Fludrocortisone Plus Hydrocortisone Versus Hydrocortisone Alone as Adjunctive Therapy in Septic Shock: A Retrospective Cohort Study.

BACKGROUND: Trials evaluating hydrocortisone (HC) for septic shock are conflicting with all finding decreased time to shock reversal but few with mortality difference. Those with improved mortality included fludrocortisone (FC), but it is unknown if FC affected the outcome or is coincidental as there are no comparative data. OBJECTIVE: The objective of this study was to determine the effectiveness and safety of FC + HC versus HC alone as adjunctive therapy in septic shock. METHODS: A single-center, retrospective cohort study was conducted of medical intensive care unit (ICU) patients with septic shock refractory to fluids and vasopressors. Patients receiving FC + HC were compared with those receiving HC. Primary outcome was time to shock reversal. Secondary outcomes included in-hospital, 28-, and 90-day mortality; ICU and hospital length of stay (LOS); and safety. RESULTS: There were 251 patients included (FC + HC, n = 114 vs HC, n = 137). There was no difference in time to shock reversal (65.2 vs 71 hours; P = 0.24). Cox proportional hazards model showed time to first corticosteroid dose, full-dose HC duration, and use of FC + HC were associated with shorter shock duration, while time to vasopressor therapy was not. However, in 2 multivariable models controlling for covariates, use of FC + HC was not an independent predictor of shock reversal at greater than 72 hours and in-hospital mortality. No differences were seen in hospital LOS or mortality. Hyperglycemia occurred more frequently with FC + HC (62.3% vs 45.6%; P = 0.01). CONCLUSION AND RELEVANCE: FC + HC was not associated with shock reversal at greater than 72 hours or decreased in-hospital mortality. These data may be useful for determining corticosteroid regimen in patients with septic shock refractory to fluids and vasopressors. Future prospective, randomized studies are needed to further evaluate the role of FC in this patient population.

Risk of Coronavirus Disease 2019-Associated Pulmonary Aspergillosis Based on Corticosteroid Duration in Intensive Care Patients.

Background: Coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) is a potential complication in critically ill COVID-19 patients. Corticosteroids are standard of care for hospitalized COVID-19 patients but carry an increased risk of secondary infections including CAPA. The objective of this study was to evaluate if duration of corticosteroid therapy ≤10 days versus >10 days affects the risk of developing CAPA. Methods: This was a retrospective cohort study of adult patients with severe COVID-19 pneumonia requiring mechanical ventilation who received at least 3 days of corticosteroid treatment. Incidence of CAPA and secondary outcomes were compared using appropriate bivariable analyses. Steroid duration was evaluated as an independent predictor in a logistic regression model. Results: A total of 278 patients were included (n = 169 for ≤10 days' steroid duration; n = 109 for >10 days). CAPA developed in 20 of 278 (7.2%) patients. Patients treated with >10 days of corticosteroid therapy had significantly higher incidence of CAPA (11.9% vs 4.1%; P = .0156), and steroid duration >10 days was independently associated with CAPA (odds ratio, 3.17 [95% confidence interval, 1.02-9.83]). Secondary outcomes including inpatient mortality (77.1% vs 43.2%; P < .0001), mechanical ventilation-free days at 28 days (0 vs 1.5; P < .0001), and secondary infections (44.9% vs 28.4% P = .0220) were worse in the >10 days cohort. Conclusions: Corticosteroid treatment >10 days in critically ill COVID-19 patients is associated with an increased risk of CAPA. Patients may require corticosteroids for reasons beyond COVID-19 and clinicians should be cognizant of risk of CAPA with prolonged courses.

An Updated Review of Clostridium difficile Treatment in Pediatrics.

Clostridium difficile infection (CDI) continues to have clinical and economic impact across all health care settings. Pediatrics accounts for a small percentage of worldwide infection; however, screening and diagnosis are confounded by asymptomatic colonization in young infants. Metronidazole and oral vancomycin have historically been the agents used to manage CDI in both pediatrics and adults. Newer agents and alternative therapies, such as fecal microbiota transplantation, may offer additional benefit. Recent guidelines updates from the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America separate pediatric and adult recommendations for epidemiology, diagnosis, and treatment. This review will discuss the risk factors, management, prevention, and updated guideline recommendations for CDI in the pediatric population.

Rituximab for Treatment of Refractory Anti-NMDA Receptor Encephalitis in a Pediatric Patient.

