Histopathological techniques for the diagnosis of combat-related invasive fungal wound infections.

BACKGROUND: Effective management of trauma-related invasive fungal wound infections (IFIs) depends on early diagnosis and timely initiation of treatment. We evaluated the utility of routine staining, histochemical stains and frozen section for fungal element identification. METHODS: A total of 383 histopathological specimens collected from 66 combat-injured United States military personnel with IFIs were independently reviewed by two pathologists. Both periodic acid-Schiff (PAS) and Gomori methenamine silver (GMS) stains were used on 74 specimens. The performance of the two special stains was compared against the finding of fungal elements via any histopathological method (ie, special stains or hematoxylin and eosin). In addition, the findings from frozen sections were compared against permanent sections. RESULTS: The GMS and PAS results were 84 % concordant (95 % confidence interval: 70 to 97 %). The false negative rate of fungal detection was 15 % for GMS and 44 % for PAS, suggesting that GMS was more sensitive; however, neither stain was statistically significantly superior for identifying fungal elements (p = 0.38). Moreover, 147 specimens had frozen sections performed, of which there was 87 % correlation with permanent sections (60 % sensitivity and 98 % specificity). In 27 permanent sections, corresponding cultures were available for comparison and 85 % concordance in general species identification was reported. CONCLUSIONS: The use of both stains does not have an added benefit for identifying fungal elements. Furthermore, while the high specificity of frozen section may aid in timely IFI diagnoses, it should not be used as a stand-alone method to guide therapy due to its low sensitivity.

Stenotrophomonas maltophilia infections: Clinical characteristics in a military trauma population.

Stenotrophomonas maltophilia is a pathogen with unique resistance patterns. We assessed 70 combat casualties with S. maltophilia clinical isolates to examine its role as a nosocomial pathogen in critically-ill trauma patients. Incidence density was 0.36 S. maltophilia infections per 100 patient-days (95% CI: 0.29-0.44). Patients predominantly had blast trauma (97%) and were critically injured (injury severity score [ISS] >25; 80%). Restricting to patients with ISS >15, 50 patients with S. maltophilia infections were compared to 441 patients with infections attributed to other gram-negative bacilli. Patients with S. maltophilia infections had significantly more operating room visits prior to isolation, traumatic or early surgical amputations, longer hospitalization (median 71 vs 47 days), and higher overall mortality (10% vs 2%; P = 0.01). Initial and serial (≥7 days between initial and subsequent isolation) S. maltophilia isolates had high susceptibility to trimethoprim-sulfamethoxazole and minocycline. Evaluation of newer agents awaiting CLSI breakpoints, including moxifloxacin, showed promising results.

After the Battlefield: Infectious Complications among Wounded Warriors in the Trauma Infectious Disease Outcomes Study.

INTRODUCTION: During recent wars in Iraq and Afghanistan, improved survivability in severe trauma corresponded with a rise in the proportion of trauma-related infections, including those associated with multidrug-resistant organisms (MDROs). Significant morbidity was reported in association with the infections. There is also concern regarding potential long-term impacts of the trauma-related infectious complications. Therefore, to meet the critical need of prospective collection of standardized infection-related data to understand the disease burden and improve outcomes of wounded personnel, the Trauma Infectious Disease Outcomes Study (TIDOS) was developed. Herein, we review accomplishments and key peer-reviewed findings of TIDOS. METHODS: The TIDOS project is a multicenter observational study of short- and long-term infectious complications following deployment-related trauma. Wounded military personnel medevac'd to Landstuhl Regional Medical Center (LRMC; Germany) before transfer to a participating US military hospital between June 2009 and December 2014 were eligible for inclusion. An infectious disease module to supplement the Department of Defense Trauma Registry by collecting infection-related data from all trauma patients admitted to participating hospitals was developed. Specimens from trauma patients were also collected and retained in a microbiological isolate repository. During the initial hospitalization, patients were given the opportunity to enroll in a prospective follow-up cohort study. Patients who received Department of Veterans Affairs (VA) care were also given the opportunity to consent to ongoing VA follow-up. RESULTS: A total of 2,699 patients transferred to participating military hospitals in the USA, of which 1,359 (50%) patients enrolled in the TIDOS follow-up cohort. In addition, 638 enrolled in the TIDOS-VA cohort (52% of TIDOS enrollees who entered VA healthcare). More than 8,000 isolates were collected from infection control surveillance and diagnostic evaluations and retained in the TIDOS Microbiological Repository. Approximately 34% of the 2,699 patients at US hospitals developed a trauma-related infection during their initial hospitalization with skin and soft-tissue infections being predominant. After discharge from the US hospitals, approximately one-third of TIDOS cohort enrollees developed a new trauma-related infection during follow-up and extremity wound infections (skin and soft-tissue infections and osteomyelitis) continued to be the majority. Among TIDOS cohort enrollees who received VA healthcare, 38% developed a new trauma-related infection with the incident infection being diagnosed a median of 88 days (interquartile range: 19-351 days) following hospital discharge. Data from TIDOS have been used to support the development of Joint Trauma System clinical practice guidelines for the prevention of combat-related infections, as well as the management of invasive fungal wound infections. Lastly, due to the increasing proportion of infections associated with MDROs, TIDOS investigators have collaborated with investigators across military laboratories as part of the Multidrug-Resistant and Virulent Organisms Trauma Infections Initiative with the objective of improving the understanding of the complex wound microbiology in order to develop novel infectious disease countermeasures. CONCLUSIONS: The TIDOS project has focused research on four initiatives: (1) blast-related wound infection epidemiology and clinical management; (2) DoD-VA outcomes research; (3) Multidrug- Resistant and other Virulent Organisms Trauma Infections Initiative; and (4) Joint Trauma System clinical practice guidelines and antibiotic stewardship. There is a continuing need for longitudinal data platforms to support battlefield wound research and clinical practice guideline recommendation refinement, particularly to improve care for future conflicts. As such, maintaining a research platform, such as TIDOS, would negate the lengthy time needed to initiate data collection and analysis.

