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.

Oxidant and antioxidant balance in children with bacteremia.

BACKGROUND: There is a crucial balance between oxidant and antioxidant defense mechanisms. We aimed to evaluate the role of the balance of these systems in children with bloodstream infection. METHODS: We analyzed prospectively oxidant and antioxidant stress parameters from serum samples of children with BSI besides demographic and clinical data of children. Serum levels of the total antioxidant status (TAS), total oxidant status (TOS), albumin, plasma thiol, disulphide, catalase (CAT), myeloperoxidase (MPO), ischemia-modified albumin (IMA) levels, ferroxidase and arylesterase (ARES) activity were evaluated in both patients and healthy controls. RESULTS: A total of 113 children were evaluated, 50 of them had bacteremia and the remaining 63 were healthy subjects. The median TOS values were 18.5 µmol H2O2/L and 13.1 µmol H2O2/L in patient and control groups, respectively with a statistically significant difference between groups. The mean serum IMA levels were 0.8±0.1 absorbance unit (ABSU) in patients and 0.5±0.09 ABSU in control, the difference between groups was statistically significant. The native thiol, total thiol levels and the disulphide levels were significantly lower in the patient group as compared with the control group. The myeloperoxidase level was 136 U/L in patients and 107 in controls with a statistically significant difference between groups. CONCLUSIONS: TOS, IMA, MPO, and particularly plasma thiols seem good candidates for accurate diagnosis of bacteremia in children.

Etiological and Clinical Profile of Acute Nonbacterial Encephalitis in Children: A Single-Center Prospective Study.

Encephalitis is a serious neurological syndrome caused by inflammation of the brain. The diagnosis can be challenging and etiology remains unidentified in about half of the pediatric cases. We aimed to investigate demographic, clinical, laboratory, electroencephalographic and neuroimaging findings, and outcome of acute encephalitis of nonbacterial etiology. This prospective study included children hospitalized with the diagnosis of acute encephalitis between 2017 and 2019. Microbiological investigations of the cerebrospinal fluid (CSF) were recorded. All CSF specimens were tested for anti-N methyl D-aspartate receptor (NMDAR) antibodies. In total, 31 children aged 10 months to 17 years (median = 6 years) were included. Pathogens were confirmed in CSF in three patients (9.7%): varicella zoster virus, herpes simplex virus type 1 (HSV-1), and both HSV-1 and NMDAR antibodies. Presenting features included encephalopathy (100%), fever (80.6%), seizure (45.2%), focal neurological signs (29%), and ataxia (19.4%). On clinical follow-up of median 9 (6-24) months, six patients showed neurological deficits: together with two patients who died in hospital, total eight (25.8%) patients were considered to have unfavorable outcome. Need for intubation, receiving immunomodulatory treatment, prolonged hospitalization, and high erythrocyte sedimentation rate at admission were associated with unfavorable outcome. The etiology of encephalitis remains unexplained in the majority of children. HSV-1 is the most frequently detected virus, consistent with the literature. The fact that anti-NMDAR encephalitis was detected in one child suggests autoimmune encephalitis not being rare in our center. The outcome is favorable in the majority while about one-fifth of cases suffer from sequelae.

Adhesion molecules as diagnostic and severity biomarkers in pediatric community-acquired pneumonia.

BACKGROUND: Discrimination of the cases with severe and mild pneumonia is crucial due to the requirement of hospitalization, additional management, and treatment protocols. We aimed to analyze the role of IL6 (Interleukin), IL8, IL10, VCAM-1 (soluble Vascular Cell Adhesion Molecule), and sSELE (soluble E-selectin) in the diagnosis and prognostic evaluation of community-acquired pneumonia (CAP). METHODS: Pediatric patients with severe pneumonia (SP) were hospitalized and patients with mild disease (MP) were treated in the community. IL6, IL8, IL10, VCAM-1, and sSELE levels of the patients were investigated and compared with the age- and gender-matched healthy subjects. RESULTS: A total of 113 patients fulfilling the criteria for a diagnosis of CAP were enrolled in the study, 62 (54.8%) of which had SP and 51 (45%) had MP. MP and SP groups were significantly different in terms of IL8, IL10, and sSELE levels. Patients with SP and MP had significantly different WBC, ESR, and CRP values, as well. CONCLUSIONS: Besides classical acute phase parameters, inflammatory response parameters such as IL6 and VCAM-1 levels may be helpful in diagnosis of pneumonia. In terms of determination of disease severity in pediatric CAP, systemic inflammatory markers like IL8 and IL10 and adhesion molecules like sSELE seem useful in clinical settings.

