Inherited cancer syndromes and the thyroid: an update.

PURPOSE OF REVIEW: Knowledge related to hereditary thyroid cancer syndromes has expanded enormously. This review identifies contributions that have changed approaches to diagnosis and broadened treatment options for patients with hereditary medullary and nonmedullary thyroid cancers related to multiple endocrine neoplasia type 2 (MEN2), Cowden syndrome, and familial adenomatous polyposis (FAP). RECENT FINDINGS: A new risk-stratification scheme based on type of RET gene mutation informs the age at which prophylactic thyroidectomy and diagnostic screening for MEN-associated endocrine diseases should occur. Two new US Food and Drug Administration-approved targeted medical therapies are now available for medullary thyroid cancer. There is better understanding of more aggressive clinical features and increased lifetime cancer risks for patients with well differentiated thyroid cancers as part of families with and without Cowden syndrome or FAP. This has led to a clearer appreciation for the role and timing of thyroid ultrasound screening in these populations. It has also informed the appropriate extent of thyroid surgery and the circumstances in which prophylactic thyroidectomy is reasonable to consider as part of hereditary syndromes other than MEN2. SUMMARY: Recognition and early diagnosis of these syndromes allows for comprehensive medical care and may improve thyroid cancer-related outcomes. Ultrasound-based screening programs to detect thyroid disease are advised for patients and family members with hereditary cancer syndromes.

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-γ, and tumor necrosis factor-α, and among nontrauma patients, men had higher admission levels of interleukin-8 and tumor necrosis factor-α. 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.

A Novel Missense CASR Gene Sequence Variation Resulting in Familial Hypocalciuric Hypercalcemia.

Background/Objective: Familial hypocalciuric hypercalcemia (FHH) is an uncommon cause of hypercalcemia; however, it is important to consider and rule out in patients with suspected primary hyperparathyroidism (PHPT), ideally, before proceeding with surgery. Herein, we present a patient where this process identified a calcium-sensing receptor gene (CASR) sequence variant currently labeled as a variant of unknown significance (VUS), yet the patient's family pedigree suggests that it is in fact a pathogenic CASR sequence variant. Case Report: A 35-year-old woman was referred to the Endocrine Surgery clinic for evaluation of "recurrent PHPT" and need for reoperative parathyroidectomy. Before referral, she was treated with subtotal parathyroidectomy for the presumed diagnosis of PHPT-related symptomatic hypercalcemia. Postoperatively, she had persistent symptoms. Upon referral, additional relevant information was elicited that suspected FHH instead of PHPT, including a family history of hypercalcemia with CASR VUS in multiple family members and hypocalciuria in the patient. She underwent genetic testing revealing a missense CASR VUS in exon 3 c.392C>A (p.Ala110Asp), the same as in her mother. Medical management instead of reoperation was advised for the diagnosis of FHH. Discussion: To our knowledge, this CASR sequence variation has not been previously reported in the literature. Reporting newly discovered sequence variations with the context of a family's medical history is important because it allows for the recognition of new pathogenic variants. This expands the registry of already known sequence variations and their associated clinical pathology for future patients undergoing genetic testing. Conclusion: This CASR variant represents a novel pathogenic sequence variation causing FHH.

Identification of risk factors for the development of clostridium difficile-associated diarrhea following treatment of polymicrobial surgical infections.

