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Khafaja S, Salameh Y, Boutros CF, Awad C, Faour K, Tfaily N, Merhi S, Zein ZE, Karroum SB, Oweini D, Fayad D, Araj GF, Zakhour R, Dbaibo GS. Increased rate of multidrug-resistant gram-negative bacterial infections in hospitalized immunocompromised pediatric patients. Front Cell Infect Microbiol 2025; 14:1382500. [PMID: 39835279 PMCID: PMC11743943 DOI: 10.3389/fcimb.2024.1382500] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2024] [Accepted: 11/21/2024] [Indexed: 01/22/2025] Open
Abstract
Introduction Multidrug resistant Gram-negative bacterial infections are considered a major public health threat. Immunocompromised pediatric patients are at a great risk of severe or overwhelming infections. The aim of this study was to describe the frequency of infections with multidrug resistant (MDR) Gram-negative bacteria (GNB) in immunocompromised pediatric patients and to determine the risk factors. In addition, we aimed to identify the antimicrobial resistance patterns of these isolates. Materials and methods This was a retrospective observational study conducted at the American University of Beirut Medical Center (AUBMC) from 2009 to 2017. The study included immunocompromised patients 18 years of age or younger with infections caused by Gram-negative bacteria isolated from a sterile site, or nonsterile site in the setting of clinical infection. Results A total of 381 episodes of infection with GNB in 242 immunocompromised pediatric patients were identified. The mean age was 7.7 years. The most common pathogens were Enterobacterales followed by Pseudomonas and Acinetobacter spp. MDR GNB infections predominated causing 72% of the episodes, with alarming MDR rates among Escherichia coli (95.7%) and Klebsiella pneumoniae (82.7%). The overall rate of MDR GNB isolated increased from 62.7% in 2015 to 90% in 2017. Thrombocytopenia, chemotherapy and previous colonization or infection with the same organism during the past 12 months were found to be independent risk factors for infection with MDR GNB. Conclusion This study provides data on the epidemiology of infections with MDR GNB in immunocompromised pediatric patients and illustrates the alarmingly high prevalence of these infections. This necessitates the frequent revisiting of treatment guidelines in these high-risk patients and the implementation of judicious antimicrobial stewardship programs and infection control policies to stabilize or decrease the prevalence of these infections.
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Affiliation(s)
- Sarah Khafaja
- Center for Infectious Diseases Research (CIDR) and WHO Collaborating Center for Reference and Research on Bacterial Pathogens, American University of Beirut, Beirut, Lebanon
- Department of Pediatrics and Adolescent Medicine, American University of Beirut Medical Center, Beirut, Lebanon
| | - Yara Salameh
- Center for Infectious Diseases Research (CIDR) and WHO Collaborating Center for Reference and Research on Bacterial Pathogens, American University of Beirut, Beirut, Lebanon
| | - Celina F. Boutros
- Center for Infectious Diseases Research (CIDR) and WHO Collaborating Center for Reference and Research on Bacterial Pathogens, American University of Beirut, Beirut, Lebanon
| | - Cherine Awad
- Department of Pediatrics and Adolescent Medicine, American University of Beirut Medical Center, Beirut, Lebanon
| | - Kawthar Faour
- Center for Infectious Diseases Research (CIDR) and WHO Collaborating Center for Reference and Research on Bacterial Pathogens, American University of Beirut, Beirut, Lebanon
| | - Nadim Tfaily
- Center for Infectious Diseases Research (CIDR) and WHO Collaborating Center for Reference and Research on Bacterial Pathogens, American University of Beirut, Beirut, Lebanon
| | - Sarah Merhi
- Center for Infectious Diseases Research (CIDR) and WHO Collaborating Center for Reference and Research on Bacterial Pathogens, American University of Beirut, Beirut, Lebanon
| | - Zeinab El Zein
- Center for Infectious Diseases Research (CIDR) and WHO Collaborating Center for Reference and Research on Bacterial Pathogens, American University of Beirut, Beirut, Lebanon
- Department of Pediatrics and Adolescent Medicine, American University of Beirut Medical Center, Beirut, Lebanon
| | - Samer Bou Karroum
- Center for Infectious Diseases Research (CIDR) and WHO Collaborating Center for Reference and Research on Bacterial Pathogens, American University of Beirut, Beirut, Lebanon
| | - Dana Oweini
- Center for Infectious Diseases Research (CIDR) and WHO Collaborating Center for Reference and Research on Bacterial Pathogens, American University of Beirut, Beirut, Lebanon
| | - Danielle Fayad
- Center for Infectious Diseases Research (CIDR) and WHO Collaborating Center for Reference and Research on Bacterial Pathogens, American University of Beirut, Beirut, Lebanon
| | - George F. Araj
- Center for Infectious Diseases Research (CIDR) and WHO Collaborating Center for Reference and Research on Bacterial Pathogens, American University of Beirut, Beirut, Lebanon
- Clinical Microbiology Laboratory, American University of Beirut Medical Center, Beirut, Lebanon
- Department of Pathology and Laboratory Medicine, American University of Beirut Medical Center, Beirut, Lebanon
| | - Ramia Zakhour
- Department of Pediatrics and Adolescent Medicine, American University of Beirut Medical Center, Beirut, Lebanon
| | - Ghassan S. Dbaibo
- Center for Infectious Diseases Research (CIDR) and WHO Collaborating Center for Reference and Research on Bacterial Pathogens, American University of Beirut, Beirut, Lebanon
- Department of Pediatrics and Adolescent Medicine, American University of Beirut Medical Center, Beirut, Lebanon
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Micozzi A, Luise C, Lisi C, Moleti L, Santilli S, Gentile G. Benefits and Safety of Empiric Antibiotic Treatment Active Against KPC-Producing Klebsiella pneumoniae for Febrile Neutropenic Episodes in Colonized Children with Acute Leukemia-An 8-Year Retrospective Observational Study. Antibiotics (Basel) 2024; 13:1017. [PMID: 39596712 PMCID: PMC11591089 DOI: 10.3390/antibiotics13111017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2024] [Revised: 10/23/2024] [Accepted: 10/25/2024] [Indexed: 11/29/2024] Open
Abstract
In children with acute leukemia (AL), the mortality rate from Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae bloodstream infection (KPC-KpBSI) exceeds 50%, highest when active treatment is delayed. Neutropenic KPC-K. pneumoniae carriers are at high risk of KPC-KpBSI, and preemptive empiric antibiotic treatment (EAT) of febrile neutropenic episodes (FNEs) active against KPC-K. pneumoniae may reduce this mortality. We conducted an 8-year (2014-2021) retrospective observational study of 112 febrile neutropenic episodes (FNEs) in 32 children with AL who were KPC-K. pneumoniae carriers: standard EAT for 39 FNEs and active EAT for 73 FNEs (52 ceftazidime/avibactam (CAZAVI)-based and 21 colistin-based combinations, and 5 CAZAVI monotherapy). Successful outcomes (survival from FNE) were observed in 94%; seven were fatal, with four due to infectious causes. KPC-KpBSIs caused 10/112 FNEs, 10/20 g-negative BSIs, and 3 deaths. The mortality rate of KPC-KpBSI was 30%. Active EAT was successful in 97% of the FNEs, compared to 87% with standard EAT. All deaths from KPC-KpBSI occurred in patients who received standard EAT, while none occurred with active EAT. KPC-KpBSI mortality rate with initial inactive treatment was 60%. CAZAVI-based EAT was successful in all FNEs, with a higher success rate without any modification compared to colistin-based EAT, where nephrotoxicity occurred in 14%. Therefore, active EAT, mainly a CAZAVI-based combination, was effective, safe, and associated with low overall and KPC-KpBSI-related mortality.
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Affiliation(s)
- Alessandra Micozzi
- Haematology, Department of Translational and Precision Medicine, Sapienza University of Rome, 00161 Rome, Italy; (C.L.); (G.G.)
| | - Cristina Luise
- Haematology, Azienda Ospedaliera di Rilievo Nazionale Antonio Cardarelli, 80131 Naples, Italy;
| | - Chiara Lisi
- Haematology, Department of Translational and Precision Medicine, Sapienza University of Rome, 00161 Rome, Italy; (C.L.); (G.G.)
| | - Luisa Moleti
- Department of Haematology, Oncology and Dermatology, Azienda Policlinico Umberto I, 00161 Rome, Italy;
| | - Stefania Santilli
- Department of Diagnostics, Azienda Policlinico Umberto I, 00161 Rome, Italy;
| | - Giuseppe Gentile
- Haematology, Department of Translational and Precision Medicine, Sapienza University of Rome, 00161 Rome, Italy; (C.L.); (G.G.)
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Wen SCH, Harris PNA, Forde B, Permana B, Chatfield MD, Lau CL, Spurling G, Bauer MJ, Balch R, Chambers H, Schlapbach LJ, Clark JE, Dougherty S, Blyth CC, Britton PN, Clifford V, Haeusler GM, McMullan B, Wadia U, Paterson DL, Irwin AD. Characterization of Gram-negative Bloodstream Infections in Hospitalized Australian Children and Their Clinical Outcomes. Clin Infect Dis 2024; 79:734-743. [PMID: 38917034 PMCID: PMC11426278 DOI: 10.1093/cid/ciae341] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2024] [Revised: 06/06/2024] [Accepted: 06/21/2024] [Indexed: 06/27/2024] Open
Abstract
BACKGROUND Gram-negative bloodstream infections (GNBSIs) more commonly occur in children with comorbidities and are increasingly associated with antimicrobial resistance. There are few large studies of GNBSIs in children that relate the clinical presentation, pathogen characteristics, and outcomes. METHODS A 3-year prospective study of GNBSIs in children aged <18 years was conducted in 5 Australian children's hospitals between 2019 and 2021. The clinical characteristics, disease severity, and outcomes were recorded. Causative pathogens underwent antibiotic susceptibility testing and whole genome sequencing. RESULTS There were 931 GNBSI episodes involving 818 children. Median age was 3 years (interquartile range, 0.6-8.5). A total of 576/931 episodes (62%) were community onset, though 661/931 (71%) occurred in children with comorbidities and a central venous catheter was present in 558/931 (60%). Central venous catheter (145/931) and urinary tract (149/931) were the most common sources (16% each). One hundred of 931 (11%) children required intensive care unit admission and a further 11% (105/931) developed GNBSIs in intensive care unit. A total of 659/927 (71%) isolates were Enterobacterales, of which 22% (138/630) were third-generation cephalosporin resistant (3GCR). Extended spectrum beta-lactamase genes were confirmed in 65/138 (47%) 3GCR Enterobacterales. Most common extended spectrum beta-lactamase genes were blaCTX-M-15 (34/94, 36%) and blaSHV-12 (10/94, 11%). There were 48 deaths overall and 30-day in-hospital mortality was 3% (32/931). Infections with 3GCR Enterobacterales were independently associated with higher mortality (adjusted odds ratio, 3.2; 95% confidence interval, 1.6-6.4). CONCLUSIONS GNBSIs in children are frequently healthcare associated and affect children younger than age 5 years. Infections with 3GCR Enterobacterales were associated with worse outcomes. These findings will inform optimal management guidelines and help prioritize future antimicrobial clinical trials.
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Affiliation(s)
- Sophie C H Wen
- The University of Queensland, Centre for Clinical Research, Brisbane, Queensland, Australia
- Infection Management Prevention Service, Children's Health Queensland, Brisbane, Queensland, Australia
| | - Patrick N A Harris
- The University of Queensland, Centre for Clinical Research, Brisbane, Queensland, Australia
| | - Brian Forde
- The University of Queensland, Centre for Clinical Research, Brisbane, Queensland, Australia
| | - Budi Permana
- The University of Queensland, Centre for Clinical Research, Brisbane, Queensland, Australia
- Herston Infectious Diseases Institute, Metro North Health, Brisbane, Queensland, Australia
| | - Mark D Chatfield
- The University of Queensland, Centre for Clinical Research, Brisbane, Queensland, Australia
| | - Colleen L Lau
- The University of Queensland, Centre for Clinical Research, Brisbane, Queensland, Australia
| | - Geoffrey Spurling
- The University of Queensland, General Practice Clinical Unit, Brisbane, Queensland, Australia
| | - Michelle J Bauer
- The University of Queensland, Centre for Clinical Research, Brisbane, Queensland, Australia
| | - Ross Balch
- The University of Queensland, Centre for Clinical Research, Brisbane, Queensland, Australia
| | - Henry Chambers
- School of Medicine, University of California San Francisco, San Francisco, California, USA
| | - Luregn J Schlapbach
- The University of Queensland, Child Health Research Centre, Brisbane, Queensland, Australia
| | - Julia E Clark
- Infection Management Prevention Service, Children's Health Queensland, Brisbane, Queensland, Australia
| | - Sonia Dougherty
- Infection Management Prevention Service, Children's Health Queensland, Brisbane, Queensland, Australia
| | - Christopher C Blyth
- Wesfarmer Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, Perth, Western Australia, Australia
- Department of Infectious Diseases, Perth Children's Hospital, Perth, Western Australia, Australia
- Department of Microbiology, PathWest Laboratory Network, Perth, Western Australia, Australia
- School of Medicine, University of Western Australia, Perth, Western Australia, Australia
| | - Philip N Britton
- Department of Infectious Diseases and Microbiology, The Children's Hospital Westmead, Sydney, New South Wales, Australia
- Sydney Medical School and Sydney Infectious Diseases, University of Sydney, Sydney, New South Wales, Australia
| | - Vanessa Clifford
- Infectious Diseases Unit, Royal Children's Hospital, Melbourne, Victoria, Australia
| | - Gabrielle M Haeusler
- Infectious Diseases Unit, Royal Children's Hospital, Melbourne, Victoria, Australia
- Clinical Infections Group, Murdoch Children's Research Institute, Melbourne, Victoria, Australia
| | - Brendan McMullan
- Infectious Diseases and Microbiology, Sydney Children's Hospital, Sydney, New South Wales, Australia
- Faculty of Medicine and Health, University of New South Wales, Sydney, New South Wales, Australia
| | - Ushma Wadia
- Wesfarmer Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, Perth, Western Australia, Australia
- Department of Infectious Diseases, Perth Children's Hospital, Perth, Western Australia, Australia
- School of Medicine, University of Western Australia, Perth, Western Australia, Australia
| | - David L Paterson
- ADVANCE-ID, Saw Swee Hock School of Public Health, National University of Singapore, Singapore
- Infectious Diseases Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Adam D Irwin
- The University of Queensland, Centre for Clinical Research, Brisbane, Queensland, Australia
- Infection Management Prevention Service, Children's Health Queensland, Brisbane, Queensland, Australia
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Sardzikova S, Andrijkova K, Svec P, Beke G, Klucar L, Minarik G, Bielik V, Kolenova A, Soltys K. Gut diversity and the resistome as biomarkers of febrile neutropenia outcome in paediatric oncology patients undergoing hematopoietic stem cell transplantation. Sci Rep 2024; 14:5504. [PMID: 38448687 PMCID: PMC10918076 DOI: 10.1038/s41598-024-56242-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2023] [Accepted: 03/04/2024] [Indexed: 03/08/2024] Open
Abstract
The gut microbiota of paediatric oncology patients undergoing a conditioning regimen before hematopoietic stem cell transplantation is recently considered to play role in febrile neutropenia. Disruption of commensal microbiota and evolution of opportune pathogens community carrying a plethora of antibiotic-resistance genes play crucial role. However, the impact, predictive role and association of patient´s gut resistome in the course of the therapy is still to be elucidated. We analysed gut microbiota composition and resistome of 18 paediatric oncology patients undergoing hematopoietic stem cell transplantation, including 12 patients developing febrile neutropenia, hospitalized at The Bone Marrow Transplantation Unit of the National Institute of Children´s disease in Slovak Republic and healthy individuals (n = 14). Gut microbiome of stool samples obtained in 3 time points, before hematopoietic stem cell transplantation (n = 16), one week after hematopoietic stem cell transplantation (n = 16) and four weeks after hematopoietic stem cell transplantation (n = 14) was investigated using shotgun metagenome sequencing and bioinformatical analysis. We identified significant decrease in alpha-diversity and nine antibiotic-resistance genes msr(C), dfrG, erm(T), VanHAX, erm(B), aac(6)-aph(2), aph(3)-III, ant(6)-Ia and aac(6)-Ii, one week after hematopoietic stem cell transplantation associated with febrile neutropenia. Multidrug-resistant opportune pathogens of ESKAPE, Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae and Escherichia coli found in the gut carried the significant subset of patient's resistome. Over 50% of patients treated with trimethoprim/sulfamethoxazole, piperacillin/tazobactam and amikacin carried antibiotic-resistance genes to applied treatment. The alpha diversity and the resistome of gut microbiota one week after hematopoietic stem cell transplantation is relevant predictor of febrile neutropenia outcome after hematopoietic stem cell transplantation. Furthermore, the interindividual diversity of multi-drug resistant opportunistic pathogens with variable portfolios of antibiotic-resistance genes indicates necessity of preventive, personalized approach.
