Differences in the epidemiology, clinical characteristics, distribution of microorganisms and outcomes between COVID-19 patients and non-COVID-19 patients with ICU- associated BSIs: a one-center retrospective study

doi:10.21203/rs.3.rs-4688303/v1

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Differences in the epidemiology, clinical characteristics, distribution of microorganisms and outcomes between COVID-19 patients and non-COVID-19 patients with ICU- associated BSIs: a one-center retrospective study

https://doi.org/10.21203/rs.3.rs-4688303/v1

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Background

We aimed to study the differences between patients with COVID-19 and non-COVID-19 ICU-associated BSIs in terms of epidemiological, clinical, microbiological and outcome data.

Methods

Patients who developed BSI >48 hours after admission to the ICU among patients with COVID-19 and non-COVID-19 who were followed during a two-year pandemic period at a university hospital in the ICU were selected.

Descriptive statistics were used for differences between patients with COVID-19 and without COVID-19. Logistic regression analysis was used to determine mortality risk factors in BSI patients.

Results

Infection of the lower respiratory tract was much more common in COVID-19 patients (43.3% to 26%, p =0,000). The abundance of Acinetobacter baumanii, a microorganism causing BSI was significantly greater in COVID-19 patients than in non-COVID-9 patients (5.6% to 24.4%; p = 0.000), and the prevalence of Gram-negative MDR bacteria (61.7 to 81.7%, p = 0.020) was greater.

The duration of antibiotic use in the hospital was associated with the BSI, where Gram-negative MDR bacteria are active (p = 0,000), and the appropriateness of empirical treatment (p = 0.031) was more common in the COVID-19 group.

In our study, we discovered that patients with COVID-19 had lower levels of acute-phase reagents commonly used for BSI but more severe clinical symptoms during BSI.

COVID-19 survivors had shorter survival times after BSI (p = 0.032) than non-COVID-19 survivors.

Conclusions

The increased use of antibiotics in hospitals for patients with severe COVID-19 and deficiencies in infection control measures have led to an increase in MDR microorganisms.

COVID-19

bloodstream infection

ICU-acquired infections

multidrug resistant bacteria

During the COVID-19 (coronavirus disease 2019) pandemic, the healthcare system has developed a density due to severe patients requiring follow-up in the intensive care unit (ICU) due to respiratory failure requiring mechanical fan support, shock, dyseminate coagulopathy, and organ failure [1, 2]. In addition to various problems, bacterial infections were found to be significantly more common in patients followed in the ICU than in patients in service [3], and this has been found to increase the morbidity rate of mortality [4]. Although bloodstream infections in patients with COVID-19 have been studied in various studies [5–7], few studies have examined their differences compared with those in non-COVID-19 patients [8, 9].

It has been suggested that the abundance of Gram-positive cocci (especially coagulase-negative staphylococci (CNS) and enterococci) is greater in COVID-19 patients than in non-COVID-19 patients [8, 10]. Reports have also shown that Gram-negative bacteria originating from hospitals are more common [7, 11]. It has also been shown that candidaemia is more common in pregnant patients than in the general population [12].

It was noted that the incidence of infections caused by multidrug-resistant bacteria increased during the pandemic period, and the importance of taking inadequate measures to control infections and unnecessary use of antibiotics was emphasized [9, 13, 14].

Our study included a longer period of time than studies in the literature and planned to examine the basic features of BSI in COVID-19 and non-COVID-19 patients, including differences in the distribution of microorganisms, source of infection, and mortality, during a two-year pandemic period.

Patients aged >18 years who were studied at a third-tier university hospital in the ICU between 18 March 2020 and 18 April 2022 and who developed >48 hours of BSI from ICU infection were examined. The patients were divided into two groups: the COVID-19 group, in which the patients were SARS-CoV-2-PCR positive or compatible with typical radiological findings for COVID-19, and the non-COVID-19 group, in which the patients were PCR negative with radiological findings that were not compatible with COVID-19. Patient information was obtained retrospectively from the hospital system.

Microbiology

• Biochemical tests, disk diffusion tests or BD Phoenix automated system (Becton Dickinson, USA) were used to identify microorganisms grown in blood culture and their sensitivity to antibiotics.

• Recommendations of the European Committee on Antimicrobial Susceptibility Testing (EUCAST) have determined the sensitivity of bacteria to antibiotics by means of a disc diffusion test based on the zone diameter or MIC levels in an automated system.

• •The production of extended-spectrum beta lactamase (ESBL) in bacteria of the Enterobacteriaceae family was determined by the zonal diameters of ceftriaxone and ceftazidime <25 mm and <22 mm, respectively (by disc diffusion), or by MIC levels >1 mg/L.

