Bivalirudin dosing during prolonged intermittent renal replacement therapy: a case report.

As patients transition between dialysis modalities, and from the intra- to the inter-dialytic period, medications with a narrow therapeutic index that are cleared in dialysis may require dose adjustments and close monitoring. Three cases of patients receiving bivalirudin while converting from continuous to prolonged intermittent renal replacement therapy are reported. Details provided include flow rates and ultrafiltrate volume. In these cases, it appears pre-emptive dose adjustments may be unwarranted, and clinicians should be aware of potential rebound after cessation of dialysis.

Oral Vancomycin for Secondary Prophylaxis of Clostridium difficile Infection.

OBJECTIVE: To summarize and critically appraise the evidence regarding oral vancomycin prophylaxis (OVP) to prevent recurrent Clostridium difficile infections (RCDIs), identify potential consequences of this emerging practice, and highlight future directions of study. DATA SOURCES: A MEDLINE literature search of English-language publications from 1947 through September 2018 was performed using the search terms vancomycin and C difficile and prophylaxis. Clinical trials were identified on the National Library of Medicine clinical trials registry. STUDY SELECTION AND DATA EXTRACTION: All clinical studies (n = 3) assessing oral vancomycin for secondary prophylaxis of C difficile infection (CDI) were evaluated by all authors. Other search results and references in selected publications were used for background and discussion. DATA SYNTHESIS: OVP reduced the risk of RCDI in high-risk patients taking systemic antibiotics. Variable dosing regimens and lack of safety data are limitations. OVP may have an adverse impact on the gastrointestinal microbiome, but this was not examined in the clinical studies. Relevance to Patient Care and Clinical Practice: Although current studies are limited by methodological concerns, clinicians can consider vancomycin 125 mg orally once or twice daily in high-risk patients receiving broad-spectrum antibacterial agents. Results of ongoing trials will define the most appropriate regimen and its impact on outcomes, including collateral damage. CONCLUSIONS: OVP reduces the risk of RCDIs and should be considered on a case-by-case basis. Caution is warranted before routine use is implemented because the impact on long-term outcomes has not been assessed and the optimal regimen has not been defined.

Effectiveness and safety of oral anticoagulants in patients with sickle cell disease and venous thromboembolism: a retrospective cohort study.

Patients with sickle cell disease (SCD) experience initial and recurrent venous thromboembolism (VTE) more commonly and at a younger age than the general population, and it confers a higher mortality for patients with SCD. However, limited evidence is available to guide anticoagulant use for VTE treatment in this population. The primary objective of this study is to characterize the effectiveness and safety of direct oral anticoagulants (DOAC) and warfarin for VTE treatment among patients with SCD. This single-center retrospective study includes adult patients with SCD who were diagnosed with VTE. Data was obtained from review of electronic health records for the 6 months after VTE diagnosis. Among the 22 patients treated initially with a DOAC, 6 (27%) developed recurrent VTE, none experienced major bleeding, and 3 (14%) experienced clinically relevant non-major bleeding (CRNMB). Similarly, of 15 patients initially treated with warfarin, 3 (20%) developed a recurrent VTE, 1 (7%) experienced major bleeding, and 2 (13%) experienced CRNMB. Twelve patients received more than one oral anticoagulant during the study period, most commonly due to a recurrent VTE, concern for non-adherence, or subtherapeutic INR. Overall, the incidence of VTE recurrence and bleeding events were similar between groups, but occurred at a higher rate than those found in major clinical trials of anticoagulant agents. Prescribers should continue to individualize therapeutic decision-making regarding oral anticoagulant therapy for VTE treatment for individuals with SCD based on patient-specific factors and anticipated ability to adhere to the drug regimen or required monitoring.

Rapidity of Correction of Hyponatremia Due to Syndrome of Inappropriate Secretion of Antidiuretic Hormone Following Tolvaptan.

