Jennifer D. Twilla

Vancomycin‐resistant Enterococcus bacteremia: An evaluation of treatment with linezolid or daptomycin

BACKGROUND Due to high rates of resistance and a limited number of efficacious antimicrobials for vancomycin-resistant Enterococcus (VRE), appropriate antibiotic selection is vital to treatment success. The purpose of this study was to assess clinical and microbiologic outcomes associated with the use of linezolid or daptomycin in the treatment of VRE bacteremia. METHODS A retrospective analysis of adult patients with VRE bacteremia between January 2004 and July 2009 was conducted at a tertiary care hospital in the United States. Clinical and microbiologic outcomes for both therapies were evaluated using multiple criteria. RESULTS Of the 361 patients with VRE bacteremia identified, 201 were included in the study (linezolid group, n = 138; daptomycin group, n = 63). More patients in the daptomycin group had hematologic malignancies (33% vs 14%) or received liver transplants (13% vs 4%). There was no difference in clinical or microbiologic cure between the linezolid and daptomycin groups (74% vs 75% and 94% vs 94%, respectively). Recurrence was documented in 3% of linezolid patients vs 12% of daptomycin patients (P = 0.0321). Reinfection was noted in 1% of patients in the linezolid group vs 6% of patients in the daptomycin group (P not significant). The average length of stay (LOS) was 37 days for the linezolid group vs 40 days for the daptomycin group (P not significant). Overall mortality was 20%, occurring in 25/138 linezolid patients vs 15/63 daptomycin patients (P not significant). CONCLUSIONS No differences in clinical or microbiologic cure rates, LOS, or mortality were identified between the groups. Various factors may have contributed to the significantly higher recurrence of VRE bacteremia in daptomycin patients. This study suggests that linezolid and daptomycin appear equally efficacious in the treatment of VRE bacteremia.

Telavancin for the treatment of methicillin-resistant Staphylococcus aureus osteomyelitis

Sir, With a rapid increase in invasive infections caused by methicillinresistant Staphylococcus aureus (MRSA), there is a demand for antimicrobials with enhanced activity against MRSA. The concentration-dependent, bactericidal lipoglycopeptide telavancin was approved in 2009 for treatment of complicated skin and skin-structure infections due to susceptible organisms. The emergence of glycopeptide resistance and clinical failures of vancomycin therapy in invasive MRSA infections, including osteomyelitis, has led to the unlabelled use of alternatives to vancomycin for treatment of these infections. We report four patients with MRSA osteomyelitis who failed standard vancomycin therapy and were successfully retreated with telavancin and surgical intervention. A patient was admitted with inability to ambulate for 1 day. This was preceded by a 4 day history of progressive leg weakness and a 2 month history of lower back pain. There also was a history of multiple carbuncles of the face, neck and buttocks, but no antimicrobial therapy had been administered for these. No fever was present. White blood cell (WBC) count, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were elevated. Magnetic resonance imaging (MRI) revealed T4–7 vertebral osteomyelitis as well as T5–6 discitis with an anterior epidural phlegmon and stenosis with spinal cord compression. T5–6 laminectomy with drainage of the epidural abscess and decompression of the spinal cord was performed. Treatment with cefepime 2 g intravenously (iv) every 8 h and vancomycin 18 mg/kg iv every 12 h was begun. Blood cultures were negative, but MRSA was identified from culture of the abscess 72 h later. Vancomycin MIC was 2 mg/L, linezolid MIC was 2 mg/L and daptomycin MIC was 1 mg/L. Therapy was changed to daptomycin 6 mg/kg iv daily. After the back pain and WBC were noted to have improved, the patient was discharged to a physical rehabilitation centre to complete a planned 8 week course of daptomycin. Two weeks later, because of progressive leg weakness, fever and re-elevation of WBC, ESR and CRP values, the patient was readmitted. MRI showed recurrent epidural abscess at T5–6. T4–6 laminectomy was performed with drainage of the recurrent abscess and cord decompression. Culture of the abscess again grew MRSA (vancomycin MIC 2 mg/L, daptomycin MIC 1 mg/L and telavancin MIC 0.38 mg/L). Treatment was changed to telavancin 10 mg/kg iv daily. While receiving 10 weeks of telavancin therapy, there was resolution of fever and leucocytosis and normalization of ESR and CRP values. Gradual recovery of leg strength and ability to ambulate was noted. There was no evidence of recurrent infection 4 months after completion of telavancin. A patient with the sudden onset of leg weakness and urinary incontinence was transferred from another hospital after a lengthy hospitalization with MRSA bacteraemia (vancomycin MIC 1 mg/L, linezolid MIC 2 mg/L and daptomycin MIC ≤0.5 mg/L) from cellulitis complicated by sepsis, respiratory failure with pneumonia, renal dysfunction and hepatic encephalopathy. Despite sequential treatment with adequate doses of vancomycin (14 days), linezolid (7 days) and daptomycin (14 days), the MRSA bacteraemia persisted with unchanged MIC values. Fever was absent. WBC, ESR and CRP values were elevated. Transthoracic echocardiography and transoesophageal echocardiography (TOE) did not reveal valvular vegetations. MRI showed an epidural abscess extending from T6 to L2, L1 vertebral osteomyelitis and a left psoas abscess. Telavancin 10 mg/kg iv daily was begun. T6–7 decompressive laminectomy was performed and the abscess was evacuated. Cultures of the blood and abscess grew MRSA with unchanged MIC values of vancomycin, linezolid and daptomycin. Telavancin MIC was 0.25 mg/L. Telavancin was administered for 8 weeks with improvement in leg weakness and normalization of WBC, ESR and CRP values. There was no evidence of recurrence 7 months after completion of telavancin. A patient presented with a 1 week history of right hip pain after a fall. Fever and leucocytosis were present. There was a remote history of a gunshot wound to the right hip. CT revealed a 2 cm mass in the left upper lung and a large right hip effusion. MRI was consistent with right hip septic arthritis and osteomyelitis of the right acetabulum, femoral head, femoral neck and lesser trochanter. Blood cultures grew MRSA (vancomycin MIC 1 mg/L, linezolid MIC 1 mg/L and daptomycin MIC ≤0.5 mg/L). Ceftriaxone 2 g iv daily and vancomycin 13 mg/kg iv every 12 h were begun and continued for 5 days. Research letters