• Colistine sensitivity assessed by an automated system or broth microdilution method.

• Klebsiella pneumoniae, Acinetobacter baumanii and Pseudomonas aeruginosa, which are resistant to carbapenem from Gram-negative bacteria, and vancomycin-resistant enterococci (VRE) and methicillin-resistant S.aureus (MRSA), which are from Gram-positive bacteria, are considered multidrug resistant (MDR)[15].

Definitions

• ICU-acquired BSI was defined as the reproduction of a bacterium considered to be a pathogen in the patient's blood culture on the third day of BSI adjustment and thereafter. Bacteriemia is caused by typical skin contaminants (e.g., coagulase-negative staph (CNS), Corynebacterium spp., etc.), reproduction in two or more vials of four vials of blood cultures taken at different times, clinical signs of infection, and initiation of antibiotic therapy, as validated by the clinic. The Gram-negative bacteria S. aureus and fungus were also considered pathogens when reproduced in a single vial. If enterococci and streptococci were not identified at the species level, if they were reproduced in two or more vials, the pathogen was accepted by the clinic, and treatment was initiated. Streptococci other than viridans were considered pathogenic if clinically compatible.

• In patients with multiple bacteriemia periods, only the initial period was recorded, but the active fungus was also included in the subsequent period.

• Diagnosis of bloodstream infection (primary or secondary) and other infections that cause BSI, based on CDC criteria [16-19].

Statistical analysis

IBM SPSS Statistics 22 was used. For the quantitative data, Student's t test and the Mann‒Whitney U test were used; for the qualitative data, the χ2 test, Fisher's definitive test, Fisher–Freeman–Halton test, and Yates's continuity correction were used. Logistic regression analysis was applied to the analysis of multivariable variance. The Kaplan‒Meier method and the log-rank test were used for right-wing analysis.

Our study included 234 patients, including 127 with COVID-19 and 107 without COVID-19. The differences between the general characteristics of the patients are shown in Table 1. The SAPS-2 score (p = 0.06) at the time of admission to the ICU was greater for those who did not have COVID-19.

Table 1

General characteristics of the patients
Variables	COVID-19	Non-COVID-19	All	p
Age, mean (std)	64,54 ± 12,02	65,95 ± 15,37	65,19 ± 13,64	0.442
Charlson Comorbidity Index (median) [IQR]	3 (2–4)	4 (2–6)	3 (2–5)	0.024*
SAPS II, mean (std)	6,51 ± 1,31	6,04 ± 1,25	6,29 ± 1,30	0.006*
Length of stay ICU (days), median [IQR]	16 (10–24)	19 (12–27)	16 (10,8–26)	0.120
Duration of invasive mechanical ventilation (days), median [IQR] (n = 213)	13 (8–18)	12 (6–22,5)	13 (8–21)	0.872
Time from hospital admission to ICU admission, median [IQR]	3 (0–6)	2 (0–5,75)	3 (0–6)	0,794
Gender
Male,%	76 (%59.8)	66 (%61.7)	142 (%60,7)	0.774
Female,%	51 (%40.2)	41 (%38.3)	92 (%39.3)	0.774
SVC, %	124 (%97.6)	104 (%97.2)	228 (%97.4)	0.574
HFNC/NIMV, %	20 (%15.7)	15 (%14)	35 (%15)	0.853
Antibiotic use in the last 3 months, %	39 (%30.7)	48 (%44.9)	87 (%37.1)	0.026*
High-flow nasal cannula (HFNC), Noninvasive mechanical ventilation (NIMV), Santral venous catheter (SVC)

A total of 83.5% of COVID-19 patients and 60.7% of non-COVID-19 patients were receiving invasive mechanical ventilation at BSI onset. The requirement for invasive mechanical ventilation for at least 2 days during the duration of stay in the ICU was 94.5% in the COVID-19 group and 86.9% in the non-COVID-19 group (p = 0.074).

Desaturation at the time of BSI (p = 0.022) was significantly more common in non-COVID-19 patients. C-reactive protein (CRP) (p = 0.019) and procalcitonin (p = 0.001) were lower in COVID-19 patients than in non-COVID-19 patients. COVID-19 patients were more likely to have lower respiratory tract infections as a source of BSI than non-COVID-19 patients were (% 26 vs 43.3; p = 0,000).

The sequential organ failure assessment (SOFA) score (p = 0,000) and Pitt bacteraemia score (P = 0.000) at the time of BSI, the number of days on which antibiotics were used before BSI (p = 0.045), and the proportion of patients requiring invasive mechanical ventilation at the time of HABSI (P = 0.000)were greater in the COVID-19 group than in the non-COVID-19 group.

