Antibiotic associated diarrhea in outpatient pediatric antibiotic therapy.

BACKGROUND: Antibiotic-associated diarrhea is one of the most frequent side effects of antimicrobial therapy. We assessed the epidemiological data of antibiotic-associated diarrhea in pediatric patients in our region. METHODS: The prospective multi-center study included pediatric patients who were initiated an oral antibiotic course in outpatient clinics and followed in a well-established surveillance system. This follow-up system constituded inclusion of patient by the primary physician, supply of family follow-up charts to the family, passing the demographics and clinical information of patient to the Primary Investigator Centre, and a close telephone follow-up of patients for a period of eight weeks by the Primary Investigator Centre. RESULTS: A result of 758 cases were recruited in the analysis which had a frequency of 10.4% antibiotic-associated diarrhea. Among the cases treated with amoxicillin-clavulanate 10.4%, and cephalosporins 14.4% presented with antibiotic-associated diarrhea. In the analysis of antibiotic-associated diarrhea occurrence according to different geographical regions of Turkey, antibiotic-associated diarrhea episodes differed significantly (p = 0.014), particularly higher in The Eastern Anatolia and Southeastern Anatolia. Though most commonly encountered with cephalosporin use, antibiotic-associated diarrhea is not a frequent side effect. CONCLUSION: This study on pediatric antibiotic-associated diarrhea displayed epidemiological data and the differences geographically in our region.

Outcome predictors of influenza for hospitalization and mortality in children.

Severity of disease caused by influenza virus and the influencing factors that may be different. Moreover, the disease course actually may not be determined specifically in children because of lower seroprotection rates of children. Herein, the results clinic and outcome data of children with influenza from Turkey were reported. We present here the results from 2013 to 2017. Nasopharyngeal swab samples of the children with influenza were investigated via multiplex polymerase chain reaction. A total of 348 children were diagnosed with influenza; 143 (41.1%) were influenza A, 85 (24.4%) were influenza B, and 120 (34.5%) were mixt infection with other respiratory viruses. Fifty-four percent of children admitted to intensive care unit (ICU) were under 2 years of age (p = .001). Having an underlying disease was detected as the main predictor for both hospitalization and ICU stay according to multiple logistic regression analysis (odds ratio [OR], 11.784: 95% confidence interval [CI], 5.212-26.643; p = .001 and OR, 4.972: 95% CI, 2.331-10.605; p = .001, respectively). Neurological symptoms most frequently seen in cases who died (44.4%; p = .02). Lymphopenia was relatively higher (55.6%) and thrombocytopenia was most frequently seen in cases who died (77.8%) with a significant ratio (p = .001). Underlying diseases was found a risk factor for influenza being hospitalized and being admitted to ICU. Children under 2 years of age and with underlying diseases should be vaccinated particularly in countries where the influenza vaccination is still not routinely implemented in the immunization schedule. Highlights Underlying diseases is a risk factor for influenza to be hospitalized and admitted to ICU. Influenza vaccination is of great importance to prevent life-threatening complications of influenza, particularly in children require ICU admission. The possibility to reduce the outpatient visit number by vaccination has a great impact on disease burden in addition to the underestimated crucial social benefits, as well.

The use of serum endothelial adhesion molecules in pediatric patients with leukemia with febrile neutropenia to predict bacteremia.

