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Division of Infectious Diseases

Should We Add Daptomycin to β-Lactams in the Initial Treatment of Methicillin-susceptible S. aureus Bacteremia?

Content from Dr. Razan El Ramahi, originally posted in IDSA journal club. 

Despite the availability of active antibiotics to treat Staphylococcus aureus bacteremia (SAB), controversy still exists regarding the optimal antibiotic strategy and whether combination antibiotics improve outcomes. In small clinical studies, a possible benefit was observed by adding daptomycin to β-lactams in the treatment of SAB. However, the numbers of methicillin-susceptible S. aureus (MSSA) cases in these studies, published in Antimicrobial Agents and Chemotherapy and Clinical Therapeutics, respectively, were small.

In a larger cohort, recently reported in Clinical Infectious Diseases, Grillo et al. retrospectively reviewed adult MSSA cases at a single tertiary hospital to examine the impact of combining β-lactam therapy with daptomycin (BL/D-C) on mortality compared to β-lactam monotherapy (BL-M). BL/D-C therapy had to be administered for ≥ 72 hours in the first 4 days of treatment. Among 350 cases of MSSA bacteremia, 136 (38.8 percent) received BL/D-C and the rest received BL-M. Patients in the BL/D-C group were more likely to have endocarditis, more severe disease, and persistent bacteremia. Despite those differences, there was no significant difference found in 7-, 30- and 90-day mortality between the two groups. After propensity score matching, the difference in mortality remained non-significant. Subanalysis of patients with high-risk sources (endocarditis and unknown) also did not show significant difference in mortality between those who received BL/D-C or BL-M.

In this relatively larger cohort of patients with MSSA bacteremia, combination therapy with daptomycin and anti-staphylococcal BL failed to show survival benefit compared to BL monotherapy. Although it had a retrospective design, propensity score matching was used to try to minimize selection bias. The study results highlight that, in addition to appropriate empiric therapy, mortality in SAB is also driven by other factors such as severe disease, host comorbidities, and adequacy of identifying and controlling the source. A randomized controlled trial is underway in which the effects of adding daptomycin to β-lactams in MSSA bacteremia are being studied.

(Grillo et al. Clin Infect Dis. 2019;69(9):1480–1488.)


 

Novel Coronavirus – What You Need to Know Now

Content courtesy of Dr. Angela Hewlett

Coronaviruses are common respiratory pathogens, and generally cause mild symptoms of the ‘common cold’.  However, other coronavirus strains have been known to cause outbreaks that lead to more severe disease like pneumonia, and even death.  Examples of these include SARS and MERS, which are both coronaviruses with mortality rates of 10% and 34%, respectively. Here is a newly published article on Coronaviruses from JAMA: https://jamanetwork.com/journals/jama/fullarticle/2759815

From:https://www.npr.org/sections/goatsandsoda/2020/01/22/798277557/how-does-wuhan-coronavirus-compare-to-mers-sars-and-the-common-cold

An outbreak of a novel coronavirus (nCoV) not previously identified in humans began in Wuhan, China (a city of 11 million people) at the end of December.  The first cases were linked to a seafood market, but subsequent cases have demonstrated that human-to-human transmission is occurring, likely via the respiratory route.   Thus far, 571 confirmed cases and 17 deaths have been reported.  Most of the deaths have occurred in elderly patients with multiple comorbid conditions.  The majority of nCoV cases have occurred in Wuhan, China, but multiple travel-related cases have been seen in other countries, including the United States.  It is highly likely that more travel-related cases will be detected as the outbreak evolves.  A laboratory test is now available, and scientists are working on a vaccine, although this process could take some time.

While it is important to continue to monitor the nCoV situation closely, it is also necessary to keep this in perspective.  Influenza causes between 12,000 and 61,000 deaths in the United States every year, and we are in the middle of a very active influenza season.  People should remember to get their flu shot, wash their hands, cover their cough, and stay home from work or school if they are ill.  These basic infection control measures help prevent the spread of any respiratory disease.    

Check out the Facebook live video of UNMC ID experts, Drs. Lawler, Hewlett & Rupp answering questions: https://www.facebook.com/NebraskaMed/videos/624298111651330/

CDC resources on status updates, travel information and more here: https://www.cdc.gov/coronavirus/2019-ncov/index.html?CDC_AA_refVal=https%3A%2F%2Fwww.cdc.gov%2Fcoronavirus%2Fnovel-coronavirus-2019.html

WHO resources: https://www.who.int/csr/don/17-january-2020-novel-coronavirus-japan-ex-china/en/

 

Blood culture contamination–it’s a big deal

Blood cultures are a key diagnostic test to detect bacteremia and appropriately treat patients with sepsis and are performed approximately 30 million times in the United States yearly. Unfortunately, contamination of blood cultures occurs in the 0.5% to 5% of samples (approximately 25% of positive blood cultures are due to contamination) which leads to inappropriate antibiotic treatment, additional unneeded tests, extended hospital length of stay, and excess cost.

Up to 40% of patients with contaminated blood cultures are started on unnecessary antibiotics and blood culture contamination results in an 80% increase in total microbiology charges and from 1-5 extra days in the hospital. On a national scale, blood culture contamination results in nearly 1 million extra hospital days, 200,000 courses of unneeded antibiotics, and over $1 billion of excess cost. It’s a big deal!

