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Background:Klebsiella pneumoniae is a nosocomial pathogen that causes severe infections in immunocompromised patients. The aim of the study was to conduct a microbiological and clinical analysis of K. pneumoniae infections in children with malignancies or undergoing hematopoietic cell transplantation in Poland. Methods: We conducted a retrospective, multicenter study including children and adolescents under 19 years old treated between 2012 and 2021. We analyzed patients' characteristics, microbiological data, and the outcomes of antibiotic therapy. Results: A total of 9121 newly diagnosed children were treated for malignancy and 1697 pediatric patients underwent hematopoietic cell transplantation. K. pneumoniae infections were diagnosed in 527 patients. Their overall incidence was 4.86% in pediatric hematology and oncology patients and 4.95% in patients who underwent hematopoietic cell transplantation. The incidence of infection was higher in patients with acute leukemia than with solid tumors (7.8% vs. 4.1%; OR = 2.0; 95% CI = 1.6-2.4; p < 0.0001). The most frequent source of infection was in the urinary tract at 55.2%. More than 57% of K. pneumoniae strains were extended-spectrum ß-lactamase-positive and almost 34% were multidrug-resistant. Infections with K. pneumoniae contributed to death in 3.22% of patients. Conclusions: K. pneumoniae is one of the most critical pathogens in children suffering from malignancies or undergoing hematopoietic cell transplantation. The incidence of multidrug-resistant K. pneumoniae strains is increasing and contributing to poor clinical outcome.
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A retrospective observational study was conducted among healthcare workers (HCWs) in a tertiary paediatric hospital. The study covered the period before and after implementation of the vaccination programme and evaluated the incidence of new SARS-CoV-2 infections in both periods. Risk factors of the new SARS-CoV-2 infection and COVID-19 vaccine effectiveness was also assessed in a real-world setting. The overall incidence of SARS-CoV-2 infections among HCWs in the study period was 19.4% with a high proportion of asymptomatic individuals (45.1%). The incidence before vaccination was 16.6% and nurses had a higher risk of infection, while physicians had a reduced risk (OR 1.80, 95% CI 1.29-2.52; and OR 0.45, 95% CI 0.30-0.68). Within two months of implementation, the programme achieved a high (88.9%) vaccination coverage in our cohort, although some disparities in vaccination rates were observed. In particular, older individuals, physicians, those working in clinical settings, and those previously uninfected were more likely to be vaccinated. The overall incidence of SARS-CoV-2 infection after vaccination deployment was 6.4% (40.0% in unvaccinated individuals and 3.2% in individuals vaccinated with at least one dose). The estimated vaccine efficacy was high (95.0%) in fully vaccinated HCWs and similar to those observed previously in clinical trials and real-world settings.
Subject(s)
COVID-19 Vaccines , COVID-19 , Health Personnel , Hospitals, Pediatric , SARS-CoV-2 , Tertiary Care Centers , Vaccination , Humans , COVID-19/epidemiology , COVID-19/prevention & control , Retrospective Studies , Female , Male , Incidence , Health Personnel/statistics & numerical data , Hospitals, Pediatric/statistics & numerical data , Adult , COVID-19 Vaccines/administration & dosage , SARS-CoV-2/immunology , Vaccination/statistics & numerical data , Middle Aged , Risk FactorsABSTRACT
Since the discovery of antibiotics in the early 20th century, significant changes have occurred in their usage principles [...].
