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Although there is literature evaluating infectious complications associated with combat-related injuries from Iraq and Afghanistan, none have evaluated pneumonia specifically. Therefore, we assessed a series of pneumonia cases among wounded military personnel admitted to Landstuhl Regional Medical Center, and then evacuated further to participating U.S. military hospitals. Of the 423 casualties evacuated to the U.S., 36 developed pneumonia (8.5%) and 30 of these (83.3%) were ventilator-associated. Restricting to 162 subjects admitted to intensive care, 30 patients had pneumonia (18.5%). The median Injury Severity Score was higher among subjects with pneumonia (23.0, versus 6.0; p<0.01). There were 61 first-isolate respiratory specimens recovered from 31 pneumonia subjects, of which 56.1% were gram-negative, 18.2% were gram-positive, and 18.2% were fungal. Staphylococcus aureus and Pseudomonas aeruginosa were most commonly recovered (10.6%, and 9.1%, respectively). Thirteen bacterial isolates (26.5%) were multidrug-resistant. Outcome data were available for 32 patients, of which 26 resolved their infection without progression, 5 resolved after initial progression, and 1 died. Overall, combat-injured casualties suffer a relatively high rate of pneumonia, particularly those requiring mechanical ventilation. Although gram-negative pathogens were common, S. aureus was most frequently isolated. Continued focus on pneumonia prevention strategies is necessary for improving combat care.

A total of 102 methicillin-resistant Staphylococcus aureus (MRSA) isolates collected from 50 injured service members (June 2009 to December 2011) at U.S. military treatment facilities were analyzed for the conventional mecA gene and mecC homologue by using standard PCR-based methods. The prevalence of the mecC homologue was zero.

Background: During the conflicts in Iraq and Afghanistan, more than 52,000 U.S. military members were wounded in action. The battlefield mortality rate was lower than in past conflicts, however, those surviving often had complex soft tissue and bone injuries requiring multiple surgeries. This report describes the rates, types, and risks of infections complicating the care of combat casualties. Patients and Methods: Infection and microbiology data obtained from the Trauma Infectious Disease Outcomes Study (TIDOS), a prospective observational study of infections complicating deployment-related injuries, were used to determine the proportion of infection, types, and associated organisms. Injury and surgical information were collected from the Department of Defense Trauma Registry. Multivariable Cox proportional hazards and logistic regression models were used to evaluate potential factors associated with infection. Results: From 2009–2012, 1,807 combat casualties were evacuated to U.S. TIDOS-participating hospitals. Among the 1,807 patients, the proportion of overall infections from time of injury through initial U.S. hospitalization was 34% with half being skin, soft tissue, or bone infections. Infected wounds most commonly grew Enterococcus faecium, Pseudomonas aeruginosa, Acinetobacter spp. or Escherichia coli. In the multivariable model, amputation, blood transfusions, intensive care unit admission, injury severity scores, mechanical ventilation, and mechanism of injury were associated with risk of infection. Conclusions: One-third of combat casualties from Iraq and Afghanistan develop infections during their initial hospitalization. Amputations, blood transfusions, and overall injury severity are associated with risk of infection, whereas more easily modifiable factors such as early operative intervention or antibiotic administration are not.

BACKGROUND: During recent wars, 26% of combat casualties experienced open fractures and these injuries frequently are complicated by infections, including osteomyelitis. Risk factors for the development of osteomyelitis with combat-related open tibia fractures have been examined, but less information is known about recurrence of this infection, which may result in additional hospitalizations and surgical procedures. QUESTIONS/PURPOSES: (1) What is the risk of osteomyelitis recurrence after wartime open tibia fractures and how does the microbiology compare with initial infections? (2) What factors are associated with osteomyelitis recurrence among patients with open tibia fractures? (3) What clinical characteristics and management approaches are associated with definite/probable osteomyelitis as opposed to possible osteomyelitis and what was the microbiology of these infections? METHODS: A survey of US military personnel injured during deployment between March 2003 and December 2009 identified 215 patients with open tibia fractures, of whom 130 patients developed osteomyelitis and were examined in a retrospective analysis. No patients with bilateral osteomyelitis were included. Twenty-five patients meeting osteomyelitis diagnostic criteria were classified as definite/probable (positive bone culture, direct evidence of infection, or symptoms with culture and/or radiographic evidence) and 105 were classified as possible (bone contamination, organism growth in deep wound tissue, and evidence of local/systemic inflammation). Patients diagnosed with osteomyelitis were treated with débridement and irrigation as well as intravenous antibiotics. Fixation hardware was retained until fracture union, when possible. Osteomyelitis recurrence was defined as a subsequent osteomyelitis diagnosis at the original site ≥ 30 days after completion of initial treatment. This followup period was chosen based on the definition of recurrence so as to include as many patients as possible for analysis. Factors associated with osteomyelitis ...

