Christopher A. Guidry

Trial of Short-Course Antimicrobial Therapy for Intraabdominal Infection

BACKGROUND The successful treatment of intraabdominal infection requires a combination of anatomical source control and antibiotics. The appropriate duration of antimicrobial therapy remains unclear. METHODS We randomly assigned 518 patients with complicated intraabdominal infection and adequate source control to receive antibiotics until 2 days after the resolution of fever, leukocytosis, and ileus, with a maximum of 10 days of therapy (control group), or to receive a fixed course of antibiotics (experimental group) for 4±1 calendar days. The primary outcome was a composite of surgical-site infection, recurrent intraabdominal infection, or death within 30 days after the index source-control procedure, according to treatment group. Secondary outcomes included the duration of therapy and rates of subsequent infections. RESULTS Surgical-site infection, recurrent intraabdominal infection, or death occurred in 56 of 257 patients in the experimental group (21.8%), as compared with 58 of 260 patients in the control group (22.3%) (absolute difference, -0.5 percentage point; 95% confidence interval [CI], -7.0 to 8.0; P=0.92). The median duration of antibiotic therapy was 4.0 days (interquartile range, 4.0 to 5.0) in the experimental group, as compared with 8.0 days (interquartile range, 5.0 to 10.0) in the control group (absolute difference, -4.0 days; 95% CI, -4.7 to -3.3; P<0.001). No significant between-group differences were found in the individual rates of the components of the primary outcome or in other secondary outcomes. CONCLUSIONS In patients with intraabdominal infections who had undergone an adequate source-control procedure, the outcomes after fixed-duration antibiotic therapy (approximately 4 days) were similar to those after a longer course of antibiotics (approximately 8 days) that extended until after the resolution of physiological abnormalities. (Funded by the National Institutes of Health; STOP-IT ClinicalTrials.gov number, NCT00657566.).

Hypocaloric compared with eucaloric nutritional support and its effect on infection rates in a surgical intensive care unit: a randomized controlled trial

BACKGROUND Proper caloric intake goals in critically ill surgical patients are unclear. It is possible that overnutrition can lead to hyperglycemia and an increased risk of infection. OBJECTIVE This study was conducted to determine whether surgical infection outcomes in the intensive care unit (ICU) could be improved with the use of hypocaloric nutritional support. DESIGN Eighty-three critically ill patients were randomly allocated to receive either the standard calculated daily caloric requirement of 25-30 kcal · kg(-1) · d(-1) (eucaloric) or 50% of that value (hypocaloric) via enteral tube feeds or parenteral nutrition, with an equal protein allocation in each group (1.5 g · kg(-1) · d(-1)). RESULTS There were 82 infections in the hypocaloric group and 66 in the eucaloric group, with no significant difference in the mean (± SE) number of infections per patient (2.0 ± 0.6 and 1.6 ± 0.2, respectively; P = 0.50), percentage of patients acquiring infection [70.7% (29 of 41) and 76.2% (32 of 42), respectively; P = 0.57], mean ICU length of stay (16.7 ± 2.7 and 13.5 ± 1.1 d, respectively; P = 0.28), mean hospital length of stay (35.2 ± 4.9 and 31.0 ± 2.5 d, respectively; P = 0.45), mean 0600 glucose concentration (132 ± 2.9 and 135 ± 3.1 mg/dL, respectively; P = 0.63), or number of mortalities [3 (7.3%) and 4 (9.5%), respectively; P = 0.72]. Further analyses revealed no differences when analyzed by sex, admission diagnosis, site of infection, or causative organism. CONCLUSIONS Among critically ill surgical patients, caloric provision across a wide acceptable range does not appear to be associated with major outcomes, including infectious complications. The optimum target for caloric provision remains elusive.

