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C. difficile in Liver Transplant Patients
Authors list: Chetan Mittal, MD; Samia Arshad, MPH, Marisa Miceli, MD, Syed Hassan MD, Sravan Jeepalyam, Samantha Bruni, Gordon Jacobsen, MS, Mayur Ramesh, MD, George Alangaden, MD
Background: Diarrhea caused by Clostridium difficile infection (CDI) is a common cause of morbidity and is associated with increased in-hospital mortality among solid organ transplant (SOT) recipients. The incidence of CDI in liver transplant recipients (LTR) is 3-7%. However, there is limited data on the recent epidemiology, predictors of CDI, recurrence rates, and outcomes of CDI in LTR.
Methods: A 10-year retrospective cohort study was performed of all LTR (2000 to 2010). CDI was defined as a patient with diarrhea and a stool C. difficile toxin positive test. Data collected included demographics, Charlson’s comorbidity index, MELD score, indication for LT, length of hospital stay , time to onset of CDI, community versus hospital onset of CDI, hospital vs. community acquired infection, severity of CDI, rates of recurrence and relapse and overall mortality. Predictors of CDI were calculated using Cox proportional hazard model with adjusted analysis for age, gender and race.
Results: 970 LTR were followed for an average of 5.3 ± 3.4 years. Overall prevalence of CDI was 19% (n=183) that occurred at a median of 51 days post-LT. Severe CDI was diagnosed in 29.1%. CDI recurrence rate was 16.9%, (average time to recurrence of 62.5± 26.5 days) and CDI relapse rate was 9.7%. Although most CDI cases were hospital acquired 62% (n=113), 38% had onset in the community. Independent predictors of post-LTR CDI were year of transplant (HR 1.137, 95% CI 1.06-1.22; p<0.001), white race (HR 1.47, 95% CI 1.09-2.1; p = 0.035), MELD score (HR 1.03, 95% CI 1.01-1.045, p = 0.003) and length of stay for LT (HR 1.01, 95% CI 1.005-1.02, p = <0.001). The highest rates of CDI in LTR occurred in 2007-2008 and paralleled the highest rates noted in our general hospital population. Significant mortality was observed among LTR who developed CDI as compared to those without CDI (p= 0.003).
Conclusions: CDI is a common complication amongst LTR and is associated with a significantly higher
overall mortality rate. Aggressive detection and prompt treatment of CDI in both inpatient and outpatient LTR is critical to improve outcomes.
Functional Consequences of Substitution Mutations in MepR, a Repressor of the Staphylococcus aureus MepA Multidrug Efflux Pump Gene
Bryan Schindler, Ph.D., Susan M. Seo1, Pauline L. Jacinto2, Muthiah Kumaraswami3, Ivan Birukou4,5, Richard G. Brennan4, Glenn W. Kaatz1,2
1The John D. Dingell Department of Veterans Affairs Medical Center, Detroit, Michigan 48201
2Department of Medicine, Division of Infectious Diseases, Wayne State University School of Medicine,Detroit, Michigan, 3Center for Molecular and Translational Human Infectious Diseases Research, The Methodist Hospital Research Institute, and Department of Pathology and Genomic Medicine, The Methodist Hospital System,Houston, Texas, 4Department of Biochemistry, Duke University School of Medicine,4 Durham, NC
Background: The expression of mepA, encoding the Staphylococcus aureus MepA MATE family multidrug efflux pump, is repressed by the autoregulatory winged helix-turn-helix MarR family protein MepR. Substitution mutations in MepR affecting its function result in mepA overexpression, with A103V most common among clinical strains. This and several other substitution mutations in MepR were studied.
Methods: A total of 64 mepA-overexpressing strains were identified by qRT-PCR in our strain collection, with mutations in mepR resulting in amino acid substitutions present in 22 (34.4%). The functional consequences of these substitutions were investigated with plasmid-based mepR derivatives in host strains having mepR::lacZ and mepA::lacZ transcriptional fusions using a beta-galactosidase assay. Results for F27L and A103V substitutions were confirmed by gel shift assays. All mutations were mapped onto the known structure of apo-MepR to provide structure-function correlations.
Results: Severe compromises in repressor function were observed for Q18P, F27L, G97E, and A103V substitutions, with the negative consequences of mutations generally greatest at the mepR operator. Gel shift assays confirmed that the binding of the F27L and A103V mutant proteins to the mepR and mepA operators was poor. One mutant protein contained two substitutions (T94P + T132M); T132M appeared to compensate for the functional defect incurred by T94P. Another contained 10 substitutions, which did not seriously affect its repressor function and may be an extreme example of compensation.
Discussion: The F27L and A103V substitutions clearly affected target site binding, most likely through repositioning of DNA-interacting regions. It is likely that all functionally significant mutations had this effect which may occur via interference with structural plasticity, alteration of helical arrangements, or possibly association of MepR monomers. Further insight into the structural consequences of these mutations awaits the structural determination of DNA-bound MepR.