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Affiliation(s)
- Sara Sardzikova
- Department of Microbiology and Virology, Faculty of Natural Sciences, Comenius University in Bratislava, Bratislava, Slovakia
| | - Kristina Andrijkova
- Department of Microbiology and Virology, Faculty of Natural Sciences, Comenius University in Bratislava, Bratislava, Slovakia
| | - Peter Svec
- Department of Paediatric Haematology and Oncology, Children's Haematology and Oncology Clinic and Faculty of Medicine, Comenius University in Bratislava, Bratislava, Slovakia
| | - Gabor Beke
- Institute of Molecular Biology, Slovak Academy of Sciences, Bratislava, Slovakia
| | - Lubos Klucar
- Institute of Molecular Biology, Slovak Academy of Sciences, Bratislava, Slovakia
| | | | - Viktor Bielik
- Department of Biological and Medical Science, Faculty of Physical Education and Sport, Comenius University in Bratislava, Bratislava, Slovakia
| | - Alexandra Kolenova
- Department of Paediatric Haematology and Oncology, Children's Haematology and Oncology Clinic and Faculty of Medicine, Comenius University in Bratislava, Bratislava, Slovakia
| | - Katarina Soltys
- Department of Microbiology and Virology, Faculty of Natural Sciences, Comenius University in Bratislava, Bratislava, Slovakia.
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Liberati C, Donà D, Maestri L, Petris MG, Barbieri E, Gallo E, Gallocchio J, Pierobon M, Calore E, Zin A, Brigadoi G, Mariani M, Mesini A, Saffioti C, Ugolotti E, Gregori D, Giaquinto C, Castagnola E, Biffi A. Application of the Weighted-Incidence Syndromic Combination Antibiogram (WISCA) to guide the empiric antibiotic treatment of febrile neutropenia in oncological paediatric patients: experience from two paediatric hospitals in Northern Italy. Ann Clin Microbiol Antimicrob 2024; 23:16. [PMID: 38360651 PMCID: PMC10870518 DOI: 10.1186/s12941-024-00673-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2023] [Accepted: 01/30/2024] [Indexed: 02/17/2024] Open
Abstract
BACKGROUND Guidelines about febrile neutropenia in paediatric patients are not homogeneous; the best empiric treatment of this condition should be driven by local epidemiology. The Weighted-Incidence Syndromic Combination Antibiogram (WISCA) addresses the need for disease-specific local susceptibility evidence that could guide empiric antibiotic prescriptions based on outcome estimates of treatment regimens obtained as a weighted average of pathogen susceptibilities. This study developed a WISCA model to inform empirical antibiotic regimen selection for febrile neutropenia (FN) episodes in onco-haematological paediatric patients treated at two Italian paediatric tertiary centres. METHODS We included blood cultures from patients with a bloodstream infection and neutropenia admitted to the Paediatric Haematology-Oncology wards in Padua and Genoa Hospitals from 2016 to 2021. WISCAs were developed by estimating the coverage of 20 antibiotics as monotherapy and of 21 combined regimens with a Bayesian probability distribution. RESULTS We collected 350 blood cultures, including 196 g-negative and 154 g-positive bacteria. Considering the most used antibiotic combinations, such as piperacillin-tazobactam plus amikacin, the median coverage for the pool of bacteria collected in the study was 78%. When adding a glycopeptide, the median coverage increased to 89%, while the replacement of piperacillin-tazobactam with meropenem did not provide benefits. The developed WISCAs showed that no monotherapy offered an adequate coverage rate for the identified pathogens. CONCLUSIONS The application of WISCA offers the possibility of maximizing the clinical utility of microbiological surveillance data derived from large hospitals to inform the choice of the best empiric treatment while contributing to spare broad-spectrum antibiotics.
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Affiliation(s)
- Cecilia Liberati
- Division of Paediatric Infectious Diseases, Department for Women's and Children's Health, University of Padua, Padua, Italy
| | - Daniele Donà
- Division of Paediatric Infectious Diseases, Department for Women's and Children's Health, University of Padua, Padua, Italy.
| | - Linda Maestri
- Division of Paediatric Infectious Diseases, Department for Women's and Children's Health, University of Padua, Padua, Italy
| | - Maria Grazia Petris
- Division of Paediatric Haematology, Oncology and Stem Cell Transplant, Department for Women's and Children's Health, University of Padua, Padua, Italy
| | - Elisa Barbieri
- Division of Paediatric Infectious Diseases, Department for Women's and Children's Health, University of Padua, Padua, Italy
| | - Elisa Gallo
- Unit of Biostatistics, Epidemiology and Public Health, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padua, Padua, Italy
| | - Jacopo Gallocchio
- Unit of Biostatistics, Epidemiology and Public Health, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padua, Padua, Italy
| | - Marta Pierobon
- Division of Paediatric Haematology, Oncology and Stem Cell Transplant, Department for Women's and Children's Health, University of Padua, Padua, Italy
| | - Elisabetta Calore
- Division of Paediatric Haematology, Oncology and Stem Cell Transplant, Department for Women's and Children's Health, University of Padua, Padua, Italy
| | - Annachiara Zin
- Division of Paediatric Infectious Diseases, Department for Women's and Children's Health, University of Padua, Padua, Italy
| | - Giulia Brigadoi
- Division of Paediatric Infectious Diseases, Department for Women's and Children's Health, University of Padua, Padua, Italy
| | - Marcello Mariani
- Infectious Diseases Unit, Department of Pediatrics, IRCCS Istituto Giannina Gaslini, 16147, Genoa, Italy
| | - Alessio Mesini
- Infectious Diseases Unit, Department of Pediatrics, IRCCS Istituto Giannina Gaslini, 16147, Genoa, Italy
| | - Carolina Saffioti
- Infectious Diseases Unit, Department of Pediatrics, IRCCS Istituto Giannina Gaslini, 16147, Genoa, Italy
| | - Elisabetta Ugolotti
- Infectious Diseases Unit, Department of Pediatrics, IRCCS Istituto Giannina Gaslini, 16147, Genoa, Italy
| | - Dario Gregori
- Unit of Biostatistics, Epidemiology and Public Health, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padua, Padua, Italy
| | - Carlo Giaquinto
- Division of Paediatric Infectious Diseases, Department for Women's and Children's Health, University of Padua, Padua, Italy
| | - Elio Castagnola
- Infectious Diseases Unit, Department of Pediatrics, IRCCS Istituto Giannina Gaslini, 16147, Genoa, Italy
| | - Alessandra Biffi
- Division of Paediatric Haematology, Oncology and Stem Cell Transplant, Department for Women's and Children's Health, University of Padua, Padua, Italy
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Liu YC, Lu CY, Yen TY, Chang LY, Chen JM, Lee PI, Huang LM. Clinical characteristics and outcomes of carbapenem-resistant Enterobacterales bacteremia in pediatric patients. JOURNAL OF MICROBIOLOGY, IMMUNOLOGY, AND INFECTION = WEI MIAN YU GAN RAN ZA ZHI 2023; 56:84-92. [PMID: 36376217 DOI: 10.1016/j.jmii.2022.09.010] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/30/2022] [Revised: 09/28/2022] [Accepted: 09/30/2022] [Indexed: 11/13/2022]
Abstract
BACKGROUND/PURPOSE Clinical data on carbapenem-resistant Enterobacterales (CRE) bacteremia in the pediatric population are limited. This study investigated the clinical characteristics and outcomes of pediatric CRE bacteremia. METHODS Clinical data on bacteremia caused by carbapenem-susceptible and carbapenem-resistant Enterobacterales, including Escherichia coli, Klebsiella spp., Enterobacter spp., Serratia marcescens, Proteus mirabilis, Citrobacter spp., and Morganella spp., in pediatric patients from a children's hospital in Taiwan were retrospectively retrieved and analyzed. RESULTS From January 2013 to December 2021, 471 clinical isolates of Enterobacterales bacteremia were identified in 451 episodes from 379 pediatric patients. Among all the isolates, the predominant species were E. coli (199/471, 42.2%), Klebsiella spp. (168/471, 35.6%), and Enterobacter spp. (59/471, 12.5%), with carbapenem-resistance rates of 1.5%, 11.9%, and 25.0%, respectively. Overall, 40 (8.4%) showed a carbapenem resistance phenotype. Patients' all-cause mortality rate at 14 days was significantly higher in CRE bacteremia episodes than non-CRE ones (12.5% vs. 3.6%, p < 0.05). The predicting factor of a CRE bacteremia episode was the causative agent of Enterobacter spp. (adjusted OR of 2.551, CI 1.073-6.066, p < 0.05) and ESBL-producing phenotype (adjusted OR 14.268, CI 5.120-39.762, p < 0.001). CONCLUSION Bloodstream infections caused by CRE are associated with a higher mortality rate in the pediatric population. Attention must be paid to preventing and managing pediatric patients with CRE infections.
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Affiliation(s)
- Yu-Cheng Liu
- Division of Pediatric Infectious Diseases, Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan
| | - Chun-Yi Lu
- Division of Pediatric Infectious Diseases, Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan; College of Medicine, National Taiwan University, Taipei, Taiwan.
| | - Ting-Yu Yen
- Division of Pediatric Infectious Diseases, Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan
| | - Luan-Yin Chang
- Division of Pediatric Infectious Diseases, Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan; College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Jong-Min Chen
- Division of Pediatric Infectious Diseases, Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan
| | - Ping-Ing Lee
- Division of Pediatric Infectious Diseases, Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan; College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Li-Min Huang
- Division of Pediatric Infectious Diseases, Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan; College of Medicine, National Taiwan University, Taipei, Taiwan
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Factors associated with mortality from gram-negative bacterial infections in children with cancer. PEDIATRIC HEMATOLOGY ONCOLOGY JOURNAL 2023. [DOI: 10.1016/j.phoj.2023.01.005] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023] Open
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8
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Mukkada S, Melgar M, Bullington C, Chang A, Homsi MR, Gonzalez ML, Antillon F, Su Y, Tang L, Caniza MA. High morbidity and mortality associated with primary bloodstream infections among pediatric patients with cancer at a Guatemalan tertiary referral hospital. Front Public Health 2022; 10:1007769. [PMID: 36466535 PMCID: PMC9713936 DOI: 10.3389/fpubh.2022.1007769] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2022] [Accepted: 10/27/2022] [Indexed: 11/18/2022] Open
Abstract
Infectious complications remain major contributors to adverse outcomes in patients treated for non-communicable disease, particularly in resource limited settings. We performed a 5-year retrospective study of primary bloodstream infections at a dedicated pediatric oncology center in Guatemala. Two hundred and twelve episodes occurring in 194 unique patients qualified for inclusion. Patients required intensive care unit admission in 55% of episodes and death occurred in 24% of episodes. Despite subspecialty support in infectious diseases, poor outcomes, including prolonged hospitalization and mortality, were frequent. Our findings suggest that investments in laboratory and clinical data collection are critical to understanding the contributors to poor outcomes and therefore to improving the quality of bloodstream infection management in resource limited settings.
