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Active surveillance of carbapenem-resistant Gram-negative healthcare-associated infections in a low-middle-income country city

ABSTRACT

Background:

Carbapenem-resistance in healthcare-associated infections (HCAIs) is of great concern, and it is urgent to improve surveillance. We aimed to describe and analyze HCAIs trends on Gram-negative antimicrobial susceptibility in a city from a developing country, following the implementation of an active surveillance program.

Methods:

This is an aggregated study describing data from 24 hospitals with intensive care units, including a trend analysis by Joinpoint regression between January 2012 and December 2017.

Results:

There were 23,578 pathogens in 39,832 HCAIs, from which 16,225 were Gram-negatives (68.8%). Carbapenem susceptibility was lowest in A. baumannii (15.4–25.9%), K. pneumoniae (51.0–55.9%), and P. aeruginosa (64.9–84.1%) and highest in E. coli (96.5–99.2%). Only K. pneumoniae showed a significant Joinpoint at 95% confidence interval: −10.71% (−18.02; −2.75) from 2012 to 2014, p = 0.02, and 6.54% (−2.00; 15.83) from 2015 to 2017, p = 0.12, which was most influenced by urinary tract infections: −9.98% (−16.02; −3.48) from 2012 to 2014, p = 0.01, and 9.66% (−1.75; 22.39) from 2015 to 2017, p = 0.09.

Conclusion:

Although we found a significant change toward an improvement in carbapenem susceptibility in K. pneumoniae, resistance is high for most pathogens. These data should encourage health institutions to improve their prevention and control strategies.

Keywords:
Healthcare-associated infections; Carbapenem resistance; Active surveillance; Low-middle-income countries

Introduction

The burden of healthcare-associated infections (HCAIs) in developing countries is of great concern, and there is an urgent need to improve surveillance and infection control practices.11 Allegranzi B, Nejad SB, Combescure C, et al. Burden of endemic health-care-associated infection in developing countries: systematic review and meta-analysis. Lancet. 2011;377:228-41.

HCAIs caused by multidrug-resistant organisms (MDRO) are associated with high mortality rates and increased hospital length of stay and costs.22 Dick AW, Perencevich EN, Pogorzelska-Maziarz M, Zwanziger J, Larson EL, Stone PW. A decade of investment in infection prevention: a cost-effectiveness analysis. Am J Infect Control. 2015;43:4-9. Therefore, national, regional, and local continuous surveillance programs are important to assist health institutions on HCAIs and avoid the emergence of MDRO.33 Friedman ND, Carmeli Y, Walton AL, Schwaber MJ. Carbapenem-resistant enterobacteriaceae: a strategic roadmap for infection control. Infect Control Hosp Epidemiol. 2017;38:580-94.

The World Health Organization (WHO) has pointed out a priority list of antibiotic-resistant bacteria to guide research and development of new antibiotics. Carbapenem-resistant Gram-negative bacilli (A. baumannii, P. aeruginosa, and Enterobacterales) were listed as “number one priority” for implementation of active surveillance, prevention, and control actions in healthcare organizations.44 Tacconelli E, Carrara E, Savoldi A, et al. Discovery, research, and development of new antibiotics: the WHO priority list of antibiotic-resistant bacteria and tuberculosis. Lancet Infect Dis. 2018;18:318-27. Interestingly, an European surveillance report from 2009 to 2012 showed that carbapenem-resistant K. pneumoniae occurrence varied from 0% to 60.5%, and carbapenem-resistant P. aeruginosa occurrence was >10% in 19 of 29 reporting countries.55. Antimicrobial resistance and healthcare-associated infections – annual epidemiological report 2014 [2012 data]. Annu Epidemiol Rep Commun Dis Eur. 2015.

In Brazil, data on surveillance of MDRO related to HCAIs are limited, and incidence trends of HCAIs due to carbapenem-resistant A. baumannii has been described in a 12-month period in the city of Porto Alegre in southern Brazil.66 Martins AF, Kuchenbecker RS, Pilger KO, Pagano M, Barth AL. High endemic levels of multidrug-resistant Acinetobacter baumannii among hospitals in southern Brazil. Am J Infect Control. 2012;40:108-12. Based on that study, eight clonal groups were identified by molecular typing, and three of these were found in 12 public hospitals included in the report.

