Choosing antibiotics for intra-abdominal infections: what do we mean by "high risk"?

BACKGROUND: The definition of "high risk" in intra-abdominal infections remains vague. The purpose of this study was to investigate patient characteristics associated with a high risk of isolation of resistant pathogens from an intra-abdominal source. METHODS: All complicated intra-abdominal and abdominal organ/space surgical site infections treated over a ten-year period in a single hospital were analyzed. Infections were categorized by pathogen(s). Organisms designated "resistant" were those that had a reasonable probability of being resistant to the broad-spectrum agents imipenem/cilastatin and piperacillin/tazobactam, and included non-fermenting gram-negative bacilli (e.g., Pseudomonas aeruginosa), resistant gram-positive pathogens, vancomycin-resistant enterococci, and fungi. Patient characteristics were analyzed to define associations with the risk of isolation of "resistant" pathogens. RESULTS: A total of 2,049 intra-abdominal infections were treated during the period of study, of which 1,182 had valid microbiological data. The two genera of pathogens isolated from more than 25% of health care-associated infections and more commonly than from community-acquired infections were Enterococcus spp. (29%) and Candida spp. (33%). Health care association, corticosteroid use, organ transplantation, liver disease, pulmonary disease, and a duodenal source all were associated with resistant pathogens. By multivariable analysis, several acute and chronic measures of disease were predictive of death, with a strong interaction between solid organ transplantation, resistant pathogens, and death. Other links between specific pathogens and patient characteristics were documented, for example, between fungal infection and a gastric, duodenal, or small bowel source, and between liver transplantation and vancomycin-resistant enterococci. CONCLUSIONS: On the basis of clinical characteristics, it may be possible to identify patients with intra-abdominal infections caused by pathogens that are potentially resistant to broad-spectrum antibacterial agents. Under these circumstances, and if warranted clinically, broadened coverage probably ought to include specific anti-enterococcal and anti-candidal therapy.

Reduction in rates of methicillin-resistant Staphylococcus aureus infection after introduction of quarterly linezolid-vancomycin cycling in a surgical intensive care unit.

BACKGROUND: The burden of infection with antibiotic-resistant gram-positive cocci, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE), continues to increase, leading to substantial morbidity and high mortality rates, particularly in intensive care units (ICUs). Creative interventions may be required to reverse or stabilize this trend. METHODS: The efficacy of empiric cycling of antibiotics active against gram-positive organisms was tested in a before-after intervention in a single surgical ICU. Four years of baseline data were compared with two years of data compiled after the implementation of a strategy where the empiric antibiotic of choice for the treatment of gram-positive infections (linezolid or vancomycin) was changed every three months. Whatever the initial choice of drug, if possible, the antibiotic was de-escalated after final culture results were obtained. The rates of all gram-positive infections were analyzed, with a particular focus on MRSA and VRE. Concurrently, similar outcomes were followed for patients treated on the same services but outside the ICU, where cycling was not practiced. RESULTS: During the four years prior to cycling, 543 infections with gram-positive organisms were acquired in the ICU (45.3/1,000 patient-days), including 105 caused by MRSA (8.8/1,000 patient days) and 21 by VRE (1.8/1,000 patient-days). In the two years after implementation of cycling, 169 gram-positive infections were documented (28.1/1,000 patient-days; p < 0.0001 vs. non-cycling period), including 11 caused by MRSA (1.8/1,000 patient-days; p < 0.0001 vs. non-cycling period). The percentage of S. aureus infections caused by MRSA declined from 67% to 36%. The rate of infection with VRE was unchanged. Outside the ICU, the yearly numbers of infections with both MRSA and VRE increased over time. CONCLUSION: Quarterly cycling of linezolid and vancomycin in the ICU is a promising method to reduce infections with MRSA.

Outbreak of resistant Pseudomonas aeruginosa infections during a quarterly cycling antibiotic regimen.

