Risk Factors and Costs Associated With Clostridium difficile Colitis in Patients With Prosthetic Joint Infection Undergoing Revision Total Hip Arthroplasty.

BACKGROUND: With the increased demand for primary total hip arthroplasty (THA) and corresponding rise in revision procedures, it is imperative to understand the factors contributing to the development of Clostridium difficile colitis. We aimed to provide a detailed analysis of: (1) the incidence of; (2) the demographics, lengths of stay, and total costs for; and (3) the risk factors and mortality associated with the development of C. difficile colitis after revision THA. METHODS: The National Inpatient Sample database was queried for all individuals diagnosed with a periprosthetic joint infection and who underwent all-component revision THA between 2009 and 2013 (n = 40,876). Patients who developed C. difficile colitis during their inpatient hospital stay were identified. Multilevel logistic regression analysis was conducted to assess the association between hospital- and patient-specific characteristics and the development of C. difficile colitis. RESULTS: The overall incidence of C. difficile colitis after revision THA was 1.7%. These patients were significantly older (74 vs 65 years), had greater lengths of hospital stay (19 vs 9 days), accumulated greater costs ($51,641 vs $28,282), and were more often treated in an urban hospital compared to their counterparts who did not develop C. difficile colitis (P < .001 for all). Patients with colitis also had a significantly higher in-hospital mortality compared to those without (5.6% vs 1.4%; P < .001). CONCLUSION: While C. difficile colitis infection is an uncommon event following revision THA, it can have potentially devastating consequences. Our analysis demonstrates that this infection is associated with a longer hospital stay, higher costs, and greater in-hospital mortality.

Clostridium difficile Infection: An Orthopaedic Surgeon's Guide to Epidemiology, Management, and Prevention.

Clostridium difficile infection is a growing concern in health care and is a worrisome complication in orthopaedics. The incidence and severity of this infection are increasing, although the incidence following orthopaedic surgery is comparatively lower than that seen in patients in most other surgical specialties. The typical geriatric orthopaedic patient may have many risk factors that increase the likelihood of C difficile infection, including advanced age, residence in a long-term care facility, multiple comorbidities, the use of perioperative antibiotics, and a long length of stay. Many antibiotics used for prophylaxis in orthopaedic procedures have been correlated with an increased incidence of C difficile infection. The indications for C difficile testing may vary, and diagnostic methods differ in sensitivity and specificity. The prevention of this infection is multifaceted and consists of practitioner and patient hand hygiene, antibiotic stewardship, contact precautions, and proper environmental cleaning. The main treatment options are metronidazole for mild cases and vancomycin for moderate to severe disease. Up to 40% of cases may have one or more recurrence. Further research is needed to identify novel therapeutic and prevention strategies for C difficile infection.

Stress ulcer prophylaxis with a proton pump inhibitor versus placebo in critically ill patients (SUP-ICU trial): study protocol for a randomised controlled trial.

BACKGROUND: Critically ill patients in the intensive care unit (ICU) are at risk of clinically important gastrointestinal bleeding, and acid suppressants are frequently used prophylactically. However, stress ulcer prophylaxis may increase the risk of serious adverse events and, additionally, the quantity and quality of evidence supporting the use of stress ulcer prophylaxis is low. The aim of the SUP-ICU trial is to assess the benefits and harms of stress ulcer prophylaxis with a proton pump inhibitor in adult patients in the ICU. We hypothesise that stress ulcer prophylaxis reduces the rate of gastrointestinal bleeding, but increases rates of nosocomial infections and myocardial ischaemia. The overall effect on mortality is unpredictable. METHODS/DESIGN: The SUP-ICU trial is an investigator-initiated, pragmatic, international, multicentre, randomised, blinded, parallel-group trial of stress ulcer prophylaxis with a proton pump inhibitor versus placebo (saline) in 3350 acutely ill ICU patients at risk of gastrointestinal bleeding. The primary outcome measure is 90-day mortality. Secondary outcomes include the proportion of patients with clinically important gastrointestinal bleeding, pneumonia, Clostridium difficile infection or myocardial ischaemia, days alive without life support in the 90-day period, serious adverse reactions, 1-year mortality, and health economic analyses. The sample size will enable us to detect a 20 % relative risk difference (5 % absolute risk difference) in 90-day mortality assuming a 25 % event rate with a risk of type I error of 5 % and power of 90 %. The trial will be externally monitored according to Good Clinical Practice standards. Interim analyses will be performed after 1650 and 2500 patients. CONCLUSION: The SUP-ICU trial will provide high-quality data on the benefits and harms of stress ulcer prophylaxis with a proton pump inhibitor in critically ill adult patients admitted in the ICU. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02467621 .

