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Risk factors for central venous catheter-related bloodstream infection in neonates
ARTICLE IN PRESS American Journal of Infection Control 000 (2019) 1−2
Contents lists available at ScienceDirect
American Journal of Infection Control journal homepage: www.ajicjournal.org
Brief Report
Risk factors for central venous catheter-related bloodstream infection in neonates Janita Ferreira PhD a,*, Paulo Augusto Moreira Camargos PhD b, Viviane Rosado PhD a, ~o MD a, Roberta Maia de Castro Romanelli PhD b Paulo Henrique Orlandi Moura a b
~o de Controle de Infec¸c o ~es Hospitalares, Hospital das Clínicas da Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil Comissa Faculdade de Medicina da Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
Key Words: Catheter-related sepsis Neonate Newborn
We found that low birth weight and type of central venous catheter were associated with catheter-related bloodstream infection in neonates. In the multivariate analysis, only central venous catheter type (dissected veins, tunneled catheters, and short-term nontunneled catheters) remained significantly associated with catheter-related bloodstream infection. © 2019 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.
Intravascular devices are widely used in neonatal units for the treatment of premature and low-birth-weight newborns. However, central venous catheters (CVCs) are the main risk factor for neonatal sepsis, and catheter-related bloodstream infection (CRBSI) is one of the main causes of high mortality and morbidity in infants.1-3 The diagnosis of CRBSI remains challenging as microbiological evidence implicating the CVC as a source of infection is necessary to establish the diagnosis. However, scientific literature and surveillance reports have limited data on CRBSI rates and risk factors.4,5 Considering the clinical and epidemiological importance of CRBSI in neonatology, it is important to identify the factors associated with the occurrence of sepsis in newborns with a catheter in place. METHODS Study population and design This prospective cohort study was carried out from January 2012 to December 2018 at a referral center. All high-risk newborns who had at least one CVC during the study period (peripherally inserted central catheter [PICC], umbilical venous catheter [UVC], and other types of CVC, that is, dissected veins, tunneled long-term catheters, and short-term nontunneled catheters) were included. * Address correspondence to Janita Ferreira PhD, Avenida Alfredo Balena, 110. ^nia, Belo Horizonte, MG 30130-100, Brazil. 1 andar/CCIH, Santa Efige E-mail address: [email protected] (J. Ferreira). Conflicts of interest: None to report.
Definitions All episodes of laboratory-confirmed bloodstream infection (LCBI) were identified, and cases that met the criteria for CRBSI were recorded as outcome. The laboratory-confirmed bloodstream infection diagnosis was confirmed in neonates with a recognized pathogen cultured from one or more blood cultures, and the organism was not related to an infection at another site. It was also confirmed in neonates with signs associated with sepsis in which the common skin contaminant organism was detected from 2 or more blood cultures or the coagulase-negative Staphylococcus was detected from at least one peripheral blood culture from a patient with a CVC.6 The definitive diagnosis of CRBSI requires the isolation of the same organism from percutaneous blood culture and catheter sample. The diagnosis requires that 2 blood samples be drawn from a catheter hub and a peripheral vein, respectively, that when cultured, meet the criteria for differential time to positivity, which is the growth of microbes from a blood sample drawn from the catheter at least 2 hours before microbial growth is detected in a blood sample obtained from a peripheral vein. The diagnostic criteria for CRBSI is that when the device is removed, the growth of >15 colony-forming units from a 5-cm segment of the catheter tip by semiquantitative culture.7 Statistical analysis Data on CRBSI notifications and risk factors for CRBSI were entered into a spreadsheet (Microsoft Excel, release 14.0; Microsoft Inc., Redmond, WA) and analyzed using IBM SPSS Statistics for Windows, version 19.0 (IBM Inc., Armonk, NY).
https://doi.org/10.1016/j.ajic.2019.12.004 0196-6553/© 2019 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.
ARTICLE IN PRESS J. Ferreira et al. / American Journal of Infection Control 00 (2019) 1−2
2
The statistical analysis of variables associated with the response variable considered the first episode of CRBSI of each device. In the comparative analysis of risk factors between groups, x2 tests were used to assess the categorical variables, while Student t test or nonparametric Mann-Whitney tests were used to assess the continuous variables. Statistical significance was defined as P < .05. The variables that showed an association with CRBSI with P < .20 in univariate analysis were included in a multivariate Poisson regression model to assess the effect of each independent variable on the occurrence of CRBSI. This study was approved by the Institutional Review Board.
