Does Early Concordant Antibiotic Treatment Reduce Mortality Among Hospitalized Patients with Carbapenem-Resistant Acinetobacter baumannii Bacteremia? A Retrospective Cohort Study
Abstract
1. Introduction
2. Methods
2.1. Definitions
2.2. Microbiological Methods
2.3. Data Collection
2.4. Statistical Analysis
3. Results
4. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Sati, H.; Carrara, E.; Savoldi, A.; Hansen, P.; Garlasco, J.; Campagnaro, E.; Boccia, S.; Castillo-Polo, J.A.; Magrini, E.; Garcia-Vello, P.; et al. WHO Bacterial Priority Pathogens List Advisory Group. The WHO Bacterial Priority Pathogens List 2024: A prioritisation study to guide research, development, and public health strategies against antimicrobial resistance. Lancet Infect. Dis. 2025, 25, 1033–1043. [Google Scholar] [CrossRef]
- Available online: https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance (accessed on 21 November 2023).
- Isler, B.; Doi, Y.; Bonomo, R.A.; Paterson, D.L. New Treatment Options against Carbapenem-Resistant Acinetobacter baumannii Infections. Antimicrob. Agents Chemother. 2019, 63, e01110-18. [Google Scholar] [CrossRef]
- Perez, F.; Hujer, A.M.; Hujer, K.M.; Decker, B.K.; Rather, P.N.; Bonomo, R.A. Global challenge of multidrug-resistant Acinetobacter baumannii. Antimicrob. Agents Chemother. 2007, 51, 3471–3484. [Google Scholar] [CrossRef] [PubMed]
- Opal, S.M.; Calandra, T. Antibiotic usage and resistance: Gaining or losing ground on infection in critically ill patients? JAMA 2009, 302, 2367–2368. [Google Scholar] [CrossRef]
- Visca, P.; Seifert, H.; Towner, K.J. Acinetobacter infection—an emerging threat to human health. IUBMB Life 2011, 63, 1048–1054. [Google Scholar] [CrossRef]
- Meyers, B.R.; Sherman, E.; Mendelson, M.H.; Velasques, G.; Srulevitch-Chin, E.; Hubbard, M.; Hirschman, S.Z. Bloodstream infections in the elderly. Am. J. Med. 1989, 86, 379–384. [Google Scholar] [CrossRef]
- Reunes, S.; Rombaut, V.; Vogelaers, D.; Brusselaers, N.; Lizy, C.; Cankurtaran, M.; Labeau, S.; Petrovic, M.; Blot, S. Risk factors and mortality for nosocomial bloodstream infections in elderly patients. Eur. J. Intern. Med. 2011, 22, e39–e44. [Google Scholar] [CrossRef]
- Blot, S.; Cankurtaran, M.; Petrovic, M.; Vandijck, D.; Lizy, C.; Decruyenaere, J.; Danneels, C.; Vandewoude, K.; Piette, A.; Vershraegen, G.; et al. Epidemiology and outcome of nosocomial bloodstream infection in elderly critically ill patients: A comparison between middle-aged, old, and very old patients. Crit. Care Med. 2009, 37, 1634–1641. [Google Scholar] [CrossRef]
- Lolans, K.; Rice, T.W.; Munoz-Price, L.S.; Quinn, J.P. Multicity outbreak of carbapenem-resistant Acinetobacter baumannii isolates producing the carbapenemase OXA-40. Antimicrob. Agents Chemother. 2006, 50, 2941–2945. [Google Scholar] [CrossRef]
- Busani, S.; Serafini, G.; Mantovani, E.; Venturelli, C.; Giannella, M.; Viale, P.; Mussini, C.; Cossarizza, A.; Girardis, M. Mortality in patients with septic shock by multidrug resistant bacteria. J. Intensive Care Med. 2017, 34, 48–54. [Google Scholar] [CrossRef]
