Abstract
Background
Infectious outbreaks caused by carbapenemase-producing Enterobacterales (CPE) in hospitals constitute a global health threat.
Objective
To characterise CPE infectious outbreaks in public hospitals in Chile during 2017–2024.
Methods
Retrospective epidemiological surveillance study using national public health data across three periods: baseline pre-pandemic (2017–2019), pandemic (2020−2022), and post-pandemic (2023–2024).
Results
Seventy-two CPE outbreaks, 945 associated cases and 21 attributable deaths were notified. Median CPE outbreak size in the pre-pandemic period (4 cases) peaked during the pandemic (7 cases) and recovered afterwards post-pandemic (4 cases). Median outbreak duration decreased over time (pre-pandemic period: 75 days; pandemic: 45 days; post-pandemic: 9 days). Klebsiella pneumoniae was the primary cause (83.3% of outbreaks, 92.6% of cases) and KPC the most common carbapenemase detected (54.2% of outbreaks, 53.7% of cases). OXA-48-like and KPC + NDM co-production were observed from 2021 onwards, and IMP was first identified in 2024.
Conclusions
The size of CPE outbreaks in Chilean public hospitals increased significantly during the pandemic and shrunk back to pre-pandemic values afterwards. CPE outbreak duration decreased sharply from the pandemic onwards. Since 2021, carbapenemases detected in CPE hospital outbreaks have diversified in Chile.
Keywords: Infectious disease outbreaks, Cross infection, Enterobacterales, Carbapenems, Bacterial drug resistance
Highlights
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The study documents significant changes in the frequency, size, duration and attack rate of outbreaks caused by carbapenemase-producing Enterobacteriaceae (CPE) in Chilean public hospitals across three distinct epidemiological periods: prepandemic, pandemic and post-pandemic. It also shows a worrisome diversification of carbapenemases from the pandemic years onwards.
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The study presents comprehensive spatial and temporal data of CPE outbreaks at a national level, including relevant information about the number of patients at risk, the level of complexity of the hospitals where the outbreaks occurred, the clinical services affected, the anatomical location of the infections, the causative etiological agents and their carbapenemase-production mechanisms.
Introduction
Carbapenemase-producing Enterobacterales (CPE) pose a growing threat to public health due to their ability to spread rapidly and their resistance to carbapenems, which are considered last-resort antibiotics [1], [2], [3]. Five key carbapenemase enzymes cause most CPE infections globally: Klebsiella pneumoniae carbapenemase (KPC), New Delhi metallo-beta-lactamase (NDM), oxicilinase (OXA), imipenemase (IMP) and Verona Integron-encoded metallo beta-lactamase (VIM) [4]. CPE infection outbreaks are not infrequent in hospitals [5] and have been associated with high morbidity and mortality [6], [7], as well as considerable healthcare costs [8].
Before the coronavirus disease 2019 (COVID-19) pandemic, the emergence of CPE had been described in Latin America and the Caribbean, having KPC become endemic in some countries [9]. In Chile, the Public Health Institute reported the first indigenous CPE case in April 2012 [10] and documented an exponential increase of KPC (from 12 to 265 strains), NDM (from 1 to 40 strains), and VIM (from 1 to 17 strains) in the 2014–2017 period [11]. The COVID-19 pandemic was experienced in Chile in four waves, with the first wave occurring from May to August 2020 and the last from January to April 2022 [12]. Half-way into that exceptional epidemiological period, OXA-48-like carbapenemases were detected for the first time in the country in an outbreak caused by Klebsiella pneumoniae in May 2021 [13]. During the pandemic, CPE dissemination intensified in Latin American and Caribbean countries and multiple carbapenemase co-production was identified in some strains [14].
The frequency of infections caused by CPE in Chilean hospitals has been evaluated in diverse studies. A single-hospital pre-pandemic study conducted during 2012–2015 documented nosocomial acquisition in 77% of CPE cases, as well as the frequent detection of Klebsiella pneumoniae in 95.1% and OXA-48-like carbapenemases in 77% [15]. Another single-centre study conducted between 2018 and 2022 reported significant increase of CPE infections from 12.8% in the pre-pandemic era to 51.9% after the pandemic onset [16]. Similarly, a multi-centre study in 11 hospitals performed during 2019–2022 informed a rise of CPE infections from 11% to 38% while identifying strains with dual production of KPC and NDM [17]. However, there is a paucity of data on the specific burden of CPE infections and infection outbreaks in hospitals during the most recent post-pandemic years. This study aimed to characterise CPE infection outbreaks in public hospitals in Chile between 2017 and 2024, while describing their spatial and temporal evolution before, during, and after the COVID-19 pandemic.
