Antimicrobial Susceptibility of Neisseria gonorrhoeae in Adult Patients Seeking Care at Military Hospitals in Thailand From 2014 to 2020

ABSTRACT Introduction The effective dual antibiotics ceftriaxone (CRO) and azithromycin (AZM) have successfully treated Neisseria gonorrhoeae (GC) infection, however, the CRO- and AZM-resistant strains have been sporadically detected globally and in Thailand. Furthermore, there are no currently antimicrobial susceptibility profiles of the GC isolates obtained from soldiers reported in Thailand. Hence, this is the first study to describe the antimicrobial susceptibility profiles of GC isolates obtained from predominately soldiers who seeking care at Military Camp Hospitals, in Thailand from 2014 to 2020. Materials and Methods A total of 624 symptomatic gonococcal samples were received from 10 military hospitals during 2014-2020. They were collected from urethral swabs and inoculated into selective media. The suspected GC isolates were subcultured and presumptively identified using conventional microbiology techniques. Antimicrobial susceptibility test was performed by Etest to determine minimal inhibitory concentration (μg/mL) against AZM, benzylpenicillin, cefepime, cefixime, ceftriaxone (CRO), ciprofloxacin, spectinomycin, and tetracycline using the criteria outlined in the Clinical and Laboratory Standards Institute guidelines. This study was approved by Institutional Review Board, Royal Thai Army Medical Department under protocol number S036b/56 and Walter Reed Army Institute of Research, and Silver Spring, MD under protocol number WR #2039. Results A total of 624 samples were collected from symptomatic gonococcal infectious patients with 91.5% (571/624) of samples obtained from soldiers. Of those, 78% (488/624) were identified as GC and 92% (449/488) of them were isolated from soldiers. All GC samples collected were susceptible to CRO (first-line treatment) with only one GC isolate identified as non-susceptible to cefepime and three isolates identified as non-susceptible to AZM. Conclusion The recommended dual treatment of GC infections with CRO and AZM is currently an effective empirical treatment for patients who are seeking care at military hospitals in Thailand. Nevertheless, cefepime is a fourth-generation cephalosporin with documented high activity against GC strains equal to other “third-generation” cephalosporins such as CRO. Due to the active duty of military personnel, they concerned about the confidentiality and frequently seek treatment at civilian clinics. Additionally, due to the availability of antibiotics over the counter in Thailand, many choose the option to self-medicate without a physician’s prescription. These could be subsequently driven the gradual increase of multidrug-resistant gonococcal strains throughout the country. Thus, the GC surveillance would be needed for further Force Health Protection and public health authorities in response to the drug-resistant GC threats.

Cross-Cutting Lessons Learned During the COVID-19 Pandemic—the Walter Reed Army Institute of Research Experience

ABSTRACT Introduction At the start of the coronavirus disease 2019 (COVID-19) pandemic, Walter Reed Army Institute of Research (WRAIR) mobilized to rapidly conduct medical research to detect, prevent, and treat the disease in order to minimize the impact of the pandemic on the health and readiness of U.S. Forces. WRAIR’s major efforts included the development of the Department of Defense (DoD) COVID-19 vaccine candidate, researching novel drug therapies and monoclonal antibodies, refining and scaling-up diagnostic capabilities, evaluating the impact of viral diversity, assessing the behavioral health of Soldiers, supporting U.S. DoD operational forces overseas, and providing myriad assistance to allied nations. WRAIR personnel have also filled key roles within the whole of government response to the pandemic. WRAIR had to overcome major pandemic-related operational challenges in order to quickly execute a multimillion-dollar portfolio of COVID-19 research. Consequently, the organization learned lessons that could benefit other leaders of medical research organizations preparing for the next pandemic. Materials and Methods We identified lessons learned using a qualitative thematic analysis of 76 observation/recommendation pairs from across the organization. These lessons learned were organized under the Army’s four pillars of readiness (staffing, training, equipping, and leadership development). To this framework, we added organizing and leading to best capture our experiences within the context of pandemic response. Results The major lessons learned for organizing were: (1) the pandemic created a need to rapidly pivot to new scientific priorities; (2) necessary health and safety precautions disrupted the flow of normal science and put programs at risk of missing milestones; (3) relationships with partners and allies facilitated medical diplomacy and advancement of U.S. national military and economic goals; and (4) a successful response required interoperability within and across multiple organizations. For equipping: (1) existing infrastructure lacked sufficient capacity and technical capability to allow immediate countermeasure development; (2) critical supply chains were strained; and (3) critical information system function and capacity were suddenly insufficient under maximum remote work. For staffing and training: (1) successful telework required rapid shifts in management, engagement, and accountability methods; and (2) organizational policies and processes had to adapt quickly to support remote staffing. For leading and leadership development (1) engaged, hopeful, and empathetic leadership made a difference; and (2) the workforce benefitted from concerted leadership communication that created a shared understanding of shifting priorities as well as new processes and procedures. Conclusions An effective pandemic response requires comprehensive institutional preparedness that facilitates flexibility and surge capacity. The single most important action leaders of medical research organizations can take to prepare for the next pandemic is to develop a quick-reaction force that would activate under prespecified criteria to manage reprioritization of all science and support activities to address pandemic response priorities at the velocity of relevance.

