Advertisement

Comparison of pneumonia and nonpneumonia-related Acinetobacter baumannii complex bacteremia: A single-center retrospective study

  • Jun Xu
    Affiliations
    Intensive Care Unit, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 79 Qingchun Rd, Hangzhou, 310003, P. R. China
    Search for articles by this author
  • Yulu Xu
    Affiliations
    Intensive Care Unit, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 79 Qingchun Rd, Hangzhou, 310003, P. R. China
    Search for articles by this author
  • Xia Zheng
    Correspondence
    Address correspondence to Xia Zheng, MD Intensive Care Unit, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Rd, Hangzhou, 310003, P. R. China.
    Affiliations
    Intensive Care Unit, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 79 Qingchun Rd, Hangzhou, 310003, P. R. China
    Search for articles by this author
Open AccessPublished:August 07, 2022DOI:https://doi.org/10.1016/j.ajic.2022.08.004

      Highlights

      • The incidence of ABC bacteremia has changed from 2009 to 2020.
      • The pneumonia-related ABC bacteremia was not a risk factor for 30-day mortality.
      • Immunosuppression, higher APACHE II, and SOFA were risk factors for 30-day mortality.

      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). 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 ICU patients diagnosed with ABC bacteremia at a tertiary care hospital from January 2009 to December 2020 were collected, and sorted into groups of ABC bacteremia with and without pneumonia.

      Results

      Significant changes in the incidence of ABC bacteremia and antibiotic resistance were observed over the 12-year study. Compared with nonpneumonia-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 a higher 30-day mortality rate. In multivariate analysis, immunosuppression, higher APACHE II score, and SOFA score were independent risk factors for 30-day mortality. Moreover, the risk of death was 1.919 times higher in the pneumonia-related group.

      Conclusions

      Although pneumonia-related ABC bacteremia had worse outcomes, it was not an independent risk factor for death statistically. Immunosuppression and disease severity levels increased the risks of death in ICU patients with ABC bacteremia.

      Key Words

      Background

      Acinetobacter baumannii complex (ABC), a group of aerobic nonfermenting 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).
      • Antunes LCS
      • Visca P
      • Towner KJ.
      Acinetobacter baumannii: evolution of a global pathogen.
      ABC is frequently distributed in ICU environments and can colonize human mucosal surfaces and medical devices.
      • Ababneh Q
      • Abulaila S
      • Jaradat Z.
      Isolation of extensively drug resistant Acinetobacter baumannii from environmental surfaces inside intensive care units.
      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.
      • Antunes LCS
      • Visca P
      • Towner KJ.
      Acinetobacter baumannii: evolution of a global pathogen.
      Compared with ABC infections at other sites, clinicians focus on ABC bacteremia due to its high mortality rate,
      • Russo A
      • Bassetti M
      • Ceccarelli G
      • et al.
      Bloodstream infections caused by carbapenem-resistant Acinetobacter baumannii: Clinical features, therapy and outcome from a multicenter study.
      longer hospital stays, and greater costs.
      • Nelson RE
      • Schweizer ML
      • Perencevich EN
      • et al.
      Costs and mortality associated with multidrug-resistant healthcare-associated acinetobacter infections.
      The reported mortality rate in patients with ABC bacteremia is 30%-65%.
      • Wisplinghoff H
      • Bischoff T
      • Tallent SM
      • Seifert H
      • Wenzel RP
      • Edmond MB.
      Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study.
      ,
      • Ballouz T
      • Aridi J
      • Afif C
      • et al.
      Risk factors, clinical presentation, and outcome of acinetobacter baumannii bacteremia.
      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 MDR and CR ABC, which is also associated with a higher mortality.
      • Russo A
      • Bassetti M
      • Ceccarelli G
      • et al.
      Bloodstream infections caused by carbapenem-resistant Acinetobacter baumannii: Clinical features, therapy and outcome from a multicenter study.
      ,
      • Vázquez-López R
      • Solano-Gálvez SG
      • Juárez Vignon-Whaley JJ
      • et al.
      Acinetobacter baumannii resistance: a real challenge for clinicians.
      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, a Charlson comorbidity index>3, lower albumin levels, a respiratory tract bacteremia origin, carbapenem resistance, and inappropriate initial antimicrobial therapy.
      • Russo A
      • Bassetti M
      • Ceccarelli G
      • et al.
      Bloodstream infections caused by carbapenem-resistant Acinetobacter baumannii: Clinical features, therapy and outcome from a multicenter study.
      ,
      • Gu Y
      • Jiang Y
      • Zhang W
      • et al.
      Risk factors and outcomes of bloodstream infections caused by Acinetobacter baumannii: a case–control study.
      • Du X
      • Xu X
      • Yao J
      • et al.
      Predictors of mortality in patients infected with carbapenem-resistant Acinetobacter baumannii: a systematic review and meta-analysis.
      • Zhou H
      • Yao Y
      • Zhu B
      • et al.
      Risk factors for acquisition and mortality of multidrug-resistant Acinetobacter baumannii bacteremia.
      • Son HJ
      • Cho EB
      • Bae M
      • et al.
      Clinical and microbiological analysis of risk factors for mortality in patients with carbapenem-resistant acinetobacter baumannii bacteremia.
      • Yu SN
      • Kim T
      • Park SY
      • et al.
      Predictors of acute kidney injury and 28-day mortality in carbapenem-resistant acinetobacter baumanni complex bacteremia.
      Zhou et al
      • Zhou H
      • Yao Y
      • Zhu B
      • et al.
      Risk factors for acquisition and mortality of multidrug-resistant Acinetobacter baumannii bacteremia.
      and Liu et al
      • Liu CP
      • Shih SC
      • Wang NY
      • et al.
      Risk factors of mortality in patients with carbapenem-resistant Acinetobacter baumannii bacteremia.
      have suggested that a respiratory tract bacteremia origin may be an independent risk factor for mortality, although other studies
      • Gu Y
      • Jiang Y
      • Zhang W
      • et al.
      Risk factors and outcomes of bloodstream infections caused by Acinetobacter baumannii: a case–control study.
      ,
      • Liat SA
      • Anat GG
      • Haim BZ
      • et al.
      Risk factors for mortality due to Acinetobacter baumannii bacteremia in patients with hematological malignancies – a retrospective study.
      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.
      • Meng X
      • Fu J
      • Zheng Y
      • et al.
      Ten-year changes in bloodstream infection with acinetobacter baumannii complex in intensive care units in Eastern China: a retrospective cohort study.
      Therefore, we performed this single-center retrospective study to explore differences in clinical profile and prognosis between patients with pneumonia- and nonpneumonia-related ABC bacteremia, and identified possible independent risk factors for 30-day mortality.