OBJECTIVE: To identify risk factors for Clostridium difficile-associated diarrhea (CDAD) in surgical patients following treatment of polymicrobial infections. SUMMARY BACKGROUND DATA: Infections among surgical patients are frequently anaerobic or mixed aerobic-anaerobic infections and are therefore subject to polymicrobial antibiotic coverage, including metronidazole. While multiple antibiotics are known to contribute to the development of CDAD, the role of preventive antibiotics is unproven. METHODS: An 11-year dataset of consecutive infections treated in surgical patients at a single hospital was reviewed. All intra-abdominal, surgical site, or skin/skin structure infections were identified. Each infection was evaluated for antibiotic coverage and subsequent CDAD. Antibiotic usage was assessed using chi analysis. A multiple logistic regression was used to identify independent predictors of CDAD. RESULTS: A total of 4178 intra-abdominal, surgical site, or skin/skin structure infections were identified. Of these infections, 98 were followed by CDAD. Only carbapenem use affected the incidence of CDAD: 3.5% of infections treated with a carbapenem were followed by CDAD, whereas only 2.1% of infections treated without carbapenems were followed by CDAD (P = 0.04). Metronidazole had no association with future CDAD. Only age and Acute Physiology and Chronic Health Evaluation II (APACHE II) score were independently associated with CDAD by multiple logistic regression analysis. CONCLUSIONS: Older patients with a high severity of illness are at greatest risk for developing CDAD following treatment of polymicrobial infections. No specific antibiotic class, including fluoroquinolones, is associated with an increased incidence of CDAD in this population. Although use of metronidazole in the treatment of polymicrobial infections is appropriate for anaerobic coverage, it does not reduce the risk of future CDAD.

Obesity and site-specific nosocomial infection risk in the intensive care unit.

BACKGROUND: Obese patients are at higher than normal risk for postoperative infections such as pneumonia and surgical site infections, but the relation between obesity and infections acquired in the intensive care unit (ICU) is unclear. Our objective was to describe the relation between body mass index (BMI) and site-specific ICU-acquired infection risk in adults. METHODS: Secondary analysis of a large, dual-institutional, prospective observational study of critically ill and injured surgical patients remaining in the ICU for at least 48 h. Patients were classified into BMI groups according to the National Heart, Lung and Blood Institute guidelines: or= 40.0 kg/m(2) (severely obese). The primary outcomes were the number and site of ICU-acquired U.S. Centers for Disease Control and Prevention-defined infections. Multivariable logistic and Poisson regression were used to determine age-, sex-, and severity-adjusted odds ratios (ORs) and incidence rate ratios associated with differences in BMI. RESULTS: A total of 2,037 patients had 1,436 infection episodes involving 1,538 sites in a median ICU length of stay of 9 days. After adjusting for age, sex, and illness severity, severe obesity was an independent risk factor for catheter-related (OR 2.2; 95% confidence interval [CI] 1.5, 3.4) and other blood stream infections (OR 3.2; 95% CI 1.9, 5.3). Cultured organisms did not differ by BMI group. CONCLUSION: Obesity is an independent risk factor for ICU-acquired catheter and blood stream infections. This observation may be explained by the relative difficulty in obtaining venous access in these patients and the reluctance of providers to discontinue established venous catheters in the setting of infection signs or symptoms.

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.

High levels of endogenous estrogens are associated with death in the critically injured adult.

BACKGROUND: Sex hormones exhibit predictable changes in their physiologic patterns during critical illness. Endogenous estrogens are elevated in both genders as a result of the peripheral conversion of androgens to estrogens by the aromatase enzyme. Elevated endogenous estrogens have been associated with death in medical and mixed surgical intensive care unit (ICU) patients. Our objective was to determine the relationship between endogenous estrogens and outcomes in critically injured patients. METHODS: A prospective cohort of injured patients remaining in the ICU for at least 48 hours at two trauma centers was enrolled. Sex hormones (estradiol, progesterone, testosterone, prolactin, and dehydroepiandrosterone-sulfate) were assayed and mortality was assessed. A logistic regression model was used to determine the association between estradiol and death. The area under the receiver operating characteristic (AUROC) curve was used to estimate the accuracy of estradiol in predicting death. RESULTS: Nine hundred ninety-one patients were enrolled with a 13.4% mortality rate. Despite no detectable difference in mortality among genders, estradiol was significantly elevated in nonsurvivors (16 pg/mL vs. 35 pg/mL, p < 0.001). Estradiol was a marker for injury severity with the most severely injured patients exhibiting the highest levels. The ability of estradiol to predict death (AUROC = 0.65) was comparable with Trauma and Injury Severity Score (AUROC = 0.65) and superior to Injury Severity Score (AUROC = 0.54) in this cohort. CONCLUSIONS: Serum estradiol is a marker of injury severity and a predictor of death in the critically injured patient, regardless of gender. Whether or not estradiol plays a causal role in outcomes is unclear, but estrogen modulation represents a potential therapy for improving outcomes in critically ill trauma patients.