A Comprehensive Assessment Across the Healthcare Continuum: Risk of Hospital-Associated Clostridium difficile Infection Due to Outpatient and Inpatient Antibiotic Exposure.

BACKGROUND: Limitations in sample size, overly inclusive antibiotic classes, lack of adjustment of key risk variables, and inadequate assessment of cases contribute to widely ranging estimates of risk factors for Clostridium difficile infection (CDI). OBJECTIVE: To incorporate all key CDI risk factors in addition to 27 antibiotic classes into a single comprehensive model. DESIGN: Retrospective cohort study. SETTING: Kaiser Permanente Southern California. PATIENTS: Members of Kaiser Permanente Southern California at least 18 years old admitted to any of its 14 hospitals from January 1, 2011, through December 31, 2012. METHODS: Hospital-acquired CDI cases were identified by polymerase chain reaction assay. Exposure to major outpatient antibiotics (10 classes) and those administered during inpatient stays (27 classes) was assessed. Age, sex, self-identified race/ethnicity, Charlson Comorbidity Score, previous hospitalization, transfer from a skilled nursing facility, number of different antibiotic classes, statin use, and proton pump inhibitor use were also assessed. Poisson regression estimated adjusted risk of CDI. RESULTS: A total of 401,234 patients with 2,638 cases of incident CDI (0.7%) were detected. The final model demonstrated highest CDI risk associated with increasing age, exposure to multiple antibiotic classes, and skilled nursing facility transfer. Factors conferring the most reduced CDI risk were inpatient exposure to tetracyclines and first-generation cephalosporins, and outpatient macrolides. CONCLUSIONS Although type and aggregate antibiotic exposure are important, the factors that increase the likelihood of environmental spore acquisition should not be underestimated. Operationally, our findings have implications for antibiotic stewardship efforts and can inform empirical and culture-driven treatment approaches.

Predicting the risk for hospital-onset Clostridium difficile infection (HO-CDI) at the time of inpatient admission: HO-CDI risk score.

OBJECTIVE: To predict the likelihood of hospital-onset Clostridium difficile infection (HO-CDI) based on patient clinical presentations at admission DESIGN: Retrospective data analysis SETTING: Six US acute care hospitals PATIENTS: Adult inpatients METHODS: We used clinical data collected at the time of admission in electronic health record (EHR) systems to develop and validate a HO-CDI predictive model. The outcome measure was HO-CDI cases identified by a nonduplicate positive C. difficile toxin assay result with stool specimens collected >48 hours after inpatient admission. We fit a logistic regression model to predict the risk of HO-CDI. We validated the model using 1,000 bootstrap simulations. RESULTS: Among 78,080 adult admissions, 323 HO-CDI cases were identified (ie, a rate of 4.1 per 1,000 admissions). The logistic regression model yielded 14 independent predictors, including hospital community onset CDI pressure, patient age ≥65, previous healthcare exposures, CDI in previous admission, admission to the intensive care unit, albumin ≤3 g/dL, creatinine >2.0 mg/dL, bands >32%, platelets ≤150 or >420 109/L, and white blood cell count >11,000 mm3. The model had a c-statistic of 0.78 (95% confidence interval [CI], 0.76-0.81) with good calibration. Among 79% of patients with risk scores of 0-7, 19 HO-CDIs occurred per 10,000 admissions; for patients with risk scores >20, 623 HO-CDIs occurred per 10,000 admissions (P<.0001). CONCLUSION: Using clinical parameters available at the time of admission, this HO-CDI model demonstrated good predictive ability, and it may have utility as an early risk identification tool for HO-CDI preventive interventions and outcome comparisons.

