Next Article in Journal
Human Antimicrobial Use in Bangladesh: Five-Year Trend Analysis Including COVID-19 Pandemic Era
Previous Article in Journal
Unexplained High Prevalence of ESBL-Escherichia coli Among Cattle and Pigs in Peru
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Antibiotics
Volume 14
Issue 9
10.3390/antibiotics14090866
antibiotics-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

Impact of the COVID-19 Pandemic on Carbapenem-Resistant Klebsiella pneumoniae in Northern Region, Brazil: A Shift Towards NDM Producers

by
Thalyta Braga Cazuza Barros
1,
Yan Corrêa Rodrigues
2,
Amália Raiana Fonseca Lobato
1,
Lívia Maria Guimarães Dutra
1,
Herald Souza dos Reis
1,
Ana Judith Pires Garcia
1,3,
Fernanda do Espírito Santo Sagica
4,
Cintya de Oliveira Souza
1 and
Danielle Murici Brasiliense
1,*
1
Bacteriology and Mycology Deparment, Evandro Chagas Institute, Ministry of Health, Ananindeua 67030-000, Pará, Brazil
2
Serra Talhada Academic Unit (UAST), Federal Rural University of Pernambuco (UFRPE), Av. Gregório Ferraz Nogueira, s/n, Serra Talhada 56909-535, Pernambuco, Brazil
3
Central Laboratory of the State of Pará, Belém 66823-010, Pará, Brazil
4
Education Deparment, Evandro Chagas Institute, Ministry of Health, Ananindeua 67030-000, Pará, Brazil
*
Author to whom correspondence should be addressed.
Antibiotics 2025, 14(9), 866; https://doi.org/10.3390/antibiotics14090866
Submission received: 17 July 2025 / Revised: 19 August 2025 / Accepted: 21 August 2025 / Published: 28 August 2025
(This article belongs to the Section Genetic and Biochemical Studies of Antibiotic Activity and Resistance)
Browse Figures
Review Reports Versions Notes

Abstract

Background: The global impact of the SARS-CoV-2 pandemic on antimicrobial resistance (AMR) patterns has been significant. In northern Brazil, Carbapenem-resistant Klebsiella pneumoniae (CRKP) are a major concern, with an observed shift from Klebsiella pneumoniae carbapenemase (KPC) to New Delhi metallo-β-lactamase (NDM) during the pandemic. Methods: This cross-sectional study analyzed 775 carbapenem-resistant K. pneumoniae isolates collected from 25 hospitals in the Brazilian Amazon Region (states of Pará and Acre) between 2018 and 2021. The isolates were tested for the presence of carbapenemase genes (blaKPC, blaNDM, blaOXA-48, blaIMP, blaVIM, blaAIM, blaDIM, blaGIM and blaSIM). Results: Of the isolates analyzed, n = 653/775 (84%) were carbapenemase producers, with the most prevalent being blaKPC n = 446/775 (57.5%) and blaNDM n = 243/775 (31.4%). A significant increase in NDM producers was observed during the pandemic, rising from n = 1/250 (8.4%) pre-pandemic to n = 222/525 (42.3%) during the pandemic, while KPC producers declined from n = 172/250 (68.8%) to n = 274/525 (52.2%) (p < 0.001). Adult intensive care units (ICUs) were the primary source of isolates n = 357/775 (46%), with a notable increase in tracheal secretion and surveillance swab samples during the pandemic. Regression analysis confirmed a strong upward trend in the prevalence of blaNDM (R2 = 0.778). Conclusions: The shift from KPC to NDM producers in northern Brazil highlights an evolving AMR landscape, partly driven by the pandemic. Strengthened infection control measures, antimicrobial stewardship and continuous surveillance are essential to mitigate the spread of NDM-producing K. pneumoniae in settings with limited resources.

1. Introduction

Antimicrobial resistance (AMR) is recognized as one of the most pressing global health threats, posing severe challenges to the treatment of infectious diseases worldwide [1]. The increasing prevalence of multidrug-resistant (MDR) microorganisms, particularly in healthcare settings, has significantly impacted clinical outcomes, resulting in higher rates of morbidity and mortality. Among these organisms, Klebsiella pneumoniae (Kp) has emerged as a leading cause of hospital-acquired infections, particularly in intensive care units (ICUs), due to its ability to acquire resistance mechanisms is a major concern [2,3]. In parallel, there has been a growing emergence of hypervirulent Klebsiella pneumoniae (hvKp) strains, which are responsible for community-acquired infections, often in otherwise healthy individuals. These microorganisms represent an emerging pathotype, exhibiting greater virulence compared to classical K. pneumoniae (cKp). The emergence of such strains has occurred, in part, through the acquisition of hvKp-specific virulence determinants by extensively drug-resistant cKp strains (XDR-cKp), leading to nosocomial infections caused by isolates with both hypervirulent and multidrug-resistant phenotypes [4].
The global health crisis driven by the SARS-CoV-2 pandemic has further exacerbated the AMR problem. During the pandemic, factors such as the inappropriate and excessive use of antibiotics in patients without bacterial co-infections, the overwhelming burden on healthcare systems, and the disruption of routine infection control measures, have contributed to an increase in AMR rates [5,6].
An example of this can be observed in studies conducted in Lebanon, which investigated the prevalence of inappropriate antibiotic use during the COVID-19 pandemic. The findings indicated that 40.2% of respondents reported using antibiotics during SARS-CoV-2 infection, and among them, 49% did so without a medical prescription. These data underscore that the majority of antibiotic consumption occurs outside the hospital setting, which facilitates improper use and highlights a significant lack of adequate public awareness [7].
Of particular concern is the increase in carbapenem-resistant Klebsiella pneumoniae (CRKP), a pathogen known for its capacity to harbor carbapenemase-encoding genes, which confer resistance to a wide range of antibiotics [8]. This scenario has also accelerated the spread of highly resistant strains with difficult-to-treat (DTR) and extensively drug resistant (XDR) phenotypes in healthcare settings, making the treatment of these infections more challenging given the reported limitations of antimicrobials [9,10].
In Brazil, the epidemiology of carbapenem resistance in K. pneumoniae in healthcare settings is predominantly associated with spread of high-risk clones (HRCs) containing mobile genetic elements and Klebsiella pneumoniae carbapenemase (KPC), a class A β-lactamase enzyme that has become endemic in the country [11,12,13,14].
However, in recent years, particularly following the onset of the SARS-CoV-2 pandemic, the prevalence of microorganisms producing New Delhi metallo-β-lactamase (NDM) has increased in healthcare settings in Brazil and other countries [15,16,17].
This is concerning not only because of the potential for the emergence and dissemination of other resistance mechanisms, but also because of resistance to newer β-lactamase inhibitors in metallo-β-lactamase producers, which makes treatment options even more limited.
The Northern region of Brazil has seen a concerning rise in CRKP infections but remains understudied in terms of detailed epidemiological data. This deficit is reflected in the scarcity of studies on AMR involving healthcare services in the Northern region, which presents several public health and basic sanitation infrastructure challenges in most states and municipalities in this region [18].
To clarify the epidemiology of CRKP in hospitals in the Northern region and assess the impact of the pandemic, this study investigated the prevalence and distribution of CRKP isolates collected from 25 hospitals in the Northern region of Brazil before and during the COVID-19 pandemic (2018–2021). By comparing temporal trends in carbapenemase production, this study sheds light on the evolving landscape of AMR in a region with limited resources.