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BACKGROUND: Pentraxins are inflammatory proteins and markers of acute-phase responses. They are divided into short and long subgroups based on the length of the N-terminal region. The most studied short pentraxin is the C-reactive protein (CRP), which is known to be expressed in various inflammatory conditions, including surgical procedures. On the other hand, much less is known about the kinetics of long pentraxin 3 (PTX3) in surgical patients, especially in the pediatric population. The aim of this prospective study was to determine the early postoperative kinetics of PTX3 in relation to procalcitonin (PCT) and CRP levels in children undergoing congenital heart surgery with cardiopulmonary bypass (CPB). METHODS: A total of 21 children (9 boys and 12 girls, mean age 12 months) were included in the study. Blood samples for determination of CRP, PCT, and PTX3 levels were collected before the surgery and then immediately after its completion (postoperative day 0, POD 0) and subsequently at POD 1, 2, and 3. RESULTS: Serum PTX3 concentrations increased significantly between POD 0 and POD 1 (mean values were 12.2 and 72.4 ng/ml, respectively, p<0.001), decreased between POD 1 and POD 2 (mean values were 72.4 and 23.6 ng/ml, respectively, p<0.001), and normalized on POD 3 (the mean value was 1.2 ng/ml). CONCLUSIONS: PTX3 concentrations are markedly elevated during the first postoperative day. Under normal circumstances, PTX3 rises and falls quickly, and its second rise in the early postoperative period may be abnormal, however, further studies are necessary.
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Pediatric cardiac surgery requires perioperative antibiotic prophylaxis (PAP) to reduce the risk of surgical site infections. However, the complexity of these procedures and the metabolic immaturity of children impede the establishment of PAP regimens that are both efficacious and in line with antimicrobial stewardship (AMS). In this study, we compared two PAP regimens: cefazolin with gentamicin (in a retrospective group) and cefazolin only (prospectively) in children undergoing elective cardiac surgery. In the prospective group, additional elements of AMS were introduced, i.e., restricted access to cefazolin and more diligent use of empirical antibiotics proceeded by consultation with an AMS team. The rate of surgical site infections (SSI), the scope of PAP deviations, and the postoperative use of antibiotics other than PAP within 30 days after surgery were analyzed. There were no significant differences in the rate of SSIs between the groups (3.9% vs. 1.2% in the prospective and retrospective groups, respectively (p = 0.35)). However, in the prospective group, the PAP violation was significantly reduced compared with the retrospective group (full compliance with the PAP regimen was 45.5% vs. 4.8%, p < 0.001, respectively). In addition, a reduction of postoperative antibiotic use was observed in the prospective group (0.991 vs. 1.932 defined daily doses, respectively).
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OBJECTIVES: To determine the recommended concentrations of cefazolin to be used for antibiotic prophylaxis during paediatric cardiac surgery with extracorporeal circulation (ECC). METHODS: Twenty paediatric patients undergoing cardiac surgery with ECC and cefazolin antibiotic prophylaxis were included in the study. Blood samples for measurement of total cefazolin plasma concentration were collected at the following measurement time points: directly after skin incision, 15 min after ECC start, 5 min after ECC cessation and at skin closure. The target concentration was set for ≥40 mg/l, which corresponded to ≥8 mg/l of unbound cefazolin concentration. RESULTS: The median total cefazolin plasma concentrations at the measurement time points were 62.8, 67.7, 45.8 and 34.2 mg/l, respectively, and target concentrations were achieved in 90%, 85%, 65% and 40% of children, respectively. Among patients who received ≥30 mg of cefazolin per 100 ml of ECC priming, target concentrations after ECC cessation were reached in 80% of patients, while in those with <30 mg cefazolin per 100 ml in 20% of patients (P = 0.031). CONCLUSIONS: Direct extrapolation of antibiotic prophylaxis recommendations from adults to children may result in suboptimal antibiotic concentrations. An additional cefazolin dose to ECC priming appears necessary and the dosing should be based on ECC priming volume rather than on the weight of the patient.