Anti-N-methyl d-aspartate receptor (anti-NMDAR) encephalitis is a devastating disease that is increasingly being identified in both children and adults with psychosis, language disturbances, behavioral changes, and motor deficits. Currently no consensus guidelines exist for the optimal management of patients with this disease, although intravenous immune globulin (IVIG) therapy is often considered first-line pharmacotherapy. We present a case of an otherwise healthy 4 year-old-child who presented with seizures, loss of age-appropriate language skills, and behavioral changes, in whom anti-NMDAR was subsequently diagnosed. After marked intolerance to corticosteroid therapy and inadequate clinical response to IVIG, immunotherapy with rituximab was initiated. The patient had rapid return of language skills and complete resolution of dyskinesia after a single rituximab infusion, with no residual deficits at her 6-month follow-up visit. Early intervention in patients with anti-NMDAR encephalitis is of paramount importance for successful outcomes and baseline recovery. Only approximately half of patients respond to first-line immunotherapy, necessitating further evaluation of alternative therapies and the development of a treatment algorithm for practitioners. This case report builds upon previous findings illustrating rapid symptom resolution after rituximab infusion and adds to the available body of evidence for management of pediatric patients with anti-NMDAR.

Epidemiology of Methicillin-Resistant Staphylococcus aureus Diabetic Foot Infections in a Large Academic Hospital: Implications for Antimicrobial Stewardship.

INTRODUCTION: Diabetic foot infections (DFIs) are the leading cause of non-traumatic lower extremity amputations in the United States. Antimicrobials active against methicillin-resistant Staphylococcus aureus (MRSA) are recommended in patients with associated risk factors; however, limited data exist to support these recommendations. Due to the changing epidemiology of MRSA, and the consequences of unnecessary antibiotic therapy, guidance regarding the necessity of empirical MRSA coverage in DFIs is needed. We sought to 1) describe the prevalence of MRSA DFIs at our institution and compare to the proportion of patients who receive MRSA antibiotic coverage and 2) identify risk factors for MRSA DFI. METHODS: This was a retrospective cohort study of all adult, culture-positive DFI patients managed at University Hospital, San Antonio, TX between January 1, 2010 and September 1, 2014. Patient eligibility included a principal ICD-9-CM discharge diagnosis code for foot infection and a secondary diagnosis of diabetes. The primary outcome was MRSA identified in the wound culture. Independent variables assessed included patient demographics, comorbidities, prior hospitalization, DFI therapies, prior antibiotics, prior MRSA infection, and laboratory values. Multivariable logistic regression was used to identify risk factors for MRSA DFI. RESULTS: Overall, 318 patients met inclusion criteria. Patients were predominantly Hispanic (79%) and male (69%). Common comorbidities included hypertension (76%), dyslipidemia (52%), and obesity (49%). S. aureus was present in 46% of culture-positive DFIs (MRSA, 15%). A total of 273 patients (86%) received MRSA antibiotic coverage, resulting in 71% unnecessary use. Male gender (OR 3.09, 95% CI 1.37-7.99) and bone involvement (OR 1.93, 1.00-3.78) were found to be independent risk factors for MRSA DFI. CONCLUSIONS: Although MRSA was the causative pathogen in a small number of DFI, antibiotic coverage targeted against MRSA was unnecessarily high.

Monotherapy with minocycline or trimethoprim/sulfamethoxazole for treatment of Stenotrophomonas maltophilia infections.

OBJECTIVES: Stenotrophomonas maltophilia is a Gram-negative bacillus intermittently isolated from hospitalized patients. Trimethoprim/sulfamethoxazole is considered the treatment of choice for S. maltophilia infections, though limited by toxicities. Minocycline is utilized at our institution for S. maltophilia infections due to its improved tolerability and in vitro susceptibility rates. Our objective was to evaluate the effectiveness of minocycline monotherapy compared with trimethoprim/sulfamethoxazole monotherapy for treatment of S. maltophilia infections. METHODS: Patients were identified via microbiology laboratory data and those with at least one positive culture for S. maltophilia were cross-referenced with pharmacy data to detect patients who received trimethoprim/sulfamethoxazole or minocycline. Patients initially receiving combination therapy were excluded. Our primary outcome was treatment failure, defined as receipt of alternative antibiotics with in vitro activity against S. maltophilia, isolation of S. maltophilia on repeat culture or death within 30 days of treatment. RESULTS: Forty-five patients were evaluated. Overall mortality rate was 9% and equal between groups; 41% of patients (9/22) who received trimethoprim/sulfamethoxazole and 30% (7/23) of patients who received minocycline experienced treatment failure (P = 0.67). Patients who received minocycline were more likely to have had a recent acute kidney injury (AKI) (43.5% versus 9%; P = 0.017) or chronic lung disease (52% versus 9%; P = 0.003). Logistic regression showed consistent results of non-inferiority of the primary outcome when controlling for rates of underlying lung pathology and recent AKI (P = 0.728). CONCLUSIONS: Treatment failure did not differ between patients receiving trimethoprim/sulfamethoxazole or minocycline monotherapy for treatment of S. maltophilia infections.

