Jasmine R. Marcelin

Cytomegalovirus infection in liver transplant recipients: Updates on clinical management

Cytomegalovirus (CMV) infection is a common complication after liver transplantation, and it is associated with multiple direct and indirect effects. Management of CMV infection and disease has evolved over the years, and clinical guidelines have been recently updated. Universal antiviral prophylaxis and a pre-emptive treatment strategy are options for prevention. A currently-recruiting randomized clinical trial is comparing the efficacy and safety of the two prevention strategies in the highest risk D+R- liver recipients. Drug-resistant CMV infection remains uncommon but is now increasing in incidence. This highlights the currently limited therapeutic options, and the need for novel drug discoveries. Immunotherapy and antiviral drugs with novel mechanisms of action are being investigated, including letermovir (AIC246) and brincidofovir (CMX001). This article reviews the current state of CMV management after liver transplantation, including the updated practice guidelines, and summarizes the data on investigational drugs and vaccines in clinical development.

Efficacy of Antitoxin Therapy in Treating Patients With Foodborne Botulism: A Systematic Review and Meta-analysis of Cases, 1923–2016

Background Botulism is a rare, potentially severe illness, often fatal if not appropriately treated. Data on treatment are sparse. We systematically evaluated the literature on botulinum antitoxin and other treatments. Methods We conducted a systematic literature review of published articles in PubMed via Medline, Web of Science, Embase, Ovid, and Cumulative Index to Nursing and Allied Health Literature, and included all studies that reported on the clinical course and treatment for foodborne botulism. Articles were reviewed by 2 independent reviewers and independently abstracted for treatment type and toxin exposure. We conducted a meta-analysis on the effect of timing of antitoxin administration, antitoxin type, and toxin exposure type. Results We identified 235 articles that met the inclusion criteria, published between 1923 and 2016. Study quality was variable. Few (27%) case series reported sufficient data for inclusion in meta-analysis. Reduced mortality was associated with any antitoxin treatment (odds ratio [OR], 0.16; 95% confidence interval [CI], .09-.30) and antitoxin treatment within 48 hours of illness onset (OR, 0.12; 95% CI, .03-.41). Data did not allow assessment of critical care impact, including ventilator support, on survival. Therapeutic agents other than antitoxin offered no clear benefit. Patient characteristics did not predict poor outcomes. We did not identify an interval beyond which antitoxin was not beneficial. Conclusions Published studies on botulism treatment are relatively sparse and of low quality. Timely administration of antitoxin reduces mortality; despite appropriate treatment with antitoxin, some patients suffer respiratory failure. Prompt antitoxin administration and meticulous intensive care are essential for optimal outcome.

Erysipelothrix rhusiopathiae bloodstream infection – A 22‐year experience at Mayo Clinic, Minnesota

Erysipelothrix rhusiopathiae is a facultatively anaerobic Gram‐positive bacillus found mostly in swine, fish and sheep. E. rhusiopathiae classically causes cutaneous eruptions in butchers, fish handlers and veterinarians. Based solely on case reports, 90% of E. rhusiopathiae bloodstream infections (BSI) have been associated with infective endocarditis (IE). To assess the true frequency of IE in E. rhusiopathiae BSI as well as other clinical associations, we performed a retrospective cohort analysis of E. rhusiopathiae BSI at Mayo Clinic. This is a single‐centre, retrospective study conducted between 1/1/1994 and 20/6/2016 at Mayo Clinic in Rochester, MN. Medical records were reviewed for demographics, E. rhusiopathiae BSI, anti‐microbial susceptibilities, incidence of IE, patient comorbidities, intensive care unit (ICU) admission and duration of antibiotics. Five cases of E. rhusiopathiae BSI were identified. Risk factors included animal exposures, immunosuppression, diabetes and kidney disease. All cases involved penicillin‐sensitive strains and high‐grade BSI. Four cases showed no signs of IE on transesophageal echocardiogram. All patients recovered fully with intravenous antibiotics. Our retrospective review illustrates that E. rhusiopathiae can cause invasive BSI in the absence of IE and that the previously reported 90% association between BSI and IE may be overestimated due to reporting bias. E. rhusiopathiae should be suspected in any patient with Gram‐positive bacilli in blood cultures and the aforementioned risk factors. A limitation of our study was the low sample size, and future studies may involve multicentre collaborations and the use of polymerase chain reaction (PCR) or serologic testing to increase the number of diagnoses..

