The Complex Epidemiology of Carbapenem-Resistant Enterobacter Infections: A Multicenter Descriptive Analysis.

BACKGROUND: The pandemic of carbapenem-resistant Enterobacteriaceae (CRE) was primarily due to clonal spread of bla KPC producing Klebsiella pneumoniae. Thus, thoroughly studied CRE cohorts have consisted mostly of K. pneumoniae. OBJECTIVE: To conduct an extensive epidemiologic analysis of carbapenem-resistant Enterobacter spp. (CREn) from 2 endemic and geographically distinct centers. METHODS: CREn were investigated at an Israeli center (Assaf Harofeh Medical Center, January 2007 to July 2012) and at a US center (Detroit Medical Center, September 2008 to September 2009). bla KPC genes were queried by polymerase chain reaction. Repetitive extragenic palindromic polymerase chain reaction and pulsed-field gel electrophoresis were used to determine genetic relatedness. RESULTS: In this analysis, 68 unique patients with CREn were enrolled. Sixteen isolates (24%) were from wounds, and 33 (48%) represented colonization only. All isolates exhibited a positive Modified Hodge Test, but only 93% (27 of 29) contained bla KPC. Forty-three isolates (63%) were from elderly adults, and 5 (7.4%) were from neonates. Twenty-seven patients died in hospital (40.3% of infected patients). Enterobacter strains consisted of 4 separate clones from Assaf Harofeh Medical Center and of 4 distinct clones from Detroit Medical Center. CONCLUSIONS: In this study conducted at 2 distinct CRE endemic regions, there were unique epidemiologic features to CREn: (i) polyclonality, (ii) neonates accounting for more than 7% of cohort, and (iii) high rate of colonization (almost one-half of all cases represented colonization). Since false-positive Modified Hodge Tests in Enterobacter spp. are common, close monitoring of carbapenem resistance mechanisms (particularly carbapenemase production) among Enterobacter spp. is important.

Outcomes of carbapenem-resistant Enterobacteriaceae isolation: matched analysis.

BACKGROUND: Carbapenem-resistant Enterobacteriaceae (CRE) isolation is associated with poor outcomes. The matched cohort study design enables investigation of specific role of resistance in contributing to patients' outcomes. Patients with CRE were matched to 3 groups: (1) patients with extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL), (2) patients with carbapenem-susceptible non-ESBL Enterobacteriaceae, and (3) uninfected controls. METHODS: Patients with CRE isolated at Detroit Medical Center (September 1, 2008, to August 31, 2009) were matched (1:1 ratio) to the 3 groups based on (1) bacteria type, (2) hospital/facility, (3) unit/clinic, (4) calendar year, and (5) time at risk (ie, from admission to culture). Multivariable logistic regression models for outcomes were constructed. RESULTS: Ninety-one patients with CRE were enrolled. CRE isolation was not an independent predictor for in-hospital mortality in any of the models (ie, vs uncolonized controls, vs ESBL, vs non-ESBL Enterobacteriaceae, and vs all 3 non-CRE groups combined), despite high significance of association in bivariate analyses. CRE isolation was independently associated with deterioration in functional status [odds ratio, 9; P = .002] and being discharged to a long-term care facility after being admitted to the hospital from home [odds ratio, 13.7; P < .001]. CONCLUSION: Underlying condition and comorbidities are the principal factors responsible for in-hospital mortality in CRE infections; however, in-hospital mortality is not independently correlated to the offending pathogen. In addition, we found that the pathogen contributes significantly to patients' degree of morbidity.

Surgical site infections in genital reconstruction surgery for gender reassignment, Detroit: 1984-2008.

