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Managing Bacterial Infections in the Era of COVID-19

Lodise, Thomas PharmD, PhD; Tillotson, Glenn Simon PhD, FIDSA, FCCP

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Infectious Diseases in Clinical Practice: September 2020 - Volume 28 - Issue 5 - p 251-254
doi: 10.1097/IPC.0000000000000894
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We are living in unprecedented times. Despite some positive indications that we are nearing the apex in certain countries, COVID-19 (SARS-CoV-2) will continue to have an enormous impact on our society and, in particular, the healthcare system until therapeutic and preventive measures have been approved and made widely available. Even with the most optimistic predictions, we will have not a vaccine for another 12 to 18 months.1 Rapid point of care and serology testing will facilitate our ability to resume our normal activities, but there is still a lot we need to learn about COVID-19. We are still not entirely clear on viral transmission and spread. Recent data indicate that it is readily transmitted in the air,2 and the virus seems to colonize many body sites beyond the nares and oropharyngeal area (i.e., gastrointestinal tract). It seems that a person still may be able to transmit the virus in the presence of negative nares and oropharyngeal polymerase chain reactions. We do still do not know the true asymptomatic carrier rate or the percentage of individuals with innate immunity. Although unlikely, we do not know whether a person who has had a SARS-CoV-2 infection can get reinfected. As we work to better understand the epidemiology of COVID-19, we should continue to expect a consistent base case load of COVID-19 with localized outbreaks across communities and regions for the foreseeable future, even with point of care and serologic testing.

One of the most important things we can do until a vaccine is widely available is to strictly follow social distancing directives and protect our most vulnerable patient populations from contracting COVID-19 infection. Older people and people with preexisting medical conditions, such as chronic lung disease or moderate to severe asthma, serious heart conditions, conditions that can cause a person to be immunocompromised, diabetes, chronic kidney disease, and liver disease, are highly susceptible to becoming severely ill with the virus. Similar to H1N1, individuals with obesity are also at a high risk for severe illness from COVID-19 regardless of age.3 Unfortunately, many of the high-risk COVID-19 patients are also at an increased risk for developing serious bacterial infections that often result in hospitalization. More than half of all antibiotics given to treat active infections in hospitals are prescribed for 3 infections: lower respiratory tract infection such as community-acquired pneumonia (CAP), skin and soft tissue infection (SSTI), and urinary tract infection (UTI).4 In the United States alone, there are approximately 7 million emergency room visits5 and 1 million hospital admissions annually due to pneumonia,6 3 million emergency room visits and 870,000 hospital admissions annually due to SSTIs,7,8 and 3 million emergency room visits and 500,000 hospital admissions annually due to UTIs.9–11 On average, the cost of a hospitalization is approximately 8 to 10,000 USD for each one of these infectious conditions.9,12 Hospital readmissions are also commonplace; an estimated 10% to 20% of patients with CAP, SSTI, and UTI will have a subsequent hospital readmission within 30 days.13 Combined, the US hospital costs associated with managing these infections exceeds 30 billion dollars each year.6–10,14,15

COVID-19 IN THE HOSPITAL SETTING

In the era of COVID-19, it is important that we look to optimize the quality and efficiency of care for our patients who are at a “high risk” for COVID-19 when they develop common infections such as CAP, SSTI, and UTI. The role of the hospital pharmacist is paramount in managing polypharmacy, which is essential to the care of these patients. In addition, there should be directed antimicrobial stewardship initiatives to ensure that patients with CAP, SSTI, and UTI are treated appropriately with the least amount of time possible in healthcare facilities. As part of caring for COVID-19 patients, there are increasing reports that upwards of 1 in 5 frontline healthcare workers are acquiring COVID-19.16 It is extremely challenging for many hospitals to limit the transmission of the virus, as COVID-19 patients are overwhelming their institutions and resources. Even among hospitals that have not yet reached maximal capacity, there is often a lack of negative pressure rooms and other essential personal protective equipment to adequately protect these frontline healthcare workers. Similar to antibiotic-resistant pathogens such as methicillin-resistant Staphylococcus aureus (MRSA), carbapenem resistant enterobacteriaceae (CRE), and extendes spectrum B lactamase producing (ESBL)-producing Enterobacteriaceae, monitoring the potential spread of COVID-19 in hospitals and among healthcare workers is a critical priority.

