A Local Experience of Antibiotic Lock Therapy as an Adjunctive Treatment for Central Venous Catheter-Related Bloodstream Infections in Pediatric Oncology and Hematology Patients
Abstract
:1. Introduction
Antibiotic Lock Therapy
2. Materials and Methods
2.1. Definitions
- -
- After obtaining a set of blood cultures, drawn at the same time and with an identical amount of blood; positivity in the CVC culture should occur at least 2 h before the percutaneous blood culture.
- -
- A positive isolate in at least one peripheral blood culture and evidence of CVC colonization by the same microorganism. CVC colonization is proven when the tip or reservoir is cultured (catheter must be removed).
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- At least 2 blood cultures drawn from the CVC must have the same microorganism on 2 different occasions.
2.2. Methods
2.3. Antibiotic Selection
2.4. Ethical Considerations
2.5. Statistical Analysis
3. Results
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Tsai, H.C.; Huang, L.M.; Chang, L.Y.; Lee, P.I.; Chen, J.M.; Shao, P.L.; Hsueh, P.R.; Sheng, W.H.; Chang, Y.C.; Lu, C.Y. Central venous catheter-associated bloodstream infections in pediatric hematology-oncology patients and effectiveness of antimicrobial lock therapy. J. Microbiol. Immunol. Infect. 2015, 48, 639–646. [Google Scholar] [CrossRef] [PubMed]
- Bergmann, K.; Hasle, H.; Asdahl, P.; Handrup, M.M.; Wehner, P.S.; Rosthøj, S.; Schrøder, H. Central Venous Catheters and Bloodstream Infection During Induction Therapy in Children with Acute Lymphoblastic Leukemia. J. Pediatr. Hematol. Oncol. 2016, 38, e82–e87. [Google Scholar] [CrossRef]
- Zakhour, R.; Hachem, R.; Alawami, H.M.; Jiang, Y.; Michael, M.; Chaftari, A.M.; Raad, I. Comparing catheter-related bloodstream infections in pediatric and adult cancer patients. Pediatr. Blood Cancer 2017, 10, e26537. [Google Scholar] [CrossRef] [PubMed]
- Cecinati, V.; Brescia, L.; Tagliaferri, L.; Giordano, P.; Esposito, S. Catheter-related infections in pediatric patients with cancer. Eur. J. Clin. Microbiol. Infect. Dis. 2012, 31, 2869–2877. [Google Scholar] [CrossRef] [PubMed]
- Ares, G.; Hunter, C.J. Central venous access in children: Indications, devices, and risks. Curr. Opin. Pediatr. 2017, 29, 340–346. [Google Scholar] [CrossRef] [PubMed]
- Hansen Carter, J.; Langley, J.M.; Kuhle, S.; Kirkland, S. Risk factors for central line–associated bloodstream infection in pediatric oncology patients with a totally implantable venous access port: A cohort study. Infec. Control Hosp. Epidemiol. 2017, 64, 336–342. [Google Scholar]
- Linder, L.A.; Gerdy, C.; Jo, Y.; Wilson, A. Changes in Central Line-Associated Bloodstream Infection Rates Among Children with Immune Compromised Conditions: An 11-Year Review. J. Pediatr. Oncol. Nurs. 2018, 35, 382–391. [Google Scholar] [CrossRef] [PubMed]
- Worth, L.J.; Daley, A.J.; Spelman, T.; Bull, A.L.; Brett, J.A.; Richards, M.J. Central and peripheral line-associated bloodstream infections in Australian neonatal and paediatric intensive care units: Findings from a comprehensive Victorian surveillance network, 2008–2016. J. Hosp. Infect. 2018, 99, 55–61. [Google Scholar] [CrossRef] [PubMed]
