The Deadly Risk of Hospital-Acquired Infections and Antimicrobial Resistance for COVID-19 Patients
Patricio V. Marquez and Albert Figueras
As of mid-February 2021, the ongoing COVID-19 pandemic has resulted in more than 108 million confirmed cases and over 2.3 million deaths. The surging patient caseloads hospitalized or admitted to intensive care units (ICU) have pushed hospitals and ICU closer to 100% capacity in many countries, creating an extraordinary strain on resources and personnel and making quality-of-care standards harder to maintain.
As with other viral diseases, the effect of COVID-19 disease on the immune response of the host, facilitates concurrent bacterial infections. In the case of patients with severe COVID-19 disease, due to prolonged stay in the ICU and the use of mechanical ventilators, there is an added risk of co-infection by multidrug-resistant bacteria and fungus. This situation may have been aggravated by the fact that during the first months of the pandemic, when the general knowledge about the virus was null or limited, many antibiotics, such as of azithromycin, used to treat many different types of infections caused by bacteria, such as respiratory infections, were highly prescribed to COVID patients “just in case” or to test if there was any response. The unexpectedly high rate of antibiotic prescribing during the early months of the COVID-19 pandemic (April-August 2020) in the UK has also been attributed to the increase in remote consultations, which might lead clinicians to take greater precautions in cases of possible infection given the greater diagnostic uncertainty that results from an inability to examine patients and perform investigations during telephone appointments.
We pose the question of whether the growing number of hospitalizations and ICU use due to COVID-19 is increasing the risk of health-care associated infections (HCAIs), also known as “nosocomial” infections, and consequently, if the number of HCAIs due to multi-resistant bacteria is increasing during the pandemic.
The importance of this question is that these infections may affect patients in any type of setting where they receive care or after discharge, as well as staff working in health care facilities. HCAIs result in prolonged hospital stays, long-term disability, increased resistance of microorganisms to antimicrobials, high costs for patients and families, and unnecessary deaths.
ICU and Risk for Patients of Acquiring Infection due to Multiple Antibiotic Resistant Organisms
The World Health Organization (WHO), estimated that before the pandemic, hundreds of millions of patients around the world were affected by HCAIs. Patients admitted to intensive care units (ICU) are particularly at risk of acquiring infection due to multiple antibiotic-resistant strains of notorious nosocomial pathogens (including Enterococcus spp., Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Escherichia coli).
The problem of drug-resistant infections is troubling. A review on antimicrobial-resistant infections (AMR) estimated that 700,000 deaths each year globally might be due to drug-resistant bacterial infections, including multidrug-resistant and extensively drug-resistant tuberculosis, posing a major public health threat as routine surgeries and minor infections could become life-threatening once again and the inroads made in controlling infectious diseases of the last fifty years could be jeopardized.
A recent systematic scoping review shows that ICU-acquired infection rates are quite high in low- and middle-income countries (LMICs), with an average prevalence rate of 22.4 infected patients per 100 in the ICU. This rate is somewhat higher than the rate observed in some high-income countries. ICU mortality was also found to be much higher in LMICs (33.6%) than in high-income countries (< 20%). Moreover, LMIC patients died relatively early during their ICU stay, and their mean age at death was lower than in high-income countries (50 years versus 60 years, respectively).
Multidrug-resistant infections (MDR) played a much more dominant role in LMIC ICUs than in those in high-income countries, due to high percentages of Pseudomonas resistant to carbapenems, a class of antibiotics that were developed to treat bacteria that are resistant to other drugs and that can cause severe blood infections and pneumonia. These include Acinetobacte baumannii, a Gram-negative bacterium that causes pneumonia, bloodstream infections, and meningitis, and Klebsiella pneumoniae, a bacterium that is harmless when present in the intestines but that can cause severe infections if spread to other parts of the body. The determinants of antimicrobial resistance in LMICs include overconsumption of antibiotics and the lack of barriers against the spread of selected resistant pathogens in healthcare settings.
Secondary infections and COVID-19
Although limited due to the still ongoing spread of COVID-19 disease worldwide, some initial studies confirm the reality of this risk. While in one study it was observed that the incidence of bacterial co-infections in COVID-19 cases is lower than in previous influenza pandemics, available data show that co-infection rates increase in patients admitted to the ICU (super-infections by antibiotic-resistant bacteria occur in 1.3% of patients in ICU and 0% in non-ICU care, and M. tuberculosis-COVID-19 co-infections are also reported). Data presented in the study from other assessments also show that secondary infections significantly decreased survival of COVID-19 patients, particularly when they were admitted to ICU. For example, studies in Wuhan, China found that secondary infections were observed in 10% and 15%, of admitted hospital patients identified as having laboratory-confirmed COVID-19 disease, with 31% of them requiring mechanical ventilation in ICU care and 0% in non-ICU care, and a secondary infection was reported in 50% of non-survivors and only 1% of survivors. Another study reported that COVID-19 patients with severe illness were 14.2, 18.2, and 2.9 times more likely to have co-infections with bacteria, fungi, and other viruses, respectively, than those not severely ill, and deaths associated with co-infections by bacteria, fungi and other viruses occurred in 55.6%, 44.4%, and 44.4%, respectively, of patients in the ICU, and in 26.1%, 13.0%, and 8.7%, respectively, of patients transferred from ICU to the general wards.