2. Results

Of the 946 carbapenem-resistant Klebsiella spp. isolates received at the Evandro Chagas Institute, 171 were excluded due to duplication, contamination, or incorrect identification. These isolates did not belong to the Klebsiella genus. This left a total of 775 isolates for analysis. K. pneumoniae was the predominant species among the isolates, comprising over n = 754 (97%) of the total samples. The remaining isolates included K. aerogenes n = 13 (2%), K. oxytoca n = 5 (0.65%), and K. ozaenae n = 1 (0.13%). Of these isolates, 703 isolates were collected from health services in Pará State, and 72 isolates were collected from Acre State.
Analysis of the age groups demonstrated a predominance of isolates from elderly patients n = 301/775 (38.8%) and adults n = 288/775 (37.2%), with lower frequencies observed among children n = 83/775 (10.7%), young individuals n = 26/775 (3.3%) and newborns n = 12/775 (1.5%). Statistically significant variations were observed when comparing the pre-pandemic and pandemic periods in the adult group, which increased from 80 isolates (32%) in the pre-pandemic period to 209 isolates (39.8%) during the pandemic (p = 0.036). These and other values are better visualized in Table 1. Conversely, the pediatric group showed a significant decrease, from 45 isolates (18%) before the pandemic to 38 isolates (7.2%) during the pandemic (p = 0.001), as detailed in Table 1. The isolates were recovered from various clinical specimens, the majority of which were obtained from surveillance swabs n = 203/775 (26.2%), tracheal secretions n = 180/775 (23.2%), urine n = 170/775 (21.9%), and whole blood n = 121/775 (15.6%). Other clinical specimens of lower frequency can be seen in Figure 1.
Comparing the pre-pandemic period (2018–2019) with the pandemic period (2020–2021) revealed a significant increase in isolates obtained from tracheal secretions and surveillance swabs (Figure 2). The number of isolates obtained from tracheal secretions rose from 46 (18.4%) in the pre-pandemic period to 134 (25.5%) during the pandemic (p = 0.028). Similarly, the number of isolates obtained from surveillance swabs increased from 55 (22%) to 148 (28.2%) (p = 0.040) during the same period (Table 1). These findings reflect the increased use of invasive devices and enhanced surveillance measures, particularly among patients with SARS-CoV-2 infection, during the pandemic.
The majority of carbapenem-resistant Klebsiella spp. isolates were recovered from patients admitted to adult ICUs, accounting for n = 357/775 (46%) of the total isolates. This was followed by patients admitted to medical clinic wards, accounting for n = 225/775 (29%). The number of isolates from adult ICUs increased significantly during the pandemic, rising from 99 (40%) pre-pandemic to 267 (49%) during the pandemic period (p = 0.013). Isolates from pediatric ICUs and neonatal ICUs were less frequent, representing 4.4% and 1.8% of the total isolates, respectively. Notably, there was a significant decrease in neonatal ICU isolates during the pandemic period, falling from 3.2% pre-pandemic to 1.1% during the pandemic (p = 0.044) (Table 1).
Of the 775 isolates analyzed, n = 651/775 (84%) were confirmed to be carbapenemase producers, harboring one or more carbapenemases encoding genes. The most frequently detected gene was blaKPC n = 446/775 (57.5%), followed by blaNDM n = 243/775 (31.4%). Detection rates for other carbapenemase genes, such as blaGES n = 14/775 (1.8%), blaOXA-48, and blaIMP, were very low, with only one isolate harboring each of the latter two genes. The blaVIM, blaGIM, blaAIM, blaSIM, and blaDIM genes were not detected (Table 2). Although K. pneumoniae accounted for the highest frequency among carbapenemase-producing isolates, the blaKPC and blaNDM genes were also detected in non-classical Klebsiella species. For blaKPC, K. aerogenes presented 7 out of 13 isolates; K. ozaenae presented 1 out of 1; and K. oxytoca presented 2 out of 5. For blaNDM, K. oxytoca also presented 2 out of 5 isolates.
KPC-producing carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates were detected in 23 of the 25 hospitals included in the study, with 18 hospitals located in Pará State and five in Acre State. Among these, n = 236/446 (52.9%) of KPC-positive patients were admitted to intensive care units (ICUs), underscoring the substantial prevalence of these resistant strains in critical care settings. The most frequent species was K. pneumoniae, accounting for n = 436/446 (97.7%) of the isolates. The blaKPC gene was predominantly detected in isolates from tracheal secretions n = 119/446 (27%), urine n = 105/446 (24%), surveillance swabs n = 88/446 (20%), and blood n = 67/446 (15%). The most prevalent age groups among the individuals evaluated were the elderly, accounting for n = 165/446 (37.0%), and adults, with n = 160/446 (35.8%). Lower proportions were observed among children n = 43/446 (9.6%), young individuals n = 20/446 (4.4%), and neonates n = 3/446 (1.3%). The detection rate of KPC-positive CRKP was n = 67/105 (64.0%) in 2018, increasing to n = 107/145 (74.0%) in 2019. However, during the pandemic years, the detection rate declined, dropping to n = 76/138 (55.0%) in 2020 and further to n = 200/387 (52.0%) in 2021 (Table 2). When comparing the pre-pandemic period (2018–2019) with the pandemic period (2020–2021), the detection rate of KPC decreased significantly from 69% to 52% (p < 0.000). This analysis revealed a slight downward trend in the detection of KPC-producing CRKP isolates over the study period. A Pearson’s chi-square test indicated a significant difference (p < 0.000) in the frequency of KPC between 2019 and 2021 (Table 1). However, linear regression analysis demonstrated a weak correlation between the time period and the detection rate of the blaKPC gene (R2 = 0.182), suggesting that temporal factors had a minimal influence on the decline of this carbapenemase (Figure 3).
On the other hand, NDM was the second most frequently detected carbapenemase, identified in n = 243/775 (31.4%) of the CRKP isolates. Isolates were identified in 17 out of the 25 hospitals included in the study, with 14 located in the capital of the state of Pará and 3 in municipalities in the countryside. No isolates were detected from the state of Acre. The predominant bacterial species was K. pneumoniae, accounting for n = 241/243 (99.1%) of the isolates. Among the blaNDM producing isolates, n = 111/243 (45.7%) were obtained from patients admitted to Intensive Care Units (ICUs). Additionally, n = 78/243 (32.1%) of the isolates were recovered from clinical wards, n = 13/243 (5.3%) from pediatric ICUs, and n = 2/243 (0.8%) from neonatal ICUs.
The blaNDM gene was primarily detected in surveillance swabs n = 95/243 (39%), blood n = 45/243 (19%), urine n = 42/243 (17%), and wound secretions n = 36/243 (15%). Regarding age distribution, adults and elderly individuals were the most affected groups, each representing n = 101/243 (41.5%) of cases. Lower frequencies were observed among children n = 22/243 (9%), neonates n = 6/243 (2.4%), and young individuals n = 5/243 (2%). Although the detection rate of blaNDM was lower than that of blaKPC in all years analyzed, a significant increase was observed over the study period. The detection rate rose from n = 3/105 (3.0%) in 2018 to n = 19/145 (13.0%) in 2019, followed by n = 54/138 (39.0%) in 2020, and n = 172/387 (44.0%) in 2021. A Pearson’s chi-square test revealed a highly significant association between these variables (p < 0.000), indicating a strong upward trend. Linear regression analysis showed a high correlation between the increase in blaNDM detection and the progression of time (R2 = 0.778), confirming the marked rise in NDM prevalence, particularly during the COVID-19 pandemic (Figure 3).