1278. Testing the Synergistic Effect of Ceftazidime-Avibactam Plus Aztreonam on Metallobetalactamase-Producing Non-Fermenting Gram-negative Bacteria

Background Metallo-betalactamases (MBL) are rapidly becoming a more widespread form of antimicrobial resistance. MBL are class B betalactamases that use zinc rather than serine in their active site and are only inactivated by monobactams, such as aztreonam. Unfortunately, most MBL-producing organisms also produce aztreonam-inactivating beta-lactamases. Synergy between ceftazidime-avibactam and aztreonam is well documented for MBL-producing Enterobacteriaceae but has not been tested extensively in non-fermenting Gram-negative bacteria. This study evaluates the susceptibilities of non-fermenting Gram-negative bacteria via E-test to this combination in vitro, in order to provide support for use to treat infections from these organisms. Methods The antibiotic combination ceftazidime-avibactam+aztreonam was tested against a total of 33 isolates, including MBL-producing Pseudomonas aeruginosa, Pseudomonas putida, and the intrinsically aztreonam resistant Acinetobacter baumanii using the E-test method. MBL-producing Enterobacteriaceae were included as positive controls. All isolates were also tested against ceftazidime alone, aztreonam alone, and ceftazidime-avibactam. Bacterial isolates were procured from the Multidrug-resistant organism Repository & Surveillance Network at the Walter Reed Army Institute of Research. Antimicrobial resistance genes were previously identified by whole genome sequencing Results Of 13 Pseudomonas spp. isolates tested, 9 were resistant, 3 were intermediate, and 1 was susceptible to aztreonam. Synergistic testing of ceftazidime-avibactam+aztreonam reduced the MIC of 4 Pseudomonas isolates by 1-2 doubling dilutions. While Acinetobacter spp. are usually considered intrinsically resistant to aztreonam, synergistic testing of ceftazidime-avibactam+aztreonam reduced the MIC of all 12 isolates tested by 1 to 3 doubling dilutions. Conclusion The ability of ceftazidime-avibactam+aztreonam to reduce the MICs of Acinetobacter baumanii and MBL-producing Pseudomonas aeruginosa is a potentially promising therapeutic option when faced with growing antimicrobial resistance. Disclosures All Authors: No reported disclosures

Novel discovery of Extended Spectrum β-lactamase (ESBL) Pluralibacter gergoviae in acute urinary tract infection and urolithiasis

Introduction/Objective This case study describes the diagnosis, treatment, whole genome sequencing (WGS) and antibiotic resistance characterization from the ESBL-producing Pluralibacter gergoviae, a multi-drug resistant organism (MDRO) with a previously-documented presence in foodstuffs and cosmetics. Methods/Case Report A 39-year-old Hispanic American woman was admitted to the emergency department (ED) for fever, suprapubic tenderness, and pyuria. Three days prior to admission, patient underwent elective bilateral lithotripsy for retained nephrolithiasis. Seven days prior to ED admission, patient had an “Orgasm Shot” (O-Shot) which consists of platelet rich plasma that is drawn from the patient and injected into her vulvar area and around her clitoris to increase stimulation potential during orgasm. The patient was started on broad spectrum antibiotics, receiving Vancomycin and Ceftriaxone 1 gram 1 gram IV every 12 hours, intravenously. Urine cultures yielded two organisms, including a lactose fermenting as well as a non-lactose fermenting Gram negative rod. Mass spectrometry-based identification was successful in identifying the non-lactose fermenting colony as Pseudomonas aeruginosa, which also identified from a blood culture collected from the patient upon presentation to the ED. The lactose fermenting colony resulted in no identification by mass spectrometry but was identified using biochemical methods as Pluralibacter gergoviae, a recently-reclassified taxonomy previously identified as Enterobacter gergoviae. The P. gergoviae isolate was submitted to the Multidrug-Resistant Organism Repository (MRSN) at Walter Reed Army Institute of Research (WARIR) for WGS on Illumina Miseq. Sequencing and phenotypic/ genotypic data on isolate confirmed this as an ESBL P. gergoviae organism. Results (if a Case Study enter NA) NA Conclusion Summary data on possible epidemiological associations, antibiotic susceptibility testing, antibiotic resistance genes identified, and information on the antibiotic resistance plasmids will be presented. These findings from the WGS data, antibiotic susceptibilities will provide a lessons-learned for other clinical microbiology labs on how to identify unusual organisms such as P. gergoviae.