Data from the Brazilian SCOPE study (Surveillance and Control of Pathogens of Epidemiological Importance), showed that 58.5% of 2563 cases of bloodstream infections at 16 hospitals were caused by Gram-negative bacteria. Additionally, Acinetobacter spp. and P. aeruginosa isolates were resistant to carbapenem in 55.9% and 36.8% of cases, respectively.77 Marra AR, Camargo LFA, Pignatari ACC, et al. Nosocomial bloodstream infections in Brazilian hospitals: analysis of 2,563 cases from a prospective nationwide surveillance study. J Clin Microbiol. 2011;49:1866-71.

In Curitiba, another capital city located in south Brazil, the prevalence of MDRO in HCAIs was described for the first time in 2012 by the Municipal Health Department through the Working Group in HCAIs.88 Toledo PVM, Arend LN, Pilonetto M, Costa Oliveira JC, Luhm KR. Surveillance programme for multidrug-resistant bacteria in healthcare-associated infections: an urban perspective in South Brazil. J Hosp Infect. 2012;80:351-3. In that study, analysis from 2011 showed that carbapenem-resistant A. baumannii and third-generation-cephalosporin-resistant K. pneumoniae were the most frequent MDRO in HCAIs and, carbapenem-resistant Enterobacterales prevalence in HCAIs varied from 2.1 to 8.0%.

Therefore, this study aimed to describe epidemiological trends and analyze possible changes in Gram-negative carbapenem susceptibility reported in HCAIs from January 2012 to December 2017, in the city of Curitiba, state of Paraná (PR), Brazil, following the implementation of an active surveillance program.

Methods

Study design

This is an aggregated data study that gathered information on HCAIs reports from the Municipal and State Health Departments of Curitiba, PR. This study was approved by the research ethics committee of Pontifícia Universidade Católica do Paraná (Certificate of Presentation for Ethical Appreciation, 87394318.0.0000.0020).

Setting

This study was conducted in Curitiba, PR, a city of 434.89 km2 located in southern Brazil, with a population of 1,751,907 (2010), demographic density of 4027.04 inhabitants/km2 (2010), and per capita Gross Domestic Product of approximately U$ 8358.74 (2017), according to the Brazilian Institute of Geography and Statistics (Instituto Brasileiro de Geografia e Estatística).99 Brasil. Instituto Brasileiro de Geografia e Estatística. IBGE. Available from: https://cidades.ibge.gov.br/brasil/pr/curitiba/panorama [accessed 22.11.19].
https://cidades.ibge.gov.br/brasil/pr/cu...

Data were abstracted from January 2012 through December 2017, following the implementation of an active surveillance program by the Curitiba Municipal Health Department in October 2010, through the Working Group in HCAIs. This municipal surveillance program consists of monthly notifications, by hospital infection control teams, of whole institution data on HCAIs etiological pathogens and sites such as bloodstream infection (BSI), urinary tract infection (UTI), respiratory tract infection (RTI), and surgical infection (SSI). All participating hospitals were instructed to notify the microorganisms only once per infection episode. The data was validated monthly by the team responsible for this monitoring at the municipal health department. No specific data were requested related to negative or unsolicited cultures. In addition to Municipal Health Department notification, institutions were also to report data on admissions and rate of HCAIs in a web-based platform monitored by the Paraná State Health Department.

As part of the surveillance program, to ensure adequate data collection, meetings were held with all hospitals involved. Time framing was defined as semiannual presentations of surveillance data to the participating hospitals and educational workshops held in each of these opportunities. Finally, in 2012, the Working Group in Healthcare-Associated Infections developed and issued a local technical note to guide healthcare institutions on the prevention and control of MDRO.1010 Brasil. Secretaria Municipal de Saúde de Curitiba. Nota Técnica N01/2012: Prevenção e Controle de Bactérias Multirresistentes e Manejo de Multirresistentes em Infecções Relacionadas à Assistência à Saúde. Available from: https://www.paressaude.com.br/download.php?arquivo=/home/202441.cloudwaysapps.com/sevyexubcn/public_html/admin/uploads/notas-tecnicas/1990-NORMA_TECNICA_CURITIBA.pdf [accessed 22.11.19].
https://www.paressaude.com.br/download.p...