      Patients and methods

      Study design

      A retrospective study was conducted in the 29-bed ICU of the First Affiliated Hospital, College of Medicine, Zhejiang University January 2009 to December 2020. The study was reviewed and approved by the Ethics Committees of The First Affiliated Hospital, College of Medicine, Zhejiang University (IIT20210605A).

      Patient selection, variables, and definitions

      Using laboratory records, ICU patients (aged≥ 18 years) with symptoms and signs of infection and at least 1 ABC-positive blood culture were enrolled. 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. A total of 188 patients were eligible for inclusion in the study and were sorted into groups of ABC bacteremia with and without pneumonia (Fig 1).
      Fig 1
      Fig 1Study flow chart. ABC, Acinetobacter baumannii complex.
      The paper and electronic medical records were reviewed and the following data were collected: general patient data (ie, age, gender, and underlying diseases), primary admission diagnosis, invasive procedures before bacteremia (ie, central venous catheter (CVC) placement, temporary dialysis tube placement, tracheal intubation, etc.), antibiotic and steroid exposure, Charlson comorbidity index, the Pitt bacteremia, 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 (MV) time, and 7- and 30-day mortality. The primary outcome was 30-day mortality and the secondary outcomes were total hospital and ICU stay durations, MV time, microbiological eradication rate, and 7-day mortality.
      Pneumonia-related bacteremia was defined using three items based on The Centers for Disease Control and Prevention (CDC) guidelines (https://www.cdc.gov/nhsn/pdfs/pscmanual/4psc_clabscurrent.pdf). 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. The severity of illness was rated using the Pitt bacteremia, APACHE II, or SOFA score 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 (ie, hypogammaglobulinemia or combined variable immunodeficiency).
      • Jung JY
      • Park MS
      • Kim SE
      • et al.
      Risk factors for multi-drug resistant Acinetobacter baumanniibacteremia in patients with colonization in the intensive care unit.
      Appropriate antimicrobial therapy was defined as the administration of at least 1 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.
      • Liu CP
      • Shih SC
      • Wang NY
      • et al.
      Risk factors of mortality in patients with carbapenem-resistant Acinetobacter baumannii bacteremia.
      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.
      • Rhodes A
      • Evans LE
      • Alhazzani W
      • et al.
      Surviving sepsis campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016.
      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.
      • Vasilev K
      • Reshedko G
      • Orasan R
      • et al.
      A Phase 3, open-label, non-comparative study of tigecycline in the treatment of patients with selected serious infections due to resistant Gram-negative organisms including Enterobacter species, Acinetobacter baumannii and Klebsiella pneumoniae.

      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) or a MALDI Biotyper (Bruker). Based on the Vitek system, it is unable to identify species. 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.

