A 12-year retrospective single-center comparison of pneumonia- and non-pneumonia-related Acinetobacter baumannii complex bacteremia

DOI: https://doi.org/10.21203/rs.3.rs-1439017/v1

Abstract

Background

Acinetobacter baumannii complex (ABC) is a group of increasingly prevalent opportunistic pathogens that cause a variety of life-threatening nosocomial infections, especially in the intensive care unit (ICU). It is unclear whether ABC bacteremia differs with infection site. This study assessed the differences between pneumonia- and non-pneumonia-related ABC bacteremia and possible independent risk factors for 30-day mortality.

Methods

The clinical data of 188 patients diagnosed with ABC bacteremia in our 29-bed ICU between January 2009 and December 2020 were collected. Of these, 44 cases (23.4%) were defined as pneumonia-related ABC bacteremia and 144 (76.6%) as non-pneumonia-related ABC bacteremia.

Results

Significant changes in the incidence of ABC bacteremia and antibiotic resistance were observed over the 12-year study, with an overall 30-day mortality rate of 61.7%. Compared with non-pneumonia-related ABC bacteremia, pneumonia-related ABC bacteremia was associated with a higher rate of hypertension, less prior tigecycline use, more carbapenem-resistant (CR) strains, and had a higher 30-day mortality rate. Univariate analysis showed that hematological malignancy, previous corticosteroid use, prior exposure to quinolone and anti-fungal agents, CR strains, monomicrobial bacteremia, respiratory tract bacteremia origin, lower albumin and higher lactate levels at the time of bacteremia, immunosuppression, septic shock, and severity of illness based on the Pitt bacteremia score, Acute Physiology and Chronic Health Evaluation II (APACHE II), and Sequential Organ Failure Assessment (SOFA) scores at the time of bacteremia were associated with poor outcomes. In multivariate analysis, immunosuppression, and higher APACHE II and SOFA scores, were risk factors for 30-day mortality. Moreover, the risk of death was 1.919 times higher in the pneumonia-related group.

Conclusions

Our study described the clinical characteristics and independent predictors of 30-day mortality in patients with pneumonia- and non-pneumonia-related ABC bacteremia. Although pneumonia-related ABC bacteremia had worse outcomes, it was not an independent risk factor for death statistically. Detection of immune status and maintenance of organ function may be effective therapeutic strategies to improve patient outcomes.

Background

Acinetobacter baumannii complex (ABC), a group of aerobic non-fermenting Gram-negative coccobacilli, has become one of the most prominent opportunistic nosocomial pathogens. It causes severe nosocomial infections worldwide, especially in intensive care units (ICUs) [1]. ABC is frequently distributed in ICU environments and colonizes the human skin, mouth, and nasopharynx. Infections caused by ABC at multiple anatomical sites include ventilator-associated pneumonia (VAP), bloodstream infection (BSI), abdominal infection, skin and soft tissue infections, and catheter-associated urinary tract infections [24].

Compared with ABC infections at other sites, clinicians focus on ABC bacteremia due to its high mortality rate [5], longer hospital stays, and greater costs [6]. The reported mortality rate in patients with ABC bacteremia is 30–65% [7, 8]. Furthermore, due to increased antibiotic exposure, the incidences of multidrug-resistant (MDR) and carbapenem-resistant (CR) ABC are increasing alarmingly. Clinical treatment becomes very difficult once bacteremia is caused by MDRABC and CRABC, which is also associated with higher mortality [5, 9]. Many studies have shown that the epidemiology of ABC bacteremia and the antimicrobial susceptibility profiles of ABC isolates vary greatly depending on the region, year, and even hospital ward. Therefore, it is necessary to investigate changes in the prevalence, microbiological characteristics, treatments, and prognosis in a local context. Reported risk factors for mortality in patients with ABC bacteremia include old age, malignancy, acute kidney injury, septic shock, ICU stay, previous antibiotic use, and illness severity, as defined by the Pitt bacteremia, Acute Physiology and Chronic Health Evaluation II (APACHE II) or Sequential Organ Failure Assessment (SOFA) score, Charlson comorbidity index > 3, lower albumin levels, respiratory tract as the origin of bacteremia, carbapenem resistance, and inappropriate initial antimicrobial therapy [5, 1014]. Studies have suggested that a respiratory tract bacteremia origin may be an independent risk factor for mortality [12, 15], although other studies have refuted this. Whether pneumonia-related ABC bacteremia is an independent risk factor still needs to be assessed by clinical studies. A recent retrospective cohort study of Chinese ICUs found that the incidence of ABC bacteremia and prevalence of antibiotic resistance increased markedly during the past decade, along with increasing pneumonia-related infections and worrisome mortality [16].

