Dana M. Blyth

Lessons of war: Combat-related injury infections during the Vietnam War and Operation Iraqi and Enduring Freedom.

In over a decade of war, numerous advancements have been made to improve overall combat-related mortality, but infectious complications remain a leading cause of both morbidity and mortality in combat-related injured personnel. Here we will attempt to compare the challenges and lessons of combat-related injuries and infections from the Vietnam War with those of OIF/OEF. Throughout the Vietnam War and OIF/OEF, there have been similar infection-related challenges faced in caring for combat-related trauma patients. Both conflicts reinforced the importance of rapid medical evacuation and definitive surgical management of war wounds. They revealed the constant evolution of infecting organisms and the challenge of increasing antimicrobial resistance. We have also seen that with decreased mortality of severely injured personnel new morbidities must be addressed. Using the foundation of fragmented research from the Vietnam War, previously successful models were assembled into joint service research institutions which have allowed these questions to be addressed. However, many questions regarding measures to reduce infectious complications in our combat-injured personnel remain unanswered. Continued research building on established knowledge is critical for continued improvements in the care of combat-related trauma patients.

Cutaneous leukocytoclastic vasculitis associated with levofloxacin therapy

Many cases of cutaneous vasculitis are drug-induced with histology revealing leukocytoclastic vasculitis (LCV). We present a case of levofloxacin-associated LCV successfully treated with prednisone and cessation of the offending drug. Although case reports describe a link between LCV and older fluoroquinolones, such as ciprofloxacin and ofloxacin, recent reports have implicated the newer fluoroquinolone levofloxacin. Recognition of fluoroquinolone-induced cutaneous vasculitis is important as continuation or re-exposure of the offending agent may have life-threatening consequences.

Resistance Patterns and Clinical Significance of Candida Colonization and Infection in Combat-Related Injured Patients From Iraq and Afghanistan

Among combat-injured patients from Iraq and Afghanistan, 5% had Candida spp. isolated from wounds. The crude mortality rate of 7.1% was similar to invasive mold infections, and may serve as a marker of those at higher risk for death.

Clinical utility of fungal screening assays in adults with severe burns

BACKGROUND Fungal wound infection is a leading cause of burn wound infections, and diagnosis is often delayed as it conventionally requires culture and histopathology. Fungal screening assays have sped diagnosis of invasive fungal infections in other populations. Few studies have evaluated the performance of fungal screening assays outside of the hematologic malignancy and hematopoietic stem cell transplant populations. METHODS We performed a three year retrospective analysis of all fungal screening assays in burn patients in the ICU between 2008 and 2011. The primary goal was to evaluate the correlation between the two available fungal screening assays, (1→3)-β-d-glucan (BG) and galactomannan (GM) assay, and fungal wound colonization (FWC) and infection (FWI). We also evaluated previously hypothesized causes of false positives and their associations with false positives in the burn population. RESULTS We identified 53 patients [median 29% total body surface area burned (TBSA), IQR 17-51] with BG or GM serological tests available, of which 15 had a FWI or FWC. FWC/FWI was associated with higher TBSA (p=0.02). BG and GM correlated with TBSA (BG 0.57, p<0.01; GM 0.35, p=0.02), but neither assay was associated with FWI/FWC or species of fungus involved when FWI/FWC was diagnosed. CONCLUSIONS Positive BG and GM fungal screening assays are not associated with FWI/FWC, or with species of fungus when FWC/FWI is present. BG false positives are common and associated with higher TBSA burns.

