*Article* **The Burden of Carbapenem-Resistant** *Acinetobacter baumannii* **in ICU COVID-19 Patients: A Regional Experience**

**Giorgia Montrucchio 1,2,\*,†, Silvia Corcione 3,4,†, Tommaso Lupia 3, Nour Shbaklo 3, Carlo Olivieri 5, Miriam Poggioli 5, Aline Pagni 6, Davide Colombo 6, Agostino Roasio 7, Stefano Bosso 7, Fabrizio Racca 8, Valeria Bonato 8, Francesco Della Corte 9, Stefania Guido 9, Andrea Della Selva 10, Enrico Ravera 10, Nicoletta Barzaghi 11, Martina Cerrano 11, Pietro Caironi 12, Giacomo Berta 12, Cecilia Casalini 13, Bruno Scapino 13, Michele Grio 14, Massimiliano Parlanti Garbero 14, Gabriella Buono 15, Federico Finessi 15, Simona Erbetta 16, Paola Federica Sciacca 16, Gilberto Fiore 16, Alessandro Cerutti 16, Sergio Livigni 17, Daniela Silengo 17, Fulvio Agostini 18, Maurizio Berardino 18, Mauro Navarra 19, Silvia Vendramin 19, Enzo Castenetto 20, Marco Maria Liccardi 20, Emilpaolo Manno 21, Luca Brazzi 1,2 and Francesco Giuseppe De Rosa <sup>3</sup>**

	- <sup>13</sup> S.C. Anestesia e Rianimazione, Ospedale di Ivrea, ASL TO4, 10015 Ivrea, Italy
	- <sup>14</sup> S.C. Anestesia e Rianimazione, Ospedale di Rivoli, 10098 Rivoli, Italy
	- <sup>15</sup> S.C. Rianimazione Generale, AO Ordine Mauriziano, 10128 Turin, Italy
	- <sup>16</sup> S.C. Anestesia e Rianimazione Moncalieri-Carmagnola, ASL TO5, 10023 Chieri, Italy
	- <sup>17</sup> S.C Anestesia e Rianimazione Ospedale S. Giovanni Bosco, ASL Città di Torino, 10144 Turin, Italy
	- <sup>18</sup> S.C. Anestesia e Rianimazione, Presidio CTO, AOU Città della Salute e della Scienza, 10126 Turin, Italy
	- <sup>19</sup> S.C. Anestesia e Rianimazione, Ospedale Martini, ASL Città di Torino, 10149 Turin, Italy
	- <sup>20</sup> S.C. Anestesia e Rianimazione, Ospedale di Chivasso, ASL TO4, 10034 Chivasso, Italy
	- <sup>21</sup> S.C. Anestesia e Rianimazione, Ospedale Maria Vittoria, ASL Città di Torino, 10144 Turin, Italy
	- **\*** Correspondence: giorgiagiuseppina.montrucchio@unito.it
	- † These authors contributed equally to this work.

**Abstract:** Since the beginning of the COVID-19 pandemic, the impact of superinfections in intensive care units (ICUs) has progressively increased, especially carbapenem-resistant *Acinetobacter baumannii* (CR-Ab). This observational, multicenter, retrospective study was designed to investigate the characteristics of COVID-19 ICU patients developing CR-Ab colonization/infection during an ICU stay and evaluate mortality risk factors in a regional ICU network. A total of 913 COVID-19 patients were admitted to the participating ICUs; 19% became positive for CR-Ab, either colonization or infection (*n* = 176). The ICU mortality rate in CR-Ab patients was 64.7%. On average, patients developed colonization or infection within 10 ± 8.4 days from ICU admission. Scores of SAPS II and SOFA were significantly higher in the deceased patients (43.8 ± 13.5, *p* = 0.006 and 9.5 ± 3.6, *p* < 0.001, respectively). The mortality rate was significantly higher in patients with extracorporeal membrane oxygenation (12; 7%, *p* = 0.03), septic shock (61; 35%, *p* < 0.001), and in elders (66 ± 10, *p* < 0.001). Among the 176 patients, 129 (73%) had invasive infection with CR-Ab: 105 (60.7%) Ventilator-Associated Pneumonia (VAP), and 46 (26.6%) Bloodstream Infections (BSIs). In 22 cases (6.5%), VAP was associated with concomitant BSI. Colonization was reported in 165 patients (93.7%). Mortality was significantly higher in patients with VAP (*p* = 0.009). Colonized patients who did not develop invasive infections had a higher survival rate (*p* < 0.001). Being

**Citation:** Montrucchio, G.; Corcione, S.; Lupia, T.; Shbaklo, N.; Olivieri, C.; Poggioli, M.; Pagni, A.; Colombo, D.; Roasio, A.; Bosso, S.; et al. The Burden of Carbapenem-Resistant *Acinetobacter baumannii* in ICU COVID-19 Patients: A Regional Experience. *J. Clin. Med.* **2022**, *11*, 5208. https://doi.org/10.3390/ jcm11175208

Academic Editor: Daniel L. Herr

Received: 11 July 2022 Accepted: 26 August 2022 Published: 2 September 2022

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colonized by CR-Ab was associated with a higher risk of developing invasive infections (*p* < 0.001). In a multivariate analysis, risk factors significantly associated with mortality were age (OR = 1.070; 95% CI (1.028–1.115) *p* = 0.001) and CR-Ab colonization (OR = 5.463 IC95% 1.572–18.988, *p* = 0.008). Constant infection-control measures are necessary to stop the spread of *A. baumannii* in the hospital environment, especially at this time of the SARS-CoV-2 pandemic, with active surveillance cultures and the efficient performance of a multidisciplinary team.

