Breath Biomarkers of Influenza Infection.

Background: Volatile organic compounds (VOCs) are produced systemically due to varied physiological states such as oxidative stress and are excreted through the lungs. Benchtop and preliminary clinical data suggest that breath testing may be a useful diagnostic modality for viral respiratory tract infections. Methods: Patients with influenza-like illness (ILI) presenting to a single clinic in San Antonio, Texas, from 3/2017 to 3/2019 submitted a 2-minute breath sample in addition to a nasopharyngeal swab collected for polymerase chain reaction (PCR) assay for respiratory pathogens. VOCs were assayed with gas chromatography-mass spectrometry (GC-MS), and data were analyzed to identify breath VOC biomarkers that discriminated between ILI patients with and without a polymerase chain reaction (PCR) assay that was positive for influenza. Results: Demographic, clinical, PCR, and breath data were available for 237 episodes of ILI, among which 32 episodes (13.5%) were PCR positive for influenza. Twenty candidate VOCs identified patients with influenza with greater than random accuracy. A predictive algorithm using 4 candidate biomarkers identified this group with 78% accuracy (74% sensitivity, 70% specificity). Based on their mass spectra, most of these biomarkers were n-alkane derivatives, consistent with products of oxidative stress. Conclusions: A breath test for VOC biomarkers accurately identified ILI patients with PCR-proven influenza. These findings bolster those of others that a rapid, accurate, universal point-of-care influenza diagnostic test based on assay of exhaled-breath VOCs may be feasible. The next step will be a study of patients with ILI using a simplified method of breath collection that would facilitate translation for use in clinical practice.

Pan-drug resistant Providencia rettgeri contributing to a fatal case of COVID-19.

Following prolonged hospitalization that included broad-spectrum antibiotic exposure, a strain of Providencia rettgeri was cultured from the blood of a patient undergoing extracorporeal membrane oxygenation treatment for hypoxic respiratory failure due to COVID-19. The strain was resistant to all antimicrobials tested including the novel siderophore cephalosporin, cefiderocol. Whole genome sequencing detected ten antimicrobial resistance genes, including the metallo-ß-lactamase bla NDM-1, the extended-spectrum ß-lactamase bla PER-1, and the rare 16S methyltransferase rmtB2.

Fatal Isoniazid Hepatotoxicity in the Deployed Environment.

Deployed clinicians have limited resources at their disposal to augment medical decision-making and management. All deploying personnel undergo predeployment medical assessment to evaluate their fitness for deployment. The purpose of predeployment screening is to allow for anticipation of medical needs that may arise which could challenge the available medical resources in an expeditionary environment. Medical standards for deployment are published, identifying disqualifying conditions and medications. A history of latent tuberculosis infection is not disqualifying for deployment. Isoniazid is not specifically mentioned as a disqualifying medication, though it is well known to have the potential of causing drug-induced liver injury. Here, a case of fatal isoniazid-induced drug-induced liver injury in a deployed setting is presented with a review of current latent tuberculosis infection literature. Our goal is for the reader to form their own opinion whether or not isoniazid should be used in the forward environment.

Outbreak of cyclosporiasis in a U.S. Air Force training population, Joint Base San Antonio-Lackland, TX, 2018.

Diarrheal illnesses have an enormous impact on military operations in the deployed and training environments. While bacteria and viruses are the usual causes of gastrointestinal disease outbreaks, 2 Joint Base San Antonio-Lackland, TX, training populations experienced an outbreak of diarrheal illness caused by the parasite Cyclospora cayetanensis in June and July 2018. Cases were identified from outpatient medical records and responses to patient questionnaires. A confirmed case was defined by diarrhea and laboratory confirmation, and patients without a positive lab were classified as suspected cases. In cluster 1, 46 suspected and 7 confirmed cases occurred among technical training students who reported symptom onset from 12 June to 21 June. In cluster 2, 18 suspected and 14 confirmed cases in basic military training trainees reported symptom onset from 29 June to 8 July. Numerous lessons from cluster 1 were applied to cluster 2. Crucial lessons learned during this cyclosporiasis outbreak included the importance of maintaining clinical suspicion for cyclosporiasis in persistent gastrointestinal illness and obtaining confirmatory laboratory testing for expedited diagnosis and treatment.