Risk factors and outcomes associated with colonization due to carbapenem-resistant Enterobacteriaceae (CRE) among patients exposed to long-term acute care centers (LTACs) and acute care facilities
A. Bhargava, K. Hayakawa, H. Samran, S. Datla, P. Lephart, C. Reyes-Sachin, T Chopra, D Marchaim, KS. Kaye
Background: Reservoirs for CRE include hospitals and LTACs, and patients with CRE often transfer between LTACs and hospitals. At Detroit Medical Center (DMC), patients with an exposure to LTACs within the past year have been screened for CRE carriage by peri-rectal swab at the time of admission.
Methods: A retrospective case control study was conducted at DMC (an 8-hospital healthcare system) from June 2009 through December 2011. Cases were defined as patients with a positive CRE screening culture and controls were patients with negative CRE screening cultures. Controls were matched in a 2:1 ratio to cases according to the admitting hospital, admission unit and calendar time.
Results: 905 surveillance cultures were performed on 679 patients. 48 (7.1%) cases and 96 (14.2%) controls were identified. Mean age of the cohort was 69 ±15 years, 67 (46.5%) were male, and 121 (84%) were African American. 53 patients (36.8%) were admitted directly from home, 57 (62.4%) from other hospitals, and 16 (17.6%) from LTACs. In matched multivariate analysis, independent predictors of CRE included congestive hear failure (hazards ratio [HR]: 5.34; 95% CI 1.83-15.58), diabetes mellitus (HR: 3.39; 95% CI 1.16-9.97) and exposure to penicillins (HR: 3.25; 95% CI 1.14-9.29). Dependent functional status (HR: 0.31; 95% CI 0.12-0.82) was associated with decreased risk for CRE colonization.
Subsequent to surveillance cultures being drawn, CRE infection occurred in 8 (17%) cases and 1 (1%) control (OR: 19.0; 95%CI 2.30-156.94).
An Unrecognized Case of Norwegian Scabies causing an outbreak in healthcare workers.
Victoria Tarazi, Matthew O’Brien
Henry Ford Hospital Department of Infectious Diseases
Introduction: Pruritis in a patient with HIV infection can be an early primary symptom or a consequence of severe immunocompromise. Early identification and diagnosis of infectious causes of pruritis in AIDS can have implications reaching far beyond the individual patient. We report a case of infestation with Sarcoptes scabei mite in a patient with end-stage AIDS which was initially unrecognized and resulted in transmission to a number of health care workers (HCWs.)
Case: A 40 year old woman with AIDS (CD4 <5 and HIV viral load of 33,000) was admitted with a syncopal episode. At the time of admission on December 8, 2012, patient was noted to have bilateral macular lesions on her hands; an RPR for secondary syphilis was negative. This prompted a dermatology consult and subsequent skin scrapings that revealed live Sarcoptes scabei mites. The patient was diagnosed with Norwegian scabies. Prior to this admission the patient had been hospitalized for one month, (October 23rd to November 28th,) for the treatment of CMV myelopathy. Multiple healthcare workers, including nursing staff, had been in close contact with her daily. In November of 2012 the first symptomatic nurse presented to her primary care physician with rash and pruritus. The diagnosis of scabies in the nurse was not made until after the patient was readmitted on December 8th, by which time more healthcare workers had been diagnosed.
Discussion: This is an outbreak of scabies in an acute-care hospital involving HCWs on the infectious diseases service. The index dense infestation and lack of diagnosis for several weeks contributed to the outbreak. The disease among HCWs was not identified early because of failure to recognize a pruritic rash as scabies in the patient. Recognizing this infestation cannot be understated and a comprehensive approach to prophylaxis of all persons exposed is required to prevent or eradicate an outbreak.
Diagnosis and Management of CAUTI
Jehad Sibai, MD*; Karen Jones, RN; Mohamad G. Fakih, MD, MPH, Division of Infectious Disease, Department of Infection Prevention, St. John Hospital and Medical Center
Background: The diagnosis and management of catheter associated urinary tract infections (CAUTIs) starts by obtaining a urine culture, often triggered by subjective observations that may not relate to infection.
Methods: We conducted a survey of resident physicians (RPs) of 4 specialties: internal medicine, surgery, emergency medicine, and family medicine. The survey addressed knowledge and management of catheterized patients with positive urine cultures. The survey included questions on when to obtain a urine culture (19 questions), and the management of a positive urine culture in a catheterized patient (13 questions).