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Affiliation(s)
- Sheena Mukkada
- Department of Global Pediatric Medicine, St. Jude Children's Research Hospital, Memphis, TN, United States,Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN, United States,*Correspondence: Sheena Mukkada
| | - Mario Melgar
- Unidad Nacional de Oncología Pediátrica, Guatemala, Guatemala,Hospital Roosevelt, Guatemala, Guatemala
| | - Craig Bullington
- University of Tennessee Health Sciences Center, Memphis, TN, United States
| | - Alicia Chang
- Unidad Nacional de Oncología Pediátrica, Guatemala, Guatemala
| | - Maysam R. Homsi
- Department of Global Pediatric Medicine, St. Jude Children's Research Hospital, Memphis, TN, United States
| | - Miriam L. Gonzalez
- Department of Global Pediatric Medicine, St. Jude Children's Research Hospital, Memphis, TN, United States
| | - Federico Antillon
- Unidad Nacional de Oncología Pediátrica, Guatemala, Guatemala,School of Medicine, Francisco Marroquin University, Guatemala, Guatemala
| | - Yin Su
- Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, TN, United States
| | - Li Tang
- Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, TN, United States
| | - Miguela A. Caniza
- Department of Global Pediatric Medicine, St. Jude Children's Research Hospital, Memphis, TN, United States,Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN, United States
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9
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Slatnick LR, Miller K, Scott HF, Loi M, Esbenshade AJ, Franklin A, Lee-Sherick AB. Serum lactate is associated with increased illness severity in immunocompromised pediatric hematology oncology patients presenting to the emergency department with fever. Front Oncol 2022; 12:990279. [PMID: 36276165 PMCID: PMC9583361 DOI: 10.3389/fonc.2022.990279] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2022] [Accepted: 09/19/2022] [Indexed: 11/30/2022] Open
Abstract
Introduction Determining which febrile pediatric hematology/oncology (PHO) patients will decompensate from severe infection is a significant challenge. Serum lactate is a well-established marker of illness severity in general adult and pediatric populations, however its utility in PHO patients is unclear given that chemotherapy, organ dysfunction, and cancer itself can alter lactate metabolism. In this retrospective analysis, we studied the association of initial serum lactate in febrile immunosuppressed PHO patients with illness severity, defined by the incidence of clinical deterioration events (CDE) and invasive bacterial infection (IBI) within 48 hours. Methods Receiver operating characteristic (ROC) curves were reported using initial lactate within two hours of arrival as the sole predictor for CDE and IBI within 48 hours. Using a generalized estimating equations (GEE) approach, the association of lactate with CDE and IBI within 48 hours was tested in univariate and multivariable analyses including covariates based on Quasi-likelihood under Independence Model Criterion (QIC). Additionally, the association of lactate with secondary outcomes (i.e., hospital length of stay (LOS), intensive care unit (PICU) admission, PICU LOS, non-invasive infection) was assessed. Results Among 897 encounters, 48 encounters had ≥1 CDE (5%), and 96 had ≥1 IBI (11%) within 48 hours. Elevated lactate was associated with increased CDE in univariate (OR 1.77, 95%CI: 1.48-2.12, p<0.001) and multivariable (OR 1.82, 95%CI: 1.43-2.32, p<0.001) analyses, longer hospitalization (OR 1.15, 95%CI: 1.07-1.24, p<0.001), increased PICU admission (OR 1.68, 95%CI: 1.41-2.0, p<0.001), and longer PICU LOS (OR 1.21, 95%CI: 1.04-1.4, p=0.01). Elevated lactate was associated with increased IBI in univariate (OR 1.40, 95%CI: 1.16-1.69, p<0.001) and multivariable (OR 1.49, 95%CI: 1.23-1.79, p<0.001) analyses. Lactate level was not significantly associated with increased odds of non-invasive infection (p=0.09). The QIC of the model was superior with lactate included for both CDE (305 vs. 325) and IBI (563 vs. 579). Conclusions These data demonstrated an independent association of elevated initial lactate level and increased illness severity in febrile PHO patients, suggesting that serum lactate could be incorporated into future risk stratification strategies for this population.
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Affiliation(s)
- Leonora Rose Slatnick
- Department of Pediatrics, Center for Cancer and Blood Disorders, University of Colorado Anschutz Medical Center, Children’s Hospital Colorado, Aurora, CO, United States
- *Correspondence: Leonora Rose Slatnick,
| | - Kristen Miller
- Department of Pediatrics, Center for Cancer and Blood Disorders, University of Colorado Anschutz Medical Center, Children’s Hospital Colorado, Aurora, CO, United States
| | - Halden F. Scott
- Department of Pediatrics, Section of Pediatric Emergency Medicine, University of Colorado Anschutz Medical Center, Children’s Hospital Colorado, Aurora, CO, United States
| | - Michele Loi
- Department of Pediatrics, Center for Cancer and Blood Disorders, University of Colorado Anschutz Medical Center, Children’s Hospital Colorado, Aurora, CO, United States
- Department of Pediatrics, Division of Critical Care Medicine, University of Colorado Anschutz Medical Center, Children’s Hospital Colorado, Aurora, CO, United States
| | - Adam J. Esbenshade
- Department of Pediatrics, Vanderbilt University Medical Center and Vanderbilt Ingram Cancer Center, Nashville, TN, United States
| | - Anna Franklin
- Department of Pediatrics, Center for Cancer and Blood Disorders, University of Colorado Anschutz Medical Center, Children’s Hospital Colorado, Aurora, CO, United States
| | - Alisa B. Lee-Sherick
- Department of Pediatrics, Center for Cancer and Blood Disorders, University of Colorado Anschutz Medical Center, Children’s Hospital Colorado, Aurora, CO, United States
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10
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Wattier RL, Esbenshade AJ. From "More is Better" to "Less is More": A Commentary on Antimicrobial Use in Pediatric Oncology. J Pediatric Infect Dis Soc 2022; 11:229-238. [PMID: 35099542 DOI: 10.1093/jpids/piab111] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2021] [Accepted: 12/09/2021] [Indexed: 11/14/2022]
Abstract
Reducing avoidable antimicrobial exposure to pediatric patients with cancer is achievable and necessary to promote optimal short- and long-term outcomes. Multiple evidence-based practices are already well established but should be more consistently implemented. Important opportunities exist to further improve the evidence to guide selective antimicrobial use in pediatric oncology.
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Affiliation(s)
- Rachel L Wattier
- Department of Pediatrics, Division of Infectious Diseases and Global Health, University of California San Francisco, San Francisco, California, USA
| | - Adam J Esbenshade
- Department of Pediatrics, Division of Hematology/Oncology, Vanderbilt University, Nashville, Tennessee, USA
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11
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The interplay between anticancer challenges and the microbial communities from the gut. Eur J Clin Microbiol Infect Dis 2022; 41:691-711. [PMID: 35353280 DOI: 10.1007/s10096-022-04435-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2021] [Accepted: 03/15/2022] [Indexed: 11/03/2022]
Abstract
Cancer being an increasing burden on human health, the use of anticancer drugs has risen over the last decades. The physiological effects of these drugs are not only perceived by the host's cells but also by the microbial cells it harbors as commensals, notably the gut microbiota. Since the early '50 s, the cytotoxicity of anticancer chemotherapy was evaluated on bacteria revealing some antimicrobial activities that result in an established perturbation of the gut microbiota. This perturbation can affect the host's health through dysbiosis, which can lead to multiple complications, but has also been shown to have a direct effect on the treatment efficiency.We, therefore, conducted a review of literature focusing on this triangular relationship involving the microbial communities from the gut, the host's disease, and the anticancer treatment. We focused specifically on the antimicrobial effects of anticancer chemotherapy, their impact on mutagenesis in bacteria, and the perspectives of using bacteria-based tools to help in the diagnostic and treatment of cancer.
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12
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Commission for Hospital Hygiene and Infection Prevention (KRINKO). Infection prevention requirements for the medical care of immunosuppressed patients: recommendations of the Commission for Hospital Hygiene and Infection Prevention (KRINKO) at the Robert Koch Institute. GMS HYGIENE AND INFECTION CONTROL 2022; 17:Doc07. [PMID: 35707229 PMCID: PMC9174886 DOI: 10.3205/dgkh000410] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
In Germany, guidelines for hygiene in hospitals are given in form of recommendations by the Commission for Hospital Hygiene and Infection Prevention (Kommission für Krankenhaushygiene und Infektionsprävention, "KRINKO"). The KRINKO and its voluntary work are legitimized by the mandate according to § 23 of the Infection Protection Act (Infektionsschutzgesetz, "IfSG"). The original German version of this document was published in February 2021 and has now been made available to the international professional public in English. The guideline provides recommendations on infection prevention and control for immunocompromised individuals in health care facilities. This recommendation addresses not only measures related to direct medical care of immunocompromised patients, but also management aspects such as surveillance, screening, antibiotic stewardship, and technical/structural aspects such as patient rooms, air quality, and special measures during renovations.
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Ginzburg A, Goldstein G, Raviv D, Cohen H, Weinreb S, Harlev D, Nitsan-Luques A, Abou Saoud MY, Strahilevitz J, Averbuch D. Bacteremia in Children with Solid Tumors: Etiology, Antimicrobial Susceptibility, Factors Associated with Multidrug Resistance, and Mortality. Microb Drug Resist 2022; 28:601-610. [PMID: 35363049 DOI: 10.1089/mdr.2021.0256] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022] Open
Abstract
This retrospective study aims to describe the etiology and resistance patterns of pathogens causing bacteremia in children with solid tumors in a tertiary pediatric hematology-oncology center in Jerusalem, Israel (2011-2019). Factors associated with multidrug-resistant (MDR) bacteremia and mortality were analyzed. A total of 228 pathogens were isolated in 126 patients; 61.0% were gram-negative rods (GNR) and 38.2% were gram-positive cocci (GPC). The most common pathogens were Klebsiella pneumoniae (19.3%), Escherichia coli (17.5%), and coagulase-negative staphylococci (16.2%). The proportion of MDR-GNR was 18.2%, while the proportion of MDR-GPC was 55.2%. In logistic regression analysis, breakthrough bacteremia on a penicillin-group antibiotic (odds ratio [OR] 5.69, [95% confidence interval 1.42-22.76], p-value = 0.014) was associated and underlying diagnosis of neuroblastoma was inversely associated (OR 0.17, [0.04-0.81], p-value = 0.026) with MDR-GNR bacteremia; while the previous hospitalizations' duration (OR 1.032/day, [1.01-1.06], p-value = 0.007) and oncologic treatment intensity (OR 2.19, [1.08-4.45, p-value = 0.03) were associated with MDR-GPC bacteremia. Shock, prolonged profound neutropenia, and pediatric intensive care unit (PICU) admission were associated with 7-day mortality; and relapsed disease, oncologic treatment intensity, prolonged profound neutropenia, and PICU admission-with 30-day mortality in the univariate analyses. Empirical antibiotic choice should be based on factors associated with MDR infections in this specific population.
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Affiliation(s)
- Amit Ginzburg
- Pediatric Infectious Diseases Unit, Faculty of Medicine, Hebrew University of Jerusalem, Hadassah Medical Center, Jerusalem, Israel
| | - Gal Goldstein
- The Dyna & Fala Weinstock Department of Pediatric Hematology Oncology, Faculty of Medicine, Hebrew University of Jerusalem, Hadassah Medical Center, Jerusalem, Israel
| | - Dror Raviv
- The Dyna & Fala Weinstock Department of Pediatric Hematology Oncology, Faculty of Medicine, Hebrew University of Jerusalem, Hadassah Medical Center, Jerusalem, Israel
| | - Hodaya Cohen
- The Dyna & Fala Weinstock Department of Pediatric Hematology Oncology, Faculty of Medicine, Hebrew University of Jerusalem, Hadassah Medical Center, Jerusalem, Israel
| | - Sigal Weinreb
- The Dyna & Fala Weinstock Department of Pediatric Hematology Oncology, Faculty of Medicine, Hebrew University of Jerusalem, Hadassah Medical Center, Jerusalem, Israel
| | - Dan Harlev
- The Dyna & Fala Weinstock Department of Pediatric Hematology Oncology, Faculty of Medicine, Hebrew University of Jerusalem, Hadassah Medical Center, Jerusalem, Israel
| | - Adi Nitsan-Luques
- The Dyna & Fala Weinstock Department of Pediatric Hematology Oncology, Faculty of Medicine, Hebrew University of Jerusalem, Hadassah Medical Center, Jerusalem, Israel
| | - Mohammad Yacoub Abou Saoud
- The Dyna & Fala Weinstock Department of Pediatric Hematology Oncology, Faculty of Medicine, Hebrew University of Jerusalem, Hadassah Medical Center, Jerusalem, Israel
| | - Jacob Strahilevitz
- Department of Clinical Microbiology and Infectious Diseases, Faculty of Medicine, Hebrew University of Jerusalem, Hadassah Medical Center, Jerusalem, Israel
| | - Diana Averbuch
- Pediatric Infectious Diseases Unit, Faculty of Medicine, Hebrew University of Jerusalem, Hadassah Medical Center, Jerusalem, Israel
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14
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Contemporary Treatment of Resistant Gram-Negative Infections in Pediatric Patients. Infect Dis Clin North Am 2022; 36:147-171. [DOI: 10.1016/j.idc.2021.11.007] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
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15
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Maarbjerg SF, Kiefer LV, Albertsen BK, Schrøder H, Wang M. Bloodstream Infections in Children With Cancer: Pathogen Distribution and Antimicrobial Susceptibility Patterns Over a 10-Year Period. J Pediatr Hematol Oncol 2022; 44:e160-e167. [PMID: 34310474 DOI: 10.1097/mph.0000000000002258] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2020] [Accepted: 05/30/2021] [Indexed: 11/26/2022]
Abstract
Bloodstream infections (BSIs) adversely affect clinical outcome in children with cancer. Over 1 decade, this retrospective cohort study describes pathogen distribution in BSIs and antimicrobial susceptibility against empirical antibiotics frequently prescribed in children with cancer. The antibiotic efficacy was evaluated through the determination of minimal inhibitory concentrations for piperacillin-tazobactam and meropenem and by disk diffusion for remaining antibiotics. From 2004 to 2013, 398 BSIs occurred in 196 children with cancer (median age: 5.4 y), resulting in 457 bacteria. Overall, 266 (58.2%) were Gram-positive, and 191 (41.8%) were Gram-negative with a significant Gram-positive increase over time (P=0.032). Coagulase-negative staphylococci (74, 16.2%), viridans group streptococci (67, 14.7%), Escherichia coli (52, 11.4%), and Staphylococcus aureus (39, 8.5%) were the most common pathogens. Susceptibility to piperacillin-tazobactam (95.9%, P=0.419) and meropenem (98.9%, P=0.752) was stable over time, and resistance was observed among viridans group streptococci against piperacillin-tazobactam (18%) and meropenem (7%) and among Enterobacterales against piperacillin-tazobactam (3%). Vancomycin showed 98% Gram-positive activity, gentamicin 82% Gram-negative activity and ampicillin, cefotaxime, and cefuroxime were active in 50%, 72%, and 69% of pathogens, respectively, and BSI-related mortality was 0%. In conclusion, over 1 decade, we report an increase in Gram-positive BSIs, and stable, low-resistance rates against currently recommended empirical antibiotics, piperacillin-tazobactam and meropenem.
