Osteomyelitis Caused by Bacillus Calmette-Guérin Vaccination in a Healthy Toddler.

Bacillus Calmette-Guérin (BCG) osteomyelitis in immunocompetent children is a rare complication of BCG immunization which presents with nonspecific findings and often leads to delayed diagnosis. We report a 1-year and 10-month-old male infant with complaining of knee pain and limping for 5 months. He received surgical debridement due to suspicion of malignancy but BCG osteomyelitis of the distal femur was diagnosed with the culture of the specimens which revealed to have Mycobacterium bovis-BCG strain. He was successfully treated with antituberculous therapy lasting for 1 year.

Proven and probable invasive fungal infections in children with acute lymphoblastic leukaemia: results from an university hospital, 2005-2013.

Despite improvements in diagnosis and treatment, invasive fungal infections (IFIs) are still a major cause of morbidity and mortality in immunocompromised patients. The data on IFI among children with acute lymphoblastic leukaemia (ALL) are still scarce, and our aim was to estimate the risk, aetiology and outcome of proven and probable IFIs in children with ALL who did not receive primary prophylaxis over an 8-year period. Between January 2005 and February 2013, 125 children who were treated for ALL at the Pediatric Hematology Department of the Medical School of Ege University were retrospectively reviewed. Proven and probable IFIs were defined according to revised definitions of the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group. The proven and probable IFI incidence was 30/125 (24%). Profound neutropenia was detected in 18 (60%) patients, and prolonged neutropenia was detected in 16 (53.3%) of the patients. The most isolated agents were non-albicans Candida spp. The crude and attributable mortality was 20% and 13.3% respectively. Profound neutropenia was associated with mortality (P < 0.05). The younger patients were especially at risk for proven IFI. Prolonged neutropenia, to be in the induction phase of chemotherapy, and profound neutropenia were found to be the most common predisposing factors for IFI episodes.

Mannose-binding lectin gene codon 54 polymorphism susceptible to brucellosis in Turkish children.

Genetic factors are as important as environmental factors in susceptibility to brucellosis. Among these genetic factors, mannose-binding lectin (MBL) deficiency contributes to susceptibility to animal brucellosis. The aim of the study is to determine the influence of codon 54 polymorphisms in the MBL gene on susceptibility to brucellosis. Forty-three patients diagnosed with brucellosis and 106 healthy children were admitted in the study. In the patient group, 19 (44.2%) subjects had AA, 22 (51.1%) subjects had AB and 2 (4.6%) subjects had BB genotypes for codon 54 polymorphism. Eighty-two (77.4%) of the healthy children had AA genotype, while 24 (22.6%) had AB genotype. Our results revealed that genotype frequencies carrying MBL variant allele at codon 54 among the patients were significantly higher compared to those found in the control group (55.8% and 22.6%, respectively; p = 0.0001, odds ratio [OR] = 4.316, 95% confidence interval [CI]: 2.030-9.177). Our data suggest that children with MBL codon 54 AB or BB genotype are more susceptible to brucellosis.

Evaluation of device-associated infections in a neonatal intensive care unit.

Device-associated infections are common in Neonatal Intensive Care Units (NICUs) in accordance with the frequent use of invasive devices, and they must be continuously and closely monitored for infection control. Six hundred newborn infants hospitalized longer than 72 hours in Ege University Children's Hospital NICU between January 2008 and December 2010 were prospectively followed for occurrence of device-associated infections (central venous catheter- and umbilical catheter-associated blood stream infections [CVC/UC BSI] and ventilator-associated pneumonia [VAP]). In a total of 10,052 patient days, the VAP rate was 13.76/1000 ventilator days with a ventilator utilization ratio of 0.29, and the CVC/UC BSI rate was 3.8/1000 catheter days with a catheter utilization ratio of 0.24. The CVC/UC BSI rate was lower than national averages, being close to rates reported from developed countries. The VAP rate was higher than the national and international rates and was associated with prolonged mechanical ventilation and very low birth weight. VAP also appeared to be an important risk factor for mortality. The most frequent agents were gram-negative pathogens for VAP and coagulase-negative staphylococci for CVC/UC BSIs, with resistance patterns similar to the previous years. In conclusion, with device utilization rates similar to those in developed countries, our CVC/UC BSI rate was comparable, but the VAP rate was higher than that of the developed countries. Necessary precautions are urgently needed to decrease VAP rates and VAP-related mortality.