Methods
Study design
Retrospective epidemiological surveillance study of CPE outbreaks in public hospitals documented in the System of Information of Quality and Healthcare Results (SICARS) of the Chilean National Program for the Prevention and Control of Healthcare-Associated Infections (PNCI) from January 2017 to December 2024. The Chilean legislation establishes a mandatory notification of outbreaks for all hospitals in the country through the SICARS computer platform; therefore, through the system, the notification of all hospital outbreaks across the country is accessible. Every hospital in the country has highly trained infection prevention and control teams, who are responsible for carrying out continuous active epidemiological surveillance and are responsible for making the proper notification of outbreaks, as well as implementing the necessary control measures according to national standards for epidemiological surveillance of healthcare-associated infections [18].
The public healthcare system of Chile includes a total of 196 hospitals distributed throughout 16 regions, with a total capacity of 26,592 beds and a coverage of 80% of the population (see hospitals' geographical distribution and characteristics in Supplementary Table 1). In contrast, although the private healthcare system comprises a total of 232 hospitals, it only serves 20% of the population. This study only includes information from hospitals within the public healthcare network, which are classified according to their problem-solving capacity and infrastructure as High Complexity, Medium Complexity and Low Complexity. The study was divided into three periods: pre pandemic (2017–2019), pandemic (2020–2022), and post-pandemic (2023–2024).
Outbreak ascertainment and case definitions
An outbreak of hospital-acquired infection caused by CPE was defined as an unusual and significant increase in the incidence of CPE infection among hospitalized patients, generally occurring within a short period of time, caused by one or more strains of carbapenemase-producing microbial species of Enterobacterales. Operationally, according to current legislation in Chile from the Ministry of Health, an outbreak is defined as the detection of three or more cases of infections with an epidemiological and microbiological link. The microbiological link between outbreak cases was defined as the detection of the same pathogenic species and the same carbapenemase enzyme in clinical cultures recovered from those cases. To be highlighted, all public hospitals in the country have at least commercial phenotypic detection tests for microbiological detection and typing of carbapenemases. Additionally, high-complexity hospitals may have PCR testing.
The size of a CPE outbreak was defined as the number of cases associated with the outbreak. CPE outbreak duration was defined as the time elapsed between the date of collection of the sample in which the strain or strains causing the first case (index case) were isolated and the date of identification of the last case associated with the outbreak. The reported outbreaks only include confirmed cases of infection that meet standardized operational definitions for the entire country by the Ministry of Health for epidemiological surveillance purposes.
Study variables
Variables collected included the spatial and temporal distribution of CPE hospital outbreaks, the number of associated cases and their age group, the number of deceased patients related to the infection through clinical medical audit, the number of contact patients at risk (patients hospitalized in the same unit or clinical service where a case of CPE infection has been detected during the same time period), the level of complexity of the hospitals where the outbreaks occurred, the clinical services affected, the anatomical location of the infections, the causative etiological agents and their carbapenemase-production mechanisms. Of note, we did not assess CPE screening among contacts. According to Chilean national guidelines, there is no recommendation or indication for collecting samples for colonization studies in hospitalized patients. Analyzing this variable could have introduced a confounding effect derived from potential differences in risk-adapted screening practices for CPE across hospitals. The main outcomes sought were the frequency, size, duration, attack and lethality rates of CPE outbreaks, and their proportion in relation to outbreaks caused by any Enterobacterales species.
Sources of information
Authorization was obtained from the Chilean Ministry of Health to make a secondary use of the database of hospital infection outbreaks recorded in SICARS, which contains the epidemiological information for each outbreak. The national hospital discharge database [19], which is freely accessible information published by the Department of Health Statistics and Information of the Chilean Ministry of Health, was also used to retrieve information on hospital discharges, national bed capacity, and hospital complexity.
Statistical analysis
Categorical variables were summarised as frequencies and quantitative variables as mean values and standard deviations or as medians and interquartile ranges, depending on whether data were normally distributed or not. The pre-pandemic period from 2017 to 2019 was considered the baseline period for comparing results between periods. Differences between periods in CPE outbreak size and duration were analysed using the Student's t-test or the Mann-Whitney test, depending on the normality of the data distributions. Differences between periods in attack and lethality rates and in the relative weight of CPE outbreaks were analysed using the chi-square test or Fisher's exact test. The hypothesis test for proportions was used to calculate confidence intervals for the differences between proportions, and the Bootstrap statistic was used to calculate the difference between medians.Statistical analyses were performed using Stata v. 18 (Stata Corp, TX, US).