Compared to non-COVID-19 patients, empirical treatment was significantly less appropriate for COVID-19 patients (p = 0.031), and an increased antibiotic therapy spectrum (p = 0.009) was needed (Table 2).

Table 2

Comparison of BSI-related data between COVID-19 patients and non-COVID-19 patients.
Variables	COVID-19	Non-COVID-19	All	p
SOFA	11 (8–13)	8 (5–11)	10 (7–12)	0.000*
Pitt bacteriemia score	8 (5–8)	6 (1–8)	6 (4–8)	0.000*
Time from ICU admission to BSI (days)	10 (7–15)	8 (5–14)	9 (6–14)	0.071
Spent use of antibiotics before BSI (days)	10 (8–17)	9 (3–18)	10 (6–17)	0.045*
CRP (mg/dl)	113,3 (59,8-204,4)	159,1 (76,5-233,2)	127,7 (68,9-207,01)	0.019*
Procalsitonin (ng/ml)	0,9 (0,35 − 2,4)	1,85 (0,63 − 7,5)	1,21 (0,38 − 3,45)	0.001*
Time from BSI to death (days)	6 (3–13,3)	10 (4–20)	7 (3–16)	0.045*
Source of BSI
Lower respiratory tract, %	55 (%43.3)	22 (%20.6)		0.000*
Primary BSI, %	40 (%31.5)	28 (%26.2)		0.371
Requiring invasive mechanical ventilation at the time of BSI, %	106 (%83.5)	65 (%60.7)		0.000*
Clinical findings at BSI time
Desaturation	76 (%59.8)	48 (%44.9)	124 (%53)	0.022*
Requirement for inotropes/increased amount in the patient receiving inotropes	69 (%54.3)	61 (%57)	130 (%55.5)	0.681
Appropriateness of empirical treatment	58 (%45.7)	64 (%59.8)	122 (%52.1)	0.031*
Decreased antibiotic therapy spectrum	0 (%0)	4 (%3.7)	4 (%1.7)	⁻
İncreased antibiotic therapy spectrum	68 (%53.5)	39 (%36.4)	107 (%45.7)	0.009*
30-day mortality (time from BSI)	106 (%83.5)	79 (%73.8)	185 (%79)	0.071
The results are reported as the n (%) for categorical variables and as the median (IQR) for continuous variables.
SOFA: Sequential Organ Failure Assessment Scale CRP: C-reactive protein

[CB- COVID-19 patient with bacteremia, NCB- non-COVID-19 patient with bacteremia]

COVID-19 patients died earlier after the onset of BSI (p = 0.045) than non-COVID-19 patients. There was no significant difference in mortality between the two groups (p = 0.071), but there was a significant difference in survival (P = 0.032) (Fig. 1).

In COVID-19 patients, 63.8% of the microorganisms that caused BSI were Gram-negative bacteria, 37.8% were Gram-positive bacteria, and 7.1% were fungi. (Table 3).

Table 3

Distribution of microorganisms causing BSI in COVID-19 patients and non-COVID-19 patients.
Microorganism	COVID-19 (n = 127)	Non-COVID-19 (n = 107)
Gram-negative bacteria	81 (%63.8)	59 (%55.1)	0.179
Enterobacteriaceae spp.	49 (%38.6)	44 (%41.1)	0.693
Klebsiella pneumoniae	46 (%36.2)	36 (%33.6)	0.681
Nonfermentative Gram-negative bacilli	33 (%26)	18 (%16.8)	0.125
Acinetobacter baumanii	31 (%24.4)	6 (%5.6)	0.000*
Gram-positive bacteria	48 (%37.8)	40 (%37.4)	0.948
Enterococcus spp	26 (%20.5)	15 (%14)	0.262
S.aureus	12 (%9.4)	13 (%12.1)	0.650
Coagulase negative staphylococci (CNS)	11 (%8.7)	12 (%11.2)	0.665
Fungi	9 (%7.1)	12 (%11.2)	0.384

Compared to non-COVID-19 patients, there were no significant differences in bacterial distribution except for the prevalence of Acinetobacter baumanii. (24,4% vs.56%, p = 0.000). Enterococci were relatively more abundant in COVID-19 patients, but the difference was not statistically significant (20.5% vs 14%, p = 0.262).