MANAGEMENT STRATEGIES

When managing patients with CAP, SSTI, and UTI, we can minimize their contact in healthcare facilities by creating standardized processes to divert hospital admissions in appropriate patients and minimizing hospital length of stay (LOS) among those that are admitted to appropriate patients and to minimize hospital LOS among those who are admitted patients. Studies indicate that a substantial proportion of patients hospitalized for the treatment of an infection are unnecessarily admitted. Although there are a variety of reasons for this, data suggest that inconsistent initial site-of-care criteria are applied.17,18 Furthermore, data indicate that many patients with serious infections are often admitted for the sole purpose of receiving intravenous (IV) antibiotics at infusion centers.19 Studies show that patients hospitalized with infections often remain in the hospital after they achieve clinical stability or acute infection resolves, and it is possible to discharge these patients with continued oral or IV antibiotic therapy without compromising their outcomes.20,21 In addition to reducing the risk of acquiring COVID-19, early hospital discharge of suitable patients with CAP, SSTI, and UTIs would also allow precious healthcare resources to be reallocated elsewhere during this critical time in the pandemic.

INSTITUTIONAL PATHWAYS AND APPROPRIATE PATIENT GROUPS

Severely ill patients and those with unstable comorbid conditions and presenting with CAP, SSTI, and UTI will still need to be admitted. In patients with mild to moderate symptoms and stable comorbidities who are confirmed to be COVID-19 negative, there are 2 ways in which hospitalization can be avoided or shortened. Site-of-care severity of illness indicators and prognostic models should be used to identify patients with pneumonias, SSTI, and UTIs who may be candidates for outpatient treatment. The most notable and validated site-of-care admission criteria tool used by clinicians is the Pneumonia Severity Index (PSI), which stratifies patients with CAP into 5 mortality risk classes.22,23 On the basis of mortality risk, it is recommended that patients in risk classes I and II (PSI score ≤ 70) be treated as outpatients, patients in risk class III (PSI score, 71–90) be treated in an observation unit or with a short hospitalization (many of these patients may be candidates for outpatient treatment), and patients in risk class IV (PSI score, 91–130) or V (PSI score > 130) be treated as inpatients. Unfortunately, validated site-of-care severity of illness indicators and prognostic models are not available for SSTI and UTIs. However, institutions have created initial site-of-care pathways for SSTIs and have managed to avert hospitalizations in appropriate patients without compromising outcomes.24,25

THERAPEUTIC AGENTS

Use of oral antibiotics that achieve similar therapeutic exposure profiles as IV antibiotics26–28 can also be used to shift the care of patients with CAP, SSTI, and UTI to the outpatient. In addition to long-standing agents such as levofloxacin, moxifloxacin, and linezolid, we have several new therapeutics that have been added to our armamentarium in the past 2 years, which have oral formulations that achieve excellent therapeutic exposures. These include delafloxacin, an anti-MRSA fluoroquinolone that is US Food and Drug Administration (FDA) approved for the treatment of adults with acute bacterial skin and skin structure infections (ABSSSI) and CABP (approved for methicillin suscpeptible Staphyloccocus aureus (MSSA) only); lefamulin, a first-in-class pleuromutilin antibiotic that is FDA approved for the treatment of adults with CABP (MSSA only); and omadacycline, a next-generation tetracycline that is FDA approved for the treatment of adults with ABSSSI and CABP (IV to oral switch only, MSSA only). Switching patients from IV to oral antibiotics is one of the fundamentals pillars of antibiotic stewardship because it has been shown across a variety of disease states to reduce hospital LOS, duration of IV antibiotic treatment, adverse events, and associated costs compared with usual care and without compromising patients or resulting in increased hospital readmission rates.26–30 Use of an oral antibiotic with a bioequivalent exposure profile as an IV antibiotic can also be used to shift the care of low-risk patients with CAP, SSTI, and UTI from inpatient to outpatient antimicrobial therapy. Studies have demonstrated that this shift in care is best achieved through the use of structured institutional site-of-care clinical pathways and staff education.31