BACKGROUND: Antibiotic cycling or rotation of antimicrobial agent classes has been proposed to combat antimicrobial resistance. METHODS: A prospective cohort study was conducted in a medical intensive care unit (ICU) of a university hospital between December 1, 2000, and September 30, 2002, as part of a three-center trial under the aegis of the U.S. Centers for Disease Control and Prevention. Patients admitted to the medical ICU for > 48 h were enrolled, and demographic and microbiological data were collected until discharge or death. Baseline data were collected for four months (12/1/00 to 3/31/01) and compared with data collected after institution of a quarterly cycling regimen (cycle order: Cefepime, ciprofloxacin, piperacillin-tazobactam, imipenem-cilastatin) for the empiric treatment of gram-negative infections (4/01/01 to 9/30/02). RESULTS: Of 1,074 consecutive admissions, 301 were enrolled, 59 during baseline and 242 during the cycling periods. An outbreak of multi-drug resistant Pseudomonas aeruginosa followed cycle 2 (cefepime), coinciding with cycles 3 and 4 (ciprofloxacin and piperacillin-tazobactam) (80.0 and 73.7 vs. 37.3 isolates/100 patients enrolled for cycles 3/4 and baseline, respectively; p = 0.04). Acinetobacter spp. were isolated less frequently during the cycling periods (15.3 vs. 1.2 isolates/100 patients for baseline and cycling periods, respectively; p > or = 0.01). The crude hospital mortality rate was similar (24/59 [41%] baseline vs. 73/242 [30%] cycling; p = 0.16) between periods. However, the percentage of patients admitted to the medical ICU who subsequently acquired an infection followed by in-hospital death was higher at baseline than during cycling: 15/59 (25.4%) vs. 33/242 (13.6%)(p = 0.04). CONCLUSIONS: In this study, the cycling strategy was not definitively associated with beneficial changes in unit epidemiology and in fact may have contributed to an outbreak of multi-drug resistant P. aeruginosa.

Differences in early- and late-onset ventilator-associated pneumonia between surgical and trauma patients in a combined surgical or trauma intensive care unit.

INTRODUCTION: Ventilator-associated pneumonia (VAP) is a leading cause of morbidity in the perioperative period. Based on differences in causes, VAP has been divided into early (96 hours of admission) onset. We sought to compare differences in patient characteristics and outcome between early- and late-onset VAP in trauma and nontrauma surgical patients. METHODS: A retrospective analysis of prospectively collected data were performed for all surgical and trauma patients admitted to the surgical or trauma intensive care unit of an academic medical center from December 1996 to March 2005 who developed VAP. Patients with early- and late-onset VAP were compared with regard to patient characteristics, cause, and outcome using bivariate and multivariate analyses. RESULTS: Three hundred thirty VAPs were identified in 233 trauma (71%) and 97 nontrauma surgery patients (29%). There was no statistically significant difference in recurrence, mortality, or length of stay between early- and late-onset VAP in trauma patients. Mortality for late- onset VAPs in nontrauma patients was 44% versus 23% for early-onset VAPs (p = 0.09). On a per case basis, trauma patients had significantly better mortality (11% vs. 41%) and length of stay (33.1 +/- 1.4 vs. 55.8 +/- 4.1 days) than nontrauma surgical patients with VAP (p < 0.0001), although the rate of VAP-related death favored the nontrauma patients (1.8 deaths of 100 intensive care unit trauma admissions vs. 1.1 deaths of 100 intensive care unit nontrauma admissions, p = 0.05). CONCLUSIONS: Although there is a trend toward worse outcome in nontrauma patients with late-onset VAP, trauma patients with late- and early-onset VAP behave similarly. On a per case basis, trauma patients have significantly better outcomes than nontrauma surgical patients with VAP when cared for within the same surgical or trauma intensive care unit.

Single-institutional experience with the surgical infection prevention project in intra-abdominal surgery.

BACKGROUND: The incidence of surgical site infection (SSI) is becoming a key component of standard measures of quality of performance. We hypothesized that institutional implementation of a protocol targeting known risk factors would reduce the incidence of SSI associated with intra-abdominal surgery. METHODS: Beginning in June 2004, a quality control initiative was implemented to prevent SSI in patients undergoing intra-abdominal surgical procedures at an academic medical center. This protocol included administration of the proper prophylactic antibiotic 0-60 minutes before incision, continued antibiotic administration for or=36 degrees C), along with good glycemic control (goal<200 mg/dL 48 h postoperatively) in diabetic patients. Baseline data collected during the initial four months of protocol development (379 patients) were compared with data collected during the last four months of the 11-month study period (390 patients). RESULTS: Compliance with antibiotic selection increased from 89 percent to 97 percent (p

Cost of Gram-negative resistance.