Results
Between 2017 and 2024, the PNCI of the Chilean Ministry of Health received a total of 131 notifications of hospital-acquired infection outbreaks caused by enterobacteria and 1302 associated cases, including 72 CPE outbreaks (55.0% of total number of enterobacterial outbreaks), 945 associated cases (72.6% of total number of cases associated with enterobacterial outbreaks) and 21 attributable deaths (84.0% of total number of deaths attributable to any enterobacterial outbreak). Among Enterobacterales hospital outbreaks, those caused by CPE more than tripled in proportion over time (pre-pandemic: 6/30, 20.0%; pandemic: 34/59, 57.6%; post-pandemic: 32/42, 76.2%). Median pre-pandemic size of CPE outbreaks (4 cases, IQR 3–11 cases) peaked during the pandemic (7 cases, IQR 4–11 cases) and returned to the baseline value in the post-pandemic period (4 cases, IQR 3–6 cases). Median duration of CPE outbreaks declined across periods (pre-pandemic: 75 days, IQR 25–107 days; pandemic: 45 days, IQR 16–90 days; post-pandemic: 10 days, IQR 2–27 days). The attack rate of outbreaks rose markedly from the baseline pre-pandemic period (39/2769; 1.4%) to the pandemic (642/16,822; 3.8%) and the post-pandemic period (264/9537; 3.2%). (see details in Table 1 and Supplementary Table 2).
Table 1.
Description of outbreaks caused by carbapenemase-producing Enterobacterales in Chilean public hospitals, 2017–2024.
| Variables | 2017–2019 (A) |
2020–2022 (B) |
2023–2024 (C) |
Total (A + B + C) |
PE [95% CI] (p-value) (Difference B-A) |
PE [95% CI] (p-value) (Difference C-A) |
|---|---|---|---|---|---|---|
| No. of outbreaks (%)a | 6/30 (20.0) | 34/59 (57.6) | 32/42 (76.2) | 72/131 (55.0) | 37.6 [18.5–56.7] (<0.001) | 56.0 [36.7–75.3] (<0.001) |
| No. of associated cases (%)a | 39/158 (24.7) | 642/821 (78.2) | 264/323 (81.7) | 945/1302 (72.6) | 53.0 [45.7–60.3] (<0.001) | 57.0 [49.1–65.0] (<0.001) |
| No. of attributable deaths (%)a | 0/2 (0) | 4/6 (66.7) | 17/17 (100) | 21/25 (84.0) | 67.0 [29.4–100.5] (0.4) | 100 [100−100] (0.5) |
| No. of associated deaths (%)a | 1/5 (20.0) | 8/14 (57.1) | 29/31 (93.6) | 38/50 (76.0) | 37.0 [−6.6–80.6] (0.3) | 74.0 [38.0–110.0] (<0.001) |
| No. of exposed patients (%)a | 2769/6742 (41.1) | 16,822/20,693(81.3) | 9537/10,111(94.3) | 29,128/37,546 (77.6) | 40.0 [38.7–41.3] (<0.001) | 37.0 [35.6–38.4] (<0.001) |
| Median size, cases (IQR) | 4 (3−11) | 7 (5–11) | 4 (3–6) | 5 (4–9) | 7 [−1.4–9.4] (<0.001) | 4 [3.5–4.5] (<0.001) |
| Median duration, days (IQR) | 75 (25–107) | 47 (19–92) | 10 (2–27) | 29 (8–72) | 45.5 [27.4–63.6] (<0.001) | 9 [−2.3–20.3] (0.1) |
| Attack rate (%) | 39/2769 (1.4) | 642/16,822 (3.8) | 264/9537 (2.8) | 945/29,128 (3.2) | 2.4 [1.9–2.9] (<0.001) | 1.4 [0.9–2.0] (<0.001) |
| Attributable lethality rate (%) | 0/39 (0) | 4/642 (0.6) | 17/264 (6.4) | 21/945 (2.2) | 0.6 [0.0–1.2] (0.6) | 6.4 [3.5–9.4] (0.1) |
| Associated lethality rate (%) | 1/39 (2.6) | 8/642 (1.3) | 29/264 (11.0) | 38/945 (4.0) | −1.3 [−6.4–3.8] (0.5) | 8.4 [2.1–14.7] (0.1) |
Abbreviations: PE, Point Estimates; CPE, Carbapenemase-producing Entereobacteriaceae; IQR, Interquartile range.