[CR-AB: Carbapenem-resistant Acinetobacter baumanii CR-KP: Carbapenem-resistant Klebsiella pneumoniae]

An increase in MDR bacteria was observed in the COVID-19 group (Fig. 2). MDR bacteria were significantly more common in those who did not have COVID-19 (48.5% vs. 69.5%, p = 0.02). This difference was more pronounced in Gram-negative bacteria. The incidence of MDR bacteria among Gram-negative bacteria was significantly greater in non-COVID-19 patients than in COVID-19 patients (81.7% vs. 61.7%, p = 0.020). The main reason for the difference between the Gram-negative bacteria was the greater number of carbapenem-resistant Acinetobacter baumanii in those with COVID-19.

No correlation was found between the use of antibiotics in the last 3 months and the number of days antibiotics were used before BSI, but there was a correlational statistics between the presence of Gram-negative MDR bacteria and the number of days antibiotics were used before BSI (p = 0,009) (Table 4).

Table 4

Evaluation of correlational statistics between MDR bacteria and the use of antibiotics
	MDR (+)	MDR (-)	p
Use of antibiotics in the last 3 months	48 (%37.2)	29 (%33.7)	0.601
Spent use of antibiotics before BSI (days)	11 (8–19)	7 (3–13,3)	0.000*
	Gram-negative MDR (+)	Gram-negative MDR (-)
Use of antibiotics in the last 3 months, %	40 (%38.5)	19 (%27.9)	0.209
Spent use of antibiotics before BSI (days)	12 (9–19)	8,5 (4,3–14)	0.000*
	Gram-positive MDR (+)	Gram-positive MDR (-)
Use of antibiotics in the last 3 months, %	8 (%32)	19 (%30.2)	1.000
Spent use of antibiotics before BSI (days)	7 (5–19)	9 (5–14)	0.978
The results are reported as n (%) for categorical variables and as the median [IQR] for continuous variables.

According to the multivariate analysis, the Pitt bacteraemia score was found to be a risk factor for mortality in patients with BSIs [OR: 1,548 (95% CI: 1,235-1,939)]. The diagnosis of COVID-19 was not a risk factor for mortality. (Table 5).

Table 5

Evaluation of mortality risk factors in patients with BSI
	Univariate analysis		p	Multivariate analysis
	Nonsurvivors	Survivors	p	OR (%95 Cl)	p value
Age, mean (std)	66,32 ± 12,76	60,9 ± 15,99	0.013*
Charlson Comorbidity Index, (median) [IQR]	3 (2–5)	2 (0,5 − 3,5)	0.008*
SAPS II, mean (std)	6,47 ± 1,28	5,6 ± 1,13	0.000*
Duration of invasive mechanical ventilation (days), (median) [IQR]	13 (8–22)	9 (4–16,8)	0.013*
SOFA, (median) [IQR]	11 (8–13)	5 (3,5–8)	0.000*
Pitt bacteriemia score, (median) [IQR]	8 (6–8)	1 (0–4,5)	0.000*	1.548 (1,235-1,939)	0.000*
	n (%)	n (%)
Requiring invasive mechanical ventilation at the time of BSI, %	157 (%84.9)	14 (%28.6)	0.000*
Lower respiratory tract infection, %	67 (%36.2)	10 (%20.4)	0.055
COVID-19, %	106 (%57.3)	21 (%42.9)	0.071
Appropriateness of empirical treatment, %	98 (%53)	24 (%49)	0.619
Acinetobacter baumanii, %	30 (%16.2)	7 (%14.3)	0.913
Gram-negative MDR, %	90 (%77.6)	14 (%56)	0.048*
The results are reported as n (%) for categorical variables and as the median (IQR) for continuous variables.

The need for mechanical ventilation before BSI was significantly greater in patients without COVID-19 than in patients with COVID-19. Nevertheless, desaturation occurred more frequently in those with COVID-19 than in those without COVID-19. One reason for this is that the most common source of BSI in the COVID-19 group was respiratory infection. In addition, the diagnosis of VIP requires that there be an increase in PEEPs [18]. Since COVID-19 patients have ARDS in the foreground, KDI may have worsened the situation. The increased need for mechanical ventilation in COVID-19 patients is one of the major causes of respiratory infection. Studies have also shown that the incidence of VİP in COVID-19 patients in the ICU is 40% [3]. This finding also suggested that COVID-19 patients need more mechanical ventilation before receiving an ICD and that they have more severe symptoms of ARDS, which could facilitate the development of VIP in particular. The widespread use of the prone position may also have increased the incidence of VİP-causing microaspirations [20], and this treatment may have been more common in COVID-19 patients for the reasons mentioned earlier. Moreover, in patients with COVID-19, pulmonary infarction, which is more common due to coagulopathy, may increase the risk of secondary infection [21].