OBJECTIVE: Febrile neutropenia (FN) represents a life-threatening complication in hematological malignancies. We aimed to analyze the utility of soluble vascular cell adhesion molecule 1 (sVCAM-1), intercellular adhesion molecule 1 (sICAM-1), vascular endothelial growth factor (VEGF) levels compared with C-reactive protein (CRP) and procalcitonin (PCT) during febrile neutropenia episodes of pediatric patients with leukemia. METHODS: Two plasma samples, on day 0 (initial of episode) and day 3 (48-72 h after episode), for VCAM-1, ICAM-1 and VEGF, CRP and PCT were prospectively collected concomitantly during each febrile neutropenic episode between December 2016 and December 2017. The primary outcome was bacteremia and the secondary outcome was intensive care unit (ICU) admission. RESULTS: Twenty-two (28.6%) acute lymphoblastic lymphoma (ALL), seventeen (22.1%) acute myeloblastic lymphoma (AML) patients and thirty-eight (49.3%) control patients with no known underlying disease or fever were included in this study. Of the 39 patients; 16 (41%) had bacteremia. Mean serum sVCAM1 and sICAM1 levels were significantly higher in control group, compared to FN patients (p < 0.001). Mean serum sVCAM2 level was significantly higher in FN patients with bacteremia compared to FN patients without bacteremia (144.97 ± 70.35 pg/mL vs 85.45 ± 53.76 pg/mL, p = 0.022). Mean sVCAM1 and 2 levels were higher in FN patients with ICU admission. In this study, we found that sVCAM-1 and VEGF, when combined to CRP and PCT, could predict gram-negative bacteremia in FN episodes of pediatric hematological malignancy. CONCLUSION: Serum endothelial adhesion molecules, excluding sVCAM-1, cannot predict bacteremia and ICU admission alone in FN patients; but may be associated with clinical outcome when used with PCT and CRP.

Evaluation of more than one billion outpatient prescriptions and eight-year trend showing a remarkable reduction in antibiotic prescription in Turkey: A success model of governmental interventions at national level.

PURPOSE: To present the antibiotic prescription trend between 2011-2018 at primary healthcare in Turkey in order to evaluate the effects of interventions at national level for providing rational prescription of antibiotics. METHODS: Electronic prescription data of the family physicians collected from January 1, 2011 to December 31, 2018 in 81 provinces of Turkey were recorded through the Prescription Information System and screened for the antimicrobial drugs. The interventions to promote rational antibiotic use during 2011-2018 in Turkey includes reminding the legislation to stop access of antibiotics without prescription, monitoring of antibiotic prescription behaviors of primary healthcare physicians, and education of healthcare workers and the public on the appropriate use of antibiotics. RESULTS: A total of 1 054 261 396 prescriptions for outpatients of all age groups were recorded during this period. Of the prescriptions written by family physcians, 34.94% were containing at least one antibiotic in 2011, which declined to 24.55% in 2018. Antibiotics constituted 13.99% of all the items in prescriptions in 2011 and 10.47% in 2018. Percentage of total antibiotic expenditure to the total drug expanditure decreased from 14.14% to 4.12% during 2011-2018. The most commonly prescribed antibiotics were amoxicillin and enzyme inhibitor combination, cefdinir, and cefuroxime during 2011-2018, with an increasing trend for prescription of first-line antibiotic, amoxicillin, in recent years. CONCLUSIONS: Governmental interventions at national level have contributed to reducing antibiotic prescription and increasing preference of first-line antibiotics at primary healthcare level in Turkey over a course of 8 years. Turkey's model of governmental interventions may set an example for other countries with high consumption of antibiotics, and contribute to the actions against antimicrobial resistance worldwide.

Is Posaconazole Really Effective in Adolescent patients as a Prophylactic Agent: Experience of a Tertiary Care Center.

BACKGROUND: Invasive fungal infections (IFIs) are a leading cause of morbidity and death in immunocompromised patients. Data on efficacy and pharmacokinetics of posaconazole in pediatric patients are rare (1 to 5). Herein, we retrospectively analyzed adolescent patients who had received posaconazole as antifungal prophylaxis. METHODS: We retrospectively analyzed patients who received posaconazole as primary or secondary antifungal prophylaxis. RESULTS: A total of 34 adolescent patients, 19 men (55.9%) and 15 women (44.1%) with a mean age of 15.8±2.1 years were included. Twenty-five of 34 (73.5%) patients were on primary and nine of 34 (26.5%) patients were on secondary antifungal prophylaxis. Diagnosis of the patients receiving posaconazole as primary antifungal prophylaxis were acute myeloid leukemia (n=12, 48%), hematopoietic stem cell transplantation (n=7, 28%), acute lymphoblastic leukemia (n=5, 20%), and Fanconi aplastic anemia (n=1, 4%). Five patients (55.6%) with hematopoietic stem cell transplantation, 1 patient with acute myeloid leukemia (11.1%), 1 patient with Fanconi aplastic anemia (11.1%), and 2 (22.2%) patients with chronic granulomatous disease received posaconazole as secondary antifungal prophylaxis. Twelve of 25 (48%) patients receiving posaconazole as primary antifungal prophylaxis were complicated by IFI; 4 of them were proven, 6 probable, and 2 with possible IFI. Three of 9 patients (33.3%) receiving posaconazole as secondary antifungal prophylaxis was complicated by IFI (P=0.29), 2 of them were probable and 1 was possible IFI. Five of 25 patients (20%) receiving posaconazole as primary prophylaxis died because of IFI. CONCLUSION: Improvement of antifungal prophylaxis in patients with high risk of invasive infections seems clearly necessary, and analyzing serum posaconazole levels and individualizing dosing may be 1 approach to improve outcomes.