Subject(s)
Cardiac Surgical Procedures , Cefazolin , Adult , Anti-Bacterial Agents/therapeutic use , Antibiotic Prophylaxis , Cardiac Surgical Procedures/adverse effects , Cardiopulmonary Bypass/adverse effects , Cefazolin/therapeutic use , Child , Humans , Surgical Wound Infection/prevention & controlABSTRACT
Data on the prevalence of the SARS-CoV-2 antibody in healthcare workers (HCWs) is scarce, especially in pediatric settings. The purpose of this study was to evaluate SARS-CoV-2 IgG-positivity among HCWs of a tertiary pediatric hospital. In addition, follow-up of the serological response in the subgroup of seropositive HCWs was analysed, to gain some insight on the persistence of IgG antibodies to SARS-CoV-2. We performed a retrospective analysis of voluntary SARS-CoV-2 IgG testing, which was made available free of charge to HCWs of the Children's Memorial Health Institute in Warsaw (Poland). Plasma samples were collected between July 1 and August 9, 2020, and tested using the Abbott SARS-CoV-2 IgG assay. Of 2,282 eligible participants, 1,879 (82.3%) HCWs volunteered to undergo testing. Sixteen HCWs tested positive for SARS-CoV-2 IgG, corresponding to a seroprevalence of 0.85%. Among seropositive HCWs, three HCWs had confirmed COVID-19. Nine (56.3%) of the seropositive HCWs reported neither symptoms nor unprotected contact with confirmed SARS-CoV-2 cases in the previous months. A decline in the IgG index was observed at a median time of 86.5 days (range:84â128 days) after symptom onset or RT-PCR testing. Further studies are necessary to elucidate the duration of persistence of anti-SARS-CoV-2 antibodies, as well as the correlation between seropositivity and protective immunity against reinfection. Regardless of the persistence of antibodies and their protective properties, such low prevalence indicates that this population is vulnerable to a second wave of the COVID-19 pandemic.
Subject(s)
Antibodies, Viral/blood , COVID-19 , Health Personnel/statistics & numerical data , Immunoglobulin G/blood , SARS-CoV-2/immunology , Adult , COVID-19/epidemiology , COVID-19/immunology , Female , Hospitals, Pediatric/statistics & numerical data , Humans , Male , Middle Aged , Pandemics , Poland , Prevalence , Retrospective Studies , Seroepidemiologic Studies , Tertiary Care Centers/statistics & numerical dataABSTRACT
BACKGROUND: There are limited data on factors that determine viral load (VL) in congenital cytomegalovirus (cCMV) infection. Single nucleotide polymorphisms (SNPs) might influence individual host response to infection. This study aimed to investigate the association between SNPs in genes encoding cytokines or cytokine receptors and VL in newborns with cCMV. MATERIAL AND METHODS: Eight polymorphisms (IL1B rs16944, IL12B rs3212227, IL28B rs12979860, CCL2 rs1024611, DC-SIGN rs735240, TLR2 rs5743708, TLR4 rs4986791 and TLR9 rs352140) were analyzed in study population of 233 newborns, including 92 cCMV-infected newborns (73 symptomatic and 19 asymptomatic) by TaqMan SNP Predesigned Genotyping Assays. The association analysis was performed using SNPStats software and STATISTICA10. RESULTS: The association between IL12B polymorphism and viruria was observed (p = 0.029). In multiple comparison tests, heterozygous T/G genotype of IL12B was associated with higher viruria than T/T genotype (p = 0.041) in cCMV-infected newborns. In allele analysis, T allele of IL12B was associated with higher viremia (p = 0.037) in symptomatic newborns. We observed higher VL in symptomatic newborns in comparison to asymptomatic (median viremia: 1.7 × 104 copies/mL vs. 2.0 × 103 copies/mL (p = 0.002), median viruria: 1.0 × 107 copies/mL versus 6.9 × 105 copies/mL (p = 0.001), respectively). CONCLUSIONS: IL12B rs3212227 was associated with VL in cCMV. Symptomatic newborns had significantly higher viremia and viruria. The role of SNPs in pathogenesis of cCMV warrants further investigations.