In relation to any Entereobacteriaceae outbreak.
CPE outbreak notifications were received from hospitals in 11 out of the 16 Chilean regions (Antofagasta, Atacama, Coquimbo, Valparaíso, Metropolitan Santiago, Libertador General Bernardo O'Higgins, Maule, Biobío, Araucanía, Los Ríos and Los Lagos) during 2017–2024. Five of these regions (Metropolitan Santiago, Antofagasta, Valparaíso, Libertador General Bernardo O'Higgins and Araucanía) reported outbreaks in more than one study period. In particular, the Metropolitan region of Santiago was the only one affected before, during and after the pandemic, and accounted for the largest number of CPE outbreaks (n = 49, 59.7%), associated cases (n = 646, 68.9%) and attributable deaths (n = 13, 61.9%). In contrast, five regions (Arica, Tarapacá, Ñuble, Aysén and Magallanes) did not register any CPE outbreaks within the studied periods (see details in Table 2 and Supplementary Table 3).
Table 2.
Description of outbreaks caused by carbapenemase-producing Enterobacterales in Chilean public hospitals by region, 2017–2024.
| Regiona, b | Outbreaks No. (%) |
Cases No. (%) |
Attributable Deaths No. (%) |
Hospital Discharges No. |
Attack Rate per Discharge ‰ |
Attributable Lethality Rate % |
|---|---|---|---|---|---|---|
| Antofagasta | 5 (6.9) | 53 (5.6) | 1 (4.8) | 268,660 | 0.20 | 1.9 |
| Atacama | 1 (1.4) | 4 (0.4) | – | 155,470 | 0.03 | – |
| Coquimbo | 2 (2.8) | 106 (11.2) | 1 (4.8) | 365,716 | 0.29 | 0.9 |
| Valparaíso | 6 (8.3) | 35 (3.7) | – | 403,139 | 0.09 | 0 |
| Metropolitan Santiago | 43 (59.7) | 646 (68.4) | 13(61.9) | 2,851,576 | 0.23 | 2.0 |
| Libertador General Bernardo O'Higgins | 5 (6.9) | 31 (3.3) | . | 419,124 | 0.07 | – |
| Maule | 1 (1.4) | 5 (0.5) | – | 619,364 | 0.01 | – |
| Bío Bío | 1 (1.4) | 19 (2.0) | 3 (14.3) | 1,036,359 | 0.02 | 15.8 |
| Araucanía | 5 (6.9) | 28 (3.0) | 2 (9.5) | 648,705 | 0.04 | 7.1 |
| Los Ríos | 1 (1.4) | 3 (0.3) | 0 (0) | 279,685 | 0.01 | – |
| Los Lagos | 2 (2.8) | 15 (1.6) | 1 (4.8) | 484,766 | 0.03 | 6.7 |
| Total | 72 (100) | 945 (100) | 21 (100) | 7,532,564 | 0.13 | 2.2 |
Ordered from North to South.
The regions of Arica, Tarapacá, Ñuble, Aysén and Magallanes did not have any EPC outbreaks during 2017–2024.
Nearly all CPE outbreaks occurred in high-complexity hospitals (n = 71, 98.6%) and most of them were identified in adult critical care units (CCUs) (n = 45, 62.5%). Of note, before the pandemic there was an exceptional report of an outbreak that simultaneously affected adults admitted to the CCU and wards. However, simultaneous outbreaks in both adult CCUs and wards became more common during the pandemic (n = 5) and post-pandemic (n = 8) periods. Among paediatric patients, two simultaneous outbreaks were identified at the same time in CCUs and wards, one during the pandemic and another after the pandemic (see details in Table 3).
Table 3.
