Introduction: The human lung harbors a diverse microbiota that influences respiratory health. In people living with HIV (PLHIV), chronic inflammation and immunosuppression increase susceptibility to community-acquired pneumonia (CAP) and pulmonary function decline. However, the role of the lung microbiota in these outcomes remains poorly understood. Therefore, we sought to explore the relationship between lung microbiota composition and pulmonary function in PLHIV, with and without CAP. Methods: We conducted a prospective cohort study in three hospitals in Medellín, Colombia (2016–2018). Adult patients with HIV and/or CAP were included, with respiratory samples and spirometry performed at hospital admission and at six-month follow-up. The subcohort analyzed comprised 12 patients: 5 with HIV+CAP, 3 with CAP, and 4 with HIV. Spirometric parameters (FVC, FEV1, FEV1/FVC, FEF25–75) and microbial diversity (Shannon index, OTUs) were assessed. Lung microbiota profiling was performed by 16S rRNA gene sequencing. Results: Median age was 58 years, and 66.7% were male. In the HIV+CAP group, Mycobacterium tuberculosis was detected in 60% and Pneumocystis jirovecii in 40% of cases. From baseline to follow-up, median FEV1 increased from 1.80 L to 2.09 L, and FEF25–75 from 3.13 L/s to 3.00 L/s; FEV1/FVC remained stable (0.82). Median change in Shannon index was 0.5 (IQR: 0.1–1.5), and OTUs –6 (IQR: –40 to 19), indicating individual fluctuations in microbial diversity. The predominant phyla were Firmicutes, Proteobacteria, Fusobacteria, Bacteroidetes, and Actinobacteria. At the genus level, Streptococcus, Haemophilus, Veillonella, Neisseria, and Fusobacterium were most abundant. In this subcohort of PLHIV and/or CAP patients, changes in pulmonary function coexisted with variability in lung microbiota diversity between admission and follow-up. Conclusions: The identification of dominant taxa and characterization of their dynamics provides a basis for further studies assessing the interaction between lung microbiota and respiratory impairment in immunocompromised populations.

The lung microbiota plays a key role in respiratory health, but its composition in individuals living with HIV and diagnosed with community-acquired pneumonia (CAP) remains underexplored. A prospective cohort study in Medellín, Colombia recruited individuals with CAP and/or HIV between 2016 and 2018. Clinical and microbiological data were collected at baseline, with bronchoalveolar lavage samples obtained at baseline and induced sputum samples collected at baseline and 6-month follow-up. Microbiota composition was analyzed in these samples using Illumina MiSeq sequencing of the 16S ribosomal RNA gene. Among 248 screened participants, 64 were included: HIV and CAP (n = 27), CAP (n = 7), and HIV (n = 30); 70.3% were males, and 76.6% were between 25 and 64 years old. The HIV and CAP group had a lower proportion of receiving antiretroviral treatment and a higher prevalence of advanced immunosuppression. The most frequent micro-organisms identified by conventional methods in the HIV and CAP group were Mycobacterium tuberculosis (40.7%) and Pneumocystis jirovecii (18.5%). The dominant phyla (Firmicutes, Proteobacteria, Fusobacteria, Bacteroidetes, and Actinobacteria) and genera (Streptococcus, Haemophilus, Veillonella, Neisseria, and Fusobacterium) were identified in the overall study population, including both baseline and 6-month follow-up samples. The HIV and CAP group showed changes in bacterial diversity and relative abundance over 6 months. These findings provide insights into the dynamic lung microbiota in individuals coinfected with HIV and CAP, highlighting the impact of HIV and CAP on microbial composition and diversity, which may inform future studies exploring clinical outcomes.