Antimicrobial Prophylaxis with Combat-Related Open Soft-Tissue Injuries

Introduction All Department of Defense (DoD) guidance documents recommend cefazolin or clindamycin as post-trauma antibiotic prophylaxis for open soft-tissue injuries. Although not advocated, some patients with open soft-tissue injuries also received expanded Gram-negative coverage (EGN) prophylaxis based on the judgment of front-line trauma providers. During the study period, revised guidelines in 2011/2012 re-emphasized recommendations for using cefazolin or clindamycin, and stewardship efforts in the DoD trauma community aimed to reduce the practice of adding EGN to guideline-recommended antibiotic prophylaxis. Our objective was to examine antibiotic utilization among wounded military personnel with open extremity soft-tissue injuries over a 5-yr period and assess the impact on infectious outcomes in patients who received EGN prophylaxis versus guideline-directed prophylaxis. Methods The study population included military personnel with open extremity soft-tissue injuries sustained in Iraq and Afghanistan (2009-2014) who transferred to participating hospitals in the USA following medical evacuation. The analysis was restricted to patients who were hospitalized for at least seven days at a U.S. facility and excluded those who sustained open fractures. Post-trauma antibiotic prophylactic regimens were defined as narrow if they followed recommended guidance (e.g., IV cefazolin or clindamycin) or EGN coverage when the narrow regimen also included fluoroquinolones and/or aminoglycosides. Intravenous amoxicillin-clavulanate, which is commonly used at non-U.S. coalition theater hospitals, was also classified as narrow because it conformed to coalition antibiotic prophylaxis guidelines. This study was approved by the Infectious Disease Institutional Review Board of the Uniformed Services University of the Health Sciences. Results A total of 287 wounded personnel with open soft-tissue injuries were assessed, of which 212 (74%) received narrow prophylaxis and 75 (26%) received EGN coverage (p < 0.001). Among patients in the narrow prophylaxis group, 81% were given cefazolin and/or clindamycin, while 19% received amoxicillin-clavulanate. In the EGN group, 88% and 12% received a fluoroquinolone and aminoglycoside, respectively. Use of EGN coverage significantly declined during the study period from 39% in 2009-2010 to 11% in 2013-2014 (p < 0.001). Approximately 3% of patients who received a narrow regimen developed an extremity skin and soft-tissue infection, while there were no skin and soft-tissue infections among patients in the EGN coverage group. Nonetheless, this was not a significant difference (p = 0.345). In addition, the proportion of non-extremity infections was not significantly different between narrow and EGN regimen groups (11% and 15%, respectively). There were also no significant differences between the narrow and EGN regimen groups related to duration of hospitalization (median of 19 versus 20 d). Conclusion Use of non-guideline directed EGN-based post-trauma antibiotic prophylaxis does not improve infectious outcomes nor does it shorten hospital stay.

Early infectious outcomes after addition of fluoroquinolone or aminoglycoside to posttrauma antibiotic prophylaxis in combat-related open fracture injuries

BACKGROUND We examined combat-related open extremity fracture infections as a function of whether posttrauma antimicrobial prophylaxis included expanded Gram-negative (EGN) coverage. METHODS Military personnel with open extremity fractures sustained in Iraq and Afghanistan (2009–2014) who transferred to participating hospitals in the United States were assessed. The analysis was restricted to patients with a U.S. hospitalization period of ≥7 days. Prophylaxis was classified as narrow (e.g., IV cefazolin, clindamycin, and/or amoxicillin-clavulanate) or EGN, if the prophylactic regimen included fluoroquinolones and/or aminoglycosides. RESULTS The study population included 1,044 patients, of which 585 (56%) and 459 (44%) received narrow and EGN coverage, respectively (p < 0.001). Skin and soft-tissue infections (SSTIs) were more common among patients who received narrow prophylaxis compared to EGN coverage (28% vs. 22%; p = 0.029), whereas osteomyelitis rates were comparable between regimens (8%). Similar findings were noted when endpoints were measured at 2 and 4 weeks postinjury. There was no significant difference related to length of hospitalization between narrow and EGN regimens (median: 34 and 32 days, respectively) or operating room visits (median: 5 and 4). A higher proportion of EGN coverage patients had Gram-negative organisms isolated that were not susceptible to fluoroquinolones and/or aminoglycosides (49% vs. 40%; p < 0.001). In a Cox proportional model, narrow prophylaxis was independently associated with an increased risk of extremity SSTIs (hazard ratio: 1.41; 95% confidence interval: 1.09–1.83). DISCUSSION Despite seeing a small benefit with EGN coverage related to a reduction of SSTIs, it does not decrease the risk of osteomyelitis, and there seems to be a cost of increased antibiotic resistance associated with use. Overall, our findings support the current post-combat trauma antibiotic prophylaxis guidelines, which recommend the use of cefazolin or clindamycin with open fractures. LEVEL OF EVIDENCE Prognostic/Epidemiological, Level II; Therapy, level IV.