Effect on hearing of oral valganciclovir for asymptomatic congenital cytomegalovirus infection.

Congenital cytomegalovirus (CMV) infection is the leading nongenetic cause of congenital sensorineural hearing loss (SNHL). Hearing loss due to congenital CMV infection either has onset after the newborn period or shows progressive decline in auditory thresholds. Although 90% of the congenitally infected infants are asymptomatic at birth, evidence is accumulating that these infants are at risk for audiologic, neurologic and developmental sequelae. In symptomatically infected infants, ganciclovir therapy administered in the neonatal period prevents hearing deterioration. However, preventative therapy of asymptomatic congenital CMV disease is controversial. Here in, we reported a male newborn with asymptomatic congenital CMV with bilateral SNHL. Oral treatment with valganciclovir in patient resulted in progressive improvement of SNHL, which effectively reduced the CMV viral load and was well tolerated without apparent adverse effects.

Experience of pandemic influenza with H1N1 in children with leukemia.

It is not exactly known the risks from infection with pandemic influenza (H1N1) 2009 in children with leukemia. Here the authors present their experience in 5 children with leukemia. Pandemic influenza (H1N1) 2009 was detected in 5 patients (F/M: 3/2) at their institution. The ages of these patients were between 2 and 16 years. Four had acute lymphoblastic leukemia (ALL) and 1 acute myeloblastic leukemia (AML). Three of the ALL patients had the diagnosis of pandemic influenza (H1N1) 2009 at the same time as they were diagnosed with ALL. The remaining 2 patients were receiving intensive chemotherapy. All patients had fever, rhinorrhea, and cough. Although bronchopneumonia was seen in 3 patients, only 1 revealed respiratory distress. Stomach ache and diarrhea was seen in the patient who had no pneumonia. All treated as inpatients, but none of them required hospitalization in intensive care unit. One to 3 days after the symptoms of influenza appeared, oseltamivir (Tamiflu) was given to all patients in combination with broad-spectrum antibiotics. Fever declined to normal ranges in 1 to 3 days after treatment was started. The patients received oseltamivir for 5 to 7 days. Cell culture tests were found to be positive for influenza A and polymerase chain reaction (PCR) revealed H1N1 for all 5 patients. Although this is a very small case series, pandemic influenza (H1N1) 2009 did not seem to be very dangerous for children with leukemia if the oseltamivir treatment was given early when symptoms of influenza appeared.

Surface TREM-1 as a Prognostic Biomarker in Pediatric Sepsis.

OBJECTIVES: To investigate the association between the triggering receptor expressed on myeloid cells-1 (TREM-1) levels and prognosis in septic children. METHODS: Patients admitted to pediatric intensive care units (PICU) of three tertiary centers were included in this prospective observational study. Serum samples were taken at admission from patients who were hospitalized with sepsis. RESULTS: Of the 87 patients included, 34 (39.1%) had severe sepsis and 53 (60.9%) had septic shock. The median age was 2 y (2 mo to 16 y). TREM-1 values were found to be significantly higher in septic shock patients 129 pg/ml (min 9.85- max 494.90) compared to severe sepsis 105 pg/ml (min 8.21- max 289.17) (p = 0.048). Despite higher TREM-1 levels been measured in non-survivors compared to survivors, it was not statistically significant [168.98 pg/ml (min 9.85- max 494.90) vs. 110.79 pg/ml (min 8.21- max 408.90), (p = 0.075)]. CONCLUSIONS: Admission TREM-1 levels were higher in septic shock compared to severe sepsis patients. There was no association between mortality and TREM-1 levels in sepsis. TREM-1 measurements should be used carefully in pediatric sepsis prognosis.

A case of Mondini dysplasia with recurrent Streptococcus pneumoniae meningitis.