Subject(s)
Cytomegalovirus Infections , Polymorphism, Single Nucleotide , Viral Load , Cytomegalovirus Infections/congenital , Cytomegalovirus Infections/genetics , Genotype , Humans , Infant, Newborn , Viremia/congenital , Viremia/geneticsABSTRACT
Background: Infectious complications (IC) caused by bacterial strains often impede anticancer therapy. The study aimed to retrospectively analyze bacterial IC that could help predict the risk and optimize the empirical treatment for bacterial infections in pediatric cancer patients. Patients and Methods: Over a 72-month period, all-in 5,599 children with cancer: 2,441 patients with hematological malignancy (HM including acute leukemias, Hodgkin and non-Hodgkin lymphomas [NHLs], and Langerhans cell histiocytosis) and 3,158 with solid tumors (STs including central nervous system tumors, neuroblastoma, Wilms' tumor, soft tissue sarcoma, germ cell tumors, Ewing sarcoma, osteosarcoma, hepatoblastoma, and others) were enrolled into the study. Episodes of bacterial infectious complications (EBICs) confirmed by microbiological findings were reported by each hospital and analyzed centrally. Results: At least 1 EBIC was diagnosed in 2,155 (36.8%) children (1,281 [59.4%] with HM and 874 [40.6%] with ST; p < 0.001). All-in 4,860 EBICs were diagnosed including 62.2% episodes in children with HM and 37.8% in children with ST (p < 0.001). Having analyzed the source of infections, blood stream infections predominated, apart from NHL patients in whom the most common type was gut infections. The profile of bacteria strains was different in HM and ST groups (p < 0.001). However, in both groups the most common Gram-negative pathogen was Enterobacteriaceae, with the rate being higher in the HM group. Among Gram-negative strains low susceptibility to ceftazidime, whereas among Enterococcus spp. low susceptibility to vancomycin was noticed. The rate of multidrug-resistant (MDR) pathogens was high, especially for Gram negatives (47.7% vs. 23.9%; p < 0.001). The survival after infections was comparable for HM and ST patients (p = 0.215). Conclusions: The risk of bacterial IC in HM patients was higher than in the ST group. The high rate of MDR strains was detected in pediatric cancer patients, especially in those with HM.
Subject(s)
Anti-Bacterial Agents/pharmacology , Bacterial Infections/etiology , Bacterial Infections/microbiology , Neoplasms/complications , Adolescent , Anti-Bacterial Agents/therapeutic use , Bacterial Infections/drug therapy , Child , Child, Preschool , Drug Resistance, Multiple, Bacterial/drug effects , Female , Humans , Infant , Male , Neoplasms/pathology , Poland/epidemiology , Retrospective Studies , Young AdultABSTRACT
Human cytomegalovirus (CMV) is a major cause of morbidity in fetuses following intrauterine infection. The glycoprotein (g) envelope trimeric gH/gL/gO and pentameric gH/gL/pUL128/pUL130/pUL131A complexes are required for CMV entry into fibroblasts and endothelial/epithelial cells, respectively, and both are targets for neutralizing antibodies. The role of sequence variability among viral strains in the outcome of congenital CMV infection is controversial. Variation in the CMV UL75 gene encoding glycoprotein H (gH), the UL115 (gL), the UL74 (gO), and the UL128 locus (UL128L) encoding three structural proteins (pUL128, pUL130, and pUL131A) was determined in 82 newborns with congenital CMV infection and 113 infants with postnatal or unproven congenital CMV infection. Genotyping was performed by sequencing analysis of PCR-amplified fragments and the PCR-restriction fragment length polymorphism (RFLP) method, and the viral load was measured by quantitative real-time PCR. The obtained results demonstrated that (1) different CMV variants and mixed CMV infections can be detected in newborns infected congenitally; (2) the gH1 genotype, UL130 variant 6, and UL131A variant 1 were associated with some signs/symptoms within cohort of pediatric patients, mainly consisting of infants with symptomatic CMV infection. The results revealed that pUL130, pUL131A, and gH polymorphisms seemed to be associated with the outcome of CMV infection in infants.