Because blood culture contamination is an underappreciated but important clinical problem and because recent studies document it can be markedly decreased, a thorough review of blood culture contamination was recently published:

Blood culture contamination often stems from bacteria that reside on the skin, in the hair follicles, or dermal sebaceous glands and are inadvertently included in the blood sample when the phlebotomy needle is inserted across the skin into the blood vessel. In the past, a blood culture contamination rate of less than 3% was deemed acceptable. However, more recent studies have demonstrated that contamination rates of less than 1% are readily achievable.

Methods that should be employed to decreased blood culture contamination include the following:

  1. Patient selection: Blood cultures should only be performed in patients with a reasonable likelihood of bacteremia/fungemia.
  2. Skin disinfection: Use an alcohol-containing disinfectant to scrub the phlebotomy site; allow for adequate drying time.
  3. Cap disinfection: Disinfect blood culture vial caps with alcohol.
  4. Phlebotomy site: Don’t draw blood cultures through vascular catheters unless the catheter is thought to be the source of sepsis.
  5. Standardized kits: Use of standardized kits and procedures has proven helpful in preventing contamination.
  6. Phlebotomy teams: Educate and train individuals who perform blood cultures in aseptic technique.
  7. Surveillance and feedback: Monitor blood culture contamination and provide data to individuals and patient care units.
  8. Multidisciplinary teams: Sustained improvement in blood culture contamination is best achieved through a team approach.
  9. Initial specimen diversion: Use of commercially available devices has been shown to decrease contamination rates to less than 1%.

Because hair follicles, sebaceous glands, and deeper layers of the epidermis can serve as a sanctuary site for microbes and skin fragments contaminated with bacteria can be dislodged with venipuncture, a technique to sequester the initial portion of a blood sample (presumably containing the contaminating bacteria) has been developed. When we used this device in our Emergency Department to obtain blood cultures, the contamination rate decreased from 1.78% to 0.22% (P = 0.001). Rupp M, Cavalieri J, Marolf C, Lyden E. 2017. Reduction in blood culture contamination through use of initial specimen diversion device. Clinical Infectious Diseases. 65: 201–205.

Bottom line: Blood culture contamination is a big deal – resulting in inappropriate antibiotic use and excess hospital stay and economic cost. The long held quality benchmark of 3% contamination should not be complacently tolerated. Through application of comprehensive preventative techniques, blood culture contamination rates of less than 1% should be achievable.

Content written by Dr. Mark Rupp based on recent publication release: Doern GV, Carroll KC, Diekema DJ, Garey KW, Rupp ME, Weinstein MP, Sexton DJ. A comprehensive update on the problem of blood culture contamination and a discussion of methods for addressing the problem. Clinical Microbiology Reviews. January 2020. 


 

Antimicrobial Stewardship & Sepsis – A Great Debate

Optimal management of sepsis has long-been a holy grail in medicine. One area that remains fraught with debate is how to effectively balance the need for emergent antimicrobial administration with principles of antimicrobial stewardship. A recent Point–Counterpoint series on “Should Broad-Spectrum Antibiotics Be Routinely Administered to All Patients with Sepsis as Soon as Possible”published in CHEST highlights the debate. Disselkamp et al argue yes, early administration of broad-spectrum antibiotics increases the likelihood of adequate coverage AND is associated with decreased mortality. This does not negate the need for commitment to stewardship, but “If we do not use antibiotics for patients with life-threatenining organ dysfunction, who are we saving them for?”

Conversely,  Patel and Bergl argue that although delayed antibiotics due increase mortality in sepsis, the strong recommendation for empiric broad-antimicrobial therapy is inappropriate due to a paucity of high-quality evidence and risk of harm(such as adverse drug events, Clostridiodes difficile infection) with “indiscriminate broad-spectrum antibiotics.” They further argue that appropriate antibiotic therapy may not always be broad-spectrum, and the assumption that broad-spectrum is required is both flawed and potentially costly to patients and healthcare systems.

Further, perhaps this debate is not the most critical for our sepsis patients currently. Kashiouris et al demonstrated that delays in first antimicrobial execution (time from order to administration) are common and carry increased mortality, particularly for patients with many comorbidities. Regardless of what antibiotics are ordered, if not administered within the first hour, mortality continues to rise.

Do we have time to determine optimal antimicrobial therapy in sepsis when we frequently fail to administer it fast enough?

How do we determine the greater good? Immediate mortality or potential downstream morbidity and mortality from adverse events?

Our patients are relying on us for life-saving, timely antibiotics in sepsis and septic shock. Every minute matters – the time to diagnosis of sepsis, the time to ordering antibiotics, and the time to administration. Focusing on the drug choice, or time to ordering, is no longer enough. We must take a greater ownership over the entire process, including considering the speed of delivery, simultaneously, if we want to optimize care.

Originally posted on the IDSA News Journal Club

 

References:

Point: Yes; Disselkamp M, Yataco AO, Simpson SQ. Point: should broad-spectrum antibiotics be routinely administered to all patients with sepsis as soon as possible? Yes. Chest. 2019 Oct 1;156(4):645-7.