Incidence and Effects of Seasonality on Nonpurulent Lower Extremity Cellulitis After the Emergence of Community-Acquired Methicillin-Resistant Staphylococcus aureus

&NA; Nonpurulent lower extremity cellulitis (NLEC) is a common clinical diagnosis, with &bgr;‐hemolytic streptococci and Staphylococcus aureus considered to be the most frequent causes. In 1999, the US Public Health Service alerted clinicians to the presence of community‐acquired methicillin‐resistant S aureus (CA‐MRSA) infections in 4 children in the upper Midwest. Since then, it has become a well‐recognized cause of skin and soft‐tissue infections, in particular, skin abscess. A previous population‐based study of NLEC in Olmsted County, Minnesota, reported an unadjusted incidence rate of 199 per 100,000 person‐years in 1999, but it is unknown whether CA‐MRSA subsequently has affected NLEC incidence. We, therefore, sought to determine the population‐based incidence of NLEC since the emergence of CA‐MRSA. Age‐ and sex‐adjusted incidence (per 100,000 persons) of NLEC was 176.6 (95% CI, 151.5‐201.7). Incidence differed significantly between sexes with age‐adjusted sex‐specific rates of 133.3 (95% CI, 104.1‐162.5) and 225.8 (95% CI, 183.5‐268.0) in females and males, respectively. Seasonal incidence differed, with rates of 224.6 (95% CI, 180.9‐268.4) in warmer months (May‐September) compared with 142.3 (95% CI, 112.8‐171.9) in colder months (January‐April and October‐December). Despite emergence and nationwide spread of CA‐MRSA since 1999 in the United States, the incidence of NLEC in Olmsted County was lower in 2013 than in 1999, particularly in females. This suggests that CA‐MRSA is not a significant cause of NLEC and that NLEC cases are seasonally distributed. These findings may be important in formulation of empirical therapy for NLEC and in patient education because many patients with NLEC are prone to recurrent bouts of this infection.

Coadministration of liposomal amphotericin B and contrast medium does not increase risk of kidney injury

ABSTRACT Intravenous radiographic contrast medium and amphotericin B are commonly required in the care of patients with fungal infections. Both interventions have proposed nephrotoxicity through similar mechanisms. We systematically examined patients who received coadministration of liposomal amphotericin B (AmBisome; GE Healthcare) and intravenous contrast medium within a 24-h period and compared the results for those patients with the results for patients who underwent non-contrast medium studies. We found 114 cases and 85 controls during our study period. Overall, no increased risk of renal injury was seen with coadministration of these 2 agents. Adjustment for age, baseline kidney function, and other clinical factors through propensity score adjustment did not change this result. Our observations suggest that, when clinically indicated, coadministration of contrast medium and liposomal amphotericin B does not present excess risk compared with that from the administration of liposomal amphotericin B alone.

Mycobacterium avium intracellulare complex causing olecranon bursitis and prosthetic joint infection in an immunocompromised host

Abstract Case A 73-year-old immunocompromised male presented with recurrent left elbow swelling due to Mycobacterium avium intracellulare complex (MAC) olecranon bursitis. 3 years after completing MAC treatment, he underwent right total knee arthroplasty (TKA). 1 year later, he developed TKA pain and swelling and was diagnosed with MAC prosthetic joint infection (PJI). He underwent TKA resection, reimplantation, and 12 months of anti-MAC therapy. This patient is the seventh case report of MAC olecranon bursitis and the third case report of MAC PJI. He is the only report of both MAC olecranon bursitis and PJI occurring in the same patient. Informed consent This patient was informed and agreed to the publication of this material.

Seasonal and environmental variation of lower extremity cellulitis incidence among emergency department patients in three geographic locations

Abstract Background Recent investigation has suggested a higher incidence of lower extremity cellulitis (LEC) during the summer, but it is not clear if this phenomenon is limited only to certain climates or locations. We sought to investigate this phenomenon and further elucidate the relationship with environmental climate factors in three different geographic locations. Methods This was a retrospective study of all patients with at least 1 ICD-9 code recorded during an emergency department (ED) visit at Mayo Clinic in Scottsdale, AZ; Jacksonville, FL; and Rochester, MN; between January 1, 2009 and December 12, 2014. Demographics were defined using ICD-9 data. Temperature data was obtained from the National Oceanic and Atmospheric Administration website. The climates of each location were classified according to the Köppen Climate Classification System as hot desert (AZ), humid subtropical (FL) or humid continental (MN) climate types. The primary outcome was LEC (ICD-9 code 682.7) expressed as a proportion of 1000 ED visits (LEC visits/1,000 EDV), to account for seasonal variation in ED usage. Univariate and multivariate regression were performed for analysis. Results There were 627,292 ED visits among 288,349 patients during the study period. The incidence of LEC visits/1,000 EDV was significantly different across sites (9.36 in FL, 7.95 in AZ, and 7.39 in MN, P <0.0001 for any difference). In the humid climate types (FL and MN), the peak incidences of LEC occurred in the warmest month; July in FL (11.77 LEC visits/1,000 EDV) and August in MN (9.69 LEC visits/1000 EDV). In AZ, the peak incidence occurred in November, the fourth coolest month (9.44 LEC visits/1000 EDV) (Figure 1). There was a significant positive correlation between the high daily temperature and the incidence of LEC cellulitis in all three sites (Figure 2). After controlling for total daily ED visits, gender, and age, the high temperature for the day was significantly associated with occurrence of LE cellulitis at each site (P <0.0001). Conclusion The incidence of LEC presenting to the ED is associated with environmental temperature across different geographic locations and climate types, but slight variations in seasonality of infection was observed. Investigation to determine whether other environmental factors, in particular, humidity, are associated with the incidence of LEC is ongoing. Disclosures All authors: No reported disclosures.

