A. baumannii has become an important pathogen of nosocomial infections, which can easily cause epidemics, especially in the ICU, and XDRAB has received particular attention in this regard [14]. A. baumannii was previously considered to be a low-virulence opportunistic pathogen with no impact on the prognosis of hospitalized patients [15]; however, recent studies have shown that A. baumannii, especially multidrug-resistant strains, are commonly isolated in critically ill patients, and are associated with a high mortality rate ranging from 52% to 66% [16]. The mortality rate from XDRAB pneumonia in this study was 58.3%, which is similar to that reported by Boral et al. [17], confirming the high mortality rate of this pathogen. Therefore, it is particularly important to deepen the exploration of strategies for the treatment of XDRAB infection.
The first challenge is the selection of an appropriate antibacterial drug for the treatment of XDRAB infection, which requires an extensive evaluation of the role of various drugs with potential anti-Acinetobacter activity on the treatment outcome. Commonly used antibacterial drugs that are currently recommended for the treatment of A. baumannii infections include sulbactam and a compound preparation of sulbactam-containing β-lactam antibiotics, carbapenem antibiotics, polymyxin antibiotics, tigecycline, tetracycline, aminoglycoside, and quinolone [16, 18]. In cases of XDRAB infection, a two-drug or even a three-drug combination is often used. Although some studies have shown potential benefits of combined regimens, these results are mostly based on animal experiments, in vitro studies, and uncontrolled clinical studies with a small number of cases, and the conclusions are inconsistent [19]. The possibly effective two-drug combination regimens are (1) sulbactam or a compound preparation containing sulbactam as the basis in combination with one of carbapenems, minocycline (or doxycycline), polymyxin, or aminoglycoside antibiotics [20-22]; and (2) tigecycline as the basis combined with a compound preparation containing sulbactam, aminoglycoside antibiotics, or quinolone [23-26]. The three-drug combination regimens include a compound preparation containing sulbactam (or sulbactam) combined with doxycycline and carbapenem antibiotics [20].
All of the recommended drugs with anti-Acinetobacter activity had been used on the patients included in this study with confirmed XDRAB infection, except for polymyxin antibiotics. This is because polymyxin has a limited effect due to its low blood concentration in the lung and cerebrospinal fluid. Kim et al. [27] reported that the clinical response rate of patients with XDRAB pneumonia who received polymyxin or tigecycline as the basis treatment was 48% and 47%, respectively, with no significant difference. Yilmaz et al. [28] reported that the clinical and microbial treatment response rates for the single use of polymyxin, polymyxin combined with sulbactam, and polymyxin combined with carbapenem in the treatment of multidrug-resistant or XDRAB pneumonia were 63.6%, 55%, and 60%, respectively, with no significant differences. In a meta-analysis, Jung et al. [19] found no significant difference in the clinical and microbial treatment response rates of polymyxin or tigecycline alone, or in combination with carbapenem and sulbactam. Liu et al. [29] also reported no significant difference in the prognosis of patients with multidrug-resistant A. baumannii pneumonia who were treated with or without tigecycline. Consistently, in the present study, there was no significant difference in the use of various antibacterial drug combinations (including monotherapy, two-drug combinations, and three-drug combinations) during infection between the survival group and the death group.
Although the recommended anti-A. baumannii antibacterial drug combinations were used at our hospital, following these guidelines did not significantly improve the prognosis or bacterial clearance rate. There are several potential reasons to explain these observations. First, A. baumannii is a low-virulence pathogen. Therefore, even if extensive drug resistance appears, the toxicity would not necessarily be enhanced. Second, antimicrobial drugs cannot effectively clear XRDAB, and therefore other adjuvant treatments are required. Third, the prognosis may be mainly affected by factors other than treatment, such as the underlying condition.
Jung et al. [19] found that advanced age, multiple organ failure, and a severe disease condition had a negative effect on bacterial clearance; effective airway management (e.g. tracheostomy, sputum suction) was conducive to bacterial clearance; and the use of antibacterial drugs had no obvious effect on prognosis, which are all consistent with the present findings. Multivariate logistic analysis showed that age and APACHE II score were independent risk factors affecting prognosis, and that tracheotomy is a protective factor.
Patients with advanced age, multiple organ failure, and severe disease conditions are mostly bedridden, and may even be in a coma and confined to bed for a long time. This situation is typically accompanied by a decreased cough reflex, resulting in poor sputum-discharging and clearance ability of the respiratory tract [30]. Therefore, it is necessary to strengthen airway management, especially the body position and mechanical-assisted sputum discharge. For patients with thick sputum and weakness in expectoration, tracheotomy should be performed as soon as possible. It is currently believed that long-term tracheal intubation is more likely to cause airway damage, infection, and patient discomfort, and requires more doses of sedatives. Therefore, for patients who require long-term mechanical ventilation, tracheotomy should be performed as soon as possible to replace tracheal intubation [31-32], as tracheotomy results in a more stable artificial airway. This also allows patients to eat by mouth, and tracheotomy is further conducive to the removal of pulmonary secretions, which can improve the overall prognosis [33-35]. Kimura [36] reported that mechanical ventilation with tracheotomy could effectively prolong the median survival of patients with lateral sclerosis. However, the optimal timing of tracheotomy remains controversial [35]. The National Association for Medical Direction of Respiratory Care recommends that patients who have been under tracheal intubation for more than 3 weeks should receive tracheotomy as a substitute [37]. At present, early tracheotomy is preferred. Timely tracheotomy can reduce the complications of long-term tracheal intubation (e.g. larynx injury, airway injury, bacterial growth) and reduce the rate of pulmonary infection, making the infection easier to be controlled, which is closely related to shorter hospital stays, lower treatment costs, and lower mortality [38-40].
Regarding the prognosis of drug-resistant A. baumannii infections, it has been reported that the virulence of the drug-resistant bacterium itself does not increase, and therefore neither would the mortality rate, and that it is instead the severity of the underlying disease that will ultimately affect the prognosis [1], in line with our results. At present, the APACHE II score is the most widely used and authoritative critical illness condition evaluation system in clinical ICU wards, which can provide an objective and scientific basis for the rational use of medical resources and prognostic judgements [7]. However, the APACHE II scale is mainly designed for ICU inpatients and is not specific to pneumonia, and few studies have directly assessed its prognostic value in patients with pneumonia. This study shows that an APACHE Ⅱ score ≥20 can indicate a poor prognosis in patients with XDRAB hospital-acquired pneumonia, similar to the findings of Liu et al. [29].
This study also has some limitations, which should be mentioned. This was a retrospective study, we were lacking data on polymyxin treatment, and this was a single-centre study with a relatively small sample size. Therefore, further in-depth research using prospective multi-centre studies with a large sample size are needed.