Urinary Tract Infections after Combat-Related Genitourinary Trauma.

Background: We examined clinical outcomes among combat casualties with genitourinary injuries after blast trauma. Methods: Characteristics, clinical care, urologic complications, and infections for subjects enrolled in the Trauma Infectious Disease Outcomes Study (TIDOS) were collected from Department of Defense (DOD) and Department of Veterans Affairs (VA) sources. Logistic regression identified predictors for urinary tract infections (UTIs) after genitourinary trauma. Results: Among 530 TIDOS enrollees who entered VA care, 89 (17%) sustained genitourinary trauma. The majority of subjects (93%) were injured via a blast and 27% had a dismounted complex blast injury (DCBI). Sexual dysfunction was reported with 36% of subjects, whereas 14% had urinary retention/incontinence and 8% had urethral stricture. Urologic complications were comparable between patients with and without DCBIs. Nineteen (21%) subjects had one or more UTI with a total of 40 unique UTI events (25% during initial hospitalization and 75% during subsequent DOD or VA care). The UTI incidence rate was 0.89 per patient-year during initial hospitalization, 0.05 per patient-year during DOD follow-up, and 0.07 per patient-year during VA healthcare. Subjects with UTIs had a higher proportion of bladder injury (53% vs. 13%; p < 0.001), posterior urethral injury (26% vs. 1%; p = 0.001), pelvic fracture (47% vs. 4%; p < 0.001), soft-tissue infection of the pelvis/hip (37% vs. 4%; p = 0.001), urinary catheterization (47% vs. 11%; p < 0.001), urinary retention or incontinence (42% vs. 6%; p < 0.001), and stricture (26% vs. 3%; p = 0.004) compared with patients with genitourinary trauma and no UTI. Independent UTI risk factors were occurrence of a soft-tissue infection at the pelvis/hip, trauma to the urinary tract, and transtibial amputation. Conclusions: Among combat casualties with genitourinary trauma, UTIs are a common complication, particularly with severe blast injury and urologic sequelae. Episodes of UTIs typically occur early after the initial injury while in DOD care, however, recurrent infections may continue into long-term VA care.

Epidemiology of Trauma-Related Infections among a Combat Casualty Cohort after Initial Hospitalization: The Trauma Infectious Disease Outcomes Study.

BACKGROUND: The Trauma Infectious Disease Outcomes Study (TIDOS) cohort follows military personnel with deployment-related injuries in order to evaluate short- and long-term infectious complications. High rates of infectious complications have been observed in more than 30% of injured patients during initial hospitalization. We present data on infectious complications related to combat trauma after the initial period of hospitalization. PATIENTS AND METHODS: Data related to patient care for military personnel injured during combat operations between June 2009 and May 2012 were collected. Follow-up data were captured from interviews with enrolled participants and review of electronic medical records. RESULTS: Among 1,006 patients enrolled in the TIDOS cohort with follow-up data, 357 (35%) were diagnosed with one or more infection during their initial hospitalization, of whom 160 (45%) developed a trauma-related infection during follow-up (4.2 infections per 10,000 person-days). Patients with three or more infections during the initial hospitalization had a significantly higher rate of infections during the follow-up period compared with those with only one inpatient infection (incidence rate: 6.6 versus 3.1 per 10,000 days; p < 0.0001). There were 657 enrollees who did not have an infection during initial hospitalization, of whom 158 (24%) developed one during follow-up (incidence rate: 1.6 per 10,000 days). Overall, 318 (32%) enrolled patients developed an infection after hospital discharge (562 unique infections) with skin and soft-tissue infections being predominant (66%) followed by osteomyelitis (16%). Sustaining an amputation or open fracture, having an inpatient infection, and use of anti-pseudomonal penicillin (≥7 d) were independently associated with risk of an extremity wound infection during follow-up, whereas shorter hospitalization (15-30 d) was associated with a reduced risk. CONCLUSIONS: Combat-injured patients have a high burden of infectious complications that continue long after the initial period of hospitalization with soft-tissue and osteomyelitis being predominant. Further research on the long-term impact and outcomes of combat-associated infection is needed.

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.