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Affiliation(s)
| | | | | | | | - Mikala Wang
- Clinical Microbiology, Aarhus University Hospital, Aarhus, Denmark
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16
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Antibiotic-Resistant Infections and Treatment Challenges in the Immunocompromised Host: An Update. Infect Dis Clin North Am 2021; 34:821-847. [PMID: 33131573 DOI: 10.1016/j.idc.2020.08.005] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
This article reviews antibiotic resistance and treatment of bacterial infections in the growing number of patients who are immunocompromised: solid organ transplant recipients, the neutropenic host, and persons with human immunodeficiency virus and AIDS. Specific mechanisms of resistance in both gram-negative and gram-positive bacteria, as well as newer treatment options are addressed elsewhere and are only briefly discussed in the context of the immunocompromised host.
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17
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The Pattern of Microorganisms and Drug Susceptibility in Pediatric Oncologic Patients with Febrile Neutropenia. J Pathog 2021; 2021:6692827. [PMID: 33854800 PMCID: PMC8021465 DOI: 10.1155/2021/6692827] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2020] [Accepted: 03/18/2021] [Indexed: 11/18/2022] Open
Abstract
Objective The study aimed to describe the pattern of causative microorganisms, drug susceptibility, risk factors of antibiotic-resistant bacterial infection, and clinical impact of these organisms on pediatric oncology patients with febrile neutropenia. Methods A retrospective descriptive study of oncologic patients aged less than 15 years who were diagnosed with febrile neutropenia in King Chulalongkorn Memorial Hospital was conducted between January 2013 to December 2017. Characteristics and clinical outcomes of febrile neutropenia episodes, causative pathogens, and their antibiotic susceptibilities were recorded. Result This study included 267 patients with 563 febrile neutropenia episodes. The median (range) age was 5.1 years (1 month-15 years). The most common underlying disease was acute lymphoblastic leukemia (42.7%). Of 563 febrile episodes, there were 192 (34.1%) with microbiologically documented infection. Among these 192 episodes of microbiologically documented infection, there were 214 causative pathogens: 154 bacteria (72%), 32 viruses (15%), 27 fungus (12.6%), and 1 Mycobacterium tuberculosis (0.4%). Gram-negative bacteria (48.6%) accounted for most of the causative pathogens. Twenty-three percent of them were multidrug resistant, and 18% were carbapenem resistant. Among Gram-positive bacterial infection which accounted for 23.4% of all specimens, the proportion of MRSA was 20%. The 2-week mortality rate was 3.7%. Drug-resistant Gram-negative bacterial infection caused significant adverse events and mortality compared to nonresistant bacterial infection (p < 0.05). Conclusion There is high rate of drug-resistant organism infection in pediatric oncology patients in a tertiary-care center in Thailand. Infection with drug-resistant Gram-negative bacterial infection was associated with significant morbidity and mortality. Continuous surveillance for the pattern of drug-resistant infections is crucial.
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18
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Castagnola E, Bagnasco F, Mesini A, Agyeman PKA, Ammann RA, Carlesse F, Santolaya de Pablo ME, Groll AH, Haeusler GM, Lehrnbecher T, Simon A, D’Amico MR, Duong A, Idelevich EA, Luckowitsch M, Meli M, Menna G, Palmert S, Russo G, Sarno M, Solopova G, Tondo A, Traubici Y, Sung L. Antibiotic Resistant Bloodstream Infections in Pediatric Patients Receiving Chemotherapy or Hematopoietic Stem Cell Transplant: Factors Associated with Development of Resistance, Intensive Care Admission and Mortality. Antibiotics (Basel) 2021; 10:antibiotics10030266. [PMID: 33807654 PMCID: PMC8000765 DOI: 10.3390/antibiotics10030266] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2021] [Revised: 02/21/2021] [Accepted: 03/01/2021] [Indexed: 01/01/2023] Open
Abstract
Bloodstream infections (BSI) are a severe complication of antineoplastic chemotherapy or hematopoietic stem cell transplantation (HSCT), especially in the presence of antibiotic resistance (AR). A multinational, multicenter retrospective study in patients aged ≤ 18 years, treated with chemotherapy or HSCT from 2015 to 2017 was implemented to analyze AR among non-common skin commensals BSI. Risk factors associated with AR, intensive care unit (ICU) admission and mortality were analyzed by multilevel mixed effects or standard logistic regressions. A total of 1291 BSIs with 1379 strains were reported in 1031 patients. Among Gram-negatives more than 20% were resistant to ceftazidime, cefepime, piperacillin-tazobactam and ciprofloxacin while 9% was resistant to meropenem. Methicillin-resistance was observed in 17% of S. aureus and vancomycin resistance in 40% of E. faecium. Previous exposure to antibiotics, especially to carbapenems, was significantly associated with resistant Gram-negative BSI while previous colonization with methicillin-resistant S. aureus was associated with BSI due to this pathogen. Hematological malignancies, neutropenia and Gram-negatives resistant to >3 antibiotics were significantly associated with higher risk of ICU admission. Underlying disease in relapse/progression, previous exposure to antibiotics, and need of ICU admission were significantly associated with mortality. Center-level variation showed a greater impact on AR, while patient-level variation had more effect on ICU admission and mortality. Previous exposure to antibiotics or colonization by resistant pathogens can be the cause of AR BSI. Resistant Gram-negatives are significantly associated with ICU admission and mortality, with a significant role for the treating center too. The significant evidence of center-level variations on AR, ICU admission and mortality, stress the need for careful local antibiotic stewardship and infection control programs.
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Affiliation(s)
- Elio Castagnola
- Infectious Diseases Unit, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy;
- Correspondence:
| | - Francesca Bagnasco
- Epidemiology and Biostatistics Unit, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy;
| | - Alessio Mesini
- Infectious Diseases Unit, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy;
| | - Philipp K. A. Agyeman
- Department of Pediatrics, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland;
| | - Roland A. Ammann
- Pediatric Hematology/Oncology, Department of Pediatrics, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland;
- Kinderaerzte KurWerk, 3400 Burgdorf, Switzerland
| | - Fabianne Carlesse
- Pediatric Oncology Institute, GRAACC/Federal University of Sao Paulo, Sao Paulo 04023-062, Brazil;
| | | | - Andreas H. Groll
- Infectious Disease Research Program, Center for Bone Marrow Transplantation and Department of Paediatric Haematology and Oncology, University Children’s Hospital Muenster, 48149 Muenster, Germany;
| | - Gabrielle M. Haeusler
- The Paediatric Integrated Cancer Service, Parkville, VIC 3052, Australia;
- Department of Infectious Diseases, Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia
- Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC 3010, Australia
| | - Thomas Lehrnbecher
- Division of Pediatric Hematology and Oncology, Hospital for Children and Adolescents, University Hospital, Johann Wolfgang Goethe University, 60323 Frankfurt am Main, Germany; (T.L.); (M.L.)
| | - Arne Simon
- Pediatric Oncology and Hematology, Children’s Hospital Medical Center, University Clinics, 6642 Homburg, Germany;
| | - Maria Rosaria D’Amico
- Department Hemato-Oncology, AORN Santobono-Pausilipon, 80129 Napoli, Italy; (M.R.D.); (G.M.)
| | - Austin Duong
- Child Health Evaluative Sciences, The Hospital for Sick Children, Peter Gilgan Centre for Research & Learning, Toronto, ON M5G 0A4, Canada; (A.D.); (S.P.); (Y.T.); (L.S.)
| | - Evgeny A. Idelevich
- Institute of Medical Microbiology, University Hospital Munster, 48149 Munster, Germany;
| | - Marie Luckowitsch
- Division of Pediatric Hematology and Oncology, Hospital for Children and Adolescents, University Hospital, Johann Wolfgang Goethe University, 60323 Frankfurt am Main, Germany; (T.L.); (M.L.)
| | - Mariaclaudia Meli
- Pediatric Hemato-Oncology Unit, Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy; (M.M.); (G.R.)
| | - Giuseppe Menna
- Department Hemato-Oncology, AORN Santobono-Pausilipon, 80129 Napoli, Italy; (M.R.D.); (G.M.)
| | - Sasha Palmert
- Child Health Evaluative Sciences, The Hospital for Sick Children, Peter Gilgan Centre for Research & Learning, Toronto, ON M5G 0A4, Canada; (A.D.); (S.P.); (Y.T.); (L.S.)
| | - Giovanna Russo
- Pediatric Hemato-Oncology Unit, Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy; (M.M.); (G.R.)
| | - Marco Sarno
- Pediatric Unit, Santa Maria Delle Grazie Hospital, ASL Napoli 2 Nord, Pozzuoli, 80027 Napoli, Italy;
| | - Galina Solopova
- Dmitry Rogachev Federal Scientific-Clinical Center of Children’s Hematology, Oncology and Immunology, 117997 Moscow, Russia;
| | - Annalisa Tondo
- Paediatric Haematology/Oncology Department, Meyer Children’s University Hospital, 50134 Florence, Italy;
| | - Yona Traubici
- Child Health Evaluative Sciences, The Hospital for Sick Children, Peter Gilgan Centre for Research & Learning, Toronto, ON M5G 0A4, Canada; (A.D.); (S.P.); (Y.T.); (L.S.)
| | - Lillian Sung
- Child Health Evaluative Sciences, The Hospital for Sick Children, Peter Gilgan Centre for Research & Learning, Toronto, ON M5G 0A4, Canada; (A.D.); (S.P.); (Y.T.); (L.S.)
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Anforderungen an die Infektionsprävention bei der medizinischen Versorgung von immunsupprimierten Patienten. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 2021; 64:232-264. [PMID: 33394069 PMCID: PMC7780910 DOI: 10.1007/s00103-020-03265-x] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
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Resistance to Antibiotics of Uropathogen Bacteria Isolated From Urine and Blood in Pediatric Cancer Patients: A Single Center, 12-year Study. Pediatr Infect Dis J 2020; 39:1106-1110. [PMID: 33021597 DOI: 10.1097/inf.0000000000002854] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Resistant pathogens have become a major healthcare problem in children with cancer, causing different kinds of infections such as the bloodstream ones, most common, and most frequently described and the urinary tract ones, of which less data are available. We analyzed and compared the proportions, and the trends of resistance in pathogens isolated from blood and urines in children with cancer followed in IRCCS Istituto Giannina Gaslini, Genova, Italy, from January 2007 to December 2018. Overall, 345 strains detected in urines and 282 in bloodstream infections were analyzed. Enterobacteriales were the most frequently isolated pathogens. During the study period in urines, there was a significant increase of resistance to ceftazidime, ciprofloxacin, piperacillin/tazobactam, and trimethoprim-sulfamethoxazole, but pathogens from blood were significantly more frequently resistant to amikacin, piperacillin/tazobactam, and combination therapy piperacillin/tazobactam+amikacin, even if with a decreasing trend during the study period. These data confirm the importance of surveillance of isolated microorganism and antibiotic resistance in cancer children.
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Cefepime Versus Cefepime Plus Amikacin as an Initial Antibiotic Choice for Pediatric Cancer Patients With Febrile Neutropenia in an Era of Increasing Cefepime Resistance. Pediatr Infect Dis J 2020; 39:931-936. [PMID: 32453199 DOI: 10.1097/inf.0000000000002751] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
BACKGROUND We investigated the treatment outcomes before and after the addition of amikacin to cefepime monotherapy as an initial empirical antibiotic treatment in pediatric cancer patients with febrile neutropenia. METHODS This was a retrospective historical cohort study. The subjects were pediatric cancer patients who visited the emergency room at the Samsung Medical Center, Seoul, Korea, due to chemotherapy-induced febrile neutropenia, between January 2011 and December 2016. Since September 2014, the empirical antimicrobial treatment regimen for febrile neutropenia was changed from high-dose cefepime monotherapy to combination therapy of adding a single dose of amikacin. RESULTS Two hundred twenty-five bacteremia episodes in 164 patients were reported during the study period. Bacteremia caused by cefepime-resistant Gram-negative bacteria was observed in 16% of patients before September 2014 and in 21% of the patients after September 2014 (P = 0.331). Use of appropriate empirical antibiotic treatments increased from 62% to 83% following addition of amikacin to cefepime treatment (P = 0.003). The duration of fever was shorter in the cefepime plus amikacin group than in the cefepime group (22 vs. 34 hours, P = 0.014); however, rates of septic shock and pediatric intensive care unit hospitalizations were not significantly different between the 2 groups (septic shock, both 7%, P = 0.436; pediatric intensive care unit 3% vs. 1%, P = 0.647). CONCLUSIONS We observed no additional benefit of amikacin addition to high-dose cefepime monotherapy. Therefore, adding amikacin to cefepime monotherapy in conditions where cefepime-resistant Gram-negative bacteremia amounts to 20% or less may not be justified.
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Cojutti PG, Maximova N, Schillani G, Hope W, Pea F. Population pharmacokinetics of continuous-infusion ceftazidime in febrile neutropenic children undergoing HSCT: implications for target attainment for empirical treatment against Pseudomonas aeruginosa. J Antimicrob Chemother 2020; 74:1648-1655. [PMID: 30838391 DOI: 10.1093/jac/dkz065] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2018] [Revised: 12/30/2018] [Accepted: 01/23/2019] [Indexed: 11/12/2022] Open
Abstract
OBJECTIVES To conduct a population pharmacokinetic analysis of continuous-infusion ceftazidime in a retrospective cohort of paediatric HSCT patients who were empirically treated for febrile neutropenia (FN) and who underwent therapeutic drug monitoring of ceftazidime steady-state plasma concentrations (Css) for optimization of drug exposure. METHODS A non-parametric approach with Pmetrics was used for pharmacokinetic analysis and covariate evaluation. Monte Carlo simulations were performed to calculate the PTA of the pharmacodynamic determinant of efficacy (Css/MIC ≥4) against Pseudomonas aeruginosa with continuous-infusion ceftazidime dosages of 1-6 g daily. The Css safety threshold was arbitrarily placed at 100 mg/L and advisable dosages were used. RESULTS A total of 46 patients with 70 ceftazidime Css values were included. Estimated glomerular filtration rate (eGFR) and body surface area were the covariates associated with drug clearance. At the EUCAST clinical breakpoint of 8 mg/L, simulations showed that continuous-infusion ceftazidime dosages of 4-6 g daily attained optimal PTAs (>90%) across most of 16 different clinical scenarios based on four classes of eGFR (50-145, 145.1-200, 200.1-286 and 286.1-422 mL/min/1.73 m2) and body surface area (0.30-0.64, 0.65-0.88, 0.89-1.34 and 1.35-1.84 m2). In patients with body surface area 0.30-0.64 m2 and eGFR ≤200 mL/min/1.73 m2 the advisable dose of 3 g daily allowed only suboptimal PTAs (<75%). The cumulative fraction of response against MIC distribution of P. aeruginosa was >87%. CONCLUSIONS Continuous-infusion ceftazidime dosages ranging from 3 to 6 g daily according to different classes of eGFR and body surface area may allow optimized empirical treatment of P. aeruginosa infections in paediatric HSCT patients with FN.