3. Discussion

This study analyzed the prevalence and distribution of CRKP isolates in Northern Brazil before and during the COVID-19 pandemic, revealing a significant shift in the epidemiology of CRKP as a direct impact of the COVID-19 pandemic. The marked increase in NDM-producing CRKP isolates during the pandemic, rising from a low prevalence in 2018 and 2019 to a significant share by 2020 and 2021, was a key finding. This surge in NDM producers was statistically significant, indicated by strong linear regression analysis. Conversely, KPC-producing CRKP, while still prevalent, showed a decline in detection rates from 69% in the pre-pandemic years (2018–2019) to 52% during the pandemic (2020–2021). This suggests an evolving resistance landscape that has critical implications for patient outcomes and healthcare practices and aligns with global trends where emerging resistance mechanisms are reshaping the AMR profile in healthcare settings. Understanding these trends is essential for developing effective strategies to mitigate the impact of CRKP in a region already facing substantial public health and resource limitations.
The observed trends in Northern Brazil reflect shifts noted globally, where NDM-producing K. pneumoniae has gained prominence [19,20,21].
While KPC has historically dominated in Brazil and other regions, the rapid increase in NDM-producing strains during the COVID-19 pandemic marks a critical epidemiological change [22,23,24,25]. Similar trends have been reported in several countries in Europe, North America, and Latin America, where NDM detection increased significantly among ICU patients during the pandemic, and in China and India, where the spread of NDM in carbapenem-resistant Enterobacteriaceae affected both adult and pediatric populations [26,27,28,29,30].
Similar results were observed during a large surveillance study in Brazil that showed a 60% increase in resistance genes during the COVID-19 pandemic, especially blaNDM in Enterobacterales [17].
The decrease in KPC detection over time, despite its still-high prevalence, aligns with previous reports of KPC being endemic in Brazil and in the North region [25,31,32]. The fact that KPC-producing isolates remained common in hospitals during the pandemic reflects the difficulty in eradicating these strains. However, the relatively stable levels of KPC producers compared to the sharp increase in NDM isolates suggest that NDM may overtake KPC as the dominant carbapenemase in K. pneumoniae clinical strains in the future.
The disproportionate impact of the pandemic on adult ICUs, as demonstrated by the significant increase in isolates from these wards, emphasizes the need for enhanced infection control and antimicrobial stewardship programs. Similar findings have been reported globally, where ICUs faced the brunt of the COVID-19 pandemic’s impact on AMR [33,34,35,36].
The surge in tracheal secretions and surveillance swabs further reflected the increased use of invasive devices and heightened infection control surveillance during COVID-19 patient care [37,38,39].
On the other hand, the increase in CRKP obtained from surveillance swabs is also relevant for epidemiological and infection control purposes, since colonized patients may develop infections with these microorganisms [40,41].
Pereira et al. (2021) [42] observed that among 70 patients with COVID-19 colonized by CRKP in ICUs, 14 developed infectious processes on average eight days after detection of colonization.
The increase in NDM-producing CRKP during the COVID-19 pandemic can be attributed to several factors. The pandemic led to the overuse of broad-spectrum antibiotics as empirical treatment or prevention for bacterial co-infections in COVID-19 patients, creating selective pressure that favored resistant organisms. This pattern has been observed in other studies where inappropriate antibiotic use during the pandemic contributed to the spread of resistant strains [43,44,45].
Interestingly, this study found a significant decrease in K. pneumoniae isolates from neonatal ICUs during the pandemic, with rates dropping from 3.2% pre-pandemic to 1.1% during the pandemic (p = 0.044). This reduction may be attributed to stricter infection control measures implemented to protect vulnerable neonatal populations, such as increased hygiene protocols, restricted visitor access, and heightened surveillance. Furthermore, the decrease may reflect shifts in healthcare resource allocation, where resources were redirected to adult ICUs managing COVID-19 cases. This redistribution could have reduced the use of invasive procedures in neonatal units, subsequently lowering opportunities for transmission. During the pandemic, neonatal units were likely prioritized for infection prevention to reduce risks of COVID-19 transmission, which may have indirectly lowered the transmission of other healthcare-associated infections, including K. pneumoniae [46,47,48].
The study revealed notably low detection rates for blaGES n = 14/775 (1.8%), blaOXA-48 n = 1/775 (0.12%), and blaIMP n = 1/775 (0.12%) among Klebsiella spp. isolates. This limited presence may reflect specific regional resistance patterns, where NDM and KPC are more prevalent, potentially due to transmission dynamics within healthcare settings. The low incidence of blaOXA-48 and blaIMP among CRKP could indicate that these resistance mechanisms are not yet widely circulating in Northern Brazil, suggesting potential geographic or epidemiologic barriers to their spread [49].
The reliance on invasive medical devices such as ventilators and central lines, particularly in ICU settings, provided further opportunities for the transmission and colonization of resistant strains. In Northern Brazil, these challenges were exacerbated by limited healthcare resources and inconsistent infection control practices. The disruption of routine surveillance and preventive strategies facilitated the spread of NDM-producing CRKP, aligning with global observations of increased AMR during healthcare crises.
Epidemic high-risk clones of K. pneumoniae, such as ST258, ST11, ST15, and ST307, have played a leading role in the global spread of antimicrobial resistance. These clones are characterized by their ability to acquire and disseminate resistance genes rapidly, making them highly adaptable in diverse clinical environments [50,51].
The global dissemination of carbapenemase-producing K. pneumoniae can largely be attributed to these high-risk clones, which are associated with outbreaks in hospitals and have been linked to increased morbidity and mortality. In the context of CRKP, high-risk clones facilitate the spread of resistance mechanisms such as KPC, NDM, and OXA-48 carbapenemases. In Brazil, epidemic clones such as ST11 and ST437 have been identified in CRKP isolates, contributing to the dissemination of carbapenemase genes, including KPC and NDM. The presence of these clones exacerbates the public health challenge posed by AMR, as they contribute to sustained transmission within healthcare facilities [22,40,52,53].
The rise in NDM-producing CRKP has significant implications for clinical management and public health. Clinically, the increasing prevalence of NDM producers limits treatment options due to their resistance to most beta-lactam antibiotics, including newer beta-lactam/beta-lactamase inhibitor combinations. This often necessitates the use of less effective or more toxic alternatives, such as colistin, which is associated with nephrotoxicity and variable efficacy. In this context, the urgency of research and implementation of new antimicrobial strategies that expand the available therapeutic options is reinforced. One promising approach involves the use of bacterial metallophores, organic molecules produced by bacteria that are capable of sequestering metal ions essential for their growth and the expression of virulence factors. Overall, there is an increasing need to identify novel therapeutic pathways that are effective in combating multidrug-resistant microorganisms [54].
The COVID-19 pandemic revealed vulnerabilities in infection control that contributed to the spread of resistant pathogens. Addressing these gaps requires comprehensive and standardized infection control protocols, including rigorous hand hygiene, effective disinfection practices, and the proper use of Personal Protective Equipment (PPE). Healthcare facilities should implement strict patient isolation and cohorting measures to prevent cross-transmission. Regular training for healthcare staff on updated infection prevention practices and AMR stewardship is crucial for maintaining high compliance levels. Active surveillance to identify colonized or infected patients early can significantly curb transmission, supported by rapid diagnostic tools that enable timely intervention [55,56].
If current trends persist, NDM may surpass KPC as the dominant carbapenemase in Northern Brazil, complicating treatment regimens and straining healthcare resources. Strengthening antimicrobial stewardship to ensure judicious antibiotic use and investing in training for rapid diagnostic capabilities are key to managing this challenge. This study highlights the pressing need for further research into the factors driving the increased prevalence of NDM-producing CRKP. Investigations should focus on the genetic mechanisms facilitating NDM spread, the socio-economic impacts, and the long-term outcomes for patients with these infections. Continuous surveillance and comprehensive studies will inform public health strategies and guide policymaking to better address AMR challenges in the future.