Subject(s)
Cytomegalovirus Infections/virology , Cytomegalovirus/genetics , Membrane Glycoproteins/genetics , Mutation , Viral Load/genetics , Viral Proteins/genetics , Antibodies, Neutralizing/immunology , Cytomegalovirus/classification , Cytomegalovirus Infections/congenital , Cytomegalovirus Infections/genetics , Cytomegalovirus Infections/pathology , Epithelial Cells/metabolism , Epithelial Cells/virology , Female , Fibroblasts/metabolism , Fibroblasts/virology , Genotype , Humans , Infant , Infant, Newborn , Male , Viral Envelope Proteins/genetics , Virus InternalizationABSTRACT
The aim of this nationwide study was to describe the epidemiology and profile of bacterial infections (BI), invasive fungal disease (IFD) and viral infections (VI) in patients with de novo and relapsed/refractory (rel/ref) acute myeloid leukemia (AML). Within the studied group of 250 children with primary AML, at least one infectious complication (IC) was diagnosed in 76.0% (n = 190) children including 85.1% (n = 504) episodes of BI, 8.3% (n = 49) - IFD and 6.6% (n = 39) - VI. Among 61 patients with rel/ref AML, at least one IC was found in 67.2% (n = 41) of children including 78.8% (n = 78) of BI, 14.1% (n = 14) of IFD and 7.1% (n = 7) of VI. In all AML patients, within BI Gram-negative strains were predominant. Half of these strains were multi-drug resistant. Characteristics of IFD and VI were comparable for de novo and rel/ref AML. The infection-related mortality was significantly higher, while survival from infection was significantly lower in patients with rel/ref disease.
Subject(s)
Infections/etiology , Infections/mortality , Leukemia, Myeloid, Acute/complications , Leukemia, Myeloid, Acute/mortality , Adolescent , Child , Child, Preschool , Disease Management , Disease Susceptibility , Drug Resistance, Microbial , Drug Resistance, Neoplasm , Female , Humans , Incidence , Infant , Infections/diagnosis , Infections/drug therapy , Leukemia, Myeloid, Acute/pathology , Leukemia, Myeloid, Acute/therapy , Male , Mortality , RecurrenceABSTRACT
INTRODUCTION: Since the first report of vancomycin-resistant enterococci (VRE) in Poland, in 1996, these strains have spread in Polish hospitals, mainly due to selective pressure associated with increased use of vancomycin in the treatment of infections caused by methicillin-resistant staphylococci and Clostridium difficile. At the beginning of 2016 a growing number of patients colonized with VRE in the gastrointestinal tract was observed in the Children's Memorial Health Institute (IPCZD). Some of these patients were transferred from other hospitals, and VRE colonization was found on admission. AIM: To analyze genetic similarity of VRE strains isolated from patients hospitalized in IPCZD and two other hospitals in Mazovian district, genetic typing by pulsed field gel electrophoresis (PFGE) was performed. MATERIALS AND METHODS: VRE strains were isolated from rectal swabs, and other clinical samples such as blood, cerebrospinal fluid, other body fluids, and environmental samples. A total of 56 VRE strains from IPCZD, 20 strains from Siedlce and 4 strains from patients from Grochowski Hospital in Warsaw were typed by PFGE. RESULTS: PFGE typing revealed 4 VRE clones containing several strains with identical restriction patterns. Among VRE strains isolated from neonates hospitalized in IPCZD, two clones with 24 and 20 identical strains were found. Respectively, 16 (67%) and 12 (60%) isolates were originated from rectal swabs from patients at admission to the hospital. Clonal strains were identified in all three hospitals included in the study. CONCLUSIONS: Our results showed that VRE strains had spread in the region. Isolation of clonal strains on admission to the hospital suggested independent VRE introductions from environment or other hospitals. Identification of clonal strains obtained from rectal swabs and other clinical samples during hospitalization indicated horizontal transmission.