BACKGROUND: Tolvaptan effectively corrects hyponatremia due to the syndrome of inappropriate secretion of antidiuretic hormone (SIADH), but undesired overcorrection can occur. We hypothesized that pretherapy parameters can predict the rapidity of response to tolvaptan in SIADH. STUDY DESIGN: Multicenter historical cohort study. SETTING & PARTICIPANTS: Adults with SIADH or congestive heart failure (CHF) treated with tolvaptan for a serum sodium concentration ≤ 130 mEq/L at 5 US hospitals. PREDICTORS: Demographic and laboratory parameters. OUTCOMES: Rate of change in serum sodium concentration. MEASUREMENTS: Spearman correlations, analysis of variance, and multivariable linear mixed-effects models. RESULTS: 28 patients with SIADH and 39 patients with CHF treated with tolvaptan (mean baseline serum sodium, 120.6 and 122.4 mEq/L, respectively) were studied. Correction of serum sodium concentration > 12 mEq/L/d occurred in 25% of patients with SIADH compared to 3% of those with CHF (P<0.001). Among patients with SIADH, the increase in serum sodium over 24 hours was correlated with baseline serum sodium concentration (r=-0.78; P<0.001), serum urea nitrogen concentration (SUN; r=-0.76; P<0.001), and estimated glomerular filtration rate (r=0.58; P=0.01). Baseline serum sodium and SUN concentrations were identified as independent predictors of change in serum sodium concentration in multivariable analyses. When patients were grouped into 4 categories according to baseline serum sodium and SUN median values, those with both low baseline serum sodium (≤121 mEq/L) and low baseline SUN concentrations (≤10mg/dL) exhibited a significantly greater rate of increase in serum sodium concentration (mean 24-hour increase of 15.4 mEq/L) than the other 3 categories (P<0.05). Among patients with CHF, only baseline SUN concentration was identified as an independent predictor of change in serum sodium concentration over time. LIMITATIONS: Lack of uniformity in serial serum sodium concentration determinations and documentation of water intake. CONCLUSIONS: Baseline serum sodium and SUN values are predictive of the rapidity of hyponatremia correction following tolvaptan use in SIADH. We advise caution when dosing tolvaptan in patients with both low serum sodium and SUN concentrations.

Fosaprepitant for the Management of Refractory Pain in a Patient with Cancer-Related Dermatomyositis.

OBJECTIVE: Optimal pain management often requires multiple pharmacological interventions with the goal of disrupting the pain-signaling pathway and targeting the underlying pathophysiology. Off label use of nonpain medications may have a role in treating refractory pain syndromes. BACKGROUND: We report a case of a 60-year-old female with refractory nociceptive and neuropathic pain. Conventional therapies were either ineffective or fraught with side effects. Given the underlying inflammatory nature of her pain syndrome, and the role of substance P (SP) in pain transmission and modulation, we decided to use fosaprepitant, an SP and neurokinin-1 (NK1) receptor antagonist. The patient tolerated fosaprepitant and experienced acceptable analgesia without compromising her mental functioning. DESIGN: Study and analysis of a case of a patient with refractory mixed, nociceptive, and neuropathic pain syndrome treated with fosaprepitant. RESULTS AND DISCUSSION: Fosaprepitant is a potentially novel adjuvant therapy for the treatment of refractory inflammatory pain syndromes in palliative care.

Hepatorenal Acute Kidney Injury and the Importance of Raising Mean Arterial Pressure.

BACKGROUND: The efficacy of vasoconstrictors in hepatorenal syndrome (HRS) is variable. We hypothesized that the effectiveness of vasoconstrictor therapy in improving kidney function ultimately relates to the magnitude of the achieved mean arterial pressure (MAP) increase. METHODS: A retrospective study was conducted to identify cirrhotic individuals treated with vasoconstrictors for acute kidney injury (AKI) presumably caused by HRS to examine the relationship between change in MAP and change in serum creatinine (sCr) using multivariate mixed linear regression. RESULTS: Among 73 patients treated with midodrine/octreotide, change in MAP inversely correlated with change in sCr (p = 0.0005). The quartile with the greatest increase in MAP (+15.9 to +29.4 mm Hg) was associated with a subsequent absolute decrease in sCr. The strength of the correlation increased when the analysis was restricted to those who met the HRS criteria (n = 27, p = 0.002), where the third (+5.3 to +15.6 mm Hg) and fourth (+15.9 to +20.9 mm Hg) quartiles of MAP change were associated with a decrease in sCr. A similar but stronger correlation was found among 14 patients treated with norepinephrine either after failing midodrine/octreotide (n = 10) or de novo (n = 4; p = 0.002), where a rise in MAP of +19.2 to 25 mm Hg was associated with a larger reduction in sCr. Associations remained significant after adjustment for baseline parameters. CONCLUSIONS: The magnitude of MAP rise during HRS therapy with midodrine/octreotide or norepinephrine correlated with a reduction in sCr concentration. Our results suggest that achieving a pre-specified target of MAP increase might improve renal outcomes in hepatorenal AKI.

Case-control study and case series of pseudohyperphosphatemia during exposure to liposomal amphotericin B.