Therefore, we performed this single-center retrospective study to explore differences in clinical profile and prognosis between patients with pneumonia- and non-pneumonia-related ABC bacteremia and identified possible independent risk factors for 30-day mortality.

Methods

Research Objects 

A retrospective study was conducted in the 29-bed ICU of the First Affiliated Hospital, College of Medicine, Zhejiang University from 2009 to 2020. Using laboratory records, ICU patients (aged≥ 18 years) with symptoms and signs of infection and at least one ABC-positive blood culture were enrolled, and their complete clinical data were obtained. For patients with multiple episodes of ABC bacteremia, only the first episode was included. Exclusion criteria were aged <18 years, incomplete medical history, ABC bacteremia only isolated from a central catheter line tip culture without a peripheral positive blood culture, no sepsis, and a diagnosis of ABC bacteremia before ICU admission. Patients with coinfection by other pathogens at other sites were not excluded. The study was reviewed and approved by the Ethics Committees of The First Affiliated Hospital, College of Medicine, Zhejiang University (IIT20210605A). 

Definitions 

Pneumonia-related bacteremia was defined using three items based on The Centers for Disease Control and Prevention (CDC) guidelines. The drug susceptibility results were consistent for positive blood and sputum cultures; a sputum culture was collected within the infection window (3 days before and after the first positive blood test), and the clinical diagnostic criteria for pneumonia were met. A diagnosis of pneumonia required new or increased infiltration on chest radiography with two or more of the following: purulent respiratory tract secretions (>25 neutrophils per high-power field); positive sputum culture from a quantitative bacterial culture; and no pulmonary edema or other pulmonary infiltrative diseases. The severity of illness was rated using the Pitt bacteremia, APACHE II, or SOFA score, at ICU admission or at the time of bacteremia. Previous corticosteroid use was defined as the use of corticosteroids at a mean minimum dose of 0.3 mg/kg/d of prednisone equivalent for at least 72 hours, within 30 days before the onset of bacteremia. Chronic renal failure was defined as an estimated glomerular filtration rate of <60 mL/min/1.73 m2. Liver cirrhosis was diagnosed based on laboratory and radiological evidence. Immunosuppression was defined as a history of any of the following: corticosteroid therapy for 15 days (at least 10 mg/d of prednisone or an equivalent drug); seropositivity for human immunodeficiency virus; solid organ or bone marrow transplantation; radiotherapy or chemotherapy for an underlying malignancy during the 6 months before hospital admission; and acquired immune deficiency disorder (i.e., hypogammaglobulinemia or combined variable immunodeficiency) [17]. BSI concurrent with another pathogen was defined as one or more other pathogens isolated from blood cultures obtained within 48 hours of collecting the first ABC-positive blood sample, irrespective of whether the isolate came from the same or a different blood culture bottle. Appropriate antimicrobial therapy was defined as the administration of at least one antimicrobial agent, to which a pathogen was sensitive in vitro within 48 hours of bacteremia, via an approved route and at a dosage appropriate for end-organ function [15]. Septic shock was defined as sepsis-induced hypotension persisting despite adequate fluid resuscitation according to the Sepsis 3.0 guidelines jointly issued by the Society of Critical Care Medicine (SCCM) and the European Society of Intensive Care Medicine (ESCIM) in 2016[18]. Microbiological eradication was determined if documented or presumed, the baseline isolate was absent in repeat cultures obtained from the original infection site, or a clinical cure made repeat culture unnecessary [19].

Identification and antimicrobial susceptibility testing

Blood specimens drawn at the bedside under sterile conditions were processed in an automated blood culture machine. The blood isolates were identified by the Vitek system (bioMe ́rieux, France) or a MALDI Biotyper (Bruker, USA). Based on the Vitek system, it is unable to identify species. The susceptibility of the ABC isolates was assessed by the Vitek system. The susceptibility results were interpreted according to the Clinical Laboratory Standards Institute criteria. Intermediate resistance was regarded as resistance in our study.