In studies conducted on microorganisms that cause BSI in COVID-19 patients, there are conflicting results regarding the distribution of the microorganism. The bacterial distribution in our study was similar to that in Italy, Hungary, Serbia, Romania, Bulgaria, Greece, Croatia and India, where carbapenem resistance exceeds 50% and Gram-negative bacteria are endemic. A retrospective study in India revealed that Gram-negative bacteria caused 82.8% of bloodstream infections in COVID-19 patients, with Acinetobacter baumanii accounting for 32.8% and Klebsiella pneumoniae accounting for 21.9%. All Gram-positive bacteria are enterococci [7].

Moreover, bacteraemia of unknown cause was also found to be common in COVID-19 patients. In Buetti et al.'s study comparing COVID-19 and non-COVID-19 patients with ICU-acquired BSI, the source of bacteremia was not identified in 47.4% of COVID-19 patients and 25% of non-COVID-19 patients. This condition has been associated with bacteria, especially enterococci [8]. In our study, the source of bacteremia was unknown in 73% of the patients with COVID-19 with enterococcal bacteraemia. In the non-COVID-19 group of patients with enterococcal bacteraemia, the predominant sources of bacteraemia were catheter-related infections and intra-abdominal infections, with an unknown bacteraemia rate of 26%. In addition, 77% of the polymicrobial bacteria in the COVID-19 group were enterococci. Enterococcus spp. and Klebsiella pneumoniae together account for 46% of polymicrobial bacteraemia cases, but the source of this type of bacteraemia is unknown. In non-COVID-19 patients, the association of two Gram-negative bacteria in polymicrobial bacteria, which are generally proven intra-abdominal infections, was common. It has been previously noted that bacteria belonging to the intestinal microbiota, most commonly enterococci, are commonly found as the causative agent of BSI in COVID-19 patients in the ICU [8, 22–24]. This has been associated with causes such as SARS-CoV-2-associated coagulopathy affecting micro- and macrocirculation, thus likely increasing the risk of bacterial translocation (e.g., in the gastrointestinal tract), the frequent occurrence of endothelial dysfunctions of the digestive system in patients with COVID-19, and the increased incidence of mesenteric infarction [8, 25].

Acinetobacter baumannii was isolated significantly more often in the COVID-19 group than in the non-COVID-19 group. In the COVID-19 group, in 77.5% of patients with Acinetobacter baumanii bacteraemia, the source of infection was ventilator-related pneumonia. Fan et al. studied the microbiota of lung tissue in 20 patients who died from mechanical ventilation and COVID-19 and found that the microbiome was enriched with species of Acinetobacter, including carbapenem-resistant Acinetobacter baumannii [26]. In a study in which Russo et al. studied Acinetobacter baumanii infections in non-COVID-19 patients between 2019 and 2021, the prevalence of bacteraemia was significantly greater in those with COVID-19 than in non-COVID-19 patients (56% vs. 8%). Nearly 60% of bacteremias are caused by VAP, and bacteremia has been identified as a risk factor for mortality [27]. In European countries, the first two years of the pandemic showed a significant increase in the rate of circulatory infections caused by Acinetobacter baumannii compared to the previous three years. Especially in countries where carbapenem resistance exceeds 50%, statistically significant increases have been observed, most of which are in the U.S. [28]. In our country, the rates of resistance to carbapenem in Acinetobacter baumannii are similar during pandemic periods, as they were 90% prior to pandemics.

The prominence of Acinetobacter baumanii, which is known to be able to spread epidemics easily through contamination of health workers' hands, medical instruments, and hospital surfaces, suggests a lack of measures to control infections. Among the reasons is the failure of health workers to give due importance to measures to control infections due to their intensity and inadequate hand hygiene. The use of double gloves has been considered a priority for protection against COVID-19. The continued use of the same gloves disinfected with alcohol, the same contact precautions for all patients during care, or overall use of the gloves were caused by a lack of material or workload density.

Many publications have indicated that MDR bacteria rates increased during the pandemic. A single-center retrospective study was performed in a university hospital in Croatia on ICU-associated BSI in COVID-19 patients during the pandemic. Among Acineobacter baumanii strains, 87.5% of Klebsiella pneumoniae strains and 20.5% of enterococci strains are resistant to vancomycin [14]. This finding was similar to the data in our study. Some of the factors that led to MDR bacteraemia were not enforcing infection control measures well enough and the fact that 93.4% of patients had received antibiotics before the BSI [29]. In a retrospective study of MDR Gram-negative bacterial infections among ICU patients at a single center in Italy, the incidence of carbapenem-resistant Acinetobacter baumanii was significantly greater (78.9% vs 38.6%) in those with COVID-19 than in those without COVID-19 and has never been identified as a factor in the COVID-19 group, similar to our study on Pseudomonas aeruginosa [14]. During the COVID-19 pandemic, many hospitals have experienced outbreaks in the ICU often caused by Gram-negative MDR bacteria. Among the Gram-negative bacteria, carbapenem-resistant Acinetobacter baumanii is the most frequently occurring [30] and has been found to be associated with high mortality [27].

