Eda Karadag Oncel

Black tongue associated with Kocuria (Micrococcus) kristinae bacteremia in a 4-month-old infant

A 4-month-old female infant was admitted to the hospital with a history of prolonged diarrhea and severe failure to thrive. The patients diarrhea started when she was 2 months old which prompted hospitalization a month later for further investigation. Discontinuation of enteral feeding resulted in resolution of her diarrhea, and total parenteral nutrition was continued via a central venous catheter (CVC). After 10 days, she developed fever. Physical examination was unremarkable except for a black discoloration of the tongue (Fig. 1). Empirical antibiotic treatment was provided with ceftriaxone. However, early report of a grampositive growth in blood cultures at 48 h prompted addition of vancomycin to the treatment regimen. This growth was later identified as Kocuria (Micrococcus) kristinae, which was detected in two separate aerobic blood cultures. The patient showed a dramatic response to vancomycin treatment, and blood cultures obtained 48 h later from the indwelling CVC and from a peripheral vein were negative. The black discoloration of the tongue completely resolved a week after initiation of vancomycin treatment (Fig. 2), and combination antibiotic therapy was discontinued after a total of 14 days. To the best of our knowledge, this is the first reported case in the English literature of K. kristinae bacteremia as a cause of black hairy tongue. Fig. 1 Black discoloration of the dorsal tongue

Meningitis caused by Neisseria Meningitidis, Hemophilus Influenzae Type B and Streptococcus Pneumoniae during 2005–2012 in Turkey: A multicenter prospective surveillance study

Successful vaccination policies for protection from bacterial meningitis are dependent on determination of the etiology of bacterial meningitis. Cerebrospinal fluid (CSF) samples were obtained prospectively from children from 1 month to ≤ 18 years of age hospitalized with suspected meningitis, in order to determine the etiology of meningitis in Turkey. DNA evidence of Neisseria meningitidis (N. meningitidis), Streptococcus pneumoniae (S. pneumoniae), and Hemophilus influenzae type b (Hib) was detected using multiplex polymerase chain reaction (PCR). In total, 1452 CSF samples were evaluated and bacterial etiology was determined in 645 (44.4%) cases between 2005 and 2012; N. meningitidis was detected in 333 (51.6%), S. pneumoniae in 195 (30.2%), and Hib in 117 (18.1%) of the PCR positive samples. Of the 333 N. meningitidis positive samples 127 (38.1%) were identified as serogroup W-135, 87 (26.1%) serogroup B, 28 (8.4%) serogroup A and 3 (0.9%) serogroup Y; 88 (26.4%) were non-groupable. As vaccines against the most frequent bacterial isolates in this study are available and licensed, these results highlight the need for broad based protection against meningococcal disease in Turkey.

Can the mild clinical course of crimean–congo hemorrhagic fever in children be explained by cytokine responses?

Cytokines are possibly one of the factors responsible for death due to Crimean–Congo hemorrhagic fever (CCHF). This study aimed to determine the differences between the cytokine levels in children and adult patients with CCHF; the influence of cytokines; and the severity of the course of the disease, which seems to be milder in children. Thirty‐four children and 36 adult patients diagnosed with CCHF between 2010 and 2011 were included in this study. Diagnosis was performed by serology or by the polymerase chain reaction for CCHF virus. Levels of IFN‐γ, TNF‐α, IL‐1β, IL‐2, IL‐4, IL‐5, IL‐6, IL‐9, IL‐10, IL‐12 p70, IL‐13, IL‐17A, and IL‐22 were measured in all serum samples. Although the disease had a fatal course in three adult patients, there were no deaths in children. Statistically significant differences were not observed between the cytokine concentrations in the adults and children. No differences were detected between the serum cytokine levels in the children with moderate and those with a severe clinical course of the disease. In the adult patients with fatal outcome, significantly higher serum levels of IL‐2, IL‐5, IL‐9, IL‐12 p70, and IL‐13 were detected as compared to the cytokine levels in patients who survived the infection. No differences were detected between the serum levels of IFN‐γ, IL‐1β, IL‐17A, IL‐22, IL‐10, IL‐6, IL‐4, and TNF‐α in the patients who died and those who survived. Thus, the milder clinical course in children with CCHF cannot be explained by the cytokine network alone. The incomplete maturation of the immune system and timing and scale of immune responses could change the outcome dramatically. J Med. Virol. 85:1955–1959, 2013.