      Statistical methods

      The mean ± standard deviation was calculated for continuous variables with a normal distribution, and median (interquartile range) was calculated for those with a non-normal distribution. Student's t test and the Mann-Whitney test were used to analyzing continuous variables, as appropriate. Categorical variables were evaluated by the χ2 test or Fisher's exact test. All significance tests were 2-sided and P-values <.05 were considered statistically significant. All variables with a P-value <.05 in the univariate analyses were included in the multivariate analysis. Linear regression was used to test the multicollinearity between statistically significant variables (P-value <.05) in univariate analyses and tolerance and variance inflation factor (VIF) were calculated. We used SPSS software (ver. 26.0; IBM Corp) 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 CR ABC increased from 78.95% to 100%. The frequency of ABC bacteremia peaked in 2015 and then decreased until 2020. For 2017-2020, the rate of carbapenem resistance was 100%, except in 2018, when it was 60% (Fig 2).
      Fig 2
      Fig 2The annual frequency of ABC bacteremia and the annual trend of CR ABC bacteremia from January 2009 to December 2020. Data are presented as integer or percentage. Blue bars, the frequency of ABC bacteremia during 2009-2020; Data point-fold line chart, the proportion of CR ABC by year.

      The different clinical characteristics of patients with pneumonia-related and nonpneumonia-related ABC bacteremia

      The 188 patients were divided into two groups with pneumonia-(23.4%, 44/188) and nonpneumonia-(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=.051) and tended to have the underlying disease of hypertension (P=.003). The 2 groups did not differ significantly in gender, prior use of corticosteroids, length of ICU prior to culture, invasive procedures, and the severity of illness based on the Charlson comorbidity index. Antibiotic exposure prior to their admission to the ICU was no statistical difference, except for tigecycline (P=.030). On the day of bacteremia, there were no significant differences in serum albumin, immunosuppression, appropriate antimicrobial therapy, infection severity based on the Pitt bacteremia score, APACHE II score, SOFA score, septic shock, or maximum lactate between the 2 groups. The proportion of carbapenem-resistant strains in the pneumonia-related group and the nonpneumonia-related group was 100% and 88.2%, respectively (P=.014).
      Table 1Demographic and clinical characteristics of 188 patients with ABC bacteremia with and without pneumonia
      Patient characteristicsPneumonia-related bacteremia (n=44)Nonpneumonia-related bacteremia (n=144)P
      Age65.3 ± 15.159.5 ± 17.5.051
      Male sex11 (25.0)41 (28.5).652
      Underlying diseases
       Hypertension25 (56.8)46 (31.9).003
       Diabetes mellitus9 (20.5)23 (16.0).489
       Coronary artery disease9 (20.5)22 (15.3).418
       Solid-organ malignancy11 (25.0)24 (16.7).214
       Hematological malignancy2 (4.5)11 (7.6).736
       Post-transplantation2 (4.5)5 (3.5).667
       Chronic Renal Failure8 (18.2)23 (16.0).730
       Liver cirrhosis4 (9.1)10 (6.9).734
       Chronic obstructive pulmonary disorder12 (27.3)23 (16.0).092
       Cerebrovascular disease7 (15.9)10 (6.9).079
       Connective tissue disorder5 (11.4)13 (9.0).770
      Charlson Comorbidity Index2.6 ± 2.32.3 ± 2.3.348
      Corticosteroid use13 (29.5)30 (20.8).229
      Length of ICU prior to culture7.0 (2.3, 11.8)7.0 (3.0,14.0).569
      Invasive devices and procedures
       Recent major surgery (with 1 mo)12 (27.3)58 (40.3).118
       Mechanical ventilation
        Endotracheal tube42 (95.5)121 (84.0).051
        Tracheostomy12 (27.3)40 (27.8).948
       Fiberoptic bronchoscopy12 (27.3)21 (14.6).053
       Central venous catheter35 (79.5)109 (75.7).597
       Peripherally inserted central catheter4 (9.1)13 (9.0).990
       Urinary catheter39 (88.6)130 (90.3).777
       Continuous renal replacement therapy20 (45.5)51 (35.4).229
       Percutaneous drainage16 (36.4)58 (40.3).642
      Previous antibiotic used (with 1 mo)
       Antipseudomonal penicillins + beta lactamase inhibitors29 (65.9)85 (59.0).414
       Antipseudomonal cephalosporins7 (15.9)36 (25.0).209
       Carbapenems32 (72.7)95 (66.0).402
       Quinolone17 (38.6)40 (27.8).170
       Aminoglycosides2 (4.5)9 (6.3).956
       Tigecycline1 (2.3)20 (13.9).030
       Antifungal agents22 (50.0)57 (39.6).221
      On bacteraemia day
       Serum albumin31.1 ± 5.23.5 ± 2.5.444
       Immunosupression20 (45.5)54 (37.5).345
       Proportion of carbapenem-resistant strains44 (100.0)127 (88.2).014
       Appropriate antimicrobial therapy7 (15.9)34 (23.6).270
      Severity of infection
       Pitt bacteremia score5.9 ± 2.95.2 ± 3.2.187
       APACHE II score26.9 ± 9.425.4 ± 11.0.404
       SOFA score11.7 ± 5.510.5 ± 5.5.188
       Septic shock27 (61.4)66 (45.8).071
       Maximum lactate (in 24 h)3.5 ± 2.54.2 ± 3.8.155
      Data are presented as n (%) or mean ± SD or median [IQR].
      APACHE, Acute Physiology and Chronic Health Evaluation; IQR, interquartile range; SD, standard deviation; SOFA, Sequential Organ Failure Assessment.
      The bold values represent significant p<0.05.
      The outcomes of 188 patients with ABC bacteremia are shown in Table 2. Patients with pneumonia-related ABC bacteremia were similar to patients with nonpneumonia-related ABC bacteremia with respect to the length of ICU stay, duration of MV, microbiological eradication, and 7-day mortality. The 30-day mortality rate was significantly higher in the pneumonia-related group (75.0% vs 57.6%, P=.038), which led to a shorter hospital stay instead.
      Table 2Outcomes of 188 patients with ABC bacteremia with and without pneumonia
      Pneumonia-related bacteremia (n=44)Nonpneumonia-related bacteremia (n=144)P
      Duration of ICU13.0 (6,19.8)17.0 (8.0,31.0).079
      Duration of hospital16.5 (8.0,29.5)27 (12.5,42.0).013
      Duration of MV13 (6,17.8)12.5 (4.0,29.0).700
      7-d mortality24 (54.5)60 (41.7).133
      30-d mortality33 (75.0)83 (57.6).038
      Microbiological eradication12 (27.3)61 (42.4).072
      Data are presented as n (%) or median [IQR].
      ICU, intestine care unit; IQR, interquartile range; MV, mechanical ventilation.
      The bold values represent significant p<0.05.