Description of outbreaks of carbapenemase-producing Enterobacterales in Chilean public hospitals by hospital type, clinical service affected and anatomical location of infection, 2017–2024.
| Variables (%) | 2017–2019 No. (%) (A) |
2020–2022 No. (%) (B) |
2023–2024 No. (%) (C) |
Total No. (%) (A + B + C) |
PE [95% CI] (p-value) (Diff. B-A) |
PE [95% CI] (p-value) (Diff. C-A) |
|---|---|---|---|---|---|---|
| Hospital Type | 6 (100.0) | 34 (100.0) | 32 (100.0) | 72 (100.0) | – | – |
| High Complexity | 6 (100.0) | 33 (97.1) | 32 (100.0) | 71 (98.6) | −3.0 [−8.7–2.7] (0.7) | – |
| Medium and Low Complexity | 0 (0.0) | 1 (2.9) | 0 (0.0) | 1 (1.4) | 2.9 [−2.7–8.5] (0.7) | – |
| Clinical Service | 6 (100.0) | 34 (100.0) | 32 (100.0) | 72 (100.0) | – | – |
| Adult Critical Care Unit | 5 (83,3) | 26 (76.5) | 14 (43.8) | 45 (62.5) | −6.0 [−39.2–27.2] (0.7) | −39.0 [−73.6 - -4.4] (0.1) |
| Adult Ward and Critical Care Unit | 1 (16,7) | 5 (14.7) | 8 (25.0) | 14 (19.4) | −2.0 [−34.4–30.4] (0.9) | 8.0 [−25.6–41.6] (0.7) |
| Adult Ward | 0 (0.0) | 3 (8.8) | 9 (31.0) | 12 (16.7) | 9.0 [−0.6–18.6] (0.5) | 31.0 [15.0–47.0] (0.1) |
| Paediatric Critical Care Unit and Ward | 0 (0.0) | 0 (0.0) | 1 (3.1) | 1 (1.4) | – | 3.0 [−2.9–8.9] (0.7) |
| Infection location | 39 (100.0) | 642 (100.0) | 264 (100.0) | 945 (100.0) | – | – |
| Ventilator-associated pneumonia | 5 (12.8) | 180 (28.0) | 44 (16.7) | 229 (24.2) | 15.0 [3.9–26.1] (0.04) | 4.0 [−7.5–15.5] (0.5) |
| Urinary Tract Infection | 6 (15.4) | 149 (23.2) | 58 (22.0) | 213 (22.5) | 8.0 [−3.7–19.7] (0.3) | 7.0 [−5.3–19.3] (0.3) |
| Bloodstream Infection | 2 (5.1) | 155 (24.1) | 50 (18.9) | 207 (21.9) | 19.0 [11.4–26.6] (0.01) | 14.0 [5.7–22.3] (0.03) |
| Lower Respiratory Infection Other Than Pneumonia | 6 (15.4) | 65 (10.1) | 21 (8.0) | 92 (9.7) | −5.0 [−16.4–6.4] (0.3) | −7.0 [−18.7–4.7] (0.2) |
| Skin Infections, mucous membranes and Burns | 2 (5.1) | 32 (5.0) | 21 (8.0) | 55 (5.8) | 0.0 [−7.1–7.1] (1.0) | 3.0 [−4.6–10.6] (0.5) |
| Surgical Wound Infection | 5 (12.8) | 25 (3.9) | 22(8.3) | 52 (5.5) | −9.0 [−19.7–1.7] (0.01) | −5.0 [−16.1–6.1] (0.3) |
| Intra-abdominal Infection | 6 (15.4) | 12 (1.9) | 27 (10.2) | 45 (4.8) | −13.0 [−24.3 - -1.7] (<0.001) | −5.0 [−16.5–6.5] (0.3) |
| Non-Ventilator-associated Pneumonia | 5 (12.8) | 18 (2.8) | 15 (5.7) | 38 (4.0) | −10.0 [−20.63–0.6] (0.001) | −12.4 [−23.0 to −1.8] (<0.001) |
| Central Nervous System Infection | 2 (5.1) | 4 (0.6) | 3 (1.1) | 9 (1.0) | −4.4 [−11.3–2.5] (0.04) | −4.0 [−10.9–29.5] (0.06) |
| Unclassified Infections | 0 (0.0) | 0 (0.0) | 2 (0.8) | 2 (0.2) | – | 0.8 [−0.3–1.9] (0.6) |
| Osteomyelitis | 0 (0.0) | 1 (0.2) | 1 (0.4) | 2 (0.2) | 0.2 [−0.2–0.6] (0.8) | 0.4 [−0.4–1.2] (0.7) |
| Mediastinitis | 0 (0.0) | 1 (0.2) | 0 (0.0) | 1 (1.0) | 0.2 [−0.2–0.6] (0.8) | – |
Abbreviations: PE, Point Estimates.
