Summary
Background
Acinetobacter baumannii is an opportunistic drug-resistant Gram-negative coccobacillus associated with nosocomial infections, representing a worldwide public health problem.
Aim
The aim of this study was to analyse the dissemination of A. baumannii in two hospital buildings in Mexico through phenotypic and genotypic characterization of clinical isolates obtained for three years.
Methods
Clinical strains were collected from two buildings in a tertiary-care hospital in Monterrey, Mexico. After species identification by MALDI-TOF MS and PCR, antimicrobial susceptibility was determined by disk diffusion and microdilution methods, carbapenemase-encoding genes (OXA-23, -24, -51, and -58) were searched, and clonal diversity was analysed by PFGE and MLST.
Findings
Among 204 specimens, 87.3% and 50.5% of the isolates were classified as multidrug-resistant (MDR) and difficult-to-treat-resistant (DTR), respectively. The OXA-24 gene was detected in 95% of the isolates. Most isolates (n=181) were grouped into 15 clones, four which predominated and disseminated after five months. Among ST detected (ST1694, ST758, ST124, and ST490), ST124, which belongs to the high-risk CC636 clonal complex, is reported for the first time in Mexico.
Conclusions
Long-term persistence and dissemination of A. baumannii clones were observed in specific hospital wards from two buildings in a tertiary-care hospital in Mexico. High antimicrobial resistance, such as MDR and DTR, were observed in this hospital. DTR surveillance and early recognition of MDR A. baumannii clones should be performed routinely to prevent their dissemination.
Keywords: Acinetobacter, Dissemination, Carbapenemases, OXA-24, Difficult-to-treat resistant
Introduction
Acinetobacter baumannii is an opportunistic Gram-negative coccobacillus that is closely associated with nosocomial infections, mainly ventilator-associated pneumonia, particularly hospitalized in the intensive care unit (ICU) or immunocompromised patients [1]. A. baumannii can also cause bacteraemia, meningitis, urinary tract, and skin and soft tissue infections [2]. Clinical A. baumannii strains frequently exhibit resistance to the most prescribed antibiotics, including carbapenems, which can increase mortality by up to 70% [1,3,4]. Carbapenem resistance is considered a marker for extensively drug-resistant bacteria (XDR), as carbapenems are β-lactam antibiotics with the broadest spectrum and highest efficiency against bacterial infections [2].
This pathogen also represents a worldwide public health problem due to its ability to survive on different surfaces of the hospital environment [5]. Nosocomial outbreaks due to A. baumannii can be difficult to eradicate due to its remarkable resistance to disinfectants and its rapid capacity to develop tolerance to antibacterial agents, contributing to prolonged colonization and transmission [2]. The assessment of clonal relationship can unveil useful data which will allow the understanding of the epidemiology, geographical distribution, and evolution of clonal strains of A. baumannii thereby laying the foundations of an effective infection control program. The aim of this study was to analyse the dissemination of A. baumannii in two hospital buildings in Mexico through phenotypic and genotypic characterization of clinical isolates obtained for three years.
Materials and methods
Study site
The University Hospital “Dr. José Eleuterio Gonzalez” located in Monterrey, Mexico, is a multi-building hospital and medical school complex which comprises two separate hospitals. The main building began operations in 1944, and it currently has 600 beds. The secondary building was first used in 2020 for the diagnosis and treatment of suspected or confirmed COVID-19 cases; it currently has 85 beds. The distance between both buildings is approximately 400 meters. The University Hospital receives referrals from neighbouring state hospitals, and it has approximately 25,000 admissions and 200,000 emergency room visits per year. This study was performed with approval from the Ethics Committee (approval number IF23-00003).
Clinical isolates identification
The strains were consecutively obtained from January 1st, 2019, to December 31st, 2021. Cultures were identified at genus level by matrix-assisted laser desorption/ionization coupled to time-of-flight mass spectrometry (MALDI-TOF MS, Microflex LT system, Bruker Daltonics, Bremen, Germany) that was used according to the manufacturer's recommendations. Species identification was performed by recA and spacer region of the internal transcript genes amplification using the primers reported by Chen et al. [6]. Primers were for recA were P-rA1 (5′-CCTGAATCTTCTGGTAAAAC) and P-rA2 (5′-GTTTCTGGGCTGCCAAACATTAC) and P-Ab.ITSF (5′-CATTATCACGGTAATTAGTG) and P-Ab-ITSB (5′-AGAGCACTGTGCACTTAAG) for the ITS region.