**Keywords:** *Acinetobacter baumannii*; *Acinetobacter* infections; intensive care unit; COVID-19; SARS-CoV-2; nosocomial infections; carbapenems; multidrug resistance; antimicrobial drug resistance; critical care

#### **1. Introduction**

The Gram-negative aerobic bacillus *Acinetobacter baumannii (A. baumannii*) primarily causes hospital-acquired infections in especially fragile patients with prolonged hospitalization and with long-term exposition to broad-spectrum antibiotic treatment. It is characterized by disinfection resistance, and its high pathogenicity is increased by the production of a polysaccharide capsule and by the ability to form biofilms [1]. Furthermore, due to the acquisition of multiple antimicrobial resistance, especially to carbapenems, it has been recognized as a major public health concern [2] and considered as "priority 1" (critical) in the World Health Organization (WHO)'s first list of "priority pathogens" resistant to antibiotics, including the 12 families of bacteria most dangerous for human health and for which new antimicrobials are urgently required [3].

It is well known that *A. baumannii* exhibits a wide variety of mechanisms of resistance to antibiotic agents, as differential clones had been isolated in Europe [4]. *A. baumannii* includes several mechanisms of resistance such as lipopolysaccharide expression disorders, permeability alterations due to porins, and the production of active efflux pumps. In particular, resistance to carbapenems is related to numerous beta-lactamases with carbapenemase activity, including type OXA carbapenemases—both constitutive or acquired. Moreover, a transmissible resistance mechanism of colistin, called mobile colistin resistance (MCR), was discovered. Up to ten families with MCR and more than 100 variants of Gram-negative bacteria have been reported worldwide. Even though few have been reported from *Acinetobacter* spp. and *Pseudomonas* spp., it is important to closely monitor the epidemiology of MCR genes in these pathogens [1,4].

*A. baumannii* can survive for long periods on surfaces, including human skin and dry surfaces (up to 33 days) [5], and this ability might facilitate its persistence in intensive care units (ICUs), rightly considered as the epicenters of carbapenem-resistant *A. baumannii* (CR-Ab) infections [6,7]. Some specific factors may increase the potential of cross-transmission: the heavy colonization of the patient, the colonization of the surfaces surrounding the patients, and the total number of patients colonized in the unit at the same time [8]. CR-Ab also has a further important feature, namely its tendency to generate outbreaks, generally transmitted through the hands of healthcare workers, contaminated equipment, and the healthcare environment [7,9,10].

The most frequently reported risk factors for CR-Ab infections are prior colonization, the severity of illness, the need for mechanical ventilation (particularly in case of prolonged duration), immunosuppression, malignancies, chronic pulmonary diseases, respiratory failure on admission, previous antimicrobial therapy, previous sepsis in ICU, previous use of carbapenems and third generation cephalosporins, long ICU stay [11], and a consequent greater degree of exposure to infected or colonized patients in the hospital environment [12,13].

Overall, CR-Ab is accountable for more than 12% of the cases of hospital-acquired bloodstream infections (BSI) in the ICU, with wide geographic variations: it is frequent in Southern Europe, Middle Eastern countries, Asia, and South America, whereas it is rare in Northern European countries and Australia [14]. CR-Ab is a common cause of ICU-acquired pneumonia, particularly late-onset pneumonia [15].

Since the beginning of the COVID-19 pandemic, the impact of superinfections in ICU patients has progressively increased and many studies have shown that the rate of BSIs [16] and Ventilator-Associated Pneumonia (VAP) [17] is raised compared to that observed in non-COVID-19 patients [18–21]. It has also been reported that the prevalence of Gram-negative multi-drug resistant organisms, especially *A. baumannii*, known to increase mortality, seems to have escalated [22,23].

In Italy, various experiences of multidrug-resistant (MDR) bacterial infection in COVID-19 and its impact on patient outcomes have been published, [24] but few describe specifically *A. baumannii* cases. Several studies showed that MDR infection arose after a median time of 8 [4–11] days and the incidence rate ratio of MDR infection in ICU increased in the COVID-19 period [25,26].

Despite the above evidence and the interest in superinfections from multidrug-resistant pathogens, particularly CR-Ab in ICU patients with COVID-19 [27], to date, no multicenter study has been conducted with the aim of better describing the phenomenon.

The present multicenter retrospective study was designed to investigate the characteristics of COVID-19 ICU patients who developed CR-Ab colonization or infection during their ICU stay and evaluate risk factors for ICU mortality in a regional ICU network.

#### **2. Materials and Methods**

#### *2.1. Study Design and Population*

This was an observational, multicenter, and retrospective study. Nineteen COVID-19 ICUs in the Piedmont Region, Italy, were invited to participate in an observational, multicenter, retrospective study to describe the incidence of colonization and infection with CR-Ab in SARS-CoV2 pneumonia patients admitted to ICUs between 1 July and 31 December 2021.

The data sources were the hospital administrative records and the Microbiology Laboratory database. Data acquisition and analysis were performed in accordance with the protocols approved by the local Ethics Committee (Ethics Committee: Comitato Etico Interaziendale A.O.U. Città della Salute e della Scienza di Torino—A.O. Ordine Mauriziano— A.S.L. Città di Torino; ethics approval number 0031285). Written informed consent was waived according to Italian regulations due to the retrospective nature of this study. The study was conducted according to the guidelines of the Declaration of Helsinki.

All consecutive adult (≥18 years) patients admitted to the ICU and presenting CR-Ab colonization or infection during the study period were enrolled. All patients were followed up until the hospital discharge to compute: ICU, 28-day and overall mortality, length of ICU and hospital stay.