OBJECTIVE: It is unclear that infections with Gram-negative rods resistant to at least one major class of antibiotics (rGNR) have a greater effect on patient morbidity than infections caused by sensitive strains (sGNR). We wished to test the hypothesis that rGNR infections are associated with higher resource utilization. DESIGN: Retrospective observational cohort study of prospectively collected data. SETTING: University hospital surgical intensive care unit and ward. PATIENTS: Surgical patients with at least one GNR infection. MEASUREMENTS: We compared admissions treated for rGNR infection with those with sGNR infections. Primary outcomes were total hospital costs and hospital length of stay. Other outcomes included antibiotic treatment cost, in-hospital death, and intensive care unit length of stay. After univariate analysis comparing outcomes after rGNR infection with those after sGNR infection, multivariate linear regression models for hospital cost and length of stay were created to account for potential confounders. MAIN RESULTS: Cost data were available for 604 surgical admissions treated for at least one GNR infection (Centers for Disease Control and Prevention criteria), 137 (23%) of which were rGNR infections. Admissions with rGNR infections were associated with a higher severity of illness at the time of infection (Acute Physiology and Chronic Health Evaluation II score, 17.6 +/- 0.6 vs. 13.9 +/- 0.3), had higher median hospital costs ($80,500 vs. $29,604, p < .0001) and median antibiotic costs ($2,607 vs. $758, p < .0001), and had longer median hospital length of stay (29 vs. 13 days, p < .0001) and median intensive care unit length of stay (13 days vs. 1 day, p < .0001). Infection with rGNR within the first 7 days of admission was independently predictive of increased hospital cost (incremental increase in median hospital cost estimated at $11,075; 95% confidence interval, $3,282-$20,099). CONCLUSIONS: Early infection with rGNR is associated with a high economic burden, which is in part related to increased antibiotic utilization compared with infection with sensitive organisms. Efforts to control overuse of antibiotics should be pursued.

Does body mass index affect infection-related outcomes in the intensive care unit?

BACKGROUND: Obesity is a worldwide healthcare concern, but its impact on critical care (intensive care unit; ICU) outcomes is not well understood. The general hypothesis is that obesity worsens ICU outcomes, but published reports fail to demonstrate this effect consistently. We hypothesized that increasing BMI would be an independent predictor of higher mortality rates in the surgical/trauma ICU. METHODS: Data on patients with infections, defined by U.S. Centers for Disease Control and Prevention criteria, were collected prospectively from a single university surgical/trauma ICU. From 1996 to 2003, 807 such patients had measurable BMIs on admission to the ICU and were divided into underweight (<18.5 kg/m(2)), normal weight (18.5-24.9 kg/m(2)), overweight (25.0-29.9 kg/m(2)), obese (30.0-39.9 kg/m(2)), and morbidly obese (> or =40.0 kg/m(2)). The primary outcome was in-hospital death. Bivariate and multivariate analyses were performed. RESULTS: In-hospital death was associated with increasing age, increasing average Acute Physiology and Chronic Health Evaluation (APACHE) II score, history of diabetes (p = 0.001), cardiac disease (p = 0.001), hypertension (p = 0.044), history of cerebrovascular disease (p = 0.021), renal insufficiency (p = 0.007), need for hemodialysis (p < 0.001), history of pulmonary disease (p = 0.012), requirement for mechanical ventilation while in the ICU (p = 0.107), history of malignant disease (p < 0.001), and history of liver disease (p < 0.001). The multivariate analysis selected age (odds ratio [OR] 1.03 per integer; confidence interval [CI] 1.0, 1.05), APACHE II score (OR 1.17 per integer; CI 1.12, 1.74), diabetes (OR 2.20; CI 1.32, 3.65), mechanical ventilation (OR 1.88; CI 1.21, 2.94), malignancy (OR 2.54; CI 1.43, 4.47), and liver disease (OR 5.01; CI 2.69, 9.32) as significant risk factors. When controlling for these variables, none of the BMI groups had an independent association with death compared with the normal weight group. CONCLUSION: Contrary to the hypothesis, the data suggest no discernable independent association of increasing BMI with heightened mortality rate in the surgical/trauma ICU patient with infection.