The most frequent infections experienced by cases associated to CPE outbreaks were Ventilator-Associated Pneumonia (VAP) (229 cases, 24.2%), Urinary Tract Infection (UTI) (213 cases, 22.5%) and Bloodstream Infection (BSI) (207 cases, 21.9%), together accounting for 68.6% of the total number of cases. Significant temporal variations were observed in the proportions of VAP when comparing the baseline pre-pandemic period (12.8%) with the pandemic period (28.0%). Similarly, BSI grew significantly from the pre pandemic period (5.1%) to the pandemic (24.1%) and the post pandemic period (18.9%). In contrast, a comparison of proportions of other infection types between the pre-pandemic and the pandemic period showed remarkable declines in intra-abdominal infection (from 15.4 to 1.9%), non-ventilator-associated pneumonia (from 12.8 to 2.8%), surgical wound infection (from 12.8 to 3.9%), and central nervous system infection (from 5.1 to 0.6%) (see details in Table 3 and Supplementary Table 4).
Klebsiella pneumoniae was identified as the main etiological agent of CPE outbreaks throughout the three study periods, causing a total of 60 outbreaks (83.3%) and 875 cases (92.6%). Other Enterobacterales species recovered in smaller proportions were Enterobacter cloacae (8 outbreaks, 11.1%; 49 cases, 5.2%), Serratia marcescens (3 outbreaks, 4.2%; 18 cases, 1.9%) and Citrobacter freundii (1 outbreak, 1.4%; 3 cases, 0.3%). KPC was the most common carbapenemase-producing enzyme detected in a total of 483 (51.1%) cases, followed by NDM, in 365 (38.6%) cases, and OXA-48-like, in 62 (6.6%) cases. From the pandemic period onwards, new carbapenem-producing enzymes were detected for the first time, alone or in dual co-production, including Klebsiella pneumonie KPC + NDM (n = 13), Enterobacter cloacae KPC (n = 13) and KPC + NDM (n = 6), Serratia marcescens KPC + NDM (n = 7), and Klebsiella pneumoniae IMP (n = 3). Among Klebsiella pneumoniae carbapenemase-producing enzymes, KPC declined in proportion substantially from baseline pre-pandemic years (57.6%) to post-pandemic years (34.3%) whereas NDM grew in prevalence between the two periods (42.4 vs. 63.0%) (see Table 4 and Supplementary Table 5 for further details).
Table 4.
Description of etiological agents of carbapenemase-producing Enterobacterales outbreaks in Chilean public hospitals, 2017–2024.
| Etiological Agents (%) | 2017–2019 No. (%) (A) |
2020–2022 No. (%) (B) |
2023–2024 No. (%) (C) |
Total No. (%) (A + B + C) |
PE [95% CI] (p-value) (Difference B-A) |
PE [95% CI] (p-value) (Difference C-A) |
|---|---|---|---|---|---|---|
| Klebsiella pneumoniae | 33 (100.0) | 623 (100.0) | 219 (100.0) | 875 (100.0) | ||
| KPC | 19 (57.6) | 376 (60.4) | 75 (34.3) | 470 (53.7) | 2.0 [41.2–74.8] (0.8) | −24.0 [−42.0 - -6.0] (0.01) |
| NDM | 14 (42.4) | 175 (28.1) | 138 (63.0) | 327 (37.4) | −14.0 [−31.2–3.2] (0.08) | 21.0 [3.0–39.0] (0.02) |
| OXA-48- Like | 0 (0.0) | 59 (9.5) | 3 (1.4) | 62 (7.1) | 9.5 [7.2–11.8] (0.06) | 0.1 [−0.3–0.5] (0.9) |
| KPC + NDM | 0 (0.0) | 13 (2.1) | 0 (0.0) | 13 (1.5) | 2.1 [1.0–3.2] (0.4) | – |
| IMP | 0 (0.0) | 0 (0.0) | 3 (1.4) | 3 (0.3) | – | 1.4 [−0.02–3.0] (0.5) |
| Enterobacter cloacae | 3 (100.0) | 8 (100.0) | 38 (100.0) | 49 (100.0) | – | 34.0 [18.9–49.1] (0.2) |
| KPC | 0 (0.0) | 0 (0.0) | 13 (34.2) | 13 (26.5) | 100 [100–100] (0.001) | 50.0 [34.1–65.9] (0.1) |
| NDM | 0 (0.0) | 8 (100.0) | 19 (50.0) | 27 (55.1) | – | 16.0 [4.3–27.7] (0.5) |
| KPC + NDM | 0 (0.0) | 0 (0.0) | 6 (15.8) | 6 (12.4) | – | −100 [−100−−100] (<0.001) |
| VIM | 3 (100) | 0 (0.0) | 0 (0.0) | 3 (6.1) | 100 [−100−−100] (0.001) | – |
| Serratia marcescens | – | 11 (100.0) | 7 (100.0) | 18 (100) | – | – |
| NDM | – | 11 (100) | – | 11 (61.1) | – | – |
| KPC + NDM | – | – | 7 (100) | 7 (63.6) | – | – |
| Citrobacter freundii | 3 (100.0) | 0 (0.0) | 0 (0.0) | 3 (100.0) | – | – |
| NDM | 3 (100.0) | 0 (0.0) | 0 (0.0) | 3 (100.0) | – | – |
| Total cases | 39 (100.0) | 642 (100.0) | 264 (100.0) | 945 (100) |
Abbreviations: PE, Point Estimates; KPC, Klebsiella pneumoniae carbapenemase; NDM, New Delhi metallo beta-lactamase; OXA, Oxicilinase; IMP, Imipenem beta-lactamase; VIM: Verona integron-encoded metallo beta-lactamase.
