Risk factors for nosocomial infections after cardiac surgery in

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Pediatrics and Neonatology (2017) xx, 1e6

Available online at www.sciencedirect.com

ScienceDirect journal homepage: http://www.pediatr-neonatol.com

Original Article

Risk factors for nosocomial infections after cardiac surgery in newborns with congenital heart disease Heladia Garcıá a, Beatriz Cervantes-Luna a, ćtor Gonza ´lez-Cabello a, Guadalupe Miranda-Novales b,* He a Neonatal Intensive Care Unit, Pediatric Hospital, National Medical Center, XXI Century, Mexican Institute of Social Security, Mexico b Hospital Epidemiology Research Unit, Health Research Coordination, Mexican Institute of Social Security, Mexico

Received Mar 2, 2017; received in revised form Jul 5, 2017; accepted Nov 15, 2017

Available online - - -

Key Words cardiac surgery; congenital heart disease; newborn; nosocomial infection

Background: Congenital heart diseases are among the most common congenital malformations. Approximately 50% of the patients with congenital heart disease undergo cardiac surgery. Nosocomial infections (NIs) are the main complications and an important cause of increased morbidity and mortality associated with congenital heart diseases. This study’s objective was to identify the risk factors associated with the development of NIs after cardiac surgery in newborns with congenital heart disease. Methods: This was a nested caseecontrol study that included 112 newborns, including 56 cases (with NI) and 56 controls (without NI). Variables analyzed included perinatal history, associated congenital malformations, Risk-Adjusted Congenital Heart Surgery (RACHS-1) score, perioperative and postoperative factors, transfusions, length of central venous catheter, nutritional support, and mechanical ventilation. Statistical analysis: Differences were calculated with the ManneWhitney-U test, Pearson X2, or Fisher’s exact test. A multivariate logistic regression was used to determine the independent risk factors. Results: Sepsis was the most common NI (37.5%), and the main causative microorganisms were gram-positive cocci. The independent risk factors associated with NI were non-cardiac congenital malformations (OR 6.1, CI 95% 1.3e29.4), central venous catheter indwelling time > 14 days (OR 3.7, CI 95% 1.3e11.0), duration of mechanical ventilation > 7 days (OR 6.6, CI 95% 2.1e20.1), and 5 transfusions of blood products (OR 3.1, CI 95% 1.3e8.5). Mortality attributed to NI was 17.8%. Conclusion: Newborns with non-cardiac congenital malformations and with >7 days of mechanical ventilation were at higher risk for a postoperative NI. Efforts must focus on

* Corresponding author. E-mail address: [email protected] (G. Miranda-Novales). https://doi.org/10.1016/j.pedneo.2017.11.014 1875-9572/Copyright ª 2017, Taiwan Pediatric Association. Published by Elsevier Taiwan LLC. This is an open access article under the CC BYNC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Please cite this article in press as: Garcıá H, et al., Risk factors for nosocomial infections after cardiac surgery in newborns with congenital heart disease, Pediatrics and Neonatology (2017), https://doi.org/10.1016/j.pedneo.2017.11.014

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H. Garcıá et al preventable infections, especially in bloodstream catheter-related infections, which account for 20.5% of all NIs. Copyright ª 2017, Taiwan Pediatric Association. Published by Elsevier Taiwan LLC. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/ by-nc-nd/4.0/).