Far Forward Behavioral Health Service Delivery in Future Combat Environments: A Qualitative Needs Assessment

ABSTRACT Introduction It is expected that future multi-domain operational (MDO) combat environments will be characterized by limited capabilities for immediate combat stress control support services for soldiers or immediate evacuation from theater. The operational requirements of the future battlefield make it unlikely that current models for behavioral health (BH) treatment could be implemented without significant adjustments. We conducted a qualitative study with Special Forces medics and operators and soldiers who had deployed to austere conditions in small groups in an effort to inform construction of a BH service delivery model for an MDO environment. The objectives of this study were (1) characterizing stressors and BH issues that were encountered and (2) describing mitigation strategies and resources that were useful or needed in these types of deployments. Materials and Methods Six focus groups were conducted at three army installations with 23 active duty soldiers, including three groups of medics using a semi-structured interview guide focused on stressors they encountered during deployments to austere conditions, and the impact of those stressors on mission and focus. Focus group recordings were transcribed, imported into NVivo software (version 12), and independently coded by two researchers. An analysis was then conducted to develop themes across participants. The study was reviewed by the Walter Reed Army Institute of Research Human Subjects Protection Board. Results Behavioral health concerns were commonly cited as a stressor in far forward environments. Other common stressors included ineffective or inexperienced leaders, as well as poor team dynamics (e.g., communication and cohesion). Four primary strategies were mentioned as mitigations for deployment stressors: leadership, morale, resilience training, and strength of the team. When asked about resources or training that would have helped with these types of deployments, participants frequently mentioned the availability of BH providers and development of new and realistic BH skills trainings for non-providers and leaders. Conclusions Current models for treating BH problems need to be adapted for the future MDO environments in which soldiers will be expected to deploy. Understanding what issues need to be addressed in these environments and how they can best be delivered is an important first step. This study is the first to use qualitative results from those who have already deployed to such environments to describe the stressors and BH issues that were most commonly encountered, the mitigation strategies used, and the resources that were useful or needed.

US Army Drill Sergeants: Stressors, Behavioral Health, and Mitigating Factors

ABSTRACT Introduction The role of the drill sergeant is one of the most challenging within the US Army, involving unusually long hours and little time off, for a minimum of 2 years. The current study sought to examine the behavioral health of this population and identify risk factors that might be addressed by policy changes. Materials and Methods In total, 856 drill sergeants across all Army basic training sites completed surveys from September to November of 2018. Drill sergeants identified factors that had caused stress or worry during their assignment. Rates were measured for behavioral health outcomes including depression, insomnia, anxiety, burnout, functional impairment, alcohol misuse, aggression, and low morale. Potential risk and resilience factors included time as a drill sergeant, sleep, route of assignment, general leadership, health-promoting leadership, and drill sergeant camaraderie. The study was approved by the Walter Reed Army Institute of Research Institutional Review Board. Results The most commonly experienced stressors were finding time to exercise, lack of sleep, and long work hours. Percentages of drill sergeants meeting behavioral health screening criteria were 19% for depression, 27% for moderate-to-severe insomnia, 14% for generalized anxiety disorder, 48% for high burnout, 32% for functional impairment, 35% for moderate alcohol misuse, 32% for off-duty aggression, and 25% for low morale. Rates for most outcomes were associated with time spent as a drill sergeant, with behavioral health issues peaking during 13-18 months. Poorer outcomes were also associated with fewer hours of sleep and initial unhappiness regarding involuntary assignment to the role of drill sergeant, while better outcomes were associated with higher ratings of general leadership, health-promoting leadership, and drill sergeant camaraderie. Conclusions This study is the first to examine behavioral health and morale of drill sergeants and to identify risk and resilience factors. Suggestions for policy changes include increasing the number of drill sergeants to decrease workload and allow sufficient time for recovery and sleep.