Multisystem inflammatory syndrome in children

As the COVID-19 pandemic continues, children can be infected with the virus that causes COVID-19. Clinical symptoms of children with COVID from China, where the disease was first reported, generally were less severe than adults. However, at the end of April 2020 in Europe, it was observed that some children with SARS-CoV-2 infection developed fever, abdominal pain, shock, myocardial insufficiency and they needed to be taken care of in intensive care unit. This new disease has been called multisystem inflammatory syndrome in children (MIS-C). Although the pathogenesis of MIS-C is unclear, it progresses with signs of multiorgan involvement as a result of uncontrolled inflammation of the immune system and even causes death. Therefore, the diagnosis and treatment of patients with MIS-C should be managed quickly. In this review, the pathophysiology, clinical and laboratory findings, diagnostic methods, and treatment regimens of MIS-C were discussed.

Global surveillance, travel, and trade during a pandemic

Pandemics have had very important consequences in human history. Lots of people lost their lives and countries have been intensively affected in terms of socioeconomic problems. Unfortunately, avoidance of pandemics and limiting the spread are still currently not always possible. Maybe the most important factor for this is the increasing frequency of traveling. Increasing airline traveling rate also increases the rate of spread. Global organizations like the World Health Organization and United Nations are trying to play a supreme role over the countries. Pandemics do not have borders; therefore, efforts should be given globally, definition of pandemic should be established as soon as possible, and protective measures should be shared with countries. If these are not done, severe health consequences and serious economic problems are inevitable.

Respiratory viral infections in infants with possible sepsis.

BACKGROUND: Knowledge of infections leading to sepsis is needed to develop comprehensive infection prevention and sepsis, as well as early recognition and treatment strategies.The aim of this study was to investigate the etiology of sepsis and evaluate the proportion of respiratory viral pathogens in infants under two years of age with possible sepsis. METHODS: The prospective study was performed in two years. Multiplex reverse transcriptase polymerase chain reaction (RT-PCR) was performed to detect viral pathogens. All patients who were included in this study had sepsis symptoms as defined by the Surviving Sepsis Campaign. RESULTS: We compared 90 patients with sepsis into three groups as patients (n = 33) who had only viral positivity in nasopharyngeal swab, patients (17) had proven bacterial infection with or without viral infection, and patients (40) without the pathogen detection. Human rhinovirus (16.7%) and influenza (7.8%) were the most commonly seen viruses. A cough was more common in the viral infection group than other groups ( P = 0.02) and median thrombocyte count was lower in the bacterial infection group than the others ( P = 0.01). Patients having bacterial sepsis had the longest duration of hospitalization than the other groups ( P = 0.04). During winter and spring seaons, patients with sepsis had more viral infection; however, in summer and autumn period, patients were mostly in a state that we could not prove infection agents ( P = 0.02). CONCLUSIONS: Our results suggest that respiratory tract viruses may play an important role in patients with sepsis and they should be kept in mind, especially during winter and spring seasons. In overall infection, viral respiratory viruses as a single pathogen with a detection rate of 36.6% in sepsis etiology.

A case of Raoultella ornithinolytica urinary tract infection in a pediatric patient.

Raoultella ornithinolytica is a Gram-negative, non-motile, encapsulated, biofilm producing, facultative aerobic bacillus and is found in natural environment. Human infections with R.ornithinolytica is rare in children with only five cases having been reported previously. The present case report describes an urinary tract infection caused by R. ornithinolytica that was identified by MALDI-TOF MS and successfully treated with antibiotic therapy in a 6.5-year-old female child.

