Targeted metagenomic assessment reflects critical colonization in battlefield injuries.

IMPORTANCE: Microbial contamination in combat wounds can lead to opportunistic infections and adverse outcomes. However, current microbiological detection has a limited ability to capture microbial functional genes. This work describes the application of targeted metagenomic sequencing to profile wound bioburden and capture relevant wound-associated signatures for clinical utility. Ultimately, the ability to detect such signatures will help guide clinical decisions regarding wound care and management and aid in the prediction of wound outcomes.

Resistance patterns and clinical outcomes of Klebsiella pneumoniae and invasive Klebsiella variicola in trauma patients.

Recent reclassification of the Klebsiella genus to include Klebsiella variicola, and its association with bacteremia and mortality, has raised concerns. We examined Klebsiella spp. infections among battlefield trauma patients, including occurrence of invasive K. variicola disease. Klebsiella isolates collected from 51 wounded military personnel (2009-2014) through the Trauma Infectious Disease Outcomes Study were examined using polymerase chain reaction (PCR) and pulsed-field gel electrophoresis. K. variicola isolates were evaluated for hypermucoviscosity phenotype by the string test. Patients were severely injured, largely from blast injuries, and all received antibiotics prior to Klebsiella isolation. Multidrug-resistant Klebsiella isolates were identified in 23 (45%) patients; however, there were no significant differences when patients with and without multidrug-resistant Klebsiella were compared. A total of 237 isolates initially identified as K. pneumoniae were analyzed, with 141 clinical isolates associated with infections (remaining were colonizing isolates collected through surveillance groin swabs). Using PCR sequencing, 221 (93%) isolates were confirmed as K. pneumoniae, 10 (4%) were K. variicola, and 6 (3%) were K. quasipneumoniae. Five K. variicola isolates were associated with infections. Compared to K. pneumoniae, infecting K. variicola isolates were more likely to be from blood (4/5 versus 24/134, p = 0.04), and less likely to be multidrug-resistant (0/5 versus 99/134, p<0.01). No K. variicola isolates demonstrated the hypermucoviscosity phenotype. Although K. variicola isolates were frequently isolated from bloodstream infections, they were less likely to be multidrug-resistant. Further work is needed to facilitate diagnosis of K. variicola and clarify its clinical significance in larger prospective studies.

Microbiology of French military casualties repatriated from overseas for an open traumatic injury.

BACKGROUND: This study aimed to describe the microbiological epidemiology of repatriated French soldiers with an open traumatic injury, and to measure the proportion of multidrug-resistant bacteria (MDRB). METHODS: Retrospective study including all French soldiers repatriated in 2011 and 2012 in Parisian military hospitals for open traumatic injury. Results of clinical samples and MDRB screening were collected. The antibiotic susceptibility was assessed using the agar disk diffusion method. Characterization of resistance mechanisms was performed using PCR. Genotyping of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) isolates was performed using rep-PCR. RESULTS: A total of 139 patients were included; 70% of them were repatriated from Afghanistan. At admission, 24/88 were positive for MDRB (28%), mainly ESBL-E but no carbapenemase-producing Enterobacteriaceae and vancomycin-resistant Enterococcus faecium were identified. Forty-five patients had lesion sample collection, and 28/45 had a positive culture. The most frequently isolated pathogens were Enterobacter cloacae, Pseudomonas aeruginosa, and Escherichia coli. For eight patients, a MDRB was isolated from the wound, mainly ESBL-E (7/8) but also one methicillin-resistant Staphylococcus aureus and one imipenem-resistant Acinetobacter baumannii. Among ESBL-E, the PCR evidenced the high prevalence of CTX-M15 enzymes. Rep-PCR performed on the 23 ESBL-producing E. coli isolates highlighted numerous profiles. CONCLUSIONS: Controlling the spread of ESBL-E is currently challenging for French Armed Forces. Despite any evidence of an epidemic clone, a high-level compliance with hygiene precautions is required throughout the chain of care to avoid cross contamination.

[Pathogen Spectrum of Complex Wounds in Germany from War Zones]. / Verändertes Keimspektrum von Komplexwunden in Deutschland durch die Behandlung von Verletzten aus Konfliktländern.

Background Treatment of the injured from war zones with wounds with multi-resistant pathogens is becoming more common in Germany, especially in German Armed Forces Hospitals. In most cases, the pre-treatment of these patients has been inadequate and they have a high load of rare pathogens. In Germany, hospitals have to evaluate these pathogens by law. The aim of this study was to review current German guidelines and data on the array of pathogens of complex trauma wounds in Germany and to compare patients with wounds and multi-resistant pathogens from war zones treated in Germany. Patients and Methods A PubMed search was performed on all multiresistant pathogens, antibiotic resistance and guidelines in Germany from 2005 to 2015. The databases and recommendations of the Robert Koch Institute, the Paul Ehrlich Society and the National Reference Centre for the Surveillance of Nosocomial Infections were analysed. The screening results of injured patients from war zones treated in the German Armed Forces Hospital Ulm were included. Results The array of pathogens for nosocomial infections has not changed, but the ratios of the pathogens has altered. Methicilin-resistant Staphylococcus aureus (MRSA) has decreased, but vancomycin-resistant enterococci have increased continuously. Enterococcus faecium (E. faecium) now make up the largest fraction of VRE. The databases do not yet provide data on the relatively new classification of multiresistant gramnegative (MRGN) pathogens. MRGN pathogens play the main role in injured patients from war zones. Conclusion In the last ten years, there have been changes in the resistance and ratios of multi-resistant pathogens. MRSA has decreased over the last ten years, but reserve antibiotics are increasingly needed. VRE are increasing and even some reserve antibiotics have lost their efficacy because of the use of modern antibiotics. There are not yet any German datasets available on 3- and 4-MRGN. These pathogens play the main role in injured patients from war zones treated in Germany: it is crucial to perform routine screening and to take all precautions, including isolation. Surgical wound therapy is of increasing importance and uncritical and expensive antibiotic therapy is becoming becomes less important.