Table 2 Multivariate analyses of the variables and the occurrence of catheter-related bloodstream infection Variable
p
OR
95% CI
Type of CVC: UVC Type of CVC: PICC Type of CVC: Other Surgery Low birth weight Duration of indwelling time
0.000 0.000 0.377 0.578 0.816
0.69 0.84 1.0 0.94 1.0 1.0
0.56-085 0.73-0.96 0.87-1.04 1.0 0.99-1.0
CI, confidence interval; OR, odds ratio; PICC, peripherally inserted central catheter; UVC, umbilical venous catheter.
RESULTS A total of 1,983 high-risk newborns were admitted to the neonatal unit. Of them, 1,495 used at least one CVC and were included in this study. During the study period, 2,783 catheters were used, among which 49.0% were PICC, 39.5% were UVC, and 11.5% were other types of CVCs. The mean indwelling time of UVC, PICC, and other types of CVC were 4.0 days, 13.8 days, and 16.3 days, respectively. A total of 316 episodes of Laboratory-confirmed bloodstream infection in newborns with CVC were reported, of which 102 met the criteria for CRBSI. A comparative analysis was performed and showed a statistically significant association between the occurrence of CRBSI and the type of catheter and low birth weight (Table 1). The multivariate analysis included 4 variables: CVC type, birth weight, duration of indwelling time, and previous surgery. However, only other CVCs remained significantly associated with CRBSI (P < .001). Patients with UVC presented an OR of 0.69 (95% confidence interval [CI]: 0.56−0.85), while those with PICC presented an odds ratio of 0.84 (95% confidence interval 0.73-0.96) compared with those who used other CVCs (Table 2). DISCUSSION The results of the multivariate analysis in this study revealed that only other types of CVCs (dissected veins, tunneled long-term catheters, and short-term nontunneled catheters) were associated with the response variable; UVC presented a protection of 31%, while PICC presented a protection of 16%. A previous case-control study of 1,414 high-risk newborns conducted in the same neonatal unit demonstrated that previous surgery, in addition to the presence of CVC, was associated with late-onset bloodstream infections in hospitalized neonates.8 Table 1 Univariate analyses of the variables and the occurrence of catheter-related bloodstream infection CRBSI Variable
No n (%)
Yes n (%)
Total (%)
P
Sex: female Sex: male Type of CVC: UVC Type of CVC: PICC Type of CVC: Other Surgery: yes Surgery: no Adverse event: yes Adverse event: no Gestational age Duration of indwelling time Low birth weight
109 (50.9) 105 (49.1) 15 (7.0) 155 (72.4) 44 (20.6) 42 (19.6) 172 (80.4) 15 (7.0) 199 (93.0) -
47 (46.1) 55 (53.9) 1 (1.0) 61 (59.8) 40 (39.2) 28 (27.5) 74 (72.5) 6 (5.9) 96 (94.1) -
156 (49.4) 160 (50.6) 16 (5.1) 216 (68.4) 84 (26.6) 70 (22.2) 246 (77.8) 21 (6.6) 295 (93.4) -
.420*
PICC, peripherally inserted central catheter; UVC, umbilical venous catheter. *x2 test. y t test. z Mann-Whitney test.