The influence of highly active antiretroviral therapy (HAART) upon hepatitis B virus (HBV) vaccine responses in HIV-infected individuals is unclear. After classification of vaccinees as non-responders (HBsAb <10 IU/L) or responders (HBsAb ≥10 IU/L) in our HIV cohort, multivariate logistic regression was used to assess factors associated with subsequent vaccine response. Of 626 participants vaccinated from 1988–2005, 217 (35%) were vaccine responders. Receipt of ≥3 doses of vaccine (OR 1.83, 95% CI 1.24–2.70), higher CD4 count at vaccination (OR 1.09, 95% CI 1.05–1.13 per 50 cells/μl increase), and use of HAART (OR 2.37, 95% CI 1.56–3.62) were all associated with increased likelihood of developing a response. However, only 49% of those on HAART at last vaccination responded, and 62% of those on HAART, with CD4 count ≥350, and HIV RNA <400 copies/mL responded. Compared to those on HAART with CD4 count ≥350, those not on HAART with CD4 count ≥350 had significantly reduced odds of developing a vaccine response (OR 0.47, 95% CI 0.30–0.70). While HAART use concurrent with HBV immunization was associated with increased probability of responding to the vaccine, the response rate was low for those on HAART. These data provide additional evidence of HAART benefits, even in those with higher CD4 counts, but also highlight the need for improving HBV vaccine immunogenicity.

INTRODUCTION: Invasive fungal infections (IFI) are associated with high morbidity and mortality. A better method of risk stratifying trauma patients for combat-related IFI is needed to improve clinical outcomes while minimizing morbidity related to overtreatment. We sought to develop combat-related IFI clinical decision support (CDS) tools to assist providers to make treatment decisions both near the point of injury and subsequently at definitive treatment centers. MATERIALS AND METHODS: We utilized a training dataset containing information from 227 combat-injured military personnel to build a Bayesian belief network (BBN) to predict the likelihood of developing IFI using information available at the point of initial resuscitation (THEATER model) and in the tertiary care setting (MEDCEN model). After selecting BBN models, external validation used a separate test dataset of 350 wounded warriors. Furthermore, the performance of the BBN models was compared with a "two-rule model" alone (based on physician experience) and combinations of the BBN models plus the two-rule model. The two-rule model contains plausible IFI criteria, but it has not been formally evaluated, and they are not currently actual clinical guidelines. RESULTS: We found receiver operating characteristic areas under the curve (AUC) of 0.70 (95% CI: [0.62, 0.77]) and 0.68 (95% CI: [0.59, 0.76]) for the THEATER and MEDCEN BBN models, respectively, on cross-validation. External validation with the highest AUC BBN models produced THEATER AUC of 0.68 (95% CI: [0.58, 0.78]) and MEDCEN AUC of 0.67 (95% CI: [0.57, 0.78]). With the incorporation of two-rule model in low IFI-prevalence populations, external validation AUC increased to 0.77 (95% CI: [0.69, 0.84]) for the THEATER model and 0.76 (95% CI:[0.68, 0.85]) for the LRMC model. The two-rule model alone has an AUC of 0.72 (95% CI: [0.63, 0.81]). CONCLUSIONS: Overall, the IFI tools produced clinically useful, robust models. However, the clinical utility of these models is highly dependent upon the ...

Malaria chemoprophylaxis is used as a preventive measure in military personnel deployed to malaria-endemic countries. However, limited information is available on compliance with chemoprophylaxis among trauma patients during hospitalization and after discharge. Therefore, we assessed antimalarial primary chemoprophylaxis and presumptive antirelapse therapy (primaquine) compliance among wounded United States military personnel after medical evacuation from Afghanistan (June 2009–August 2011) to Landstuhl Regional Medical Center in Landstuhl, Germany, and then to three U.S. military hospitals. Among admissions at Landstuhl Regional Medical Center, 74% of 2,540 patients were prescribed primary chemoprophylaxis and < 1% were prescribed primaquine. After transfer of 1,331 patients to U.S. hospitals, 93% received primary chemoprophylaxis and 33% received primaquine. Of 751 trauma patients with available post-admission data, 42% received primary chemoprophylaxis for four weeks, 33% received primaquine for 14 days, and 17% received both. These antimalarial chemoprophylaxis prescription rates suggest that improved protocols to continue malaria chemoprophylaxis in accordance with force protection guidelines are needed.