1. Introduction In Mexico, congenital heart disease (CHD) is a significant cause of mortality in children under one year of age. According to a recent data analysis, mortality increased from 114.4 to 146.4/100,000 live births from 2008 to 2013. Almost one-third of the deaths occurred during the first week of life.1 The prevalence of CHD in Mexico is still unknown, but it is assumed to be similar to worldwide prevalence (6e8 per 1000 live births).2 In 2008, a Mexican Association of Specialists in Congenital Heart Disease (abbreviation in Spanish AMECC) was created to implement a national plan for regionalization of care for patients with CHD.3,4 Early diagnoses of CHD in fetuses and newborns, along with specialized cardiovascular surgeons and national referral centers, have improved the prognosis for neonates due to corrective surgery. In Mexico, approximately 50% of patients with cardiac defects undergo surgical repair, and 30% of them require open heart surgery with cardiopulmonary bypass.5,6 In the postoperative period, a systemic uncontrolled inflammatory response has been documented due to complex humoral and cellular interactions, contributing to organ dysfunction and derived complications.7,8 Infectious complications vary from center to center, but in Latin America, the prevalence is high (40e50%).9e13 Common infections in these patients are central lineassociated bloodstream infections, ventilator-associated pneumonia, nosocomial pneumonia, and surgical site infections.14e21 In a systematic analysis by Dresbach et al.,13 20 of 23 papers published in English reported risk factors for nosocomial infections (NIs). One of the general risk factors for NIs was the group of neonates (OR 5.89, CI 95% 2.96e11.58). Because of the heterogeneity of the studies, it was not possible to compare the results for specific risk factors and provide definite data. Some of the risk factors mentioned in several studies are prematurity, malnutrition, cyanotic lesion, duration of surgical procedure, more than one surgical intervention, complexity score (RACHS-1), delayed sternal closure, number of blood transfusions, preoperative length of hospital stay, central venous catheter (CVC) indwelling time, and length of total parenteral nutrition.10e24 The present study’s objective was to identify the risk factors for NI after cardiac surgery in newborns with CHD, in a neonatal intensive care unit (NICU).

acquired an NI during postoperative care after cardiac surgery. A control was a patient randomly selected, who did not develop an NI. The ratio of case:control was 1:1. Both a case and a control must fulfill the selection criteria. Inclusion criteria: newborns admitted to the NICU with clinical and two-dimensional echocardiogram-based diagnosis of CHD, which was established by pediatric cardiologist, and who underwent cardiac surgery during hospitalization. Exclusion criteria: patients who died within 48 h postoperatively, those with infection within the first 48 h after hospitalization, and premature patients with patent ductus arteriosus as the only lesion. NIs were defined according to the Centers for Disease Control and Prevention criteria and the National Health Care Safety Network.25,26 The following infections were included: central line-associated bloodstream infection, clinical sepsis, pneumonia, ventilator-associated pneumonia (VAP), surgical-site infection, clinical sepsis, intra-abdominal infection, and endocarditis. Sepsis was defined according to the proposed definition in the International Sepsis Forum definition of infection in the intensive care unit.27 Data collected included demographic and perinatal characteristics, type of CHD, antimicrobial prophylaxis, length of hospital stay before surgery, CVC indwelling time, type of surgery and complexity score (RACHS-1),22 duration of surgical procedure, duration of cardio-pulmonary bypass, duration of aortic cross-clamp, delayed sternal closure, respiratory support, chest drain, multiple surgeries, transfusions and total parenteral nutrition. Data of the isolated pathogens were collected from the bacteriology laboratory. NI diagnosis was corroborated by two investigators.

2.1. Statistical analysis The mortality rate associated with NI was calculated as the ratio between the number of deaths among all children with an NI. Analysis for categorical variables was performed using chi-square or Fisher’s exact tests, and for quantitative variables, ManneWhitney U tests were used. Odds ratio and 95% confidence interval were calculated. A multivariate logistic regression was used to identify independent risk factors for NI. Variables with a p value 0.10 were introduced in the model. Statistical significance was set at p 0.05. Analyses were performed with the Software SPSS v.17.