4. Materials and Methods

4.1. Study Design and Selection of Bacterial Isolates

This is a cross-sectional, epidemiological, and analytical study that is part of the Antimicrobial Resistance Surveillance Study in North region, Brazil. It includes carbapenem-resistant (CR) Klebsiella spp. isolates obtained from various clinical specimens and surveillance swabs (axillary or rectal). The latter represents an important tool for hospital surveillance, aimed at screening patients colonized or infected with multidrug-resistant bacteria, thereby contributing directly to the prevention and control of nosocomial infections.
The patients were from adult, pediatric, and neonatal intensive care units (ICUs), as well as medical clinics, in 25 public and private healthcare facilities located in the Northern region of Brazil, including the states of Pará and Acre (Figure 4). Most of the healthcare facilities were in Belém city (N = 17), the capital of the state of Pará, while three were in other municipalities in the state of Pará. In the state of Acre, the five healthcare facilities included in this study were in the state capital, Rio Branco.
A total of 946 CR Klebsiella spp. isolates were received between January 2018 and December 2021. Only one bacterial isolate per patient was considered for the study. Duplicates, contaminated samples, and isolates not belonging to the Klebsiella genus were excluded (N = 171), leaving 775 K. pneumoniae isolates for analysis.
Preliminary bacterial identification and antimicrobial susceptibility testing (AST) were performed at the healthcare facilities. The isolates were then sent to Public Health Central Laboratories (LACENs) and subsequently to the Evandro Chagas Institute (IEC), where the laboratory analyses were conducted. These included seeding for thermal extraction of bacterial DNA and subsequent Polymerase Chain Reaction (PCR) and agarose gel electrophoresis.

4.2. Presence of Carbapenemases Encoding Genes

Bacterial isolates were subjected to DNA extraction following the protocol described by Vaneechoutte et al. (1995) [57] and subsequently tested for the presence of blaKPC, blaNDM, blaOXA-48, blaIMP, blaVIM using conventional polymerase chain reaction (PCR). Primer sequences, master mix composition, and cycling conditions were previously described by Han et al. [58].
PCR was performed using the GoTaqTM G2 Flexi DNA Polymerase kit (Promega, Madison, WI, USA) under the following conditions: one initial cycle at 95 °C for 2 min, followed by 35 amplification cycles (95 °C for 30 s, 52 °C for 40 s, and 72 °C for 50 s), and a final extension at 72 °C for 10 min. In addition, other less frequently detected carbapenemase-encoding genes, such as blaGES, blaGIM, blaAIM, blaSIM, and blaDIM, were also screened using conventional PCR with primers designed according to Mendes et al. (2007) [59] and Han et al. (2020) [58]
PCR amplicons were visualized by agarose gel electrophoresis. A positive control was included in each run. The amplified products were visualized on 1% agarose gels stained with SafeDye nucleic acid stain (Cellco, São Paulo, Brazil).

4.3. Statistical Analysis

The data used in this study were obtained from the antimicrobial resistance surveillance database which is maintained by the Evandro Chagas Institute (IEC). Descriptive analyses were performed using Microsoft Excel 2010, and the results were presented in the form of graphs and tables. The data covered patient demographics (age groups), clinical specimen types, hospital wards, sample collection dates, and carbapenemase gene detection results. To assess the impact of the pandemic, samples collected in 2018 and 2019 were categorized as the ‘pre-pandemic period’, while those collected in 2020 and 2021 were categorized as the ‘pandemic period’. The study periods were stratified into quarters according to the monthly distribution within each year, in order to improve temporal organization and facilitate trend analysis.
Correlation analyses between variables were conducted using Pearson’s chi-square test and linear regression, with a significance level set at p ≤ 0.05. The 95% confidence interval was calculated using Statistical Package for the Social Sciences (SPSS) v20.0 and Biostat v5.3 software. Pearson’s chi-squared test was used to analyze the relationship between the pre-pandemic (2018–2019) and pandemic (2020–2021) periods of COVID-19 and various factors, including the type of clinical specimen, hospital ward, and detected carbapenemases. Additionally, the Linear Detection Rate (DR) was calculated by dividing the number of positive samples for KPC and NDM by the total number of samples received during the study period [60]. Regression analysis was performed using DR values to predict trends in carbapenemase detection increases or decreases over time.

5. Conclusions

This study provides a comprehensive analysis of CRKP in Northern Brazil, highlighting a significant shift from KPC to NDM-producing strains, particularly during the COVID-19 pandemic. The rise in NDM poses a serious challenge to treatment options, as these strains are resistant to newer antibiotics. The findings in the study also stress the need for strengthened infection control, antimicrobial stewardship, and ongoing surveillance to curb the spread of NDM-producing pathogens, especially in ICUs. Continued monitoring is crucial to managing future threats of antimicrobial resistance in the region.

Author Contributions

Conceptualization, T.B.C.B. and D.M.B.; methodology, T.B.C.B., A.J.P.G., L.M.G.D., A.R.F.L., Y.C.R., H.S.d.R. and C.d.O.S.; validation, D.M.B.; investigation, T.B.C.B.; resources, D.M.B.; data curation, T.B.C.B., F.d.E.S.S. and A.R.F.L.; writing—original draft preparation, T.B.C.B., D.M.B., and Y.C.R.; writing—review and editing, T.B.C.B., H.S.d.R., C.d.O.S. and D.M.B.; supervision, D.M.B.; project administration, D.M.B. All authors have read and agreed to the published version of the manuscript.

Funding

This study was funded and supported by the Evandro Chagas Institute, Secretariat of Health Surveillance, Brazilian Ministry of Health.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

The data used in this study can be made available upon request to the corresponding author, considering the sensitivity of patient information and the confidentiality requirements of the research.

Acknowledgments

The authors thank the microbiology laboratory of the hospital for sending the isolates.