ABSTRACT Post-market surveillance of test performance is a critical function of public health agencies and clinical researchers that ensures tests maintaining diagnostic characteristics following their regulatory approval. Changes in product quality, manufacturing processes over time, or the evolution of new variants may impact product performance. During the COVID-19 pandemic, a plethora of point-of-care tests (POCTs) was released onto the Canadian market. This study evaluated the performance characteristics of several of the most widely distributed POCTs in Canada, including four rapid antigen tests (Abbott Panbio, BTNX Rapid Response, SD Biosensor, and Quidel QuickVue) and two molecular tests (Abbott ID NOW and Lucira Check IT). All tests were challenged with 149 SARS-CoV-2 clinical positives, including multiple variants up to and including Omicron XBB.1.5, as well as 29 clinical negatives. Results were stratified based on whether the isolate was Omicron or pre-Omicron as well as by reverse transcriptase quantitative PCR Ct value. The test performance of each POCT was consistent with the manufacturers' claims and showed no significant decline in clinical performance against any of the variants tested. These findings provide continued confidence in the results of these POCTs as they continue to be used to support decentralized COVID-19 testing. This work demonstrates the essential role of post-market surveillance in ensuring reliability in diagnostic tools. IMPORTANCE Post-market surveillance of diagnostic test performance is critical to ensure their reliability after regulatory approval. This is especially critical in the context of the COVID-19 pandemic as the use of point-of-care tests (POCTs) became widespread. Our study focused on four rapid antigen tests (Abbott Panbio, BTNX Rapid Response, SD Biosensor, and Quidel QuickVue) and two molecular tests (Abbott ID NOW and Lucira Check IT) that were widely distributed across Canada, assessing their performance using many SARS-CoV-2 variants, including up to Omicron subvariant XBB.1.5. Overall, we found no significant difference in performance against any variant, reinforcing confidence in their use. As concerns in test efficacy have been raised by news outlets, particularly regarding the BTNX Rapid Response, this work is even more timely and crucial. Our research offers insights into the performance of widely used COVID-19 POCTs but also highlights the necessity for post-market surveillance.

Legionella infections have a propensity for occurring in HIV-infected individuals, with immunosuppressed individuals tending to present with more severe disease. However, understanding regarding the Legionella host response in immune compromised individuals is lacking. This study investigated the inflammatory profiles associated with Legionella infection in patients hospitalized with HIV and pneumonia in Medellín, Colombia from February 2007 to April 2014, and correlated these profiles with clinical outcomes. Sample aliquots from the Colombian cohort were shipped to Canada where Legionella infections and systemic cytokine profiles were determined using real-time PCR and bead-based technology, respectively. To determine the effect of Legionella coinfection on clinical outcome, a patient database was consulted, comparing laboratory results and outcomes between Legionella-positive and -negative individuals. Principal component analysis revealed higher plasma concentrations of eotaxin, IP-10 and MCP-1 (p = 0.0046) during Legionella infection. Individuals with this immune profile also had higher rates of intensive care unit admissions (adjusted relative risk 1.047 [95% confidence interval 1.027–1.066]). Results demonstrate that systemic markers of monocyte/macrophage activation and differentiation (eotaxin, MCP-1, and IP-10) are associated with Legionella infection and worse patient outcomes. Further investigations are warranted to determine how this cytokine profile may play a role in Legionella pneumonia pathogenesis or immunity.

Throughout the coronavirus disease 2019 (COVID-19) pandemic, wastewater surveillance has been used to monitor trends in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) prevalence in the community. A major challenge in establishing wastewater surveillance programs, especially in remote areas, is the need for a well-equipped laboratory for sample analysis. Currently, no options exist for rapid, sensitive, mobile, and easy-to-use wastewater tests for SARS-CoV-2. The performance of the GeneXpert system, which offers cartridge-based, rapid molecular clinical testing for SARS-CoV-2 in a portable platform, was evaluated using wastewater as the input. The GeneXpert demonstrated a SARS-CoV-2 limit of detection in wastewater below 32 copies/mL with a sample processing time of less than an hour. Using wastewater samples collected from multiple sites across Canada during February and March 2021, a high overall agreement (97.8%) was observed between the GeneXpert assay and laboratory-developed tests regarding the presence or absence of SARS-CoV-2. Additionally, with the use of centrifugal filters, the detection threshold of the GeneXpert system was improved to <10 copies/mL in wastewater. Finally, to support on-site wastewater surveillance, GeneXpert testing was implemented in Yellowknife, a remote community in Northern Canada, where its use successfully alerted public health authorities to undetected transmission of COVID-19. The identification of SARSCoV-2 in wastewater triggered clinical testing of recent travelers and identification of new COVID-19 cases/clusters. Taken together, these results suggest that GeneXpert is a viable option for surveillance of SARS-CoV-2 in wastewater in locations that do not have access to established testing laboratories. IMPORTANCE Wastewater-based surveillance is a powerful tool that provides an unbiased measure of COVID-19 prevalence in a community. This work describes a sensitive wastewater rapid test for SARS-CoV-2 based on a widely distributed technology, the GeneXpert. The advantages of an easy-to-use wastewater test for SARS-CoV-2 are clear: it supports surveillance in remote communities, improves access to testing, and provides faster results allowing for an immediate public health response. The application of wastewater rapid testing in a remote community facilitated the detection of a COVID-19 cluster and triggered public health action, clearly demonstrating the utility of this technology. Wastewater surveillance will become increasingly important in the postvaccination pandemic landscape as individuals with asymptomatic/mild infections continue transmitting SARS-CoV-2 but are unlikely to be tested.