Clinical Data Collection

The paper and electronic medical records were reviewed and the following data were collected: general patient data (i.e., age, gender, and underlying diseases), primary admission diagnosis, invasive procedures before bacteremia (i.e., central venous catheter (CVC) placement, temporary dialysis tube placement, tracheal intubation, etc.), antibiotic and steroid exposure, Charlson comorbidity index, Pitt bacteremia score, APACHE II, and SOFA scores, the blood culture and antimicrobial susceptibility results, laboratory test results, clinical manifestations of bacteremia, treatment, microbiological eradication, total hospital, and ICU stay durations, mechanical ventilation time, and 7- and 30-day mortality.

Statistical Methods

The mean ± standard deviation was calculated for continuous variables with a normal distribution, and the median (interquartile range) was calculated for those with a non-normal distribution. Student’s t-test and the Mann–Whitney test were used to analyze continuous variables, as appropriate. Categorical variables were evaluated by the χ2 test or Fisher’s exact test. All significance tests were two-sided and p-values <0.05 were considered statistically significant. All variables with a p-value <0.1 in the univariate analyses were included in the multivariate analysis. We used SPSS software (ver. 26.0; IBM Corp., Armonk, NY, USA) for the statistical analysis and Python 3.8 for visualizations.

Results

Patient Demographics and the Incidence of ABC Bacteremia by Year

The study enrolled 188 patients with ABC bacteremia during the 12-year period from 2009 to 2020. Their average age was 60.9 ± 17.1 years old and 136 (72.3%) were male. The median total ICU stay was 15 days, and the overall 30-day mortality was 61.7%. For the period 2009–2014, there was no significant change in the frequency of ABC bacteremia by year, while the proportion of CRABC increased from 78.95–100%. The frequency of ABC bacteremia peaked in 2015 and then decreased until 2020. For the years 2017–2020, the rate of carbapenem resistance was 100%, except in 2018, when it was 60% (Fig. 1).

The Different Clinical Characteristics Of Patients With Pneumonia-related And Non-pneumonia-related Abc Bacteremia

The 188 patients were divided into two groups with pneumonia-(23.4%, 44/188) and non-pneumonia-(76.6%, 144/188) related ABC bacteremia. Table 1 shows their demographics and clinical characteristics. The pneumonia-related group was slightly older (65.3 ± 15.1 vs. 59.5 ± 17.5, p = 0.051) and the only underlying disease that differed between the two groups was hypertension (p = 0.003). Gender, disease severity, and organ dysfunction at ICU admission, as determined by Charlson comorbidity index and APACHE II, and SOFA scores, were similar. Compared with the patients with non-pneumonia-related ABC bacteremia, patients with pneumonia-related ABC bacteremia underwent more endotracheal tube procedures (p = 0.051) and fiberoptic bronchoscopy (p = 0.053), while there were no differences in other invasive procedures. On the day of bacteremia, there were no significant differences in immunosuppression, concurrent infection with another pathogen, or infection severity based on the Pitt bacteremia score, APACHE II, or SOFA scores between the two groups. Unexpectedly, despite a lack of statistical significance, there were more cases of septic shock with lower lactate on the day of bacteremia in the pneumonia-related group. The 30-day mortality rate was significantly higher in the pneumonia-related group (75.0% vs. 57.6%, p = 0.038), which led to shorter hospital and ICU stays instead (Table 2).

Table 1

Demographic and clinical characteristics of 188 patients with ABC bacteremia with and without pneumonia

Patient characteristics

Pneumonia-related bacteremia (n = 44)

Non-pneumonia-related bacteremia (n = 144)

P

Age

65.3 ± 15.1

59.5 ± 17.5

0.051

Male sex

11(25.0)

41(28.5)

0.652

Underlying diseases

     

Hypertension

25(56.8)

46(31.9)

0.003

Diabetes mellitus

9(20.5)

23(16.0)

0.489

Coronary artery disease

9(20.5)

22(15.3)

0.418

Solid-organ malignancy

11(25.0)

24(16.7)

0.214

Hematological malignancy

2(4.5)

11(7.6)

0.736

Post-transplantation

2(4.5)

5(3.5)

0.667

Chronic Renal Failure

8(18.2)

23(16.0)

0.730

Liver cirrhosis

4(9.1)

10(6.9)

0.734

Chronic obstructive pulmonary disorder

12(27.3)

23(16.0)

0.092

Cerebrovascular disease

7(15.9)

10(6.9)

0.079

Connective tissue disorder

5(11.4)

13(9.0)