.001*
.117* .707* .323y .117z .037y
Data from a Canadian cohort study showed no statistically significant difference in the risk of catheter-associated sepsis in preterm newborns less than 30 weeks of gestation who only used PICC, compared with those who used umbilical catheters. Therefore, no association was observed between sepsis and CVC type.9 A systematic literature review performed to assess the risk of bloodstream infection associated with intravascular devices in newborns demonstrated that only a few studies have provided information on these infections in Brazil.10 CONCLUSIONS The risk factor associated with the occurrence of CRBSI in this study was CVC type (dissected veins, tunneled catheters, and shortterm nontunneled catheters). The UVC might have been identified as a protective factor against CRBSI as the indwelling time is restricted to 4 days in this neonatal unit. The study hospital is a tertiary care and reference center that provides high-risk prenatal care and follow-up fetal medicine. The facility provides care for newborns with extremely severe clinical conditions and those requiring surgical treatments, in addition to premature and low-birth weight neonates, which may have affected the risk assessment in the present study. Therefore, further studies are needed to better evaluate the risk of CRBSI in the neonatal population. We emphasize that the identification of risk factors related to the occurrence of CRBSI in neonates are essential for the planning and implementation of prevention and control interventions. References 1. Couto R, Pedrosa T, Tofani C, Pedroso E. Risk factors for nosocomial infection in a neonatal intensive care. Infect Control Hosp Epidemiol 2006;27:571-5. 2. Kawagoe J, Segre C, Pereira C, Cardoso M, Silva C, Fukushima J. Risk factors for nosocomial infections in critically ill newborns: 5 year prospecive cohort study. Am J Infect Control 2001;29:109-14. 3. Rallis D, Karagianni P, Papakotoula I, Nikolaos N, Tsakalidis C. Significant reduction of central line-associated bloodstream infection rates in a tertiary neonatal unit. Am J Infect Control 2016;44:485-7. rios Diagno sticos de Infec¸c o ~ es Relacionadas a Assiste ^ncia a Sau de. 4. ANVISA. Crite Brasília: ANVISA; 2017. 5. Riboli D, Lyra J, Silva E, et al. Diagnostic accuracy of semi-quantitative and quantitative culture techniques for the diagnosis of catheter-related infections in newborns and molecular typing of isolated microorganisms. BMC Infect Dis 2014;14:283-91. rios Nacionais de Infec¸c o ~ es Relacionadas a Assiste ^ncia 6. ANVISA. Neonatologia: Crite a Sau de. Brasília: ANVISA; 2017. 7. Mermel L, Allon M, Bouza E, et al. Clinical practice guidelines for the diagnosis and management of intravascular catheter-related infection: 2009. Update by Infections Diseases Society of America. IDSA Guidelines 2009;49: 1-45. ~o MVA, et al. Risk factors and lethality of labo8. Romanelli RMC, Anchieta LM, Moura ratory-confirmed blodstream infection caused by non-skin contaminant pathogens in neonates. J Pediatr (Rio J) 2013;89:189-96. 9. Shalabi M, Adel M, Yoon E, Aziz K, Lee S, Shah P. Risk of infection using peripherally inserted central and umbilical catheters in preterm neonates. Pediatrics 2015;136:1073-9. 10. Rosado V, Camargos P, Anchieta L, et al. Risk factors for central venous catheterrelated infections in a neonatal population-systematic review. J Pediatr (Rio J) 2018;94:3-14.
Contents lists available at ScienceDirect
American Journal of Infection Control journal homepage: www.ajicjournal.org
Brief Report
Risk factors for central venous catheter-related bloodstream infection in neonates Janita Ferreira PhD a,*, Paulo Augusto Moreira Camargos PhD b, Viviane Rosado PhD a, ~o MD a, Roberta Maia de Castro Romanelli PhD b Paulo Henrique Orlandi Moura a b
~o de Controle de Infec¸c o ~es Hospitalares, Hospital das Clínicas da Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil Comissa Faculdade de Medicina da Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
Key Words: Catheter-related sepsis Neonate Newborn
We found that low birth weight and type of central venous catheter were associated with catheter-related bloodstream infection in neonates. In the multivariate analysis, only central venous catheter type (dissected veins, tunneled catheters, and short-term nontunneled catheters) remained significantly associated with catheter-related bloodstream infection. © 2019 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.
Intravascular devices are widely used in neonatal units for the treatment of premature and low-birth-weight newborns. However, central venous catheters (CVCs) are the main risk factor for neonatal sepsis, and catheter-related bloodstream infection (CRBSI) is one of the main causes of high mortality and morbidity in infants.1-3 The diagnosis of CRBSI remains challenging as microbiological evidence implicating the CVC as a source of infection is necessary to establish the diagnosis. However, scientific literature and surveillance reports have limited data on CRBSI rates and risk factors.4,5 Considering the clinical and epidemiological importance of CRBSI in neonatology, it is important to identify the factors associated with the occurrence of sepsis in newborns with a catheter in place. METHODS Study population and design This prospective cohort study was carried out from January 2012 to December 2018 at a referral center. All high-risk newborns who had at least one CVC during the study period (peripherally inserted central catheter [PICC], umbilical venous catheter [UVC], and other types of CVC, that is, dissected veins, tunneled long-term catheters, and short-term nontunneled catheters) were included. * Address correspondence to Janita Ferreira PhD, Avenida Alfredo Balena, 110. ^nia, Belo Horizonte, MG 30130-100, Brazil. 1 andar/CCIH, Santa Efige E-mail address: [email protected] (J. Ferreira). Conflicts of interest: None to report.