Permissive Hypercapnia in the Management of Congenital Diaphragmatic Hernia: Our Institutional Experience

BACKGROUND Congenital diaphragmatic hernia (CDH) is a potentially lethal anomaly associated with pulmonary hypoplasia and persistent pulmonary hypertension. Permissive hypercapnia is a strategy designed to reduce lung injury from mechanical ventilation in infants. It has been shown to be a potentially superior method of ventilator management for patients with CDH. In 2001, the Divisions of Neonatology and Pediatric Surgery at the University of Virginia Childrens Hospital established permissive hypercapnia as the management strategy for treatment of CDH. We hypothesized that permissive hypercapnia would be associated with improved outcomes in this patient population. STUDY DESIGN This retrospective review compares outcomes of infants treated for CDH in the extracorporeal membrane oxygenation (ECMO) era before and after initiation of permissive hypercapnia at a single institution. Outcomes were compared using univariate statistical analysis. RESULTS Ninety-one patients were available for analysis and were divided into 2 groups: 42 (Group 1) treated before and 49 (Group 2) treated after implementation of permissive hypercapnia. Survival was higher in Group 2 (85.8% vs 54.8%; p = 0.001; relative risk [RR] 3.17). Morbidity was lower in Group 2 and approached statistical significance (65.3% vs 83.3%; p = 0.052). Patients in Group 2 were repaired later, had a lower rate of ECMO use, and were extubated earlier. There was no difference in hospital stay. CONCLUSIONS The use of permissive hypercapnia for infants with CDH was associated with decreased mortality, a longer period of ventilation before repair with a shorter period of ventilation after repair, a lower rate of ECMO use, and no lengthening of hospital stay. Permissive hypercapnia remains the standard of care for ventilation of infants with CDH at our institution.

Sex- and Diagnosis-dependent Differences in Mortality and Admission Cytokine Levels Among Patients Admitted for Intensive Care*

Objectives:To investigate the role of sex on cytokine expression and mortality in critically ill patients. Design:A cohort of patients admitted to were enrolled and followed over a 5-year period. Setting:Two university-affiliated hospital surgical and trauma ICUs. Patients:Patients 18 years old and older admitted for at least 48 hours to the surgical or trauma ICU. Interventions:Observation only. Measurements and Main Results:Major outcomes included admission cytokine levels, prevalence of ICU-acquired infection, and mortality during hospitalization conditioned on trauma status and sex. The final cohort included 2,291 patients (1,407 trauma and 884 nontrauma). The prevalence of ICU-acquired infection was similar for men (46.5%) and women (44.5%). All-cause in-hospital mortality was 12.7% for trauma male patient and 9.1% for trauma female patient (p = 0.065) and 22.9% for nontrauma male patients and 20.6% for nontrauma female patients (p = 0.40). Among trauma patients, logistic regression analysis identified female sex as protective for all-cause mortality (odds ratio, 0.57). Among trauma patients, men had significantly higher admission serum levels of interleukin-2, interleukin-12, interferon-&ggr;, and tumor necrosis factor-&agr;, and among nontrauma patients, men had higher admission levels of interleukin-8 and tumor necrosis factor-&agr;. Conclusions:The relationship between sex and outcomes in critically ill patients is complex and depends on underlying illness. Women appear to be better adapted to survive traumatic events, while sex may be less important in other forms of critical illness. The mechanisms accounting for this gender dimorphism may, in part, involve differential cytokine responses to injury, with men expressing a more robust proinflammatory profile.

Vancomycin and nephrotoxicity: Just another myth?

BACKGROUND Vancomycin is considered the drug of choice for methicillin-resistant Staphylococcus aureus infection; however, it has also been linked with nephrotoxicity in the past, sometimes leading to its substitution with linezolid. We hypothesized that patients treated with vancomycin for gram-positive (GP) infections would have an increased incidence of rise in creatinine and need for hemodialysis (HD) compared with patients receiving linezolid. METHODS This was a retrospective cohort study of a prospectively maintained database of all surgical patients treated with either vancomycin or linezolid for GP infections in a single intensive care unit from 2001 to 2008 and managed under a cycling antibiotic protocol. Patients were followed up until hospital discharge. Categorical and continuous variables were evaluated. Multivariable logistic regression was performed. RESULTS A total of 545 patients were treated for 1,046 GP infections (571 with vancomycin, 475 with linezolid) over 7 years. Patient demographics were similar between groups; however, the vancomycin group was associated with a longer treatment course (16.2 [0.5] days vs. 14.3 [0.5] days; p = 0.022). Unadjusted outcomes were similar between groups. Multivariable analysis revealed that Acute Physiology and Chronic Health Evaluation II score predicted an increase in creatinine levels greater than 1.0 following antibiotic therapy (relative risk [RR], 3.01; 95% confidence interval [CI], 1.22–7.42) and subsequent need for HD (RR, 3.07; 95% CI, 1.23–7.62). In addition, initial creatinine level predicted an increase in creatinine levels greater than 1.0 following antibiotic therapy (RR, 4.36; 95% CI, 1.46–12.99) and subsequent need for HD (RR, 10.83; 95% CI, 3.19–36.77). Linezolid was found to be protective regarding rise in creatinine levels greater than 1.0 following antibiotic therapy; however, this was only experienced when vancomycin trough levels greater than 20 were encountered (RR, 5.4;95% CI, 1.19–24.51). CONCLUSION These data suggest that vancomycin is minimally nephrotoxic and has a similar nephrotoxic profile as compared with linezolid when appropriate dosing is used, even among critically ill patients with complex infections. LEVEL OF EVIDENCE Therapeutic/care management, level II.