Physical and Mental Health of US Air Force Military Training Instructors.

INTRODUCTION: Many epidemiologic studies have been performed in military recruit populations, but little is known about the health of those who conduct the training. This study aims to characterize the physical and mental health of a military trainer cohort. MATERIALS AND METHODS: All US Air Force military training instructors (MTIs) who served between 1 October 2011 and 30 September 2016 were included in this retrospective descriptive study. All International Classification of Diseases, Ninth or Tenth Revision codes received by MTIs as inpatients or outpatients in the TRICARE system were obtained and mapped to Clinical Classifications Software levels. After excluding routine and administrative codes, the relative burden of disease by diagnostic category and subcategory was calculated, with further classification of musculoskeletal conditions by anatomic site. For all conditions accounting for at least 1.0% of the burden of care, incidence density rates and incidence rate ratios (IRRs) with 95% confidence intervals (CIs) were calculated to compare males and females. RESULTS: A total of 1,269 MTIs received 32,601 non-administrative, non-routine diagnoses while accumulating 50,376 person-months of exposure during the surveillance period. Musculoskeletal conditions were the greatest contributor to overall disease burden, accounting for 39.1% of all diagnoses, followed by mental health (10.4%), respiratory (10.1%), and neurologic and sensory (9.8%). The burden attributed to mental health conditions decreased by 54% over the 5-year period. Twenty-three conditions accounted for at least 1.0% of the healthcare burden. The highest incidence conditions were connective tissue disease (27.18 per 1,000 person-months), non-traumatic joint disorders (25.74), upper respiratory infections (25.14), and back pain (23.70). As compared to males, females had a higher incidence of several conditions, including adjustment disorders (IRR: 2.57; 95% CI: 1.61, 4.11) and anxiety disorders (IRR: 2.24; 95% CI: 1.33, 3.77). CONCLUSIONS: Musculoskeletal conditions are the leading contributor to burden of care among US Air Force MTIs, followed by mental health, respiratory, and neurologic and sensory conditions. The burden of healthcare among US Air Force MTIs more closely resembles active component service members than recruit trainees.

Chemoprophylaxis against group A streptococcus during military training.

Chemoprophylaxis with intramuscular benzathine penicillin G has been used widely by the U.S. military to prevent epidemics of group A streptococcus infections during basic training. The recent global shortage of benzathine penicillin prompted a detailed analysis of this issue in 2017 by military preventive medicine and infectious disease authorities in San Antonio, Texas, and San Diego, California, USA. This paper explores the history of group A streptococcus and chemoprophylaxis in the U.S. military training environment, current policy and practice, and challenges associated with widespread chemoprophylaxis. In light of the history presented, preventive medicine authorities at basic training centers should be extremely cautious about discontinuing benzathine penicillin chemoprophylaxis.

Disseminated Tuberculosis Presenting as Chronic Orchiepididymitis in a Military Trainee: A Case Report and Review of the Literature.

Orchiepididymitis is a clinical diagnosis. The acute form secondary to sexually transmitted or enteric pathogens is well known to primary care providers. However, chronic orchiepididymitis may be secondary to genitourinary tuberculosis (TB), and physicians in countries with a low prevalence of TB might not consider it in their differential diagnosis. Indeed, cognitive errors, such as anchoring or availability bias, may contribute to a delayed diagnosis of genitourinary TB. We present a case of chronic orchiepididymitis as a result of disseminated TB in a Cameroonian male who was visiting the United States for military training. He experienced diagnostic delay and was ultimately diagnosed by orchiectomy. Early consideration of a diagnosis of TB for chronic or recurrent orchiepididymitis in a patient with epidemiologic risk factors is of utmost importance because delayed diagnosis could lead to organ loss.