Definitions All episodes of laboratory-confirmed bloodstream infection (LCBI) were identified, and cases that met the criteria for CRBSI were recorded as outcome. The laboratory-confirmed bloodstream infection diagnosis was confirmed in neonates with a recognized pathogen cultured from one or more blood cultures, and the organism was not related to an infection at another site. It was also confirmed in neonates with signs associated with sepsis in which the common skin contaminant organism was detected from 2 or more blood cultures or the coagulase-negative Staphylococcus was detected from at least one peripheral blood culture from a patient with a CVC.6 The definitive diagnosis of CRBSI requires the isolation of the same organism from percutaneous blood culture and catheter sample. The diagnosis requires that 2 blood samples be drawn from a catheter hub and a peripheral vein, respectively, that when cultured, meet the criteria for differential time to positivity, which is the growth of microbes from a blood sample drawn from the catheter at least 2 hours before microbial growth is detected in a blood sample obtained from a peripheral vein. The diagnostic criteria for CRBSI is that when the device is removed, the growth of >15 colony-forming units from a 5-cm segment of the catheter tip by semiquantitative culture.7 Statistical analysis Data on CRBSI notifications and risk factors for CRBSI were entered into a spreadsheet (Microsoft Excel, release 14.0; Microsoft Inc., Redmond, WA) and analyzed using IBM SPSS Statistics for Windows, version 19.0 (IBM Inc., Armonk, NY).
https://doi.org/10.1016/j.ajic.2019.12.004 0196-6553/© 2019 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.
ARTICLE IN PRESS J. Ferreira et al. / American Journal of Infection Control 00 (2019) 1−2
2
The statistical analysis of variables associated with the response variable considered the first episode of CRBSI of each device. In the comparative analysis of risk factors between groups, x2 tests were used to assess the categorical variables, while Student t test or nonparametric Mann-Whitney tests were used to assess the continuous variables. Statistical significance was defined as P < .05. The variables that showed an association with CRBSI with P < .20 in univariate analysis were included in a multivariate Poisson regression model to assess the effect of each independent variable on the occurrence of CRBSI. This study was approved by the Institutional Review Board.
Table 2 Multivariate analyses of the variables and the occurrence of catheter-related bloodstream infection Variable
p
OR
95% CI
Type of CVC: UVC Type of CVC: PICC Type of CVC: Other Surgery Low birth weight Duration of indwelling time
0.000 0.000 0.377 0.578 0.816
0.69 0.84 1.0 0.94 1.0 1.0
0.56-085 0.73-0.96 0.87-1.04 1.0 0.99-1.0
CI, confidence interval; OR, odds ratio; PICC, peripherally inserted central catheter; UVC, umbilical venous catheter.
RESULTS A total of 1,983 high-risk newborns were admitted to the neonatal unit. Of them, 1,495 used at least one CVC and were included in this study. During the study period, 2,783 catheters were used, among which 49.0% were PICC, 39.5% were UVC, and 11.5% were other types of CVCs. The mean indwelling time of UVC, PICC, and other types of CVC were 4.0 days, 13.8 days, and 16.3 days, respectively. A total of 316 episodes of Laboratory-confirmed bloodstream infection in newborns with CVC were reported, of which 102 met the criteria for CRBSI. A comparative analysis was performed and showed a statistically significant association between the occurrence of CRBSI and the type of catheter and low birth weight (Table 1). The multivariate analysis included 4 variables: CVC type, birth weight, duration of indwelling time, and previous surgery. However, only other CVCs remained significantly associated with CRBSI (P < .001). Patients with UVC presented an OR of 0.69 (95% confidence interval [CI]: 0.56−0.85), while those with PICC presented an odds ratio of 0.84 (95% confidence interval 0.73-0.96) compared with those who used other CVCs (Table 2). DISCUSSION The results of the multivariate analysis in this study revealed that only other types of CVCs (dissected veins, tunneled long-term catheters, and short-term nontunneled catheters) were associated with the response variable; UVC presented a protection of 31%, while PICC presented a protection of 16%. A previous case-control study of 1,414 high-risk newborns conducted in the same neonatal unit demonstrated that previous surgery, in addition to the presence of CVC, was associated with late-onset bloodstream infections in hospitalized neonates.8 Table 1 Univariate analyses of the variables and the occurrence of catheter-related bloodstream infection CRBSI Variable
No n (%)
Yes n (%)
Total (%)
P
Sex: female Sex: male Type of CVC: UVC Type of CVC: PICC Type of CVC: Other Surgery: yes Surgery: no Adverse event: yes Adverse event: no Gestational age Duration of indwelling time Low birth weight
109 (50.9) 105 (49.1) 15 (7.0) 155 (72.4) 44 (20.6) 42 (19.6) 172 (80.4) 15 (7.0) 199 (93.0) -
47 (46.1) 55 (53.9) 1 (1.0) 61 (59.8) 40 (39.2) 28 (27.5) 74 (72.5) 6 (5.9) 96 (94.1) -
156 (49.4) 160 (50.6) 16 (5.1) 216 (68.4) 84 (26.6) 70 (22.2) 246 (77.8) 21 (6.6) 295 (93.4) -
.420*
PICC, peripherally inserted central catheter; UVC, umbilical venous catheter. *x2 test. y t test. z Mann-Whitney test.