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

      Table 3 shows risk factors for 30-day mortality in patients with ABC bacteremia. 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%.
      Table 3Risk factors for 30-day mortality in patients with ABC bacteremia
      Multivariate analysis
      Patient characteristicsMortality (n=116)Survival (n=72)Univariate analysis, POR (95% CI)P
      Age62.5 ± 15.558.2 ± 19.1.109 (-9.619,.980)
      Male sex81 (69.8)55 (76.4).328 (.365,1.402)
      Underlying diseases
       Hypertension46 (39.7)25 (34.7).498 (.670,2.277)
       Diabetes mellitus21 (18.1)11 (15.3).616 (.552,2.721)
       Coronary artery disease21 (18.1)10 (13.9).449 (.605,3.106)
       Solid-organ malignancy21 (18.1)14 (19.4).818 (.432,1.941)
       Hematological malignancy13 (11.2)0 (0).002 (.520,.666).096
       Post-transplantation6 (5.2)1 (1.4).254 (.457,32.848)
      Chronic Renal Failure23 (19.8)8 (11.1).117 (.833,4.700)
       Liver cirrhosis12 (10.3)2 (2.8).055 (.877,18.600)
       Chronic obstructive pulmonary disorder21 (18.1)14 (19.4).818 (.432,1.941)
       Cerebrovascular disease11 (9.5)6 (8.3).789 (.407,3.264)
       Connective tissue disorder13 (11.2)5 (6.9).334 (.576,4.962)
      Charlson Comorbidity Index2.5 ± 2.42.0 ± 2.2.146 (-1.179,.176)
      Corticosteroid use39 (33.6)4 (5.6)<.001 (2.926,25.341).095
      Length of ICU prior to culture7.0 (2.0,13.0)7.5 (4.3,14.0).310 (-4.682,17.186)
      Invasive devices and procedures
      Recent major surgery (within 1month)37 (31.9)33 (45.8).055 (.302,1.015)
       Mechanical ventilation
        Endotracheal tube104 (89.7)59 (81.9).130 (.819,4.455)
        Tracheostomy30 (25.9)22 (30.6).484 (.413,1.521)
       Fiberoptic bronchoscopy19 (16.4)14 (19.4).591 (.378,1.741)
       Central venous catheter94 (81.0)50 (69.4).068 (.949,3.723)
       Peripherally inserted central catheter10 (8.6)7 (9.7).798 (.318,2.415)
       Urinary catheter104 (89.7)65 (90.3).890 (.349,2.493)
       Continuous renal replacement therapy47 (40.5)24 (33.3).323 (.737,2.518)
       Percutaneous drainage43 (37.1)31 (43.1).414 (.428,1.419)
      Possible source of bacteremia
       Lung71 (61.2)38 (52.8).255 (.779,2.558)
       Intra-abdomen16 (13.8)14 (19.4).304 (.302,1.456)
       Catheter-related14 (12.1)10 (13.9).716 (.356,2.033)
       Urinary tract5 (4.3)5 (6.9).654 (.168,2.163)
       Unknown11 (9.5)5 (6.9).544 (.467,4.220)
      Previous antibiotic used (within 1 mo)
       Anti-pseudomonal penicillins +