Economic evaluation of micafungin versus liposomal amphotericin B (LAmB) for treating patients with candidaemia and invasive candidiasis (IC) in Turkey.

Micafungin was reported to be non-inferior to liposomal amphotericin B (LAmB) in treating patients with candidaemia and invasive candidiasis (IC). The current study aimed to evaluate the economic impact of using micafungin versus LAmB for treatment of candidaemia and IC in Turkey. A decision analytic model, which depicted economic consequences upon administration of micafungin or LAmB for treating patients with candidaemia and IC in the Turkish hospitals, was constructed. Patients were switched to an alternative antifungal agent if initial treatment failed due to mycological persistence. All patients were followed up until treatment success or death. Outcome probabilities were obtained from published literature and cost inputs were derived from the latest Turkish resources. Expert panels were used to estimate data that were not available in the literature. Cost per patient treated for each intervention was then calculated. Sensitivity analyses including Monte Carlo simulation were performed. For treatment of candidaemia and IC, micafungin (€4809) was associated with higher total cost than LAmB (€4467), with an additional cost of €341 per treated patient. Cost of initial antifungal treatment was the major cost driver for both comparators. The model outcome was robust over a wide variation in input variables except for drug acquisition cost and duration of initial antifungal treatment with micafungin or LAmB. LAmB is cost-saving relative to micafungin for the treatment of candidaemia and IC from the Turkish hospital perspective, with variation in drug acquisition cost of the critical factor affecting the model outcome.

Presepsin: A new marker of catheter related blood stream infections in pediatric patients.

BACKGROUND: Catheter related blood stream infections (CRBSI) are mostly preventable hospital-acquired conditions. We aimed to investigate the value of presepsin in detection of CRBSI in hospitalized children. METHODS: Hospitalized pediatric patients who had clinical suspicion of CRBSI were followed. Results of peripheral blood cultures and blood cultures from central venous catheters, procalcitonin (PCT), C-reactive protein (CRP), total white blood cell (WBC) counts were recorded. Serum samples for presepsin were studied at the same time with the samples of healthy controls. The patients with positive blood cultures were defined as proven CRBSI and with negative cultures as suspected CRBSI. RESULTS: Fifty-eight patients and 80 healthy controls were included in the study. Proven CRBSI group consisted of 36 patients (62%) with positive blood cultures and compared with the suspected CRBSI group (n = 22, 36%) with negative culture results. There was no difference between proven and suspected CRBSI groups concerning WBC, PCT, CRP and presepsin. Presepsin was significantly higher in patient groups when compared with healthy controls. The receiver operating characteristic curve area under the curve was 0.98 (%95 CI: 0.97-1) and best cut-off value was 990 pg/ml. CONCLUSION: In hospitalized pediatric patients with CRBSI, presepsin may be a helpful rapid marker in early diagnosis.

Cost-effectiveness analysis of anidulafungin vs fluconazole for the treatment of invasive candidiasis (IC) in Turkey.

Anidulafungin has been shown to be non-inferior to, and possibly more efficacious, than fluconazole in treating patients with invasive candidiasis (IC). This study aimed to determine the cost-effectiveness of anidulafungin vs fluconazole for treatment of IC in the Turkish setting. A decision analytic model was constructed to depict downstream economic consequences of using anidulafungin or fluconazole for treatment of IC in the Turkish hospitals. Transition probabilities (ie treatment success, observed or indeterminate treatment failures) were obtained from a published randomised clinical trial. Cost inputs were from the latest Turkish resources. Data not available in the literature were estimated by expert panels. Sensitivity analyses were performed to assess the robustness of the model outcome. While anidulafungin [TL 17 171 (USD 4589)] incurred a higher total cost than fluconazole [TL 8233 (USD 2200) per treated patient, treatment with anidulafungin was estimated to save an additional 0.58 life-years, with an incremental cost-effectiveness ratio of TL 15 410 (USD 4118) per life-years saved. Drug acquisition cost and hospitalisation were the main cost drivers for anidulafungin and fluconazole arms respectively. The model findings were robust over a wide range of input variables except for anidulafungin drug cost. Anidulafungin appears to be a cost-effective therapy in treating IC from the Turkish hospital perspective.