Multicenter Hospital-Based Prospective Surveillance Study of Bacterial Agents Causing Meningitis and Seroprevalence of Different Serogroups of Neisseria meningitidis, Haemophilus influenzae Type b, and Streptococcus pneumoniae during 2015 to 2018 in Turkey.

The etiology of bacterial meningitis in Turkey changed after the implementation of conjugated vaccines against Streptococcus pneumoniae and Haemophilus influenzae type b (Hib) in the Turkish National Immunization Program (NIP). Administration of Hib vaccine and PCV-7 (7-valent pneumococcal conjugate vaccine) was implemented in NIP in 2006 and 2009, respectively. In 2011, PCV-7 was replaced with PCV-13. Meningococcal vaccines have not yet been included in Turkish NIP. This prospective study comprised 27 hospitals located in seven regions of Turkey and represented 45% of the population. Children aged between 1 month and 18 years who were hospitalized with suspected meningitis were included. Cerebrospinal fluid (CSF) samples were collected, and bacterial identification was made according to the multiplex PCR assay results. During the study period, 994 children were hospitalized for suspected meningitis, and Hib (n = 3, 2.4%), S. pneumoniae (n = 33, 26.4%), and Neisseria meningitidis (n = 89, 71%) were detected in 125 samples. The most common meningococcal serogroup was MenB. Serogroup W comprised 13.9% (n = 5) and 7.5% (n = 4) of the meningococci in 2015 to 2016 and 2017 to 2018, respectively. Serogroup C was not detected. There were four deaths in the study; one was a pneumococcus case, and the others were serogroup B meningococcus cases. The epidemiology of meningococcal diseases has varied over time in Turkey. Differing from the previous surveillance periods, MenB was the most common serogroup in the 2015-to-2018 period. Meningococcal epidemiology is so dynamic that, for vaccination policies, close monitoring is crucial.IMPORTANCE Acute bacterial meningitis (ABM) is one of the most common life-threatening infections in children. The incidence and prevalence of ABM vary both geographically and temporally; therefore, surveillance systems are necessary to determine the accurate burden of ABM. The Turkish Meningitis Surveillance Group has been performing a hospital-based meningitis surveillance study since 2005 across several regions in Turkey. Meningococcus was the major ABM-causing agent during the 2015-to-2018 period, during which MenB was the dominant serogroup.

Surveillance of penicillin resistance of Neisseria meningitidis strains from invasive infections between 2013 and 2018 in Turkey.

Neisseria meningitidis (N. meningitidis) is regarded as the leading cause of bacterial meningitis in many regions of the world. The empiric antimicrobial treatment is mainly based on antimicrobial resistance and patient characteristics. We aimed to analyze susceptibility patterns of N. meningitidis strains isolated in Turkey. Invasive meningococci collected in a multicenter, hospital-based, epidemiological surveillance study of pediatric (0-18 years of age) bacterial meningitis cases between 2013 and 2018 were studied. Five isolates (8.7%) displayed resistance to penicillin-G, while 13 isolates (22.8%) had intermediate susceptibility. All isolates were cefotaxime and rifampin susceptible. The data shows appropriateness of third-generation cephalosporins in empirical use for meningococcal infections in children. Since Turkey is located in a transition zone geographically, surveillance reports are very crucial.

[Perianal abscess in children: A pediatric infectious disease perspective]. / Absceso perianal en niños: perspectiva desde el campo de la infectología pediátrica.