Mondini's dysplasia is a developmental anomaly of the middle ear characterized by cochlear malformation with dilation of the vestibular aquaduct, vestibule, and ampullar ends of the semicircular canals. These deformities may result in a connection between subarachnoid space and the middle ear resulting in recurrent episodes of meningitis. Additionally, it is commonly associated with hearing impairment. We describe here a boy with recurrent meningitis and unilateral sensorineural hearing loss. Mondini dysplasia was demonstrated with computed tomographic scans of the temporal bones in the search for pathogenesis of recurrent meningitis.

Role of angiotensin-converting enzyme gene polymorphisms in children with sepsis and septic shock.

BACKGROUND: Sepsis is characterized by a systemic inflammatory response. Its development and outcome are associated with host defense, pathogenicity of the microorganism and genetic polymorphisms. Genetic polymorphisms of the immune system genes have been shown to have a close relationship with the clinical outcomes of sepsis. Angiotensin-converting enzyme (ACE) plays a major role in the host defense against invading pathogens. It is therefore likely that polymorphisms in the ACE gene may have an important effect on determining the development and the outcome of sepsis. METHODS: Ninety-eight children diagnosed as having sepsis and 287 healthy children were included in the study. Insertion/deletion polymorphisms were analyzed using reverse-hybridization assay. RESULTS: The carriers of I allele (D/I genotype and I/I genotype) were found to have an increased risk of developing sepsis compared to the controls. CONCLUSION: DD genotype may play a positive role against the development of sepsis in healthy children.

The prospective evaluation of risk factors and clinical influence of carbapenem resistance in children with gram-negative bacteria infection.

BACKGROUND: Carbapenem-resistant gram-negative (CRGN) infections have been increasing in recent years and associated with significant morbidity, mortality, and health care costs. The aim of this study was to evaluate the epidemiologic and clinical risk characteristics, risk factors, and outcome of CRGN infections and to compare with carbapenem-sensitive gram-negative (CSGN) infections in children. METHODS: Newly diagnosed CRGN infections in hospitalized children younger than age 18 years were prospectively recorded and all patients infected with a CSGN pathogen in the same unit within 48 hours of diagnosis were included in a control group between April 1, 2014, and December 31, 2014. RESULTS: Twenty-seven patients with CRGN infections and 28 patients with CSGN infections were enrolled in this study. Ventilator-associated pneumonia was the most common type of infection in both groups. Prior exposure to carbapenems (relative risk [RR], 11.368; 95% confidence interval [CI], 1.311-98.589), prolonged hospitalization (RR, 5.100; 95% CI, 1.601-16.242) were found to be independent risk factors for acquiring CRGN infections. Septic shock was significantly more frequent in the CRGN group (RR, 9.450; 95% CI, 1.075-83.065). The in-hospital mortality was higher in the CRGN group (RR, 7.647; 95% CI, 1.488-39.290). CONCLUSIONS: Prior carbapenem exposure and prolonged hospitalization are the most important risk factors for acquiring CRGN infections in our hospital. This study demonstrated, similar to previous reports, that carbapenem resistance increases morbidity, mortality, and health care costs.

Brain Abscess in Children: A Rare but Serious Infection.

Brain abscess is a rare disease in childhood requiring prompt medical and/or surgical treatment. The objective was to review presentation, management, and outcome of brain abscess in children. We reviewed the clinical and radiological features and outcomes of 18 children (10 females, 8 males), with a median age of 48 months (range 1-182), that presented with brain abscesses and admitted to a tertiary pediatric infectious department between December 2010 and January 2017. One (5.5%) patient underwent craniotomy and 14 (77.7%) had burr hole aspirations. The most common localization was the frontal lobe (33.3%). The survival rate was 94.4%, and long-term neurological sequelae affected 27.7% of the patients. Empiric treatment choices require knowledge of common pathogens and local resistance. The most predominant infections were still upper respiratory infections. Clinicians may treat the children with appropriate choice and duration of antibiotic treatment for upper respiratory tract infections.

Purine nucleoside phosphorylase deficiency in a patient with spastic paraplegia and recurrent infections.