Participants

All hospitals with intensive care unit (ICU) that adhered to the notification program were included. Hospitals with exclusive maternity care were excluded.

Variables and data source

All data were made available by the Municipal and State Health Departments, and to characterize the group of selected hospitals, data were collected regarding the number of beds and administrative area (private or public). Information related to the number of hospitalizations was also included. For HCAIs definitions, the use of the national criteria provided by the Brazilian Health Surveillance Agency 1111 Brasil Agência Nacional de Vigilância Sanitária A. Critérios Diagnósticos de Infecção Relacionada à Assistência à Saúde. Available from: http://portal.anvisa.gov.br/documents/33852/3507912/Caderno+2+-+Critérios+Diagnósticos+de+Infecção+Relacionada+à+Assistência+à+Saúde/7485b45a-074f-4b34-8868-61f1e5724501 [accessed 22.11.19].
http://portal.anvisa.gov.br/documents/33...
, which is based on the Centers for Disease Control and Prevention criteria, was recommended. Moreover, for laboratories that provided microbiological support to hospitals, the use of Clinical and Laboratory Standards Institute for microbial sensitivity test parameters was suggested and about antimicrobial susceptibility methods, conventional (Kirby–Bauer) or any automated method of susceptibility test were accepted. The notification of pathogens as an etiological agent of HCAIs was performed in a grouped manner by the defined site of infection.

According to the Municipal Health Department Surveillance Program, the reported pathogens included subgroups of non-fermenting Gram-negative, fermenting Gram-negative, and Gram-positive bacteria and fungi. For each group of bacteria, specific antimicrobial susceptibility was monitored. However, based on the purpose of this study, only data on carbapenems and Gram-negative bacteria were analyzed. Hospitals were instructed to report susceptibility to carbapenems in P. aeruginosa, A. baumannii, K. pneumoniae, E. coli, Enterobacter cloacae, and other Enterobacterales that included Serratia spp., Citrobacter spp., Proteus spp., Morganella spp. in a grouped manner. A colonization report was not included in this analysis.

Statistics analysis

Data on the number of admissions, number of HCAIs, and notified pathogens related to each site of infection were collected. The incidence rate of HCAIs was estimated using the number of HCAIs per 100 admissions. Carbapenem susceptibility was calculated using the number of carbapenem-susceptible (meropenem and/or imipenem) notified cases in the defined site divided by total number of that specific pathogen at the same site. The Joinpoint Regression Program 4.6.0.0 was used to verify the trend related to carbapenem susceptibility in Gram-negative bacteria.1212 Kim H, Fay MP, Feuer EJ, Midthune DN. Permutation tests for joinpoint regression with applications to cancer rates. Stat Med. 2000;19:335-51. The slope was significantly different from zero at the alpha level of 0.05 and 95% confidence interval (CI). Data were grouped in semiannual periods; therefore, the semiannual percent change (SAPC) provided by the program was related to 6-month periods. The software IBM SPSS Statistics 23.0 was used for descriptive statistics on infection rates and susceptibility profile.

Results

Profile of included institutions

Out of the 33 hospitals with ICU in Curitiba, 29 (87.8%) participated in the monthly notification of microorganisms since the surveillance program started in 2010. Of these, five have an exclusive maternity profile and were thus excluded. Therefore, data from 24 hospitals were included in our analysis.

Regarding institutions characteristics, 13 are private, five are public, and six have a mixed profile (public and private). Of the total number of beds, 31% (1297) are in private hospitals, 29% (1222) in public hospitals, and 40% (1652) in those with mixture profile. Seventeen establishments have only adult care, six have both adult and pediatric care, and one hospital has only pediatric care.

HCAI incidence rate

During the study period, 39,832 new HCAIs were noted in 1,503,634 admissions (2.65%; minimum 0.22%; maximum 12.41%).

Microorganisms reported in HCAIs

The majority of notified microorganisms in HCAIs were Gram-negative (Table 1). Non-fermenting Gram-negative microorganisms were predominant in RTI. However, in UTI and SSI, fermenting Gram-negative microorganisms were the most frequent. In BSI, altogether fermenting and non-fermenting Gram-negative microorganisms outnumbered Gram-positive microorganisms.

