By Vibhu Sharma, MD
Associate Professor of Medicine, University of Colorado, Denver
SYNOPSIS: This retrospective analysis of prospectively collected data showed that critically ill patients with SARS-CoV-2 infection are at increased risk for hospital-acquired infections.
SOURCE: Grasselli G, Scaravilli V, Mangioni D, et al. Hospital-acquired infections in critically ill patients with COVID-19. Chest 2021;160:454-465.
This report of a retrospective analysis of prospectively obtained data describes the epidemiology and clinical outcomes of hospital-acquired infections (HAIs) in critically ill patients diagnosed with SARS-CoV-2 infection between February 2020 and May 2020 in eight Italian hospitals. Routine surveillance cultures were the norm in the institutions where this study was done; this included weekly tracheal aspirates, perineal and nasal swabs, and urine cultures, with additional cultures as clinically indicated. A designated infectious disease physician and intensive care physician adjudicated final diagnoses at each institution, with intensive care and infectious disease physicians at the sponsoring institution available for consultation in case there were disagreements or questions. Overall, 774 consecutive patients were included in the analysis, most of whom received mechanical ventilation (n = 689, 89%). The median age of enrollees was 62 years, most of whom were men (77%).
In total, 359 patients (46%) were diagnosed with HAIs. The probability of an HAI increased rapidly with duration of intensive care unit (ICU) stay. The first HAI was described a median of 12 days (interquartile range [IQR], 8-18 days) from hospital admission and eight days (IQR, 5-12 days) from ICU admission. Importantly, none of the 82 non-intubated patients admitted to intensive care developed an HAI. Overall mortality in the ICU was 30%. Patients with an HAI complicated by septic shock had a mortality rate of approximately 52%. Ventilator-associated pneumonia (VAP) was the most common, accounting for 50% of total HAIs; bloodstream infections (BSIs) (34%) and catheter-related infections (10%) accounted for most of the rest. The proportion of BSIs was higher than what was described in similar critically ill patients prior to the pandemic.
With respect to bacteriology of the HAIs, as expected, most VAPs were caused by gram-negative bacteria, followed by Staphylococcus aureus. Extended-spectrum beta-lactamase (ESBL)-producing and carbapenamase-producing organisms accounted for 19% and 42% of these gram-negative bacteria, respectively. Slightly more than half (55%) of S. aureus isolates were methicillin-resistant (MRSA). Overall, one-third of all HAIs were the result of multidrug-resistant organisms (MDRO). Invasive fungal infections were rare; invasive aspergillosis was identified in 2% of patients and an identical number were diagnosed with invasive candidal infection. Patients with SARS-CoV-2 infections were treated with steroids and other immunomodulators that may increase the risk of serious HAI; however, use of these drugs was not associated with an increased risk of HAI.
COMMENTARYThe major limitation of this study is that it reports data from a single province in Italy, limiting generalizability of the results. An additional limitation that also may limit generalizability to current practice is that the study reports the bacteriology of HAIs early in the pandemic, with a short duration of study (three months). Since the end of the study in May 2020, there has been a substantial change in the management of critically ill patients with SARS-CoV-2 infection, with a shift to early institution of noninvasive ventilation and a more delayed strategy with respect to invasive ventilation compared to prior. Furthermore, there also has been an increase in the use of immunomodulatory therapies. Both of these factors may contribute to a change in the distribution of HAIs now compared to early 2020. However, it was encouraging that this report did not find an increase in infection with immunomodulatory therapies.
Routine microbiologic surveillance with weekly cultures from multiple sites is not the standard of care in most critical care units in the United States, and it is plausible that this may have led to an overdiagnosis of HAIs. VAP was diagnosed using cutoffs for bacterial growth of 104 colony forming units (CFU)/mL for bronchoalveolar lavage (BAL) and 105 CFU/mL for endotracheal aspirate in addition to clinical criteria. The use of quantitative thresholds in the diagnosis of VAP is controversial and not recommended for diagnostic use in this setting.1,2 Approximately 30% of isolated organisms were MDRO, which is an unusually high proportion, a finding that also may limit generalizability.
The reports of invasive aspergillosis and invasive candidiasis are intriguing. Invasive aspergillosis was diagnosed definitively if positive cultures were obtained from lung tissue or positive stains were found on microscopy of needle aspirates/biopsies of lung tissue. The diagnosis was probable if positive stains were obtained from BAL fluid or if the patient worsened clinically (e.g., pleuritic chest pain, hemoptysis, recrudescent fever despite adequate antibiotic therapy) with suggestive imaging findings. Globally, bronchoscopies were not performed routinely early in the pandemic, and in many medical centers still are not performed routinely. Fungal infections may have been underdiagnosed and/or undertreated in other institutions with lower use of invasive diagnostic strategies. While the authors reported invasive aspergillosis in ~2% of all HAIs, other larger studies have reported higher numbers ranging from 5% to 15%.3 The reason for this difference is unclear and may reflect variation in diagnostic criteria or intensity of diagnostic studies.
Invasive candidiasis was diagnosed if blood cultures were positive or if serum (1,3)-beta-D-glucan was positive with no other diagnosis to explain sepsis, both of which are reasonable diagnostic strategies. Only two patients were diagnosed with Clostridium difficile infection; this may relate to almost universal use of personal protective equipment.
In summary, this study is an informative epidemiologic report on the incidence of HAIs in critically ill patients with SARS-CoV-2 infection, keeping in mind the caveats described.
REFERENCES
- Fujitani S, Yu VL. Quantitative cultures for diagnosing ventilator-associated pneumonia: A critique. Clin Infect Dis 2006;43(Suppl 2):S106-S113.
- Kalil AC, Metersky ML, Klompas M, et al. Management of adults with hospital-acquired and ventilator-associated pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis 2016;63:e61-e111.
- Borman AM, Palmer MD, Fraser M, et al. COVID-19-associated invasive aspergillosis: Data from the UK National Mycology Reference Laboratory. J Clin Microbiol 2020;59:e02136-20.
This retrospective analysis of prospectively collected data showed that critically ill patients with SARS-CoV-2 infection are at increased risk for hospital-acquired infections.
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