Subject(s)
Enterococcus faecium/isolation & purification , Gram-Positive Bacterial Infections/diagnosis , Hospitals , Vancomycin-Resistant Enterococci/isolation & purification , Electrophoresis, Gel, Pulsed-Field , Humans , Infant, Newborn , Molecular Typing , PolandABSTRACT
Background: Prophylactic antibiotic therapy is given routinely in the peri-operative period to prevent surgical site infection. However, in pediatric cardiac surgery, an optimal schedule has not been defined. Pediatric recommendations follow the guidelines for adults, which might be improper because of the inherent challenges in pediatric research and the heterogeneity of the population. Implementation of an effective prophylaxis protocol is needed for children undergoing cardiac surgery, especially in view of worldwide antibiotic overuse and the development of drug resistance. In this review, we analyze the current knowledge supported by up-to-date publications about antibiotic prophylaxis in pediatric cardiac surgery. Methods: The PubMed® database was searched for full-text journal articles describing peri-operative antibiotic prophylaxis in pediatric cardiac surgery published since 2000. Antibiotics used for standard prophylaxis with dosing schema, time of the first dose, additional dosage in extracorporeal circulation (ECC) priming, and prophylaxis duration were analyzed. Additionally, we looked for special clinical situations such as antibiotic prophylaxis in children with the sternum left open after surgery and patients with ß-lactam allergy or pre-operative methicillin-resistant Staphylococcus aureus (MRSA) colonization or those requiring extracorporeal membrane oxygenation (ECMO). Results: A total of 1,546 articles were evaluated, and we identified 20 for further analysis. On the basis of the current peri-operative antibiotic prophylaxis recommendations for cardiac surgery and the papers reviewed, we tried to propose a schedule for peri-operative antibiotic prophylaxis in pediatric cardiac surgery. Conclusions: There is a need for careful use and examination of the schedule proposed because the pharmacokinetics of antibiotics in pediatric patients with ECC is not fully understood. This should be evaluated further. Formulating uniform recommendations concerning peri-operative antibiotic prophylaxis is difficult.
Subject(s)
Anti-Bacterial Agents/administration & dosage , Antibiotic Prophylaxis/methods , Perioperative Care/methods , Surgical Wound Infection/prevention & control , Thoracic Surgery/methods , Thoracic Surgical Procedures/adverse effects , Hospitals, Pediatric , HumansABSTRACT
OBJECTIVES: Escherichia coli is one of the major causative agents of nosocomial infections. Here we report the first draft genome sequence of an E. coli strain (no. 158) isolated in Poland carrying blaCTX-M-15, blaCMY-42, blaOXA-1, aac(3)-IIa and aac(6')-Ib-cr genes together with mutations in the gyrA and parC genes. METHODS: Total DNA was sequenced using an Illumina NextSeq 500 platform. The draft genome of E. coli strain 158 was assembled using SPAdes 3.9 assembler. Contigs were annotated using the Prokka v.1.12 algorithm. Species confirmation, multilocus sequence typing (MLST), serotyping, molecular virulence and resistance traits, and plasmid replicons were analysed using appropriate bioinformatics tools available at the Centre for Genomic Epidemiology website. Additional in silico analyses were also conducted. RESULT: The genome size was estimated at 4883487bp, with 4601 predicted coding sequences. The presence of blaCTX-M-15, blaCMY-42, blaOXA-1, aac(3)-IIa and aac(6')-Ib-cr genes was detected in addition to other antimicrobial resistance genes as well as mutations in the gyrA (Ser83Leu and Asp87Asn) and parC (Ser80Ile) genes. The investigated strain E. coli 158 belongs to ST410. CONCLUSION: To our knowledge, this is the first draft genome of an E. coli strain co-harbouring blaCTX-M-15, blaCMY-42, blaOXA-1, aac(3)-IIa and aac(6')-Ib-cr genes with mutations in gyrA and parC reported in Poland. The reported genome sequence contains valuable information on genetic features of antimicrobial resistance mechanisms of E. coli in Poland.
