To assess prevalence of congenital cytomegalovirus (CMV)-coded diagnosis among American Indian/Alaska Native (AI/AN) infants who received Indian Health Service (IHS)-funded care during 2000-2017. Using data from the Indian Health Service National Data Warehouse, we identified AI/AN infants with congenital CMV-coded diagnosis, defined as presence of a diagnostic code for congenital CMV disease or CMV infection (International Classification of Diseases, Ninth Revision or Tenth Revision, Clinical Modification 771.1, 078.5, P35.1, B25.xx) within 90 days of life. We calculated prevalence of congenital CMV-coded diagnosis overall, by age at first CMV-coded diagnosis, and by geographical region. During 2000-2017, 54 (1.5/10,000) of 354,923 AI/AN infants had a congenital CMV-coded diagnosis; 32 (0.9/10,000) had their first CMV-coded diagnosis within 45 days of life, and 22 (0.6/10,000) between 46 and 90 days of life. Prevalence of congenital CMV-coded diagnosis varied by region (range 0.9/10,000 in Southern Plains to 3.7/10,000 in Alaska, P = 0.0038). Among the 54 infants with a congenital CMV-coded diagnosis, 48% had clinical signs such as jaundice, petechiae, or microcephaly, compared to 25% of 354,869 infants without a CMV-coded diagnosis (P < 0.01); and 1 (2%) vs. 277 (0.1%), respectively, died (P < 0.05). The prevalence of congenital CMV-coded diagnosis among AI/AN infants who received care at IHS facilities was slightly lower than in other studies based on health claims data and varied by geographical region.

Infectious Disease Hospitalizations: United States, 2001 to 2014.

BACKGROUND: Infectious disease epidemiology has changed over time, reflecting improved clinical interventions and emergence of threats such as antimicrobial resistance. This study investigated infectious disease hospitalizations in the United States from 2001 to 2014. METHODS: Estimated rates of infectious disease hospitalizations were calculated by using the National (Nationwide) Inpatient Sample. Infectious disease hospitalizations were defined as hospitalizations with a principal discharge diagnosis of an infectious disease. Diagnoses according to site of infection and sepsis were examined, as was occurrence of in-hospital death. The leading nonsepsis infectious disease secondary diagnoses for hospitalizations with a principal diagnosis of sepsis were identified. RESULTS: The mean annual age-adjusted infectious disease hospitalization rate was 1,468.2 (95% CI, 1,459.9-1,476.4) per 100,000 population; in-hospital death occurred in 4.22% (95% CI, 4.18-4.25) of infectious disease hospitalizations. The mean annual age-adjusted infectious disease hospitalization rate increased from 2001-2003 to 2012-2014 (rate ratio, 1.05; 95% CI, 1.01-1.09), as did the percentage of in-hospital death (4.21% [95% CI, 4.13-4.29] to 4.30% [95% CI, 4.26-4.35]; P = .049). The diagnoses with the highest hospitalization rates among all sites of infection and sepsis diagnoses were the lower respiratory tract followed by sepsis. The most common nonsepsis infectious disease secondary diagnoses among sepsis hospitalizations were "urinary tract infection," "pneumonia, organism unspecified," and "intestinal infection due to Clostridium [Clostridioides] difficile." CONCLUSIONS: Although hospital discharge data are subject to limitations, particularly for tracking sepsis, lower respiratory tract infections and sepsis seem to be important contributors to infectious disease hospitalizations. Prevention of infections that lead to sepsis and improvements in sepsis management would decrease the burden of infectious disease hospitalizations and improve outcomes, respectively.

Sustained Decline in Acute Gastroenteritis-Associated Hospitalizations and Outpatient Visits Among American Indian/Alaska Native Children After Rotavirus Vaccine Introduction, 2001-2014.

We examined the uptake of rotavirus vaccine and compared trends in acute gastroenteritis (AGE)-associated hospitalizations and outpatient visits among American Indian and Alaska Native (AI/AN) children aged <5 years before and after introduction of the rotavirus vaccine. The rates of AGE-associated hospitalization and outpatient visits among AI/AN children remained below prevaccine levels.

Burden of Pneumonia-Associated Hospitalizations: United States, 2001-2014.

BACKGROUND: The epidemiology of pneumonia has likely evolved in recent years, reflecting an aging population, changes in population immunity, and socioeconomic disparities. METHODS: Using the National (Nationwide) Inpatient Sample, estimated numbers and rates of pneumonia-associated hospitalizations for 2001-2014 were calculated. A pneumonia-associated hospitalization was defined as one in which the discharge record listed a principal diagnosis of pneumonia or a secondary diagnosis of pneumonia if the principal diagnosis was respiratory failure or sepsis. RESULTS: There were an estimated 20,361,181 (SE, 95,601) pneumonia-associated hospitalizations in the United States during 2001-2014 (average annual age-adjusted pneumonia-associated hospitalization rate of 464.8 per 100,000 population [95% CI, 462.5-467.1]). The average annual age-adjusted pneumonia-associated hospitalization rate decreased over the study period (P < .0001). In-hospital death occurred in 7.4% (SE, 0.03) of pneumonia-associated hospitalizations. Non-Hispanic American Indian/Alaskan Natives and non-Hispanic blacks had the highest average annual age-adjusted rates of pneumonia-associated hospitalization of all race/ethnicities at 439.2 (95% CI, 415.9-462.5) and 438.6 (95% CI, 432.5-444.7) per 100,000 population, respectively. During 2001-2014, the proportion of pneumonia-associated hospitalizations colisting an immunocompromising condition increased from 18.7% (SE, 0.2) in 2001 to 29.9% (SE, 0.2) in 2014. Total charges for pneumonia-associated hospitalizations in 2014 were over $84 billion. CONCLUSIONS: Pneumonia is a major cause of morbidity and mortality in the United States. Differences in rates and outcomes of pneumonia-associated hospitalizations between sociodemographic groups warrant further investigation. The immunocompromised population has emerged as a group experiencing a disproportionate burden of pneumonia-associated hospitalizations.