To finally control nosocomial CRAB in our ICU, we successfully applied a “five-component bundle”, which consisted of reinforcement of previously recommended measures [7, 10, 11, 17] and innovative actions. The novel procedure Cycling radical cleaning and disinfection allowed us to avoid ICU closure and limiting admissions. Moreover, contrary to previously reported experiences [20,21,22], we did not need cohorting of patients. This intervention, although being labor-intensive, was applicable in our open space ICU, a type of ICU which is the most affected by nosocomial epidemics [28]. Our experience can help hospitals with single ICUs facing similar outbreaks and endemicity.
Since in many hospitals it is unthinkable to close the hospital’s only ICU, this procedure should be considered in such settings as it can be completed on average in 6 h with an additional crew of trained staff. It also avoids restricting ICU admissions. Furthermore, patient cohorting is hard to implement in an open space ICU and has a high probability of failure because of low compliance and difficulties in full cohorting of all medical staff, cleaning staff and consultants. Nurse cohorting, which often requires an additional nurse shift, is even more difficult.
To date, no published interventions avoided at least temporary closure or cohorting of colonized patients to limit CRAB spread in an ICU (Additional file 1). Moreover, considering that ward closures and temporary limiting admissions contributed to the largest part of the total costs for outbreak control [29], these findings could be valuable.
The efficacy of a multimodal approach on CRAB outbreak control has been widely underlined in several guidelines and single center experiences [8,9,10,11,12,13,14,15,16,17,18,19,20]. However, our intervention study added a new element in the control of this hard-to-treat pathogen and clarified the transmission dynamics of CRAB, an issue still under investigation [30]. Environmental contamination appeared to represent the most frequent source of CRAB cross-transmission in ICU.
By using intervention time-series analysis, we demonstrated that an ICP bundle including enhanced environmental cleaning had a decisive impact on nosocomial CRAB ICU incidence density against a background of stable AHR and antibiotic use. The short-term Intervention was three times more effective than the long-term one, because it eliminated the chronic load of environmental bacterial contamination.
Valencia-Martìn et al. underlined that the major limitation of the design of a multimodal program is that it usually precludes the understanding of which is the most effective strategy to eradicate CRAB from ICUs, given that all strategies are applied simultaneously [16]. Indeed, we cannot determine the effect of each individual component of the bundle. Another relevant observation is that the colonization pressure, represented in the time series by the Non-ICU CRAB ID, works as an amplifier of nosocomial cases. This underlines that screening strategies and immediate implementation of contact isolation of CRAB carriers are key elements to prevent CRAB nosocomial transmission and subsequent infections.
Additionally, in line with previous evidence [5], we demonstrated that standard cleaning with self-monitoring is insufficient to control the CRAB environmental spread. There are several promising emerging technologies for environmental cleaning and disinfection, but they are expensive, poorly tolerable and require a substantial amount of time before room release for any new patient [14, 20]. As an example, the “No-touch” cleaning methods, such as UV and pressurized hydrogen peroxide, are undoubtedly promising but require the room to be tightly closed and unoccupied. Due to these limitations, we used 10% sodium hypochlorite and hydrogen peroxide whilst focusing on increasing compliance through the routine use of the CDC Environmental Checklist for Monitoring Terminal Cleaning [31]. We strongly believe that mechanical removal of biofilm may be more relevant than the type of disinfectant used with regard to Acinetobacter [21]. In order to reinforce compliance, we decided to keep on monitoring the completeness of the cycling radical environmental cleaning and disinfection by using fluorescein spray, not only to confirm that all surfaces were cleaned, but also to raise awareness and educate cleaning staff about terminal cleaning. This method has the advantages of being fast, easy to use and cost-effective, meeting the need for an external validation of room cleaning, which is mandatory in such endemic setting.
With regard to CRAB active screening strategies, an universal consensus has not been reached yet [10]. The Task force on management and prevention of Acinetobacter baumannii infections in the ICU has recommended weekly rectal, pharyngeal and tracheal swabs [9]. A recently published program by Valencia-Martìn et al. found a sensitivity of 96% combining rectal and pharyngeal swabs compared to 78% of rectal swab only [16]. We chose to implement active screening with rectal and skin swabs, but also respiratory samples such as endotracheal aspirates. The best performance was obtained by skin samples (100%), followed by the rectal samples (86%). As the results of CRAB screening are not immediately available, we suggest applying contact precautions to all ICU patients until outbreak termination.
Environmental sampling of A. baumannii through standard swabbing has proven to be sub-optimal [13], with sensitivity rates ranging from 0 to 18%, according to several factors such as the extension of the outbreak and the sampling technique used. By using BHI pre-moistened sterile gauze pads, more than 50% of our environmental samples were positive for CRAB. On the basis of this gain in sensitivity, the BHI pre-moistened method became the method of choice for CRAB environmental detection in the whole hospital.
The CRAB isolates obtained from the environmental sampling represented a precious resource to investigate transmission in the ICU and to understand how the outbreak evolved. Indeed, sequencing data strongly suggest that transmission events not fully explained by patients’ overlapping stays could primarily result from contamination of the environment, leading to a more complicated transmission network. In this context, WGS played a fundamental role in distinguishing highly related clones accounting for different introduction events, and in identifying potential environmental reservoirs close to the patient leading to perpetuation over time. The high discriminatory power provided by WGS has already been proven by other authors [32, 33], even if these studies were not able to demonstrate a link with an environmental source. Noteworthy, WGS could provide a key contribution to identify specific virulence-associated genetic variants. Indeed, a non-functional adeN was recently associated with a drastic increase in the virulence potential and with a hyper invasiveness in in vivo models using G. mellonella and the A549 cell line, respectively (33). During the outbreak, only two patients who acquired a CRAB clone with inactivation of adeN survived, probably due to their younger age and less immune-compromised status. Such increase in virulence may have contributed to the high mortality rates of our outbreak, which unfortunately did not differ from that reported in literature [34,35,36], despite the compassionate use of cefiderocol [37] in two patients.
Finally, our results should be interpreted with caution considering the main limitations: first, this is a single center study whose conclusions are not directly transferable to other facilities; second, it has been conducted in a 12 bed ICU with only 3 isolation rooms and this could have facilitated the cross-transmission; third, the low use of antibiotics and the high consumption of AHR, as well as their lack of abrupt changes during the Intervention and post-intervention periods, may have hampered observing the logical and expected impact of these factors on the resistance; fourth, this analysis does not allow to compare the impact of antibiotics and AHR use vs the effect of the ICP bundle, because we were only able to measure the impact of the two kinds of outbreak interventions.