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Affiliation(s)
- Pier Giorgio Cojutti
- Institute of Clinical Pharmacology, Santa Maria della Misericordia University Hospital, ASUIUD, Udine, Italy
- Department of Medicine, University of Udine, Udine, Italy
| | - Natalia Maximova
- Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste, Italy
| | - Giulia Schillani
- Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste, Italy
| | - William Hope
- Antimicrobial Pharmacodynamics and Therapeutics, Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK
| | - Federico Pea
- Institute of Clinical Pharmacology, Santa Maria della Misericordia University Hospital, ASUIUD, Udine, Italy
- Department of Medicine, University of Udine, Udine, Italy
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Rr P, Tan EEK, Sultana R, Thoon KC, Chan MY, Lee JH, Wong JJM. Critical illness epidemiology and mortality risk in pediatric oncology. Pediatr Blood Cancer 2020; 67:e28242. [PMID: 32187445 DOI: 10.1002/pbc.28242] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2019] [Accepted: 02/16/2020] [Indexed: 11/09/2022]
Abstract
OBJECTIVE Pediatric oncology patients admitted to the pediatric intensive care unit (PICU) are at high risk of mortality. This study aims to describe the epidemiology of and the risk factors for mortality in these patients. STUDY DESIGN This is a retrospective cohort study including all consecutive PICU oncology admissions from 2011 to 2017. Demographic and clinical risk factors between survivors and nonsurvivors were compared. Both univariate and multivariate Cox proportional hazard regression models were used to quantify the association between 60-day mortality and admission categories, accounting for other covariates (Pediatric Risk Of Mortality [PRISM] III score and previous bacteremia). MAIN OUTCOME MEASURES The primary outcome was 60-day mortality. RESULTS The median (interquartile range) age and PRISM III scores of pediatric oncology patients admitted to the PICU were 7 (3, 12) years and 3 (0, 5), respectively. The most common underlying oncological diagnoses were brain tumors (73/200 [36.5%]) and acute lymphoblastic leukemia (36/200 [18.0%]). Emergency admissions accounted for approximately half of all admissions (108/200 [54.0%]), including cardiovascular (24/108 [22.2%]), neurology (24/108 [22.2%]), respiratory (22/108 [20.4%]), and "other" indications (38/108 [35.2%]). The overall 60-day mortality was 35 of 200 (17.5%). Independent risk factors for mortality were emergency respiratory and neurology categories of admission (adjusted hazard ratio[aHR]: 5.62, 95% confidence interval [95% CI]: 1.57, 20.19; P = .008 and aHR: 6.96, 95% CI: 2.04, 23.75; P = .002, respectively) and previous bacteremia (aHR: 3.37, 95% CI: 1.57, 7.20; P = .002). CONCLUSION Emergency respiratory and neurology admissions and previous bacteremia were independent risk factors for 60-day mortality for pediatric oncological patients admitted to the PICU.
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Affiliation(s)
- Pravin Rr
- Department of Pediatrics, KK Women's & Children's Hospital, Singapore.,Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Enrica Ee Kar Tan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore.,Department of Pediatric Subspecialties, Pediatric Hematology/Oncology Service, KK Women's & Children's Hospital, Singapore.,Duke-NUS Medical School, Singapore
| | - Rehena Sultana
- Center for Quantitative Medicine, Duke-NUS Medical School, The Academia, Singapore
| | - Koh Cheng Thoon
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore.,Duke-NUS Medical School, Singapore.,Infectious Disease Service, Department of Pediatrics, KK Women's & Children's Hospital, Singapore.,Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore
| | - Mei-Yoke Chan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore.,Department of Pediatric Subspecialties, Pediatric Hematology/Oncology Service, KK Women's & Children's Hospital, Singapore.,Duke-NUS Medical School, Singapore.,Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore
| | - Jan Hau Lee
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore.,Duke-NUS Medical School, Singapore.,Children's Intensive Care Unit, Department of Pediatric Subspecialties, KK Women's & Children's Hospital, Singapore
| | - Judith Ju-Ming Wong
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore.,Duke-NUS Medical School, Singapore.,Children's Intensive Care Unit, Department of Pediatric Subspecialties, KK Women's & Children's Hospital, Singapore
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Gram-negative Bacteremia in Children With Hematologic Malignancies and Following Hematopoietic Stem Cell Transplantation: Epidemiology, Resistance, and Outcome. J Pediatr Hematol Oncol 2019; 41:e493-e498. [PMID: 31318820 DOI: 10.1097/mph.0000000000001556] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
Gram-negative rod (GNR) infections adversely affect the outcome of patients with malignancies and following hematopoietic stem cell transplantation (HSCT). This retrospective observational study aimed to describe the epidemiology, outcome, and resistance patterns of GNR bacteremia in children with hematologic malignancies (HM) and after HSCT during the period spanning from 2010 to 2014 in a tertiary children's hospital. A total of 270 children were included in the analysis; 65 (24%) developed 85 episodes of GNR bacteremia; the rate was 36/122 (29.5%) in post-HSCT and 29/178 (16.3%) in HM patients (P<0.05). Overall, 10% of the GNRs were carbapenem resistant. In multivariate analysis, prolonged neutropenia (≥7 d; odds ratio: 19.5, 95% confidence interval: 2.6-148.4) and total hospitalization for a duration of >30 days in the last 3 months (odds ratio: 17.5, 95% confidence interval: 1.4-224.4) were associated with carbapenem-resistant GNR bacteremia. Thirty-day mortality following GNR bacteremia was 0% in HM and 7/52 episodes (13.5%) in HSCT patients (P<0.05). Carbapenem-resistant versus carbapenem-sensitive bacteremia was associated with longer duration of bacteremia (mean: 3.8 vs. 1.7 d), higher risk for intensive care unit hospitalization (44.4% vs. 10.1%), and higher mortality rate (33% vs. 5.8%) (P<0.05). To summarize, GNR bacteremia was frequent, especially in post-HSCT children. Carbapenem resistance adversely affects patients' outcome, increasing morbidity and mortality. Empirical antibiotic therapy must be adjusted to the local resistance patterns.
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Abstract
OBJECTIVES To describe characteristics of liver transplant patients with severe sepsis in the PICU. DESIGN Retrospective descriptive analysis. SETTING Tertiary children's hospital PICU. PATIENTS Liver transplant recipients admitted January 2010 to July 2016 for pediatric severe sepsis. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Between January 2010 and July 2016, 173 liver transplants were performed, and 36 of these patients (21%) were admitted with severe sepsis (54 episodes total). Median age at admission was 2 years (1-6.5 yr), 47.2% were male. Bacterial infections were the most common (77.8%), followed by culture negative (12.9%) and viral infections (7.4%). Fungal infections accounted for only 1.9%. Median time from transplant for viral and culture negative infections was 18 days (8.25-39.75 d) and 25 days (9-41 d), whereas 54.5 days (17-131.25 d) for bacterial infections. Bloodstream and intra-abdominal were the most common bacterial sites (45% and 22.5%, respectively). Multidrug-resistant organisms accounted for 47.6% of bacterial sepsis. Vancomycin-resistant Enterococcus and extended-spectrum beta-lactamase producers were the most frequently identified multidrug-resistant organisms. Patients with multidrug-resistant organism sepsis demonstrated higher admission Pediatric Logistic Organ Dysfunction scores (p = 0.043) and were noted to have an odds ratio of 3.8 and 3.6 for mechanical ventilation and multiple organ dysfunction syndrome, respectively (p = 0.047 and p = 0.044). Overall mortality was 5.5% (n = 2 patients), with both deaths occurring in multidrug-resistant organism episodes. CONCLUSIONS We report that multidrug-resistant organisms are increasingly being identified as causative pathogens for sepsis in pediatric liver transplant recipients and are associated with significantly higher odds for mechanical ventilation and higher organ failure. The emergence of multidrug-resistant organism infections in pediatric liver transplant patients has implications for patient outcomes, antibiotic stewardship, and infection prevention strategies.
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Multidrug-resistant Gram-negative Bacterial Bloodstream Infections in Children's Hospitals in Japan, 2010-2017. Pediatr Infect Dis J 2019; 38:653-659. [PMID: 30672891 DOI: 10.1097/inf.0000000000002273] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
BACKGROUND The risk factors of multidrug-resistant (MDR) Gram-negative bacilli (GNB) bloodstream infection (BSI) are not yet known in children. Our aim was to evaluate risk factors and outcomes associated with MDR GNB BSI in children. METHODS Patients with GNB BSI were enrolled between April 2010 and March 2017 at 8 children's hospitals in Japan. Clinical and microbiologic data were collected retrospectively. The risk factors and outcomes of MDR and non-MDR GNB BSI were compared. RESULTS In total, 629 GNB BSI episodes met the case definition. The median age and proportion of males were 2 years (interquartile range, 0.3-8.7) and 50.7%, respectively. An underlying disease was found in 94% of patients. The proportion of BSI cases that developed >48 hours after admission was 76.2%. MDR comprised 24.5% of BSI cases. The MDR rate did not change over time (P = 0.540). The effective coverage rate of the initial empiric therapy for the MDR and non-MDR BSI cases was 60.4% and 83.4%, respectively (P < 0.001). The all-cause mortality rate at 28 days for all BSI, MDR-BSI and non-MDR BSI cases was 10.7%, 13.6% and 9.7%, respectively (P = 0.167). MDR BSI was independently associated with cancer chemotherapy within 30 days (odds ratio [OR] 43.90), older age (OR 1.05) and admission to the neonatal ward (OR 0.019). CONCLUSIONS One-fourth of GNB BSI cases were MDR. Cancer chemotherapy and older age were risk factors for MDR GNB BSI in children's hospitals. MDR did not increase the all-cause mortality rate.
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A.A.W. IWP, Irwanto I, Dharmawati I, Setyaningtyas A, Puspitasari D, Wahyu AD, Kuntaman K. MICROBIAL PATTERN AND ANTIBIOTIC SUSCEPTIBILITY IN PEDIATRIC INTENSIVE CARE UNIT DR. SOETOMO HOSPITAL, SURABAYA. INDONESIAN JOURNAL OF TROPICAL AND INFECTIOUS DISEASE 2019. [DOI: 10.20473/ijtid.v7i5.5737] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023] Open
Abstract
Gram-negative bacterial are known as common pathogen caused infection in Pediatric Intensive Care Unit (PICU). Microbial Pattern and Antibiotic Susceptibility are needed as clinical data for selected appropriate antibiotic therapy. In PICU Dr. Soetomo hospital until now still lacking of Microbial Pattern and Antibiotic Susceptibility data. This descriptive study is to recognized Microbial Pattern and Antibiotic Susceptibility in PICU patients from blood, urine, sputum, stool, cerebrospinal fluid, endotracheal tube, pus swab and pleural fluid culture specimens. Patients whose admitted into PICU without signs of infections were excluded from the study. The inclusion criteria are patients with sign infection as follows: fever < 36,5°C or > 37.5°C, leukocyte < 4000/mm3 or > 10000/mm3, marker infections CRP >10 mg/L or PCT >0,3 ng/mL, bradycardia or tachycardia, tachypnea, infiltrates on chest X-ray, turbid urine, dysuria, thrombophlebitis, abdominal pain or tenderness, and mucous or skin lesion. Medical record data from 2011 to 2016, revealed 1138 patients had positive microbial culture result, wherein positive result came from blood 44.46%, urine 19.15%, sputum 11.59%, stool 8.96%, cerebrospinal fluid 7.50%, endotracheal tube 4.04%, pus swab 2.89%, and pleural fluid 1.41%. The microorganisms found in PICU Dr. Soetomo was dominated with gram negative bacteria. Commonest bacterial that recognized from blood was B. cepacea, urine was E. coli, sputum was P. aeruginosa, Stool was E. coli, Cerebrospinal fluid was S. cohnii, endotracheal tube was K. pneumoniae ESBL, pus swab was S. aureus, and pleural fluid was S. maltophilia. Both gram-negative bacteria and gram-positive bacteria isolates revealed multiple drug resistance to commonly used antibiotic, but still had good susceptibility for antibiotic such as; amikacin, cefoperazone-sulbactam, linezolid, vancomycin and carbapenem group.
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28
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Activity of ceftolozane-tazobactam and comparators when tested against Gram-negative isolates collected from paediatric patients in the USA and Europe between 2012 and 2016 as part of a global surveillance programme. Int J Antimicrob Agents 2019; 53:637-643. [DOI: 10.1016/j.ijantimicag.2019.01.015] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2018] [Revised: 01/15/2019] [Accepted: 01/27/2019] [Indexed: 02/05/2023]
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Haeusler GM, Slavin MA, Bryant PA, Babl FE, Mechinaud F, Thursky KA. Management of fever and neutropenia in children with cancer: A survey of Australian and New Zealand practice. J Paediatr Child Health 2018; 54:761-769. [PMID: 29655245 DOI: 10.1111/jpc.13899] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2017] [Revised: 11/19/2017] [Accepted: 12/13/2017] [Indexed: 11/30/2022]
Abstract
AIM Variation in the management of fever and neutropenia (FN) in children is well described. The aim of this study was to explore the current management of FN across Australia and New Zealand and highlight areas for improvement. METHODS A practice survey was administered to paediatric health-care providers via four clinical and research networks. Using three clinical case vignettes, we explored risk stratification, empiric antibiotics, initial investigations, intravenous-oral switch, ambulatory management and antibiotic duration in children with cancer and FN. RESULTS A response was received from 104 participants from 16 different hospitals. FN guideline compliance was rated as moderate or poor by 24% of respondents, and seven different fever definitions were described. There was little variation in the selected empiric monotherapy and dual-therapy regimens, and almost all respondents recommended first-dose antibiotics within 1 h. However, 27 different empiric antibiotic combinations were selected for beta-lactam allergy. An incorrect risk status was assigned to the low-risk case by 27% of respondents and to the high-risk case by 41%. Compared to current practice, significantly more respondents would manage the low-risk case in the ambulatory setting provided adequate resources were in place (43 vs. 85%, P < 0.0001). There was variation in the use of empiric glycopeptides as well as use of aminoglycosides beyond 48 h. CONCLUSION Although the antibiotics selected for empiric management of FN are appropriate and consistent, variation and inaccuracies exist in risk stratification, the selection of monotherapy over dual therapy, empiric antibiotics chosen for beta-lactam allergy, use of glycopeptides and duration of aminoglycosides.