Antimicrobial susceptibility testing and resistance-associated gene detection
Following the 2023 Clinical and Laboratory Standards Institute guidelines in the M100 document [7], disk diffusion phenotypic susceptibility tests were carried out for all antibiotics except colistin, which was carried out using broth microdilution. The antibiotic disks used contained the following concentrations: gentamicin (10 μg), imipenem (10 μg), meropenem (10 μg), piperacillin-tazobactam (100/10 μg), cefepime (30 μg), ceftazidime (30 μg), levofloxacin (5 μg), doxycycline (30 μg), sulbactam-ampicillin (10/10 μg) and tigecycline (15 μg). A cation-adjusted Müeller-Hinton broth was used for colistin broth microdilution testing. A 400 μg/mL stock solution of colistin sulfate was prepared, and the analyzed concentrations were from 2 to 32 μg/mL. Pseudomonas aeruginosa ATCC 27853 was used as quality control. Besides, Escherichia coli ATCC 25922 and a clinical strain of Proteus mirabilis (intrinsic colistin resistance) were used as positive and negative controls, respectively.
Isolates were considered as multidrug-resistant (MDR) when they were resistant to three or more antibiotic categories, while those resistant to more than one antibiotic in almost all (except one or two) antibiotic categories were extensively drug-resistant (XDR) [8]. Isolates were difficult-to-treat resistant (DTR) when they showed resistance to all first-line treatment options. For A. baumannii, this included intermediate susceptibility or resistance to carbapenems, extended-spectrum cephalosporin, fluoroquinolones, piperacillin-tazobactam, and ampicillin-sulbactam [9]. MDR classification focuses on resistance to multiple antimicrobial categories whereas DTR correlates with clinical implications and identifies isolates resistant to first-line treatment options. In addition, main A. baumannii carbapenemases subgroups, including carbapenemase-encoding genes for oxacillinases (OXA-23, OXA-24, OXA-51, and OXA-58), were screened by PCR using primers and conditions previously reported [10]. Isolates that tested positive for the OXA-24 gene were further analyzed by OXA-24/40 gene amplification and sequencing and comparison of nucleotide sequences with the GenBank database to determine OXA-24 specific variants [11]. These genes were selected for this study as they are the most frequent carbapenemase genes detected in A. baumannii strains circulating in our hospital and are known as the main contributors to carbapenem resistance in A. baumannii in our region.
Clonal diversity determination
Genomic DNA was extracted from the isolates and digested with SmaI restriction enzyme (Nippon Genetics). PFGE was performed using the CHEF-DR III system (Bio-Rad, CA, USA) in which a 1% agarose gel was run at 14°C with an initial time of 0.5 s and a final time of 15 s, at 6 V/cm2 for 20 h. PFGE band patterns were visually analysed and if the restriction patterns presented 100% similarity, the isolates were classified as a clone according to criteria previously suggested by Tenover et al. [12]. The similarity coefficients were generated from a similarity matrix and were calculated using Jaccard's coefficient in the SPSS Statistics 25 software (IBM Corporation, Somers, NY, USA).
Multi-locus sequence typing (MLST) was performed on 21 randomly selected strains according to the Oxford scheme, according to Bartual et al. [13]. The products were sequenced on a 3730xl DNA Analyzer by Macrogen Inc. (Seoul, Korea). The sequences were assembled in the PubMLST program and submitted to the database to determine the sequence types (ST).
Clonal diversity was analyzed using PFGE for local epidemiological investigations, while MLST provided a global perspective.