      beta lactamase inhibitors
      73 (62.9)41 (56.9).414 (.705,2.338)
       Antipseudomonal cephalosporins30 (25.9)13 (18.1).215 (.763,3.286)
       Carbapenems84 (72.4)43 (59.7).071 (.950,3.299)
       Quinolone43 (37.1)14 (19.4).011 (1.218,4.888).141
       Aminoglycosides5 (4.3)6 (8.3).339 (0.146,1.687)
       Tigecycline12 (10.3)9 (12.5).648 (0.322,2.025)
       Anti-fungal agents60 (51.7)19 (26.4).001 (1.579,5.658).176
      On bacteraemia day
       Serum albumin29.7 ± 5.131.9 ± 4.9.005 (0.654,3.619).164
       Immunosupression60 (51.7)14 (19.4)<.001 (2.231,8.831)3.883 (1.665,9.058).002
       Proportion of carbapenem-resistant strains110 (94.8)61 (84.7).019 (1.165,9.379).790
       Pneumonia-related33 (28.4)11 (15.3).038 (1.033,4.706).171
       Appropriate antimicrobial therapy22 (18.9)19 (26.4).231 (.324,1.315)
      Severity of infection
       Pitt bacteremia score6.4 ± 2.93.6 ± 2.7<.001 (-3.596, -1.919).902
       APACHE II score30.0 ± 9.918.8 ± 7.7<.001 (-13.832, -8.737)1.084 (1.025,1.148).005
       SOFA score13.2 ± 5.16.9 ± 3.6<.001 (-4.010, -1.623)1.244 (1.110,1.395)<.001
       Septic shock78 (67.2)15 (20.8)<.001 (3.919,15.525).145
       Maximum lactate (in 24 h)5.1 ± 4.12.3 ± 1.2<.001 (-3.539, -1.939).157
      Data are presented as n (%) or mean ± SD or median [IQR].
      APACHE, Acute Physiology and Chronic Health Evaluation; IQR, interquartile range; SD, standard deviation; SOFA, Sequential Organ Failure Assessment.
      The bold values represent significant p<0.05.
      In univariate analyses, poor outcomes were associated with hematological malignancy, previous corticosteroid use, prior exposure to quinolone and antifungal 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. The tolerance and variance inflation factor (VIF) was calculated to prove that there is no multicollinearity in above variables.
      On multivariate logistic regression analysis, immunosuppression (OR 3.883, 95%CI 1.665-9.058, P=.002), APACHE II score (OR 1.084, 95%CI 1.025-1.148, P=.005) and SOFA score (OR 1.244, 95%CI 1.110-1.395, P<.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=.171).