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Affiliation(s)
- Gabrielle M Haeusler
- Department of Infectious Diseases, Peter MacCallum Cancer Centre, University of Melbourne, Melbourne, Victoria, Australia.,NHMRC National Centre for Infections in Cancer, University of Melbourne, Melbourne, Victoria, Australia.,Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia.,Paediatric Integrated Cancer Service, Victoria State Government, Melbourne, Victoria, Australia.,Department of Infection and Immunity, Monash Children's Hospital, Melbourne, Victoria, Australia
| | - Monica A Slavin
- Department of Infectious Diseases, Peter MacCallum Cancer Centre, University of Melbourne, Melbourne, Victoria, Australia.,NHMRC National Centre for Infections in Cancer, University of Melbourne, Melbourne, Victoria, Australia.,Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia.,Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia.,Victorian Infectious Diseases Service, The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia
| | - Penelope A Bryant
- Murdoch Children's Research Institute, Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia.,Infectious Diseases Unit, Royal Children's Hospital, Melbourne, Victoria, Australia
| | - Franz E Babl
- Murdoch Children's Research Institute, Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia.,Department of Emergency Medicine, Royal Children's Hospital, Melbourne, Victoria, Australia
| | - Francoise Mechinaud
- Murdoch Children's Research Institute, Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia.,Children's Cancer Centre, Royal Children's Hospital, Melbourne, Victoria, Australia
| | - Karin A Thursky
- Department of Infectious Diseases, Peter MacCallum Cancer Centre, University of Melbourne, Melbourne, Victoria, Australia.,NHMRC National Centre for Infections in Cancer, University of Melbourne, Melbourne, Victoria, Australia.,Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia.,Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia.,Victorian Infectious Diseases Service, The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.,NHMRC National Centre for Antimicrobial Stewardship, The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia
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30
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Slavova-Azmanova N, Haddow L, Hohnen H, Coombs G, Robinson JO, Ives A. Admissions for antibiotic-resistant infections in cancer patients during first year of cancer diagnosis: a cross-sectional study. Intern Med J 2018; 47:1306-1310. [PMID: 29105268 DOI: 10.1111/imj.13609] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2016] [Revised: 04/20/2017] [Accepted: 05/07/2017] [Indexed: 12/01/2022]
Abstract
In this study, linked Western Australian health data were used to determine presence of an antibiotic-resistant infection (ABRI) for all people diagnosed with a primary invasive cancer in 2009. Of 10 858 cancer cases, 154 (1.42%) had an ABRI. Patients with an ABRI were older (71.5 vs 66 years), and more had died in the year following diagnosis (37.7 vs 20.2%, P < 0.001). The ABRI cohort had a higher proportion of colorectal, genitourinary and haematological cancers (19.5 vs 11.9%; 14.3 vs 9.7% and 16.9 vs 5.8%, respectively). Hospital admissions with an ABRI were longer (22.3 vs 2.9 days, P < 0.001) and had a higher proportion of unplanned admissions (60.3 vs 15.2%), admissions through emergency department (36.8 vs 8.3%) and intensive care admissions (14.9 vs 1.7%, P < 0.001). Patients with solid tumours who developed an ABRI were more likely to have received chemotherapy (35.9 vs 27.8%, P = 0.04). In haematological cancer patients, a greater proportion of the admissions with an ABRI occurred after radiation therapy or chemotherapy (P = 0.01 and P = 0.005, respectively). This study is the first to report population-level data on ABRI in cancer patients. Patients with an ABRI had more hospital admissions and poorer outcomes.
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Affiliation(s)
- Neli Slavova-Azmanova
- Cancer and Palliative Care Research and Evaluation Unit, UWA Medical School, Faculty of Health and Medical Sciences, The University of Western Australia, Perth, Western Australia, Australia
| | - Livia Haddow
- Cancer and Palliative Care Research and Evaluation Unit, UWA Medical School, Faculty of Health and Medical Sciences, The University of Western Australia, Perth, Western Australia, Australia
| | - Harry Hohnen
- Cancer and Palliative Care Research and Evaluation Unit, UWA Medical School, Faculty of Health and Medical Sciences, The University of Western Australia, Perth, Western Australia, Australia
| | - Geoffrey Coombs
- School of Veterinary and Life Sciences, Murdoch University, Perth, Western Australia, Australia.,School of Biomedical Sciences, Curtin University, Perth, Western Australia, Australia.,Pathwest Laboratory Medicine, Fiona Stanley Hospital, Perth, Western Australia, Australia
| | - James O Robinson
- Pathwest Laboratory Medicine, Fiona Stanley Hospital, Perth, Western Australia, Australia.,Department of Microbiology and Infectious Diseases, Royal Perth Hospital, Perth, Western Australia, Australia
| | - Angela Ives
- Cancer and Palliative Care Research and Evaluation Unit, UWA Medical School, Faculty of Health and Medical Sciences, The University of Western Australia, Perth, Western Australia, Australia
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Antibiotic-resistant Gram-negative Blood Stream Infections in Children With Cancer: A Review of Epidemiology, Risk Factors, and Outcome. Pediatr Infect Dis J 2018; 37:495-498. [PMID: 29432384 DOI: 10.1097/inf.0000000000001938] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
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Naylor NR, Atun R, Zhu N, Kulasabanathan K, Silva S, Chatterjee A, Knight GM, Robotham JV. Estimating the burden of antimicrobial resistance: a systematic literature review. Antimicrob Resist Infect Control 2018; 7:58. [PMID: 29713465 PMCID: PMC5918775 DOI: 10.1186/s13756-018-0336-y] [Citation(s) in RCA: 321] [Impact Index Per Article: 45.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2017] [Accepted: 03/14/2018] [Indexed: 01/02/2023] Open
Abstract
Background Accurate estimates of the burden of antimicrobial resistance (AMR) are needed to establish the magnitude of this global threat in terms of both health and cost, and to paramaterise cost-effectiveness evaluations of interventions aiming to tackle the problem. This review aimed to establish the alternative methodologies used in estimating AMR burden in order to appraise the current evidence base. Methods MEDLINE, EMBASE, Scopus, EconLit, PubMed and grey literature were searched. English language studies evaluating the impact of AMR (from any microbe) on patient, payer/provider and economic burden published between January 2013 and December 2015 were included. Independent screening of title/abstracts followed by full texts was performed using pre-specified criteria. A study quality score (from zero to one) was derived using Newcastle-Ottawa and Philips checklists. Extracted study data were used to compare study method and resulting burden estimate, according to perspective. Monetary costs were converted into 2013 USD. Results Out of 5187 unique retrievals, 214 studies were included. One hundred eighty-seven studies estimated patient health, 75 studies estimated payer/provider and 11 studies estimated economic burden. 64% of included studies were single centre. The majority of studies estimating patient or provider/payer burden used regression techniques. 48% of studies estimating mortality burden found a significant impact from resistance, excess healthcare system costs ranged from non-significance to $1 billion per year, whilst economic burden ranged from $21,832 per case to over $3 trillion in GDP loss. Median quality scores (interquartile range) for patient, payer/provider and economic burden studies were 0.67 (0.56-0.67), 0.56 (0.46-0.67) and 0.53 (0.44-0.60) respectively. Conclusions This study highlights what methodological assumptions and biases can occur dependent on chosen outcome and perspective. Currently, there is considerable variability in burden estimates, which can lead in-turn to inaccurate intervention evaluations and poor policy/investment decisions. Future research should utilise the recommendations presented in this review. Trial registration This systematic review is registered with PROSPERO (PROSPERO CRD42016037510).
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Affiliation(s)
- Nichola R. Naylor
- National Institute for Health Research Health Protection Research Unit in Healthcare Associated Infection and Antimicrobial Resistance at Imperial College, Hammersmith Campus, London, W12 0NN UK
| | - Rifat Atun
- National Institute for Health Research Health Protection Research Unit in Healthcare Associated Infection and Antimicrobial Resistance at Imperial College, Hammersmith Campus, London, W12 0NN UK
- Harvard University, 665 Huntington Avenue, Boston, MA 02115 USA
| | - Nina Zhu
- National Institute for Health Research Health Protection Research Unit in Healthcare Associated Infection and Antimicrobial Resistance at Imperial College, Hammersmith Campus, London, W12 0NN UK
| | - Kavian Kulasabanathan
- Imperial College London, Sir Alexander Fleming Building, South Kensington Campus, London, UK
| | - Sachin Silva
- Harvard University, 665 Huntington Avenue, Boston, MA 02115 USA
| | - Anuja Chatterjee
- National Institute for Health Research Health Protection Research Unit in Healthcare Associated Infection and Antimicrobial Resistance at Imperial College, Hammersmith Campus, London, W12 0NN UK
| | - Gwenan M. Knight
- National Institute for Health Research Health Protection Research Unit in Healthcare Associated Infection and Antimicrobial Resistance at Imperial College, Hammersmith Campus, London, W12 0NN UK
| | - Julie V. Robotham
- National Institute for Health Research Health Protection Research Unit in Healthcare Associated Infection and Antimicrobial Resistance at Imperial College, Hammersmith Campus, London, W12 0NN UK
- Modelling and Economics Unit, National Infection Service, Public Health England, 61 Colindale Avenue, London, NW9 5EQ UK
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Pathogen Distribution and Antimicrobial Resistance Among Pediatric Healthcare-Associated Infections Reported to the National Healthcare Safety Network, 2011-2014. Infect Control Hosp Epidemiol 2017; 39:1-11. [PMID: 29249216 DOI: 10.1017/ice.2017.236] [Citation(s) in RCA: 91] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
OBJECTIVE To describe pathogen distribution and antimicrobial resistance patterns for healthcare-associated infections (HAIs) reported to the National Healthcare Safety Network (NHSN) from pediatric locations during 2011-2014. METHODS Device-associated infection data were analyzed for central line-associated bloodstream infection (CLABSI), catheter-associated urinary tract infections (CAUTI), ventilator-associated pneumonia (VAP), and surgical site infection (SSI). Pooled mean percentage resistance was calculated for a variety of pathogen-antimicrobial resistance pattern combinations and was stratified by location for device-associated infections (neonatal intensive care units [NICUs], pediatric intensive care units [PICUs], pediatric oncology and pediatric wards) and by surgery type for SSIs. RESULTS From 2011 to 2014, 1,003 hospitals reported 20,390 pediatric HAIs and 22,323 associated pathogens to the NHSN. Among all HAIs, the following pathogens accounted for more than 60% of those reported: Staphylococcus aureus (17%), coagulase-negative staphylococci (17%), Escherichia coli (11%), Klebsiella pneumoniae and/or oxytoca (9%), and Enterococcus faecalis (8%). Among device-associated infections, resistance was generally lower in NICUs than in other locations. For several pathogens, resistance was greater in pediatric wards than in PICUs. The proportion of organisms resistant to carbapenems was low overall but reached approximately 20% for Pseudomonas aeruginosa from CLABSIs and CAUTIs in some locations. Among SSIs, antimicrobial resistance patterns were similar across surgical procedure types for most pathogens. CONCLUSION This report is the first pediatric-specific description of antimicrobial resistance data reported to the NHSN. Reporting of pediatric-specific HAIs and antimicrobial resistance data will help identify priority targets for infection control and antimicrobial stewardship activities in facilities that provide care for children. Infect Control Hosp Epidemiol 2018;39:1-11.
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Dumford DM, Skalweit M. Antibiotic-Resistant Infections and Treatment Challenges in the Immunocompromised Host. Infect Dis Clin North Am 2017; 30:465-489. [PMID: 27208768 DOI: 10.1016/j.idc.2016.02.008] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
This article reviews antibiotic resistance and treatment of bacterial infections in the growing number of patients who are immunocompromised: solid organ transplant recipients, the neutropenic host, and persons with human immunodeficiency virus and AIDS. Specific mechanisms of resistance in both gram-negative and gram-positive bacteria, as well as newer treatment options are addressed elsewhere, and are only briefly discussed in the context of the immunocompromised host.
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Affiliation(s)
- Donald M Dumford
- Akron General Medical Center, 1 Akron General Way, Akron, OH 44302, USA; Northeast Ohio Medical University, 4209 St. Rt. 44, PO Box 95, Rootstown, Ohio 44272, USA.
| | - Marion Skalweit
- Louis Stokes Cleveland Department of Veterans Affairs, 10701 East Blvd 111(W), Cleveland, OH 44106, USA; Case Western Reserve University School of Medicine, 2109 Adelbert Road, Cleveland, OH 44106, USA
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Haeusler GM, Thursky KA, Mechinaud F, Babl FE, De Abreu Lourenco R, Slavin MA, Phillips R. Predicting Infectious ComplicatioNs in Children with Cancer: an external validation study. Br J Cancer 2017; 117:171-178. [PMID: 28609435 PMCID: PMC5520507 DOI: 10.1038/bjc.2017.154] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2016] [Revised: 05/09/2017] [Accepted: 05/11/2017] [Indexed: 12/04/2022] Open
Abstract
BACKGROUND The aim of this study was to validate the 'Predicting Infectious ComplicatioNs in Children with Cancer' (PICNICC) clinical decision rule (CDR) that predicts microbiologically documented infection (MDI) in children with cancer and fever and neutropenia (FN). We also investigated costs associated with current FN management strategies in Australia. METHODS Demographic, episode, outcome and cost data were retrospectively collected on 650 episodes of FN. We assessed the discrimination, calibration, sensitivity and specificity of the PICNICC CDR in our cohort compared with the derivation data set. RESULTS Using the original variable coefficients, the CDR performed poorly. After recalibration the PICNICC CDR had an area under the receiver operating characteristic (AUC-ROC) curve of 0.638 (95% CI 0.590-0.685) and calibration slope of 0.24. The sensitivity, specificity, positive predictive value and negative predictive value of the PICNICC CDR at presentation was 78.4%, 39.8%, 28.6% and 85.7%, respectively. For bacteraemia, the sensitivity improved to 85.2% and AUC-ROC to 0.71. Application at day 2, taking into consideration the proportion of MDI known (43%), further improved the sensitivity to 87.7%. Length of stay is the main contributor to cost of FN treatment, with an average cost per day of AUD 2183 in the low-risk group. CONCLUSIONS For prediction of any MDI, the PICNICC rule did not perform as well at presentation in our cohort as compared with the derivation study. However, for bacteraemia, the predictive ability was similar to that of the derivation study, highlighting the importance of recalibration using local data. Performance also improved after an overnight period of observation. Implementation of a low-risk pathway, using the PICNICC CDR after a short period of inpatient observation, is likely to be safe and has the potential to reduce health-care expenditure.