.001*
.117* .707* .323y .117z .037y
Data from a Canadian cohort study showed no statistically significant difference in the risk of catheter-associated sepsis in preterm newborns less than 30 weeks of gestation who only used PICC, compared with those who used umbilical catheters. Therefore, no association was observed between sepsis and CVC type.9 A systematic literature review performed to assess the risk of bloodstream infection associated with intravascular devices in newborns demonstrated that only a few studies have provided information on these infections in Brazil.10 CONCLUSIONS The risk factor associated with the occurrence of CRBSI in this study was CVC type (dissected veins, tunneled catheters, and shortterm nontunneled catheters). The UVC might have been identified as a protective factor against CRBSI as the indwelling time is restricted to 4 days in this neonatal unit. The study hospital is a tertiary care and reference center that provides high-risk prenatal care and follow-up fetal medicine. The facility provides care for newborns with extremely severe clinical conditions and those requiring surgical treatments, in addition to premature and low-birth weight neonates, which may have affected the risk assessment in the present study. Therefore, further studies are needed to better evaluate the risk of CRBSI in the neonatal population. We emphasize that the identification of risk factors related to the occurrence of CRBSI in neonates are essential for the planning and implementation of prevention and control interventions. References 1. Couto R, Pedrosa T, Tofani C, Pedroso E. Risk factors for nosocomial infection in a neonatal intensive care. Infect Control Hosp Epidemiol 2006;27:571-5. 2. Kawagoe J, Segre C, Pereira C, Cardoso M, Silva C, Fukushima J. Risk factors for nosocomial infections in critically ill newborns: 5 year prospecive cohort study. Am J Infect Control 2001;29:109-14. 3. Rallis D, Karagianni P, Papakotoula I, Nikolaos N, Tsakalidis C. Significant reduction of central line-associated bloodstream infection rates in a tertiary neonatal unit. Am J Infect Control 2016;44:485-7. rios Diagno sticos de Infec¸c o ~ es Relacionadas a Assiste ^ncia a Sau de. 4. ANVISA. Crite Brasília: ANVISA; 2017. 5. Riboli D, Lyra J, Silva E, et al. Diagnostic accuracy of semi-quantitative and quantitative culture techniques for the diagnosis of catheter-related infections in newborns and molecular typing of isolated microorganisms. BMC Infect Dis 2014;14:283-91. rios Nacionais de Infec¸c o ~ es Relacionadas a Assiste ^ncia 6. ANVISA. Neonatologia: Crite a Sau de. Brasília: ANVISA; 2017. 7. Mermel L, Allon M, Bouza E, et al. Clinical practice guidelines for the diagnosis and management of intravascular catheter-related infection: 2009. Update by Infections Diseases Society of America. IDSA Guidelines 2009;49: 1-45. ~o MVA, et al. Risk factors and lethality of labo8. Romanelli RMC, Anchieta LM, Moura ratory-confirmed blodstream infection caused by non-skin contaminant pathogens in neonates. J Pediatr (Rio J) 2013;89:189-96. 9. Shalabi M, Adel M, Yoon E, Aziz K, Lee S, Shah P. Risk of infection using peripherally inserted central and umbilical catheters in preterm neonates. Pediatrics 2015;136:1073-9. 10. Rosado V, Camargos P, Anchieta L, et al. Risk factors for central venous catheterrelated infections in a neonatal population-systematic review. J Pediatr (Rio J) 2018;94:3-14.