Duration of antibiotic therapy for ventilator-associated pneumonia caused by non-fermentative gram-negative bacilli.

BACKGROUND AND PURPOSE: Chastre et al. compared eight and 15 days of antibiotic therapy for ventilator-associated pneumonia (VAP), finding no difference in outcome with the exception of VAP caused by non-fermentative gram-negative bacilli (NFGNB), for which a higher recurrence rate was seen in the shorter-duration group (JAMA 2003;290:2588-2598). We recently examined our institutional experience with VAP caused by NFGNB to determine whether shorter courses of antibiotic therapy were associated with higher rates of recurrence. METHODS: Data collected on all patients completing treatment for VAP in a surgical/trauma intensive care unit from December 1996 to October 2004 were analyzed retrospectively for the relations between the duration of antibiotic therapy and recurrence and in-hospital mortality rates. RESULTS: Of the 452 episodes of VAP, 154 were associated with NFGNB. Twenty-seven patients were treated with 3-8 days (mean 6.4 +/- 0.3 days) of antibiotics, whereas 127 received nine or more days (mean 17.1 +/- 0.7 days) of therapy. The recurrence rate for infections treated with the shorter course was 22% vs. 34% for patients receiving nine or more days of antibiotics (p = 0.27). The mortality rates were 22% and 14%, respectively (p = 0.38). Similar trends were demonstrated for infections caused by other organisms. CONCLUSIONS: We did not find a higher recurrence rate in patients with VAP caused by NFGNB who received shorter courses of antibiotic therapy. On the contrary, those patients receiving shorter courses trended toward lower rates of recurrence. Pending further prospective trials addressing the duration of antibiotic treatment for patients with VAP caused by NFGNB, shorter courses of treatment, perhaps based on improvement in clinical parameters, may be warranted.

Can we define the ideal duration of antibiotic therapy?

BACKGROUND: Because of the increasing development of antimicrobial resistance, there is a greater responsibility within the medical community to limit the exposure of patients to antibiotics. We tested the hypothesis that shorter courses of antibiotics are associated with similar or better results than longer durations. We also sought to investigate the difference between a fixed duration of therapy and one based on physiologic measures such as fever and leukocytosis. METHODS: All infectious episodes on the general surgery units of the University of Virginia Health System from December 15, 1996, to July 31, 2003, were analyzed retrospectively for the relation between the duration of antibiotic therapy and infectious complications (recurrent infection with the same organism or at the same site). All infections associated with either fever or leukocytosis were categorized into quartiles on the basis of the absolute length of antibiotic administration or the duration of treatment following resolution of fever or leukocytosis. Multivariate logistic regression models were developed to estimate the independent risk of recurrence associated with a longer duration of antibiotic use. RESULTS: Of the 5,561 treated infections, 4,470 were associated with fever (temperature > or =38 degrees C) or leukocytosis (white blood cell count > or =11,000/mm(3)). For all infections, whether analyzed by absolute duration or time from resolution of leukocytosis or fever, the first or second quartiles (0-12 days, 0-9 days, 0-9 days, respectively) were associated with the lowest recurrence rates (14-18%, 17-23%, 18-19%, respectively). Individual analysis of intra-abdominal infections and pneumonia yielded similar results. The fixed-duration groups received fewer days of antibiotics on average, with outcomes similar to those in the physiologic parameters group. CONCLUSIONS: Shorter courses of antibiotics were associated with similar or fewer complications than prolonged therapy. In general, adopting a strategy of a fixed duration of therapy, rather than basing duration on resolution of fever or leukocytosis, appeared to yield similar outcomes with less antibiotic use.

Does enteral glutamine supplementation decrease infectious morbidity?