Results: 106 (77.9%) RPs participated in the survey. Only 32 (30.2%) RPs rated their knowledge regarding CAUTI as excellent or above average. In addition, 67 (63.2%) discussed their impression and plan with their attending more than 50% of the time. RPs showed very poor knowledge on what triggers ordering a urine culture in patients with an indwelling catheter with 75 (70.8%) obtaining a culture for foul smelling urine, 67 (63.2%) for hematuria, 84 (79.2%) for cloudy urine, 57 (53.8%) for sediments in urine, 39 (36.8%) for darker looking urine, and 46 (43.4%) for a chronic urinary catheter on admission. Residents tended to order more urine cultures the higher the urine white cell counts: for 25 (n=71, 67%), for 100 (n=94, 88.7%), and for 500 (n=101, 95.3%). For asymptomatic bacteriuria, 80 (75.5%) would change the catheter, 45 (42.5%) will treat with antibiotics, and 47 (44.3%) would treat bacteriuria for a patient going for a non-urologic surgery. The mean scores assessing knowledge and management were 10±3.1 (out of 19 points), and 8.2±1.6 (out of 13 points) respectively. There were no significant differences in scores based on residency type, year of training, RPs discussing case with attending prior to management or RPs’ perception of their knowledge related to diagnosis and treatment of CAUTI.
Conclusions: There are significant opportunities for improvement in training resident physicians regarding the appropriate reasons for collecting urine cultures, the clinical diagnosis of CAUTI, and management. We suggest programs evaluate their residents’ knowledge and practice, and implement educational interventions if needed.
Assesment of Serum Procalcitonin Levels during COPD Exacerbation in Geriatric Patients
Razi Syed, MD; Daniel Havlichek, MD
Background: Procalcitonin is precursor peptide of hormone calcitonin. It is composed of 116 amino acids and is produced by parafollicular cells (C cells) of the thyroid and by the neuroendocrine cells of the lung and the intestine and is released in response to bacterial toxin. Exacerbations of COPD are triggered by a variety of factors such as airway irritants, mucous plugs, and infection. Patients without bacterial infection will not benefit from antibiotics and may be harmed by inappropriate antibiotic use with complications like rash, Clostridium difficile diarrhea, phlebitis etc.
Objective: To determine if serum procalcitonin levels are helpful in differentiating simple COPD exacerbation vs COPD with pneumonia in the geriatric population
Methods: It was a non-randomized, non-blinded observational study approved by MSU and Sparrow IRBs. Funded by MSU Pearl Aldrich Grant. Patients >65yrs old who were admitted to hospital with a diagnosis of COPD or COPD and pneumonia were asked to participate in the trial. All patients with an admission diagnosis of pneumonia had infiltrate on chest X-ray on admission. Following informed consent serum was collected for procalcitonin determination. Patient chart review occurred following patient discharge.
Results: 10 patients with admission diagnosis of COPD and 8 patients with admission diagnosis of COPD/pneumonia were enrolled. All patients with simple COPD exacerbation had negative procalcitonin results. Two out of eight patients in COPD/pneumonia group had elevated procalcitonin.One patient in COPD group had negative procalcitonin despite positive sputum bacterial culture. Three patients in COPD/Pneumonia group had negative procalcitonin despite positive bacterial sputum cultures. Based on this study, the serum procalcitonin test has sensitivity of 25%, specificity of 100%, positive predictive value of 100% and negative predictive value of 62 %
Conclusions: This study suggests that the specificity and positive predictive value of procalcitonin is very high and its a good marker to rule in bacterial infection however it’s not a good marker to rule out the infection and cannot be used alone because of low negative predictive value.
Status Epilepticus from Severe HHV-6 Encephalitis after Stem Cell Transplant
P Chordia*, PH Chandrasekae, Department of Infectious Disease, Wayne State University.
Reactivation of human herpes virus-6 (HHV-6) after stem cell transplantation occurs frequently and is associated with a wide range of clinical manifestations that include nonspecific symptoms such as fevers and rash to severe life threatening post-transplantation limbic encephalitis. Currently guidelines for screening and prophylaxis of HHV-6 reactivation in stem cell transplant recipients do not exist. We report a case of severe HHV-6 encephalitis in an allogeneic peripheral stem cell transplant recipient presenting as status epilepticus unresponsive to antiepileptic therapy. Through our case we would like to highlight the need for increased awareness for this entity and the early initiation of empiric treatment while awaiting confirmatory tests. We believe that standardization of testing for HHV-6 and clinical correlation will help guide preemptive therapy of HHV-6 encephalitis while minimizing drug related adverse events.
Keywords: HHV-6, encephalitis, stem cell transplantation.
Decreased Functional Status as a Risk Factor for Severe Clostridium difficile Infection among Hospitalized Older Adults
A. Krishna Rao, MD,a,b Dejan Micic, MD,a Elizabeth Chenoweth, BA,g Lili Deng, MD, MA,a,c,d Andrzej T. Galecki, MD, PhD,a,c,d Cathrin Ring, MS,a,b Vincent B. Young, MD, PhD,a,b,e David M. Aronoff, MD,a,b,e Preeti N. Malani, MDa,b,c,f aDepartment of Internal Medicine, bDivision of Infectious Diseases, cDivision of Geriatric and Palliative Medicine, dDepartment of Biostatistics, and the eDepartment of Microbiology and Immunology, University of Michigan Health System, Ann Arbor, MI, fGeriatric Research Education and Clinical Center (GRECC), Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, MI, gUniversity of Michigan Medical School, Ann Arbor, MI
Background: Clostridium difficile infection (CDI) is a major cause of morbidity and mortality in hospitalized older adults, who are among the patients at highest risk of severe infection. The role of impaired functional status as a risk factor for severe CDI remains poorly understood. We conducted a prospective cohort study to explore this relationship.