Bacterial agents causing meningitis during 2013–2014 in Turkey: A multi-center hospital-based prospective surveillance study

ABSTRACT This is an observational epidemiological study to describe causes of bacterial meningitis among persons between 1 month and 18 y of age who are hospitalized with suspected bacterial meningitis in 7 Turkish regions. covering 32% of the entire population of Turkey. We present here the results from 2013 and 2014. A clinical case with meningitis was defined according to followings: any sign of meningitis including fever, vomiting, headache, and meningeal irritation in children above one year of age and fever without any documented source, impaired consciousness, prostration and seizures in those < 1 y of age. Single tube multiplex PCR assay was performed for the simultaneous identification of bacterial agents. The specific gene targets were ctrA, bex, and ply for N. meningitidis, Hib, and S. pneumoniae, respectively. PCR positive samples were recorded as laboratory-confirmed acute bacterial meningitis. A total of 665 children were hospitalized for suspected acute meningitis. The annual incidences of acute laboratory-confirmed bacterial meningitis were 0.3 cases / 100,000 population in 2013 and 0.9 cases/100,000 in 2014. Of the 94 diagnosed cases of bacterial meningitis by PCR, 85 (90.4%) were meningococcal and 9 (9.6%) were pneumococcal. Hib was not detected in any of the patients. Among meningococcal meningitis, cases of serogroup Y, A, B and W-135 were 2.4% (n = 2), 3.5% (n = 3), 32.9% (n = 28), and 42.4% (n = 36). No serogroup C was detected among meningococcal cases. Successful vaccination policies for protection from bacterial meningitis are dependent on accurate determination of the etiology of bacterial meningitis. Additionally, the epidemiology of meningococcal disease is dynamic and close monitoring of serogroup distribution is comprehensively needed to assess the benefit of adding meningococcal vaccines to the routine immunization program.

Distribution of Streptococcus pneumoniae Serotypes That Cause Parapneumonic Empyema in Turkey

ABSTRACT Streptococcus pneumoniae is the most common etiological cause of complicated pneumonia, including empyema. In this study, we investigated the serotypes of S. pneumoniae that cause empyema in children. One hundred fifty-six children who were diagnosed with pneumonia complicated with empyema in 13 hospitals in seven geographic regions of Turkey between 2010 and 2012 were included in this study. Pleural fluid samples were collected by thoracentesis and tested for 14 serotypes/serogroups using a Bio-Plex multiplex antigen detection assay. The serotypes of S. pneumoniae were specified in 33 of 156 samples. The mean age ± the standard deviation of the 33 patients was 6.17 ± 3.54 years (range, 0.6 to 15 years). All of the children were unvaccinated according to the vaccination reports. Eighteen of the children were male, and 15 were female. The serotypes of the non-7-valent pneumococcal conjugated vaccine (non-PCV-7), serotype 1, serotype 5, and serotype 3, were detected in eight (14.5%), seven (12.7%), and five (9.1%) of the samples, respectively. Serotypes 1 and 5 were codetected in two samples. The remaining non-PCV-7 serotypes were 8 (n = 3), 18 (n = 1), 19A (n = 1), and 7F/A (n = 1). PCV-7 serotypes 6B, 9V, 14, 19F, and 23F were detected in nine (16.3%) of the samples. The potential serotype coverages of PCV-7, PCV-10, and PCV-13 were 16.3%, 45.4%, and 60%, respectively. Pediatric parapneumonic empyema continues to be an important health problem despite the introduction of conjugated pneumococcal vaccines. Active surveillance studies are needed to monitor the change in S. pneumoniae serotypes that cause empyema in order to have a better selection of pneumococcal vaccines.