The cost-benefit of federal investment in preventing Clostridium difficile infections through the use of a multifaceted infection control and antimicrobial stewardship program.

OBJECTIVE: To determine the potential epidemiologic and economic value of the implementation of a multifaceted Clostridium difficile infection (CDI) control program at US acute care hospitals DESIGN: Markov model with a 5-year time horizon PARTICIPANTS: Patients whose data were used in our simulations were limited to hospitalized Medicare beneficiaries ≥65 years old. BACKGROUND: CDI is an important public health problem with substantial associated morbidity, mortality, and cost. Multifaceted national prevention efforts in the United Kingdom, including antimicrobial stewardship, patient isolation, hand hygiene, environmental cleaning and disinfection, and audit, resulted in a 59% reduction in CDI cases reported from 2008 to 2012. METHODS: Our analysis was conducted from the federal perspective. The intervention we modeled included the following components: antimicrobial stewardship utilizing the Antimicrobial Use and Resistance module of the National Healthcare Safety Network (NHSN), use of contact precautions, and enhanced environmental cleaning. We parameterized our model using data from CDC surveillance systems, the AHRQ Healthcare Cost and Utilization Project, and literature reviews. To address uncertainty in our parameter estimates, we conducted sensitivity analyses for intervention effectiveness and cost, expenditures by other federal partners, and discount rate. Each simulation represented a cohort of 1,000 hospitalized patients over 1,000 trials. RESULTS In our base case scenario with 50% intervention effectiveness, we estimated that 509,000 CDI cases and 82,000 CDI-attributable deaths would be prevented over a 5-year time horizon. Nationally, the cost savings across all hospitalizations would be $2.5 billion (95% credible interval: $1.2 billion to $4.0 billion). CONCLUSIONS: The potential benefits of a multifaceted national CDI prevention program are sizeable from the federal perspective.

The morbidity of Clostridium difficile infection after elective colonic resection-results from a national population database.

BACKGROUND: Clostridium difficile (CD), a gram-positive rod bacterium, resides normally within the human colon. Antibiotic treatment alters normal colonic flora, potentiating abnormal overgrowth of CD. METHODS: This study examined the 2004 to 2006 Nationwide Inpatient Sample to determine outcomes of CD colitis after 695,010 elective colonic resections. RESULTS: CD infection, occurring in 1.4% of patients, was associated with higher pulmonary (12.1% vs 6.4%) and gastrointestinal (12.8% vs 10.5%) complications as well as an increased length of stay (22.6 vs 10.9 days) and mortality (16.2% vs 4.9%; all P < .001). CD colitis patients more frequently held Medicare insurance (68% vs 51%) and underwent small segmental colonic resection as opposed to a defined anatomic resection (20.0% vs 9.9%; P < .001). An underlying diagnosis of colon cancer was associated with a lower incidence of CD colitis (odds ratio, .71; 95% confidence interval, .59-.84; P < .001). CONCLUSIONS: CD colitis is associated with worse outcomes after elective colonic resection.

A systems ergonomics analysis of the Maidstone and Tunbridge Wells infection outbreaks.

This paper describes a systems ergonomics analysis of the recent outbreaks of Clostridium difficile, which occurred over the period 2005-07 within the UK Maidstone and Tunbridge Wells NHS Trust. The analysis used documents related to the outbreak, alongside the construction of a system model in order to probe deeper into the nature of contributory factors within the Trust. The findings from the analysis demonstrate the value of looking further at cross-level and whole-system aspects of infection outbreaks. In particular, there is a need for further study of the causal relationships that exist between hospital management and clinical management levels within the system. Finally, the paper discusses ways forward and strategies that could be adopted in order to limit the outbreak of hospital-related infections and shape future research. The approach used for the system analysis described in the paper could be used by healthcare practitioners and ergonomists to probe deeper into the causes of infection outbreaks and to extend the scope of interventions aimed at preventing their occurrence.