- Kouni, S.; Tsolia, M.; Roilides, E.; Dimitriou, G.; Tsiodras, S.; Skoutelis, A.; Kourkouni, E.; Gkentzi, D.; Iosifidis, E.; Spyridis, N.; et al. Establishing nationally representative central line-associated bloodstream infection surveillance data for paediatric patients in Greece. J. Hosp. Infect. 2019, 101, 53–59. [Google Scholar] [CrossRef]
- Van den Bosch, C.H.; van der Bruggen, J.T.; Frakking, F.N.J.; van Scheltinga, C.E.T.; van de Ven, C.P.; van Grotel, M.; Wellens, L.M.; Loeffen, Y.G.; Fiocco, M.; Wijnen, M.H. Incidence, severity and outcome of central line related complications in pediatric oncology patients; A single center study. J. Pediatr. Surg. 2019, 54, 1894–1900. [Google Scholar] [CrossRef]
- Zanwar, S.; Jain, P.; Gokarn, A.; Devadas, S.K.; Punatar, S.; Khurana, S.; Bonda, A.; Pruthy, R.; Bhat, V.; Qureshi, S.; et al. Antibiotic lock therapy for salvage of tunneled central venous catheters with catheter colonization and catheter-related bloodstream infection. Transpl. Infect. Dis. 2019, 21, e13017. [Google Scholar] [CrossRef] [PubMed]
- Norris, L.B.; Kablaoui, F.; Brilhart, M.K.; Bookstaver, P.B. Systematic review of antimicrobial lock therapy for prevention of central-line-associated bloodstream infections in adult and pediatric cancer patients. Int. J. Antimicrob. Agents 2017, 50, 308–317. [Google Scholar] [CrossRef] [PubMed]
- Moon, H.M.; Kim, S.; Yun, K.W.; Kim, H.Y.; Jung, S.E.; Choi, E.H.; Lee, H.J. Clinical Characteristics and Risk Factors of Long-term Central Venous Catheter-associated Bloodstream Infections in Children. Pediatr. Infect. Dis. J. 2018, 37, 401–406. [Google Scholar] [CrossRef]
- San-Juan, R.; Martínez-Redondo, I.; Fernández-Ruiz, M.; Corbella, L.; Hernández-Jiménez, P.; Silva, J.T.; López-Medrano, F.; Recio, R.; Orellana, M.Á.; Aguado, J.M. A short course of antibiotic treatment is safe after catheter withdrawal in catheter-related bloodstream infections due to coagulase-negative staphylococci. Eur. J. Clin. Microbiol. Infect. Dis. 2019, 38, 977–983. [Google Scholar] [CrossRef]
- Kim, E.Y.; Saunders, P.; Yousefzadeh, N. Usefulness of anti-infective lock solutions for catheter-related bloodstream infections. Mt. Sinai. J. Med. 2010, 77, 549–558. [Google Scholar] [CrossRef]
- Korbila, I.P.; Bliziotis, I.A.; Lawrence, K.R.; Falagas, M.E. Antibiotic-lock therapy for long-term catheter-related bacteremia: A review of the current evidence. Expert Rev. Anti Infect. Ther. 2007, 5, 639–652. [Google Scholar] [CrossRef] [PubMed]
- Schiffer, C.A.; Mangu, P.B.; Wade, J.C.; Camp-Sorrell, D.; Cope, D.G.; El-Rayes, B.F.; Gorman, M.; Ligibel, J.; Mansfield, P.; Levine, M. Central venous catheter care for the patient with cancer: American Society of Clinical Oncology clinical practice guideline. J. Clin. Oncol. 2013, 31, 1357–1370. [Google Scholar] [CrossRef]
- Wolf, J.; Allison, K.J.; Tang, L.; Sun, Y.; Hayden, R.T.; Flynn, P.M. No evidence of benefit from antibiotic lock therapy in pediatric oncology patients with central line-related bloodstream infection: Results of a retrospective matched cohort study and review of the literature. Pediatr. Blood Cancer 2014, 61, 1811–1815. [Google Scholar] [CrossRef]
- Mermel, L.A.; Allon, M.; Bouza, E.; Craven, D.E.; Flynn, P.; O’Grady, N.P.; Raad, I.I.; Rijnders, B.J.A.; Sherertz, R.J.; Warren, D.K. Clinical Practice Guidelines for the Diagnosis and Management of Intravascular Catheter-Related Infection: 2009 Update by the Infectious Diseases Society of America. Clin. Infect. Dis. 2009, 49, 1–45, Erratum in Clin. Infect. Dis. 2010, 50, 457; Erratum in Clin. Infect. Dis. 2010, 50, 1079. [Google Scholar] [CrossRef]