In a study by Buetti et al. [9], antibiotic use in the week prior to BSI was more common in those with COVID-19 than in those without COVID-19, suggesting that this caused more MDR bacteria. A systematic compilation of MDR bacterial outbreaks in COVID-19 patients revealed that an increase in antibiotic use was a significant contributing factor to the outbreak in seven studies. [30]. In our study, there was no correlation between antibiotic use and MDR bacteria in the group of patients with BSIs in the last 3 months.The use of antibiotics before BSI in the hospital was significantly longer for those with Gram-negative MDR bacteria.

During BSI, SOFA and Pitt bacteraemia scores were significantly greater in those with COVID-19 than in those without COVID-19. In a single-center retrospective study in a university hospital in Italy where the incidence of MDR Gram-negative bacteria in the ICU was compared with that in non-COVID-19 patients, the rate of septic shock during bacteraemia and the Pitt bacteraemia score were significantly greater in those with COVID-19 [14].

In a study comparing COVID-19 patients with non-COVID-19 patients [8], there was no significant difference between the 60-day mortality rates. Another study [9] showed that the 28-day mortality rate was significantly greater for those with COVID-19 than for those without COVID-19, and there was a significant difference in survival. In our study, there was no difference in 60-day mortality rates between patients with COVID-19 and without COVID-19, but when evaluated with the log rank test for survival time, survival times were lower in COVID-19 patients than in non-COVID-19 patients, with statistically significant differences between the two groups (p = 0.032; p < 0.05). This may be associated with a heavier organ failure chart during BSI in the COVID-19 group and a higher SAPS-II score during admission to the ICU. In a study by Buetti et al. [9], the SOFA score at the time of BSI was found to be an independent risk factor for mortality. In our study, Pitt bacteraemia scores were found to be an independent risk factor for mortality in patients with BSIs. Several studies have shown that a diagnosis of COVID-19 in patients with BSIs is a risk factor for mortality, but our study did not find this association [9, 14].

This study has several limitations.The first is that the study was retrospective. Furthermore, it is not possible that our findings can be generalized to the entire population because they were obtained from a single center. We did not have data on what antibiotics patients used. Furthermore, due to the constraints of the pandemic period, we were unable to identify certain bacteria at the species level.

Given that bacteraemia is more severe in COVID-19 patients than in other patients, the survival rate is lower, and there are higher rates of multidrug-resistant bacteria, unnecessary antibiotic use should be avoided especially in these patients, and more attention should be given to infection control measures.The training of staff on compliance with hand hygiene and contact insulation measures should be a focus.

BSIs: Bloodstream infections,

COVID-19: Coronavirus disease

ICU:Intensive care unit

MDRO: Multidrug-resistance microorganisms

CRP: C-reactive protein

LDH: Lactate dehydrogenase

SOFA: Sequential organ failure assessment

CR-AB: Carbapenem-resistant Acinetobacter baumanii

CR-KP: Carbapenem-resistant Klebsiella pneumoniae

VRE: Vancomycin-resistant enterococci

MRSA: Methicillin-resistant S.aureus

ESBL: Extended-spectrum beta lactamase

Ethics approval and consent to participate

This study was reviewed and approved by the Istanbul University Clinical Research Ethics Committee (1523529-23). Informed consent was obtained from all participants. All procedures were performed in accordance with the principles of the Declaration of Helsinki. Written informed consent was obtained from all participants and legally authorized representative of minor participants involved in the study.

Consent for publication

Not applicable.

Availability of data and materials

The datasets used and/or analysed during the current study available from the corresponding author on reasonable request.

Competing interests

The authors declare that there are no competing interests.

Funding

No financial support was received.

Authors' contributions

Halit Özsüt was responsible for the organization and coordination of the trial. Çağla Keskin Sarıtaş was the chief investigator and was responsible for the data analysis. Çağla Keskin Sarıtaş, Halit Özsüt, Seniha Başaran, and Aysun Benli developed the trial. All authors contributed to the writing of the final manuscript. All members of the study team contributed to the management or administration of the trial.

