Risk factors for nosocomial rectal colonization with carbapenem-resistant Acinetobacter baumannii in hospital: a matched case–control study

Carbapenem-resistant Acinetobacter baumannii (CRAB) is emerging worldwide as a major cause of healthcare-associated infections (HAIs), especially in intensive care units (ICUs) [1‐4]. Worryingly, during the last decade, the Italian antimicrobial resistance rates were among the highest in Europe and CRAB became hyper-endemic [5]. Its growing importance in the hospital setting is due both to the ability of these bacteria to accumulate mechanisms of resistance to antibiotics, and the ability to survive in unfavourable conditions for long periods of time [6]. CRAB infections frequently occur in patients with severe underlying diseases, the critically ill, the elderly, immunocompromised, severely debilitated or with life-threatening conditions and also in patients transferred from long-term health care facilities (LTHCFs) [7, 8]. Risk factors mainly associated with CRAB infection and colonization are invasive procedures, indwelling devices and previous antibiotic treatment [9]. Moreover, cross-transmission of CRAB among hospitalized patients is promoted by poor adherence to hand hygiene practices and by repeated contact with the contaminated environment [4, 10‐13]. Therefore, the rapid identification of CRAB asymptomatic carrier could allow an earlier introduction of infection contact precautions to prevent transmission to other patients and to the hospital environment [14]. An early recognition of CRAB carrier can also assist to identifying patients at risk of subsequent CRAB infection. Indeed, Latibeaudiere et al. demonstrated that previous CRAB colonization increased by 8 times the risk to develop a CRAB infection [4, 15]. Several studies have been carried out worldwide with the aim of identifying risk factors for colonization and infection with A. baumannii, in particular focusing on CRAB [16‐19]. Unfortunately, most of these studies were retrospective and conducted during CRAB outbreaks. Furthermore, many studies were limited to ICUs where colonization and infections with Acinetobacter spp. are more frequent [1, 16, 20, 21], while only a few studies investigated non-ICUs settings [3, 19]. Only two studies involved LTHCFs [17, 22]. The most common outcome was risk factors for CRAB infection and subsequent mortality. These heterogeneous studies conducted in different epidemiological situations had methodological limitations mainly due to different selection criteria between cases and controls, and did not allow conclusive findings [1, 20, 23, 24]. This study aims to identify the main risk factors associated with rectal CRAB nosocomial colonization in a CRAB-endemic acute care facility.

In this study, 45 (33.4%) patients colonized with CRAB were considered as cases; for each patient two controls were selected up to a total of 90 (66.6%) controls. One hundred and two (75.5%) patients were hospitalized in medical departments, including geriatric and internal medicine, 21 (15.5%) patients in ICUs and 12 (9%) in surgical departments. The baseline characteristics of the two matching groups and the comparisons are described in Table 1.

Several parameters proved to be statistically significant risk factors in the univariate analysis (Table 2). An ICU admission during hospitalization increased the risk of acquiring a rectal colonization with CRAB in hospital by 3.2 times, while patients transferred from a LTHCF had a 16 time higher risk of nosocomial rectal CRAB colonization compared to patients living at home. Considering comorbidities, peripheral cardiovascular disease and dementia increased the risk of being colonized with CRAB. Other variables significantly associated to risk of rectal colonization with CRAB were the use of permanent devices and the use of invasive devices in a hospital environment. Among these were the use of vascular catheters, such as central venous catheterization (CVC) or the use of Peripherally Inserted Central Catheter (PICC) or Midline, urinary catheter (UC), nasogastric tube (NG) and mechanical ventilation (MV). Other factors that were significantly associated were tracheostomy and percutaneous endoscopic gastrostomy (PEG), which respectively determined an elevated risk for rectal CRAB colonization of 10.5 and 11 times.

Concerning therapy, the use of antibiotics and antibiotic polytherapy during hospitalization was found to be very strong risk factors in the univariate analysis. With regard to the different antibiotic classes, carbapenems and glycopeptides statistically increased the rate of rectal colonization with CRAB, but not the use of 3rd generation Cephalosporins (3GC). Moreover, corticosteroid therapy was found to be a significant risk factor for CRAB. In the multivariate logistic regression analysis shown in Table 2, a significant independent risk factor for rectal CRAB colonization was the use of permanent devices. The use of UC and MV increased the risk by 5 and 40 times respectively. McCabe score elevated the risk for CRAB rectal colonization by 5.45 times. Another significant risk factor was LOS. Among antibiotic exposure, only carbapenems were significantly associated with rectal CRAB. Finally, there was no association with mortality.