Point: No; Patel JJ, Bergl PA. Counterpoint: should broad-spectrum antibiotics be routinely administered to all patients with sepsis as soon as possible? No. Chest. 2019 Oct 1;156(4):647-9.

Kashiouris MG, Zemore Z, Kimball Z, Stefanou C, Fisher B, de Wit M, Pedram S, Sessler CN. Supply Chain Delays in Antimicrobial Administration After the Initial Clinician Order and Mortality in Patients With Sepsis. Critical care medicine. 2019 Oct 1;47(10):1388-95.


 

Surveillance for vascular catheter associated complications in home health care is needed

Content written by Dr. Mark Rupp. 

Impressive gains in the prevention of central line associated bloodstream infections (CLABSI) have been realized in recent years in US hospitals. However, with efforts to improve efficiency and decrease hospital length of stay, patients are increasingly being discharged to home health care to receive intravenous therapy. The rate of complications associated with vascular catheterization in the home care setting is largely undefined.

In a recent issue of the American Journal of Infection Control, authors Regina Nailon and Mark Rupp detail results from a surveillance system encompassing 10 home health agencies from 4 states over a 51 month period (Nailon RE, Rupp ME. Surveillance of Home Health Central Venous Catheter Care Outcomes: Challenges and Future Directions. American Journal of Infection Control 47:1382-1387, 2019). During a period of greater than 250,000 device days of observation, 913 catheter occlusions and 73 CLABSIs were noted. For adults, the occlusion rate was 5.87 events per 1000 catheter days and CLABSI occurred at a rate of 0.22 per 1000 catheter days. For pediatric age patients, the rates for occlusion and CLABSI per 1000 catheter days were 1.85 and 0.13, respectively. The data were reported to participating agencies on a quarterly basis with deidentified individual agency data compared to aggregate rates. Based on the quality reports, some agencies instituted quality improvement and noted substantial decreases in complication rates.

An unknown proportion of the millions of patients receiving home health care receive treatment through a vascular catheter. This study demonstrates that a small, but substantial, percentage of home healthcare patients experience serious adverse complications associated with intravascular catheters. Clearly, a comprehensive surveillance system is needed to monitor outcomes and improve practices in this sizable group of patients.  The study also emphasizes the need for standardized education and care practices for patients and their families who provide a substantial portion of catheter care at home.

As James Harrington related: “Measurement is the first step that leads to control and eventually to improvement. If you can’t measure something, you can’t understand it. If you can’t understand it, you can’t control it. If you can’t control it, you can’t improve.”

Or, more succinctly… what gets measured, gets managed.


 

Farewell 2019…another year of growth for UNMCID

2019 continued the theme of growth for our Division of Infectious Diseases. We have added several new faculty to our group (and still actively hiring), continued to redesign the College of Medicine Infectious Diseases curriculum, established a new Community Infectious Diseases service line, expanded our social media presence, joined and led multiple national Infectious Diseases committees, and again hosted the successful regional HIV and Antimicrobial Stewardship conferences. We had a huge presence at #IDWeek2019, with 10 of our faculty either presenting or moderating on the national stage, and many more presenting posters. We are extremely proud of our trainees – the Division supported eight students, residents, and fellows to attend, three of whom gave oral presentations! Finally, we expanded our ID fellowship program and matched three fantastic physicians to join us next summer (with a goal of a final complement of six ID fellows by 2021).

Amidst all of that, our Division was once again among the top publication performers in the Department of Medicine, with our faculty publishing over 70 peer-reviewed journal articles and book chapters crossing several areas of expertise, including HIV, Biopreparedness, Infections in Solid-organ and Stem-cell transplant patients, Antimicrobial Stewardship, Hospital Epidemiology & Infection Control, Diversity & Equity, Social Media, and Infections in critically-ill patients. Curious about the depth and breadth of expertise at UNMC ID? Below is a full list of the publications for your perusal, with convenient links to the referenced articles. It’s long, so consider bookmarking and keep referring to it whenever you need a bit of expertise.

We want to thank Librarian Teresa Hartman (@thartman2u) at the UNMC McGoogan Library for helping us compile this list of publications.

Stay tuned to our blog and follow us on Twitter @UNMC_ID to see all that we have in store for 2020!