Subject(s)
DNA Gyrase/genetics , DNA Topoisomerase IV/genetics , Drug Resistance, Multiple, Bacterial , Escherichia coli/genetics , Genome, Bacterial , beta-Lactamases/genetics , Anti-Bacterial Agents/pharmacology , Child , Cross Infection/microbiology , Escherichia coli/drug effects , Escherichia coli Infections/microbiology , Humans , Microbial Sensitivity Tests , Mutation , Poland , Whole Genome SequencingABSTRACT
The objective of this nation-wide study was to evaluate the epidemiology and profile of bacterial (BI), viral (VI), and invasive fungal disease (IFD) in patients treated for non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL) between the years 2013-2015. In the analyzed period of time, within the studied group of 328 children diagnosed and treated for lymphomas, at least one infectious complication (IC) was diagnosed i.e. 39.3% children. In these patients there were 350 episodes of IC, therein 80.6% episodes of BI, 11.1% episodes of VI, and 8.3% episodes of IFD. In both groups, NHL and HL patients, a stable level of bacterial infections, with an increase in resistance rates, and increased levels of viral and fungal infections were observed. Profile of BI does not depend on lymphoma type, with predominance of Gram-negative bacteria and higher prevalence of MDR pathogens. The overall survival of lymphoma patients with IC was comparable for different types of infections.
Subject(s)
Bacterial Infections/epidemiology , Hodgkin Disease/therapy , Invasive Fungal Infections/epidemiology , Lymphoma, Non-Hodgkin/therapy , Virus Diseases/epidemiology , Adolescent , Antibiotic Prophylaxis/methods , Bacterial Infections/microbiology , Bacterial Infections/prevention & control , Child , Child, Preschool , Drug Resistance, Multiple, Bacterial , Female , Hodgkin Disease/immunology , Hodgkin Disease/mortality , Humans , Incidence , Infant , Invasive Fungal Infections/microbiology , Invasive Fungal Infections/prevention & control , Kaplan-Meier Estimate , Lymphoma, Non-Hodgkin/immunology , Lymphoma, Non-Hodgkin/mortality , Male , Poland/epidemiology , Prevalence , Risk Factors , Virus Diseases/prevention & control , Virus Diseases/virologyABSTRACT
The original version of the article, "Circulating T Cells of Patients with Nijmegen Breakage Syndrome Show Signs of Senescence" incorrectly listed the affiliation of the fourth author, Iwona Solarska. The correct affiliation is "Molecular Biology Laboratory, Institute of Hematology and Transfusion Medicine.
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PURPOSE: We aimed to measure the underdiagnosis of Clostridium difficile infection across Poland and the distribution of PCR-ribotypes of C. difficile. MATERIAL AND METHODS: Twenty seven Polish healthcare facilities (HCFs) participated in this prospective study. Each HCF systematically sent all diarrhoeal stools received from inpatients at their laboratories on two days (one in January 2013 and one in July 2013), independently of CDI test request, to the National Coordinating Laboratory (NCL) for standardized testing of CDI. Positive samples (using two-stage algorithm), had CDI, confirmed by qPCR and toxigenic culture. C. difficile isolates were characterized by PCR-ribotyping. Hospitals were questioned about their methods and testing policy for CDI during the study period: September 2011 to August 2013. RESULTS: During the study period, participating hospitals reported a mean of 33.2 tests for CDI per 10 000 patient-days and a mean of 8.4 cases of CDI per 10 000 patient-days. The overall prevalence of positive CDI patients at NCL was 16.5%. Due to absence of clinical suspicion, 19.1% of these patients were not diagnosed by the local diagnostic laboratory. We identified 23 different PCR-ribotypes among 87C. difficile strains isolated from patients. PCR-ribotype 027 (48%) was the most prevalent. CONCLUSIONS: The incidence of CDI in Poland in study period was very high. It should be noted however, that there is a lack of clinical suspicion and underestimation of the need to perform diagnostic tests for CDI in hospitalized patients. This will have an impact on the reported epidemiological status of CDI in Poland.
