Acinetobacter baumannii is a significant opportunistic pathogen widely present in medical environments, capable of causing severe nosocomial infections (1). Prolonged and excessive use of carbapenem antibiotics, such as imipenem and meropenem, exposes bacteria to high drug concentrations, leading to the emergence of drug-resistant strains. The transmission of carbapenem-resistant Acinetobacter baumannii (CRAB) in healthcare settings is facilitated by the spread of resistance genes between bacteria and inadequate infection control measures in hospitals (2, 3). The rates of resistance of Acinetobacter baumannii to meropenem and imipenem increased from 30.1 and 39.0% in 2005 to 71.5 and 72.3% in 2021, respectively, with the detection rate of CRAB gradually increased (4). Recent studies demonstrated that CRAB has the highest detection rate in the respiratory tract (60 ~ 87%), especially in ventilator-associated pneumonia (VAP) (5, 6).

VAP ranks among the most common nosocomial infections in the intensive care unit (ICU), contributing to increased mortality rates and healthcare expenditures, which were found to be associated with the delayed recognition and treatment of VAP due to drug-resistant A. baumannii (1, 7). Some studies have found that CRAB-VAP is not only closely associated with patients’ clinical outcomes (such as length of hospital stay and treatment costs) but also significantly correlated with patients’ prognosis (such as mortality rate and incidence of complications) (8, 9). Therefore, the treatment strategy for CRAB-VAP is particularly important.

In 2023, the Infectious Diseases Society of America (IDSA) guidelines recommended medications for treating CRAB, including ampicillin-sulbactam, polymyxins, and tetracycline derivatives. Tigecycline, as one of the few antibiotics effective against CRAB, was a crucial component of treatment regimens, especially when patients have concurrent renal insufficiency or when certain medications are unavailable (such as the intravenous formulation of minocycline, not marketed in China) (10–13). However, a study has shown that compared to other antimicrobial drugs, the use of tigecycline in treating CRAB-VAP increases the risk of patient mortality, leading to controversy over its efficacy and suggesting that it may not be suitable for treating CRAB-VAP (14). Therefore, investigating high-risk populations for tigecycline treatment failure in CRAB-VAP is imperative to select more suitable alternatives early in the treatment and reduce the likelihood of treatment failure.

Hence, this study conducted a multicenter retrospective study to evaluate the clinical characteristics and risk factors of CRAB-VAP patients who failed treatment with tigecycline and constructed a nomogram model of risk factors for treatment failure with a view to providing clinical diagnosis and treatment.

CRAB is widely found in medical environments and has a high tolerance, presenting a great challenge to healthcare around the world. In 2019, the Centers for Disease Control and Prevention listed CRAB as an emergency threat in reporting antibiotic resistance threats (23). Therefore, the therapeutic strategies for CRAB-VAP have attracted much attention (11, 24). The use of tigecycline as a broad-spectrum antibiotic in the treatment of CRAB-VAP has indeed sparked a debate. On the one hand, certain studies suggest its effectiveness for some CRAB-VAP patients, offering them a useful treatment option. However, on the other hand, some research also indicates poor outcomes with tigecycline therapy for CRAB-VAP, potentially leading to increased overall mortality rates (10). This study differs from previous research in that it does not compare tigecycline with other antibacterial drugs to observe its efficacy and safety in CRAB treatment. Instead, it introduces a novel therapeutic approach: selecting appropriate drugs based on patients’ clinical characteristics to offer a new perspective for CRAB treatment.

In this study, 189 patients were finally included, of which 106 patients were successfully treated, and the treatment of 83 patients failed. The CRAB-VAP failure rate caused by tigecycline treatment was high at 43.9%, which was consistent with the results of previous studies. Several risk factors had been linked to the failed treatment with CRAB-VAP, such as age, hypoproteinemia, and surgical intervention 14 days before treatment, which was homogeneous with this study’s results. As the patients get older, body function gradually degenerates, organ function and immunity also decline, and the compensatory ability to tolerate infection decreases, resulting in an increased risk of anti-infection treatment failure (25). Protein is one of the important components of the body, involved in the body’s metabolism and cell regeneration. Hypoproteinemia can lead to malnutrition in patients, which can affect the treatment of infections (26). In addition, tigecycline is a high-protein-binding drug, which can lead to an increase in free drugs in the body, an increase in drug clearance, reduced blood concentration, and then affect the anti-infection effect (27). Patients experience a local inflammatory response during surgical procedures to cut and manage trauma, and long-term surgical operations would also consume energy and nutrition, putting patients in a semi-healthy state and reducing the body’s ability to resist infection (28).