Results
A. baumannii clinical isolates
During the three-year study period, 204 clinical isolates were obtained from the University Hospital “Dr. José Eleuterio González". Less than half of the patients were in the COVID unit (32.8%, n = 67), followed by the intensive care unit (23.0%, n = 47), surgical intensive care unit (20.0%, n = 41), medicine ward (9.3%, n = 19), surgical ward (5.9%, n = 12), orthopaedics (4.4%, n = 9), emergency room (2.0%, n = 4), medical/surgical ward (1.0%, n = 2), plastic surgery ward (1.0%, n = 2), and neurology (0.5%, n = 1).
Isolates were recovered from lower respiratory tract infection ([endotracheal aspirate, bronchoalveolar lavage and sputum] 78.9%, n = 161), skin and soft tissue ([wound and tissue] 10.8%, n = 22), abscess (4.4%, n = 9), bone (2.9%, n = 6), catheter (1.5%, n = 3), blood (1%, n = 2), and synovial fluid (0.5%, n = 1).
Antimicrobial susceptibility profile and carbapenem resistance-associated genes
Isolates had resistance greater than 90% (n = 184) for imipenem, meropenem, piperacillin-tazobactam, cefepime, ceftazidime, and levofloxacin. On the contrary, isolates presented low percentages of resistance to doxycycline (11.3%, n = 25) and no resistance to colistin (minimal inhibitory concentration ≤ 2 μg/mL), as shown in Table I. After isolates were classified according to their susceptibility profiles, 87.3% (n = 178) were classified as MDR, 7.4% (n = 15) were XDR, and 50.5% (n = 103) of the isolates were classified as DTR. Furthermore, the OXA-51 gene was detected in all the isolates and the OXA-24 gene in 95% (n = 194) of the isolates. OXA-24 positive isolates were all confirmed by sequencing as OXA-72 variant, subtype of OXA-24. OXA-23 and OXA-58 genes were not detected in any of the isolates (Table I).
Table I.
Antimicrobial susceptibility of A. baumannii isolates
| Characteristic |
Main building No. (%) |
Secondary building No. (%) |
Total No. (%) |
||||||
|---|---|---|---|---|---|---|---|---|---|
| Total of isolates |
141 |
63 |
204 |
||||||
| Antimicrobial susceptibility profile | |||||||||
| Antibiotic | S | I | R | S | I | R | S | I | R |
| Piperacillin tazobactam | 11 (7.8) | 1 (0.7) | 129 (91.4) | 5 (7.9) | 0 (0.0) | 58 (92.0) | 16 (7.8) | 1 (0.5) | 187 (91.7) |
| Ampicillin-sulbactam | 54 (38.3) | 15 (10.6) | 72 (51.1) | 42 (66.7) | 4 (6.3) | 17 (88.9) | 96 (47.1) | 19 (9.3) | 89 (43.6) |
| Cefepime | 11 (7.8) | 3 (2.1) | 127 (90.1) | 6 (9.5) | 0 (0.0) | 57 (90.5) | 17 (8.3) | 1 (0.5) | 184 (90.2) |
| Ceftazidime | 8 (5.7) | 1 (0.7) | 132 (93.6) | 7 (11.1) | 0 (0.0) | 56 (88.9) | 15 (7.3) | 1 (0.5) | 188 (92.6) |
| Imipenem | 9 (6.4) | 0 (0.0) | 132 (93.6) | 5 (7.9) | 1 (1.6) | 57 (90.5) | 14 (6.9) | 1 (0.5) | 189 (92.6) |