Discussion
The present study documents significant temporal variations in the frequency, size, duration and attack rate of infectionoutbreaks caused by CPE in public hospitals in Chile across the pre-pandemic, pandemic, and post-pandemic years. It also identifies a worrisome diversification of carbapenemase producers and a significant increase in the proportion of CPE outbreaks among outbreaks caused by any Enterobacterales species from the pandemic onset onwards. Our results align with those of previous epidemiological and clinical studies conducted in the region of Americas [9], [14] and Chile [11], [13], [15], [16], [17]. It is important to note that CPE surveillance must detect transmission early while avoiding false outbreak signals. Single cases and even pairs of cases may arise independently due to importation, admission of previously colonized patients, or improved screening intensity. Requiring three or more cases in a defined time–place window increases specificity, reducing the likelihood that chance or unrelated introductions are misclassified as an outbreak, while still maintaining acceptable sensitivity for early detection. The Chilean operational definition of an outbreak is more stringent that those of the World Health Organization, CDC and ECDC, where two or more cases with an epidemiological link are considered. However, the minimum requirement of three related cases is aligned with outbreak definitions established in other national public health agencies [20].
Interestingly, the size of CPE outbreaks peaked during the COVID-19 pandemic while it was substantially and similarly smaller in the pre- and post-pandemic periods. The correlation between CPE outbreaks and the COVID-19 pandemic has been attributed to the increased use of wide-spectrum antibiotic in COVID-19 patients [21], [22], [23]. In addition, most patients with COVID-19 required admission to CCU and were connected to invasive devices such as mechanical ventilation and central venous catheters, which are associated with increased healthcare-associated infections, including those due to CPE [24]. Indeed, adult patients receiving critical care were the main group of cases associated with CPE outbreaks in our study, and VAP and BSI, typical CCU infections, were observed to increase significantly during the pandemic. However, these results should be interpreted with caution, since they reflect a correlation between occurrence of CPE outbreaks and the pandemic but not a cause-effect association.
Intriguingly, while the number of CPE outbreaks increased over the course of the study, they decreased in size after the pandemic and in duration, both during and after the pandemic. One could speculate that a potentially growing rate of CPE carriage among patients admitted to hospital, because of inadequate antibiotic consumption practices in the general population, might result in increased risk of CPE transmission from carrier to non-carrier inpatients and, ultimately, in increased risk of CPE outbreak occurrence. In this regard, in a previous study using information extracted from the National Medical Supply Centre of Chile, we reported that the purchase of carbapenem antibiotics, as a proxy of antibiotic consumption in the Chilean population, showed a 3-fold increase from 0.02 units per person during the pre-pandemic years to 0.06 units per person in 2023 [25]. On the other hand, a possible explanation for the decrease in size and duration of outbreaks after the pandemic could be attributed to the global strategy recommended by the World Health Organization to strengthen and scale up genomic surveillance around the world once the pandemic was over [26]. Actions to implement this strategy include the use of rapid molecular screening and genomic sequencing technologies for surveillance of pathogens with pandemic and epidemic potential, such as CPE and other multi-drug resistant bacteria. Diverse studies conducted in other countries in recent years have shown the usefulness of these genomic tools to detect and control hospital outbreaks in less time [27], [28].