Antibiotic therapy, disabilities and medical devices play a crucial role in rectal CRAB colonization. Our findings support active screening strategies targeted to early identification of CRAB asymptomatic carriers in an endemic hospital setting, including non-ICU departments, a previously underestimated setting. The early identification of specific risk factors for colonization with CRAB could become the cornerstone of a cost-saving prevention strategy. In our population, diagnosis of a fatal condition and longer LOS had the greatest impact on CRAB nosocomial acquisition, especially in elderly patients. Cases had a twofold longer LOS compared to control patients, suggesting that longer hospitalization could facilitate CRAB acquisition. The risk of CRAB colonization was increased by several factors: carbapenem exposure increased the risk by fivefold; permanent devices and MV increased the risk by 10 and 40 times respectively. Finally, among comorbidities and intrinsic risk factors [3], only peripheral vascular disease and dementia were found to be associated to CRAB colonization in our hospital setting. Several studies have shown that CRAB colonization represents the main significant risk factor for the development of CRAB-related infections, with very difficult therapeutic management due to limited antimicrobial treatment options, present and future [3, 15]. In this scenario, active surveillance cultures with rectal screening represent one of the most important strategies of a multimodal approach in order to counter CRAB hospital spreading in highly endemic settings [4]. To our knowledge, few studies have investigated the risk factors for colonization and most of them are focused on ICUs or aimed at highlighting the variables involved in the development of infection rather than colonization [19, 21, 23]. These limitations could be explained by the fact that rectal screening on admission is not universally performed outside the ICU, so it is very difficult to distinguish between community-associated and nosocomial colonization. Until now the identified risk factors for CRAB nosocomial acquisition are: disease severity measured by scores (e.g. APACHE II, McCabe), antibiotic use, invasive procedures such as catheterisations, enteral feeding or MV, ICU stay, and LOS [3, 16, 19, 21, 27]. Therefore, multiple and permanent devices should always set up a wake-up call to screen patients admitted in non-ICU departments in endemic hospitals. Although polytrauma, blood transfusions and major surgery are significant known risk factors for CRAB acquisition [16] the limited number of surgical patients in our study did not allow us to explore this finding. In our study only antibiotic polytherapy and exposure to carbapenems were found to be significant risk factors for CRAB colonization, in the overall study population. Antibiotic therapy, in particular fluoroquinolones, 3GC and aminoglycosides, both before and during hospitalization, have previously been identified as risk factors for rectal CRAB colonization and infection [3, 15, 16, 19, 21, 27]. Moghnieh et al., identified a colonization risk score for XDR A.baumannii in ICU patients, and confirmed the role of carbapenem and piperacillin-tazobactam exposure [21], while Tacconelli et al. [27], showed that methicillin-resistant Staphylococcus aureus isolation and beta-lactam use were among the independent risk factors for CRAB colonization and infection. Our study has several strengths. First, it focused on CRAB colonization and not systemic infection. This is extremely important in order to better identify risk factors for colonization by eliminating possible confounders associated with CRAB infection. Second, our study is the first to conduct a risk factor analysis according to the type of department, with a majority of patients from outside the ICU. The sub-analysis by department showed that patients admitted to different departments have different risk factors and that, as far as our centre is concerned, most of the colonization occurred in geriatric and internal medicine settings. We found that antibiotic exposure had a different effect depending on the department. In ICU, antibiotic use was the main risk factor for nosocomial CRAB colonization, and in particular the use of carbapenems and 3GC significantly increased the risk by 33 times and 14.7 times, respectively. In internal medicine department, the use of antibiotic polytherapy, carbapenems and penicillins (especially piperacillin/tazobactam) were among the most important risk factors for rectal CRAB colonization. The use of piperacillin/tazobactam has been poorly investigated in previous studies probably because most focused on ICU-CRAB carriers, while the highest consumption of this antibiotic occurs in medical department [3, 26]. Conversely, in the geriatric setting the most important risk factors to become a CRAB carrier were the presence of invasive devices, both permanent and positioned during the hospital stay, rather than antibiotic exposure. A third strong point of our study is its design. The matching by department and date of screening allowed us to control for the variation of CRAB colonization pressure and the cross-transmission in the department, which are potential confounders of the main associations considered in this study. In fact, the likelihood of a patient to receive an antibiotic prescription in a specific setting and the timing may be influenced by the perceived risk of a multidrug resistant organism (MDRO) infection, as physicians might be more prone to prescribe a broad spectrum antibiotic when other patients in the department are colonized or infected by MDROs. Furthermore, concurrent selection of controls provided an accurate estimate of relative risk even in case–control studies assessing non-rare outcomes. We excluded community-colonized patients through an active surveillance on admission. This study has some limitations. It is a single-centre retrospective study carried out in a CRAB endemic area. For this reason, our model may not be applicable to different settings, and the results must be generalized with caution. Furthermore, the design of the study did not allow us to consider some important parameters such as risk factors related to infection control strategies. Since the controls for each CRAB case were selected through a matching by department and date of screening, it was not possible to analyse the role that the roommate had in the acquisition of CRAB colonization. Another limitation of our study is the selection bias due to the case–control approach. We have not analysed all the patients colonized in the time frame considered, but 45 randomly selected patients who tested positive for rectal screening after at least 4 days of hospitalization. In addition, we excluded respiratory and urinary CRAB colonization because the retrospective nature of the study did not allow a precise discrimination between colonization and infection in these different specimens. Unfortunately, no specific risk factors were identified for the surgical department, because the surgical sample was too small. Further investigations are needed in this setting.

As CRAB colonization is one of the most important risk factors for CRAB infection, targeted infection prevention and control (IPC) practices are crucial to limit CRAB spreading in hospitals, not only in ICUs, but also general departments where this pathogen is widely found. Rectal screening could represent a cornerstone to limit CRAB dissemination in endemic settings. By identifying the main risk factors associated to in-hospital rectal CRAB-acquisition in different wards, this study provides new real-life elements to limit CRAB cross-transmission and to target CRAB-IPC interventions. In the era of MDROs clinicians should strictly adhere to and apply bundles for permanent devices and invasive procedures management in order to target their use. Finally, our study supports the fundamental principles of antimicrobial stewardship, i.e. limiting the use of inappropriate antibiotic therapy, avoiding polytherapy and reducing carbapenem use in CRAB endemic hospitals.