| Meropenem | 10 (7.1) | 0 (0.0) | 131 (92.9) | 5 (7.9) | 1 (1.6) | 57 (90.5) | 15 (7.3) | 1 (0.5) | 188 (92.2) |
| Gentamicin | 16 (11.3) | 18 (12.8) | 107 (75.8) | 8 (12.7) | 13 (20.6) | 42 (66.7) | 24 (11.8) | 24 (11.8) | 149 (73.4) |
| Levofloxacin | 9 (6.4) | 1 (0.7) | 131 (92.9) | 5 (7.9) | 0 (0.0) | 58 (92.0) | 14 (6.9) | 1 (0.5) | 189 (92.6) |
| Doxycycline | 117 (82.9) | 2 (1.4) | 22 (15.6) | 62 (98.4) | 0 (0.0) | 1 (1.5) | 179 (87.7) | 2 (1.0) | 23 (11.3) |
| Tigecycline | 50 (35.5) | 29 (20.6) | 62 (44.0) | 19 (30.15) | 11 (17.5) | 33 (52.4) | 69 (33.8) | 40 (19.6) | 95 (46.6) |
| Colistin | 0 (0.0) | 141 (100.0) | 0 (0.0) | 0 (0.0) | 63 (100.0) | 0 (0.0) | 0 (0.0) | 204 (100) | 0 (0.0) |
| Antimicrobial resistance classification | |||||||||
| MDR | 119 (84.4) | 59 (93.6) | 178 (87.3) | ||||||
| XDR | 15 (7.4) | 0 (0.0) | 15 (7.4) | ||||||
| DTR | 84 (59.6) | 19 (30.6) | 103 (50.5) | ||||||
| Carbapenem resistance associated genes | |||||||||
| OXA-23 | 0 (0.0) | 0 (0.0) | 0 (0.0) | ||||||
| OXA-24 | 134 (95.0) | 60 (90.2) | 193 (95.0) | ||||||
| OXA-72 variant | 134 (95.0) | 60 (90.2) | 193 (95.0) | ||||||
| OXA-51 | 141 (69.1) | 63 (30.9) | 204 (100) | ||||||
| OXA-58 | 0 (0.0) | 0 (0.0) | 0 (0.0) | ||||||
DTR: difficult-to-treat resistant; I: intermediate; MDR, multidrug-resistant; R: resistance; S: susceptible; XDR, extensive drug-resistant.
Clonal diversity
The PFGE analysis of 204 isolates showed 38 distinct restriction patterns (data not shown). Only 23 isolates presented unique pulsotypes and 181 isolates were grouped into 15 remaining patterns. Isolates that presented 100% similarity in their restriction pattern were classified as clones. Of the total clones, 3 presented more than twenty isolates and were classified as predominant clones. Clone A was the most predominant (22.1%, n = 45), followed by clone B (20.1%, n = 41), and clone C (10.3%, n = 21). In addition, clone D (8.8%, n= 18), clone E (6.9% n=14), clone F (5.4%, n = 11), clone G (2.9%, n = 6), clone H (2.9%, n = 6), clone I (2.5%, n = 5), clone J (2.0%, n = 4), and clones K, L, M, N and O (1.0%, n = 2, each) were detected.
MLST analysis revealed four different sequence types (ST1694, ST758, ST124, and ST490) in 19 isolates. The clones identified by PFGE did not correspond perfectly to the sequence STs obtained through MLST. ST758 and ST124 belong to clonal complex (CC) 636, ST490 belongs to CC110 and ST1694 is not assigned to any clonal complex. Two new ST were identified, 20-0013 strain showed 6 matched alleles close to ST233/ST758/ST1694 and 21–0535 strain showed 5 matched alleles close to ST758 and ST1973. Clones A, B, G and I correspond to ST1694; clones C, D, and J correspond to ST758; clones D, I, and K correspond to ST124; and clone E corresponds to ST490 (Table II).
Table II.