Treatment of Acute Hepatic Encephalopathy Comparing the Effects of Adding Rifaximin to Lactulose on Patient Outcomes

Objectives: Rifaximin is approved for the reduction of hepatic encephalopathy (HE) recurrence in patients with chronic liver disease (CLD); however, few studies have evaluated the benefit of adding rifaximin to lactulose for treatment of acute HE. The aim of this study was to determine the impact of combination therapy with lactulose and rifaximin on hospital length of stay (LOS) and readmission rates. Methods: A retrospective study of patients admitted to an adult hospital within the Methodist LeBonheur Healthcare (MLH) System in Memphis, Tennessee, between 2007 and 2012 was conducted. Patients were identified via International Classification of Diseases, Ninth Revision (ICD-9) coding for liver cirrhosis. Results: Of the 173 patients included, 87 (50%) received lactulose monotherapy and 62 (36%) combination therapy, while 24 (14%) underwent therapy escalation. Median LOS was 6 days in monotherapy group and 8 days in combination group (P = .9). At 180 days, patients receiving combination therapy had fewer readmissions for HE than those receiving monotherapy (2.4% vs 16.2%, P = .02). Conclusion: Addition of rifaximin to lactulose for treatment of acute HE did not reduce hospital LOS; however, it did result in lower readmission rates for HE at 180 days.

Evaluation of venous thromboembolism prophylaxis in patients with chronic liver disease

BACKGROUND The incidence of venous thromboembolism (VTE) in chronic liver disease (CLD) patients has been reported to be 0.5% to 6.3%. Studies report the use of thromboprophylaxis in CLD patients as suboptimal, with at least 75% of patients receiving no prophylaxis. OBJECTIVE To describe the use of VTE prophylaxis in CLD patients. DESIGN A retrospective review. SETTING Tertiary-care academic medical center. PATIENTS Inpatient admissions from August 2009 through July 2011 with CLD diagnosis. INTERVENTION None. MEASUREMENTS Initiation and type of thromboprophylaxis, incidence of VTE, bleeding events, hospital length of stay, in-hospital mortality, 30-day readmission for VTE. RESULTS Of the 410 patients included, 225 (55%) patients received thromboprophylaxis. For patients with international normalized ratio (INR) >2.0, a significant decrease in overall thromboprophylaxis use and pharmacologic prophylaxis use was seen compared to those with INR 1.4 to 2.0 (P = 0.013 and P < 0.001, respectively). Overall incidence of VTE was 0.7%. Fifteen bleeding events occurred (3.7%): 9 on mechanical prophylaxis, 1 on pharmacologic, 3 on combination, and 2 with no prophylaxis. The majority of patients experiencing a bleeding event had an INR >2.0 (P = 0.001). CONCLUSION The use of thromboprophylaxis in CLD patients is higher in our study than previous reports but remains suboptimal. Use of VTE pharmacologic prophylaxis does not appear to increase bleeding in CLD patients with INR ≤2.0. Further studies are needed to provide additional safety data.

