COVID-19 Clinical Care: Study Shows That Most COVID-19 Patients At Risk Of Fatal Secondary Bacterial Co-Infection When In ICU

COVID-19 Clinical Care: British researchers from the University of Nottingham and several hospitals under the Nottingham University Hospital NHS Trust, University College London Hospitals NHS Foundation, Salford Royal NHS Foundation,  Trust Guy’s and St Thomas’ NHS Foundation Trust and the University of Manchester have in a new study found that a high proportion of patients admitted to intensive care units (ICU) with COVID-19 acquire a secondary bacterial co-infection during their hospital stays.


 
The study team found limited evidence for community-acquired bacterial co-infection in hospitalized adults with COVID-19, but a high rate of Gram-negative infection acquired during ICU stay.
 
The new retrospective cohort study of patients admitted to seven hospital ICUs in England up to May 18th, 2020 found that the longer the ICU stay, the more significant the proportion of patients who developed nosocomial (hospital-acquired) infections.
 
Although bacterial co-infection within 48 hours of ICU admission was uncommon, the proportion of pathogens detected started to increase after 48 hours. The pathogens mostly consisted of Gram-negative bacteria, particularly Klebsiella pneumoniae and Escherichia coli.
 
Significantly, it was found that patients who developed these infections were significantly more likely to die in ICU than those without co-infections.
 
The study findings were published on a preprint server and are currently being peer reviewed. https://www.medrxiv.org/content/10.1101/2020.10.27.20219097v1
 
Dr Vadsala Baskaran from Nottingham University Hospital NHS Trust told Thailand Medical News, “This pragmatic multicenter study provides novel data on both community-acquired and nosocomial co-infection in patients with COVID-19 requiring ICU care in England."
 
The study team says the finding that co-infection among COVID-19 patients is uncommon early on during hospitalization supports the recommendations that empirical antibiotics should not be used at the point of admission unless a bacterial infection is suspected.
 
The team added that it is possible that reducing unnecessary exposure to such antibiotics could lower the risk of patients later acquiring Gram-negative infections that are potentially resistant to antibiotics,
 
Importantly gram-positive bacteria are more susceptible to treatment with antibiotics than Gram-negative bacteria since they have a single-layered cell wall that is more easily penetrated than the double-layered cell wall of Gram-negative bacteria.
 
The researchers recommend that a high level of microbiological vigilance is maintained when managing patients hospitalized with COVID-19
 
Such co-infections with other pathogens during viral pandemics has been reported previously. For example during the 1918 influenza pandemic, reports estimated that almost all (95%) of severe infections and death had been complicated by bacterial co-infection, predominantly co-infection with  Streptococcus pneumoniae and Staphylococcus a ureus.
 
Following SARS-CoV-2 infection, the immune response includes an increase in the proinflammatory cytokine interleukin 6 and the inflammation marker C-reactive protein, with levels increasing the more severe the disease.  
 
The study team said that the role that co-pathogens play during SARS-CoV-2 infection is not well understood.
 
In addition, the lack of effective antiviral treatments for SARS-CoV-2, as well as the difficulty distinguishing between secondary bacterial co-infection and severe COVID-19 alone, has led to the widespread use of empirical antibiotics as a first-line treatment approach for hospitalized COVID-19 patients.
 
The study team said, “Over the spring wave of the pandemic, 83.1% of hospitalized patients in the UK received empirical antibiotic treatment. A better understanding of the incidence of co-infection in patients with COVID-19 infection and the pathogens involved is necessary for effective antimicrobial stewardship.”
 
In order to determine the incidence and nature of co-infection among critically ill COVID-19 patients in England, the team conducted a retrospective study of 254 patients who had completed ICU stays at seven acute hospitals across England.
 
Study participants (aged 16 years or older) with COVID-19 pneumonia who had been receiving treatment from the point of disease emergence up to May 18th, 2020, had either died while in ICU or had been discharged from hospital.
 
For the study, the proportion of co-infection was determined at three-time points: on ICU admission, within 48 hours of admission and beyond 48 hours of admission, to distinguish between patients with community- versus hospital-acquired co-infection.
 
The study team identified 139 clinically significant pathogens among 83 (32.7%) of the 254 patients studied.
 
It was observed that Bacterial co-infection within 48 hours of hospital admission was uncommon, occurring in 4 (1.6%) of the patients on admission and 14 (5.5%) of the patients within 48 hours of admission.
 
Importantly the most common pathogens identified within the first 48 hours of admission were the Gram-positive bacteria Staphylococcus aureus and Streptococcus pneumoniae.
 
The study team found that the proportion of co-pathogens started to increase after 48 hours in ICU.
 
However, beyond 48 hours of ICU admission, the proportion of co-pathogens detected increased until the end of the stay (either death or hospital discharge).
 
Importantly aside from two fungal organisms, all of the co-pathogens identified were Gram-negative bacteria, predominantly Klebsiella pneumoniae, and Escherichia coli.
 
In another article that Thailand Medical News had covered in July, a study found that a proportion of COVID-19 patients had a drug resistant fungal infection in their lungs caused by a new hybrid strain of the Aspergillus Latus fungus. https://www.thailandmedical.news/news/breaking-covid-19-news-scientists-discover-drug-resistant-hybrid-fungus-aspergillus-latus-involved-in-lung-infections-of-certain-covid-19-patients
 
Dr Baskaran added, “These pathogens are commonly associated with hospital and ventilator-acquired pneumonia and have been reported as common co-pathogens in COVID-19 infections, particularly ICU cohorts. The predominance of Gram-negative bacteria in these studies likely reflects nosocomial infection following prolonged ICU stay and empirical antibiotic use.”
 
Significantly univariate analyses showed that patients aged 50-64 years were more likely to have a bacterial co-infection than those aged 18-49 years. COVID-19 patients with these co-infections were also at a significant 78% greater likelihood of dying in the ICU than patients who did not have a bacterial co-infection.
 
 The study team added, “The research 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 warned that the high rate of co-infection at a later stage during hospitalization and involving nosocomial pathogens is concerning.
 
Dr Baskaran added, “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.”
 
The study team concluded, “In the setting of seasonal changes in respiratory pathogens, ongoing surveillance for co-infections in patients hospitalized with COVID-19, ideally through prospective studies with standardized sampling protocols, is advised.”
 
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