Six cases during 2012-2015 and literature review of Chryseobacterium indologenes infections in pediatric patients.

Chryseobacterium indologenes is a widespread bacteria in the environment, especially hospitals, and a rarely reported human pathogen. The lowest frequency has been reported in children under 5 years of age. Clinical manifestations of C. indologenes include nosocomial pneumoniae, biliary tract infection, peritonitis, surgical wound infection, intravascular catheter-related bacteremia, cellulitis, and primary bacteremia. There is a knowledge gap in the management of C. indologenes infections, especially pertaining children, because of multiple antibiotic resistance and limited data in the literature concerning effective empirical treatment. In the published literature, a total of 16 cases of C. indologenes infections were reported in the pediatric age group. Herein, we present our experience in 6 children with C. indologenes infections. Early and prompt management of C. indologenes infections, particularly in children with mechanic ventilation, with polymicrobial infections, and under the age of 2 years, is of major importance because these factors seem to have a negative effect on the prognosis of infections caused by C. indologenes. Ciprofloxacin and TPM-SMX may be the best therapeutic choices for a combined initial empirical treatment of the patients.

Multidisciplinary assessment of congenital insensitivity to pain syndrome.

BACKGROUND: Congenital insensitivity to pain and anhidrosis (CIPA) is a rare clinical condition characterized by the absence of normal subjective and objective responses to noxious stimuli in patients with intact central and peripheral nervous systems. CASE PRESENTATIONS: Two patients with CIPA are reported. The first patient was a 13-year-old girl who presented to our hospital with multiple joint destructions secondary to osteomyelitis. The second patient was a 10-year-old boy who presented with multiple hand lesions and right leg osteomyelitis. Our patients were treated with multiple debridements and intravenous antibiotics according to our hospital protocol. CONCLUSION: Early recognition of the disease is important. The treatment for this condition is focused more on the prevention of bone injuries and joint infection, as opposed to a cure. There are no standard techniques or guidelines available to treat this rare disease. Overall, effective CIPA treatment is built around family education and patient training.

Evaluation of hypothalamic-pituitary function in children following acute bacterial meningitis.

BACKGROUND: Previous studies in adults and case reports in children have shown increased frequency of hypothalamo-pituitary dysfunction after infectious diseases of the central nervous system. The aim of this study was to evaluate the function of hypothalamo-pituitary axis in children with a history of bacterial meningitis. METHODS: Patients diagnosed with bacterial meningitis between April 2000 and June 2011 was included. Baseline and stimulated hormonal tests were performed as required for hormonal evaluations following a diagnosis of meningitis. RESULTS: Pituitary function was assessed following a period of 8-135 months (mean 53 months) after bacterial meningitis. Thirty-seven cases (27 male, 15 pubertal) with mean age of 11.1 ± 4.4 years were included. Mean height SDS was 0.01 ± 1.07 and mean BMI SDS was 0.54 ± 1.15 all patients had a SDS above -2 SD. Baseline cortisol and low dose ACTH stimulation revealed normal adrenal functions in all patients. Gonadotropin deficiency was not detected in any of the pubertal cases. Four cases (10.8%) had low IGF1 and IGFBP3 z-scores (<-2 SD) according to age, sex and Tanner stage, but peak GH response in clonidin test was >10 ng/ml in three of them suggesting neurosecretary dysfunction of GH in these cases. The fourth case has died before the test. No one had TSH deficiency and diabetes insipidus, only one case had mild hyperprolactinemia. CONCLUSIONS: Our findings suggest that hypothalamo-pituitary dysfunction is not as common in childhood as in adulthood. The most remarkable finding was neurosecretary dysfunction of GH in some cases.

Candidaemia in a paediatric centre and importance of central venous catheter removal.