In response to the high rates of colonization and infection by multidrug-resistant gram-negative bacilli (MDR GNB), many military treatment facilities (MTFs) have implemented additional infection control practices, such as active surveillance cultures for asymptomatic colonization. Results of surveillance cultures (June 2009 – May 2012) collected from patients at Landstuhl Regional Medical Center (Landstuhl RMC), Germany, and three U.S. MTFs were analyzed to evaluate trends in MDR GNB colonization over time and across facilities. At Landstuhl RMC, 6.6 percent of patients were colonized on admission with MDR GNB compared to 12.4 percent of patients admitted to the participating U.S. MTFs. Escherichia coli was the predominant organism, representing 82.4 percent of MDR isolates at Landstuhl RMC and 67.1 to 83.3 percent at U.S. MTFs. Other common MDR GNB included Acinetobacter calcoaceticus-baumannii complex and Klebsiella pneumoniae. Although Pseudomonas aeruginosa was often isolated from the surveillance cultures, it was never multidrug-resistant. Annual rates of MDR GNB colonization were not significantly different over the three-year period. Ongoing research includes assessment of predictive factors for MDR GNB colonization and the relationship between colonization and infection.

Combat trauma wounds with invasive fungal infections (IFIs) are often polymicrobial with fungal and bacterial growth, but the impact of the wound microbiology on clinical outcomes is uncertain. Our objectives were to compare the microbiological features between IFI and non-IFI wounds and evaluate whether clinical outcomes differed among IFI wounds based upon mold type. Data from U.S. military personnel injured in Afghanistan with IFI wounds were examined. Controls were matched by the pattern/severity of injury, including blood transfusion requirements. Wound closure timing was compared between IFI and non-IFI control wounds (with/without bacterial infections). IFI wound closure was also assessed according to mold species isolation. Eighty-two IFI wounds and 136 non-IFI wounds (63 with skin and soft tissue infections [SSTIs] and 73 without) were examined. The time to wound closure was longer for the IFI wounds (median, 16 days) than for the non-IFI controls with/without SSTIs (medians, 12 and 9 days, respectively; P < 0.001). The growth of multidrug-resistant Gram-negative rods was reported among 35% and 41% of the IFI and non-IFI wounds with SSTIs, respectively. Among the IFI wounds, times to wound closure were significantly longer for wounds with Mucorales growth than for wounds with non-Mucorales growth (median, 17 days versus 13 days; P < 0.01). When wounds with Mucorales and Aspergillus spp. growth were compared, there was no significant difference in wound closure timing. Trauma wounds with SSTIs were often polymicrobial, yet the presence of invasive molds (predominant types: order Mucorales, Aspergillus spp., and Fusarium spp.) significantly prolonged the time to wound closure. Overall, the times to wound closure were longest for the IFI wounds with Mucorales growth.

Escherichia coli is the most common colonizing and infecting organism isolated from U.S. service members injured during deployment. Our objective was to evaluate the phenotypic and genotypic changes of infecting and colonizing E. coli organisms over time and across facilities to better understand their transmission patterns. E. coli isolates were collected via surveillance cultures and infection workups from U.S. military personnel injured during deployment (June 2009 to May 2011). The isolates underwent antimicrobial susceptibility testing, pulsed-field gel electrophoresis, and multiplex PCR for phylotyping to determine their resistance profiles and clonality. A total of 343 colonizing and 136 infecting E. coli isolates were analyzed, of which 197 (57%) and 109 (80%) isolates, respectively, produced extended-spectrum β-lactamases (ESBL). Phylogroup A was predominant among both colonizing (38%) and infecting isolates (43%). Although 188 unique pulsed-field types (PFTs) were identified from the colonizing isolates, and 54 PFTs were identified from the infecting isolates, there was a lack of PFT overlap between study years, combat zones, and military treatment facilities. On a per-subject basis, 26% and 32% of the patients with serial colonizing isolates and 10% and 21% with serial infecting isolates acquired changes in their phylogroup and PFT profiles, respectively, over time. The production of ESBL remained high over time and across facilities, with no substantial changes in antimicrobial susceptibilities. Overall, our results demonstrated an array of genotypic and phenotypic differences for the isolates without large clonal clusters; however, the same PFTs were occasionally observed in the colonizing and infecting isolates, suggesting that the source of infections may be endogenous host organisms.