INTRODUCTION: There are limited data on the aetiology and management of perianal abscesses (PAs). The aim of this retrospective study was to define the characteristics of children with PAs; describe our experience with PA from the perspective of paediatric infectious medicine and determine the factors that influence clinical outcomes. METHODS: We performed a retrospective review of cases of PA in children with no underlying disease managed in a tertiary referral hospital between January 2005 and July 2015. We collected data on demographic characteristics, symptoms, abscess size and location, abscess recurrences, laboratory and microbiological findings, treatment modalities, diagnosis of systemic illness at the end of the diagnostic workup and clinical outcomes. RESULTS: We included a total of 47 patients in the study, with a predominance of male patients (93.6 vs 6.4%, P<.001). The median age was 7.7 months (IQR 1.8-13.7 months), and 40 children (85.1%) were younger than 2 years of age. Four PAs drained spontaneously and 7 healed without need of drainage (23.4%). Drainage by simple incision was applied to 36 patients (76.5%) and six PAs required fistulotomy (12.7%). Recurrent abscesses were found in 25 patients (53.1%). Three patients with recurrent PA were diagnosed with inflammatory bowel disease at the end of the diagnostic evaluation. CONCLUSIONS: Based on the findings of our study, measurement of white blood cell counts and serum levels of acute phase reactants may be useful in the initial evaluation of children with PA. In light of the high relapse rates observed in surgically managed patients, it seems reasonable to use a conservative approach in patients aged less than 2 years.

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.

Prevalence and seasonal distribution of viral etiology of respiratory tract infections in inpatients and outpatients of the pediatric population: 10 year follow-up.

Aykaç K, Karadag-Öncel E, Bayhan C, Tanir-Basaranoglu S, Akin MS, Özsürekci Y, Alp A, Cengiz AB, Kara A, Ceyhan M. Prevalence and seasonal distribution of viral etiology of respiratory tract infections in inpatients and outpatients of the pediatric population: 10 year follow-up. Turk J Pediatr 2018; 60: 642-652. The aim of this study was to investigate the prevalence and seasonal distribution of respiratory viruses in pediatric patients. Nasopharyngeal swab specimens, demographic and clinical information were collected from 1240 pediatric patients aged < 18 years between 2006 and 2015 in Hacettepe University Children`s Hospital. Multiplex RT-PCR (multiplex reverse transcriptase polymerase chain reaction) was performed to detect viral pathogens. A total of 1240 pediatric outpatients and inpatients who had been admitted to the hospital with symptoms of upper and lower respiratory tract infections (RTIs) were enrolled. Viruses were identified in 339 (27.3%) of cases, with the leading three viruses being respiratory syncytial virus (RSV, 74/339; 21.8%), human rhinovirus (62/339; 18.3%), and multiple viruses (56/339; 16.5%). Most of the patients were diagnosed with lower RTI (264/339; 77.8%) and antibiotics were administered to three quarters of positive patients (254/339; 74.9%). With an overall viral agent detection rate of 27.3%, the findings of the present study suggest that other respiratory pathogens, whether viral or bacterial, may also lead to hospital visits due to respiratory tract symptoms in children.

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.

Future Directions and Molecular Basis of Ventilator Associated Pneumonia.

Mechanical ventilation is a lifesaving treatment and has complications such as ventilator associated pneumonia (VAP) that lead to high morbidity and mortality. Moreover VAP is the second most common hospital-acquired infection in pediatric intensive care units. Although it is still not well understood, understanding molecular pathogenesis is essential for preventing and treating pneumonia. A lot of microbes are detected as a causative agent of VAP. The most common isolated VAP pathogens in pediatric patients are Staphylococcus aureus, Pseudomonas aeruginosa, and other gram negative bacteria. All of the bacteria have different pathogenesis due to their different virulence factors and host reactions. This review article focused on mechanisms of VAP with molecular pathogenesis of the causative bacteria one by one from the literature. We hope that we know more about molecular pathogenesis of VAP and we can investigate and focus on the management of the disease in near future.

A comparison of blood stream infections with extended spectrum beta-lactamase-producing and non-producing Klebsiella pneumoniae in pediatric patients.

BACKGROUND: Rapid development and global spread of multidrug resistant Klebsiella pneumonia (K. pneumoniae) as a major cause of nosocomial infections is really remarkable. The aim of this study was to explore risk factors for health care associated blood stream infections (BSI) caused by ESBL-producing K. pneumoniae in children and analyze clinical outcomes. METHODS: A retrospective review of patients younger than 18 years-old with blood stream infection caused by K. pneumoniae was performed. Patients with ESBL-producing K. pneumoniae isolates were compared with ESBL-non-producing isolates in terms of risk factors, outcome and mortality. RESULTS: Among 111 K. pneumoniae isolates 62% (n = 69) were ESBL -producing K. pneumoniae. The median total length of hospitalization and median length of stay in hospital before infection was significantly higher in patients with ESBL-producing isolates than ESBL-non-producing. Use of combined antimicrobial treatment was significantly different between ESBL-producing and ESBL-non-producing groups, 75.4% and 24.6%, respectively (p = 0.001). Previous aminoglycoside use was higher in cases with ESBL -producing isolates (p = 0.001). Logistic regression analysis showed a significant correlation between mortality and use of combined antibiotics (OR 4.22; p = 0.01). CONCLUSION: ESBL production in K. pneumoniae isolates has a significant impact on clinical course of BSIs. Total length of hospitalization, length of hospital stay before infection, prior combined antibiotic use and use of aminoglycosides were significant risk factors for development of ESBL-producing K. pneumoniae related BSI.