Whence Resistance?

BACKGROUND: Antimicrobial resistance results from a complex interaction between pathogenic and non-pathogenic bacteria, antimicrobial pressure, and genes, which together comprise the total body of potential resistance elements. The purpose of this study is to review and evaluate the importance of antimicrobial pressure on the development of resistance in a single surgical intensive care unit. METHODS: We reviewed a prospectively collected dataset of all intensive care unit (ICU)-acquired infections in surgical and trauma patients over a 6-y period at a single hospital. Resistant gram-negative pathogens (rGNR) included those resistant to all aminoglycosides, quinolones, penicillins, cephalosporins, or carbapenems; resistant gram-positive infections (rGPC) included methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant enterococci (VRE). Each resistant infection was evaluated for prior or concomitant antibiotic use, previous treatment for the same (non-resistant) organism, and concurrent infection with the same organism (genus and species, although not necessarily resistant) in another ICU patient. RESULTS: Three hundred and thirty resistant infections were identified: 237 rGNR and 93 rGPC. Infections with rGNR occurred frequently while receiving antibiotic therapy (65%), including the sensitive form of the subsequent resistant pathogen (42.2%). Infections with rGPC were also likely to occur on antimicrobial therapy (50.6%). Treatment of a different patient for an infection with the same resistant pathogen in the ICU at the time of diagnosis, implying potential patient-to-patient transmission occurred more frequently with rGNR infections (38.8%). CONCLUSION: Antimicrobial pressure exerts a substantial effect on the development of subsequent infection. Our data demonstrate a high estimated rate of de novo emergence of resistance after treatment, which appears to be more common than patient-to-patient transmission. These data support the concept that efforts to limit antimicrobial usage will be more efficacious than enhanced isolation procedures when trying to reduce antimicrobial resistance.

Characteristics of benign and malignant thyroid disease in familial adenomatous polyposis patients and recommendations for disease surveillance.

BACKGROUND: Familial adenomatous polyposis (FAP) is a hereditary colon cancer syndrome that involves multiple extracolonic organs, including the thyroid. Several studies have estimated the rate of thyroid cancer in FAP to occur at five times the rate of the general population, but no current consensus defines screening for thyroid cancer in this cohort. This study seeks to define the features of benign and malignant thyroid disease in FAP patients, to compare thyroid cancer cases found through screening with those found incidentally, and to propose disease surveillance recommendations. METHODS: Prospective screening for early thyroid cancer detection with thyroid ultrasound (US) was performed on FAP patients at the time of annual colonoscopy since November 2008. Clinical and US data were reviewed to characterize the observed thyroid nodules. Nonscreening-detected cases (NSD) were found through review of the colon cancer registry database. RESULTS: Eighteen NSD were found, compared with 15 screening-detected (SD) cases, out of 205 total patients screened (Mage=42 years; 55% female). The mean tumor size was larger in the NSD group than the SD group (p=0.04), and they tended to demonstrate more positive lymph nodes and more complications than the SD group. In the screened cohort, at least one thyroid nodule was detected in 106 (51.7%) patients, with 90% of these seen on initial exam. A total of 40/106 (37.7%) patients required fine-needle aspiration biopsy of a dominant nodule (Msize=14 mm), and 28/40 (70%) of these were performed at the first US visit. Suspicious US features were present in 16/40 (40%) patients, including five sub-centimeter nodules. Cytology and/or nodule US was abnormal in 15/205 screened patients, leading to surgery and revealing 14 papillary and one medullary thyroid cancer. CONCLUSIONS: Given the age and sex distribution of the screened cohort, this study reveals a higher-than-expected prevalence of both benign and malignant thyroid disease in the FAP population. Additionally, SD cases seemed to consist of smaller-sized cancers that required less radical therapy compared to NSD cases. Since it was found that the initial US in the screening program accounted for the majority of detected nodules (90%) and biopsies (70%), baseline and subsequent thyroid US surveillance is recommended in all FAP patients.