Assessment of the potential risk of infection associated with Clostridium difficile from porcine xenografts.

There are numerous concerns over the potential for transfer of pathogens between species during clinical xenotransplantation, and although current clinical application is limited, porcine xenografts have been previously used to treat patients with severe burns. Donor animals providing the xenografts are sourced from a healthy commercial herd, however, as pigs are a known source of zoonotic agents, a number of diseases are required to be excluded from pigs used for xenotransplantation purposes. Many studies have indicated the relevance of viral zoonoses, however, little has been done with regard to the potential for transfer of pathogens related to health care associated infections. Clostridium difficile is a major cause of neonatal enteritis in pigs and an important feature of this organism is that pigs can be asymptomatic carriers. This study has examined the incidence of C. difficile PCR ribotypes present in healthy donor pigs to determine if pig faeces, and in particular, contamination of skin with faecal matter, is a potential route for the transfer of C. difficile. Animals were found to have human ribotype 017 present in the faecal matter, however, no C. difficile was isolated from skin samples taken from the same animals. In addition, due to the risk factors associated with C. difficile infection, the antimicrobial susceptibility of the C. difficile isolates has been determined.

Clostridium difficile-associated diarrhoea in hospitalised patients.

OBJECTIVE: The aim of the present study was to evaluate the incidence, risk factors and cost implications of Clostridium difficile-associated diarrhoea (CDAD) in hospitalized adult patients. METHODS: Eighty-seven hospitalized adult patients, positively identified as having CDAD, were reviewed retrospectively to determine the risk factors and cost implications of CDAD. RESULTS: The clinical manifestations, in addition to diarrhoea, included elevated temperature (= 37.8 degrees C; 42.5%), abdominal pain (63. 2%) and leucocytosis (=12 x 109 cells/l; 52.9%). Eight patients underwent endoscopy, and pseudomembranous colitis was confirmed in all of these patients. Nine patients died during their hospital stay. Cefotaxime and cefuroxime were the agents most commonly associated with CDAD. There was a significant difference (P < 0.001) between the sex distribution of CDAD patients and adult hospital patients (69% of CDAD patients were female vs. 52% of general adult hospital population). Significantly (P < 0.001) more patients with CDAD were admitted from the nursing home (NH) setting. The mean age of patients with CDAD admitted from NHs (n = 19) was older than those cases admitted from the community (n = 68) by 14 years (P < 0.001). The length of hospital stay was significantly (P < 0.001) longer for patients with CDAD (16.9 vs. 3.89 days). No differences (P = 0.306) were found in the response times for CDAD patients treated with either oral metronidazole (n = 39) or oral vancomycin (n = 48). The mean response time was, however, significantly longer in the CDAD patients admitted from NHs (4.2 days) compared with those admitted from the community (2.5 days), although the former patients were older and had significantly more comorbidity (P < 0.001). The mean cost per one treated-case of CDAD (bed, laboratory requests and treatment therapy) was calculated as pound2860. CONCLUSION: Patients admitted from NHs are at increased risk of development of CDAD; receiving cefotaxime or cefuroxime axetil (oral form), being elderly and being female are risk factors for the development of CDAD. Treatment of CDAD with oral metronidazole or oral vancomycin gives rise to similar response times and efficacy.

Implementation of sequential therapy programs--a microbiologist's view.