BACKGROUND: Although some studies have demonstrated lower infectious morbidity in patients receiving supplemental glutamine, there remains no consensus on the utility of such treatment. This study was designed to investigate the effects of supplemental enteral glutamine on the rate and outcomes of infection in critically ill surgical patients. METHODS: All 185 surgical and trauma patients admitted to a single university surgical trauma intensive care unit (STICU) over an approximately three-year period who were to receive enteral nutrition support were assigned sequentially to one of three diets: standard 1-kCal/mL feedings with added protein (Group 1), standard feedings with glutamine 0.6 g/kg per day (Group 2), or immune-modulated feedings with a similar amount of glutamine (Group 3). Group compositions and patient characteristics were similar at baseline. Data were collected prospectively on infections acquired during hospitalization. RESULTS: A total of 119 patients had at least one infection: 59% of the patients in Group 1, 64% of Group 2, and 69% of Group 3 (p = NS). There were no differences among the groups in the mean number of infections. The most common sites in all groups were the lungs, blood, and urine; and the frequencies of these infections did not differ between groups. Minor differences were found between groups in the organisms isolated. Antibiotic usage did not differ. CONCLUSION: Supplemental enteral glutamine in the dose studied does not appear to influence the acquisition or characteristics of infection in patients admitted to a mixed STICU.

Screening practices of patients presenting for resection of a colorectal neoplasm.

Multiple studies demonstrate the efficacy of colorectal cancer (CRC) screening in patients over 50 years of age. However, there is a lack of consensus regarding which screening method to use, and compliance has been poor. The objective of this study was to identify the CRC screening practices at two institutions and determine the relationship between screening and pathologic stage for patients presenting with a colorectal neoplasm. This study, conducted at the University of Virginia (UVA) Health System and the Salem Veterans Affairs Medical Center (VAMC) between October 30, 2000, and September 1, 2004, included 198 patients > or = 50 years who presented for resection of a primary colorectal neoplasm. Pathologic stage and prior screening were identified retrospectively through chart review and patient response to an anonymous survey. Prior screening was demonstrated in 71 per cent of patients. Colonoscopy was the most commonly used modality. There was a higher percentage of CRC screening at VAMC compared with UVA (80% vs 62%, P < 0.0008). Patients at UVA were more likely screened with colonoscopy, whereas fecal occult blood testing (FOBT) was most common at VAMC (P < 0.0001). Prior CRC screening and cancer stage were inversely related. Ninety-one per cent of patients with benign polyps had been screened prior to diagnosis, compared with 72 per cent of patients with stage I and II cancer and 54 per cent of patients with stage III and IV cancer (P < 0.05). Of patients presenting for surgery, 71 per cent underwent CRC screening. Variability exists in the methods employed for CRC screening. CRC screening facilitates diagnosis at an early stage.

Does the addition of glutamine to enteral feeds affect patient mortality?

OBJECTIVE: Studies have failed to consistently demonstrate improved survival in intensive care unit (ICU) patients receiving immune-modulating nutrient-enhanced enteral feeds when compared with standard enteral feeds. The objective was to study in a prospective fashion the effects of adding glutamine to standard or immune-modulated (supplemented with omega-3 fatty acids, beta-carotene, and amino acids such as glutamine and arginine) tube feeds. DESIGN: Prospective, unblinded study using sequential allocation. SETTING: A university surgical trauma ICU. PATIENTS: All surgical and trauma patients admitted to the surgical trauma ICU at a university hospital over a 3-yr period who were to receive enteral feeds (n = 185). INTERVENTIONS: Sequential assignment to three isocaloric, isonitrogenous diets was performed as follows: standard 1-kcal/mL feeds with added protein (group 1), standard feeds with the addition of 20-40 g/day (0.6 g/kg/day) glutamine (group 2), or an immune-modulated formula with similar addition of glutamine (group 3). The goal for all patients was 25-30 kcal/kg/day and 2 g/kg/day protein. MEASUREMENTS AND MAIN RESULTS: Patients were followed until discharge from the hospital. The primary end point was in-hospital mortality, and multiple secondary end points were recorded. In-hospital mortality for group 1 was 6.3% (four of 64) vs. 16.9% (ten of 59, p = .09) for group 2 and 16.1% (ten of 62, p = .09) for group 3. After controlling for age and severity of illness, the difference in mortality between patients receiving standard tube feeds and all patients receiving glutamine was not significant (p < or = .11). There were no statistically significant differences between the groups for secondary end points. CONCLUSIONS: The addition of glutamine to standard enteral feeds or to an immunomodulatory formula did not improve outcomes. These findings suggest that enteral glutamine should not be routinely administered to patients with surgical critical illness.

Impact of immunomodulatory oligodeoxynucleotides on cytokine production in the lipopolysaccharide-stimulated human whole blood model.