- Grand, H.L. Lock therapy for treatment and prevention of intravascular non-hemodialysis catheter-related infection. In UpToDate; Connor, R.F., Ed.; Wolters Kluwer: Alphen aan den Rijn, Netherlands, 2022. [Google Scholar]
- Arora, R.S.; Roberts, R.; Eden, T.O.; Pizer, B. Interventions other than anticoagulants and systemic antibiotics for prevention of central venous catheter-related infections in children with cancer. Cochrane Database Syst. Rev. 2010, 12, CD007785. [Google Scholar] [CrossRef]
- Gahlot, R.; Nigam, C.; Kumar, V.; Yadav, G.; Anupurba, S. Catheter-related bloodstream infections. Int. J. Crit. Illn. Inj. Sci. 2014, 4, 162–167. [Google Scholar] [CrossRef] [PubMed]
- Schoot, R.A.; van Dalen, E.C.; van Ommen, C.H.; van de Wetering, M.D. Antibiotic and other lock treatments for tunnelled central venous catheter-related infections in children with cancer. Cochrane Database Syst. Rev. 2013, 25, CD008975. [Google Scholar] [CrossRef] [PubMed]
- Fernández-Hidalgo, N.; Almirante, B. Antibiotic-lock therapy: A clinical viewpoint. Expert Rev. Anti Infect. Ther. 2014, 12, 117–129. [Google Scholar] [CrossRef] [PubMed]
- Zou, G. A Modified Poisson Regression Approach to Prospective Studies with Binary Data. Am. J. Epidemiol. 2004, 159, 702–706. [Google Scholar] [CrossRef] [PubMed]
- Wolf, J.; Connell, T.G.; Allison, K.J.; Tang, L.; Richardson, J.; Branum, K.; Borello, E.; Rubnitz, J.E.; Gaur, A.H.; Hakim, H.; et al. Treatment and secondary prophylaxis with ethanol lock therapy for central line-associated bloodstream infection in paediatric cancer: A randomised, double-blind, controlled trial. Lancet Infect. Dis. 2018, 18, 854–863. [Google Scholar] [CrossRef] [PubMed]
- Mermel, L.A.; Alang, N. Adverse effects associated with ethanol catheter lock solutions: A systematic review. J. Antimicrob. Chemother. 2014, 69, 2611–2619. [Google Scholar] [CrossRef] [PubMed]
- Khosroshahi, H.T.; Mahdipur, H.; Parkhideh, S.; Basmenji, S.; Khalilzadeh, M.; Tozihi, M. The effectiveness of systemic antibiotic therapy with and without ethanol-locked solution in the treatment of hemodialysis-related catheter infection. Saudi. J. Kidney Dis. Transpl. 2015, 26, 477–481. [Google Scholar]
- Center for Disease Control and Prevention. CDC/NHSN Surveillance Definitions for Specific Types of Infections. Chapter 4: Bloodstream Infection Event (Central Line-Associated Bloodstream Infection and Non-central Line Associated Bloodstream Infection). January 2020. Available online: https://www.cdc.gov/nhsn/pdfs/pscmanual/4psc_clabscurrent.pdf (accessed on 1 January 2024).
- Chaftary, A.M.; Jordan, M.; Hachem, R.; Al Hamal, Z.; Jiang, Y.; Youssif, A.; Garoge, K.; Deshmukh, P.; Raad, I. A clinical approach to the surveillance definition of central line-associated bloodstream infection in cancer patients with mucosal barrier injury. Am. J. Infect. Control. 2016, 44, 931–934. [Google Scholar] [CrossRef]
- Hecht, S.M.; Ardura, M.I.; Yildiz, V.O.; Oullette, C.P. Central venous catheter management in high-risk children with bloodstream infections. Pediatr. Infect. Dis. J. 2020, 39, 17–22. [Google Scholar] [CrossRef]
