COVID-19, a viral pneumonia with an unusual outbreak, is considered as a new public health concern threatening us worldwide. Recent studies show that 2019-nCoV or SARS-CoV-2 originated from an animal source and later adapted to other variants as it crossed the species barrier to ultimately infect humans [21, 22]. In recent months, less attention has been paid to hospital-acquired infections and opportunistic microorganisms, which could be due to the outbreak of COVID-19 and its consequent long-term hospitalization of patients, and high workload on the healthcare personnel.
In this study, with a focus on secondary infection of the lower respiratory tract of patients, A. baumannii was the most common organism followed by S. aureus. In recent years, emerging strains of both species that have acquired additional genetic features have shown to be commonly associated with hypervirulence and resistant to many types of antibiotics [23, 24]. According to our infection control committee and laboratory reports, these were associated with other bacteria including Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, Enterobacter spp., Serratia marcescens, and Citrobacter freundii, etc. that were previously isolated from the ICU wards and non COVID-19 patients admitted to our ICUs. In addition, both A. baumannii and S. aureus were among the most isolated bacteria from non COVID-19 ICU patients in Iran and other countries . In a 2019 study conducted in Tehran, Iran, Klebsiella pneumoniae and Acinetobacter had the highest rates of incidence in ICUs . In a 2018 study, A. baumannii and Klebsiella spp. were the most common organism isolated in Mysuru, India . In 2014, the most common ICU-acquired strains were Acinetobacter baumannii, Pseudomonas aeruginosa, Stenotrophomonas maltophilia, Staphylococcus aureus, Enterococcus spp., and Klebsiella pneumonia in Shanghai, China .
In the present study, our first samplings were performed in the patients who were admitted to ICUs for ≥9 days, except for 1 case with 2 days of admission. Certainly, this duration was an excellent opportunity for bacteria to infect the patients, and thus all of our first cultures were positive with secondary infection (19/19, 100%). This incidence rate is higher than similar recently published articles. In Fu et al. study, 13.9% (5 of 36) of the patients in the ICU were diagnosed with severe acute respiratory syndrome coronavirus 2 and secondary bacterial infection. In another report that was published from a UK secondary care setting, amongst 836 patients identified as SARS-CoV-2, 27 cases (3.2%) had early confirmed bacterial isolates identified (0–5 days post admission) rising to 51 cases (6.1%) during the admission [12, 13].
In addition, our result indicates a higher incidence than other published studies on non COVID-19 patients. In a study conducted in Shiraz, Iran, in 2009, Hassanzadeh et al. suggested that ICU-acquired infections were documented in 51.7% of ICU patients, with a mortality rate of 10.9% (5 patients) . One of the reasons for the increase in infection rate in our study can be due to the simultaneous infection of the virus and bacterium. As previously mentioned, viruses can facilitate the attachment and colonization of the bacteria in the respiratory tract, which is certainly no exception for COVID-19; however, understanding the accurate mechanisms of interactions between novel coronavirus and other bacteria requires further research. Nevertheless, other factors such as ICU type, used equipment rate, admission/ discharge criteria, high workload/nurse ratio, etc. can also affect the quality of care and the rate of ICU acquired nosocomial infection [30, 31], especially in pandemics.
Except for colistin, A. baumannii strains showed widespread resistance to all different classes of antibiotics and no inhibition zone was observed in the disk diffusion method. Resistant isolates of the bacteria, especially A. baumannii, are not uncommon among admitted patients in the hospitals and hospital-acquired infections have become a major concern to health systems. Wang et al. showed that the resistance rate of A. baumannii isolates was approximately > 98% to piperacillin, imipenem, ceftriaxone, ciprofloxacin, and ceftazidime . Castilho et al. also reported that A. baumannii isolates from ICUs in Goiânia, Brazil, were classified as multi-drug resistant (MDR) with a high incidence of resistance to carbapenems. The development of resistance to carbapenems and other β-lactams may be due to the production of the MBLs. These are one of the most common participating in resistance mechanisms that can inactivate a wide range of β-lactam antibiotics . Nevertheless, no MBL-producing A. baumannii strain was isolated. However, the bacteria may use other strategies to resist the effects of antibiotics [34, 35].
In our study, one of the strains of S. aureus was identified as MRSA. This organism plays an important role in the severe complication of infections in ICU environments. The probability of acquiring MRSA may increase (> 2.5–4 times) in patients with longer stays in the ward, i.e. more than one week . Different studies have also shown that lower respiratory tract infections caused by MRSA can be associated with a significant level of mortality in the patients admitted to ICUs [37, 38].