Methods: We collected information on demographics; clinical characteristics; and CDI severity markers (fever [T >38°C]; acute organ dysfunction; white blood cell count >15 000/mm3; lack of response to therapy; intensive care unit admission, need for colectomy, or death due to CDI). Presence of any CDI severity marker conferred a positive severity score. Pre-admission functional status was assessed by ability to perform activities of daily living (ADLs); patients were assigned to an ADL Class (independent, some assistance, or full assistance). Secondary outcomes included length of stay; 90-day mortality and readmission; and CDI recurrence.
Results: We identified 90 hospitalized patients with CDI (mean age 66.6, SD 10.2). Fifty-eight patients (64.4%) had severe CDI as measured by a positive severity score. At baseline, 25 (27.8%) required assistance with ADLs. On univariate analysis, an ADL Class of “full assistance” was associated with severity score (OR 7, CI 95 1.83-26.79, P = .004). In a multivariable model which included age, ADL Class, congestive heart failure, diabetes mellitus, depression, weighted Charlson-Deyo comorbidity score, immunosuppression, prior CDI, and PPI use, an ADL Class of “full assistance” retained its association with severity score (OR 8.1, CI 95 1.24-52.95, P = .029). ADL Class was not associated with secondary outcomes.
Conclusion: Among this cohort of hospitalized older adults, impaired functional status was an independent risk factor for severe CDI.
Arnold Markowitz, MD, Lydia Lohrer ( Detroit Free Press)
Lyme disease in Michigan appears to be under diagnosed when compared to surrounding state data. The potential reasons for this are lack of physician reporting, different laboratory testing, and potentially inconsistent criteria for diagnosis. Because of this a number of patients may be undertreated in terms of antimicrobial selection and duration and the resultant possibilities of CFS, Fibromyalgia, adult ADD, may be consequences of under diagnoses. Having had multiple patient contacts over the last several years and having sent specimens to several different laboratories, I have found that there is a high incidence of both false negative and false positive serologic testing. Specimens have been evaluated at Quest, Labcorp and Igenics and rarely produce the same serologic western blot bands.
Because the diagnosis requires verification through laboratory studies it would be incumbent on practitioners to have a uniform protocol for serological diagnosis of Lyme disease. The current concept of a screening ELISA test followed by a confirmatory Western Blot has been shown to be erroneous in that many positives will be screened out of the secondary testing because of an initial false negative ELISA assay. Additionally, many laboratories are inconsistent in providing results of serologic testing. with clinical signs and symptoms to ascertain the most reliable testing laboratory available.
Arnold Markowitz, M.D.
A forty seven year old patient, K.H., presented to the hospital with focal neurologic disease. His prior medical history was negative with the exception of a zoster outbreak. MRI studies defined what appeared to be a primary central nervous system mass corresponding to the zoster outbreak. Drainage of the lesion proved to an abscess caused by Nocardia farcinici. The patient had no history of an underlying immunological deficiency, but was found to have a CD4 count of 167 and a CD8 of 73 after he had been on dexamethasone. His HIV studies were negative. The patient was treated with Bactrim, immipenem, amicacyn, chl. Over a period of several months, the residual neurosurgical site showed complete resolution and the patient was switched to oral Bactrim to continue an additional three months after his first six month course of parenteral therapy. The only other risk factors that were identified was that the patient was a podiatrist with possible exposure to various skin organisms and an avid jogger who spent his mornings wending through various rural fields. This case report reflects that Nocardia farcinici may present as an isolated abscess in an otherwise healthy patient. Further, it appears to have a favorable response as compared to Nocardia in clearly immunocompromised patients. He continues to practice his profession as well as participating in jogging and the outdoors.
Accessory Gene Regulator (agr) Typing among Bloodstream Isolates of Methicillin-Resistant and Methicillin-Sensitive Staphylococcus Aureus Infections, an Update.
A David MD1, K Sawarynski, PhD1,2, K Powell1, C Rice MD1, Z Levine MD1, M Sims, MD, PhD1,2. Beaumont Health System, Royal Oak, MI, Oakland University William Beaumont School of Medicine, Rochester, MI,
Background: Staphylococcus aureus virulence is controlled in part by the accessory gene regulator (agr) which has 4 subtypes (I-IV). Prior studies, including our own, have suggested the agr II subtype is a risk factor for mortality in MRSA bacteremia. The agr gene is poorly studied in MSSA. The agr II subtype is generally the most common in MRSA but recent data has suggested a shift away from agr II. We assessed the frequency of agr subtypes and their risk for mortality in MRSA and MSSA. We compared the current MRSA data to our prior data to ascertain whether or not there has been a shift in agr subtype in our institution.