With the Panbio severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen test being deployed in over 120 countries worldwide, understanding conditions required for its ideal performance is critical. Recently on social media, this kit was shown to generate false positives when manufacturer recommendations were not followed.

Legionnaires' disease incidence is on the rise, with the majority of cases attributed to the intracellular pathogen, Legionella pneumophila. Nominally a parasite of protozoa, L. pneumophila can also infect alveolar macrophages when bacteria-laden aerosols enter the lungs of immunocompromised individuals. L. pneumophila pathogenesis has been well characterized; however, little is known about the >25 different Legionella spp. that can cause disease in humans. Here, we report for the first time a study demonstrating the intracellular infection of an L. bozemanae clinical isolate using approaches previously established for L. pneumophila investigations. Specifically, we report on the modification and use of a green fluorescent protein (GFP)-expressing plasmid as a tool to monitor the L. bozemanae presence in the Acanthamoeba castellanii protozoan infection model. As comparative controls, L. pneumophila strains were also transformed with the GFP-expressing plasmid. In vitro and in vivo growth kinetics of the Legionella parental and GFP-expressing strains were conducted followed by confocal microscopy. Results suggest that the metabolic burden imposed by GFP expression did not impact cell viability, as growth kinetics were similar between the GFP-expressing Legionella spp. and their parental strains. This study demonstrates that the use of a GFP-expressing plasmid can serve as a viable approach for investigating Legionella non-pneumophila spp. in real time.

AbstractObjectivesAntigen-based rapid diagnostics tests (Ag-RDTs) are useful tools for SARS-CoV-2 detection. However, misleading demonstrations of the Abbott Panbio COVID-19 Ag-RDT on social media claimed that SARS-CoV-2 antigen could be detected in municipal water and food products. To offer a scientific rebuttal to pandemic misinformation and disinformation, this study explored the impact of using the Panbio SARS-CoV-2 assay with conditions falling outside of manufacturer recommendations.MethodsUsing Panbio, various water and food products, laboratory buffers, and SARS-CoV-2-negative clinical specimens were tested, with and without manufacturer buffer. Additional experiments were conducted to assess the role of each Panbio buffer component (tricine, NaCl, pH, and tween-20), as well as the impact of temperatures (4°C, 20°C, and 45°C) and humidity (90%) on assay performance.ResultsDirect sample testing (without the kit buffer), resulted in false positive signals resembling those obtained with SARS-CoV-2-positive controls tested under proper conditions. The likely explanation of these artifacts is non-specific interactions between the SARS-CoV-2-specific conjugated and capture antibodies, as proteinase K treatment abrogated this phenomenon, and thermal shift assays showed pH-induced conformational changes under conditions promoting artifact formation. Omitting, altering, and reverse engineering the kit buffer all supported the importance of maintaining buffering capacity, ionic strength, and pH for accurate kit function. Interestingly, the Panbio assay could tolerate some extremes of temperature and humidity outside of manufacturer claims.ConclusionsOur data support strict adherence to manufacturer instructions to avoid false positive SARS-CoV-2 Ag-RDT reactions, otherwise resulting in anxiety, overuse of public health resources, and dissemination of misinformation.

Prior studies have shown that HIV patients develop permanent pulmonary dysfunction following an episode of community-acquired pneumonia (CAP). However, the mechanism causing pulmonary dysfunction remains an enigma. HIV patients experience chronic inflammation. We hypothesized that CAP exacerbates inflammation in HIV patients resulting in an accelerated decline in lung function. A prospective cohort pilot study enrolled HIV patients hospitalized in Medellin, Colombia, with a diagnosis of CAP. Sixteen patients were eligible for the study; they were split into 2 groups: HIV and HIV+CAP. Plasma, sputum, and pulmonary function test (PFT) measurements were retrieved within 48h of hospital admission and at 1 month follow-up. The concentrations of 13 molecules and PFT values were compared between the 2 cohorts. The HIV+CAP group had lower lung function compared to the HIV group; forced vital capacity (FVC)% predicted and forced expiratory volume in 1s (FEV1)% predicted decreased, while FEV1/FVC remained constant. APRIL, BAFF, CCL3, and TIMP-1 correlated negatively with FVC% predicted and FEV1% predicted; the relationships however were moderate in strength. Furthermore, the concentrations of BAFF, CCL3, and TIMP-1 were statistically significant between the 2 groups (P <= 0.05). Our results indicate that HIV patients with CAP have a different inflammatory pattern and lower lung function compared to HIV patients without CAP. BAFF, CCL3, and TIMP-1 were abnormally elevated in HIV patients with CAP. Future studies with larger cohorts are required to verify these results. In addition, further investigation is required to determine if BAFF, CCL3, and TIMP-1 play a role in the process causing pulmonary dysfunction.