Add-On Therapy with Ertapenem in Infections with Multidrug Resistant Gram-Negative Bacteria: Pediatric Experience.

Optimal therapy for infections with carbapenem resistant GNB is not well established due to the weakness of data. Patients presenting with bloodstream infections caused by multidrug resistant Klebsiella pneumoniae were treated with a combination treatment. Optimal therapy for infections with carbapenem resistant Gram-negative bacteria is a serious problem in pediatric patients. We presented three cases who were successfully treated with addition of ertapenem to the combination treatment for bacteremia with multidrug resistant Klebsiella pneumoniae. Dual carbapenem treatment approach is a new approach for these infections and requires more data in children.

Current epidemiology of resistance among Gram-negative bacilli in paediatric patients in Turkey.

OBJECTIVES: The increasing incidence of infections caused by drug-resistant Gram-negative organisms has led to a re-emergence worldwide. This study attempted to investigate the changes in resistance of Gram-negative bacteria to different classes of antibiotics and the treatment options for invasive infections. METHODS: A retrospective study was performed between January 2012 and January 2017 in a Turkish tertiary care university hospital. A total of 302 patients with Gram-negative bacteraemia (n=274; 90.7%) or meningitis (n=28; 9.3%) were identified and their demographic, clinical and microbiological features were evaluated. RESULTS: A total of 302 patients with Gram-negative bacterial infection (bacteraemia or meningitis) were investigated. Klebsiella spp. was the most frequent causative agent (n=119; 39.4%), followed by Escherichia coli (n=67; 22.2%), Acinetobacter spp. (n=42; 13.9%), Pseudomonas spp. (n=41; 13.6%) and Enterobacter spp. (n=33; 10.9%). In total, 115 isolates (38.1%) were multidrug-resistant (MDR), 63 (20.9%) were extensively drug-resistant (XDR) and 6 (2.0%) were pandrug-resistant (PDR). Over the years, peak antibiotic resistance occurred in 2013, with an increase in the following years. CONCLUSIONS: These data indicate that the resistance pattern of Gram-negative bacteria may change over the years in hospital settings. Therefore, active surveillance of the resistance patterns of micro-organisms is necessary for better management of infections caused by highly resistant bacteria.

Human Bocavirus: Can It Trigger Hemophagocytic Lymphohistiocytosis?

With improvements in molecular diagnostic methods, report of Human bocavirus (HBoV) as an etiologic agent in many studies on viral respiratory and gastrointestinal infections has been increasing. Two pediatric patients who presented with secondary hemophagocytic lymphohistiocytosis were examined for etiologic causes, including viruses. Whole bacterial and fungal cultures and viral serological studies were negative. Viral polymerase chain reaction of nasopharyngeal secretions showed HBoV. One was successfully treated with intravenous immunoglobulins, whereas the other died with multiorgan failure. Here we report 2 pediatric patients with secondary hemophagocytic lymphohistiocytosis and detection of HBoV as the sole agent, predicting an association.

Invasive pneumococcal disease: From a tertiary care hospital in the post-vaccine era.

A breakthrough infection occurring with 13-valent pneumococcal conjugate vaccine (PCV13) in Turkey are previously described. A breakthrough infection is defined as IPD in a child who had received ≥ 1 PCV-7 or PCV-13 and for which the pneumococcal isolate was a vaccine serotype. During one year period, among 6 patients with invasive pneumococcal infection, 2 patients were considered to have a vaccine failure with serotype 19F. Antibiotic resistance results were remarkable; macrolide resistance were observed in all strains except one, and high and intermediate penicillin resistance were determined in 2 strains.