      Discussion

      Acinetobacter baumannii complex is a group of nosocomial pathogens that has 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 MDR and CR ABC can lead to higher mortality.
      • Liu Y
      • Wang Q
      • Zhao C
      • et al.
      Prospective multi-center evaluation on risk factors, clinical characteristics and outcomes due to carbapenem resistance in Acinetobacter baumannii complex bacteraemia: experience from the Chinese Antimicrobial Resistance Surveillance of Nosocomial Infections (CARES) Network.
      Several studies have suggested that respiratory tract colonization or infection is a risk factor for ABC bacteremia,
      • Liu Y
      • Wang Q
      • Zhao C
      • et al.
      Prospective multi-center evaluation on risk factors, clinical characteristics and outcomes due to carbapenem resistance in Acinetobacter baumannii complex bacteraemia: experience from the Chinese Antimicrobial Resistance Surveillance of Nosocomial Infections (CARES) Network.
      but few have compared the clinical characteristics of pneumonia- and nonpneumonia-related ABC bacteremia.
      • Liu CP
      • Shih SC
      • Wang NY
      • et al.
      Risk factors of mortality in patients with carbapenem-resistant Acinetobacter baumannii bacteremia.
      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, and compared the differences between pneumonia- and nonpneumonia-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.
      • Jin L
      • Zhao C
      • Li H
      • Wang R
      • Wang Q
      • Wang H.
      Clinical profile, prognostic factors, and outcome prediction in hospitalized patients with bloodstream infection: results from a 10-Year Prospective Multicenter Study.
      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.
      • Yang Y
      • Guo Y
      • Yin D
      • et al.
      In Vitro Activity of Cefepime-Zidebactam, Ceftazidime-Avibactam, and Other Comparators against Clinical Isolates of Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii: results from China Antimicrobial Surveillance Network (CHINET) in 2018.
      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.
      • Meng X
      • Fu J
      • Zheng Y
      • et al.
      Ten-year changes in bloodstream infection with acinetobacter baumannii complex in intensive care units in Eastern China: a retrospective cohort study.
      In this study, the resistance rate to imipenem was 95.7% in year 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.
      • Liu CP
      • Shih SC
      • Wang NY
      • et al.
      Risk factors of mortality in patients with carbapenem-resistant Acinetobacter baumannii bacteremia.
      Although researchers have reported risk factors for MDR and CR acquisition in ABC bacteremia,
      • Zhou H
      • Yao Y
      • Zhu B
      • et al.
      Risk factors for acquisition and mortality of multidrug-resistant Acinetobacter baumannii bacteremia.
      ,
      • Son HJ
      • Cho EB
      • Bae M
      • et al.
      Clinical and microbiological analysis of risk factors for mortality in patients with carbapenem-resistant acinetobacter baumannii bacteremia.
      ,
      • Young KS
      • il CS
      • Bang JH
      Risk factors associated with bloodstream infection among patients colonized by multidrug-resistant Acinetobacter baumannii: a 7-year observational study in a general hospital.
      only Teng et al compared pneumonia and non-pneumonia patients with ABC bacteremia.
      • Teng SO
      • Yen MY
      • Ou TY
      • Chen FL
      • Yu FL
      • Lee WS.
      Comparison of pneumonia- and non-pneumonia-related Acinetobacter baumannii bacteremia: impact on empiric therapy and antibiotic resistance.
      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, severity of illness (as defined by the Pitt bacteremia score), and inappropriate empirical antimicrobial treatment.
      • Du X
      • Xu X
      • Yao J
      • et al.
      Predictors of mortality in patients infected with carbapenem-resistant Acinetobacter baumannii: a systematic review and meta-analysis.
      Three recent studies all found that a high Pitt bacteremia score was an independent risk factor for ABC bacteremia-related mortality.
      • Gu Y
      • Jiang Y
      • Zhang W
      • et al.
      Risk factors and outcomes of bloodstream infections caused by Acinetobacter baumannii: a case–control study.
      ,
      • Zhou H
      • Yao Y
      • Zhu B
      • et al.
      Risk factors for acquisition and mortality of multidrug-resistant Acinetobacter baumannii bacteremia.
      ,
      • Park SY
      • Si HJ
      • Eom JS
      • Lee JS.
      Survival of carbapenem-resistant Acinetobacter baumanniibacteremia: colistin monotherapy versus colistin plus meropenem.
      Moreover, Zhou et al and Park et al showed that bacteremia occurring after 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 CR Acinetobacter baumannii bacteremia.
      • Yu SN
      • Kim T
      • Park SY
      • et al.
      Predictors of acute kidney injury and 28-day mortality in carbapenem-resistant acinetobacter baumanni complex bacteremia.
      ,
      • Kim T
      • Park KH
      • Yu SN
      • et al.
      Early intravenous colistin therapy as a favorable prognostic factor for 28-day mortality in patients with CRAB bacteremia: a multicenter propensity score-matching analysis.
      Liat et al found that, to be a protective factor, appropriate antibiotic therapy must be strarted within 48 hours.
      • Liat SA
      • Anat GG
      • Haim BZ
      • et al.
      Risk factors for mortality due to Acinetobacter baumannii bacteremia in patients with hematological malignancies – a retrospective study.
      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.
      • Cecconi M
      • Evans L
      • Levy M
      • Rhodes A.
      Sepsis and septic shock.
      CR Acinetobacter baumannii 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 CR Acinetobacter baumannii bacteremia.
      • Kim T
      • Park KH
      • Yu SN
      • et al.
      Early intravenous colistin therapy as a favorable prognostic factor for 28-day mortality in patients with CRAB bacteremia: a multicenter propensity score-matching analysis.
      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,
      • Son HJ
      • Cho EB
      • Bae M
      • et al.
      Clinical and microbiological analysis of risk factors for mortality in patients with carbapenem-resistant acinetobacter baumannii bacteremia.
      which differed from Lee et al.
      • Lee YT
      • Sun JR
      • Wang YC
      • et al.
      Multicentre study of risk factors for mortality in patients with Acinetobacter bacteraemia receiving colistin treatment.
      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. Similar results were reported by Lim et al suggested that host factors and severity of infections reflected by APACHE are the main determinants of the outcome rather than the use of active antimicrobial therapy.
      • Lim SK
      • Lee SO
      • Choi SH
      • et al.
      The outcomes of using colistin for treating multidrug resistant Acinetobacter species bloodstream infections.
      Therefore, further research needs to determine whether inactive microbial therapy can improve 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-venter 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, the completeness of data may be deficient leading to the misclassification bias. Fourth, 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 CR ABC is very high. Patients with pneumonia-related ABC bacteremia had a higher rate of hypertension, less prior tigecycline use, more CR strains, and a higher 30-day mortality rate. Our results also suggest that immunosuppression and higher APACHE II and SOFA scores were risk factors of 30-day mortality. We believe that the clinicians should pay more attention to patient's immune status and the severity of the disease to improve the prognosis.