Another option, especially when there are concerns with patient adherence and prolonged IV therapy in the outpatient setting, is use of the single IV dose lipoglycopeptide antibiotics such as oritavancin or dalbavancin32 to avert and shorten hospitalization.33 These agents are FDA approved as single-dose IV therapies for the treatment of ABSSSI caused or suspected to be caused by certain gram-positive pathogens, including MRSA.34–38 Because the phamcokinetic-pharmacodynamic profile of oritavancin and dalbavancin allow for single-dose treatment, these therapies can potentially be used to shift the site of care for stable patients, who have limited comorbidities and are admitted solely for the administration of IV antibiotics from the hospital to the outpatient setting. There is also the potential to use these single-dose IV therapies to facilitate early discharge of patients with SSTI after their acute infection resolves. In addition to robust phase III clinical trial to support their use for patients with SSTI, there are a growing number of real-world evidence studies to support their use to shift the site of care from the inpatient setting to the outpatient setting. Results from a large multicenter cohort analysis of outpatients with SSTIs showed that patients who received oritavancin had lower 30-day subsequent hospital admission rates while maintaining similar costs relative to those who received IV vancomycin.39 There are also data that suggest that oritavancin may be associated with lower 30-day readmission rates relative to the national average of 20%.40 In an assessment of patients who received oritavancin to facilitate hospital discharge at a community hospital, no readmissions were observed within 14 days of discharge.41 Similarly, in an evaluation of oritavancin for ABSSSI patients across 3 hospital-based outpatient infusion centers, the 30-day subsequent admission rate was reported to be 6.1%.25 Finally, Estrada et al24 examined 2 cohorts of SSTI patients: 1 group received IV oritavancin at an outpatient infusion clinic, whereas the other group received IV oritavancin upon discharge from hospital to complete treatment. In this study, the outpatient group showed a 6.1% 30-day hospital admission rate, and the cohort that received oritavancin on hospital discharge had a nearly identical 30-day readmission rate of 6.6%.

CONCLUSIONS

In conclusion, an important consideration in managing CAP, SSTIs, and UTI patients in the current COVID-19 pandemic is to minimize their contact in healthcare facilities. This can be accomplished by creating standardized processes to avoid hospital admissions in appropriate patients and minimizing hospital LOS among those who are admitted. Historically, this has been done with oral antibiotics with excellent bioavailability. The availability of single-dose IV antibiotics, such as oritavancin, provides a more practical way to transition patients from the inpatient to the outpatient setting, as well as safeguarding against poor patient adherence, which is commonplace among patients prescribed oral antibiotics. This proposed practice of shifting the site of care of appropriate patients with CAP, SSTI, and UTI is congruent with antibiotic stewardship efforts in the hospital setting, which seek to improve patient outcomes, reduce the development of antimicrobial resistance, and minimize unnecessary costs without negatively impacting the quality of care.