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Affiliation(s)
- Gabrielle M Haeusler
- The Paediatric Integrated Cancer Service, 50 Flemington Road, Parkville, Victoria 3052, Australia
- Department of Infectious Diseases, Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, Victoria 3000, Australia
- Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria 3010, Australia
- Department of Infection and Immunity, Monash Children’s Hospital, Department of Paediatrics, Monash University, Clayton, Victoria 3168, Australia
| | - Karin A Thursky
- Department of Infectious Diseases, Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, Victoria 3000, Australia
- Department of Medicine, University of Melbourne, Parkville, Victoria 3010, Australia
- NHMRC National Centre for Antimicrobial Stewardship, The Peter Doherty Institute for Infection and Immunity, 792 Elizabeth Street, Melbourne, Victoria 3000, Australia
- Victorian Infectious Diseases Service, The Peter Doherty Institute for Infection and Immunity, 792 Elizabeth Street, Melbourne, Victoria 3000, Australia
| | - Francoise Mechinaud
- Children’s Cancer Centre, Royal Children’s Hospital, 50 Flemington Road, Parkville, Victoria 3052, Australia
| | - Franz E Babl
- Department of Emergency Medicine, Royal Children's Hospital, 50 Flemington Road, Parkville, Victoria 3052, Australia
- Murdoch Children's Research Institute, 50 Flemington Road, Parkville, Victoria 3052, Australia
- Department of Paediatrics, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, Victoria 3010, Australia
| | - Richard De Abreu Lourenco
- Centre for Health Economics Research and Evaluation, University of Technology Sydney, 15 Broadway, Ultimo, New South Wales 2007, Australia
| | - Monica A Slavin
- Department of Infectious Diseases, Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, Victoria 3000, Australia
- Department of Medicine, University of Melbourne, Parkville, Victoria 3010, Australia
- Victorian Infectious Diseases Service, The Peter Doherty Institute for Infection and Immunity, 792 Elizabeth Street, Melbourne, Victoria 3000, Australia
| | - Robert Phillips
- Centre for Reviews and Dissemination, University of York, Heslington, York YO10 5DD, UK
- Leeds Children’s Hospital, Leeds General Infirmary, Great George Street, Leeds LS1 3EX, UK
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Geoghegan S, Erviti A, Caballero MT, Vallone F, Zanone SM, Losada JV, Bianchi A, Acosta PL, Talarico LB, Ferretti A, Grimaldi LA, Sancilio A, Dueñas K, Sastre G, Rodriguez A, Ferrero F, Barboza E, Gago GF, Nocito C, Flamenco E, Perez AR, Rebec B, Ferolla FM, Libster R, Karron RA, Bergel E, Polack FP. Mortality due to Respiratory Syncytial Virus. Burden and Risk Factors. Am J Respir Crit Care Med 2017; 195:96-103. [PMID: 27331632 DOI: 10.1164/rccm.201603-0658oc] [Citation(s) in RCA: 109] [Impact Index Per Article: 13.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023] Open
Abstract
RATIONALE Respiratory syncytial virus (RSV) is the most frequent cause of hospitalization and an important cause of death in infants in the developing world. The relative contribution of social, biologic, and clinical risk factors to RSV mortality in low-income regions is unclear. OBJECTIVES To determine the burden and risk factors for mortality due to RSV in a low-income population of 84,840 infants. METHODS This was a prospective, population-based, cross-sectional, multicenter study conducted between 2011 and 2013. Hospitalizations and deaths due to severe lower respiratory tract illness (LRTI) were recorded during the RSV season. All-cause hospital deaths and community deaths were monitored. Risk factors for respiratory failure (RF) and mortality due to RSV were assessed using a hierarchical, logistic regression model. MEASUREMENTS AND MAIN RESULTS A total of 2,588 (65.5%) infants with severe LRTI were infected with RSV. A total of 157 infants (148 postneonatal) experienced RF or died with RSV. RSV LRTI accounted for 57% fatal LRTI tested for the virus. A diagnosis of sepsis (odds ratio [OR], 17.03; 95% confidence interval [CI], 13.14-21.16 for RF) (OR, 119.39; 95% CI, 50.98-273.34 for death) and pneumothorax (OR, 17.15; 95% CI, 13.07-21.01 for RF) (OR, 65.49; 95% CI, 28.90-139.17 for death) were the main determinants of poor outcomes. CONCLUSIONS RSV was the most frequent cause of mortality in low-income postneonatal infants. RF and death due to RSV LRTI, almost exclusively associated with prematurity and cardiopulmonary diseases in industrialized countries, primarily affect term infants in a developing world environment. Poor outcomes at hospitals are frequent and associated with the cooccurrence of bacterial sepsis and clinically significant pneumothoraxes.
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Affiliation(s)
| | | | | | | | | | - Juan Ves Losada
- 3 Hospital de Alta Complejidad El Cruce "Dr. Néstor Kirchner," Florencio Varela, Argentina
| | | | | | | | | | | | - Andrea Sancilio
- 5 Hospital Interzonal General de Agudos "Evita," Lanús, Argentina
| | - Karina Dueñas
- 5 Hospital Interzonal General de Agudos "Evita," Lanús, Argentina
| | - Gustavo Sastre
- 6 Hospital Zonal General de Agudos Descentralizado "Evita Pueblo," Berazategui, Argentina
| | - Andrea Rodriguez
- 6 Hospital Zonal General de Agudos Descentralizado "Evita Pueblo," Berazategui, Argentina
| | - Fernando Ferrero
- 7 Hospital General de Niños "Pedro de Elizalde," Buenos Aires, Argentina
| | - Edgar Barboza
- 8 Hospital Zonal General de Agudos "Dr. Narciso López," Lanús, Argentina
| | - Guadalupe Fernández Gago
- 9 Institute for Development and Research in Pediatrics "Prof. Dr. Fernando E. Viteri," Children's Hospital of La Plata (Min Sal/CIC-PBA), La Plata, Argentina
| | - Celina Nocito
- 10 Hospital Interzonal General de Agudos "Dr. Pedro Fiorito," Avellaneda, Argentina
| | - Edgardo Flamenco
- 11 Hospital Zonal General de Agudos "Dr. Arturo Oñativia," Rafael Calzada, Argentina
| | | | - Beatriz Rebec
- 13 Hospital Interzonal General de Agudos "Presidente Perón," Avellaneda, Argentina
| | | | | | - Ruth A Karron
- 14 Johns Hopkins University, Baltimore, Maryland; and
| | | | - Fernando P Polack
- 1 Fundación INFANT, Buenos Aires, Argentina.,15 Vanderbilt University, Nashville, Tennessee
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Non-fermentative Gram-negative rods bacteremia in children with cancer: a 14-year single-center experience. Infection 2017; 45:327-334. [DOI: 10.1007/s15010-017-0988-1] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2016] [Accepted: 01/31/2017] [Indexed: 12/21/2022]
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Alp S, Akova M. Antibacterial Resistance in Patients with Hematopoietic Stem Cell Transplantation. Mediterr J Hematol Infect Dis 2017; 9:e2017002. [PMID: 28101308 PMCID: PMC5224809 DOI: 10.4084/mjhid.2017.002] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2016] [Accepted: 11/11/2016] [Indexed: 12/18/2022] Open
Abstract
Recipients of hematopoietic stem cell transplantation (HSCT) are at substantial risk of bacterial, fungal, viral, and parasitic infections depending on the time elapsed since transplantation, presence of graft-versus-host disease (GVHD), and the degree of immunosuppression. Infectious complications in HSCT recipients are associated with high morbidity and mortality. Bacterial infections constitute the major cause of infectious complications, especially in the early post-transplant period. The emergence of antibacterial resistance complicates the management of bacterial infections in this patient group. Multidrug-resistant bacterial infections in this group of patients have attracted considerable interest and may lead to significant morbidity and mortality. Empirical antibacterial therapy in patients with HSCT and febrile neutropenia has a critical role for survival and should be based on local epidemiology. This review attempts to provide an overview of risk factors and epidemiology of emerging resistant bacterial infections and their management in HSCT recipients.
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Affiliation(s)
- Sehnaz Alp
- Associate Professor, Hacettepe University, Faculty of Medicine, Department of Infectious Diseases and Clinical Microbiology, Ankara, Turkey
| | - Murat Akova
- Professor, Hacettepe University, Faculty of Medicine, Department of Infectious Diseases and Clinical Microbiology, Ankara, Turkey
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Forsythe A, Christian R. Effectiveness of prophylactic intravenous immunoglobulins in preventing infection in pediatric oncology patients: a systematic review protocol. JBI DATABASE OF SYSTEMATIC REVIEWS AND IMPLEMENTATION REPORTS 2016; 14:48-55. [PMID: 28009666 DOI: 10.11124/jbisrir-2016-003224] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/31/2022]
Abstract
REVIEW QUESTION/OBJECTIVE The objective of this review is to identify the effectiveness of prophylactic intravenous immunoglobulins (IVIGs) for the prevention of infection in pediatric oncology patients, and to identify which types of patients would benefit from the intervention, such as patients with specific diagnoses or those with previous infections. A further objective of this review is to identify the effectiveness of prophylactic IVIGs on the prevention of diffuse interstitial pneumonitis and mortality in pediatric oncology patients.The review questions are.
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Affiliation(s)
- Amy Forsythe
- 1University of Mississippi Medical Center, Jackson, Mississippi, USA 2UMMC School of Nursing Evidence-based Practice and Research Team: a Joanna Briggs Institute Affiliated Group
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Lee JH, Kim SK, Kim SK, Han SB, Lee JW, Lee DG, Chung NG, Cho B, Jeong DC, Kang JH, Kim HK. Increase in Antibiotic-Resistant Gram-Negative Bacterial Infections in Febrile Neutropenic Children. Infect Chemother 2016; 48:181-189. [PMID: 27659431 PMCID: PMC5047999 DOI: 10.3947/ic.2016.48.3.181] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2016] [Revised: 07/28/2016] [Accepted: 07/29/2016] [Indexed: 11/24/2022] Open
Abstract
BACKGROUND The incidence of bacteremia caused by Gram-negative bacteria has increased recently in febrile neutropenic patients with the increase of antibiotic-resistant Gram-negative bacterial infections. This study aimed to identify the distribution of causative bacteria and the proportion of antibiotic-resistant bacteria in bacteremia diagnosed in febrile neutropenic children. MATERIALS AND METHODS The medical records of febrile neutropenic children diagnosed with bacteremia between 2010 and 2014 were retrospectively reviewed. The causative bacteria and proportion of antibiotic-resistant bacteria were investigated and compared yearly during the study period. The clinical impact of antibiotic-resistant bacterial infections was also determined. RESULTS A total of 336 bacteremia episodes were identified. During the entire study period, 181 (53.9%) and 155 (46.1%) episodes were caused by Gram-negative and Gram-positive bacteria, respectively. Viridans streptococci (25.9%), Klebsiella spp. (16.7%), and Escherichia coli (16.4%) were the most frequent causative bacteria. The overall distribution of causative bacteria was not significantly different annually. Antibiotic-resistant bacteria were identified in 85 (25.3%) episodes, and the proportion of antibiotic-resistant bacteria was not significantly different annually. Extended-spectrum β-lactamase-producing E. coli and Klebsiella spp. were most common among antibiotic-resistant Gram-negative bacteria, and they accounted for 30.6% (n = 34) of the identified E. coli and K. pneumoniae. Methicillin-resistant coagulase-negative staphylococci were most common among antibiotic-resistant Gram-positive bacteria, and it accounted for 88.5% (n = 23) of the identified coagulase-negative staphylococci. Antibiotic-resistant bacterial infections, especially antibiotic-resistant Gram-negative bacterial infections, caused significantly higher mortality due to bacteremia compared with non-antibiotic-resistant bacterial infections (P < 0.001). CONCLUSION Recently, Gram-negative bacteria caused more bacteremia cases than Gram-positive bacteria in febrile neutropenic children, and antibiotic-resistant Gram-negative bacterial infections increased. Antibiotic-resistant bacterial infections caused poorer prognosis compared with non-antibiotic-resistant bacterial infections, and therefore, continuous surveillance for changing epidemiology of antibiotic-resistant bacterial infections and their clinical impact is necessary.
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Affiliation(s)
- Joon Hee Lee
- Department of Pediatrics, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Seul Ki Kim
- Department of Pediatrics, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Seong Koo Kim
- Department of Pediatrics, College of Medicine, The Catholic University of Korea, Seoul, Korea
- The Catholic Blood and Marrow Transplantation Center, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Seung Beom Han
- Department of Pediatrics, College of Medicine, The Catholic University of Korea, Seoul, Korea
- The Vaccine Bio Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Korea.
| | - Jae Wook Lee
- Department of Pediatrics, College of Medicine, The Catholic University of Korea, Seoul, Korea
- The Catholic Blood and Marrow Transplantation Center, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Dong Gun Lee
- The Catholic Blood and Marrow Transplantation Center, College of Medicine, The Catholic University of Korea, Seoul, Korea
- The Vaccine Bio Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Korea
- Division of Infectious Diseases, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Nack Gyun Chung
- Department of Pediatrics, College of Medicine, The Catholic University of Korea, Seoul, Korea
- The Catholic Blood and Marrow Transplantation Center, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Bin Cho
- Department of Pediatrics, College of Medicine, The Catholic University of Korea, Seoul, Korea
- The Catholic Blood and Marrow Transplantation Center, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Dae Chul Jeong
- Department of Pediatrics, College of Medicine, The Catholic University of Korea, Seoul, Korea
- The Vaccine Bio Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Jin Han Kang
- Department of Pediatrics, College of Medicine, The Catholic University of Korea, Seoul, Korea
- The Vaccine Bio Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Hack Ki Kim
- Department of Pediatrics, College of Medicine, The Catholic University of Korea, Seoul, Korea
- The Catholic Blood and Marrow Transplantation Center, College of Medicine, The Catholic University of Korea, Seoul, Korea
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Castagnola E, Ruberto E, Guarino A. Gastrointestinal and liver infections in children undergoing antineoplastic chemotherapy in the years 2000. World J Gastroenterol 2016; 22:5853-5866. [PMID: 27433098 PMCID: PMC4932220 DOI: 10.3748/wjg.v22.i25.5853] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2016] [Revised: 05/27/2016] [Accepted: 06/15/2016] [Indexed: 02/06/2023] Open
Abstract
AIM: To review gastrointestinal and liver infections in children undergoing antineoplastic chemotherapy. To look at gut microflora features in oncology children.