Due to the COVID-19 crisis conditions, we were not able to carry out MIC and other phenotypic confirmatory tests for evaluating extended-spectrum beta-lactamases or ESBLs, etc., as well as molecular assays for detecting resistance genes. Nevertheless, these pathogens showed extremely high rates of resistance to the majority of the antibacterial agents tested. This could not only delay the process of treatment and recovery of COVID-19 patients but also increase the mortality rate.
Based on our local strategies, all patients in the current study routinely received ceftriaxone and azithromycin (except for some contraindications or interactions) before admission to the ICUs. In the cases of the infection in ICU, these were changed to extended-spectrum antibiotics such as meropenem and vancomycin, but no changes in the isolation of our resistant bacteria were observed at different stages of sampling. However, the treatment protocols have been changed by the ICU medical team based on the obtained results of the cultures and the pattern of antibiotic resistance, e.g. in this study, combination therapy with meropenem, colistin, and ampicillin-sulbactam was used for the treatment of infections caused by the resistant strains of Acinetobacter.
Among our patients, three cases had no underlying diseases. One patient, infected by a susceptible strain of Staphylococci, was discharged, while two other patients, infected with multidrug-resistant A. baumannii, expired. Due to some limitations, the sample size of the current study was not sufficient for comparing and accurate statistical evaluation. However, further work is required to investigate whether there are increased mortality rates associated with patients co-infected with COVID-19 and antibiotic-resistant bacteria.
The median length of ICU stay among patients in our study was higher, 15 days (interquartile range, 2 to 39), compared with Zhou et al. study, which reported a length of stay of 8.0 days (4.0–12.0) of all patients with COVID-19 admitted to their ICU. Moreover, no bacterial pathogens were detected in their patients on admission . It seems that the length of ICU stay can be prolonged, if patients become co-infected. A study on respiratory co-infection in patients with pandemic 2009 influenza A (H1N1) virus infection showed that ICU length of stay was 3 days longer among patients who had co-infection .
In addition, infections and antibiotic resistance in ICU patients can also result in higher cost of treatment, and increased mortality . In a study conducted by Toufen and colleagues on ICU patients in Brazil, the rate of mortality was 28.8%, while the patients with infection had a mortality rate of 34.7% and the most frequently reported infections were related to respiratory infections (58.5%) . Chastre et al. study also suggested that the mortality rate of VAP in ICU patients varies from 20 to 50%, and even higher when caused by high-risk pathogens .
According to previous studies, viral-bacterial synergistic interactions are reviewed and the mortality rate can be further increased when there is simultaneous an acute respiratory viral infection and a bacterial infection. A multicenter retrospective cohort study conducted by Arabi et al. on 330 MERS SARI (Middle East Respiratory Syndrome Severe Acute Respiratory Infection) patients who were admitted to the participating ICUs showed that 18% (60 cases) and 5% (17 cases) of them had bacterial and viral co-infections, respectively . It has also been estimated that one-third of the world’s population (~ 500 million people) may have been clinically infected during the 1918–19 influenza pandemic, which resulted in the death of at least 50 million people worldwide (https://www.cdc.gov/flu/pandemic-resources/1918-pandemic-h1n1.html). The findings suggest that the vast majority of individuals who died during the pandemic were infected by a bacterial infection .
The co-infection of the influenza virus with Staphylococcus aureus, especially MRSA, has been previously documented. In a study performed by Bhat et al. during the 2003–2004 influenza season, bacterial co-infections were identified in 24 of 102 cases. Accordingly, S. aureus was the most common etiology (11 cases); six of these 11 cases were detected as methicillin-resistant strains . Randolph et al. also reported that among 838 children with influenza A (H1N1) virus admitted to a pediatric intensive care unit during the 2009 influenza A (H1N1) pandemic, 71 (8.5%) had a presumed diagnosis of early S. aureus co-infection of the lung with 48% positive for MRSA . Moreover, Jia et al. project on mouse model findings also showed that secondary infection with methicillin-resistant Staphylococcus aureus after infection with influenza virus was associated with high mortality rates . Another study by Liu et al. also confirmed that the co-infection of avian influenza A (H7N9) virus and extensively antibiotic-resistant A. baumannii in the patients with invasive mechanical ventilation is a key factor for the severity of the disease and high mortality .