Acknowledgements

Not applicable

Gao Yd, Ding M, Dong X, Zhang Jj, Kursat Azkur A, Azkur D, Gan H, Sun Yl, Fu W, Li W: Risk factors for severe and critically ill COVID‐19 patients: a review. Allergy 2021, 76(2):428-455.
Wu Z, McGoogan JM: Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention. jama 2020, 323(13):1239-1242.
Soriano MC, Vaquero C, Ortiz-Fernández A, Caballero A, Blandino-Ortiz A, de Pablo R: Low incidence of co-infection, but high incidence of ICU-acquired infections in critically ill patients with COVID-19. The Journal of infection 2021, 82(2):e20.
Musuuza JS, Watson L, Parmasad V, Putman-Buehler N, Christensen L, Safdar N: Prevalence and outcomes of co-infection and super-infection with SARS-CoV-2 and other pathogens: A Systematic Review and Meta-analysis (preprint). 2020.
Sharayah A, Burke S, Hajjaj N, Steck M, Patolia S: EFFECT OF CORTICOSTEROIDS ON NOSOCOMIAL INFECTIONS IN PATIENTS WITH COVID-19, A SYSTEMATIC REVIEW OF RANDOMIZED CLINICAL TRIALS. Chest 2021, 160(4):A1755.
Kuwahara M, Kamigaito M, Nitta S, Hasegawa K, Murakami H, Kobayashi T, Shirai K, Kohama K, Hirata J-i: Effect of tocilizumab treatment on patients with coronavirus disease 2019 and bacteremia: a retrospective cohort study. Infectious diseases and therapy 2022, 11(1):533-541.
Palanisamy N, Vihari N, Meena DS, Kumar D, Midha N, Tak V, Sharma A, Bohra GK, Kothari N, Dutt N: Clinical profile of bloodstream infections in COVID-19 patients: a retrospective cohort study. BMC infectious diseases 2021, 21:1-9.
Buetti N, Ruckly S, de Montmollin E, Reignier J, Terzi N, Cohen Y, Siami S, Dupuis C, Timsit J-F: COVID-19 increased the risk of ICU-acquired bloodstream infections: a case–cohort study from the multicentric OUTCOMEREA network. Intensive care medicine 2021, 47:180-187.
Buetti N, Tabah A, Loiodice A, Ruckly S, Aslan AT, Montrucchio G, Cortegiani A, Saltoglu N, Kayaaslan B, Aksoy F: Different epidemiology of bloodstream infections in COVID-19 compared to non-COVID-19 critically ill patients: a descriptive analysis of the Eurobact II study. Critical Care 2022, 26(1):319.
Engsbro AL, Israelsen SB, Pedersen M, Tingsgaard S, Lisby G, Andersen CØ, Benfield T: Predominance of hospital-acquired bloodstream infection in patients with Covid-19 pneumonia. Infectious Diseases 2020, 52(12):919-922.
Søgaard KK, Baettig V, Osthoff M, Marsch S, Leuzinger K, Schweitzer M, Meier J, Bassetti S, Bingisser R, Nickel CH: Community-acquired and hospital-acquired respiratory tract infection and bloodstream infection in patients hospitalized with COVID-19 pneumonia. Journal of Intensive Care 2021, 9:1-10.
Bayo SM, Ruíz MPP, Hijazo MM, Usón MCV: Bacteremia during COVID-19 pandemic in a tertiary hospital in Spain. Enfermedades Infecciosas y Microbiología Clínica 2022, 40(4):183-186.
Sturdy A, Basarab M, Cotter M, Hager K, Shakespeare D, Shah N, Randall P, Spray D, Arnold A: Severe COVID-19 and healthcare-associated infections on the ICU: time to remember the basics? Journal of Hospital Infection 2020, 105(4):593-595.
Cogliati Dezza F, Arcari G, Alessi F, Valeri S, Curtolo A, Sacco F, Ceccarelli G, Raponi G, Alessandri F, Mastroianni CM: Clinical impact of COVID-19 on multi-drug-resistant gram-negative bacilli bloodstream infections in an intensive care unit setting: two pandemics compared. Antibiotics 2022, 11(7):926.
Polly M, de Almeida BL, Lennon RP, Cortês MF, Costa SF, Guimarães T: Impact of the COVID-19 pandemic on the incidence of multidrug-resistant bacterial infections in an acute care hospital in Brazil. American journal of infection control 2022, 50(1):32-38.
Bloodstream infection event (central line-associated bloodstream infection and non-central line-associated bloodstream infection) [https://www.cdc.gov/nhsn/pdfs/pscmanual/4psc_clabscurrent.pdf]
Identifying Healthcare-associated Infections (HAI) for NHSN Surveillance [https://www.cdc.gov/nhsn/pdfs/pscmanual/2psc_identifyinghais_nhsncurrent.pdf]