Furthermore, this study found that no. of microbial clearance was an independent risk factor for the failure of tigecycline treatment. CRAB is known to be extremely resistant, often presenting as multidrug resistance or pan-drug resistance (29). Current treatment options are very limited and cannot completely kill CRAB (30, 31). Therefore, current treatment regimens usually only use effective antimicrobial drugs to control the replication and growth of pathogens rather than completely remove them, and many clinical studies also take the disappearance of clinical infection manifestations as a clinical outcome. However, this study found that CRAB clearance might have an important impact on treatment outcomes (32). Patients who failed treatment with CRAB-VAP should choose bactericidal antimicrobial agents during treatment as a part of the treatment regimen.

In this study, it was unexpectedly found that a daily dose of 200 mg of tigecycline was an independent risk factor for treatment failure compared to a daily dose of 100 mg. In a study, it was demonstrated that for susceptible CRAB strains (MIC ≤0.5 mcg/ml), daily administration of 200 mg of tigecycline can increase the drug’s concentration in plasma and lungs. However, the article also indicates that as the MIC increases to MIC ≥1 mcg/ml, less than 10% of patients can achieve effective treatment (33). This highlights the significant impact of the MIC values of CRAB strains on treatment outcomes. The use of tigecycline in CRAB infections has led to a shift in its MIC values. Research indicates that from 2016 to 2021, the MIC of A. baumannii isolates against tigecycline increased from 1 mcg/ml to 2 mcg/ml, with a more significant increase in Asia (34). Elevated MIC levels pose a risk for tigecycline treatment failure. Studies suggest that when the MIC is greater than 2, this drug should not be selected for treating CRAB infection (35, 36). Monte Carlo simulation results demonstrate that with the standard tigecycline regimen (100 mg loading dose, 50 mg maintenance dose, 12 h), the probability of target attainment (PTA) is 72 and 11% when the MIC is 1 mcg/ml and 2 mcg/ml, respectively. However, doubling the dosage to 100 mg every 12 h increases the corresponding PTA values to 99 and 71% (37). Therefore, it is recommended to double the dosage when the tigecycline MIC against A. baumannii is 2 mcg/ml (22). The patients included in this study had MIC ≤1 mcg/ml and MIC = 2 mcg/ml. In clinical practice, patients with MIC = 2 mcg/ml are more likely to receive a daily dose of 200 mg. Consequently, a daily dose of 200 mg increases the risk of treatment failure and may be more relevant to the population using this dose, particularly those with large MIC values. Unfortunately, due to the relatively small number of patients with MIC ≤1 mcg/ml in this study, the relationship between MIC and treatment failure cannot be definitively clarified.

Additionally, this study showed that the timing of medication administration, combination therapy regimen, the severity of organ dysfunction, and the duration of drug therapy do not significantly affect treatment outcomes. Previous studies have indicated that combined antimicrobial therapy is recommended for CRAB infection, and long-term treatment can reduce the 30-day mortality rate (10, 38). However, this study indicated no significant differences in these factors between the two groups.

This study was characterized by the analysis of the effect of the patient dosing regimen on the failed treatment with CRAB-VAP, which was conducive to the reasonable selection of antimicrobial drugs for CRAB. This study had several limitations, which include a small sample size, a lack of information on laboratory test indicators, and the limitations of the study area. These factors may have biased the study. Future prospective studies need to address these limitations.

This study showed that age, yes. of hypoproteinemia, a daily dose of 200 mg, yes. of medication within 14 days prior to surgical intervention, and no. of microbial clearance were significant risk factors for the failed treatment with CRAB-VAP. Additionally, although this study did not demonstrate the relationship between MIC and treatment outcomes, MIC variation may significantly affect the outcome of tigecycline therapy. The AUC area showed this predictive nomogram had good discrimination performance. This prediction model can help doctors predict factors of failed treatment with CRAB-VAP, and correct or avoid risk factors in clinical treatment, but the results should be based on the clinical experience of doctors and other auxiliary examinations.

The original contributions presented in the study are included in the article/Supplementary material, further inquiries can be directed to the corresponding author.

The studies involving humans were approved by Ethics Committee of First Hospital of Shanxi Medical University. The studies were conducted in accordance with the local legislation and institutional requirements. Written informed consent for participation was not required from the participants or the participants’ legal guardians/next of kin in accordance with the national legislation and institutional requirements.

KS: Data curation, Methodology, Project administration, Supervision, Writing – original draft, Writing – review & editing. FP: Data curation, Writing – review & editing. KX: Writing – review & editing. YL: Writing – original draft. XZ: Data curation, Writing – review & editing. NS: Data curation, Writing – review & editing. CL: Data curation, Writing – review & editing.