Sequential antimicrobial therapy is not new, but confusion about the timing and nature of the switch often negates perceived advantages. A common problem is the choice of oral antibiotic to follow empirical administration of an intravenous second or third generation cephalosporin. Where guidelines do not exist, particularly when data are lacking as the the best option, the Delphi technique of obtaining a consensus agreement by review of a series of case histories is recommended. Majority verdicts are used to determine what is acceptable practice, and as such the approach is also suitable for audit. Savings through reduced drug acquisition costs and shorter lengths of stay have been highlighted. However, other less obvious potential benefits of sequential antimicrobial therapy include reduced incidence of intravascular catheter infection because of shorter line dwell times and less endoluminal contamination. Sequential antimicrobial therapy may also be used as part of a policy to reduce the selective pressure, particularly due to cephalosporin use, for endemic hospital pathogens such as Clostridium difficile and extended spectrum producing gram-negative baccilli.

Epidemiology of community-acquired Clostridium difficile-associated diarrhea.

The epidemiology of clinically recognized community-acquired Clostridium difficile-associated diarrhea was assessed in a retrospective cohort study of members of a health maintenance organization (HMO). Potential cases were identified through positive toxin assay results and confirmed by review of automated full-text medical records. Of 51 cases identified (7.7 per 100,000 person-years), 42 (82%) were diagnosed and treated exclusively in the ambulatory care setting; 33 cases occurred within 42 days after 494,491 exposures to antibiotics dispensed by an HMO pharmacy. Antibiotic-specific attack rates varied from 0 to 2040 cases per 100,000 exposures. Increased age was associated with C. difficile-associated diarrhea (P < .001). Age-adjusted antibiotic-specific attack rates were at least 10-fold higher (P < .05) for nitrofurantoin, cefuroxime, cephalexin plus dicloxacillin, ampicillin/clavulanate plus cefaclor, and ampicillin/clavulanate plus cefuroxime than for ampicillin or amoxicillin; several other antibiotics were associated with similar but not significantly increased risks.

Clostridium difficile colonization in residents of long-term care facilities: prevalence and risk factors.

OBJECTIVE: To determine the period prevalence of Clostridium difficile disease and asymptomatic carriage in the residents of long-term care facilities (LTCF) and to characterize the risk factors for colonization or associated disease. DESIGN: Period prevalence survey. SETTING: Two long-term care facilities in St. Paul, MN. PARTICIPANTS: Specimens were collected from 225 LTCF residents. MEASUREMENTS: The dependent variable was the culture result for C. difficile, which was isolated and identified using selective culture media and a commercial anaerobe identification kit. Tissue culture assay was used to detect the ability of each C. difficile isolate to produce toxin. Independent variables (including gender, age, race, current medical diagnoses, severity of underlying disease, case mix, current clinical symptoms, current medications, antibiotic use within 4 weeks prior to specimen procurement, and other pertinent history) were obtained from the current medical record of each participant. RESULTS: Of 225 stool cultures that were obtained, 16 (7.1%) were positive for C. difficile. None of the residents with a positive culture was symptomatic. History of nosocomial infection and the use of antibiotics in general, cephalosporins, trimethoprim/sulfamethoxazole (TMP/SMX), and histamine-2 blockers were significantly associated with positive C. difficile culture (P < or = 0.05) by univariate analyses. Trends towards significance (0.05 < 0.10) were noted for narcotic use, previous hospitalization, LTCF, and non-insulin-dependent diabetes mellitus. Logistic regression analysis revealed significant, independent predictors of positive culture: antibiotic use in general (P = 0.028; relative risk = 3.31), histamine-2 antagonist use (P = 0.038; relative risk = 3.27), cephalosporin use (P = 0.038; relative risk = 4.66), and TMP/SMX use (P = 0.007; relative risk = 8.45). CONCLUSIONS: The use of antibiotics, particularly cephalosporins and TMP/SMX, is a significant risk factor for asymptomatic carriage of C. difficile in long-term care facilities. The use of H-2 blockers was also a significant risk factor for carriage; however, this finding has not been reported previously and should be confirmed by independent studies. These medications should be used judiciously in the LTCF population. When diarrheal diseases are encountered in LTCF residents, a high index of suspicion for C. difficile infection should be maintained and the appropriate diagnostic and therapeutic measures taken.

[A protocol for prognostic evaluation of newborns with necrotizing enterocolitis]. / Protocolo para valoración pronóstica en recién nacidos con enterocolitis necrótica.