- Russo, A.; Bassetti, M.; Ceccarelli, G.; Carannante, N.; Losito, A.R.; Bartoletti, M.; Corcione, S.; Granata, G.; Santoro, A.; Giacobbe, D.R.; et al. ISGRI-SITA (Italian Study Group on Resistant Infections of the Società Italiana Terapia Antinfettiva). Bloodstream infections caused by carbapenem-resistant Acinetobacter baumannii: Clinical features, therapy and outcome from a multicenter study. J. Infect. 2019, 79, 130–138. [Google Scholar] [CrossRef]
- Nutman, A.; Glick, R.; Temkin, E.; Hoshen, M.; Edgar, R.; Braun, T.; Carmeli, Y. A case-control study to identify predictors of 14-day mortality following carbapenem-resistant Acinetobacter baumannii bacteraemia. Clin. Microbiol. Infect. 2014, 20, O1028–O1034. [Google Scholar] [CrossRef]
- Paul, M.; Shani, V.; Muchtar, E.; Kariv, G.; Robenshtok, E.; Leibovici, L. Systematic review and meta-analysis of the efficacy of appropriate empiric antibiotic therapy for sepsis. Antimicrob. Agents Chemother. 2010, 54, 4851–4863. [Google Scholar] [CrossRef]
- Kadri, S.S.; Lai, Y.L.; Warner, S.; Strich, J.R.; Babiker, A.; Ricotta, E.E.; Demirkale, C.Y.; Dekker, J.P.; Palmore, T.N.; Rhee, C.; et al. Inappropriate empirical antibiotic therapy for bloodstream infections based on discordant in-vitro susceptibilities: A retrospective cohort analysis of prevalence, predictors, and mortality risk in US hospitals. Lancet Infect. Dis. 2020, 21, 241–251. [Google Scholar] [CrossRef]
- Kumar, A.; Roberts, D.; Wood, K.E.; Light, B.; Parrillo, J.E.; Sharma, S.; Suppes, R.; Feinstein, D.; Zanotti, S.; Taiberg, L.; et al. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit. Care Med. 2006, 34, 1589–1596. [Google Scholar] [CrossRef]
- Kim, T.; Lee, E.J.; Park, S.Y.; Yu, S.N.; Lee, Y.M.; Park, K.H.; Park, S.Y.; Jeon, M.H.; Choo, E.J.; Kim, T.H.; et al. Natural prognosis of carbapenem-resistant Acinetobacter baumannii bacteremia in patients who did not receive appropriate antibiotic treatment: A retrospective multicenter study in Korea. Medicine 2018, 97, e12984. [Google Scholar] [CrossRef]
- Kim, T.; Park, K.H.; Yu, S.N.; Park, S.Y.; Park, S.Y.; Lee, Y.M.; Jeon, M.H.; Choo, E.J.; Kim, T.H.; Lee, M.S.; 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. 2019, 34, e256. [Google Scholar] [CrossRef] [PubMed]
- Toh, B.E.; Paterson, D.L.; Kamolvit, W.; Zowawi, H.; Kvaskoff, D.; Sidjabat, H.; Wailan, A.; Peleg, A.Y.; Huber, C.A. Species identification within Acinetobacter calcoaceticus-baumannii complex using MALDI-TOF MS. J. Microbiol. Methods 2015, 118, 128–132. [Google Scholar] [CrossRef] [PubMed]
- ISO 20776-1 (2006); Clinical Laboratory Testing and In Vitro Diagnostic Test Systems–Susceptibility Testing of Infectious Agents. ISO: Geneva, Switzerland, 2006.
- CDC/NHSN Infectious Diseases Definitions. Available online: https://www.cdc.gov/nhsn/pdfs/pscmanual/4psc_clabscurrent.pdf (accessed on 1 January 2025).