2019 UNMC ID Faculty Publications

  1. Abdalla, M. Y., Ahmad, I. M., Rachagani, S., Banerjee, K., Thompson, C. M., Maurer, H. C., . . . Kumar, S. (2019). Enhancing responsiveness of pancreatic cancer cells to gemcitabine treatment under hypoxia by heme oxygenase-1 inhibition. Translational Research, 207, 56-69. doi:10.1016/j.trsl.2018.12.008
  2. Aitken, S. L., Nagel, J. L., Abbo, L., Alegria, W., Barreto, J. N., Dadwal, S., . . . Seo, S. K. (2019). Antimicrobial stewardship in patients with cancer: The time is now. JNCCN Journal of the National Comprehensive Cancer Network, 17(7), 772-775. doi:10.6004/jnccn.2019.7318
  3. Anemüller, R., Belden, K., Brause, B., Citak, M., Del Pozo, J. L., Frommelt, L., . . . Zimmerli, W. (2019). Hip and knee section, treatment, antimicrobials: Proceedings of international consensus on orthopedic infections. Journal of Arthroplasty, 34(2), S463-S475. doi:10.1016/j.arth.2018.09.032
  4. Beam, E. L., Schwedhelm, M. M., Boulter, K. C., Vasa, A. M., Larson, L., Cieslak, T. J., . . . Hewlett, A. L. (2019). Ebola virus disease: Clinical challenges, recognition, and management. Nursing Clinics of North America, 54(2), 169-180. doi:10.1016/j.cnur.2019.02.001
  5. Bos, L. D. J., & Kalil, A. C. (2019). Changes in lung microbiome do not explain the development of ventilator-associated pneumonia. Intensive Care Medicine, 45(8), 1133-1135. doi:10.1007/s00134-019-05691-1
  6. Calabrò, F., Coen, M., Franceschini, M., Franco-Cendejas, R., Hewlett, A., Segreti, J., & Senneville, E. (2019). Hip and knee section, treatment, antimicrobial suppression: Proceedings of international consensus on orthopedic infections. Journal of Arthroplasty, 34(2), S483-S485. doi:10.1016/j.arth.2018.09.034
  7. Cawcutt, K. A., Erdahl, L. M., Englander, M. J., Radford, D. M., Oxentenko, A. S., Girgis, L., . . . Silver, J. K. (2019). Use of a coordinated social media strategy to improve dissemination of research and collect solutions related to workforce gender equity. Journal of Women’s Health, 28(6), 849-862. doi:10.1089/jwh.2018.7515
  8. Cawcutt, K. A., Hankins, R. J., Micheels, T. A., & Rupp, M. E. (2019). Optimizing vascular-access device decision-making in the era of midline catheters.Infection. Control and Hospital Epidemiology, 40(6), 674-680. doi:10.1017/ice.2019.49
  9. Cawcutt, K. A., & Kalil, A. C. (2019). Saved from sepsis: Can immunotherapy improve acute and postacute outcomes? Critical Care Medicine, 47(5), 733-735. doi:10.1097/CCM.0000000000003702
  10. Cawcutt, K. A., Marcelin, J. R., & Silver, J. K. (2019). Using social media to disseminate research in infection prevention, hospital epidemiology, and antimicrobial stewardship. Infection Control and Hospital Epidemiology, 40(11), 1262-1268. doi:10.1017/ice.2019.231
  11. Cawcutt, K. A., & Zimmer, A. (2019). Management of infection in patients with kidney transplant. Critical care nephrology: Third edition (pp. 552-560.e1) Elsevier Inc. doi:10.1016/B978-0-323-44942-7.00095-9
  12. Chaisson, R. E., Ramchandani, R., & Swindells, S. (2019). One month of rifapentine plus isoniazid to prevent HIV-related tuberculosis. reply. The New England Journal of Medicine, 381(11), e23. doi:10.1056/NEJMc1908492
  13. Choi, S. -., Britigan, B. E., & Narayanasamy, P. (2019). Dual inhibition of klebsiella pneumoniae and pseudomonas aeruginosa iron metabolism using gallium porphyrin and gallium nitrate. ACS Infectious Diseases, 5(9), 1559-1569. doi:10.1021/acsinfecdis.9b00100
  14. Choi, S. -., Britigan, B. E., & Narayanasamy, P. (2019). Iron/heme metabolism-targeted gallium(III) nanoparticles are active against extracellular and intracellular pseudomonas aeruginosa and acinetobacter baumannii. Antimicrobial Agents and Chemotherapy, 63(4) doi:10.1128/AAC.02643-18
  15. Choi, S. -., Britigan, B. E., & Narayanasamy, P. (2019). Treatment of virulent mycobacterium tuberculosis and HIV coinfected macrophages with gallium nanoparticles inhibits pathogen growth and modulates macrophage cytokine production. Msphere, 4(4) doi:10.1128/mSphere.00443-19
  16. Churchyard, G. J., & Swindells, S. (2019). Controlling latent TB tuberculosis infection in high-burden countries: A neglected strategy to end TB. PLoS Medicine, 16(4) doi:10.1371/journal.pmed.1002787
  17. Cieslak, T. J., Herstein, J. J., Kortepeter, M. G., & Hewlett, A. L. (2019). A methodology for determining which diseases warrant care in a high-level containment care unit. Viruses, 11(9) doi:10.3390/v11090773