Gastric bypass improves survival compared with propensity-matched controls: a cohort study with over 10-year follow-up.

BACKGROUND The purpose of this study is to evaluate the long-term survival following gastric bypass using propensity-matched controls. METHODS We identified all patients who either received a gastric bypass (GBP) or met criteria to receive a GBP between January 1, 2002 and December 31, 2003. Propensity matching was performed. Long-term, all-cause mortality data were collected and evaluated using Kaplan-Meier curves. RESULTS Four hundred thirty GBP cases and 5,323 controls were identified from the enrollment period. Ultimately, 802 cases and controls (1:1 matching, 93.2% match rate) were identified using propensity matching. Median follow-up was similar between groups. Overall mortality was lower for the GBP group (odds ratio .48, 95% confidence interval .29 to .78). GBP demonstrated significantly increased survival when compared with controls (P = .002). Similar patterns were noted among diabetics. CONCLUSION We have demonstrated that gastric bypass provides a clear long-term survival advantage compared with nonsurgical propensity-matched controls.

Vancomycin-Associated Nephrotoxicity: The Obesity Factor

BACKGROUND Current recommendations suggest that vancomycin dosing utilize actual rather than ideal body weight in obese patients. Thus, obese patients may be at greater risk for nephrotoxicity. The purpose of this study was to compare the incidence of nephrotoxicity in vancomycin-treated obese and lean patients at our institution, where unadjusted, actual body weight-based dosing (capped at 2 g per dose twice daily) is used. We expected obese patients to experience a greater incidence of nephrotoxicity than lean patients. METHODS This study examined a retrospective cohort of patients treated with vancomycin for gram-positive or mixed infections in our facility from 2005-2009 who were not receiving hemodialysis at the time of admission. Patients were stratified by body mass index (BMI; obese ≥30 kg/m(2) vs. lean <30 kg/m(2)). Relative risk (RR), 95% confidence intervals (CIs), and p values were computed using a generalized estimating equation to accommodate a correlated data structure corresponding to multiple episodes of infection per individual. Multivariable analysis was performed. RESULTS A total of 530 patients (207 obese; 323 lean) with 1,007 episodes of infection were treated with vancomycin. Patient demographics, co-morbidities, sites of infection, and infecting organisms were similar in the two groups. Female gender (p=0.042), diabetes mellitus (DM) (p=0.018), and hypertension (HTN) (p=0.0009) were more often associated with obesity, whereas allografts (p=0.022) and peripheral vascular disease (p=0.036) were more often present in lean patients. The Acute Physiology and Chronic Health Evaluation II score >21 was the only variable associated with nephrotoxicity (p=0.039). After adjusting for statistically significant variables, obesity was found not to be associated with a greater risk of nephrotoxicity (RR=0.98; 95% CI=0.93-1.04; p=0.59). CONCLUSION No difference in nephrotoxicity was observed between lean and obese patients treated with vancomycin at our institution.

Resistant Pathogens, Fungi, and Viruses

Although originally described in Staphylococcus aureus, resistance among bacteria has now become a race to determine which classes of bacteria will become more resistant. Availability of antibacterial agents has allowed the development of entirely new diseases caused by nonbacterial pathogens, related largely to fungi that are inherently resistant to antibacterials. This article presents the growing body of knowledge of the herpes family of viruses, and their occurrence and consequences in patients with concomitant surgical disease or critical illness. The focus is on previously immunocompetent patients, as the impact of herpes viruses in immunosuppressed patients has received thorough coverage elsewhere.

