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.
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
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%.
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.
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