Is Abnormal Urine Protein/Osmolality Ratio Associated with Abnormal Renal Function in Patients Receiving Tenofovir Disoproxil Fumarate?

Background Risk factors for and optimal surveillance of renal dysfunction in patients on tenofovir disoproxil fumarate (TDF) remain unclear. We investigated whether a urine protein-osmolality (P/O) ratio would be associated with renal dysfunction in HIV-infected persons on TDF. Methods This retrospective, single-center study investigated the relationship between parameters of renal function (estimated glomerular filtration rate (eGFR) and P/O-ratio) and risk factors for development of kidney dysfunction. Subjects were HIV-infected adults receiving TDF with at least one urinalysis and serum creatinine performed between 2010 and 2013. Regression analyses were used to analyze risk factors associated with abnormal P/O-ratio and abnormal eGFR during TDF therapy. Results Patients were predominately male (81%); (65%) were Caucasian. Mean age was 45.1(±11.8) years; median [IQR] TDF duration was 3.3 years. [1.5–7.6]. Median CD4+ T cell count and HIV viral load were 451 cells/μL [267.5–721.5] and 62 copies/mL [0–40,150], respectively. Abnormal P/O-ratio was not associated with low eGFR. 68% of subjects had an abnormal P/O-ratio and 9% had low eGFR. Duration of TDF use, age, diabetes and hypertension were associated with renal dysfunction in this study. After adjustment for age, subjects on TDF > 5 years had almost a four-fold increased likelihood of having an abnormal P/O-ratio than subjects on TDF for < 1yr (OR 3.9; 95% CI 1.2–14.0; p = 0.024). Conclusion Abnormal P/O-ratio is common in HIV-infected patients on TDF but was not significantly associated with low eGFR, suggesting that abnormal P/O-ratio may be a very early biomarker of decreased renal function in HIV infected patients.

Intramuscular Ceftriaxone with Oral Antibiotic Therapy in the Treatment ofOutpatient Cellulitis

Purpose: Oral antibiotics are the treatment of choice for outpatient cellulitis; however, intramuscular (IM) antibiotics are frequently used in addition to oral antibiotics in the clinic setting. This study compared outcomes among patients with cellulitis who were administered IM ceftriaxone in addition to oral antibiotics versus those who received oral antibiotics alone. Methods: This study was a retrospective chart review of 982 adult primary care patients designed to evaluate rates of treatment failure of outpatient cellulitis among patients who received IM ceftriaxone and oral antibiotics versus oral antibiotics alone. Treatment failure was defined as: 1) hospital admission for intravenous (IV) antibiotics within 30 days of diagnosis, 2) prolonged antibiotic course, or 3) requiring a different antibiotic after initial antibiotic course. Results: Of the 982 patients in the study cohort, 104 (10.6%) received IM ceftriaxone in addition to oral antibiotics while 878 (89.4%) did not. In the IM ceftriaxone group, hospitalization within 30 days was seen in 10.6% vs. 4.2% of the oral treatment only group (p=0.004). Initial outpatient use of IM ceftriaxone was associated with a 3.031 (95% CI 1.928-4.765, p<0.001) increased adjusted odds ratio for treatment failure. Age, gender, race, the use of tobacco, and diagnosis of diabetes mellitus were not associated with adverse outcomes when controlling for all other variables. Conclusions: The patients who received an initial dose of IM ceftriaxone in addition to oral antibiotics were more likely to experience treatment failure than the non-ceftriaxone cohort. With increasing emergence of antibiotic resistant organisms, antibiotic prescribing practices must be reviewed to ensure efficacy and minimize risks associated with unnecessary antibiotic exposure.

Fever and Cardiac Arrest in a Patient With a Left Ventricular Assist Device

A 68-year-old avid deer hunter with ischemic cardiomyopathy underwent left ventricular assist device (LVAD) implantation for destination therapy two years ago. He was living an active lifestyle, tracking deer and fishing in a Midwestern forest in November. His wife removed an engorged tick on his thorax. A few days later, he experienced fever, confusion, and ataxia and was hospitalized with septic shock and ventricular fibrillation. The LVAD site had no signs of trauma, drainage, warmth, or tenderness. A peripheral blood smear revealed intraleukocytic anaplasma microcolony inclusions. After completing 14 days of doxycycline, he recovered. Typical non-device-associated infections in LVAD recipients include pneumonia, urinary tract infection, or Clostridium difficile colitis. Human granulocytic anaplasmosis (HGA) is a very atypical non-LVAD infection, and the incidence of tickborne illnesses in LVAD recipients is unknown.