BACKGROUND: Gender reassignment surgery (i.e., male-to-female or female-to-male) entails a series of complex surgical procedures. We conducted a study to explore epidemiologic characteristics of patients who underwent genital reconstruction operations as components of gender reassignment and to analyze risk factors for surgical-site infections (SSIs) following these operations. METHODS: The study was a retrospective cohort study conducted from 1984-2008 at Harper University Hospital, a tertiary hospital with 625 beds in Detroit, Michigan. Surgical site infection was defined according to established criteria. RESULTS: Records were available for 82 patients who underwent a total of 1,383 operations as part of genital-reconstruction processes. Thirty-nine (47.6%) of the patients underwent female-to-male reassignment (FTM) and 43 (52.4%) underwent male-to-female reassignment (MTF). The average age of the study cohort was 39.5±9.8 y. Of the patients in the cohort, 56 (68.3%) were Caucasian and 67 (81.7%) were single. The average number of operative encounters per patient was 11.8±4.6 for FTM and 4.9±2.4 for MTF. Forty-three (52.4%) patients developed an SSI at least once during their genital reconstruction process, of whom 34 (87%) were in the FTM group and nine (21%) in the MTF group (p<0.001). Staphylococci were the most common pathogens (61%) isolated in these infections, followed by Enterobacteriaceae (50%), Enterococcus (39%), and Pseudomonas aeruginosa (33.3%). Surgical site infection was associated independently with an increased frequency of operative procedures and operating room encounters. CONCLUSIONS: More than 50% of patients who underwent genital reconstruction operations developed an SSI at some point during the genital reconstruction process. Surgical site infections are more common in FTM than in MTF reconstruction operations, and for both FTM and MTF, SSIs are associated independently with an increased frequency of total operative procedures and encounters.

The role of antimicrobial stewardship in curbing carbapenem resistance.

Antimicrobial resistance is a continuing, growing, worldwide iatrogenic complication of modern medical care. Carbapenem resistance among certain pathogens poses a significant challenge. In order to reduce the spread of these nearly untreatable pathogens, preventative efforts should be directed at reducing patient-to-patient transmission and preventing the emergence of resistance among susceptible strains. One theoretical intervention to reduce the emergence of resistance is establishing and strictly adhering to an antimicrobial stewardship program. However, data pertaining to the direct effect of stewardship in curtailing carbapenem resistance among epidemiologically significant organisms are scarce. In this report, we review the potential biases associated with data interpretation in this research field, and we review the data pertaining to the impact of stewardship in curbing carbapenem resistance in three significant groups of pathogens: Pseudomonas aeruginosa, Enterobacteriaceae and Acinetobacter baumannii.

Recent exposure to antimicrobials and carbapenem-resistant Enterobacteriaceae: the role of antimicrobial stewardship.

BACKGROUND: Carbapenem-resistant Enterobacteriaceae (CRE) are rapidly emerging worldwide. Control group selection is critically important when analyzing predictors of antimicrobial resistance. Focusing on modifiable risk factors can optimize prevention and resource expenditures. To identify specific predictors of CRE, patients with CRE were compared with 3 control groups: (1) patients with extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae, (2) patients with non-ESBL-containing Enterobacteriaceae, and (3) uninfected controls. DESIGN: Matched multivariable analyses. PATIENTS AND SETTING: Patients possessing CRE that were isolated at Detroit Medical Center from September 1, 2008, to August 31, 2009. METHODS: Patients were matched (1∶1 ratio) to the 3 sets of controls. Matching parameters included (1) bacteria type, (2) hospital/facility, (3) unit/clinic, (4) calendar year, and (5) time at risk (ie, from admission to culture). Matched multivariable analyses were conducted between uninfected controls and patients with CRE, ESBL, and non-ESBL Enterobacteriaceae. Models were also designed comparing patients with CRE to patients with ESBL, patients with non-ESBL Enterobacteriaceae, and all 3 non-CRE groups combined. RESULTS: Ninety-one unique patients with CRE were identified, and 6 matched models were constructed. Recent (less than 3 months) exposure to antibiotics was the only parameter that was consistently associated with CRE, regardless of the group to which CRE was compared, and was not independently associated with isolation of ESBL or non-ESBL Enterobacteriaceae. CONCLUSIONS: Exposure to antibiotics within 3 months was an independent predictor that characterized patients with CRE isolation. As a result, antimicrobial stewardship efforts need to become a major focus of preventive interventions. Regulatory focus regarding appropriate antimicrobial use might decrease the detrimental effects of antibiotic misuse and spread of CRE.

The burden of multidrug-resistant organisms on tertiary hospitals posed by patients with recent stays in long-term acute care facilities.