Conflicts of Interest

The authors declare no competing interests.

References

  1. GBD 2021 Antimicrobial Resistance Collaborators. Global burden of bacterial antimicrobial resistance 1990-2021: A systematic analysis with forecasts to 2050. Lancet 2024, 404, 1199–1226. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
  2. Bertagnolio, S.; Dobreva, Z.; Centner, C.M.; Olaru, I.D.; Donà, D.; Burzo, S.; Huttner, B.D.; Chaillon, A.; Gebreselassie, N.; Wi, T.; et al. WHO global research priorities for antimicrobial resistance in human health. Lancet Microbe 2024, 5, 100902. [Google Scholar] [CrossRef]
  3. Tacconelli, E.; Carrara, E.; Savoldi, A.; Harbarth, S.; Mendelson, M.; Monnet, D.L.; Pulcini, C.; Kahlmeter, G.; Kluytmans, J.; Carmeli, Y.; et al. Discovery, research, and development of new antibiotics: The WHO priority list of antibiotic-resistant bacteria and tuberculosis. Lancet Infect. Dis. 2018, 18, 318–327. [Google Scholar] [CrossRef]
  4. Russo, T.A.; Marr, C.M. Hypervirulent Klebsiella pneumoniae. Clin. Microbiol. Rev. 2019, 32, 3. [Google Scholar] [CrossRef]
  5. Al Sulayyim, H.J.; Ismail, R.; Al Hamid, A.; Ghafar, N.A. Antibiotic Resistance during COVID-19: A Systematic Review. Int. J. Environ. Res. Public Health 2022, 19, 11931. [Google Scholar] [CrossRef] [PubMed]
  6. Abubakar, U.; Al-Anazi, M.; Alanazi, Z.; Rodríguez-Baño, J. Impact of COVID-19 pandemic on multidrug resistant gram positive and gram negative pathogens: A systematic review. J. Infect. Public Health 2023, 16, 320–331. [Google Scholar] [CrossRef] [PubMed]
  7. Chaaban, T.; Ezzeddine, Z.; Ghssein, G. Antibiotic misuse during the COVID-19 pandemic in Lebanon: A cross-sectional study. COVID 2024, 4, 921–929. [Google Scholar] [CrossRef]
  8. Pan American Health Organization. Antimicrobial Resistance, Fueled by the COVID-19 Pandemic. Policy Brief November 2021. 2022. Available online: https://iris.paho.org/handle/10665.2/55864 (accessed on 28 June 2023).
  9. Kadri, S.S.; Adjemian, J.; Lai, Y.L.; Spaulding, A.B.; Ricotta, E.; Prevots, D.R.; Palmore, T.N.; Rhee, C.; Klompas, M.; Dekker, J.P.; et al. Difficult-to-treat resistance in gram-negative bacteremia at 173 US hospitals: Retrospective cohort analysis of prevalence, predictors, and outcome of resistance to all first-line agents. Clin. Infect. Dis. 2018, 67, 1803–1814. [Google Scholar] [CrossRef]
  10. CDC. COVID-19: U.S. Impact on Antimicrobial Resistance, Special Report 2022; Centers for Disease Control and Prevention: Atlanta, GA, USA, 2022.
  11. Migliorini, L.B.; de Sales, R.O.; Koga, P.C.M.; Doi, A.M.; Poehlein, A.; Toniolo, A.R.; Menezes, F.G.; Martino, M.D.V.; Gales, A.C.; Brüggemann, H.; et al. Prevalence of blaKPC-2, blaKPC-3 and blaKPC-30—Carrying Plasmids in Klebsiella pneumoniae Isolated in a Brazilian Hospital. Pathogens 2021, 10, 332. [Google Scholar] [CrossRef] [PubMed]
  12. Conceição-Neto, O.C.; da Costa, B.S.; Pontes Lda, S.; Silveira, M.C.; Justo-da-Silva, L.H.; de Oliveira Santos, I.C.; Teixeira, C.B.T.; Tavares e Oliveira, T.R.; Hermes, F.S.; Galvão, T.C.; et al. Polymyxin resistance in clinical isolates of K. pneumoniae in Brazil: Update on molecular mechanisms, clonal dissemination and relationship with KPC-producing strains. Front. Cell. Infect. Microbiol. 2022, 12, 898125. [Google Scholar] [CrossRef]
  13. Andrade, L.N.; Vitali, L.; Gaspar, G.G.; Bellissimo-Rodrigues, F.; Martinez, R.; Darini, A.L.C. Expansion and evolution of a virulent, extensively drug-resistant (polymyxin B-resistant), QnrS1-, CTX-M-2-, and KPC-2-producing Klebsiella pneumoniae ST11 international high-risk clone. J. Clin. Microbiol. 2014, 52, 2530–2535. [Google Scholar] [CrossRef]
  14. Boralli, C.M.D.S.; Paganini, J.A.; Meneses, R.S.; da Mata, C.P.S.M.; Schürch, A.C.; Paganelli, F.L.; Willems, R.J.L.; Camargo, I.L.B.C. Characterization of blaKPC-2 and blaNDM-1 plasmids of a K. pneumoniae ST11 outbreak clone. Antibiotics 2023, 12, 926. [Google Scholar] [CrossRef]
  15. Camargo, C.H. Current status of NDM-producing Enterobacterales in Brazil: A narrative review. Braz. J. Microbiol. 2022, 53, 1339–1344. [Google Scholar] [CrossRef] [PubMed]
  16. Rodrigues, Y.C.; Lobato, A.R.F.; Guerra, L.M.G.D.; Brasiliense, D.M. The spread of NDM-1 and NDM-7-producing Klebsiella pneumoniae is driven by multiclonal expansion of high-risk clones in healthcare institutions in the state of Pará, Brazilian Amazon region. Antibiotics 2021, 10, 1527. [Google Scholar] [CrossRef] [PubMed]
  17. Ministério Brasil da Saúde; Secretaria de Vigilância em Saúde e Ambiente. Boletim Epidemiológico: Resistência aos Antimicrobianos; Ministério da Saúde: Brasília, Brazil, 2024; Volume 55. Available online: https://www.gov.br/saude/pt-br/centrais-de-conteudo/publicacoes/boletins/epidemiologicos/edicoes/2024/boletim-epidem-vol-55-n-2 (accessed on 7 July 2025).
  18. Pimentel, F.G.; Buchweitz, C.; Onocko Campos, R.T.; Hallal, P.C.; Massuda, A.; Kieling, C. Realising the future: Health challenges and achievements in Brazil. SSM Ment. Health 2023, 4, 100250. [Google Scholar] [CrossRef]
  19. Emeraud, C.; Mahamat, A.; Jousset, A.B.; Bernabeu, S.; Goncalves, T.; Pommier, C.; Girlich, D.; Birer, A.; Rodriguez, C.; Pawlotsky, J.-M.; et al. Emergence and rapid dissemination of highly resistant NDM-14-producing Klebsiella pneumoniae ST147, France, 2022. Eurosurveillance 2023, 28, 2300095. [Google Scholar] [CrossRef]
  20. Fu, B.; Yin, D.; Sun, C.; Shen, Y.; Liu, D.; Bai, R.; Zhang, R.; Shen, J.; Hu, F.; Wang, Y. Clonal and horizontal transmission of blaNDM among Klebsiella pneumoniae in children’s intensive care units. Microbiol. Spectr. 2022, 10, e0157421. [Google Scholar] [CrossRef]
  21. Kedišaletše, M.; Phumuzile, D.; Angela, D.; Andrew, W.; Mae, N.-F. Epidemiology, risk factors, and clinical outcomes of carbapenem-resistant Enterobacterales in Africa: A systematic review. J. Glob. Antimicrob. Resist. 2023, 35, 297–306. [Google Scholar] [CrossRef]
  22. Camargo, C.H.; Yamada, A.Y.; Souza AR de Reis, A.D.; Santos, M.B.N.; de Assis, D.B.; de Carvalho, E.; Takagi, E.H.; Cunha, M.P.V.; Tiba-Casas, M.R. Genomic diversity of NDM-producing Klebsiella species from Brazil, 2013–2022. Antibiotics 2022, 11, 1395. [Google Scholar] [CrossRef]
  23. Scavuzzi, A.M.L.; Firmo, E.F.; de Oliveira, É.M.; Lopes, A.C.d.S. Emergence of bla NDM-1 associated with the aac(6’)-Ib-cr, acrB, cps, and mrkD genes in a clinical isolate of multi-drug resistant Klebsiella pneumoniae from Recife-PE, Brazil. Rev. Soc. Bras. Med. Trop. 2019, 52, e20180352. [Google Scholar] [CrossRef]