BACKGROUND: In studying potential immunotherapeutics for sepsis, we used a lipopolysaccharide (LPS)-stimulated whole blood model to test the immunomodulating capacity of cytosine-phospho-guanine oligodeoxynucleotides (CpG ODNs). We hypothesized that CpG ODNs would have considerable counterinflammatory effects on LPS-induced cytokine production. METHODS: We administered 4 micromol/L of CpG ODNs (2216, D19, 2006, K3, or 1668) or guanine-phospho-cytosine (GpC) ODNs (control D or control K) immediately after LPS (10 ng/mL) stimulation of heparinized human whole blood. Samples were incubated for 1, 3, 6, 12, and 24 hours. Media and LPS were used as negative and positive controls. Cell-free supernatants were obtained and evaluated for interferon gamma (IFN-gamma), interleukin (IL)-12(p40), tumor necrosis factor alpha, IL-6, IL-10, IFN-alpha, IL-8, and IL-1beta by ELISA. RESULTS: Compared to LPS alone, significantly reduced levels of IFN-gamma, IL-12(p40), tumor necrosis factor alpha, and IL-6 were associated with both CpG and GpC ODNs administration to LPS-stimulated whole blood. IL-10 levels were concomitantly increased. However, IFN-alpha generation was CpG specific as was increased IL-8 levels. Lastly, only 2216 was associated with decreased IL-1beta levels. CONCLUSIONS: CpG ODNs and GpC ODNs in the LPS-stimulated whole blood model demonstrate differential counterinflammatory effects, but only CpG ODNs were associated with proinflammatory cytokine production. With further examination, we may find that these observed immunomodulatory differences could potentially be exploited for therapeutic benefit.

Wound infection after elective colorectal resection.

INTRODUCTION: Surgical site infection (SSI) is a potentially morbid and costly complication following major colorectal resection. In recent years, there has been growing attention placed on the accurate identification and monitoring of such surgical complications and their costs, measured in terms of increased morbidity to patients and increased financial costs to society. We hypothesize that incisional SSIs following elective colorectal resection are more frequent than is generally reported in the literature, that they can be predicated by measurable perioperative factors, and that they carry substantial morbidity and cost. METHODS: Over a 2-year period at a university hospital, data on all elective colorectal resections performed by a single surgeon were retrospectively collected. The outcome of interest was a diagnosis of incisional SSI as defined by the Center of Disease Control and Prevention. Variables associated with infection, as identified in the literature or by experts, were collected and analyzed for their association with incisional SSI development in this patient cohort. Multivariate analysis by stepwise logistic regression was then performed on those variables associated with incisional SSI by univariate analysis to determine their prognostic significance. The incidence of SSI in this study was compared with the rates of incisional SSI in this patient population reported in the literature, predicted by a nationally based system monitoring nosocomial infection, and described in a prospectively acquired intradepartmental surgical infection data base at our institution. RESULTS: One hundred seventy-six patients undergoing elective colorectal resection were identified for evaluation. The mean patient age was 62 +/- 1.2 years, and 54% were men. Preoperative diagnoses included colorectal cancer (57%), inflammatory bowel disease (20%), diverticulitis (10%), and benign polyp disease (5%). SSIs were identified in 45 patients (26%). Twenty-two (49%) SSIs were detected in the outpatient setting following discharge. Of all preoperative and perioperative variables measured, increasing patient body mass index and intraoperative hypotension independently predicted incisional SSI. Although we could not measure statistically increased length of hospital stay associated with SSI, a representative population of patients with SSI accumulated a mean of $6200/patient of home health expenses related to wound care. Our rates of SSI were substantially higher than that reported generally in the literature, predicted by the National Nosocomial Infection System, or described by our own institutional surgical infection data base. CONCLUSIONS: The incidence of incisional SSI in patients undergoing elective colorectal resection in our cohort was substantially higher than generally reported in the literature, the NNIS or predicted by an institutional surgical infection complication registry. Although some of these differences may be attributable to patient population differences, we believe these discrepancies highlight the potential limitations of systematic outcomes measurement tools which are independent of the primary clinical care team. Accurate surgical complication documentation by the primary clinical team is critical to identify the true frequency and etiology of surgical complications such as incisional SSI, to rationally approach their reduction and decrease their associated costs to patients and the health care system.