Retrospective cohort study evaluating the incidence of diabetic foot infections among hospitalized adults with diabetes in the United States from 1996-2010.

BACKGROUND: The prevalence of diabetes has increased over the last 2 decades; however, the national incidence of diabetic foot infections (DFIs) in the United States is unknown. We sought to determine national trends in DFIs among hospitalized adults in the United States over 15 years. METHODS: This was a retrospective cohort study of the U.S. National Hospital Discharge Survey from 1996-2010. Adult patients with a principal diagnosis of foot infection and a secondary diagnosis of diabetes were identified using ICD-9-CM codes. Incidence was defined as DFI discharges per 100 diabetes discharges. Independent risk factors for DFI among diabetics were identified using multivariable logistic regression. RESULTS: These data represent 1,059,552 DFI discharges over the study period. The incidence of DFI decreased from 1996 (2.3 DFIs/100 diabetes discharges) to 2010 (1.1 DFI/100 diabetes discharges). The proportion of patients experiencing lower-extremity amputation declined from 33.2% in 1996 to 17.1% in 2010. Peripheral vascular disease (odds ratio [OR], 2.89; 95% confidence interval [CI], 2.87-2.91), peripheral neuropathy (OR, 2.62; 95% CI, 2.60-2.64), and male sex (OR, 1.67; 95% CI, 1.66-1.68) were the leading risk factors for DFI. CONCLUSION: The incidence of DFI among hospitalized adults in the United States declined by more than half from 1996-2010.

Staphylococcus lugdunensis bacteremia and endocarditis treated with cefazolin and rifampin.

PURPOSE: This case report describes the treatment of a rare infection caused by Staphylococcus lugdunensis with cefazolin and rifampin. SUMMARY: A 48-year-old man with significant comorbidities was admitted to our institution with complaints of malaise, shortness of breath, and vague persistent pain. He was diagnosed with S. lugdunensis infective endocarditis and was treated with cefazolin continuous infusion for 10 days without resolution of bacteremia. As surgical intervention was deemed inappropriate, rifampin was added to the treatment regimen for its antibiofilm activity. After rifampin initiation, resolution of bacteremia was rapidly achieved. Subsequent blood cultures remained negative, and the patient was discharged home in stable condition to complete six weeks of i.v. cefazolin and rifampin therapy. The patient continued treatment, as documented by the infusion center, weekly for five weeks. The patient was rehospitalized during his sixth week of treatment due to impending respiratory failure, whereupon he was intubated and admitted to the intensive care unit. The patient's cardiac status gradually worsened over the following days, and he ultimately died. Blood cultures from days 1 and 2 of hospitalization revealed no bacterial growth at five days. CONCLUSION: Cefazolin and rifampin therapy in a hospitalized patient with bacteremia and aortic valve endocarditis caused by S. lugdunensis resulted in rapid eradication of the bacteremia. After more than five weeks of cefazolin-rifampin treatment, the patient was rehospitalized with worsening cardiac function and died. Blood cultures during the second admission were negative.

Simeprevir and sofosbuvir for treatment of chronic hepatitis C infection.