Prevention of stent thrombosis with reduced dose of prasugrel in two patients undergoing treatment of cerebral aneurysms with pipeline embolisation devices.

Prevention of intracranial stent thrombosis with dual-antiplatelet therapy is widely used in neuroendovascular procedures. However, the rising incidence of inadequate platelet inhibition with clopidogrel may increase complications following stent placement, especially with newer devices that possess a larger total metal surface area. While there are recent reports of prasugrel as an alternative to clopidogrel, there is no clinical evidence in neurointerventional patients regarding the use of a lower maintenance dose as an alternative strategy to gain adequate platelet inhibition while possibly reducing the risk of bleeding. We present 6-month efficacy and safety outcomes of two patients undergoing elective pipeline embolisation that were found to have inadequate platelet response to clopidogrel and subsequently transitioned to prasugrel 5 mg daily for the prevention of stent thrombosis.

Nitrofurantoin-induced hepatotoxicity: a rare yet serious complication.

Abstract Nitrofurantoin is a commonly prescribed antibiotic for the treatment of recurrent uncomplicated urinary tract infections. Its importance has been emphasized by the current international clinical practice guidelines for the management of uncomplicated cystitis. Since its introduction into clinical practice, nitrofurantoin has been associated with various adverse effects, including hepatotoxicity. We searched the English-language literature using PubMed and SCOPUS for the period 1961 through the end of February 2013. Key search terms included “nitrofurantoin AND hepatotoxicity” as well as “nitrofurantoin AND hepatitis.” When studies or case reports were found, we assessed articles cited in those publications. A broad spectrum of liver toxicity associated with nitrofurantoin use has been reported, ranging from acute hepatitis, granulomatous reaction, cholestasis, or autoimmune-mediated hepatitis to chronic active hepatitis that could lead to cirrhosis or death. The mechanism of hepatotoxicity is poorly understood, but it is believed to be the result of an immunologic process or a direct cytotoxic reaction. It has been postulated that prolonged exposure to nitrofurantoin, female sex, advanced age, and reduced renal function increase the risk of developing hepatotoxicity. For the management of severe cases, corticosteroids have been used along with nitrofurantoin discontinuation. Because of mixed results, the utility of corticosteroids has not been proven and should be used judiciously. Given the severity and seriousness of the adverse effect of hepatotoxicity, clinicians should weigh the risks and benefits of nitrofurantoin before initiating therapy, especially in long-term prophylaxis in high-risk patients. Clinicians also should be well versed in recognizing and managing liver injury associated with nitrofurantoin.

Hemolytic Anemia Induced by Pegloticase Infusion in a Patient With G6PD Deficiency.

To the Editor: P egloticase is a recombinant form of uricase, which is an enzyme that promotes the conversion of uric acid to allantoin subsequently decreasing uric acid levels. Rasburicase and pegloticase share similar mechanisms of action; however, pegloticase is pegylated, which affords a longer half-life and less frequent administration compared with rasburicase. Pegloticase is given as an infusion, which can cause a hypersensitivity reaction, requiring premedication with antihistamines and corticosteroids. However, limited information exists with regard to hemolysis after pegloticase infusions. In contrast, there have been multiple reports of hemolytic anemia after rasburicase administration, typically occurring within 2 to 4 days of initiation. Although the incidence is low (<1%), the severity of the potential reaction resulted in a boxed warning in the package labeling. During the conversion of uric acid to allantoin, an oxidation reaction is catalyzed by the uricase enzyme, which produces hydrogen peroxide as a by-product. The inability of the body to break down hydrogen peroxide in G6PD-deficient patients can result in hemolytic anemia. Although pegloticase is contraindicated in G6PD deficiency because of risk of hemolytic anemia development, there are limited data available regarding routine testing in high-risk patient populations before receiving this medication. We report a case of hemolytic anemia in a patient with G6PD deficiency after receiving pegloticase infusion. A 57-year-old African American man presented to the emergency department complaining of 3 days of weakness and tea-colored urine and 1 day of diarrhea. On the day of admission, he also reported experiencing shortness of breath with weakness along with a new finding of yellowing of his eyes. His medical history included human immunodeficiency virus, alcoholic cirrhosis, hypertension, diabetes, gout, and depression. Home medications were as follows: raltegravir 800 mg oral daily, abacavir-lamivudine 600 mg/ 300 mg oral daily, amlodipine 5 mg oral