Table 1
Distribution of microorganisms notified in HCAIs, in 24 hospitals with ICUs (2012-17).

The frequency of Gram-negative species varied according to the HCAI site (Table 2). In SSI, E. coli (20.7%), K. pneumoniae (20.7%), and Enterobacter spp. (16.1%) were the most frequently notified Gram-negative pathogens. In RTI, the first ranked Gram-negative pathogens were P. aeruginosa (28.7%), K. pneumoniae (24.9%), and A. baumannii (21.7%). In BSI, K. pneumoniae was the most frequent Gram-negative pathogen (32.1%), followed by Enterobacter spp. (14.5%) and other Enterobacterales (14.5%). Finally, in UTI, E. coli was the most frequent pathogen (33.3%), followed by K. pneumoniae (30.8%) and P. aeruginosa (12.6%).

Table 2
Carbapenem susceptibility profile of Gram-negative HCAIs, in 24 hospitals with ICUs (2012-17).

Susceptibility profile

Regarding carbapenem susceptibility profile (Table 2), E. coli preserved susceptibility in all infection sites (>95%). In contrast, A. baumannii had the lowest susceptibility in all sites (15.4–25.9%). Carbapenem susceptibility of K. pneumoniae varied from 51% to 54%, considering the HCAI main sites. Furthermore, P. aeruginosa seemed to preserve carbapenem susceptibility in SSI (84.1%) but showed lower susceptibility (64.9–69.2%) in other sites.

Regarding trends in susceptibility profile (Table 3), some Gram-negative microorganisms showed changes in their trends. Notably, K. pneumoniae showed a 10.71% reduction in carbapenem susceptibility between 2012 and 2014, followed by a significant change in the tendency reflecting one Joinpoint, with an increase of 6.54% in the susceptibility profile from 2015 to 2017.

Table 3
Carbapenem susceptibility trend analysis in Gram-negative bacteria recovered in HCAIs (2012-17).

The trend analysis for K. pneumoniae in each infection site (Table 4) showed similar variation only in UTI (Fig. 1). First, from 2012 to the first semester of 2015, the SAPC (95% CI) was −9.98% (−16.03, −3.48; p = 0.01). Subsequently, the SAPC (95% CI) was 9.66% (−1.75, 22.39; p = 0.09).

Table 4
Carbapenem susceptibility trend analysis in K. pneumoniae noted in HCAIs per site (2012-17).
Fig. 1
Carbapenem susceptibility trend analysis per semester in Klebsiella pneumoniae recovered in UTI, in 24 hospitals with ICUs (2012–17).

▪Observed SAPC (1–7): −9.98*; SAPC (7–12): 9.66.

UTI, urinary tract infection; ICUs, intensive care units; SAPC, semiannual percent change by Joinpoint regression.


Discussion

The most important findings in our study were as follows: (a) Gram-negative pathogens were the most frequent in all infection sites, and carbapenem susceptibility was lowest in A. baumannii, followed by K. pneumoniae and P. aeruginosa. (b) K. pneumoniae was the most common pathogen in BSIs with relevant carbapenem resistance in about half of the notifications. (c) The carbapenem susceptibility profile of K. pneumoniae has changed at a certain point in the study period, most influenced by UTI.

Regarding the proportion of Gram-negative pathogens in HCAIs, according to Allegranzi,11 Allegranzi B, Nejad SB, Combescure C, et al. Burden of endemic health-care-associated infection in developing countries: systematic review and meta-analysis. Lancet. 2011;377:228-41. Gram-negative bacilli were the most common nosocomial isolates, in both mixed populations and high risk-patients, based on information on pathogens causing HCAIs in developing countries in 28 of 220 selected studies.11 Allegranzi B, Nejad SB, Combescure C, et al. Burden of endemic health-care-associated infection in developing countries: systematic review and meta-analysis. Lancet. 2011;377:228-41. Moreover, among Gram-negative pathogens, carbapenem nonsusceptible (Carb-NS) A. baumannii is considered one of the most relevant pathogens at the WHO priority list of antibiotic-resistant bacteria.44 Tacconelli E, Carrara E, Savoldi A, et al. Discovery, research, and development of new antibiotics: the WHO priority list of antibiotic-resistant bacteria and tuberculosis. Lancet Infect Dis. 2018;18:318-27.