Purine nucleoside phosphorylase deficiency is a rare autosomal recessive immunodeficiency disease. The characteristic features of the disease include severe T cell immune defects with recurrent infections, a failure to thrive, and progressive neurological findings. To date, 35 cases of purine nucleosidase phosphorylase deficiency have been reported worldwide. A 2-year-old female patient was hospitalized due to recurrent infections starting from 6 months and a fever that had continued for a month. The parents were first cousins. Physical examination showed a failure to thrive, herpetic lesions around the lips, painful lesions on the tongue and the buccal mucosa, lung infection, and spastic paraparesis in the lower extremities. She had motor and mental retardation. Laboratory tests revealed lymphopenia; low CD3, CD4, and CD8 counts; normal immunoglobulin levels; low uric acid; and very low purine nucleoside phosphorylase enzyme activity (1.4 nmol/h/mg; normal range, 490-1530). DNA sequencing of the purine nucleosidase phosphorylase gene revealed a missense homozygous mutation, a G to A transition at exon 4 position 64 (349G>A transition), which led to a substitution of alanine by threonine at codon 117 (Ala117Thr). Both parents were heterozygous for the mutation. This is the second purine nucleosidase phosphorylase deficient case to have been presented and carrying this mutation worldwide. Various antibiotics, antifungal drugs, and intravenous immunoglobulin were used to treat the infections during her 3 months. This form of treatment proved to be unresponsive, resulting in her subsequent death at 26 months of age.

Association between mannose binding lectin polymorphisms and predisposition to bacterial meningitis.

The aim of this study was to examine the presence of any association between mannose binding lectin (MBL) gene variants and bacterial meningitis. Codon 54 (B allele) and codon 57 (C allele) polymorphisms in exon 1 of the MBL gene were investigated in 50 healthy controls and 31 patients diagnosed as purulent meningitis. Codon 57 polymorphism was not found in our patient and control groups. B allele frequency was significantly higher in the patient group (22%) compared to the control group (3%). AB genotype was determined in 39% and 6% of patient and healthy control groups, respectively, and the difference was statistically significant. AA genotype was determined in 61% of the patient group and in 94% of the control group, and it was statistically low in the patient group. These results suggest that codon 54 polymorphism in the MBL gene may play a role in susceptibility to bacterial meningitis in children.

Mild encephalitis/encephalopathy with reversible splenial lesion (MERS) associated with Streptococcus pneumoniae Bacteraemia.

Mild encephalopathy with a reversible splenial lesion (MERS) is a clinico-radiological syndrome that can be related to infectious and non-infectious conditions. Patients present with mild neurological symptoms, and magnetic resonance imaging typically demonstrate a reversible lesion with transiently reduced diffusion in the splenium of the corpus callosum. Here, we describe MERS in a 10-year-old boy who presented with fever and consciousness and who completely recovered within a few days. Streptococcus pneumoniae was the causative agent. Although viruses (especially influenza A and B) are the most common pathogen of MERS, for proper management, bacteria should be considered, as they may also lead to this condition.

Diagnostic Accuracy of Interleukin-6, Interleukin-8, and Interleukin-10 for Predicting Bacteremia in Children with Febrile Neutropenia.

Despite improvements in diagnosis and treatment, infections are still a major cause of morbidity and mortality in children with febrile neutropenia. In the majority of febrile episodes, the source of infection cannot be defined. In this study, we aimed to identify the earlier predictors of bacteremia/fungemia and a useful cytokine to identify the source of infection and to discriminate the patients with culture-confirmed bacterial/fungal infection. The most sensitive cytokine was interleukin (IL)-10 and the most specific was IL-8 in predicting culture-confirmed cases. IL-8 had greater sensitivity and specificity in determination of gram-negative bacterial infections with a higher negative predictive value; therefore, IL-8 can be used particularly to rule out gram-negative bacterial infections. IL-6, IL-8, and IL-10 circulating levels were shown to be higher in cases of infection. Further studies are needed to recommend a routine practice for predicting culture-confirmed bacterial infections.

A fatal case of tuberculous meningitis in a child with juvenile idiopathic arthritis: a diagnostic challenge.