0.770

Charlson Comorbidity Index

2.6 ± 2.3

2.3 ± 2.3

0.348

Corticosteroid use

13(29.5)

30(20.8)

0.229

Length of ICU prior to culture

7.0(2.3, 11.8)

7.0(3.0,14.0)

0.569

Invasive devices and procedures

     

Recent major surgery(with 1 month)

12(27.3)

58(40.3)

0.118

Mechanical ventilation

     

Endotracheal tube

42(95.5)

121(84.0)

0.051

Tracheostomy

12(27.3)

40(27.8)

0.948

Fiberoptic bronchoscopy

12(27.3)

21(14.6)

0.053

Central venous catheter

35(79.5)

109(75.7)

0.597

Peripherally inserted central catheter

4(9.1)

13(9.0)

0.990

Urinary catheter

39(88.6)

130(90.3)

0.777

Continuous renal replacement therapy

20(45.5)

51(35.4)

0.229

Percutaneous drainage

16(36.4)

58(40.3)

0.642

Previous antibiotic used (with 1 month)

     

Anti-pseudomonal penicillins + beta lactamase inhibitors

29(65.9)

85(59.0)

0.414

Antipseudomonal cephalosporins

7(15.9)

36(25.0)

0.209

Carbapenems

32(72.7)

95(66.0)

0.402

Quinolone

17(38.6)

40(27.8)

0.170

Aminoglycosides

2(4.5)

9(6.3)

0.956

Tigecycline

1(2.3)

20(13.9)

0.030

Anti-fungal agents

22(50.0)

57(39.6)

0.221

On bacteraemia day

     

Serum albumin

31.1 ± 5.2

3.5 ± 2.5

0.444

Immunosupression

20(45.5)

54(37.5)

0.345

Proportion of carbapenem-resistant strains

44(100.0)

127(88.2)

0.014

Concurrent infection with another pathogen

15(34.1)

58(40.3)

0.461

Appropriate antimicrobial therapy

7(15.9)

34(23.6)

0.270

Severity of infection

     

Pitt bacteremia score

5.9 ± 2.9

5.2 ± 3.2

0.187

APACHE II score

26.9 ± 9.4

25.4 ± 11.0

0.404

SOFA score

11.7 ± 5.5

10.5 ± 5.5

0.188

Septic shock

27(61.4)

66(45.8)

0.071

Maximum lactate (in 24h)

3.5 ± 2.5

4.2 ± 3.8

0.155

Data are presented as n (%) or mean ± SD or median [IQR]; S.D., standard deviation; IQR, interquartile range; APACHE, Acute Physiology and Chronic Health Evaluation; SOFA, Sequential Organ Failure Assessment

Table 2

Outcomes of 188 patients with ABC bacteremia with and without pneumonia

 

Pneumonia-related bacteremia (n = 44)

Non-pneumonia-related bacteremia (n = 144)

P

Duration of ICU

13.0(6,19.8)

17.0(8.0,31.0)

0.079

Duration of hospital

16.5(8.0,29.5)

27(12.5,42.0)

0.013

Duration of MV

13(6,17.8)

12.5(4.0,29.0)

0.700

7-day mortality

24(54.5)

60(41.7)

0.133

30-day mortality

33(75.0)

83(57.6)

0.038

Microbiological eradication

12(27.3)

61(42.4)

0.072

Data are presented as n (%) or median [IQR]; IQR, interquartile range; ICU, intestine care unit; MV, mechanical ventilation;

Risk Factors For 30-day Mortality In Patients With Abc Bacteremia

Table 3 shows univariate comparisons of patients with different clinical outcomes. Taking death within 30 days after ABC bacteremia diagnosis as the main endpoint, 116 cases died and 72 survived. The 30-day mortality rate of patients with ABC bacteremia was 61.7%. In univariate analyses, poor outcomes were associated with hematological malignancy, previous corticosteroid use, prior exposure to quinolone and anti-fungal agents, CR strains, monomicrobial bacteremia, respiratory tract as the origin of bacteremia, lower albumin and higher lactate levels at the time of bacteremia, immunosuppression, septic shock, and severity of illness based on the Pitt bacteremia, APACHE II, and SOFA scores at the time of bacteremia. On multivariate logistic regression analysis, immunosuppression (OR 3.883, 95%CI 1.665–9.058, p = 0.002), APACHE II score (OR 1.084, 95%CI 1.025–1.148, p = 0.005) and SOFA score (OR 1.244, 95%CI 1.110–1.395, p < 0.001) at the time of bacteremia remained independent risk factors for 30-day mortality. The risk of death was 1.919 times higher in the pneumonia-related group, although there was no statistical difference (p = 0.171). The results of the multivariate analysis are shown in Table 4.