Characteristics of surgical patients receiving inappropriate empiric antimicrobial therapy.

BACKGROUND: Inappropriate antibiotics have been observed to result in an increased duration of antibiotic treatment and hospital length of stay, development of multidrug-resistant organisms, and mortality rate compared with appropriate antibiotic treatment. Few studies have evaluated independent risk factors associated with inappropriateness. The purpose of this study was to identify independent predictors of inappropriate, empiric antimicrobial therapy for the treatment of severe sepsis. METHODS: This was a retrospective analysis of a prospectively maintained database of all surgical/trauma patients admitted to a tertiary care center from 1996 to 2007 and treated for sepsis. "Appropriate" empiric antibiotic treatment was determined by sensitivity testing. Demographics and comorbidities, infection sites, infection organisms, and outcomes between strata were compared. Differences in outcome were estimated using relative risk and 95% confidence intervals for correlated data. RESULTS: A total of 2,855 patients (7,158 infections) were identified. Independent predictors of inappropriate, empiric antimicrobial therapy for the treatment of severe sepsis included site of infection and organism type. Severity of illness, age, medical conditions, and community versus health care-associated infections were not associated with inappropriate therapy. Although inappropriate empiric therapy was associated with a longer length of stay and duration of antimicrobial use, it did not result in higher mortality. CONCLUSION: Our study observed that inappropriate empiric antibiotic selection is related to site of infection and pathogen. Other clinical variables do not appear to predict inappropriateness of antibiotic treatment. Efforts should be focused on early broad-spectrum therapy and more rapid microbiologic methods. LEVEL OF EVIDENCE: Therapeutic/care management study, level II.

Does it Matter if we get it right? Impact of appropriateness of empiric antimicrobial therapy among surgical patients.

Previous studies have shown conflicting evidence regarding the impact of inappropriate, initial antibiotic therapy. The purpose of this study was to evaluate the impact of inappropriate empiric antimicrobial therapy for the treatment of infection among surgical patients. We hypothesized that inappropriate empiric antimicrobial therapy would predict increased mortality risk compared with appropriate therapy. This was a retrospective analysis of a prospectively maintained database of all surgical patients admitted to a tertiary care center from 1996 to 2007 and treated for sepsis. "Appropriate" empiric antibiotic treatment was determined by sensitivity testing. Demographics and comorbidities, infection sites, infection organisms, and outcomes were compared between inappropriately and appropriately treated groups. Multivariable log-binomial regression was performed. There were 2,855 patients (7,158 infectious episodes) identified by culture analysis as either appropriately or inappropriately treated. Three hundred seventeen (15%) inappropriately treated infectious episodes resulted in death compared with 718 (14%) of the appropriately treated infectious episodes. After adjusting for statistically significant variables, inappropriately treated episodes of infection were not found to be associated with an increased risk for mortality compared with appropriately treated episodes of infection (relative risk, 1.0; 95% confidence interval, 0.99 - 1.02; P = 0.36). Our study observed no difference in mortality between appropriately and inappropriately treated infections within a surgical population.

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.

The prevalence of undiagnosed and unrecognized primary hyperparathyroidism: a population-based analysis from the electronic medical record.