- Chen, S.J.; Chao, T.F.; Chiang, M.C.; Kuo, S.C.; Chen, L.Y.; Yin, T.; Chen, T.L.; Fung, C.P. Prediction of patient outcome from Acinetobacter baumannii bacteremia with Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation (APACHE) II scores. Intern. Med. 2011, 50, 871–877. [Google Scholar] [CrossRef] [PubMed]
- Falagas, M.E.; Kasiakou, S.K.; Rafailidis, P.I.; Zouglakis, G.; Morfou, P. Comparison of mortality of patients with Acinetobacter baumannii bacteraemia receiving appropriate and inappropriate empirical therapy. J. Antimicrob. Chemother. 2006, 57, 1251–1254. [Google Scholar] [CrossRef]
- Tamma, P.D.; Heil, E.L.; Justo, J.A.; Mathers, A.J.; Satlin, M.J.; Bonomo, R.A. Infectious Diseases Society of America 2024 Guidance on the Treatment of Antimicrobial-Resistant Gram-Negative Infections. Clin. Infect. Dis. 2024, ciae403. [Google Scholar] [CrossRef] [PubMed]
- Qiao, F.; Huang, W.; Gao, S.; Cai, L.; Zhu, S.; Wei, L.; Kang, Y.; Tao, C.; Zong, Z. Risk factor for intestinal carriage of carbapenem-resistant Acinetobacter baumannii and the impact on subsequent infection among patients in an intensive care unit: An observational study. BMJ Open 2020, 10, e035893. [Google Scholar] [CrossRef]
- Karakonstantis, S.; Ioannou, P.; Kofteridis, D.P. Are cefiderocol or sulbactam/durlobactam better than alternative best available treatment for infection by carbapenem-resistant A. baumannii? A systematic literature review. Infection 2025. [Google Scholar] [CrossRef] [PubMed]
Concordant Treatment (N = 122) | Discordant Treatment (N = 291) | p-Value | |
---|---|---|---|
Baseline characteristics | |||
Age (years), median (IQR) | 69 (62–78) | 71 (62–81) | 0.1 |
Age ≥ 65 years, n (%) | 82 (67%) | 200 (69%) | 0.8 |
Female, n (%) | 49 (40%) | 119 (41%) | 0.9 |
CCI, median (IQR) | 4 (2–6) | 4 (3–7) | 0.07 |
CCI ≥ 3 points, n (%) | 89 (73%) | 236 (81%) | 0.08 |
Home residency, n (%) | 53 (43%) | 133 (46%) | 0.9 |
Body mass index (kg/m2), median (IQR) | 26 (23–30) | 26 (23–30) | 0.9 |
Prior hospitalization within 3 months, n (%) | 69 (57%) | 143 (49%) | 0.2 |
Ischemic heart disease, n (%) | 19 (16%) | 54 (19%) | 0.6 |
Congestive heart failure, n (%) | 26 (21%) | 64 (22%) | 1 |
Diabetes mellitus, n (%) | 28 (23%) | 77 (26%) | 0.5 |
Chronic kidney disease, n (%) | 3 (2%) | 8 (3%) | 1 |
Solid tumor, n (%) | 20 (16%) | 51 (18%) | 0.9 |
Hematological malignancy, n (%) | 13 (11%) | 27 (9%) | 0.7 |
Bone marrow transplantation, n (%) | 6 (5%) | 6 (2%) | 0.2 |
Solid organ transplantation, n (%) | 11 (9%) | 12 (4%) | 0.06 |
Characteristics at bacteremia onset | |||
SOFA score, median (IQR) | 4 (2–5) | 4 (3–7) | 0.2 |
SOFA score ≥ 5 points, n (%) | 14 (11%) | 32 (11%) | 0.8 |