HIV and pneumonia infections have both been shown to negatively impact lung function. However, evidence of the role of inflammation on lung dysfunction in HIV and pneumonia co-infected individuals remains limited. We aimed to systematically review the association of inflammatory markers and lung abnormalities in HIV and pneumonia co-infected individuals. This systematic review was registered with the International Prospective Register of Systematic Reviews on August 15, 2017 (registration number CRD42017069254) and used 4 databases (Cochrane Central Register of Controlled Trials, PubMed Central, Clinical Trials.gov and Google Scholar). All clinical trial, observational, and comparative studies targeting adult (> 18 years old) populations with HIV, pneumonia, or both, that report on immune response (cytokine, chemokine, or biomarker), and lung abnormality as an outcome were eligible. Data selection, risk of bias and extraction were performed independently by 2 blinded reviewers. Due to heterogeneity among the articles, a qualitative synthesis was performed. Our search strategy identified 4454 articles of which, 7 met our inclusion criteria. All of the studies investigated the ability of circulating biomarkers to predict lung damage in HIV. None of the articles included patients with both HIV and pneumonia, nor pneumonia alone. Markers of inflammation (IL-6, TNF-α, CRP), innate defense (cathelicidin), monocyte and macrophage activation (sCD14, sCD163 and, IL-2sRα), endothelial dysfunction (ET-1) and general immune health (CD4/CD8 ratio) were associated with lung abnormalities in HIV. This review highlights the lack of available information regarding the impact of inflammatory mediators on lung function in HIV and pneumonia populations, therefore opportunities to prevent lung damage with available anti-inflammatory treatment or to investigate new ones still remain.

Due to poor diagnostics and increased co-infections, HIV-associated Legionella infections are underreported. We aimed to retrospectively determine the frequency of Legionella infections in bronchoalveolar lavage (BAL) from HIV-associated pneumonia patients hospitalized in Medellin, Colombia, between February 2007 and April 2014. Although culture was negative, 17 BAL (36%) were positive for Legionella by quantitative polymerase chain reaction, most of which were in the Mycobacterium tuberculosis or Pneumocystis jirovecii co-infected patients, and included L. anisa (n = 6), L. bozemanae (n = 4), L. pneumophila (n = 3), and L. micdadei (n = 2). All L. bozemanae and L. micdadei associated with Pneumocystis, while all L. pneumophila associated with M. tuberculosis. Legionella probable cases had more complications and higher mortality rates (P = 0.02) and were rarely administered empirical anti-Legionella therapy while in hospital. Clinicians should be aware of the possible presence of Legionella in HIV and M. tuberculosis or P. jirovecii co-infected patients.

Abstract Background HIV patients face higher rates of morbidity compared with the general population, largely due to the earlier development of age related diseases (cardiovascular, kidney, and liver disease). While it is likely that chronic immune activation and inflammation are the main contributors to this process, it’s relation to lung injury in HIV remains unknown. Despite restoration of systemic immune function following Antiretroviral Therapy, the risk for lower respiratory tract infection remain elevated in the HIV population. The objective of the study was to assess the relationship between pulmonary inflammation and lung injury. Methods A prospective cohort study was performed, participants include patients hospitalized in Hospital Universitario San Vicente Fundación and Clínica SOMA, in Colombia. Patients were eligible if they were over the age of 18 and had a documented HIV infection or if they have HIV with newly diagnosed community acquired pneumonia (CAP). The main exclusion criteria were chronic lung disease and immunosuppression that is not due to HIV. Patients belonged to two groups: HIV and HIV + CAP. Plasma, sputum samples and pulmonary function test measurements (PFT) were retrieved within 48 hours of hospital admission and at one month follow-up. The concentrations of 13 biomarkers were measured and correlated with PFT values, followed by a comparison between the two groups. Results Principle Component Analysis revealed that CCL3, CCL4, BAFF, APRIL, and TIMP-1 accounts for the majority of the variation between the two groups. Furthermore, Kruskal–Wallis testing demonstrates that BAFF and CCL3 are elevated in the HIV + CAP group, compared with the HIV group (P < 0.005). Other markers of bacterial translocation and monocyte activation did not differ between these groups. FVC and FEV1 measurements are lower in the HIV + CAP group compared with the HIV group, while FEV1/FVC remain constant. Conclusion The results of this study identify a unique constellation of biomarkers in HIV patients with CAP, this constellation of biomarkers consists of pro-inflammatory cytokines and regulators of extracellular matrix remodeling, hinting at the occurrence of an inflammatory and tissue injuring process in the lungs. This is supported by the restrictive ventilation pattern seen in this group of patients. Disclosures All authors: No reported disclosures.