A Tertiary Care Center's Experience with Novel Molecular Meningitis/Encephalitis Diagnostics and Implementation with Antimicrobial Stewardship.

Background: Novel molecular techniques, such as the Biofire FilmArray Meningitis/Encephalitis (ME) panel, are increasingly used to improve pathogen detection and time to detection (TtD). The Brooke Army Medical Center antibiotic stewardship program evaluated the impact of the ME panel on empiric antimicrobial usage. Methods: Negative ME panels were analyzed for days of therapy (DOT). The ME panel became available at Brooke Army Medical Center on January 1, 2016 and a retrospective chart review was performed on all hospitalized patients tested by ME panel through April 30, 2016. Demographic data, cerebral spinal fluid (CSF) leukocyte count, immunocompromised status, and intensive care unit admission status were collected. TtD by ME panel and CSF culture were compared and DOT for common antimicrobials were quantified. Positive ME panels were analyzed for same demographic data, diagnoses, and microbiologic workup including CSF cultures and send out polymerase chain reactions. Results: Of the 77 ME panels performed during the study period, 54 (70%) were conducted on inpatients and included in the analysis. The majority of patients were males (n = 29, 54%) and the median age was 24 yr (interquartile range [IQR] 45; range 1 d to 83 yr). A total of eight (15%) patients were immunocompromised and 17 (31%) required intensive care unit level of care. The median TtD with the ME panel and CSF culture was 2.75 (IQR 2.16, 3.64) and 68.5 (IQR 63.87, 78.37) h, respectively. For negative ME panels, the overall median DOT for antimicrobials was 3 (IQR 1.5, 4.0) d, whereas the median DOT for individual agents was 2 (IQR 1.0, 4.0) d for vancomycin (n = 15), 1.5 (IQR 1.0, 2.25) d for ceftriaxone (n = 16), 3 (IQR 3.0, 4.0) d for ampicillin (n = 15), 3.5 (IQR 2.75, 4.0) d for gentamicin (n = 8), 3.5 (IQR 2.25, 4.0) d for cefotaxime (n = 6), and 5 (IQR 3.0, 5.5) d for acyclovir (n = 7); the median CSF leukocyte is of 2 cells/mm3 (IQR 1.0, 7.5). DOT excluded cases of positive ME panels: human herpes virus-6 (n = 2), herpes simplex virus-2 (n = 3), enterovirus (n = 1), and Streptococcus pneumoniae (n = 1). Of these, there were two discordance diagnoses between ME panel and convention microbiologic methods. S. pneumonia was detected on the ME panel and not on the CSF culture. One bone marrow transplant recipient had symptoms of encephalitis caused by human herpes virus-6 detected only by the ME panel, the send out human herpes virus-6 polymerase chain reaction was negative. Conclusion: The ME panel appears to improve diagnostic yield in our facility, and there is potential for improvement in decreasing empiric antimicrobial usage, particularly in patients with a negative ME panel and absence of CSF pleocytosis. This demonstrates the need for antibiotic stewardship program involvement to assist in implementation of rapid diagnostic tests through methods such as education, clinical guidelines, and prospective audit and feedback to improve meningitis and encephalitis management.

Teaching Antimicrobial Stewardship to Infectious Disease Fellows Through Simulated Interdisciplinary Scenarios.

Introduction: While several approaches have been described to teach antimicrobial stewardship (AS) practices, fewer have been aimed at infectious disease physicians. We developed a series of simulated AS meetings to train infectious disease fellows in the synthesis of AS interventions. Methods: Three simulated AS committee scenarios were developed. Background lectures were given 1 week prior to the simulation during which multidisciplinary roles were assigned. Precourse work included review of primary literature pertinent to the scenario. Simulations were conducted over 1.5 hours. Individual and team performances were evaluated. Pre- and postsurveys were collected from fellows and faculty members to assess the format. Results: Six infectious disease fellows participated in the series. Fellows demonstrated information synthesis and improvements in individual and team performance. Eighty-three percent of fellows before the simulation series and 100% postseries reported educating others on AS principles in the previous month. Fellows were satisfied with the series and requested more scenarios. Eight faculty members completed surveys. Thirty-eight percent of faculty before the series and 63% after completion reported that fellows viewed antimicrobial preauthorization as useful or necessary. Faculty supported the format, found it useful in evaluation of learners, and perceived that fellows benefited from the approach. Discussion: Simulation is an effective and enjoyable way to train infectious disease fellows in AS and team utilization. Fellows demonstrated improvement in AS knowledge, skills, and attitudes and developed evidence-based interdisciplinary plans to solve AS challenges. Faculty also viewed this strategy as effective and sustainable.