Timing of Infectious Disease Clinical Rotation Is Associated With Infectious Disease Fellowship Application

Abstract Background With declining interest in infectious disease (ID) noted among internal medicine (IM) residents, national attention has been directed at methods to recruit more prospective ID applicants. The factors driving the recent decline in ID fellowship applications have thus far only been evaluated in survey studies. Since 2008 at our institution, all IM interns were required to complete a 4-week inpatient ID rotation. We evaluated this rotation to determine if any experiential factors could be linked to future ID interest. Methods Categorical IM interns rotating on the mandatory ID rotation at our institution between July 1, 2008, and June 30, 2015, were included. Interns were grouped by eventual application to ID fellowship (IDA) and nonapplication (non-IDA). Consult numbers and types and characteristics of team members during the rotation were compared. Results Between July 2008 and June 2015, 143 IM interns met inclusion criteria. Ten (7%) were IDA. There was no difference in number of consults seen, intern, team member, faculty, or fellow characteristics among groups. However, 90% of IDA compared with 46% of non-IDA rotated during the first 6 months of internship (P = .01). Conclusions During a 7-year period, those interns randomly assigned to rotate on ID in the first 6 months of their intern year were more likely to become future ID applicants. This supports prior self-reported survey data that early exposure to the field may impact future career choice and suggests that incorporating ID early into the intern experience may increase recruitment.

U.S. Combat-related Invasive Fungal Wound Infection (IFI) Epidemiology and Wound Microbiology: Afghanistan Theater 2009-2014

Abstract Background Culturing combat-related wounds often yields both fungi and bacteria. It is difficult to differentiate fungal contamination from infection, and objective criteria that identify patients at risk for IFI are needed. This study was designed to characterize IFI among US combat casualties in the Afghanistan Theater. Methods This retrospective study includes subjects with any labortory evidence of fungi (either histopathology or cultures). Wounds with ongoing necrosis and labortory evidence of infection were classified as IFI). Wounds with labortory evidence of fungal infection, but without ongoing necrosis were classified as either highly suspicious wounds based on objective clinical criteria (i.e., presence of systemic and local signs of infection and use of antifungals for ≥10 days) or non-IFI wounds if they failed to meet clinical criteria. Results Of 1932 subjects, 246 (12.7%) had labortory evidence of fungal infection. There were a total of 143 IFI wounds (n = 94), 157 non-IFI wounds (n = 96), and 113 high suspicion wounds (n = 56). IFI subjects had significantly higher injury severity scores (ISS median: 39.5 vs. 33), Sequential Organ Failure Assessment (SOFA) scores (7 vs. 2) and were more likely to require mechanical ventilation (66 vs. 28%). IFI patients also had higher ISS (93 vs. 84% with ISS >25) and SOFA scores (7 vs. 4) compared with the subjects with high suspicion wounds. IFI wounds often grew molds belonging to the order Mucorales compared with high suspicion (19 vs. 10%, P = 0.04) and non-IFI wounds (19 vs. 7%, P = 0.02). About half of the IF wounds grew fungi of the order Mucorales either isolated alone or in conjunction with other fungi, in comparison, 25% of the high suspicion wounds and 11% of the non-IFI wounds grew fungi of the order Mucorales. Three groups of fungi belonging to the order Mucorales, genus Aspergillus and Fusarium accounted for 83% of the IFI wounds and 74% of the high suspicion wounds. Conclusion Labortory evidence of fungal infection is common among combat casualties. Clinical characteristics and wound microbiology allows us to group subjects into groups at low and high risk of IFI. Fungi of the order Mucorales, genus Aspergillus and Fusarium should not be considered contaminants. The presence of these fungi should obligate close clinical follow-up and debridement as needed. Disclosures All authors: No reported disclosures.