Characteristics of the A. baumannii isolates selected for MLST analysis
| CC | ST | Clone | Isolate | Year | Building | Ward | Specimen | Resistance classification | OXA-72 |
|---|---|---|---|---|---|---|---|---|---|
| 636 | 124 | K | 19–0149 | 2019 | Main | SICU | ET | MDR/DTR | Yes |
| I | 20–0026 | 2020 | Main | SICU | ET | MDR/DTR | Yes | ||
| D | 21–0123 | 2021 | Main | Surg | Abscess | MDR/DTR | Yes | ||
| D | 21–0175 | 2021 | Secondary | ICU | Wound | MDR | Yes | ||
| 758 | D | 20–0205 | 2020 | Secondary | ICU | ET | MDR | Yes | |
| C | 20–0216 | 2020 | Secondary | ICU | ET | MDR | Yes | ||
| C | 20–0221 | 2020 | Secondary | ICU | ET | MDR | Yes | ||
| NR | 20–0296 | 2020 | Secondary | ICU | Abscess | non-MDR | No | ||
| J | 21–0056 | 2021 | Secondary | ICU | ET | MDR/DTR | Yes | ||
| 110 | 490 | E | 19–1597 | 2019 | Main | ICU | ET | MDR | Yes |
| N/A | 1694 | G | 19–0705 | 2019 | Main | ICU | ET | MDR/DTR | Yes |
| B | 19–1454 | 2019 | Main | SICU | ET | XDR/DTR | Yes | ||
| NR | 19–2484 | 2019 | Main | Surg | Wound | MDR | Yes | ||
| NR | 19–2600 | 2019 | Main | IM | Sputum | non-MDR | No | ||
| A | 20–0001 | 2020 | Main | IM | Sputum | MDR/DTR | Yes | ||
| I | 20–0033 | 2020 | Main | SICU | ET | XDR/DTR | Yes | ||
| A | 20–0082 | 2020 | Main | ICU | ET | MDR/DTR | Yes | ||
| A | 20–0098 | 2020 | Main | ICU | ET | XDR/DTR | Yes | ||
| A | 20–0107 | 2020 | Main | ICU | ET | MDR/DTR | Yes | ||
| N/A | N/A | B | 21–0535 | 2021 | Main | Surg | ET | XDR/DTR | Yes |
| N/A | N/A | F | 20–0013 | 2020 | Main | ICU | ET | MDR | Yes |
DTR: difficult-to-treat resistant; ET: endotracheal aspirate; ICU: intensive care unit; IM: medicine ward; MDR: multidrug-resistant; Surg: surgical ward; Ortho: orthopaedics; non-MDR: non-multidrug-resistant; N/A: not applicable; NR: not related; XDR: extensive drug-resistant; SICU: Surgical Intensive Care Unit.
Description of intrahospital bacterial dissemination
According to our results, both the surgical ICU and the ICU were the hospital wards with the greatest clonal diversity. Clones A, B, and D predominated in the different hospital wards tested.
In both buildings of the hospital (main and secondary), exclusive clones to each building were detected, which were not detected in the other building. In the main building, clones A, B, D, E, and I were detected, mainly in the intensive care unit, surgical intensive care unit, medicine ward, and surgical ward. Furthermore, although clone H was the only clone detected in Neurology, it was also detected in different wards located on different levels of the main building (emergency room, surgical intensive care unit, medical/surgical ward, and surgical ward) (Figure 1). No instances of clones C or L were found within the main building. Instead, the secondary building showed the presence of clones A, B, C, D, E, H, J, and L. Neither clones F, G, I, K, M, N, or O were detected in that building. Four predominant clones (A, B, E, and H) were present in the main building and promptly emerged in the secondary building, which persisted throughout the study period. In contrast, two clones (D and J) were initially present in the secondary building and later emerged in different wards of the main building (Figure 2).
Figure 1.
Distribution of A. baumannii clones in the buildings of the University Hospital. The distribution of the several relevant floors of the main building (A, B, C, D) and the secondary building (E) is shown. A) The second floor contains the Medicine and Neurology wards. B) The third floor contains the Plastic Surgery and Obstetrics wards. C) The fourth floor contains the Surgical, Orthopaedics, and Medical/Surgical wards. D) The fifth floor contains the Intensive Care Units and Surgical Intensive Care Unit. E) The secondary building.
Figure 2.
Temporal and spatial distribution of A. baumannii clones in the buildings of the University Hospital. Dates represent the first isolation of each clone in the respective building. A) Main building (which opened in 1944), in which clones F, G, I, K, M, N, and O were exclusively detected. B) The secondary building (which opened in March 2020), in which clones C and L were exclusively detected.
All four detected STs were found in from the main building while only ST758 was distributed in the secondary building.
Discussion
A. baumannii has become a critical threat worldwide as it can cause frequent nosocomial outbreaks due to its ability to survive in the hospital environment, primarily targeting patients with comorbidities or in the ICU, who could be vulnerable to A. baumannii infections due to prolonged hospitalization, and other risk factors such as invasive procedures, host factors, length of ICU stay, prior use of broad-spectrum antimicrobial agents and compromised immune system [5,14,15].