In fact, one of the major concerns on carbapenem resistance in our study is related to A. baumannii. Multidrug-resistant A. baumannii has been described in several outbreaks,1313 Munier AL, Biard L, Legrand M, et al. Incidence, risk factors and outcome of multi-drug resistant Acinetobacter baumannii nosocomial infections during an outbreak in a burn unit. Int J Infect Dis. 2019;79:179-84.,1414 Bogaty C, Mataseje L, Gray A, et al. Investigation of a Carbapenemase-producing Acinetobacter baumannii outbreak using whole genome sequencing versus a standard epidemiologic investigation. Antimicrob Resist Infect Control. 2018;7:1-7. and clonal dissemination is greatly important in these events. For example, in a study conducted in eight hospitals of PR, Brazil,1515 Cieslinski JM, Arend L, Tuon FF, et al. Molecular epidemiology characterization of OXA-23 carbapenemase-producing Acinetobacter baumannii isolated from 8 Brazilian hospitals using repetitive sequence-based PCR. Diagn Microbiol Infect Dis. 2013;77:337-40. the molecular epidemiological features from 46 strains of Carb-NS A. baumannii in 2009–2011 showed that all isolates carried the bla Oxacilinase (OXA)-23 gene. Seven clones were identified, and the main cluster included 32 (69.5%) of the total isolates, even though hospitals were several kilometers apart. Thus, we believe that our data, in addition to the presented discussion, could alert authorities and institutions to develop strategies aiming at better control.

P. aeruginosa is also a common pathogen in HCAIs, especially in RTI. A 1-day point prevalence survey in 28 Brazilian ICUs identified that 40.5% of the 303 analyzed patients had at least one ICU-acquired infection.1616 Braga IA, Campos PA, Gontijo-Filho PP, Ribas RM. Multi-hospital point prevalence study of healthcare-associated infections in 28 adult intensive care units in Brazil. J Hosp Infect. 2018;99:318-24. The most frequent infections included pneumonia (53.0%) and BSI (27.6%), and P. aeruginosa was the most common pathogen in pneumonia (30.4%). Our data showed similar findings with occurrence of 28.7% of 5010 notified bacteria in RTI.

According to the National Healthcare Safety Network report in 2015–2017, among 15,706 tested isolates of P. aeruginosa in device-associated infections 20.7% were resistant to carbapenems.1717 Weiner-Lastinger LM, Abner S, Mstat JRE. Antimicrobial-resistant pathogens associated with adult healthcare-associated infections: summary of data reported to the National Healthcare Safety Network, 2015–2017. Infect Control Hosp Epidemiol. 2019;:1-18. Our data identified that out of 932 notified carbapenem resistant RTI, 35.1% of was caused by this pathogen, underscoring the relevant occurrence at this site of infection. Meanwhile, regarding the molecular epidemiology of this carbapenem resistance, one study conducted in Paraná (Brazil), between January 2009 and December 2012, identified that SPM-1 (São Paulo metallo-beta-lactamase) was the main metallo-beta-lactamase identified in Carb-NS P. aeruginosa in southern Brazil, with genetic similarity among some isolates suggesting clonal expansion.1818 Kalluf KO, Arend LN, Wuicik TE, Pilonetto M, Tuon FF. Molecular epidemiology of SPM-1-producing Pseudomonas aeruginosa by rep-PCR in hospitals in Parana, Brazil. Infect Genet Evol. 2017;49:130-3.

Shifting focus to carbapenem-resistant Enterobacterales (CRE), which includes K. pneumoniae, we presented in our study that this was the most common pathogen in BSIs with considerable carbapenem resistance. In a Brazilian nationwide surveillance study between 2007 and 2010 in 16 hospitals, Gram-negative organisms caused 58.5% of 2563 BSIs, in which Klebsiella spp. and Acinetobacter spp. were the most prevalent Gram-negative pathogens.77 Marra AR, Camargo LFA, Pignatari ACC, et al. Nosocomial bloodstream infections in Brazilian hospitals: analysis of 2,563 cases from a prospective nationwide surveillance study. J Clin Microbiol. 2011;49:1866-71.