Characteristics | Values |
---|---|
Age, months, median (IQR) | 42.1 (22.8–91.83) |
Male, n (%) | 42 (72.4) |
Underlying condition, n (%) | |
Hematologic tumor | 30 (51.7) |
leukemia | 26 (44.8) |
lymphoma | 4 (6.9) |
Solid tumor | 19 (32.7) |
brain tumor | 1 (1.7) |
non-brain solid tumor | 18 (31) |
Other hematologic conditions | 9 (15.5) |
sickle cell disease | 4 (6.9) |
beta-thalassemia major | 4 (6.9) |
Langerhans histiocytosis | 1 (1.7) |
WBC cells/mm3 median (IQR) | 2400 (400–7000) |
Severe neutropenia, n (%) | |
yes | 21 (36.2) |
no | 37 (63.8) |
Total parenteral nutrition, n (%) | 3 (5.2) |
Type of catheter, n (%) | |
Port-a-Cath ® | 51 (87.9) |
Hickman ® | 7 (12.1) |
Catheter insertion site, n (%) | |
subclavian | 15 (25.9) |
jugular | 8 (13.8) |
femoral | 1 (1.7) |
superior cava vein | 1 (1.7) |
missing data | 33 (56.9) |
Days from CVC insertion to infection, median (IQR) | 192 (67.5–545.5) |
Culture Isolates | Frequency (% of the Total) | ALT in Therapeutic Management (Salvage Achieved) | No ALT in Therapeutic Management (Salvage Achieved) |
---|---|---|---|
Gram-positive cocci | 34 (58.6) | ||
CoNS | 24 | 21 (16) | 3 (2) |
S. aureus | 5 | 2 (1) | 3 (0) |
Enterococci | 1 | - | 1 (1) |
Streptococci | 4 | 2 (2) | 2 (2) |
Gram-positive bacilli | 1 (1.7) | ||
Corynebacterium spp. | 1 | 1 (1) | - |
Gram-negative bacilli | 18 (31.1) | 13 (6) | 5 (0) |
E. coli | 4 | 4 (3) | - |
ESBL-producing E. coli | 1 | 1 (0) | - |
Klebsiella spp. | 2 | 1 (0) | 1 (0) |
Enterobacter cloacae | 4 | 4 (1) | - |
Enterobacter asburiae | 1 | 1 (0) | - |
Pseudomonas spp. | 1 | - | 1 (0) |
Serratia marcescens | 1 | - | 1 (0) |
Burkholderia spp. | 3 | 1 (1) | 2 (0) |
Acinetobacter spp. | 1 | 1 (1) | - |
Candida spp. | 2 (3.4) | - | 2 (0) |
Polymicrobial | 3 (5.2) | 2 (2) | 1 (0) |
Total | 58 (100) | 41 (28) | 17 (5) |
Characteristics of Patients | Without ALT (n = 17) | With ALT (n = 41) | p Value |
---|---|---|---|
Age, months, median (IQR) | 57.63 (27.45–98.9) | 41.6 (22.67–139.37) | 0.844 |
Male, n (%) | 11 (64.7) | 31 (75.6) | 0.520 |
Underlying condition, n (%) | 0.313 | ||
Hematologic tumor | 7 (41.2) | 23 (56.1) | |
Solid tumor | 6 (35.3) | 13 (31.7) | |
Other hematologic conditions | 4 (23.5) | 5 (12.2) | |
sickle cell disease | 3 | 1 | |
beta-thalassemia major | 1 | 3 | |
Langerhans histiocytosis | 0 | 1 | |
WBC cells/mm3 median (IQR) | 1900 (200–6550) | 2900 (600–700) | 0.261 |
Severe neutropenia, n (%) | 0.268 | ||
Yes | 8 (47.1) | 13 (31.7) | |
Parenteral nutrition, n | 2 (11.8) | 1 (2.4) | 0.203 |
Type of catheter, n | 0.178 | ||
Port-a-Cath ® | 13 (76.5) | 38 (92.7) | |
Hickman ® | 4 (23.5) | 3 (7.3) | |
Catheter insertion site, n (%) | 0.583 | ||
subclavian | 4 (57.1) | 11 (61.1) | |
jugular | 2 (28.6) | 6 (33.3) | |
femoral | 1 (14.3) | 0 | |
superior cava vein | 0 | 1 (5.6) | |
Days from CVC insertion to infection, median (IQR) | 159.5 (21.75–331) | 229 (98.5–747) | 0.108 |
Gram-positive cocci | 9 | 25 | 0.260 |
Gram-positive bacilli | 0 | 1 | |
Gram-negative bacilli | 5 | 13 | |
Fungi | 2 | 0 | |
Polymicrobial | 1 | 2 |
Antibiotics | Frequency n, (%) |
---|---|
Vancomycin 5 mg/mL | 26 (63.4) |
Amikacin 5 mg/mL | 9 (22) |
Ciprofloxacin 1 mg/mL | 3 (7.3) |
Gentamicin 5 mg/mL | 2 (4.9) |
Cefazolin 5 mg/mL | 1 (2.4) |
Total | 41 (100) |
