The present study reported 31 patients with SBI during hospitalization for COVID-19 treatment, with an incidence rate of 1.9% and a 30-day high mortality of 67.7%. In this retrospective study, the clinical features, laboratory findings, treatments, and outcomes of the patients with SBI were described. Increased risk of death was noted for the following three subgroups: patients infected with CRGNB, patients with complications of sepsis and patients with acute cardiac injury.
The mortality of hospitalized patients with COVID-19 is high and SBI is one of the important causes of their deaths.[5] For bloodstream infections, optimized management strategies include early diagnosis, appropriate empiric and targeted antibacterial therapy and prompt effective source control.[19] However, in previously published studies,[7, 8, 10, 11] only the etiology and the risk factors of SBI have been reported. The clinical features, treatment measures and disease progression of patients with the onset of SBI have not been previously reported. To the best of our knowledge, the present study is the first to review the clinical course of SBI with COVID-19.
Following calculation of the incidence of SBI, patients with CNS were excluded in these blood cultures. These patients had either no significant changes in clinical features, or the pathogens were isolated only once per patient, which was considered a skin symbiotic bacterial contamination. The incidence of SBI reported in the present study was consistent with the strictly calculated incidences reported in New York City and London, which were 1.6% [8]and 2.5% [10], respectively.
In the present study, the 30-day mortality following SBI onset and the hospital mortality were higher than the mortality of severe ill patients of COVID-19.[3] These indices were also higher than the mortality (50%) of SBI in Copenhagen University Hospital.[7] This outcome is probably related to 71% of SBI cases in the study, which were caused by CRKP or CRAB. A higher distribution was noted in the non-survivors. According to these reports,[20, 21] the mortality rate of patients with bloodstream infection caused by CRKP was as high as 41.6%~58.7%. The mortality rate of bloodstream infections caused by CRAB was also very high, reaching 54.7%.[22] Bloodstream infection itself is an event with an extreme impact on mortality. In addition, it occurs during the treatment of COVID-19, which may increase the risk of death. The detection of CRGNB is one of the risk factors for patient death following bloodstream infections.[23–26] The findings confirmed that the non-survivors had higher CRGNB distribution. It was speculated that in SBI patients with COVID-19, CRGNB also affected the outcomes of the patients.
Although most patients with SBI indicated fever at the time of onset, other patients did not show this symptom. Almost all patients did not present with chills or fear of cold. This led to the conclusion that the difficulty of clinical diagnosis of SBI was increased. The clinical diagnosis of SBI requires a comprehensive judgment based on changes in the patient temperature, breathing, blood pressure and state of consciousness.
The current research demonstrated that conventional infection indicators, such as procalcitonin, C-reactive protein and white blood cell counts were elevated during SBI onset, which strongly supported the judgment of bacterial infections and enabled clinicians to administer antimicrobials/antibacterial agents in time. In some patients, procalcitonin and C-reactive protein exceeded 2 ng/mL and 100 mg/L, respectively, indicating the severity of the infections and suggesting that more active treatment should have been provided.
All patients in the SBI group were treated with empirical combined application of antibacterial drugs and the majority of the treatment options were based on carbapenems, combined with glycopeptides or linezolid to treat possible positive bacterial infection. However, this approach did not show obvious benefits, which was related to the fact that most of the pathogens were carbapenem-resistant bacteria. Patients with previous antibacterial use, mechanical ventilation and previous ICU stay were susceptible to carbapenem-resistant bacteria.[27] For such patients, the risk of drug resistance should be fully considered. The application of carbapenems may be ineffective. The present study demonstrated that in empirical treatment, timely administration of sensitive antibacterial drugs exhibited no obvious benefit in improving the mortality of the patients. We speculated that the potentially serious condition of the patients exhibited a more important impact on mortality and may mask the influence of antibacterial therapy.[28]
Although several reports have been performed on the treatment of CRKP bloodstream infections, it is not certain whether it is applicable to patients with COVID-19. In the targeted treatment stage, seven programs were applied in 12 patients with CRKP SBI, revealing no clinically effective treatment program. The combination regimen based on ceftazidime/avibactam may be more effective. 71% (5/7) of the patients survived within 30 days. It is also worth mentioning that one patient was treated with ceftazidime/avibactam combined with colistin and sulbactam preparations and his condition was finally improved leading to his discharge. Previous studies have reported that ceftazidime/avibactam is an effective treatment for CRKP bloodstream infections, which can significantly reduce the mortality of the patients.[29–31] The effectiveness of the ceftazidime/avibactam-based regimen in the treatment of CRKP bloodstream infections secondary to COVID-19 requires further investigation.
In a study by Xu and colleagues,[32] sulbactam-based treatment options may be more effective for CRAB bloodstream infections. In the present study, 4 patients used 3 regimens, including carbapenem plus colistin, tigecycline plus colistin and tigecycline plus sulbactam preparations (2/4). Unfortunately, they all failed. The risk of CRAB bloodstream infections secondary to COVID-19 was more serious.
The present study demonstrated that patients, who belonged in the non-survivor group, were more likely to have complications, such as sepsis and acute cardiac injury following SBI onset. The essence of sepsis involves a life-threatening organ dysfunction caused by a dysregulated host in response to infection.[14, 33] If timely and effective treatment is not implemented, sepsis is fatal. The majority of the pathogens of SBIs with COVID-19 are CRGNB, which are difficult to treat and more difficult to result in successful treatment. Therefore, when sepsis occurs, the risk of death increases.
As identified in previous studies, acute cardiac injury is a common complication of sepsis and the resulting cardiac dysfunction is also one of the main causes of death in patients with sepsis.[34, 35] Acute cardiac injury is the most reported cardiac abnormality in COVID-19 and is strongly associated with mortality.[36, 37] Prior to SBI onset, several patients experienced acute cardiac injury. When SBI occurs, the patient cardiac injury aggravates and the risk of death increases.
The present study contains certain limitations. First, the number of samples of SBIs was small, which could not fully reveal the risk factors for the mortality of SBIs. Secondly, this was a single-center retrospective study. Further multi-center studies and prospective research data are required to explore the optimal treatments for SBI with COVID-19. Finally, this designated hospital is specialized in treating mainly patients with severe or critically ill COVID-19. Therefore, the incidence of SBIs may be higher than the incidence of the entire COVID-19.
In conclusion, this retrospective study indicated that SBIs with COVID-19 were associated with high 30-day mortality. The survival time of the non-survivors was likely to be within 7 days following SBI onset. Increased risk of death was noted for the following three subgroups: patients infected with CRGNB, patients with complications of sepsis and patients with acute cardiac injury.