Refugees of the Syrian Civil War: Impact on Reemerging Infections, Health Services, and Biosecurity in Turkey.

After the Arab Spring uprising, Syria descended into a civil war in 2011. By March 2016, the United Nations reported that 13.5 million Syrians required humanitarian assistance, including 6.6 million internally displaced persons and more than 4.8 million refugees outside of Syria. Turkey is currently hosting the largest number of Syrian refugees-more than 2.7 million. A limited number of refugees are living in camps settled around the border, and others are spread throughout Turkey. This explosive and unexpected increase in the Syrian population in Turkey has had several negative impacts on health and social determinants. The overload of healthcare facilities has led to shortages in childhood immunization programs, drugs, and access to clean water and food supplies. According to Ministry of Health data, more than 7.5 million Syrians were examined at outpatient clinics, and 299,240 were hospitalized; most of those hospitalized were injured and wounded victims who require and have been occupying intensive care units. The refugees generally live in crowded and unsanitary conditions, which may lead to the spread of respiratory, skin, gastrointestinal, and genital system infections. Currently, measles, poliomyelitis, leishmaniasis, and multidrug-resistant tuberculosis are the reemerging infections being most frequently recorded. Multidrug-resistant gram-negative bacterial infections seem to be an increasing problem in gunshot or surgical wounds. Hepatitis A, malaria, and varicella have been seen with a high incidence among the refugees. There are many problems waiting to be resolved for health and living standards in Turkey.

Testing of antibiotic releasing implant coatings to fight bacteria in combat-associated osteomyelitis - an in-vitro study.

PURPOSE: Surgical procedures to prevent osteomyelitis after trauma can be supported by local application of antibiotics. This in-vitro study investigated the release and impact of antibiotics from implant coatings against bacteria associated with combat-related osteomyelitis. METHODS: K-wires were coated with poly(D,L-lactide) and ciprofloxacin, gentamicin, colistin, daptomycin or cefoxitin in different concentrations. The release was quantified and antimicrobial activity tested for different gram-positive or gram-negative bacteria, alone and in combination. To exclude toxic effects, primary osteoblast-like cells were exposed to antibiotic coating concentrations. RESULTS: All antibiotics alone and in combination showed an initial burst release with dose dependent antimicrobial activity and no negative effects on osteoblast-like cells, except for cefoxitin. CONCLUSIONS: Implant coatings can be customized with single or double antibiotic coatings to effectively fight different bacteria and also mixed infections in the treatment of a combat-acquired osteomyelitis. However, optimal drug load and degradation behaviour of individual antibiotics have to be considered.

Antifungal wound penetration of amphotericin and voriconazole in combat-related injuries: case report.

BACKGROUND: Survivors of combat trauma can have long and challenging recoveries, which may be complicated by infection. Invasive fungal infections are a rare but serious complication with limited treatment options. Currently, aggressive surgical debridement is the standard of care, with antifungal agents used adjunctively with uncertain efficacy. Anecdotal evidence suggests that antifungal agents may be ineffective in the absence of surgical debridement, and studies have yet to correlate antifungal concentrations in plasma and wounds. CASE PRESENTATION: Here we report the systemic pharmacokinetics and wound effluent antifungal concentrations of five wounds from two male patients, aged 28 and 30 years old who sustained combat-related blast injuries in southern Afghanistan, with proven or possible invasive fungal infection. Our data demonstrate that while voriconazole sufficiently penetrated the wound resulting in detectable effluent levels, free amphotericin B (unbound to plasma) was not present in wound effluent despite sufficient concentrations in circulating plasma. In addition, considerable between-patient and within-patient variability was observed in antifungal pharmacokinetic parameters. CONCLUSION: These data highlight the need for further studies evaluating wound penetration of commonly used antifungals and the role for therapeutic drug monitoring in providing optimal care for critically ill and injured war fighters.

Pathogens present in acute mangled extremities from Afghanistan and subsequent pathogen recovery.

Given the changing epidemiology of infecting pathogens in combat casualties, we evaluated bacteria and fungi in acute traumatic wounds from Afghanistan. From January 2013 to February 2014, 14 mangled lower extremities from 10 explosive-device injured casualties were swabbed for culture at Role 3 facilities. Bacteria were recovered from all patients on the date of injury. Pathogens recovered during routine patient care were recorded. The median injury severity score was 29, median initial Role 3/4 blood product support was 32 units, and median evacuation time was 42 minutes to first surgical care. Gram-positive bacteria were found in some wounds but not methicillin-resistant Staphylococcus aureus or vancomycin-resistant Enterococcus. Most wounds were colonized with low-virulence, environmental gram-negative bacteria, and not recovered again during therapy, reflecting wound contamination. Only one wound had the same bacteria (E. cloacae) throughout care at the Role 3, 4, and 5 facilities. Three cultures from two patients had multidrug-resistant bacteria (E. cloacae, E. coli), all detected at Role 5 facilities. Molds were not detected at Role 3, whereas one patient had a mold at Role 4 and 5. Mangled lower extremity injuries have a high contamination rate with environmental organisms, which are not typically associated with infections during the course of the patient's care.