Nicole Bohm

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 μg/mL and daptomycin MIC 3 μg/mL (and later, 4 μg/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.

Dabigatran-associated subdural hemorrhage: using thromboelastography (TEG(®)) to guide decision-making.

Novel oral anticoagulants present challenges and uncertainties in the management of hemorrhagic emergencies. An 84-year-old man taking dabigatran presented with a subdural hematoma requiring neurosurgical intervention. Routine coagulation assays were prolonged at admission and following administration of Factor VIII Inhibitor Bypassing Activity (FEIBA). Thromboelastography (TEG®) was utilized to assess clot dynamics prior to placement of a subdural drain, which was safely inserted despite a prolonged thrombin time (TT). Exclusive reliance on the TT may delay necessary interventions. TEG® may be a valuable tool to investigate hemostasis in patients on dabigatran requiring emergent procedures.

Bullous dermatosis associated with vancomycin extravasation.

Abstract: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.

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.

Case Report and Cohort Analysis of Drug-Induced Liver Injury Associated with Daptomycin

ABSTRACT A patient receiving daptomycin developed asymptomatic transaminitis and hyperbilirubinemia without concurrent multiorgan dysfunction or elevation of his creatinine kinase level. After ruling out other etiologies, the liver injury was attributed to daptomycin and was subsequently resolved. A single-center retrospective cohort analysis of baseline and follow-up liver function panels (n = 614) from all admissions from 2008 to 2013 during which daptomycin was administered did not reveal any other cases of probable or definite drug-induced liver injury associated with daptomycin.

Appropriateness of direct oral anticoagulant dosing for venous thromboembolism treatment

Adherence to FDA-approved dosing for the direct oral anticoagulants (DOACs) based on renal function, hepatic function, and concomitant medications in a real-world setting has not been evaluated. The purpose of this retrospective cohort analysis was to determine the prescribing accuracy of DOAC dosing for venous thromboembolism (VTE) treatment compared with enoxaparin. The secondary outcomes were to describe the incidence of in-hospital VTE recurrence and bleeding on DOAC therapy. The study included 168 patients with 261 admissions for the DOAC group and 639 patients with 841 admissions for the enoxaparin group. Dosing was appropriate in 235/261 (90.0%) of patient admissions in the DOAC group. Among the DOAC doses administered, 233/2246 (10.4%) were contraindicated based on renal function, hepatic function, or drug interactions compared with 322/7293 (4.4%) of administered enoxaparin doses evaluated based on renal function, p < 0.001. Three recurrent VTEs, 3 major bleeding events, 1 probable major bleeding event, and 3 clinically relevant non-major bleeding events were observed during the study period. Although a majority of DOAC doses administered were appropriate, further education and close monitoring of these agents are warranted to increase appropriateness of therapy and improve patient safety.

Case-Control Study and Case Series of Pseudohyperphosphatemia during Exposure to Liposomal Amphotericin B

ABSTRACT 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.

Daptomycin Dosing Strategies in Patients Receiving Thrice-Weekly Intermittent Hemodialysis

Objective: To determine the optimal dosing regimen of daptomycin in patients receiving thrice-weekly hemodialysis. Data Sources: Literature was accessed via PubMed using the terms daptomycin and hemodialysis through July 2013. Reference citations from publications identified were reviewed. Study Selection and Data Extraction: English language articles meeting the search criteria were evaluated. Studies were included if they addressed either thrice-weekly or intradialytic daptomycin administration. Data Synthesis: Daptomycin is approved for the treatment of bloodstream infections due to methicillin-resistant Staphylococcus aureus and other Gram-positive organisms. Rapid bactericidal activity and limited potential for drug interactions make daptomycin an attractive agent. However, the daptomycin prescribing information recommends dosing every 48 hours in patients receiving hemodialysis, which results in dyssynchrony of dosing and dialysis sessions every other week. Studies evaluating a dosing regimen of daptomycin thrice weekly, coinciding with dialysis, indicate that pharmacokinetic and pharmacodynamic parameters are appropriate for therapeutic success. However, to maintain adequate serum drug concentrations throughout the 72-hour interdialytic period, an additional 50% of the dose should be provided to account for the longer interval. Intradialytic dosing, with the administration of daptomycin infusion beginning during the final 30 minutes of dialysis, may also require a dose increase. Limited clinical outcomes data have been reported, but no significant safety concerns have been identified. Conclusions: Administration of daptomycin doses thrice weekly on hemodialysis days appears to be both safe and reasonable. Doses should be increased preceding the 72-hour interdialytic period or if daptomycin is infused during dialysis.

Evaluating the safety and effectiveness of venous thromboembolism prophylaxis in patients with sickle cell disease.

Nearly every component of hemostasis is altered in sickle cell disease (SCD), yet little evidence exists to guide utilization of venous thromboembolism prophylaxis (VTEP) in this population. This retrospective cohort study included 135 adult patients admitted with a diagnosis of SCD vaso-occlusive crisis to the general medicine service at a tertiary care academic medical center from August 1, 2011 to August 1, 2013. If VTEP was discontinued, the medical record was reviewed for suspicion of VTE, hemorrhage, heparin-induced thrombocytopenia (HIT), or other adverse events. The primary objective was to characterize the safety and effectiveness of VTEP in SCD. The secondary objective was to assess the correlation of VTE with risk factors documented in the general medical population. Most patients (116/135, 85.9%) were prescribed VTEP upon admission, with early discontinuation in 23 patients (19.8%). Reasons for discontinuation included suspicion of VTE (10/116, 8.6%), hemorrhage (5/116, 4.3%), and/or HIT (4/116, 3.4%). Since patients with SCD receiving standard VTEP regimens appear to have similar outcomes compared to medically ill patients in prospective studies, using these regimens appears to be safe when indicated in the opinion of the provider. Once daily injections may be preferred in order to optimize adherence.

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.