3. Results 2. Material and methods A nested caseecontrol study was carried out with newborns who underwent cardiac surgery from January 2012 to June 2014 in a pediatric tertiary care level hospital, in Mexico City, Mexico. The Ethics Institutional Review Board approved the study. A case was defined as a patient who

From January 2012 to June 2014, 155 patients with CHD underwent cardiac surgery, 56 patients developed a NI and 56 controls were selected. General characteristics were similar for both cases and controls, with some differences; newborns with NIs had lower Apgar scores, a higher frequency of other congenital

Please cite this article in press as: Garcıá H, et al., Risk factors for nosocomial infections after cardiac surgery in newborns with congenital heart disease, Pediatrics and Neonatology (2017), https://doi.org/10.1016/j.pedneo.2017.11.014

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Nosocomial infections after cardiac surgery

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malformations (21.4% vs. 3.5%, p Z 0.01), and a longer hospital stay (Table 1). 75% (84) had a cyanotic CHD, 19.7% (22) complex acyanotic, and simple acyanotic 5.3% (6). The most frequent surgical procedure in both groups was the systemic to pulmonary artery shunt (Supplementary Table 1S). Open surgery was performed in 58.9% (n Z 33) of the cases and 48.2% (n Z 27) of the controls (p Z 0.25). During the study period, 73 NIs occurred in 56 newborns: 39 patients had one infection, 15 patients had two infections, and two patients had three different infections. The most frequent infection was bloodstream infections (57.5%), with 27 cases of sepsis and 15 catheter-associated infections. Surgical-site infections were the third most common, followed by lower respiratory tract infections (Table 2). The microorganisms isolated from blood cultures were gram-positive species in 63.1%, gram-negative species in 31.6%, and Candida spp. in two cases. From respiratory secretions, the pathogens were mainly gram-negative rods, and two patients had infection with Staphylococcus aureus. Of the 11 cases with surgical site infections, only five had a positive culture, of which three had S. aureus, and two had Klebsiella pneumoniae. Two patients developed peritonitis associated with the use of peritoneal dialysis; in both cases, gram-negative rods were isolated. Only two cases of candidemia were documented (Table 3). The overall mortality was 41% (n Z 46/112). In 10 cases, the main cause of death was the NI (10/56, 17.8%). The difference (p Z 0.02) in the mortality rate between the cases and the controls was attributable to the infections (Supplementary Material Table 2S). Table 1

Table 2

Distribution of nosocomial infections (n Z 73).

Sepsis Bloodstream catheter-associated infection Surgical site infection Ventilator-associated pneumonia Pneumonia Endocarditis Peritonitis Total

n

%

27 15 11 10 5 3 2 73

37.0 20.5 15.0 13.7 6.9 4.1 2.7 100

Significant risk factors in the univariate analysis associated with postoperative NIs were non-cardiac congenital malformations, previous hospital stay > 7 days, chest drain, CVC indwelling time > 14 days, duration of mechanical ventilation > 7 days, number of transfusions (5), and reinterventions (cardiac surgery) (Table 4). The independent risk factors in the multivariate analysis were noncardiac malformations (Supplementary Table 3S) and duration of mechanical ventilation > 7 days with the highest ORs and CVC indwelling time > 14 days and 5 transfusions (Table 5).

4. Discussion Infectious complications are among the main complications in the postoperative period in newborns with CHD who need

General characteristics of the newborns included in the study (n Z 112). Cases (NI) (n Z 56)

Gestational age (weeks) Birthweight (g) Apgar 10 Apgar 50 Age admitted at NICU (days) Total hospital stay at NICU (days)

Gender Male Female Birth Cesarean section Vaginal delivery Risk category (RACHS-1) 1 2 3 4 5 6

Controls (without NI) (n Z 56)

pb

Md

Range

Md

Range

39 2855 8 9 9.5 40

28e42 1040e3850 2e9 3e9 3e15a 10e150

38 2950 8 9 8 14

32e41 1200e4400 4e9 6e10 3e22a 2e124

0.50 0.45 0.01 0.004 0.71 0.02

n

%

n

%

pc

32 24

57.1 42.9

29 27

51.8 48.2

40 16

71.4 28.6

37 19

66.1 33.9

0 6 31 18 0 1

0 10.7 55.4 32.1 0 1.8

2 9 34 9 1 1

3.6 16.1 60.7 16.1 1.8 1.8

0.70

0.68

0.49 0.40 0.56 0.04 1.0 1.0

Md, median; NI, nosocomial infection. a Interquartile range. b ManneWhitney U test. c p: Pearson square-chi or Fisher’s exact test.