INTRODUCTION: The Department of Defense (DoD) and the Department of Veterans Affairs (VA) provide comprehensive HIV treatment and care to their beneficiaries with open access and few costs to the patient. Individuals who receive HIV care in the VA have higher rates of substance abuse, homelessness and unemployment than individuals who receive HIV care in the DoD. A comparison between individuals receiving HIV treatment and care from the DoD and the VA provides an opportunity to explore the impact of individual-level characteristics on clinical outcomes within two healthcare systems that are optimized for clinic retention and medication adherence. METHODS: Data were collected on 1065 patients from the HIV Atlanta VA Cohort Study (HAVACS) and 1199 patients from the US Military HIV Natural History Study (NHS). Patients were eligible if they had an HIV diagnosis and began HAART between January 1, 1996 and June 30, 2010. The analysis examined the survival from HAART initiation to all-cause mortality or an AIDS event. RESULTS: Although there was substantial between-cohort heterogeneity and the 12-year survival of participants in NHS was significantly higher than in HAVACS in crude analyses, this survival disparity was reduced from 21.5% to 1.6% (mortality only) and 26.8% to 4.1% (combined mortality or AIDS) when controlling for clinical and demographic variables. CONCLUSION: We assessed the clinical outcomes for individuals with HIV from two very similar government-sponsored healthcare systems that reduced or eliminated many barriers associated with accessing treatment and care. After controlling for clinical and demographic variables, both 12-year survival and AIDS-free survival rates were similar for the two study cohorts who have open access to care and medication despite dramatic differences in socioeconomic and behavioral characteristics.

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 ...

The Trauma Infectious Disease Outcomes Study began in June 2009 as combat operations were decreasing in Iraq and increasing in Afghanistan. Our analysis examines the rate of infections of wounded U.S military personnel from operational theaters in Iraq and Afghanistan admitted to Landstuhl Regional Medical Center between June 2009 and December 2013 and transferred to a participating U.S. hospital. Infection risk factors were examined in a multivariate logistic regression analysis (expressed as odds ratios [OR]; 95% confidence intervals [CI]). The study population includes 524 wounded military personnel from Iraq and 4766 from Afghanistan. The proportion of patients with at least one infection was 28% and 34% from the Iraq and Afghanistan theaters, respectively. The incidence density rate was 2.0 (per 100 person-days) for Iraq and 2.7 infections for Afghanistan. Independent risk factors included large-volume blood product transfusions (OR: 10.68; CI: 6.73–16.95), high injury severity score (OR: 2.48; CI: 1.81–3.41), and improvised explosive device injury mechanism (OR: 1.84; CI: 1.35–2.49). Operational theater (OR: 1.32; CI: 0.87–1.99) was not a risk factor. The difference in infection rates between operational theaters is primarily due to increased injury severity in Afghanistan from a higher proportion of blast-related trauma during the study period.

In 2008, a clinical practice guideline (CPG) was developed for the prevention of infections among military personnel with combat-related injuries. Our analysis expands on a prior 6-month evaluation and assesses CPG adherence with respect to antimicrobial prophylaxis for U.S. combat casualties medically evacuated to Landstuhl Regional Medical Center over a 1-year period (June 2009 through May 2010), with an eventual goal of continuously monitoring CPG adherence and measuring outcomes as a function of compliance. We classified adherence to the CPG as receipt of recommended antimicrobials within 48 hours of injury. A total of 1106 military personnel eligible for CPG assessment were identified and 74% received antimicrobial prophylaxis. Overall, CPG compliance within 48 hours of injury was 75%. Lack of antimicrobial prophylaxis contributed 2 to 22% to noncompliance varying by injury category, whereas receipt of antibiotics other than preferred was 11 to 30%. For extremity injuries, antimicrobial prophylaxis adherence was 60 to 83%, whereas it was 80% for closed injuries and 68% for penetrating abdominal injuries. Overall, the results of our analysis suggest an ongoing need to improve adherence, monitor CPG compliance, and assess effectiveness.

Background: An outbreak of invasive fungal infections (IFI) began in 2009 among United States servicemen who sustained blast injuries in Afghanistan. In response, the military trauma community sought a uniform approach to early diagnosis and treatment. Toward this goal, a local clinical practice guideline (CPG) was implemented at Landstuhl Regional Medical Center (LRMC) in early 2011 to screen for IFI in high-risk patients using tissue histopathology and fungal cultures.