The aim of this study is to identify differences in distribution of Candida species, resistance to antifungals and clinical outcome, as well as the identification of potential risk factors associated with candidaemia in children. We conducted a retrospective analysis in children ≤18 years with blood culture proven candidaemia identified between 2004 and 2012. Patients were divided into two groups (Group 1, <3 months, n = 51; Group 2, ≥3 months, n = 197) to identify any potential difference between the neonatal and early infantile periods in terms of risk factors and distribution of Candida species. A total of 248 distinct episodes of candidaemia were identified over the study period. The most frequently isolated Candida species were C. albicans (53.2%), followed by C. parapsilosis (26.2%), C. tropicalis (8.1%). Of the 248 episodes, 71 episodes (28.6%) resulted in death within 30 days from the onset of candidaemia. In Group 1, failure of central venous catheter (CVC) removal was found to be associated with a 20.5-fold increase in mortality [95% CI (3.9, 106.5); P < 0.001], compared to a 5.9-fold increased risk with hypoalbuminaemia [95% CI (1.03, 34.1); P = 0.046]. For Group 2, the increased risk was 23-fold for failure of CVC removal [95% CI (7.48, 70.77); P < 0.001], 7.4-fold for mechanical ventilation [95% CI (2.64, 21.08); P < 0.001], 4.4-fold for hypoalbuminaemia [95% CI (1.56, 12.56); P = 0.005], 3.1-fold for neutropaenia [95% CI (1.31, 7.69); P = 0.010] and 2.2-fold for male gender [95% CI (1.02, 4.71); P = 0.043]. Therapeutic choices should be guided by sound knowledge of local epidemiological trends in candidaemia. Removal of CVC significantly reduces mortality and is an essential step in the management of candidaemia.

Evaluation of multiplex real time polymerase chain reaction and procalcitonin in the diagnosis of sepsis.

BACKGROUND: Sepsis is one of the most serious and life-threatening clinical conditions of childhood. This study has been designed to evaluate how useful multiplex real-time polymerase chain reaction (PCR) is in the early diagnosis of responsible microorganisms of sepsis and to specify how serial procalcitonin level measurement is helpful to support diagnosis of sepsis. METHODS: A total of 79 blood samples from 69 consecutive patients were collected for this prospective study between 01 Sept 2009 - 29 Feb 2012. RESULTS: In the evaluation of patients who are diagnosed with sepsis out of 69 patients with 79 clinical sepsis, 24 (30.37%) had positive blood culture and 19 (24%) samples were positive for PCR. When blood culture and multiplex real-time PCR results were compared, multiplex real-time PCR had a sensitivity of 75% and specificity of 100%. When the 2 microorganisms that multiplex real-time PCR cannot detect are excluded sensitivity increased to 81.8% and specificity did not differ. Procalcitonin levels on the day sepsis is suspected had a mean level of 13.91 ng/mL (+/- 49.26), on the 1st day (after 24 hours) the mean level of procalcitonin was 15.05 ng/mL (+/- 43.95), on the 2nd day (after 48 hours) it was 14.89 ng/mL (+/- 41.57). Mean procalcitonin levels of 50 children admitted with complaints other than infection and systemic inflammation was 0.06 ng/mL (+/- 0.04). CONCLUSIONS: In conclusion, multiplex real-time PCR test would be useful in the early diagnosis of sepsis. Studying procalcitonin levels is helpful in the early diagnosis of sepsis but does not have any correlation with the isolation of microorganisms in blood culture and survival.

Comparison of Physicians' Attitudes and Practice Regarding Vaccination during Pregnancy in Turkey.

This study aimed to investigate the knowledge, attitudes, and behaviors of family physicians (FPs), pediatricians (PPs), and obstetricians and gynecologists (OGs) regarding vaccine administration during pregnancy in Turkey as factors that contribute to decision-making. The survey was distributed among FPs, OGs, and PPs, and participants were asked to rate their knowledge on specific topics using a five-point scale ranging from "Not Effective" to "Effective". The tetanus and diphtheria (Td) vaccine was highly recommended by 94.9% of physicians and considered very effective. Among the physicians surveyed, 80% of PPs and 66.0% of OGs were aware of the disease burden of pertussis. We also found that 74.5% of FPs and 77.2% of PPs believed they needed more information about vaccination during pregnancy. All physicians surveyed agreed or strongly agreed that explaining the disease risks and benefits of vaccination increases the vaccine acceptance rate. The results of this survey study indicate that the knowledge and awareness of physicians need to be improved to increase vaccination rates during pregnancy in Turkey, and it is essential to incorporate influenza and tetanus, diphtheria, and pertussis (TdaP) vaccines into the standard maternal immunization schedule for newborns.