Serotype distribution of Streptococcus pneumoniae in children with invasive diseases in Turkey: 2008–2014

Successful vaccination policies for protection from invasive pneumococcal diseases (IPD) dependent on determination of the exact serotype distribution in each country. We aimed to identify serotypes of pneumococcal strains causing IPD in children in Turkey and emphasize the change in the serotypes before and after vaccination with 7-valent pneumococcal conjugate vaccine (PCV-7) was included and PCV-13 was newly changed in Turkish National Immunization Program. Streptococcus pneumoniae strains were isolated at 22 different hospitals of Turkey, which provide healthcare services to approximately 65% of the Turkish population. Of the 335 diagnosed cases with S. pneumoniae over the whole period of 2008–2014, the most common vaccine serotypes were 19F (15.8%), 6B (5.9%), 14 (5.9%), and 3 (5.9%). During the first 5 y of age, which is the target population for vaccination, the potential serotype coverage ranged from 57.5 % to 36.8%, from 65.0% to 44.7%, and from 77.4% to 60.5% for PCV-7, PCV-10, and PCV-13 in 2008–2014, respectively. The ratio of non-vaccine serotypes was 27.2% in 2008–2010 whereas was 37.6% in 2011–2014 (p=0.045). S. penumoniae serotypes was less non-susceptible to penicillin as compared to our previous results (33.7 vs 16.5 %, p=0.001). The reduction of those serotype coverage in years may be attributed to increasing vaccinated children in Turkey and the increasing non-vaccine serotype may be explained by serotype replacement. Our ongoing IPD surveillance is a significant source of information for the decision-making processes on pneumococcal vaccination.

Elevated chemokine levels during adult but not pediatric Crimean–Congo hemorrhagic fever

BACKGROUND Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne viral zoonosis. Clinical reports indicate the severity of CCHF is milder in children than adults. The chemokines are important chemo-attractant mediators of the host immune system. OBJECTIVES The main aim of the study was to identify whether or not there were any differences in chemokine levels between the pediatric and adult patients and control groups, and whether there was any correlation with disease severity. STUDY DESIGN The serum levels of select chemokines including chemokine (C-C) ligand 2 (CCL2), CCL3, CCL4, chemokine (C-X-C) ligand 8 (CXCL8), CXCL9, and granulocyte-colony stimulating factor (G-CSF) in 29 adult and 32 pediatric CCHF patients and in 35 healthy children and 40 healthy adult control groups were studied by flow cytometric bead immunoassay method. RESULTS Great variability was detected in the serum levels of the chemokines for both the adult and pediatric patients and controls. With the exception of G-CSF, the median serum levels of CCL2, CCL3, CCL4, CXCL8, and CXCL9 were found to be significantly higher in the adult patients compared to adult controls (2364.7 vs. 761 pg/ml; 714.1 vs. 75.2 pg/ml; 88.6 vs. 25.5 pg/ml; 217.9 vs. 18.3 pg/ml; 875 vs. 352.2 pg/ml, respectively, p < 0.0001 for all comparisons). Among the chemokines the median CCL4 and G-CSF levels were significantly higher in the pediatric patients compared to pediatric controls (40.3 vs. 7.1 pg/ml, p < 0.0001; 0.1 vs. 0.1 pg/ml, p = 0.049, respectively). CONCLUSION The results of this study showed prominent chemokine raising in adult CCHF patients compared to children CCHF patients.

Effectiveness of a new bioequivalent formulation of oseltamivir (Enfluvir®) on 2010-2011 seasonal influenza viruses: an open phase IV study.