In fact, it is interesting to mention that CRE has become increasingly prevalent worldwide, mainly by harboring mobile genetic elements.1919 Logan LK, Weinstein RA. The epidemiology of Carbapenem-resistant enterobacteriaceae: the impact and evolution of a global menace. J Infect Dis. 2017;215(Suppl. 1):S28-36. In Curitiba, PR (Brazil), the clonal diversity of several isolates from clinical samples and rectal swabs obtained between April 2010 and July 2012 was detected in 641 positive samples for KPC-2-producing K. pneumoniae (Klebsiella pneumoniae carbapenemase). Moreover, in 129 samples randomly selected for clonality evaluation, seven different clones were identified, showing the polyclonallity of the Curitiba outbreak.2020 Arend LN, Toledo P, Pilonetto M, Tuon FF. Molecular epidemiology of Klebsiella pneumoniae carbapenemase-producing Enterobacteriaceae in different facilities in Southern Brazil. Am J Infect Control. 2015;43:137-40.

In addition to the potential for clonal dissemination, using invasive medical devices and carbapenem consumption are also important factors that can facilitate acquiring CRE in the setting of a local outbreak.2121 Loon van K, Voor in ‘t holt AF, Vos MC. A systematic review and meta-analyses of the clinical epidemiology of carbapenem-resistant enterobacteriaceae. Antimicrob Agents Chemother. 2018;62:1-18, e01730-17. Thus, efforts should be focused on the prevention and control of this dissemination, as it happened in Israel.2222 Dickstein Y, Temkin E, Ish Shalom M, Schwartz D, Carmeli Y, Schwaber MJ. Trends in antimicrobial resistance in Israel, 2014–2017. Antimicrob Resist Infect Control. 2019;8:1-5. In this country, there was no significant change in the proportion of Carb-NS K. pneumoniae isolates in BSI between 2014 and 2017 (4.6 to 4.0%, p = 0.36). According to these authors, the lowest proportion of Carb-NS K. pneumoniae observed in Israel occurred in the context of a national effort to control an outbreak witch expanded the actions of prevention, control, and resistance monitoring in the country.2323 Schwaber MJCY. An ongoing national intervention to contain the spread of carbapenem-resistant enterobacteriaceae. Clin Infect Dis. 2014;5:697-703.

Regarding the susceptibility profile trend, our data analysis showed a reduction in carbapenem susceptibility in K. pneumoniae between 2012 and 2014, but from 2015, an improvement was observed, mostly influenced by UTI. It is not possible to affirm which reasons were related to this change, since this study did not include analysis of directed interventions by each institution. However, as it is an ecological study, it is possible to raise questions that could have influenced this finding.

Effective control strategies to prevent the establishment of CRE endemicity in a region include early detection through target laboratory protocols and containment of spread through comprehensive infection control measures.33 Friedman ND, Carmeli Y, Walton AL, Schwaber MJ. Carbapenem-resistant enterobacteriaceae: a strategic roadmap for infection control. Infect Control Hosp Epidemiol. 2017;38:580-94. Furthermore, as the duration of urinary catheterization is the predominant risk factor for catheter-associated UTI, preventive measures directed at limiting the placement and early removal or urinary catheters can significantly reduce these infection rates.2424 Chenoweth CE, Gould CV, Saint S. Diagnosis, management, and prevention of catheter-associated urinary tract infections. Infect Dis Clin North Am. 2014;28:105-19. Finally, it is important to determine the influence of carbapenem consumption on CRE control. A study that analyzed data of 134 patients with CRE infection between 2011 and 2016, at a tertiary care hospital in Thailand, showed an increase in CRE incidence rate of 1.02 per 100,000 patient-days for a defined daily dose per 1000 patient-days increase in carbapenem consumption (p < 0.001).2525 Chotiprasitsakul D, Srichatrapimuk S, Kirdlarp S, Pyden AD, Santanirand P. Epidemiology of carbapenem-resistant Enterobacteriaceae: a 5-year experience at a tertiary care hospital. Infect Drug Resist. 2019;12:461-8. Our study did not include antimicrobial monitoring data as this information had not been requested by the municipal health department to hospitals until then. However, we believe that efforts should be made in this direction to incorporate this surveillance in the prevention and control measures of CRE.