Risk Associated With Complications and Mortality After Urgent Surgery vs Elective and Emergency Surgery: Implications for Defining “Quality” and Reporting Outcomes for Urgent Surgery

Importance Given the current climate of outcomes-driven quality reporting, it is critical to appropriately risk stratify patients using standardized metrics. Objective To elucidate the risk associated with urgent surgery on complications and mortality after general surgical procedures. Design, Setting, and Participants This retrospective review used the American College of Surgeons National Surgery Quality Improvement Program database to capture all general surgery cases performed at 435 hospitals nationwide between January 1, 2013, and December 31, 2013. Data analysis was performed from November 11, 2015, to February 16, 2017. Exposures Any operations coded as both nonelective and nonemergency were designated into a novel category titled urgent. Main Outcomes and Measures The primary outcome was 30-day mortality; secondary outcomes included 30-day rates of complications, reoperation, and readmission in urgent cases compared with both elective and emergency cases. Results Of 173 643 patients undergoing general surgery (101 632 females and 72 011 males), 130 235 (75.0%) were categorized as elective, 22 592 (13.0%) as emergency, and 20 816 (12.0%) as nonelective and nonemergency. When controlling for standard American College of Surgeons National Surgery Quality Improvement Program preoperative risk factors, with elective surgery as the reference value, the 3 groups had significantly distinct odds ratios (ORs) of experiencing any complication (urgent surgery: OR, 1.38; 95% CI, 1.30-1.45; P < .001; and emergency surgery: OR, 1.65; 95% CI, 1.55-1.76; P < .001) and of mortality (urgent surgery: OR, 2.32; 95% CI, 2.00-2.68; P < .001; and emergency surgery: OR, 2.91; 95% CI, 2.48-3.41; P < .001). Surgical procedures performed urgently had a 12.3% rate of morbidity (n = 2560) and a 2.3% rate of mortality (n = 471). Conclusions and Relevance This study highlights the need for improved risk stratification on the basis of urgency because operations performed urgently have distinct rates of morbidity and mortality compared with procedures performed either electively or emergently. Because we tie quality outcomes to reimbursement, such a category should improve predictive models and more accurately reflect the quality and value of care provided by surgeons who do not have traditional elective practices.

Improvements in Pulmonary and General Critical Care Reduces Mortality following Ventilator-Associated Pneumonia

BACKGROUND Ventilator-associated pneumonia (VAP) is the most common hospital-acquired infection in the intensive care unit, with substantial subsequent mortality. The mortality following VAP declined in the 1980s and 1990s. Experts suggest that little progress has been made in the outcomes from VAP since several novel interventions have failed. We nonetheless hypothesized that mortality following VAP has continued to decrease owing to advances in pulmonary critical care. METHODS We identified all adult patients with Centers for Disease Control and Prevention–defined, intensive care unit–acquired VAP between January 1, 1997, and December 31, 2008, from a prospectively collected database. RESULTS A total of 793 cases of VAP occurred in the study period. Cases were divided into four periods (1997–1999, 2000–2002, 2003–2005, or 2006–2008) to compare outcomes over time. Acute Physiology and Chronic Health Evaluation II scores were stable, while mortality was significantly lower in Period 4 when compared with Periods 1 and 2 (p = 0.004 and 0.009, respectively). A logistic regression model predicting death (c statistic = 0.871) revealed age (odds ratio, 1.03; 95% confidence interval, 1.02–1.05), Acute Physiology and Chronic Health Evaluation II score (1.09, 1.05–1.14), white blood cell count (1.03, 1.00–1.06), transplant recipient (3.45, 1.40–8.53), transfusions (3.25, 1.37–7.68), and pulmonary disease (3.01, 1.67–5.45) were independent predictors of death, as was the presence of trauma (0.10, 0.06–0.18), chronic steroid therapy (0.39, 0.17–0.91), and patient length of stay (0.99, 0.98–0.99), with odds ratios less than 1.0. In addition, those patients treated in Period 1 (2.23, 1.16–4.29) or Period 2 (2.13, 1.12–4.06) had twice the risk of death following an episode of VAP when compared with those treated in the most recent period. CONCLUSION We have shown that mortality following an episode of VAP continues to decrease over time and attribute this to advancements in pulmonary and general critical care rather than any specific interventions. LEVEL OF EVIDENCE Prognostic study, level II.