  24. Wink, P.L.; Martins, A.S.; Volpato, F.; Zavascki, A.P.; Barth, A.L. Increased frequency of blaNDM in a tertiary care hospital in southern Brazil. Braz. J. Microbiol. 2021, 52, 299–301. [Google Scholar] [CrossRef]
  25. Santos, A.P.; Gonçalves, L.C.; Oliveira, A.C.C.; Queiroz, P.H.P.; Ito, C.R.M.; Santos, M.O.; Carneiro, L.C. Bacterial co-infection in patients with COVID-19 hospitalized (ICU and not ICU): Review and meta-analysis. Antibiotics 2022, 11, 894. [Google Scholar] [CrossRef]
  26. van Duin, D.; Doi, Y. The global epidemiology of carbapenemase-producing Enterobacteriaceae. Virulence 2017, 8, 460–469. [Google Scholar] [CrossRef] [PubMed]
  27. Desikan, P.; Bose, P.; Rangnekar, A. NDM-beta-lactamase-1: Where do we stand? Indian J. Med. Res. 2022, 155, 243. [Google Scholar]
  28. Wu, W.; Feng, Y.; Tang, G.; Qiao, F.; McNally, A.; Zong, Z. NDM metallo-β-lactamases and their bacterial producers in health care settings. Clin. Microbiol. Rev. 2019, 32, e00115–e00118. [Google Scholar] [CrossRef]
  29. de Lima das Chagas, A.; da Silva Araújo, J.C.; Serra, J.C.P.; de Araújo, K.M.; de Oliveira Cunha, M.; Correia, A.D.R.; Gonçalves, L.M.B.; Carneiro, L.C. Co-Infection of SARS-CoV-2 and Klebsiella pneumoniae: A Systematic Review and Meta-Analysis. Diagnostics 2024, 14, 1149. [Google Scholar] [CrossRef]
  30. Safavi, M.; Bostanshirin, N.; Hajikhani, B.; Yaslianifard, S.; van Belkum, A.; Goudarzi, M.; Hashemi, A.; Darban-Sarokhalil, D.; Dadashi, M. Global genotype distribution of human clinical isolates of New Delhi metallo-β-lactamase-producing Klebsiella pneumoniae; A systematic review. J. Glob. Antimicrob. Resist. 2020, 23, 420–429. [Google Scholar] [CrossRef]
  31. Raro, O.H.F.; da Silva, R.M.C.; Filho, E.M.R.; Sukiennik, T.C.T.; Stadnik, C.; Dias, C.A.G.; Oteo Iglesias, J.; Pérez-Vázquez, M. Carbapenemase-Producing Klebsiella pneumoniae From Transplanted Patients in Brazil: Phylogeny, Resistome, Virulome and Mobile Genetic Elements Harboring blaKPC–2 or blaNDM–1. Front. Microbiol. 2020, 11, 1563. [Google Scholar] [CrossRef] [PubMed]
  32. Santos, A.L.S.D.; Rodrigues, Y.C.; de Melo, M.V.H.; Santos, P.A.S.D.; da Costa Oliveira, T.N.; Sardinha, D.M.; Lima, L.N.G.C.; Brasiliense, D.M.; Lima, K.V.B. First insights into clinical and resistance features of infections by Klebsiella pneumoniae among oncological patients from a referral center in Amazon region, Brazil. Infect. Dis. Rep. 2020, 12, 110–120. [Google Scholar] [CrossRef] [PubMed]
  33. Moolla, M.S.; Reddy, K.; Fwemba, I.; Nyasulu, P.S.; Taljaard, J.J.; Parker, A.; Louw, E.H.; Nortje, A.; Parker, M.A.; Lalla, U.; et al. Bacterial infection, antibiotic use and COVID-19: Lessons from the intensive care unit. S. Afr. Med. J. 2021, 111, 575–581. [Google Scholar]
  34. Oliveira, K.; Filipak, D.; da Silva, A.K.; Carneiro, M.B. Infecções bacterianas em pacientes com COVID-19 internados em UTI adulto: Incidência e atuação farmacêutica. Rev. Bras. Farm. Hosp. Serviços Saúde 2023, 14, 967. [Google Scholar] [CrossRef]
  35. O’Toole, R.F. The interface between COVID-19 and bacterial healthcare-associated infections. Clin. Microbiol. Infect. 2021, 27, 1772–1776. [Google Scholar] [CrossRef] [PubMed]
  36. de Oliveira Santos, J.V.; da Costa Júnior, S.D.; de Fátima Ramos Dos Santos Medeiros, S.M.; Cavalcanti, I.D.L.; de Souza, J.B.; Coriolano, D.L.; da Silva, W.R.C.; Alves, M.H.M.E.; Cavalcanti, I.M.F. Panorama of bacterial infections caused by epidemic resistant strains. Curr. Microbiol. 2022, 79, 175. [Google Scholar] [CrossRef] [PubMed]
  37. GBD 2021 Lower Respiratory Infections Collaborators. Global, regional, and national incidence and mortality burden of non-COVID-19 lower respiratory infections and aetiologies, 1990–2021: A systematic analysis from the Global Burden of Disease Study 2021. Lancet Infect. Dis. 2024, 24, 974–1002. [Google Scholar] [CrossRef] [PubMed]
  38. Hedberg, P.; Ternhag, A.; Giske, C.G.; Strålin, K.; Özenci, V.; Johansson, N.; Spindler, C.; Hedlund, J.; Mårtensson, J.; Nauclér, P. Ventilator-associated lower respiratory tract bacterial infections in COVID-19 compared with non-COVID-19 patients. Crit. Care Med. 2022, 50, 825–836. [Google Scholar] [CrossRef]
  39. François, B.; Laterre, P.-F.; Luyt, C.-E.; Chastre, J. The challenge of ventilator-associated pneumonia diagnosis in COVID-19 patients. Crit. Care 2020, 24, 289. [Google Scholar] [CrossRef]
  40. Rodrigues, L.K.C.; Soares, C.F.; Ton, J.T.; Soares, N.; Peixoto, R.R.; Zimmerli, S.Â.; Vasconcelos, M.P. Perfil bacteriano de pacientes admitidos em unidade de terapia intensiva do centro de medicina tropical de Rondônia durante a pandemia do COVID-19. Braz. J. Infect. Dis. 2021, 25, 101428. [Google Scholar] [CrossRef]
  41. UFTM. Prevenção E Controle Das Infecções E Colonizações Por Microrganismos Multirresistentes; UFTM: Uberaba, Brazil, 2022. [Google Scholar]
  42. Pereira Rodrigues, A. Colonização por Microrganismos Multirresistentes em pacientes adultos com COVID-19 internados em Unidade de Terapia Intensiva. GOIÂNIA. 2021. Available online: https://repositorio.pucgoias.edu.br/jspui/handle/123456789/2511 (accessed on 1 November 2023).
  43. Calderón-Parra, J.; Muiño-Miguez, A.; Bendala-Estrada, A.D.; Ramos-Mart’inez, A.; Muñez-Rubio, E.; Fernández Carracedo, E.; Tejada Montes, J.; Rubio-Rivas, M.; Arnalich-Fernandez, F.; Beato Pérez, J.L.; et al. Inappropriate antibiotic use in the COVID-19 era: Factors associated with inappropriate prescribing and secondary complications. Analysis of the registry SEMI-COVID. PLoS ONE 2021, 16, e0251340. [Google Scholar] [CrossRef]
  44. Chitungo, I.; Dzinamarira, T.; Nyazika Tinashe, K.; Herrera, H.; Musuka, G.; Murewanhema, G. Inappropriate antibiotic use in Zimbabwe in the COVID-19 era: A perfect recipe for antimicrobial resistance. Antibiotics 2022, 11, 244. [Google Scholar] [CrossRef]
  45. Kamara, I.F.; Kumar, A.M.V.; Maruta, A.; Fofanah, B.D.; Njuguna, C.K.; Shongwe, S.; Moses, F.; Tengbe, S.M.; Kanu, J.S.; Lakoh, S.; et al. Antibiotic use in suspected and confirmed COVID-19 patients admitted to health facilities in Sierra Leone in 2020–2021: Practice does not follow policy. Int. J. Environ. Res. Public Health 2022, 19, 4005. [Google Scholar] [CrossRef]
  46. Liu, W.; Yang, Q.; Xu, Z.-E.; Hu, Y.; Wang, Y.; Liu, Z.; Zhao, Q.; Wang, Z.; Wei, H.; Hua, Z. Impact of the COVID-19 pandemic on neonatal admissions in a tertiary children’s hospital in southwest China: An interrupted time-series study. PLoS ONE 2022, 17, e0262202. [Google Scholar] [CrossRef]
  47. Rodriguez-Medina, D.; Avalos-Huizar, L.M.; Bolio-Pontigo, W.; Soto-Castañeda, M.G.; Cárdenas-Valdez, J.C.; Medina-R’ios, C.K. Changes in Neonatal Intensive Care Unit statistics during the COVID-19 pandemic. Bol. Med. Hosp. Infant. Mex. 2024, 81, 31–35. [Google Scholar] [CrossRef]