Table 3

Univariate analysis of risk factors for 30-day mortality in patients with ABC bacteremia.

Patient characteristics

Mortality

(n = 116)

Survival

(n = 72)

P

Age

62.5 ± 15.5

58.2 ± 19.1

0.109

Male sex

81(69.8)

55(76.4)

0.328

Underlying diseases

     

Hypertension

46(39.7)

25(34.7)

0.498

Diabetes mellitus

21(18.1)

11(15.3)

0.616

Coronary artery disease

21(18.1)

10(13.9)

0.449

Solid-organ malignancy

21(18.1)

14(19.4)

0.818

Hematological malignancy

13(11.2)

0(0)

0.002

Post-transplantation

6(5.2)

1(1.4)

0.254

Chronic Renal Failure

23(19.8)

8(11.1)

0.117

Liver cirrhosis

12(10.3)

2(2.8)

0.055

Chronic obstructive pulmonary disorder

21(18.1)

14(19.4)

0.818

Cerebrovascular disease

11(9.5)

6(8.3)

0.789

Connective tissue disorder

13(11.2)

5(6.9)

0.334

Charlson Comorbidity Index

2.5 ± 2.4

2.0 ± 2.2

0.146

Corticosteroid use

39(33.6)

4(5.6)

< 0.001

Length of ICU prior to culture

7.0(2.0,13.0)

7.5(4.3,14.0)

0.310

Invasive devices and procedures

     

Recent major surgery (within 1month)

37(31.9)

33(45.8)

0.055

Mechanical ventilation

     

Endotracheal tube

104(89.7)

59(81.9)

0.130

Tracheostomy

30(25.9)

22(30.6)

0.484

Fiberoptic bronchoscopy

19(16.4)

14(19.4)

0.591

Central venous catheter

94(81.0)

50(69.4)

0.068

Peripherally inserted central catheter

10(8.6)

7(9.7)

0.798

Urinary catheter

104(89.7)

65(90.3)

0.890

Continuous renal replacement therapy

47(40.5)

24(33.3)

0.323

Percutaneous drainage

43(37.1)

31(43.1)

0.414

Previous antibiotic used (within 1month)

     

Anti-pseudomonal penicillins +

beta lactamase inhibitors

73(62.9)

41(56.9)

0.414

Antipseudomonal cephalosporins

30(25.9)

13(18.1)

0.215

Carbapenems

84(72.4)

43(59.7)

0.071

Quinolone

43(37.1)

14(19.4)

0.011

Aminoglycosides

5(4.3)

6(8.3)

0.339

Tigecycline

12(10.3)

9(12.5)

0.648

Anti-fungal agents

60(51.7)

19(26.4)

0.001

On bacteraemia day

     

Serum albumin

29.7 ± 5.1

31.9 ± 4.9

0.005

Immunosupression

60(51.7)

14(19.4)

< 0.001

Proportion of carbapenem-resistant strains

110(94.8)

61(84.7)

0.019

Pneumonia-related

33(28.4)

11(15.3)

0.038

Concurrent infection with another pathogen

38(32.8)

35(48.6)

0.030

Appropriate antimicrobial therapy

22(18.9)

19(26.4)

0.243

Severity of infection

     

Pitt bacteremia score

6.4 ± 2.9

3.6 ± 2.7

< 0.001

APACHE II score

30.0 ± 9.9

18.8 ± 7.7

< 0.001

SOFA score

13.2 ± 5.1

6.9 ± 3.6

< 0.001

Septic shock

78(67.2)

15(20.8)

< 0.001

Maximum lactate (in 24h)

5.1 ± 4.1

2.3 ± 1.2

< 0.001

Data are presented as n (%) or mean ± SD or median [IQR]; S.D., standard deviation; IQR, interquartile range; APACHE, Acute Physiology and Chronic Health Evaluation; SOFA, Sequential Organ Failure Assessment

Table 4

Risk factors for 30-day mortality in patients with ABC bacteremia in Logistic regression analysis