BACKGROUND: Long-term acute care (LTAC) facilities admit patients with complex, advanced disease states. Study aims were to determine the burden posed on hospitals associated with LTAC exposure and analyze the differences between "present on admission" (POA) multidrug-resistant (MDR), gram-negative organisms (GNO) and POA MDR gram-positive organisms (GPO). METHODS: A multicenter retrospective study was conducted in 13 hospitals from southeast Michigan, from September 1, 2008, to August 31, 2009. Cultures obtained in the first 72 hours of hospitalization (ie, POA) of MDR-GPO and MDR-GNO were reviewed. LTAC exposures in the previous 6 months and direct admission from a LTAC were recorded. RESULTS: Overall, 5,297 patients with 7,147 MDR POA cultures were analyzed: 2,619 (36.6%) were MDR-GNO, and 4,528 (63.4%) were MDR-GPO. LTAC exposure in the past 6 months was present in 251 (5.2%) infectious episodes and was significantly more common among POA MDR-GNO than MDR-GPO (158 [8.6%] and 94 [3.1%], respectively, odds ratio, 2.87; P < .001). Recent LTAC exposure was strongly associated with both carbapenem-resistant Enterobacteriaceae (CRE) (31.6% of all CRE cases, P < .001) and Acinetobacter baumannii (14.9% of all A baumannii cases, P < .001). CONCLUSION: Nearly 10% of MDR-GNO POA had recent LTAC exposure. Hospital efforts to control the spread of MDR-GNO should focus on collaborations and communications with referring LTACs and interventions targeted towards patients with recent LTAC exposure.

Leucoaraiosis, nigrostriatal denervation and motor symptoms in Parkinson's disease.

Leucoaraiosis is associated with motor symptoms in otherwise normal older adults. Comorbid leucoaraiosis is predicted to contribute also to motor features in Parkinson's disease but previous studies of white matter changes in Parkinson's disease show variable results. No prior studies have compared directly the effects of both leucoaraiosis and the degree of nigrostriatal dopaminergic denervation on motor features. We investigated the effect of leucoaraiosis severity on motor impairment independent of the degree of nigrostriatal dopaminergic denervation in Parkinson's disease. Seventy-three subjects with Parkinson's disease (Hoehn and Yahr stages 1-3) underwent brain magnetic resonance and [(11)C]dihydrotetrabenazine vesicular monoamine transporter type 2 positron emission tomography imaging. Automated assessment of supratentorial fluid-attenuated inversion recovery magnetic resonance hyperintense white matter voxels was performed using cerebellar white matter as the intensity reference. White matter signal hyperintensity burden was log-transformed and normalized for brain volume. Unified Parkinson's Disease Rating Scale total and subscore ratings were assessed to determine motor impairment. Subjects receiving dopaminergic medications were examined in the clinically defined 'OFF' state. Multivariate regression analysis with measures of white matter signal hyperintensity burden and nigrostriatal denervation as independent variables demonstrated a significant overall model for total motor Unified Parkinson's Disease Rating Scale scores (F = 11.4, P < 0.0001) with significant regression effects for both white matter signal hyperintensity burden (t = 2.0, ß = 0.22, P = 0.045) and striatal monoaminergic binding (t = -3.5, ß = -0.38, P = 0.0008). Axial motor impairment demonstrated a robust association with white matter signal hyperintensity burden (t = 4.0, ß = 0.43, P =0.0001) compared with striatal monoaminergic binding (t = -2.1, ß = 0.22, P = 0.043). White matter signal hyperintensity burden regression effects for bradykinesia had borderline significance. No significant white matter signal hyperintensity burden effects were found for rigidity or tremor subscores. White matter signal hyperintensity burden was significantly higher in the subgroup with postural instability and gait difficulties compared with the tremor-predominant subgroup despite no significant differences in age or duration of disease. These findings indicate that increased white matter signal hyperintensity burden is associated with worse motor performance independent of the degree of nigrostriatal dopaminergic denervation in Parkinson's disease. Comorbid white matter disease is a greater determinant of axial motor impairment than nigrostriatal dopaminergic denervation.