A modified Vásquez-Estévez protocol for prognostic appraisal of newborns with necrotizing enterocolitis was retrospectively applied to 23 confirmed cases from year 1987 throughout 1989 in general metropolitan hospital at Santiago, Chile. Cases were classified as low (0-12 points) or high (13-30) risk according to its corresponding score. Case fatality rates ranged from 7.1% to 77.7% in low and high risk groups, respectively. Sensibility was 87.5%, specificity 86.6% and efficiency 86.6%. Instrument application was easy. It concluded that this is a valuable tool for the prognostic evaluation of necrotizing enterocolitis. A wider and deeper prospective application would allow to measure more exactly its usefulness in other settings.

Assessment of hindgut function in premature newborns.

Anorectal manometry was performed on 32 small for dates and or preterm infants, using a micro-tip pressure transducer. A normal rectoanal reflex was observed in otherwise normal infants on the first day of life. During the neonatal period, hindgut function in these infants was studied longitudinally using the minimum excitation energy (MER) to elicit a rectoanal reflex. Data suggest that hindgut dysfunction (indicated by a significant increase in MER) develops prior to the onset of abdominal distension or necrotizing enterocolitis (NEC), rather than being present from birth. Consequently, this abnormality of function probably does not initiate the process that leads to NEC. This increase in MER may be a warning that the infant is about to develop abdominal distension or NEC.

Management of antibiotic-associated pseudomembranous colitis.

The diagnosis, etiology, epidemiology, and drug therapy of antibiotic-associated pseudomembranous colitis (AAPMC) are reviewed. AAPMC is an uncommon but potentially serious adverse reaction to therapy with almost any oral or injectable antibiotic and certain antineoplastic agents that alter intestinal flora. Proliferation of Clostridium difficile and subsequent release of clostridial cytotoxins cause pseudomembranous lesions and symptoms such as watery diarrhea, cramping abdominal pain, and low-grade fever. Symptoms can appear from four days after the start of antibiotic or antineoplastic therapy to 10 weeks after therapy has been discontinued. Drug therapy of AAPMC is directed at reducing the amount of Cl. difficile in the colon and promoting normalization of intestinal flora. Mild cases of AAPMC may respond to discontinuation of the etiologic agent and replacement of fluid and electrolytes. Therapy with an anticlostridial antibiotic is indicated in severe cases; although a seven- to 10-day course of oral vancomycin hydrochloride is the most widely recognized therapy, the drug is expensive and unpalatable. Good results have been reported with oral metronidazole and with bacitracin, both of which are less expensive than vancomycin. For all of these therapies, relapse rates are 20-39%. Anion exchange resins may be useful in mild cases of AAPMC. Successful management of AAPMC depends on a complex and ill-defined interrelationship between normal intestinal flora, patient immune response, antibiotic therapy, and the infecting clostridium strain. For moderate or severe cases of AAPMC, therapy should begin with metronidazole or bacitracin and vancomycin should be reserved for refractory cases, relapses, or patients with allergies to the other agents.

Treatment of antibiotic-associated pseudomembranous colitis.

The experience of this laboratory with the treatment of Clostridium-induced colitis in experimental animals and in patients was reviewed. Optimal results in hamsters were achieved with the antibiotics vancomycin, metronidazole, and tetracycline. Cholestyramine was less effective. The outcome for animals given corticosteroids and Clostridium sordellii antitoxin systemically was not different from that for untreated control animals. The second facet of the study was a retrospective review of therapy in 272 patients with C. difficile-induced diarrhea or colitis. No specific therapy was given to 56 patients who had mild symptoms or were improving at the time the toxin was detected. The therapy most frequently used was oral vancomycin, which was given to 189 patients, including 100 with confirmed pseudomembranous colitis. The response rate was 97%, but 46 patients (24%) relapsed when treatment was discontinued. Response to cholestyramine was favorable in 12 of 19 patients. The results with metronidazole and bacitracin were uniformly good, although the experience was limited.