Methods: All available MRSA and MSSA isolates from bacteremic patients between 7/2009 and 12/2011 were recovered. Clinical and demographic data on those cases were collected from hospital records. Each strain’s agr subtype was identified by multiplex polymerase chain reaction. Analysis was carried out using SAS® for Windows ver 9.2.
Results: We analyzed clinical MRSA and MSSA isolates from 434 inpatients with bacteremia. Of these 51.2% (222) were MRSA and 48.8% (212) were MSSA. The agr distribution among MRSA was the following: 25.7% (57) agr I, 73.9 % (164) agr II, 0.4% (1) agr III. This is significantly less agr II then seen in our study of 2006-07 isolates which was 84.5% agr II and 15.5% agr I (p=0.003). The agr distribution among MSSA was the following: 38.7% (82) agr I, 37.7 % (80) agr II, 23.1 % (49) agr III, 0.5% (1) agr IV. MRSA was more common in older patients, mean age 65 vs. 59 for MSSA (p=0.002). The distribution of MRSA by gender was equal (51% female vs 49% male) but MSSA was more common in men (61% vs 39%). Patients with MSSA were more likely to survive to discharge, 86% vs. 79% (p=0.04) but this advantage disappeared at 30 days, 81% vs. 77% (p=0.35). There was no significant difference in mortality among the agr subtypes.
Conclusions: The agr II subtype remains the predominant subtype in MRSA isolates but was significantly lower than in 2006-07. The agr I and II subtypes are equally common in MSSA isolates followed by agr III. The agr IV subtype is very rare in clinical isolates. We did not identify a difference in mortality in either MRSA or MSSA linked to agr subtype Patients with MSSA were younger, more often male and had better survival at discharge than those with MRSA.
Keywords: agr, S. aureus, bacteremia
Not the usual suspects: Two curious cases of Gram Negative Endocarditis
Joseph Adrian L. Buensalido, Pauline L. Jacinto, Odaliz Abreu Lanfranco and Milagros P. Reyes, Harper University Hospital, Division of Infectious Diseases
Gram negative endocarditis is uncommon but has high morbidity and mortality. Now we see more health care-associated infections as the primary source especially with an increasing elderly population, multiple co-morbidities and more invasive procedures.
We report an 81 year old woman with atherosclerosis-related co-morbidities, coronary and femoral stents, plus an implanted cardiac defibrillator presenting with 2 weeks of lethargy and poor intake. She had a right foot lesion that looked embolic with lab results consistent with sepsis, 3 days of Escherichia coli bacteremia from pyelonephritis, and a small vegetation on the mitral leaflet seen via transesophageal echo (TEE). Then we saw a 52 year old diabetic woman with end-stage renal disease dialyzed via a one month old femoral arteriovenous graft (AVG) and infected for 2 weeks. She also had a history of recurrent line-related bacteremias. She presented with 3 days of feeling unwell, weakness and severe sepsis. Her AVG was grossly infected and exposed. She had 1 day of extended-spectrum beta lactamase (ESBL) Klebsiella pneumoniae bacteremia. The graft was surgically removed on the same day. TEE had tiny, linear mobile vegetations on the aortic valve.
In Case 1, pyelonephritis with >2 days of bacteremia and embolic phenomenon heightened suspicion for endocarditis. The source in case 2 was an infected AVG, which would not usually have required a TEE because of the short bacteremia. But the combination of diabetes, dialysis, recurrent bacteremias and a now frankly infected and exposed graft with an ESBL organism led to further investigation. The unifying factor in these 2 cases is immersion in the health care system, which is a risk for development of gram negative endocarditis.
CTX-M extended-spectrum ?-lactamase(ESBL)-producing Escherichia coli: Epidemiology and Clinical Impacts in a tertiary U.S. medical center
Harish Pulluru, MBBS, Dror Marchaim, MD, Ashish Bhargava, MD, Paul R. Lephart, Karen Bush, Keith. S. Kaye, MD, MPH, Kayoko Hayakawa, MD, PhD.
Detroit Medical Center (DMC), Wayne State University, Detroit, Michigan.
Indiana University, Bloomington, Indiana.
Over the recent years, the more traditional TEM and SHV type ESBLs in ESBL-producing E.coli (ESBLEC) are being replaced by CTX-M type ESBLs. The objective was to determine independent risk factors for the isolation of CTX-M type ESBLEC in a tertiary medical center located in southeast Michigan.
We conducted a case-control study by collecting unique cases with clinical ESBLEC isolation during the confined study period (2/2010-7/2011) and conducted PCR analysis for the detection of CTX-M ?-lactamase genes. Patients with CTXMEC isolation and with available detailed medical records were matched to uninfected controls in a 1:1 ratio.
