Bacterial co-infection risk in COVID-19 low at hospitalization, may rise post-ICU admission

Bacterial co-infection rates are low upon hospital admission in patients with confirmed COVID-19. However, rates may increase during intensive care unit (ICU) stay, a retrospective study from England showed.

The study cohort comprised 254 adults (age ≥16 years; median age 59 years, 64.6 percent male) with PCR-confirmed COVID-19 pneumonia admitted to seven intensive care units (ICUs) in England. Only patients who were discharged or died while in ICU were included. Organisms causing co-infections were assessed ≤48 and >48 hours after hospital admission to identify the presence of community- and hospital-acquired infections, respectively.

Median duration between symptom onset and hospitalization was 7 days, and 1 day between hospitalization and ICU admission. Median length of ICU stay was 9 days. A total of 172 patients were discharged from the ICU, 85.5 percent (n=147) were discharged from hospital and 1.2 percent (n=2) died. The remaining 23 patients remained hospitalized at study end.

One hundred and fifty-one patients (59.5 percent) were mechanically ventilated within 24 hours of hospitalization. During hospitalization, 158 patients (62.2 percent) received advanced respiratory support (invasive ventilation, CPAP via trans-laryngeal tube, extracorporeal respiratory support).

Thirty-five patients (13.8 percent) were prescribed antibiotics before hospitalization, while 89.8 percent (n=228) were prescribed antibiotics within 48 hours of hospitalization. Almost 95 percent of patients were receiving antibiotics at some point during hospitalization.

A total of 139 clinically significant organisms were detected in 83 patients (32.7 percent) between hospitalization to end of ICU stay, with a median 9 days to co-infections/co-colonization. [J Med Microbiol 2021;70:001350]

On the day of hospitalization, four patients (1.6 percent) had potential co-pathogens. This increased to 5.5 percent (n=14) within 48 hours of hospitalization (14 bacterial and one viral pathogen). The most common pathogens were Staphylococcus aureus and Streptococcus pneumoniae which were detected in four and two patients, respectively.

Between 48 hours of hospitalization and end of ICU stay, 124 potential co-pathogens (122 bacterial and two fungal) were identified in 77 patients (30.3 percent), primarily from day 8 (95 pathogens), with a co-infection/co-colonization rate of 27 per 1,000 person-days. The most frequent co-pathogens were Gram-negative bacteria, including Klebsiella spp. and Escherichia coli, which were detected in 23 and 20 patients, respectively. The two fungal co-pathogens were Aspergillus fumigatus and Candida parapsilosis.

“The predominance of Gram-negative bacteria … likely reflects nosocomial infection following prolonged ICU stay and empirical antibiotic use,” the authors noted.

Compared with patients who did not have co-infections/co-colonization, those who did were at an elevated risk of in-ICU mortality (crude odds ratio [OR], 1.78, 95 percent confidence interval [CI], 1.03–3.08; p=0.04), as well as a longer duration of hospitalization (from admission to end of ICU stay; subhazard ratio for likelihood of ICU discharge, 0.53, 95 percent CI, 0.39–0.71; p<0.001). 

Univariate analysis also showed that patients aged 50–64 years had a higher risk of co-infections/co-colonization than those aged 18–49 years (crude OR, 2.28, 95 percent CI, 1.14–4.53; p=0.019). Co-infection/co-colonization risk did not vary by sex, ethnicity, and comorbidities.

Upfront antibiotics unnecessary?

About 95 percent of mortality during the 1918 influenza pandemic was complicated by bacterial pneumonia. [Nat Rev Microbiol 2014;12:252-262] However, the presence and impact of co-pathogens on COVID-19 infection is currently uncertain, said the authors.

“The lack of an effective antiviral agent against SARS-CoV-2 combined with challenges in differentiating secondary bacterial co-infection from severe COVID-19 infection alone, has fostered the widespread use of empirical antibiotics in the immediate management of patients hospitalized with COVID-19 infection.”

“[O]ur data indicate that early in hospitalization, bacterial co-infection in COVID-19 is very uncommon and support the recommendations that empirical antibiotics should not be started routinely in primary care or at the point of hospital admission without clinical suspicion of bacterial infection,” they pointed out.

It is possible that co-infection rates are higher among those with more severe disease, particularly those admitted to the ICU. “It is plausible that reducing unnecessary early antibiotic exposure in patients with COVID-19 could reduce their risk of late, Gram-negative, potentially antibiotic resistant infections,” they suggested.

They cautioned that limiting the cohort to patients with ICU outcomes means that the findings may not apply to frailer patients who are not candidates for ICU admission or those with prolonged ICU stay, among whom co-infection may be more common.

The authors also recommended microbiological vigilance now that dexamethasone, use of which may be associated with an increased risk of bacterial co-infection, is a standard-of-care treatment for patients hospitalized with COVID-19 in many countries.