Variables

OR

CI 95%

P

Immunosupressiona

3.883

1.665–9.058

0.002

APACHE II scorea

1.084

1.025–1.148

0.005

SOFA scorea

1.244

1.110–1.395

< 0.001

pneumonia-related

1.919

0.754–4.882

0.171

OR, odds ratio; CI, confidence interval; APACHE, Acute Physiology and Chronic Health Evaluation; SOFA, Sequential Organ Failure Assessment
aOn day of bacteremia

Discussion

Acinetobacter baumannii complex is a group of nosocomial pathogens that have emerged as a devastating public health threat in healthcare settings, and particularly in ICUs, where it is widely distributed and can colonize human mucosal surfaces and invade the bloodstream in critically ill patients with impaired immune function. There are few treatment options and infections caused by MDRABC and CRABC can lead to higher mortality [20]. Several studies have suggested that respiratory tract colonization or infection is a risk factor for ABC bacteremia [20], but few have compared the clinical characteristics of pneumonia- and non-pneumonia-related ABC bacteremia [15]. This 12-year retrospective single-center study examined long-term changes in incidence and antibiotic resistance among patients with ABC bacteremia in an ICU in eastern China, compared the differences between pneumonia- and non-pneumonia-related ABC bacteremia, and identify possible independent risk factors for 30-day mortality.

A nationwide prospective cohort study conducted from 2007 to 2016 in 16 teaching hospitals across China suggested that A. baumannii was one of the top four pathogens responsible for bacteremia, accounting for approximately 7.03% of bloodstream bacterial isolates [21]. Data from the China Antimicrobial Surveillance Network (CHINET) revealed significant increases in the rates of resistance to carbapenem antibiotics, which ranged from 31% in 2005 to 79.2% in 2018 [22]. A recent study revealed that the frequency of ABC bacteremia increased significantly in the ICUs in eastern China during 2009–2018, as did the resistance rate to carbapenem [16]. In this study, the resistance rate to imipenem was 95.7% in the years 2017–2018, which is higher than in the CHINET data. We analyzed the clinical data of patients with ABC bacteremia during the past 12 years. Carbapenem-sensitive strains accounted for only 9.0% of the total number of cases and the proportion of CR strains was 100% in 2017, 2019, and 2020. There was a sudden drop in 2018 and the possible cause was that we performed strict rectification after a hospital sense event. However, the frequency of ABC bacteremia decreased recently (2015–2020), contrary to previous research. In our hospital in 2020, ABC had fallen out of the top 10 pathogens for bacteremia, suggesting that bacterial epidemiological studies in local hospitals are even more important.

ABC is commonly isolated from intubated patients in ICUs; in this study, lower respiratory tract infections were the most common source of ABC bacteremia acquired in the ICU. The reported mortality rate was higher in cases in which the respiratory tract was the source of bacteremia [15]. Although many studies have reported risk factors for MDR and CR acquisition in ABC bacteremia [12, 13, 23], only Teng et al. compared pneumonia and non-pneumonia patients with ABC bacteremia [24]. As shown in Table 1, our pneumonia-related group had a significantly higher rate of hypertension and significantly more CR strains, while the non-pneumonia-related group had a significantly higher rate of previous tigecycline use. Compared with the non-pneumonia-related group, patients with pneumonia-related ABC bacteremia had a higher 30-day mortality rate, which decreased the total hospital stay because of the high mortality. This finding differed slightly from that of Teng et al (2015). This might be because our study examined ICU patients, while most of their cases were from general wards. In addition, despite the lack of statistical significance, the patients with pneumonia-related ABC bacteremia in our study had a higher rate of septic shock and low lactate levels, implying that respiratory tract-colonized ABC can invade the blood.

Next, we analyzed patients with different prognoses. In univariate and multivariate analysis, immunosuppression and the APACHE II and SOFA scores at the time of bacteremia were independent risk factors for 30-day mortality in patients with ABC bacteremia. We also found that patients with pneumonia-related ABC bacteremia were more likely to have a poor prognosis, although it was not an independent risk factor for 30-day mortality on multivariate analysis. We reviewed the literature on ABC bacteremia in the last 10 years. In 2019, a systematic review and meta-analysis of 10 eligible studies of 923 patients with ABC bacteremia reported that risk factors for attributable mortality included neutropenia, chronic liver disease, chronic renal failure, steroid therapy, immunosuppressant use, septic shock, the severity of illness (as defined by the Pitt bacteremia score), and inappropriate empirical antimicrobial treatment [11]. Three recent studies all found that a high Pitt bacteremia score was an independent risk factor for ABC bacteremia-related mortality [10, 12, 25]. Moreover, Zhou et al. and Park et al. showed that bacteremia occurring after the pneumonia was an independent risk factor for death, while the results of Gu et al. and our study countered this conclusion. Kim et al. and Yu et al. all showed that catheter-related infection and early colistin therapy were independent favorable prognostic factors associated with 28-day mortality in patients with CRAB bacteremia [14, 26]. Liat et al. found that, to be a protective factor, appropriate antibiotic therapy must be started within 48 hours [27]. All of these studies had very small sample sizes, so larger studies are required to confirm our findings.