Hyperammonemic Encephalopathy due to Valproic Acid and Topiramate Interaction

Valproic acid-induced hyperammonemic encephalopathy is a rare yet serious adverse drug reaction. Medication interactions such a valproic acid and topiramate can precipitate an event. We present the case of a 52-year-old female that presented with acute mental status change and hypersomnolence due to hyperammonemia caused by a valproic acid derivative. The patient improved after withdrawal of the offending medications and treatment with lactulose. Clinicians should remain hypervigilant in monitoring for valproic acid-induced hyperammonemic encephalopathy and risk factors such as polypharmacy.

Evaluation of prokinetic agents used in the treatment of gastroparesis

Abstract Background/Aim: Hospitalizations due to gastroparesis have increased in the last 20 years with limited advancements in pharmacologic therapy. Although therapy primarily consists of prokinetic agents, little is known about their effects on hospital outcomes. The aim of our study was to determine whether common prokinetic therapies (metoclopramide and erythromycin) improve outcomes in gastroparesis patients. Methods: A retrospective review of adult patients admitted with a primary diagnosis of gastroparesis between 7 January 2011 and 7 January 2014 was conducted. Patients were divided into two groups based on whether they received prokinetic therapy (PRO) during hospitalization or not (NO). Groups were compared to determine length of stay (LOS), 30-day readmission rates, and risk factors affecting these outcomes. Results: Of the 82 patients included in our study, 57 received prokinetic therapy. Mean length of stay (LOS) was 5.8 ± 4.2 days, with a significantly shorter LOS in the NO group (3.7 ± 1.9 vs. 6.7 ± 4.5; p = 0.002). Among patients studied, 30.5% were readmitted within 30 days from discharge with no significant reduction in the PRO group (35.1% PRO vs. 20% NO; p =0.23). Patients with idiopathic gastroparesis had significantly longer LOS (6.9 ± 4.6 vs. 4.2 ± 2.8; p = 0.003). In the PRO group, those who received intravenous (IV) therapy had a significantly shorter LOS (4.9 ± 2.5 IV vs. 8.0 ± 5.3 oral; p = 0.01). Conclusions: Treatment of gastroparesis patients with prokinetic agents did not shorten the LOS nor decrease 30-day readmission rates. In those receiving prokinetics, the IV route was associated with reduced LOS.

A review on cardiovascular effects of newer hypoglycaemic medications

Abstract Cardiovascular disease (CVD) is the most prevalent cause of morbidity and mortality in diabetic patients. Improvement in cardiovascular complications with glycaemic control and managing cardiovascular risk factors is well established. However, the impact of hypoglycaemic medications on CVD is of increasing importance. In 2008, the U.S. Food and Drug Administration issued study regulations for hypoglycaemic agents after rosiglitazone was shown to increase the incidence of myocardial infarction, and the European Medicines Agency provided their own guidance in 2012. As a result, multiple studies have been published evaluating the cardiovascular safety of newer hypoglycaemic medications. Empagliflozin and liraglutide are among the newer agents that have shown cardiovascular benefit and are now recommended for patients with CVD or are at an increased risk of CVD per the 2017 American Diabetes Association Guidelines. Given the influx of new literature and other ongoing studies, it is important to understand the cardiovascular safety of newer hypoglycaemic medications. The purpose of this article is to provide a comprehensive review of clinical trials conducted evaluating cardiovascular outcomes of newer hypoglycaemic medications and their role within diabetic management. Key Messages With the prevalence of cardiovascular disease in diabetic patients, clinicians should develop a medication regimen that provides both sufficient efficacy for diabetes while also maintaining cardiovascular safety. Of the new diabetic classes, empagliflozin, a sodium-glucose co-transporter 2 inhibitor, and liraglutide, a glucagon-like peptide-1 receptor agonist, have shown cardiovascular benefit in diabetic patients with established cardiovascular disease and are now recommended in current guidelines for this population. Ongoing trials will give more insight to whether cardiovascular benefit is a class effect with sodium-glucose co-transporter 2 inhibitors and glucagon-like peptide-1 receptor agonists and the cardiovascular safety of dipeptidyl peptidase-4 inhibitors.