      Acknowledgment

      This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

      References

        • Antunes LCS
        • Visca P
        • Towner KJ.
        Acinetobacter baumannii: evolution of a global pathogen.
        Pathog Dis [Internet]. 2014; 71 ([cited September 15, 2021]. Available at:): 292-301
        • Ababneh Q
        • Abulaila S
        • Jaradat Z.
        Isolation of extensively drug resistant Acinetobacter baumannii from environmental surfaces inside intensive care units.
        Am J Infect Control [Internet]. 2022; 50 ([cited July 27, 2022]. Available at:): 159-165
        • Russo A
        • Bassetti M
        • Ceccarelli G
        • et al.
        Bloodstream infections caused by carbapenem-resistant Acinetobacter baumannii: Clinical features, therapy and outcome from a multicenter study.
        J Infect [Internet]. 2019; 79 ([cited 2021 Sep 8]. Available from:): 130-138
        • Nelson RE
        • Schweizer ML
        • Perencevich EN
        • et al.
        Costs and mortality associated with multidrug-resistant healthcare-associated acinetobacter infections.
        Infect Control Hosp Epidemiol [Internet]. 2016; 37 ([cited September 8, 2021]. Available at:): 1212-1218
        • Wisplinghoff H
        • Bischoff T
        • Tallent SM
        • Seifert H
        • Wenzel RP
        • Edmond MB.
        Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study.
        Clin Infect Dis. 2004; 39: 309-317
        • Ballouz T
        • Aridi J
        • Afif C
        • et al.
        Risk factors, clinical presentation, and outcome of acinetobacter baumannii bacteremia.
        Front Cell Infect Microbiol [Internet]. 2017; 7 (Accessed August 21, 2021): 156
        • Vázquez-López R
        • Solano-Gálvez SG
        • Juárez Vignon-Whaley JJ
        • et al.
        Acinetobacter baumannii resistance: a real challenge for clinicians.
        Antibiotics [Internet]. 2020; 9 ([cited June 8, 2021]. Available at:): 205
        • Gu Y
        • Jiang Y
        • Zhang W
        • et al.
        Risk factors and outcomes of bloodstream infections caused by Acinetobacter baumannii: a case–control study.
        Diagn Microbiol Infect Dis [Internet]. 2021; 99 ([cited 2021 Aug 21]. Available at:)115229
        • Du X
        • Xu X
        • Yao J
        • et al.
        Predictors of mortality in patients infected with carbapenem-resistant Acinetobacter baumannii: a systematic review and meta-analysis.
        Am J Infect Control [Internet]. 2019; 47 ([cited August 21, 2021]. Available at:): 1140-1145
        • Zhou H
        • Yao Y
        • Zhu B
        • et al.
        Risk factors for acquisition and mortality of multidrug-resistant Acinetobacter baumannii bacteremia.
        Medicine (Baltimore) [Internet]. 2019; 98 (Accessed June 8, 2021): e14937
        • Son HJ
        • Cho EB
        • Bae M
        • et al.
        Clinical and microbiological analysis of risk factors for mortality in patients with carbapenem-resistant acinetobacter baumannii bacteremia.
        Open Forum Infect Dis [Internet]. 2020; 7 ([cited August 21, 2021]. Available at:): ofaa378
        • Yu SN
        • Kim T
        • Park SY
        • et al.
        Predictors of acute kidney injury and 28-day mortality in carbapenem-resistant acinetobacter baumanni complex bacteremia.
        Microb Drug Resist [Internet]. 2021; 27 ([cited August 21, 2021]. Available at:): 1029-1036
        • Liu CP
        • Shih SC
        • Wang NY
        • et al.
        Risk factors of mortality in patients with carbapenem-resistant Acinetobacter baumannii bacteremia.
        J Microbiol Immunol Infect [Internet]. 2014; : 1-7https://doi.org/10.1016/j.jmii.2014.10.006
        • Liat SA
        • Anat GG
        • Haim BZ
        • et al.
        Risk factors for mortality due to Acinetobacter baumannii bacteremia in patients with hematological malignancies – a retrospective study.
        Leuk Lymphoma [Internet]. 2019; 0: 1-6https://doi.org/10.1080/10428194.2019.1599113
        • Meng X
        • Fu J
        • Zheng Y
        • et al.
        Ten-year changes in bloodstream infection with acinetobacter baumannii complex in intensive care units in Eastern China: a retrospective cohort study.
