Factors influencing antimicrobial resistance and outcome of Gram-negative bloodstream infections in children
- 494 Downloads
The aim of this study was to collect data about pediatric Gram-negative bloodstream infections (BSI) to determine the factors that influence multidrug resistance (MDR), clinical course and outcome of children affected by Gram-negative sepsis.
In this observational, prospective, multicenter study we collected cases of pediatric Gram-negative BSI during a 2-year period. We analyzed epidemiological, microbiological and clinical factors that associated with acquisition of MDR infections and outcome.
One-hundred and thirty-five BSI episodes were analyzed. Median age of children was 0.5 years (IQR 0.1–6.17, range 0–17 years). Predominant bacteria were Enterobacteriaceae (68.3 %), and Pseudomonas spp. (17.9 %). Multidrug resistance was detected in 45/134 cases (33.6 %), with the highest rates in Escherichia coli, Enterobacter and Pseudomonas spp. Acquisition of MDR pathogens was significantly associated with prior cephalosporin treatment, older age, admission to hemato-oncology unit, polymicrobial infections, higher rate of development of septic shock, and multiple organ failures. All-cause mortality was 17.9 %. Presence of septic shock at presentation and parenteral nutrition were associated with higher mortality. Pseudomonas spp., and Enterobacter spp. BSIs had the highest rate of mortality. Inappropriate empiric antibiotic therapy was more frequent in MDR patients, although not significantly associated with poor outcome.
Rates of multidrug resistance and mortality in children with Gram-negative bloodstream infections remain high in our settings. Empiric broad-spectrum antibiotics and combination therapy could be recommended, especially in children with malignant diseases, patients admitted to the PICU, and for cases with septic shock, who have higher mortality risk.
KeywordsBloodstream infection Pediatric Gram negative Sepsis Outcome Multidrug resistant
The authors thank the patients and their parents for giving their consent to our study. We are very grateful to Natasa Pesti, Krisztina Németh, Klára Tóth, Mária Szénási, Judit Ventilla, Miklós Szabó, MD, Gabriella Kiss, MD, Emőke Székely, MD, András Szatmári, MD, Csaba Vilmányi, MD, János Sinkó, MD, Gábor Kovács, MD, Gergely Kriván, MD, Lídia Balogh, MD, István Máttyus, MD, András Trethon, MD, Marianne Konkoly-Thege, MD, Katalin Kamotsay, MD, Katalin Kristóf, MD and to all nurses, colleagues, and assistants of departments and laboratories that participated in this study for their contribution. This study was financially supported by the Hungarian Research Fund, OTKA K 108481.
Compliance with ethical standards
Conflict of interest
On behalf of all authors, the corresponding author states that there is no conflict of interest.
This study has been approved by the Scientific and Research Ethics Council of the Hungarian Medical Research Council under the reference number 845-0/2010-1018EKU (39/PI/010). Informed consent has been attained from the parents of all infants and children whose clinical data have been used in this study.