BACKGROUND: The electronic medical record (EMR) of a large, tertiary referral center was examined to study the prevalence of undiagnosed and unrecognized primary hyperparathyroidism (PHPT). METHODS: The EMR was queried for outpatient serum calcium >10.5 mg/dL over a 2-year period. RESULTS: Of 2.7 million patients, 54,198 (2%) had hypercalcemia (>10.5 mg/dL). In a 2-year sample of 7,269 patients, 1.3% (95 patients) had a recorded diagnosis of PHPT, and 0.3% (16 patients) had parathyroidectomy. Of the remaining patients, parathyroid hormone (PTH) values were recorded in 32% (2,337 patients). Of patients with PTH measured, 71% (1,662 patients) had PHPT (PTH > 30 pg/mL). Patients with calcium of 11.1­11.5 mg/dL were most likely to have PHPT (55%). Patients with calcium >12 mg/dL were most likely to have PTH measured (52%). Of hypercalcemic patients, 67% never had PTH obtained, 28% of whom were likely to have PHPT. It is estimated that 43% of hypercalcemic patients are likely to have PHPT. The estimated prevalence of PHPT in the general population is 0.86%. CONCLUSION: PHPT is a more common disorder than previously documented. It is crucial to evaluate even mild hypercalcemia, because 43% of these patients have PHPT. PHPT is underdiagnosed and undertreated.

Should patients with Cowden syndrome undergo prophylactic thyroidectomy?

BACKGROUND: Cowden syndrome (CS) is dominantly inherited and predisposes patients to tumors in multiple organs. We characterized CS-associated malignant and benign thyroid disease. METHODS: Of data from 3,477 prospectively recruited CS patients with known genetic analysis, we analyzed 225 PTEN mutation+ patients whose treatment occurred at our center (n = 25) or other hospitals nationwide (n = 200). RESULTS: A total of 32 of 225 PTEN mutation+ patients (14%) had thyroid cancer: 52% papillary, 28% follicular-variant papillary, 14% follicular, and 6% anaplastic. Median age at diagnosis was 35 years compared with 49 years for Surveillance Epidemiology and End Results population data. Initial thyroid ultrasonography in 16 of 25 patients revealed thyroiditis/goiters in all >13 years age, leading to FNA in 7 (64%), thyroidectomy in 3 (27%), and new cancer diagnosis in 2 (18%). Three with severe autism required intraoperative sedation for ultrasonography. A total of 9 of 25 patients were monitored after multiple partial thyroidectomies for goiters by age 42 (n = 5), thyroiditis, or cancer detected by age 36 (n = 3). CONCLUSION: PTEN mutation+ patients with CS have an enormous prevalence of thyroid disease. Earlier screening may be advisable because thyroiditis and nodules are seen by the time patients reach adolescence, and cancer diagnosis occurs on average 14 years earlier than expected. Furthermore, the risks observed may justify prophylactic total thyroidectomy in select, if not all, patients, particularly those with developmental disorders.

Aggressive versus conservative initiation of antimicrobial treatment in critically ill surgical patients with suspected intensive-care-unit-acquired infection: a quasi-experimental, before and after observational cohort study.