The prognosis of tuberculous meningitis, a rare form of extrapulmonary tuberculosis, depends on the stage of treatment initiation. We report a fatal case of tuberculous meningitis. The patient had received successive tumor necrosis factor (TNF) antagonists and abatacept to treat juvenile idiopathic arthritis, with negative results for polymerase chain reaction and acid-fast bacilli on smear, had normal cerebrospinal fluid (CSF) adenosine deaminase and glucose levels. Six weeks post-admission, the CSF culture demonstrated Mycobacterium tuberculosis. The altered immunological responses caused by anti-TNF treatment made the diagnosis challenging. Clinicians should bear this in mind and, if suspected, treatment should be initiated immediately.

Utility of the serum galactomannan assay for the diagnosis of invasive aspergillosis in children with acute lymphoblastic leukemia.

OBJECTIVES: Invasive aspergillosis (IA) is an important cause of mortality and morbidity in children with hematological malignancies. The monitoring of serum galactomannan (GM) antigen is considered useful in the diagnosis of IA . The aim of this study was to determine the utility of serum GM monitoring in the early diagnosis of IA and the role of positive antigenemia in the management of children with acute lymphoblastic leukemia (ALL). METHODS: The cases of 141 children who were being treated for ALL in the Division of Pediatric Hematology of the Medical School of Ege University between January 2006 and February 2015 were reviewed retrospectively. Cases of proven and probable IA were defined according to the European Organization for the Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) criteria. RESULTS: The incidence of proven and probable IA was 3.5% (5/141). The incidence of positive GM antigenemia among 3264 serum samples was 5.5% (n=179). Of the cases detected, 21.7% were true-positive, 52.1% were false-positive, and the remaining 26.1% were classified as 'undetermined.' An increase in the incidence of true-positive tests and induction of antifungal therapy was determined through multiple consecutive positive tests. CONCLUSIONS: GM may be detected in the serum before the clinical signs of IA appear, but its sensitivity and specificity are variable. False-positivity is a significant disadvantage, and consecutive positive GM must be taken into account in the case of clinical and imaging findings that are relevant to IA.

Pyoderma gangrenosum in a six-month-old boy.

Pyoderma gangrenosum (PG) is an uncommon, chronic ulcerative condition of the skin that was first described in 1930. It can occur in any age group, but only 4% of the patients are infants or children. An underlying systemic disease is present in approximately 50% of the patients with PG. The most common associations include inflammatory bowel disease, arthritis, lymphoproliferative disorders and chronic recurrent multifocal osteomyelitis (CRMO). PG has been reported in association with CRMO in only a few children whose ages were between 18 months and 12 years. We report a six-month-old boy who was diagnosed as CRMO based on his clinical examination and histological findings. This is the youngest case reported in the literature (under 12 months of age) with PG associated with CRMO.

Comparison of endotracheal aspirate and non-bronchoscopic bronchoalveolar lavage in the diagnosis of ventilator-associated pneumonia in a pediatric intensive care unit.

Ventilator-associated pneumonia (VAP) is defined as pneumonia occuring in any period of mechanical ventilation. There is no optimal diagnostic method in current use and in this study we aimed to compare two non-invasive diagnostic methods used in diagnosis of VAP in children. This prospective study was conducted in 8 bedded Pediatric Intensive Care Unit at Ege University Children´s Hospital. Endotracheal aspiration (ETA) and non-bronchoscopic bronchoalveolar lavage (BAL) were performed in case of developing VIP after 48 hours of ventilation. Quantitative cultures were examined in Ege University Department of Diagnostic Microbiology, Bacteriology Laboratory. Fourty-one patients were enrolled in the study. The mean age of study subjects was 47.2±53.6 months. A total of 28 in 82 specimens taken with both methods were negative/negative; 28 had positive result with ETA and a negative result with non-bronchoscopic BAL and both results were negative in 26 specimens. There were no patients whose respiratory specimen culture was negative with ETA and positive with non-bronchoscopic BAL. These results imply that there is a significant difference between two diagnostic methods (p < 0.001). Negative non-bronchoscopic BAL results are recognized as absence of VAP; therefore, ETA results were compared with this method. ETA's sensitivity, specificity, negative and positive predictive values were 100%, 50%, 100% and 48% respectively. The study revealed the ease of usability and the sensitivity of non-bronchoscopic BAL, in comparison with ETA.