A total of 319 CTXMEC cases were identified from different sources [urine (n=241), wounds (n=32) sputum (n=22) and blood (n=22)] and were matched to 319 uninfected controls. In 247 (77.4%) cases, CTXMEC was present at the time of hospital admission. The mean age of the study cohort was 64±17.9 years and 305 (47.8%) were male. Independent risk factors for the isolation of CTXMEC were determined (Table). Although it’s statistically insignificant, the in-hospital mortality rates were higher in CTXMEC group, (5.7% vs. 3.8%, p=0.08). Median total length of stay was greater among CTXMEC cases than controls (7 [IQR: 4-12] vs. 4 [2-6], p<0.001). CTXMEC cases were more frequently discharged to long-term care facilities after being admitted from home (18.6% vs. 3.5%, p<0.001), and were more frequently re-admitted within 6 months after discharge (58.6% vs. 41.7%, P<0.001) than were controls.
We identified exposure to oxyimino-cephalosporins and history of urinary tract infection or catheter use as independent risk factors for isolation of CTXMEC. Utilization of healthcare resources was greater among CTXMEC cases than in controls.
Table. Multivariate Analysis of Risk factors for the isolation of CTX-M-ESBL E.coli A
CTX-M-ESBL E.coli cases vs uninfected controls
Indwelling urinary catheter B
History of UTI
Oxyimino-cephalosporins C in the past 3 months
Dependent functional status on admission
Charlson combined comorbidity index (>5)
A Controlled for vancomycin exposures in the past 3 months.
B For cases, at time of at CTXMEC isolation; for controls at time of admission.
C Includes ceftriaxone, cefepime, ceftazidime.
Progressive Multifocal Leukoencephalopathy (PML) in a setting of Idiopathic CD4 Lymphocytopenia (ICL)
Ashish Bhargava, Samran Haider, William Joseph Kupsky, Jonathan Cohn, Detroit Medical Center, Wayne State University
PML is a fatal neurodegenerative disease that is caused by JC virus. It is an opportunistic infection in HIV infected patients, with incidence as high as 4-6%. The second largest group comprises of patients treated with biologic agents. Rarely PML also occurs in patients with ICL. CDC defines ICL as CD4+Tcells <300 /microL or a CD4+cell count < 20% of the total T cell on two occasions, with no evidence of infection on HIV testing and absence of any defined immunodeficiency or therapy associated with depressed levels of CD4+ T cells. We present a patient with PML in the setting of ICL. A 63-year-old female presented with worsening dizziness, new onset diplopia and slurring of speech. Her initial symptom of dizziness started 6 weeks earlier but progressed to recurrent headaches and motion sickness with symptomatic treatment. Workup at outside facility showed 3 mm focal, nodular enhancing lesion in the left cerebellar hemisphere. She was given a trial of prednisone treatment without improvement. On presentation, she was afebrile. She had a bilateral horizontal nystagmus, worse on the left side, wide based gait, significant vertigo and moderate dysmetria, dysdiadochokinesia on the left side. Isolated severe lymphocytopenia in peripheral blood prompted further work up. Immunological tests showed a CD4+ count of 10 and a CD8+ count of 12. Results were negative for HIV 1 and 2 (EIA), HIV viral load, VDRL and RPR. Her PCR for HSV 1 and 2, and EBV serology were also found to be negative. MRI showed a 9 mm enhancing nodular lesion in left cerebellar hemisphere. An open needle biopsy revealed marked atypia in the astrocytes and rare nuclei with abnormal inclusion like material suggestive of PML. CSF testing showed 32700 DNA copies/ml of JC virus. Her neurological condition rapidly declined after hospital admission. She received one dose of cidofovir but her condition continued to decline. On 19th day, she developed new cerebral and left thalamic hemorrhage with evidence of brain stem infarction. She expired secondary to an asystole. Literature review showed only 8 cases of PML in ICL setting. Seven of them had declining course with mortality in four patients. Since immunodeficiency cannot be corrected in ICL, the outcome of patients with PML remains poor.
Epidemiology of Carbapenem-Resistant Enterobacteriaceae (CRE) colonization among patients with exposure to long-term acute care centers (LTACs) and acute care facilities
A. Bhargava, K. Hayakawa, KC. Alluri, S. Haider, S. Datla, T Chopra, D Marchaim, KS. Kaye
Background: At DMC, patients with exposure to LTACs within the year prior to hospital admission are screened for CRE colonization via peri-rectal swab culture. This study describes the epidemiology and outcomes associated with CRE colonization among persons with hospital and LTAC exposure
Methods: A retrospective cohort study was conducted at DMC from 6/09-12/11. Patients with a positive CRE surveillance culture at the time of hospital admission were included
Results: 905 surveillance cultures were performed on 679 patients. 48 unique patients (7.1%) with CRE carriage were identified. Mean age of the cohort was 68±15 years, 29 (60%) were female, and 41(85%) were African American. 25 patients (52%) were functionally dependent. 21 patients (44%) were admitted directly from home, 17(35%) from other hospitals, and 6 (13%) from LTACs Mean Charlson’s score was 5.5±2.4 and 23 patients (48%) had chronic skin ulcers. 35 subjects (73%) had a history of hospitalization and 31 (65%) had had invasive procedures within 3 months of admission. 18 patients (38%) had indwelling permanent devices. 38 (80%) patients had recently received antibiotics (predominantly ?-lactams). During hospital admission following CRE screening culture, 13 (27%) had a subsequent clinical culture positive for CRE and 8(17%) developed a CRE infection. Median duration from surveillance culture to both clinical culture positivity and CRE infection was 14 days. 14 patients (30%) were subsequently intubated and 8 (17%) died during hospitalization.