BACKGROUND: Antimicrobial treatment in critically ill patients can either be started as soon as infection is suspected or after objective data confirm an infection. We postulated that delaying antimicrobial treatment of patients with suspected infections in the surgical intensive care unit (SICU) until objective evidence of infection had been obtained would not worsen patient mortality. METHODS: We did a 2-year, quasi-experimental, before and after observational cohort study of patients aged 18 years or older who were admitted to the SICU of the University of Virginia (Charlottesville, VA, USA). From Sept 1, 2008, to Aug 31, 2009, aggressive treatment was used: patients suspected of having an infection on the basis of clinical grounds had blood cultures sent and antimicrobial treatment started. From Sept 1, 2009, to Aug 31, 2010, a conservative strategy was used, with antimicrobial treatment started only after objective findings confirmed an infection. Our primary outcome was in-hospital mortality. Analyses were by intention to treat. FINDINGS: Admissions to the SICU for the first and second years were 762 and 721, respectively, with 101 patients with SICU-acquired infections during the aggressive year and 100 patients during the conservative year. Compared with the aggressive approach, the conservative approach was associated with lower all-cause mortality (13/100 [13%] vs 27/101 [27%]; p=0·015), more initially appropriate therapy (158/214 [74%] vs 144/231 [62%]; p=0·0095), and a shorter mean duration of therapy (12·5 days [SD 10·7] vs 17·7 [28·1]; p=0·0080). After adjusting for age, sex, trauma involvement, acute physiology and chronic health evaluation (APACHE) II score, and site of infection, the odds ratio for the risk of mortality in the aggressive therapy group compared with the conservative therapy group was 2·5 (95% CI 1·5-4·0). INTERPRETATION: Waiting for objective data to diagnose infection before treatment with antimicrobial drugs for suspected SICU-acquired infections does not worsen mortality and might be associated with better outcomes and use of antimicrobial drugs. FUNDING: National Institutes of Health.

Effective cohorting and "superisolation" in a single intensive care unit in response to an outbreak of diverse multi-drug-resistant organisms.

BACKGROUND: Cohorting patients in dedicated hospital wards or wings during infection outbreaks reduces transmission of organisms, yet frequently, this may not be feasible because of inadequate capacity, especially in the intensive care unit (ICU). We hypothesized that cohorting isolation patients in one geographic location in a single ICU and using enhanced isolation procedures ("superisolation") can prevent the further spread of highly multi-drug-resistant organisms (MDRO). METHODS: Six patients dispersed throughout our Surgical Trauma Burn ICU had infections with carbapenem-resistant, non-clonal gram-negative MDRO, namely Klebsiella pneumoniae, Citrobacter freundii, Stenotrophomonas maltophilia, Aeromonas hydrophilia, Proteus mirabilis, Pseudomonas aeruginosa, and Providencia rettgeri. Five of the six patients also had simultaneous isolation of vancomycin-resistant enterococci (VRE). Under threat of unit closure and after all standard isolation procedures had been enacted, these six patients were moved to the front six beds of the unit, the front entrance was closed, and all traffic was redirected through the back entrance. Nursing staff were assigned to either two isolation or two non-isolation patients. In accordance with the practice of Semmelweis, rounds were conducted so as to end at the rooms of the patients with the most highly-resistant bacterial infections. RESULTS: A few months after these interventions, all six patients had been discharged from the ICU (three alive and three dead), and no new cases of infection with any of their pathogens (based on species and antibiogram) or VRE occurred. The mean ICU stay and overall hospital length of stay for these six patients were 78.3 days and 117.2 days respectively, with a mortality rate of 50%. CONCLUSION: Cohorting patients to one area and altering work routines to minimize contact with patients with MDRO (essentially designating a "high-risk" zone) may be beneficial in stopping patient-to-patient spread of highly resistant bacteria without the need for a dedicated isolation unit.

Diagnosis-dependent relationships between cytokine levels and survival in patients admitted for surgical critical care.

BACKGROUND: Death after trauma, infection, or other critical illness has been attributed to unbalanced inflammation, in which dysregulation of cytokines leads to multiple organ dysfunction and death. We hypothesized that admission cytokine profiles associated with death would differ based on admitting diagnosis. STUDY DESIGN: This 5-year study included patients admitted for trauma or surgical intensive care for more than 48 hours at 2 academic, tertiary care hospitals between October 2001 and May 2006. Cytokine analysis for interleukin (IL)-1, -2, -4, -6, -8, -10, -12, interferon-gamma, and tumor necrosis factor (TNF)-alpha was performed using ELISA on specimens drawn within 72 hours of admission. Mann-Whitney U test was used to compare median admission cytokine levels between alive and deceased patients. Relative risks and odds of death associated with admission cytokines were generated using univariate analysis and multivariate logistic regression models, respectively. RESULTS: There were 1,655 patients who had complete cytokine data: 290 infected, nontrauma; 343 noninfected, nontrauma; and 1,022 trauma. Among infected patients, nonsurvivors had higher median admission levels of IL-2, -8, -10, and granulocyte macrophage-colony stimulating factor; noninfected, nontrauma patients had higher IL-6, -8, and IL-10; and nonsurviving trauma patients had higher IL-4, -6, -8, and TNF-alpha. IL-4 was the most significant predictor of death and carried the highest relative risk of dying in trauma patients, and IL-8 in nontrauma, noninfected patients. In infected patients, no cytokine independently predicted death. CONCLUSIONS: Cytokine profiles of certain disease states may identify persons at risk of dying and allow for selective targeting of multiple cytokines to prevent organ dysfunction and death.