Ventilator-Associated Event (VAE) [https://www.cdc.gov/nhsn/pdfs/pscmanual/10-vae_final.pdf]
Urinary tract infection (catheter-associated urinary tract infection [CAUTI] and non-catheter-associated urinary tract infection [UTI]) and other urinary system infection [USI]) events. [https://www.cdc.gov/nhsn/pdfs/pscmanual/7psccauticurrent.pdf]
Rouzé A, Martin-Loeches I, Povoa P, Makris D, Artigas A, Bouchereau M, Lambiotte F, Metzelard M, Cuchet P, Boulle Geronimi C: Relationship between SARS-CoV-2 infection and the incidence of ventilator-associated lower respiratory tract infections: a European multicenter cohort study. Intensive care medicine 2021, 47:188-198.
Helms J, Tacquard C, Severac F, Leonard-Lorant I, Ohana M, Delabranche X, Merdji H, Clere-Jehl R, Schenck M, Fagot Gandet F: High risk of thrombosis in patients with severe SARS-CoV-2 infection: a multicenter prospective cohort study. Intensive care medicine 2020, 46(6):1089-1098.
Giacobbe DR, Battaglini D, Ball L, Brunetti I, Bruzzone B, Codda G, Crea F, De Maria A, Dentone C, Di Biagio A: Bloodstream infections in critically ill patients with COVID‐19. European journal of clinical investigation 2020, 50(10):e13319.
Cataldo MA, Tetaj N, Selleri M, Marchioni L, Capone A, Caraffa E, Di Caro A, Petrosillo N: Incidence of bacterial and fungal bloodstream infections in COVID-19 patients in intensive care: An alarming “collateral effect”. Journal of global antimicrobial resistance 2020:290.
Giacobbe DR, Labate L, Tutino S, Baldi F, Russo C, Robba C, Ball L, Dettori S, Marchese A, Dentone C: Enterococcal bloodstream infections in critically ill patients with COVID-19: a case series. Annals of medicine 2021, 53(1):1779-1786.
Bonazzetti C, Morena V, Giacomelli A, Oreni L, Casalini G, Galimberti LR, Bolis M, Rimoldi M, Ballone E, Colombo R: Unexpectedly high frequency of enterococcal bloodstream infections in coronavirus disease 2019 patients admitted to an Italian ICU: an observational study. Critical care medicine 2021, 49(1):e31-e40.
Fan J, Li X, Gao Y, Zhou J, Wang S, Huang B, Wu J, Cao Q, Chen Y, Wang Z: The lung tissue microbiota features of 20 deceased patients with COVID-19. Journal of Infection 2020, 81(3):e64-e67.
Russo A, Gavaruzzi F, Ceccarelli G, Borrazzo C, Oliva A, Alessandri F, Magnanimi E, Pugliese F, Venditti M: Multidrug-resistant Acinetobacter baumannii infections in COVID-19 patients hospitalized in intensive care unit. Infection 2022:1-10.
Kinross P, Gagliotti C, Merk H, Plachouras D, Monnet DL, Högberg LD, Group E-NS: Large increase in bloodstream infections with carbapenem-resistant Acinetobacter species during the first 2 years of the COVID-19 pandemic, EU/EEA, 2020 and 2021. Eurosurveillance 2022, 27(46):2200845.
Dobrović K, Škrobo T, Selec K, Jelić M, Čivljak R, Peršec J, Sakan S, Bušić N, Mihelčić A, Hleb S: Healthcare-Associated Bloodstream Infections Due to Multidrug-Resistant Acinetobacter baumannii in COVID-19 Intensive Care Unit: A Single-Center Retrospective Study. Microorganisms 2023, 11(3):774.
Thoma R, Seneghini M, Seiffert SN, Vuichard Gysin D, Scanferla G, Haller S, Flury D, Boggian K, Kleger G-R, Filipovic M: The challenge of preventing and containing outbreaks of multidrug-resistant organisms and Candida auris during the coronavirus disease 2019 pandemic: report of a carbapenem-resistant Acinetobacter baumannii outbreak and a systematic review of the literature. Antimicrobial Resistance & Infection Control 2022, 11(1):12.

No competing interests reported.

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Differences in the epidemiology, clinical characteristics, distribution of microorganisms and outcomes between COVID-19 patients and non-COVID-19 patients with ICU- associated BSIs: a one-center retrospective study

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