The effective management of sepsis and septic shock should focus on timely intervention, including removal of infection source, early initiation of appropriate antimicrobial therapy, fluid resuscitation, and resolution of organ dysfunction [28]. CRAB bacteremia is resistant to the currently used antibiotics, except for tigecycline and polymyxin. Kim et al. found that early colistin therapy can reduce the mortality of septic shock patients with CRAB bacteremia [26]. Among antibiotic strategies, Son et al. showed that colistin combined with tigecycline or other antibiotics was significantly associated with lower mortality after adjusting for confounding factors [13], which differed from Lee et al [29]. For physicians who lack clinical experience, starting appropriate antimicrobial therapy at the time of bacteremia is very difficult because of bacterial resistance. We found no significant difference in appropriate treatment rates between survivors and those who died. We also found that immunosuppression and illness severity, as defined by the APACHE II and SOFA scores, were significantly associated with higher mortality. Therefore, the assessment of critically ill patients with ABC bacteremia should include host factors, particularly immune status, and the severity of disease. More studies are needed to clarify whether immunotherapy can improve patient outcomes.

Our study has some limitations. Its main limitation was the small number of ABC bacteremia patients, which decreased the power of our statistical analyses. Second, the study used a retrospective, observational, single-center design, potentially limiting the generalizability of our results to other hospitals. Further randomized controlled trials with larger sample sizes and multicenter designs are required. Third, since this study was retrospective, we could not determine whether the virulence of ABC strains changed significantly over time.

Conclusions

In short, our study found that the number of patients with ABC bacteremia has decreased over the past 5 years, but the proportion of CRABC is very high. Patients with hypertension, less prior tigecycline use, and more CR strains were more likely to be infected with pneumonia-related ABC bacteremia. Immunosuppression and higher APACHE II and SOFA scores were risk factors of 30-day mortality. The treatment plan was evaluated according to the patient’s immune status and the severity of the disease to improve the alertness of clinicians with regard to these cases and to provide guidance for the reasonable treatment of ABC bacteremia, especially in those with pneumonia.

List Of Abbreviations

ABC

Acinetobacter baumannii complex

ICU

Intensive care unit

CR

Carbapenem-resistant

APACHE II

Acute physiology and chronic health evaluation II

SOFA

Sequential organ failure assessment

VAP

Ventilator-associated pneumonia

BSI

Bloodstream infection

MDR

Multidrug-resistant

CDC

Centers for disease control and prevention

SCCM

Society of critical care medicine

ESCIM

The European society of intensive care medicine

CVC

Central venous catheter

S.D.

Standard deviation

IQR

Interquartile range

OR

Odds ratio

CI95

95% Confidence interval

CHINET

the China Antimicrobial Surveillance Network

MV

Mechanical ventilation

Declarations

Ethics approval and consent to participate

The studies involving human participants were reviewed and approved by the Ethics Committees of The First Affiliated Hospital, College of Medicine, Zhejiang University (IIT20210605A). Being a retrospective study, the need of informed consent was waived by the Ethics Committees of The First Affiliated Hospital, College of Medicine, Zhejiang University.

Consent for publication

Not applicable.

Availability of data and materials 

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request. Patient data used in this study is confidential according to the national legislation and the institutional requirements. To protect patient confidentiality and participant’s privacy, data used for this study can be obtained in anonymous form only according to the data privacy act.

Competing interests

The authors declare that they have no competing interests.

Funding

Not applicable.

Authors’ contributions

Jun Xu contributed to manuscript writing and data analysis. Yulu Xu contributed to data collection. Xia Zheng contributed to study design and revise manuscript. All authors approved the final manuscript and are responsible for the content.

Acknowledgements

Not applicable.

Author information

1Intensive Care Unit, The First Affiliated Hospital, College of Medicine, Zhejiang University,79 Qingchun Road, Hangzhou, 310003, P. R. China

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