Reasons for CVC Removal | No Adjunctive ALT | Adjunctive ALT | Total |
---|---|---|---|
Type of microorganism | 7 | 1 | 8 |
Infectious Relapses | 0 | 2 | 2 |
Local site infection | 1 | 3 | 4 |
Hemodynamic instability | 1 | 0 | 1 |
Persistent signs and symptoms | 3 | 3 | 6 |
No data | 0 | 4 | 4 |
Total | 12 | 13 | 25 |
General Features | CVC Not Removed (n = 28) | CVC Removed (n = 13) | p Value |
---|---|---|---|
Age, months, median (IQR) | 40 (23.4–215.8) | 31.8 (21.8–58.4) | 0.272 |
Male, n (%) | 22 (78.6%) | 4 (30.7%) | 0.698 |
Underlying condition, n (%) | 0.305 | ||
Hematologic tumor | |||
leukemia | 12 | 9 | |
lymphoma | 2 | 0 | |
Solid tumor | 10 | 3 | |
Other hematologic conditions | |||
sickle cell disease | 1 | 0 | |
beta-thalassemia major | 3 | 0 | |
Langerhans histiocytosis | 0 | 1 | |
No BMT/ with BMT, n (%) | 19 (86.4)/3 (13.6) | 13 (100)/0 (0) | 0.279 |
WBC cells/mm3 median (IQR) | 2650 (573–5625) | 3000 (600–10,700) | 0.612 |
Severe neutropenia, n (%) | 0.493 | ||
no | 18 (64.3) | 10 (43.5) | |
yes | 10 (35.7) | 3 (56.5) | |
Total parenteral nutrition, n (%) | 1 (3.5) | 0 (0) | 1 |
Type of catheter, n (%) | 0.539 | ||
Port-a-Cath ® | 25 (89.3) | 13 (100) | |
Hickman ® | 3 (10.7) | 0 | |
Catheter insertion site, n (%) | 1 | ||
subclavian | 7 (58.3) | 4 (66.7) | |
jugular | 4 (33.4) | 2 (33.4) | |
femoral | 0 | 0 | |
superior cava vein | 1 (8.3) | 0 | |
not recorded/missing data | 0 | 0 | |
Type of ALT | 0.0336 | ||
vancomycin | 20 (71.4) | 6 (45.1) | |
amikacin | 4 (14.3) | 5 (38.5) | |
ciprofloxacin | 2 (7.1) | 1 (8.2) | |
cefazolin | 1 (3.6) | 0 | |
gentamicin | 1 (3.6) | 1 (8.2) | |
ESBL, n (%) | 0 | 1 (8.2) | 0.325 |
RR (CI 95%) | p Value | |
---|---|---|
Antibiotic lock therapy | 0.390 (0.164–0.928) | 0.033 |
Age | 1.00 (1.00–1.00) | 0.195 |
Type of underlying condition | ||
all hematologic conditions | 0.611 (0.226–1.654) | 0.332 |
solid tumor | 0.401 (0.152–1.054) | 0.064 |
Severe neutropenia | 0.549 (0.206–1.468) | 0.232 |
Time from CVC insertion to infection (days) | 1.000 (0.999–1.001) | 0.457 |
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de Frutos Porras, E.; Cobo-Vázquez, E.; Hernanz Lobo, A.; Santos Sebastián, M.d.M.; Pérez Fernández, E.; Garrido Colino, C.; Cela, E.; Navarro Gómez, M.L. A Local Experience of Antibiotic Lock Therapy as an Adjunctive Treatment for Central Venous Catheter-Related Bloodstream Infections in Pediatric Oncology and Hematology Patients. Children 2024, 11, 983. https://doi.org/10.3390/children11080983
de Frutos Porras E, Cobo-Vázquez E, Hernanz Lobo A, Santos Sebastián MdM, Pérez Fernández E, Garrido Colino C, Cela E, Navarro Gómez ML. A Local Experience of Antibiotic Lock Therapy as an Adjunctive Treatment for Central Venous Catheter-Related Bloodstream Infections in Pediatric Oncology and Hematology Patients. Children. 2024; 11(8):983. https://doi.org/10.3390/children11080983
Chicago/Turabian Stylede Frutos Porras, Elena, Elvira Cobo-Vázquez, Alicia Hernanz Lobo, María del Mar Santos Sebastián, Elia Pérez Fernández, Carmen Garrido Colino, Elena Cela, and María Luisa Navarro Gómez. 2024. "A Local Experience of Antibiotic Lock Therapy as an Adjunctive Treatment for Central Venous Catheter-Related Bloodstream Infections in Pediatric Oncology and Hematology Patients" Children 11, no. 8: 983. https://doi.org/10.3390/children11080983