This study assessed the clonal dissemination of A. baumannii clinical isolates in two hospital buildings from a tertiary-care hospital in Mexico. Our hospital's analysis of clonal temporal and spatial distribution showed long-term persistence and dissemination in some specific hospital wards, including the critical wards (surgical ICU and the ICU). In our hospital, the clinical impact of the endemic presence of resistant A. baumannii on the nosocomial environment has led to stricter infection control measures in surgical practice, reinforced antibiotic stewardship programs for antimicrobial use optimization, and increased reliance on isolation rooms to prevent nosocomial transmission, all of which has strained hospital resources. Prior to the COVID-19 pandemic, the main building of our hospital was the only active building. The secondary building was still inactive for patient care, and when the COVID-19 pandemic occurred in our region, this building was inaugurated exclusively for COVID-19 diagnosis and patients' admittance and clinical care. The main building remained exclusively for the treatment of non-COVID-19 patients. In our hospital, the rate of hospital-acquired pneumonia increased within that specific timeline, most of which were treated at the COVID hospital, which might explain the rate of A. baumannii isolates (32.8%) detected in that building. Also, from July 2020 to December 2021, an intensive therapy ward from the main building was closed and thus the number of intubated patients decreased.
Persistence of MDR bacteria within a hospital can occur either due to clone appearance and spread or persistence and coexistence of many clonal lineages [16]. According to our results, both scenarios are likely in our hospital because multiple clones were found, and the same groups were found in different wards and buildings of the hospital. The bacterial colonization of new hospitals has been reported before. An endemic A. baumannii clone OXA-23 producer was disseminated into a new ICU in a Brazilian hospital. Whilst the ICU environment was not contaminated, the authors suggested that the hands of healthcare workers could have contributed to the dissemination [17]. The study of the dynamics of the bacterial colonization process in a newly opened hospital ward from Berlin showed that after only a few weeks, the detection of antibiotic resistance determinants increased on the hospital floor, in which Acinetobacter was the most abundant genera [18]. Carbapenem-resistant Pseudomonas aeruginosa strains were detected colonizing the sewage system five months after opening the surgical intermediate and ICU of a newly constructed building in Germany [19]. A possible explanation for the clonal diversity and high dissemination of A. baumannii could be the transfer of patients or healthcare workers from one building to another or within hospital wards. In our hospital, healthcare workers did not move from one building to the other. COVID positive patients detected from the main building were moved into the COVID building in less than 24 h after the COVID result, which might have influenced the dynamics of intrahospital dissemination of A. baumannii clones. Patients were also moved in their same hospital beds and hospital equipment, which might have helped in the persistence of A. baumannii. COVID patients had individual rooms whereas patients in the ICU from the main building had room separations but shared common areas. In another study, the bacteria found in bedrails resembled the skin microbiota of patients and MDR associated genes were also found on the hospital room surfaces [23]. In our hospital, OXA-24 producer clones disseminated from the main building to the secondary building after five months, confirming intrahospital dissemination. Additionally, the ability of A. baumannii to survive desiccation with minimal nutrient requirements facilitates transmission via contaminated hands of healthcare workers [20] or medical equipment, coupled with the ability to live on environmental surfaces for up to 60 days, even retaining its virulence after extended starvation [21,22]. In our study, we failed to perform environmental sampling to confirm this potential environmental transmission of A. baumannii through the hospital.
In hospital settings, patients may be more exposed to carbapenem-resistant A. baumannii. Carbapenemase-producing A. baumannii strains were most involved in the hospital dissemination, as most clones harboured OXA-51 and OXA-24 genes. In Latin American countries, carbapenemases with the greatest dissemination are class D enzymes, which include OXA-23, OXA-58, OXA-72, OXA-143, and OXA-253. However, in northern Mexico, OXA-72 genes are more predominant [24,25], as shown in our results.