        Front Med [Internet]. 2021; 8 ([cited September 10, 2021] Available at:)715213
        • Jung JY
        • Park MS
        • Kim SE
        • et al.
        Risk factors for multi-drug resistant Acinetobacter baumanniibacteremia in patients with colonization in the intensive care unit.
        BMC Infect Dis [Internet]. 2010; 10 ([cited September 17, 2021]. Available at:): 228
        • Rhodes A
        • Evans LE
        • Alhazzani W
        • et al.
        Surviving sepsis campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016.
        Intensive Care Med [Internet]. 2017; 43 ([cited September 17, 2021]. Available at:): 304-377
        • Vasilev K
        • Reshedko G
        • Orasan R
        • et al.
        A Phase 3, open-label, non-comparative study of tigecycline in the treatment of patients with selected serious infections due to resistant Gram-negative organisms including Enterobacter species, Acinetobacter baumannii and Klebsiella pneumoniae.
        J Antimicrob Chemother [Internet]. 2008; 62 ([cited September 17, 2021]. Available at:): i29-i40
        • Liu Y
        • Wang Q
        • Zhao C
        • et al.
        Prospective multi-center evaluation on risk factors, clinical characteristics and outcomes due to carbapenem resistance in Acinetobacter baumannii complex bacteraemia: experience from the Chinese Antimicrobial Resistance Surveillance of Nosocomial Infections (CARES) Network.
        J Med Microbiol [Internet]. 2020; 69 ([cited September 15, 2021]. Available at:): 949-959
        • Jin L
        • Zhao C
        • Li H
        • Wang R
        • Wang Q
        • Wang H.
        Clinical profile, prognostic factors, and outcome prediction in hospitalized patients with bloodstream infection: results from a 10-Year Prospective Multicenter Study.
        Front Med [Internet]. 2021; 8 ([cited August 21, 2021]. Available at:)629671
        • Yang Y
        • Guo Y
        • Yin D
        • et al.
        In Vitro Activity of Cefepime-Zidebactam, Ceftazidime-Avibactam, and Other Comparators against Clinical Isolates of Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii: results from China Antimicrobial Surveillance Network (CHINET) in 2018.
        Antimicrob Agents Chemother [Internet]. 2020; 65 ([cited September 14, 2021]. Available at)
        • Young KS
        • il CS
        • Bang JH
        Risk factors associated with bloodstream infection among patients colonized by multidrug-resistant Acinetobacter baumannii: a 7-year observational study in a general hospital.
        Am J Infect Control [Internet]. 2020; 48 ([cited August 21, 2021]. Available at): 581-583
        • Teng SO
        • Yen MY
        • Ou TY
        • Chen FL
        • Yu FL
        • Lee WS.
        Comparison of pneumonia- and non-pneumonia-related Acinetobacter baumannii bacteremia: impact on empiric therapy and antibiotic resistance.
        J Microbiol Immunol Infect [Internet]. 2015; 48: 525-530https://doi.org/10.1016/j.jmii.2014.06.011
        • Park SY
        • Si HJ
        • Eom JS
        • Lee JS.
        Survival of carbapenem-resistant Acinetobacter baumanniibacteremia: colistin monotherapy versus colistin plus meropenem.
        J Int Med Res [Internet]. 2019; 47 (Accessed June 8, 2021): 5977-5985
        • Kim T
        • Park KH
        • Yu SN
        • et al.
        Early intravenous colistin therapy as a favorable prognostic factor for 28-day mortality in patients with CRAB bacteremia: a multicenter propensity score-matching analysis.
        J Korean Med Sci [Internet]. 2019; 34 ([cited August 21, 2021]. Available at:): e256
        • Cecconi M
        • Evans L
        • Levy M
        • Rhodes A.
        Sepsis and septic shock.
        Lancet Lond Engl. 2018; 392: 75-87
        • Lee YT
        • Sun JR
        • Wang YC
        • et al.
        Multicentre study of risk factors for mortality in patients with Acinetobacter bacteraemia receiving colistin treatment.
        Int J Antimicrob Agents [Internet]. 2020; 55 ([cited August 21, 2021]. Available at)105956
        • Lim SK
        • Lee SO
        • Choi SH
        • et al.
        The outcomes of using colistin for treating multidrug resistant Acinetobacter species bloodstream infections.
        J Korean Med Sci [Internet]. 2011; 26 ([cited July 27, 2022]. Available at): 325