REFERENCES

1. Craven J. COVID-19 vaccine tracker: Regulatory Affairs Professionals Society (RAPS). Available at: https://www.raps.org/news-and-articles/news-articles/2020/3/covid-19-vaccine-tracker. Accessed May 5, 2020.
2. National Research Council. Rapid Expert Consultation on the Possibility of Bioaerosol Spread of SARS-CoV-2 for the COVID-19 Pandemic (April 1, 2020). Washington, DC: The National Academies Press:2020:3.
3. Centers for Disease Control and Prevention. Groups at higher risk for severe illness. Available at: https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/groups-at-higher-risk.html. Accessed May 4, 2020.
4. Magill SS, Edwards JR, Beldavs ZG, et al. Prevalence of antimicrobial use in US acute care hospitals, May-September 2011. JAMA. 2014;312(14):1438–1446.
5. Self WH, Grijalva CG, Zhu Y, et al. Rates of emergency department visits due to pneumonia in the United States, July 2006-June 2009. Acad Emerg Med. 2013;20(9):957–960.
6. Torio C, Moore B; Agency for Healthcare Research and Quality. National inpatient hospital costs: the most expensive conditions by payer, 2013. Healthcare Cost and Utilization Project (HCUP) Statistical Brief #204. In: Rockville, MD; 2016.
7. Kaye KS, Patel DA, Stephens JM, et al. Rising United States hospital admissions for acute bacterial skin and skin structure infections: recent trends and economic impact. PLoS One. 2015;10(11):e0143276.
8. Edelsberg J, Taneja C, Zervos M, et al. Trends in US hospital admissions for skin and soft tissue infections. Emerg Infect Dis. 2009;15(9):1516–1518.
9. Carreno JJ, Tam IM, Meyers JL, et al. Corrigendum to: longitudinal, nationwide, cohort study to assess incidence, outcomes, and costs associated with complicated urinary tract infection. Open Forum Infect Dis. 2020;7(1):ofz536.
10. Flores-Mireles AL, Walker JN, Caparon M, et al. Urinary tract infections: epidemiology, mechanisms of infection and treatment options. Nat Rev Microbiol. 2015;13(5):269–284.
11. Healthcare Cost and Utilization Project. Emergency Department Visits—159 Urinary Tract Infections. CCS [Internet]. Agency for Healthcare Research and Quality. 2014. Available at: https://www.hcup-us.ahrq.gov/reports/statbriefs/sb179-Emergency-Department-Trends.pdf. Accessed June 3, 2020.
12. Suaya JA, Mera RM, Cassidy A, et al. Incidence and cost of hospitalizations associated with Staphylococcus aureus skin and soft tissue infections in the United States from 2001 through 2009. BMC Infect Dis. 2014;14:296.
13. Centers for Medicare and Medicaid Services. Hospital Readmission Reduction Program 2018. Available at: https://www.cms.gov/Medicare/Quality-Initiatives-Patient-Assessment-Instruments/Value-Based-Programs/HRRP/Hospital-Readmission-Reduction-Program.html. Updated December 4, 2018.
14. Jain S, Self WH, Wunderink RG, et al. Community-acquired pneumonia requiring hospitalization among U.S. adults. N Engl J Med. 2015;373(5):415–427.
15. Healthcare Costs and Utilization Project. Healthcare Costs and Utilization Project—hospital inpatient national statistics 2016 [Internet]. Available at: https://hcupnet.ahrq.gov/-query/ey. Accessed March 29, 2019.
16. Galvin G. The great unknown: how many health care workers have coronavirus?U.S. News & World Report. Available at: https://www.usnews.com/news/national-news/articles/2020-04-03/how-many-health-care-workers-have-coronavirus. Accessed May 3, 2020.
17. Lodise TP, Fan W, Sulham KA. Hospital admission patterns in adult patients with skin and soft tissue infections: identification of potentially avoidable hospital admissions through a retrospective database analysis. Hosp Pract. 2015;43(3):137–143.
18. Dean NC, Jones JP, Aronsky D, et al. Hospital admission decision for patients with community-acquired pneumonia: variability among physicians in an emergency department. Ann Emerg Med. 2012;59(1):35–41.
19. Talan DA, Salhi BA, Moran GJ, et al. Factors associated with decision to hospitalize emergency department patients with skin and soft tissue infection. West J Emerg Med. 2015;16(1):89–97.
20. Dryden M, Saeed K, Townsend R, et al. Antibiotic stewardship and early discharge from hospital: impact of a structured approach to antimicrobial management. J Antimicrob Chemother. 2012;67(9):2289–2296.
21. Gray A, Dryden M, Charos A. Antibiotic management and early discharge from hospital: an economic analysis. J Antimicrob Chemother. 2012;67(9):2297–2302.