METHODS: We selected studies published after year 2000, excluding trials on transplanted pediatric patients. We searched English language publications in MEDLINE using the keywords: “gastrointestinal infection AND antineoplastic chemotherapy AND children”, “gastrointestinal infection AND oncology AND children”, “liver infection AND antineoplastic chemotherapy AND children”, “liver abscess AND chemotherapy AND child”, “neutropenic enterocolitis AND chemotherapy AND children”, “thyphlitis AND chemotherapy AND children”, “infectious diarrhea AND children AND oncology”, “abdominal pain AND infection AND children AND oncology”, “perianal sepsis AND children AND oncology”, “colonic pseudo-obstruction AND oncology AND child AND chemotherapy”, “microflora AND children AND malignancy”, “microbiota AND children AND malignancy”, “fungal flora AND children AND malignancy”. We also analysed evidence from several articles and book references.
RESULTS: Gastrointestinal and liver infections represent a major cause of morbidity and mortality in children undergoing antineoplastic chemotherapy. Antineoplastic drugs cause immunosuppression in addition to direct toxicity, predisposing to infections, although the specific risk is variable according to disease and host features. Common pathogens potentially induce severe diseases whereas opportunistic microorganisms may attack vulnerable hosts. Clinical manifestations can be subtle and not specific. In addition, several conditions are rare and diagnostic process and treatments are not standardized. Diagnosis may be challenging, however early diagnosis is needed for quick and appropriate interventions. Interestingly, the source of infection in those children can be exogenous or endogenous. Indeed, mucosal damage may allow the penetrance of endogenous microbes towards the bowel wall and their translocation into the bloodstream. However, only limited knowledge of intestinal dysbiosis in oncology children is available.
CONCLUSION: The diagnostic work-up requires a multimodal approach and should be implemented (also by further studies on new biomarkers) for a prompt and individualized therapy.
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Simon A, Furtwängler R, Graf N, Laws HJ, Voigt S, Piening B, Geffers C, Agyeman P, Ammann RA. Surveillance of bloodstream infections in pediatric cancer centers - what have we learned and how do we move on? GMS HYGIENE AND INFECTION CONTROL 2016; 11:Doc11. [PMID: 27274442 PMCID: PMC4886351 DOI: 10.3205/dgkh000271] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Pediatric patients receiving conventional chemotherapy for malignant disease face an increased risk of bloodstream infection (BSI). Since BSI may represent an acute life-threatening event in patients with profound immunosuppression, and show further negative impact on quality of life and anticancer treatment, the prevention of BSI is of paramount importance to improve and guarantee patients' safety during intensive treatment. The great majority of all pediatric cancer patients (about 85%) have a long-term central venous access catheter in use (type Broviac or Port; CVAD). Referring to the current surveillance definitions a significant proportion of all BSI in pediatric patients with febrile neutropenia is categorized as CVAD-associated BSI. This state of the art review summarizes the epidemiology and the distinct pathogen profile of BSI in pediatric cancer patients from the perspective of infection surveillance. Problems in executing the current surveillance definition in this patient population are discussed and a new concept for the surveillance of BSI in pediatric cancer patients is outlined.
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Affiliation(s)
- Arne Simon
- Pädiatrische Onkologie und Hämatologie, Universitätsklinikum des Saarlandes, Homburg, Germany
| | - Rhoikos Furtwängler
- Pädiatrische Onkologie und Hämatologie, Universitätsklinikum des Saarlandes, Homburg, Germany
| | - Norbert Graf
- Pädiatrische Onkologie und Hämatologie, Universitätsklinikum des Saarlandes, Homburg, Germany
| | - Hans Jürgen Laws
- Klinik für Pädiatrische Onkologie, Hämatologie und Immunologie, Universitätskinderklinik, Heinrich-Heine-Universität, Düsseldorf, Germany
| | - Sebastian Voigt
- Klinik für Pädiatrie m. S. Onkologie / Hämatologie / Stammzelltransplantation, Charité – Universitätsmedizin Berlin, Germany
| | - Brar Piening
- Institut für Hygiene und Umweltmedizin, Charité – Universitätsmedizin Berlin, Germany
| | - Christine Geffers
- Institut für Hygiene und Umweltmedizin, Charité – Universitätsmedizin Berlin, Germany
| | - Philipp Agyeman
- Pädiatrische Infektiologie und Pädiatrische Hämatologie-Onkologie, Universitätsklinik für Kinderheilkunde, Inselspital, Bern, Switzerland
| | - Roland A. Ammann
- Pädiatrische Infektiologie und Pädiatrische Hämatologie-Onkologie, Universitätsklinik für Kinderheilkunde, Inselspital, Bern, Switzerland
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Andermann TM, Bhatt AS. Antibiotics in Hematopoietic Cell Transplantation: Adversaries or Allies? Biol Blood Marrow Transplant 2016; 22:972-974. [PMID: 27095689 DOI: 10.1016/j.bbmt.2016.04.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2016] [Accepted: 04/06/2016] [Indexed: 02/02/2023]
Affiliation(s)
- Tessa M Andermann
- Department of Infectious Diseases, Stanford University, Stanford, California
| | - Ami S Bhatt
- Departments of Medicine (Hematology & Blood and Marrow Transplantation) and Genetics, Stanford University, Stanford, California.
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Castagnola E, Caviglia I, Pescetto L, Bagnasco F, Haupt R, Bandettini R. Antibiotic susceptibility of Gram-negatives isolated from bacteremia in children with cancer. Implications for empirical therapy of febrile neutropenia. Future Microbiol 2016; 10:357-64. [PMID: 25812459 DOI: 10.2217/fmb.14.144] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
BACKGROUND Monotherapy is recommended as the first choice for initial empirical therapy of febrile neutropenia, but local epidemiological and antibiotic susceptibility data are now considered pivotal to design a correct management strategy. AIM To evaluate the proportion of Gram-negative rods isolated in bloodstream infections in children with cancer resistant to antibiotics recommended for this indication. MATERIALS & METHODS The in vitro susceptibility to ceftazidime, piperacillin-tazobactam, meropenem and amikacin of Gram-negatives isolated in bacteremic episodes in children with cancer followed at the Istituto "Giannina Gaslini", Genoa, Italy in the period of 2001-2013 was retrospectively analyzed using the definitions recommended by EUCAST in 2014. Data were analyzed for any single drug and to the combination of amikacin with each β-lactam. The combination was considered effective in absence of concomitant resistance to both drugs, and not evaluated by means of in vitro analysis of antibiotic combinations (e.g., checkerboard). RESULTS A total of 263 strains were evaluated: 27% were resistant to piperacillin-tazobactam, 23% to ceftazidime, 12% to meropenem and 13% to amikacin. Concomitant resistance to β-lactam and amikacin was detected in 6% of strains for piperacillin-tazobactam, 5% for ceftazidime and 5% for meropenem. During the study period there was a nonsignificant increase in the proportions of strains resistant to β-lactams indicated for monotherapy, and also increase in the resistance to combined therapies. CONCLUSION in an era of increasing resistance to antibiotics guideline-recommended monotherapy could be not appropriate for initial empirical therapy of febrile neutropenia. Strict local survey on etiology and antibiotic susceptibility is mandatory for a correct management of this complication in cancer patients.
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Affiliation(s)
- Elio Castagnola
- Infectious Diseases Unit, Istituto Giannina Gaslini, Genoa, Italy
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Management of fever and neutropenia in paediatric cancer patients: room for improvement? Curr Opin Infect Dis 2015; 28:532-8. [PMID: 26381997 DOI: 10.1097/qco.0000000000000208] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
PURPOSE OF REVIEW Fever and neutropenia is the most common complication in the treatment of childhood cancer. This review will summarize recent publications that focus on improving the management of this condition as well as those that seek to optimize translational research efforts. RECENT FINDINGS A number of clinical decision rules are available to assist in the identification of low-risk fever and neutropenia however few have undergone external validation and formal impact analysis. Emerging evidence suggests acute fever and neutropenia management strategies should include time to antibiotic recommendations, and quality improvement initiatives have focused on eliminating barriers to early antibiotic administration. Despite reported increases in antimicrobial resistance, few studies have focused on the prediction, prevention, and optimal treatment of these infections and the effect on risk stratification remains unknown. A consensus guideline for paediatric fever and neutropenia research is now available and may help reduce some of the heterogeneity between studies that have previously limited the translation of evidence into clinical practice. SUMMARY Risk stratification is recommended for children with cancer and fever and neutropenia. Further research is required to quantify the overall impact of this approach and to refine exactly which children will benefit from early antibiotic administration as well as modifications to empiric regimens to cover antibiotic-resistant organisms.
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Ivády B, Kenesei É, Tóth-Heyn P, Kertész G, Tárkányi K, Kassa C, Ujhelyi E, Mikos B, Sápi E, Varga-Heier K, Guóth G, Szabó D. Factors influencing antimicrobial resistance and outcome of Gram-negative bloodstream infections in children. Infection 2015; 44:309-21. [DOI: 10.1007/s15010-015-0857-8] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2015] [Accepted: 10/17/2015] [Indexed: 11/29/2022]
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Caselli D, Cesaro S, Fagioli F, Carraro F, Ziino O, Zanazzo G, Meazza C, Colombini A, Castagnola E. Incidence of colonization and bloodstream infection with carbapenem-resistant Enterobacteriaceae in children receiving antineoplastic chemotherapy in Italy. Infect Dis (Lond) 2015; 48:152-5. [PMID: 26393496 DOI: 10.3109/23744235.2015.1087647] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/30/2023] Open
Abstract
Few data are available on the incidence of carbapenemase-producing Enterobacteriaceae (CPE) infection or colonization in children receiving anticancer chemotherapy. We performed a nationwide survey among centers participating in the pediatric hematology-oncology cooperative study group (Associazione Italiana Ematologia Oncologia Pediatrica, AIEOP). During a 2-year observation period, we observed a threefold increase in the colonization rate, and a fourfold increase of bloodstream infection episodes, caused by CPE, with a 90-day mortality of 14%. This first nationwide Italian pediatric survey shows that the circulation of CPE strains in the pediatric hematology-oncology environment is increasing. Given the mortality rate, which is higher than for other bacterial strains, specific monitoring should be applied and the results should have implications for health-care practice in pediatric hematology-oncology.
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Affiliation(s)
- Desiree Caselli
- a Azienda Ospedaliera Universitaria Meyer Children Hospital , Firenze
| | - Simone Cesaro
- b Pediatric Hematology Oncology, Azienda Ospedaliera Universitaria Integrata , Verona
| | - Franca Fagioli
- c Pediatric Onco-Hematology, Stem Cell Transplantation and Cellular Therapy Division, Regina Margherita Children's Hospital , Torino
| | - Francesca Carraro
- c Pediatric Onco-Hematology, Stem Cell Transplantation and Cellular Therapy Division, Regina Margherita Children's Hospital , Torino
| | - Ottavio Ziino
- d Pediatric Hematology Oncology, ARNAS Civico , Palermo
| | | | - Cristina Meazza
- f Pediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale Tumori , Milano
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Trubiano JA, Worth LJ, Thursky KA, Slavin MA. The prevention and management of infections due to multidrug resistant organisms in haematology patients. Br J Clin Pharmacol 2015; 79:195-207. [PMID: 24341410 DOI: 10.1111/bcp.12310] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2013] [Accepted: 12/09/2013] [Indexed: 12/15/2022] Open
Abstract
Infections due to resistant and multidrug resistant (MDR) organisms in haematology patients and haematopoietic stem cell transplant recipients are an increasingly complex problem of global concern. We outline the burden of illness and epidemiology of resistant organisms such as gram-negative pathogens, vancomycin-resistant Enterococcus faecium (VRE), and Clostridium difficile in haematology cohorts. Intervention strategies aimed at reducing the impact of these organisms are reviewed: infection prevention programmes, screening and fluoroquinolone prophylaxis. The role of newer therapies (e.g. linezolid, daptomycin and tigecycline) for treatment of resistant and MDR organisms in haematology populations is evaluated, in addition to the mobilization of older agents (e.g. colistin, pristinamycin and fosfomycin) and the potential benefit of combination regimens.
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Affiliation(s)
- Jason A Trubiano
- Department of Infectious Diseases, Peter MacCallum Cancer Centre, East Melbourne, VIC
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Costa PDO, Atta EH, Silva ARAD. Infection with multidrug-resistant gram-negative bacteria in a pediatric oncology intensive care unit: risk factors and outcomes. J Pediatr (Rio J) 2015; 91:435-41. [PMID: 26057184 DOI: 10.1016/j.jped.2014.11.009] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2014] [Revised: 11/05/2014] [Accepted: 11/12/2014] [Indexed: 12/25/2022] Open
Abstract
OBJECTIVE This study aimed at evaluating the predictors and outcomes associated with multidrug-resistant gram-negative bacterial (MDR-GNB) infections in an oncology pediatric intensive care unit (PICU). METHODS Data were collected relating to all episodes of GNB infection that occurred in a PICU between January of 2009 and December of 2012. GNB infections were divided into two groups for comparison: (1) infections attributed to MDR-GNB and (2) infections attributed to non-MDR-GNB. Variables of interest included age, gender, presence of solid tumor or hematologic disease, cancer status, central venous catheter use, previous Pseudomonas aeruginosa infection, healthcare-associated infection, neutropenia in the preceding 7 days, duration of neutropenia, length of hospital stay before ICU admission, length of ICU stay, and the use of any of the following in the previous 30 days: antimicrobial agents, corticosteroids, chemotherapy, or radiation therapy. Other variables included initial appropriate antimicrobial treatment, definitive inadequate antimicrobial treatment, duration of appropriate antibiotic use, time to initiate adequate antibiotic therapy, and the 7- and 30-day mortality. RESULTS Multivariate logistic regression analyses showed significant relationships between MDR-GNB and hematologic diseases (odds ratio [OR] 5.262; 95% confidence interval [95% CI] 1.282-21.594; p=0.021) and healthcare-associated infection (OR 18.360; 95% CI 1.778-189.560; p=0.015). There were significant differences between MDR-GNB and non-MDR-GNB patients for the following variables: inadequate initial empirical antibiotic therapy, time to initiate adequate antibiotic treatment, and inappropriate antibiotic therapy. CONCLUSIONS Hematologic malignancy and healthcare-associated infection were significantly associated with MDR-GNB infection in this sample of pediatric oncology patients.
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Affiliation(s)
- Patrícia de Oliveira Costa
- Center of Hematopoietic Stem Cell Transplantation, Instituto Nacional do Câncer (INCA), Rio de Janeiro, RJ, Brazil.
| | - Elias Hallack Atta
- Center of Hematopoietic Stem Cell Transplantation, Instituto Nacional do Câncer (INCA), Rio de Janeiro, RJ, Brazil
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