Pseudohyperphosphatemia due to an interaction between liposomal amphotericin B and the Beckman Coulter PHOSm assay occurs sporadically and remains underrecognized in clinical practice. This retrospective case-control study compares the incidences of hyperphosphatemia in adult inpatients exposed to liposomal amphotericin B or a triazole. A case series of patients with confirmed pseudohyperphosphatemia is described. A total of 80 exposures to liposomal amphotericin B and 726 exposures to triazoles were identified. Among subjects without chronic kidney disease and no concomitant acute kidney injury, hyperphosphatemia occurred more often during liposomal amphotericin B therapy than during triazole therapy (40% [14/35 cases] versus 10% [47/475 cases] of cases; P < 0.01; adjusted odds ratio, 5.2 [95% confidence interval {CI}, 2.3 to 11.9]). Among individuals with chronic kidney disease and no concomitant acute kidney injury, hyperphosphatemia also occurred more often during liposomal amphotericin B exposure (59% [10/17 cases] versus 20% [34/172 cases] of cases; P < 0.01; adjusted odds ratio, 6.0 [95% CI, 2.0 to 18.0]). When acute kidney injury occurred during antifungal exposure, the frequencies of hyperphosphatemia were not different between treatments. Seven episodes of unexpected hyperphosphatemia during liposomal amphotericin B exposure prompted a confirmatory test using an endpoint-based assay that found lower serum phosphorus levels (median difference of 2.5 mg/dl [range, 0.6 to 3.6 mg/dl]). Liposomal amphotericin B exposure confers a higher likelihood of developing hyperphosphatemia than that with exposure to a triazole antifungal, which is likely attributable to pseudohyperphosphatemia. Elevated phosphorus levels in patients receiving liposomal amphotericin B at institutions using the Beckman Coulter PHOSm assay should be interpreted cautiously.

Evaluation of Ward Management of Diabetic Ketoacidosis.

Ward management of diabetic ketoacidosis (DKA) using subcutaneous insulin in specific patient populations is safe and effective, but insulin administered by continuous infusion has not been analyzed in this setting. This retrospective cohort study utilizing a nursing-driven, continuous infusion insulin calculator demonstrated safe and effective treatment of patients with DKA on medicine wards.

Hemarthrosis in a patient on warfarin receiving ceftaroline: a case report and brief review of cephalosporin interactions with warfarin.

OBJECTIVE: To report a possible interaction between warfarin and ceftaroline, resulting in hemarthrosis, and provide readers with an understanding of mechanisms of interaction between cephalosporins and warfarin. CASE SUMMARY: Ceftaroline was prescribed for an 85-year-old female with a therapeutic international normalized ratio (INR) hospitalized for the treatment of cellulitis. She was subsequently readmitted with shoulder pain and a supratherapeutic INR. The patient was diagnosed with hemarthrosis, presumably related to elevated INR. Evaluation using the drug interaction probability scale for warfarin and ceftaroline yielded a score consistent with a possible or probable interaction. DISCUSSION: Cephalosporins may interact with warfarin through a variety of mechanisms, including potentiation of hypoprothrombinemia related to certain side chain groups, inhibition of P-glycoprotein, or alteration of gastrointestinal flora. All mechanisms reported in the medical literature as of April 2012 are briefly examined, but the latter is the most reasonable mechanism for a ceftaroline interaction with warfarin. CONCLUSIONS: Health care providers should consider closely monitoring patients receiving antibiotics with activity against Enterobacteriaceae and warfarin, even if no direct mechanism of interaction has been reported. Further research regarding a ceftaroline-warfarin interaction is warranted.

Bullous dermatosis associated with vancomycin extravasation.

Cutaneous side effects related to vancomycin therapy have been reported including histamine-related reactions, linear IgA bullous dermatosis, Stevens-Johnson syndrome, maculopapular rash and drug rash with eosinophilia and systemic symptoms. In all instances, these reports were due to the systemic administration of vancomycin and subsequent immunological reactions to the medication. Drug extravasation into soft tissues can result in a variety of clinical outcomes usually related to physiochemical properties of the drug extravasated and its diluents or pharmacologic effects on the vasculature and tissue. The authors report a patient who experienced vancomycin extravasation that resulted in a localized bullous eruption resembling linear IgA bullous dermatosis, a phenomenon not previously described in the literature.

Multidrug-resistant Enterococcus faecium endocarditis treated with combination tigecycline and high-dose daptomycin.

OBJECTIVE: To report a case of multidrug-resistant Enterococcus faecium requiring combination antibacterial therapy. CASE SUMMARY: A 39-year-old female presented with chest pain and a history of endocarditis 3 years prior to admission. Blood cultures were positive for E. faecium. She was treated initially with daptomycin 6 mg/kg daily, which was later increased to 8 mg/kg daily despite poor gentamicin clearance. A variety of antibiotics were used in combination with daptomycin, but the patient remained febrile, with positive blood cultures revealing vancomycin minimum inhibitory concentration (MIC) greater than 256 microg/mL and daptomycin MIC 3 microg/mL (and later, 4 microg/mL). Following the addition of tigecycline, the patient experienced rapid clinical and microbiologic improvement, and blood cultures remained negative 9 weeks after discharge. DISCUSSION: Limited clinical data support the use of daptomycin for the treatment of E. faecium endocarditis, and information regarding the effects of escalating doses and combination therapy is scant. After failing multiple combination regimens, this patient responded to a combination of tigecycline and daptomycin. Daptomycin 8 mg/kg daily did not result in creatine kinase elevation in the face of evidence of possible renal dysfunction. CONCLUSIONS: Increasing doses of daptomycin may enhance efficacy without compromising safety, even in patients with some renal dysfunction. The combination of daptomycin and tigecycline may be useful for the treatment of multidrug-resistant E. faecium.