22. Metlay JP, Waterer GW, Long AC, et al. Diagnosis and treatment of adults with community-acquired pneumonia. An official clinical practice guideline of the American Thoracic Society and Infectious Diseases Society of America. Am J Respir Crit Care Med. 2019;200(7):e45–e67.
23. Fine MJ, Hough LJ, Medsger AR, et al. The hospital admission decision for patients with community-acquired pneumonia. Results from the pneumonia patient outcomes research team cohort study. Arch Intern Med. 1997;157(1):36–44.
24. Estrada S, Delaportas D, Lodise T, et al. The real world economic and clinical management of adult patients with skin and soft tissue (SSTI) infections with oritavancin: data from two multi-center observational cohort studies. Drugs Real World Outcomes. June 2020.
25. Whittaker C, Lodise T, Nhan E, et al. Expediting discharge in hospitalized, adult patients with skin and soft tissue infections who received empiric vancomycin therapy with oritavancin: description of findings from an institutional pathway. Drugs Real World Outcomes. June 2020.
26. Nathwani D, Eckmann C, Lawson W, et al. Pan-European early switch/early discharge opportunities exist for hospitalized patients with methicillin-resistant Staphylococcus aureus complicated skin and soft tissue infections. Clin Microbiol Infect. 2014;20(10):993–1000.
27. Oosterheert JJ, Bonten MJ, Schneider MM, et al. Effectiveness of early switch from intravenous to oral antibiotics in severe community acquired pneumonia: multicentre randomised trial. BMJ. 2006;333(7580):1193.
28. Mazumder S. Intravenous-to-oral switch therapy. 2018. Available at: https://emedicine.medscape.com/article/237521-overview. Accessed April 25, 2020.
29. Barlam TF, Cosgrove SE, Abbo LM, et al. Implementing an antibiotic stewardship program: guidelines by the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America. Clin Infect Dis. 2016;62(10):e51–e77.
30. Centers for Disease Control and Prevention. Core Elements of Hospital Antibiotic Stewardship Programs. Atlanta, GA: US Department of Health and Human Services, CDC; 2019.
31. Carratala J, Garcia-Vidal C, Ortega L, et al. Effect of a 3-step critical pathway to reduce duration of intravenous antibiotic therapy and length of stay in community-acquired pneumonia: a randomized controlled trial. Arch Intern Med. 2012;172(12):922–928.
32. Tobudic S, Forstner C, Burgmann H, et al. Real-world experience with dalbavancin therapy in gram-positive skin and soft tissue infection, bone and joint infection. Infection. 2019;47(6):1013–1020.
33. Wunsch S, Krause R, Valentin T, et al. Multicenter clinical experience of real life dalbavancin use in gram-positive infections. Int J Infect Dis. 2019;81:210–214.
34. Corey GR, Good S, Jiang H, et al. Single-dose oritavancin versus 7–10 days of vancomycin in the treatment of gram-positive acute bacterial skin and skin structure infections: the SOLO II noninferiority study. Clin Infect Dis. 2015;60(2):254–262.
35. Corey GR, Kabler H, Mehra P, et al. Single-dose oritavancin in the treatment of acute bacterial skin infections. N Engl J Med. 2014;370(23):2180–2190.
36. Lodise TP, Redell M, Armstrong SO, et al. Efficacy and safety of oritavancin relative to vancomycin for patients with acute bacterial skin and skin structure infections (ABSSSI) in the outpatient setting: results from the SOLO clinical trials. Open Forum Infect Dis. 2017;4(1):ofw274.
37. Melinta Therapeutics Inc. Orbactiv® (Oritavancin) Full Prescribing Information (Package Insert). Parsippany, NJ;2018.
38. Durata Therapeutics U.S. Limited. Prescribing Information: DALVANCE (dalbavancin) for injection, for intravenous use. Parsippany, NJ; 2018.
39. Lodise TP, Palazzolo C, Reksc K, et al. Comparisons of 30-day admission and 30-day total healthcare costs between patients who were treated with oritavancin or vancomycin for a skin infection in the outpatient setting. Open Forum Infect Dis. 2019;6(12):ofz475.
40. Fisher JM, Feng JY, Tan SY, et al. Analysis of readmissions following hospitalization for cellulitis in the United States. JAMA Dermatol. 2019;155(6):720–723.
41. Co D, Roebuck L, VanLandingham J. Evaluation of oritavancin use at a community hospital. Hosp Pharm. 2018;53(4):272–276.
Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc.