Abstract

Background: This study aims to investigate the infection patterns and antibiotic utilization in critically ill patients receiving extracorporeal membrane oxygenation treatment.

Methods: Between January 2019 and January 2024, a total of 165 patients (109 males, 56 females; median age: 58 years; range, 48 to 67 years) who were hospitalized for at least 24 h and underwent extracorporeal membrane oxygenation, and received ?1 antibiotic treatment in the cardiovascular intensive care unit were retrospectively analyzed. Microbiological culture results, pathogen resistance patterns, antibiotics used, and their doses during extracorporeal membrane oxygenation were evaluated based on the literature and the Sanford Antimicrobial Guide database.

Results: The median number of days spent on extracorporeal membrane oxygenation was 4 (range, 2 to 7) days. Klebsiella pneumoniae (28.8%) and Acinetobacter baumannii (21.1%) were frequently detected in culture results. The median number and duration of antibiotics were 2 (range, 1 to 3) and 2 (range, 1 to 4) days, respectively. Cephalosporins (39%) and penicillins (30%) were the most commonly used antibiotics. At least one antibiotic dose inappropriateness was detected in 56 (33.9%) patients. A total of 366 antibiotic administrations included 73 (19.9%) dose inappropriateness. Continuous renal replacement therapy, sepsis/septic shock, and extracorporeal membrane oxygenation duration >4 days were identified as risk factors increasing antibiotic inappropriateness (p<0.05).

Conclusion: Our study results indicate that patients receiving extracorporeal membrane oxygenation frequently experience antibiotic resistance and the proliferation of Gram-negative bacteria. In our study, antibiotic dosing was inappropriate in approximately one-third of patients receiving extracorporeal membrane oxygenation. Based on these findings, adherence to the literature should be increased while selecting antibiotics and doses for patients.

Extracorporeal membrane oxygenation (ECMO) is known to significantly alter the already complex physiology and, thus, drug pharmacokinetics in critically ill patients.[1-3] Recently, significant advances have been made in elucidating antibiotic pharmacokinetics and dosing requirements during ECMO support in adult critically ill patients, and more clinical pharmacokinetic data have emerged to determine antibiotic dosing in these patients.[4-6]

Previous pharmacokinetic data primarily derived from pediatric populations are not fully applicable to adult critically ill patients. Recent studies focusing on adults provide more relevant insights into ECMO-specific drug dosing challenges.[7] An improved understanding of pharmacokinetic changes in critically ill patients on ECMO is essential to ensure optimal antibiotic dosing in these complex cases. Furthermore, therapeutic drug monitoring (TDM) is a vital recommendation to manage antibiotic dosing in this patient population.[8] Reviews of studies on antimicrobial dosing in patients on ECMO have concluded that while dosing recommendations are available for some drugs, there are few or no data for other vital anti-infectives.[2,7,8] A study examining the drug administration profile in patients undergoing ECMO showed that antimicrobials were among the most frequently administered drugs.

In the present study, we aimed to investigate the infection patterns and antibiotic utilization in critically ill patients receiving ECMO treatment and to evaluate the microbiological cultures during the period when ECMO was applied to patients, the antimicrobial susceptibility of the pathogens, the type of antibiotics used, their classification, and the appropriateness of the dose.

Methods

This single-center, retrospective study was conducted at Dr. Siyami Ersek Thoracic and Cardiovascular Surgery Training and Research Hospital, Intensive Care Unit between January 1st, 2019 and January 1^st, 2024. Patients aged ≥18 years who were hospitalized in the cardiovascular intensive care unit (CICU) and had a hospitalization longer than 24 h, on ECMO, and received at least one antibiotic treatment were included in the study. Peripheral access was not used in this cohort. All patients received venoarterial (VA) ECMO as postcardiotomy support following cardiac surgery. No cases were initiated for primary respiratory failure or ARDS. No patients in the study period received venovenous (VV) ECMO. Patients with missing data and those whose data could not be reached were excluded from the study. Microbiological culture growth during ECMO, antimicrobial susceptibility of pathogens, antibiotics used, and doses of antibiotics were retrospectively examined in the patients included in the study. Initially, a total of 197 patients were evaluated, of whom 165 met the inclusion criteria after excluding 12 patients with no antibiotic use and 20 patients with missing data. Finally, a total of 165 patients (109 males, 56 females; median age: 58 years; range, 48 to 67 years) were included. The study flowchart is shown in Figure 1. Written informed consent was obtained from each patient. The study protocol was approved by the Altınbaş University Health Sciences Scientific Research Ethics Committee (Date: 12.07.2024, No: 12.07.2024/2). The study was conducted in accordance with the principles of the Declaration of Helsinki.

Figure 1. Study flowchart.

Data collection and assessment
Clinical data such as patients' age, sex, demographic data, comorbidities, renal and hepatic function status, length of hospital stay, mortality status, acute phase reactants and other laboratory values, culture results, TDM levels, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, characteristics of ECMO treatment, ECMO modalities, ECMO start and end dates, antibiotics used during ECMO and dosage were obtained from the hospital information management system and patient files.

The initiation of antibiotic therapy during ECMO was based on clinical judgment by the attending intensivist or cardiovascular surgeon. Infectious Diseases consultation was not routinely involved in initial decision-making. Given the retrospective design, the specific rationale for empirical initiation was not always recorded.

Multiple sources were used to evaluate the doses of antibiotics used during ECMO.[1,3,4,7-10] The Sanford Antimicrobial Guide database was used to assess the dose adjustments of antibiotics used by patients who received continuous renal replacement therapy (CRRT) or had an estimated glomerular filtration (eGFR) value of <60 mL/min/1.73 m² during the ECMO process. Antibiotic doses were classified as "low" if they were lower than the specified sources, "normal" if they were within the recommended range, and "high" if they were higher than the recommended doses (Table 1). Accordingly, antibiotic use that is outside the normal recommended dose range was considered an "inappropriate dose". The appropriateness of antibiotic dosing, which ideally should be evaluated using TDM, was assessed based on established guidelines due to the unavailability of TDM data.

Table 1. Dosage recommendations for antibiotics in patients under extracorporeal membrane oxygenation according to guidelines

Patient culture results and pathogen growth were classified based on both resistance profiles and gram staining characteristics. Microbiological culture samples included deep tracheal aspirates, wound sites, and blood. Resistance thresholds were determined in accordance with European Committee on Antimicrobial Susceptibility Testing (EUCAST) standards. Antibiotics administered during ECMO were assessed for antimicrobial susceptibility using the EUCAST clinical breakpoints for resistance (Table 2).[11]

Table 2. European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints for antibiotics

The identification of pathogens and classification of resistance patterns were based solely on the susceptibility results (i.e., susceptible, intermediate, or resistant) reported in routine antibiogram tests. No additional microbiological or molecular methods were performed by the investigators.

Statistical analysis
The study sample size was calculated based on the number of patients admitted to the CICU who received ECMO treatment within one year. Using data indicating that approximately 50 patients underwent ECMO treatment annually, it was estimated that a minimum of 75 patients would be required for a five-year retrospective evaluation to achieve statistical significance with an alpha level of 0.05 and 95% power. However, given the rarity of the population under study and the retrospective nature of the research, all patients who met the inclusion criteria during the five-year period were included to maximize the robustness of the findings. This approach ensured a comprehensive evaluation of the study population.

Statistical analysis was performed using the IBM SPSS version 29.0 software (IBM Corp., Armonk, NY, USA). Continuous data were expressed in mean ± standard deviation (SD) or median and interquartile range (IQR), while categorical data were expressed in number and frequency. The Kolmogorov-Smirnov test was used to determine whether continuous variables followed a normal distribution. The Mann-Whitney U test was used to compare patients with and without dose inappropriateness in terms of ECMO duration, age, number of comorbidities, total length of hospital stay, APACHE II score, and mechanical ventilation (MV) duration. Categorical data were compared using the chi-square tests. Risk factors associated with inappropriate antibiotic use were compared among categorical data. Continuous variables were categorized into median-based groups for analysis. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated from 2×2 contingency tables using chi-square analysis for categorical variables. Multivariate regression was not performed due to the limited sample size and the exploratory nature of the study. A p value of <0.05 was considered statistically significant.

Results

All patients received VA ECMO. The primary indications for ECMO were coronary artery bypass grafting (66.1%) and Benthall procedure (7.2%). A total of 52 patients (31.5%) received CRRT. The median duration of ECMO support was 4 (range, 2 to 7) days (Table 3).

Table 3. Patients' sociodemographic and clinical information

Among the 165 patients, 52 (31.5%) had positive microbiological cultures. Sample sources included deep tracheal aspirates (76.6%), wound sites (16.6%), and blood cultures (6.8%). Resistance to administered antibiotics was identified in 32 (19.4%) patients. Gram-negative bacteria constituted 82.6% of isolates, with Klebsiella pneumoniae (28.8%) and Acinetobacter baumannii ( 21.1%) being the most frequent. Enterobacter cloacae w as a lso n otable (11.5%). Gram-positive cocci accounted for 17.4% of isolates (Figure 2).

Figure 2. Distribution of microbiological isolates and their resistance/sensitivity profiles (n=52).

The median number of antibiotics used per patient was 2 (range, 1 to 3), and the median duration of antibiotic therapy was 2 (range, 1 to 4) days. Antibiotics were prescribed empirically in 94% of cases and guided by culture in 6%. Cephalosporins (39%) and penicillins (30%) were the most frequently used antibiotic classes, followed by carbapenems (7.3%) and other antibacterials (23.7%).

Inappropriate antibiotic dosing was identified in 56 patients (33.9%). Out of 366 total antibiotic administrations, 73 (19.9%) were classified as having inappropriate dosing. As shown in Figure 3, most antibiotics were administered at recommended (normal) doses, with cefazoline and ampicillin-sulbactam having the highest number of appropriate administrations. However, dose inappropriateness, both underdosing and overdosing, was more frequently observed with agents such as vancomycin, meropenem, and daptomycin.

Figure 3. Appropriateness of antibiotic dosing by antibiotic class.

There were no significant associations between antibiotic inappropriateness and variables such as age, sex, total length of hospital stay, number of comorbidities, duration of MV, discharge status, or microbial susceptibility. However, a higher number of antibiotics was significantly associated with inappropriateness (median: 3 vs. 1 , p <0.001). T he presence of CRRT, sepsis/septic shock, and ECMO duration >4 days were all significant risk factors (p<0.05), with OR and CI details (Table 4).

Table 4. Analysis of risk factors for antibiotic dose inappropriateness

Among patients with positive microbiological cultures (n=52), the mortality rate was 89.1%, compared to 80.0% in patients without culture growth (n=113). However, this difference was not statistically significant (p=0.143).

Discussion

In the present study, we investigated the infection patterns and antibiotic utilization in critically ill patients receiving ECMO treatment. Our study results demonstrated that Gram-negative bacteria, particularly Klebsiella pneumoniae and Acinetobacter baumannii, predominated among the isolated pathogens, and that inappropriate antibiotic dosing was observed in nearly one-third of ECMO patients, underscoring the complexity of antimicrobial management in this population. A high prevalence of multidrug-resistant (MDR) pathogens, particularly Gram-negative bacteria, underscores the need for individualized antimicrobial strategies. The findings align with previous studies emphasizing the importance of culture-guided therapy and TDM in optimizing antibiotic use.[9]

The ECMO-specific and critical illness-related factors, such as fluid resuscitation, hepatic and renal failure, and hypoalbuminemia, further complicate antibiotic pharmacokinetics and pharmacodynamics.[12-14] However, evidence-based guidelines for adequate antibiotic dosing in ECMO patients still remain limited.[7] In the center where this study was conducted, a population similar to those described in the literature was studied. Since TDM was not performed in this center and dose adjustments were made only according to the Sanford Antimicrobial Guide database, the appropriateness of the dose was checked using various sources in the literature.

Critically ill patients on ECMO are at an increased risk for nosocomial infections, which are associated with higher mortality.[15] In this study, Gram-negative bacilli, particularly Klebsiella pneumoniae and Acinetobacter baumannii, were the most frequently isolated pathogens. Similar findings were reported by Kühn et al.[16] where Gram-negative bacteria accounted for the majority of pathogens. Infections caused by MDR pathogens remain a severe complication in ECMO patients, requiring antibiotics tailored to pathogen susceptibility. Several studies have shown higher resistance rates to common antibiotics, such as carbapenems and β-lactams, in ECMO patients, necessitating alternative therapeutic strategies.[10,17]

Although carbapenems and cephalosporins are commonly recommended against MDR-Gram-negative bacteria, resistance to these agents has risen in recent years. To illustrate, Acinetobacter baumannii h as d emonstrated a resistance rate exceeding 80% to carbapenems.[18] This study revealed high rates of antibiotic resistance but noted that many patients did not receive antibiotics appropriate for the resistant pathogens detected. Therefore, selecting antibiotics based on pathogen-specific susceptibility profiles is essential for optimizing outcomes in ECMO patients.

Most antibiotics in this study were prescribed empirically (94%), with only 6% guided by culture results. This practice aligns with ICU standards where rapid empirical therapy is crucial for managing severe infections.[16] However, prolonged empirical antibiotic use without timely culture-based modifications risks promoting resistance. To date, few studies have addressed the antibiotic profiles commonly used in ECMO patients. While drugs like meropenem and piperacillin-tazobactam are frequently evaluated, data on other agents remain limited.[3] Notably, subtherapeutic levels of piperacillin and meropenem have been documented in ECMO patients.[16] This highlights the need for judicious antibiotic use and robust antimicrobial stewardship programs to minimize resistance and optimize dosing.

The low rate of culture-guided therapy (6%) highlights a heavy reliance on empirical antibiotic use in this cohort. This may reflect the urgency of care in postcardiotomy ECMO patients and logistical delays in obtaining microbiological results. Nonetheless, it underscores the need for improved microbiological sampling, faster diagnostic turnaround, and early infectious diseases consultation to support antimicrobial stewardship practices.

Dosing inappropriateness was observed in 33.9% of patients, with 19.9% of antibiotic administrations falling outside recommended guidelines. Subtherapeutic levels of hydrophilic antibiotics, such as beta-lactams, are common due to ECMO-induced changes in drug pharmacokinetics.[3,5,13] These findings emphasize the necessity of personalized dosing strategies guided by patient-specific factors, including ECMO modality, organ function, and concurrent medications. Implementing TDM, when feasible, may help achieve optimal drug exposure and minimize underdosing or toxicity.[13]

In the present study, CRRT, sepsis/septic shock, and prolonged ECMO duration were identified as significant risk factors for antibiotic dosing errors. Approximately one-third of the patients in this study required CRRT, which complicates dosing further.[19] Concurrent ECMO and CRRT often diminish the accuracy of dosing equations, such as eGFR and Cockcroft-Gault, increasing the need for TDM.[20] Sepsis-related factors, including fluid shifts and altered organ perfusion, further disrupt antibiotic pharmacokinetics, making precise dosing even more challenging.[21,22]

The ECMO circuit itself may sequester drugs, particularly lipophilic and protein-bound antibiotics, leading to subtherapeutic levels. This phenomenon necessitates dose adjustments or more frequent monitoring to ensure effective therapy.[23] Prolonged ECMO duration has been associated with increased nosocomial infections and antibiotic resistance, emphasizing the need for careful management in these patients.[18,24]

It is of utmost importance to note that all patients received VA ECMO, which may have different implications for infection risk and antibiotic p harmacokinetics compared to VV ECMO. However, our study did not aim to compare ECMO modalities.

The relatively low rate of culture-confirmed infections (31.5%) may be attributed to prior antibiotic use, low culture sensitivity, or insufficient sampling, which are common challenges in critically ill ECMO patients.

Although culture-positive patients showed a numerically higher mortality rate (89.1% vs. 80.0%), this difference did not reach statistical significance. This may reflect the overall severity of illness in the cohort rather than the presence of documented infection alone.

Nonetheless, the present study has certain limitations. First, its retrospective design prevents causal inference, and the lack of TDM may reduce the precision of dosing evaluations. Second, infections were only counted when microbiologically confirmed, which might underestimate the true clinical infection rate due to potential culture negativity. Third, the study was conducted at a single center, limiting the generalizability of the findings, and relied on data recorded in the hospital information system, which may be subject to documentation bias.

However, this study has notable strengths. It is one of the largest clinical cohorts evaluating antibiotic use during ECMO in adult patients. Unlike pharmacokinetic models, our real-world data provide valuable insight into current practice, revealing a high rate of dosing inappropriateness associated with CRRT and sepsis. The findings underline the urgent need for improved antimicrobial stewardship and individualized dosing strategies in this complex patient population.

Based on our findings, we suggest that in postcardiotomy VA ECMO patients, empirical broad-spectrum antibiotic coverage should be guided by the unit's local resistance patterns, particularly targeting Gram-negative organisms such as Klebsiella pneumoniae and Acinetobacter baumannii. Early Infectious Diseases consultation may be beneficial in refining antibiotic selection, particularly in patients requiring prolonged ECMO or those with CRRT, as these were associated with higher rates of dose inappropriateness. Institutional implementation of antimicrobial stewardship protocols in CICUs may further support appropriate antibiotic use in this high-risk population.

In conclusion, our study underscores the significant challenges of managing infections and antibiotic dosing in extracorporeal membrane oxygenation patients. High rates of antibiotic resistance and dosing errors necessitate improved adherence to antimicrobial guidelines and individualized strategies. Key risk factors, such as renal replacement therapy, sepsis, and extracorporeal membrane oxygenation duration, should inform future interventions. Prospective studies incorporating therapeutic drug monitoring and culture-guided therapy are needed to refine antimicrobial protocols for extracorporeal membrane oxygenation patients. While this retrospective design limits causal inference, the study was not intended to establish causality but to describe infection patterns, antibiotic practices, and potential risk factors. We believe that these findings would inform future prospective or interventional studies in extracorporeal membrane oxygenation patients.

Data Sharing Statement: The data that support the findings of this study are available from the corresponding author upon reasonable request.

Author Contributions: Idea/concept, data collection: Y.E.A., A.G.K.K.; Writing: Y.E.A., A.G.K.K., N.A.; Statistical analysis: Y.E.A., N.A.; Checking-writing: Y.E.A., A.G.K.K., N.A., N.Y.

Conflict of Interest: The authors declared no conflicts of interest with respect to the authorship and/or publication of this article.

Funding: The authors received no financial support for the research and/or authorship of this article.

References

1) Shekar K, Fraser JF, Smith MT, Roberts JA. Pharmacokinetic changes in patients receiving extracorporeal membrane oxygenation. J Crit Care 2012;27:741.e9-18. doi: 10.1016/j. jcrc.2012.02.013.

2) Sherwin J, Heath T, Watt K. Pharmacokinetics and dosing of anti-infective drugs in patients on extracorporeal membrane oxygenation: A review of the current literature. Clin Ther 2016;38:1976-94. doi: 10.1016/j. clinthera.2016.07.169.

3) Cheng V, Abdul-Aziz MH, Roberts JA, Shekar K. Optimising drug dosing in patients receiving extracorporeal membrane oxygenation. J Thorac Dis 2018;10:S629-41. doi: 10.21037/ jtd.2017.09.154.

4) Ruiz-Ramos J, Gras-Martín L, Ramírez P. Antimicrobial pharmacokinetics and pharmacodynamics in critical care: Adjusting the dose in extracorporeal circulation and to prevent the genesis of multiresistant bacteria. Antibiotics (Basel) 2023;12:475. doi: 10.3390/antibiotics12030475.

5) Spriet I, De Waele JJ. Adequate antimicrobial dosing in critically ill patients receiving extracorporeal membrane oxygenation: Where to go from here? Am J Respir Crit Care Med 2023;207:649-51. doi: 10.1164/rccm.202210-2000ED.

6) Shekar K, Abdul-Aziz MH, Cheng V, Burrows F, Buscher H, Cho YJ, et al. Antimicrobial exposures in critically ill patients receiving extracorporeal membrane oxygenation. Am J Respir Crit Care Med 2023;207:704-20. doi: 10.1164/ rccm.202207-1393OC.

7) Kim M, Mahmood M, Estes LL, Wilson JW, Martin NJ, Marcus JE, et al. A narrative review on antimicrobial dosing in adult critically ill patients on extracorporeal membrane oxygenation. Crit Care 2024;28:326. doi: 10.1186/s13054-024-05101-z.

8) Abdul-Aziz MH, Roberts JA. Antibiotic dosing during extracorporeal membrane oxygenation: Does the system matter? Curr Opin Anaesthesiol 2020;33:71-82. doi: 10.1097/ ACO.0000000000000810.

9) Duceppe MA, Kanji S, Do AT, Ruo N, Cavayas YA, Albert M, et al. Pharmacokinetics of commonly used antimicrobials in critically ill adults during extracorporeal membrane oxygenation: A systematic review. Drugs 2021;81:1307-29. doi: 10.1007/s40265-021-01557-3.

10) Karaiskos I, Lagou S, Pontikis K, Rapti V, Poulakou G. The "Old" and the "New" antibiotics for MDR gram-negative pathogens: For whom, when, and how. Front Public Health 2019;7:151. doi: 10.3389/fpubh.2019.00151.

11) Eucast: Clinical breakpoints and dosing of antibiotics. Available at: https://www.eucast.org/clinical_breakpoints [Accessed: 30.12.2024].

12) Gomez F, Veita J, Laudanski K. Antibiotics and ECMO in the adult population-persistent challenges and practical guides. Antibiotics (Basel) 2022;11:338. doi: 10.3390/ antibiotics11030338.

13) Hagel S, Fiedler S, Hohn A, Brinkmann A, Frey OR, Hoyer H, et al. Therapeutic drug monitoring-based dose optimisation of piperacillin/tazobactam to improve outcome in patients with sepsis (TARGET): A prospective, multicentre, randomised controlled trial. Trials 2019;20:330. doi:10.1186/s13063-019-3437-x.

14) Worku B, Khin S, Gaudino M, Gambardella I, Iannacone E, Ebrahimi H, et al. Renal replacement therapy in patients on extracorporeal membrane oxygenation support: Who and how. Int J Artif Organs 2021;44:531-8. doi:10.1177/0391398820980451.

15) Gao X, Wang W. The etiological and drug resistance characteristics of multidrug-resistant pathogens in patients requiring extracorporeal membrane oxygenation: A retrospective cohort study. Infect Drug Resist 2023;16:4929-41. doi: 10.2147/IDR.S421413.

16) Kühn D, Metz C, Seiler F, Wehrfritz H, Roth S, Alqudrah M, et al. Antibiotic therapeutic drug monitoring in intensive care patients treated with different modalities of Extracorporeal Membrane Oxygenation (ECMO) and renal replacement therapy: A prospective, observational singlecenter study. Crit Care 2020;24:664. doi: 10.1186/s13054- 020-03397-1.

17) Nguyen M, Joshi SG. Carbapenem resistance in Acinetobacter baumannii, and their importance in hospitalacquired infections: A scientific review. J Appl Microbiol 2021;131:2715-38. doi: 10.1111/jam.15130.

18) Li ZJ, Zhang DF, Zhang WH. Analysis of nosocomial ınfection and risk factors in patients with ECMO treatment. Infect Drug Resist 2021;14:2403-10. doi: 10.2147/IDR. S306209.

19) Shekar K, Fraser JF, Taccone FS, Welch S, Wallis SC, Mullany DV, et al. The combined effects of extracorporeal membrane oxygenation and renal replacement therapy on meropenem pharmacokinetics: A matched cohort study. Crit Care 2014;18:565. doi: 10.1186/s13054-014-0565-2.

20) Hoff BM, Maker JH, Dager WE, Heintz BH. Antibiotic dosing for critically ill adult patients receiving intermittent hemodialysis, prolonged intermittent renal replacement therapy, and continuous renal replacement therapy: An update. Ann Pharmacother 2020;54:43-55. doi:10.1177/1060028019865873.

21) Ferrer R, Martin-Loeches I, Phillips G, Osborn TM, Townsend S, Dellinger RP, et al. Empiric antibiotic treatment reduces mortality in severe sepsis and septic shock from the first hour: Results from a guideline-based performance improvement program. Crit Care Med 2014;42:1749-55. doi:10.1097/CCM.0000000000000330.

22) Taccone FS, Laterre PF, Dugernier T, Spapen H, Delattre I, Wittebole X, et al. Insufficient ?-lactam concentrations in the early phase of severe sepsis and septic shock. Crit Care 2010;14:R126. doi: 10.1186/cc9091.

23) Park J, Shin DA, Lee S, Cho YJ, Jheon S, Lee JC, et al. Investigation of key circuit constituents affecting drug sequestration during extracorporeal membrane oxygenation treatment. ASAIO J 2017;63:293-8. doi: 10.1097/ MAT.0000000000000489.

24) Liu Y, Wang Q, Zhao C, Chen H, Li H, Wang H, 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 2020;69:949-59. doi: 10.1099/jmm.0.001222.