Conclusions: CRE carriage occurred in subjects with extensive exposures to healthcare, indwelling devices and antimicrobials. Subsequent clinical culture positivity for CRE occurred in > 25% of patients and CRE infection in > 15% of patients. Three-month mortality exceeded 25%.
Risk Factors and Outcomes of Patients with Bloodstream Infections due to Nocardia Species
Deepak Garg MD1, Pauline Jacinto MD2,3, Karam Obeid MD1,2, Pranatharthi Chandrasekar, MD2,3
Leonard B. Johnson MD1,2
1Division of Infectious Disease, St. John Hospital and Medical Center
2Department of Internal Medicine, Wayne State University
3Division of Infectious Diseases, Wayne State University
Background: Nocardiosis is an uncommon infection caused by the aerobic, gram positive filamentous organism Nocardia. Although the rate of Nocarida-related infections appears to be increasing with the increased longevity and numbers of immunosupressed patients, Nocardia bacteremia is still rare. The objective of our study is to identify the risk factors and prognosis of patients with Nocardia bacteremia.
Methods: We performed a retrospective chart review study in two large tertiary care centers in Detroit, Michigan. All patients with positive clinical samples for Nocarida, over an 11-year period, were identified. Patients with no blood cultures performed within 48 hours of the nocardiosis diagnosis were excluded. We compared demographics, clinical, laboratory and radiological data of patients with nocardiosis associated with bacteremia to patients without bacteremia.
Results: During the study period we identified 23 patients with nocardiosis. Seven (30%) were bacteremic and 16 (70%) were not. Fourteen (61%) were immunocompromised and nine (39.1%) had indwelling endovascular devices. The groups were similar in terms of age, gender, underlying immunocompromised conditions and frequency of underlying endovascular devices. Patients who were bacteremic were more likely to be receiving TMP/SMX prophylaxis at the time of diagnosis (43% vs. 6%, p=0.03). None of the other clinical and laboratory factors reached statistical significance. The overall mortality rate was 38% with higher mortality rates among those with bacteremia (71% vs. 21%, p<0.001).
Conclusion: Patients with Nocardia bacteremia were similar to non-bacteremic cases except for higher rates of TMP/SMX prophylaxis at time of infection and higher mortality rates. Presence of an endovascular device was not higher among those with Nocardia bacteremia and attempts should be made to find other potential primary sites before considering the device as the source of infection.
Clinical Value of Chest Computerized Tomography (CT) Scans in Patients Admitted With Pneumonia
Deepak Garg MD, Leonard B. Johnson MD, Susan Szpunar PhD, Joel Fishbain MD
Background: Chest radiography (CXR) is essential in the diagnosis of pneumonia. Supplemental testing with a computerized tomography (CT) scan has been recommended when patients are “not responding to therapy”. While CT scans may detect new findings, the optimal timing and clinical benefit is unclear.
Methods: We performed a retrospective chart review study of patients admitted with pneumonia from 1/1/11-10/31/11 at a large urban hospital. Patients were included if they had a diagnosis of pneumonia with in 48 hours of admission and had an abnormal CXR. Data collected included demographics, CXR results, laboratory studies, CURB 65 score, outcomes, modified Charlson Weighted Index of Comorbidity (CWIC), CT scans and diagnostic or therapeutic procedures performed.
Results: 200 patients met inclusion criteria. 53% were female and mean age was 63 ± 19.1 years. 69 patients (34.5%) had a CT scan of the chest after admission (performed on average 34.2±38.9 hours after admission). CXR findings associated with the performance of a CT scan included the absence of infiltrates or consolidation (p=0.004). CT scans were performed more often in patients admitted from the community compared to other healthcare facilities (p=0.007). A CT scan was performed in patients who had lower CURB65 scores (p<0.037) and were younger (mean age 58.4 vs 66 years of age, p<0.002). A total of 19 procedures were performed, including 15/69 (21.7%) with CT and 4/126 (3.2%) without (p<0.0001). All 15 patients who had CT scan and a procedure performed were admitted from the community. Length of stay in hospital was not affected by CT scan (8.6 vs. 6.8 days, p=0.08).
Conclusion: CT scans were performed in 34.5% of patients admitted with pneumonia and were more likely to be performed in younger patients with lower severity of illness and were more likely admitted from the community with normal CXRs. Additional procedures resulting from CT scan only resulted in those presenting from the community.