Human immunodeficiency virus (HIV)-infected individuals are more susceptible to respiratory tract infections by other infectious agents (viruses, bacteria, parasites, and fungi) as their disease progresses to acquired immunodeficiency syndrome. Despite effective antiretroviral therapy, bacterial pneumonia (the most frequently occurring HIV-associated pulmonary illness) remains a common cause of morbidity and mortality in the HIV-infected population. Over the last few decades, studies have looked at the role of atypical bacterial pneumonia (i.e. pneumonia that causes an atypical clinical presentation or responds differently to typical therapeutics) in association with HIV infection. Due to the lack of available diagnostic strategies, the lack of consideration, and the declining immunity of the patient, HIV co-infections with atypical bacteria are currently believed to be underreported. Thus, following an extensive database search, this review aimed to highlight the current knowledge and gaps regarding atypical bacterial pneumonia in HIV. The authors discuss the prevalence of Chlamydophila pneumoniae, Mycoplasma pneumoniae, Coxiella burnetii, Legionella species and others in the HIV-infected population as well as their clinical presentation, methods of detection, and treatment. Further studies looking at the role of these microbes in association with HIV are required. Increased knowledge of these atypical bacteria will lead to a more rapid diagnosis of these infections, resulting in an improved quality of life for the HIV-infected population.

A sampling trip to Central Gold Mine, Nopiming Provincial Park, Canada, was taken in September 2011. Abundance, distribution, and physiology of aerobic anoxygenic phototrophs (AAP) from 4 locations were studied. Enumeration revealed 14.6% of culturable microbes were AAP. Five strains (NM4.16, NM4.18, C4, C9, C11) were chosen for analysis. All grow best on complex media without vitamin requirements and with an optimal pH 7.0-8.0, with strain C4 preferring pH 6.0. Strain NM4.18 tolerates the highest pH 11.0. Optimal temperature for all is 28 °C (range of 2-37 °C except NM4.16, which survives 45 °C). Strains C9, C11, and NM4.18 grew in 1.0%, 2.0%, and 5.0% NaCl, respectively, while NM4.16 and C4 grew only without NaCl. Isolates were all highly resistant to toxic metal(oid) oxides: tellurite (1500 μg/mL, all), tellurate (1500 μg/mL, C11), selenite (5000 μg/mL, C9, C11, and NM4.18), selenate (1000 μg/mL, C9 and C11), and orthometavanadate and metavanadate (5000 μg/mL, C11 and NM4.18). They could reduce tellurite to the less toxic elemental tellurium. Full 16S rRNA gene sequencing revealed all strains are Alphaproteobacteria, with C4 and NM4.16 closely related to Porphyrobacter colymbi (99.4% and 99.7% sequence similarity, respectively), C9 to Brevundimonas variabilis (99.1%), C11 to Brevundimonas bacteroides (98.6%), and NM4.18 to Erythromonas ursincola (98.5%).

Background: Owing to its ability to form spores and toxins, Bacillus anthracis is considered a bioterror agent. Although current therapeutic strategies can be effective, treatment does not prevent sporulation and toxin production. Objectives: To quantify the combined effect of a protein synthesis inhibitor and a bactericidal agent on B. anthracis toxin production, sporulation and cell growth.Methods: Susceptibility and synergy titrations were conducted on B. anthracis Sterne and 03-0191 strains using linezolid and levofloxacin. The effect of antibiotic exposure on cell viability was evaluated using a continuous medium replacement model. In vitro static models were used to study the effect of linezolid and levofloxacin on sporulation and toxin production. Spores were quantified using the heat shock method. Toxin was quantified via commercial ELISA.Results: Synergy titrations indicated that the combination was synergistic or indifferent; however, in all models antagonism was observed. In the spore model, linezolid resulted in the lowest sporulation rates, while combination therapy resulted in the highest. In the toxin model, linezolid prevented toxin production altogether.Conclusions: This study advances our understanding of the effects of combination therapy on B. anthracis infection. Used alone, linezolid therapy abolishes toxin production and reduces sporulation. These results suggest that studies using a step-wise approach using linezolid initially to stop sporulation and toxin production followed by levofloxacin to rapidly kill vegetative B. anthracis can be recommended.