OBJECTIVE The aim of this multicenter prospective study was to evaluate the efficacy of a new bioequivalent formulation of oseltamivir for the treatment of influenza A, influenza B, and H1N1 during the 2010-2011 influenza season. METHODS We compared the symptoms and signs of 300 pediatric patients presenting to three university hospitals with an influenza-like illness between January and March 2011. Nasal swab specimens were collected from all children and tested by reverse-transcription polymerase chain reaction (RT-PCR) for influenza viruses. After randomization, half of the participants were prescribed oseltamivir, while the other half were observed conservatively. Forty patients who were followed-up for influenza prior to the study were also included in the evaluation. RESULTS Influenza was confirmed by RT-PCR in 129 children, 71 of whom were prescribed oseltamivir. The durations of the symptoms fever, cough, nasal congestion, and rhinorrhea were significantly shorter for patients who were treated with oseltamivir compared with untreated patients (p<0.002 for all symptoms). Early initiation of oseltamivir therapy (within 48 h of the onset of symptoms) was associated with more favorable outcomes and an earlier recovery than in patients for whom treatment was delayed (beyond 48 h). Thirty-seven patients (28.7%) had H1N1, 44 (34.1%) had influenza A, 46 (35.7%) had influenza B, one (0.8%) had H1N1 plus influenza A, and one (0.8%) had influenza A plus influenza B viruses. In the comparison of the duration of symptoms according to the different virus types, a statistically significant difference was only observed in patients with influenza B who had a longer duration of cough (p<0.001), nasal congestion (p<0.001), and rhinorrhea (p<0.001). CONCLUSIONS Oseltamivir is an effective treatment for the management of seasonal influenza and H1N1, and should be initiated immediately without waiting for laboratory confirmation of diagnosis.

Kluyvera ascorbata infections in children: a case series.

Kluyvera is a relatively newly described member of the Enterobacteriaceae family that rarely causes infections in humans. In the pediatric population, it is described in association with clinically significant infections ranging from urinary tract infections to sepsis with multiorgan failure. Our aim is to determine the clinical significance of K. ascorbata infections in the pediatric population at our institution. We retrospectively analyzed clinical microbiology data as from 2006 and identified four clinically significant isolates in this period. The isolates were from four cases who presented with sepsis, bacteremia associated with central venous catheter, pyelonephritis and intraabdominal collection. The ages of these patients ranged between seven months to 17 years. All patients received prompt antimicrobial treatment on the basis of susceptibility testing and good clinical response was obtained in all patients. Successful treatment options include third-generation cephalosporins, aminoglycosides, betalactams with beta-lactamase inhibitors and carbapenems. Clinicians should be aware of the spectrum of disease and increasing clinical importance associated with this pathogen.

Early lactic acidosis associated with linezolid therapy in paediatric patients

Linezolid, an oxazolidinone class antibiotic, is used to treat Gram-positive infections, including those due to meticillin-resistant staphylococci and vancomycin-resistant enterococci. In paediatric clinical trials, the frequency of possible linezolid-related adverse events ranged from 18.8% to 25.6%. The most commonly reported side effects are gastrointestinal disturbances, headache, rash and liver function alterations. Lactic acidosis has been reported as a side effect of linezolid treatment, and limited data suggest it may be more common in children. We report on our experience of treating 50 children aged 1 month to years with linezolid. Eight patients (16%) developed lactic acidosis and another eight (16%) had lactic acidaemia without acidosis. Onset of lactic acidaemia (median 1.5 days; range 1-72 days) and lactic acidosis (median 2 days; range 1-13 days) tended to be early. Being an ICU patient and requiring mechanical ventilation significantly increased the risk of lactic acidaemia or acidosis (OR=22.75, 95% CI 4.24-122.09; OR=32.67, 95% CI 5.83-183.19, respectively; P<0.001). All 16 patients were able to continue linezolid treatment. Linezolid therapy was effective (microbiologic and/or clinical cure) in 39 patients (78%). Nine patients died whilst receiving linezolid treatment; the deaths were not considered to be a result of linezolid treatment failure. Two patients who did not respond clinically to linezolid recovered after their treatment was changed to vancomycin. Linezolid use in children appears to be as safe and effective as in adults. However, lactic acidosis appears to be more common, and occur earlier, in children.