Isolation and characterization of Streptomyces bacteriophages and Streptomyces strains encoding biosynthetic arsenals.

The threat to public health posed by drug-resistant bacteria is rapidly increasing, as some of healthcare's most potent antibiotics are becoming obsolete. Approximately two-thirds of the world's antibiotics are derived from natural products produced by Streptomyces encoded biosynthetic gene clusters. Thus, to identify novel gene clusters, we sequenced the genomes of four bioactive Streptomyces strains isolated from the soil in San Diego County and used Bacterial Cytological Profiling adapted for agar plate culturing in order to examine the mechanisms of bacterial inhibition exhibited by these strains. In the four strains, we identified 104 biosynthetic gene clusters. Some of these clusters were predicted to produce previously studied antibiotics; however, the known mechanisms of these molecules could not fully account for the antibacterial activity exhibited by the strains, suggesting that novel clusters might encode antibiotics. When assessed for their ability to inhibit the growth of clinically isolated pathogens, three Streptomyces strains demonstrated activity against methicillin-resistant Staphylococcus aureus. Additionally, due to the utility of bacteriophages for genetically manipulating bacterial strains via transduction, we also isolated four new phages (BartholomewSD, IceWarrior, Shawty, and TrvxScott) against S. platensis. A genomic analysis of our phages revealed nearly 200 uncharacterized proteins, including a new site-specific serine integrase that could prove to be a useful genetic tool. Sequence analysis of the Streptomyces strains identified CRISPR-Cas systems and specific spacer sequences that allowed us to predict phage host ranges. Ultimately, this study identified Streptomyces strains with the potential to produce novel chemical matter as well as integrase-encoding phages that could potentially be used to manipulate these strains.

Marijuana Screening and Trauma Outcomes.

OBJECTIVE: The objective of this study was to determine if positive marijuana toxicology screen is associated with worse outcomes following trauma. METHODS: A 3-year retrospective study was conducted on adult trauma patients using a Level II trauma registry. Patients were included if they had marijuana toxicology results available and were excluded if they tested positive for polysubstance. Endpoints of interest were mortality, injury severity score, length of stay (LOS), Glasgow coma Scale, and blood requirements. RESULTS: Three hundred and eighty-one patients met the criteria. There was no difference between the two groups with regard to mortality (1.63% vs. 3.05%, odds ratio [OR]: 0.52 [0.13-2.14]) or LOS (1 day vs. 1 day, P = 0.125), and P > 0.05 for all other metrics besides age (31.53 years vs. 50.20 years, P = 0). OR for suffering major trauma in patients <55 years was 2.26 (16.88% vs. 8.26%, OR: 2.26 [1.02-5.01]), and patients 55 years and older were more likely to present with lower blood pressure (129.12 mmHg vs. 140.85 mmHg, P = 0.002) and higher heart rate (95.25 bpm vs. 83.47 bpm, P = 0.026). CONCLUSIONS: A positive screen for marijuana in the setting of a trauma is not associated with increased mortality or hospital LOS. These results warrant further investigation of the effects of marijuana on trauma outcomes.

Recreational Drugs and Outcomes in Trauma Patients.

OBJECTIVE: The objective of the study is to determine if marijuana, methamphetamine, or cocaine is associated with worse outcomes following trauma. METHODS: A retrospective cross-sectional study was conducted on 731 trauma patients. Data collected from Natividad Medical Center's trauma registry were used to analyze reports of adult patients from July 1, 2014, to July 1, 2017. Analyzed endpoints were mortality, rates of major trauma, mean Injury Severity Score (ISS), and length of stay (LOS). RESULTS: Odds ratios for mortality contained null value in each group. Odds ratios for suffering major trauma for marijuana and amphetamines were 1.2 and 2.6, respectively. P values for ISS were >0.05 for each group. P values for LOS were >0.05 for marijuana and cocaine and 0.01 for amphetamines. CONCLUSIONS: A positive screen for marijuana, amphetamine, or cocaine is not associated with increased mortality for victims of trauma. Amphetamines are associated with higher rates of major trauma and longer LOS. Marijuana is associated with higher rates of major trauma. Cocaine is not associated with the likelihood of suffering major trauma or length of stay.

Effects of Body Mass Index on Outcome Measures of the Patients with Penetrating Injuries; A Single Center Experience.

OBJECTIVE: To determine if there was any decrease in measures of injury severity or outcome with obese patients (body mass index greater than or equal to 30 kg/m2) as compared to non-obese patients (body mass index less than 30 kg/m2). METHODS: We conducted a retrospective review of the trauma database maintained by Natividad Medical Center's Level 2-Trauma program. From July 1st, 2014 to July 1st, 2017 there were 371 cases of penetrating trauma in adults between the ages of 18-80 years old. Overall 311 patients had BMI data recorded. We divided these 311 patients into two groups: penetrating injury due to firearm (n= 198) and penetrating injury due to stabbing or piercing (n=113). We compared non-obese patients against obese patients for age, gender, Injury Severity Score (ISS), length of stay (LOS), Intensive Care Unit LOS, units of blood given, direct transfer from ED to operating room, and mortality. RESULTS: A total of 311 patients were included in the study, 198 (63.6%) patients suffered from gunshot wounds and 113 (36.4) from stab or piercing wounds. The mean age was 33.6 ± 12.8 and there were 283 (91%) men among the victims. Overall 87 (28%) required emergent surgery and a 19 (6.1%) mortality rate was recorded. In the gunshot wound group there was no significant difference between non-obese and obese patients for age (p=0.400), gender (p=0.900), ISS (p=0.544), LOS (p=0.273), Intensive Care Unit LOS (p=0.729), units of blood given (p=0.300), or mortality (p=0.855). We found that in the stab or piercing group there was no significant difference between non-obese and obese patients for age (p=0.900), gender (p=0.900), ISS (p=0.580), LOS (p=0.839), Intensive Care Unit LOS (p=0.305), units of blood given (p=0.431), or mortality (p=0.321). CONCLUSION: Our findings indicate that in our patient population, there was no significant difference in markers of injury severity, morbidity, or mortality in adult non-obese patients as comparted with obese patients.  Furthermore, there was no significant difference between the two groups in operative rates, suggesting that obesity may not confer a protective effect in penetrating trauma.

Massive Blood Transfusions and Outcomes in Trauma Patients; An Intention to Treat Analysis.

OBJECTIVE: To determine if there exists an upper limit for amount of blood transfused in trauma patients before it reaches a point of futility. METHODS: A prospective cohort study was conducted on 131 patients who received massive blood transfusion (MBT), defined as 10 U or higher of PRBCs received in the initial 24 hours. Data collected from a Level II trauma center registry were used to analyze reports of adult patients from July 2014 to 2017. Cohorts were divided by amount of blood received - 0 to 9 U, 10-19 U, 20 to 29 U, 30-39 U, 40 U or higher - odds ratio for mortality and p-values for mean Injury Severity Score and overall hospital length of stay were calculated for each group. RESULTS: Odds ratios for massive blood transfusion groups from 10 units to 39 units each contained the null value, while our 40 units and above group did not (OR 12.52, 95% CI 1.3-117.7). CONCLUSION: Although this study is limited by its sample size, these results suggests that 40 units of PRBCs may be a threshold at which survival rates begin to decrease significantly.