  48. Cena, L.; Biban, P.; Janos, J.; Lavelli, M.; Langfus, J.; Tsai, A.; Youngstrom, E.A.; Stefana, A. The collateral impact of COVID-19 emergency on neonatal intensive care units and family-centered care: Challenges and opportunities. Front. Psychol. 2021, 12, 630594. [Google Scholar] [CrossRef] [PubMed]
  49. Santos, R.P.; Nunes, M.P.; Chaves Jde, R.A.B.; Justino Gda, C.; Chaves, N.M.; de Lima, V.G.; da Silva, A.S.; Marsola, L.R. Prevalência de carbapenemases em hospital Universitário na região amazônica no período de 2020 a 2022. Braz. J. Infect. Dis. 2023, 27, 103414. [Google Scholar] [CrossRef]
  50. Arcari, G.; Carattoli, A. Global spread and evolutionary convergence of multidrug-resistant and hypervirulent Klebsiella pneumoniae high-risk clones. Pathog. Glob. Health 2023, 117, 328–341. [Google Scholar] [CrossRef]
  51. Tang, M.; Kong, X.; Hao, J.; Liu, J. Epidemiological Characteristics and Formation Mechanisms of Multidrug-Resistant Hypervirulent Klebsiella pneumoniae. Front. Microbiol. 2020, 11, 581543. [Google Scholar] [CrossRef] [PubMed]
  52. Palmeiro, J.K.; de Souza, R.F.; Schörner, M.A.; Passarelli-Araujo, H.; Grazziotin, A.L.; Vidal, N.M.; Venancio, T.M.; Dalla-Costa, L.M. Molecular epidemiology of multidrug-resistant Klebsiella pneumoniae isolates in a Brazilian tertiary hospital. Front. Microbiol. 2019, 10, 1669. [Google Scholar] [CrossRef]
  53. Aires, C.A.M.; Pereira, P.S.; de Araujo, C.F.M.; Chagas, T.P.G.; Oliveira, J.C.R.; Buonora, S.N.; Albano, R.M.; Carvalho-Assef, A.P.D.; Asensi, M.D. Multiclonal expansion of Klebsiella pneumoniae isolates producing NDM-1 in Rio de Janeiro, Brazil. Antimicrob. Agents Chemother. 2017, 61, e01048-16. [Google Scholar] [CrossRef] [PubMed]
  54. Ezzeddine, Z.; Ghssein, G. Towards new antibiotics classes targeting bacterial metallophores. Microb. Pathog. 2023, 182, 106221. [Google Scholar] [CrossRef]
  55. Shbaklo, N.; Lupia, T.; De Rosa, F.G.; Corcione, S. Infection Control in the era of COVID-19: A narrative review. Antibiotics 2021, 10, 1244. [Google Scholar] [CrossRef]
  56. Mahmoudi, H. Bacterial co-infections and antibiotic resistance in patients with COVID-19. GMS. Hyg. Infect. Control 2020, 15, Doc35. [Google Scholar]
  57. Vaneechoutte, M.; Dijkshoorn, L.; Tjernberg, I.; Elaichouni, A.; De Vos, P.; Claeys, G.; Verschraegen, G. Identification of Acinetobacter Genomic Species by Amplified Ribosomal DNA Restriction Analysis. J. Clin. Microbiol. 1995, 33, 11–15. [Google Scholar] [CrossRef]
  58. Han, R.; Shi, Q.; Wu, S.; Yin, D.; Peng, M.; Dong, D.; Zheng, Y.; Guo, Y.; Zhang, R.; Hu, F.; et al. Dissemination of Carbapenemases (KPC, NDM, OXA-48, IMP, and VIM) Among Carbapenem-Resistant Enterobacteriaceae Isolated from Adult and Children Patients in China. Front. Cell. Infect. Microbiol. 2020, 10, 314. [Google Scholar] [CrossRef] [PubMed]
  59. Mendes, R.E.; Kiyota, K.A.; Monteiro, J.; Castanheira, M.; Andrade, S.S.; Gales, A.C.; Pignatari, A.C.C.; Tufik, S. Rapid detection and identification of metallo-beta-lactamase-encoding genes by multiplex real-time PCR assay and melt curve analysis. J. Clin. Microbiol. 2007, 45, 544–547. [Google Scholar] [CrossRef] [PubMed]
  60. Kiffer, C.R.V.; Rezende, T.F.T.; Costa-Nobre, D.T.; Marinonio, A.S.S.; Shiguenaga, L.H.; Kulek, D.N.O.; Arend, L.N.V.S.; Santos, I.C.d.O.; Sued-Karam, B.R.; Rocha-de-Souza, C.M.; et al. A 7-Year Brazilian National Perspective on Plasmid-Mediated Carbapenem Resistance in Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii Complex and the Impact of the Coronavirus Disease 2019 Pandemic on Their Occurrence. Clin. Infect. Dis. 2023, 77, S29–S37. [Google Scholar] [CrossRef] [PubMed]
Antibiotics 14 00866 g001
Figure 1. Frequency of carbapenem-resistant Klebsiella spp. isolates by clinical specimen.
Figure 1. Frequency of carbapenem-resistant Klebsiella spp. isolates by clinical specimen.
Antibiotics 14 00866 g001
Antibiotics 14 00866 g002
Figure 2. Frequency of Carbapenem-Resistant Klebsiella spp. Isolates per Clinical Sample: Pre-Pandemic vs. Pandemic Periods. (*) Statistically significant results.
Figure 2. Frequency of Carbapenem-Resistant Klebsiella spp. Isolates per Clinical Sample: Pre-Pandemic vs. Pandemic Periods. (*) Statistically significant results.
Antibiotics 14 00866 g002
Antibiotics 14 00866 g003
Figure 3. Time trend pattern for blaNDM and blaKPC detection rate by quarter from 2018 to 2021.
Figure 3. Time trend pattern for blaNDM and blaKPC detection rate by quarter from 2018 to 2021.
Antibiotics 14 00866 g003
Antibiotics 14 00866 g004
Figure 4. Total frequency of Klebsiella spp. isolates by ward of origin.
Figure 4. Total frequency of Klebsiella spp. isolates by ward of origin.
Antibiotics 14 00866 g004
Table 1. Statistical analysis of correlation between the pre pandemic and pandemic period and variables.
Table 1. Statistical analysis of correlation between the pre pandemic and pandemic period and variables.
Pre-Pandemic Period
N (%)		Pandemic Period
N (%)		p Value
Correlation—Carbapenemases
Carbapenemase producer193 (77.2%)451 (85.9%)0.003 *
KPC producer172 (68.8%)274 (52.2%)0.000 *
NDM producer21 (8.4%)222 (42.3%)0.000 *
Correlation—Type of hospitalization ward
Adult UCI99 (39.6%)258 (49.1%)0.013 *
Pediatric UCI16 (6.4%)18 (3.4%)0.059
Neonatal UCI8 (3.2%)6 (1.1%)0.044 *
Medical clinics67 (26.8%)158 (30.1%)0.345
Correlation—Clinical sample
Whole blood33 (13.2%)88 (16.8%)0.202
Catheter tip5 (2%)11 (2.1%)0.931
Tracheal secretion46 (18.4%)134 (25.5%)0.028 *
Urine72 (28.8%)98 (18.7%)0.001 *
Surveillance swab55 (22%)148 (28.2%)0.040 *
Wound secretion9 (3.6%)23 (4.4%)0.609
Correlation—Age range
NB (Up to 1 month)7 (2.8%)5 (1%)0.051
Child (0–12)45 (18%)38 (7.2%)0.001 *
Young (13–18)10 (4%)16 (3%)0.491
Adult (19–59)80 (32%)209 (39.8%)0.036 *
Elderly (+60)105 (42%)196 (37.3%)0.213
(*) Statistically significant results.
Table 2. Detection rate of carbapenemase genes in Klebsiella spp. from 2018 to 2021.
Table 2. Detection rate of carbapenemase genes in Klebsiella spp. from 2018 to 2021.
Year of Sample CollectionCarbapenemase Genes Detected
blaKPCblaNDMblaOXA-48blaIMPblaVIMCoproduction
blaKPC + blaNDM
201864%
(67/105)		3%
(3/105)		0%
(0/0)		0%
(0/0)		0%
(0/0)		0%
(0/0)
201974%
(107/145)		13%
(19/145)		0%
(0/0)		0%
(0/0)		0%
(0/0)		1.3%
(2/145)
202055%
(76/138)		39%
(54/138)		0.7%
(1/138)		0%
(0/0)		0%
(0/0)		6.5%
(9/138)
202152%
(200/387)		44%
(172/387)		0%
(0/0)		0.2%
(1/387)		0%
(0/0)		10%
(39/387)
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