COVID-19 patients have an even higher risk of acquiring MDR bacterial infections, leading to a mortality rate even higher than that conferred by COVID-19 alone. In the case of the United States and other countries, it has been observed that as COVID-19 spread last year, the use and reuse of scarce personal protective equipment (PPE) — masks, gloves, gowns—in hospitals and nursing homes, are likely to have contributed to the spread of drug-resistant bacteria and fungi. Like Covid-19, bacteria and fungi prey on older people, the sick, and those with compromised immune systems, clinging to clothing and medical equipment. And, as resources were diverted to focus on COVID-19, facilities stopped screening for these germs, further facilitating their spread.
A documented multidrug-resistant Klebsiella pneumoniae outbreak in a Peruvian hospital during the COVID-19 period showed that MDR spread may have been facilitated by patient overcrowding that overwhelmed the capacity of the hospital, and staff burnout that may have decreased adherence to infection prevention and control practices, including using equipment not properly cleaned. A second factor could be the irrational use of antibiotics, which were given after initial suspicion that they could prevent superimposed infections; thus, azithromycin and other antibiotics in the “Watch” group (i.e., antibiotic classes that should be prescribed only for specific indications, since they are at higher risk of bacterial resistance) were routinely used in many countries, although treatment guidelines do not recommend their use in patients with mild or moderate disease unless the suspicion of bacterial co-infection is high. The last factor was limited and inappropriate use of PPE (e.g., availability of only 1 set of PPE to be used with all patients and throughout the shift, which could have facilitated the spread of germs).
Similarly, a retrospective analysis in an Italian hospital showed that COVID-19-affected hospitalized patients in two ICUs experienced Klebsiella pneumoniae co-infections. As in the case of Peru, placing COVID-19-affected patients in devoted wards or ICUs without separating those co-infected with drug-resistant bacteria, along the limited availability of gloves and gowns for staff, and an increased rate of antimicrobial prescription in the absence of clear guidelines, may have contributed to the propagation and hospital transmission of these germs.
Other mechanisms that may have facilitated the spread of drug-resistant pathogens were the use of ventilators, required for the treatment of the sickest COVID-19 patients, where drug-resistant infections cling and then spread, and the heavy and regular use of steroids, that while effectively alleviating the virus’s most dangerous symptoms, can leave the immune system compromised in a way that allows other germs to more easily infiltrate the body.
It should be clear, from the data presented above, that renewed attention must be paid to reduce the number of ICU-acquired HAIs and the risk of spread of resistant nosocomial pathogens that pose an increasing threat to patients with COVID-19 disease, particularly the critically ill.
There are clearly defined strategies to minimize and control the onset of these events, including various guidelines on ICU design, organization, and operation that are available in many countries. Environmental contamination with multidrug-resistant organisms on hospital surfaces and ICU equipment (e.g., ventilators), may facilitate their spread to patients long after they are shed, leading to a protracted transmission cycle. Methods of disinfection, such as ultraviolet light and hydrogen peroxide vapor, reduce the burden of bacterial pathogens, including spores, in the environment. These methods, however, take time and require sealing of patient rooms, including temporary closure of air supply and return. Patient care equipment used for patients that harbor multidrug-resistant organisms should be disposable to reduce the risk of cross-transmission. Equipment that is shared among patients, such as blood pressure devices, cooling blankets, and portable radiology cassettes, should be disinfected thoroughly between patients. Items like fabric privacy curtains, which are readily and widely contaminated with resistant organisms, can be removed or replaced with disposable curtains. Waterborne HAIs may occur during the many uses of potable water in the healthcare environment, since species of Stenotrophomonas, Pseudomonas, Aeromonas, and Sphingomonas can colonize plumbing fixtures (e.g., drains, faucets, or aerators). Some basic steps should be taken to prevent transmission of these germs, such as ensuring adequate levels of free chlorine in hospital water, selecting sinks that have low-splash design, and avoiding placement of patient care supplies around handwashing sinks, where they could be contaminated by splash-back from the drain. In an outbreak setting in which plumbing fixtures are implicated, plumbing might require disassembly, special cleaning and disinfection procedures, or even replacement.
The use of antibiotics in hospitals and ICUs and among patients also merits careful monitoring and should be stopped when the probability of a bacterial co-infection is low among COVID-19 patients, to prevent the development and transmission of MDR strains in healthcare systems. To this end, continuous antibiotic stewardship activities in hospitals and ICU need to be supported to improve the quality of care and avert adverse outcomes, including antimicrobial resistance, by optimizing dosing and selection of drugs, along with reducing duration of therapy.
In moving forward, while aiming to eliminate the spread of COVID-19 in the upcoming months with the help of public health measures such as vaccines, mask wearing, hand hygiene, and social distancing, we also need to be mindful that measures are also needed to prevent the spread of drug-resistant germs, including reducing inappropriate use of antibiotics. MDR can negatively impact rich and poor countries alike, because patients who remain infectious for a longer period of time pose an increased risk of spreading drug-resistant microorganisms to others, in the same way as contaminated environments with multidrug-resistant organisms can transmit them in hospitals wards and ICUs.
So, in the face of increasing use of critical care resources and high risk of nosocomial infection in the context of increasing antimicrobial resistance, infection prevention should be considered a leading priority in hospitals and ICUs during the COVID-19 pandemic and beyond.