PURPOSE: Chronic hepatitis C infection affects a large proportion of the world's population and can lead to significant morbidity and mortality. The standard of care for treatment of hepatitis C infection has been peginterferon and ribavirin, with or without a first-generation protease inhibitor. In late 2013 and early 2014, sofosbuvir and simeprevir obtained regulatory approval, offering the first possibility for all-oral treatment regimens. We provide a review of the clinical efficacy and safety of sofosbuvir- and simeprevir-containing regimens. METHODS: Studies were identified in PubMed using the terms sofosbuvir and simeprevir in combination with hepatitis C. Abstracts of additional studies presented at professional meetings but not yet published were also reviewed. All Phase 3 trials published by August 1, 2014, as well as Phase 2 studies for which there was not a corresponding Phase 3 trial, were included in the review. FINDINGS: Simeprevir was studied with peginterferon and ribavirin in 7 published Phase 3 trials, with overall efficacy rates of 59% to 100%. Sofosbuvir was studied with ribavirin and with or without peginterferon in 6 Phase 3 trials with overall efficacy rates of 50% to 93%. Patient groups with lower response rates tended to have cirrhosis and be older, men, and previous null responders. Simeprevir and sofosbuvir were studied in combination in 1 Phase 2a study with overall efficacy of 92%. Additional studies demonstrated the efficacy and safety of sofosbuvir regimens in patients before and after liver transplantation. Overall, the simeprevir- and sofosbuvir-containing regimens were tolerated better or as well as peginterferon and ribavirin regimens, with fatigue, headache, and nausea the most common adverse events. IMPLICATIONS: Results from numerous Phase 3 clinical trials indicate that sofosbuvir- and simeprevir-containing regimens are highly effective and safe for the treatment of chronic hepatitis C infection. The approval of these 2 agents has led to a complete overhaul of published guidelines, with sofosbuvir- and simeprevir-containing regimens included in preferred regimens.

Safety and tolerability of high-dose weekly liposomal amphotericin B antifungal prophylaxis.

Children with hematologic malignancies are at an increased risk of invasive fungal infections and a greater risk has been seen with exposure to building construction. Prophylaxis with high-dose (IV) liposomal amphotericin B (L-AmB) 10 mg/kg once weekly was initiated in our high risk children based on previous pharmacokinetic studies. This treatment regimen was associated with a 26% incidence of adverse infusion reactions.

Retrospective analysis of resected primary colorectal cancer revealed no correlation between node harvest and node involvement.

OBJECTIVE: To analyze the correlation between lymph nodes harvest (LNH) and lymph nodes involvement (LNI). METHODS: A retrospective analysis was done from January 2002 - August 2008 (6.5 years). The data was obtained from medical records, pathology and radiology. The patients with primary colorectal carcinoma (CRC) including synchronous or metachronous cancer, were included. These patients were treated with curative or palliative intent. Exclusion criteria was recurrent colorectal cancer, cancer not operated, cancer not resected (stoma-only, open-close) and endomucosal resection. LNH and LNI were obtained. The data was analyzed and also compared with the literature and the national audit. RESULTS: There were 177 resections (mean=28 +/- 3 per annum). Male to female ratio was 0.9:1 and median age was 71 years. There were 112 (63.3%) colonic and 65 (36.7%) rectal cancers. There were 14 Anterio-posterior resections (APRs) (21.5% of all rectal resections). Eighty four percent of resections were elective (OR=2.2 p=0.003 compared to the national audit). Metastasis was found in 14.6% at presentation. Adenocarcinoma (not otherwise specified) NOS constituted 94% of all histology results. Median lymph node harvest was 12 (mean=13.4 p=0.08). There was no significant LNH-LNI correlation (r=0.17 p=0.02). Survival figures for stages I-III CRC revealed 3-year disease-free survival of 82% (all-stage=69%). CONCLUSION: LNI as a function of tumour and host behaviour is of prognostic significance whereas LNH may be a quality assurance (QA) tool.

A multicenter study of the pharmacokinetics of lisinopril in pediatric patients with hypertension.

The pharmacokinetic (PK) parameters of lisinopril were obtained in 46 children aged 6 months to 15 years. A lisinopril suspension (0.15 mg/kg per day) was administered to patients <6 years of age; the remaining children received lisinopril tablets, the daily dose being adjusted according to body weight, i.e., 2.5 mg if <25 kg, 5 mg if 25-45 kg, and 10 mg if >45 kg. Blood was drawn predose and on eight occasions postdose in children aged 4-15 years, and on five occasions in those aged <4 years. PK data are reported for the 46 children in terms of age groups: Group I (n=9), aged 6-23 months; Group II (n=8), aged 2-5 years; Group III (n=12), aged 6-11 years; Group IV (n=17), aged 12-15 years. The dose of lisinopril ranged from 3.07 mg/m(2) per day in Group I to 4.78 mg/m(2) per day in Group IV. C(max) of lisinopril, which occurred 5-6 h postdose, varied from 22 ng/ml in Groups I and II to 44 ng/ml in Groups III and IV; AUC(0-24 h) ranged from 301-311 ng.h/ml in Groups I and II to 550-570 ng.h/ml in Groups III and IV. No serious adverse events related to lisinopril were reported.