Overall, we believe the results of our study provide support for infection control teams and stewardship efforts to improve and monitor infection control measures besides antibiotic consumption at local healthcare institutions along with bacterial resistance.

Some limitations of our study include the ecological nature and unavailability of laboratory confirmation by case of notified isolates in HCAIs, as data were reported by the hospitals in a grouped manner. Furthermore, as the surveillance program did not request separated notifications inside and outside the ICUs, it was not possible to detail findings more specifically related to ICU and device associated HCAIs. Also, as for this analysis, the data on patient-days per institution was not available, it was not possible to calculate the incidence density per 1000 patient-days for carbapenem-resistant Gram-negative bacteria. Finally, the possibility of underreporting or even some manual errors in HCAIs data notification by the hospital team should be considered, which could not be controlled in our study, generating residual bias.

In conclusion, the analysis presented in this study consists of important and updated surveillance information to support health institutions and authorities to develop control and prevention actions. Moreover, it should encourage future research on interventions capable of improving local epidemiology of microbial resistance, such as the establishment of directed protocols for antimicrobial treatment of infections, improvement in hospital infection control programs, and reduction of carbapenem consumption.

  • Financial disclosures
    None declared.

Acknowledgment

This study was supported by CAPES – Coordination for the Improvement of Higher Education Personnel, Ministry of Education, Brazil.

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    Dick AW, Perencevich EN, Pogorzelska-Maziarz M, Zwanziger J, Larson EL, Stone PW. A decade of investment in infection prevention: a cost-effectiveness analysis. Am J Infect Control. 2015;43:4-9.
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    Friedman ND, Carmeli Y, Walton AL, Schwaber MJ. Carbapenem-resistant enterobacteriaceae: a strategic roadmap for infection control. Infect Control Hosp Epidemiol. 2017;38:580-94.
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    Tacconelli E, Carrara E, Savoldi A, et al. Discovery, research, and development of new antibiotics: the WHO priority list of antibiotic-resistant bacteria and tuberculosis. Lancet Infect Dis. 2018;18:318-27.
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    Martins AF, Kuchenbecker RS, Pilger KO, Pagano M, Barth AL. High endemic levels of multidrug-resistant Acinetobacter baumannii among hospitals in southern Brazil. Am J Infect Control. 2012;40:108-12.
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    Marra AR, Camargo LFA, Pignatari ACC, et al. Nosocomial bloodstream infections in Brazilian hospitals: analysis of 2,563 cases from a prospective nationwide surveillance study. J Clin Microbiol. 2011;49:1866-71.
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    Toledo PVM, Arend LN, Pilonetto M, Costa Oliveira JC, Luhm KR. Surveillance programme for multidrug-resistant bacteria in healthcare-associated infections: an urban perspective in South Brazil. J Hosp Infect. 2012;80:351-3.
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    Kim H, Fay MP, Feuer EJ, Midthune DN. Permutation tests for joinpoint regression with applications to cancer rates. Stat Med. 2000;19:335-51.
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    Cieslinski JM, Arend L, Tuon FF, et al. Molecular epidemiology characterization of OXA-23 carbapenemase-producing Acinetobacter baumannii isolated from 8 Brazilian hospitals using repetitive sequence-based PCR. Diagn Microbiol Infect Dis. 2013;77:337-40.
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    Kalluf KO, Arend LN, Wuicik TE, Pilonetto M, Tuon FF. Molecular epidemiology of SPM-1-producing Pseudomonas aeruginosa by rep-PCR in hospitals in Parana, Brazil. Infect Genet Evol. 2017;49:130-3.
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    Logan LK, Weinstein RA. The epidemiology of Carbapenem-resistant enterobacteriaceae: the impact and evolution of a global menace. J Infect Dis. 2017;215(Suppl. 1):S28-36.
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Publication Dates

  • Publication in this collection
    16 June 2021
  • Date of issue
    2021

History

  • Received
    5 July 2020
  • Accepted
    13 Jan 2021
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