  18. El Ramahi, R., & Freifeld, A. (2019). Epidemiology, diagnosis, treatment, and prevention of influenza infection in oncology patients. Journal of Oncology Practice, 15(7), 177-184. doi:10.1200/JOP.19.00350
  19. Endres, J. L., Yajjala, V. K., Fey, P. D., & Bayles, K. W. (2019). Construction of a sequence-defined transposon mutant library in staphylococcus aureus. Humana Press Inc. doi:10.1007/978-1-4939-9570-7_3
  20. Fehring, T. K., Fehring, K. A., Hewlett, A., Higuera, C. A., Otero, J. E., & Tande, A. (2019). What’s new in musculoskeletal infection. Journal of Bone and Joint Surgery – American Volume, 101(14), 1237-1244. doi:10.2106/JBJS.19.00403
  21. Flexner, C., Thomas, D. L., & Swindells, S. (2019). Creating demand for long-acting formulations for the treatment and prevention of HIV, tuberculosis, and viral hepatitis. Current Opinion in HIV and AIDS, 14(1), 13-20. doi:10.1097/COH.0000000000000510
  22. Florescu, D. F., Schaenman, J. M., & on behalf of the AST Infectious Diseases Community of Practice. (2019). Adenovirus in solid organ transplant recipients: Guidelines from the american society of transplantation infectious diseases community of practice. Clinical Transplantation, 33(9) doi:10.1111/ctr.13527
  23. Florescu, D. F., & Stohs, E. J. (2019). Approach to infection and disease due to adenoviruses in solid organ transplantation. Current Opinion in Infectious Diseases, 32(4), 300-306. doi:10.1097/QCO.0000000000000558
  24. Gandhi, M., Smeaton, L. M., Vernon, C., Scully, E. P., Gianella, S., Poongulali, S., . . . for the Women’s Health Inter-Network Scientific Committee (WHISC). (2019). Low rate of sex-specific analyses in presentations at the conference on retroviruses and opportunistic infections (CROI) meeting, 2018: Room to improve. Journal of Acquired Immune Deficiency Syndromes, 81(5), E158-E160. doi:10.1097/QAI.0000000000002073
  25. Gibbs, S. G., Herstein, J. J., Le, A. B., Beam, E. L., Cieslak, T. J., Lawler, J. V., . . . Lowe, J. J. (2019). Review of literature for air medical evacuation high-level containment transport. Air Medical Journal, 38(5), 359-365. doi:10.1016/j.amj.2019.06.006
  26. Gibbs, S. G., Herstein, J. J., Le, A. B., Beam, E. L., Cieslak, T. J., Lawler, J. V., . . . Lowe, J. J. (2019). Need for aeromedical evacuation high-level containment transport guidelines. Emerging Infectious Diseases, 25(5), 1033-1034. doi:10.3201/eid2505.181948
  27. Gnann, J. W., Jr., Agrawal, A., Hart, J., Buitrago, M., Carson, P., Hanfelt-Goade, D., . . . the National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group. (2019). Lack of efficacy of high-titered immunoglobulin in patients with west nile virus central nervous system disease. Emerging Infectious Diseases, 25(11), 2064-2073. doi:10.3201/eid2511.190537
  28. Hankins, R., Majorant, O. D., Rupp, M. E., Cavalieri, R. J., Fey, P. D., Lyden, E., & Cawcutt, K. A. (2019). Microbial colonization of intravascular catheter connectors in hospitalized patients. American Journal of Infection Control, 47(12), 1489-1492. doi:10.1016/j.ajic.2019.05.024
  29. Havens, J. P., Podany, A. T., Scarsi, K. K., & Fletcher, C. V. (2019). Clinical pharmacokinetics and pharmacodynamics of etravirine: An updated review. Clinical Pharmacokinetics, doi:10.1007/s40262-019-00830-9
  30. Havens, J. P., Scarsi, K. K., Sayles, H., Klepser, D. G., Swindells, S., & Bares, S. H. (2019). Acceptability and feasibility of a pharmacist-led human immunodeficiency virus pre-exposure prophylaxis program in the midwestern united states. Open Forum Infectious Diseases, 6(10) doi:10.1093/ofid/ofz365
  31. Hewlett, A. L., Hohenberger, H., Murphy, C. N., Helget, L., Hausmann, H., Lyden, E., . . . Hicks, R. (2019). Evaluation of the bacterial burden of gel nails, standard nail polish and natural nails on the hands of health care workers. [Beurteilung der bakteriellen Belastung von Gelnägeln, Standard-Nagellack und Naturnägel auf den Händen von Gesundheitspersonal] Krankenhaushygiene Und Infektionsverhutung, 41(2), 40-43. doi:10.1016/j.khinf.2019.03.001
  32. Kalil, A. C. (2019). Controversies in nosocomial pneumonias in 2019. Clinical Microbiology and Infection, 25(10), 1171-1172. doi:10.1016/j.cmi.2019.07.003
  33. Kalil, A. C., Gilbert, D. N., Winslow, D. L., Masur, H., & Klompas, M. (2019). Reply to al-hasan and justo. Clinical Infectious Diseases, 68(8), 1432. doi:10.1093/cid/ciy679
  34. Kalil, A. C., Holubar, M., Deresinski, S., & Chambers, H. F. (2019). Is daptomycin plus ceftaroline associated with better clinical outcomes than standard of care monotherapy for staphylococcus aureus bacteremia? Antimicrobial Agents and Chemotherapy, 63(11) doi:10.1128/AAC.00900-19
  35. Kalil, A. C., & Lisboa, T. (2019). To procalcitonin, or not to procalcitonin? Chest, 155(6), 1085-1087. doi:10.1016/j.chest.2019.02.327
  36. Kalil, A. C., & Machado, F. R. (2019). Quick sequential organ failure assessment is not good for ruling sepsis in or out. Chest, 156(2), 197-199. doi:10.1016/j.chest.2019.06.003
  37. Kalil, A. C., & Thomas, P. G. (2019). Influenza virus-related critical illness: Pathophysiology and epidemiology. Critical Care, 23(1) doi:10.1186/s13054-019-2539-x
  38. Kalil, A. C., & Zavascki, A. P. (2019). Can ceftolozane–tazobactam treat nosocomial pneumonia? The Lancet Infectious Diseases, 19(12), 1266-1267. doi:10.1016/S1473-3099(19)30523-7
  39. Keshavjee, S., Amanullah, F., Cattamanchi, A., Chaisson, R., Dobos, K. M., Fox, G. J., . . . Nahid, P. (2019). Moving toward tuberculosis elimination critical issues for research in diagnostics and therapeutics for tuberculosis infection. American Journal of Respiratory and Critical Care Medicine, 199(5), 564-571. doi:10.1164/rccm.201806-1053PP
  40. Kuhn, J. H., Adachi, T., Adhikari, N. K. J., Arribas, J. R., Bah, I. E., Bausch, D. G., . . . Yoti, Z. (2019). New filovirus disease classification and nomenclature. Nature Reviews Microbiology, doi:10.1038/s41579-019-0187-4
  41. Li, X., Gong, W., Wang, H., Li, T., Attri, K. S., Lewis, R. E., . . . Wen, H. (2019). Erratum: O-GlcNAc transferase suppresses inflammation and necroptosis by targeting receptor-interacting Serine/Threonine-protein kinase 3 (immunity (2019) 50(3) (576–590.e6), (S1074761319300305), (10.1016/j.immuni.2019.01.007)). Immunity, 50(4), 1115. doi:10.1016/j.immuni.2019.03.008
  42. Li, X., Gong, W., Wang, H., Li, T., Attri, K. S., Lewis, R. E., . . . Wen, H. (2019). O-GlcNAc transferase suppresses inflammation and necroptosis by targeting receptor-interacting Serine/Threonine-protein kinase 3. Immunity, 50(3), 576-590.e6. doi:10.1016/j.immuni.2019.01.007
  43. Marcelin, J. R., Bares, S. H., & Fadul, N. (2019). Improved infectious diseases physician compensation but continued disparities for women and underrepresented minorities. Open Forum Infectious Diseases, 6(2) doi:10.1093/ofid/ofz042
  44. Marcelin, J. R., Brewer, C., Beachy, M., Lyden, E., Winterboer, T., Murphy, C. N., . . . Van Schooneveld, T. C. (2019). Hardwiring diagnostic stewardship using electronic ordering restrictions for gastrointestinal pathogen testing. Infection Control and Hospital Epidemiology, 40(6), 668-673. doi:10.1017/ice.2019.78
  45. Marcelin, J. R., Manne-Goehler, J., & Silver, J. K. (2019). Supporting inclusion, diversity, access, and equity in the infectious disease workforce. Journal of Infectious Diseases, 220, S50-S61. doi:10.1093/infdis/jiz213
  46. Marcelin, J. R., Siraj, D. S., Victor, R., Kotadia, S., & Maldonado, Y. A. (2019). The impact of unconscious bias in healthcare: How to recognize and mitigate it. Journal of Infectious Diseases, 220, S62-S73. doi:10.1093/infdis/jiz214
  47. Mathur, S., Roberts-Toler, C., Tassiopoulos, K., Goodkin, K., McLaughlin, M., Bares, S., . . . ACTG A5322 Study Team. (2019). Detrimental effects of psychotropic medications differ by sex in aging people with HIV. Journal of Acquired Immune Deficiency Syndromes (1999), 82(1), 88-95. doi:10.1097/QAI.0000000000002100
  48. Mehta, B., Pedro, S., Ozen, G., Kalil, A., Wolfe, F., Mikuls, T., & Michaud, K. (2019). Serious infection risk in rheumatoid arthritis compared with non-inflammatory rheumatic and musculoskeletal diseases: A US national cohort study. RMD Open, 5(1) doi:10.1136/rmdopen-2019-000935
  49. Nailon, R. E., & Rupp, M. E. (2019). Surveillance of home health central venous catheter care outcomes: Challenges and future directions. American Journal of Infection Control, 47(11), 1382-1387. doi:10.1016/j.ajic.2019.04.177
  50. Nailon, R. E., Rupp, M. E., & Lyden, E. (2019). A day in the life of a CVAD. Journal of Infusion Nursing, 42(3), 125-131. doi:10.1097/NAN.0000000000000321
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Evaluating Next-Generation Melioidosis Diagnostics

In addition to being one of our ID physicians, Dr. James Lawler serves as the Director or International Programs and Innovation at the Global Center for Health Security, a center that will focus on training federal personnel to manage highly infectious diseases, and Director of Clinical and Biodefense Research at the National Strategic Research Institute.  His interest in global health extends to his research, and we’re excited to feature his recently published an article in Clinical Infectious Diseases titled, “Next Generation Diagnostics for Melioidosis: Evaluation of a Prototype i-STAT Cartridge to Detect Burkholderia pseudomallei Biomarkers.”

Dr. Lawler summarizes the article and its findings:

Melioidosis is the most common cause of community acquired pneumonia and sepsis in many areas of South East Asia and Northern Australia. It is a significant cause of mortality and highlights the challenges of managing drug resistant infections in resource-limited regions, where more expensive broad-spectrum antibiotic therapy is prohibitively expensive for widespread use. Melioidosis is also a threat for US service members deploying to endemic regions.

A new sensitive, rapid, and affordable diagnostic test could dramatically improve our ability to deliver directed therapy for melioidosis. We think the proof of concept study with the iSTAT-based assay shows that such a test is possible. It also makes the case for a platform to support rapid fielding of point-of-care diagnostic assays for multiple pathogens, which could be a major leap forward in managing emerging infectious diseases.

You can read more about this work here.


 

PharmToExamTable: What do we know about Etravirine for HIV?

Recently, several of our HIV pharmacist colleagues in our Division of Infectious Diseases at UNMC/Nebraska Medicine, published an invited review in Clinical Pharmacokinetics entitled: Clinical Pharmacokinetics and Pharmacodynamics of Etravirine: An Updated Review.  The first author, Dr. Josh Havens PharmD, wrote this summary describing the review article.

What prompted the review?

This was an invited review, but there was only one previously completed shortly after etravirine’s FDA approval in 2009.

What do we know about the role of etravirine in ART regimens today?

Etravirine was initially brought to market as an additional agent to be used in conjunction with ritonavir-boosted darunavir in patients who were on failing regimens.  In the phase III, DUET-1 and -2 trials, the addition of etravirine to an optimized background regimen resulted in significantly greater improvements in HIV viral suppression.

In the US, etravirine’s use has declined secondary to the advent of integrase strand transfer inhibitors and etravirine’s twice daily dosing frequency.  Further, etravirine exhibits significant potential for bi-directional drug-drug interactions with other antiretrovirals as well as concomitant medications.  In other countries, specifically in Europe, etravirine has been used with once-daily dosing.  In pharmacokinetic studies, etravirine once-daily did not significantly differ from twice daily dosing by systemic exposure (AUC), but resulted in slightly higher max concentations (Cmax) and slightly lower trough concentrations (Cmin).

Etravirine has also been studied in small populations of antiretroviral naïve patients with variable results.  In comparison to DHHS guideline recommended antiretroviral regimens, etravirine use in naïve populations was less favorable by efficacy measures.  As a result, we still see etravirine’s use in the same way it was initially approved.  Once-daily dosing may be favorable in some patients to improve adherence granted that therapeutic drug monitoring may be available to verify sufficient etravirine plasma concentrations. Additionally, etravirine is now approved for use in children down to 2 years old with weight based dosing (BID only) and offers an additional agent in the form of a dissolvable tablet for use in this population.

What are the high-level take-aways about how/when to use etravirine?

Europe uses therapeutic drug monitoring more readily for ART than the US and thus uses once daily etravirine more frequently.  Given our stance on refraining from its use in naïve populations with a regimen such as ETR + F/TAF, as was done in the UNC study (78% VS rates at week 48), we feel the most likely patient that would use etravirine would be someone with some resistance and the risk of using once daily etravirine in this type of patient would likely be greater than its benefit.

What is the biggest gap in the science/knowledge about the role of etravirine in ART?

Further studies of etravirine use once daily in both adults and children may be warranted.  Given the efficacy of INI’s, we don’t feel that ETR has a place in naïve regimens.

Read the full study here: Havens, J.P., Podany, A.T., Scarsi, K.K. et al. Clin Pharmacokinet (2019). https://doi.org/10.1007/s40262-019-00830-9

Unpacking the new IDSA Community-Acquired Pneumonia guidelines

We are always excited to have our ID fellows provide guest blog posts. Second year ID fellow Dr. Lindsey Rearigh (follow her on Twitter @LRearigh) was recently on her Antimicrobial Stewardship rotation and reviewed the latest published guidelines for Community-Acquired Pneumonia (CAP). 

The American Thoracic Society (ATS) and Infectious Diseases Society of America (IDSA) recently released updated community-acquired pneumonia (CAP) guidelines. The first immediate implication is the healthcare-associated pneumonia (HCAP) definition is gone for good. IDSA had previously retired the term in the 2016 hospital-acquired pneumonia/ventilator-acquired pneumonia (HAP/VAP) guidelines.

HCAP was previously defined as patients with any one of the following risk factors: residence in a nursing home or other long-term care facility, hospitalization for >/= 2 days in the last 90 days, receipt of home infusion therapy, chronic dialysis, home wound care or a family member with a known antibiotic-resistant pathogen. This category would help guide empiric antibiotic therapy (before an organism is known), which could include treatment of methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, and other multi-drug resistant pathogens.

In these new guidelines, clinicians are now recommended to empirically treat for MRSA or P. aeruginosa in adults with CAP only if locally validated risk factors for either are present. The most consistently strong individual risk factors for MRSA/P. aeruginosa include previous lower respiratory tract infection (LRTI) with MRSA or P. aeruginosa, hospitalization within last 90 days, or if the patient had received intravenous (IV) antibiotics within that time-frame. If empiric MRSA or P. aeruginosa therapy is started, the guidelines recommend de-escalation at 48hrs if cultures remain negative.

Traditional pathogens that previously accounted for CAP included Streptococcus pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, Staphylococcus aureus, Legionella species, Chlamydia pneumoniae and Moraxella catarrhalis. Now with the implementation of vaccinations, viral pathogens are thought to be more prominent causes of CAP. Streptococcus pneumoniae is still a major contributor, although declined from 90-95% to 5-15% in recent studies.

Other main updates fall into the realm of diagnostic stewardship. The guidelines do not recommend obtaining sputum and blood cultures in the outpatient or inpatient setting, except only in cases of severe CAP (admission to the ICU or intubated), or if the patient is being empirically treated for MRSA or P. aeruginosa.

Procalcitonin has previously been used to help guide clinicians in the initiation of antibiotics in LRTI, but there were concerns of varied sensitivity of the test (range 38-91%) might miss patients with bacterial causes. The guidelines recommend empiric antibiotic therapy for presumed CAP regardless of initial serum procalcitonin.

Given the rising incidence and prevalence of viral causes of CAP, more research is needed to accurately identify clinical scenarios where antibiotic therapy can be safely withheld. Overall, treatment recommendations have not significantly changed except for the de-emphasis on macrolide monotherapy, particularly in areas where macrolide resistance was >/= 25% (which is pretty much everywhere in the US).

Five days of therapy is recommended to be adequate given the patient has reached clinical stability, including normalization of vital signs, ability to eat, and returned to baseline mental status.

If you are looking for a longer play-by-play summary of the new guidelines on Twitter, including a robust discussion of the mention of ceftaroline for CAP, click here for a thorough assessment by @ASPphysician, Dr. Andrew Morris.

Following up on pharmacist-led HIV pre-exposure prophylaxis

Earlier this year we featured a study by UNMC ID Drs. Sara Bares and Susan Swindells: “Midwest pharmacists’ familiarity, experience, and willingness to provide pre-exposure prophylaxis (PrEP) for HIV.”  We’re excited to share an update on their work building inter-professional relationships to increase PrEP education and use in Nebraska that was recently published in Open Forum Infectious Diseases: “Acceptability and feasibility of a pharmacist-led HIV pre-exposure prophylaxis (PrEP) program in the Midwestern United States.”

We spoke with first author Dr. Joshua Havens, UNMC ID HIV Program Clinical Pharmacist, about this recent publication.

What is the current work about?

The uptake of HIV pre-exposure prophylaxis (PrEP) is generally highest within large urban cities on the Western and Eastern coasts of the US.  Parts of the Midwest and the South are underserved in many ways but especially for PrEP access.  A provider paradox exists in determining the optimal setting where PrEP provision should take place (i.e. HIV provider, primary care clinic, STI clinic, etc).  It would seem that the primary care setting may be the first access point for PrEP provision of high-risk individuals, but many primary care providers are uncomfortable with providing PrEP for various reasons including increased daily patient loads, discomfort with HIV antiretrovirals, stigma, etc.  Further, patients have reported that they do not feel comfortable with discussing their sexual activity with their primary care provider.

Our study investigated the feasibility of pharmacists as collaborative HIV pre-exposure prophylaxis (PrEP) providers in several different settings (HIV clinic, primary care clinic, and a community pharmacy).  We aimed to capture the number of patients that chose to participate in the study, their retention in care over a year, patient satisfaction with the program, and the pharmacist’s acceptability with the program.

What were some of your key findings?

Our study enrolled 60 patients over 6 months most of which were Caucasian, gay or bisexual men with some sort of insurance coverage. Sexually transmitted infections (STI) were present in 23% of the population at baseline. The majority of the patients chose to participate in the study with nearly all enrolling at either the HIV clinic or community pharmacy settings (only 5 patients participated at a primary care site). Over the time course of the study, retention in PrEP care at all study sites fell. Overall, there was a high rate of patient satisfaction with the pharmacist-led program. Additionally, the pharmacist providers found the program to be acceptable.

The community pharmacy site for the study offered same day appointments in a private setting. All of the point of care screening and testing (HIV, creatinine, syphilis) was done by the pharmacist provider and the STI specimen collections (urine, pharyngeal, rectal) were self-collected by the patients after education was provided. All of these were free of charge during the study period and couriered delivery and processing of STI specimens were completed at a central laboratory with any incident STI’s communicated back to the study team to arrange for subsequent treatment. All of these processes pose as logistical challenges if the community pharmacy model were to be duplicated. Specifically, there is no point of care tesing for either Hepatitis B serology or rapid plasma regain (RPR). As a result, the initiation of PrEP in the community pharmacy would be challenging and the may be more appropriate for follow-up PrEP care. Further, the logistical challenges of STI specimen collection, processing, and treatment would present more challenges at the community pharmacy setting. Thus, these issues would need to be abated prior to implementing a pharmacist-led PrEP program in the community pharmacy setting.

What are some future directions for this work?

Larger scale research studies exploring ways to alleviate the logistical challenges noted in our study, PrEP persistence, and sustainability within the pharmacist-led PrEP model would help to strengthen its utility.

You can read more about this work here.

 


 

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