Future trends in the treatment of serious Gram-positive infections.

Gram-positive organisms are the most common bacterial pathogens that cause diseases in humans, with streptococci and staphylococci occurring most frequently. Immunization has been extremely successful in eradicating some Gram-positive infections, such as diphtheria and tetanus, and relatively successful for pneumococci. Staphylococcus aureus vaccines are under investigation. In terms of antimicrobial susceptibility, some Gram-positive organisms have remained sensitive to most antimicrobials, whereas others, including staphylococci, pneumococci and enterococci, have developed clinically relevant resistance. Extensive exposure to antimicrobials in the hospital setting has caused the spread of clones mainly in the hospital environment, yet multiresistance is now also found in community-acquired diseases. Community-acquired methicillin-resistant S. aureus (CA-MRSA) and resistant pneumococci are the most important examples, but even viridans streptococci are becoming resistant to some antibiotics. Moreover, MRSA and vancomycin-resistant enterococci (VRE) are found in pets and farm animals. Because of these concerns, new antimicrobials have been developed during the past decade, including quinupristin/dalfopristin, linezolid, tigecycline, daptomycin and dalbavancin. Also under investigation are beta-lactams, streptogramins and quinolones with activity against MRSA, penicillin-resistant pneumococci and VRE. Finally, infection-control measures, including the identification of carriers of multiresistant organisms and appropriate isolation, must continue to be implemented.

Effects of preoperative skin preparation on postoperative wound infection rates: a prospective study of 3 skin preparation protocols.

OBJECTIVE: To compare the effects of different skin preparation solutions on surgical-site infection rates. DESIGN: Three skin preparations were compared by means of a sequential implementation design. Each agent was adopted as the preferred modality for a 6-month period for all general surgery cases. Period 1 used a povidone-iodine scrub-paint combination (Betadine) with an isopropyl alcohol application between these steps, period 2 used 2% chlorhexidine and 70% isopropyl alcohol (ChloraPrep), and period 3 used iodine povacrylex in isopropyl alcohol (DuraPrep). Surgical-site infections were tracked for 30 days as part of ongoing data collection for the National Surgical Quality Improvement Project initiative. The primary outcome was the overall rate of surgical-site infection by 6-month period performed in an intent-to-treat manner. SETTING: Single large academic medical center. PATIENTS: All adult general surgery patients. RESULTS: The study comprised 3,209 operations. The lowest infection rate was seen in period 3, with iodine povacrylex in isopropyl alcohol as the preferred preparation method (3.9%, compared with 6.4% for period 1 and 7.1% for period 2; P = .002). In subgroup analysis, no difference in outcomes was seen between patients prepared with povidone-iodine scrub-paint and those prepared with iodine povacrylex in isopropyl alcohol, but patients in both these groups had significantly lower surgical-site infection rates, compared with rates for patients prepared with 2% chlorhexidine and 70% isopropyl alcohol (4.8% vs 8.2%; P = .001). CONCLUSIONS: Skin preparation solution is an important factor in the prevention of surgical-site infections. Iodophor-based compounds may be superior to chlorhexidine for this purpose in general surgery patients.