In Vitro activity of Manuka Honey and polyhexamethylene biguanide on filamentous fungi and toxicity to human cell lines.

Soft-tissue invasive fungal infections are increasingly recognized as significant entities directly contributing to morbidity and mortality. They complicate clinical care, requiring aggressive surgical debridement and systemic antifungal therapy. To evaluate new topical approaches to therapy, we examined the antifungal activity and cytotoxicity of Manuka Honey (MH) and polyhexamethylene biguanide (PHMB). The activities of multiple concentrations of MH (40%, 60%, 80%) and PHMB (0.01%, 0.04%, 0.1%) against 13 clinical mould isolates were evaluated using a time-kill assay between 5 min and 24 h. Concentrations were selected to represent current clinical use. Cell viability was examined in parallel for human epidermal keratinocytes, dermal fibroblasts and osteoblasts, allowing determination of the 50% viability (LD50) concentration. Antifungal activity of both agents correlated more closely with exposure time than concentration. Exophiala and Fusarium growth was completely suppressed at 5 min for all PHMB concentrations, and at 12 and 6 h, respectively, for all MH concentrations. Only Lichtheimia had persistent growth to both agents at 24 h. Viability assays displayed concentration-and time-dependent toxicity for PHMB. For MH, exposure time predicted cytotoxicity only when all cell types were analyzed in aggregate. This study demonstrates that MH and PHMB possess primarily time-dependent antifungal activity, but also exert in vitro toxicity on human cells which may limit clinical use. Further research is needed to determine ideal treatment strategies to optimize antifungal activity against moulds while limiting cytotoxicity against host tissues in vivo.

Epidemiology and antimicrobial susceptibilities of wound isolates of obligate anaerobes from combat casualties.

Data from recent conflicts related to war wounds and obligate anaerobes are limited. We define the epidemiology and antimicrobial susceptibility of obligate anaerobes from Iraq and Afghanistan casualties (6/2009-12/2013), as well as their association with clinical outcomes. Susceptibility against eleven antibiotics (7 classes) was tested. Overall, 59 patients had 119 obligate anaerobes identified (83 were first isolates). Obligate anaerobes were isolated 7-13 days post-injury, primarily from lower extremity wounds (43%), and were largely Bacteroides spp. (42%) and Clostridium spp. (19%). Patients with pelvic wounds were more likely to have Bacteroides spp. and concomitant resistant gram-negative aerobes. Seventy-three percent of isolates were resistant to ≥1 antimicrobials. Bacteroides spp. demonstrated the most resistance (16% of first isolates). Patients with resistant isolates had similar outcomes to those with susceptible strains. Serial recovery of isolates occurred in 15% of patients and was significantly associated with isolation of Bacteroides spp., along with resistant gram-negative aerobes.

Reactive arthritis after Shigella gastroenteritis in American military in Afghanistan.

In Afghanistan in mid June 2011, 2 US Marines developed reactive arthritis manifested by conjunctivitis, urethritis, arthritis, and circinate balanitis. Their symptoms were preceded by an outbreak in their unit of gastroenteritis caused by Shigella species after ingesting contaminated chicken. Gastroenteritis has plagued military operations for millennia. This report emphasizes that personnel can develop reactive arthritis after bouts of gastrointestinal infections that are common in deployed environments. It is highly recommended to maintain vigilance in keeping reactive arthritis on the differential diagnosis in deployed personnel after bouts of gastroenteritis.