Due to the lack of clinical suspicion, poor diagnostic performance, increased patient immunosuppression, and the increased chance of co-infection, HIV-associated Legionella community-acquired pneumonia (CAP) is currently under-reported. Thus, this study aimed to determine the frequency of Legionella in CAP-infected HIV patients. Following initial diagnosis, DNA extracted from bronchoalveolar lavage (BAL) from CAP-infected HIV patients hospitalized at Hospital San Vicente Fundación in Medellin, Colombia were assayed for the presence of Legionella species (PAN Legionella, L. Anisa, L. bozemanii, L. micdadei, L. pneumophila and L. pneumophila serogroup 1) using singleplex real-time PCR (qPCR). Results were validated with agarose gel electrophoresis and reconfirmed using pre-amplification qPCR. Of the 59 HIV-infected individuals in the study, majority were non-smokers (64.4%), male (77.9%), and highly immunosuppressed (CD4 cell count <200 cells/μL). Initial CAP diagnoses were M. tuberculosis (37.3%), P. jiroveci (32.2%) and others (30.5%). Initial screening of pooled BAL samples indicated that majority of positive PAN Legionella were associated with M. tuberculosis and P. jiroveci. Of the 14 individual M. tuberculosis-infected patient BAL assayed, 10 were positive for PAN Legionella. Likewise, 6/9 P. jiroveci-infected BAL were also positive. Of all of the detected Legionellaceae infections, 31.3% were L. Anisa, 25.0% L. bozemanii, 18.8% L. pneumophila, and 12.5% L. micdadei, and 37.5% uncharacterized. Interestingly, none of the L. pneumophila infections were due to serogroup 1. Of note, all L. bozemanii and L. micdadei infections were associated with P. jiroveci, while all L. pneumophila infections were associated with M. tuberculosis. Legionella-infected patients had more complications and higher mortality rates compared with un-infected patients. Results indicate that Legionella are prevalent in the BAL of HIV co-infected patients. Clinicians should be aware of the possibility of the presence of Legionella—and not just L. pneumophila—in HIV-associated CAP. The role Legionella plays in clinical presentation, disease severity and inflammation remains to be determined. If further investigation supports these findings, this could change the way that CAP is managed in HIV-infected individuals. All authors: No reported disclosures.

Background: Bacillus anthracis, the causative agent of anthrax, is a spore forming and toxin producing rod-shaped bacterium that is classified as a category A bioterror agent. This pathogenic microbe can be transmitted to both animals and humans. Clinical presentation depends on the route of entry (direct contact, ingestion, injection or aerosolization) with symptoms ranging from isolated skin infections to more severe manifestations such as cardiac or pulmonary shock, meningitis, and death. To date, anthrax is treatable if antibiotics are administered promptly and continued for 60 days. However, if treatment is delayed or administered improperly, the patient's chances of survival are decreased drastically. In addition, antibiotics are ineffective against the harmful anthrax toxins and spores. Therefore, alternative therapeutics are essential. In this review article, we explore and discuss advances that have been made in anthrax therapy with a primary focus on alternative pre-approved and novel antibiotics as well as anti-toxin therapies.Methods: A literature search was conducted using the University of Manitoba search engine. Using this search engine allowed access to a greater variety of journals/articles that would have otherwise been restricted for general use. In order to be considered for discussion for this review, all articles must have been published later than 2009.Results: The alternative pre-approved antibiotics demonstrated high efficacy against B. anthracis both in vitro and in vivo. In addition, the safety profile and clinical pharmacology of these drugs were already known. Compounds that targeted underexploited bacterial processes (DNA replication, RNA synthesis, and cell division) were also very effective in combatting B. anthracis. In addition, these novel compounds prevented bacterial resistance. Targeting B. anthracis virulence, more specifically the anthrax toxins, increased the length of which treatment could be administered.Conclusions: Several novel and pre-existing antibiotics, as well as toxin inhibitors, have shown increasing promise. A combination treatment that targets both bacterial growth and toxin production would be ideal and probably necessary for effectively combatting this armed bacterium.