Subject(s)
Clostridium Infections/epidemiology , Diarrhea/epidemiology , Diarrhea/microbiology , Hospitalization , Clostridioides difficile/classification , Clostridioides difficile/physiology , Clostridium Infections/diagnosis , Diagnostic Errors , Diarrhea/diagnosis , Humans , Poland/epidemiology , Prevalence , Prospective Studies , RibotypingABSTRACT
PURPOSE: The Nijmegen breakage syndrome (NBS) is an inherited genetic disorder characterized by a typical facial appearance, microcephaly, growth retardation, immunodeficiency, and a strong predisposition to malignancies, especially of lymphoid origin. NBS patients have a mutation in the NBN gene which involves the repair of DNA double-strand breaks (DSBs). Here we studied the peripheral T cell compartment of NBS patients with a focus on immunological senescence. METHODS: The absolute numbers and frequencies of the different T cell subsets were determined in NBS patients from young age till adulthood and compared to age-matched healthy individuals (HI). In addition, we determined the expression of senescent T cell markers and the signal joint T cell receptor excision circles (sjTRECs) content. RESULTS: Our results demonstrate that NBS patients have reduced T cell numbers. NBS patients showed lower numbers of αß+ T cells, but normal γδ+ T cell numbers compared to HI. Concerning the αß+ T cells, both CD4+ as well as CD8+ T cells were excessively reduced in numbers compared to aged-matched HI. In addition, NBS patients showed higher frequencies of the more differentiated T cells expressing the senescent cell marker CD57 and did not express co-stimulatory molecule CD28. These effects were already present in the youngest age group. Furthermore, NBS patients showed lower sjTREC content in their T cells possibly indicative of a lower thymic output. CONCLUSIONS: We conclude that circulating T cells from NBS patients show signs of a senescent phenotype which is already present from young age on and which might explain their T cell immune deficiency.
Subject(s)
Cellular Senescence/genetics , Lymphocyte Count , Nijmegen Breakage Syndrome/blood , Nijmegen Breakage Syndrome/etiology , Phenotype , T-Lymphocyte Subsets/immunology , T-Lymphocyte Subsets/metabolism , Adolescent , Adult , B-Lymphocyte Subsets/immunology , B-Lymphocyte Subsets/metabolism , Biomarkers , Cellular Senescence/immunology , Child , Child, Preschool , Female , Humans , Immunophenotyping , Infant , Male , Mutation , Nijmegen Breakage Syndrome/diagnosis , Nijmegen Breakage Syndrome/metabolism , Receptors, Antigen, T-Cell/genetics , Receptors, Antigen, T-Cell, alpha-beta/genetics , Receptors, Antigen, T-Cell, alpha-beta/metabolism , Receptors, Antigen, T-Cell, gamma-delta/genetics , Receptors, Antigen, T-Cell, gamma-delta/metabolism , Recombination, Genetic , Young AdultABSTRACT
The aim of the present study was to investigate serum levels of novel markers: interleukin 17A (IL-17A), anaphylatoxin C5a and chemokine regulated upon activation normal T-cell expressed and secreted (RANTES) in neonates with clinically suspected early-onset neonatal sepsis (EONS), and to compare their values with those of non-infected neonates. Eighteen neonates with clinical signs and symptoms of EONS were enrolled in this study. Fifty healthy, non-infected neonates served as the control group. In all neonates serum levels of IL-17A, C5a and RANTES were measured by solid-phase sandwich enzyme-linked immunosorbent assay (ELISA). At the time of investigation serum levels of anaphylatoxin C5a were significantly higher in neonates with clinical symptoms of EONS than in non-infected neonates (median 65.35 vs. 50.4 ng/ml, p = 0.034), whereas levels of RANTES were similar and levels of IL-17A were under detection limit of the method. Based on these preliminary results, serum levels of C5a may be a useful marker of inflammation in early onset neonatal sepsis. Because traditional methods of microbiological diagnostics in EONS are frequently unsuccessful, the search for an alternative laboratory biomarkers is of great clinical importance. Thus, there is a strong need for further studies evaluating usefulness of this anaphylatoxin in EONS diagnosis on a larger group of patients.