1980 Correspondence / American Journal of Emergency Medicine 37 (2019) 1963-1988

anet alfa is currently the only FDA approved agent for the reversal of FXa inhibitors and should at minimum facilitate discussions amongst facilities on whether or not to add to their institutional formulary.

The American College of Cardiology has issued a guidance sheet, which now recommends andexanet alfa as first line therapy for the reversal of apixaban and rivaroxaban. Absent from their formal recommendation is edoxaban, but this is secondary to the low vol- ume of subjects who were enrolled in the ANDEXA-4 trial who were receiving edoxaban. The Society of Critical Care Medicine/ Neurocritical care Society guidelines have not updated since andexanet alfa’s approval but do have a section that mentions if available to consider andexanet alfa use. Also, it is important to highlight the heterogeneity between the majority of the studies evaluating PCC or andexanet alfa as it relates to how they mea- sured hemostasis and safety parameters. In addition, each study that has evaluated FXa inhibitor reversal has not had a comparator group, which can lead to major confounders and bias. While an FDA approved agent for FXa inhibitor reversal was certainly wel- comed there remains ambiguity as to which agent should be uti- lized first, as Salvage therapy, or even combination.

Brian W. Gilbert PharmD ^* Jacob A. Reeder PharmD

Wesley Medical Center Department of Pharmacy, 550 N. Hillside Ave,

Wichita, KS 67214, United States of America

* Corresponding author.

E-mail address: [email protected] (B.W. Gilbert)

Mohammed A. Alkhalifah MD

Wesley Medical Center Department of Pharmacy, 550 N. Hillside Ave,

Wichita, KS 67214, United States of America

David A. Moran PharmD

Wesley Medical Center Department of Pharmacy, 550 N. Hillside Ave,

Wichita, KS 67214, United States of America

Michael A. Corvino PharmD

Fetter Health Care Network, 51 Nassau St, Charleston, SC, United States

of America

15 March 2019

https://doi.org/10.1016/j.ajem.2019.04.007

References

1. Uppuluri E, McComb M, Shapiro N. Implementation of a direct oral anticoagulation screening service at a large academic medical center provided by a pharmacist-managed antithrombosis clinic as a method to expand antithrombotic stewardship efforts. J Pharm Pract 2018 Sep 13 [Epub ahead of print].
2. Howard M, Lipshutz A, Roess B, et al. Identification of risk factors for inappropriate and suboptimal initiation of direct oral anticoagulants. J Thromb Thrombolysis 2017;43(2):149-56. Feb.
3. Baker DE. Coagulation factor Xa (recombinant), inactivated-zhzo (andexanet alfa). Hosp Pharm 2018;53(5):286-91. Oct.
4. Frontera J, Lewin J, Rabinstein A, et al. Guideline for reversal of antithrombotics in intracranial hemorrhage: a statement for healthcare professionals from the Neurocritical Care Society and Society of Critical Care Medicine. Neurocrit Care 2016 Feb;24(1):6-46.
5. , https://www.acc.org/~/media/Non-Clinical/Images/Tools%20and%20Practice

   %20Support/Mobile%20Resources/ManageAnticoag/B18120_ManageAnticoag_ App_Fact_Sheet.pdf.

   Tao J, Bukanova EN, Akhtar S. Safety of 4-factor prothrombin complex concentrate (4F-PCC) for emergent reversal of factor Xa inhibitors. J Intensive Care 2018;6:34. Jun 14.

6. Schulman S, Gross PL, Ritchie B, et al. prothrombin complex concentrate for major bleeding on factor Xa inhibitors: a prospective cohort study. Thromb Haemost 2018 May;118(5):842-51.
7. Majeed A, Agren A, Holmstrom M, et al. Management of rivaroxaban- or apixaban-associated major bleeding with prothrombin complex concentrates: a cohort study. Blood 2017;130(15):1706-12. Oct 12.
8. Santibanez M, Lesch CA, Lin L, et al. Tolerability and effectiveness of 4-factor prothrombin complex concentrate (4F-PCC) for warfarin and non-warfarin reversals. J Crit Care 2018;48:183-90. Dec.
9. Dager WE, Roberts AJ, Nishijima DK. Effect of low and moderate dose FEIBA to reverse major bleeding in patients on direct oral anticoagulants. Thromb Res 2018;173:71-6. Nov 16.
10. Allison TA, Lin PJ, Gass JA, et al. Evaluation of the use of low-dose 4-factor prothrombin complex concentrate in the reversal of direct oral anticoagulants in bleeding patients. J Intensive Care Med 2018 Sep 24 [Epub ahead of print].
11. Gerner ST, Kuramatsu JB, Sembill JA. Association of prothrombin complex concentrate administration and hematoma enlargement in non-vitamin K antagonist oral anticoagulant-related intracerebral hemorrhage. Ann Neurol 2018;83(1):186-96. Jan.
12. Andexxa (andexanet alfa) [prescribing information]. South San Francisco, CA: Portola Pharmaceuticals, Inc; May 2018.
13. Connolly SJ, Milling Jr TJ, Eikelboom JW. Andexanet alfa for acute major bleeding associated with factor Xa inhibitors. N Engl J Med 2016;375 (12):1131-41. Sep 22.
14. Connolly SJ, Milling Jr TJ, Eikelboom JW. Andexanet alfa for acute major bleeding associated with factor Xa inhibitors. N Engl J Med 2019 [Feb 7, Epub ahead of print].