Insights into associations between spa type and multidrug resistance efflux pump gene overexpression in clinical isolates of Staphylococcus aureus
Pauline Jacinto, M.D., Department of Medicine, Division of Infectious Diseases, Wayne State University School of Medicine, Bryan D. Schindler1, Susan M. Seo1, Glenn W. Kaatz1,2
1The John D. Dingell Department of Veterans Affairs Medical Center, Detroit
2Department of Medicine, Division of Infectious Diseases, Wayne State University School of Medicine,
Background: Increased expression of multidrug resistance efflux pump (MDR-EP) genes contributes to antimicrobial and biocide resistance in clinical isolates of Staphylococcus aureus. Exposure of non-MDR-EP overexpressing clinical isolates to biocides and dyes can lead to the emergence of mutants which constitutively overexpression of one or more MDR-EP genes. We recently reported a strong association between norA overexpression and spa type t002 MRSA and a similar, yet weaker association between mepA overexpression and spa type t008 MSSA in clinical isolates. Although these associations are suggestive of clonal dissemination, it is also possible that closely related strains are prone to mutations resulting in overexpression of specific MDR-EP genes.
Methods: Twelve non-MDR-EP gene overexpressing clinical isolates (spa types t002, t008, and non-t002-t008; both MRSA and MSSA) were exposed to ethidium bromide (EB). EB-resistant mutants were selected by single-step (at 2x and 4x the parent EB MIC) and gradient-plate methods. Parents and their derivatives were compared based on the following: (1) susceptibily to EB and other agents (with and without the efflux pump inhibitor reserpine), (2) EB efflux assays, and (3) quantitative RT-PCR of commonly overexpressed MDR-EP genes.
Results: All mutant strains had 8-16 fold increases in their EB MIC and had augmented efflux activity in EB efflux assays. Overall, 33 of 60 and 17 of 60 mutants overexpressed mepA and norA, with or without overexpression of other genes, respectively. There were no observed associations between t002 or t008 and norA or mepA overexpression, respectively, regardless of meticillin susceptibility. mepA overexpression predominated amongst t002 strains while mdeA overexpression stood out amongst t008 and non-t002-t008 strains.
Discussion: While these results do not support an association between a specific spa type and a predilection toward overexpression of a specific MDR-EP gene, they do support the possibility of widespread clonal dissemination to explain previously observed associations between spa type, meticillin susceptibility, and MDR-EP gene overexpression amongst clinical S. aureus isolates.
A Rare Case of Syncephalastrum racemosum Invasive Pulmonary Infection after Liver Transplantation
Hadeel Zainah, MD Henry Ford Hospital
Introduction: Zygomycosis is a rare cause of pathologic, systemic infection. It is an opportunistic infection of the immunocompromised host and often fatal. In particular Syncephalastrum sp, first described in 1886, are primarily isolated in cases of otomycosis and cutaneous infection but have also been reported in other locations. We describe the first case of pulmonary infection caused by this fungus.
Case Presentation: A 58-year-old immunocompromised female presented 41 days post living-donor liver transplant. During her stay, she was on oral tacrolimus 0.5 mg twice daily, methylprednisolone IV 10 mg daily, in addition to oral valgancyclovir, oral fluconazole and nebulized penthamidine for opportunistic infection prophylaxis.
Post operatively she developed acute gastrointestinal bleeding and multi-organ system failure. During her protracted intensive-care-unit stay she developed respiratory failure, became ventilator dependent and underwent bronchoscopy for evaluation of a left upper lung cavitary lesion. On bronchoscopy she was found to have a necrotic lesion in the right upper bronchus determined by pathologic review to be a Syncephalastrum racemosum infection. Subsequent imaging revealed progressive bilateral pulmonary lesions and the patient succumbed to overwhelming sepsis and fulminant liver failure eleven days later.
Conclusion: Syncephalastrum racemosum pulmonary infection is a rare but serious infection that requires high index of suspicion in the typical immunocompromised host.
Epidemiology and Outcome of Methicillin-Resistant Staphylococcus aureus Health-Care Associated Pneumonia
Hadeel Zainah, MD Henry Ford Hospital
Objectives: Methicillin-resistant Staphylococcus aureus (MRSA) is an important cause of healthcare-associated pneumonia (HCAP). HCAP confers high morbidity and mortality. In this study, we evaluated risk factors and clinical outcomes of MRSA-HCAP.
Methods: Between 08/2008 and 09/2010 we conducted a retrospective, single-center study. 783 patients with MRSA isolated from respiratory cultures were screened. The primary outcome was 28-day mortality. Results were computed using univariate and multiple logistic regression analysis.
Results: The analysis included 63 patients (54.78 %) with MRSA HCAP. The mean age (±SD) was 65.95 ± 15.4 years. 37 (58.7 %) were males. 56 (88.9 %) had at least one associated comorbid medical condition. 42 (66.7 %) were treated with vancomycin, 4(6.3 %) with linezolid and the remaining 17 (27%) were switched between the two antimicrobials. Mean APACHE II (± SD) score was 18.8 (±7.3). Mortality rate was 28.6 %. APACHE-II score, chronic obstructive pulmonary disease (COPD) and superinfection were found to be independent risk factors for 28-day mortality.
Conclusions: MRSA is a significant etiology of HCAP which is more prevalent in the elderly. The associated mortality rate could be high and driven by several factors including APACHE II score and preexisting COPD.