Regarding STs detected in our study, ST758 and ST124 belong to the Ibero-American CC636, a complex widespread in Europe, Asia, South Africa, and in America in the United States, Mexico, and Colombia. CC636 is a high-risk clone frequently presenting MDR, including carbapenem resistance [[25], [26], [27]]. ST490 belongs to CC110 while ST1694 is not assigned to any clonal complex. CC110 has been previously reported in Mexico, Brazil, Colombia, Argentina, the United States, and Korea [25,26,28]. ST1694, ST758, and ST490 found in this study have been previously reported in Mexico [25,29], suggesting a wide distribution of their clones. Instead, the presence of ST124 in Mexico is reported for the first time; previous studies reported it in Colombia and the United States [26,30]. Of note, none of the STs found in this study were associated with CC92Oxf/CC2Pas, reported as the most prevalent A. baumannii MDR in 34 countries [31].
During the pandemic period, antimicrobial resistance increased in different microorganisms including A. baumannii [32]. In our study, bacterial isolates were resistant to commonly prescribed antibiotics for A. baumannii infections. Most isolates showed resistance greater than 90% to carbapenems, cephalosporins, and fluoroquinolones. Susceptibility was shown only to doxycycline (87.7%) and to colistin (100%). Our data shows an increase (20−70%) in resistance to levofloxacin, gentamicin, ceftazidime, imipenem, meropenem, and tigecycline in our hospital from the 2007–2012 period [33] to the 2019–2021 period. Similarly, drug resistance rates are steadily increasing among A. baumannii isolates worldwide, according to the data reported by the SENTRY Antimicrobial Surveillance Program [34], which reported high XDR rates in Europe (66.4%) and Latin America (61.5%), although we observed lower XDR rates (7.4%). Furthermore, half the isolates (50.5%) were DTR, which refers to non-susceptibility to all first-line antimicrobial agents. These data are concerning in our region, as the limitation of available therapeutic options for DTR infections might lead to treatment failure and higher mortality rates [35]. In our region, treatment options for DTR A. baumannii should also include new antimicrobial agents, such as eravacycline, sulbactam-durlobactam, and cefiderocol, which show improved clinical outcomes [36,37]. DTR surveillance of A. baumannii strains should be incorporated into our hospital as a routine practice.
Some limitations of this study was only testing the isolates using disk diffusion methods and no broth microdilution, besides not including all antimicrobial agents required to be able to perform pan-drug resistance classification as recommended, which could be the included in following studies. Likewise, the assessment of other mechanisms responsible for drug resistance by other methodologies could provide detailed insight into drug resistance evolution and dissemination in our hospital setting. Lastly, we did not perform the analysis and surveillance of environmental samples, nor did we assess bacterial colonization in either patients or health workers, which could have aided the establishment of dissemination dynamics.
Conclusions
Long-term persistence and dissemination of A. baumannii clones were observed in specific hospital wards from two buildings in a tertiary-care hospital in Mexico, which disseminated after five months. High antimicrobial resistance was observed to most prescribed antibiotics for A. baumannii infections and carbapenemase-producing A. baumannii strains were most involved in the hospital dissemination. In addition, alarmingly high rates of MDR and DTR were observed in this hospital. Given the limitation of available therapeutic options for DTR infections in our hospital which might cause failed treatment and higher mortality rates, infection control programs should perform DTR surveillance and early recognition of the presence of MDR A. baumannii clones to prevent their dissemination within the hospital environment.
CRediT authorship contribution statement
Samantha Villarreal-Cruz: Methodology, Data curation, Formal analysis, Investigation, Validation, Visualisation, Writing – original draft, Writing – review & editing. Adrián Camacho-Ortiz: Resources, Supervision, Writing – review & editing. Samantha Flores-Treviño: Investigation; Visualisation, Writing – original draft, Writing – review & editing. Licet Villarreal-Treviño: Supervision, Writing – review & editing. Paola Bocanegra-Ibarias: Conceptualisation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Supervision, Validation, Visualisation, Writing – original draft, Writing – review & editing.
Funding statement
This work was supported by Fondo Sectorial de Investigacion para la Educacion of the Consejo Nacional de Ciencia y Tecnología (CONACyT) under Grant [number A1-S-16970].
Competing interests
The authors have no relevant financial or non-financial interests to disclose.
Acknowledgment
We are grateful to the Epidemiology Department for technical support and the Ethics Committee of the University Hospital “Dr. José Eleuterio González”.
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