    antibiotic selection and isolate susceptibility profile in patients who failed ciprofloxacin or TMP-SMX for pyelonephritis

    To the Editor

    We read with interest the retrospective study by Vogler and Pavich assessing treatment failure in women diagnosed with uncomplicated pyelonephritis who were discharged from the emergency department on an oral fluoroquinolone (FQ) or trimethoprim-sulfamethoxazole (TMP-SMX) versus an oral cepha- losporin. The primary endpoint of treatment failure occurred in 0% of patients receiving an oral cephalosporin and 23% of patients receiving FQ or TMP-SMX [1].

    The authors stated in their discussion that the high resistance rates reported in their institution’s weighted antibiogram may have predisposed the FQ/TMP-SMX group to higher treatment fail- ure. However, according to their secondary objective analysis, only 3% of organisms isolated were resistant to ciprofloxacin. In con- trast, 23% of organisms isolated were resistant to TMP-SMX. It would be of interest to know which antibiotic the ten patients who failed treatment received, either ciprofloxacin or TMP-SMX, and the isolates’ susceptibility profile. The current presentation of data with TMP-SMX and ciprofloxacin being analyzed together, despite the strikingly different resistance rates, raises the question of whether the authors’ conclusion that ”treatment with oral cephalosporins may be a more appropriate therapy for uncompli- cated pyelonephritis versus fluoroquinolones or trimethoprim-sul- famethoxazole” is appropriate without addressing if antibiotic resistance, particularly to TMP-SMX, was the main contributor to treatment failure in the FQ/TMP-SMX group. The manner in which the patient outcomes data were analyzed and presented leaves this as an unanswered question.

    Moreover, we appreciate the authors’ concern with prescribing empiric ciprofloxacin and TMP-SMX since their reported weighted- average antibiogram data demonstrated Escherichia coli non-sus- ceptibility rates of 23% and 24% to ciprofloxacin and TMP-SMX, respectively. Further validating this concern is the Infectious Dis- eases Society of America guideline recommendation of using an initial one-time parenteral dose of ceftriaxone or consolidated 24-hour dose of an aminoglycoside for acute pyelonephritis when the prevalence of FQ resistance exceeds 10%, or if the uropathogen susceptibility to TMP-SMX is unknown [2]. It was noted in the arti-

    Correspondence / American Journal of Emergency Medicine 37 (2019) 1963-1988 1981

    cle that appropriate one-time doses of long-acting parenteral antibiotics were more frequently given in the cephalosporin group compared to the FQ/TMP-SMX group (78% vs. 53%, respectively). It would be of interest to see an analysis that separates patients dis- charged on TMP-SMX and FQ who received appropriate one-time doses of parenteral antibiotics from those who did not. This would allow for a clearer assessment into identifying any relationship between treatment failure and resistance (as mentioned above) or receipt of one-time dose antibiotics. We believe these are important parameters that the authors should have explored to determine why patients in the FQ/TMP-SMX group were less likely to be given an appropriate one-time dose of a long-acting par- enteral antibiotic and perhaps address this through appropriate intervention at their institution.

    Ultimately, the study demonstrated no treatment failures with oral cephalosporin therapy. Nevertheless, the conclusion that oral cephalosporins may be more appropriate therapy for uncompli- cated pyelonephritis compared to FQs and TMP-SMX should be interpreted with caution.

    Funding

    This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

    Potential conflicts of interest

    William R. Truong: No conflict. Kimberly J. Won: No conflict. Jason Yamaki: No conflict.

    Acknowledgments

    nerve sheath diameter (ONSD) measurement associated with hyponatremia in emergency department [1].

    We congratulate the authors for the originality of their article, but we would like to comment some aspects regarding the ONSD ultrasound evaluation.