The attack rate of CPE outbreaks rose significantly during the pandemic and remained high afterwards. This result could be indicative of a growing ability of carbapenemase-producing strains to diversify and spread among exposed patients. To be noted, new carbapenemase producers (Enterobacter cloacae KPC and Klebsiella pneumoniae IMP) and carbapenemase combinations (Klebsiella pneumoniae KPC + NDM, Enterobacter cloacae KPC + NDM, Serratia marcescens KPC + NDM) that were involved in CPE outbreaks appeared during and after the pandemic, reflecting the diversification of causal strains. To be noted, no carbapenemase-producing Escherichia coli cases associated to hospital outbreaks were notified during the study period, despite routine surveillance detection of this enterobacterium in Chile. This result is consistent with those of other studies that have reported the unfrequent involvement of Escherichia coli in hospital outbreaks [29].
Our results are in consistency with the emergence of dual and multiple carbapenemase combinations in Latin America and globally, especially in the post-pandemic era [17], [30], [31]. Particularly surprising was the detection of several strains of Klebsiella pneumoniae IMP in 2024. Such strains had only been detected before in some studies conducted in East Asian countries [32], [33]. The diversification of carbapenemase-producing strains reveals a gradually more complex epidemiology of CPE in Chile, posing a significant challenge to the treatment of infected cases. This study has some limitations. First, the secondary use of databases as sources of information could lead to selection bias and measurement bias resulting in lack of representativeness and poor data quality. However, mandatory notifications of healthcare-associated infection outbreaks are communicated to a centralised electronic public health information management system in Chile according to an epidemiological surveillance protocol that minimises the risk of underreporting and introducing bias in the data. Secondly, although the first pandemic wave in Chile started in May 2020 and the last pandemic wave ended in April 2022, for reasons of simplification we assumed 2020–2022 as the pandemic period. Nevertheless, we conducted a sensitivity analysis, and results did not vary significantly when modifying the timelines of three study periods according to the May 2020–April 2022 pandemic duration. Third, although no significant differences in attributable and associated outbreak lethality rates were observed over time, this result should be considered with caution, as it may be due to a low statistical power derived from the small number of deaths registered among CPE cases. Four, although the Public Health Institute of Chile has standardized and validated microbiological and molecular procedures for the detection of Enterobacterales and carbapenemases nationwide, it does not routinely or centrally maintain a detailed record of changes in the diagnostic tests used by individual hospitals. Consequently, variability in the uniform implementation of these procedures across hospitals and over the study period cannot be entirely ruled out.
In conclusion, CPE infection outbreaks in Chilean hospitals increased in frequency, complexity and attack rate during and after the pandemic, driven by the diversification of carbapenemase producers. In contrast, their size diminished substantially after the pandemic and their duration reduced, both during and after the pandemic.Ongoing genomic surveillance, robust prevention and infection control in hospitals, and development of new and more effective treatment options are essential to continue containing the challenging CPE outbreak threat in hospitals.
Credit authorship contribution statement
Cristian Lara: Writing – review & editing, Writing – original draft, Visualization, Software, Project administration, Methodology, Investigation, Formal analysis, Data curation, Conceptualization. Mauro Orsini: Formal analysis, Data curation. Mónica Pohlenz: Methodology, Formal analysis, Data curation. Alejandro Guerra: Formal analysis, Data curation. Sofía Kutscher: Formal analysis, Data curation, Conceptualization. Carmen Muñoz-Almagro: Writing – original draft, Visualization, Validation. Pedro Brotons: Writing – original draft, Validation, Supervision, Project administration, Methodology, Conceptualization.
Ethical approval statement
In accordance with the Chilean legislation, this study did not require a previous evaluation by a scientific ethics committee, as the analysis was conducted on aggregated public health epidemiological surveillance data, ensuring that no personally identifiable information was included.
Funding source
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Declaration of competing interest
No conflicts of interest to declare.
Acknowledgment
We are grateful to the infection control teams at each hospital in the country for their highly technical work and the timely and accurate reporting of information to the Chilean Ministry of Health.
Footnotes
Supplementary data to this article can be found online at https://doi.org/10.1016/j.gloepi.2026.100271.
Appendix A. Supplementary data
Supplementary material
References
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