Mechanical ventilation, n (%) | 63 (52%) | 115 (40%) | 0.03 |
Central venous catheter, n (%) | 67 (55%) | 152 (52%) | 0.7 |
CRAB or CRE carriage, n (%) | 20 (16%) | 26 (9%) | 0.06 |
Late bacteremia onset (≥7 days of admission), n (%) | 82 (67%) | 182 (63%) | 0.4 |
White blood cell count (×103 cells/µL), median (IQR) | 10 (6–16) | 9 (6–15) | 0.5 |
Creatinine level (mg/dL), median (IQR) | 1.2 (0.7–1.9) | 1.2 (0.8–2) | 0.3 |
Albumin level (g/dL), median (IQR) | 3 (2.6–3.5) | 3 (2.5–3.5) | 0.9 |
Albumin level ≤ 3 g/dL, n (%) | 62 (51%) | 159 (55%) | 0.6 |
Bacteremia source | |||
Pneumonia, n (%) | 69 (57%) | 127 (44%) | 0.1 |
Urinary tract, n (%) | 4 (3%) | 8 (3%) | 0.1 |
CLABSI, n (%) | 10 (8%) | 18 (6%) | 0.1 |
Intraabdominal, n (%) | 3 (2%) | 10 (3%) | 0.1 |
Surgical site infection, n (%) | 2 (2%) | 14 (5%) | 0.1 |
Primary bacteremia, n (%) | 34 (28%) | 114 (39%) | 0.1 |
Outcome | |||
30 days mortality, n (%) | 64 (52%) | 196 (67%) | 0.04 |
Variable | Adjusted OR (95% CI) | p-Value |
---|---|---|
Age ≥ 65 vs. <65 years | 1.3 (0.7–2.5) | 0.4 |
Mechanical ventilation at time of bacteremia Yes vs. No | 1.9 (1.1–3.1) | 0.02 |
Late bacteremia presentation (≥7 days) vs. earlier presentation (<7 days) | 1.1 (0.6–1.9) | 0.8 |
CCI ≥3 vs. <3 points | 2.7 (1.3–5.5) | <0.01 |
Rectal carriage of CRAB or CRE Yes vs. No | 1.9 (1.02–3.8) | 0.04 |
Prior hospitalization within 3 months Yes vs. No | 1.5 (0.9–2.6) | 0.1 |
Variable | Survived (N = 153) | Deceased (N = 260) | p-Value |
---|---|---|---|
Baseline characteristics | |||
Age (years), median (IQR) | 67 (51–76) | 73 (65–81) | <0.01 |
Age ≥ 65 years, n (%) | 82 (54%) | 200 (78%) | <0.01 |
Female gender, n (%) | 57 (37%) | 111 (43%) | 0.3 |
CCI, median (IQR) | 4 (2–7) | 5 (3–7) | 0.05 |
CCI ≥ 3 points, n (%) | 106 (69%) | 219 (84%) | <0.01 |
Body mass index (kg/m2), median (IQR) | 25 (23–29) | 26 (23–30) | 0.8 |
Home residency, n (%) | 65 (42%) | 121 (47%) | 0.4 |
Prior hospitalization within 3 months, n (%) | 76 (50%) | 136 (52%) | 0.6 |
Ischemic heart disease, n (%) | 22 (14%) | 51 (20%) | 0.2 |
Congestive heart failure, n (%) | 20 (13%) | 70 (27%) | <0.01 |
Diabetes mellitus, n (%) | 31 (20%) | 74 (28%) | 0.07 |
Chronic kidney disease, n (%) | 6 (4%) | 5 (2%) | 0.2 |
Solid tumor, n (%) | 30 (20%) | 41 (16%) | 0.3 |
Hematological cancer, n (%) | 10 (7%) | 30 (12%) | 0.1 |
Bone marrow transplantation, n (%) | 2 (1%) | 10 (4%) | 0.2 |
Solid organ transplantation, n (%) | 12 (8%) | 11 (4%) | 0.1 |
Clinical characteristics at time of bacteremia onset | |||
SOFA score, median (IQR) | 3 (2–5) | 5 (4–8) | <0.01 |
SOFA score ≥ 5 points, n (%) | 11 (7%) | 35 (13%) | <0.01 |
Mechanical ventilation, n (%) | 54 (35%) | 124 (48%) | 0.01 |
Central venous catheter, n (%) | 85 (56%) | 134 (52%) | 0.4 |
Late bacteremia onset (≥7 days of admission), n (%) | 88 (58%) | 176 (68%) | 0.05 |
CRAB or CRE carriage, n (%) | 19 (12%) | 27 (10%) | 0.5 |
CRAB pneumonia, n (%) | 74 (48%) | 122 (47%) | 0.7 |
Primary bacteremia, n (%) | 47 (31%) | 101 (39) | 0.1 |
White blood cell count (×103 cells/µL), median (IQR) | 10 (7–16) | 9 (6–14) | 0.5 |
Creatinine level (mg/dL), median (IQR) | 0.9 (0.7–1.7) | 1.4 (0.8–2) | 0.3 |
Albumin level (g/dL), median (IQR) | 3.1 (2.6–3.5) | 3 (2.5–3.5) | 0.2 |
Albumin level ≤ 3 g/dL, n (%) | 68 (44%) | 118 (45%) | 0.7 |
Early concordant treatment *, n (%) | 58 (38%) | 64 (25%) | 0.005 |
Variable | Adjusted OR (95% CI) | p-Value |
---|---|---|
Early concordant treatment * vs. discordant treatment | 0.36 (0.13–1.02) | 0.053 |
Age ≥ 65 vs. <65 years | 4 (1.1–17) | 0.04 |
CCI ≥ 3 vs. <3 points | 2.5 (0.5–14.3) | 0.3 |
Mechanical ventilation Yes vs. No | 1.6 (0.57–4.6) | 0.4 |
Congestive heart failure Yes vs. No | 1.2 (0.3–5) | 0.8 |
Late bacteremia presentation (≥7 days) vs. earlier presentation (<7 days) | 3.33 (0.77–16.66) | 0.09 |
SOFA score ≥ 5 vs. <5 | 7.14 (2–25) | <0.01 |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Atamna, A.; Wazana, Y.; Ben-Zvi, H.; Shochat, T.; Bishara, J.; Nutman, A. Does Early Concordant Antibiotic Treatment Reduce Mortality Among Hospitalized Patients with Carbapenem-Resistant Acinetobacter baumannii Bacteremia? A Retrospective Cohort Study. J. Clin. Med. 2025, 14, 6485. https://doi.org/10.3390/jcm14186485
Atamna A, Wazana Y, Ben-Zvi H, Shochat T, Bishara J, Nutman A. Does Early Concordant Antibiotic Treatment Reduce Mortality Among Hospitalized Patients with Carbapenem-Resistant Acinetobacter baumannii Bacteremia? A Retrospective Cohort Study. Journal of Clinical Medicine. 2025; 14(18):6485. https://doi.org/10.3390/jcm14186485
Chicago/Turabian StyleAtamna, Alaa, Yaara Wazana, Haim Ben-Zvi, Tzippy Shochat, Jihad Bishara, and Amir Nutman. 2025. "Does Early Concordant Antibiotic Treatment Reduce Mortality Among Hospitalized Patients with Carbapenem-Resistant Acinetobacter baumannii Bacteremia? A Retrospective Cohort Study" Journal of Clinical Medicine 14, no. 18: 6485. https://doi.org/10.3390/jcm14186485
APA StyleAtamna, A., Wazana, Y., Ben-Zvi, H., Shochat, T., Bishara, J., & Nutman, A. (2025). Does Early Concordant Antibiotic Treatment Reduce Mortality Among Hospitalized Patients with Carbapenem-Resistant Acinetobacter baumannii Bacteremia? A Retrospective Cohort Study. Journal of Clinical Medicine, 14(18), 6485. https://doi.org/10.3390/jcm14186485