    In their study, Demir et al. utilized B mode ultrasound to mea- sure ONSD in patients with hyponatremia, to detect potential intracranial pressure elevation. However, we consider this ultra- sound technique unreliable for this purpose, because of the bloom- ing effect [2-9]. B mode has been used for more than 50 years to diagnose several ocular and orbital diseases [10-12], but for mea- surements of small structures, such as ONSD, it has proven to be quite untrustworthy due to this effect. In fact, with decreasing the gain, the ONSD appears larger, so the absence of a standard gain setting when performing the examination means we cannot calibrate the author’s results with others already published.

    This effect may be overlooked with large structures, but not when resolution below 0.5 mm is assumed, as for ONSD appraisal. For this reason we suggest the use of Standardized A Scan tech- nique, a blooming effect free ultrasound method that displays easily noticeable high spikes from the interface between arachnoid and subarachnoidal fluid, making these measurements more accu- rate and objective [13,14]. Moreover, A scan examination also allows the ”30 degrees test”, which can discriminate between ONSD increase caused by raised intracranial pressure, and ONSD increase associated with other diseases, such as Optic neuritis or

    optic nerve meningioma [15-18].

    Furthermore, we would like to advise performing ocular ultra- sonography with open eyelids, using methylcellulose and anes- thetic drops, to clearly visualize the eye, making the probe orientation much more accurate, avoiding errors in detecting gaze direction [19,20].

    None.

    William R. Truong PharmD

    Livio Vitiello MD Maddalena De Bernardo MD, PhD ^*

    Nicola Rosa MD

    Department of Pharmacy, St. Joseph Hospital, Orange, CA, USA

    Kimberly J. Won PharmD Jason Yamaki PharmD, PhD ^*

    Department of Pharmacy Practice, Chapman University School of

    Pharmacy, Irvine, CA, USA

    Corresponding author.

    E-mail address: [email protected] (J. Yamaki)

    30 March 2019

    Department of Medicine, Surgery and Dentistry, ”Scuola Medica Saler-

    nitana“, University of Salerno, Salerno, Italy

    * Corresponding author at: Department of Medicine, Surgery and Dentistry, ”Scuola Medica Salernitana”, University of Salerno, Via S.

    Allende, 84081 Baronissi, Salerno, Italy.

    E-mail address: [email protected] (M. De Bernardo)

    26 March 2019

    https://doi.org/10.1016/j.ajem.2019.04.009

    https://doi.org/10.1016/j.ajem.2019.04.008

    References

    Vogler S, Pavich E. Pyelonephritis treatment in the community emergency department: cephalosporins vs. first-line agents. Am J Emerg Med 2018;36 (11):2054-7.

15. Gupta K, Hooton TM, Naber KG, et al. International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: a 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clin Infect Dis 2011;52(5): e103-20.

    A-scan ultrasonography to detect Intracranial hypertension in patients with hyponatremia

    Dear Editor,

    We read with great interest the significant paper written by Demir et al. concerning predictive and prognostic value of optic

    References

    Demir TA, Yilmaz F, Sonmez BM, Karadas MA, Okudan RN, Keskin O. Association of optic nerve sheath diameter measurement withhyponatremia in emergency department. Am J Emerg Med 2018. https://doi.org/10.1016/j. ajem.2018.12.054.

16. De Bernardo M, Rosa N. Transbulbar B-mode sonography in Multiple sclerosis: clinical and biological relevance. Ultrasound Med Biol 2018;44(2):508.
17. De Bernardo M, Rosa N. Clarification on using ultrasonography to detect intracranial pressure. JAMA Ophthalmol. 2017;135(9):1004-5.
18. De Bernardo M, Marotta G, Rosa N. Sonography of the optic nerve sheath diameter. J Ultrasound Med 2018;37(7):1845.
19. De Bernardo M, Rosa N. Transorbital sonography to evaluate optic nerve in hypertensive encephalopathy. J Stroke Cerebrovasc Dis 2018;27(4):1124.
20. Rosa N, De Bernardo M. Measurement of the optic nerve in a resource-limited setting. J Neurosci Rural Practice 2017;8(2):310-1.
21. Tenuta M, De Bernardo M, Rosa N. Comments on ”Neuromuscular ultrasonography of Cranial nerves“. J Clin Neurol 2017;13(2):212-3.
22. De Bernardo M, Vitiello L, Rosa N. Optic nerve ultrasonography to predict increased intracranial pressure in idiopathic intracranial hypertension. Neuroradiol J 2019. https://doi.org/10.1177/1971400919832001.
23. De Bernardo M, Vitiello L, Rosa N. Optic nerve Ultrasound measurement in multiple sclerosis. Acta Neurol Scand 2019;139(4):399-400.