Results of the Behavioral Health Readiness Evaluation and Decision-Making Instrument Study

ABSTRACT Introduction Recent reports have demonstrated behavioral health (BH) system and individual provider challenges to BH readiness success. These pose a risk to winning on the battlefield and present a significant safety issue for the Army. One of the most promising areas for achieving better BH readiness results lies in improving readiness decision-making support for BH providers. The Walter Reed Army Institute of Research (WRAIR) has taken the lead in addressing this challenge by developing and empirically testing such tools. The results of the Behavioral Health Readiness Evaluation and Decision-Making Instrument (B-REDI) field study are herein described. Methods The B-REDI study received WRAIR Institutional Review Board approval, and BH providers across five U.S. Army Forces Command installations completed surveys from September 2018 to March 2019. The B-REDI tools/training were disseminated to 307 providers through random clinic assignments. Of these, 250 (81%) providers consented to participate and 149 (60%) completed both initial and 3-month follow-up surveys. Survey items included a wide range of satisfaction, utilization, and proficiency-level outcome measures. Analyses included examinations of descriptive statistics, McNemar’s tests pre-/post-B-REDI exposure, Z-tests with subgroup populations, and chi-square tests with demographic comparisons. Results The B-REDI resulted in broad, statistically significant improvements across the measured range of provider proficiency-level outcomes. Net gains in each domain ranged from 16.5% to 22.9% for knowledge/awareness (P = .000), from 11.1% to 15.8% for personal confidence (P = .001-.000), and from 6.2% to 15.1% for decision-making/documentation (P = .035-.002) 3 months following B-REDI initiation, and only one (knowledge) failed to maintain a statistically significant improvement in all of its subcategories. The B-REDI also received high favorability ratings (79%-97% positive) across a wide array of end-user satisfaction measures. Conclusions The B-REDI directly addresses several critical Army BH readiness challenges by providing tangible decision-making support solutions for BH providers. Providers reported high degrees of end-user B-REDI satisfaction and significant improvements in all measured provider proficiency-level domains. By effectively addressing the readiness decision-making challenges Army BH providers encounter, B-REDI provides the Army BH health care system with a successful blueprint to set the conditions necessary for providers to make more accurate and timely readiness determinations. This may ultimately reduce safety and mission failure risks enterprise-wide, and policymakers should consider formalizing and integrating the B-REDI model into current Army BH practice.

Walter Reed Army Institute of Research (WRAIR): Fifty Years of Achievements That Impact Science and Society

Thirty-four historical achievements since 1970 that emanated from scientific research at the Walter Army Institute of Research are identified and documented. Impact areas include vaccines, drug development, and clinical assays to prevent or treat infectious diseases; neuropsychiatric management of warrior performance and combat casualty; blood delivery management; and radiation protection.

ESSENCE, the Electronic Surveillance System for the Early Notification of Community-Based Epidemics (Preprint)

BACKGROUND The Electronic Surveillance System for the Early Notification of Community-Based Epidemics (ESSENCE) is a secure web-based tool that enables health care practitioners to monitor health indicators of public health importance for detection and tracking of disease outbreaks, consequences of severe weather, and other events of concern. The ESSENCE concept began in an internally funded project at the Johns Hopkins University Applied Physics Laboratory (JHU/APL), advanced with funding from the State of Maryland, and broadened in 1999 as a collaboration with the Walter Reed Army Institute for Research. Versions of the system have been further developed by JHU/APL in multiple military and civilian programs for timely detection and tracking of health threats. OBJECTIVE Aims of this article are to describe the components and development of a biosurveillance system increasingly coordinating all-hazards health surveillance as well as infectious disease monitoring among large and small health departments, to list key features and lessons learned in the growth of this system, and to describe the range of initiatives and accomplishments of local epidemiologists using it. METHODS Features of ESSENCE include spatial and temporal statistical alerting, custom querying, user-defined alert notifications, geographical mapping, remote data capture, and event communications. For visualization, configurable and interactive modes of data stratification and filtering, graphical and tabular customization, user preference management, and sharing features allow users to query data and view geographic representations, time series and data details pages, and reports. These features allow ESSENCE users to gather and organize the resulting wealth of information into a coherent view of population health status and communicate findings among users. RESULTS The resulting broad utility, applicability and adaptability of this system led to adoption of ESSENCE by the Centers for Disease Control and Prevention (CDC), numerous state and local health departments, and the Department of Defense (DOD) both nationally and globally. An open-source version SAGES is available for global, resource-limited settings. Resourceful users of the US NSSP ESSENCE have applied it to surveillance of infectious diseases, severe weather and natural disaster events, mass gatherings, chronic diseases and mental health, and injury and substance abuse. CONCLUSIONS With emerging high-consequence communicable diseases and other health conditions, the continued user-requirements-driven enhancements of ESSENCE demonstrate an adaptable disease surveillance capability focused on the everyday needs of public health. The challenge of a live system for widely distributed users with multiple different data sources and high throughput requirements has driven an novel, evolving architecture design.