Alice Gallo De Moraes, MD, is a pulmonary and critical care consultant at Mayo Clinic in Rochester, Minnesota.

Alice Gallo De Moraes, MD

Recognizing and treating sepsis promptly saves lives. Some suggest that every patient admitted to the hospital for COVID-19 has sepsis secondary to COVID-19 infection. Conventional 

wisdom has taught us that antibiotics are ineffective for viral infections, but conventional sepsis has focused heavily on bacterial infections, providing less guidance regarding the management of viral infections, including COVID-19.

Classically, pneumonia is diagnosed based on clinical symptoms coupled with a new infiltrate on an imaging study; however, this alone does not distinguish viral from bacterial pneumonia, particularly in COVID-19 infection. Early on, it was particularly challenging to determine if COVID-19 infection with or without secondary bacterial pneumonia was present due to the lag time in results from COVID-19 tests. This challenge continues to be exacerbated in hospital courses complicated by acute respiratory distress syndrome, pulmonary embolism, volume overload, and risk of nosocomial infection. Consequently, antibiotics are often administered amid diagnostic uncertainty for refractory hypoxia and fevers because it remains difficult to determine if the cause is bacterial colonization, ventilator-associated pneumonia, a pulmonary embolism, or simply worsening COVID-19 when a patient is too unstable to travel for more definitive chest imaging.

Bronchoalveolar lavage would have been a welcome tool to evaluate for infection, but this was frequently limited 

due to risk of aerosol generation and the potential transmission of COVID- 19, particularly early in the pandemic when personal protective equipment was limited and transmission was not fully understood. Instead, we relied on chest x-rays, blood cultures, urinalyses, sputum cultures, and tracheal aspirates to identify a possible infection.

ISSUES WITH SEPSIS MANAGEMENT/SURVIVING SEPSIS GUIDELINES

Earlier versions of the Surviving Sepsis Campaign COVID-19 guidelines recommended administering 30 mL/kg of crystalloid in patients with septic shock and elevated blood lactate levels.

 However, fluid resuscitation in some patients resulted in volume overload with resultant pulmonary edema, which increased the complexity of providing supportive care, particularly among those with acute respiratory distress syndrome. The Surviving Sepsis Campaign guidelines for COVID-19 primarily were composed of 9 strong recommendations, 6 of which were centered on principles of ventilation, along with many weak recommendations.

 Even with the updated guidelines, no guidance was given on the use of antibiotics in patients with COVID-19.

Many clinicians underestimated the impact of hypoxia on serum lactate levels in COVID-19 infection and overvalued procalcitonin, leading to the overuse of antibiotics. The role of procalcitonin in COVID-19 infection remains unclear. Although procalcitonin levels are generally low in viral infections, they can be a marker of disease severity in COVID-19,

 leading to potentially inappropriate antibiotic use.

 Treating hypoxia with oxygen in the absence of antibiotics normalized serum lactate levels in many patients, and subsequently, many critical care clinicians have learned the importance of individualizing patient care for septic patients.

HOSPITAL-ACQUIRED INFECTIONS IN THE INTENSIVE CARE UNIT (ICU)

The COVID-19 pandemic has been an intellectual and emotional rollercoaster: large volumes of patients overwhelming the health care system, fear of contracting COVID-19,

 a plethora of published papers to keep up with, supply chain shortages, burned-out health care workers, and countless patient deaths despite our best efforts.

Removing invasive lines (which were utilized longer than normal due to prolonged mechanical ventilation and prone positioning) and urinary catheters was deprioritized as we emphasized convenience amid a stretched health care workforce: reliable intravenous access for antibiotics, sedation, vasopressors, more timely labs, accurate intake and output to prevent volume overload in patients with acute respiratory distress syndrome, and even rectal tubes to preserve personal protective equipment.

Several retrospective studies have demonstrated how common ventilator-associated pneumonia is in ICU patients with severe COVID-19.

 As hospital COVID-19 cases surged, there were significant increases in the prevalence of central line-associated bloodstream infections (CLABSIs), catheter-associated urinary tract infections (CAUTIs), ventilator-associated events, and methicillin-resistant 

 Burnout was associated with hospital infections even before the pandemic.

 Typical practices and resources to monitor and prevent the development of hospital-acquired infections (HAIs) were necessarily redirected to the COVID-19 response, increasing the risk for the development of HAIs.

In some hospitals, the use of a multiplex pneumonia panel provided an opportunity to avoid inappropriate initiation of antibiotics for negative polymerase chain reaction (PCR) results, initiate targeted antimicrobial therapy for positive PCR results, and enable more rapid de-escalation and discontinuation of antibiotics if the pneumonia panel was negative prior to the finalization of sputum cultures.

 Sometimes starting, broadening, or continuing antibiotics felt like the only tool available to attempt to save a patient on maximum ventilator settings in multiorgan failure, even though it was unclear if antibiotics would help.

In a systematic review, the prevalence of antibiotic prescribing in patients with COVID-19 was 74.6%, but estimated bacterial coinfection was only 8.6%, suggesting a high risk of unnecessary antibiotic use in COVID-19. Unsurprisingly, increased age, increased severity of illness, and mechanical ventilation were all associated with increased antibiotic use.

Prepandemic, we rarely reached for empiric voriconazole beyond patients with solid organ or bone marrow transplants; however, finding pulmonary aspergillosis infections

 in patients with COVID-19 later in the course changed that for us. To this day, the combination of vancomycin and cefepime frequently started in febrile, prone patients with COVID-19 with refractory hypoxia and persistent infiltrate on chest x-rays in some ICUs is affectionately termed the portmanteau vancopime.

The conflict between trying to practice good antibiotic stewardship to reduce the potential for the development of multidrug-resistant organisms while still doing everything we thought was best for our patients to decrease mortality did not wane despite more experience caring for patients with COVID-19.

Despite the challenges of managing sepsis in patients with COVID-19 due to diagnostic uncertainty, the pandemic provided some valuable lessons: the importance of appropriately recognizing and treating sepsis, diligent adherence to best practices in infection control to prevent the development of CLABSIs and CAUTIs, daily evaluations of the necessity of invasive lines and catheters in the ICU, and refining, de-escalating, or discontinuing antibiotics based on microbiologic culture results.

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Conflicting priorities of infection control, antimicrobial stewardship, and critical care make the management of sepsis secondary to SARS-CoV-2 infection challenging.

Alice Gallo De Moraes, MD

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