- 4.Al-Hasan MN, Eckel-Passow JE, Baddour LM. Impact of healthcare-associated acquisition on community-onset Gram-negative bloodstream infection: a population-based study: healthcare-associated Gram-negative BSI. Eur J Clin Microbiol Infect Dis. 2012;31:1163–71. doi: 10.1007/s10096-011-1424-6.CrossRefPubMedPubMedCentralGoogle Scholar
- 8.Ares MA, Alcantar-Curiel MD, Jimenez-Galicia C, Rios-Sarabia N, Pacheco S, De la Cruz MA. Antibiotic resistance of gram-negative bacilli isolated from pediatric patients with nosocomial bloodstream infections in a Mexican tertiary care hospital. Chemotherapy. 2013;59:361–8. doi: 10.1159/000362085.PubMedGoogle Scholar
- 9.Lye DC, Earnest A, Ling ML, Lee TE, Yong HC, Fisher DA, et al. The impact of multidrug resistance in healthcare-associated and nosocomial Gram-negative bacteraemia on mortality and length of stay: cohort study. Clin Microbiol Infect. 2012;18:502–8. doi: 10.1111/j.1469-0691.2011.03606.x.CrossRefPubMedGoogle Scholar
- 11.Tabah A, Koulenti D, Laupland K, Misset B, Valles J, Bruzzi de Carvalho F, et al. Characteristics and determinants of outcome of hospital-acquired bloodstream infections in intensive care units: the EUROBACT International Cohort Study. Intensive Care Med. 2012;38:1930–45. doi: 10.1007/s00134-012-2695-9.CrossRefPubMedGoogle Scholar
- 14.Trecarichi EM, Pagano L, Candoni A, Pastore D, Cattaneo C, Fanci R, et al. Current epidemiology and antimicrobial resistance data for bacterial bloodstream infections in patients with hematologic malignancies: an Italian multicentre prospective survey. Clin Microbiol Infect. 2014. doi: 10.1016/j.cmi.2014.11.022.Google Scholar
- 16.Folgori L, Livadiotti S, Carletti M, Bielicki J, Pontrelli G, Ciofi Degli Atti ML, et al. Epidemiology and clinical outcomes of multidrug-resistant, Gram-negative bloodstream infections in a European Tertiary Pediatric Hospital During a 12-month period. Pediatr Infect Dis J. 2014;33:929–32. doi: 10.1097/inf.0000000000000339.CrossRefPubMedGoogle Scholar
- 18.Caini S, Hajdu A, Kurcz A, Borocz K. Hospital-acquired infections due to multidrug-resistant organisms in Hungary, 2005–2010. Euro Surveill. 2013;18:13–20.Google Scholar
- 22.Brierley J, Carcillo JA, Choong K, Cornell T, Decaen A, Deymann A, et al. Clinical practice parameters for hemodynamic support of pediatric and neonatal septic shock: 2007 update from the American College of Critical Care Medicine. Crit Care Med. 2009;37:666–88. doi: 10.1097/CCM.0b013e31819323c6.CrossRefPubMedPubMedCentralGoogle Scholar
- 23.Bernard GR, Artigas A, Brigham KL, Carlet J, Falke K, Hudson L, et al. The American-European Consensus Conference on ARDS. Definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am J Respir Crit Care Med. 1994;149:818–24. doi: 10.1164/ajrccm.149.3.7509706.CrossRefPubMedGoogle Scholar
- 24.Magiorakos AP, Srinivasan A, Carey RB, Carmeli Y, Falagas ME, Giske CG, et al. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect. 2012;18:268–81. doi: 10.1111/j.1469-0691.2011.03570.x.CrossRefPubMedGoogle Scholar
- 34.Tumbarello M, Sanguinetti M, Montuori E, Trecarichi EM, Posteraro B, Fiori B, et al. Predictors of mortality in patients with bloodstream infections caused by extended-spectrum-beta-lactamase-producing Enterobacteriaceae: importance of inadequate initial antimicrobial treatment. Antimicrob Agents Chemother. 2007;51:1987–94. doi: 10.1128/aac.01509-06.CrossRefPubMedPubMedCentralGoogle Scholar
- 36.Miedema KG, Winter RH, Ammann RA, Droz S, Spanjaard L, de Bont ES, et al. Bacteria causing bacteremia in pediatric cancer patients presenting with febrile neutropenia–species distribution and susceptibility patterns. Support Care Cancer. 2013;21:2417–26. doi: 10.1007/s00520-013-1797-4.CrossRefPubMedGoogle Scholar
- 37.Zaoutis TE, Goyal M, Chu JH, Coffin SE, Bell LM, Nachamkin I, et al. Risk factors for and outcomes of bloodstream infection caused by extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella species in children. Pediatrics. 2005;115:942–9. doi: 10.1542/peds.2004-1289.CrossRefPubMedGoogle Scholar
- 38.Peralta G, Lamelo M, Alvarez-Garcia P, Velasco M, Delgado A, Horcajada JP, et al. Impact of empirical treatment in extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella spp. bacteremia. A multicentric cohort study. BMC Infect Dis. 2012;12:245. doi: 10.1186/1471-2334-12-245.CrossRefPubMedPubMedCentralGoogle Scholar