Respiratory failure or multiple organ failure is the direct cause of death in patients with COVID-19, and SBIs have an important role in this process . Among the 1495 patients with COVID-19, the incidence of SBIs was 6.8%. The incidence of SBIs was lower than the data in previous studies (10% ~ 15%, Wuhan, China), which may be due to the larger sample size in the present study [2, 3]. In the mild ill COVID-19 patients, there was no SBI that met the inclusion and exclusion criteria; thus, it was impossible to compare the differences between the mild group and the severe group. The incidence in the critical group was much higher than in the severe group, which was consistent with the higher rate of central catheter placement and invasive mechanical ventilation in critical patients . Almost half (49.0%) of the patients with SBIs died during hospitalization, which was consistent with the previous study (50%) . Compared with the severe group, the critical group had significantly increased mortality. Recent studies related to COVID-19 reported that the male gender was a risk factor for disease severity status, and age 65 or older was a risk factor related to death [3, 17, 18]. In our research, no differences in gender and age were found between the severe and critical groups, which suggested that gender and age were not risk factors for death in patients with SBIs. A. baumannii and K. pneumoniae were the main pathogens of SBIs, and the infection rates of A. baumannii, CRAB, K. pneumoniae and CRKP in critical group were significantly higher than in the severe group. As the mortality of CRAB and CRKP has always been high, we believe it is one of the reasons why the mortality rate in the critical group was higher than that in the severe group.
According to the sites of SBIs, lung infections were the main type, which may be related to the decrease of airway defense function after SARS-CoV-2 infection . Invasive operations such as trachea intubation and ventilator-assisted breathing during hospitalization may also be the causes of SBIs in the lungs. There were 35 patients with bloodstream infections, 27 of which were bloodstream infections mixed with lung infections. We compared the bacteria of mixed infections and found that 21 patients had the same bacteria in the lungs and bloodstream, including K. pneumoniae (66.7%, 14/21) and A. baumannii (33.3%, 7/21). In these 21 patients, lung infections occurred first, followed by bloodstream infections. The antibiogram reportings of K. pneumoniae and A. baumannii isolated from qualified sputum specimens and blood specimens were the same. It is possible that the migration of K. pneumoniae or A. baumannii from the lungs resulted in bloodstream infections in these patients.
A total of 159 strains of bacteria isolated in this study were mainly Gram-negative bacteria. The top three bacteria of secondary lung infections were A. baumannii, K. pneumoniae, and S. maltophilia. The etiological distribution was different from the previously reported bacteria of hospital-acquired pneumonia (HAP) [20, 21]. The proportion of A. baumannii and K. pneumoniae was significantly increased, and the proportion of Pseudomonas aeruginosa (P. aeruginosa) and Staphylococcus aureus (S. aureus) was decreased, which suggested that the initial empirical antimicrobial program of HAP should not be completely copied if SBIs occur in the lungs. The lower proportion of P. aeruginosa and S. aureus suggests that it is not necessary to first choose antimicrobial with antibacterial activity of P. aeruginosa and S. aureus for SBIs in the lungs. The choice of antimicrobial program could be more suitable to treat the infections of A. baumannii and K. pneumoniae. The antimicrobial susceptibility tests showed that most of A. baumannii and K. pneumoniae were multi-drug resistant bacteria. The isolation rates of CRAB and CRKP were 91.7 and 76.6%, respectively. When patients suffer from SBIs, the possibility of infections by drug-resistant strains should be adequately considered. The resistance rate of tigecycline and cefoperazone sulbactam was relatively lower, and the combination could be considered for the initial empirical treatment of SBIs in the lungs. According to reports [22, 23], the avibactam compound has a better effect on carbapenem-resistant K. pneumoniae; yet, there is still no systematic research in patients with COVID-19.
Although the bacteria of secondary bloodstream infections were mainly Gram-negative bacteria, the proportion of Gram-positive bacteria was relatively higher than lung infections. If the bacteria derived from lung infections were excluded from the statistics, Gram-positive bacteria would be the main bacteria for bloodstream infections. In this study, we found that 80.0% (16/20) of patients infected with Gram-positive bacteria were given central venous catheter implantation during hospitalization. Our results revealed that the bloodstream infections of Gram-positive bacteria were associated with central venous catheter implantation. Therefore, we suggest that the management of venous catheters in severe patients should be strengthened to avoid bloodstream infections. According to antimicrobial susceptibility tests, methicillin resistance was found in 100% of Staphylococcus aureus and Coagulase negative staphylococci, and vancomycin resistance was not yet found. This suggests that vancomycin can be used as the empirical choice for Gram-positive bacteria if secondary bloodstream infections occur.
The number of secondary urinary tract infections was relatively small, and E. coli was still the main bacterium. According to antimicrobial susceptibility tests, the isolation rate of ESBL-producing E. coli was 75%. As the initial empirical choice, β-lactams combinations with β-lactamase inhibitors could be recommended, rather than levofloxacin and ceftriaxone.
This study has several limitations. First, this was a single-center study performed in the Wuhan Union Hospital. The etiology and antimicrobial resistance in different medical institutions or different regions may be different. The results should be externally examined when applied in other institutions. Second, during the epidemic, the main focus was dedicated to treating COVID-19 patients; thus, there was no enough time to examine the mechanism of bacterial resistance. Third, our analysis of the treatment effect of SBIs was insufficient, which should be carried out in further research.