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H. Garcıá et al Table 3

Distribution of microorganisms isolated in newborns with nosocomial infection.

Microorganisms

Blood culture

Tracheal aspirate

Needle aspiration of wound

Gram-positive Staphylococcus aureus Staphylococcus epidermidis Staphylococcus hominis Enterococcus faecium Gram-negative Klebsiella pneumoniae Escherichia coli Pseudomonas aeruginosa Serratia marcensens Enterobacter cloacae Acinetobacter baumanii Yeast Candida albicans Total

24 10 7 5 2 12 6 4

2 2

3 3

9 1 2 3

2 2

1 1 2 2 38

Peritoneal fluid

2 1

1 1 2 e

e

e

11

5

2

surgical intervention. All published studies that analyze risk factors for NIs include newborns and infants in the same age group.10,11,13,15,28 Some studies include all type of complications.29 In the present study, the bloodstream infections were the most frequent, as also reported by Magliola29 in Argentina, Bravo-Pe ´rez9 in Cuba, Levy11 in Israel, and Pas30 quali reporting from 33 hospitals in the United States. In Mexico, Duarte17 reported pneumonia as the most frequent NI followed by sepsis. The occurrence of lower respiratory tract infection varied in different reports; from 11.6% in U.S.A. hospitals30 to 60% and 65.6% in Spain and Mexico.16,17 One study from Chile reported the surgical site infection as the leading NI, followed by urinary tract infection associated with the urinary catheter.28 Gram-positive cocci, especially S. aureus, are one of the principal etiologic agents. Mehta et al.31 found a similar distribution of bacteria, but Levy.11 and Abou20 registered a higher frequency of gram-negative rods. Gram-positive cocci are common in intravascular catheter-related infections and gram-negative rods in urinary tract infections and late ventilator-associated pneumonia.32,33 The review by Dresbach et al.13 reported the CVC indwelling time as an independent risk factor for bloodstream infection, the OR for CVC indwelling time 7e10 days was 6.2 (CI 95% 1.4e27.4), and increased for >10 days (OR 14.3, IC 95% 3.1e64.5). In this study the CVC indwelling time > 14 days was found as a general risk factor, as well as the duration of mechanical ventilation > 7 days. Transfusion of five or more blood products during and after the surgery was also an independent risk factor for NI. Costello et al.34 reported that the transfusion of three or more blood products was an independent risk factor for bloodstream catheter-related infection. In a later study, the same authors also found a greater association to develop deep surgical-site infection.35 This has also been reported in adults after cardiovascular surgery.36,37 It has been suggested that blood transfusion can induce immunosuppression due to a decreased function of natural killer cells, a defective presentation of antigens, an altered T-

Total, n (%) 29 (51.8) 15 7 5 2 25 (44.6) 10 6 3 2 2 2 2 (3.6) 2 56 (100)

lymphocyte helper/suppressor ratio, and a reduced cellmediated immunity.38 One seldom reported independent risk factor is the coexistence of non-cardiac malformations (Supplementary Material Table 3S). Some of the genetic disorders (trisomy 13 and 18) contribute to mortality, but do not necessarily increase the risk for NI. Patients with DiGeorge syndrome have a primary immunodeficiency, and Down syndrome is associated to a higher risk of respiratory infections and sepsis, probably due to an intrinsic defect of B-cell differentiation, needed for the secondary response to different microorganisms.39 Mehta et al.31 also mentioned a high rate of surgical site infection in patients with other malformations or genetic disorders. The mortality rate was higher in patients with NI. Magliola et al.29 reported a mortality rate of 14%, and Abou et al.20 reported a mortality rate of 11% in children with infection compared with only 2% in children without infection. Pasquali et al.30 also found a low mortality rate (6% with infection and 2.8% without infection). Duarte et al.17 found a difference of 5% in the mortality rate between children with and without infection. The study has several limitations. Complete perinatal data were not always available. Due to the design, type of CHD and surgical procedures varied in number, and the adjustment with the complexity score may not be the best way to homogenize the groups, even though, duration and type of surgery was similar in the groups, so the difference was not statistically significant. It will be very difficult to gather information of a large and similar number of CHD for comparison in a study of one center. This could reflect the importance of the postoperative factors in the development of infections. The presence of non-cardiac malformations implies additional interventions to improve patients’ condition. Most of the published studies do not analyze neonates separately, so the available information is limited for comparison. For definite results, each type of infection should be associated with specific risk factors. In this study the controls were selected randomly to avoid


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Nosocomial infections after cardiac surgery Table 4

5

Univariate analysis of the risk factors associated with postoperative nosocomial infection.

Pre- and perioperative factors Non-cardiac malformations Previous hospital stay (>7 days) Previous infection Birthweight (14 days) Duration of MVd (>7 days) Total parenteral nutrition (TPN) Duration of TPN (>14 days) Chest drain Delayed sternal closure (>3 days) Reintervention (cardiac surgery) Other surgeries

Cases (n Z 56)

Controls (n Z 56)

ORa

CI 95%b

pc

12 30 27 5 17 52 45

3 14 18 4 16 51 39

4.8 3.4 1.9 1.2 1.0 1.2 1.7

1.2e18.1 1.5e7.7 0.9e4.2 0.3e5.01 0.4e2.45 0.3e5.0 0.7e4.2

0.01 0.001 0.08 0.72 0.83 0.72 0.19

19 54 33 33 43 30 46 21

11 51 17 27 43 21 50 27

2.1 2.6 3.3 1.5 1.0 1.9 0.5 1.5

0.8e4.96 0.4e14.2 1.5e7.1 0.7e3.2 0.4e2.40 0.90e4.0 0.1e1.63 0.73e3.2

0.08 0.24 0.002 0.25 1.00 0.08 0.28 0.25

55 35 45 17 9 56 39 13 4

51 16 16 10 5 50 36 4 3

5.3 4.1 10.2 2.0 1.9 2.1 1.2 3.9 1.3

0.6e47.7 1.8e9.2 4.2e24.6 0.82e4.8 0.61e6.2 1.7e2.5 0.5e2.80 1.2e12.0 0.29e6.3

0.09 0.0001 0.001 0.12 0.25 0.01 0.54 0.01 0.69

*Transfusions of blood products were registered during and after the surgical procedure. a Odds ratio. b Confidence interval 95%. c Pearson X2. d Mechanical ventilation.

Table 5 Risk factors for postoperative nosocomial infections in the multivariate analysis.

Non-cardiac malformations CVC indwelling time > 14 days Duration of MVc > 7 days Number of transfusions 5 a b c

ORa

CI 95%b

p

6.1 3.7 6.6 3.1

1.3e29.4 1.3e11.0 2.1e20.1 1.3e8.5

0.02 0.01 0.001 0.02

Odds ratio. Confidence interval 95%. Mechanical ventilation.

overmatching, and it was decided to control the confounding variables with the multivariate analysis. A continuous surveillance along with initiative to implement better practices needs to be enforced, as most of the NI are considered preventable.40 In our NICU a program that target bloodstream catheter-related infections and ventilator-associated pneumonia could reduce more than 30% of the NI. By removing the central venous catheter as soon as possible and achieving early extubation,41 the higher risk associated to prolonged catheter use and duration of mechanical ventilation will decrease. Also it is necessary to evaluate carefully the need of transfusion of blood derivatives.

A multidisciplinary team and supplies to comply with preventive measures is imperative to achieve the goal.

Conflict of interest None.

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H. Garcıá et al 25. Centers for Disease Control. CD/NHSN surveillance definitions for all specific types of infection. 2017. Available at: https:// www.cdc.gov/nhsn/pdfs/pscmanual/pcsmanual_current.pdf. Accessed 8 October 2016. 26. Horan TC, Andrus M, Dudeck MA. CDC/NHSN surveillance definition of health care associated infection and criteria for specific types of infections in the acute care setting. Am J Infect Control 2008;36:309e32. 27. Calandra T, Cohen J, International Sepsis Forum Definition of Infection in the ICU Consensus Conference. The international sepsis forum consensus conference on definitions of infection in the intensive care unit. Crit Care Med 2005;33:1538e48. 28. Barriga J, Cerda J, Abarca K, Ferre ´s M, Fajuri P, Riquelme M, et al. Nosocomial infections after cardiac surgery in infants and children with congenital heart disease. Rev Chilena Infectol 2014;31:16e20 [Article in Spanish]. 29. Magliola R, Althabe M, Moreno G, Lenz AM, Pilan ML, Landry L, et al. Cardiac surgical repair in newborns: five years’ experience in neonatal open surgery. Arch Argent Pediatr 2009;107: 417e22 [Article in Spanish]. 30. Pasquali SK, He X, Jacobs ML, Hall M, Gaynor JW, Shah SS, et al. Hospital variation in postoperative infection and outcome after congenital heart Surgery. Ann Thorac Surg 2013;96:657e63. 31. Mehta PA, Cunningham KC, Colella BC, Alferis G, Weiner BL. Risk factors for sternal wound and other infections in pediatric cardiac surgery patients. Pediatr Infect Dis J 2000;19: 1000e4. 32. Hooven TA, Polin RA. Healthcare-associated infections in the hospitalized neonate: a review. Early Hum Dev 2014;90:S4e6. 33. Bizzarro MJ. Healthcare-associated infections in the neonatal intensive care unit: barriers to continued success. Semin Perinatol 2012;36:437e44. 34. Costello JM, Graham DA, Morrow DF, Potter-Bynoe G, Sandora TJ, Laussen PC. Risk factors for central line-associated bloodstream infection in a pediatric cardiac intensive care unit. Pediatr Crit Care Med 2009;10:453e9. 35. Costello JM, Graham DA, Morrow DF, Morrow J, PotterBynoe G, Sandora TJ, et al. Risk factors for surgical site Infection after cardiac surgery in children. Ann Thorac Surg 2010;89:1833e42. 36. Banbury MK, Brizzio ME, Rajeswaran J, Lytle BW, Blackstone EH. Transfusion increases the risk of postoperative infection after cardiovascular Surgery. J Am Coll Surg 2006; 202:131e8. 37. Leal-Noval SR, Rinco ń-Ferrari MD, Garcıá-Curiel A, HerruzoAvile ´s A, Camacho-Laran ã P, Garnacho-Montero J, et al. Transfusion of blood components and postoperative infection in patients undergoing cardiac surgery. Chest 2001;119: 1461e8. 38. Blajchman MA. Immunomodulation and blood transfusion. Am J Ther 2002;9:389e95. 39. Carsetti R, Valentini D, Marcellini V, Scarsella M, Marasco E, Giustini F, et al. Reduced numbers of switched memory B cells with high terminal differentiation potential in Down syndrome. Eur J Immunol 2015;45:903e14. 40. Bowen JR, Callander I, Richards R, Lindrea KB, Sepsis prevention in NICUs group. Decreasing infection in neonatal intensive care units through quality improvement. Arch Dis Child Fetal Neonatal Ed 2017;102:F51e7. 41. DeSena HC, Nelson DP, Cooper DS. Cardiac intensive care for the neonate and child after cardiac surgery. Curr Opin Cardiol 2015;30:81e8.

Appendix A. Supplementary data Supplementary data related to this article can be found at https://doi.org/10.1016/j.pedneo.2017.11.014.