Share and Cite

MDPI and ACS Style

Barros, T.B.C.; Rodrigues, Y.C.; Lobato, A.R.F.; Dutra, L.M.G.; dos Reis, H.S.; Garcia, A.J.P.; Sagica, F.d.E.S.; Souza, C.d.O.; Brasiliense, D.M. Impact of the COVID-19 Pandemic on Carbapenem-Resistant Klebsiella pneumoniae in Northern Region, Brazil: A Shift Towards NDM Producers. Antibiotics 2025, 14, 866. https://doi.org/10.3390/antibiotics14090866

AMA Style

Barros TBC, Rodrigues YC, Lobato ARF, Dutra LMG, dos Reis HS, Garcia AJP, Sagica FdES, Souza CdO, Brasiliense DM. Impact of the COVID-19 Pandemic on Carbapenem-Resistant Klebsiella pneumoniae in Northern Region, Brazil: A Shift Towards NDM Producers. Antibiotics. 2025; 14(9):866. https://doi.org/10.3390/antibiotics14090866

Chicago/Turabian Style

Barros, Thalyta Braga Cazuza, Yan Corrêa Rodrigues, Amália Raiana Fonseca Lobato, Lívia Maria Guimarães Dutra, Herald Souza dos Reis, Ana Judith Pires Garcia, Fernanda do Espírito Santo Sagica, Cintya de Oliveira Souza, and Danielle Murici Brasiliense. 2025. "Impact of the COVID-19 Pandemic on Carbapenem-Resistant Klebsiella pneumoniae in Northern Region, Brazil: A Shift Towards NDM Producers" Antibiotics 14, no. 9: 866. https://doi.org/10.3390/antibiotics14090866

APA Style

Barros, T. B. C., Rodrigues, Y. C., Lobato, A. R. F., Dutra, L. M. G., dos Reis, H. S., Garcia, A. J. P., Sagica, F. d. E. S., Souza, C. d. O., & Brasiliense, D. M. (2025). Impact of the COVID-19 Pandemic on Carbapenem-Resistant Klebsiella pneumoniae in Northern Region, Brazil: A Shift Towards NDM Producers. Antibiotics, 14(9), 866. https://doi.org/10.3390/antibiotics14090866

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop